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Table of Content

    15 April 2021, Volume 24 Issue 11
    Monographic Research
    Chinese General Practice Experts Consensus on the Use of Benazepril Hydrochloride and Hydrochlorothiazide Tablets in Primary Care 
    General Practitioner Branch of Chinese Medical Doctor Association
    2021, 24(11):  1309-1316.  DOI: 10.12114/j.issn.1007-9572.2021.00.440
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    Medical Doctor Association There is sufficient evidence that the fixed-dose single-pill combination can improve the therapy adherence and the rate of meeting the target blood pressure level in patients with hypertension,improving their prognosis.Benazepril hydrochloride and hydrochlorothiazide tablets(BHHT) have been used for hypertension for many years,which has proved to play a positive role in the treatment and management of hypertension in primary care by a great deal of clinical evidence.However,due to doubts about clinical use of BHHT,especially medicines containing hydrochlorothiazide,these medicines are underused seriously in primacy care by general practitioners(GPs).To increase GPs’ understanding of BHHT and guide them to rationally use BHHT to promote standardized management of hypertension in primary care,China General Practitioner Association,Chinese Medical Doctor Association invited a panel of general practice experts to compile this consensus based on the latest high-quality evidence and relevant guidelines,which mainly includes characteristics and clinical benefits of BHHT,clinical application of BHHT in hypertension and hypertension with other diseases,and the main points for clinical application of BHHT in primary care,to guide the rational and standardized application of BHHT in primary care.
    Consensus on Health Management of Climacteric Women in Primary Medical Institutions Edition 
    Chinese Medical Doctor Association (CMDA)'s General Practitioners Sub-association,The Primary Care Branch of Beijing Institute of Obstetrics & Gynecology
    2021, 24(11):  1317-1324.  DOI: 10.12114/j.issn.1007-9572.2021.00.402
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    In order to standardize the health management of climacteric women in primary medical institutions,identify and intervene menopausal related problems positively at early stage to reduce menopausal related health problems and lay the foundation for health in old age.Experts from the Community and Primary Branch of the Beijing Obstetrics and Gynecology Association formulated the “Consensus on climacteric Women's Health Management in primary medical institutions edition” based on evidence-based medical evidence,the status quo of primary medical institutions,and relevant guidelines for menopausal management.The health management of climacteric women mainly includes the establishment of health records,systematic health education,regular health examinations,general health guidance and drug treatment,etc.The issuance of this consensus is of great significance to improve the health management of climacteric women in primary medical institutions.
    Interpretation of the KDOQI Clinical Practice Guideline for Nutrition in CKD:2020 Update 
    CHENG Gaiping,QIN Wei,LIU Jing,LIU Yuan
    2021, 24(11):  1325-1332.  DOI: 10.12114/j.issn.1007-9572.2021.00.166
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    CHENG Gaiping1,QIN Wei2,LIU Jing1,LIU Yuan1*
    In September 2020,The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative(KDOQI)updated its clinical practice guideline for nutrition in CKD.Since the publication of the initial KDOQI nutrition guideline 20 years ago,there has been a great accumulation of new evidence about the nutritional management of kidney disease.The guideline was expanded to include patients with end-stage kidney disease or advanced CKD,patients with stages 1-5 CKD without ongoing dialysis and patients with a functional kidney transplant.The updated guideline statements cover 6 primary areas:nutritional assessment,medical nutrition therapy,dietary protein and energy intake,nutritional supplementation,micronutrients,and electrolytes.The guidelines mainly include dietary management rather than all possible nutritional interventions.Focusing on the main contents of the guideline,the paper interpreted main recommendations and discussed the application in light of the actual situation in China.
    Interpretation of Consensus Guidelines for Perioperative Care in Neonatal Intestinal Surgery:Enhanced Recovery After Surgery (ERAS?) Society Recommendations 
    SHI Zeyao,WU Yang,LI Xiaowen,WAN Xingli,CHEN Qiong,HU Yanling
    2021, 24(11):  1333-1338.  DOI: 10.12114/j.issn.1007-9572.2021.00.424
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    Enhanced Recovery After Surgery (ERAS) refers to a series of optimized management measures taken during the perioperative period under the guidance of evidence-based medicine.Since the concept of ERAS was proposed in 2001,the ERAS? Society has issued more than 10 surgical guidelines,covering various fields such as obstetrics and gynecology,orthopedics,and cardiovascular surgery.In May 2020,the ERAS? Society issued its first neonatal surgical guidelines,which provides multiple evidence-based recommendations for neonatal perioperative management.This article interprets the guidelines,aiming to offer evidence-based suggestions for physicians and nurses to improve the quality of perioperative care in neonatal intestinal surgery,thereby enhancing the survival quality of the neonates.
    Clinical Characteristics and Risk Factors for Critical-ill Events in Children with Severe Influenza 
    WANG Yakun,HOU Wei,JIA Meixuan,WANG Qian,ZHANG Wenchao,TIAN Liyuan
    2021, 24(11):  1339-1343.  DOI: 10.12114/j.issn.1007-9572.2021.00.415
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    Background  Influenza is an acute respiratory infectious disease caused by influenza virus,which can cause outbreaks and epidemics in the world,and may result in serous outcomes in children。But the mechanism for critical-ill events occurring in children is still under exploration.Objective To explore the clinical characteristics and risk factors of critical-ill events in children with severe influenza.Methods We selected 76 children with severe influenza who were admitted to Hebei Children's Hospital from December 2018 to March 2019,and divided them into severe group(52 cases)and critically ill group(24 cases)according to disease severity.We collected their general clinical data(gender,months of age,influenza type,presence or absence of underlying diseases,complication involved system,white blood cell count,neutrophil count,hemoglobin,platelet count,C-reactive protein(CRP),calcitonin,lactate dehydrogenase(LDH),imaging findings,etiological results and other information,and compared the differences between severe and critically ill cases.Results Nineteen of 76 cases(25.0%)had underlying diseases.The most common complication of severe influenza was respiratory system involvement(100.0%),followed by nervous system involvement(28.9%),and digestive system involvement(15.8%).Critically ill cases had higher incidence of nervous system involvement and LDH level and lower hemoglobin level than severe cases(P<0.05).Chest imaging found 56 cases of pulmonary light or patchy shadows,30 cases of lung consolidation,9 cases of pleural effusion,10 cases of uneven light transmittance in both lungs and 8 cases of air leak syndrome.All the decreased had lung consolidation,among whom 3 also had air leak syndrome,and 2 also had pleural effusion.The incidence of lung consolidation in critically ill group was higher than that in severe group(P<0.05).Sixty-seven of the 76 cases(88.2%)were detected with other pathogenic microorganisms.A total of 67 cases(88.2%)were found with virus infection,among whom 59(77.6%)mainly with adenovirus.A total of 23 cases(30.3%)were found with bacteria infection,and 11(14.5%)of them mainly with Haemophilus influenzae.Ten cases(13.2%)were found with Mycoplasma pneumoniae infection.The detection rate of bacteria as the cause of influenza in critically ill group was higher than that of severe group(P<0.05).Conclusion Most children with severe influenza will suffer from respiratory system involvement.Lung consolidation,nervous system involvement,anemia,increased LDH,and bacterial infections may increase the risk of critical illness.
    Factors Associated with Rotavirus Enteritis with Convulsions in Infants 
    HU Shuying,WANG Liying,LI Minglei,PAN Yuyu,LIU Xiaoyu,LYU Zufang
    2021, 24(11):  1344-1348.  DOI: 10.12114/j.issn.1007-9572.2021.00.413
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    Background Rotavirus enteritis is a main cause of diarrhea among infants.It is an epidemic more commonly happened in autumn and winter,which can cause damage to the digestive system such as the gastrointestinal tract and liver,and to multiple systems such as breathing,circulation,and nerves,and can lead to death in severe cases.Rotavirus enteritis with central nervous system damage can cause symptoms such as convulsion,coma,and limb paralysis,of which convulsion is the most common,but the pathogenesis is not fully clear.To reduce the possibility of developing convulsion and brain damage associated with rotavirus enteritis,it is of great clinical significance to identify high risk factors of convulsion and timely deliver interventions based on analyzing its causes and clinical manifestations.Objective To explore the influencing factors of rotavirus enteritis complicated with convulsions in infants.Methods One hundred and thirty-four infants with rotavirus enteritis(including 47 with convulsions and 87 without)were recruited from Department of Pediatric Medicine,Weifang People's Hospital from January 2018 to December 2019.After admission,fecal sample was collected for performing rotavirus antigen test using ELISA.Fasting venous blood sample was collected for performing routine and biochemical blood tests.Mid-stream urine sample was collected for performing routine urine test.Information was recorded,including sex,age,vomiting frequency,diarrhea frequency,status of fever and dehydration,levels of serum sodium,potassium,chlorine and calcium,glucose,CO2-binding capacity,creatine kinase isoenzyme MB(CK-MB)and other indicators.Multivariate logistic regression analysis was used to explore the influencing factors of rotavirus enteritis complicated with convulsions.Results Rotavirus enteritis infants with convulsions had much more diarrhea frequencies and higher serum CK-MB,and lower fever prevalence,and lower levels of serum calcium,glucose and CO2-binding capacity compared to those without(P<0.05).Multivariate logistic regression analysis showed that fever 〔OR=0.131,95%CI(0.045,0.383)〕,serum calcium 〔OR=66.923,95%CI(5.630,795.468)〕,serum glucose 〔OR=1.958,95%CI(1.316,2.915)〕,and CK-MB〔OR=0.989,95%CI(0.979,1.000)〕 were associated with rotavirus enteritis complicated with convulsions(P<0.05).Conclusion Diarrhea frequency,status of fever,serum levels of calcium,glucose,CO2-binding capacity and CK-MB,especially status of fever,serum calcium,glucose and CK-MB,may affect the occurrence of convulsions in rotavirus enteritis in infants.To prevent convulsion incidence,it is suggested to analyze the patient's detailed medical history and biochemical examination results to early identify risk factors for convulsions and deliver targeted interventions timely.
    Relationship of the Risk of Adulthood Depression with Serum CRP,IP-10,TGF-β1 and Childhood Trauma:a Case-control Study 
    PAN Yuli,ZENG Xuan,LIN Xiujin,YU Miuyu,ZHANG Shengjie,CHEN Fenglan,WU Junduan
    2021, 24(11):  1349-1353.  DOI: 10.12114/j.issn.1007-9572.2021.00.160
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    Background Cytokine hypothesis is one of the most important theories of the mechanism of depression.Numerous studies have suggested that childhood trauma was closely relevant to the occurrence of depression.Knowing the relationship of serum indices,and childhood trauma with depression might provide a theoretical basis for further studies of the pathogenesis.Objective To investigate the relationships of serum CRP,IP-10,TGF-β1 levels and childhood trauma with the risk of adulthood depression.Methods A case-control study design was adopted in this study with 48 adult patients with depression and 51 healthy adult controls from Mental Health Department,The Second Affiliated Hospital of Guangxi Medical University were included during May 2018 to May 2019.Serum CRP,IP-10 and TGF-β1 levels were measured by double-antibody sandwich ELISA.The 28-item Childhood Trauma Questionnaire-Short Form was used to assess childhood trauma.Multivariate Logistic regression was used to identify the risk factors of adulthood depression.Results Compared with control group,the case group showed significantly lower average level of TGF-β 1(P<0.01),and higher scores of emotional abuse,physical abuse,sexual abuse and emotional neglect(P<0.05).Logistic regression analysis showed that lower level of serum TGF-β1,low level of serum TGF-β1,emotional abuse,physical abuse,sexual abuse and emotional neglect increased the risk of depression(OR=5.60,7.86,11.20,7.62,4.43,3.34,P<0.05).Conclusion Serum TGF-β1 levels and childhood trauma experience might have impact on the risk of depression in adulthood.
    Frailty Prevalence and Associated Factors in Elderly Heart Failure Patients with Preserved Ejection Fraction 
    YANG Qiqi,SUN Ying,XING Yunli,ZHANG Yanyang,LUO Zhi,WANG Yubo
    2021, 24(11):  1354-1358.  DOI: 10.12114/j.issn.1007-9572.2021.00.411
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    Background Chronic heart failure is associated with high prevalence of frailty in older adult patients,which may increase the rate of hospitalization and mortality.Early recognition and intervention of frailty may improve the prognosis of elderly.However,relevant evidence is limited.Objective To investigate the prevalence and associated factors of frailty in elderly patients with preserved ejection fraction(HFpEF).Methods A total of 95 patients with stable chronic HFpEF(≥65 years old) who hospitalized in Department of Geriatrics,Beijing Friendship Hospital,Capital Medical University from April 2017 to May 2019 due to various causes were selected,and divided into two groups:non-frailty(healthy and pre-frail)(n=64,<3 points) and frailty(n=31,≥3 points) by the Fried Frailty Phenotype.Demographic information(age,gender,height,weight,BMI,smoking history(defined as consuming cigarettes more than 20 a year),comorbidity prevalence(hypertension,diabetes,coronary heart disease,chronic obstructive pulmonary disease,chronic kidney disease,stroke,peripheral vascular disease),and polypharmacy(defined as the use of at least five medications),laboratory test results(white blood cell count,hemoglobin,platelet count,alanine aminotransferase,creatinine,glycosylated hemoglobin,fasting blood glucose,total cholesterol,triacylglycerol,high-sensitivity C-reactive protein,serum iron,albumin,prealbumin),and echocardiographic indicators(left ventricular ejection fraction,left atrial diameter,left ventricular end diastolic dimension,right ventricular diameter,and E/A ratio) were collected.Activities of Daily Living(ADL) scale and the Instrumental Activities of Daily Living(IADL) scale were used to assess the activities of daily living.The Nutritional Risk Screening(NRS2002) scale was used to assess the nutritional risk.Charlson Comorbidity Index was used to assess the comorbidity risk.Multivariate Logistic regression analysis was used to explore the influencing factors of frailty.Results Compared to non-frail group,the frail group had a greater mean age,higher rate of polypharmacy and higher mean score of Charlson Comorbidity Index(P<0.05).Moreover,The frail group had lower mean ADL,IADL and albumin levels as well as greater mean left atrial diameter(P<0.05).Multivariate Logistic regression analysis revealed that older age and polypharmacy were associated with frailty (P<0.05).Conclusion The prevalence of frailty was 32.6% among elderly patients with HFpEF,which was associated with older age and polypharmacy.
    Effect of Intracoronary and Intravenous Bivalirudin Administration of on No-reflow during PCI and Short-term Outcome in Acute ST-segment Elevation Myocardial Infarction Patients 
    LI Xiufen,XIE Yang,PA Erhati·Tuerxun,JIANG Shubin
    2021, 24(11):  1359-1364.  DOI: 10.12114/j.issn.1007-9572.2021.00.423
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    Background Coronary no-reflow is an important factor associated with the effect of emergency PCI in patients with acute ST-segment elevation myocardial infarction (STEMI),which is also a prognostic factor as it increases the risk of death.So it is essential to identify effective drug treatment to improve the effect of PCI and reduce the possibility of developing coronary no-reflow.Objective To perform a comparative analysis of intracoronary with intravenous administration of bivalirudin and intravenous administration of bivalirudin in patients with acute STEMI in terms of safety and effects on no-reflow during PCI and short-term outcome.Methods Participants were 110 inpatients who were diagnosed with acute STEMI and underwent PCI within 12 hours of symptom onset in Xinjiang Medical University Affiliated TCM Hospital from June 2017 to January 2019.They were evenly randomized into observation group with intracoronary with intravenous administration of bivalirudin,and control group with intravenous administration of bivalirudin.Intraoperative and postoperative observation indices(number of diseased coronary artery vessels,infarct-related artery(IRA),preoperative TIMI flow grade of target vessel,Gensini score,door-to-balloon time,number of thrombus aspiration cases,number of implanted stents,rate of poststenotic dilation,rate of postoperatively using ACEIs or ARBs,rate of postoperatively usingβ-blockers),therapeutic evaluation indices〔corrected TIMI frame count(CTFC) of the IRA measured immediately after stent implantation,and rate of coronary no-reflow during PCI,degree of ST-segment depression within four hours after PCI,serum CK-MB and LVEF at 24 hours after PCI〕,and major adverse cardiovascular events(MACE) within 30 days after PCI were compared between the two groups.Multivariate logistic regression analysis was used to investigate the effect of intracoronary and intravenous bivalirudin bolus administration during PCI on some therapeutic indices.Results There were no significant differences in intraoperative and postoperative observation indices between the two groups(P>0.05).The CTFC of the IRA measured immediately after stent implantation,rate of coronary no-reflow and degree of ST-segment depression within four hours after PCI differed significantly between the two groups(P<0.05).Multivariate Logistic regression analysis showed that intracoronary and intravenous bivalirudin bolus administration during PCI was associated with reduced number of CTFC of the IRA measured immediately after stent implantation 〔OR=0.423,95%CI(0.321,0.656),P=0.005〕,reduced possibility of developing coronary no-reflow 〔OR=0.431,95%CI(0.262,0.812),P=0.002〕,and greater degree of ST-segment depression within four hours after PCI〔OR=1.532,95%CI(0.627,2.517),P=0.003〕.Conclusion The results of this study demonstrate that intracoronary and intravenous bivalirudin administration during PCI could reduce the incidence of coronary no-reflow and the risks of acute heart failure and all-cause death,and improve short-term clinical outcome in acute STEMI patients with good safety.
    New Risk Factors of Cardiac Valve Calcification in Patients with Chronic Kidney Disease 
    TANG Rining,WANG Xiaochen,WANG Liting,CHEN Sijie,ZHANG Yuxia,ZHANG Shuofan
    2021, 24(11):  1365-1371.  DOI: 10.12114/j.issn.1007-9572.2021.00.409
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    Background Cardiac valve calcification(CVC)may maximally increase the risk of developing cardiovascular disease in patients with chronic kidney disease(CKD).Increasing understanding of bone mineral metabolism and the use of new non-calcium phosphate binders and calcimimetic agents in CKD patients,requires a new analysis of clinical characteristics of this population.And there are few studies on CVC in CKD patients as a risk factor for cardiovascular disease.Objective To explore the prevalence and risk factors of CVC in patients with CKD stages 3-5.Methods Patients with CKD stages 3-5 with and without dialysis treated in Department of Nephrology,Zhongda Hospital,Southeast University from August 2014 to July 2019 were selected and their demographic,serological and imaging data were collected.According to the presence of CVC,they were divided into calcification group and non-calcification group.Logistic regression and subgroup analyses were used to explore the risk factors of CVC.Results  Of the included 1 383 cases,619(44.8%)were identified with CVC,of whom 426(30.8%)with aortic valve calcification(AVC),37(2.7%)with mitral valve calcification(MVC),150(10.9%)with both AVC and MVC,and 6(0.4%)with other diseases.Compared to non-calcification group,calcification group had higher proportions of women,dialysis recipients,previous or present users of statins,and cases with elevated C-reactive protein(more than 3 mg/L),greater mean age,higher prevalence of concomitant diabetes,concomitant hypertension,concomitant coronary heart disease,concomitant cerebral infarction and left ventricular hypertrophy,and higher mean levels of serum calcium,albumin and alkaline phosphatase(P<0.05).Calcification group also showed lower proportion of previous or present users of calcium carbonate,and lower mean levels of creatinine,triglyceride,total cholesterol and low-density lipoprotein(P<0.05).In multivariate logistic regression analysis,older age 〔OR=1.065,95%CI(1.053,1.077)〕,dialysis 〔OR=1.917,95%CI(1.423,2.582)〕,concomitant coronary heart disease 〔OR=1.608,95%CI(1.134,2.281)〕,lower level of hemoglobin 〔OR=0.993,95%CI(0.987,0.999)〕,higher level of alkaline phosphatase 〔OR=1.002,95%CI(1.000,1.003)〕 and elevated C-reactive protein(more than 3 mg/L)〔OR=1.478,95%CI(1.095,1.995)〕 were significantly associated with the presence of CVC in patients with CKD(P<0.05).Advanced age 〔OR=1.078,95%CI(1.057,1.099)〕 and history of statins use 〔OR=1.853,95%CI(1.003,3.424)〕 were risk factors of CVC in non-dialysis patients with 3-5 stages of CKD(P<0.05).Advanced age 〔OR=1.081,95%CI(1.061,1.101)〕,long dialysis duration 〔OR=1.123,95%CI(1.067,1.181)〕,hypertension 〔OR=3.071,95%CI(1.453,6.490)〕 and history of calcium carbonate use〔OR=0.515,95%CI(0.300,0.882)〕 were risk factors for CVC in patients with CKD stage 5D and dialysis duration more than one year(P<0.05).Conclusion The prevalence of CVC in patients with CKD stages 3-5 was 44.8% in our study.And the prevalence of AVC was higher than that of MVC.Elevated alkaline phosphatase,lower level of hemoglobin,older age,dialysis,concomitant coronary heart disease and elevated C-reactive protein may be potential risk factors of CVC in these patients.
    Evaluation of Predictive Parameters of Urinary Tract Infection in Patients with Acute Renal Colic 
    CHEN Chunlan,XU Heping,ZHUO Xiaoan,KUANG Lei,LI Jindie
    2021, 24(11):  1372-1375.  DOI: 10.12114/j.issn.1007-9572.2021.00.109
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    Background Acute renal colic(ARC) is an emergency that can be treated conservatively,but its combination with urinary tract infection(UTI) can be life-threatening.Infection evaluation parameters include white blood cell count(WBC) and C-reactive protein(CRP) levels,but they may not significant increase.Objective To evaluate the prevalence of UTI in ARC patients diagnosed based on urine culture,and the predictive value of emergency routine blood and urine tests in ARC with UTI.Methods 200 consecutive patients with ARC due to ureteral calculi were recruited from Emergency Department,Hainan General Hospital from December 2017 to December 2018,196 ARC patients met the inclusion and exclusion criteria,including 26 with UTI(infected group) and 170 without(non-infected group) diagnosed by 3 times of urine culture.General information,including gender,age,time from onset of symptoms to emergency visit,average temperature,history of diabetes and immunodeficiency was collected.White blood cell count,and serum CRP were measured,and nitrite urine test and midstream urine culture were performed.Multivariate logistic regression analysis was used to explore the influencing factors of emergency ARC with UTI.ROC curve analysis was used to evaluate the clinical value of predictive parameters in emergency ARC with UTI.Results The infected group had higher age,higher prevalence of positive result of nitrite in urine and higher average serum CRP than non-infected group(P<0.05).Multivariate Logistic regression analysis showed that age,nitrite in urine,and CRP were the influencing factors of UTI in ARC patients(P<0.05).For the prediction of UTI in ARC,the AUC of age was 0.754〔95%CI(0.688,0.813)〕 with 65.4% sensitivity,76.5% specificity,93.5% negative predictive value(NPV) and 29.8% positive predictive value(PPV) when the optimal cut-off point was determined as 56 years old,the AUC of serum CRP was 0.682〔95%CI(0.612,0.747)〕 with 53.9% sensitivity,80.6% specificity,91.9% NPV and 29.8% PPV when the optimal cut-off point was determined as 8.3 mg/L,and the AUC of positive result of nitrite in urine was 0.698〔95%CI(0.597,0.905)〕 with 69.2% sensitivity,93.0% specificity,94.2% NPV,and 30.3% PPV.Conclusion Age,nitrite in urine,and serum CRP are associated with UTI in ARC.≥56 years old,serum CRP≥8.3 mg/L,and positive nitrite result in urine may have higher predictive value for UTI in ARC.
    Effects of a New Tuberculosis Vaccine Strain on T Cell Immune Memory and Proliferation Capacity 
    SHAO Meng,WU Fang,ZHANG Jie,DONG Jiangtao,LIU Xiaoling,WU Jiangdong,ZHANG Le,ZHAO Haijun,ZHANG Wanjiang
    2021, 24(11):  1376-1382.  DOI: 10.12114/j.issn.1007-9572.2021.00.159
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    Background Tuberculosis(TB) is a global chronic infectious disease with the highest mortality caused by an infective agent.But there is a lack of safe and effective vaccines to prevent adult tuberculosis.Vaccination mainly uses body's immune memory to prevent the re-invasion of pathogens.Therefore,studying the immune memory and proliferation capacity of T cells is crucial for the development of new tuberculosis vaccines.Objective To investigate the effects of a new tuberculosis vaccine strain(B/R strain) on T cell immune memory and proliferation capacity.Methods In January 2019,48 SPF female C57BL/6 mice aged 6-8 weeks were randomly divided into PBS group,BCG group,H37Ra group and B/R strain group,with 12 mice in each group,and were subcutaneously inoculated,respectively.At 8,12,and 16 weeks after immunization,the splenic lymphocytes of three mice in each group were extracted and cultured in vitro,and the levels of central memory lymphocytes(TCM) and effector memory lymphocytes(TEM) were detected by flow cytometry.ELISA was used to detect antigen-specific Th1/Th2 cytokines(IL-2,IFN-γ and IL-4) levels secreted by splenic lymphocytes.CFSE labeling method was used to detect the proliferation of CD4+ and CD8+ T lymphocytes.Results At 8,12,and 16 weeks after immunization,the TCM and TEM levels of CD4+ in BCG,H37Ra,and B/R strain groups were higher than those of PBS group(P<0.05).At 8 weeks post-inoculation,the level of CD4+ TEM in B/R group was lower than that in H37Ra group(P<0.05).At 16 weeks post-inoculation,B/R strain group showed higher level of TCM of CD4+ than H37Ra and BCG groups(P<0.05),and higher level of TEM of CD4+ than BCG group(P<0.05).At 8,12,and 16 weeks after immunization,the TCM and TEM levels of CD8+ in BCG,H37Ra,and B/R strain groups were higher than those of PBS group(P<0.05).At 12 weeks post-inoculation,the level of TEM of CD8+ in B/R strain group was higher than that in H37Ra and BCG groups(P<0.05).At 16 weeks post-inoculation,the TCM and TEM levels of CD8+ in B/R strain group were higher than those of BCG group(P<0.05).At 8,12,and 16 weeks post-inoculation,IL-2 and IFN-γ levels in PBS group were lower than those of other three groups(P<0.05).At 12 weeks post-inoculation,the level of IFN-γ in B/R strain group was higher than that of BCG group(P<0.05).At 16 weeks post-inoculation,IFN-γ and IL-2 levels in B/R strain group were higher than those of BCG and H37Ra groups(P<0.05).The proliferation rates of CD4+ and CD8+ T lymphocytes in BCG,H37Ra and B/R strain groups were higher than those of PBS group(P<0.05).The proliferation rates of CD4+ and CD8+ T lymphocytes in B/R strain group were higher than those of BCG and H37Ra groups(P<0.05).Conclusion The immunizing with the B/R strain in mice could awake up the body to produce higher levels of protective immune memory cells,mainly Th1 type immune responses,and enhance the proliferation capacity of T cells.
    Efficacy of Dietary Therapy and Antioxidant Dietary Supplements in Adults with Non-alcoholic Fatty Liver Disease 
    WANG Duan,MA Wenjun,YAO Yuantao,LI Zhen,ZHENG Ying,LI Yuanhong,SONG Jiayin,ZHANG Yanjun,XIAO Benxi
    2021, 24(11):  1383-1389.  DOI: 10.12114/j.issn.1007-9572.2021.00.412
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    Background Non-alcoholic fatty liver disease(NAFLD)has become the first major chronic liver disease in China,bringing about severe disease burden.Due to lack of effective drug therapies,dietary therapy is an essential and important treatment for NAFLD.However,there is still a lack of guidance and standards for carrying out nutritional therapy and evaluating the efficacy.Objective To investigate the effects of individualized precision dietary therapy with antioxidant dietary supplements(grape seed extract)on body composition,liver hardness,serum indicators of liver function and inflammation in NAFLD patients.Methods One hundred NAFLD patients aged 18-65 years were recruited from Nutrition Department,and Fatty Liver Disease Subspecialty Clinic,GI Medicine Department,Guangdong Provincial People's Hospital using convenient sampling from April 2018 to July 2019.Those with an even appointment number and with an odd appointment number were equally and randomly assigned to control and treatment arms(each n=50),respectively.All patients were given individualized nutrition therapy by nutrition specialists based on the principle of " eating balanced meals on a modified diet with limited carbohydrate,energy and low glycemic load".The cases in the treatment arm additionally received antioxidant dietary supplements,2 tablets once daily.Information was obtained,including age,sex,anthropometric indicators〔height,body weight,BMI,neck circumference(NC),waist circumference(WC)and hip circumference(HC)〕,body composition〔fat mass(FM),muscle mass,basal metabolic rate(BMR)and visceral fat rating(VFR)〕,liver hardness〔stiffness and controlled attenuation parameter(CAP)〕,serum indicators〔alanine aminotransferase(ALT),aspartate transaminase(AST),gamma-glutamyl transpeptidase(GGT),triglyceride(TG),total cholesterol,high-density lipoprotein(HDL),free fatty acid(FFA),total 25-hydroxy vitamin D,superoxide dismutase(SOD),high-sensitivity C-reactive protein(hs-CRP)〕 and lipid accumulation product(LAP) index.Pre-post treatment changes in each arm and inter-arm differences were analyzed.Results Nine dropouts(4 controls and 5 cases)were excluded,the remaining 91 patients were finally enrolled.BMI,NC,WC,and HC were significantly decreased after treatment in patients of both arms(P<0.05).Body weight,FM,BMR,VFR,LAP index,CAP,ALT,GGT,and hs-CRP were decreased after treatment in the control arm(P<0.05).In the treatment arm,body weight,FM,VFR,LAP index,liver hardness,CAP,ALT,GGT,TG,FFA,and hs-CRP were decreased,and HDL and SOD were increased after treatment(P<0.05).The treatment arm showed lower FFA concentration and higher SOD level after treatment compared to the control arm(P<0.05).Conclusion  In NAFLD patients,individualized precision dietary therapy developed and delivered by nutrition specialists and regular follow-ups could improve parameters of anthropometry,body composition,liver hardness,serum biochemical indicators of liver function and inflammation.Antioxidant dietary supplements were synergistic with dietary therapy in improving lipid metabolism,reducing the concentration of FFA and increasing the SOD level.
    General Practitioners Should Understand the Subtype of Essential Hypertension "Longitudinal Hypertension" 
    NIE Liantao, RUAN Bingxin, ZHANG Fangfang, JING Yan, HUANG Juxiang, YAN Qiongwen, ZHOU Yuhan, LI Shifeng, LI Zhongjian
    2021, 24(11):  1389-1393.  DOI: 10.12114/j.issn.1007-9572.2021.00.444
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    General Practitioners Should Understand The Subtype Of Essential Hypertension-Longitudinal Hypertension

    NIE Liantao1ZHANG Fangfang1JING Yan1HUANG Juxiang1YAN Qiongwen1ZHOU Yuhan1

    LI Shifeng1LI Zhongjian1RUAN Bingxin2

    1.Department of    Electrocardiography,     the Second   Affiliated        Hospital of    Zhengzhou University,450014,China

    2.Department of Electrocardiography,Nanning first people's Hospital,530022,China

    *Corresponding author:LI Zhongjian,Professor, chief technologist; E-mail: lizhongjian56@126.com AbstractIn clinical work and daily lifetarget organ damage caused by blood pressure ≥ 140/90mmHg1mmHg=0.133kPausually attracts attentionbut target organ damage caused by blood pressure <140/90mmHg will often be ignored.Thereforein order to improve the innovative concept and research orientation of hypertension,the research team proposed "longitudinal hypertension".This article found that the transverse hypertension emphasizes the “quantity” change caused by blood pressure≥140/90mmHg while the “longitudinal hypertension” emphasizes both "quantity" change and "quality" change of each individual through the introdution of the conceptdiagnostic criteria and advantages of "longitudinal hypertension"

    similaritiesanddifferences between “longitudinal hypertension” and transverse hypertension.Thereforeas primary health caregiversgeneral practitioners should understand and master the essenceconceptdiagnosis and treatment methods of "longitudinal hypertension".At the same timethe research team also hopes to discuss and improve the existence and application value of "longitudinal hypertension" with colleagues.

    Keywordsgeneral practitioner, essential hypertension, transversehypertension, longitudinal hypertension, electrocardiography, morphology

    Five thousand years of traditional Chinese Medicinehas the concept and characteristics of "one person, one pulse diagnosis" and "one person, one prescription".That is to say, the method and traditional idea of syndrome differentiation and treatment according to people are in the same line with the idea of modern evidence-based medicine.In clinical work and daily life,the damage of heart, brain, kidney, eyes, ears (sudden deafness/tinnitus) and other target organs caused by blood pressure140/90mmHg (1mmHg=0.133 kPa) often attracts people's attention.However, the target organ damage caused by blood pressure <140/90mmHg is not recognized, understood or even valued by people, but it can also lead to the same outcomes as the target organ damage caused by blood pressure140/90mmHg, such as cerebral thrombosis, cerebral hemorrhage, myocardial infarction and even sudden cardiac death.Based on this, our team proposes the concept and diagnostic method of "longitudinal hypertension"(or atypical hypertension) for the first time.That is to say, the patient's blood pressure increases 20-30mmHg compared with that at the age of 18 years old, accompanied by clinical manifestations of hypertension and objective examination indications of target organ damage,which can be diagnosised "longitudinal hypertension".Why does "longitudinal hypertension" cause damage to human target organs?Because everyone's appearance, height, weight, appetite, sleep and so on are different, so the basic blood pressure (blood pressure at the age of 18years old) and blood pressure with age (adult) will bedifferent.Howto determine, judge and "customize"one person's "longitudinal hypertension"?Clinically, it can be combined with the subjective and objective indicators of patients.Subjectiveindicators-hypertension symptoms:headache,dizziness, head discomfort, blurred vision, stiff neck, fatigue, etc.Objective indicators-functional examinations (occasional blood pressure measurement, ambulatory blood pressure measurement, home self-test blood pressure measurement, cardiac function examination, etc.),electrical examinations (ECG, vectorcardiogram, Holter, etc.),morphological examinations (echocardiography, X-ray, CT, MRI, etc.) andlaboratory examinations.As an innovative idea and research direction to improve hypertension, longitudinal hypertension proposed in this paper is essentially different from transverse hypertension. For example, transverse hypertension emphasizes the change of "quantity" of blood pressure140/90mmHg, while longitudinal hypertension emphasizes not only the change of "quantity", but also the change of "quality" of each individual.Therefore, general practitioners should understand and master the essence, concept, diagnosis and treatment of "longitudinal hypertension", so as to contribute to the prevention and control of cardiovascular and cerebrovascular diseases in healthy China 2030.

    1.What is the globally accepted blood pressure assessment method?

    1.1 Blood pressure measurement At present, there are three main methods for blood pressure diagnosis, level classification and evaluation of antihypertensive effect in the world, including clinic blood pressure, ambulatory blood pressure and home self-test blood pressure. However, the European hypertension guidelines[1] no longer recommend clinic blood pressure as the only standard for screening and diagnosis of hypertension, but pay attention to ambulatory blood pressure and home blood pressure monitoring for the detection and identification of white coat hypertension and cryptorchidism Occult hypertension. The new guidelines for hypertension in the United States[2] also agree with this view.

    1.2 Diagnostic criteria of hypertension At present, the diagnostic criteria of hypertension (Europe, China[13]): (1) the diagnostic criteria of clinic blood pressure:140/90mmHg without using antihypertensive drugs measured three times on different days; (2) the diagnostic criteria of ambulatory blood pressure: 24h ambulatory mean blood pressure130/80mmHg, daytime135/85mmHg, night120/70mmHg (3) the diagnostic criteria of home self-test blood pressure:

    135/85mmHg.American diagnostic criteria for hypertension: 130/80mmHg without using antihypertensive drugs measured three times on different days.The continuous adjustment and change of the diagnostic criteria for hypertension is due to the continuous understanding of the harm of hypertension. From the first generation of hypertension criteria 160/95mmHg to the second generation of hypertension criteria 140/90mmHg, and then to the new American guidelines 130/80mmHg, all lie in the prevention and control of cardiovascular and cerebrovascular events[4].Studies have shown that blood pressure >115/75 mmHg, blood pressure growth and the risk of cardiovascular and cerebrovascular events are log linear correlation.The concept put forward of prehypertension or high normotensive blood pressure120~139/80~89mm Hgdemonstrates that the risk of hypertension and coronary heart disease in prehypertensive population is significantly higher compared with the population <120/80mmHg, which suggests that there may be early damage of target organs such as heart, brain, kidney, eye and blood vessel in prehypertensive patients[5].The epidemiological datas in China showed that 32.1% of the population aged 35-54 years has prehypertension, and the risk of stroke, coronary heart disease and cardiovascular events increases by 56.0%, 44.0% and 52.0% respectively[6].There are more than 10 million people with hypotension in China[7].With the increase of blood pressure to a certain extent, there will be hypertension related clinical symptoms and target organ damage.Therefore, the adjustment of diagnostic criteria for hypertension should be based on evidence-based medicine, and there are differences in race, diet structure and living habits between China and foreign countries,which needs consistent and need more in-depth study.

    1.3 Target of antihypertension Chinese guidelines[3] recommend that patients with low risk stratification of hypertension: <140/90mmHg, patients with high risk stratification of hypertension: < 130/80mmHg,consistenting with the new antihypertensive goal of the European guidelines[1], but contrary to the 2017 USA guidelines[2],The target of American blood pressure control is < 130/80mmHg for patients with stable coronary heart disease, chronic heart failure, chronic kidney disease, diabetes, even elderly patients in good condition aged over 65 years old .In Chinese guidelines, on the basis of the above, there are age stratification: (1) for patients over 80 years old with hypertension, the blood pressure is reduced to <150/90mmHg first, and then to <140/90mm Hg if they can tolerate it; (2) for elderly weakened patients with hypertension, the systolic blood pressure control target is < 150 mm Hg, but not less than 130 mm Hg as far as possible.According to the 2018 European hypertension guidelines[1], the lower limit of blood pressure control should be 120/70mmHg for general hypertensive patients, and 130/70mmHg for chronic kidney disease patients and elderly patients over 65 years old. The new guidelines of China, the United States, and Europe define the goal of reducing blood pressure in hypertension, which aims to avoid the risk of excessive blood pressure and adverse cardiovascular events.

    In conclusion, the guidelines and diagnostic criteria for hypertension at home and abroad are still imperfect.For example: (1) the diagnosis and treatment of hypertension (transverse hypertension) only emphasizes the value of blood pressure, age, risk factors and so on to start antihypertensive treatment and effect evaluation, but does not fully evaluate the objective indicators of clinical symptoms and target organ damage; "Longitudinal hypertension" ,the special subtype of essential hypertension (blood pressure140/90mmHg), is not covered or ignored / not recognized, or blood pressure<140/90mmHg is not covered, but patients do have objective evidence of clinical symptoms and target organ damage of hypertension.Therefore, our research team first innovatively put forward the concept of "longitudinal hypertension" (or atypical hypertension), with the purpose of improving the current deficiencies in the diagnosis and treatment of hypertension at home and abroad, so as to promote the health of the whole people and achieve the grand goal of a healthy world.

    2.What is longitudinal hypertension (atypical hypertension)?

    2.1 Origin of "longitudinal hypertension" Hypertension is divided into primary hypertension and secondary hypertension. Secondary hypertension is caused by other diseases, drug treatment effect is poor or invalid.With primary disease cured, blood pressure then becomes normal.While,the primary hypertension cann’t determine the causes through a variety of examination methods,nor be radically cured,but drug treatment is effective.Our research team believes that primary hypertension and secondary hypertension with blood presure140/90mmHg are transverse hypertension, which can also be called typical hypertension.The main results are as follows: (1) In the absence of antihypertensive drugs, the blood pressure measured in three clinics on different days is 140/90 mm Hg (Europe, China);(2) According to the 2017 American hypertension standard, blood pressure130/80mmHg, which is the scope of hypertension recommended by accepted guidelines.The "longitudinal hypertension" proposed by our research team should belong to primary hypertension, which is actually a subtype of primary hypertension (also known as atypical hypertension), or a special type of hypertension.

    2.2 Concept of "longitudinal hypertension" The patient has abnormal clinical manifestations and instrument examination of hypertension,whose blood pressure is less than 140/90 mmHg but increased by 20-30 mmHg compared with his own 18-year-old blood pressure (adult basic blood pressure) .Above conditions meet the individual diagnostic criteria of hypertension,which can also be called atypical hypertension / progressive hypertension / historical hypertension / temporal hypertension / progressive hypertension / individual precise hypertension / private customized hypertension.According to Article 11 of the civil code of the people's Republic of China[8], 18-year-old subjects are regarded as the baseline reference of "longitudinal hypertension". It is pointed out that citizens over 18 years old are adults. If minors (0-17 years old) are selected as the subjects, their age span is large, and it is not easy to operate or even error in the actual observation and comparison work.People who do not monitor their blood pressure at the age of 18 can obtain adult basic blood pressure by two methods: (1) clinical consultation:most people know that their basic blood pressure is low and often have a series of clinical manifestations caused by low blood pressure, which is easy for patients to know when they are young; (2) through 24-hour ambulatory blood pressure monitor:looking for the lowest values of systolic blood pressure and diastolic blood pressureb in 24-hour ambulatory blood pressure, combined with the patients' clinical symptoms and abnormal changes related to the increase of blood pressure in routine electrocardiogram, can be determined.

    2.3 Diagnostic criteria of "longitudinal hypertension" (1) The patient's blood pressure is less than 140/90mmHg, but with 20-30mmHg higher than that of 18 years old; (2) The patient has clinical manifestations of hypertension; (3) special examination (functional / electrical / morphological / biochemical examination, etc.) showes abnormal indications of target organ damage inhypertension.

    2.4 Diagnostic methods and key points of "longitudinal hypertension" (1) functional examination: occasional blood pressure / whole day mean blood pressure increased by 20-30 mmHg compared with that at the age of 18; (2) electrical examination: ECG / vectorcardiogram / Holter diagnosis: left atrium / left ventricle hypertrophy; myocardial ischemia (ST-T change); arrhythmia; (3) morphological examination: color Doppler ultrasound / X-ray / CT / MRI diagnosis: left atrium/ Left ventricular hypertrophy; arrhythmia; abnormal cardiac function; (4) biochemical examination: hypertension related indicators are abnormal.

    3.What are the advantages of longitudinal hypertension monitoring? What should general practitioners do?

    3.1 Advantages of "longitudinal hypertension"monitoring Based on the origin, concept, diagnostic criteria, diagnostic methods and key points of "longitudinal hypertension", as general practitioner, we should change our thinking, change the traditional medical concept, change the point of view that clinical and medical technology can not communicate, and adopt specific diagnosis and treatment methods for specific patients.Through the introduction of primary hypertension, secondary hypertension and "longitudinal hypertension"(atypical hypertension / progressive hypertension / historical hypertension / temporal hypertension / progressive hypertension / individual precise hypertension / private customized hypertension) proposed by our research team,General practitioners have a preliminary understanding of "longitudinal hypertension", especially the practicability, rationality and scientificity of "longitudinal hypertension" in clinical diagnosis and treatment of hypertension, and it is significant to enrich the theory and practice system of hypertension, especially based on evidence-based medicine.It is concluded that the definition and nomenclature of "longitudinal hypertension" is more conducive to the development of clinical hypertension work.In order to keep "longitudinal hypertension" in mind, the advantages of monitoring "longitudinal hypertension" are described as follows: (1) "longitudinal hypertension" has the characteristics of atypical hypertension / progressive hypertension / historical hypertension / temporal hypertension / progressive hypertension / individual precise hypertension, and more has the characteristics of "private customized hypertension" diagnosis and treatment,which is relative to transverse hypertension.(2) Transverse hypertension focuses on group and individual blood pressure >140/ 90 mmHg,which emphasizes the change of "quantity" but ignores the change of "quality" (clinical manifestation and target organ damage of hypertension);"Longitudinal hypertension" emphasizes that blood pressure of the group and individual is 20-30mmHg larger than themselves, which not only emphasizes the change of "quantity" of each individual, but also emphasizes the change of "quality" of each individual.

    3.2 general practitioners As a general practitioner, he should master the following skills: (1) he should be familiar with the symptoms and manifestations of hypertension; (2) he should be familiar with ECG / vectorcardiogram / ambulatory ECG / ambulatory blood pressure / ultrasound, X-ray, CT, MRI / laboratory examination and other hypertension diagnosis and treatment skills, and conduct ECG / vectorcardiogram / ambulatory ECG / ambulatory blood pressure examination for individuals / groups.In particular, the routine ECG can be used as a screening test for hypertension, which is not only a green test, but also can be widely used, because the ECG examination is cheap, and can be repeated for many times. It is not harmful to the human body, and the subjects are more willing to accept it, which has guiding significance for the diagnosis and treatment of "longitudinal high blood pressure";(3) he should understand and recognize that hypertension is a syndrome that causes damage to multiple organs (heart, brain, kidney, eyes, ears, etc.).

    4.What are the similarities and differences between transverse hypertension and "longitudinal hypertension"?

    4.1 Similarities and differences between transverse hypertension and longitudinal hypertension 4.1.1 Differences between transverse hypertension and longitudinal hypertension (1) Transverse hypertension,whose blood pressure140/90mmHg, increases by 20-30mmHg or even higher on the basis of 18 years old;"Longitudinal hypertension",whose blood pressure < 140/90mmHg, increases by 20-30mmHg or even higher on the basis of 18-year-old blood pressure, but the blood pressure is always <140/90mmHg.

    4.1.2 Common points of transverse hypertension and "longitudinal hypertension" (1) Both types of hypertension have symptoms of hypertension, such as headache, dizziness, blurred vision, deafness, tinnitus, and fatigue; (2) both types of hypertension have ECG changes caused by target organ damage: left atrial / left ventricular hypertrophy, myocardial ischemia (ST-T change), arrhythmia.

    4.2 Diagnosis and evaluation of transverse hypertension and "longitudinal hypertension" Both transverse hypertension and longitudinal hypertension can cause abnormal changes in the function, electricity, morphology, biochemistry and clinical symptoms of target organs such as heart, brain, kidney, eyes and ears.According to this, we can apply functional examination (clinic blood pressure, ambulatory blood pressure, cardiac function;cardiac electrical examination: routine electrocardiogram, vectorcardiogram, dynamic electrocardiogram) combined with clinical symptoms to comprehensively analyze and judge, accurately diagnose transverse hypertension and "longitudinal hypertension". At the same time, we can apply the above examination methods to accurately evaluate the treatment effect of transverse hypertension and "longitudinal hypertension" .According to the observation and research of ECG Department of the Second Affiliated Hospital of Zhengzhou University in the past 20 years, it is found that the application of ECG technology can early detect and accurately diagnose the ECG changes caused by transverse hypertension and "longitudinal hypertension" cardiac electrical damage, such as left atrial / left ventricular hypertrophy, myocardial ischemia (ST-T change), arrhythmia.The application of ECG technology can also accurately evaluate the treatment effect of transverse hypertension and "longitudinal hypertension", such as atrial / ventricular depolarization wave and repolarization wave: Ptfv1 disappeared / QRS wave voltage decreased / ST segment depression returned to normal / T wave abnormal change improved / arrhythmia improved after treatment.

    4.3 Relationship between "longitudinal hypertension" and physiological hypertension caused by agingsystem The blood pressure rise caused by longitudinal hypertension includes: (1) 20-30 mm Hg increase on the basis of the blood pressure at the age of 18; (2) symptoms of hypertension, such as headache, distension, dizziness, blurred vision, deafness, tinnitus and fatigue; (3) electrical changes of the heart (ECG changes) caused by target organ damage of hypertension: left atrium/ Left ventricular hypertrophy, myocardial ischemia (ST-T change), arrhythmia.Physiological blood pressure elevation is characterized by: (1) there may be a slow increase of blood pressure with age, but never a sudden increase of 20-30 mm Hg; (2) no symptoms of hypertension; (3) no changes of ECG caused by target organ damage of hypertension.

    4.4 Treatment goals of transverse hypertension and "longitudinal hypertension" In terms of treatment, the goals of transverse hypertension and "longitudinal hypertension" are the same, and there is no difference.The specific manifestations are: (1) ambulatory blood pressure examination:

    mean systolic / diastolic blood pressure reduces 20-30mmHg than before, even more;(2) The clinical symptoms are relieved or disappeared;(3) Cardiac electrical examination: atrial / ventricular depolarization wave and repolarization wave: Ptfv1 disappeared / QRS wave voltage decreased / ST segment depression returned to normal / T wave abnormal change improved / arrhythmia improved after treatment.

    What is the application prospect of longitudinal hypertension?

    5.1         The origin, concept, diagnostic criteria, diagnostic methods and key points,diagnostic difference and common ground between longitudinal hypertension and transverse hypertension proposed by our research team,which expectes colleagues to discuss and improve the existence and application value of "longitudinal hypertension".

    5.2         Our research team has carried out "longitudinal hypertension" for 20 years, and has accumulated a large number of cases and experience in diagnosis and treatment, but lack of multi center, big data and other evidence-based medicine verification and support.To carry out the research work of "longitudinal hypertension" can realize the normal blood pressure of the whole people, reduce the damage to human target organs caused by hypertension, promote the physical and mental health of the whole people, and build a "2030 healthy China".

    The author's contribution: Li Zhongjian is responsible for the conception and design of the article, the overall supervision and management of the article; Zhang Fangfang, Yan qiongwen and Zhou Yuhan are responsible for the implementation and feasibility analysis of the research; Nie liantao and Ruan Bingxin are responsible for writing the paper; Jing Yan and Huang Juxiang are responsible for the revision of the paper; Li Shifeng is responsible for the quality control and review of the article.

    There is no conflict of interest in this article

    Feference

    [1]     WHELTON P,CAREY R,ARONOW W,etal.2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA

    Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.[J] .J Am Coll Cardiol,2018,71(19): e127-e248.DOI:10.1016/j.jacc.2017.11.006

    [2]     WILLIAMS B,MANCIA G,SPIERING W,et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension.[J] .Eur Heart J,2018,39(33):3021-3104.DOI:10.1093/eurheartj/ehy339

    [3]     Hypertension Alliance (China), hypertension branch of China Association for the promotion of international exchange in health care, revision committee of Chinese guidelines for the prevention and treatment of hypertension, etc. Chinese guidelines for the prevention and treatment of hypertension (revised in 2018) [J]. Chinese Journal of Cardiology,2019,24(1):25-56.DOI:

    10.3969/j.issn.1007-5410.2019.01.002 http://rs.yiigle.com/CN113805201901/1118901.htm

    [4]     VASAN R,LARSON M,LEIP E, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease.[J] .N Engl J Med, 2001, 345(18):1291-1297. DOI:10.1056/NEJMoa003417

    [5]     GILES T,MATERSON B,COHN J,et al. Definition and classification of hypertension: an update.[J] .J Clin Hypertens

    (Greenwich), 2009, 11(11): 611-614.DOI:10.1111/j.1751-7176.2009.00179.x

    [6]     SUN X,YUAN H.Review of sub-clinical Lesions in prehypertension[J.Advancesin cardiovascular diseases2010,31(2): 197-200.DOI10.3969/j.issn.1004-3934.2010.02.015

    [7]     XIAO Y,LIU Z,YANG T.Thoughts on the changes of diagnostic criteria of hypertension in the past century[J]. Chinese Journal of Hypertension2017,25(3):204-206.DOI:CNKI:SUN:ZGGZ.0.2017-03-003

    [8]     China legal system press. Civil code of the people's Republic of China [M]. Beijing: China legal system press,2020:2-10

     

    Appendix: Interview with the author about the aticle:general practitioners should understand the subtype of essential hypertension "longitudinal hypertension"

    Problem 1: The diagnostic criteria for hypertension is determined by a large amount of evidence-based medicine in the world. An important reason for not lowering the diagnostic criteria in China is that if the diagnostic criteria is lowered a little, the management population will increase significantly. At present, the main contradiction in China is the low awareness rate and treatment rate of hypertension. How to balance this problem?

    1.The new guidelines in the United States have been similarly questioned, but there is an account in the guidelines. The cost of reducing the standard of hypertension and expanding the treatment population is far less than the cost of target organ damage caused by elevated blood pressure, and the direct beneficiaries are the patients themselves and the health of the national population. Therefore, the new guidelines in the United States recommend that the blood pressure should be controlled below 130/80mmHg (1 mmHg=0.133kPa) in a tolerable situation.

    2.There is no change in the diagnostic criteria of hypertension in China, which is due to the consideration of race, diet structure, lifestyle and other reasons. It is also the goal of Chinese experts to find the criteria suitable for the Chinese population. However, in clinical work, blood pressure <140/90mmHg, patients with symptoms and abnormal changes of target organ damage by instrument examination are many.We can't ignore this kind of people just because we are worried about the expansion of the management population, which will lose the significance of individual diagnosis and treatment of doctors,nor can we achieve the grand goal of healthy China. 3. The low awareness rate can be made up by increasing the popularization of science and other measures,the low treatment rate is due to the single diagnosis of hypertension in the world, which is basically diagnosed only by measuring the blood pressure in the clinical room.The lack of ambulatory blood pressure monitoring and a variety of instruments to evaluate the diagnosis and treatment of target organ damage caused by hypertension makes it difficult for patients to understand the damage caused by hypertension.We propose that "longitudinal hypertension" is a subtype of essential hypertension, which is a supplement and improvement to essential hypertension. To summarize the characteristics and diagnosis process of this kind of population is not only the need of clinical practice, but also the need of patients, but also the need of healthy China.

    Problem 2: Hidden hypertension and white coat hypertension exist in hypertension, which are related to target organ damage.What is the difference between longitudinal hypertension and the above two types of hypertension?

    Hidden hypertension is high blood pressure (blood pressure>140/90mmHg) measured by family and normal blood pressure in clinical room. White coat hypertension is high blood pressure (blood pressure>140/90mmHg) measured in clinical room and normal blood pressure at home. Both of them are high blood pressure (blood pressure>140/90mmHg) and can lead to target organ damage. Our "longitudinal hypertension" is different from the above two kinds of hypertension. The blood pressure is less than 140/90mmHg, and it also has target organ damage.

    Problem 3: The symptoms of hypertension are not specific. The ECG of tall and thin people shows high voltage in the left ventricle and the left atrium increased with age.How to judge whether it is physiological or caused by blood pressure fluctuation?

    1. Although the symptoms of hypertension are not specific, that reflect the clinical symptoms of some patients with hypertension, which has certain guiding significance for the diagnosis of hypertension;

    2.High and thin people can show high voltage of left ventricle, but it may be: (1) it is related to thin chest wall; (2) it is related to hypertension; (3) the two coexist;

    3.The increase of age is not the enlargement of left atrium, but the prolongation and broadening of ECG P wave duration.The prolongation and broadening of P wave duration can be seen in two cases, one is the abnormal conduction caused by atrial block, the other is the enlargement of left atrium caused by hypertension, the stretching of atrial myocytes and the dilatting or thinning of atrial wall.The former is caused by atrial block, ECG manifestations the extension of P-wave duration and the decrease of P-wave amplitude.The latter is caused by the increase of blood pressure and atrial enlargement, ECG manifestationsP-wave amplitude is higher than that of atrial block, P-wave bimodal, Ptfv1 abnormality, left ventricular high voltage, left ventricular hypertrophy, ST-T abnormality, arrhythmia, etc.

    Question 4: what the article wants to emphasize is that everyone needs different blood pressure and different blood pressure threshold. The article should put forward a calculation method for individuals, which is similar to risk assessment. Is this more reasonable?

    We emphasize that the blood pressure threshold of each person is different, and put forward the specific diagnosis basis and process of longitudinal hypertension: (1) the blood pressure in the clinical room is less than 140/90mmHg or the 24-hour ambulatory mean blood pressure is less than 130/80mmHg; (2) the patients have symptoms of hypertension; (3) the blood pressure of the patient increases 20-30 mmHg over his blood pressure when 18 years old; (4) The instrument examination has the basis of hypertension target organ damage, such as: ECG examination: A. left atrial / left ventricular hypertrophy, B. myocardial ischemia (ST-T change), C. arrhythmia; eye and ear examination showed changes of hypertension damage.

    Of course, we can also evaluate the score of patients with longitudinal hypertension, such as: ECG abnormal change 1 item 1 point, 2 items 2 points, 3 items 3 points; clinical symptoms:1 item 1 point, 2 items 2 points, 3 items 3 points; blood pressure increment: younger basal blood pressure increased by 10mmHg 1 point, increased by 20mm Hg 2 points, increased by 30mmHg 3 points and other specific quantitative indicators.

    Question 5: it is mentioned in this paper that the blood pressure level of "longitudinal hypertension" should be compared with the blood pressure level of 18-year-old people. How can people who do not monitor their blood pressure at 18-year-old diagnose "longitudinal hypertension"?

    People who do not monitor their blood pressure at the age of 18 can obtain adult basic blood pressure by two methods: (1) clinical consultation:most people know that their basic blood pressure is low and often have a series of clinical manifestations caused by low blood pressure, which is easy for patients to know when they are young; (2) through 24-hour ambulatory blood pressure monitor:looking for the lowest values of systolic blood pressure and diastolic blood pressureb in 24-hour ambulatory blood pressure, combined with the patients' clinical symptoms and abnormal changes related to the increase of blood pressure in routine electrocardiogram, can be determined.According to this method, our research team has been in clinical application for nearly 20 years.

    To sum up, there are still many unsatisfactory places for our team to creatively put forward the concept of "longitudinal hypertension" in the world.However, our research team firmly believes that in the process of continuous improvement, it will bring gospel to the accurate diagnosis, treatment and effect evaluation of patients with hypertension around the world, which may have more long-term significance for the early prevention of patients with hypertension, and has far-reaching and evidence-based medicine strategic guiding significance for the realization of healthy China.

     

     

    [Expert profile] Li Zhongjian, chief technician, professor, master's supervisor, special reviewer of American circulation magazine, international well-known ECG expert, and doctoral/Master's thesis review expert of the academic degree center of the Ministry of education in 2020.Director of Zhengzhou University institute of electrocardiology, director of Henan electrocardiology diagnosis and treatment center,Visiting professor of Xiamen University.Director of Henan key medical discipline (ECG diagnosis specialty),former deputy director of China electrocardiographic information society/electrocardiographic consultation center, director of national and provincial electrocardiographic continuing education. Outstanding worker of electrocardiography in China, "my favorite health guard"and "outstanding person of scientific and technological innovation" in Henan Province.He obtained 17 scientific research achievements and projects, 13 national patents and 200 papers.At the invitation of the National Space Center and many international conferences, he gave lectures on "ECG identification research" and "fetal ECG";He was invited to attend many international conferences such as "world heart conference" and "international society of ambulatory electrocardiography and noninvasive electrocardiography";In China, he is the first person to put forward the scientific idea of "adhering to the road of electrocardiology with Chinese characteristics",leading the Department to win the national "youth civilization".

     


    Relationship between Blood Pressure Level and Renin-aldosterone System Activity in Patients with Essential Hypertension:a Meta-analysis 
    YUAN Bo,MA Qing,LI Wenfei,LI Zhipeng
    2021, 24(11):  1394-1399.  DOI: 10.12114/j.issn.1007-9572.2021.00.422
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    Background Increased aldosterone is an important risk factor for cardiac hypertrophy,heart failure and renal impairment,leading to more serious damage to the target organs of hypertension such as heart and kidney.Except for primary aldosteronism(PA),clinical evidence shows that plasma rennin activity and aldosterone are elevated in some patients with essential hypertension.However,there are few studies on the correlation between blood pressure level and plasma renin activity and aldosterone levels in patients with essential hypertension,and the conclusions are also inconsistent.Objective To investigate the relationship between blood pressure and renin-aldosterone system activity,and the potential pathophysiological mechanism of hyperaldosteronemia in essential hypertension patients,to provide a theoretical basis for early treatment of essential hypertension and delaying the development of related target organ damages.Methods The databases of PubMed,Embase,CNKI,CQVIP and Wanfang Data Knowledge Service Platform were searched from inception to January 2020 to identify articles about the relationship between blood pressure and renin-aldosterone system activity in patients with essential hypertension.Two researchers independently screened the literature based on the inclusion and exclusion criteria,extracted the data,and evaluated the quality using the Newcastle-Ottawa Scale.RevMan 5.2 was used to conduct meta-analysis.Results A total of 16 articles with Chinese essential hypertensive individuals(n=1 885)compared to healthy controls(n=1 438)as the participants were included.All scored above 5 points on the Newcastle-Ottawa Scale.The results of meta-analysis showed that plasma renin activity〔MD=0.40,95%CI(0.04,0.76)〕in essential hypertensive individuals was significantly higher〔MD=60.03,95%CI(22.28,97.79)〕than that of controls in general(P<0.05).But the supine and standing values of plasma renin activity 〔MD=-1.27,95%CI(-1.37,-1.16);MD=-1.67,95%CI(-1.88,-1.46)〕were lower in essential hypertensive individuals(P<0.05).Essential hypertensive individuals had higher plasma aldosterone level than the controls 〔MD=60.03,95%CI(22.28,97.79)〕on the whole.They also showed higher supine and standing plasma aldosterone levels〔MD=0.07,95%CI(0.06,0.09);MD=0.22,95%CI(0.05,0.39)〕(P<0.05).Conclusion (1)Plasma renin activity and aldosterone levels in patients with essential hypertension were different from those with normal blood pressure.The supine and standing values of plasma renin activity were decreased,and supine and standing values of plasma aldosterone were elevated in essential hypertensive patients.(2)In some patients with essential hypertension,the changes of plasma renin and aldosterone are inconsistent,suggesting that elevated aldosterone may be not renin-dependent in essential hypertension,and mineralocorticoid receptor antagonists should be chosen for antihypertension.
    Efficacy and Safety of Revefenacin in Chronic Obstructive Pulmonary Disease:a Meta-analysis 
    LI Ling,YANG Ming,LI Xuefeng,LIU Fu
    2021, 24(11):  1400-1405.  DOI: 10.12114/j.issn.1007-9572.2021.00.414
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    Background Revefenacin is the first anti-muscarinic drug that needs to be administered only once a day for maintenance therapy in patients with chronic obstructive pulmonary disease(COPD).There is no systematic review of its treatment of COPD in China.Objective To perform a systematic review of the efficacy and safety of revefenacin in COPD,to provide a basis for the selection of drug treatments for COPD.Methods The databases of CNKI,Wanfang Data Knowledge Service Platform,CQVIP,CBM,PubMed,EMBase,The Cochrane Library and ClinicalTrials.gov were searched for clinical studies of revefenacin in treating COPD from inception to May 2019.Literature enrollment was performed using strict inclusion criteria and exclusion criteria.The first author,publication time,NCT number,country(region),intervention,sample size,sex,age,race,course of treatment,indices of efficacy〔trough forced expiratory volume in one second(trough FEV1),peak FEV1,response rate to St.George's Respiratory Questionnaire(SGRQ)〕 and indices of safety(common and serious adverse reactions)regarding the eligible studies were recorded.The Cochrane Collaboration's tool for assessing risk of bias was used to evaluate the methodological quality.RevMan 5.3 was used for meta-analysis.Results A total of 6 randomized controlled trials were included,with a total sample size of 2 175 participants,and high methodological quality.According to the result of meta-analysis:the improvement of trough FEV1 in remifenaxine group was better than that in placebo group 〔MD=146.78,95%CI(133.52,160.05),P<0.000 01〕.Peak FEV1 〔MD=129.50,95%CI(115.69,143.31),P<0.000 01〕,and the SGRQ response rate in remifenaxine group were lower than those of placebo group 〔OR=1.60,95%CI(1.29,1.98),P<0.000 1〕.Both groups showed no significant differences in the incidence of severe adverse reactions〔OR=0.93,95%CI(0.44,1.94),P=0.84〕,upper respiratory tract infection 〔OR=1.42,95%CI(0.72,2.82),P=0.31〕,headache 〔OR=0.88,95%CI(0.49,1.58),P=0.66〕,and cough 〔OR=1.06,95%CI(0.62,1.82),P=0.82〕.The incidence of dyspnea in remifenaxine group was higher than that in placebo group 〔OR=0.54,95%CI(0.33,0.87),P=0.01〕.Conclusion Revefenacin is effective and safe in the treatment of COPD.
    Protein-energy Malnutrition Prevalence and Influencing Factors in Rural Left-behind Children under 1 Year Old in Zunyi Area 
    ZHANG Fangxia,HU Ying,SONG Yanan1,CHENG Yu1,XIANG Yunfeng1,JIN Hongjiao2,LEI Li2,GOU Enjin,LI Qing,WANG Xuqin,LUO Limei,LIN Yong,QU Tingnian,HUANG Bo
    2021, 24(11):  1406-1409.  DOI: 10.12114/j.issn.1007-9572.2021.00.137
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    Background Protein-energy nutrition plays an important role not only in cognitive development,but also in the nervous system,growth and development,cardiovascular system,and its influence on physical and intellectual development of 0-1-year-old children may be long-term,unrecoverable.Therefore,research and analysis of children's protein-energy malnutrition(PEM)status and influencing factors are of great significance for preventing PEM and related diseases in left-behind children.However,there is no detailed information on the PEM and health problems of left-behind children(≤1 year old)in rural Zunyi City.Objective To investigate the PEM prevalence and influencing factors in rural left-behind children under 1 year old in Zunyi area.Methods From August 2017 to September 2019,a random stratified sampling method was used to select rural left-behind children under 1 year old in Zunyi area for PEM screening.An interview-based or telephone-based questionnaire survey was conducted with the caregivers of the children to collect the sex,age in months,absorption status,diet structure,measured height and weight of the children,and average height of their parents,annual household income per capita,as well as their caregivers' education level.Multivariate Logistic regression analysis was used to explore the influencing factors of PEM in these children.Results A total of 700 questionnaires were distributed and 650(92.9%)responsive ones were returned.The prevalence of PEM in the children was 32.5%(211/650).PEM prevalence differed obviously in the children by their age in months,absorption status,diet structure,and their parents' average height,annual household income per capita,as well as their caregivers' education level(P<0.05).The results of multivariate Logistic regression analysis showed that children's age in months〔OR=9.562,95%CI(4.737,19.299)〕,absorption status〔OR=2.508,95%CI(1.678,3.747)〕,diet structure〔OR=0.298,95%CI(0.196,0.453)〕,average height of children's parents〔OR=0.317,95%CI(0.208,0.481)〕,annual household income per capita〔OR=0.367,95%CI(0.240,0.561)〕and education level of their caregivers 〔OR=0.482,95%CI(0.330,0.704)〕were associated with PEM(P<0.05).Conclusion The prevalence of PEM in rural left-behind children under 1 year old in Zunyi area was relatively high.Children's age in months,absorption status,diet structure,average height of children's parents,annual household income per capitaand education level of their caregivers may be associated with  PEM.
    Clinical Characteristics of Hospitalized Children with Hand-foot-mouth Disease in Kunming from 2008 to 2017 
    WANG Meifen,FU Tiantian,LUO Yunjiao,PENG Junchao,DU Lijiang,DU Zengqing,GAN Quan,MA Wei,LU Zhiying,LIU Chunli,JIANG Hongchao
    2021, 24(11):  1410-1417.  DOI: 10.12114/j.issn.1007-9572.2020.00.475
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    Background Hand-foot-mouth disease(HFMD) is a global infectious disease caused by more than 20 kinds of enterovirus infections.Since 2008,HFMD has been a high-incidence acute infectious disease in China,with a high prevalence of severe cases,endangering children's health.Objective To study the clinical characteristics and influencing factors of hospitalized pediatric HFMD cases using the data of a large clinical sample collected from Yunnan Province during 2008 to 2017.Methods A retrospective design was used.Data of HFMD children with hospitalization experience during 2008 to 2017 were collected through the electronic medical record system of Kunming Children's Hospital,including number of cases,onset time,age,gender,clinical classification and staging of HFMD,and were analyzed using statistical methods.Results (1)A total of 11 510 HFMD cases were hospitalized in this hospital during this 10-year period.The disease was prevalent throughout the year,and showed a single peak pattern,with a peak period from April to August.(2)Boys outnumbered girls,with a male to female ratio of 1.13:1.The children had an average age-of-onset of(2.37±1.50) years,but showed an uneven age-of-onset distribution,the youngest was 37 days,and the oldest was 14 years old,and those under 3 years had the highest incidence rate,accounting for the largest percentage of the total〔86.72%(9 982/11 510)〕.There were 3 368 common cases(29.26%),and 8 142 severe cases (70.74%).Of the severe cases,intermediate-to-severe and critical cases accounted for 40.75%(4 690/8 142),and 29.99%(3 452/8 142),respectively,and the percentage of cases aged less than 3 years accounted for 88.02%.The incidence of severe and critical HFMD differed significantly across all age groups(P<0.05).(3)In the early stage of critical HFMD,the prevalence of hypertension,increased heart rate,accelerated respiration,poor blood circulation in tips of fingers and toes,limb paralysis,and urinary retention was 100.00%(3 452/3 452),94.84%(3 273/3 452),86.44%(2 983/3 452),69.76%(2 408/3 452),1.83%(63/3 452),and 0.41%(14/3 452),respectively.(4)The examination of stool samples from 88.91%(10 234/11 510) of the cases revealed the presence of EV71 in 3 843 cases(33.39%),COA16 in 1 112 cases(9.66%),and other enteropathogens in 3 560 cases(30.93%).The main pathogens were EV71 and COA16 in 2008—2013,and were EV71 and other enteroviruses in 2014—2017.EV71 was the major pathogen for critical HFMD.Conclusion The hospitalized children with HFMD and severe cases were mainly under 3 years old.EV71 was the main pathogen causing severe HFMD.Hypertension,increased heart rate,accelerated respiration,and poor circulation in tips of fingers and toes may be the early signals of critical HFMD,which should be controlled and treated.actively.
    Research Status of Clinical Trials of Drugs and Interventions for Anxiety Disorders 
    LI Maijia,YE Tianyuan,QI Dongmei,CHENG Xiaorui,LIU Xijian
    2021, 24(11):  1418-1425.  DOI: 10.12114/j.issn.1007-9572.2021.00.069
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    As one of the most common mental diseases,there is no ideal clinical treatment for anxiety disorder.This paper summarized and analyzed the listed drugs for the treatment of anxiety disorders as well as the chemical drugs,traditional Chinese medicines and non-pharmaceutical interventions that are still in clinical trials at home and abroad,and commented on their mechanisms,advantages and disadvantages,so as to provide reference for the research and development of new drugs and clinical treatment measures for anxiety disorders.
    Advances in Mechanisms Underlying the Comorbidity of Depression and Cardiovascular Disease 
    WANG Mingxin,LI Suxia,SONG Tao
    2021, 24(11):  1426-1430.  DOI: 10.12114/j.issn.1007-9572.2021.00.430
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    There are bidirectional associations between depression and cardiovascular disease (CVD).In other words,people with depression are more likely to develop CVD than the general population and vice versa.And depression is an independent risk factor for prognosis in patients with CVD.This review summarizes epidemiological evidence on the relationship between depression and CVD,as well as the potential mechanisms of comorbidity of the two,including the influences of unhealthy lifestyle,inflammation,hypothalamic-pituitary-adrenal axis dysfunction and autonomic dysfunction.The discovery of these mechanisms may have important implications for the prevention and treatment of coexistence of depression and CVD,and may suggest that early screening and management of depression in CVD patients are very important and achievable goals.However,more studies are needed to determine the optimal management option for patients with depression and CVD.
    Advances in Immune Characteristics and Immune Regulation in the Elderly 
    WANG Jian,GONG Yanfeng
    2021, 24(11):  1431-1435.  DOI: 10.12114/j.issn.1007-9572.2020.00.373
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    Distinctive physiological changes occur with aging in immune system and other human body systems.How to determine therapies to effectively boost the weakened immune system in the elderly,is a major medical challenge of the 21st century.Probiotics and thymosin,two immunity-modulators,have obtained increasing attention in terms of benefiting the immune system in the elderly.Here we reviewed the role of immunity,immune characteristics of the elderly,recent advances in immunomodulators,problems existing in current studies on immunosenescence,and the application prospect of probiotics combined with thymosin in modulating immunity in the elderly,with a view to providing clinical and theoretical basis for promoting the health of the elderly.
    Clinical Diagnostic and Therapeutic Perspectives in Primary Gare Practice:a Case Study of Dysuria 
    ZHOU Ya,WANG Jing
    2021, 24(11):  1436-1440.  DOI: 10.12114/j.issn.1007-9572.2020.00.519
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    This paper describes the diagnosis and treatment process of a patient with dysuria.Professor John Murtagh's safe diagnostic strategy was used for the diagnosis,which is composed of five clinical questions:(1)What most common diseases can cause dysuria?(2)What serious disorders must not be ignored?(3)What conditions are often omitted?(4)Could the patient have an underlying illness?(5)Is the patient's family member attempting to say something? Based on the comprehensive analysis of medical history,physical examination and auxiliary examination,the diagnosis of benign prostatic hyperplasia was confirmed.The important significance of the diagnosis of this case is as follows:(1)General practitioners should master the management process for dysuria patients and attach importance to the screening of residents at high risk of dysuria from an elderly community.(2)Dysuria in elderly men indicates benign prostatic hyperplasia probably,but it also may be an alarm signal of prostatic cancer.(3)Upholding patient-centered general practice views,attention should be paid to both physical and mental conditions of the patient during the consultation.
    Clinical Diagnostic and Therapeutic Approaches in Primary Care Practice:a Case Study of an Infant with Fever and Rash 
    PAN Shanshan,WANG Jing
    2021, 24(11):  1441-1444.  DOI: 10.12114/j.issn.1007-9572.2020.00.524
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    We reported an infant with fever with rash encountered by a general practitioner.The diagnostic procedure was carried out from a general practice approach with John Murtagh's safe diagnostic strategy-a method of five clinical questions was adopted:(1)What common diseases may manifest cause fever with rash?(2)What serious disorders must not be missed?(3)Could the patient have a masquerading illness?(4)What conditions are often missed?(5)Is the patient's family member trying to say something?Besides detailed consultation,careful physical examination and auxiliary examination were also carried out,and the infant was eventually diagnosed with Kawasaki disease.The implications of this case are:(1)Kawasaki disease may be considered if the infant has fever with lymphadenopathy,and bacterial infection suggested by routine blood test as well as poor responses to antibiotic therapy.(2)Infantile febrile disease with rash following medication should not be simply attributed to drug allergy,which may be alerted to the possibility of Kawasaki disease.(3)Attention should be paid to distinguish facial manifestations,such as conjunctival hyperemia,erythema and cracking of lips,erythema of oral mucosa and “strawberry” tongue of Kawasaki disease from those of acute febrile disease during asking medical history and conducting physical examination.At the same time,psychological counseling should be given to the family members of the infant,based on the view of individual-centered and family-based general practice.