Table of Content

15 March 2021, Volume 24 Issue 8

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Monographic Research

Mechanism and Management of Primary Resistance to Targeted Therapy in NSCLC Patients Harboring EGFR Sensitive Mutations　

LIANG Wenhua, LI Caichen, LIANG Hengrui, ZHAO Yi, LI Feng, ZHONG Ran, XIONG Shan, LI Jianfu, CHENG Bo, CHEN Zisheng, LIU Xiwen, CAI Xiuyu, XIE Zhanhong, WANG Wei, LIU Jun, HE Jianxing

2021, 24(8):  901-916.  DOI: 10.12114/j.issn.1007-9572.2021.00.153

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Clinical evidence has showed that targeted therapy with small molecule inhibitors produces good efficacy in patients with non-small cell lung cancer（NSCLC）harboring epidermal growth factor receptor（EGFR）sensitive mutations，but there are also some patients who display primary resistance or insensitivity to the therapy.As the response rate and level to the initial therapy are determinants for patients'long-term survival，we reviewed evidence about major mechanisms leading to primary resistance，including the impact of the structure of EGFR mutation subtypes，primary EGFR T790M mutation，concurrent EGFR mutations，and immune status on the therapy response，as well as their associations，then proposed targeted management strategies，such as treatment targeting the genetic mutation or the mutation site，precise targeted therapy，cocktail therapy and so on，and evaluated the development trend of treatment for primary resistance to targeted therapy.All these aimed at helping medical workers with clinical practice and research.


Role and Containment of Asymptomatic Cases in COVID-19 Transmission　

LIU Qiao，LIU Jue，LIU Min

2021, 24(8):  917-922.  DOI: 10.12114/j.issn.1007-9572.2021.00.416

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COVID-19 has been plaguing global health for nearly a year.During the past year，many governments took arious measures such as closing schools and office-buildings，imposing social distancing to cut off the virus' transmission route.However，in the gradual return to normality，asymptomatic patients will，and already have，pose grave challenges.This paper reviews the proportion of asymptomatic COVID-19 cases in the global population，the role these cases have played in the transmission，and measures to restrict COVID-19 transmission through asymptomatic cases.


Interpretation of the 2020 GOLD's Global Strategy for Prevention，Diagnosis and Management of COPD（Ⅰ）：Pharmacological Treatment of Stable COPD　

LI Zhenghuan，ZHANG Xiaoyun，CHEN Yang，SONG Xueli，QIN Zhongming，LI Hong

2021, 24(8):  923-929.  DOI: 10.12114/j.issn.1007-9572.2021.00.155

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Chronic obstructive pulmonary disease（COPD）is now the third leading cause of death in the world，after ischemic heart disease and stroke.However，clinical practices in China still have many challenges to address COPD as an important public health issue，such as insufficient patient education，missing follow-up data，non-standardized management of stable COPD and/or acute exacerbations，which may be important causes of frequent aggravation and deterioration of conditions，leading to increased difficulties in treating and higher possibility of poor outcome after late treatment as well as increased social and economic burden of COPD.Therefore，it is of great practical significance to accelerate the standardization of prevention，diagnosis and management of COPD to improve the accuracy and effectiveness of diagnosis and treatment of COPD.To provide a reference for emergency and respiratory clinicians to better treat COPD patients clinically，in view of domestic diagnosis，treatment and studies regarding COPD，we comprehensively interpreted the 2020 GOLD's Global Strategy for Prevention，Diagnosis and Management of COPD in three parts from a clinical perspective： pharmacological and non-pharmacological treatment of stable COPD and management of exacerbations.This paper is the first part of interpretation，mainly including diagnostic evaluation，initial management and follow-up management.


Progress in the Treatment of Chronic Cough　

2021, 24(8):  930-940.  DOI: 10.12114/j.issn.1007-9572.2021.00.113

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As a common disease，chronic cough seriously affects the quality of life of patients，and its prevalence rate is as high as 12%.Nevertheless，there is a lack of effective treatment in clinic.This paper summarizes the classification，etiology and mechanism of chronic cough，reviews the existing and emerging treatment methods of chronic cough，and finds that targeted therapy and non-drug therapy are of great significance in improving the prognosis of patients with chronic cough.With the further development of targeted drugs and the further discovery of new treatment methods，the treatment of chronic cough is no longer without medicine available，but will tend to be precise and systematic.


TSH Suppression Therapy May Affect Bone Health，How to Manage Differentiated Thyroid Cancer Scientifically？

SUN Lei，LI Mei

2021, 24(8):  941-946.  DOI: 10.12114/j.issn.1007-9572.2021.00.074

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Differentiated thyroid cancer（DTC）is the most common type of thyroid cancer.TSH suppression therapy after thyroidectomy can reduce the risk of tumor recurrence and metastasis.However，long-term TSH suppression therapy can reduce bone mineral density and increase the risk of osteoporosis and bone fracture，which should be highly valued.We analyze the effects and mechanism of TSH suppression therapy on bone，and suggest the physicians to choose individualized treatment based on consideration of DTC recurrence risk，treatment responses and bone imaging information，risks of side effects and to monitor bone metabolic biomarkers，bone mineral density，risk of bone fracture，so as to take effective measures for the protection of bone，which including maintaining a healthy lifestyle，supplementing calcium and vitamin D，and using anti-osteoporosis drugs when necessary.


Disease Severity-related Factor and Associations of Metabolism-related Hormones and Clinical Related Parameters in Patients with Obstructive Sleep Apnea-hypopnea Syndrome　

YU Yue，TAN Huiwen，LIU Yishu，ZENG Yin，XIAO Li

2021, 24(8):  947-953.  DOI: 10.12114/j.issn.1007-9572.2021.00.142

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Background　Obstructive sleep apnea-hypopnea syndrome（OSAHS）is a common clinical sleep disorder.The concentration of metabolic hormones and the obesity，a major risk factor for OSAHS，may trigger abnormal sleep-related events in patients with OSAHS，but the causes are still unclear.and there are few studies exploring the relationship of leptin，orexin，and Ghrelin with polysomnography（PSG）parameters in patients with OSAHS.Objective　 To explore the influencing factors of the severity of OSAHS，and the correlation of serum leptin，orexin，Ghrelin and metabolic and PSG parameters in patients with OSAHS.Methods　We enrolled 58 patients with PSG diagnosed OSAHS from December 2017 to December 2018 from the Sleep Medicine Center，Shengjing Hospital of China Medical University.According to the apnea-hypopnea index（AHI），they were divided into mild group（5 times / h≤AHI≤15 times / h，n=6），moderate group（15 times/h<AHI≤30 times / h，n=11）and severe group（AHI>30 times / h，n=41）.PSG was conducted at the night of admission day and on the next early morning，peripheral arterial blood was drawn.The concentration of leptin，orexin，and Ghrelin were tested by ELISA.General clinical data were collected，including sex，age，BMI，history of smoking，drinking，hypertension，diabetes，and chronic rhinitis，neck，waist and hip circumferences，pre-sleep and morning systolic and diastolic blood pressures，total time in bed，total sleep time，AHI，total number of microarousals，number of microarousals lasting for longer than 15 seconds，microarousal index，the percent of the total time with oxygen saturation level lower than 90%（T90%），the lowest oxygen saturation，arterial partial pressure of oxygen（PaO2），arterial partial pressure of carbon dioxide（PaCO2），fasting blood glucose，total cholesterol，triacylglycerol，high-density lipoprotein，low-density lipoprotein，leptin，Ghrelin，and orexin levels.Ordinal Logistic regression analysis was used to explore the influencing factors of OSAHS severity .Spearman's rank correlation or Pearson correlation analysis was used to explore the associations of metabolic and clinical related parameters.Results　 The mild，moderate and severe groups showed statistically significant differences in AHI，microarousal index，T90% and the lowest oxygen saturation（P<0.05）.Ordinal logistic regression analysis showed that T90%〔OR=1.138，95%CI（1.026，1.262）〕was an independent factor associated with the severity of OSAHS（P<0.05）.Leptin level was positively correlated with BMI（r=0.482），waist circumference（r=0.429），hip circumference（r=0.576），and pre-sleep systolic blood pressure（r=0.261），but was negatively correlated with PaO2（P<0.05）.Ghrelin level was negatively correlated with smoking history（rs=-0.273），drinking history（rs=-0.309），pre-sleep systolic blood pressure（r=-0.391）and diastolic blood pressure（r=-0.282）（P<0.05）.Orexin was negatively correlated with total time in bed（r=-0.320，P<0.05）.Conclusion　T90% is a simple indicator that could effectively identity people at high risk of OSAHS，which is of some guiding significance to the evaluation of OSAHS severity.The interaction of factors such as hypoxia and obesity can promote the increase of leptin concentration in OSAHS patients，and induce the onset of leptin resistance，resulting in metabolic disorders.Orexin may play a role in maintaining wakefulness.Ghrelin plays a certain role in the physiological process of regulating blood pressure，which may provide a new idea or direction for the prevention，diagnosis and treatment of OSAHS patients cardiovascular diseases.Sleep fragmentation shortens the duration of sleep，and promotes the increase of orexin levels in the body，leading to higher risk of developing obesity.


The Relationship between Trajectory of Body Mass Index Based on Age and the Incidence of Hypertension in Adults Aged 20 to 59 Years　

GAO Zhongchun，ZOU Bo，LAN Gongsai，WANG Guanjun

2021, 24(8):  954-958.  DOI: 10.12114/j.issn.1007-9572.2021.00.140

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Background　Body mass index（BMI）is the most sensitive physical measurement index for predicting hypertension in adults.At present，most studies focus on the impact of BMI measuring on a single time point or the variation of BMI during a specific period on hypertension.But there is limited research on the association between the trajectory of BMI based on age and the occurrence of hypertension.Objective　To explore the relationship between trajectory of BMI and the incidence of hypertension in adults aged 20 to 59 years.Methods　People who had participated in health checkups for at least three times at a tertiary class hospital in Qingdao during 2015 to 2019 were selected as the research objects.And physical examination results〔height，weight，systolic blood pressure（SBP），diastolic blood pressure（DBP）〕，laboratory test indicators〔fasting blood glucose（FPG），serum total cholesterol（TC），triacylglycerol（TG），low density lipoprotein cholesterol（LDL-C），high density lipoprotein cholesterol（HDL-C）〕 were collected.The age，BMI，SBP and DBP at the first physical examination and the age at the diagnosis of hypertension were recorded.Latent class linear mixed model（LCLMM）was used to identify the dynamic variations of BMI trajectories relating to age and then the subjects were grouped according to its trajectory.Then Cox regression model was used to analyze the association between BMI trajectories and the incidence of hypertension in adults aged 20 to 59 years.Hazard ratios （HR）and 95% confidence interval（CI）were reported.Results　A total of 2 683 samples were included and four distinct BMI trajectories，which were classified to the medium-slow increase group（1 681 cases，62.7%）and the medium-level-rapid increase group（639 cases，23.8%），high level-rapid increase group （272 cases，10.1%），low level-rapid increase group（91 cases，3.4%）were identified through LCLMM.The incidence of hypertension，age，BMI，SBP，DBP and FPG level，TC level，TG level，LDL-C level，HDL-C level 〔on first physical examination intermediate level-slow rise group，medium level-rapid rise group，high level-rapid rise group，low level-rapid rise group were compared，the difference was statistically significant（P<0.05）.Taking the medium-slow rise group as a reference，after adjusting for confounding factors，the risk of hypertension in medium-rapid rise group，high-level-rapid rise group and low-level-rapid rise group 〔HR（95%CI）〕were respectively 1.47（91.09，1.98），2.56（1.85，3.55），and 6.35（3.36，12.01）.Conclusion　Adults with faster BMI increments along with age have a higher risk of hypertension.In the future，adults BMI trajectories should be focused on and especially the population with faster BMI increments，so as to identify high-risk groups as soon as possible and control population obesity in time，achieving the purpose of early prevention of hypertension.


Differences in Clinical Characteristics when REM Sleep Behavior Disorder Precedes or Comes after the Onset of Parkinson's Disease　

YANG Xu

2021, 24(8):  959-963.  DOI: 10.12114/j.issn.1007-9572.2020.00.626

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Background　Rapid eye movement（REM） sleep behavior disorder（RBD） is important not only as a preclinical symptom but also an aggravating symptom of Parkinson's disease（PD）.However，it is not known whether the onset of RBD in relation to PD affects the clinical characteristics of PD.Objective　To study the clinical characteristics of PD between patients with RBD occurring before and after the onset of PD.Methods　Participants were recruited from Dalian Friendship Hospital between October 2013 and May 2018，including 136 PD patients from Department of Neurology，and 30 volunteered health examinees with normal cognitive function（control group） from the Physical Examination Center.Descriptive variables including age，sex ratio，dose of dopaminergic agents〔levodopa dose equivalents（LEDs）〕，duration of PD morbidity，Hoehn and Yahr stage，prevalence of tremor，laterality of PD symptoms，Mini-Mental State Examination（MMSE） score，prevalence of OH，self-reported hallucinations，and dementia were compared across PD patients with and without RBD and controls，and across PD patients with RBD before and after the onset of PD and controls.Results　PD patients included 47 with RBD（consisting of 9 with RBD before the onset of PD，and 38 with RBD after the onset of PD） and 89 without RBD.Those with RBD had longer mean duration of PD morbidity，higher prevalence of advanced Hoehn-Yahr stages，using greater dosage of LEDs，hallucinations，OH，and dementia，and lower mean MMSE score than those without RBD（P<0.05）.PD patients with RBD had higher prevalence of hallucination，OH and dementia than the controls，and so did PD patients without RBD（P<0.05）.PD patients with RBD before the onset of PD had lower mean MMSE score and higher prevalence of dementia than those with RBD after the onset of PD（P<0.05）.The mean MMSE score was lower and the prevalence of dementia was greater in PD patients with RBD before or after the onset of PD compared to controls（P<0.05）.Conclusion　The occurrence of RBD after the onset of PD might be an important factor aggravating cognitive function.


Changes and Significance of Muscularization of Pulmonary Arterioles in a Rat Model of Pulmonary Hypertension Induced by Cigarette Smoke　

SUN Desheng，LIU Hongyan，LIU Xiansheng，OUYANG Yao，XU Yongjian

2021, 24(8):  964-967.  DOI: 10.12114/j.issn.1007-9572.2021.00.458

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Background　It is controversial that whether there is a direct causal association between cigarette smoke and pulmonary hypertension，a common pulmonary vascular disease.Studies have found that some smokers have remodeling of pulmonary small vessels in the early stage，even when the lung function is normal and there is no obvious hypoxia.However，the specific mechanism is still unclear.The remodeling of pulmonary small vessels is the main pathological mechanism of pulmonary hypertension.Some studies have shown that pulmonary vascular remodeling in experimental mice is related to the muscularization of pulmonary small vessels.Objective　To investigate the degree and significance of pulmonary arterioles muscularization in a rat model of pulmonary hypertension induced by cigarette smoke.Methods　This experiment was carried out from January to May 2018，16 healthy SD rats were randomly and equally divided into control group and model group.Rats in the model group received the intervention with cigarette smoke for 4 months for establishing.a pulmonary hypertension model，while those in the control group did not.At the end of 4 months，the activity，diet，hair and other general conditions of both groups of rats were observed，and the right ventricular systolic pressure and mean right ventricular pressure were measured.Right ventricular hypertrophy index，right ventricular weight to body weight（RV/BW） ratio were calculated.The expression of α-SMA in pulmonary small vessels was detected by immunohistochemistry to evaluate the degree of muscularization（non，partial and complete） of pulmonary arterioles.Results　The control group showed no abnormalities in their activities，diet，hair and other general conditions，while the model group showed obvious tiredness，often curled up in the corners，did not actively seek food，and their hair became more withered.The model group had higher mean right ventricular systolic pressure and average right ventricular pressure，and lower，average body weight than the control group（P<0.05）.The model group also showed greater average right ventricular hypertrophy index and RV/BW ratio（P<0.05）.Moreover，the model group showed lower proportion of non-muscularization in small pulmonary vessels（P<0.05）.The proportion of muscularized small pulmonary blood vessels in the model group was higher（P<0.05）.Specifically，the proportions of partial and complete muscularization were all higher（P<0.05）.Conclusion　Exposure to cigarette smoke may directly lead to pulmonary hypertension，which may be related to the aggravation of pulmonary arterioles muscularization.

Influence of Preoperative Frailty before Operation on Knee Function Rehabilitation in Elderly Patients after Unilateral Total Knee Arthroplasty　

FANG Wen，WANG Xiuhong，WANG Junhua，JIANG Zhiyue，DONG Lianghong，LI Jing

2021, 24(8):  968-976.  DOI: 10.12114/j.issn.1007-9572.2020.00.617

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Background　Total knee arthroplasty（TKA） is an optimal method for advanced severe knee osteoarthritis（KOA）.However，high prevalence of complications such as postoperative pain and joint stiffness，and postoperative knee dysfunction and other problems，seriously affecting the surgical effect and postoperative recovery process.Rapid development of geriatric surgery has revealed that preoperative physiological reserve state（for example，frailty） may be more closely associated with postoperative outcome of elderly patients than the surgery.Objective　To explore the effect of preoperative frailty on knee function rehabilitation in elderly patients after unilateral total knee arthroplasty.Methods　By use of purposive sampling，totally 230 elderly osteoarthritis inpatients with initial unilateral TKA were selected from the Affiliated Hospital of Guizhou Medical University，Guizhou Orthopedics Hospital and the Fourth People's Hospital of Guiyang during November 2018 to April 2019.They were divided into frail group（n=156） and non-frail group（n=74） according to FRAIL Scale score（scoring>2 points indicates frailty）before surgery.The time of the first postoperative ambulation，incidence of early postoperative complications and postoperative use time of walking AIDS were recorded to compared between two groups.On the 3rd，and 7th days，at the 2nd week，1 and 3 months after surgery，postoperative FPS-R score and knee flexion of two groups were evaluated.And postoperative AKS function score was evaluated at the 2nd week after surgery.Results　Compared with non-frail group，frail group ambulated postoperatively much later，used walking AIDS longer postoperatively，and had higher incidence of early postoperative complications（P<0.05）.There was an interaction between treatment time and frailty status on the FPS-R score（P<0.001）.Both treatment time and frailty status exerted significant main effects on the FPS-R score（P<0.001）.The FPS-R score of the frail group was higher than that of non-frail group at each time point after operation（P<0.001）.There was an interaction between treatment time and frailty status on the knee flexion（P<0.001）.Both treatment time and frailty status exerted significant main effects on the knee flexion（P<0.001）.The knee flexion of the frail group was less than that of non-frail group at each time point after operation（P<0.001）.There was an interaction between time and group on the knee function AKS score（P<0.001）.Both treatment time and frailty status exerted significant main effects on the AKS function score（P<0.05）.The AKS function score of the frail group was lower than that of non-frail group at each time point after operation（P<0.001）.There was a positive correlation between preoperative FRAIL score and postoperative FPS-R score（P<0.001）.And there was a negative correlation between preoperative FRAIL score and postoperative knee flexion or AKS function score（P<0.001）.Conclusion　Preoperative frailty may have negative influence on the recovery process of the joint function after TKA，which could enhance postoperative knee pain and delay the recovery of knee flexion function.At the same time，it may increase the risk of early postoperative complications，delay the time of first postoperative ambulation and prolongate the time of postoperative use of walking AIDS.


Research on the Effect of Network-based Inpatient Blood Glucose Team Management on Blood Glucose Levels and Health Economics of Patients with Hyperglycemia in Surgical Departments　

ZHU Ying，YANG Miao，XIA Wei，ZHOU Hui，TANG Nie，ZHU Xianjun，LI Pengqiu，YANG Yan

2021, 24(8):  977-981.  DOI: 10.12114/j.issn.1007-9572.2021.00.154

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Background　Due to the lacking of the relative knowledge of blood glucose management by surgeons，the blood glucose control of hyperglycemic patients in surgical departments is often not ideal.However，the traditional blood glucose management consultation mode has the disadvantages of low efficiency and difficulty in follow-up.Objective　In order to make the inpatient blood glucose management more efficient，the impact of the mode of inpatient blood glucose management team combined with network-based glucose minitoring system（NBGMS）on the blood glucose control of patients with hyperglycemia in the surgical department was explored in this study，as well as the impact on the length and the cost of hospitalization.Methods　Patients with hyperglycemia in non-critical surgery departments admitted from 2018-01-01 to 2018-06-30 were selected and intervened actively in the mode of inpatient blood glucose management team combined with NBGMS（team management group）.Patients with hyperglycemia in non-critical surgery departments admitted from 2017-01-01 to 2017-06-30 were selected and managed in the regular consultation mode（conventional consultation group）.The blood glucose control level of the two management modes was compared，and the multiple regression model was used to analyze the influencing factors of the hospitalization time and expenses of patients with hyperglycemia.Results　Compared with routine consultation group：（1）the test rate of glycosylated hemoglobin，the average number of blood glucose tests per person per day，the proportion of patients who used basal insulin during hospitalization，and the proportion of patients who received intravenous insulin during hospitalization in team management group were all significantly higher（P<0.05）；（2）the average blood glucose level，the incidence of hyperglycemia，and the incidence of severe hyperglycemia of the team management group were significantly lower and the target blood glucose compliance rate was significantly higher（P<0.01）；（3）the blood glucose drift，blood glucose variation coefficient and maximum blood glucose fluctuation range of the team management group were significantly lower（P<0.01）；（4）the incidence of nosocomial infection and hospitalization expenses were significantly lower（P<0.05）.Multiple linear regression analysis showed that the influencing factors of hospitalization length included blood glucose drift（B=0.506，t=5.360，P<0.01）and whether there was nosocomial infection（B=10.694，t=32.281，P<0.01）；the influencing factors included the maximum blood glucose fluctuation range（B=0.008，t=2.731，P=0.006）and the length of hospitalization（B=0.112，t=37.501，P<0.01）.Conclusion　The mode of inpatient blood glucose management team combined with NBGMS could improve the hyperglycemia and glucose variability of patients in surgical departments effectively，and then shorten the length of stay and reduce the medical costs.


Analysis of the Status Quo and Influencing Factors of Beijing Community General Practitioners on Chronic Obstructive Pulmonary Disease　

LIU Qing，CHEN Yahong，WANG Zhong，YU Jing，WU Yonghao

2021, 24(8):  982-988.  DOI: 10.12114/j.issn.1007-9572.2021.00.401

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Background　At present，chronic obstructive pulmonary disease （COPD for short），as a preventable and controllable chronic disease，has become one of the most prominent public health and medical problems in our country，and the prevention and treatment of COPD in grassroots community is particularly important.Understanding the cognitive ability and current status of community general practitioners on COPD can provide a better scientific basis for the prevention and treatment of respiratory diseases in grassroots level.Objective　To investigate the status quo of cognition of COPD among general practitioners in community health service institutions in Beijing， and analyze the influencing factors to provide scientific basis for the prevention and treatment of respiratory diseases at the grassroots level.Methods　From September 28 to October 4 in 2020，a survey was conducted on the frontline general practitioners in 34 community health service centers and 159 community health service stations in Beijing. Self-designed questionnaire，after joint demonstration，the final draft of the questionnaire formed through star technology platform was published on the WeChat work group.The content of the questionnaire includes the basic information and the approaches to update and learn professional knowledge and general practitioners，the ways to carry out patient education of general practitioners，the knowledge test of COPD prevention and treatment ability（60 points or more is a pass，60 points or less is not enough）. The different demographic characteristics，approaches to obtaining professional knowledge，and the way to conduct patient education of the community health service organization and the situation about the passing of COPD prevention and control ability test of general practitioners were analyzed.And the binary Logistic regression was used to analyze the influencing factors of the prevention and control ability test of general practitioners.Results　A total of 1 226 questionnaires were distributed，and 1 226 valid questionnaires were returned.The recovery rate was 100.0%.（1）The total average score of the general practitioner's COPD knowledge test was （45.5±18.5） points，with 987 failing doctors and 239 passing doctors（pass rate 19.5%）.Among them，the passing rate of female doctors was higher than that of males（P<0.05）.The difference in the passing rate of doctors with different academic qualifications is statistically significant（P<0.05）；among them，the passing rate of doctors with master degree and above is higher than the doctors with bachelor degree，college degree，technical secondary school education and below，and the passing rate of doctors with bachelor degree is higher than doctors with college degree，technical secondary school education and below.The difference in the passing rate of doctors with different professional titles was statistically significant（P<0.05）；among them，the passing rate of doctors with senior and intermediate titles was higher than the passing rate of doctors with junior titles（P<0.05）.（2）The passing rate of general practitioners who had passed the COPD prevention and control ability knowledge test at the community health service center/community health service station by listening to the lectures by outside experts and the experts organized by the medical association was higher than the general practitioners without listening to the lectures by experts outside the hospital and the experts organized by the medical society on the spot（P<0.05）.（3）General practitioners who carried out patient education and education had a higher pass rate than those who did not carry out patient education（P<0.05）；general practitioners who disseminate health education manuals，health education lectures and health consultations to teach patients had a higher pass rate than general practitioners without distributing health education manuals，health education lectures and health consultations to teach patients.（4）The results of binary Logistic regression analysis showed that gender，educational background，and professional title were the influencing factors of general practitioners' passing knowledge test of COPD prevention and treatment （P<0.05）.Conclusion　The general practitioners in Beijing community health service institutions have insufficient knowledge of COPD，and further training and assessment in this area need to be further strengthened；emphasis should be placed on strengthening community male，low-educated and low-professional title grade practitioners in COPD knowledge training；among the approaches to obtain professional knowledge of COPD，it is more effective to listen to the lectures by experts outside the hospital at the community health service center/community health service station and the experts organized by the medical society on the spot；the general practitioner's cognitive level of COPD can be also improved through the distributing COPD health education manuals，conducting health education lectures and health consultations for patient education.


Efficacy and Safety of Different Pharmacological Interventions for Progressive IgA Nephropathy：a Network Meta-analysis　

LIU Tongtong，WANG Yuyang，YANG Liping，MAO Huimin，ZHAN Yongli

2021, 24(8):  989-1000.  DOI: 10.12114/j.issn.1007-9572.2020.00.637

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Background　Patients with progressive IgA nephropathy （IgAN）have a significantly increased risk of developing end-stage renal disease.However，many available treatments for progressive IgAN have a high rate of side effects and insignificant long-term benefits.So choosing an appropriate regimen with good safety and efficacy is essential for the treatment of this disease.Objective　To evaluate the efficacy and safety of different pharmacological interventions in the treatment of progressive IgAN by network meta-analysis.Methods　Randomized controlled trials （RCTs）about different pharmacological interventions for progressive IgAN were searched in PubMed，EMBase，The Cochrane Library，CNKI，Wanfang Data，CBM and VIP databases from inception to March 31，2020.Literature screening，data extraction and risk of bias evaluation were performed by two reviewers independently.Stata 14.0 and GeMTC 0.14.3 were used to conduct a network Meta-analysis of the efficacy，improvement in 24 h urinary protein and creatinine levels and treatment-emergent adverse events in these patients with different pharmacological interventions.Results　A total of 38 RCTs were included，including 3 034 patients，and 10 intervention programs：Prednisone （Pred），mycophenolate mofetil （MMF）combined with Pred，cyclophosphamide （CTX）combined with Pred，leflunomide （LEF）combined with Pred，cyclosporine （CsA）combined with Pred，traditional Chinese medicine （TCM）combined with immunosuppressant （ISD），TCM，MMF，LEF and supportive treatment.Network meta-analysis showed that：（1）In terms of the overall resonse，TCM combined with ISD was more superior to TCM〔RR=2.27，95%CI（1.14，4.65）〕，LEF combined with Pred〔RR=2.14，95%CI（1.05，4.45）〕，CTX combined Pred〔RR=3.92，95%CI（2.06，7.37）〕，Pred〔RR=3.57，95%CI（2.11，6.32）〕，LEF〔RR=5.88，95%CI（1.03，37.17）〕and supportive support treatment 〔RR=6.25，95%CI（2.86，13.82）〕（P<0.05）.Compared with CTX combined with Pred，CSA combined with Pred 〔RR=3.73，95%CI（1.54，9.10）〕 and MMF combined with Pred 〔RR=2.37，95%CI（1.33，4.44）〕 had more favorable overall resonse（P<0.05）.Compared with Pred，CSA combined with Pred 〔RR=3.37，95%CI（1.52，8.13）〕 and MMF combined with Pred 〔RR=2.13，95%CI（1.24，4.13）〕 had more favorable overall resonse（P<0.05）.（2）The incidence of adverse reactions of MMF combined with Pred〔RR=0.21，95%CI（0.09，0.49）〕，LEF combined with Pred〔RR=0.16，95%CI（0.08，0.34）〕，TCM combined with ISD〔RR=0.31，95%CI（0.13，0.72）〕，TCM〔RR=0.05，95%CI（0.01，0.22）〕，Pred〔RR=0.37，95%CI（0.18，0.73）〕and supportive treatment〔RR=0.24，95%CI（0.06，0.87）〕was lower than that of CTX combined with Pred（P<0.05）.LEF combined with Pred had a lower incidence of adverse reactions than CsA combined with Pred〔RR=0.28，95%CI（0.09，0.90）〕（P<0.05）.（3）For reducing 24 h urinary protein，MMF combined with Pred was more superior to CTX combined with Pred〔MD=0.55，95%CI（0.25，0.85）〕，LEF combined with Pred〔MD=0.53，95%CI（0.10，0.97）〕，supportive treatment〔MD=0.72，95%CI（0.24，1.20）〕，TCM〔MD=0.66，95%CI（0.16，1.15）〕，and MMF〔MD=0.62，95%CI（0.02，1.22）〕（P<0.05）.TCM combined with ISD lowered proteinuria level more significantly than CTX combined with Pred〔MD=0.42，95%CI（0.09，0.75）〕，LEF combined with Pred〔MD=0.40，95%CI（0.03，0.79）〕，Pred〔MD=0.41，95%CI（0.15，0.67）〕，TCM〔MD=0.53，95%CI（0.08，0.98）〕，and supportive treatment〔MD=0.59，95%CI（0.19，0.99）〕（P<0.05）.Compared with CTX combined with Pred〔MD=0.55，95%CI（0.04，1.06）〕，Pred〔MD=0.53，95%CI（0.07，1.01）〕，and supportive treatment〔MD=0.71，95%CI（0.11，1.32）〕，CsA combined with Pred had better effect on reducing proteinuria level （P<0.05）.（4）For reducing serum creatinine level，TCM combined with ISD was better than LEF combined with Pred 〔MD=19.69，95%CI（0.68，39.49）〕 and Pred 〔MD=14.50，95%CI（1.49，28.04）〕（P<0.05）.MMF combined with Pred showed better effects on lowering serum creatinine level than MMF〔MD=45.66，95%CI（0.40，91.16）〕（P<0.05）.Conclusion　Considering the results，MMF combined with Pred，TCM combined with ISD， LEF combined with Pred have better clinical efficacy and higher safety in the treatment of progressive IgAN.


Clinical，Anti-hyperuricemic，and Pain-relief Effects of Five Acupuncture and Moxibustion Therapies in Acute Gouty Arthritis：a Network Meta-analysis　

ZHANG Jinhuan，CHEN Yirong，LAN Kai，HU Liyu，YU Haibo

2021, 24(8):  1001-1010.  DOI: 10.12114/j.issn.1007-9572.2020.00.347

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Background　Acute episodes of gout arthritis are the main cause of suffering in patients with gout.Long-term western pharmacological therapies bring obvious adverse reactions to patients.Acupuncture and moxibustion therapies，as alternative therapeutic options，have been proved effective in acute gouty arthritis （AGA），but which one is superior to others has not been identified by evidence-based studies.Objective　To compare the clinical efficacy of five acupuncture and moxibustion therapies in AGA using network meta-analysis.Methods　We searched for randomized controlled trials （RCTs） of five acupuncture and moxibustion therapies （electroacupuncture，needling，blood-pricking，warm-needling，red-hot needling） compared with the western pharmacological therapy for AGA from databases of PubMed，EMBase，The Cochrane Library，CNKI，Wanfang Data，VIP，and CBM from inception to September 10th，2019.We used RevMan 5.3 and Stata 14.0 to analyze the data involved.Results　A total of 23 RCTs involving 1 684 patients were eligible for this study.Network meta-analysis results showed that electroacupuncture 〔OR=1.18，95%CI（1.01，1.39），P<0.05〕，warm-needling 〔OR=1.17，95%CI（1.03，1.32）〕，or red-hot needling 〔OR=1.13，95%CI（1.03，1.24），P<0.05〕 showed better overall efficacy than the western pharmacological therapy.Surface under the cumulative ranking curves （SUCRA） values according to the overall effectiveness showed that electroacupuncture was best，followed by blood-pricking，red-hot needling，warm-needling，needling，and western pharmacological therapies.Electroacupuncture 〔SMD=-144.46，95%CI（-248.77，-40.14），P<0.05〕and needling 〔SMD=-98.83，95%CI（-159.51，-38.15），P<0.05〕 were superior to western pharmacological therapies in reducing uric acid.In terms of reducing the VAS score〔only three acupuncture and moxibustion therapies （red-hot needling，needling and blood-pricking） and western pharmacological therapy were included〕，red-hot needling had better efficacy than western pharmacological therapies 〔SMD=-1.40，95%CI（-2.12，-0.68），P<0.05〕.SUCRA values based on VAS reduction showed that red-hot needling was the best，followed by blood-pricking，needling，and western pharmacological therapies.Conclusion　Electroacupuncture has the highest possibility to reduce serum uric acid and improve overall efficiency，red-hot needling can effectively relieve pain.However，due to limited quantity and quality of studies，our conclusion needs to be verified by larger sample size，multi-center and high-quality clinical studies.


Prevalence of Comorbid Depression with Cerebrovascular Disease in Hebei Province　

ZHANG Saisai，WANG Wenhui，ZHANG Dan，LIU Xiao，ZHANG Lili，ZHANG Yunshu，LI Keqing

2021, 24(8):  1011-1016.  DOI: 10.12114/j.issn.1007-9572.2021.00.141

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Background　The prevalence of depression and cerebrovascular disease is increasing year by year.Cerebrovascular disease comorbid depression affects the rehabilitation of patients.Current research mostly focuses on hospitalized patients with cerebrovascular disease.There are few studies on comorbid depression with cerebrovascular diseases in community.Objective　To investigate the prevalence and related factors of comorbid depression in patients with cerebrovascular diseases in Hebei Province，provide a basis for disease prevention and policy development.Methods　From April to August 2016，a multi-stage stratified cluster random sampling method was used to conduct a cross-sectional survey on the prevalence and related conditions of mental disorders among community residents aged 18 years and over 18 years in Hebei Province.A self-made general condition questionnaire was used to investigate the gender，age，place of residence，family history of mental illness，education level，occupation，family annual income，marital status，lifestyle（smoking，drinking，tea，regular physical exercise），psychosocial problems（whether there are group support problems，housing problems，economic problems，health care service problems）.Respondents who meet the diagnostic criteria of cerebrovascular diseases were selected as the research objects.According to whether they met the diagnosis of depression，they were divided into cerebrovascular disease comorbid depression group and cerebrovascular disease non-comorbid depression group.The prevalence and related factors of comorbid depression in patients with cerebrovascular disease were analyzed.Results　A total of 485 cases met the diagnosis of cerebrovascular diseases，including 56 cases of comorbid depression（11.55%）.There were statistically significant differences on gender composition，age distribution，family history of mental illness，family annual income distribution，smoking ratio，drinking ratio，and physical exercise between the cerebrovascular disease comorbid depression group and the cerebrovascular disease non-comorbid depression group（P<0.05）.The proportion of patients with cerebrovascular disease comorbid depressive disorder with economic problems and health care service problems was higher than that of patients with cerebrovascular disease without comorbid depression group，the difference was statistically significant （P<0.05）.Multivariate Logistic regression analysis found that family history of mental illness〔OR（95%CI）=0.177（0.061，0.520）〕，economic problems〔OR（95%CI）=0.184（0.093，0.365）〕，health service problems〔OR（95%CI）=0.194（0.087，0.432）〕were independent risk factors of comorbid depression of cerebrovascular disease（P<0.05）.Conclusion　The risk of comorbidity depression in patients with cerebrovascular disease is higher than that in the general population.Family history of mental illness，economic problems，and health care service problems may be the influencing factors of comorbid depression in cerebrovascular disease.


Prevalence of Ectopic Pregnancy in Hebei Province during the Implementation of Universal Two-child Policy：a Multicenter Study　

ZHANG Huanhuan，GUO Yanwei，ZHANG Jinhuan，YANG Jiaqi，SHAN Weiying

2021, 24(8):  1017-1021.  DOI: 10.12114/j.issn.1007-9572.2020.00.330

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Background　Ectopic pregnancy（EP）is one of the leading causes for mortality in the first trimester of pregnancy，whose prevalence and related risk factors change with the change of concepts of sexual culture，fertility policy，and the development of medical sciences.However，there have been no studies about the prevalence of the disease since the universal two-child policy implemented in 2016 in China.Objective　To explore the influence of the implementation of universal two-child policy on EP prevalence in Hebei Province.Methods　This study was conducted in a random sample of four hospitals，which were extracted from four prefecture-level cities（using a 1∶1 ratio）sampled from Hebei Province by GDP ranking and geographical location.Participants were EP patients who hospitalized in department of obstetrics and gynecology of these hospitals during 2015-2017.Clinical medical records（including age，disease prevalence，gravidity，parity，and medical history）were collected，and major changes in these data before and after the implementation of universal two-child policy （2015 and 2017）were compared，and analyzed the change trend from 2015 to 2017.Results　1 760 EP patients were included，accounting for 4.68%（1 760/37 635）of the total hospitalized pregnant patients in the same period.The prevalence of EP was much lower after the implementation of the universal two-child policy than before（χ2=57.866，P<0.001）.The number of vaginal deliveries，prevalence of pelvic and abdominal surgery，recurrent EP，and pelvic inflammatory disease increased successively in participants enrolled in 2015，2016 and 2017（P<0.05）.After the implementation of the policy，the number of vaginal（χ2=6.151，P=0.046） and cesarean deliveries（χ2=7.135，P=0.028），prevalence of pelvic and abdominal surgery（χ2=6.300，P=0.012），REP（χ2=4.659，P=0.031）and pelvic inflammatory disease increased significantly（P<0.05）.Those with REP showed higher prevalence of pelvic and abdominal surgery，cesarean section，fallopian tube surgery，and the ratio of smoking history than those with first EP（P<0.05）.Conclusion　 In Hebei，the prevalence of EP decreased after the implementation of the universal two-child policy，but the age of onset，number of vaginal and cesarean deliveries，prevalence of pelvic and abdominal surgery，REP and pelvic inflammatory disease all increased.


Circulating Tumor Cells Detection and Progress in Nasopharyngeal Carcinoma　

ZENG Lei，YANG Kaixuan

2021, 24(8):  1022-1027.  DOI: 10.12114/j.issn.1007-9572.2020.00.151

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Circulating tumor cells （CTCs） refer to tumor cells that have shed into the circulatory system from primary tumors or metastases，which are closely related to tumor recurrence and metastasis.CTCs，emerging as novel tumor biomarkers，whose value has been confirmed in the early diagnosis，efficacy evaluation and prognosis evaluation of various types of tumors，such as breast cancer，prostate cancer and colorectal cancer.In recent years，CTCs have also been studied in nasopharyngeal carcinoma.This review mainly focuses on CTCs' characteristics，detection and the research progress in nasopharyngeal carcinoma，aiming to give a reference for clinical application of CTCs.


Research Progress in the Treatment of Hormone Receptor/Human Epidermal Growth Factor Receptor 2-positive Breast Cancer　

WU Yanqi，LUO Ting

2021, 24(8):  1028-1032.  DOI: 10.12114/j.issn.1007-9572.2019.00.744

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Breast Cancer is the most common cancer among women in China.According to the expression of estrogen receptor（ER）and progesterone receptor（PR） and the status of human epidermal growth factor receptor 2（HER2） gene amplification，breast cancer has been classified into various molecular subtypes.And the prognosis of different subtypes is also different.HER2 positive breast cancer behaves more aggressively and has a worse prognosis than HER2 negative breast cancer.Moreover，there are interactive crosstalks between HR and HER2 signaling pathways so that endocrine therapy and anti-HER2 therapy could influence and restrict each other.Nowadays，how to treat HR+/HER2+ breast cancer reasonably and effectively has been one of the difficulties in the treatment of breast cancer.In this article，the treatment situation of HR+/HER2+ breast cancer and the exploration of anti-HER2 therapy，endocrine therapy，immunotherapy，PI3K/mTOR pathway inhibitors，and other aspects associated with HR+/HER2+ breast cancer have been briefly described.


Continuous Renal Replacement Therapy for Exogenous Insulin Antibody Syndrome with Diabetic Ketoacidosis：a Case Report　

FAN Yaqing，JIN Xiuping

2021, 24(8):  1033-1036.  DOI: 10.12114/j.issn.1007-9572.2020.00.178

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Exogenous insulin antibody syndrome （EIAS） is associated with insulin antibodies （IAB） induced by exogenous insulin in diabetic patients.Its main characteristic is body's resistance to insulin，with decreased glycemic control effect produced by a given concentration of insulin.Severe insulin resistance is defined as insulin requirements > 200 U/d.This article reports a 62-year-old woman with type 2 diabetes，who suffered from insulin resistance after treatment with insulin aspart 30 （NovoRapid 30 Mix） for 24 days，which further induced severe ketoacidosis，with the insulin requirement up to 100 U/h.Finally，continuous renal replacement therapy （CRRT） was used for 63 hours to treat serious acidosis，abidance hyperglycemia，and remove the circulating antibodies，and the patient's condition improved gradually.This report suggests that patients with EIAS and diabetic ketoacidosis should be treated with CRRT early，when using glucocorticoids and increasing insulin doses can not control the symptoms of acidosis and hyperglycemia，by which a poor prognosis may be prevented