Chinese General Practice

Consensus of Chinese Experts on the Remission of Type 2 Diabetes Mellitus　

Committee of Consensus of Chinese Experts on the Remission of Type Diabetes Mellitus

2021, 24(32): 4037-4048. DOI: 10.12114/j.issn.1007-9572.2021.01.105

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Type 2 diabetes mellitus（T2DM） is a progressive disease characterized by hyperglycemia，which is generally considered as a disease requiring chronic hypoglycaemic agents therapy. In recent years，a large number of research results have shown that lifestyle intervention，drug therapy，and metabolic surgery can promote the remission of T2DM combined with overweight and obesity，so that patients can avoid the use of hypoglycemic drugs for a long time. T2DM relief can help reduce the psychological burden of patients，enhance patients' confidence in complying with healthy lifestyles，and improve patients' quality of life. In the long term，it can also delay disease progression and reduce the risk of life-long complications. In order to help Chinese clinicians to standardize the clinical diagnosis and treatment related to the alleviation of T2DM in overweight and obese T2DM patients，promote the development of related research，and enable patients to obtain safe and effective intervention measures，the Consensus of Chinese Experts on the Remission of Type 2 Diabetes Mellitus was formulated.

Clinical Characteristics and Comprehensive Management of Heart Failure with Improved Ejection Fraction　

WANG Yucheng，CHEN Zhiwei，CHEN Ruizhen

2021, 24(32): 4049-4054. DOI: 10.12114/j.issn.1007-9572.2021.01.108

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Left ventricular ejection fraction （LVEF） is often used as a guideline for classification of heart failure（HF）. With the advancement of heart failure diagnosis and treatment technology，more heart failure patients have experienced improvement in LVEF. The 2021 report of multi-national heart failure societies denominates and defines heart failure with improved ejection fraction（HFimpEF），but there is still a lack of authoritative guidelines to discuss the diagnosis and treatment of HFimpEF. Therefore，this article will review the research progress of HFimpEF based on the existing research evidence，in order to discuss the clinical characteristics，diagnosis，and treatment of HFimpEF.

Imaging Evaluation of Vulnerable Carotid Plaques：Present Status and Future Prospect　

GAO Tianli

2021, 24(32): 4055-4060. DOI: 10.12114/j.issn.1007-9572.2021.01.101

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Carotid atherosclerotic stenosis is a well-established risk factor of ischemic stroke，contributing to up to 10%-20% of strokes or transient ischemic attacks. Routine cerebrovascular examination techniques can only show the degree of stenosis of the lumen，but cannot demonstrate the structure of the stenosis and the cause of the stenosis. Therefore，simply studying the degree of luminal stenosis in the diagnosis of cerebrovascular disease，is obviously insufficient to assess the characteristics of the disease and stratify the risk for preventing stroke. Non-invasive in vivo assessment of plaques and arterial walls based on the presence of imaging features such as intraplaque hemorrhage，ulceration，neovascularity，fibrous cap thickness，and lipid-rich necrotic core is a basic method to guide treatment. This review summarizes recent updates on vessel wall imaging modalities for the evaluation of carotid vulnerable plaques，such as MRI，CT and ultrasound.

Effects of the Interaction Between Shift Work and Unhealthy Lifestyle on Hypercholesterolemia in Steel Workers　

XUE Chao，LI Qinglin，WANG Han，ZHANG Shengkui，QIN Sheng，YUAN Juxiang

2021, 24(32): 4061-4067. DOI: 10.12114/j.issn.1007-9572.2021.01.026

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Background　Abnormal blood lipids show an increasing trend of prevalence in Chinese adults，among which elevated serum total cholesterol is a key risk factor for atherosclerotic cardiovascular disease. Currently，there is no consistency regarding the association of shift work and dyslipidemia. The number of Chinese shift workers is growing，but the association of shift work and unhealthy lifestyle with hypercholesterolemia has been rarely studied. Objective　To explore the association of shift length and unhealthy lifestyle with hypercholesterolemia. Methods　By use of a cluster sampling，the workers of a steel mill attending the 2017 occupational medical examination were selected. A survey was used to collect their demographics（sex，age，height，weight，family medicalhistory，and so on），shift situation（shift time，age for initiating shifts，and so on），and lifestyle（diet，physical activity，smoking，drinking，and so on） using a self-developed Health Assessment Questionnaire. Restricted cubic spline（RCS） was used to analyze the dose-response relationship between shift length and hypercholesterolemia. RCS regression line with knots was used to divide the participants by shift length. Multivariate Logistic regression model was used to analyze the relationship between shift and unhealthy lifestyle with hypercholesterolemia. The additive interaction between shift work and unhealthy lifestyle was estimated using relative excess risk due to interaction（RERI） and proportion attributable to interaction（AP）. Results　The analysis with Logistic regression models with shift length（0，greater than 0 but less than 23.8 years，and equal to or greater than 23.80 years） incorporated as independent variables，and hypercholesterolemia as the dependent variable，indicated that the risk of hypercholesterolemia increased with the prolongation of shift length in groups with shift length greater than 0 in two models（P<0.05）. But hypercholesterolemia had no significant association with either physical activity or DASH diet scoreafter adjusting for age，sex，hypertension，diabetes，family medical history and other variables（P>0.05）. Given all factors，workers with three or more unhealthy lifestyles were 1.703 times more likely to have hypercholesterolemia than those with no or only one unhealthy lifestyle. Workers with more than three unhealthy lifestyles who worked shifts within 23.8 years were 2.527 times more likely to develop hypercholesterolemia than those who never worked shifts and had no or only one unhealthy lifestyle. Among those who worked shifts for 23.8 years or less，it was found that there was an obvious additive interaction between shift shifts and unhealthy lifestyles，in which RERI was 1.559（0.186，2.928） and AP was 46.26（4.36，88.17）. Conclusion　Both shift work and unhealthy lifestyle can increase the risk of hypercholesterolemia in workers，and they have an additive effect.

Relationship of Microbiological and Inflammatory Markers with Poor Prognosis in Elderly Pulmonary Infection Patients with Different Estimated Glomerular Filtration Rate　

ZHAO Xiaoqian，LUO Leiming

2021, 24(32): 4068-4073. DOI: 10.12114/j.issn.1007-9572.2021.01.216

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Background　Lung infections mostly occur in the elderly， often in the form of comorbidities. Studies have shown that kidney function may affect the prognosis of patients with lung infections， but the mechanism of microbial changes in these patients still remains unclear，and there are few relevant reports in China. Objective　To investigate the relationship of specific etiological susceptibility and altered immune function with poor prognosis in elderly pulmonary infection patients with different estimated glomerular filtration rate. Methods　This retrospective，controlled and observational study was conducted with a cohort of elderly patients（over 65 years old）who were hospitalized due to pulmonary infection in the Second Medical Center，PLA General Hospital from January 2017 to December 2019. General conditions（gender and age），past medical history（chronic kidney disease，diabetes，dyslipidemia，chronic heart failure），and biochemical parameters detected after admission，including blood urea nitrogen（BUN），serum creatinine（Scr），aspartate aminotransferase（AST），alanine aminotransferase（ALT），serum albumin，estimated glomerular filtration rate（eGFR），routine blood parameters〔hemoglobin，white blood cell count，percentage of neutrophils，percentage of lymphocytes，total platelet count，neutrophil to lymphocyte ratio（NLR）〕and pathogenic microbes detected by sputum culture，as well as outcome（survival or death）acquired by a 90-day follow-up were collected. Multivariate Logistic regression analysis was used to explore the associated factors of death. ROC analysis of eGFR in predicting death was performed，and its optimal cut-off value was used to divide the cases into two groups〔eGFR≥47 ml•min-1•（1.73 m2）-1 and eGFR < 47 ml•min-1•（1.73 m2）-1〕 to compare intergroup differences in the distribution of pathogenic microbes and inflammatory indicators. Results　The prevalence of in-hospital death was 13.2%（68/514）. The deceased had younger mean age，lower prevalence of chronic kidney disease，higher mean levels of BUN，Scr，AST，ALT，white blood cell count and NLR，and lower mean levels of albumin，eGFR，hemoglobin and percentage of lymphocytes than survivors（P<0.05）. Multivariate Logistic regression analysis showed that age 〔OR=1.092，95%CI（1.027，1.162）〕，ALT 〔OR=1.013，95%CI（1.001，1.026）〕，albumin level〔OR=0.814，95%CI（0.759，0.873）〕，eGFR 〔OR=0.974，95%CI（0.961，0.988）〕，WBC count 〔OR=1.116，95%CI（1.030，1.210）〕and lymphocyte percentage 〔OR=0.011，95%CI（0，0.521）〕were associated with all-cause death（P<0.05）. The AUC of eGFR in predicting death was 0.614，with 47 ml•min-1•（1.73 m2）-1 was determined as the optimal cutoff value with 36.8% sensitivity，and 84.3% specificity. Compared to patients with eGFR≥47 ml•min-1•（1.73 m2）-1，those with eGFR<47 ml•min-1•（1.73 m2）-1 had higher prevalence of infection with Klebsiella pneumoniae，Escherichia coli，Staphylococcus aureus，and fungi and lower prevalence of infection with Pseudomonas aeruginosa（P<0.05）. Moreover，they also had higher mean percentage of neutrophils and NLR，as well as lower mean percentage of lymphocytes and platelet count（P<0.05）. Conclusion　Changes in immune function and susceptibility to Staphylococcus aureus infections in patients with low eGFR may be underlying causes of worsening prognosis in elderly people with pulmonary infection and reduced renal function.

Dynamic Trajectory of Exercise Rehabilitation Adherence of Patients with Atrial Fibrillation after Radiofrequency Ablation in the Internet+ Home Cardiac Rehabilitation Mode　

WANG Jie，SUN Guozhen，YANG Gang，BAO Zhipeng，LIU Shenxinyu，WANG Lin

2021, 24(32): 4074-4079. DOI: 10.12114/j.issn.1007-9572.2021.01.218

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Background　Decreased exercise endurance still exists after atrial fibrillation radiofrequency ablation. A number of studies have proved that atrial fibrillation exercise rehabilitation is effective，and adherence is a key determinant of whether the patient continues to benefit from exercise therapy. Therefore，understanding the dynamic changes and influencing factors of patients' exercise adherence after atrial fibrillation radiofrequency ablation is of great significance to establish the mechanism of internalization of external dynamics in patients' home exercise rehabilitation. Objective　To analyze the longitudinal follow-up data of home-based exercise rehabilitation in patients with atrial fibrillation after radiofrequency ablation，reveal the dynamic change of exercise adherence and explore its influencing factors，in order to provide theoretical basis for the formulation of targeted intervention strategies. Methods　A total of 72 patients with atrial fibrillation after radiofrequency ablation who were selected by convenient sampling method from February 2019 to August 2020 in the First Affiliated Hospital of Nanjing Medical University，were treated with Internet+ home exercise rehabilitation intervention for 12 weeks，and followed up to 24 weeks. The average adherence rates in seven time periods of 0-1 week，2-4 weeks，5-8 weeks，9-12 weeks，13-16 weeks，17-20 weeks and 21-24 weeks were collected. A multi-stage latent growth curve model was constructed for exercise adherence，and robust maximum likelihood estimation（MLR）was used to estimate the mean，the variance and the covariance. Taking gender，education，working status，the existence of comorbidities and frequency adherence as covariates，the latent growth curve model was constructed for intensity-time adherence and the parameters were estimated by MLR method. Results　Intensity-time adherence and frequency adherence both showed a second-stage curve increasing trend model，suggesting that there is a turning point in the development of adherence，in the 12th week of exercise. The first-stage of intensity-time adherence（from the beginning to 12th week）showed a curve increasing trend，and the increasing rate slowed down with time（Q1=-0.062，P<0.05）；The second stage（from 12 weeks to 24 weeks of exercise）showed a linear downward trend（S2=-0.081，P<0.05），and the differences in the initial level and growth rate of individuals were statistically significant（P<0.05）. Frequency adherence showed a quadratic growth trend in the first stage，reaching the peak at the 4th week of exercise，and then decreased slightly；The second stage showed a quadratic downward trend，and the rate of decline accelerated with time（Q2=0.003，P<0.05），and the differences between the individual's initial level and the acceleration of change were statistically significant（P<0.05）. Among the time-constant covariates，only the existence of comorbidities had a significant impact on intensity-time adherence at the first week（P<0.05）. Between the first week and the 24th week，frequency adherence had a positive impact on intensity-time adherence（P<0.05）. Conclusions　During the intervention period，the level of intensive-time adherence and frequency adherence are relatively low，both with a curve increasing trend and stabilizing at a higher level，while the adherence decreased gradually during the follow-up period. Patients with comorbidities had poor initial intensity-time adherence，while frequency adherence had a positive impact on intensity-time adherence.

Risk Factors of Cardiovascular Diseases in Outpatient Patients with Primary Hypertension Assessed According to a Variety of Parameters　

DENG Liqun，WANG Qian，ZHANG Donghua，ZUO Huijuan，LIN Yun

2021, 24(32): 4080-4085. DOI: 10.12114/j.issn.1007-9572.2021.01.221

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Background　Dyslipidemia，primary hypertension，diabetes，obesity，smoking，unhealthy diet and lack of physical activity are risk factors that can be changed for atherosclerotic cardiovascular diseases（ASCVD），which are used to assess 10-year risk of ASCVD. Maintaining the four behavioral factors，three physiological and biochemical parameters above in an ideal state can significantly reduce the incidence of ASCVD in the population. Objective　To analyze the level of risk factors，risk stratification，ideal cardiovascular health behaviors and factors of ASCVD in outpatient patients with primary hypertension and to comprehensively reflect the risk of ASCVD. Methods　Three thousand four hundred and fifty-one patients with primary hypertension and aged over 35 years old who were treated in Beijing Anzhen Hospital，Capital Medical University from June 2016 to June 2017 were enrolled as the research objects. The basic information of the patients was collected by face-to-face inquiry，on-site measurement and blood biochemical tests. The 10-year risk assessment and prediction model of ASCVD（hereinafter referred to as prediction tool method）proposed by Professor Wu Yangfeng and the method provided by the Chinese guidelines for cardiovascular disease prevention（hereinafter referred to as the guideline method）were used for risk evaluation of ASCVD and risk stratification. The definition of ideal cardiovascular health is based on the recommendations of the American Heart Association（AHA）（including 7 ideal health factors and behaviors）. The Kappa value was calculated，and the consistency of the two methods in the risk stratification of ASCVD was evaluated. Results　For patients with primary hypertension and aged ≥55 years old，there was significant difference in the proportions of different populations at risk of ASCVD judged by the two methods（χ2=10.608，P=0.005），and the proportion of high-risk ASCVD judged by the prediction model was higher than that preliminarily judged by the guideline method（χ2=4.219，P=0.04）. For the patients with primary hypertension aged <55 years old，there was significant difference in the proportions of different populations at risk of ASCVD judged by the two methods（χ2=534.350，P<0.001）；low-risk population（76.3%）was prominent judged by the prediction model，and the proportion of high-risk population was only 6.6%，in contrast，the proportion of high-risk population primarily judged by the guideline method was up to 29.5%. When the risk throughout the life was evaluated，66 patients（13.0%）were adjusted to be high-risk，and the final proportion of high-risk patients reached 34.5%. For patients judged to be low-risk，moderate-risk and high-risk by the prediction model method，the proportion of low-risk，moderate-risk and high-risk patients assessed by the guideline method was 51.9%，44.5% and 56.0%，respectively，with a consistency rate of 50.8%. Through the internal consistency test，the Kappa value was 0.261（u=17.010，P<0.001）. Only 2.4% of the patients had 5 healthy behaviors and factors，and 70.4% had 2-3 healthy behaviors and factors. The proportion of female primary hypertension patients with non-smoking/quitting smoking，ideal BMI，FPG<5.6 mmol / L and blood pressure<120/80 mm Hg was higher than that in males，and the proportion of TC<5.2 mmol/L was lower than that in males；there were also significant difference in the proportion of ideal physical activity and cardiovascular health parameters in patients with primary hypertension of different genders（P<0.05）. The proportion of female patients with normal cardiovascular health parameters ≥1，≥ 2，≥ 3 and ≥ 4 was higher than that in males（χ2=33.980，P<0.001；χ2=34.946，P<0.001；χ2=107.419，P<0.001；χ2=37.488，P<0.001）. Conclusion　The internal consistency of the two evaluation methods is poor. For patients with primary hypertension and aged<55 years old，the proportion of high-risk patients determined by the guidelines is also more than 1/3，which is close to the proportion of high-risk patients aged ≥ 55 years old，thus the risk of ASCVD may be overestimated in this population. For 5 cardiovascular healthy behaviors and factors，about 70% of the patients with have 2-3 healthy behaviors and factors. Control of risk factors in patients with primary hypertension and improvement of cardiovascular health may be important strategies to reduce the risk of ASCVD.

Effects of Effective Components of Yixintai on CaN and SERCA2a mRNA and Protein Expression Levels in Myocardial Tissue of a Rabbit Model of Heart Failure Due to Dilated Cardiomyopathy　

LI Ya，WEI Jiaming，LI Yuying，GUO Zhihua

2021, 24(32): 4086-4093. DOI: 10.12114/j.issn.1007-9572.2021.01.106

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Background　Dilated cardiomyopathy is a major cause of heart failure（HF）. Effective components of Yixintai（ECYXT）have proven to be very effective against HF，but the mechanism of action is not completely clear. Objective　To explore the effects of the ECYXT on the protein and mRNA expression of CaN and SERCA2a in myocardial tissue of a rabbit model of HF induced by dilated cardiomyopathy. Methods　The rabbit model of HF was established by injecting adriamycin into the marginal ear vein and giving propylthiouracil by gavage in January 2018. The rabbits successfully modeled were divided into HF model group〔n=17，single intragastric dose of 0.9% saline solution（10 ml/kg） per day〕，groups of low dose ECYXT 〔n=17，single intragastric dose of ECYXT solution（10 ml/kg） with a concentration of 2.1 g/kg per day〕，medium dose ECYXT〔n=17，single intragastric dose of ECYXT solution（10 ml/kg） with a concentration of 4.2 g/kg per day〕，high dose ECYXT〔n=17，single intragastric dose of ECYXT solution（10 ml/kg） with a concentration of 8.4 g/kg per day〕，and losartan potassium group〔n=16，single intragastric dose of losartan potassium suspension（10 ml/kg） with a concentration of 2.75 mg/kg〕. And other 20 rabbits were selected for comparison〔control group，single intragastric dose of 0.9% saline solution（10 ml/kg）per day〕. The intervention for all groups lasted for 4 weeks.When the experiment ended，serum atrial natriuretic peptide（ANP），brain natriuretic peptide（BNP），left ventricular ejection fraction（LVEF），left ventricular short-axis shortening（LVFS），and E/A ratio of the rabbits were measured，then the rabbits were sacrificed and cardiac muscles were obtained to observe the myocardial tissue morphology，and to measure the concentration of ［Ca2+］i in myocardial cells，the protein and mRNA expression of CaN and SERCA2a in myocardial tissue. Results　HF model group showed edema and necrosis of cardiomyocytes，with shrinkage of nuclei，widening of intercellular substance，and a small amount of inflammatory cells exuded，and demonstrated disordered arrangement of myocardial fibers，with some broken. Compared with HF model group，the injury of myocardial cells in each dose group of ECYXT and losartan potassium group was alleviated in varying degrees，especially in medium and high dose groups of ECYXT，and losartan potassium group. Compared with the control group，HF model group demonstrated increased levels of serum ANP and BNP，decreased LVEF，LVFS，and E/A ratio，elevated concentration of ［Ca2+］i
in myocardial cells and protein and mRNA expression levels of CaN in myocardial tissue，as well as reduced protein and mRNA expression levels of SERCA2a in myocardial tissue（P<0.01）. Compared with HF model group，three ECYXT groups and losartan potassium group had decreased serum ANP and BNP，increased LVEF，LVFS and E/A ratio，reduced concentration of ［Ca2+］i in myocardial cells，and protein and mRNA expression levels of CaN in myocardial tissue，as well as increased protein and mRNA expression levels of SERCA2a in myocardial tissue（P<0.01）. Compared with the low dose ECYXT group，medium and high dose ECYXT groups and losartan potassium group presented decreased levels of serum ANP and BNP，increased LVEF，LVFS and E/A ratio，reduced concentration of ［Ca2+］i in myocardial cells，and protein and mRNA expression levels of CaN in myocardial tissue，as well as increased protein and mRNA expression levels of SERCA2a in myocardial tissue（P<0.01）. The above-mentioned indicators in the medium dose ECYXT group were similar to those in high dose ECYXT group and losartan potassium group（P>0.05） except that the protein and mRNA expression levels of SERCA2a in myocardial tissue were increased in the latter two groups（P<0.01）. There were no significant differences in the above-mentioned indicators between high dose ECYXT group and losartan potassium group（P>0.05）. Conclusion　ECYXT could improve the protein and mRNA expression of SERCA2a in myocardial tissue，decrease the concentration of ［Ca2+］i in myocardial cells，inhibit the protein and mRNA expression of CaN in myocardial tissue，indicating that ECYXT improve heart function and HF induced by dilated cardiomyopathy in the rabbit model.

Changes and Significance of Serum Gastrin and Motilin in the Blood of Children in Pediatric Intensive Care Unit　

PENG Hao，LONG Bowen，XIAO Chen，DENG Min，ZHANG Yi

2021, 24(32): 4094-4098. DOI: 10.12114/j.issn.1007-9572.2021.01.025

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Background　Serum gastrin（GAS） and motilin（MTL） play important roles in regulating gastrointestinal motor function. Gastrointestinal dysfunction or gastrointestinal failure in critical illness is considered to be the inducement of multiple organ failure（MOF） after stress，so it is of great significance to monitor the levels of GAS and MTL. Objective　To analyze the concentration changes of GAS and MTL in the blood of different children in pediatric intensive care unit（PICU） and their clinical monitoring significance. Methods　Three hundred hospitalized children in Pediatric Intensive Care Unit of Pingxiang Maternal and Child Care Hospital from January 2018 to September 2019 were enrolled. The levels of GAS and MTL in the blood of children were measured by radioimmunoassay. The levels of GAS and MTL in blood of children with different disease severity（before and after treatment），different disease types and different gastrointestinal function states were compared. Results　The levels of GAS and MTL of extremely critically ill children before and after treatment were higher than those of non-critically ill and critically ill children （P<0.05）；after treatment，the GAS and MTL levels of non-critical，critically ill，and extremely critically ill children were compared with those before treatment，and the differences were statistically significant （P<0.05）. There was no significant difference in the levels of GAS and MTL in children with different disease types（P>0.05）. The level of GAS in children with gastrointestinal dysfunction and gastrointestinal failure was higher than that of children without gastrointestinal dysfunction，and the level of GAS in children with gastrointestinal failure was higher than that of children with gastrointestinal dysfunction （P<0.05）. The MTL level of children with gastrointestinal dysfunction was higher than that of children without gastrointestinal dysfunction and gastrointestinal failure，and the MTL level of children without gastrointestinal dysfunction was higher than that of children with gastrointestinal failure （P<0.05）. Conclusion　In children with different disease severity and gastrointestinal function status，the changes of GAS and MTL are different. In the clinic，it is possible to monitor the changes in the concentration of GAS and MTL in the blood of the children to assess the severity of the disease，the gastrointestinal function status and the effect of clinical treatment in the children.

Economic Burden of Chronic Obstructive Pulmonary Disease Induced by Tobacco Smoke Exposure in Yunnan Naxi People　

LIU Yingnan，WANG Xuming，SHEN Jingrong，CUI Wenlong，HE Lianju，ZUO Chunmei，CAI Le

2021, 24(32): 4099-4103. DOI: 10.12114/j.issn.1007-9572.2021.01.019

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Background　Chronic obstructive pulmonary disease （COPD） has become a major public health problem due to its high prevalence，cost of treatment，and economic burden of conditions associated with COPD. Objective　To analyze the economic burden of COPD attributed to active and passive smoking exposure among the Naxi People in Yunnan province. Methods　From July to August 2018，a questionnaire survey and lung function tests were conducted with the Naxi People（≥35 years old） selected from Yunnan's Yulong County by use of multi-stage stratified random sampling. Per capita direct and indirect economic burden of COPD，total economic burden of COPD，and the economic burden attributable to active/passive smoking were estimated. Results　Altogether，2 600 cases participated in the survey，and 2 531 of them（97.35%） who completed the survey effectively were finally included. The prevalence of COPD，smoking，and passive smoking among the participants was 17.66%，40.58%，and 38.29%，respectively. Men had obviously higher prevalence of active smoking and notable lower prevalence of passive smoking than women （P<0.001）. Active smokers〔OR=1.903，95%CI（1.507，2.404）〕had a higher likelihood of developing COPD than non-smokers. Passive smokers〔OR=2.195，95%CI（1.718，2.805）〕 had a higher likelihood of developing COPD than non-passive smokers. The per capita direct，indirect and economic burden of COPD for the COPD participants was 2 827.82 yuan，105.00 yuan and 2 932.82 yuan，respectively，and the total economic burden of COPD was 64.07 million yuan. The economic burden of COPD attributable to active and passive smoking was 17.18 million yuan and 20.11 million yuan，respectively. Passive smoking contributed less to economic burden of COPD than active smoking in men，while for women the opposite was true. Conclusion　Active and passive smoking may produce substantial economic burden of COPD in the Naxi people，which might be reduced by reducing the smoking prevalence via increasing tobacco control efforts.

Recurrence and Influencing Factors of First-episode Mania in BipolarⅠ Disorder：a 7-year Follow-up Study　

LU Yunping，CUI Wei，YU Chao，ZHENG Dongrui，YAN Baoping，CUI Lijun

2021, 24(32): 4104-4109. DOI: 10.12114/j.issn.1007-9572.2021.01.020

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Background　Due to complex clinical symptoms，bipolar Ⅰ disorder （BP-Ⅰ） is easily misdiagnosed or underdiagnosed，and difficult to treat，and has relatively high recurrence. The recurrence may occur often even in some cases with standardized treatment. Frequent recurrence of BP-Ⅰ can damage patients' social function significantly. However，to the best of our knowledge，there are few studies on the recurrence of BP-Ⅰ based on the long-term follow-up with the first-episode mania patients. Objective　To explore the recurrence of first-episode mania in BP-Ⅰ over a 7-year follow-up period and its influencing factors. Methods　Both outpatients and inpatients with BP-Ⅰ and first-episode mania were recruited from Mental Health Center of Hebei Province between October 2011 and October 2013. Divided into low recurrence group and high recurrence group according to the number of recurrences. The collected patients' data at the first episode cover the following aspects：（1）demographic characteristics，including gender，age，body mass index，marital status，occupation and education level; （2）psychological cognitive level，including results of Wisconsin Card Sorting Test，Stroop Color-Word Association Test（Stroop） and Social Support Rating Scale; （3）disease characteristics，including family mental health history，prevalence of stressful life events before the onset，prevalence of aggressive characteristics and psychotic symptoms，Young Mania Rating Scale score; （4）treatment details，including treatment in both acute and maintenance phases. The 7-year follow-up data were also collected，including the recurrence within the first year，single manic episodes and psychotic symptoms，the prevalence of psychotic symptoms，depressive episodes，manic episodes，and the proportion of maintenance treatment times in total number of episodes，medication adherence assessed by the Medication Adherence Scale，and functional level assessed by the Global Assessment of Functioning （GAF） at the last follow-up in the seventh year. Results　A total of 147 patients were enrolled in this program，and 101 of them who completed the follow-up were finally included，including 45 with recurrence <4 times（low recurrence group） and 56 with recurrence ≥4 times（high recurrence group）. Stroop interference ensues （SIE） in the low recurrence group was lower than that in the high recurrence group（P<0.05）. Low recurrence group had higher prevalence of receiving treatment in the maintenance phase（P<0.05）. Low recurrence group had lower recurrence rate，higher prevalence of manic episodes，and higher proportion of maintenance treatment times in total number of episodes within the first follow-up year （P<0.05）. Unconditional binary logistic regression analysis indicated that manic episode was significantly associated with the number of recurrent episodes（OR=0.170，P<0.05）. Conclusion　Low recurrence rate was noted in BP-Ⅰ patients with first-episode mania who had relatively good executive function after the first onset，received treatment in the maintenance phase，had only manic episodes after treatment for the first onset，and a higher proportion of maintenance treatment times in total number of episodes. Those who relapsed within the first year after remission had a higher rate of later recurrence. Manic episodes were found to be associated with the recurrence. The recurrent outcome of those with single manic episodes was better than that of those with alternating manic-depressive episodes.

The Effects of Obstructive Sleep Apnea on Sleep and Cognitive Function in Patients with Schizophrenia　

SONG Suqi，ZHANG Kai，ZHOU Xiaoqin，LIU Huanzhong

2021, 24(32): 4110-4115. DOI: 10.12114/j.issn.1007-9572.2021.01.220

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Background　Cognitive impairment is an important feature of schizophrenia. Obstructive sleep apnea syndrome（OSAS）not only affects sleep quality，but also has extensive cognitive impairment. However，there are few reports on the sleep and cognitive impairment of schizophrenia patients with OSAS. Objective　To compare the sleep situation and cognitive functions in schizophrenia patients with or without OSAS，in order to explore whether the sleep and cognitive function of patients with schizophrenia are affected by OSAS. Methods　Patients with schizophrenia hospitalized in the Department of Psychiatry，Chaohu Hospital of Anhui Medical University from March 2018 to December 2019 were selected as the study subjects（80 cases），and healthy population in the physical examination center of Chaohu Hospital Afiliated to Anhui Medical University during the same period were selected as the control group（31 cases）. The information of gender，age，years of education，smoking status，body mass and height of the enrolled subjects were collected by using the self-made questionnaire of general demographic data，and the body mass index（BMI）was calculated. Repetitive sets of neuropsychological status tests（RBANS，immediate memory，visual breadth，speech function，attention，delayed memory）were used to evaluate the cognitive function of the enrolled subjects，and the positive and negative syndrome scale（PANSS）was used to evaluate the clinical psychiatric symptoms，the Chinese version of Epworth Sleepiness Scale（ESS）were used to assess the patient's subjective drowsiness tendency.The sleep status of the patients was recorded through the cardiopulmonary coupling analysis（CPC）technology. The sleep parameters included total sleep time，deep sleep time，light sleep time，REM sleep time，awakening time，first falling asleep time，sleep efficiency and sleep apnea index（AHI）. Based on the standard of AHI≥5 times/h，80 patients with schizophrenia were divided into OSAS group（35 cases）and non-OSAS group（45 cases）. Pearson or Spearman rank correlation analysis was used for the correlation between the variables，and multiple linear regression analysis was used for the analysis of factors affecting cognitive function. Results　There were statistically significant differences in the instant memory scores，visual breadth scores，speech function scores，attention scores，delayed memory scores，and total RBANS scores among the three groups of study subjects（P<0.05）. Patients in the OSAS group had a shorter sleep time than the non-OSAS group（P<0.05），and the light sleep time and awakening time were longer than those in the non-OSAS group（P<0.05）. AHI，negative symptom scores，and PANSS total scores were higher than those in the non-OSAS group（P<0.05），the immediate memory score，visual breadth score，speech function score，attention score，delayed memory score，and RBANS total score were lower than those in the group without OSAS（P<0.05）. In patients with schizophrenia，immediate memory score，visual breadth score were negatively correlated with disease course，negative symptom score，and AHI（P<0.05）；The speech function score was negatively correlated with age，disease course，general psychopathological symptom score，light sleep time，wake time，and AHI（P<0.05）；Attention score was negatively correlated with age，disease course，negative symptom score and AHI（P<0.05）；Delayed memory score was negatively correlated with negative symptom score，AHI（P<0.05）；The total score of RBANS was negatively correlated with the course of disease，negative symptom score，sleep time，awakening time，and AHI（P<0.05）. The results of multiple regression analysis showed that negative symptom scores and years of education were the influencing factors of immediate memory score（P<0.05）. AHI and disease course were the influencing factors of visual breadth score and speech function score（P<0.05），and disease course was the influencing factors of the attention score（P<0.05）. The length of education，AHI were the influencing factors of the delayed memory score（P<0.05）. The length of education，the course of disease，and AHI were the influencing factors of the total score of RBANS（P<0.05）. Conclusion　The sleep and cognitive impairment of schizophrenia patients with OSAS are more severe than that of schizophrenia patients without OSAS；Sleep indicators such as light sleep time and awakening time are negatively correlated with cognitive function of schizophrenia patients；And years of education，disease course，AHI may be the influencing factors of cognitive function in patients with schizophrenia. Early CPC examination and timely intervention may reduce the sleep and cognitive impairment caused by OSAS.

Association of First-episode Schizophrenia with DRD2 Gene Polymorphism and Cognitive Function　

DONG Zhen，LIU Xin，ZHANG Lili，WANG Sujuan，LI Keqing，ZHANG Yunshu

2021, 24(32): 4116-4120. DOI: 10.12114/j.issn.1007-9572.2021.01.109

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Background　The pathogenesis of schizophrenia is associated with dopamine D2 receptor（DRD2）gene polymorphism. Cognitive dysfunction is a major symptom of schizophrenia，and may be associated with the risk of developing schizophrenia. However，there are few studies about the association of first-episode schizophrenia with DRD2 gene polymorphism and cognitive function. Objective　To examine the association of first-episode schizophrenia with DRD2 rs2514218 and cognitive function. Methods　Seventy-five patients with first-episode schizophrenia（patient group） and 75 healthy subjects（control group） who were treated at the Hebei Provincial Mental Health Center from 2018—2019 were recruited. The Chinese version of MATRICS Consensus Cognitive Battery（MCCB），including seven domains measuring cognitive functions（speed of processing，attention/vigilance，working memory，verbal learning，visual learning，reasoning and problem solving，and social cognition）：Trail Making Test：Part A（TMT-A），Continuous Performance Test（CPT），Brief Visuospatial Memory Test-Revised（BVMT-R），Hopkins Verbal Learning Test-Revised（HVLT-R），and Stroop Color Word Test（SCWT）. All participants were genotyped for DRD2 rs2514218. Results　Except for dropouts，the remaining 74 patients and 73 controls were finally included. These two groups had no significant differences in genotype distribution and allele frequencies of DRD2 rs2514218（P>0.05）. The patient group had lower average scores of TMT-A，CPT，BVMT-R，and HVLT-R，as well as less number of correct responses for SCWT than control group（P<0.01）. Multivariate logistic regression analysis found that scores of TMT-A〔OR=0.888，95%CI（0.817，0.965），P=0.005〕，CPT〔OR=0.856，95%CI（0.790，0.928），P<0.001〕，BVMT-R〔OR=0.882，95%CI（0.817，0.952），P=0.001〕 and HVLT-R〔OR=0.807，95%CI（0.734，0.888），P<0.001〕 were associated with schizophrenia，and the direction of these associations was negative. Conclusion　First-episode schizophrenia patients had impaired cognitive functions. The risk of first-episode schizophrenia was not associated with DRD2 rs2514218 SNP，but had association with some cognitive functions. Poorer speed of processing，attention/vigilance，visual learning and memory，visual learning and memory were associated with higher risk of developing schizophrenia.

Recent Advances in Cognitive Impairment in Schizophrenia：Stage-specific Features and Interventions　

WANG Xue，ZHOU Yuqiu，LIU Dongwei，WANG Weiliang，MENG Xiangyu，ZHANG Chunyu

2021, 24(32): 4121-4125. DOI: 10.12114/j.issn.1007-9572.2021.01.010

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Although cognitive impairment occurs in each stage of schizophrenia，its specific trajectory in the development of schizophrenia is still unclear. We analyzed the overall development and stage-specific features of cognitive impairment in schizophrenia，then clarified its developmental trajectory，summarized that temporal changes of cognitive impairment are relatively insignificant，and reviewed relevant interventions. After that，we inferred that schizophrenia may be a cognitive disease in essence，and recommended that future diagnosis and treatment strategies for schizophrenia should be developed based on prevention，recognition and intervention of cognitive impairment.

Meta-analysis of Vitamin D Nutritional Status of Children in Chinese Mainland　

SU Jingying，CHEN Xianrui，LIN Gangxi

2021, 24(32): 4126-4136. DOI: 10.12114/j.issn.1007-9572.2021.01.211

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Background　The global vitamin D nutritional status has attracted much attention recently. Vitamin D nutritional status may differ by country or region. There are few multicenter studies with a large sample size on vitamin D nutritional status in Chinese children. Objective　To analyze the vitamin D nutritional status in children in Chinese mainland. Methods　Studies regarding vitamin D nutritional status in children in Chinese mainland were collected by searching databases of PubMed，Embase，The Cochrane Library，Wanfang Data，CNKI，SinoMed and CQVIP from database inception to 2020-04-08. Two researchers separately extracted information from the eligible studies，encompassing the first author，publication time，the region（northern or southern China）where participants live，size，sex ratio，age of the sample，and outcome indicators〔serum 25（OH）D level，rate of vitamin D deficiency serum 25（OH）D level <20 μg/L〕，and assessed the publication bias. Meta-analysis was carried out using RevMan 5.2 and Stata 14.0. Results　A total of 29 studies with 133 441 healthy children and adolescents were enrolled. The average serum 25（OH）D level was （29.62±12.45）μg/L for all participants. Meta-analysis indicated that the prevalence of vitamin D deficiency in all participants，participants from southern and northern China，was 21.4%〔95%CI（17.5%，25.4%）〕，17.5%〔95%CI（13.1%，22.0%）〕，and 29.0%〔95%CI（19.4%，38.6%）〕，respectively. No significant sex-based differences were found in the prevalence of vitamin D deficiency 〔OR=0.99，95%CI（0.95，1.03），P=0.71〕，and average serum 25（OH）D level〔SMD=0.01，95%CI（-0.24，0.26），P=0.95〕. Infants had higher average serum 25（OH）D level than young children〔SMD=0.16，95%CI（0.06，0.27），P=0.002〕，preschool children〔SMD=0.77，95%CI（0.55，1.00），P<0.000 01〕，and school-age children and adolescents〔SMD=0.65，95%CI（0.27，1.04），P=0.000 1〕. In participants from southern China，infants had higher average serum 25（OH）D level than young children〔SMD=1.51，95%CI（0.31，2.72），P=0.01〕，preschool children〔SMD=6.22，95%CI（3.97，8.47），P<0.000 01〕，and school-age children and adolescents〔SMD=6.80，95%CI（2.95，10.65），P<0.000 5〕. In those from northern China，infants had higher average serum 25（OH）D level than young children〔SMD=1.23，95%CI（0.33，2.12），P=0.007〕and preschool children〔SMD=8.41，95%CI（2.04，14.79），P=0.01〕. Young children had higher average serum 25（OH）D level than preschool children〔SMD=0.61，95%CI（0.43，0.80），P<0.000 01〕，and school-age children and adolescents〔SMD=0.65，95%CI（0.27，1.04），P=0.001〕. In those from southern China，young children had higher average serum 25（OH）D level than preschool children〔SMD=5.53，95%CI（3.57，7.49），P<0.000 01〕，and school-age children and adolescents〔SMD=6.07，95%CI（3.04，9.10），P<0.000 1〕. In those from northern China，young children had higher average serum 25（OH）D level than preschool children 〔SMD=6.56，95%CI（1.19，11.92），P=0.02〕. Preschool children had higher average serum 25（OH）D level than school-age children and adolescents〔SMD=0.33，95%CI（0.15，0.51），P=0.000 4〕. In those from southern China，the average serum 25（OH）D level in preschool children was higher than that in school-age children and adolescents〔SMD=1.89，95%CI（0.58，3.21），P<0.005〕. In those from northern China，the average serum 25（OH）D level in preschool children was higher than that in school-age children and adolescents with no statistical difference〔SMD=4.94，95%CI（1.51，8.38），P=0.005〕. Conclusion　In Chinese mainland，the prevalence of vitamin D deficiency in children was relatively high. The vitamin D level was not associated with sex，but may be closely related to age. However，our conclusion still needs to be verified by further research.

Meta-analysis of the Predictive Value of Lipid Metabolism in Children with Henoch-Schonlei Purpura　

HAN Shanshan，DING Ying，DAI Yanlin，ZHANG Xia，WANG Long

2021, 24(32): 4137-4144. DOI: 10.12114/j.issn.1007-9572.2021.01.219

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Background　Henoch-Schonlein purpura （HSP） is one of the most common vasculitis in children. Some of them may involve the kidney and develop into Henoch Schonlein purpura nephritis，which affects the prognosis. Therefore，it is necessary to find the predictors of renal damage in the early stage of Henoch-Schonlein purpura. In recent years，more and more studies have shown that abnormal lipid metabolism may be a risk factor for HSP renal injury，but there is no systematic evidence-based study. Objective　To comprehensively collect relevant literature and evaluate whether lipid abnormalities in the early stage of HSP can be used as a predictor of HSPN. Methods　PubMed，EMBase，The Cochrane Library，China National Knowledge Infrastructure（CNKI），Wanfang Data Knowledge Service Platform，VIP and China Biology Medicine disc were searched by computer. The retrieval time were from the establishment of the databases to February 10，2020. The first author，publication year，country，diagnostic criteria，gender，age，number of cases（HSPN group / non HSPN group），observation indexes〔total cholesterol （TC），triglyceride（TG），high density lipoprotein （HDL），low density lipoprotein（LDL），apolipoprotein M（ApoM） in the two groups at the initial stage of onset〕，study type，occurrence （initial onset / recurrence），course of disease and follow-up time were collected to study the risk factors of HSPN in children. Newcastle Ottawa scale （NOS） was used to evaluate the quality of the included literature. Stata 15.1 software was used for Meta-analysis. Results　A total of 5 312 cases from 16 literatures were included. Excluding 26 cases lost to follow-up，there were 5 286 children with HSP，and 1 997 cases developed HSPN，with NOS scores ≥6 points. The results of meta-analysis showed that the levels of TC 〔WMD=0.72，95%CI （0.51，0.92）〕，TG 〔WMD=0.61，95%CI （0.45，0.77）〕 and LDL〔WMD=0.65，95%CI （0.41，0.89）〕 in HSPN group were higher than those in non HSPN group，and the level of ApoM 〔OR=0.32，95%CI （0.12，0.85）〕 was lower than those in non HSPN group. Conclusion　High levels of TC，TG and LDL may be predictors of HSPN development. The relationship between HDL level and HSPN is still unclear，which needs to be confirmed by further research. ApoM is expected to become a new independent predictor of HSPN.

Progress of Clinical Research on Frailty and Hypertension　

LUO Jianzhao，GUO Ru，SU Yanling，YANG Rong，LI Dongze，ZHAO Qian，LIAO Xiaoyang

2021, 24(32): 4145-4149. DOI: 10.12114/j.issn.1007-9572.2021.01.307

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Both frailty and high blood pressure are elderly problems related to aging. Both frailty and high blood pressure increase the risk of adverse outcomes for the elderly. Patients with frail and hypertension have received the attention of hypertension guidelines，but there is still a lack of guidance for treatment and management. An important reason is that the relationship between hypertension and frailty remains unclear，and it is controversial whther patients with frailty and hypertension can benefit from antihypertensive therapy. This paper reviews the latest clinical studies involving both frailty and hypertension，intends to analyze the relationship between frailty and hypertension from different perspectives，in order to provide new inspiration for the treatment and management of frail patients with hypertension.

The Role of m6A RNA Methylation Modification in Esophageal Cancer　

ZHU Lingyan，SHEN Yi，SHAO Yi，LIU Fen

2021, 24(32): 4150-4154. DOI: 10.12114/j.issn.1007-9572.2021.01.306

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N6-methyladenosine （m6A），as the most abundant epitranscriptomic modification in eukaryotic cells，plays an important role in the occurrence and development of tumors. At present，domestic and foreign research on how m6A methylation modification participates in the occurrence and development of esophageal cancer mainly focuses on the biological functions of cell malignant proliferation，migration and invasion. Research on the differential expression of m6A methylation modification regulators in esophageal cancer suggests that m6A methylation modification regulators are expected to become potential prognostic molecular markers for esophageal cancer. This review focuses on the biological functions of m6A methylation modification，as well as the prognostic value of m6A methylation in esophageal cancer，postoperative treatment and other aspects of research progress，aiming to provide new ideas for the prognosis and targeted therapy of esophageal cancer.

Development of Traditional Chinese Medicine Clinical Practice Guidelines Using Mixed Methods and Example Interpretation　

ZHAO Guozhen，CHEN Tengfei，GUO Yuhong，FENG Xue，SU Xiangfei，HU Jing，FENG Shuo，ZHANG Huina，DU Yuan，YAN Yumeng，WANG Yafan，LI Bo，LIU Qingquan

2021, 24(32): 4155-4159. DOI: 10.12114/j.issn.1007-9572.2021.01.215

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The development of Traditional Chinese Medicine（TCM）clinical practice guidelines is a key measure to achieve the standardization of TCM. The TCM guidelines greatly contribute to the guidance of clinical practice，but the phenomenon of inadequate use of them exists，which may be related to the contents of the guidelines. As there is a small number of high-quality TCM clinical studies，guidelines developed based on evidence-based medical data derived from them，namely，guidelines mainly based on quantitative research results，have showed limitations in their recommendations. In contrast，the evidence（quantitative and qualitative research results）from mixed methods studies may be more practical，which may better benefit the development of TCM guidelines. This paper preliminarily discussed the idea and function of mixed method research in the process of guidelines formulation，and took the Clinical practice guide in the treatment of influenza by TCM as an example. This paper discussed the problems encountered in the guideline formulation led by quantitative research and the specific application of mixed method research in the guideline formulation. It was found that mixed method research can make up for the lack of relying solely on quantitative or qualitative research results，and may become one of the main methods for future guideline formulation，but there are still certain limitations and further research is needed.

Erythropoietic Protoporphyria with Multiple Organ Failure in Children：a Case Report and Literature Review　

MA Chunmiao，YU Xinyou，LU Biao，XIE Xinbao，LIANG Lijun

2021, 24(32): 4160-4164. DOI: 10.12114/j.issn.1007-9572.2021.01.014

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Erythropoietic protoporphyria is a rare disease characterized by impaired activity of ferrochelatase caused by FECH genetic mutations. This study reviewed the clinical data and results of gene analysis of a child with erythropoietic protoporphyria and relevant studies，and discussed the features of this disease and mutation sites of pathogenic genes，in order to improve clinical understanding of erythropoietic protoporphyria. Clinical attention should be paid to warning signs of erythropoietic protoporphyria，such as recurring rashes in the parts of the skin exposed to sunlight，especially accompanied with abdominal pain and liver damage，FECH gene test is helpful for the diagnosis of the disease.

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