1.Evaluation of GRADE Clinical Research Evidence of Chinese Patent Medicine Combined with Western Medicine in Treatment of Hypertension with Dyslipidemia
Jiaheng WANG ; Yukun LI ; Liangyu CUI ; Yilan ZHENG ; Zhiwei ZHAO ; Cong REN ; Tianyue JING ; Tong YIN ; Liying WANG ; Xuejie HAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):95-105
ObjectiveTo evaluate the effect of antihypertensive and lipid-regulating Chinese patent medicine combined with conventional Western medicine in the treatment of hypertension with dyslipidemia. To carry out the evidence synthesis of clinical research and provide evidence-based evidence support for clinical decision-making. MethodThe databases including China National Knowledge Infrastructure (CNKI),Wanfang Data Knowledge Service Platform (WF),VIP,SinoMed,Embase,PubMed,Web of Science (WOS),and the Cochrane Library were searched for randomized controlled trials (RCT) of all listed Chinese patent medicines in the treatment of hypertension with dyslipidemia from the establishment of the databases to April 15,2023. The literature was screened and extracted,and the risk of bias tool 2.0 (RoB2) was used to assess the quality and risk of bias of the methodology. Revman 5.4.1 software was used to analyze the outcome indicators. Grading of Recommendations Assessment,Development and Evaluation (GRADE) was applied to assess the quality of evidence formed by clinical research data. The inclusion and recommendation of Chinese patent medicines in the National Drug Catalogue for Basic Medical Insurance,Work-related Injury Insurance and Maternity Insurance (2022) and domestic guidelines and consensus were searched to form a bubble chart. ResultA total of 15 studies were included. The evaluation of the methodological quality of each study showed that the risk of bias stemmed from the lack of blinding and allocation concealment,and low sample size. The comprehensive analysis of clinical studies showed that Dengzhan Shengmai capsules combined with rosuvastatin and amlodipine besylate,Yindan Xinnaotong capsules combined with simvastatin and levamlodipine tablets,Xiaoshuan Tongluo capsules combined with nifedipine controlled release tablets and pravastatin sodium tablets,Xinshubao capsules combined with atorvastatin calcium tablets and irbesartan,Wenyading capsules combined with enalapril,and Jiangzhining tablets combined with conventional Western medicines were all superior to conventional Western medicines used in the control group in improving systolic blood pressure (SBP),diastolic blood pressure (DBP),cholesterol (TC),triglyceride (TG),low density lipoprotein cholesterol (LDL-C),and high density lipoprotein cholesterol (HDL-C). There was no significant difference in the incidence of adverse reactions between the two groups. The GRADE evaluation of the main outcome indicators showed that the evidence quality of SBP and incidence of adverse reactions was graded as B,that of DBP as C,and that of total TC,TG,LDL-C,and HDL-C as D. The evaluation of Chinese patent medicines covered by medical insurance and recommended by guidelines and consensus showed that Yindan Xinnaotong soft capsules,Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules belonged to class B drugs of medical insurance,and were recommended for 7,6 and 3 times in the guidelines and consensus,respectively. ConclusionCompared with simple medicine treatment,Chinese patent medicine combined with conventional Western medicine has more advantages in improving blood pressure and blood lipid,and shows higher safety. Among them,Yindan Xinnaotong soft capsules,Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules have stronger clinical applicability and economy. All the trials included in this article adhered to the principle of randomization and reported the outcome measures. However,the quality of evidence in related clinical studies was low. In terms of trial design,large-sample,multi-center,blinded randomized controlled trials based on the consolidated standards of reporting trials (CONSORT) statement are still needed for comprehensive trial designs and reporting,to further improve the GRADE quality evaluation and guideline formulation under the guidance of evidence-based medicine,so as to provide higher quality evidence-based research evidence for clinical decision-making.
2.GRADE Clinical Study Evidence Evaluation and Expert Consensus on Antihypertensive Chinese Patent Medicines Combined with Western Medicines for Treatment of Hypertension
Liangyu CUI ; Yukun LI ; Tianyue JING ; Yu WANG ; Cong REN ; Tong YIN ; Zhiwei ZHAO ; Jiaheng WANG ; Chenge SUN ; Dasheng LIU ; Zhizheng XING ; Xuejie HAN ; Liying WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):106-115
ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension, synthesize and update the evidence, form expert consensus, and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure (CNKI), WanFang Data Knowledge Service Platform (WanFang), Vip Chinese Science and Technology Journal Database (VIP), Chinese Biomedical Literature Service System (Sinomed), National Library of Medicine (PubMed), Cochrane Library, Web of Science, and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31, 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment, Development, and Evaluation profiler (GRADEprofiler) 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included, and the results of literature quality evaluation and risk of bias showed that 70.31% (45/64) of the studies indicated some risks, and 29.69% (19/64) indicated high risks. Compared with conventional western medicines, the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure (SBP) and diastolic pressure (DBP), increase the effective rate of antihypertensive, reduce the incidence of adverse reactions, endothelin-1, and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive, and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive, without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive, and Xinmaitong capsules decreased DBP, with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally, four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension, antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety, but they are mostly weak recommendations in terms of efficacy, and more high-quality evidence is needed.
3.Clinical Evidence Mapping of Chinese Patent Medicines Combined with Western Medicine in Treatment of Hypertension
Yukun LI ; Liangyu CUI ; Zhiwei ZHAO ; Cong REN ; Tong YIN ; Yu WANG ; Liying WANG ; Xuejie HAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):116-123
ObjectiveTo systematically collect, analyze, and evaluate the randomized controlled trials (RCT) of Chinese patent medicine combined with western medicine in the treatment of hypertension, map the evidence, and provide reference for the future clinical research and formulation of guidelines and policies. MethodThe relevant articles were retrieved from China Biology Medicine disc, China National Knowledge Infrastructure (CNKI), VIP, Wanfang Data, PubMed, Embase, and Cochrane Library with the time interval from inception to December 31, 2022. The RCT of Chinese patent medicines combined with western medicine in the treatment of hypertension were included. The research characteristics and methodological quality were analyzed and evaluated. ResultA total of 330 RCTs of treating hypertension with Chinese patent medicines combined with Western medicine were included in this study, all of which were published in Chinese. These RCTs involved 88 Chinese patent medicines and 37 788 patients, and 46% of RCT had the sample size ≥100 patients. Eighty-seven percent of RCT showed the study period within 3 months. All the interventions in the RCTs were Chinese patent medicine + western medicine vs western medicine. Among the evaluation indicators, blood pressure, response rate, TCM syndrome score, endothelial cell function, and safety were mainly concerned. In terms of methodological quality, most articles did not mention the generation of random sequences, allocation concealment, or blinding method. The blinding evaluation of outcomes showed low risks of bias, and there was insufficient information to judge whether there was selective bias or other bias. ConclusionThere were many Chinese patent medicines used in combination with western medicine in the treatment of hypertension, and they were mainly taken orally. The existing RCT had problems such as small sample size, unclear clinical value positioning, imperfect design failing to reflect the value of Chinese patent medicines, unreasonable measurement indicators, and non-standard measurement methods. Future research should solve the above problems, improve the research quality, value, and authenticity, and enhance the reliability and extension of evidence.
4.Early prediction of severe acute pancreatitis based on improved machine learning models
Long LI ; Liangyu YIN ; Feifei CHONG ; Ning TONG ; Na LI ; Jie LIU ; Xiangjiang YU ; Yaoli WANG ; Hongxia XU
Journal of Army Medical University 2024;46(7):753-759
Objective To establish an early prediction model for the diagnosis of severe acute pancreatitis based on the improved machine learning models,and to analyze its clinical value.Methods A case-control study was conducted on 352 patients with acute pancreatitis admitted to the Gastroenterology and Hepatobiliary Surgery Departments of the Army Medical Center of PLA and Emergency and Critical Care Medicine Department of No.945 Hospital of Joint Logistics Support Force of PLA from January 2014 to August 2023.According to the severity of the disease,the patients were divided into the severe group(n=88)and the non-severe group(n=264).The RUSBoost model and improved Archimead optimization algorithm was used to analyze 39 routine laboratory biochemical indicators within 48 h after admission to construct an early diagnosis and prediction model for severe acute pancreatitis.The task of feature screening and hyperparameter optimization was completed simultaneously.The ReliefF algorithm feature importance rank and multivariate logistic analysis were used to analyze the value of the selected features.Results In the training set,the area under curve(AUC)of the improved machine learning model was 0.922.In the testing set,the AUC of the improved machine learning model reached 0.888.The 4 key features of predicting severe acute pancreatitis based on the improved Archimedes optimization algorithm were C-reactive protein,blood chlorine,blood magnesium and fibrinogen level,which were consistent with the results of ReliefF algorithm feature importance ranking and multivariate logistic analysis.Conclusion The application of improved machine learning model analyzing the laboratory examination results can help to early predict the occurrence of severe acute pancreatitis.
5.The Research Status and Thinking of Objectification of Diagnosis by Integrating Prior Knowledge and Information Technology
Chenge SUN ; Yukun LI ; Zhiwei ZHAO ; Linshuang WANG ; Liangyu CUI ; Tong YIN ; Liying WANG ; Xuejie HAN ; Dasheng LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(6):1654-1659
In order to solve the problem of strong subjectivity and difficulty in quantification,clinical objectification mainly adopts the techniques of image processing,computer vision and machine learning.The acquisition and processing of prior knowledge is a key link in the objectification of inspection,as well as an important elaboration of the quantification of subjective judgment and macro performance in objectification research.However,there is still a lack of in-depth summary and parametric processing of prior knowledge.Based on the analysis of the current research status of objectification of inspection,this paper uses data mining technology to summarize the experience of TCM inspection.Moreover,the observation information can be transformed into quantifiable digital features through natural language processing and representation learning.Meanwhile,the application of deep learning can realize automatic diagnosis and analysis of observation images to improve accuracy and efficiency,and promote the process of TCM modernization.
6.TRIM24 alleviates viral myocarditis by promoting STAT6 phosphorylation-mediated macrophage M2 polarization
Liangyu ZHU ; Xueqin LI ; Xin ZHANG ; Guoquan YIN ; Yuan ZHANG ; Kun LYU
Chinese Journal of Immunology 2024;40(8):1595-1600,1606
Objective:To study the role and preliminary molecular mechanism of TRIM24 regulating macrophage polarization in viral myocarditis(VM).Methods:VM mouse model was established by Coxsackie virus B3(CVB3),and expression of TRIM24 in myocardial tissue was detected.Cardiac inflammation level and polarization phenotype of cardiac infiltrating macrophages in a murine model of cardiac TRIM24 inhibition were detected in vivo.A polarization model of mouse bone marrow-derived macrophages(BMDMs)in vitro was established to observe the role of TRIM24 inhibition in polarizing BMDMs to M1 and M2,as well as its effects on phagocy-tosis and bactericidal function of BMDMs.Effects of TRIM24 inhibition on total STAT6 protein level and phosphorylation were investi-gated.Results:TRIM24 was significantly highly expressed in myocardial tissue of VM mice(P<0.001).Inhibition of TRIM24 expres-sion in myocardium had an attenuating effect on VM and promoted polarization of cardiac infiltrating macrophages to M2.TRIM24 was significantly down-regulated in vitro during the polarization of BMDMs toward M2(P<0.01).Inhibition of TRIM24 expression signifi-cantly promoted macrophage polarization toward M2 type and inhibited polarization toward M1 type,accompanied by a significant increase in STAT6 phosphorylation levels(P<0.01).Conclusion:TRIM24 regulates macrophage M2 polarization via activation of STAT6 signaling pathway to attenuate VM.
7.Viral myocarditis serum exosome-derived miR-320 promotes the apoptosis of mouse cardiomyocytes by inhibiting AKT/mTOR pathway and targeting phosphatidylinositol 3-kinase regulatory subunit 1 (Pik3r1).
Xin ZHANG ; Xueqin LI ; Liangyu ZHU ; Guoquan YIN ; Yuan ZHANG ; Kun LYU
Chinese Journal of Cellular and Molecular Immunology 2023;39(6):516-525
Objective To investigate the effect of viral myocarditis serum exosomal miR-320 on apoptosis of cardiomyocytes and its mechanism. Methods The model of viral myocarditis mice was established by intraperitoneal injection of Coxsackie virus B3. Serum exosomes were extracted by serum exosome extraction kit and co-cultured with cardiomyocytes. The uptake of exosomes by cardiomyocytes was detected by laser confocal microscopy. Cardiomyocytes were transfected with miR-320 inhibitor or mimic, and the expression level of miR-320 was detected by real-time quantitative PCR. Flow cytometry was used to detect cardiomyocyte apoptosis rate, and the expression levels of B cell lymphoma 2 (Bcl2) and Bcl2-related X protein (BAX) were tested by Western blot analysis. The prediction of miR-320 target genes and GO and KEGG enrichment analysis were tested by online database. The relationship between miR-320 and its target gene phosphoinositide-3-kinase regulatory subunit 1(Pik3r1) was examined by luciferase reporter gene. The effect of miR-320 on AKT/mTOR pathway protein was detected by Western blot analysis. Results Viral myocarditis serum exosomes promoted cardiomyocyte apoptosis, and increased the level of BAX while the level of Bcl2 was decreased. miR-320 was significantly up-regulated in myocardial tissue of viral myocarditis mice, and both pri-miR-320 and mature of miR-320 were up-regulated greatly in cardiomyocytes. The level of miR-320 in cardiomyocytes treated with viral myocarditis serum exosomes was significantly up-regulated, while transfection of miR-320 inhibitor counteracted miR-320 overexpression and reduced apoptosis rate caused by exosomes. Pik3r1 is the target gene of miR-320, and its overexpression reversed cardiomyocyte apoptosis induced by miR-320 up-regulation. The overexpression of miR-320 inhibited AKT/mTOR pathway activation. Conclusion Viral myocarditis serum exosome-derived miR-320 promotes apoptosis of mouse cardiomyocytes by inhibiting AKT/mTOR pathway by targeting Pik3r1.
Mice
;
Animals
;
Myocytes, Cardiac
;
Phosphatidylinositol 3-Kinase/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Myocarditis/pathology*
;
Exosomes/metabolism*
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bcl-2-Associated X Protein/metabolism*
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MicroRNAs/metabolism*
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TOR Serine-Threonine Kinases/metabolism*
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Apoptosis/genetics*
8.Explore the reasons affecting the consistency of reference intervals established by two types of indirect methods for 34 biochemical analytes
Chaochao MA ; Yicong YIN ; Li LIU ; Qian LIU ; Xin LIU ; Ying ZHANG ; Liangyu XIA ; Ling QIU
Chinese Journal of Laboratory Medicine 2023;46(10):1083-1093
Objective:To compare the differences of reference intervals (RI) established by two types of indirect methods for 34 biochemical analytes, and to explore the possible factors that affect the consistency of the two methods.Methods:This was a retrospective study. Based on data of albumin (Alb), alkaline phosphatase (ALP), alanine aminotransferase (ALT), apolipoprotein A1(ApoA1), ApolipoproteinB (ApoB), aspartate aminotransferase (AST), calcium (Ca), cholinesterase (ChE), chloride (Cl), creatinine (Cr), high-sensitivity C-reactive protein (hsCRP), Cystatin (CysC), direct bilirubin (DBil), free fatty acid (FFA), glycated albumin(GA), gamma-glutamyltransferase (GGT), glucose (Glu), high density lipoprotein cholesterol (HDL-C), potassium (K), lactate dehydrogenase (LD), low density lipoprotein cholesterol (LDL-C), lipoprotein a [Lp (a)], sodium (Na), phosphorus (P), prealbumin (PA), superoxide dismutase (SOD), total bile acid (TBA), total bilirubin (TBil), total cholesterol (TC), total carbon dioxide (TCO 2), triglyceride (TG), total protein (TP), uric acid (UA) and urea (UR) of individuals who underwent physical examination at Peking Union Medical College Hospital from January 1, 2018 to December 31, 2019, Box-Cox algorithm was used to improve the data distribution and Tukey method was used to identify outliers. Variance component model was established, and standard deviation ratio (SDR) was calculated to determine whether the RIs of 34 biochemical analytes should be established according to age or sex The non-parametric method and kosmic algorithm were used to establish the RIs and 90% confidence intervals (CIs) of 34 biochemical analytes, and the coincidence of the 90% CIs of the reference limits for two methods was compared. Results:The skewness coefficients of ALP(male, female18-59), ALT, AST, hsCRP, DBil, GGT, Lp (a), TBA, TBil, TG, Glu, HDL-C(male) and CysC, GA, UR in the elderly group deviated from 0, and their kurtosis coefficients also deviated from 3. For these biochemical analytes, the point estimates of the RIs established by the two methods differed greatly and the 90% CIs did not overlap. The analytes with good normality were Alb, ApoA1, ApoB, Ca, ChE, Cl, Cr(E), CysC(18-59), FFA, GA(18-59), HDL-C(female), K, LDL-C, Na, P, PA, SOD, TC, TCO 2, TP and UR. The consistency is good. Except for Ca, 90% CIs of reference limits for some analyte between the two methods coincide with each other. Conclusions:The consistency of different indirect methods is affected by the normality of data.
9.Case report of pseudoelevated serum testosterone in women and literature review
Wei LUO ; Li′an HOU ; Songlin YU ; Ying ZHANG ; Jialei YU ; Yicong YIN ; Li LIU ; Xiaoyue LIANG ; Xin LIU ; Yujun SU ; Shaowei XIE ; Ling QIU ; Liangyu XIA
Chinese Journal of Laboratory Medicine 2022;45(12):1275-1278
Objective:The characteristics of women with false elevated testosterone were analyze and the literature was reviewed to provide reference for clinical laboratory identification of false elevated testosterone.Methods:The characteristics of three patients with false elevated testosterone in Peking Union Medical College Hospital were analyzed retrospectively, and the results of different detection platforms and methods for the determination of testosterone levels were compared. International and domestic literatures related to false elevation of testosterone and detection methods of testosterone were searched for a comprehensive analysis from PUBMED and CNKI.Results:The levels of testosterone in 3 female patients were elevated by immunoassay and normal by mass spectrometry. They were excluded from the diagnosis of hyperandrogenemia. A total of 38 literatures related to testosterone detection were retrieved, of which 9 case reports of pseudohyperandrogenemia, among which 12 cases of pseudohyperandrogenemia were reported in 2 domestic literatures in 2021. All cases were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Previous studies have clearly indicated that the result of routine immunoassay in clinical laboratory for the determination of female testosterone have poor correlation with the results of LC-MS/MS, with varying degrees of deviation.Conclusions:Immunoassay tests for female testosterone is susceptible to interference and lead to elevated false results. It is suggested that clinical laboratories evaluate the detection methods used and establish a identification program, and confirm samples with suspected pseudoelevated testosterone elevation using other immune platforms or LC-MS/MS.
10.Reference Intervals for Thyroid-Associated Hormones and the Prevalence of Thyroid Diseases in the Chinese Population
Yutong ZOU ; Danchen WANG ; Xinqi CHENG ; Chaochao MA ; Songbai LIN ; Yingying HU ; Songlin YU ; Liangyu XIA ; Honglei LI ; Yicong YIN ; Huaicheng LIU ; Dianxi ZHANG ; Kui ZHANG ; Xiaolan LIAN ; Tengda XU ; Ling QIU
Annals of Laboratory Medicine 2021;41(1):77-85
Background:
Thyroid diseases are highly prevalent worldwide, but their diagnosis remains a challenge. We established reference intervals (RIs) for thyroid-associated hormones and evaluated the prevalence of thyroid diseases in China.
Methods:
After excluding outliers based on the results of ultrasound screening, thyroid antibody tests, and the Tukey method, the medical records of 20,303 euthyroid adults, who visited the Department of Health Care at Peking Union Medical College Hospital from January 2014 to December 2018, were analyzed. Thyroid-associated hormones were measured by the Siemens Advia Centaur XP analyzer. The RIs for thyroid-associated hormones were calculated according to the CLSI C28-A3 guidelines, and were compared with the RIs provided by Siemens. The prevalence of thyroid diseases over the five years was evaluated and compared using the chi-square test.
Results:
The RIs for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were 0.71–4.92 mIU/L, 12.2–20.1 pmol/L, 3.9–6.0 pmol/L, 65.6–135.1 nmol/L, and 1.2–2.2 nmol/L, respectively. The RIs of all hormones except TT4 differed significantly between males and females. The RIs of TSH increased with increasing age. The prevalence of overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism was 0.5% and 0.8%, 0.2% and 0.6%, 3.8% and 6.1%, and 3.3% and 4.7% in males and females, respectively, which differed from those provided by Siemens.
Conclusions
Sex-specific RIs were established for thyroid-associated hormones, and the prevalence of thyroid diseases was determined in the Chinese population.

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