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.Evaluation and application of automated quality control of automatic pipeline in clinical biochemical and immunological detection
Li′an HOU ; Xuesong SHANG ; Chaochao MA ; Liangyu XIA ; Li LIU ; Ying ZHANG ; Yujun SU ; Xin LIU ; Ling QIU
Chinese Journal of Laboratory Medicine 2024;47(1):86-93
Objective:To assess the applicability of fully automatic pipeline automated testing for internal quality control (automated quality control).Methods:Stability, assay efficiency and implementation costs of 18 biochemical tests, 5 immunoturbidimetric tests and 11 chemical illuminescent tests in the Department of Laboratory Medicine of Peking Union Hospital from January 2019 to July 2022 were evaluated using automated quality control implementation methods. The detailed method is as follows: quality control materials for biochemical, immunoturbidimetric and chemiluminescent tests were stored in the refrigerator in the pipeline which was controlled by the intermediate software, and were automatically retrieved and tested as pre-set followed by documenting and storing. The quality control setup for the biochemical tests included refreshing quality control materials daily and weekly,both of which were paralleled for 3 months. The on-line storage stability of quality control materials in the pipeline was evaluated by comparing the coefficients of variation ( CV) of the quality control results between the two patterns. Effect of automated quality control application was evaluated using 6 indicators, including the results′ variation of automatically performed and manually performed quality controls, the out-of-controlled rate, the consumption of quality control materials, the change of staff workload, the impact on the testing time of the first sample, and the failure rate of automated quality control. Results:(1) Storage stability of quality control materials in the pipeline: under the pattern of weekly refresh of the biochemical quality control materials, except for total carbon dioxide (TCO 2) (the CVs of low and high level quality control were respectively 20.24% and 21.82%) and sodium (the CV of low level quality control was 1.51%) that were greater than the allowable variation set by the laboratory, the CVs of the rest tests meet the lab requirements on the allowable variations. (2) The results′ variation of quality control in automatically performed and manually performed control patterns: in the patterns of daily refresh of biochemical quality control materials and weekly refresh of immunoturbidimetric and chemiluminescent quality control materials, the CVs of both low and high levels of quality control were lower in the automatically performed control pattern than that in manually performed pattern for 8 chemiluminescent items of dehydroepiandrosterone sulfate, estradiol, follicle stimulating hormone, luteinizing hormone, serum ferritin, serum folic acid, vitamin B12 and testosterone, 3 immunologic items of complement 3, C reactive protein and immunoglobulin G, and 10 biochemical items of alkaline phosphatase, glucose, calcium, chloride, potassium, lactate dehydrogenase, sodium, urea, low density lipoprotein cholesterol, and adenosine deaminase. The out-of-control rates of biochemistry, immunoturbidimetric and chemiluminescence tests in both quality control patterns conformed with the clinical routine work requirements. (3) Comparison of quality control materials′ consumption: compared with manually performed quality control, weekly consumption of automatically performed chemiluminescent quality control materials decreased 37.5% (from 8 ml to 5 ml); weekly consumption of automatically performed immunoturbidimetric quality control materials decreased 33.3% (from 3 ml to 2 ml). (4)Comparison of staff workload and first sample testing time: compared with manually performed quality control, automatical quality control reduced manual work by about 156 steps per week, and the daily initial testing time was earlier by 15 min on average. The failure rate was 54.5% (37/64) during the early-stage application of the automated quality control which dropped to 10.2% (13/128) in the late-stage. Conclusion:The results of automated quality control detected in the pipeline system meet the quality indicators′ requirements of the laboratory, and the application of automated quality control can improve the quality control, save costs, reduce workload, and improve work efficiency.
6.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.
7.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.
8.A case of iatrogenic hypernatremia caused by multiple myeloma-associated pseudohyponatremia
Yuan HUANG ; Lu ZHANG ; Liangyu XIA ; Jinyan LEI ; Chong WEI ; Yongzhe LI
Chinese Journal of Laboratory Medicine 2024;47(10):1212-1214
The patient was a 55-year-old man. On February 16, 2024, he was admitted to Peking Union Medical College Hospital complaining of "weakness and poor appetite for more than half a year, and found creatinine increase for 1 week". The patient was diagnosed with multiple myeloma. During the treatment in our hospital, the patient sustained"hyponatremia"(Na 124-136 mmol/L measured by indirect ion selective electrode method), and combined with the patient′s clinical symptoms and serum osmotic pressure results (327 mOsm/kg H 2O), it was considered that hyperglobulinemia led to pseudohyponatremia. So no intervention was given. Subsequent failure to recognize pseudohyponatremia during treatment in other hospitals and the administration of hypertonic saline resulted in severe iatrogenic hypernatremia. By reviewing similar cases in our hospital, we found that hyperglobulinemia/hyperlipidemia associated pseudohyponatremia was not uncommon. This case reminds us that for patients whose serum solid phase ratio is higher than normal due to various reasons, the use of indirect ion selective electrode method to determine serum sodium is prone to false low, and direct ion selective electrode method can be used to re-test blood sodium to determine whether it is true, so as to avoid iatrogenic injury to patients.
9.Exploring the Mechanism of Action of Guhuaisi Kangfu Pill for Treating Steroid-induced Osteonecrosis of the Femoral Head Based on WGCNA and Animal Experiment Validation
Wenxi LI ; Liangyu TIAN ; Jin ZHANG ; Caihong SHEN ; Zhimin YANG ; Jiaqiao GUO ; Yuju CAO
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(9):1306-1318
Objective To investigate the main pharmacological basis and mechanism of action of Guhuaisi Kangfu Pill(GHSKF)in the treatment of steroid-induced osteonecrosis of the femoral head(SONFH).Methods The active constituents and targets of GHSKF were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and other databases.The speculative targets of SONFH were screened out based on GeneCards and Online Mendelian Inheritance in Man(OMIM)databases.The gene modules and hub genes of SONFH were identified using a weighted gene co-expression network analysis(WGCNA).The intersection of the two targets and the result of WGCNA was taken to obtain the potential targets of GHSKF for the treatment of SONFH.The key active constituents were screened with the"active constituent-target"network,which was constructed by the Cytoscape software.Then,the STRING database was used to construct the protein interaction network to screen the key targets.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of key targets was performed,and the relationship between key active constituent,key targets and key signaling pathways was explored.Finally,the molecular docking between key active constituents and key targets was verified.In addition,the SONFH rat model was used for experimental verification.Results A total of 146 compounds and the corresponding 346 targets were identified based on the TCMSP database.A total of 4 187 targets of SONFH were obtained based on GeneCards and OMIM databases.In addition,twelve gene modules and 2 556 hub genes of SONFH were screened out based on WGCNA.Quercetin,luteolin and kaempferol were key active ingredients for the treatment of SONFH.Various signaling pathways such as PI3K/AKT were involved.Molecular docking showed the key active ingredients had good binding activity with the key targets.The results of animal experiments demonstrated that GHSKF could improve bone biological alterations by up-regulating AKT1,PI3K,RUNX2,and down-regulating the expression of Caspase-3 and IL-6(P<0.01),which verified some results of the network pharmacology prediction.Conclusion We analyzed the potential mechanism of action of GHSKF for the treatment of SONFH using network pharmacology and animal experiments,which may provide a reference for further research on its pharmacological basis and targets.
10.Comprehensive and deep profiling of the plasma proteome with protein corona on zeolite NaY
Congcong MA ; Yanwei LI ; Jie LI ; Lei SONG ; Liangyu CHEN ; Na ZHAO ; Xueping LI ; Ning CHEN ; Lixia LONG ; Jin ZHAO ; Xin HOU ; Li REN ; Xubo YUAN
Journal of Pharmaceutical Analysis 2023;13(5):503-513
Proteomic characterization of plasma is critical for the development of novel pharmacodynamic bio-markers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the"masking"effect caused by high-abundance proteins.The relative abundance of middle-and low-abundance proteins increased substantially from 2.54%to 54.41%,and the top 20 high-abundance proteins decreased from 83.63%to 25.77%.Notably,our method can quantify approxi-mately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins iden-tified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

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