1.Multi-evidence Integration Methodology for Traditional Chinese Medicine: the MERGE Framework
Honghao LAI ; Zhe WANG ; Ying LI ; Wenjing TANG ; Beibei WANG ; Peidong SUN ; Mingyao SUN ; Jiajie HUANG ; Zhipan XIAO ; Ying LI ; Chen ZHAO ; Hongcai SHANG ; Kehu YANG ; Jie LIU ; Long GE
Medical Journal of Peking Union Medical College Hospital 2024;15(1):172-182
In the era of evidence-based medicine, it is necessary to explore the unique advantages of traditional Chinese medicine (TCM) based on standardized technical methods and operating procedures in order to achieve the modernization and internationalization of TCM and benefit all humanity. The proposal of a three-pronged evidence system combining TCM theory, human experience and experimental evidence marks an important progress in the thinking method of the TCM evaluation system. The multi-evidence body integrated through appropriate methods provides a strong support for the clinical guideline recommendations and evidence-based health decision-making in TCM. Based on the current methodological progress of international evidence synthesis and grading, this paper proposes a novel approach for integrating multi-evidence in TCM: the MERGE framework. The aim is to establish a solid foundation for the development of this methodology and provide guidance for the advancement of evidence-based medicine framework in TCM.
2.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50%(140 cases/184 cases)and 82.40%(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P>0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P>0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P>0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00%vs.64.50%,P>0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.
3.Application of digital visualization in surgical clearance of vertebral infection lesions following percutaneous vertebroplasty
Xiaoxiao BAO ; Long WANG ; Kai SU ; Zhenhui ZHANG ; Zhe SHAO ; Wentao JIANG ; Peilin LIU ; Yongsheng KANG ; Wei MEI ; Qingde WANG
Chinese Journal of Orthopaedic Trauma 2024;26(7):631-635
Objective:To evaluate the application of digital visualization in preoperative planning for surgical clearance of vertebral infection lesions following percutaneous vertebroplasty (PVP).Methods:A retrospective study was conducted to analyze the 13 patients with infectious spondylitis following PVP who had undergone one-stage posterior debridement and interbody bone grafting combined with instrumentation at Department of Spinal Surgery, Zhengzhou Orthopaedics Hospital from January 2016 to December 2022. They were 4 males and 9 females with an age of (71.4±6.5) years. Before surgery, the CT raw data of the patients were imported into software Mimics to reconstruct a three-dimensional model of the spine. After the distribution of bone cement in the model and its relationships with the vertebral plate, pedicle, articular process, and spinal cord were observed, a safe area for spinal canal surgery was designed. Intraoperative operations were carried out according to the preoperative planning. Surgical time, intraoperative blood loss, improvements in American Spinal Injury Association (ASIA) grading, and postoperative complications were recorded. The therapeutic efficacy was evaluated by comparisons of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS), and Oswestry disability index (ODI) between preoperation, 2 weeks and 3 months postoperation, and the last follow-up.Results:Surgery went on successfully in all the 13 patients according to the preoperative planning. The surgical time was (275.9±28.3) min and the intraoperative blood loss (865.4±183.0) mL. All patients were followed up for (24.7±9.4) months. The levels of ESR, CRP, VAS, and ODI at 2 weeks, 3 months and the last follow-up were significantly lower than those before surgery ( P<0.05). At the last follow-up, X-ray and CT examinations showed good positions of internal fixation and sufficient bone graft fusion. The ASIA grading recovered from preoperative D to E in 5 patients. No incision infection, sinus formation, worsening of neurological symptoms, loosening or rupture of internal fixation, or worsening of neurological dysfunction were found. Conclusion:With the assistance of 3D visualization, the spinal cord, bone cement, and debridement area can be visualized directly to reduce nerve injury complications so that a safe and effective preoperative planning can be made for surgical clearance of vertebral infection lesions following PVP.
4.Identification of ceRNA networks in type H and L vascular endothelial cells through integrated bioinformatics methods
Zhi LIU ; Zhe RUAN ; Haitao LONG ; Ruibo ZHAO ; Yong ZHU ; Zhangyuan LIN ; Peng CHEN ; Shushan ZHAO
Journal of Central South University(Medical Sciences) 2024;49(4):562-577
Objective:Type H blood vessels are a subtype of bone-specific microvessels(CD31hiEmcnhi)that play an important regulatory role in the coupling of angiogenesis and osteogenesis.Despite reports on the distinct roles of type H and L vessels under physiological and pathological bone conditions,their genetic differences remain to be elucidated.This study aims to construct a competitive endogenous RNA(ceRNA)network of key gene for differencial expression(DE)in type H and L vascular endothelial cells(ECs)through integrated bioinformatic methods. Methods:We downloaded relevant raw data from the ArrayExpress and the Gene Expression Omnibus(GEO)database and used the Limma R-Bioconductor package to screen for DE lncRNAs,DE miRNAs,and DE mRNAs between type H and L vascular ECs.A total ceRNA network was constructed based on their interactions,followed by refinement using protein-protein interaction(PPI)networks to select upregulated and downregulated key genes.Enrichment analysis was performed on these key genes.Random validation was conducted using flow cytometry and real-time RT-PCR. Results:A total of 1 761 DE mRNAs,187 DE lncRNAs,and 159 DE miRNAs were identified,and a comprehensive ceRNA network was constructed based on their interactions.Six upregulated(Itga5,Kdr,Tjp1,Pecam1,Cdh5,and Ptk2)and 2 downregulated(Csf1r and Il10)key genes were selected via PPI network to construct a subnetwork of ceRNAs related to these key genes.Upregulated key genes were mainly enriched in negative regulation of angiogenesis and vascular apoptosis.Results from flow cytometry and real-time RT-PCR were consistent with bioinformatics analysis. Conclusion:This study proposes a ceRNA network associated with upregulated and downregulated type H and L vascular ECs based on selected key genes,providing new insights into the regulatory mechanisms of type H and L vascular ECs in bone metabolism.
5.Correlation analysis between eNOS gene single nucleotide polymorphism and systemic lupus erythematosus in Hainan
Xuan ZHANG ; Hui-Tao WU ; Qi ZHANG ; Gui-Ling LIN ; Xi-Yu YIN ; Wen-Lu XU ; Zhe WANG ; Zi-Man HE ; Ying LIU ; Long MI ; Yan-Ping ZHUANG ; Ai-Min GONG
Medical Journal of Chinese People's Liberation Army 2024;49(9):986-991
Objective To investigate the relationship between single nucleotide polymorphisms(SNPs)in the eNOS gene and genetic susceptibility to systemic lupus erythematosus(SLE)in Hainan.Methods Blood samples were collected from SLE patients(SLE group,n=214)and healthy controls(control group,n=214)from January 2020 to December 2022 at the First Affiliated Hospital of Hainan Medical College and Hainan Provincial People's Hospital.The bases of eNOS gene rs3918188,rs1799983 and rs1007311 loci in each group were detected by SNaPshot sequencing technology.Logistic regression was used to analyze the correlation between genotypes,alleles and gene models(dominant model,recessive model,and overdominant model)of the above 3 target loci of the eNOS gene and genetic susceptibility to SLE.Haplotype analysis was conducted using HaploView 4.2 software to investigate the relationship between haploid and genetic susceptibility to SLE at each site.Results The results of logistic regression analysis revealed that the CC genotype and the C allele at rs3918188 locus were risk factors for genetic susceptibility to SLE(CC vs.AA:OR=2.449,P<0.05;C vs.A:OR=2.133,P<0.001).In recessive model at rs3918188 locus,CC genotype carriers had an increased risk of SLE development compared with AA+AC genotype carriers(OR=2.774,P<0.001).In contrast,in overdominant model at this locus,AC genotype carriers had a decreased risk of SLE occurrence compared with AA+CC genotype carriers(OR=0.385,P<0.001).In addition,polymorphisms of rs1799983 and rs1007311 were not associated with susceptibility to SLE in genotype,allele type and the 3 genetic models(P>0.05).Haplotype analysis revealed a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene,but no significant correlation was found between haplotype and genetic susceptibility to SLE(P>0.05).Conclusion The CC genotype and C allele at rs3918188 locus of eNOS gene may be risk factors for SLE in Hainan,while the risk of SLE occurrence is reduced in carriers of AC genotype under the overdominant model.
6.Correlation analysis of polyclonal plasma cell proportion in the bone marrow with clinical characteristics of patients with newly diagnosed multiple myeloma
Xiaolu LONG ; Xinran WANG ; Ning AN ; Songya LIU ; Zhe LI ; Chunhui LI ; Wei MU ; Di WANG ; Chunrui LI
Chinese Journal of Hematology 2024;45(5):475-480
Objective:To explore the correlation of bone marrow polychonal plasma cell proportion (pPC% ) and clinical features in newly diagnosed multiple myeloma (NDMM) patients.Methods:A retrospective analysis of 317 patients with NDMM admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2018 to January 2023 was performed. The results of the pPC% in all patients were clear. The relationship between the pPC% and clinical characteristics was analyzed.Results:A total of 317 patients were included, comprising 180 males and 137 females. The median age at diagnosis was 61 (26-91) years, and 55.8% were 60 years or older. The pPC% in the bone marrow of patients with NDMM was different in the DS, International Staging System (ISS), and revised ISS (R-ISS) stages ( P=0.002, 0.010, and 0.049, respectively), whereas no statistical difference in pPC% was observed among patients with different FISH risk stratigrams ( P=0.971). The correlation coefficient between pPC% and hemoglobin (HGB) at the first diagnosis in patients was 0.211 ( P<0.01). The correlation coefficients with serum calcium, serum creatinine, M protein level, and β 2-microglobulin were -0.141, -0.120, -0.181, and -0.207, respectively, and the results of the significance test were P=0.012, 0.033, 0.004, and 0.002, respectively, indicating a negative correlation. Compared with the patients with a pPC% of ≥2.5%, the group of patients with a pPC% of <2.5% had significantly higher levels of light chain, serum calcium, serum creatinine, M protein, and β 2-microglobulin at the initial diagnosis ( P<0.05) ; lower HGB level ( P<0.001) ; and a higher proportion of patients in ISS stage Ⅲ ( P=0.034) . Conclusion:In this study, the pPC% in patients with NDMM was associated with clinical features of good prognosis, including higher HGB, lower serum calcium, serum creatinine, M protein quantity, β 2-microglobulin, light chain involvement, lower proportion of advanced disease (DS stage and ISS stage Ⅲ), and clinical features showing lower tumor burden.
7.Anticoagulation status and adherence in patients with atrial fibrillation hospitalized for ACS and the impact on 1-year prognosis: a multicenter cohort study.
Long Yang ZHU ; Qing LI ; Lu Yao YU ; Ying LIU ; Yi Nong CHEN ; Zhe WANG ; Shi Yu ZHANG ; Jing LI ; Ying LIU ; Yu Lan ZHAO ; Yang XI ; Lin PI ; Yi Hong SUN
Chinese Journal of Cardiology 2023;51(7):731-741
Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1∶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.
Humans
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Atrial Fibrillation/drug therapy*
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Platelet Aggregation Inhibitors/adverse effects*
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Acute Coronary Syndrome/drug therapy*
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Fibrinolytic Agents/therapeutic use*
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Retrospective Studies
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Treatment Outcome
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Anticoagulants
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Myocardial Infarction/complications*
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Hemorrhage
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Percutaneous Coronary Intervention
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Ischemic Stroke/drug therapy*
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Stroke
9. 基于网络 ? ? 学探讨 ? 脾补肾活血方治疗 缺血性 ? 中的作用机
Meng-Jun LI ; Zhan-Ke QIAO ; Yong-Kang SUN ; Chun-Long RAN ; Chen BAI ; Xiang-Zhe LIU ; Xiao-Yan FANG
Chinese Pharmacological Bulletin 2022;38(4):605-612
Aim To explore the mechanism of Danshen decoction in the treatment of colon cancer using network pharmacology and molecular docking.Methods The active components and corresponding target proteins of Salvia miltiorrhiza, Santalum album and Amo-mum villosum in Danshen decoction were screened based on Traditional Chinese Medicine Systems Pharmacology database and analysis platform.The targets of colon cancer were searched by using Genecards database, and the common targets were selected.The network diagram of traditional Chinese medicine-active components-target-disease was constructed by using Cytoscape 3.7.0.The protein protein interaction network of common targets was constructed by using STRING database.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis were carried out based on R4.0.2.The important targets in the key pathways and the important active components in the network diagram of traditional Chinese medicine-active ingredients-target-disease network were selected for Surflex Dock.Results A total of 78 active components, 142 targets, 3 239 colon cancer targets, 105 overlapping targets and 69 corresponding active components were screened out.KEGG analysis showed that the key signaling pathway was PI3K/AKT.Luteolin and Tanshinone IIA with high correlation were selected to dock with protein kinase B(AKT1).Both active components had hydrogen bonding with AKT1.Conclusions Danshen decoction plays a positive role in colon cancer treatment.The mechanism may be related to the regulation of PI3K/AKT signaling pathway.
10. Exploration of potential molecular mechanism of Chuanxiong in treatment of tension-type headache based on network pharmacology and molecular docking
Chun-Long HAN ; Xin-Jie ZHAO ; Chen BAI ; Meng-Jun LI ; Wen-Hui LI ; Xiang-Zhe LIU
Chinese Pharmacological Bulletin 2022;38(1):140-147
Aim To analyze the active ingredients of Chuanxiong, predict its target and signaling pathways in the treatment of tension-type headache, and clarify its therapeutic mechanism based on the principle of network pharmacology.Methods The effective active ingredients in Chuanxiong were retrieved from the Chinese herbal system pharmacology platform(TCMSP), and were performed by the ADME screen to collect the potential targets; the existing tension-type headache-related disease targets were collected through the GeneCards database.The targets corresponding to the active ingredients were intersected to obtain the common target as the key target.Cytoscape was used to construct and analyze the visual "drug-active ingredient-target-disease" network, and the String database was used to construct the PPI protein interaction network; through R language the GO function and KEGG pathway enrichment of common targets in the form of bubble graphs were analyzed.Lastly, molecular docking was used for preliminary verification.Results Finally 7 active ingredients, 105 compound targets and 2 139 tension-type headache-related target genes were obtained.There were 54 nodes in the protein interaction network.GO functional enrichment analysis yielded 215 entries, and KEGG pathway enrichment analysis yielded 68 signaling pathways.Molecular docking showed that FA, Chuanxiong quinone, sitosterol, ligustalin had strong affinity with CASP3, MAPK1, MAPK14.Conclusions It is suggested that Chuanxiong may treat tension-type headaches through anti-inflammatory, antioxidant and cytoprotective effects.

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