[Meta-analysis and trial sequential analysis of Tanreqing Injection in treatment of severe pneumonia in elderly].

This study aimed to systematically evaluate the effectiveness and safety of Tanreqing Injection in the treatment of severe pneumonia in the elderly. Eighteen randomized controlled trials(RCTs) involving 1 457 elderly patients with severe pneumonia were included in the study after conducting searches in both Chinese and English databases as well as clinical trial registration platforms. The quality of the included studies was assessed using the Cochrane risk of bias assessment tool. Meta-analysis were conducted using RevMan 5.4 and Stata 17 software, and trial sequential analysis(TSA) was performed using TSA 0.9.5.10 beta software. Meta-analysis results showed that compared with conventional western medicine treatment, Tanreqing Injection + conventional western medical significantly improved the clinical effectiveness in elderly patients with severe pneumonia(RR=1.26, 95%CI[1.20, 1.32], P<0.000 01), arterial oxygen partial pressure(SMD=6.23, 95%CI[3.29, 9.18], P<0.000 1), oxygenation index(SMD=11.72, 95%CI[4.41, 19.04], P=0.002), reduce procalcitonin(SMD=-6.16, 95%CI[-8.10,-4.21], P<0.000 01), C-reactive protein(SMD=-8.50, 95%CI[-11.05,-5.96], P<0.000 01), white blood cell count(SMD=-4.56, 95%CI[-5.73,-3.39], P<0.000 01), and shortened the duration of fever(SMD=-3.12, 95%CI[-4.61,-1.63], P<0.000 1), cough(SMD=-4.84, 95%CI[-6.90,-2.79], P<0.000 01), lung rales(SMD=-0.99, 95%CI[-1.54,-0.44], P=0.000 4), and mechanical ventilation time(SMD=-3.26, 95%CI[-5.03,-1.50], P=0.000 3), increase CD4~+ T-cell levels(SMD=6.73, 95%CI[5.23, 8.23], P<0.000 01) and CD8~+ T-cell levels(SMD=7.47, 95% CI[5.32, 9.61], P<0.000 01) with no significant adverse reactions. TSA confirmed the stability and reliability of the results related to clinical effectiveness. This study suggests that Tanreqing Injection, as a Chinese medicinal preparation, has a significant therapeutic effect and good safety profile in the treatment of severe pneumonia in elderly patients. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.

Efficacy and safety evaluation of Ginkgo biloba dropping pill (GBDP) on stable angina pectoris complicated with depression: A placebo-controlled, randomized, double-blind, multicenter study.

BACKGROUND: Stable angina pectoris (SAP) is a clinical condition characterized by reversible and temporary myocardial ischemia and hypoxia. A majority of SAP patients also experience depressive disorders, which adversely affect their disease prognosis and overall quality of life. However, the clinical utility of existing antidepressants is constrained by their side effects. Ginkgo biloba dropping pill (GBDP), a Chinese patented medication, has demonstrated efficacy in the treatment of both coronary heart disease and mental disorders. This prospective, randomized, double-blind, multicenter clinical trial aimed to assess the effectiveness and safety of GBDP as an adjuvant therapy for SAP complicated by depression. METHODS: Participants were randomly assigned in a 1:1 ratio to receive either GBDP or a placebo (5 pills, three times a day) in addition to standard therapy for a duration of 12 weeks. The Seattle Angina Questionnaire (SAQ) was administered every 4 weeks during the treatment, and angina event frequency was assessed weekly. The 36-item Short-Form (SF-36) and Hamilton Depression Scale (HAMD) scores were measured both before and after the treatment. RESULTS: Out of the 72 patients, 68 (n = 34 per group) completed the entire study. At the first visit (4 weeks ± 3 days), the SAQ-Angina Stability score in the GBDP group was significantly higher than that in the placebo group (p < 0.05). While the average weekly frequency of angina episodes in the placebo group notably increased after 12 weeks of treatment (p < 0.05), it displayed an improving trend in the GBDP group (p > 0.05). By the endpoint, each subcategory score of SF-36 in the GBDP group exhibited significant improvement compared to baseline (p < 0.05). The comparison of score improvement between the two groups revealed that the SF-PCS score of the GBDP group was higher than that of the placebo group (p < 0.05). HAMD scores in both groups significantly increased after treatment (p < 0.05). No discernible difference in the incidence of adverse reactions was observed between the two groups (p > 0.05). CONCLUSION: In patients with SAP complicated by depression, GBDP, when combined with standard treatment, rapidly and safely alleviates angina pectoris symptoms. It demonstrates therapeutic potential in enhancing the quality of life and alleviating depressive symptoms.

Efficacy and safety of Ginkgo biloba dropping pills in the treatment of coronary heart disease with stable angina pectoris and depression: study protocol for a randomised, placebo-controlled, parallel-group, double-blind and multicentre clinical trial.

BACKGROUND: Coronary heart disease(CHD) with stable angina pectoris is a common cardiovascular disease. It has been reported that 10%-81.4% of these patients suffer from psychological conditions,such as depression, which has been associated with more frequent angina, lower treatment satisfaction and lower perceived quality of life. Ginkgo biloba extract (GBE), the raw material of Ginkgo biloba dropping pills (GBDPs), is widely used to treat various conditions, including cardiovascular disease, ischaemic cerebrovascular disease, and depression. This clinical trial aimed to examine the efficacy and safety of GBDPs in improving the frequency of angina pectoris and the life quality of patients with stable angina pectoris and depression symptoms. METHODS: This randomised, double-blind, placebo-controlled, parallel-group and multicentre clinical trial will be conducted in four medical centres in China. We aim to recruit approximately 72 participants aged 18-75 years with depression and coronary heart disease with stable angina pectoris. Based on conventional drug treatment, participants will be randomly assignedto the treatment group (GBDPs group; n=36) or the control group (placebo group; n=36) at a 1:1 allocation ratio. After randomisation,follow-up will be done at 4 weeks, 8 weeks and 12 weeks (±3 days). Additionally, 30 healthy individuals will be enrolled to investigate the underlying pharmacological mechanisms of the effects of GBE. The primary outcomes will be the Seattle Angina Questionnaire score and the frequency of angina pectoris-related symptoms each week. The secondary outcomes will include the 36-item Short Form Health Survey quality-of-life scale, Hamilton Depression Scale and composite endpoint incidence of major adverse cardiovascular events. ETHICS AND DISSEMINATION: This trial has been approved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (approval number: ZYYECK [2020]030). Written informed consent will be obtained from all participants. The results of this trial will be publicly shared through academic conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04529148 and ChiCTR2200066908.

Identification of Molecular Markers Related to Immune Infiltration in Patients with Severe Asthma: A Comprehensive Bioinformatics Analysis Based on the Human Bronchial Epithelial Transcriptome.

Background: Severe asthma (SA), a heterogeneous inflammatory disease characterized by immune cell infiltration, is particularly difficult to treat and manage. The airway epithelium is an important tissue in regulating innate and adaptive immunity, and targeting airway epithelial cell may contribute to improving the efficacy of asthma therapy. Methods: Bioinformatics methods were utilized to identify the hub genes and signaling pathways involved in SA. Experiments were performed to determine whether these hub genes and signaling pathways were affected by the differences in immune cell infiltration. Results: The weighted gene coexpression network analysis identified 14 coexpression modules, among which the blue and salmon modules exhibited the strongest associations with SA. The blue module was mainly enriched in actomyosin structure organization and was associated with regulating stem cell pluripotency signaling pathways. The salmon module was mainly involved in cornification, skin development, and glycosphingolipid biosynthesis-lacto and neolacto series. The protein-protein interaction network and module analysis identified 11 hub genes in the key modules. The CIBERSORTx algorithm revealed statistically significant differences in CD8+ T cells (P = 0.013), T follicular helper cells (P = 0.002), resting mast cells (P = 0.004), and neutrophils (P = 0.002) between patients with SA and mild-moderate asthma patients. Pearson's correlation analysis identified 11 genes that were significantly associated with a variety of immune cells. We further predicted the utility of some potential drugs and validated our results in external datasets. Conclusion: Our results may help provide a better understanding of the relationship between the airway epithelial transcriptome and clinical data of SA. And this study will help to guide the development of SA-targeted molecular therapy.

Malignant peritoneal mesothelioma with massive ascites as the first symptom: A case report.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an extremely rare tumor with nonspecific clinical manifestations, which is extremely difficult to diagnose. Herein, we reported a case of MPM in the abdominal cavity with massive short-term ascites as the first symptom. CASE SUMMARY: A 65-year-old woman presented to the hospital with abdominal pain, distention, and shortness of breath that persisted for 15 d. The serum CA-125 level was 1075 U/mL. The abdominal computed tomography showed massive ascites and no obvious tumor lesions. The pathological examination of the ascitic fluid showed numerous heterotypic cells with some papillary structures. The immunohistochemistry and fluorescence in situ hybridization showed the deletion of CDX2 (-), WT-1 (-), Ki-67 (about 10% +), CEA (-), Glut-1 (+++), desmin (-), PD-L1 (-), and CDKN2A (P16). The final diagnosis was MPM. The patient refused tumor cytoreductive surgery and received two cycles of cisplatin plus pemetrexed bidirectional chemotherapy. In the second cycle, she received an additional cycle of hyperthermic intraperitoneal chemotherapy and immune checkpoint inhibitor therapy due to massive recalcitrant ascites. She died of disease progression 2 mo after diagnosis. CONCLUSION: In case of massive unexplained ascites, the possibility of MPM should not be excluded to avoid misdiagnosis and delay in treatment.

Insights into potential mechanisms of asthma patients with COVID-19: A study based on the gene expression profiling of bronchoalveolar lavage fluid.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a major challenge threatening the global healthcare system. Respiratory virus infection is the most common cause of asthma attacks, and thus COVID-19 may contribute to an increase in asthma exacerbations. However, the mechanisms of COVID-19/asthma comorbidity remain unclear. METHODS: The "Limma" package or "DESeq2" package was used to screen differentially expressed genes (DEGs). Alveolar lavage fluid datasets of COVID-19 and asthma were obtained from the GEO and GSV database. A series of analyses of common host factors for COVID-19 and asthma were conducted, including PPI network construction, module analysis, enrichment analysis, inference of the upstream pathway activity of host factors, tissue-specific analysis and drug candidate prediction. Finally, the key host factors were verified in the GSE152418 and GSE164805 datasets. RESULTS: 192 overlapping host factors were obtained by analyzing the intersection of asthma and COVID-19. FN1, UBA52, EEF1A1, ITGB1, XPO1, NPM1, EGR1, EIF4E, SRSF1, CCR5, PXN, IRF8 and DDX5 as host factors were tightly connected in the PPI network. Module analysis identified five modules with different biological functions and pathways. According to the degree values ranking in the PPI network, EEF1A1, EGR1, UBA52, DDX5 and IRF8 were considered as the key cohost factors for COVID-19 and asthma. The H2O2, VEGF, IL-1 and Wnt signaling pathways had the strongest activities in the upstream pathways. Tissue-specific enrichment analysis revealed the different expression levels of the five critical host factors. LY294002, wortmannin, PD98059 and heparin might have great potential to evolve into therapeutic drugs for COVID-19 and asthma comorbidity. Finally, the validation dataset confirmed that the expression of five key host factors were statistically significant among COVID-19 groups with different severity and healthy control subjects. CONCLUSIONS: This study constructed a network of common host factors between asthma and COVID-19 and predicted several drugs with therapeutic potential. Therefore, this study is likely to provide a reference for the management and treatment for COVID-19/asthma comorbidity.

Effectiveness and safety of Xinyin tablet in treatment of chronic heart failure: A protocol of systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Xinyin Tablet (XYT) has been widely used in the treatment of CHF, Which helping to improve the clinical symptoms, enhance exercise, and even may improve the long-term prognosis of patients. However, the exact effectiveness and safety of XYT for CHF has not be comprehensively researched, so we want to generalize the effectiveness and safety of XYT for CHF through the meta-analysis, which may benefit the design of future clinical trials and provide valuable references. METHODS: This protocol complies with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. From the inception until September 2020, a systematic and comprehensive electronic search about Relevant randomized controlled trials will be conducted in 4 English literature databases and 4 Chinese literature databases. The registration number: INPLASY2020100015. 2 investigators will be arranged to deal with the study selection and data extraction independently. The New York Heart Function Classification, traditional Chinese medicine (TCM) symptom scores, the scores of quality of life, 6-min walk distance (6MWD), etc. will be systematically measured as outcomes. At last, the data will be handled by Review Manager 5.3 and Stata 15.0. RESULTS AND CONCLUSION: This study is hoping to provide a high-level evidence to prove the therapeutic effect of XYT on CHF, which may enhance the application of Chinese medicine.

Efficacy and safety of high-dose Xueshuantong injection (lyophilised) in reducing the incidence of major adverse cardiovascular events in patients with unstable angina: a protocol of a randomised, parallel-arm, controlled, double-blind and multicentre clinical trial based on dual antiplatelet therapy.

INTRODUCTION: Unstable angina (UA), referred to as acute coronary syndrome (ACS), causes unexpected chest pain. Xueshuantong injection (lyophilised) (XST) is a traditional Chinese herbal injection having the potential to treat ACS. However, no clinical trial has been performed in this field. This clinical trial aims to examine the efficacy and safety of XST. METHODS AND ANALYSIS: This is a randomised, parallel-arm, controlled, double-blind and multicentre clinical trial. A total of 1200 participants with UA will be enrolled in a 1:1 ratio, with 600 patients included in the XST treatment group and 600 with 1/20th dose in the control group. The efficacy assessment and major adverse cardiovascular events will be observed, and the frequency of angina attack, angina pectoris will be examined at the start and end of the run-in period. All adverse events will be recorded, regardless of the severity, to assess the safety of XST. The baseline characteristics of patients will be summarised and compared using the t test or non-parametric statistical test. Qualitative data will be analysed using the χ2 or Fisher exact tests, Cochran-Mantel-Hasenszel test and Wilcoxon test. ETHICS AND DISSEMINATION: This trial has been approved by the Research Ethics Committee of The First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (approval number: ZYYEC [2017] 0021). Written informed consent will be obtained from all participants. The results of this trial will be disseminated to the public through academic conferences and peer-reviewed journals. TRIAL REGISTRATION: This study was registered on the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the ID ChiCTR1800015911.

Effect of nitrate treatment on functional capacity and exercise time in patients with heart failure: a systematic review and meta-analysis.

OBJECTIVES: Heart failure (HF) is a common and potentially fatal condition. In 2015, HF affected approximately 40 million people globally. Evidence showing that the use of nitrates can improve clinical outcomes in patients with HF is limited. This study aimed to assess the effect of nitrates on functional capacity and exercise time in patients with HF. METHODS: PubMed, Cochrane Library, and Embase databases were reviewed for articles on the use of nitrates and other treatments for patients with HF. The primary endpoints were the 6-minute walk test distance, exercise time, and quality of life. Secondary endpoints were all-cause mortality, arrhythmia, hospitalization, and worsening HF. The weighted mean difference, risk ratio, and 95% confidence interval were calculated. RESULTS: A total of 14 related studies that comprised 26,321 patients were included. No significant differences were found in the 6-minute walk test distance, exercise time, and quality of life between the nitrate and control treatment groups. There were also no differences in all-cause mortality, the incidence of arrhythmia, hospitalization, and worsening HF between these two groups. CONCLUSION: Patients with HF who receive nitrate treatment do not have better quality of life or exercise capacity compared with controls.

A network pharmacology strategy to investigate the anti-inflammatory mechanism of luteolin combined with in vitro transcriptomics and proteomics.

Luteolin, a natural flavonoid exists in various medicinal plants, has strong anti-inflammatory effect. However, anti-inflammatory mechanism of luteolin has not been fully explored. Hence, we systematically investigated druggability and anti-inflammatory mechanism of luteolin based on network pharmacology and in vitro experiments. The absorption, distribution, metabolism and excretion of luteolin were evaluated by TCMSP server. Targets associated with luteolin and inflammation were collected from public databases, and the overlapping targets between luteolin and inflammation were analyzed by Draw Venn diagram. Then the protein-protein interaction network of luteolin against inflammation was constructed. Further, gene function and pathway enrichment analysis were performed. Finally, in vitro experiments were carried out to estimate the accuracy of predicted target genes. ADME results indicated that luteolin has great potential to be developed into a drug. 226 overlapping targets were screened by matching 280 targets of luteolin with 9015 targets of inflammation. 9 core targets of luteolin against inflammation were identified, including MMP9, MAPK1, HSP90AA1, CASP3, ALB, EGFR, SRC, HRAS and ESR1. Gene function were mainly involved in metabolism, energy pathways and signal transduction. Metabolic pathways, pathways in cancer, PI3K-AKT signaling pathway, Ras signaling pathway and so on might be the critical pathways of luteolin against inflammation. RT-qPCR and ELISA results indicated that luteolin decreased the expression of most of core genes at protein and mRNA levels (MMP9, MAPK1, HSP90AA1, EGFR, SRC and HRAS). Luteolin is expounded to have great potential to be developed into a drug and target various genes and pathways to perform anti-inflammatory effect.

[Systematically review of modified Sanzi Yangqin Decoction for treating acute exacerbation of chronic obstructive pulmonary disease].

The randomized controlled trials( RCTs) about modified Sanzi Yangqin Decoction in the treatment of patients with exacerbation of chronic obstructive pulmonary disease( AECOPD) were collected from 7 databases( PubMed,CNKI,etc.) till December25,2018 from their inception. All the studies searched were strictly evaluated and independently screened by two researchers according to the inclusion and exclusion criteria,and the methodological quality of included studies was evaluated. In order to systematically review the efficacy and safety of modified Sanzi Yangqin Decoction for treating AECOPD,the Meta-analysis and trial sequential analysis were conducted by using Stata/SE 14. 0 and TSA 0. 9. 5. 10 Beta,respectively. A total of 22 RCTs involving 2 012 patients were included. The results of Meta-analysis suggested that: as compared with the control group,the clinical symptoms in AECOPD patients were improved( RR = 1. 19,95%CI[1. 15,1. 24],P = 0); the pulmonary functions including forced expiratory volume in one second( FEV_1)( SMD= 0. 96,95%CI[0. 39,1. 52],P= 0. 001),the percentage of forced expiratory volume in one second( FEV_1%)( SMD =0. 80,95%CI[0. 20,1. 41],P = 0. 009),forced vital capacity( FVC)( SMD = 0. 69,95% CI[0. 06,1. 31],P = 0. 032),first seconds breathing volume percentage of forced vital capacity( FEV_1/FVC) were improved( SMD = 0. 81,95%CI[0. 64,0. 97],P = 0);the arterial oxygen partial pressure( PaO_2) was improved( SMD= 0. 87,95%CI[0. 41,1. 32],P= 0); the arterial partial pressure of carbon dioxide( PaCO_2) was decreased( SMD =-0. 91,95%CI[-1. 33,-0. 49],P = 0) in the trial group. In addition,the incidence of adverse reactions in the experimental group was low,and there were no serious adverse events. The trial sequential analysis( TSA) showed that the studies included in the improvement of clinical efficacy had passed the conventional and TSA threshold at the same time,further confirming the efficacy of trial group. This research showed that,conventional Western medicine treatment,combined with modified Sanzi Yangqin Decoction in treating acute exacerbation patients with chronic obstructive pulmonary disease could improve the clinical efficiency and pulmonary functions,improve the PaO_2,decrease the PaCO_2,with a high safety. However,the quality of existing research is low,requiring more high quality clinical trials for further validation.

Traditional Chinese exercise (TCE) on pulmonary rehabilitation in patients with stable chronic obstructive pulmonary disease: Protocol for a systematic review and network meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has the characteristics of high incidence, mortality, disability rate, and heavy economic burden. Symptomatic measures such as anti-inflammatory, antispasmodic and anti-asthmatic are widely used in the treatment of COPD, and pulmonary rehabilitation has not been fully utilized. It is reported that up to 10 different kinds of Traditional Chinese exercises (TCEs) are often used for treating stable COPD. There are many randomized controlled trials (RCTs) and systematic reviews that have evaluated the efficacy of various TCEs for COPD. However, most of these studies were designed in comparison with conventional western medicine or health education. There are rarely studies to compare different TCEs head to head. Therefore, there remains uncertainty regarding the comparative efficacy among different TCEs. Thus, we plan to conduct a systematic review and Network meta-analysis (NMA) to compare the efficacy among 5 different TCEs and rank their benefits relative to each other. It is hoped that the findings of this study will facilitate the management and application of TCEs in the treatment of COPD. METHODS: A systematic and comprehensive literature search will be performed from inception to April 2019 in both English and Chinese databases, involving Medline, Cochrane Library, Embase, China National Knowledge Infrastructure Database, Wanfang Database, China Biomedical Literature Database, and Chongqing VIP information. RCTs related to TCE in the treatment of COPD will be included. Quality of included trials will be assessed according to the risk of bias tool of Cochrane Handbook 5.1.0. The GRADE approach will be used to rate the certainty of the evidence of estimates derived from NMA. Data analysis will be conducted by using STATA 14.0. RESULTS: This systematic review and NMA aims to summarize the direct and indirect evidence for different kinds of TCEs and to rank these TCEs. The findings of this NMA will be reported according to the PRISMA-NMA statement. The results of the NMA will be submitted to a peer-reviewed journal once completed. CONCLUSION: Using NMA, this study will provide an evidence profile which will be helpful to inform the selection of TCE for treating patients with COPD. The results will inform clinicians, bridge the evidence gaps, and identify promising TCE for future trials. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42019132970.

Thirteen kinds of Chinese medicine injections for acute exacerbation of chronic obstructive pulmonary disease: Protocol for a systematic review and network meta-analysis.

BACKGROUND: Chinese medicine injections (CMIs) are extensively applied to the therapy of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in mainland China. Up to 13 different kinds of CMIs are reportedly often used for treating chronic obstructive pulmonary disease, yet, rarely head to head comparison of tests are used to decide the relative consequent among the distinct CMIs. Network meta-analysis (NMA) will be performed to further compare the effects of 13 different CMI, including direct and indirect comparisons of different CMI. METHODS: From now until April 2019, a systematic and comprehensive literature search will be conducted in both English and Chinese databases, including Medline, Embase, Cochrane library, Chongqing VIP information, Wanfang Database, China national knowledge infrastructure database, and Sino Med. Randomized controlled trials will be included related to CMI therapy for AECOPD. We will assess the quality of the included trials in accordance with the risk of bias tools in Cochrane manual 5.1.0. We will use the grading of recommendations assessment development, and evaluation method to assess the certainty of the estimated evidence from the NMA. STATA 14.0 will be used for data analysis. RESULTS: The purpose of this systematic evaluation and NMA was to summarize and rank the direct and indirect evidence for 8 different types of CMI. The NMA's findings will be reported in accordance with preferred reporting items for systematic reviews and meta analyses-NMA statement. Upon completion, NMA results will be submitted to a peer-reviewed journal. CONCLUSION: With NMA, this study will provide evidence for the selection of CMI for patients with AECOPD. The results will provide information to clinicians, bridge the evidence gap and identify promising CMI targets for future trials. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42019132955.