Efficacy and safety of Sangbaipi Decoction in patients with acute exacerbation of chronic obstructive pulmonary disease: A protocol for systematic review and meta analysis.

BACKGROUND: Chinese medicine Sangbaipi decoction is extensively applied to the therapy of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in China. However, owing to the low quality, small sample size, and methodological heterogeneity of these studies, this conclusion is not convincing. Consequently, it is necessary to systematically evaluate the clinical efficacy and safety of Sangbaipi Decoction in the treatment of AECOPD patients, and provide high-quality evidence for its clinical application. METHODS: We will follow the preferred reporting items for systematic review and meta-analysis (PRISMA) for reporting the results of the review in this study. We will utilize the Review Manage software V5.3.0 (The Nordic Cochrane Center, The Cochrane Collaboration, 2014, Copenhagen, Denmark) to assess the risk of bias and visualize the results. We will use Stata software (version 15.0, StataCorp, College Station, TX) to perform the meta-analysis. ETHICS AND DISSEMINATION: This study is a systematic review and meta-analysis protocol of Sangbaipi decoction on AECOPD, participants were not recruited and data were not collected from participants, so ethical ratification is not required. RESULTS: This study will provide high-quality synthesis of the effectiveness and safety of Sangbaipi decoction for AECOPD. Upon completion, the results will be submitted to a peer-reviewed journal. CONCLUSION: The efficacy and safety assessment of Sangbaipi decoction for AECOPD will be supported by this protocol. REGISTRATION NUMBER: PROSPERO CRD 42019138405.

A network meta-analysis: The best Yiqi Fuzheng Chinese herbal injections for use based on the NP regimen to treat NSCLC.

BACKGROUND: Chinese herbal injections (CHIs) have been proven beneficial to patients with non-small cell lung cancer (NSCLC) in combination with chemotherapy. The network meta-analysis (NMA) was designed to update and expand on previous work to better evaluate the effectiveness and safety of different Yiqi Fuzheng (YQFZ) CHIs combined with the Vinorelbine plus cisplatin (NP) regimen versus NP alone for NSCLC. METHODS: We searched multiple electronic databases and identified randomized controlled trials (RCTs) concerning different YQFZ CHIs combined with the NP regimen for treating NSCLC up to March 1st, 2019. The outcomes are the objective response rate, performance status and adverse reactions (ADRs). Two individuals accomplished the quality assessment of this NMA based on the Cochrane risk of bias tool and the methodological section of the CONSORT statement. Random effects models were generated to estimate efficacy and safety outcomes. Odds ratios and corresponding 95% confidence intervals were calculated via Stata 14 software. Furthermore, the rankings for the efficacy and safety of different YQFZ CHIs for each outcome were determined by the surface under the cumulative ranking curve (SUCRA). RESULTS: Initially, a total of 4775 citations were retrieved through comprehensive searching, and 88 eligible articles involving 6695 participants and 8 CHIs were ultimately included. The cluster analysis results of the current evidence indicated that the NP regimen combined with Delisheng, Shenfu and Shenmai injections have a higher clinical effectiveness rate and better performance status compared with the NP regimen alone. Additionally, the NP regimen combined with Shenqifuzheng, Shengmai and Shenfu injections may be considered a favorable choice for reliving ADRs among patients with NSCLC. CONCLUSIONS: The current evidence demonstrated that the combination of Shenfu injection plus NP regimen could produce better outcomes than other YQFZ CHIs groups in terms of efficacy and safety. However, meticulously designed, strictly executed, high-quality trials are still required to further assess and confirm the results due to the inadequacy of the included RCTs.

[Bioinformatic analysis of differentially expressed genes and Chinese medicine prediction for ulcerative colitis].

The aim of this paper was to analyze the microarray data between ulcerative colitis(UC) patients and healthy people by bioinformatics technology, screen the differentially expressed genes of UC, and predict the potential Chinese medicines for UC. The GSE36807 gene expression profile was downloaded from the gene expression database(GEO) and the differentially expressed(both up-regulated and down-regulated) genes(DEGs) were analyzed by using R language software. The core genes in the DEGs were obtained by using String database, Cytoscape software and its plug-in analysis, and the gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) were used to analyze the core genes. Moreover, the core genes and the medical ontology information retrieval platform(Coremine Medical) were mapped to each other to screen the traditional Chinese medicines and its active ingredients for treating UC. A total of 648 DEGs were screened, including 397 up-regulated genes and 251 down-regulated genes. Up-regulation of DEGs yielded 15 core genes including CXCL8, IL1 B, MMP9, CXCL1, CXCL10, CXCL9, CXCL2, CXCL5, TIMP1, CXCL11, STAT1,LCN2, IL1 RN, MMP1 and IDO1. Their biological processes and pathways were mainly enriched in interleukins, chemokine ligands and cytokines, chemokine-mediated signaling pathways, and were closely related to inflammatory responses, defense responses, cell chemotaxis, secretory granules, IL17 signaling pathways, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and TNF signaling pathway. Potential Chinese medicines for the treatment of UC include Curcumae Longae Rhizoma, Coptidis Rhizoma, Scutellariae Radix, Dendrobii Caulis, Sanguisorbae Radix, Phellodendri Chinensis Cortex, Bletillae Rhizoma and Atractylodis Rhizoma. The analysis of DEGs and core genes could promote our understanding on pathogenesis of UC. This study provides potential gene targets and research ideas for the development of new drugs of Chinese medicine intervention for UC.

The Prognostic Value of Autophagy-Related Markers Bclin-1 and LC-3 in Colorectal Cancers: A Systematic Review and Meta-analysis.

OBJECTIVE: At present, the relationship between autophagosomes and the prognosis of various cancers has become a subject of active investigation. A series of studies have demonstrated the correlation between autophagy microtubule-associated protein light chain 3 (LC-3), Beclin-1, and colorectal cancer (CRC). Since autophagy has dual regulatory roles in tumors, the results of this correlation are also uncertain. Hence, we summarized the relationship between Beclin-1, LC-3, and CRC using systematic reviews and meta-analysis to clarify their prognostic significance in it. METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched online up to April 1, 2019. The quality of the involving studies was assessed against the Newcastle-Ottawa Scale (NOS). Pooled hazard ratio (HR) and 95% confidence interval (CI) in a fixed or random effects model were used to assess the strength of correlation between Beclin-1, LC-3, and CRC. RESULTS: A total of 9 articles were collected, involving 2,297 patients. Most literatures scored more than 6 points, suggesting that the quality of our including research was acceptable. Our finding suggested that the expression of Beclin-1 was not associated with overall survival (HR = 0.68, 95% CI (0.31-1.52), P=0.351). Nonetheless, LC-3 expression exerted significant impact on OS (HR = 0.51, 95% CI (0.35-0.74), P < 0.05). Subgroup analysis exhibited that Beclin-1 expression was associated with OS at TNM stage III (HR = 0.04, 95% CI = 0.02-0.08, P < 0.05), surgical treatment (HR = 1.53, 95% CI (1.15-2.02), P=0.003), and comprehensive treatment (HR = 0.27 95% CI (0.08-0.92), P=0.036), respectively. Similarly, the results showed the increased LC-3 expression in CRC was related to OS in multivariate analyses (HR = 0.44, 95% CI (0.34-0.57), P < 0.05), stages (HR = 0.51, 95% CI (0.35-0.74), P < 0.05), and comprehensive treatment (HR = 0.44, 95% CI (0.34-0.57), P < 0.05). CONCLUSIONS: Autophagy-related proteins of LC-3 might be an important marker of CRC progression. However, since the number of the original studies was limited, more well-designed, large-scale, high-quality studies are warranted to provide more convincing and reliable information.

Efficacy and safety of Chuankezhi injection in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis protocol.

BACKGROUND: Chuankezhi injection (CKZ) is gaining increasing popularity for chronic obstructive pulmonary disease (COPD) treatment, yet their comparative effectiveness and safety remain unclear. Therefore, we will provide a protocol to assess the efficacy and safety of CKZ for COPD. METHODS: From now until June 2020, we will conduct a comprehensive and systematic literature search in 4 Chinese and 4 English databases, and the use of CKZ in the treatment of COPD will be included in randomized controlled trials, as well as all the treatment of stable COPD during the treatment of all CKZ. The risk assessment of the bias tool in Cochrane 5.1.0 will be combined with the quality of the trial. The 2 investigators will independently perform quality assessments and data extractions for the included studies in strict accordance with inclusion and exclusion criteria and perform the meta-analysis with Stata 15 software (version 15.0, StataCorp, College Station, TX). RESULTS: Further evidence of CKZ treatment for COPD will be provided by this study. CONCLUSION: The efficacy and safety assessment of CKZ for COPD will be supported by this protocol. PROSPERO REGISTRATION NUMBER: ROSPERO CRD 42019134133.

[Meta-analysis and trial sequential analysis of modified Sangbaipi Decoction for treating acute exacerbation of chronic obstructive pulmonary disease].

The randomized controlled trials about modified Sangbaipi Decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) patients were collected from 7 databases( PubMed,CNKI,et al) from the establishment to December 5,2018. All the studies searched were strictly evaluated. Literatures were independently screened by two researchers according to the inclusion and exclusion criteria,and the methodological quality of included studies was evaluated. To systematically review the efficacy of modified Sangbaipi Decoction in 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 25 RCTs involving 1 784 patients were included. According to the results of Meta-analysis,compared with the control groups,the trial group had a higher clinical efficacy in AECOPD patients( RR =1. 18,95%CI[1. 13,1. 22],P = 0),improved pulmonary functions including forced expiratory volume in one second( FEV1,WMD =0. 44,95%CI[0. 01,0. 87],P = 0. 046),and the forced vital capacity( FVC,WMD = 0. 42,95%CI[0. 07,0. 22],P = 0),but no statistical significance in the percentage of forced expiratory volume in one second( FEV1%,P = 0. 067) and the first seconds breathing volume percentage of forced vital capacity( FEV1/FVC,P = 0. 238); it improved the arterial oxygen partial pressure( PaO2,SMD =0. 85,95%CI[0. 41,1. 30],P = 0) and decreased the arterial partial pressure of carbon dioxide( PaCO2,SMD =-0. 94,95% CI[-1. 70,-0. 18],P= 0. 016); and in terms of inflammatory markers,it improved the white blood cell count( WBC,WMD=-0. 94,95%CI[-1. 17,-0. 70],P = 0). The trial sequential analysis showed that the studies included with the improvement of clinical efficacy had passed the conventional and TSA threshold,so as to further confirm the evidence. According to the findings,in addition to conventional Western medicine treatment,modified Sangbaipi Decoction could improve the efficiency in treating acute exacerbation patients with chronic obstructive pulmonary disease,increase PaO2,and decrease PaCO2,with a high safety but no effect on pulmonary function. However,restricted by the low quality of studies included,this conclusion shall be further verified by more high-quality clinical trials.

Chuankezhi injection for asthma: Protocol of a systematic review and meta-analysis.

BACKGROUND: Asthma is a chronic inflammatory disease characterized by recurrent attacks of breathlessness and wheezing, which often worsen at night or in the early morning and vary from person to person in severity and frequency. Chuankezhi injection (CKZ), as a new Chinese medicine, was recently found to have a good clinical effect on asthma. Whereas neither systematic nor meta-analysis of randomized controlled trials (RCTs) explain the efficacy of CKZ in treating asthma. Therefore, we provide a protocol to evaluate the efficacy and safety of CKZ for asthma. METHODS: From inception until April 2019, a systematic and comprehensive literature search will be conducted in both 4 Chinese databases and 3 English databases. RCTs will be included related to CKZ for asthma. 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 (GRADE) method to assess the certainty of the estimated evidence. Data analysis will be performed using the STATA 15.0. RESULTS: This systematic review aims to assess the effectiveness and safety of CKZ for the treatment of asthma, in order to provide evidence for the clinical practice of Chinese medicine. This protocol will be conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. The results of this meta-analysis will be submitted to a peer-reviewed journal once it is completed. CONCLUSION: The consequence of this study will furnish proof to evaluate if CKZ is effective in the treatment of asthma. PROSPERO REGISTRATION NUMBER: ROSPERO CRD42019134458.

[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.

Cloning and analysis of a ferritin subunit from turbot (Scophthalmus maximus).

Ferritin is an evolutionarily conserved protein that plays an important role in iron storage and detoxification. In this study, the gene encoding a ferritin H subunit homologue (SmFer1) was cloned from turbot (Scophthalmus maximus) and analyzed at the expression and functional levels. The open reading frame of SmFer1 is 534 bp and preceded by a 5'-untranslated region that contains a putative Iron Regulatory Element (IRE). The deduced amino acid sequence of SmFer1 shares extensive sequence identities with the H ferritins of a number of fish species and contains the ferroxidase center that is preserved in ferritin H subunits. Examination of tissue specific expression indicated that SmFer1 expression was most abundant in muscle, liver, and blood. Experimental infection with bacterial pathogens induced significant induction of SmFer1; however, the magnitudes of induction effected by Gram-negative pathogens were much higher than that induced by Gram-positive pathogen. Consistently, lipopolysaccharide (LPS) challenge drastically augmented SmFer1 expression. In addition to bacterial pathogens and LPS, poly(I:C) also induced a strong but transient induction of SmFer1 which differs in profile from those induced by bacterial pathogens. In vitro iron-chelating analysis showed that recombinant SmFer1 purified from Escherichia coli was able to bind ferrous iron in a concentration-dependent manner. To examine whether SmFer1, with its iron-chelating capacity, could have any effect on the infection of bacterial pathogens, purified recombinant SmFer1 was subjected to bacteriostatic analysis and proved to be able to inhibit the growth of the fish pathogen Listonella anguillarum which enhanced SmFer1 expression upon infection. Taken together, these results suggest that SmFer1 is likely to play a role in both iron storage and immune defense against microbial infections.