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BackgroundXuebifang (XBF), a potent Chinese herbal formula, has been employed in managing diabetic peripheral neuropathy (DPN). Nevertheless, the precise mechanism of its action remains enigmatic.PurposeThe primary objective of this investigation is to employ a bioinformatics-driven approach combined with network pharmacology to comprehensively explore the therapeutic mechanism of XBF in the context of DPN.Study design and MethodsThe active chemicals and their respective targets of XBF were sourced from the TCMSP and BATMAN databases. Differentially expressed genes (DEGs) related to DPN were obtained from the GEO database. The targets associated with DPN were compiled from the OMIM, GeneCards, and DrugBank databases. The analysis of GO, KEGG pathway enrichment, as well as immuno-infiltration analysis, was conducted using the R language. The investigation focused on the distribution of therapeutic targets of XBF within human organs or cells. Subsequently, molecular docking was employed to evaluate the interactions between potential targets and active compounds of XBF concerning the treatment of DPN.ResultsThe study successfully identified a total of 122 active compounds and 272 targets associated with XBF. 5 core targets of XBF for DPN were discovered by building PPI network. According to GO and KEGG pathway enrichment analysis, the mechanisms of XBF for DPN could be related to inflammation, immune regulation, and pivotal signalling pathways such as the TNF, TLR, CLR, and NOD-like receptor signalling pathways. These findings were further supported by immune infiltration analysis and localization of immune organs and cells. Moreover, the molecular docking simulations demonstrated a strong binding affinity between the active chemicals and the carefully selected targets.ConclusionIn summary, this study proposes a novel treatment model for XBF in DPN, and it also offers a new perspective for exploring the principles of traditional Chinese medicine (TCM) in the clinical management of DPN.

Abstract Background The Gouqi-wentang formula (GQWTF) is a herbal formula used by Academician Xiao-lin Tong for the clinical treatment of T2DM. GQWTF is beneficial to qi, nourishes Yin, clears heat, and promotes fluid production, but the effective components and their mechanism of action remain unclear. Methods The main components of GQWTF were detected by LC–MS, and the multi-target mechanisms of GQWTF in T2DM were elucidated using network pharmacology analysis, including target prediction, protein–protein interaction network construction and analysis, Gene Ontology (GO) terms, Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway annotation, and other network construction. Finally, the efficacy of the GQWTF was verified using biological experiments. Results First, the “herb-channel tropism” network suggested that GQWTF focuses more on treating diseases by recuperating the liver, which is considered as an important insulin-sensitive organ. Subsequently, a total of 16 active ingredients in GQWTF were detected and screened, and their biological targets were predicted. Then, “compound-target” network was constructed, where enrichment analysis of GQWTF targets reflected its potential pharmacological activities. After T2DM-related target identification, 39 cross targets of GQWTF and T2DM were obtained, and 30 key targets highly responsible for the beneficial effect of GQWTF on T2DM were identified by PPI analysis. GO analysis of these key targets showed that many biological processes of GQWTF in treating T2DM are key in the occurrence and development of T2DM, including components related to inflammatory/immune response, insulin, and metabolism. KEGG analysis revealed the regulation of multiple signalling pathways, such as insulin resistance, PPAR signalling pathway, FoxO signalling pathway, Fc epsilon RI signalling pathway, and pathways that influence diabetes primarily by regulating metabolism as well as other T2DM directly related pathways. Furthermore, a “formula-compound-pathway-symptom” network was constructed to represent a global view of GQWTF in the treatment of T2DM. Conclusions This study explored the mechanism of action of GQWTF in T2DM by multi-component and multi-target multi pathways, which could provide a theoretical basis for the development and clinical application of GQWTF.

Abstract Background Coronavirus disease 2019 (COVID-19) is a new global public health emergency. The therapeutic benefits of Cold‒Damp Plague Formula (CDPF) against COVID-19, which was used to treat “cold‒dampness stagnation in the lung” in Trial Versions 6 and 7 of the “Diagnosis and Treatment Protocol for COVID-19”, have been demonstrated, but the effective components and their mechanism of action remain unclear. Methods In this study, a network pharmacology approach was employed, including drug-likeness evaluation, oral bioavailability prediction, protein‒protein interaction (PPI) network construction and analysis, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and virtual docking, to predict the bioactive components, potential targets, and molecular mechanism of CDPF for COVID-19 treatment. Results The active compound of herbs in CDPF and their candidate targets were obtained through database mining, and an herbs—ingredients—targets network was constructed. Subsequently, the candidate targets of the active compounds were compared to those relevant to COVID-19, to identify the potential targets of CDPF for COVID-19 treatment. Subsequently, the PPI network was constructed, which provided a basis for cluster analysis and hub gene screening. The seed targets in the most significant module were selected for further functional annotation. GO enrichment analysis identified four main areas: (1) cellular responses to external stimuli, (2) regulation of blood production and circulation, (3) free radical regulation, (4) immune regulation and anti-inflammatory effects. KEGG pathway analysis also revealed that CDPF could play pharmacological roles against COVID-19 through “multi components‒multi targets‒multi pathways” at the molecular level, mainly involving anti-viral, immune-regulatory, and anti-inflammatory pathways; consequently, a “CDPF—herbs—ingredients—targets—pathways—COVID-19” network was constructed. In hub target analysis, the top hub target IL6, and ACE2, the receptor via which SARS-CoV-2 typically enters host cells, were selected for molecular docking analyses, and revealed good binding activities. Conclusions This study revealed the active ingredients and potential molecular mechanism by which CDPF treatment is effective against COVID-19, and provides a reference basis for the wider application and further mechanistic investigations of CDPF in the fight against COVID-19.

With improved standards of living, the incidence of multiple metabolic disorders has increased year by year, especially major risk factors for cardiovascular disease such as hyperglycemia and hyperlipidemia, continues to increase. Emerging epidemiological data and clinical trials have shown the additional protective effects of some metabolic therapy drugs against cardiovascular diseases. A series of studies have found that these drugs may work by modulating the composition of gut microbiota. In this review, we provide a brief overview of the contribution of the gut microbiota to both metabolic disorders and cardiovascular diseases, as well as the response of gut microbiota to metabolic therapy drugs with cardiovascular benefits. In this manner, we link the recent advances in microbiome studies on metabolic treatment drugs with their cardiovascular protective effects, suggesting that intestinal microorganisms may play a potential role in reducing cardiovascular risk factors. We also discuss the potential of microorganism-targeted therapeutics as treatment strategies for preventing and/or treating cardiovascular disease and highlight the need to establish causal links between therapeutics for metabolic diseases, gut microbiota modulation, and cardiovascular protection.

The present study sought to examine the therapeutic effect of a novel antidiabetic monomer combination (AMC) in treating type 2 diabetes mellitus (T2DM); while also elucidating the potential functional mechanism. Male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to establish T2DM. The AMC group showed significant reduction in weight, fasting blood glucose (FBG), serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), and experienced reduced insulin resistance based on oral glucose tolerance testing (OGTT) and hyperinsulinemic-euglycemic clamp testing (“gold standard” for determining in vivo insulin sensitivity). Further, AMC restored the altered intestinal flora by increasing the abundance of the beneficial bacteria Akkermansia, and decreasing the number of harmful bacteria, including Bacteroides, Odoribacter, Prevotella 9, Alistipes, and Parabacteroides. Components of the host-microbial metabolome were also significantly changed in the AMC group compared to the HFD group, including hydroxyphenyllactic acid, palmitoleic acid, dodecanoic acid, linoleic acid, and erucic acid. Furthermore, AMC was found to inhibit inflammation and suppress signaling pathways related to insulin resistance. Lastly, spearman correlation analysis revealed relationships between altered microbial community and co-metabolite levels, co-metabolites and inflammatory cytokines. Hence, the potential mechanism responsible for AMC-mediated alleviation of insulin resistance was suggested to be involved in modulation of bacteria-cometabolism-inflammation responses.

Abstract Background Diabetic distal symmetric polyneuropathy (DSPN) is one of the most common microvascular complications of diabetes mellitus, and it has become a major public health problem worldwide because of its high and increasing prevalence, morbidity, and disability rate. The current medications for DSPN are not entirely satisfactory. Preliminary studies indicated that the Chinese herbal TangBi Formula may alleviate signs and symptoms and improve the velocity of nerve conduction in patients with DSPN. This study was designed to determine if Chinese herbal medicine used in combination with conventional treatment is more effective than conventional treatment alone. Methods/design We are conducting a multicenter, placebo-controlled, double-blind, randomized, controlled clinical trial as a means of assessing the therapeutic effects of traditional Chinese medicine (TCM) treatment. A total of 188 patients will be randomized in a 1:1 ratio to a treatment group (TangBi Formula plus mecobalamin) and a control group (placebo plus mecobalamin). The test period lasts 6 months, during which all of the patients will be given standard medical care as recommended by established guidelines. The primary outcome will be development of differences in changes in clinical symptoms and signs in patients and changes in Michigan Diabetic Neuropathy Score (MDNS) between the two groups before and after treatment. The secondary outcome will be changes in nerve conduction velocity and in single clinical signs and symptoms. Safety assessments and adverse events will also be evaluated. Discussion We postulate that patients with DSPN will benefit from therapy that includes TCM. If successful, this work will provide an evidence-based complementary therapeutic approach for treatment of DSPN. Trial registration ClinicalTrials.gov, NCT03010241 . Registered on 2 January 2017

Background: Accurate prognosis assessment is essential for surgically resected intrahepatic cholangiocarcinoma (ICC) while published prognostic tools are limited by modest performance. We therefore aimed to establish a novel model to predict survival in resected ICC based on readily-available clinical parameters using machine learning technique.Methods: A gradient boosting machine (GBM) was trained and validated to predict the likelihood of cancer-specific survival (CSS) on data from a Chinese hospital-based database using nested cross-validation, and then tested on the Surveillance, Epidemiology, and End Results (SEER) database. The performance of GBM model was compared with that of proposed prognostic score and staging system.Results: A total of 1050 ICC patients (401 from China and 649 from SEER) treated with resection were included. Seven covariates were identified and entered into the GBM model: age, tumor size, tumor number, vascular invasion, number of regional lymph node metastasis, histological grade, and type of surgery. The GBM model predicted CSS with C-Statistics ≥ 0.72 and outperformed proposed prognostic score or system across study cohorts, even in sub-cohort with missing data. Calibration plots of predicted probabilities against observed survival rates indicated excellent concordance. Decision curve analysis demonstrated that the model had high clinical utility. The GBM model was able to stratify 5-year CSS ranging from over 54% in low-risk subset to 0% in high-risk subset.Conclusions: We trained and validated a GBM model that allows a more accurate estimation of patient survival after resection compared with other prognostic indices. Such a model is readily integrated into a decision-support electronic health record system, and may improve therapeutic strategies for patients with resected ICC. [ABSTRACT FROM AUTHOR]

Background: The Gouqi-wentang formula (GQWTF) is a herbal formula used by Academician Xiao-lin Tong for the clinical treatment of T2DM. GQWTF is beneficial to qi, nourishes Yin, clears heat, and promotes fluid production, but the effective components and their mechanism of action remain unclear. Methods: The main components of GQWTF were detected by LC–MS, and the multi-target mechanisms of GQWTF in T2DM were elucidated using network pharmacology analysis, including target prediction, protein–protein interaction network construction and analysis, Gene Ontology (GO) terms, Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway annotation, and other network construction. Finally, the efficacy of the GQWTF was verified using biological experiments. Results: First, the "herb-channel tropism" network suggested that GQWTF focuses more on treating diseases by recuperating the liver, which is considered as an important insulin-sensitive organ. Subsequently, a total of 16 active ingredients in GQWTF were detected and screened, and their biological targets were predicted. Then, "compound-target" network was constructed, where enrichment analysis of GQWTF targets reflected its potential pharmacological activities. After T2DM-related target identification, 39 cross targets of GQWTF and T2DM were obtained, and 30 key targets highly responsible for the beneficial effect of GQWTF on T2DM were identified by PPI analysis. GO analysis of these key targets showed that many biological processes of GQWTF in treating T2DM are key in the occurrence and development of T2DM, including components related to inflammatory/immune response, insulin, and metabolism. KEGG analysis revealed the regulation of multiple signalling pathways, such as insulin resistance, PPAR signalling pathway, FoxO signalling pathway, Fc epsilon RI signalling pathway, and pathways that influence diabetes primarily by regulating metabolism as well as other T2DM directly related pathways. Furthermore, a "formula-compound-pathway-symptom" network was constructed to represent a global view of GQWTF in the treatment of T2DM. Conclusions: This study explored the mechanism of action of GQWTF in T2DM by multi-component and multi-target multi pathways, which could provide a theoretical basis for the development and clinical application of GQWTF. [ABSTRACT FROM AUTHOR]

With improved standards of living, the incidence of multiple metabolic disorders has increased year by year, especially major risk factors for cardiovascular disease such as hyperglycemia and hyperlipidemia, continues to increase. Emerging epidemiological data and clinical trials have shown the additional protective effects of some metabolic therapy drugs against cardiovascular diseases. A series of studies have found that these drugs may work by modulating the composition of gut microbiota. In this review, we provide a brief overview of the contribution of the gut microbiota to both metabolic disorders and cardiovascular diseases, as well as the response of gut microbiota to metabolic therapy drugs with cardiovascular benefits. In this manner, we link the recent advances in microbiome studies on metabolic treatment drugs with their cardiovascular protective effects, suggesting that intestinal microorganisms may play a potential role in reducing cardiovascular risk factors. We also discuss the potential of microorganism-targeted therapeutics as treatment strategies for preventing and/or treating cardiovascular disease and highlight the need to establish causal links between therapeutics for metabolic diseases, gut microbiota modulation, and cardiovascular protection. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) is a new global public health emergency. The therapeutic benefits of Cold‒Damp Plague Formula (CDPF) against COVID-19, which was used to treat "cold‒dampness stagnation in the lung" in Trial Versions 6 and 7 of the "Diagnosis and Treatment Protocol for COVID-19", have been demonstrated, but the effective components and their mechanism of action remain unclear. Methods: In this study, a network pharmacology approach was employed, including drug-likeness evaluation, oral bioavailability prediction, protein‒protein interaction (PPI) network construction and analysis, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and virtual docking, to predict the bioactive components, potential targets, and molecular mechanism of CDPF for COVID-19 treatment. Results: The active compound of herbs in CDPF and their candidate targets were obtained through database mining, and an herbs—ingredients—targets network was constructed. Subsequently, the candidate targets of the active compounds were compared to those relevant to COVID-19, to identify the potential targets of CDPF for COVID-19 treatment. Subsequently, the PPI network was constructed, which provided a basis for cluster analysis and hub gene screening. The seed targets in the most significant module were selected for further functional annotation. GO enrichment analysis identified four main areas: (1) cellular responses to external stimuli, (2) regulation of blood production and circulation, (3) free radical regulation, (4) immune regulation and anti-inflammatory effects. KEGG pathway analysis also revealed that CDPF could play pharmacological roles against COVID-19 through "multi components‒multi targets‒multi pathways" at the molecular level, mainly involving anti-viral, immune-regulatory, and anti-inflammatory pathways; consequently, a "CDPF—herbs—ingredients—targets—pathways—COVID-19" network was constructed. In hub target analysis, the top hub target IL6, and ACE2, the receptor via which SARS-CoV-2 typically enters host cells, were selected for molecular docking analyses, and revealed good binding activities. Conclusions: This study revealed the active ingredients and potential molecular mechanism by which CDPF treatment is effective against COVID-19, and provides a reference basis for the wider application and further mechanistic investigations of CDPF in the fight against COVID-19. [ABSTRACT FROM AUTHOR]

The present study sought to examine the therapeutic effect of a novel antidiabetic monomer combination (AMC) in treating type 2 diabetes mellitus (T2DM); while also elucidating the potential functional mechanism. Male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to establish T2DM. The AMC group showed significant reduction in weight, fasting blood glucose (FBG), serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), and experienced reduced insulin resistance based on oral glucose tolerance testing (OGTT) and hyperinsulinemic-euglycemic clamp testing ("gold standard" for determining in vivo insulin sensitivity). Further, AMC restored the altered intestinal flora by increasing the abundance of the beneficial bacteria Akkermansia , and decreasing the number of harmful bacteria, including Bacteroides , Odoribacter , Prevotella 9 , Alistipes , and Parabacteroides. Components of the host-microbial metabolome were also significantly changed in the AMC group compared to the HFD group, including hydroxyphenyllactic acid, palmitoleic acid, dodecanoic acid, linoleic acid, and erucic acid. Furthermore, AMC was found to inhibit inflammation and suppress signaling pathways related to insulin resistance. Lastly, spearman correlation analysis revealed relationships between altered microbial community and co-metabolite levels, co-metabolites and inflammatory cytokines. Hence, the potential mechanism responsible for AMC-mediated alleviation of insulin resistance was suggested to be involved in modulation of bacteria-cometabolism-inflammation responses. [ABSTRACT FROM AUTHOR]

Introduction/Aim: To assess the effectiveness and safety of Traditional Chinese patent medicines (TCPMs) for managing impaired glucose tolerance (IGT). Methods: Seven databases were searched to identify eligible trials published from incepting to May 1, 2016. Randomized controlled trials (RCTs) involving TCPM for IGT with a minimum follow-up duration of 6 months were included for analysis. Data extraction and quality assessment were performed by two reviewers independently. Data synthesis was analyzed using Review Manager 5.3 software. Subgroup analysis was carried out to assess the robustness of results of meta-analysis. Results: Eighteen trials with a total of 3172 participants met the inclusion criteria. The methodological quality of the RCTs was variable. Comparing with receiving lifestyle modification (LM) alone, TCPM plus LM was significantly better at reducing the incidence of diabetes (risk ratio [RR] 0.45; 95% confidence interval [CI] 0.36–0.57, p  < 0.00001) and normalizing the blood glucose (RR 0.72; 95% CI 0.64–0.82, p  < 0.00001). TCPM plus LM was superior in decreasing the levels of 2hPG, body mass index (BMI), fasting insulin, and 2 h insulin compared with LM alone (2hPG: mean difference [MD] −1.13; 95% CI −1.68 to −0.58, p  < 0.0001; BMI: MD −0.42; 95% CI −0.71 to −0.14, p  = 0.004; fasting insulin: MD −2.44; 95% CI −3.79 to −1.09, p  = 0.0004; and 2 h insulin: MD −8.26; 95% CI −8.47 to −8.05, p  < 0.00001). Compared with placebo plus LM, TCPM plus LM was superior in reducing diabetes (RR 0.54; 95% CI 0.42–0.69, p  < 0.00001) and normalizing blood glucose (RR 0.55; 95% CI 0.41–0.73, p  < 0.00001; the interventions were also associated with a decline in the two-hour postprandial blood glucose (2hPG) levels (MD −1.45; 95% CI −2.11 to −0.79, p  < 0.0001) and BMI levels (MD −1.12; 95% CI −2.00 to −0.24, p  < 0.0001). There were no significant differences in adverse events between two groups. Subgroup analysis found no significant difference in overall effects among all study characteristics, indicating that the overall effects were stable. Conclusions: The study indicated that TCPM combined with moderate lifestyle modification had significant effect on IGT. Further studies are needed to provide more reliable evidence. The PROSPERO registration is No. CRD42016039312. [ABSTRACT FROM AUTHOR]

Different strategies are increasingly used for early intervention in prediabetes in China, but the effects of these strategies on incident diabetes have not yet been confirmed. The aim of the present study was to assess systematically the effects of different strategies for preventing diabetes, aimed at Chinese people with prediabetes. Seven electronic databases were searched to identify eligible trials published from inception to September 20, 2016. Randomized controlled trials with a minimum follow‐up duration of 6 months were included. Standard pairwise meta‐analysis with a random‐effects model and network meta‐analysis with a frequentist framework were performed. A total of 63 studies, including 11 intervention strategies, were included. Compared with placebo, all strategies, except for lipid‐affecting drugs and sitagliptin, reduced the rate of incident diabetes with different levels of effectiveness, ranging from 0.18 (95% confidence interval [CI] 0.12, 0.27) to 0.39 (95% CI 0.20, 0.75). Ranking probability analysis indicated that metformin and β‐cell‐stimulating drugs reduced the risk of diabetes most, with probabilities of 87.4% and 81%, respectively. Ethnicity and cultural factors should be considered for diabetes prevention. Most of the included trials were of poor methodological quality, however, and the results should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Introduction: Prevention of the rapid growth in incidence of type 2 diabetes (T2DM) is a big challenge for clinicians. In China, many trials have indicated that Tianqi capsule, which contains several Chinese herbal medicines as part of a large healing system called traditional Chinese medicine, could decrease the incidence of T2DM. The review assessed the effectiveness of Tianqi capsule in prevention of T2DM. Methods: Seven electronic databases were searched to identify eligible trials published from the inception of the databases up until May 1, 2017. Randomized controlled trials (RCTs) of Tianqi capsule for impaired glucose tolerance (IGT) were included. Data extraction and quality assessment were performed according to the Cochrane review standards. A random or a fixed effect model was used to analyze outcomes which were expressed as risk ratios (RRs) or mean differences (MD), and I statistics were used to assess heterogeneity. Results: Six trials were identified that included 1027 subjects. Meta-analysis showed that subjects who received Tianqi capsule plus lifestyle modification (LM) were less likely to progress to T2DM compared to controls (RR 0.55, 95% CI 0.44-0.68). Subjects who received Tianqi capsule plus LM were more likely to have glucose return to normal compared to controls (RR 0.69; 95% CI 0.62-0.78); and they had reduced fasting plasma glucose (FBG) (MD − 0.35; 95% CI − 0.55 to − 0.16) and 2-h plasma glucose (2 h PG) (MD − 1.04; 95% CI − 1.75 to − 0.32). There was no statistical difference between the two groups for IGT stabilized incidence (RR 0.89; 95% CI 0.71-1.12). No obvious adverse events occurred. Conclusion: In patients with IGT, Tianqi capsule reduced the risk of progression to T2DM and increased the possibility of regression toward normoglycemia. As a result of the limited number of RCTs and the methodological drawbacks of the included studies, the results should be interpreted with caution. [ABSTRACT FROM AUTHOR]

In the present study, the complete mitochondrial DNA sequence of Pallas’s Leaf Warbler (Phylloscopus proregulus) was determined for the first time. The mitochondrial genome of Pallas’s Leaf Warbler is a circular molecule of 16,880 bp in size and contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 2 control regions. The base composition is 32.7% for C, 14.3% for G, 30.0% for A and 23.0% for T. These data will be useful for studying the genetic diversity within the species of Pallas’s Leaf Warbler and phylogenetic relationships among different Phylloscopidae species. [ABSTRACT FROM AUTHOR]

Incorrect author affiliation and the typo in acknowledgement section were found in the original publication. The correct author affiliations and acknowledgments are given here. [ABSTRACT FROM AUTHOR]