Common Pathophysiological Mechanisms and Treatment of Diabetic Gastroparesis.

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus, marked by gastrointestinal motility disorder, a delayed gastric emptying present in the absence of mechanical obstruction. Clinical manifestations include postprandial fullness and epigastric discomfort, bloating, nausea, and vomiting. DGP may significantly affect the quality of life and productivity of patients. Research on the relationship between gastrointestinal dynamics and DGP has received much attention because of the increasing prevalence of DGP. Gastrointestinal motility disorders are closely related to a variety of factors including the absence and destruction of interstitial cells of Cajal, abnormalities in the neuro-endocrine system and hormone levels. Therefore, this study will review recent literature on the mechanisms of DGP and gastrointestinal motility disorders as well as the development of prokinetic treatment of gastrointestinal motility disorders in order to give future research directions and identify treatment strategies for DGP.

Probiotic Fermentation of Herbal Medicine: Progress, Challenges, and Opportunities.

Fermentation is a processing method used in traditional Chinese medicine (TCM). However, traditional fermentation methods suffer from poor production control. In contrast, probiotic fermented herbal medicine (PFHM) offers advantages such as the use of pure strains, a controllable process, and the ability to produce a variety of active enzymes during fermentation. As a result, PFHM has become a research hotspot. This review focuses on the progress, challenges, and opportunities in the research of PFHM. The use of probiotic enzymes during fermentation alters the active ingredients of TCM, resulting in positive pharmacological effects such as increased active ingredients, reduced toxicity, new pharmacological effects, and the reuse of herbal residues. PFHM has the potential to transfer the metabolic transformation of the effective components of TCM by intestinal flora outside the body during production and preparation, which has a broad application prospect. However, due to the complexity of the chemical composition of TCM, the mechanism of PFHM requires further investigation. Finally, we discuss the prospects of industrializing PFHM, which is essential for promoting the innovation and modernization of TCM.

Evidence and Potential Mechanisms of Traditional Chinese Medicine for the Adjuvant Treatment of Coronary Heart Disease in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Traditional Chinese medicine (TCM) has long been used to treat diabetes mellitus and angina. It has also gained widespread clinical applications in China as a common adjuvant treatment. Although there is high-quality evidence that TCM is effective in regulating glucose and lipid metabolism, the cardiovascular protective effect of TCM in the treatment of diabetes mellitus has not been fully elucidated, especially in patients with both diabetes mellitus and coronary heart disease (CHD). We systematically assessed the efficacy and safety of TCM for the adjuvant treatment of patients with CHD and diabetes mellitus and examined the pharmacological effects and potential mechanisms of TCM medication/herbs on diabetes mellitus with CHD. We found that TCM could improve the control effect of conventional treatment on cardiac function, hemorheology, blood glucose, blood lipid, and inflammation, thus reducing the frequency of angina and the incidence of cardiovascular events and all-cause mortality. These findings indicate that TCM may be used as a complementary approach for patients with diabetes mellitus and CHD. Nevertheless, more rigorously designed randomized controlled trials and long-term evaluations are needed to support these findings.

Treatment of COVID-19 in Hemodialysis Patients Using Traditional Chinese Medicine: A Single-Center, Retrospective Study.

Background: To explore the effect of combining traditional Chinese medicine (TCM) and Western medicine in hemodialysis patients with coronavirus disease 2019 (COVID-19). Methods: This study was conducted from 27 January 2020 to 17 March 2020 in Wuhan Third Hospital Guanggu Branch, Wuhan, China. Fifty-three patients were included and divided into a control group (CG), which received Western medicine and a combined treatment group, which received TCM and Western medicine (TG). Clinical and laboratory data, TCM symptom scores, and chest computed tomography results were extracted and compared between the two groups. Results: The TG included 21 (67.7%) men and 10 (32.3%) women with a mean age of 61.02 (standard deviation [SD] 15.07, range 26-89) years. The mean dialysis duration in the TG was 49 (SD 31) months. Of all patients in the TG, 27 (87.1%) had fatigue, 18 (58.1%) had dry cough, 16 (51.6%) had anorexia, 11 (35.5%) had dyspnea, and 11 (35.5%) had fever. The CG included 14 (63.6%) men and 8 (36.4%) women with a mean age of 61.45 (SD 13.78, range 36-84) years. The mean dialysis duration in the CG was 63 (SD 46) months. Of all patients in the CG, 21 (95.5%) had fatigue, 12 (54.5%) had dry cough, 17 (77.3%) had anorexia, 12 (54.5%) had dyspnea, and 7 (31.8%) had fever. After treatment, the TCM symptom scores of the two groups decreased; the anorexia scores were lower in the TG than in the CG (p < 0.05). After treatment, albumin increased and D-dimer, C-reactive protein, and lactate dehydrogenase levels decreased in the TG. The d-dimer levels were lower and the albumin level was higher in the TG than in the CG after treatment (p < 0.05). The cure rate was higher, and the mortality rate was lower in the TG than in the CG (p < 0.05). Conclusion: A combination of TCM and Western medicine in hemodialysis patients with COVID-19 could relieve symptoms and help recovery. Further evidence from larger randomized controlled trials is needed to confirm our results.

Shumian capsule improves symptoms of sleep mood disorder in convalescent patients of Corona Virus Disease 2019.

OBJECTIVE: To evaluate the clinical effectiveness of Shumian capsule in improving the symptoms of insomnia, anxiety, depression, and other symptoms of convalescent patients of COVID-19. METHODS: Totally 200 patients were collected and randomly divided into experiment group (n = 100) and control group (n = 100). The control group was treated with Shumian capsule simulator, and the experiment group was treated with Shumian capsule. The improvement of TCM symptom score, the total effective rate and symptom disappearance rate of TCM symptoms in the two groups before and after treatment were observed, and the clinical effect was evaluated. RESULTS: One week after treatment, the scores of anxiety symptoms in the experiment group were significantly different from those in the control group (P < 0.05), but there was no significant difference in the scores of insomnia and depression between the experiment group and the control group (P > 0.05). There was no significant difference in the total effective rate and disappearance rate of TCM symptoms of insomnia, anxiety and depression between the experiment group and the control group (P > 0.05). After 2 weeks of treatment, the scores of insomnia, anxiety, depression and the total effective rate of TCM symptoms in the experiment group were significantly different from those in the control group (P < 0.05). There was no significant difference in the disappearance rate of insomnia, anxiety and depression between the experiment group and the control group (P > 0.05). There were no significant differences in heart rate, respiration, systolic blood pressure and diastolic blood pressure between the experiment group and the control group (P > 0.05). CONCLUSION: Shumian capsule can significantly improve the symptoms of insomnia, anxiety and depression in COVID-19's convalescent patients with sleep and mood disorders.

Mechanism exploration of Gouqi-wentang formula against type 2 diabetes mellitus by phytochemistry and network pharmacology-based analysis and biological validation.

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.

Traditional Chinese Medicine Decoctions Significantly Reduce the Mortality in Severe and Critically Ill Patients with COVID-19: A Retrospective Cohort Study.

Coronavirus disease (COVID-19) is a new infectious disease associated with high mortality, and traditional Chinese medicine decoctions (TCMDs) have been widely used for the treatment of patients with COVID-19 in China; however, the impact of these decoctions on severe and critical COVID-19-related mortality has not been evaluated. Therefore, we aimed to address this gap. In this retrospective cohort study, we included inpatients diagnosed with severe/critical COVID-19 at the Tongren Hospital of Wuhan University and grouped them depending on the recipience of TCMDs (TCMD and non-TCMD groups). We conducted a propensity score-matched analysis to adjust the imbalanced variables and treatments and used logistic regression methods to explore the risk factors associated with in-hospital death. Among 282 patients with COVID-19 who were discharged or died, 186 patients (66.0%) received TCMD treatment (TCMD cohort) and 96 (34.0%) did not (non-TCMD cohort). After propensity score matching at a 1:1 ratio, 94 TCMD users were matched to 94 non-users, and there were no significant differences in baseline clinical variables between the two groups of patients. The all-cause mortality was significantly lower in the TCMD group than in the non-TCMD group, and this trend remained valid even after matching (21.3% [20/94] vs. 39.4% [37/94]). Multivariable logistic regression model showed that disease severity (odds ratio: 0.010; 95% CI: 0.003, 0.037; [Formula: see text]¡ 0.001) was associated with increased odds of death and that TCMD treatment significantly decreased the odds of in-hospital death (odds ratio: 0.115; 95% CI: 0.035, 0.383; [Formula: see text]¡ 0.001), which was related to the duration of TCMD treatment. Our findings show that TCMD treatment may reduce the mortality in patients with severe/critical COVID-19.

Serological investigation of asymptomatic cases of SARS-CoV-2 infection reveals weak and declining antibody responses.

Without an effective vaccine against SARS-CoV-2, the build-up of herd immunity through natural infection has been suggested as a means to control COVID-19. Although population immunity is typically estimated by the serological investigation of recovered patients, humoral immunity in asymptomatic subjects has not been well studied, although they represent a large proportion of all SARS-CoV-2 infection cases. In this study, we conducted a serosurvey of asymptomatic infections among food workers and performed serological and cellular response analyses of asymptomatic subjects in Wuhan, the original epicenter of the COVID-19 outbreak. Our data showed that up to 5.91% of the food workers carried SARS-CoV-2 IgG antibodies asymptomatically; however, in 90.4% of them, the antibody level declined over a 2-week period. IgM and IgG antibodies, including neutralizing antibodies, were significantly lower in asymptomatic subjects than in recovered symptomatic patients with similar disease courses. Furthermore, the asymptomatic subjects showed lymphopenia and a prominent decrease in the B-cell population, as well as a low frequency of antibody-secreting cells and a low cytokine response. These factors probably contributed to the low and unsustained antibody levels in asymptomatic subjects. Our results show that asymptomatic subjects are likely to be vulnerable to SARS-CoV-2 reinfection, and neither the proportion of population immunity nor the breadth of immune responses is sufficient for herd immunity.

Therapeutic mechanisms of traditional Chinese medicine to improve metabolic diseases via the gut microbiota.

Metabolic diseases such as obesity, type 2 diabetes mellitus, and hyperlipidemia are associated with the dysfunction of gut microbiota. Traditional Chinese medicines (TCMs) have shown considerable effects in the treatment of metabolic disorders by regulating the gut microbiota. However, the underlying mechanisms are unclear. Studies have shown that TCMs significantly affect glucose and lipid metabolism by modulating the gut microbiota, particularly mucin-degrading bacteria, bacteria with anti-inflammatory properties, lipopolysaccharide- and short-chain fatty acid (SCFA)-producing bacteria, and bacteria with bile-salt hydrolase activity. In this review, we explored potential mechanisms by which TCM improved metabolic disorders via regulating gut microbiota composition and functional structure. In particular, we focused on the protection of the intestinal barrier function, modulation of metabolic endotoxemia and inflammatory responses, regulation of the effects of SCFAs, modulation of the gut-brain axis, and regulation of bile acid metabolism and tryptophan metabolism as therapeutic mechanisms of TCMs in metabolic diseases.

Luo Tong Formula Alleviates Diabetic Retinopathy in Rats Through Micro-200b Target.

Aim: Diabetic retinopathy (DR) is a serious complication of diabetes (DM). Luo Tong formula (LTF) exerts protective effects against DR in rats, but its underlying mechanism remains unknown. Methods: Sprague-Dawley rats injected with streptozotocin (STZ) were used as an experimental diabetes model. LTF or calcium dobesilate (CaD) was administered to diabetic rats via gastric gavage. After the 12 weeks of treatment, blood and tissue samples were collected to determine serum glucose and retinal structure. Blood samples were collected for blood glucose and hemorheology analysis. Gene or protein expression levels were evaluated by immunohistochemistry, western blotting and/or quantitative real-time polymerase chain reaction (PCR). Results: DM rats exhibits significantly increased blood retinal-barrier (BRB) breakdown and VEGF/VEGFR expression in the retina, and decreased miR-200b and tight junction ZO-1/Occludin/ Claudin-5 genes expression, as well as Ang-1/Tie-2 expressions in the retina compared to normal control group. LTF treatment significantly moderated histological abnormalities in diabetic rats, independent of blood glucose level; improved some hemorrheological parameters; decreased the expressions of VEGF/VEGFR and BRB breakdown, significantly increased PEDF and tight junction proteins ZO-1/Occludin, as well as increased retinal miR-200b expression compared to non-treatment diabetic rats. Moreover, LTF prevented the reduction in Ang-1/Tie-2 expression. Conclusions: LTF treatment ameliorated DR through its repair vascular and attenuate vascular leakage. A mechanism involving miR-200b may contribute to benefit effects.

Interactions Between Therapeutics for Metabolic Disease, Cardiovascular Risk Factors, and Gut Microbiota.

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.

Potential mechanism prediction of Cold-Damp Plague Formula against COVID-19 via network pharmacology analysis and molecular docking.

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.

A Novel Antidiabetic Monomers Combination Alleviates Insulin Resistance Through Bacteria-Cometabolism-Inflammation Responses.

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.

Traditional chinese medicine for diabetic retinopathy: A systematic review and meta-analysis.

BACKGROUND: Traditional Chinese medicine (TCM) has been used to treat diabetic complications including diabetic retinopathy for many years. OBJECTIVES: This review was performed to systematically assess the efficacy and safety of TCM for treating non- proliferative diabetic retinopathy (NPDR). METHODS: Retrieval from 7 electronic databases was conducted to determine eligible trials published until March 1, 2018. Randomized controlled trials of NPDR that comparing compound Chinese medicine containing the therapeutic method of activating blood and remove stasis versus controls were included for analysis. Primary outcomes were progression of retinopathy. Secondary outcomes included visual acuity, mean defect of visual field, micro-aneurysms, hemorrhage areas, exudates, capillary nonperfusion areas, hemorheological indicators, oscillatory potentials (Ops), glycated haemoglobin (HbA1c), and adverse events. Data extraction and quality assessment were performed. Results expressing as risk ratios (RRs) or mean differences (MD) were analyzed with a fixed- or random- effect model. I statistics were used to assess heterogeneity. RESULTS: A total of 33 trials and 3373 participants were included. Findings revealed that no included studies reported the progression of retinopathy. Compared with conventional medicine, TCM was significantly better at improving visual acuity (MD, -0.10; 95% confidence interval [CI] -0.16 to -0.05) and Ops (MD, -4.68, 95% CI -8.51 to -0.85), and reducing the mean defect of visual field (MD, -1.43; 95%CI, -2.17 to -0.68), micro-aneurysms (MD, -4.51; 95% CI, -6.23 to -2.79), hemorrhage areas (MD, -0.62; 95% CI, -1.06 to -0.19), plasma viscosity (MD, -0.10; 95% CI, -0.20 to 0.00), and HbA1c (MD, -0.22; 95% CI, -0.42 to -0.03). Compared with placebo, TCM was also associated with a decline in the number of microaneurysms (MD, -4.35; 95% CI, -6.25 to -2.45), exudates (MD, -0.17; 95% CI -0.31 to -0.03), capillary nonperfusion areas (MD, -0.18; 95% CI, -0.31 to -0.04), and HbA1c (MD, -0.88; 95% CI, -1.44 to -0.32). Compared with blank groups, TCM was superior at decreasing the mean defect of visual field (MD, -0.87; 95% CI -0.95 to -0.79) and the numbers of micro-aneurysms (MD, -3.35; 95% CI, -4.73 to -1.97). Adverse events were also assessed. CONCLUSION: Activating blood compound Chinese herbal medicine could help to improve visual acuity, micro-aneurysms and HbA1c. Further trials are needed to provide more reliable evidence.

Luo Tong formula attenuates retinal inflammation in diabetic rats via inhibition of the p38MAPK/NF-κB pathway.

BACKGROUND: Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and remains the leading cause of blindness in adults. Retinal inflammation is playing a crucial role in the development of DR, and targeting inflammatory mediators is a promising strategy for controlling DR. Here, we investigated compound Chinese medicine Luo Tong formula (LTF) alleviated retinal inflammatory responses in a STZ-induced diabetic rat model. METHODS: Sprague-Dawley rats were divided into four groups: control, streptozotocin-induced diabetic, LTF-treated diabetic, and calcium dobesilate (CaD)-treated diabetic rats. Blood samples were collected for blood glucose examination. Hematoxylin-eosin and periodic acid-Schiff staining were conducted for light microscopy observations. Retinal cell apoptosis was detected using the TUNEL assay. Proteins expression was quantified by Western blotting and/or immunohistochemistry, and gene expression was assessed by real-time PCR. RESULTS: Diabetic rats showed significant increases in the expression of tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), nuclear factor-κB (NF-κB), and the phospho-p38 mitogen-activated protein kinase (p-p38-MAPK)/p38 MAPK ratio compared to control rats. LTF treatment significantly improved both retinal and pancreatic pathological injury, LTF treatment also inhibited inducible the p-p38 MAPK/p38 MAPK ratio and NF-κB activation and decreased the subsequent induction of the retinal expression of proinflammatory mediators TNF-α, IL-1ß, MCP-1 and ICAM-1 compared to diabetic rats. LTF also exhibited a protective effect on islet function. CONCLUSIONS: LTF before the onset of DR can alleviate retinal pathological injury, LTF may play an anti-inflammatory role by inhibiting p38-MAPK and then inhibiting NF-κB pathway. But further studies are needed to confirm this conclusion.Trial registration This is an animal experiment, trial registration is not necessary.

Chinese herbal medicine Tangshen Formula treatment for type 2 diabetic kidney disease in the early stage: study protocol for a randomized controlled trial.

BACKGROUND: Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease and has become a heavy economic and social burden due to its high prevalence and morbidity. The most effective strategy is that patients with DKD should be diagnosed and treated early. Preliminary studies showed that the Chinese herbal Tangshen Formula (TSF) may delay the progression of DKD, reducing microalbuminuria and macroalbuminuria and improving renal function. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of TSF in patients with DKD. METHODS/DESIGN: This trial is a 13-center, randomized, double-blind, placebo-controlled study. A total of 632 participants will be randomized in a 1:1 ratio to an experiment group (TSF plus losartan) and a control group (placebo plus losartan). The trial cycle will last 24 weeks. The primary outcome will be the change in the urine microalbumin-creatinine ratio from baseline to week 24. The secondary outcome will be the change in the rate of progression to the clinical proteinuria period after intervention, the rate of urine microalbumin negative conversion, the rate of normal urinary microalbumin, the doubling rate of the baseline creatinine value and the glomerular filtration rate between the two groups. Safety in medication will also be evaluated. DISCUSSION: We hypothesize that patients with type 2 diabetes in the early stage of DKD will benefit from TSF. If successful, this study will provide evidence-based recommendations for clinicians. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03009864. Registered January 2017.

Innate Lymphoid Cells: A Link between the Nervous System and Microbiota in Intestinal Networks.

Innate lymphoid cells (ILCs) are a novel family of innate immune cells that act as key coordinators of intestinal mucosal surface immune defense and are essential for maintaining intestinal homeostasis and barrier integrity by responding to locally produced effector cytokines or direct recognition of exogenous or endogenous danger patterns. ILCs are also involved in the pathogenesis of inflammatory bowel disease (IBD). Many studies have demonstrated the occurrence of crosstalk between ILCs and intestinal microbiota, and ILCs have recently been shown to be connected to the enteric nervous system (ENS). Thus, ILCs may act as a key link between the nervous system and microbiota in intestinal networks. In this review, we briefly summarize the role of the ILCs in the intestinal tract (particularly in the context of IBD) and discuss the relationship between ILCs and the microbiota/ENS.

Utilizing network pharmacology to explore the underlying mechanism of Radix Salviae in diabetic retinopathy.

INTRODUCTION: Radix Salviae (Dan-shen in pinyin), a classic Chinese herb, has been extensively used to treat diabetic retinopathy in clinical practice in China for many years. However, the pharmacological mechanisms of Radix Salviae remain vague. The aim of this study was to decrypt the underlying mechanisms of Radix Salviae in the treatment of diabetic retinopathy using a systems pharmacology approach. METHODS: A network pharmacology-based strategy was proposed to elucidate the underlying multi-component, multi-target, and multi-pathway mode of action of Radix Salviae against diabetic retinopathy. First, we collected putative targets of Radix Salviae based on the Traditional Chinese Medicine System Pharmacology database and a network of the interactions among the putative targets of Radix Salviae and known therapeutic targets of diabetic retinopathy was built. Then, two topological parameters, "degree" and "closeness certainty" were calculated to identify the major targets in the network. Furthermore, the major hubs were imported to the Database for Annotation, Visualization and Integrated Discovery to perform a pathway enrichment analysis. RESULTS: A total of 130 nodes, including 18 putative targets of Radix Salviae, were observed to be major hubs in terms of topological importance. The results of pathway enrichment analysis indicated that putative targets of Radix Salviae mostly participated in various pathways associated with angiogenesis, protein metabolism, inflammatory response, apoptosis, and cell proliferation. The putative targets of Radix Salviae (vascular endothelial growth factor, matrix metalloproteinases, plasminogen, insulin-like growth factor-1, and cyclooxygenase-2) were recognized as active factors involved in the main biological functions of treatment, which implied that these were involved in the underlying mechanisms of Radix Salviae on diabetic retinopathy. CONCLUSIONS: Radix Salviae could alleviate diabetic retinopathy via the molecular mechanisms predicted by network pharmacology. This research demonstrates that the network pharmacology approach can be an effective tool to reveal the mechanisms of traditional Chinese medicine from a holistic perspective.

Traditional Chinese Patent Medicine for Treating Impaired Glucose Tolerance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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.

Chinese herbal medicine Shenzhuo Formula treatment in patients with macroalbuminuria secondary to diabetic kidney disease: study protocol for a randomized controlled trial.

BACKGROUND: Diabetic kidney disease (DKD) is a serious complication associated with diabetes mellitus and can cause end-stage renal disease (ESRD). Traditional Chinese medicine (TCM) is widely used in China to treat DKD, and in particular microalbuminuria and macroalbuminuria. This study will address the efficacy and safety of Shenzhuo Formula (SZF), a frequently prescribed TCM, in DKD patients with macroalbuminuria. METHODS/DESIGN: This study is a 24-week, randomized, multi-center, double-blinded, double-dummy, controlled, clinical trial that will include 120 DKD patients aged 18 to 80 years old with a 24-h urinary protein (24-h UP) level of between 0.5 g and 3 g and serum creatinine (SCr) ≤ 133 µmol/L (1.5 mg/dL) and compare SZF to irbesartan. The 24-h UP change from baseline to week 24 will represent the primary endpoint with secondary endpoints including SCr, estimated glomerular filtration rate (eGFR), TCM symptoms, urinary albumin excretion rate (UAER), etc. Safety assessments will also be evaluated. DISCUSSION: This study will provide initial evidence regarding the efficacy and safety of SZF relative to irbesartan in the treatment of DKD patients with macroalbuminuria. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-ICR-15006311 . Registered on 15 April 2015.