Key regulators of intestinal stem cells: diet, microbiota, and microbial metabolites.

Interactions between diet and the intestinal microbiome play an important role in human health and disease development. It is well known that such interactions, whether direct or indirect, trigger a series of metabolic reactions in the body. Evidence suggests that intestinal stem cells (ISCs), which are phenotypic precursors of various intestinal epithelial cells, play a significant role in the regulation of intestinal barrier function and homeostasis. The advent and evolution of intestinal organoid culture techniques have presented a key opportunity to study the association between the intestinal microenvironment and ISCs. As a result, the effects exerted by dietary factors, intestinal microbiomes, and their metabolites on the metabolic regulation of ISCs and the potential mechanisms underlying such effects are being gradually revealed. This review summarises the effects of different dietary patterns on the behaviour and functioning of ISCs and focuses on the crosstalk between intestinal microbiota, related metabolites, and ISCs, with the aim of fully understanding the relationship between these three factors and providing further insights into the complex mechanisms associated with ISCs in the human body. Gaining an understanding of these mechanisms may lead to the development of novel dietary interventions or drugs conducive to intestinal health.

Effectiveness and safety analysis of SanHanHuaShi granules for the treatment of coronavirus disease 2019: Study protocol and statistical analysis plan for a randomized, parallel-controlled, open-label clinical trial.

Background: Coronavirus disease 2019 (COVID-19) was declared a global pandemic in March 2020 by the World Health Organization (WHO). As of July 2, 2022, COVID-19 has caused more than 545 million infections and 6.3 million deaths worldwide, posing a significant threat to human health. Currently, there is still a lack of effective prevention and control strategies for the variation and transmission of SARS-CoV-2. Traditional Chinese medicine (TCM), which has a unique theoretical system, has treated various conditions for thousands of years. Importantly, recent studies have revealed that TCM contributed significantly to COVID-19. SanHanHuaShi (SHHS) granules, a Chinese herbal medicine, which has been included in Protocol for the Diagnosis and Treatment of Novel Coronavirus Disease 2019 (6th to 9th editions) issued by the National Health Commission of China and used to prevent and treat COVID-19 disease. A previous retrospective cohort study showed that SHHS could significantly reduce the severity of mild and moderate COVID-19. However, there is an absence of high-quality randomized controlled clinical studies to confirm the clinical effectiveness of SHHS. Therefore, a clinical study protocol and a statistical analysis plan were designed to investigate the efficacy and safety of SHHS for the prevention and treatment of COVID-19. This study will increase the integrity and data transparency of the clinical research process, which is of great significance for improving the practical application of SHHS granules in the future. Methods and analysis: The study was designed as a 7-day, randomized, parallel controlled, open-label, noninferiority clinical trial of positive drugs. A total of 240 patients with mild and moderate COVID-19 will be enrolled and randomly assigned to receive SanHanHuaShi granules or LianHuaQingWen granules treatment in a 1:1 ratio. Disease classification, vital signs, SARS-CoV-2 nucleic acid testing, symptoms, medications, adverse events, and safety evaluations will be recorded at each visit. The primary outcome will be the clinical symptom recovery rate. Secondary outcomes will include the recovery time of clinical symptoms, negative conversion time of SARS-CoV-2 nucleic acid test negative conversion rate, hospitalization time, antipyretic time, rate of conversion to severe patients, and time and rate of single symptom recovery. Adverse incidents and safety assessments will be documented. All data will be analyzed using a predetermined statistical analysis plan, including our method for imputation of missing data, primary and secondary outcome analyses, and safety outcomes. Discussion: The results of this study will provide robust evidence to confirm the effectiveness and safety of SHHS in the treatment of COVID-19. Clinical Trial Registration: http://www.chictr.org.cn. Trial number: ChiCTR2200058080. Registered on 29 March 2022.

State-target strategy: a bridge for the integration of Chinese and Western Medicine.

The methods ofTraditional Chinese Medicine(TCM)'s diagnosis and treatment have undergone several changes. It is crucial to build a proper model which is capable to modernize TCM into a both standardized and individualized treatment. Tong xiao-lin proposed the state-target strategy to build a bridge for the integration of Chinese and Western medicine. It is a model based on modern medical disease concepts and using the method of TCM to balance the pathological states and adopting the achievements of pharmacology of Chinese medicine to focus on the disease targets, symptom targets, and biochemical indicator targets. The reconstruction of TCM diagnosis and treatment system for diabetes is a good example to demonstrate this theory. It could improve the clinical efficacy, support the scientific research, and reinforce the standardization of TCM.

Effect of traditional Chinese medicine on gut microbiota in adults with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: Despite advances in research on type 2 diabetes mellitus (T2DM) with the development of science and technology, the pathogenesis and treatment response of T2DM remain unclear. Recent studies have revealed a significant role of the microbiomein the development of T2DM, and studies have found that the gut microbiota may explain the therapeutic effect of traditional Chinese medicine (TCM), a primary branch of alternative and complementary medicine, in the treatment of T2DM. The aim of this study was to systematically review all randomized controlled trials (RCTs) on TCM for gut microbiota to assess the effectiveness and safety of TCM in T2DM patients. METHODS: All RCTs investigating the effects of TCM interventions on modulating gut microbiota and improving glucose metabolism in the treatment of T2DM adults were included. Meta-analyses were conducted when sufficient data were available, other results were reported narratively. The study protocol was pre-specified, documented, and published in PROSPERO (registration no. CRD42020188043). RESULTS: Five studies met the eligibility criteria ofthe systematic review. All five studies reported the effects of TCM interventions on the gut microbiota modulation and blood glucose control. There were statistically significant improvements in HbA1c (mean difference [MD]: -0.69%; [95% CI -0.24, -0.14]; p = 0.01, I2 = 86%), fasting blood glucose (MD: -0.87 mmol/l; [95% CI -1.26, -0.49]; p < 0.00001, I2 = 75%) and 2-h postprandial blood glucose(MD: -0.83mmol/l; [95% CI: -1.01, -0.65]; p < 0.00001, I2 = 0%). In addition, there were also statistically significant improvements in homeostasis model assessment of insulin resistance (HOMA-IR) (standardized mean difference [SMD]: -0.99, [95% CI -1.25 to -0.73]; p < 0.00001, I2 = 0%) and homeostasis model assessment of ß-cell function (HOMA-ß) (SMD: 0.54, [95% CI 0.21 to 0.87]; p = 0.001, I2 = 0%).There was a significant change in the relative abundance of bacteria in the genera Bacteroides (standardized mean difference [SMD] 0.87%; [95% CI 0.58, 1.16], however, the change in Enterococcus abundance was not statistically significant (SMD: -1.71%; [95% CI: -3.64, 0.23]; p = 0.08) when comparing TCM supplementaltreatment with comparator groups. Other changes in the gut microbiota, including changes in the relative abundances of some probiotics and opportunistic pathogens at various taxon levels, and changes in diversity matrices (α and ß), were significant by narrative analysis. However, insufficient evidences were found to support that TCM intervention had an effect on inflammation. CONCLUSION: TCM had the effect of modulating gut microbiota and improving glucose metabolisms in T2DM patients. Although the results of the included studies are encouraging, further well-conducted studies on TCM interventions targeting the gut microbiota are needed.

The effect of traditional Chinese medicine on gut microbiota in adults with type 2 diabetes: A protocol for systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes (T2DM), which is the major type of diabetes, accounts for more than 90% of all case of diabetes, and its pathogenesis remains inconclusive. Recent studies have revealed a significant role of gut microbiota in the onset and development of T2DM. Traditional Chinese medicine (TCM) has accumulated rich clinical experience in the treatment of T2DM for thousands of years and a large amount of studies have shown that TCM has the capacity of lowering blood glucose and modulating gut microbiota. The aim of this systematic review is to evaluate all randomized controlled trials on TCM for gut microbiota to assess the effectiveness and safety of TCM in T2DM patients. METHODS: Seven electronic databases (Web of Science, PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, and VIP Information-Chinese Scientific Journal Database) will be searched from inception to present in the English and Chinese languages. Eligible randomized controlled trials evaluating the effect of TCM in T2DM patients, compared with western medicine, placebo or no intervention will be included in the study. The primary outcomes are the glucose metabolism and gut microbiota as well as its metabolites. The second outcomes are changes in weight, and changes in inflammatory markers. Two authors will independently select studies, extract data, and assess the quality of the studies by scanning the titles, abstracts, and full texts. The meta-analysis will be conducted using Review Manager version 5.3. The results will be presented as risk ratios for dichotomous data and adverse events, and as mean differences for continuous data. RESULT: The study will provide a summary of current evidence for the treatment of T2DM from the perspective of gut microbiota by using TCM based on the outcome measures. CONCLUSION: The systematic review will evaluate the efficacy of TCM in treating T2DM from the perspective of gut microbiota, providing current evidence and laying a foundation for further work in the field. PROSPERO REGISTRATION NUMBER: CRD42020188043.

Hanshiyi Formula, a medicine for Sars-CoV2 infection in China, reduced the proportion of mild and moderate COVID-19 patients turning to severe status: A cohort study.

We formulated a traditional Chinese medicine (TCM) prescription, Hanshiyi Formula (HSYF), which was approved and promoted by the Wuhan Municipal Health Commission for treating mild and moderate coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of HSYF on the progression to severe disease in mild and moderate COVID-19 patients. We conducted a retrospective cohort study of patients with mild and moderate COVID-19 in a quarantine station in Wuchang District, Wuhan. Using the real-time Internet information collection application and Centers for Disease Control for the Wuchang District, patient data were collected through patient self-reports and follow-ups. HSYF intervention was defined as the exposure. The primary outcome was the proportion of patients who progressed to a severe disease status, and a stratification analysis was performed. Univariate and multivariate regression analyses were performed to identify influencing factors that may affect the outcome. Further, we used propensity score matching (PSM) to assess the effect of HSYF intervention on the conversion of mild and moderate to a severe disease status. Totally, 721 mild and moderate COVID-19 patients were enrolled, including 430 HSYF users (exposed group) and 291 non-users (control group). No cases in the exposed group and 19 (6.5 %, P < 0.001) cases in the control group progressed to severe disease, and the difference between the two groups (exposed group-control group) was -6.5 % [95 % confidence interval (CI): (-8.87 %, -4.13 %)]. Univariate regression analysis revealed sex (male), age, fever, cough, and fatigue as risk factors for progression to severe disease. After PSM, none of the HSYF users and 7 (4.7 %, P = 0.022) non-users transitioned to severe disease, and the difference between the two groups (exposed group-control group) was -4.7 % [95 % CI: (-8.2 %, -1.2 %)]. Multivariate regression analysis revealed that sex (male) [OR: 3.145; 95 % CI: 1.036-9.545; P = 0.043] and age (> 48 years) [odds ratio (OR): 1.044; 95 % CI: 1.001-1.088; P = 0.044] were independent risk factors for conversion to severe disease. Therefore, HSYF can significantly reduce the progression to severe disease in patients with mild and moderate COVID-19, which may effectively prevent and treat the disease. However, further larger clinical studies are required to verify our results.

Interactions Between Gut Microbiota, Host, and Herbal Medicines: A Review of New Insights Into the Pathogenesis and Treatment of Type 2 Diabetes.

Herbal medicines (HMs) are a major subset of complementary and alternative medicine. They have been employed for the efficient clinical management of type 2 diabetes mellitus (T2DM) for centuries. However, the related underlying mechanisms still remain to be elucidated. It has been found out that microbiota is implicated in the pathogenesis and treatment of T2DM. An interplay between gut microbiota and host occurs mainly at the gastrointestinal mucosal barrier. The host movements influence the composition and abundance of gut microbiota, whereas gut microbiota in turn modulate the metabolic and immunological activities of the host. Intestinal dysbiosis, endotoxin-induced metabolic inflammation, immune response disorder, bacterial components and metabolites, and decreased production of short-chain fatty acids are considered significant pathogenic mechanisms underlying T2DM. The interaction between gut microbiota and HMs during T2DM treatment has been investigated in human, animal, and in vitro studies. HMs regulate the composition of beneficial and harmful bacteria and decrease the inflammation caused by gut microbiota. Furthermore, the metabolism of gut microbiota modulates HM biotransformation. In this review, we have summarized such research findings, with the aim to improve our understanding of the pathogenesis and potential therapeutic mechanisms of HMs in T2DM and to provide new insights into specific targeted HM-based therapies and drug discovery.

Efficacy of Chinese Herbal Medicine in the Treatment of Moderate-Severe Painful Diabetic Peripheral Neuropathy: A Retrospective Study.

Painful diabetic peripheral neuropathy (pDPN) is a debilitating complication of diabetes. The aim of this retrospective study was to investigate the effectiveness of a Chinese herbal medicine regimen-the modified Huangqi Guizhi Wuwu Decoction (HGWD)-in the treatment of moderate-severe pDPN. The primary objective was to estimate the improvement in neuropathic pain severity. The secondary objective was to assess the response of common symptoms to the treatment. The change in patients' blood glucose level during the whole treatment was also evaluated. By searching through our medical records of all the diabetic patients from January 2006 to January 2012, we identified and enrolled 30 moderate and severe pDPN patients in the study, for whom the treatment of neuropathic pain by regular pharmacotherapies had failed. The modified HGWD treatment was administered orally twice a day for 6 months. The numerical rating scale (NRS) level at month 6 was 2.57 ± 2.30, significantly improved compared with the baseline level of 6.03 ± 1.83 (P < 0.05). The amelioration of 3 common symptoms, namely, limb pain, limb numbness, and insomnia, was evident, and the major response of common symptoms at month 6 including limb pain, insomnia, and limb coldness was significantly increased compared with the results at month 3 (P < 0.05). Moreover, 2-hour postprandial blood glucose (2hPG) level decreased from 10.77 ± 1.29 mmol/L at baseline to 9.66 ± 0.60 mmol/L at month 6 (P < 0.05). No serious adverse events occurred throughout the treatment period. The modified HGWD was effective in the treatment of moderate and severe pDPN and can thus be offered as a new alternative treatment option for pDPN patients who failed to respond to regular pharmaceutical therapies.

Different intervention strategies for preventing type 2 diabetes mellitus in China: A systematic review and network meta-analysis of randomized controlled trials.

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 ß-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.