Unveiling the causal link between metabolic factors and ovarian cancer risk using Mendelian randomization analysis.

Background: Metabolic abnormalities are closely tied to the development of ovarian cancer (OC), yet the relationship between anthropometric indicators as risk indicators for metabolic abnormalities and OC lacks consistency. Method: The Mendelian randomization (MR) approach is a widely used methodology for determining causal relationships. Our study employed summary statistics from the genome-wide association studies (GWAS), and we used inverse variance weighting (IVW) together with MR-Egger and weighted median (WM) supplementary analyses to assess causal relationships between exposure and outcome. Furthermore, additional sensitivity studies, such as leave-one-out analyses and MR-PRESSO were used to assess the stability of the associations. Result: The IVW findings demonstrated a causal associations between 10 metabolic factors and an increased risk of OC. Including "Basal metabolic rate" (OR= 1.24, P= 6.86×10-4); "Body fat percentage" (OR= 1.22, P= 8.20×10-3); "Hip circumference" (OR= 1.20, P= 5.92×10-4); "Trunk fat mass" (OR= 1.15, P= 1.03×10-2); "Trunk fat percentage" (OR= 1.25, P= 8.55×10-4); "Waist circumference" (OR= 1.23, P= 3.28×10-3); "Weight" (OR= 1.21, P= 9.82×10-4); "Whole body fat mass" (OR= 1.21, P= 4.90×10-4); "Whole body fat-free mass" (OR= 1.19, P= 4.11×10-3) and "Whole body water mass" (OR= 1.21, P= 1.85×10-3). Conclusion: Several metabolic markers linked to altered fat accumulation and distribution are significantly associated with an increased risk of OC.

Network pharmacology combined with Mendelian randomization analysis to identify the key targets of renin-angiotensin-aldosterone system inhibitors in the treatment of diabetic nephropathy.

Background: Diabetic Nephropathy (DN) is one of the microvascular complications of diabetes. The potential targets of renin-angiotensin-aldosterone system (RAAS) inhibitors for the treatment of DN need to be explored. Methods: The GSE96804 and GSE1009 datasets, 729 RAAS inhibitors-related targets and 6,039 DN-related genes were derived from the public database and overlapped with the differentially expressed genes (DN vs. normal) in GSE96804 to obtain the candidate targets. Next, key targets were screened via the Mendelian randomization analysis and expression analysis. The diagnostic nomogram was constructed and assessed in GSE96804. Additionally, enrichment analysis was conducted and a 'core active ingredient-key target-disease pathway' network was established. Finally, molecular docking was performed. Results: In total, 60 candidate targets were derived, in which CTSC and PDE5A were screened as the key targets and had a causal association with DN as the protective factors (P < 0.05, OR < 1). Further, a nomogram exhibited pretty prediction efficiency. It is indicated that Benadryl hydrochloride might play a role in the DN by affecting the pathways of 'cytokine cytokine receptor interaction', etc. targeting the CTSC. Moreover, PDE5A might be involved in 'ECM receptor interaction', etc. for the effect of NSAID, captopril, chlordiazepoxide on DN. Molecular docking analysis showed a good binding ability of benadryl hydrochloride and CTSC, NSAID and PDE5A. PTGS2, ITGA4, and ANPEP are causally associated with acute kidney injury. Conclusion: CTSC and PDE5A were identified as key targets for RAAS inhibitors in the treatment of DN, which might provide some clinical significance in helping to diagnose and treat DN. Among the targets of RAAS inhibitors, PTGS2, ITGA4 and ANPEP have a causal relationship with acute kidney injury, which is worthy of further clinical research.

Alterations in the gut virome are associated with type 2 diabetes and diabetic nephropathy.

Although changes in gut microbiome have been associated with the development of T2D and its complications, the role of the gut virome remains largely unknown. Here, we characterized the gut virome alterations in T2D and its complications diabetic nephropathy (DN) by metagenomic sequencing of fecal viral-like particles. Compared with controls, T2D subjects, especially those with DN, had significantly lower viral richness and diversity. 81 viral species were identified to be significantly altered in T2D subjects, including a decrease in some phages (e.g. Flavobacterium phage and Cellulophaga phaga). DN subjects were depleted of 12 viral species, including Bacteroides phage, Anoxybacillus virus and Brevibacillus phage, and enriched in 2 phages (Shigella phage and Xylella phage). Multiple viral functions, particularly those of phage lysing host bacteria, were markedly reduced in T2D and DN. Strong viral-bacterial interactions in healthy controls were disrupted in both T2D and DN. Moreover, the combined use of gut viral and bacterial markers achieved a powerful diagnostic performance for T2D and DN, with AUC of 99.03% and 98.19%, respectively. Our results suggest that T2D and its complication DN are characterized by a significant decrease in gut viral diversity, changes in specific virus species, loss of multiple viral functions, and disruption of viral-bacterial correlations. The combined gut viral and bacterial markers have diagnostic potential for T2D and DN.

Gut microbiota involved in spermatogenic function of Sancai Lianmei granules in obese mice.

Obesity is a well-established cause of reduced fertility and semen quality in men. Current evidence suggests that Sancai Lianmei granules (SCLM) effectively improve sexual function and semen quality in diabetic patients, while the gut microbiota can influence disease metabolism through various mechanisms. However, the effect of SCLM on the obesity-induced decrease in semen quality and on the gut microbiota is unclear. This study aimed to investigate the effects of SCLM on spermatogenic function and gut microbiota in obese mice. Obese mice were induced by a high-fat diet, and lipid metabolism, spermatogenic function, inflammatory factors, oxidative stress, and autophagy were analyzed to determine the effects of SCLM and SCLM-fecal microbiota transplantation (FMT). In addition, changes in the gut microbiota of mice were analyzed. SCLM and SCLM + FMT could effectively reduce the levels of total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); decrease the expression of oxidative stress products malondialdehyde (MDA) and 8-hydroxyde-oxyguanosine (8-OHdG); and increase sperm density and sperm viability in obese mice while inhibiting the inflammatory responses and excessive cellular autophagy, indicating that SCLM and SCLM + FMT exerted a protective effect on spermatogenic functions. Furthermore, SCLM affected the gut microbiota composition in mice. This study determined that obesity can lead to reduced sperm motility and affect the composition of the gut microbiota, while SCLM can regulate blood lipids in mice directly or indirectly by regulating gut microbiota changes, and may improve sperm motility in obese mice by reducing oxidative stress and autophagy. In addition, FMT enhanced this effect, which may be related to the diversity of gut microbiota.

Probiotics, Pre-biotics and Synbiotics in the Treatment of Pre-diabetes: A Systematic Review of Randomized Controlled Trials.

Objectives: This study aimed to review the data from randomized controlled trials (RCTs) and identify evidence for microbiota's role and use of probiotics, pre-biotics, or synbiotics in pre-diabetes. Methods: RCTs of pro-, pre-, synbiotics for the treatment of pre-diabetes population will be summarized. We searched for EMBASE, MEDLINE, Web of Science, Cochrane Central, Clinical Trials (ClinicalTrials.gov) from inception to February 2021. Results: The gut microbiota influences host metabolic disorders via the modulation of metabolites, including short-chain fatty acids (SCFAs), the endotoxin lipopolysaccharides (LPS), bile acids (BA) and trimethylamine N-oxide (TMAO), as well as mediating the interaction between the gastrointestinal system and other organs. Due to the limited sources of studies, inconsistent outcomes between included studies. Probiotics can decrease glycated hemoglobin (HbA1c) and have the potential to improve post-load glucose levels. The supplementation of probiotics can suppress the rise of blood cholesterol, but the improvement cannot be verified. Pre-biotics are failed to show an evident improvement in glycemic control, but their use caused the changes in the composition of gut microbiota. A combination of probiotics and pre-biotics in the synbiotics supplementation is more effective than probiotics alone in glycemic control. Conclusion: In the current studies using probiotics, pre-biotics or synbiotics for the treatment of pre-diabetes, the benefits of modulating the abundance of gut microbiota were partially demonstrated. However, there is insufficient evidence to show significant benefits on glucose metabolism, lipid metabolism and body composition.

The association of plasma high-density lipoprotein cholesterol levels and cirrhosis development in obese patients with chronic hepatitis B: a cohort study.

OBJECTIVE: Metabolic disorder is a common risk factor for cirrhosis in Asia, and it will increase the risk of cirrhosis in patients with Chronic hepatitis B (CHB). However, studies on the efficacy of plasma lipid markers which predict the happening and development of cirrhosis in obese CHB patients are limited. METHODS: In total, 3327 patients who were followed for more than 4 years' follow-up in the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine joined the program. Finally, 287 obese CHB patients were included in this study according to the results of metabolic tests. The data of baseline and follow-up were collected, and the association between them was analyzed. RESULTS: Based on the follow-up results, enrolled patients were divided into a group of cirrhosis (n = 146) and a group of noncirrhosis (n = 141). Plasma glucose and high-density lipoprotein cholesterol (HDL-C) levels in the noncirrhosis group (5.2 and 1.2 mmol/L, respectively) were significantly higher than that in the cirrhosis group (5.0 and 1.0 mmol/L, respectively), while the amount of total bile acid (TBA) in the cirrhosis group was lower than that in the cirrhosis group. Levels of HDL-C and total cholesterol were associated with liver function. Plasma HDL-C was an independent indicator of cirrhosis in patients with CHB. Patients with HDL-C levels less than 1.03 mmol/L had a 2.21-fold higher incidence rate of cirrhosis, and patients over 40 years old or the levels of HDL-C less than 1.03 mmol/L were more likely to generate cirrhosis. CONCLUSIONS: Plasma HDL-C was an appropriate marker in predicting cirrhosis for patients with CHB.

Effect of sancai powder on glacemic variability of type 1 diabetes in China: A protocol for systematic review and meta-analysis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic, immune-mediated disease characterized by the destruction of insulin producing cells and persistent hyperglycemia. At present, the drugs for type 1 diabetes mellitus can reduce blood glucose rapidly and effectively, but there are risks of hypoglycemia, large fluctuation of blood glucose, and chronic complications. Related research found that compared with continuous hyperglycemia, blood glucose fluctuations are more harmful to the chronic complications of diabetes. Blood glucose variation is closely related to the occurrence and development of chronic complications of diabetes. Sancai powder (SC) is made on the basis of 3 ancient Chinese medicine formulas, which has the effect of lowering blood glucose. There have been reports on the clinical study of SC in the treatment of diabetic patients, but there is no systematic evaluation of SC in the treatment of type 1 diabetes, so it is necessary to summarize and evaluate the existing evidence. METHODS AND ANALYSIS: This study will be conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols. We will search 3 English databases and 4 Chinese databases. Two methodologically trained researchers will read titles, abstracts, and full texts, and independently select eligible literature based on inclusion and exclusion criteria. After assessing the risk of bias and extracting data, we will conduct a meta-analysis of the results, including: standard deviation of blood glucose level, coefficient of variation, mean blood glucose, postprandial blood glucose fluctuation, hypoglycemia index, glycated hemoglobin, overall impact rate, and adverse effects. The heterogeneity of the data will be tested by Cochrane x2 and I2. Based on reliable subgroup effect guidance, we established 3 hypotheses for subgroup analysis: disease status at baseline, duration of intervention, and type of concomitant medication. Sensitivity analysis will be carried out to assess the stability of the results. The publication bias assessment will then be performed by funnel plot analysis and Egger test. Finally, we will use the "grading, evaluation, development and evaluation of recommendations" system to assess the quality of evidence. RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: In our study, the evidence of SC in the treatment of reducing blood sugar fluctuation in type 1 diabetes will be comprehensively summarized and carefully evaluated. It will provide more options for clinical treatment of the disease. INPLASY REGISTRATION NUMBER: INPLASY202050052.

The effect of Sancai powder on glycemic variability of type 2 diabetes in the elderly: A randomized controlled trial.

BACKGROUND: Type 2 diabetes is a kind of metabolic disease. Its clinical characteristic is hyperglycemia. Recently, more and more elderly people suffer from type 2 diabetes, and the glycemic variability of the elderly is greater. In addition, blood sugar variation is more likely to cause diabetes complications than simple hyperglycemia. Sancai podwer (SC) is based on the theory of traditional Chinese medicine and gradually formed in the summary of clinical experience. It has the effect of lowering blood sugar and alleviating clinical symptoms of diabetes. But the existing evidence of its efficacy on glycemic variability is insufficient. So, in our study, the randomized controlled trials will be used as a research method to explore the effects of SC on glycemic variability of type 2 diabetes. METHOD: We will use randomized controlled experiments based on the recommended diagnostic criteria, inclusion and exclusion criteria. A total of 60 elderly patients with type 2 diabetes will be randomly divided into treatment group and control group, 30 cases in each group. The control group will receive conventional western medicine and the intervention group will receive SC combined with western medicine. The standard deviation and coefficient of variation of blood glucose level will be used as evaluation indexes. DISCUSSION: This study can provide evidence for the clinical efficacy and safety of SC in elderly patients with type 2 diabetes mellitus. TRIAL REGISTRATION: This study is registered on the Chinese Clinical Trial Registry: ChiCTR2000032611.

Acupuncture for the treatment of radiation-induced xerostomia among patients with cancer: A protocol for a systematic review and meta-analysis.

BACKGROUND: With the number of cancer patients growing, radiotherapy and chemotherapy have been a necessary treatment. Unfortunately, there are many side effects after radiation and chemotherapy, one of which is xerostomia that always harasses patients. Although there are many ways of treatment of xerostomia, they have many disadvantages. With the rare side effects and the excellent effect, acupuncture has been widely applied to dry mouth after radiotherapy, but it has not been recognized as the standard treatment. Because acupuncture prescription is mostly different and the sample size of studies is small, we need more high-quality meta-analysis to provide relatively reliable evidence for the treatment of radiation-induced xerostomia. The objective of this study is to assess the curative effect of acupuncture treatment of cancer patients after radiotherapy and provide more reliable evidence for acupuncture treatment of xerostomia after radiotherapy for cancer patients. METHODS: We will search the following databases: CENTRAL (The Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, PubMed, CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), Wan Fang Data Knowledge Service Platform. At any rate, 2 review authors will assess all randomized controlled trials (RCTs), seemingly conformance to the inclusion criteria, to confirm qualification, determine the risk of bias and extract data using a running data extraction form. The revolution of disagreements is a discussion. We will use the approach recommended by Cochrane reviews to assess the bias in studies. Risk ratios (RR) and 95% confidence intervals (CIs) will be used to assess the treatment effects of an intervention for dichotomous results. We will use mean differences (MD) and standard deviation (SD) to aggregate the data of every trial for continuous results. The heterogeneity test of Cochran and quantification of the I statistic will be used to assess the variation of treatment effects. Only if there are studies of semblable comparisons reporting the same results, we will conduct a meta-analysis. RESULTS: From the study, we will evaluate the efficacy of acupuncture for xerostomia patients who has cancer and been treated by radiation. CONCLUSION: The conclusion of this study will be the evidence, which can ensure the efficacy of acupuncture for cancer patients with radiation-evoked xerostomia among and provide guidance for the treatment of xerostomia. INPLASY REGISTRATION NUMBER: INPLASY202040211.