Mechanisms of intestinal epithelial cell damage by Clostridiumperfringens.

Clostridium perfringens, a Gram-positive bacterium, causes intestinal diseases in humans and livestock through its toxins, related to alpha toxin (CPA), beta toxin (CPB), C. perfringens enterotoxin (CPE), epsilon toxin (ETX), Iota toxin (ITX), and necrotic enteritis B-like toxin (NetB). These toxins disrupt intestinal barrier, leading to various cell death mechanisms such as necrosis, apoptosis, and necroptosis. Additionally, non-toxin factors like adhesins and degradative enzymes contribute to virulence by enhancing colonization and survival of C. perfringens. A vicious cycle of intestinal barrier breach, misregulated cell death, and subsequent inflammation is at the heart of chronic inflammatory and infectious gastrointestinal diseases. Understanding these mechanisms is essential for developing targeted therapies against C. perfringens-associated intestinal diseases.

Predictive role of modifiable factors in stroke: an umbrella review.

BACKGROUND: A growing number of meta-analyses reviewed the existing associations between modifiable factors and stroke. However, the methodological quality of them and quality of evidence remain to be assessed by validated tools. Thus, this umbrella review was conducted to consolidate evidence from systematic reviews and meta-analyses of cohort studies investigating the association between modifiable factors and incidence of stroke. METHODS: PubMed, Web of Science, Embase, Wanfang and China National Knowledge Infrastructure databases for systematic reviews and meta-analyses of cohort studies from inception until March 2021. Assess the methodological quality of systematic reviews 2 was used to evaluate the methodological quality of each included published meta-analysis. Excess significance test was used to investigate whether the observed number of studies (O) with nominally significant results ('positive' studies, p<0.05) was larger than the expected number of significant results (E). Statistically significant (p<0.05) associations were rated into five levels (strong, highly suggestive, suggestive, weak and no) using specific criteria. Sensitivity analyses were performed. RESULTS: 2478 records were identified through database searching. At last, 49 meta-analyses including 70 modifiable factors and approximately 856 801 stroke cases were included in the present review. The methodological quality of three meta-analyses was low, while others were critically low. Evidence of walking pace was strong. High suggestive evidence mainly included total meat, processes meat, chocolate, sodium, obesity, pulse pressure, systolic blood pressure, diastolic blood pressure, sleep duration and smoking. Suggestive evidence mainly included dietary approaches to stop hypertension (DASH) diet, vitamin C, magnesium, depression and particulate matter 2.5. After sensitivity analyses, evidence of DASH diet, magnesium and depression turned to weak. No publication bias existed, except only one study which could be explained by reporting bias. DISCUSSION: Diet with rich macronutrients and micronutrients, healthy dietary patterns and favourable physical, emotional health and environmental management should be promoted to decrease the burden of stroke. PROSPERO REGISTRATION NUMBER: CRD42021249921.

Association of polymorphisms in endothelial dysfunction-related genes with susceptibility to essential hypertension in elderly Han population in Liaoning province, China.

Hypertension is a complex disease which is mainly influenced by genetic factors. Recently, genome-wide association study (GWAS) found three novel endothelial dysfunction-related sites: Vascular endothelial growth factor A (VEGFA) rs9472135, Faciogenital dysplasia 5 (FGD5) rs11128722, Zinc Finger C3HC-type Containing 1 (ZC3HC1) rs11556924. Endothelial dysfunction is one of the early events in pathophysiology of essential hypertension. To investigate the association of endothelial dysfunction-related genes with essential hypertension, we conducted a case-control study of 431 patients with hypertension and 345 controls. The polymorphisms were detected using Taqman Probe. The alleles and genotypes of ZC3HC1 rs11556924 and VEGFA rs9472135 were not statistically different between the two groups, while the allele of FGD5 rs11128722 was different [P = 0.045, OR = 1.265, 95% CI = (1.009-1.586)], especially in the male [P = 0.035, OR = 1.496, 95% CI = (1.037-2.158)]. Analyzing the different of genotype distribution of 3 SNPs in the two groups under different genetic models, the genotypes of FGD5 rs11128722 showed difference in male under dominant model [P = 0.049, OR = 1.610, 95% CI = (1.018-2.544)]. The polymorphism of FGD5 rs11128722 had a significant difference in Body Mass Index (BMI) among different genotypes; In the additive genetic model, BMI of GA genotype was higher than that of GG (P = 0.038); GA + AA was higher than GG in the dominant genetic model (P = 0.011). In our study, we found that the polymorphisms of VEGFA rs9472135 and ZC3HC1 rs11556924 may not significantly associated with the risk of essential hypertension, and FGD5 rs11128722 may increase the risk of it, especially in elderly men.

Validation and Extension Study Exploring the Role of RNF213 p.R4810K in 2,877 Chinese Moyamoya Disease Patients.

OBJECTIVE: To validate, update, and extend the role of RNF213 p.R4810K (G>A) for predicting the phenotype of moyamoya disease (MMD) patients and explore the different effects on pediatric and adult groups. METHODS: A total of 2,877 patients conducted from 2004 to 2018 were included. Review Manage 5.3 and SPSS 20.0 were applied to complete all statistical analyses. Information on age at onset, sex, initial symptom, family history and complications were obtained via retrospective chart review. Angiographic records were evaluated. RESULTS: In China, geographic proximity to Korea or Japan may affect the carrying rate of RNF213 p.R4810K. The proportion of patients with the following characteristics was significantly higher (P <0.017) in the GA than in the GG group: female, age at onset < 18 years, infarct after transient ischemic attack, family history of MMD, and posterior cerebral artery involvement. For pediatric patients, GA showed more cerebral hemorrhage (CH) (odds ratios (ORs) [95% confidence intervals (CIs)] = 3.99 (1.61-9.88), P = 0.003), more patients were in the Suzuki early and intermediate stage (P = 0.001; P = 0.001, respectively), while for the adult group, GA indicated more female (OR [95% CIs] = 1.43 [1.15-1.79], P = 0.001), fewer patients with diabetes (0.58 [0.38-0.86], P = 0.007) and intermediate Suzuki stage (P = 3.70 × 10-4). CONCLUSIONS: The incidence and carrying rates of RNF213 p.R4810K in various regions for Chinese MMD patients were obviously different. RNF213 p.R4810K has different predictive effects on phenotypes of pediatric and adult patients.

Clinical and Genetic Risk Factors of Long-Term Outcomes after Encephaloduroarteriosynangiosis in Moyamoya Disease in China.

OBJECTIVES: This retrospective study was conducted to analyze the associations between ring finger protein 213 p.R4810K variant, clinical features and long-term outcomes in patients with moyamoya disease (MMD) after encephaloduroarteriosynangiosis treatment. MATERIALS AND METHODS: A total of 2,545 patients with MMD in China were included in this study (median of follow-up duration: 32.00 months). Multiple Cox regression models were used to assess the associations between p.R4810K variant, clinical features and long-term outcomes. RESULTS: For all patients, in multivariate Cox analysis, no association was observed between p.R4810K and long-term outcomes. Pediatric onset (HR, 0.38; 95%CI, 0.25-0.59) and headache (HR, 0.26; 95%CI, 0.08-0.83) were inversely and hypertension (HR, 1.43 95%CI, 1.06-1.94), diabetes (HR, 1.55; 95%CI, 1.00-2.40), bilateral lesions (HR, 2.73; 95%CI, 1.12-6.65) and posterior cerebral artery involvement (HR, 1.44; 95%CI, 1.08-1.90) were positively associated with follow-up stroke (all P < 0.05). Pediatric onset (HR, 0.46; 95%CI, 0.26-0.82) was inversely and hyperlipidemia (HR, 1.83; 95%CI, 1.23-2.73), smoking (HR, 1.86; 95%CI, 1.13-3.07), high Suzuki angiographic stage (HR, 1.71, 95%CI, 1.09-2.70), poor admission neurologic status (HR, 8.93; 95%CI, 6.49-12.29) and follow-up stroke (HR, 8.31; 95%CI, 6.01-11.49) were positively associated with poor neurologic outcome at the last follow-up visit (all P < 0.05). The factors were not consistent in the different groups of age at onset. CONCLUSIONS: In our study, p.R4810K may play no role in long-term outcomes in Chinese MMD. Clinical features including age at onset, initial symptoms, risk factors of stroke, imaging, poor admission neurologic status were associated with poor outcomes in MMD after EDAS.