Metformin improves insulin sensitivity in insulin sensitive tissues such as liver, muscle and fat. However, the functional roles and the underlying mechanism of metformin action in pancreatic β cells remain elusive. Here we show that, under normal growth condition, metformin suppresses MIN6 β cell proliferation and promotes apoptosis via an AMPK-dependent and autophagy-mediated mechanism. On the other hand, metformin protects MIN6 cells against palmitic acid (PA)-induced apoptosis. Our findings indicate that metformin plays a dual role in β cell survival and overdose of this anti-diabetic drug itself may lead to potential β cell toxicity.

Elderly patients with sepsis have higher morbidity, mortality, and susceptibility than adults. Young-donor faecal microbiota transplantation (FMT) can remodel and improve intestinal dysbiosis to alleviate age-related diseases via microbiota-derived acetic acid and may be a treatment option for elderly sepsis. This study aimed to elucidate the influence of remodelling of the elderly gut microbiota on sepsis via acetic acid and explore the underlying mechanism. We analyzed the gut microbiota and plasma acetic acid in elderly patients with sepsis, performed young-donor FMT, and acetic acid supplementation in a caecum ligation and puncture-induced aged septic model mice, and assessed the effects of acetic acid on the septic myocardium by examining NLRP3 inflammasome in FFAR2 knockdown mice. Elderly sepsis had higher mortality, reduced gut microbiota diversity, increased Escherichia-Shigella abundance, and reduced plasma acetic acid levels. Young-donor FMT improved the gut microbiota, increased the abundance of the probiotic genus Akkermansia and faecal acetic acid levels in the gut, and improved colon barrier function and outcomes. Intestinal acetic acid intervention improved age-related intestinal dysbiosis, organ dysfunction, and adverse effects in aged septic mice. These beneficial effects on the myocardium were mediated by activation of the FFAR2/NLRP3 axis, as evidenced by the finding that FFAR2 knockdown abrogated the amelioration of acetic acid. The elderly gut microbiota is fragile, which is related to the severity and poor prognosis of elderly sepsis. Gut microbiota remodelling improves elderly sepsis via acetic acid, which can inhibit inflammatory reactions to alleviate myocardial damage by FFAR2/NLRP3 inflammasome inactivation.

Baseline left ventricular (LV) dysfunction is associated with subsequent risks of acute kidney injury (AKI) and mortality in patients with sepsis. This study investigated the therapeutic effects of continuous renal replacement therapy (CRRT) in hemodynamically unstable patients with severe sepsis and septic shock combined with LV dysfunction. In this multicenter retrospective study, severe sepsis and septic shock patients with LV dysfunction were classified into one of two groups according to the timing of CRRT: the early group (before AKI was detected) or the control group (patients with AKI). Patients from the control group received an accelerated strategy or a standard strategy of CRRT. The primary outcome was all-cause intensive care unit (ICU) mortality. Patients were weighted by stabilized inverse probability of treatment weights (sIPTW) to overcome differences in baseline characteristics. After sIPTW analysis, the ICU mortality was significantly lower in the early group than the control group (27.7% vs. 63.5%, p < 0.001). Weighted multivariable analysis showed that early CRRT initiation was a protective factor for the risk of ICU mortality (OR 0.149; 95% CI 0.051–0.434; p < 0.001). The ICU mortality was not different between the accelerated- and standard-strategy group (52.5% vs. 52.9%, p = 0.970). Early CRRT in the absence of AKI is suggested for hemodynamically unstable patients with severe sepsis and septic shock combined with LV dysfunction since it benefits survival outcomes.

To evaluate the association between estimated glomerular filtration rate (eGFR) and atrial fibrillation (AF) in patients hospitalized for chronic heart failure (CHF) using a retrospective analysis and establish a risk model of AF development. In total, 1301 inpatients with CHF at Fujian Medical University Union Hospital were divided into two groups based on the eGFR: normal eGFR (eGFR ≥ 90 ml/min/1.73 m2) and decreased eGFR (eGFR < 90 ml/min/1.73 m2). All patients with CHF were randomly assigned to two groups in a 7:3 ratio: the training (910 patients) and validation (391 patients) groups. In the training group, univariate and multivariate logistic regression methods were employed to identify eGFR as a risk factor for the occurrence of AF in patients with CHF. Calibration curves, receiver operating characteristic curves, and decision curve analysis (DCA) were used to establish and validate two models. Of the 1,301 patients, 398 had concurrent AF. Multivariate regression analysis in the training group revealed that eGFR, heart rate, hemoglobin level, LDL-C/HDL-C ratio, left atrial diameter, left ventricular mass index, coronary heart disease were independent risk factors for AF in patients with CHF. Based on the multivariate analysis results, a nomogram model was constructed incorporating these nine independent risk factors to predict AF risk in patients with CHF. The area under the curve for the training and validation groups was 0.80 (95% confidence interval [CI]: 0.77–0.84) and 0.76 (95% CI: 0.70–0.81), respectively. The calibration curve showed good agreement between the predicted and actual values. DCA indicated that when the threshold for the training group was between 8% and 83% and that for the validation group was between 7% and 82%, using the nomogram to predict AF risk was beneficial. Decreased eGFR is an independent risk factor for the occurrence of AF in patients with CHF. The calibration curve of the constructed nomogram model demonstrated an excellent fit, showing good consistency between the predicted and actual AF risks, thus indicating that the model has strong predictive capability.

Background: Low birth weight (LBW) is one of the risk factors for coronary heart disease (CHD). The association of LBW and other risk factors with male patients with premature CHD has not been fully determined. This study aims to assess the association of LBW and other risk factors with the incidence of male patients with premature CHD.Methods We identified hospitalized male patients with premature CHD (CHD group) and healthy male subjects (control group) from January 2013 to December 2018. The differences of demographics, birth weight (BW) and other traditional risk factors were compared between the CHD group and the control group and logistic regression was used to estimate their effects on the risk of premature CHD.Results A total of 384 male subjects were enrolled in the study (183 in the CHD group vs 201 in the control group). There were significant differences in BW, smoking, diabetes and hyperlipidemia between the two groups (2.98±0.35 vs 3.37±0.39kg, P<0.001, 73.22% vs 27.36%, P<0.001, 8.74% vs 3.48%, P=0.033, 53.55% vs 37.31%, P=0.001) respectively. The risk of premature CHD increased significantly with the LBW (OR=4.530, 95% CI：1.331-15.412，P=0.016) and smoking (OR=6.748, 95% CI：4.258-10.693，P<0.001) respectively according to the multivariate logistic regression model. Conclusion LBW and smoking are independently and positively correlated with male patients with premature CHD. A history of LBW should be paid particularly attention in younger men for primordial prevention of premature CHD, especially away from tobacco.

Sepsis, a life-threatening syndrome with especially high incidence and mortality in older adults, imposes a major global health burden. Although the gut ba