Yimin Shen

Diabetic lower extremity peripheral artery disease (PAD) is a complex and multifactorial complication of diabetes mellitus, characterized by extensive distal disease burden, accelerated progression, and a markedly elevated risk of major adverse limb events. Despite considerable advances in endovascular and surgical revascularization, limb salvage rates in this population remain suboptimal, largely due to the limited efficacy of current pharmacological options in improving microvascular perfusion, accelerating wound healing, or preventing re-occlusion. In recent years, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a transformative therapeutic class, demonstrating cardiovascular protective effects beyond glycemic control. Large-scale real-world studies have generated encouraging signals regarding their potential to reduce amputation risk and promote wound healing. However, the current evidence base remains limited, and the precise molecular mechanisms by which GLP-1 RAs may protect the diabetic lower extremity require further elucidation. This review systematically examines the epidemiology and pathophysiology of diabetic lower extremity PAD, elucidates the molecular mechanisms of GLP-1 RA-mediated vascular protection, critically evaluates clinical and real-world evidence, and discusses key challenges and future directions for optimizing therapeutic outcomes in this high risk population.

Metabolic disorders are precursors to numerous chronic diseases. Phlorotannins is a kind of natural bioactive agents found in brown algae composed with polyphenolic. Due to its role in regulating blood glucose and lipid levels, it is expected to manage chronic metabolic disease. However, previous study has mainly focused phlorotannins on their metabolic effects in the native state. Due to their high molecular weight, these compounds are poorly absorbed in the intestine, which limits their oral bioavailability. This review examines the interactions between phlorotannins and gut microbiota, as well as the role of small-molecule metabolites produced by microbial degradation on host metabolism. Phlorotannins can modulate the composition of the gut microbiota, promote the production of short-chain fatty acids, and increase bile acid metabolism. Therefore, understanding the bioavailability of gut microbiota-derived phlorotannin metabolites is crucial for developing strategies to prevent obesity and manage diabetes.

Article: Bioinformatics analysis of key pathways and genes in osteosarcoma development - Panminerva Medica 2019 Oct 25 - Minerva Medica - Journals

Thyroid dysfunction and inflammation are individually implicated in the increased risk of heart failure. Given the regulatory role of thyroid hormones on immune cells, this study aimed to investigate their joint association in heart failure. Patients with pre-existing heart failure were enrolled when hospitalized between July 2019 and September 2021. Thyroid function and inflammatory markers were measured at the enrollment. The composite of all-cause mortality or rehospitalization for heart failure were studied in the following year. Among 451 participants (mean age 66.1 years, 69.4% male), 141 incident primary endpoints were observed during a median follow-up of 289 days. TT3 and FT3 levels were negatively correlated with BNP levels (r: −0.40, p < 0.001; r: −0.40, p < 0.001, respectively) and NT-proBNP levels (r: −0.39, p < 0.001; r: −0.39, p < 0.001). Multivariate COX regression analysis revealed that FT3 (adjusted HR: 0.677, 95% CI: 0.551–0.832) and NLR (adjusted HR: 1.073, 95% CI: 1.036–1.111) were associated with adverse event, and similar results for TT3 (adjusted HR: 0.320, 95% CI: 0.181–0.565) and NLR (adjusted HR: 1.072, 95% CI: 1.035–1.110). Restricted cubic splines analysis indicated a linear relationship between T3 level and adverse events. Mechanistically, primary cardiomyocytes showed strong resistance to TNF-α induced apoptosis under optimal T3 concentrations, as evidenced by TUNEL staining, flow cytometry analysis, and LDH release assay as well as increased expression of Bcl-2. Thyroid dysfunction and inflammation are independently associated with cardiovascular risk in heart failure patients, which may concurrently contribute to the ongoing cardiomyocyte loss in the disease progression.

Introduction. This network meta-analysis aimed to evaluate the efficacy and safety of different dual antiplatelet therapies (DAPTs) after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). Methods. Randomized controlled trials (RCTs) comparing longer-term (>12 months) DAPT (L-DAPT), 12-month DAPT (DAPT 12Mo), 6-month DAPT (DAPT 6Mo), 3-month DAPT followed by aspirin monotherapy (DAPT 3Mo+ASA), 3-month DAPT followed by a P2Y12 receptor inhibitor monotherapy (DAPT 3Mo+P2Y12), or 1-month DAPT with a P2Y12 receptor inhibitor monotherapy (DAPT 1Mo+P2Y12) were searched. Primary endpoints were all-cause mortality, cardiac death, myocardial infarction (MI), major bleeding, any bleeding, definite or probable stent thrombosis (ST), and net adverse clinical events (NACE). This Bayesian network meta-analysis was performed with the random-effects model. Results. Twenty-four RCTs (n=81339) were included. In comparison with L-DAPT, DAPT 6Mo (OR: 0.50, 95 CI: 0.290.83), DAPT 3Mo+P2Y12 (OR: 0.38, 95 CI: 0.180.82), DAPT 3Mo+ASA (OR: 0.44, 95 CI: 0.170.98), and DAPT 1Mo+P2Y12 (OR: 0.45, 95 CI: 0.140.93) were associated with a lower risk of major bleeding. DAPT 3Mo+P2Y12 (OR: 0.58, 95 CI: 0.380.88) reduced the risk of any bleeding when compared with DAPT 12Mo. L-DAPT decreased the risk of MI and definite or probable stent ST when compared with DAPT 6Mo. DAPT 3Mo+P2Y12 decreased the risk of NACE in comparison with DAPT 6Mo and DAPT 12Mo. No significant difference in all-cause mortality and cardiac death was observed. In patients with acute coronary syndrome, DAPT 6Mo was comparable to DAPT 12Mo. Conclusion. Short-term (13 months) DAPT is noninferior to DAPT 6Mo after DESs implantation, while L-DAPT reduces MI and definite or probable ST rates. DAPT 3Mo+P2Y12 might be a reasonable trade-off in patients with high risk of bleeding accompanied by ischemia.

Background: Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia and is characterized by the presence of insulin autoantibodies. Patients with IAS usually complain of hypoglycemia without any previous insulin received. Glucocorticoids and immunosuppressants are used to treat IAS. Case presentation: We report four patients with diabetes who were diagnosed with non-classical IAS and describe the treatment of these patients. Moreover, the differential diagnosis with hyperinsulinism is discussed. Conclusion: High levels of insulin autoantibodies, as well as hyperinsulinemic hypoglycemia, are found in patients with diabetes mellitus and prior exogenous insulin exposure. This situation that we classified as non-classical IAS should be attached importance to.

Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.