Heart failure (HF) is an end-stage cardiovascular syndrome caused by structural or functional cardiac abnormalities. Its high morbidity and mortality underscore the urgent need for novel therapeutic strategies. In recent years, the dynamic regulatory mechanisms underlying macrophage polarization in the onset and progression of HF have attracted widespread attention. The Sirtuin family, as NAD⁺ -dependent deacetylases, has emerged as a key regulatory factor in reshaping the macrophage polarization phenotype by integrating metabolic reprogramming, epigenetic regulation, and immune cell interactions. This paper systematically elaborates the molecular mechanisms by which Sirtuins (SIRT1-SIRT7) regulate metabolic reprogramming (e.g., glucose metabolism, lipid metabolism, and glutamine metabolism), coordinate epigenetic modifications (e.g., DNA methylation, histone modifications, and non-coding RNA regulation), and mediate interactions between immune cells to dynamically balance macrophage polarization. Furthermore, this review summarizes recent advances in the active components of phytomedicines, such as resveratrol, pterostilbene, astragaloside IV, quercetin, dihydromyricetin, berberine, honokiol, ginsenoside Rc, ginsenoside Rg1, and ginsenoside Rg3, in targeting the Sirtuin-macrophage polarization axis for the prevention and treatment of HF. This review aims to provide a theoretical framework and translational guidance for developing HF-targeted therapeutic strategies based on Sirtuin-mediated macrophage polarization, as well as for the research and development of related natural products.

Background: Tirzepatide (TZP) is a novel drug for type 2 diabetes mellitus (T2DM), but the gastrointestinal (GI) adverse events (AEs) is a limiting factor in clinical application. Therefore, this study systematically evaluated the GI AEs of TZP for T2DM. Methods: Clinical trials of TZP for T2DM were retrieved from eight databases published only from the establishment of the database to February 2023. Revman5.3 and TSA0.9.5.10 Beta were used for meta-analysis and trials sequential analysis (TSA). Results: Meta-analysis showed that compared with placebo, total GI AEs, nausea, decreased appetite, constipation and vomiting were significantly higher in all dose groups of TZP (P < .05), while abdominal pain and abdominal distension were comparable (P > .05). TSA showed that the differences in total GI AEs, nausea, decreased appetite and constipation were conclusive. Compared with insulin, nausea, diarrhea, vomiting and decreased appetite were significantly increased in all doses of TZP (P < .05), and dyspepsia was significantly increased with TZP 15 mg (P < .05). TSA showed that these differences were all conclusive. Compared with GLP-1 RA, decreased appetite was significantly higher with TZP 5 mg, total GI AEs, decreased appetite and diarrhea were significantly higher with TZP 10 mg (P < .05), while nausea, vomiting, dyspepsia and constipation were significantly different in all dose groups, abdominal pain were not significantly different (P < .05) and TSA showed no conclusive results in this group. Conclusion: The GI AEs of TZP were significantly higher than those of placebo and insulin, but comparable to GLP-1 RA. Nausea, diarrhea and decreased appetite are very common GI AEs of TZP, and the incidence is positively correlated with dose. GI AEs of TZP decrease gradually over time, so long-term steady medication may be expected to reduce GI AEs.

Background: Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer, and also a key period of drug intervention. However, there is still a lack of drugs to maintain the treatment of CAG until the advent of moluodan. Objective: This study was conducted to assess the clinical efficacy of moluodan in the treatment of CAG by meta-analysis and trial sequential analysis. Methods: China National Knowledge Infrastructure, China Biology Medicine, VIP, Wanfang, Embase, PubMed, the Cochrane Library, and Web of Science databases were searched, all with the time limit from database establishment to July 2022. The published randomized controlled trials of moluodan for CAG were conducted for meta-analysis and trial sequential analysis. Results: 7 studies with a total sample size of 1143 cases were included. Compared to folic acid/vitamins, moluodan alone significantly increased the effective rate of pathological detection (relative risk [RR] = 1.73, 95% confidence interval [95%CI] = [1.48,2.02], P < .00001), and moluodan in combination with folic acid/vitamins significantly increased the effective rates of pathological detection (RR = 1.37, 95%CI = [1.23,1.52], P < .00001), gastroscopy (RR = 1.37, 95%CI = [1.18,1.60], P < .0001) and symptoms (RR = 1.25, 95%CI = [1.13,1.38], P < .0001). Harbord regression showed no publication bias (P = .22). Quality of evidence evaluation demonstrated moderate quality of evidence for all indicators. Conclusions: Moluodan can improve the effective rates of pathological examination, gastroscopy and symptoms in patients with CAG, and play a role in slowing down the disease progression and reducing clinical symptoms. It may be a potential drug for the treatment of CAG and has the value of further exploration.

Background: Although anti-inflammatory and immunomodulatory measures have delayed the progression of ulcerative colitis (UC) to a certain extent, the adverse drug reactions and recurrence after recovery still trouble clinicians. Acupoint catgut embedding is a possible alternative strategy for the treatment of UC, but its clinical efficacy remains controversial. Therefore, this study systematically evaluated the clinical efficacy and safety of acupoint catgut embedding compared with conventional western medicine in the treatment of UC. Methods: VIP, Wanfang, China National Knowledge Infrastructure, China Biology Medicine, PubMed, Embase, Web of Science, the Cochrane Library databases were searched. And the publication time of the literature was limited from the time that the database was established to February 2022. Two researchers independently screened the literature, extracted data, and assessed risk of bias as required. Meta-analysis was performed with Revman 5.3. Trial sequential analysis (TSA) was performed with TSA 0.9.5.10 Beta. Publication bias was assessed by Stata 15.0. And evidence quality was appraised with GRADEpro3.6. Results: A total of 10 studies were listed, with a total sample size of 782 cases. Meta-analysis showed that compared with conventional western medicine, acupoint catgut embedding can effectively improve the total effective rate of clinical symptoms (relative risk [RR] = 1.16, 95% confidence interval [CI] = [1.09,1.24], P < .00001), endoscopic total effective rate (RR = 1.16, 95%CI = [1.08,1.25], P < .0001), clinical symptom cure rate (RR = 1.80, 95%CI = [1.37,2.38], P < .0001), and endoscopic cure rate (RR = 1.97, 95%CI = [1.36,2.86], P = .0004) of UC, but the adverse event rate (RR = 0.20, 95%CI = [0.01,4.00], P = .29) was similar. Trial sequential analysis indicated that the efficacy endpoint was conclusive. Harbord test confirmed no significant publication bias. The quality of evidence for these outcomes ranges from low to medium. Conclusion: The clinical efficacy of acupoint catgut embedding in the treatment of UC is superior to that of conventional western medicine, and the safety may be equivalent to that of conventional western medicine, which has the value of further research and exploration.

This study aimed to evaluate the causal effects of different immune cells on heart failure (HF) using Mendelian randomization (MR). Datasets for immune cell phenotypes and HF were obtained from European Bioinformatics Institute and FinnGen. Then, single nucleotide polymorphisms were screened according to the basic assumptions of MR. Subsequently, inverse variance weighted was used as primary tool for MR analysis, and Cochran Q and leave-one-out analyses were used to assess heterogeneity and robustness, respectively. MR analysis showed that cluster of differentiation (CD) 66b++ myeloid cell absolute count (AC) (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.001–1.088, P = .045), human leukocyte antigen D-related on CD14– CD16+ monocyte (OR 1.030, 95% CI 1.005–1.056, P = .019), IgD on unsw mem (OR 1.046, 95% CI 1.015–1.078, P = .003), CD4 on CD4+ (OR 1.039, 95% CI 1.009–1.070, P = .011), CD24 on IgD+ CD38– (OR 1.026, 95% CI 1.000–1.052, P = .046), CD20 on CD24 + CD27+ (OR 1.032, 95% CI 1.003–1.061, P = .029), CD19 on CD20– (OR 1.037, 95% CI 1.005–1.071, P = .023), CD62L– CD86 + myeloid dendritic cell %DC (OR 1.032, 95% CI 1.004–1.061, P = .027), human leukocyte antigen D-related + CD4 + AC (OR 1.037, 95% CI 1.003–1.072, P = .032), and effector memory CD8br AC (OR 1.048, 95% CI 1.021–1.076, P < .001) were associated with increased genetic susceptibility to HF. Cochran Q and sensitivity analyses showed that the results had no heterogeneity and were robust. This MR analysis revealed 10 immune cell phenotypes associated with increased genetic susceptibility to HF. These findings provide new directions for understanding the pathogenesis of HF and developing novel therapies.

The role of circulating immune cells in coronary atherosclerosis remains unclear. This study aimed to assess the causal effects of various immune cells on coronary atherosclerosis using Mendelian randomization (MR). Circulating immune cell datasets were obtained from genome-wide association studies, and coronary atherosclerosis datasets were obtained from FinnGen. Single-nucleotide polymorphisms satisfying the assumptions of association, independence, and exclusivity were screened in the datasets and analyzed using MR, with inverse-variance weighted as the main method. Horizontal pleiotropy, heterogeneity, and sensitivity analyses were performed using the MR-Egger, Cochran Q, and leave-one-out analyses, respectively. The MR analysis showed that effector memory double negative (DN) (cluster of differentiation [CD]4⁻CD8⁻) %DN (odds ratio [OR]: 1.042, 95% confidence interval [CI]: 1.008–1.077, P = .014), CD4 on CD39⁺ CD4⁺ (OR: 1.027, 95% CI: 1.001–1.054, P = .040), C–X3–C motif chemokine receptor 1 on CD14⁺ CD16⁻ monocytes (OR: 1.035, 95% CI: 1.010–1.060, P = .006), C–C chemokine receptor 7 on naive CD4⁺ (OR: 1.035, 95% CI: 1.006–1.076, P = .023), and immunoglobulin D⁻ CD38⁻ %lymphocytes (OR: 1.098, 95% CI: 1.016–1.187, P = .019) were associated with an increased genetic susceptibility to coronary atherosclerosis, with no horizontal pleiotropy (P ≥ .05). Cochran Q showed no heterogeneity (P ≥ .05), and the sensitivity analysis indicated that the results were robust. The MR analysis revealed various markers and immune cell subsets, including effector memory DN (CD4⁻CD8⁻) %DN, CD4 on CD39⁺ CD4⁺, C–X3–C motif chemokine receptor on CD14⁺ CD16⁻ monocytes, C–C chemokine receptor 7 on naive CD4⁺, and IgD⁻ CD38⁻ %lymphocytes, associated with increased genetic susceptibility to coronary atherosclerosis. This provides a genetic explanation for the role of specific immune cells in inducing and exacerbating coronary artery disease and offers new ideas for the exploration of immune markers and immune-targeted drugs.