Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Objective:To investigate the impact of non-high-density lipoprotein cholesterol (non-HDL-C) level on major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality in the Kailuan Study cohort undergoing revascularization.Methods:This is a prospective cohort study, with participants from the Kailuan Study cohort who participated in physical examinations from 2006 to 2020 and received revascularization therapy for the first time. According to the level of non-HDL-C, the study subjects were divided into 3 groups:<2.6 mmol/L group, 2.6-<3.4 mmol/L group, and≥3.4 mmol/L group. Annual follow-up was performed, and the endpoint events were MACCE and all-cause mortality. Cox proportional regression model was implemented to estimate the impact on MACCE and all-cause mortality associated with the different non-HDL-C groups. The partial distributed risk model was used to analyze the impact of different non-HDL-C levels on MACCE event subtypes, and death was regarded as a competitive event. The restricted cubic spline regression model was used to explore the dose-response relationship between non-HDL-C level and all-cause mortality, MACCE and its subtypes.Results:A total of 2 252 subjects were enrolled in the study, including 2 019 males (89.65%), aged (62.8±8.3) years, the follow-up time was 5.72 (3.18, 8.46) years. There were 384 cases(17.05%) of MACCE and 157 cases(6.97%) of all-cause mortality. Compared with patients with non-HDL-C≥3.4 mmol/L, patients with non-HDL-C<2.6 mmol/L were associated with a 38% reduced risk of MACCE after revascularization [ HR=0.62(95% CI: 0.48-0.80)]. Every 1 mmol/L decrease in non-HDL-C was associated with a 20% reduction in the risk of MACCE [ HR=0.80(95% CI: 0.73-0.88)]. The results of restricted cubic spline also showed that non-HDL-C levels after revascularization therapy were positively correlated with MACCE events (overall association P<0.001, non-linear association P=0.808). For all-cause mortality, compared to the non-HDL-C≥3.4 mmol/L group, the HR for all-cause mortality after revascularization in non-HDL-C<2.6 mmol/L group was 0.67(95% CI: 0.46-1.01). Every 1 mmol/L decrease in non-HDL-C was associated with a 15% reduction in the risk of all-cause mortality [ HR=0.85(95% CI: 0.73-0.99)]. The restricted cubic spline results showed a linear association between non-HDL-C levels after revascularization therapy and the risk of all-cause mortality (overall association P=0.039, non-linear association P=0.174). Conclusion:The decrease in non-HDL-C levels after revascularization were significantly associated with a reduced risk of MACCE and all-cause mortality.

Aging is a process of degenerative change that occurs as a result of time-related accumulation,associated with age-related diseases.Understanding the causes and mechanisms of aging and finding drugs that can effectively delay aging and prevent and cure age-related diseases currently present a great challenge for humans.Aging animal models thus represent an important tool in aging research,and various aging animal models have been created using different aging mechanisms.These different models having specific advantages and disadvantages,making them suitable for different research purposes.This review considers aging rodent models to provide information for aging research.

Objective To study and compare the level of adiponectin in different functional status of thyroid,to assess the association of thyroid hormones and insulin resistance with adiponectin.Methods ELISA was used to examine the fasting plasma adiponectin in 56 hyperthyroidism,30 hypothyroidism and 44 normal control subjects.FT_3,FT_4,TSH, FPG,Fins and blood fat were measured.BMI and HOMA-IR were calculated.Results There were higher level of adiponectin in hyperthyroidism than hypothyroidism and normal control subjects.Fasting plasma adiponectin was posi- tively correlated with FT_4 (r=0.36,P

Objective To establish the clinical pharmacokinetics research method for Bawei Jiangu Tablet.Methods Drug blood concentration was estimated through analyzing the ingredients and preclinical pharmaceutical research results of Bawei Jiangu Tablet.Results Corresponding cardiac glycoside value in serum of animals treated with oral use of Bawei Jiangu Tablets and cortex periplocae extracts can be detected by drug monitor system of digoxin immunoreaction, which was similar to that in animals treated with digoxin.Corresponding cardiac glycoside value had also been detetected in serum of subjects in phaseⅠclinical tolerance trial,which was related to the time and dosage of administration.Clini- cal negative control trial showed that the reaction was specific.Conclusion Pharmacokinetics study on target of toxic components with cross-reaction of periplocoside is feasible through drug monitor system of digoxin immunoreaction.