Bazi Bushen ameliorates age-related energy metabolism dysregulation by targeting the IL-17/TNF inflammatory pathway associated with SASP.

BACKGROUND: Chronic inflammation and metabolic dysfunction are key features of systemic aging, closely associated with the development and progression of age-related metabolic diseases. Bazi Bushen (BZBS), a traditional Chinese medicine used to alleviate frailty, delays biological aging by modulating DNA methylation levels. However, the precise mechanism of its anti-aging effect remains unclear. In this study, we developed the Energy Expenditure Aging Index (EEAI) to estimate biological age. By integrating the EEAI with transcriptome analysis, we aimed to explore the impact of BZBS on age-related metabolic dysregulation and inflammation in naturally aging mice. METHODS: We conducted indirect calorimetry analysis on five groups of mice with different ages and utilized the data to construct EEAI. 12 -month-old C57BL/6 J mice were treated with BZBS or ß-Nicotinamide Mononucleotide (NMN) for 8 months. Micro-CT, Oil Red O staining, indirect calorimetry, RNA sequencing, bioinformatics analysis, and qRT-PCR were performed to investigate the regulatory effects of BZBS on energy metabolism, glycolipid metabolism, and inflammaging. RESULTS: The results revealed that BZBS treatment effectively reversed the age-related decline in energy expenditure and enhanced overall metabolism, as indicated by the aging index of energy expenditure derived from energy metabolism parameters across various ages. Subsequent investigations showed that BZBS reduced age-induced visceral fat accumulation and hepatic lipid droplet aggregation. Transcriptomic analysis of perirenal fat and liver indicated that BZBS effectively enhanced lipid metabolism pathways, such as the PPAR signaling pathway, fatty acid oxidation, and cholesterol metabolism, and improved glycolysis and mitochondrial respiration. Additionally, there was a significant improvement in inhibiting the inflammation-related arachidonic acid-linoleic acid metabolism pathway and restraining the IL-17 and TNF inflammatory pathways activated via senescence associated secretory phenotype (SASP). CONCLUSIONS: BZBS has the potential to alleviate inflammation in metabolic organs of naturally aged mice and maintain metabolic homeostasis. This study presents novel clinical therapeutic approaches for the prevention and treatment of age-related metabolic diseases.

GLUT3 transcriptional activation by ZEB1 fuels the Warburg effect and promotes ovarian cancer progression.

Ovarian cancer (OvCa) is characterized by early metastasis and high mortality rates, underscoring the need for deeper understanding of these aspects. This study explores the role of glucose transporter 3 (GLUT3) driven by zinc finger E-box-binding homeobox 1 (ZEB1) in OvCa progression and metastasis. Specifically, this study explored whether ZEB1 promotes glycolysis and assessed the potential involvement of GLUT3 in this process in OvCa cells. Our findings revealed that ZEB1 and GLUT3 were excessively expressed and closely correlated in OvCa. Mechanistically, ZEB1 activates the transcription of GLUT3 by binding to its promoter region. Increased expression of GLUT3 driven by ZEB1 dramatically enhances glycolysis, and thus fuels Warburg Effect to promote OvCa progression and metastasis. Consistently, elevated ZEB1 and GLUT3 expression in clinical OvCa is correlated with poor prognosis, reinforcing the profound contribution of ZEB1-GLUT3 axis to OvCa. These results suggest that activation of GLUT3 expression by ZEB1 is crucial for the proliferation and metastasis of OvCa via fueling glycolysis, shedding new light on OvCa treatment.

Associations of Sedentary Behavior with Risks of Cardiovascular Disease Events among Chinese Adults.

AIMS: Evidence regarding the modification effects of age, sex, ethnicity, socioeconomic status, or weight status on the associations of sedentary behavior (SB) with cardiovascular diseases (CVDs) is limited. Moreover, the mechanisms for the associations also remain unclear. We aimed to investigate the possible influence of these factors on the associations of SB with CVD events and whether the associations are mediated by metabolic phenotypes. METHODS: This study included 42,619 participants aged 20-74 years, recruited from the Shanghai Suburban Adult Cohort and Biobank study. SB was assessed at baseline and integrated with health information systems to predict future CVD events. Cox proportional hazards models, interaction analyses, restricted cubic splines and causal mediation analyses were used for assessments. RESULTS: Compared to those with ＜3 h/d sedentary time, participants having SB ≥ 5 h/d had significantly higher risks of CVD (HR[95%CI]: 1.27[1.12-1.44]), coronary heart disease (CHD, 1.35[1.14-1.60]), and ischemic stroke (IS, 1.30[1.06-1.60]). The association of CHD was more pronounced in the retired individuals than their counterparts (1.45[1.20-1.76] versus 1.06[0.74-1.52], pinteraction=0.046). When SB was expressed as a continuous variable, a 1 h/d increment in SB was positively associated with risks of CVD (1.03[1.01-1.05]), CHD (1.04[1.01-1.07]), and IS (1.05[1.01-1.08]). High-density lipoprotein cholesterol (HDL-C, proportion mediated: 12.54%, 12.23%, and 11.36%, all p＜0.001), followed by triglyceride (TG, 5.28%, 4.77%, and 4.86%, all p＜0.01) and serum uric acid (SUA, 3.64%, 4.24%, and 2.29%, all p＜0.05) were major mediators through metabolic phenotypes. CONCLUSIONS: Higher SB was associated with elevated risks of CVD events. The detrimental effect of SB on CHD risk was more pronounced among retired individuals. Moreover, HDL-C, TG and SUA partially mediated the relationships between SB and CVD events. Our findings may have implications for preventing and controlling CVD associated with SB.

Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Dialysis and Cardiovascular Disease in Patients With Stage 5 Chronic Kidney Disease.

BACKGROUND: No studies have reported the long-term outcomes of initiating sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with estimated glomerular filtration rates less than 20 mL/min/1.73 m2 to predialysis. OBJECTIVE: To compare the risk for dialysis, cardiovascular events, and death between SGLT2i users and nonusers in patients with type 2 diabetes (T2D) and stage 5 chronic kidney disease (CKD). DESIGN: Target trial emulation study. SETTING: Taiwan's National Health Insurance Research Database (NHIRD). PARTICIPANTS: By applying sequential target trial emulation principle, 23 854 SGLT2i users and 23 892 SGLT2i nonusers were selected from the NHIRD for patients with T2D and stage 5 CKD from 1 May 2016 to 31 October 2021. MEASUREMENTS: Conditional Cox proportional hazards models were used to compare the risks for dialysis, hospitalization for heart failure, acute myocardial infarction (AMI), diabetic ketoacidosis (DKA), acute kidney injury (AKI), and all-cause mortality between SGLT2i users and nonusers. RESULTS: In the intention-to-treat model, compared with no SGLT2i use, SGLT2i use was associated with lower risks for dialysis (hazard ratio [HR], 0.34 [95% CI, 0.27 to 0.43]), hospitalization for heart failure (HR, 0.80 [CI, 0.73 to 0.86]), AMI (HR, 0.61 [CI, 0.52 to 0.73]), DKA (HR, 0.78 [CI, 0.71 to 0.85]), and AKI (HR, 0.80 [CI, 0.70 to 0.90]), but there was no difference in the risk for all-cause mortality (HR, 1.11 [CI, 0.99 to 1.24]). The Kaplan-Meier curves and subgroup analyses also showed that initiation of an SGLT2i in stage 5 CKD was associated with a lower risk for long-term dialysis than no SGLT2i use. LIMITATION: This result may not apply to patients without T2D. CONCLUSION: This emulated target trial showed that SGLT2i use was associated with a lower risk for dialysis, cardiovascular events, DKA, and AKI than no SGLT2i use in patients with T2D and stage 5 CKD. PRIMARY FUNDING SOURCE: National Health Research Institutes, Taiwan.

Healthier Dietary Patterns Are Associated with Better Sleep Quality among Shanghai Suburban Adults: A Cross-Sectional Study.

BACKGROUND: More is to be explored between dietary patterns and sleep quality in the Chinese adult population. METHODS: A cross-sectional study including 7987 Shanghai suburban adults aged 20-74 years was conducted. Dietary information was obtained using a validated food frequency questionnaire. Adherence to a priori dietary patterns, such as the Chinese Healthy Eating Index (CHEI), Dietary Approaches to Stop Hypertension (DASH) diet and Mediterranean diet (MD), was assessed. Sleep quality was assessed from self-reported responses to the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Logistic regression models adjusting for confounders were employed to examine the associations. RESULTS: The overall prevalence of poor sleep (PSQI score ≥ 5) was 28.46%. Factor analysis demonstrated four a posteriori dietary patterns. Participants with a higher CHEI (ORQ4 vs. Q1: 0.81, 95% CI: 0.70-0.95), DASH (ORQ4 vs. Q1: 0.70, 95% CI: 0.60-0.82) or MD (ORQ4 vs. Q1: 0.75, 95% CI: 0.64-0.87) had a lower poor sleep prevalence, while participants with a higher "Beverages" score had a higher poor sleep prevalence (ORQ4 vs. Q1: 1.18, 95% CI: 1.02-1.27). CONCLUSIONS: In Shanghai suburban adults, healthier dietary patterns and lower consumption of beverages were associated with better sleep quality.

Construction of Ni/In2O3 Integrated Nanocatalysts Based on MIL-68(In) Precursors for Efficient CO2 Hydrogenation to Methanol.

The efficient and economic conversion of CO2 and renewable H2 into methanol has received intensive attention due to growing concern for anthropogenic CO2 emissions, particularly from fossil fuel combustion. Herein, we have developed a novel method for preparing Ni/In2O3 nanocatalysts by using porous MIL-68(In) and nickel(II) acetylacetonate (Ni(acac)2) as the dual precursors of In2O3 and Ni components, respectively. Combined with in-depth characterization analysis, it was revealed that the utilization of MIL-68(In) as precursors favored the good distribution of Ni nanoparticles (∼6.2 nm) on the porous In2O3 support and inhibited the metal sintering at high temperatures. The varied catalyst fabrication parameters were explored, indicating that the designed Ni/In2O3 catalyst (Ni content of 5 wt %) exhibited better catalytic performance than the compared catalyst prepared using In(OH)3 as a precursor of In2O3. The obtained Ni/In2O3 catalyst also showed excellent durability in long-term tests (120 h). However, a high Ni loading (31 wt %) would result in the formation of the Ni-In alloy phase during the CO2 hydrogenation which favored CO formation with selectivity as high as 69%. This phenomenon is more obvious if Ni and In2O3 had a strong interaction, depending on the catalyst fabrication methods. In addition, with the aid of in situ diffuse reflectance infrared Fourier transform spectroscopy and density functional theory (DFT) calculations, the Ni/In2O3 catalyst predominantly follows the formate pathway in the CO2 hydrogenation to methanol, with HCOO* and *H3CO as the major intermediates, while the small size of Ni particles is beneficial to the formation of formate species based on DFT calculation. This study suggests that the Ni/In2O3 nanocatalyst fabricated using metal-organic frameworks as precursors can effectively promote CO2 thermal hydrogenation to methanol.

Differences in antibiotic use between COPD and non-COPD residents based on the health information system.

OBJECTIVES: To compare the differences in antibiotic use between COPD and non-COPD residents, and to explore the effect of COPD on antibiotic use. METHODS: Participants aged 40 years old or over from the Songjiang Adult Cohort were included. Information on prescription and baseline survey was collected based on the health information system. A logit-negative binomial Hurdle model was used to explore correlations between COPD and percentage of antibiotic use and average rate of antibiotic prescribing of different types of antibiotic. Multinomial logistic regression was used to assess the association between COPD and antimicrobial combination therapy and routes of administration. RESULTS: A total of 34576 individuals were included and 1594 (4.6%) were COPD patients. During the 6 years' follow-up, the percentage of antibiotic use for COPD patients was 98.4%, which was 7.88 (95%CI: 5.24-11.85) times of that for non-COPD patients after adjusting for potential confounders. The prescribing rate was 3220 prescriptions (95%CI: 3063.6-3385.2) per 1000 person-years for COPD patients, which was 1.96 (95%CI: 1.87-2.06) times of that for non-COPD patients. Other beta-lactam antibacterials, Macrolides, lincosamides and streptogramins, and quinolone antibacterials were the most commonly used types of antibiotic. Except for aminoglycoside antibacterials, both percentage of antibiotic use and rate of antibiotic prescription were increased in COPD patients. COPD patients were more likely to be prescribed a maximum of two antibiotics (OR=1.34, 95%CI: 1.20-1.50); and were more likely to use antibiotics intravenously (OR=2.77, 95%CI: 2.47-3.11). CONCLUSION: COPD patients were more likely to have increased antibiotic use in a large-scale population-based adult cohort, suggesting COPD patients are a high-priority group for the management of antibiotic use in communities.

Dairy products intake and prevalence, incidence, and recovery of non-alcoholic fatty liver disease in Chinese population.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a growing public health concern. Modifiable factors such as diet and lifestyle are of research interest in preventing or reversing the disease. The relationship between dairy products and NAFLD remains unclear. METHODS: In this cohort study, 36,122 participants aged 20-74 were enrolled by multi-stage, stratified, randomized cluster sampling from 2016 to 2017. A total of 25,085 participants finished at least one follow-up visit from 2019 to 2023. Dairy intake was collected by food frequency questionnaire at baseline. NAFLD was defined as fatty liver diagnosed by ultrasonography with excessive alcohol drink excluded. Logistic regression and Cox proportional hazard models were used to analyze the association between dairy intake and NAFLD. RESULTS: A total of 34,040 participants were included in the baseline analysis. The prevalence of NAFLD was inversely associated with dairy intake (OR>7vs 0 servings/week = 0.91, 95% CI 0.84-0.98; ORper serving/day increase = 0.95, 95% CI 0.92-0.99). 20,460 participants entered the follow-up analysis. Among 12,204 without NAFLD at baseline, 4,470 developed NAFLD after a median time of 4.3 years. The incidence of NAFLD was inversely associated with dairy intake (HR>7 vs 0 servings/week = 0.89, 95% CI 0.81-0.98; HRper serving/day increase = 0.94, 95% CI 0.89-0.99). Among 8256 with NAFLD at baseline, 3,885 recovered after 4.2-year follow-up. Total dairy intake did not show significant associations with recovery of NAFLD, and the HRs (95% CI) were 0.96 (0.87-1.06) for > 7 servings/week and 0.98 (0.93-1.03) for per serving/day increase. CONCLUSION: Dairy product intake of more than one serving per day was associated with a lower prevalence and incidence of NAFLD in Chinese population. However, total dairy intake did not show significant association in NAFLD reversal.

Hepatitis B core-related antigen dynamics and risk of subsequent clinical relapses after nucleos(t)ide analog cessation.

BACKGROUND/AIMS: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR). METHODS: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR. RESULTS: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5-40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7-67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1-62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12-2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21-0.81). CONCLUSION: Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.

Association of triglyceride-glucose index with cardiovascular disease among a general population: a prospective cohort study.

BACKGROUND: The impact of triglyceride-glucose (TyG) index, a surrogate marker for insulin resistance, on the risk of cardiovascular disease (CVD) in general populations remains controversial. We aimed to comprehensively study the relationship between TyG index with the risk of incident CVD events in the general population in Shanghai. METHODS: A total of 42,651 participants without previous history of CVD events from Shanghai Suburban Adult Cohort and Biobank (SSACB) were included. SSACB was a community-based natural population cohort study using multistage cluster sampling method. TyG index was calculated as Ln [fasting serum triglyceride (mg/dL) * fasting blood glucose (mg/dL)/2]. Kaplan-Meier curves, log-rank test and cox proportional hazards model were used to calculate the association between TyG index and incident CVD, including stroke and coronary heart disease (CHD). Restricted cubic spline analyses were used to determine whether there was a non-linear relationship between TyG index and CVD events. RESULTS: During a median follow-up of 4.7 years, 1,422 (3.3%) individuals developed CVD, including 674 (1.6%) cases of stroke and 732 (1.7%) cases of CHD. A one unit increment higher TyG index was associated with [HR(95%CI)] 1.16(1.04-1.29) in CVD and with 1.39(1.19-1.61) in stroke. Only linear relationships between TyG and CVD/stroke were observed, while no relationship was observed with CHD after adjustments for confounders. In subgroup analyses, younger (< 50y) and diabetic participants had higher risk of CVD than their counterpart groups, while hypertensive and dyslipidemic participants depicted lower risks than their counterparts. CONCLUSION: Elevated TyG index was associated with a higher risk of incident CVD and stroke. TyG index may help in the early stage of identifying people at high risk of CVD.

Recent advances in the structure and activation mechanisms of metabolite-releasing Pannexin 1 channels.

Pannexin 1 (PANX1) is a widely expressed large-pore ion channel located in the plasma membrane of almost all vertebrate cells. It possesses a unique ability to act as a conduit for both inorganic ions (e.g. potassium or chloride) and bioactive metabolites (e.g. ATP or glutamate), thereby activating varying signaling pathways in an autocrine or paracrine manner. Given its crucial role in cell-cell interactions, the activity of PANX1 has been implicated in maintaining homeostasis of cardiovascular, immune, and nervous systems. Dysregulation of PANX1 has also been linked to numerous diseases, such as ischemic stroke, seizure, and inflammatory disorders. Therefore, the mechanisms underlying different modes of PANX1 activation and its context-specific channel properties have gathered significant attention. In this review, we summarize the roles of PANX1 in various physiological processes and diseases, and analyze the accumulated lines of evidence supporting diverse molecular mechanisms associated with different PANX1 activation modalities. We focus on examining recent discoveries regarding PANX1 regulations by reversible post-translational modifications, elevated intracellular calcium concentration, and protein-protein interactions, as well as by irreversible cleavage of its C-terminal tail. Additionally, we delve into the caveats in the proposed PANX1 gating mechanisms and channel open-closed configurations by critically analyzing the structural insights derived from cryo-EM studies and the unitary properties of PANX1 channels. By doing so, we aim to identify potential research directions for a better understanding of the functions and regulations of PANX1 channels.

Automated phenotyping of postoperative delirium-like behaviour in mice reveals the therapeutic efficacy of dexmedetomidine.

Postoperative delirium (POD) is a complicated and harmful clinical syndrome. Traditional behaviour analysis mostly focuses on static parameters. However, animal behaviour is a bottom-up and hierarchical organizational structure composed of time-varying posture dynamics. Spontaneous and task-driven behaviours are used to conduct comprehensive profiling of behavioural data of various aspects of model animals. A machine-learning based method is used to assess the effect of dexmedetomidine. Fourteen statistically different spontaneous behaviours are used to distinguish the non-POD group from the POD group. In the task-driven behaviour, the non-POD group has greater deep versus shallow investigation preference, with no significant preference in the POD group. Hyperactive and hypoactive subtypes can be distinguished through pose evaluation. Dexmedetomidine at a dose of 25 µg kg-1 reduces the severity and incidence of POD. Here we propose a multi-scaled clustering analysis framework that includes pose, behaviour and action sequence evaluation. This may represent the hierarchical dynamics of delirium-like behaviours.

Enhanced Predictive Value of Lipid Accumulation Product for Identifying Metabolic Syndrome in the General Population of China.

The purpose of this research was to evaluate the lipid accumulation product (LAP)'s accuracy and predictive value for identifying metabolic syndrome (MS) in the general Chinese population compared with other obesity indicators. Baseline survey information from a population-based cohort study carried out in Shanghai's Songjiang District was used in this research. Odds ratios (OR) and a 95% confidence interval (CI) were obtained by logistic regression. The ability of each variable to detect MS was assessed using the receiver operating characteristic curve (ROC). The optimum cut-off point for each indicator was selected using Youden's index. The survey involved 35,446 participants in total. In both genders, the prevalence of MS rose as the LAP increased (p < 0.001). The LAP's AUC was 0.901 (95%CI: 0.895-0.906) in males and 0.898 (95%CI: 0.893-0.902) in females, making it substantially more predictive of MS than other variables (BMI, WC, WHR, WHtR). The optimal cutoff point of the LAP for men and women was 36.04 (Se: 81.91%, Sp: 81.06%) and 34.95 (Se: 80.93%, Sp: 83.04%). The Youden index of the LAP was 0.64 for both sexes. Our findings imply that the LAP, compared to other obesity markers in China, is a more accurate predictor of MS.

Factors Impacting Advance Decision Making and Health Care Agent Appointment among Taiwanese Urban Residents after the Passage of Patient Right to Autonomy Act.

In recent years, advance care planning (ACP) promotion in Taiwan has expanded beyond clinical practice to the broader population. This study aims to investigate people's attitudes toward ACP and to identify factors influencing their signing of advance directives (ADs) and appointment of health care agents (HCAs). METHODS: We identified 2337 ACP participants from consultation records between 2019 and 2020. The relationships among the participants' characteristics, AD completion, and HCA appointment were investigated. RESULTS: Of 2337 cases, 94.1% completed ADs and 87.8% were appointed HCAs. Welfare entitlement (OR = 0.47, p < 0.001), the place ACP progressed (OR = 0.08, p < 0.001), the participation of second-degree relatives (OR = 2.50, p < 0.001), and the intention of not being a family burden (OR = 1.65, p = 0.010) were significantly correlated with AD completion. The probability of appointing HCAs was higher in participants with family caregiving experience (OR = 1.42, p < 0.05), who were single (OR = 1.49, p < 0.05), and who expected a good death with dignity (OR = 1.65, p < 0.01). CONCLUSIONS: Our research shows that adopting ACP discussion in Taiwan is feasible, which encourages ACP conversation and facilitates AD completion. IMPLICATIONS: Male and younger adults may need extra encouragement to discuss ACP matters with their families. LIMITATIONS: due to sampling restrictions, our data were chosen from an urban district to ensure the integrity of the results. Furthermore, interview data could be collected in future research to supplement the quantitative results.

Estrogen-Like Effect of Bazi Bushen Capsule in Ovariectomized Rats.

This study aims to show the estrogen-like effect of Bazi Bushen capsule (BZBS), a Chinese herbal compound, in ovariectomized mice. Female Sprague-Dawley (SD) rats were randomly divided into six groups: a sham-operated group, a model group (OVX), a progynova group, and BZBS groups (1, 2, and 4 d/kg/d). An ovariectomy was performed on all rats except those in the sham-operated group. Micro-computed tomography (micro-CT) scanning, hematoxylin and eosin (H&E) staining, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) detection were performed after 4 months of BZBS treatment. As a result, compared with the OVX group, rats treated with BZBS showed an increased number and area of trabecular bone and bone marrow cells, and a decreased number of adipose cells. The bone volume, trabecular number, and trabecular thickness of the right tibia in the medication groups increased and the trabecular space decreased. The 17ß-estradiol and serum calcium levels in the medication groups were elevated, but the levels of serum phosphorus, sclerostin, ß-CTX, and TRACP-5b were decreased. In the medication groups, the RANKL and sclerostin levels were decreased, while the osteoprotegerin (OPG) level was increased. In conclusion, this protocol systematically evaluated the therapeutic effects and potential molecular mechanisms of Chinese herbal compounds in ovariectomized rats with a variety of techniques.

Association Between Magnitude of Differential Blood Pressure Reduction and Secondary Stroke Prevention: A Meta-analysis and Meta-Regression.

Importance: The degree to which more intensive blood pressure reduction is better than less intensive for secondary stroke prevention has not been delineated. Objective: To perform a standard meta-analysis and a meta-regression of randomized clinical trials to evaluate the association of magnitude of differential blood pressure reduction and recurrent stroke in patients with stroke or transient ischemic attack (TIA). Data Sources: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1, 1980, to June 30, 2022. Study Selection: Randomized clinical trials that compared more intensive vs less intensive blood pressure lowering and recorded the outcome of recurrent stroke in patients with stroke or TIA. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. Risk ratio (RR) with 95% CI was used as a measure of the association of more intensive vs less intensive blood pressure lowering with primary and secondary outcomes. The univariate meta-regression analyses were conducted to evaluate a possible moderating effect of magnitude of differential systolic blood pressure (SBP) and diastolic blood pressure (DBP) reduction on the recurrent stroke and major cardiovascular events. Main Outcomes and Measures: The primary outcome was recurrent stroke and the lead secondary outcome was major cardiovascular events. Results: Ten randomized clinical trials comprising 40 710 patients (13 752 women [34%]; mean age, 65 years) with stroke or TIA were included for analysis. The mean duration of follow-up was 2.8 years (range, 1-4 years). Pooled results showed that more intensive treatment compared with less intensive was associated with a reduced risk of recurrent stroke in patients with stroke or TIA (absolute risk, 8.4% vs 10.1%; RR, 0.83; 95% CI, 0.78-0.88). Meta-regression showed that the magnitude of differential SBP and DBP reduction was associated with a lower risk of recurrent stroke in patients with stroke or TIA in a log-linear fashion (SBP: regression slope, -0.06; 95% CI, -0.08 to -0.03; DBP: regression slope, -0.17; 95% CI, -0.26 to -0.08). Similar results were found in the association between differential blood pressure lowering and major cardiovascular events. Conclusions and Relevance: More intensive blood pressure-lowering therapy might be associated with a reduced risk of recurrent stroke and major cardiovascular events. These results might support the use of more intensive blood pressure reduction for secondary prevention in patients with stroke or TIA.

Shensong Yangxin Capsule Reduces the Susceptibility of Arrhythmia in db/db Mice via Inhibiting the Inflammatory Response Induced by Endothelium Dysfunction.

Purpose: The aim of our study was to investigate the mechanism by which the Chinese compound Shensong Yangxin Capsule (SSYX) reduces susceptibility to arrhythmia in db/db mice. Methods: The db/db mice without drug treatment served as the model group. Other-treated db/db mice were administered SSYX for 8 weeks. Electrocardiogram (ECG), electrical mapping, pathological changes, immunofluorescence staining, real-time quantitative PCR, and Western blot analyses were then conducted. Results: SSYX decreased arrhythmia susceptibility and shortened the abnormal ECG parameters of db/db mice. Meanwhile, SSYX restored irregular conduction direction and shortened the conduction time of the isolated heart. HE and Masson staining showed that SSYX alleviated inflammatory infiltration and collagen fiber deposition. Western blot showed that SSYX decreased the protein expression of ICAM-1, VCAM-1, and MCP-1 and increased the protein expression of occludin, ZO-1, eNOS, and Cx43. SSYX also increased the content of NO, decreased ET-1, TNF-α, IL-1ß, IL-6, MCP-1, and CCR-2 mRNA expression, and increased Kv 4.2, Kv 4.3, Cav 1.2, and Nav 1.5 mRNA expression. Furthermore, SSYX decreased the fluorescence intensity of F4/80 and iNOS, increased the fluorescence intensity of CD31 and eNOS, and improved the Cx43 and α-actinin connection structure in cardiac tissues. The above therapeutic effects of SSYX were inhibited by L-NAME. Conclusion: SSYX reduced the susceptibility of db/db mice to arrhythmia by inhibiting the inflammatory response and macrophage polarization, and this effect of SSYX occurred through protection of endothelial cell function.

Bazi Bushen mitigates epigenetic aging and extends healthspan in naturally aging mice.

Bazi Bushen (BZBS), a traditional Chinese medicine, has been proven effective in the treatment of age-related disease in mouse models. However, whether its therapeutic effects are due to antiaging mechanism has not yet been explored. In the present study, we investigated the antiaging effects of BZBS in naturally aging mice by using behavioral tests, liver DNA methylome sequencing, methylation age estimation, and frailty index assessment. The methylome analysis revealed a decrease of mCpG levels in the aged mouse liver. BZBS treatment tended to restore age-associated methylation decline and prune the methylation pattern toward that of young mice. More importantly, BZBS significantly rejuvenated methylation age of the aged mice, which was computed by an upgraded DNA methylation clock. These results were consistent with enhanced memory and muscular endurance, as well as decreased frailty score and liver pathological changes. KEGG analysis together with aging-related database screening identified methylation-targeted pathways upon BZBS treatment, including oxidative stress, DNA repair, MAPK signaling, and inflammation. Upregulation of key effectors and their downstream effects on elevating Sod2 expression and diminishing DNA damage were further investigated. Finally, in vitro experiments with senescent HUVECs proved a direct effect of BZBS extracts on the regulation of methylation enzymes during cellular aging. In summary, our work has revealed for the first time the antiaging effects of BZBS by slowing the methylation aging. These results suggest that BZBS might have great potential to extend healthspan and also explored the mechanism of BZBS action in the treatment of age-related diseases.

Early Antiplatelet Resumption and the Risks of Major Bleeding After Intracerebral Hemorrhage.

BACKGROUND: The appropriate timing of resuming antithrombotic therapy after intracerebral hemorrhage (ICH) remains unclear. The aim of this study was to compare the risks of major bleeding between early and late antiplatelet resumption in ICH survivors. METHODS: Between 2008 and 2017, ICH patients were available in the National Health Insurance Research Database. Patients with a medication possession ratio of antiplatelet treatment ≥50% before ICH and after antiplatelet resumption were screened. We excluded patients with atrial fibrillation, heart failure, under anticoagulant or hemodialysis treatment, and developed cerebrovascular events or died before antiplatelet resumption. Finally, 1584 eligible patients were divided into EARLY (≤30 days) and LATE groups (31-365 days after the index ICH) based on the timing of antiplatelet resumption. Patients were followed until the occurrence of a clinical outcome, end of 1-year follow-up, death, or until December 31, 2018. The primary outcome was recurrent ICH. The secondary outcomes included all-cause mortality, major hemorrhagic events, major occlusive vascular events, and ischemic stroke. Cox proportional hazard model after matching was used for comparison between the 2 groups. RESULTS: Both the EARLY and LATE groups had a similar risk of 1-year recurrent ICH (EARLY versus LATE: 3.12% versus 3.27%; adjusted hazard ratio [AHR], 0.967 [95% CI, 0.522-1.791]) after matching. Both groups also had a similar risk of each secondary outcome at 1-year follow-up. Subgroup analyses disclosed early antiplatelet resumption in the patients without prior cerebrovascular disease were associated with lower risks of all-cause mortality (AHR, 0.199 [95% CI, 0.054-0.739]) and major hemorrhagic events (AHR, 0.090 [95% CI, 0.010-0.797]), while early antiplatelet resumption in the patients with chronic kidney disease were associated with a lower risk of ischemic stroke (AHR, 0.065 [95% CI, 0.012-0.364]). CONCLUSIONS: Early resumption of antiplatelet was as safe as delayed antiplatelet resumption in ICH patients. Besides, those without prior cerebrovascular disease or with chronic kidney disease may benefit more from early antiplatelet resumption.