Association of frailty status with overall survival in elderly hypertensive patients: based on the Chinese Longitudinal Healthy Longevity Survey.

BACKGROUND: Hypertension and frailty often coexist in older people. The present study aimed to evaluate the association of frailty status with overall survival in elderly hypertensive patients, using data from the Chinese Longitudinal Healthy Longevity Survey. METHODS: A total of 10,493 elderly hypertensive patients were included in the present study (median age 87.0 years, 58.3% male). Frailty status was assessed according to a 36-item frailty index (FI), which divides elderly individuals into four groups: robustness (FI ≤ 0.10), pre-frailty (0.10 < FI ≤ 0.20), mild-frailty (0.20 < FI ≤ 0.30), and moderate-severe frailty (FI > 0.30). The study outcome was overall survival time. Accelerated failure time model was used to evaluate the association of frailty status with overall survival. RESULTS: During a period of 44,616.6 person-years of follow-up, 7327 (69.8%) participants died. The overall survival time was decreased with the deterioration of frailty status. With the robust group as reference, adjusted time ratios (TRs) were 0.84 (95% confidence interval [CI]: 0.80-0.87) for the pre-frailty group, 0.68 (95% CI: 0.64-0.72) for the mild frailty group, and 0.52 (95% CI: 0.48-0.56) for the moderate-severe frailty group, respectively. In addition, restricted cubic spline analysis revealed a nearly linear relationship between FI and overall survival (p for non-linearity = 0.041), which indicated the overall survival time decreased by 17% with per standard deviation increase in FI (TR = 0.83, 95% CI: 0.82-0.85). Stratified and sensitivity analyses suggested the robustness of the results. CONCLUSIONS: The overall survival time of elderly hypertensive patients decreased with the deterioration of frailty status. Given that frailty is a dynamic and even reversible process, early identification of frailty and active intervention may improve the prognosis of elderly hypertensive patients.

Integrated network pharmacology to investigate the mechanism of Salvia miltiorrhiza Bunge in the treatment of myocardial infarction.

Salvia miltiorrhiza Bunge is a natural drug for treating myocardial infarction (MI). However, the targets and mechanisms of S. miltiorrhiza Bunge in the treatment of MI are yet to be elucidated. Traditional Chinese medicine systems pharmacology (TCMSP) data were used to screen out chemical constituents, and UniProt was used to predict relevant targets. Disease targets were obtained from the Online Mendelian Inheritance in Man and GeneCards databases. We used the STRING platform to build a protein-protein interaction network and used Cytoscape_v3.8.1 software to make a Drug-Ingredients-Gene Symbols-Disease network map. The Metascape database was used to perform gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses for drug-disease overlapping gene symbols. The targets identified by network pharmacology were further verified by in vitro and in vivo experiments. Seventy-five active components of S. miltiorrhiza Bunge were obtained from the TCMSP database, while 370 disease targets and 29 cross-targets were obtained from the Genecards database. The KEGG pathway enrichment results suggested that the mechanism of S. miltiorrhiza Bunge in the treatment of MI was significantly related to the VEGF signalling pathway. In vitro and in vivo experiments were used to evaluate the reliability of some important active ingredients and targets. S. miltiorrhiza Bunge alleviated the damage to cardiac function, attenuated myocardial fibrosis and protected endothelial cell function by increasing the expression of TGF-ß and VEGFA. S. miltiorrhiza Bunge showed the therapeutic effect of MI by promoting the expression of VEGFA signalling pathway, providing a reliable basis for exploring herbal treatment of MI.

Prognostic value of albumin to fibrinogen ratio for mortality in patients with hypertrophic cardiomyopathy.

BACKGROUND: Albumin to fibrinogen ratio (AFR), a new inflammatory marker, has emerged as a useful indicator to predict adverse outcomes for several diseases. However, whether AFR could be a new useful indicator to predict mortality in HCM patients remains to be evaluated. The study explored the predictive value of AFR for HCM-related death in adult HCM patients. METHODS: A total of 404 HCM patients were eventually enrolled in the study according to the inclusion criteria. Patients were divided into two groups based on the median of baseline AFR. The association between AFR and HCM-related death was analyzed. RESULTS: During a median follow-up of 4.75 years, HCM-related death was observed in 45 patients (11.1%). The incidence of HCM-related death was significantly higher in the low AFR group (log-rank p < 0.001). With the high AFR group as reference, the unadjusted hazard ratio (HR) for HCM-related death was 2.97 (95% confidence interval [CI]: 1.53-5.75, p = 0.001) in the low AFR group, and after adjusting for potentially confounding variables, the adjusted HR for low AFR group was 3.15 (95% CI: 1.56-6.37, p = 0.001). No significant interactions between AFR and other variables were observed in subgroup analysis. Sensitivity analyses in patients with normal albumin and fibrinogen showed similar results. CONCLUSION: AFR is an independent prognostic factor for HCM-related death, adult HCM patients with a lower AFR have a higher risk of HCM-related death.

Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signaling.

Cadmium (Cd) is a ubiquitous toxic metal and environmental pollutant. Increasing studies have shown that Cd exposure increases the incidence of various endocrine system diseases, including thyrotoxicity reflected by thyroid structural damage and endocrine toxicity. However, the observed outcomes are complex and conflicting, leading to the mechanism of Cd-induced thyrotoxicity remaining obscure. In this study, 4-week-old male C57BL/6 mice were given 2 or 7 mg/kg Cadmium Chloride (CdCl2) intragastrically for 4 and 8 weeks, and the Cd-mediated thyrotoxicity was evaluated by determining alterations in thyroid structure and endocrine function, and alterations of oxidant stress, apoptosis, and pyroptosis. Our data showed that Cd exposure could reduce body weight and induce thyrotoxicity by impairing thyroid follicular morphology and endocrine function, accompanied by elevated oxidative stress and apoptosis, macrophage infiltration, and inflammatory cytokine secretion. Importantly, Cd significantly promoted thyroid follicular cell pyroptosis by increasing Nlrp3, Asc, Caspase-1, Gsdmd, IL-1ß, and IL-18 expression. Mechanistical analysis suggested that Cd treatment could inhibit antioxidant pathway by downregulating antioxidant response protein, Nrf2, and upregulating its negative feedback regulator, Keap1. Collectively, our in vivo findings suggest that Cd exposure could facilitate thyroid follicular cell pyroptosis by inhibiting Nrf2/Keap1 signaling, thereby disrupting thyroid tissue structure and endocrine function, which offers novel insights into the Cd-mediated detrimental consequences on thyroid homeostasis.

New metabolic health definition might not be a reliable predictor for mortality in the nonobese Chinese population.

BACKGROUND: Recently, a new metabolic health (MH) definition was developed from NHANES-III. In the origin study, the definition may stratify mortality risks in people who are overweight or normal weight. We aimed to investigate the association between the new MH definition and all-cause mortality in a nonobese Chinese population. METHODS: The data were collected in 1992 and then again in 2007 from the same group of 1157 participants. The association between the new MH definition and all-cause mortality were analyzed by Cox regression models with overlap weighting according to propensity score (PS) as primary analysis. RESULTS: At baseline in 1992, 920 (79.5%) participants were categorized as MH, and 237 (20.5%) participants were categorized as metabolically unhealthy (MUH) based on this new definition. During a median follow-up of 15 years, all-cause mortality occurred in 17 (1.85%) participants in MH group and 13 (5.49%) in MUH group, respectively. In the crude sample, Kaplan-Meier analysis demonstrated a significantly higher all-cause mortality in MUH group when compared to MH group (log-rank p = 0.002), and MUH was significantly associated with increased all-cause mortality when compared to MH with HR at 3.04 (95% CI: 1.47-6.25, p = 0.003). However, Kaplan-Meier analysis with overlap weighting showed that the cumulative incidence of all-cause mortality was not significantly different between MH and MUH groups (adjusted p = 0.589). Furthermore, in the primary multivariable Cox analysis with overlap weighting, adjusted HR for all-cause mortality was 1.42 (95% CI: 0.49-4.17, p = 0.519) in MUH group in reference to MH group. Other additional PS analyses also showed the incidence of all-cause mortality was not significantly different between the two groups. CONCLUSION: The new MH definition may be not appropriate for mortality risk stratification in non-obese Chinese people. Further investigations are needed.

Cadmium-coordinated supramolecule suppresses tumor growth of T-cell leukemia in mice.

Cadmium is a toxic pollutant with occupational and environmental significance, due to its diverse toxic effects. Supramolecules that conjugate and decontaminate toxic metals have potential for use in treatment of cadmium intoxication. In addition, metal-coordinating ability has been postulated to contribute to the cytotoxic effects of anti-tumor agents such as cisplatin or bleomycin. Thiacalixarenes, cyclic oligomers of p-alkylphenol bridged by sulfur atoms, are supramolecules known to have potent coordinating ability to metal ions. In this study, we show that cadmium-coordinated thiacalix[4]arene tetrasulfate (TC4ATS-Cd) exhibits an anti-proliferative effect against T-cell leukemia cells. Cadmium exhibited cytotoxicity with IC50 values ranging from 36 to 129 µM against epithelia-derived cancer cell lines, while TC4ATS-Cd elicited no significant cytotoxicity (IC50 > 947 µM). However, a number of T-cell leukemia cell lines exhibited marked sensitivity to TC4ATS-Cd. In Jurkat cells, toxicity of TC4ATS-Cd occurred with an IC50 of 6.9 µM, which is comparable to that of 6.5 µM observed for cadmium alone. TC4ATS-Cd induced apoptotic cell death through activation of caspase-3 in Jurkat cells. In a xenograft model, TC4ATS-Cd (13 mg/kg) treatment significantly suppressed the tumor growth of Jurkat cells in mice. In addition, TC4ATS-Cd-treated mice exhibited significantly less cadmium accumulation in liver and kidney compared to equimolar cadmium-treated mice. These results suggest that cadmium-coordinated supramolecules may have therapeutic potential for treatment of T-cell leukemia.

Assessing the relationship between monocyte-to-HDL cholesterol ratio and mortality in patients with hypertrophic cardiomyopathy.

OBJECTIVE: A new inflammatory marker, namely monocyte-to-high-density lipoprotein cholesterol ratio (MHR), has emerged as a useful indicator for adverse outcomes in several cardiovascular diseases; however, the relationship between MHR and the prognosis of hypertrophic cardiomyopathy (HCM) remains to be evaluated. We examined the relationship between MHR and all-cause mortality (ACM) in Chinese adult patients with HCM. METHODS: We retrospectively performed clinical evaluation in 305 patients with HCM (median age: 52.0 years, male: 54.10%). RESULTS: During a median follow-up of 4.9 years, ACM occurred in 57 (18.7%) patients. Based on the tertiles of baseline MHR, ACM increased with higher tertile. With tertile 1 as reference, adjusted ACM hazard ratios (HRs) were 2.68 for tertile 2 (95% confidence interval [CI]: 1.18-6.11, p = 0.019) and 4.85 for tertile 3 (95% CI: 2.16-10.89, p < 0.001). Stratified analysis and E-value analysis suggested the robustness of the above-mentioned results. Furthermore, adjusted smooth curve fitting exhibited a non-linear relationship between MHR and ACM (inflection point: 0.5), and the risk of ACM increased significantly with higher MHR only the value below the inflection point (HR: 4.37 per one standard deviation, 95% CI: 1.81-10.6, p = 0.001). Finally, sensitivity analysis was similar to the main findings. CONCLUSION: In Chinese adult patients with HCM, higher MHR is a strong independent predictor of ACM, and a non-linear relationship is also observed between MHR and ACM.

Hypertension in frail older adults: current perspectives.

Hypertension is one of the most common chronic diseases in older people, and the prevalence is on the rise as the global population ages. Hypertension is closely associated with many adverse health outcomes, including cardiovascular disease, chronic kidney disease and mortality, which poses a substantial threat to global public health. Reasonable blood pressure (BP) management is very important for reducing the occurrence of adverse events. Frailty is an age-related geriatric syndrome, characterized by decreased physiological reserves of multiple organs and systems and increased sensitivity to stressors, which increases the risk of falls, hospitalization, fractures, and mortality in older people. With the aging of the global population and the important impact of frailty on clinical practice, frailty has attracted increasing attention in recent years. In older people, frailty and hypertension often coexist. Frailty has a negative impact on BP management and the prognosis of older hypertensive patients, while hypertension may increase the risk of frailty in older people. However, the causal relationship between frailty and hypertension remains unclear, and there is a paucity of research regarding the efficacious management of hypertension in frail elderly patients. The management of hypertension in frail elderly patients still faces significant challenges. The benefits of treatment, the optimal BP target, and the choice of antihypertensive drugs for older hypertensive patients with frailty remain subjects of ongoing debate. This review provides a brief overview of hypertension in frail older adults, especially for the management of BP in this population, which may help in offering valuable ideas for future research in this field.

Advances in the study of vascular related protective effect of garlic (Allium sativum) extract and compounds.

Garlic (Allium sativum) is a functional food containing multiple bioactive compounds that find widespread applications in culinary and medicinal practices. It consists of multiple chemical components, including allicin and alliin. This article offers a comprehensive review of the protective effects of garlic extracts and their active constituents on the vascular system. In vitro and in vivo experiments have shown that garlic extracts and their active ingredients possess various bioactive properties. These substances demonstrate beneficial effects on blood vessels by demonstrating anti-inflammatory and antioxidant activities, inhibiting lipid accumulation and migration, preventing lipid peroxidation, promoting angiogenesis, reducing platelet aggregation, enhancing endothelial function, and inhibiting endothelial cell apoptosis. In clinical studies, garlic and its extracts have demonstrated their efficacy in managing vascular system diseases, including atherosclerosis, diabetes, and high cholesterol levels. In summary, these studies highlight the potential therapeutic roles and underlying mechanisms of garlic and its constituents in managing conditions like diabetes, atherosclerosis, ischemic diseases, and other vascular disorders.

Identification of Circulating Plasma Proteins as a Mediator of Hypertension-Driven Cardiac Remodeling: A Mediation Mendelian Randomization Study.

BACKGROUND: This study focused on circulating plasma protein profiles to identify mediators of hypertension-driven myocardial remodeling and heart failure. METHODS: A Mendelian randomization design was used to investigate the causal impact of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure on 82 cardiac magnetic resonance traits and heart failure risk. Mediation analyses were also conducted to identify potential plasma proteins mediating these effects. RESULTS: Genetically proxied higher SBP, DBP, and pulse pressure were causally associated with increased left ventricular myocardial mass and alterations in global myocardial wall thickness at end diastole. Elevated SBP and DBP were linked to increased regional myocardial radial strain of the left ventricle (basal anterior, mid, and apical walls), while higher SBP was associated with reduced circumferential strain in specific left ventricular segments (apical, mid-anteroseptal, mid-inferoseptal, and mid-inferolateral walls). Specific plasma proteins mediated the impact of blood pressure on cardiac remodeling, with FGF5 (fibroblast growth factor 5) contributing 2.96% (P=0.024) and 4.15% (P=0.046) to the total effect of SBP and DBP on myocardial wall thickness at end diastole in the apical anterior segment and leptin explaining 15.21% (P=0.042) and 23.24% (P=0.022) of the total effect of SBP and DBP on radial strain in the mid-anteroseptal segment. Additionally, FGF5 was the only mediator, explaining 4.19% (P=0.013) and 4.54% (P=0.032) of the total effect of SBP and DBP on heart failure susceptibility. CONCLUSIONS: This mediation Mendelian randomization study provides evidence supporting specific circulating plasma proteins as mediators of hypertension-driven cardiac remodeling and heart failure.

Effect of Astragaloside IV on improving cardiac function in rats with heart failure: a preclinical systematic review and meta-analysis.

Background: Astragaloside IV (ASIV) is the primary pharmacologically active compound found in Astragalus propinquus Schischkin, which has potential protective effects on cardiac function. However, there are almost no systematic evaluations of ASIV for the treatment of heart failure (HF). Methods: Preclinical studies published before 27 December 2022, were retrieved from PubMed, Web of Science, MEDLINE, SinoMed, Chinese National Knowledge Infrastructure (CNKI), VIP information database, and Wanfang Data information site. The quality of included research was evaluated using SYRCLE's RoB tool. Review Manager 5.4.1 was used to perform meta-analyses of the cardiac function parameters and other indicators. Regression analysis was conducted to observe the dose-efficacy relationship. Results: Nineteen studies involving 489 animals were included. Results indicated that compared with the control group, ASIV could enhance cardiac function indicators, including left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular pressure change rate (±dp/dtmax), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), heart weight/body weight (HW/BW) and left ventricular weight/body weight (LVW/BW). Furthermore, the regression analysis showed that the treatment of HF with ASIV was dose-dependent. Conclusion: Findings suggest that ASIV can inhibit cardiac hypertrophy by reducing cardiac preload and afterload, thereby protecting cardiac function.

Advances in the study of the vascular protective effects and molecular mechanisms of hawthorn (Crataegus anamesa Sarg.) extracts in cardiovascular diseases.

Hawthorn belongs to the rose family and is a type of functional food. It contains various chemicals, including flavonoids, terpenoids, and organic acid compounds. This study aimed to review the vascular protective effects and molecular mechanisms of hawthorn and its extracts on cardiovascular diseases (CVDs). Hawthorn has a wide range of biological functions. Evidence suggests that the active components of HE reduce oxidative stress and inflammation, regulate lipid levels to prevent lipid accumulation, and inhibit free cholesterol accumulation in macrophages and foam cell formation. Additionally, hawthorn extract (HE) can protect vascular endothelial function, regulate endothelial dysfunction, and promote vascular endothelial relaxation. It has also been reported that the effective components of hawthorn can prevent age-related endothelial dysfunction, increase cellular calcium levels, cause antiplatelet aggregation, and promote antithrombosis. In clinical trials, HE has been proved to reduce the adverse effects of CVDs on blood lipids, blood pressure, left ventricular ejection fraction, heart rate, and exercise tolerance. Previous studies have pointed to the benefits of hawthorn and its extracts in treating atherosclerosis and other vascular diseases. Therefore, as both medicine and food, hawthorn can be used as a new drug source for treating cardiovascular diseases.

The impact of hypertension on the prognosis of patients with hypertrophic cardiomyopathy: a single-center retrospective study.

Background: Hypertrophic cardiomyopathy (HCM) and hypertension coexist fairly frequently in clinical practice. However, the evidence about the impact of hypertension on the prognosis of HCM is limited. The present study aims to investigate the impact of hypertension on the prognosis of HCM patients. Methods: A total of 468 HCM patients were enrolled, and patients were divided into hypertension group (31.8%) and non-hypertension group (68.2%). The primary study endpoint was HCM-related death, consisting of heart failure (HF)-related death, stroke-related death and sudden cardiac death (SCD). Associations between hypertension and HCM-related death were analyzed by Cox regression models with the use of propensity score matching (PSM) as primary analysis. Results: There were 55 HCM-related death during a median follow-up time of 4.6 years, and the mortality rate was 2.53 per 100 person years. Kaplan-Meier analysis based on the crude cohort or PSM cohort revealed no significant difference regarding the HCM-related death between the two groups. In the crude cohort, both univariable and multivariable Cox regression analysis indicated that hypertension was not significantly associated with HCM-related death with hazard ratios (HR) at 0.74 (95% CI [0.40-1.36], p value: 0.329) and 0.77 (95% CI [0.35-1.71], p value: 0.521), respectively. Similarly, no strong evidence for an association was observed between hypertension and HCM-related death in the PSM cohort with unadjusted HR at 0.90 (95% CI [0.34-2.41]; p value: 0.838) and adjusted HR at 0.77 (95% CI [0.35-1.71]; p value: 0.521), respectively. Other propensity score methods, including overlap weighting and inverse probability treatment weighting demonstrated similar results. Sensitivity analysis also indicated that the concomitant hypertension did not significantly increase the risk of HF-related death, stroke-related death or SCD in HCM patients. Conclusion: HCM-related death did not significantly differ between hypertension and non-hypertension groups, suggesting a negative impact of hypertension on the clinical prognosis of HCM patients.

Changes in daily sleep duration and subsequent risk of mortality among older people.

BACKGROUND: Single self-reported measures of daily sleep duration are associated with adverse health outcomes; however, the association between changes in daily sleep duration and all-cause mortality has not been thoroughly evaluated among a large group of older people. METHODS: Using data from the Chinese Longitudinal Healthy Longevity Surveys, a total of 8588 older participants were included in the present study. Changes in daily sleep duration were assessed using annual changes, and Cox regression analysis examined the association of the annual changes with mortality. RESULTS: The median age of the study population was 82.00 (IQR: 72.00, 90.00) years, and 3974 (46.27%) participants were men. During a median follow-up period of 3.81 (IQR: 2.03, 6.74) years, 5100 (59.39%) deaths were recorded. After adjusting for initial daily sleep duration and other confounders, there was a non-linear relationship between annual changes in daily sleep duration and all-cause mortality. Annual changes were not associated with mortality before 0.0 h/year, and mortality risk increased after 0.0 h/year, specially after 1 h/year (adjusted HR: 1.32 per 1-hour/year increment, 95% CI: 1.18-1.47). Compared to the stable group (annual changes between -1 and 1 h), adjusted HRs for mortality were 0.98 (95% CI: 0.89-1.08) for the shorter group (annual decline more than 1 h) and 1.29 (95% CI: 1.19-1.41) for the longer group (annual increase greater than 1 h), respectively. Stratified and sensitivity analyses suggested robustness of the results. CONCLUSIONS: The present study suggested there was a non-linear relationship between annual changes in daily sleep duration and all-cause mortality among older people: longer changes were associated with higher mortality; while, shorter changes were not associated with mortality. Specially, mortality risk increased significantly with longer than 1 h of annual changes. The findings highlight the importance of closely monitoring the changes in daily sleep duration among older people.

Mechanisms of action and synergetic formulas of plant-based natural compounds from traditional Chinese medicine for managing osteoporosis: a literature review.

Osteoporosis (OP) is a systemic skeletal disease prevalent in older adults, characterized by substantial bone loss and deterioration of microstructure, resulting in heightened bone fragility and risk of fracture. Traditional Chinese Medicine (TCM) herbs have been widely employed in OP treatment owing to their advantages, such as good tolerance, low toxicity, high efficiency, and minimal adverse reactions. Increasing evidence also reveals that many plant-based compounds (or secondary metabolites) from these TCM formulas, such as resveratrol, naringin, and ginsenoside, have demonstrated beneficial effects in reducing the risk of OP. Nonetheless, the comprehensive roles of these natural products in OP have not been thoroughly clarified, impeding the development of synergistic formulas for optimal OP treatment. In this review, we sum up the pathological mechanisms of OP based on evidence from basic and clinical research; emphasis is placed on the in vitro and preclinical in vivo evidence-based anti-OP mechanisms of TCM formulas and their chemically active plant constituents, especially their effects on imbalanced bone homeostasis regulated by osteoblasts (responsible for bone formation), osteoclasts (responsible for bone resorption), bone marrow mesenchymal stem cells as well as bone microstructure, angiogenesis, and immune system. Furthermore, we prospectively discuss the combinatory ingredients from natural products from these TCM formulas. Our goal is to improve comprehension of the pharmacological mechanisms of TCM formulas and their chemically active constituents, which could inform the development of new strategies for managing OP.

Mortality Risk in Older People Who Drank Alcohol in the Past by Varying Duration of Alcohol Abstention.

INTRODUCTION: This study aims to explore the mortality risk in older people who drank alcohol in the past by varying the duration of alcohol abstention. METHODS: In total, 31,999 participants aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey (Waves 1998, 2000, 2002, 2005, 2008, 2011, 2014) were included. Duration of alcohol abstention was assessed by designed questions, and the study outcome was all-cause mortality. Cox proportional hazard models were used to examine the association. Analyses occurred from 2022 to 2023. RESULTS: During a follow-up of 140,974.8 person-years, all-cause mortality occurred in 24,257 participants. Mortality significantly increased by 23% (adjusted hazard ratio=1.23, 95% CI=1.14, 1.33, p<0.001), by 17% (adjusted hazard ratio=1.17, 95% CI=1.06, 1.31, p=0.003), and by 17% (adjusted hazard ratio=1.17, 95% CI=1.07, 1.28, p=0.001) in people who drank alcohol in the past with ≤5 years, 5-10 years, 10-20 years of alcohol abstention, respectively, compared with that among those who drink alcohol at present. After 20 years of alcohol abstention, the increased mortality risk disappeared (adjusted hazard ratio=1.06, 95% CI=0.97, 1.15, p=0.204). Stratified and sensitivity analysis revealed similar results. In addition, compared with the risk of all-cause mortality among people who never drink alcohol, the risk of all-cause mortality in those who drank alcohol in the past also significantly increased in the following 20 years after they stop drinking, and then the increased risk disappeared afterward. CONCLUSIONS: An increased risk of all-cause mortality in older people who drank alcohol in the past was observed, which disappeared after 20 years of alcohol abstention.

Magnetic molecularly-imprinted microspheres with a core-shell structure for the extraction of catalpol from both Rehmannia glutinosa Libosch and biological samples.

We report on the successful development of a magnetic molecularly imprinted polymer (MMIP) for the separation and detection of catalpol in Rehmannia glutinosa extract and biological samples. Catalpol was used as the template molecule for the MMIPs, which were synthesized using the reverse prediction approach and differential UV-visible spectra to optimize the synthesis conditions. The resulting MMIPs were characterized using techniques including scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry, which confirmed their excellent nuclear shell construction and simple rapid magnetic separation. Static and dynamic adsorption experiments were performed to assess the sensitivity, repeatability, and adsorption capacity of the MMIPs. Adsorption capacity was found to be high (59.09 µg/mg). The MMIPs also exhibited strong identification specificity for catalpol analogs (IF = 2.41). Magnetic solid phase extraction (MSPE) was optimized to establish an MSPE-HPLC approach based on the MMIPs. Under ideal conditions, the new method showed excellent determination coefficient (R2 > 0.99) in the ranges of 0.1-1.0 mg/mL and 0.03-0.18 mg/mL for R. glutinosa extract and biological material, respectively, with limits of detection of 5.4 ng/mL and 1.7 ng/mL. The novelty of this research lies in the preparation of magnetic surface MMIPs using a magnetic carrier. These MMIPs exhibit excellent magnetic properties and possess specific adsorption capability for catalpol, enabling rapid separation. They offer advantages such as low cost, high specificity, chemical stability, physical robustness, and recyclability (97.09%-106.53%, 91.32%-100.99%). The application of these polymers in the pretreatment method for determining the catalpol content in R. glutinosa extract and biological samples enhances the extraction efficiency and detection accuracy for catalpol. It eliminates interference and influences from other components in catalpol determination while exhibiting high sensitivity, good enrichment effects, excellent reusability, and a high recovery rate.

Anti-melanogenesis effect of Glechoma hederacea L. extract on B16 murine melanoma cells.

Glechoma hederacea L. (Labiatae) has been used in folk medicine to treat various ailments for centuries. We investigated the effects of G. hederacea extract on melanogenesis in B16 melanoma cells. It significantly reduced both the cellular melanin content and tyrosinase activity in a concentration-dependent manner. An MTT assay did not reveal any obvious cytotoxicity. Furthermore, we found that G. hederacea extract decreased tyrosinase and microphthalmia-associated transcription factor protein expression, but did not inhibit tyrosinase-related protein-1 and tyrosinase-related protein-2 expression. RT-PCR analysis indicated that the antimelanogenic effect of G. hederacea extract might be due to inhibition of tyrosinase gene transcription. Moreover, this effect is regulated via suppression of microphthalmia-associated transcription factor protein expression. Our data indicate that G. hederacea extract inhibits melanin synthesis in B16 melanoma cells but is not cytotoxic. Hence it might prove a useful therapeutic agent for treating hyperpigmentation and an effective component of whitening cosmetics.

Association between acupuncture and grade 1 hypertension: A systematic review and meta-analysis.

BACKGROUND: Acupuncture is a traditional therapy that can be potentially effective for treating high blood pressure. Grade 1 hypertension is a relatively mild form of hypertension. This meta-analysis aims to assess the efficacy and safety of acupuncture in patients with grade 1 hypertension. METHODS: We systematically searched the EMBASE, PubMed, Cochrane, China National Knowledge Infrastructure, and Wan Fang databases for randomised controlled trials investigating acupuncture therapy for grade 1 hypertension through March 2021. The primary outcomes were changes in blood pressure after acupuncture and efficacy of acupuncture. The secondary result was an adverse reaction to the treatment. Data were pooled and analysed using Review Manager 5.3 and Statistical Package for the Social Sciences software version 19.0. RESULTS: Ten randomised controlled trials involving 1196 patients were included. Our meta-analysis demonstrated that in terms of changes in systolic blood pressure (MD 3.62 mmHg; 95% CI, 1.34 to 5.90; I2 = 56%), diastolic blood pressure (MD 3.12 mmHg; 95% CI, 1.03 to 5.20; I2 = 77%), and treatment efficacy (RR 2.12; 95% CI, 1.38 to 3.26; I2 = 93%), acupuncture is more effective in treating grade 1 hypertension than a placebo, no treatment at all, or interventions that improve lifestyle alone, with a low incidence of adverse effects. However, we did not find a suitable subgroup to reduce heterogeneity. Interventions, acupuncture methods, and treatment courses were not the only sources of heterogeneity among the studies. CONCLUSION: Existing evidence shows that acupuncture could be used for treating hypertension; however, higher-quality randomised controlled trials are needed to better evaluate the safety and efficacy of acupuncture.

Astragalus propinquus schischkin and Salvia miltiorrhiza bunge promote angiogenesis to treat myocardial ischemia via Ang-1/Tie-2/FAK pathway.

Astragalus propinquus Schischkin and Salvia miltiorrhiza Bunge (AS) have been clinically used as adjunctive drugs in the treatment of myocardial ischemia (MI). However, the effect and mechanism of AS on MI have yet to be fully recognized. Here, we explored the cardioprotective effect of their combined use, and the mechanism of promoting angiogenesis through pericyte recruitment. Our data revealed that AS reduced MI and protects cardiac function. AS-treated MI mice exhibited reduced ST-segment displacement and repolarization time, increased ejection fraction, and less BNP and NT-proBNP expression. Pathological studies showed that, AS reduced the area of infarcted myocardium and slowed down the progress of cardiac remodelling and fibrosis. In addition, AS increased the content of platelet-derived growth factor receptors ß (PDGFR-ß), platelet endothelial cell adhesion molecule-1 (CD31) and angiogenesis-related proteins including vascular endothelial cadherin (VE-cadherin), Vascular Endothelial Growth Factor (VEGF) and transforming growth factor ß (TGF-ß). Moreover, these botanical drugs upregulated the expression of Angiopoietin-1 (Ang-1), phosphorylated angiopoietin-1 receptor (p-Tie-2), focal adhesion kinase (FAK) and growth factor receptor bound protein 7 (GRB7), indicating that the cardioprotection-related angiogenesis effect was related to pericyte recruitment, which may be through Ang-1/Tie-2/FAK pathway. In summary, AS can treat MI by protecting cardiac function, attenuating cardiac pathological changes, and hindering the progression of heart failure, which is related to angiogenesis after pericyte recruitment. Therefore, AS at a certain dose can be a promising treatment for MI with broad application prospects.