Background and aimMyocardial infarction (MI) is a leading cause of death globally, and traditional Chinese medicine (TCM) offers therapeutic potential through its multi-targeted approach. This study aims to investigate the protective mechanisms of Qing-Xin-Jie-Yu Granule (QXJYG) against MI.MethodsNetwork pharmacology was carried out to predict targets and pathways of QXJYG in the treatment of MI. An in vivo mouse model of MI was induced via left anterior descending coronary artery ligation, and hypoxia-induced H9C2 cells were performed as the in vitro model. Cardiac function was assessed by echocardiography, while histological changes were analyzed using HE and Masson's trichrome staining. The positive expression of CD31 was used to assess microvascular density in the hearts of MI mice via immunohistochemistry. Serum levels of superoxide dismutase (SOD), lactate dehydrogenase (LDH), and malondialdehyde (MDA) were evaluated, alongside LDH and MDA in cell culture supernatants. Apoptosis in cardiac tissue was detected by TUNEL staining, while apoptosis in hypoxia-induced H9C2 cells was assessed using Annexin V/PI and Hoechst 33,258 staining. Western blot analysis was conducted to evaluate the protein expression of p-p38 MAPK, p38 MAPK, Bcl-2, Bax in vivo and in vitro experiments.ResultsGO and KEGG analyses suggest that QXJYG affects potential targets related to cellular oxidative stress and apoptosis in MI. In vivo, QXJYG effectively enhanced cardiac function, increased microvessel density, lowered serum LDH and MDA levels, elevated serum SOD levels, and reduced apoptosis in cardiac tissue. It also suppressed the ratio of p-p38 MAPK/p38 MAPK, downregulated Bax protein expression, and upregulated Bcl-2 protein expression in MI mice. In vitro experiments revealed that QXJYG decreased LDH and MDA levels in the culture supernatants, reduced hypoxia-induced apoptosis, inhibited the ratio of p-p38 MAPK/p38 MAPK, decreased Bax protein expression, and enhanced Bcl-2 protein expression. The p38 MAPK inhibitor SB203580 and QXJYG combination more effectively reduced MDA levels and apoptosis in hypoxia-induced H9C2 cells than QXJYG alone.ConclusionsThis study demonstrates that QXJYG exerts cardioprotective effects against MI by improving cardiac function, reducing oxidative stress, and inhibiting apoptosis through the regulation of the p38 MAPK signaling pathway both in vivo and in vitro.

Context Qing-Xin-Jie-Yu Granule (QXJYG) has shown promise in the treatment of myocardial infarction. However, the mechanism of action of QXJYG underlying its anti-inflammation remain unknown.Objective The study aimed to evaluate the effectiveness and mechanism of QXJYG in a mouse model of myocardial infarction and hypoxia-induced H9C2 cells.Materials and methods Myocardial infarction was induced in mice via left anterior descending coronary artery ligation, and hypoxia-induced H9C2 cells was served as the in vitro model. The cardiac function was evaluated by echocardiography, while myocardial tissue pathology was examined using HE and Masson’s trichrome staining. Changes in serum markers of cardiac injury were measured using ELISA kits. The levels of inflammatory cytokines in both the serum and cardiac tissue were quantified using the Bio-Plex Pro Mouse Chemokine assay, and hypoxia-induced inflammatory factors in H9C2 cells were assessed by RT-qPCR. Additionally, western blot analysis was conducted to evaluate the expression of proteins related to the MK2/TTP signaling pathway both in vivo and in vitro experiments.Results QXJYG significantly enhanced cardiac function in mice with myocardial infarction, as evidenced by improved myocardial tissue structure, reduced collagen fiber deposition, and lowered serum levels of creatine kinase isoenzyme MB (CK-MB), cardiac Troponin T (cTnT), and brain Natriuretic Peptide (BNP). QXJYG may reduce the expression of inflammatory factors in both the heart and serum of myocardial infarction-induced mice and attenuate hypoxia-induced levels of inflammatory factors in cardiomyocytes by decreasing the ratio of p-MK2/MK2 and increasing the protein expression of TTP.Discussion and conclusions QXJYG improved cardiac function and reduced injury, fibrosis, and inflammation after myocardial infarction, likely through modulation of the MK2/TTP signaling pathway.

Hypertension onset is linked to sleep, but the precise sleep duration affecting it remains unclear. Our goal is to pinpoint the sleep duration impacting hypertension incidence, offering valuable insights for prevention and management. We conducted a systematic search in PubMed, Embase, Web of Science, CNKI, Cqvip, and Wanfang Database, up to May 30, 2023, focusing on cohort studies examining the association between nighttime sleep duration and hypertension risk in adults aged 18 and above. Two authors independently performed data extraction, quality assessment, and synthesis based on predefined criteria. A random-effects model was used to estimate pooled effect sizes with 95

The treatment of diabetic abscess remains highly challenging due to the complex wound healing environment, which includes bacterial infection, hypoxia, and pain, severely compromising patients' quality of life. Developing effective treatment strategies to address these multifaceted issues continues to pose significant challenges. In this study, a glucose-triggered gel with self-producing oxygen, photodynamic behavior, and analgesic properties is employed to address the aforementioned problems. The gel utilizes the cascade reaction of glucose oxidase and catalase to convert the excessive glucose in diabetic abscess tissue into oxygen, alleviate the hypoxia in the infected tissue, and ensure the occurrence of hypoxia photodynamic behavior to generate sufficient reactive oxygen species (ROS) to combat pathogenic bacteria. Simultaneously, borneol within the gel can not only enhance the sensitivity of bacteria to ROS by regulating the oxidative stress system but also augment the antibacterial effect of ROS. Moreover, borneol can serve as an analgesic to alleviate pain in patients. In vivo experiments have demonstrated that the combination of photodynamic and borneol therapy can eliminate the bacteria at the abscess site and enable the abscess to heal completely within 12 days. Therefore, this study established a glucose-responsive gel for a combined therapy strategy of hypoxic improvement photodynamic therapy and borneol to facilitate wound healing in diabetic abscesses.

Hypertension represents a significant chronic non-infectious disease in China, where Qingda Granule (QDG) has traditionally been employed for its management. However, the mechanisms underlying QDG’s kidney protective effects remain incompletely understood. This study investigates QDG’s role in ameliorating hypertensive kidney injury (KI) and elucidates the associated mechanisms. Network analysis identified potential therapeutic targets related to mitochondrial function and the extracellular signal-regulated kinase (ERK) cascade. Ribonucleic acid (RNA) sequencing revealed differentially expressed genes (DEGs) in hypertensive mouse kidneys, which were enriched in mitochondrial-related functions and normalized by QDG treatment. QDG attenuated angiotensin II (Ang II)-induced blood pressure elevation and enhanced renal artery flow. Both cellular and animal experiments demonstrated that QDG inhibits the ERK/ribosomal S6 kinase 1 (RSK1) signaling axis, thereby preventing Ang II-induced mitochondrial damage and renal cell apoptosis. ERK pathway inhibitors confirmed QDG’s mechanism of action through the ERK/RSK1 pathway. These findings indicate that QDG ameliorates hypertensive KI by preserving mitochondrial function through modulation of the ERK/RSK1 network, presenting a novel therapeutic approach for managing hypertensive KI in clinical practice.

Bladder cancer, the ninth most prevalent cancer, is difficult to diagnose and cure. Cystoscopy and urine cytology are used to diagnose bladder cancer, but they are invasive, expensive, and insensitive to early-stage cancers. Surgery, chemotherapy, and immunotherapy for bladder cancer are limited by systemic toxicity, drug resistance, and high recurrence rates. Thus, nanotechnology has revolutionized these issues with novel solutions. Nanoparticles’ physicochemical qualities improve MRI and fluorescence imaging sensitivity and specificity. Gold nanoparticles and quantum dots can visualize bladder cancer biomarkers in real time, making them promising functionalized nanoparticles for early detection of bladder cancer. Liposomes, polymeric nanoparticles, and dendrimers act as nanocarriers to deliver chemotherapeutic drugs targeted, regulated, and sustainably, decreasing systemic side effects and boosting therapeutic efficacy. Nanotechnology-driven immune checkpoint inhibition and nanovaccines boost anti-tumor immunity. Theranostic systems combine diagnostic and therapeutic functions into a single system for real-time monitoring and individualized response. This review discusses recent nanotechnology advances in heteranostics and theranostics for bladder cancer detection and therapy, and their ability to overcome current limits. However, nanoparticle biocompatibility, scalability, and control issues persist. The mainstreaming of nanotechnology in bladder cancer management requires interdisciplinary collaboration and research innovation to overcome these limitations and improve patient outcomes and precision medicine.

Coronary microvascular dysfunction (CMD) represents a principal etiological factor in ischemic heart disease. Nonetheless, a considerable subset of CMD patients experiences diagnostic delays attributable to the inadequacy of current diagnostic methodologies; which in turn results in deferred therapeutic interventions and elevated mortality rates. This study seeks to elucidate the distinct metabolic profile associated with CMD in rat models and to identify specific diagnostic markers that could enhance the diagnostic accuracy for CMD. In this study, 18 Wistar rats were randomly allocated into two groups: the sham group and the CMD group. The CMD group received injections of embolic microspheres into the left ventricle to establish a CMD model. Subsequently, non-targeted metabolomics and acetylated proteomics analyses were conducted. Machine-learning techniques were employed to identify the co-diagnostic markers of the disease. This study identified 53 key proteins through differential expression proteins (DEPs) and modular proteins analysis. Subsequently, four core proteins (Emc1; Ank1; Fbln2; and Hp) were determined as diagnostic markers for CMD using lasso regression, support vector machine, and random forest methodologies. Receiver operating characteristic curve analysis further demonstrated robust diagnostic performance. Gene ontology and kyoto encyclopedia of genes and genome enrichment analyses indicated that the DEPs were predominantly associated with metabolic pathways. Ultimately, the integrative analysis of proteomics and metabolomics suggested that the central metabolic mechanism underlying CMD pathogenesis may be linked to the tricarboxylic acid cycle. This study revealed specific changes in the proteomic and metabolic profiles of CMD rats and identified four diagnostic markers, which are proteins and metabolites that could be potential diagnostic biomarkers for CMD.

Ethnopharmacological relevance: Qingda granule (QDG) is effective for treating hypertension and neuronal damage after cerebral ischemia/reperfusion. However, the anti-neuroinflammatory effect of QDG on injury due to cerebral ischemia/reperfusion is unclear. Aim of the study: The objective was to evaluate the effectiveness and action of QDG in treating neuroinflammation resulting from cerebral ischemia/reperfusion-induced injury. Materials and methods: Network pharmacology was used to predict targets and pathways of QDG. An in vivo rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) as well as an in vitro model of LPS-stimulated BV -2 cells were established. Magnetic resonance imaging (MRI) was used to quantify the area of cerebral infarction, with morphological changes in the brain being assessed by histology. Immunohistochemistry (IHC) was used to assess levels of the microglial marker IBA -1 in brain tissue. Bioplex analysis was used to measure TNF-alpha, IL-1 beta, IL -6, and MCP -1 in sera and in BV -2 cell culture supernatants. Simultaneously, mRNA levels of these factors were examined using RT-qPCR analysis. Proteins of the TLR4/NF-kappa B/NLRP3 axis were examined using IHC in vivo and Western blot in vitro, respectively. While NF-kappa B translocation was assessed using immunofluorescence. Results: The core targets of QDG included TNF, NF-kappa B1, MAPK1, MAPK3, JUN, and TLR4. QDG suppressed inflammation via modulation of TLR4/NF-kappa B signaling. In addition, our in vivo experiments using MCAO/R rats demonstrated the therapeutic effect of QDG in reducing brain tissue infarction, improving neurological function, and ameliorating cerebral histopathological damage. Furthermore, QDG reduced the levels of TNF-alpha, IL-1 beta, IL -6, and MCP -1 in both sera from MCAO/R rats and supernatants from LPS-induced BV -2 cells, along with a reduction in the expression of the microglia biomarker IBA -1, as well as that of TLR4, MyD88, p-IKK, p-I kappa B alpha, p -P65, and NLRP3 in MCAO/R rats. In LPS-treated BV -2 cells, QDG downregulated the expression of proinflammatory factors and TLR4/NF-kappa B/NLRP3 signaling -related proteins. Additionally, QDG reduced translocation of NF-kappa B to the nucleus in both brains of MCAO/R rats and LPS-induced BV -2 cells. Moreover, the combined treatment of the TLR4 inhibitor TAK242 and QDG significantly reduced the levels of p -P65, NLRP3, and IL -6. Conclusions: QDG significantly suppressed neuroinflammation by inhibiting the TLR4/NF-kappa B/NLRP3 axis in microglia. This suggests potential for QDG in treating ischemia stroke.

BACKGROUND:The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS:In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS:Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION:QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION:ChiCTR2000033890.

5-Fluorouracil (5-FU) is one of the most commonly prescribed anticancer agents. However, intestinal mucositis is a well-known adverse event, which limits its therapeutic use. Refined Baohe formula (RBF) is derived from Baohe Pills with a potent gastrointestinal protective effect. However, the effects of RBF on 5-FU-induced intestinal mucositis remain unknown. Thus, this study investigated the effects and mechanism of RBF on 5-FU-induced intestinal mucositis in a CT-26 xenograft mice colorectal cancer (CRC) model. The composition of the RBF preparation was analyzed by high-pressure liquid chromatography. CT-26 cells bearing mice were intraperitoneally administered 150 mg/kg of 5-FU on day 1 to construct a 5-FU-induced intestinal injury model. Mice in the 5-FU + RBF group were intragastrically administrated with RBF (12.4 g/kg) for 4 days. Tumor volume and weight were determined, body weight and diarrhea scores were monitored, leukocytes were calculated, and hematoxylin-eosin staining, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling were performed to investigate the therapeutic efficiency and underlying mechanisms of RBF on 5-FU-induced intestinal mucositis mice. RBF didn`t affect the effect of tumor suppression, while attenuated diarrhea associated with 5-FU-induced intestinal mucositis and significantly reduced leucocyte toxicity. Additionally, RBF significantly promoted cell proliferation and inhibited cell apoptosis, and up-regulated CDK4, c-Myc, and B-cell lymphoma-2 expression, while down-regulated Bax expression, as well as enhanced both p-AKT and AKT expression in intestinal crypts of 5-FU-treated mice. RBF attenuated 5-FU-induced intestinal mucositis by inhibiting apoptosis and promoting cell proliferation by modulating the AKT pathway and its downstream effectors in a CT-26 xenograft mouse CRC model.

Ethnopharmacological relevance: Liensinine(Lien, C37H42N2O6) is an alkaloid compound from plumula nelumbinis that demonstrates an antihypertensive effect. The protective effects of Lien on target organs during hypertension are still unclear.Aim of the study: This study aimed to understand the mechanism of Lien during the treatment of hypertension, with emphasis on vascular protection.Materials and methods: Lien was extracted and isolated from plumula nelumbinis for further study. In vivo model of Ang II-induced hypertension, non-invasive sphygmomanometer was used to detect the blood pressure in and out of the context of Lien intervention. Ultrasound was used to detect the abdominal aorta pulse wave and media thickness of hypertensive mice, and RNA sequencing was used to detect the differential genes and pathways of blood vessels. The intersection of Lien and MAPK protein molecules was detected by molecular interconnecting technique. The pathological conditions of abdominal aorta vessels of mice were observed by HE staining. The expression of PCNA, & alpha;-SMA, Collagen Type I and Collagen Type III proteins were detected by IHC. The collagen expression in the abdominal aorta was detected by Sirius red staining. The MAPK/TGF-131/Smad2/3 signaling and the protein expression of PCNA and & alpha;-SMA was detected by Western blot. In vitro, MAPK/TGF-131/Smad2/3 signaling and the protein expression of PCNA and & alpha;-SMA were detected by Western blot, and the expression of & alpha;-SMA was detected by immunofluorescence; ELISA was used to detect the effect of ERK/MAPK inhibitor PD98059 on Ang II-induced TGF-131secrete; and the detection TGF-131and & alpha;-SMA protein expression by Western blot; Western blot was used to detect the effect of ERK/MAPK stimulant12-O-tetradecanoyl phorbol-13-acetate (TPA) on the protein expression of TGF-131 and & alpha;-SMA. Results: Lien displayed an antihypertensive effect on Ang II-induced hypertension, reducing the pulse wave conduction velocity of the abdominal aorta and the thickness of the abdominal aorta vessel wall, ultimately improving the pathological state of blood vessels. RNA sequencing further indicated that the differential pathways expressed in the abdominal aorta of hypertensive mice were enriched in proliferation-related markers compared with the Control group. The profile of differentially expressed pathways was ultimately reversed by Lien. Particularly, MAPK protein demonstrated good binding with the Lien molecule. In vivo, Lien inhibited Ang II-induced abdominal aorta wall thickening, reduced collagen deposition in the ventral aortic vessel, and prevented the occurrence of vascular remodeling by inhibiting MAPK/TGF-81/Smad2/3 signaling activation. In addition, Lien inhibited the activation of Ang II-induced MAPK and TGF-81/Smad2/3 signaling, attenuating the expression of PCNA and inhibiting the reduction of & alpha;-SMA, collectively playing a role in the inhibition of Ang IIinduced hypertensive vascular remodeling. PD98059 alone could inhibit Ang II-induced elevation of TGF-81 and the decrease of & alpha;-SMA expression. Further, PD98059 combined with Lien had no discrepancy with the inhibitors alone. Simultaneously TPA alone could significantly increase the expression of TGF-81 and decrease the expression of & alpha;-SMA. Further, Lien could inhibit the effect of TPA. Conclusion: This study helped clarify the protective mechanism of Lien during hypertension, elucidating its role as an inhibitor of vascular remodeling and providing an experimental basis for the research and development of novel antihypertensive therapies.

近年来,大量民间应用、个案报道及部分临床观察显示片仔癀对大肠癌等恶性肿瘤具有一定效果,但仍存在药效、作用机制不清,质控体系欠完善等瓶颈问题,大大限制了国宝名药片仔癀抗大肠癌临床应用与推广.本项目主要针对片仔癀抗大肠癌仍存在药效作用机制和靶点不清等瓶颈问题,自2010年起与漳州片仔癀药业股份有限公司及多家医院共同开展了"片仔癀抗大肠癌二次开发及推广应用"系列研究.

目的:探讨清达颗粒抑制高血压心肌肥厚的作用机制.方法:将12只5 w龄雄性自发性高血压大鼠随机分为模型组、清达颗粒组,每组6只,选取6只雄性同周龄正常血压大鼠作为对照组.清达颗粒组按0.9 g/(kg·d)给予清达颗粒干预,对照组和模型组给予等量生理盐水干预,每日1次,连续8 w.监测大鼠血压和体重,观察各组大鼠心脏重量指数、心脏收缩功能和病理形态、心房钠尿肽(ANP)、脑利钠肽(BNP)的mRNA和蛋白的表达变化,以及p38 MPAK通路相关蛋白的活化.结果:干预8 w后,与模型组比较,清达颗粒组大鼠血压显著降低(P＜0.05),心脏收缩功能显著改善(P＜0.05),心脏重量指数显著降低(P＜0.05),心肌纤维增粗肿胀、排列紊乱、溶解断裂、炎性细胞浸润等病理情况明显改善,心脏组织ANP、BNP的mRNA和蛋白的表达显著降低(P＜0.05),心脏组织p-p38/p38 MPAK蛋白的表达显著降低(P＜0.05).结论:清达颗粒通过p38 MPAK通路抑制高血压心肌肥厚.

Background Numerous pre-clinical studies showed that Qingda granule (QDG) was effective in treating hypertension. This study aims to evaluate the efficacy and safety of QDG in reducing blood pressure among patients with grade 1 hypertension at low-medium risk. Methods The study is designed as a randomized, multi-center, double-blinded, non-inferiority clinical trial. Five hundred fifty-two patients with grade 1 hypertension at low-medium risk from 13 hospitals will be recruited and randomly assigned to the QDG group ( n = 276, treated with valsartan capsule simulation agent and QDG) or control group ( n = 276, treated with valsartan capsule and QDG simulation agent). The treatment period will be 4 weeks and the follow-up period will last 4 weeks after treatment. Primary outcome will be a decreased value of systolic blood pressure and diastolic blood pressure after treatment. And second outcome will include the decreased value of diastolic blood pressure and systolic blood pressure at the end of follow-up, the percentage of participants achieving normal blood pressure at the end of treatment and follow-up, the Hamilton Anxiety Scale and TCM syndrome scores at the end of treatment and follow-up, and levels of hypertensive hormones at end of treatment and follow-up. Discussion This study will provide initial evidence regarding the clinical efficacy and safety of QDG in treating grade 1 hypertension at low-medium risk. Trial registration Chinese Clinical Trial Registry ChiCTR2000033890 . Registered on 15 June 2020.

Various studies have recognized the vital role of the abnormal spindle microtubule assembly (ASPM) gene in the progression of numerous tumors and its association with their poorer clinical outcomes. Nonetheless, the clinical significance and regulatory mechanism of ASPM in papillary renal cell carcinoma (PRCC) have not been illuminated. Herein, we designed a series of experiments to determine the functional significance of ASPM in PRCC. The expression of ASPM was significantly elevated in PRCC tissues and cells, and a higher expression level of ASPM was associated with poor clinical outcomes in patients with PRCC. Following the knockdown of ASPM, the proliferation, invasion, and migration abilities of PRCC cells were all repressed. Moreover, the silencing of ASPM attenuated the expressions of crucial proteins involved in Wnt/β-catenin signaling pathway, including Dvl-2, β-catenin, TCF4, and LEF1. Our study shows the biological significance of ASPM in PRCC and provides new insights for exploring therapeutic targets in PRCC.

Background: Hypertension onset is linked to sleep, but the precise sleep duration affecting it remains unclear. Our goal is to pinpoint the sleep duration impacting hypertension incidence, offering valuable insights for prevention and management.Methods: In this systematic review and meta-analysis, we conducted a search of five electronic databases (PubMed, Embase, Wanfang Database, China Academic Journals Comprehensive Evaluation Database, and China National Knowledge Infrastructure) for adult cohort studies reporting the relationship between sleep duration and the risk of hypertension up to May 30, 2023. We calculated pooled effect sizes to investigate the specific sleep duration influencing hypertension incidence and conducted subgroup analyses to explore the relationship between sleep duration and hypertension incidence in specific populations. The study protocol was registered with PROSPERO under the registration number CRD42022345513.Findings: Out of the 173,734 participants in this study, 41,528 developed hypertension during a follow-up period ranging from 2 to 21 years. Compared to 7–8-hour sleep duration, more than 8-hour sleep was not associated with the incidence of hypertension (pooled effect size 1.02, 95% confidence interval 0.98 to 1.06), and this trend was observed across all subgroups including age, gender, and region. When sleep duration was no more than 7 hours, the risk of developing hypertension increases progressively, with risks of 1.07 (1.00 to 1.14) for sleep duration ≤7 hours, 1.04 (1.02 to 1.07) for 6-7 hours, and 1.17 (1.06 to 1.28) for <6 hours. In individuals aged <60 years, with sleep durations 6-7 and <6 hours, the pooled risk of hypertension incidence was 1.05 (1.00 to 1.11) and 1.28 (1.10 to 1.48), and the risk for female aged <60 years and sleep＜6 hours was 1.19 (1.10 to 1.28). Cohorts from both Europe (1.25, 1.05 to 1.49) and North America (1.13, 1.04 to 1.23) displayed a positive correlation between hypertension incidence and sleep duration <6 hours. For sleep duration between 6-7 hours, North American cohorts showed a positive correlation (1.04, 1.01 to 1.08). But in gender, age, and regional subgroups, we found no significant association between sleep duration and the onset of hypertension in males, individuals over 60 years old, or the Asian population.Interpretation: A significant correlation was found between hypertension and sleep duration＜7 hours, which only applies to individuals under 60 years old. Notably, there was no observed correlation between sleep duration＞8 hours and the occurrence of hypertension. This work provides critical insight for incorporating sleep duration management into the prevention strategies and treatment guidelines of hypertension.Funding: The study was supported by a grant from the National Natural Science Foundation of China (81774135).Declaration of Interest: All authors have completed the Unified Competing Interest form and declare: no financial relationships with any organizations that might have an interest in the submitted work in the previous three year, no other relationships or activities that could appear to have influenced the submitted work.

Background: Qingda granules (QDG) exhibit antihypertension and multiple-target-organ protection. However, the therapeutic potential of QDG on hypertensive renal injury remains unknown. Therefore, the main objective of the current study is to explore the effects and underlying mechanisms of QDG treatment on renal injury in angiotensin (Ang) II-infused mice. Methods and results: Mice were infused with Ang II (500 ng/kg/min) or saline for 4 weeks with subcutaneously implanted osmotic pumps. After infusion, mice in the Ang II + QDG group were intragastrically administrated with QDG daily (1.145 g/kg/day), whereas the control group and Ang II group were intragastrically administrated with the same amount of double-distilled water. Blood pressure of the mice monitored using the CODA™ noninvasive blood pressure system revealed that QDG treatment significantly attenuated elevated blood pressure. Moreover, hematoxylin–eosin staining indicated that QDG treatment ameliorated Ang II-induced renal morphological changes, including glomerular sclerosis and atrophy, epithelial cell atrophy, and tubular dilatation. RNA-sequencing (RNA-seq) identified 662 differentially expressed transcripts (DETs) in renal tissues of Ang II-infused mice, which were reversed after QDG treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis based on DETs in both comparisons of Ang II vs. Control and Ang II + QDG vs. Ang II identified multiple enriched pathways, including apoptosis and p53 pathways. Consistently, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining and Annexin V staining revealed that QDG treatment significantly attenuated Ang II-induced cell apoptosis in renal tissues and cultured renal tubular epithelial cell lines (NRK-52E). Furthermore, western blot analysis indicated that Ang II infusion significantly upregulated the protein expression of p53, BCL2-associated X (BAX), cle-caspase-9, and cle-caspase-3, while downregulating the protein expression of BCL-2 in renal tissues, which were attenuated after QDG treatment. Conclusion: Collectively, QDG treatment significantly attenuated hypertensive renal injury, partially by attenuating renal apoptosis and suppressing p53 pathways, which might be the underlying mechanisms.

Objective: To study the effect of Betaloc in clinical intervention of uremic hemodialysis patients with heart failure. Methods: 76 patients with uremic hemodialysis complicated with heart failure received in our hospital from February 2020 to September 2021 were randomly divided into two groups. The patients in the control group received benazepril treatment intervention,and the patients in the observation group were treated with betaloc on the basis of benazepril. The clinical efficacy differences of different treatment methods were evaluated. Results: The cardiac function indexes of the two groups were compared. The left ventricular ejection fraction (LVEF) of the observation group was higher than that of the control group,and the diastolic diameter (LVEDd) was lower than that of the control group. There was significant difference between the two groups (P < 0.05) The serum BNP in the observation group was lower than that in the control group (P < 0.05),and the 6-minute walking distance in the observation group was higher than that in the control group (P < 0.05). The results of drug safety evaluation showed that there was no significant difference between the groups (P > 0.05). Conclusion: Betaloc has significant clinical advantages in the clinical treatment of uremic hemodialysis patients with heart failure. It can further improve patients’ cardiac function and eliminate many adverse symptoms of heart failure,which is worthy of promotion.