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.

Objective: To investigate the feasibility and efficacy of carrying out pediatric laparoscopic partial cystectomies (LPC) when treating benign bladder tumors and urachal cysts.Methods: Retrospectivey analyzing 4 clinical cases involving children with bladder tumors, which were collected from October 2017 to December 2018. In these clinical cases, there were 3 male children and 1 female child, aged from 4.5 to 9.4 years old, with an average age of 6.5 years. An intraperitoneal laparoscopic partial cystectomy was performed in the treatment of 3 of these patients with benign bladder tumors and in 1 patient with an urachal cyst. The surgical procedures included a partial cystectomy and a complete intracavitary bladder suture.Results: All 4 cases were successful and no operation was transferred to opensurgery. The operation time was 100–120 min, with an average time of 108 min. The intraoperative blood loss was 10–20 ml, with an average loss of 15 ml. 6 h after the operation, the patients still maintained a fluid diet and 1 case of hematuria had occurred, with the catheter removed 12 days after the operation. No postoperative urine leakage, intestinal adhesion or intestinal obstruction occurred, and the average postoperative hospitalization time was 14 days.Conclusion: Laparoscopic partial cystectomy is a safe and feasible method to be used for the treatment of benign bladder tumors and urachal cysts. It presents the advantages of being minimally invasive, and having a quick recovery and short hospitalization time. It is an alternative surgical method for the treatment of pediatric benign bladder tumors.

Background/Objectives: Apocynum venetum L. leaves have long been used in traditional medicine and have shown cardioprotective potential, but the active constituents responsible for these effects remain unclear. This study aimed to identify cardioprotective constituents in the n-butanol fraction of A. venetum leaves and clarify their mechanisms through chemical profiling, zebrafish phenotyping, and cell-based validation. Methods: The n-butanol extract was fractionated into S1–S6 and characterized by HPLC and UPLC–QE–Orbitrap–MS/MS. Cardioprotective effects were assessed in zebrafish myocardial injury models. Spectrum–effect relationships were analyzed using grey relational analysis (GRA) and orthogonal partial least squares (OPLS), and key compounds were validated in zebrafish. Transcriptomic analysis, qRT–PCR, molecular docking, and isoprenaline (ISO)-induced H9c2 cell assays were used to explore mechanisms and synergistic effects. Results: Fingerprinting analysis of subfractions S1–S6 revealed 12 common peaks and ten compounds. S1–S4 showed stronger protection against zebrafish myocardial injury than S5–S6. Spectrum–effect analysis indicated that chlorogenic acid (CGA) and 4-caffeoylquinic acid (4-CQA) were the major activity-associated constituents. CGA produced the most pronounced cardioprotective effect in zebrafish and was associated with PPARα-related metabolic pathways. In H9c2 cells, CGA combined with myricetin 3-O-glucoside showed synergistic protection. Quantitative analysis showed that CGA and 4-CQA were predominantly distributed in S1–S3, consistent with the stronger activity of these fractions. Conclusions: This study applied a spectrum–effect relationship strategy to identify CGA and 4-CQA as major cardioprotective constituents in the n-butanol fraction of A. venetum leaves, supporting the potential synergistic contribution of CGA-dominated constituent combinations and providing a basis for further pharmacological investigation.

Vascular smooth muscle cell (VSMC) senescence contributes importantly to atherosclerotic plaque progression, yet the upstream mechanisms remain incompletely understood. Here, by integrating single‐cell RNA sequencing analysis with human plaque validation, we found that TGFBR1 is enriched in senescent VSMCs in atherosclerotic lesions and correlates with senescence‐associated markers. In vivo, VSMC‐specific TGFBR1 knockin in Apoe‐deficient mice accelerated plaque development and increased VSMC senescence. Mechanistically, we identified the deubiquitinase USP5 as a previously unrecognized stabilizer of TGFBR1. USP5 directly interacted with TGFBR1 and selectively removed K48‐linked polyubiquitin chains at lysine 213, thereby preventing proteasomal degradation. Stabilized TGFBR1 suppressed the mitochondrial enzyme IDH2, driving a metabolic shift toward glycolysis that sustained apoptosis resistance in senescent VSMCs. Conversely, VSMC‐specific knockdown of USP5 reduced TGFBR1 expression, restored IDH2 expression, attenuated glycolytic remodeling, and mitigated atherosclerosis in viv o. Our findings reveal a USP5‐TGFBR1‐IDH2 axis in which site‐specific deubiquitination at K213 links receptor stability to metabolic remodeling and VSMC senescence, identifying USP5 as a potential therapeutic target for atherosclerosis.

Atherosclerosis is a chronic inflammatory disease driven by senescent vascular smooth muscle cells (VSMCs). Salvianolic acid A (SAA) exhibits cardiovascular protective effects; however, its role in atherosclerosis remains unclear. This study aimed to investigate the effects and targets of SAA in atherosclerosis. In vitro studies were performed in senescent VSMCs with heat shock protein 90 alpha (HSP90α) overexpression or knockdown, with or without SAA treatment. In vivo, ApoE ^−/− mice fed a high‐fat diet were treated with SAA and adeno‐associated virus‐mediated VSMC‐specific HSP90α overexpression or knockdown. SAA promoted apoptosis in senescent VSMCs by inhibiting HSP90α. This inhibition promoted ubiquitin‐proteasome‐dependent degradation of protein kinase B (AKT) and activation of PRKR‐Like Endoplasmic Reticulum Kinase (PERK) signaling. SAA increased endoplasmic reticulum‐mitochondrial contacts and mitochondrial calcium uptake. These effects were reversed by HSP90α overexpression. In ApoE ^−/− mice, SAA reduced the burden of senescent VSMCs, decreased the size of plaque, and increased the stability of the fibrous cap. VSMC‐specific HSP90α knockdown mimicked the protective effects of SAA, whereas HSP90α overexpression reversed SAA‐mediated effects on disease. SAA reduces the burden of senescent VSMCs in atherosclerosis by inhibiting the scaffold function of HSP90α which maintains the AKT‐PERK interaction, to reactivate PERK signaling, thereby alleviating disease progression.

As the core molecular chaperones of the cellular stress response, the heat shock protein (HSP) family has gained extensive attention for its role in the occurrence, development, and target organ damage of hypertension. This review aimed to comprehensively summarize the research progress of the HSP family in the field of hypertension, and to analyze its key roles in the pathogenesis of hypertension, including its regulatory effects on key pathological processes such as endothelial dysfunction, proliferation and migration of vascular smooth muscle cells, oxidative stress, and inflammatory responses. It also summarized the potential value of HSPs as biomarkers in the early diagnosis, condition monitoring, and prognostic evaluation of hypertension. Moreover, it discussed in depth the efficacy and safety of intervention strategies targeting HSPs, including the regulation of HSPs by gene editing, the targeted effects of small-molecule inhibitors, and the modulatory effects of natural products. We need to strengthen interdisciplinary collaboration mechanisms, accelerate the transformation of basic research results into clinical applications, carry out large-scale clinical trials, and develop specific modulators in the future, so as to ultimately provide solid scientific theoretical support and a practical clinical basis for the precise prevention and treatment of hypertension. The findings of this review not only provide novel insights into the pathogenesis of hypertension but also lay a theoretical foundation for the development of HSP-based biomarkers and targeted therapeutic strategies.