To investigate the clinical value of early (≤7 days) versus delayed (>6 weeks) laparoscopic cholecystectomy (LC) after ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGBD) in high-risk acute cholecystitis (AC), with PTGBD serving as a bridging intervention. A retrospective analysis was performed on 110 high-risk AC patients admitted between August 2021 and January 2025. Patients were divided into an early LC group (52 cases) and a delayed LC group (58 cases). Surgical indicators, inflammatory response control, hospitalization duration, treatment costs, quality of life, and postoperative complications were compared between the two groups. The early LC group demonstrated significantly superior outcomes in operative time (22.51 ± 4.32 vs. 65.28 ± 15.12 minutes, p < 0.001), intraoperative blood loss (12.16 ± 2.13 vs. 52.47 ± 6.11 mL, p < 0.001), length of hospital stay (7.12 ± 0.58 vs. 10.11 ± 1.62 days, p < 0.001), and total treatment costs (2.36 ± 0.32 vs. 3.80 ± 0.52 ten thousand yuan, p < 0.001, 1 dollar = 6.91 yuan). The incidence of moderate to severe adhesions was significantly lower in the early LC group (28.85% vs. 56.90%, p = 0.003). However, the delayed LC group exhibited lower postoperative C-reactive protein levels (12.45 ± 2.23 vs. 15.32 ± 2.78 mg/L, p < 0.001) and procalcitonin levels (0.25 ± 0.06 vs. 0.38 ± 0.05 ng/mL, p < 0.001), as well as significantly higher quality-of-life scores at 3 months postoperatively (all p < 0.001). No statistically significant differences were observed in complication rates (9.62% vs. 15.52%) or conversion-to-laparotomy rates (3.85% vs. 10.34%) between groups (p > 0.05). Early LC following PTGBD effectively shortens overall treatment duration, reduces healthcare costs, and lowers surgical complexity. However, careful consideration should be given to the potential influence of residual inflammation on long-term quality of life. Further multi-center prospective studies are warranted to validate long-term safety and to optimize individualized treatment strategies.
While surface engineering dominates the design of alkaline hydrogen evolution reaction (HER) catalysts, the critical role of subsurface architecture remains largely unexplored due to synthetic challenges. Herein, we present a "precursor hereditary" strategy that modulates the pH-dependent speciation of molybdate clusters to precisely dictate the migration kinetics of metal atoms during thermal reduction, thereby enabling the formation of a customized depth profile with optimized electronic structure. The resulting compositional gradient significantly downshifts the d-band center, balancing hydrogen adsorption/desorption energetics. Consequently, the optimized catalyst exhibits an ultralow overpotential of 61 mV at 200 mA cm-2 and outstanding kinetics. Notably, in an anion exchange membrane water electrolyzer (AEMWE), it delivers an industrial-level current density of 1.5 A cm-2 at 1.88 V and operates stably for 2 500 h with a negligible degradation rate (28 µV h-1). This work establishes a universal paradigm for manipulating atomic-scale depth profiles to bridge the gap between fundamental surface science and practical electrolyzer applications.
To evaluate the association between preoperative systemic inflammatory indices (systemic immune-inflammation index [SII], systemic inflammation response index [SIRI], and aggregate index of systemic inflammation [AISI]) and poor visual outcomes following cataract surgery. This retrospective study included 240 patients who underwent cataract surgery between April 2022 and June 2025. SII, SIRI, and AISI were calculated from complete blood counts obtained within 7 days preoperatively. Poor visual outcome at 4 weeks postoperatively was analyzed using multivariable logistic regression and restricted cubic spline models, with adjustment for potential confounders. The mean age was 69 years, and 67.1% of participants were female. SII demonstrated a nonlinear association with poor postoperative visual outcomes (p for nonlinearity = 0.029), with increased odds observed at SII values of 500-1000 and at extremely low levels. Compared with the lowest tertile, the highest SII tertile was associated with a significantly increased risk (adjusted odds ratio [OR] 2.790, 95% confidence interval [CI] 1.209-6.615; p = 0.018). After adjustment for sex, body mass index (BMI), and intraocular pressure, SIRI (tertile 3 vs. tertile 1: OR 2.019, 95% CI 1.035-3.997; p = 0.041) and AISI (tertile 2 vs. tertile 1: OR 1.977, 95% CI 1.017-3.898; p = 0.046) were also associated with poor visual outcomes. In multivariable analyses, SII and AISI remained independently associated with poor postoperative vision (OR 2.790, 95% CI 1.209-6.615; p = 0.018; OR 2.104, 95% CI 1.016-4.432; p = 0.047). Preoperative SII, SIRI, and AISI were significantly associated with worse short-term visual outcomes after cataract surgery. These indices, particularly SII and AISI, may provide clinically useful information for perioperative risk stratification. Further prospective validation studies and investigation of targeted anti-inflammatory strategies are warranted.
Objective To understand the demand of parents in Xichang city for the sexuality education training of young children,analyze its influencing factors,and then put forward corresponding health education strategies. Methods Through cluster random sampling,8 kindergartens were selected in Xichang city,Sichuan province.The knowledge,attitude and practice scale for sexuality education of young children was used to conduct a questionnaire survey among parents of young children.The chi-square test and the multivariate Logistic regression model were used for data analysis. Results Among the 1 496 parents,the demand rates for kindergarten teacher training and expert training were 53.5% and 46.3%,respectively,and the total demand rate for training was 65.4%.The results of the multivariate Logistic regression analysis showed that higher paternal educational level (OR=1.42,95%CI=1.11-1.82,P=0.006),female parenthood (OR=1.71,95%CI=1.28-2.28,P<0.001),positive attitude (OR=1.64,95%CI=1.24-2.15,P<0.001),willingness to participate in school-based early childhood sex education with children (OR=2.44,95%CI=1.67-3.49,P<0.001),and more diverse sources of knowledge (OR=15.32,95%CI=5.49-42.79,P<0.001) were positive predictors of parents' overall demand for training.Conversely,children's prior participation in sex education-related courses at school (OR=0.57,95%CI=0.38-0.85,P=0.006) was a negative predictor of such demand. Conclusions The parents in Xichang city have high demand for the sexuality education training of young children but limited ways to knowledge sources.It is recommended that sexuality education training courses both online and offline should be developed according to the characteristics of parents' needs,and the contents,methods,and ways of health education should be optimized.Special attention should be paid to the health education for male parents,parents with low educational attainment,parents with a passive attitude,and parents who have cognitive misunderstandings about or lack knowledge of children's sexuality education.Efforts should be made to popularize sexuality education knowledge,enhance parents' ability to conduct sexuality education for young children,and improve the quality of family sexuality education through home-school cooperation,thus creating a healthy growth environment for young children. 目的 了解西昌市家长对幼儿性教育培训的需求情况,并分析其影响因素,进而提出相应的健康教育策略。方法 采用整群随机抽样方法在四川省西昌市抽取8所幼儿园,对幼儿家长使用《幼儿性教育知信行量表》进行问卷调查,采用χ2检验和多因素Logistic回归模型进行数据分析。结果 1 496名家长的幼儿园教师培训需求率为53.5%,专家培训需求率为46.3%,培训总需求率为65.4%。多因素Logistic回归分析显示,父亲文化程度高(OR=1.42,95%CI=1.11~1.82,P=0.006)、女性家长(OR=1.71,95%CI=1.28~2.28,P<0.001)、态度积极(OR=1.64,95%CI=1.24~2.15,P<0.001)、愿意和孩子一起参加学校的幼儿性教育(OR=2.44,95%CI=1.67~3.49,P<0.001)、知识来源途径数量多(OR=15.32,95%CI=5.49~42.79,P<0.001)是家长培训总需求的促进因素,孩子在学校参加过性教育相关课程情况(OR=0.57,95%CI=0.38~0.85,P=0.006)是家长培训总需求的抑制因素。结论 西昌市家长幼儿性教育培训需求较高,获取知识来源途径较少。建议针对家长需求特点结合线上线下开展性教育培训课程,优化并完善健康教育内容、方式和途径。重点加强男性家长、文化程度相对较低、态度不积极以及对幼儿性教育存在认知误区或缺乏了解的家长的健康教育,普及性教育知识,提升家长的幼儿性教育能力,通过家校合作的方式提高家庭性教育质量,为幼儿营造健康的成长环境。.
Objective To examine the expression patterns,prognostic relevance,and immune regulatory functions of thymine DNA glycosylase (TDG) across a spectrum of cancer types,with a particular emphasis on its role in lung adenocarcinoma. Methods A comprehensive analysis was conducted using multiple bioinformatics databases to assess TDG expression levels in pan-cancer contexts,as well as its associations with prognosis and immune regulation.The expression and clinical relevance of TDG in lung adenocarcinoma were examined through online platforms such as UALCAN and BEST.Additionally,small interfering RNA targeting TDG was developed,and cell biological function assays were performed to determine the impact of TDG on cell functionality in lung adenocarcinoma.The LinkedOmics database was used to analyze the genes related to TDG and target kinases in lung adenocarcinoma,and their correlations with tumor status.The PRISM database was utilized to examine the correlation between TDG expression and clinical treatment response in lung adenocarcinoma. Results TDG was markedly overexpressed in a variety of cancers,including lung adenocarcinoma,papillary renal cell carcinoma,and gastric cancer (all P<0.001).It held potential as a prognostic biomarker for hepatocellular carcinoma,lung adenocarcinoma,and papillary renal cell carcinoma.The expression of TDG was intricately linked to immune cell infiltration and tumor heterogeneity.In the context of lung adenocarcinoma,the analysis using the TIMER algorithm revealed negative correlations between TDG expression and the infiltration levels of CD4+ T cells,dendritic cells,and B cells (all P<0.001).Furthermore,CIBERSORT analysis demonstrated that TDG expression was positively correlated with activated CD4+ memory T cells (P<0.001),neutrophils (P<0.001),resting NK cells (P<0.001),resting mast cells (P<0.001),M1 macrophages (P<0.001),M0 macrophages (P=0.014),and naive B cells (P<0.001),while it was negatively correlated with regulatory T cells (P<0.001),monocytes (P<0.001),activated mast cells (P<0.001),and memory B cells (P<0.001). Additionally,TDG expression was positively associated with tumor mutational burden (P<0.001),microsatellite instability (P=0.045),mutant-allele tumor heterogeneity (P=0.001),and tumor neoantigens (P<0.001) in lung adenocarcinoma.In lung adenocarcinoma,the expression of TDG was notably elevated in the tumor tissue compared with that in adjacent normal tissue (P<0.001).Male patients exhibited higher levels of TDG expression than female patients (P=0.002),and smokers demonstrated higher TDG expression than non-smokers (P<0.001).Furthermore,TDG expression was correlated with smoking cessation duration (P=0.014).Positive correlations were observed for TDG expression with both clinical T stage (P=0.003) and distant metastasis (P=0.012),while a negative correlation was found with patient prognosis (P=0.030).Furthermore,TDG emerged as an independent prognostic factor for lung adenocarcinoma.In vitro experiments revealed that silencing TDG inhibited the proliferation and migration of lung adenocarcinoma cells (both P<0.05).A correlation analysis between TDG-related genes and target kinases revealed that in lung adenocarcinoma,genes encoding aurora kinase A,cyclin-dependent kinase 2 and other enzymes exhibited positive correlations with TDG expression (all P<0.001).Furthermore,TDG expression demonstrated positive correlations with functional states including the cell cycle,DNA damage,and DNA repair processes (all P<0.001).In addition,the expression of TDG was correlated with the efficacy of treatment in the first course in clinical patients (P=0.007).Specifically,TDG expression levels were higher in the progressive disease group than in the stable disease group (P=0.016),and lower in the complete remission group than in the progressive disease group (P<0.001).Additionally,elevated TDG expression was associated with enhanced resistance to oxaliplatin (P<0.001),carmustine (P<0.001),and olaparib (P=0.004). Conclusion TDG serves as a potential prognostic biomarker,an immunotherapeutic target,and a oncogene in pan-cancer,with particular significance in lung adenocarcinoma. 目的 探究胸腺嘧啶DNA糖基化酶(TDG)在多种癌症中的表达、预后相关性、免疫调节作用及其在肺腺癌中的功能。方法 采用多种生物信息学数据库分析TDG在泛癌中的表达水平及其与预后、免疫调节的相关性。通过UALCAN、BEST等在线分析TDG在肺腺癌中的表达及其临床相关性。设计靶向TDG的小干扰RNA,利用细胞生物学功能实验评估其对肺腺癌细胞功能的影响。利用LinkedOmics数据库分析肺腺癌中TDG的相关基因、靶标激酶及其与肿瘤状态的相关性。利用PRISM数据库分析肺腺癌中TDG表达与临床治疗反应的相关性。结果 TDG在大多数癌症[如肺腺癌、肾乳头状细胞癌、胃癌(P均<0.001)等]中高表达,可作为肝细胞癌、肺腺癌和肾乳头状细胞癌的预后标志物。TDG表达与免疫细胞浸润、肿瘤的异质性密切相关[在肺腺癌中,TIMER 算法显示TDG表达与CD4+ T 细胞、树突状细胞和B 细胞的浸润水平均呈显著负相关(P均<0.001);CIBERSORT分析显示TDG表达与活化CD4+记忆性T细胞(P<0.001)、中性粒细胞(P<0.001)、静息NK细胞(P<0.001)、静息肥大细胞(P<0.001)、M1型巨噬细胞(P<0.001)、M0型巨噬细胞(P=0.014)和初始B细胞(P<0.001)均呈显著正相关,与调节性T细胞、单核细胞、活化肥大细胞和记忆B细胞均呈显著负相关(P均<0.001);TDG表达与肺腺癌中的肿瘤突变负荷(P<0.001)、微卫星不稳定性(P=0.045)、突变等位基因肿瘤异质性(P=0.001)和肿瘤新抗原(P<0.001)均呈显著正相关]。在肺腺癌中,与癌旁正常组织相比,TDG表达显著升高(P<0.001);男性患者TDG的表达水平显著高于女性(P=0.002),吸烟者TDG表达显著高于非吸烟者(P<0.001),并且TDG表达与戒烟年限显著相关(P=0.014)。此外,TDG表达与临床T分期(P=0.003)、远端转移(P=0.012)均呈显著正相关,与患者的预后呈显著负相关(P=0.030);且TDG是肺腺癌的独立预后因子。体外实验显示,沉默TDG抑制肺腺癌细胞的增殖与迁移(P均<0.05)。TDG相关基因和靶标激酶相关性分析显示,在肺腺癌中,极光激酶A、细胞周期蛋白依赖性激酶2等基因与TDG均呈显著正相关(P均<0.001);TDG的表达与细胞周期、DNA损伤、DNA修复等功能状态均呈显著正相关(P均<0.001)。TDG的表达与临床患者首程治疗效果显著相关(P=0.007);与稳定疾病组相比,进展性疾病组中TDG的表达水平更高(P=0.016);与进展性疾病组相比,完全缓解组中TDG的表达水平较低(P<0.001);TDG表达越高,患者对奥沙利铂(P<0.001)、卡莫司汀(P<0.001)、奥拉帕利(P=0.004)越抵抗。结论 在泛癌中,尤其是肺腺癌中,TDG是一种潜在的肿瘤预后生物标志物、潜在免疫治疗靶点和癌基因。.
The target cell limited (TCL) model is a cornerstone of within-host viral dynamics and is widely used to interpret viral load (VL) data and assess antiviral efficacy. We examine how TCL models predict VL reduction under drug treatments, thereby focusing on parameters that govern infection and viral production. Our simulations and analyses reveal a non-monotonic relationship: moderate drug effects can slow VL decline and prolong persistence above the limit of quantification. We provide a rigorous analytical characterization of the conditions under which this non-monotonic behavior arises. We derive an explicit formula for the critical parameter value that delineates monotonicity and show that this phenomenon broadly arises in generalized TCL models. Additionally, we propose a modified formulation with a sigmoid infection term, which reduces the extent of non-monotonicity while preserving the analytical tractability. These findings contribute to a deeper understanding of the TCL model behavior and provide a practical alternative formulation when a monotonic dose-response relationship is desired.
The continued rise in cancer-related deaths suggests that the precise nature of the disease remains poorly understood. In the field of cellular mechanics, researchers have identified mechanobiological aspects of cancer cells by examining the link between their physical and molecular properties and functions, thereby revealing some of their previously unknown characteristics. Therefore, expanding scientific insight in this area may deepen our understanding of genetic and mechanical interactions and clarify the functional mechanisms at both the cellular and subcellular levels. Accordingly, in this review, we first evaluated the cytoskeletal filaments and their structural dynamics from a mechanobiological perspective. Then, the characteristics of the mechanical behavior of cells were discussed, and the potential correlations between the mechanical and rheological properties of normal and cancer cells, alongside alterations in their genetic components, were highlighted. Subsequently, we reviewed the simulationary capabilities of existing in vitro methods for estimating the biomechanical properties of cells. Finally, by outlining the challenges and opportunities associated with this approach, we aimed to present a clearer picture of its potential in practice. We believe that this study, by providing a comprehensive overview of various mechanobiological aspects of cancer at the cellular and subcellular levels, can help researchers in developing bioengineering-based in vitro platforms to decipher the unknown traits of cancer cells, paving the way for novel diagnostic biomarkers and mechano-targeted therapies.
Pancreatic acinar cell carcinoma (PACC) is a rare malignancy, and clinical data on managing bulky hepatic metastases from PACC remain limited. Conventional radiotherapy is restricted by normal tissue tolerance, while stereotactic body radiation therapy (SBRT) leads to prohibitive toxicity when applied to large tumor volumes. Spatially fractionated radiation therapy (SFRT) creates a deliberate non-uniform peak-valley dose distribution, delivering ablative doses to discrete tumor vertices while sparing the surrounding hepatic parenchyma. This approach may enhance local control and antitumor immunity, supporting its use in combination with immunotherapy for large hepatic metastases. A 35-year-old female with metastatic PACC and a solitary 12-cm hepatic metastasis (clinical stage TxN3M1) experienced disease progression despite multiple surgical resections and six lines of systemic chemotherapy. The enlarging hepatic metastasis caused portal vein compression and anasarca. The patient received Lattice SFRT (40 Gy in four fractions) to the hepatic lesion, combined with the PD-1/CTLA-4 bispecific antibody cadonilimab and the multi-targeted tyrosine kinase inhibitor anlotinib. The target lesion decreased by 34% at 1 month and nearly 50% at 5 months, meeting RECIST partial response. No grade ≥3 toxicities were observed. This case provides clinical experience supporting the use of SFRT combined with immunotherapy for bulky refractory PACC. The combination of Lattice SFRT, dual immune checkpoint blockade, and targeted therapy appears feasible and well-tolerated in this patient. Further clinical trials are warranted to validate this combined approach.
Growing concern has emerged regarding the mental health of young adults, particularly within university settings where academic and psychosocial pressures are prominent. Exercise motivation (EM), conceptualized within self-determination theory (SDT), especially intrinsic and identified regulation, has been associated with psychological well-being. However, the structural associations among exercise motivation (EM), leisure satisfaction (LS), psychological resilience (PR), and self-efficacy (SE) in young adults remain insufficiently clarified. This cross-sectional study examined these associations in a sample of 437 university students aged 18-23 years in China. Data were collected through validated self-report instruments and analyzed using partial least squares structural equation modeling (PLS-SEM). The results indicated that exercise motivation was positively associated with leisure satisfaction (β = 0.794, p < 0.001), leisure satisfaction was positively associated with psychological resilience (β = 0.342, p < 0.001), and PR was positively associated with self-efficacy (β = 0.228, p < 0.001). Sequential mediation analysis showed that leisure satisfaction and PR jointly accounted for a significant indirect association between EM and SE (β = 0.062, p = 0.001). Model fit indices (SRMR = 0.055; NFI = 0.847) indicated an acceptable level of fit within the prediction-oriented PLS-SEM approach. These findings indicate that exercise motivation is statistically associated with psychological resources among young adults. Although causal inferences cannot be drawn due to the cross-sectional design, the study contributes to understanding motivational processes within the SDT framework and provides directions for future longitudinal research.
Extracellular matrix is a 3D reticular molecular structure that maintains the structures and functions of cells and provides biomechanical support for cell proliferation and differentiation.The increase in extracellular matrix hardness can destroy the ecological structures and biological functions of normal organs and affect the signal transduction of normal tissue and cells,being a key driver of organ fibrosis.Therefore,reducing the extracellular matrix hardness by inhibiting key signaling pathways and activating fibroblasts can reverse organ fibrosis and promote the steady development of extracellular matrix.This paper expounds the key role of extracellular matrix hardness in fibrosis diseases,providing key therapeutic targets and clinical research directions for ameliorating and reversing organ fibrosis. 细胞外基质是维持细胞结构和功能的一种3D网状分子结构,为细胞的增殖、分化提供了生物力学支撑。细胞外基质的硬度增加可以破坏正常脏器的生态结构和生物功能,影响正常组织细胞的信号传导,是脏器纤维化的关键驱动要素。因此,通过抑制关键信号通路、成纤维细胞活化等手段可以降低细胞外基质的硬度,逆转脏器纤维化,促进细胞外基质的稳态发展。本文主要对细胞外基质硬度在纤维化疾病中的关键作用进行阐述,为改善和逆转脏器纤维化提供关键治疗靶点和临床研究方向。.
Atherosclerosis (AS) is characterized by lipid deposition and the formation of arterial intimal plaques,which can lead to serious cardiovascular events such as acute coronary syndrome,myocardial infarction,or stroke.It is one of the leading causes of mortality among Chinese residents.Recent studies have demonstrated that porphyromonas gingivalis lipopolysaccharide activates the inflammatory pathway through binding to Toll-like receptors,thereby stimulating the expression of inflammatory mediators.This process induces functional impairments in macrophages and endothelial cells,promotes foam cell formation,and consequently accelerates the progression of AS.This article reviews the latest research progress in the roles and mechanisms of porphyromonas gingivalis lipopolysaccharide in AS and explores its potential value as a clinical therapeutic target,aiming to provide new insights for the prevention and treatment of AS. 动脉粥样硬化(AS)以脂质沉积及动脉内膜斑块形成为特征,可引发急性冠脉综合征、心肌梗死或中风等严重心血管事件,是我国居民主要死因之一。近年研究发现,牙龈卟啉单胞菌脂多糖通过结合Toll样受体刺激炎症介质的表达从而激活炎症通路,诱导巨噬细胞与内皮细胞功能紊乱,促进泡沫细胞的形成,从而加速AS的发生与发展。本文主要总结牙龈卟啉单胞菌脂多糖在AS中作用及机制的最新研究进展,并探讨其作为临床治疗靶点的潜在价值,以期为AS的防治提供新思路。.
Heart disease is characterized by stress-induced endoreplication preceding pathological cardiomyocyte overgrowth, yet the upstream regulatory mechanisms linking tissue hypoxia to aberrant cellular growth remain incompletely defined. Here, we identify cardiac hypoxia as a key determinant of endoreplication through activation of a hypoxia-inducible factor-1 alpha-microRNA regulatory axis that converges on mitochondrial energetic control. We show that stress-induced activation of hypoxia-inducible factor-1 alpha drives transcriptional induction of microRNA-27b-5p, which directly represses the ATP synthase subunit ATP5A1, resulting in impaired mitochondrial ATP synthesis and accumulation of intra-mitochondrial ADP. Elevated ADP serves as a rate-limiting cofactor for one-carbon metabolism, promoting formate production and de novo purine biosynthesis, thereby enabling pathological endoreplication and cardiomyocyte hypertrophic growth. Genetic gain- and loss-of-function studies targeting hypoxia-inducible factor-1 alpha, microRNA-27b, and ATP5A1 across multiple mouse models of cardiac stress, together with correlative analyses of human cardiac biopsies, establish a conserved and causal relationship between dysregulated mitochondrial energetics and pathological cardiac remodeling. Inhibition of microRNA-27b-5p attenuates established cardiac hypertrophy, improves cardiac function, and suppresses stress-induced multinucleation in vivo. Leveraging this mechanistic insight, we identify the clinically approved antifolate compound methotrexate as an effective inhibitor of stress-induced cardiac endoreplication and pathological hypertrophy in preclinical models. Collectively, these findings define a druggable hypoxia-driven metabolic pathway linking mitochondrial ATP homeostasis to pathological cardiomyocyte growth and suggest therapeutic opportunities for targeting maladaptive cardiac remodeling.
Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease. Despite available lipid-lowering therapies, lipid control remains suboptimal. Bempedoic acid offers a nonstatin oral treatment for hypercholesterolemia. However, real-world data in Asia are limited. The study aimed to investigate the effectiveness and safety of bempedoic acid in Taiwan. This prospective, pragmatic phase 4 study enrolled 180 patients with inadequately controlled hypercholesterolemia to receive bempedoic acid for 12 weeks in addition to background lipid-lowering therapy. The primary end point was the percentage change in LDL-C. Secondary end points included changes in other lipid parameters, hs-CRP (high-sensitivity C-reactive protein), and safety outcomes. Among 180 patients, 160 (88.9%) completed the study. The median percentage change in LDL-C from baseline to week 12 was -19% (interquartile range, -36.4% to -3.6%), decreasing from 117.5 to 92 mg/dL (P<0.01). The median percentage changes from baseline to week 12 were -13.3% for non-high-density lipoprotein cholesterol, -10.8% for total cholesterol, -11.5% for apolipoprotein B, and -34.0% for hs-CRP (all P<0.01). Minimal effects were noted on triglycerides (0.2%), high-density lipoprotein cholesterol (-5.5%), and lipoprotein(a) (2.6%) (all P>0.05). At week 12, 31.3% of patients achieved LDL-C targets (<100 mg/dL for primary prevention; and <55 or <70 mg/dL for secondary prevention). The safety outcomes were consistent with the locally approved label, with no new safety signals identified. Bempedoic acid offers an effective and safe oral therapeutic option for Taiwanese patients whose LDL-C levels remain inadequately controlled with existing lipid-lowering therapy, including statins. URL: https://clinicaltrials.gov; Unique identifier: NCT06925100.
Duchenne muscular dystrophy is a fatal disease characterized by persistent skeletal muscle degeneration, inflammation, and fibrosis. Gene therapy using an adeno-associated virus-derived vector and a microdystrophin transgene is currently under investigation in patients, but the impact of physical activity on long-term therapeutic outcome remains poorly understood. Recently, we reported that 21 weeks of voluntary wheel running complemented the positive endurance and muscle function outcomes of gene therapy in mdx mice. In the present study, we performed a transcriptomic analysis of the gene expression changes associated with functional recovery in the diaphragm with a focus on genes and signaling pathways related to the inflammatory response. RNA sequencing and bioinformatic analysis revealed 2,881 dysregulated genes in untreated and unexercised mdx mice including inflammatory and fibrotic signaling pathways frequently affected in Duchenne muscular dystrophy patients. Among the dysregulated genes, 774 were rescued toward WT level after adeno-associated virus microdystrophin injection. Importantly, 93% of the rescued genes were maintained by voluntary running, which indicates that physical exercise has no significant impact on the outcome of gene therapy-rescued genes in the mdx diaphragm. Our study provides vital information that could help guide DMD patient follow-up protocols after treatment with gene therapy.
Objective To analyze the accuracy of intraoperative frozen section diagnosis of thyroid lesions in Xizang and explore the methods and measures to improve the diagnosis accuracy. Methods The clinicopathological data of 371 patients with thyroid lesions surgically resected by four hospitals in Xizang from January 2020 to December 2024 were collected.With the paraffin section diagnosis after surgery as the standard,the accuracy,missed diagnosis rate,misdiagnosis rate,and delayed diagnosis rate of frozen section diagnosis were analyzed. Results The intraoperative frozen section diagnosis in 371 cases of thyroid lesions showed the accuracy of 95.42% (354/371),the missed diagnosis rate of 0.27% (1/371),the misdiagnosis rate of 0.54% (2/371),and the delayed diagnosis rate of 3.77% (14/371).One case was subjected to missed diagnosis,which was a papillary carcinoma of the thyroid gland.Two cases were misdiagnosed.One of them was diagnosed as malignant tumor during surgery but nodular goiter with atypical hyperplasia of follicular epithelium after surgery.The other case was diagnosed as medullary carcinoma during surgery but subacute thyroiditis after surgery. Conclusions Frozen section diagnosis is an important method for determining the benign or malignant nature of thyroid lesions during surgery.The diagnosis rates of follicular tumors and small lesions are low during surgery.Standardized sampling,improving the quality of frozen sections,and mastering the microscopic morphological characteristics and diagnostic criteria of frozen sections of thyroid lesions during surgery can improve the accuracy of intraoperative frozen section diagnosis. 目的 分析西藏地区甲状腺病变术中冰冻诊断的准确性,探讨提高准确性的方法和措施。方法 收集2020年1月至2024年12月西藏地区4家医院手术切除的371例甲状腺病变患者的临床病理资料,术后以石蜡诊断为标准,分析冰冻诊断准确率、漏诊率、误诊率和延迟诊断率。结果 371例甲状腺病变的术中冰冻切片病理诊断确诊率为95.42%(354/371),漏诊率为0.27%(1/371),误诊率为0.54%(2/371),延迟诊断率为3.77%(14/371)。漏诊1例,为甲状腺微小乳头状癌,冰冻漏取材。误诊2例,其中1例术中考虑恶性肿瘤,术后为结节性甲状腺肿,伴滤泡上皮非典型增生;1例术中考虑髓样癌,术后诊断亚急性甲状腺炎。结论 冰冻病理诊断是手术中确定甲状腺病变良恶性的重要方法,滤泡性肿瘤、微小病变术中确诊率较低,规范取材、提高冰冻切片质量、熟练掌握甲状腺病变术中冰冻病理的显微镜下形态学特点及诊断标准,可以提高术中冰冻病理诊断准确率。.
Endometriosis is a prevalent gynecological disorder characterized by chronic inflammation. Pyroptosis, a type of programmed proinflammatory cell death, plays a crucial role in various inflammatory diseases. However, its specific mechanism in endometriosis remains unclear. This study integrated transcriptome data of patients with endometriosis from the GEO database with a pyroptosis-related gene set to identify core pyroptosis markers associated with endometriosis. Bioinformatics methods were employed to analyze the expression profiles and diagnostic values of these genes. The expression of these genes was validated in clinical specimens using qRT-PCR. The specific role of NLRP1 in endometriosis was subsequently explored using CCK-8, wound healing, Transwell, qRT-PCR and Western blot assays on cell lines. We identified eight pyroptosis markers closely related to endometriosis, among which the expression of NLRP1, PRKACA, and IL-6 were significantly upregulated in patients with endometriosis. The expression patterns of these genes were also confirmed in clinical specimens and cell lines. The results of functional experiments indicated that NLRP1 knockdown inhibited the proliferation, migration, and invasion of 12Z cells. Mechanistic studies revealed that downregulating NLRP1 expression reduced the expression of key molecules in the NF-κB signaling pathway and downstream caspase-1, GSDMD-N. This suggests that NLRP1 promotes pyroptosis by activating the NF-κB signaling pathway, thereby driving the progression of endometriosis. This study reveals a novel mechanism through which NLRP1 activates pyroptosis through the NF-κB signaling pathway and promotes the progression of endometriosis. NLRP1 may serve as a potential diagnostic biomarker and therapeutic target for endometriosis.
Multifunctional polyurethanes face a fundamental design trade-off: enhanced cross-linking and rigidity improve mechanical robustness but inevitably restrict chain mobility, thereby compromising essential features such as self-healing and recyclability. This inherent compromise severely constrains their multifunctional application. Here, we report a supramolecular polyurethane (COPUSL) comprising a "dynamic switch" constructed from dynamic disulfide bonds and hydrogen bonds, together with a "rigid-flexible balanced network" composed of castor oil long fatty chains and polyphenol-functionalized lignin. This design endows COPUSL with excellent mechanical properties while also enabling rapid self-healing (self-healing efficiency: 87%) and efficient recyclability. Furthermore, COPUSL with introduced aromatic structures and extended conjugate systems exhibits 100% ultraviolet-blocking efficiency and a high photothermal conversion capability (surface temperature: 153 °C) due to the electron transition and energy release of the lignin structure after absorbing light energy. By systematically investigating the relaxation kinetics, dynamic behavior, and macroscopic properties, we elucidate the distinct roles of the "dynamic switch" and "rigid-flexible balanced network" in regulating the polymer architecture and connecting dynamic behavior with mechanical and functional performance. These findings provide molecular-level insights for the design of high-performance, bio-based polyurethane with tailored multifunctional responsiveness.
暂无摘要（点击查看详情）