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川芎嗪和阿魏酸作为传统活血化瘀中药川芎的主要活性成分，在近年被广泛应用于骨代谢调控中并得到越来越多的关注，已有关于两者在体外细胞实验、动物模型以及信号通路上对其抗骨质疏松和促成骨的药理作用进行了初步探索，但是尚未有综述对其进行整合总结。因此，本文将以川芎嗪和阿魏酸为两条分子线索，沿着促成骨分化与抗骨质疏松、抑制破骨细胞活化、促血管新生与骨整合协同三条功能方向，对2016—2026近年来关于这两类药物的相关研究进行检索及归纳；梳理了它们通过OPG/RANKL/RANK、NF-κB、MAPK、BMP-2/Smad、Wnt/β-catenin和Nrf2/ARE等信号通路来调节骨代谢的研究进展，讨论了二者的以成骨细胞源性的RANKL/OPG来调节和直接RANKL-RANK的信号阻断这两种模式互补地调控破骨细胞的信号网络，同时归纳了他们在骨组织工程支架和植入体表面的功能化上的应用进展。在此基础上，本文进一步分析川芎嗪与阿魏酸协同效应评价、促血管新生与成骨耦联机制、植入体骨整合大动物模型证据、体内释放动力学及长期安全性等方面尚待解决的问题，提出其向临床骨整合应用转化过程中需要关注的协同效应定量评价、血管新生—成骨耦联因果关系验证及可控递送体系设计等关键方向。

背景　我国高血压患病率随年龄增长持续上升，中老年人群同时面临社会隔离、抑郁与认知功能下降的多重风险，但目前针对三者间的纵向相互影响及其潜在作用路径仍缺乏系统认识。目的　探讨中老年高血压患者社会隔离、抑郁与认知功能的纵向交互作用及抑郁在其中的中介效应。方法　基于中国健康与养老追踪调查（CHARLS）2015年、2018年和2020年3期纵向数据，纳入3 027例确诊高血压的中老年患者。通过自报婚姻情况、居住方式、与子女联系和见面情况、社会参与情况及居住地等变量构建社会隔离指数，利用简易流调中心抑郁量表（CES-D）测量抑郁情况，认知功能采用简易精神状态检查表（MMSE）进行测量。使用交叉滞后路径模型和偏差校正Bootstrap法，检验社会隔离与抑郁和认知功能的纵向关系。结果　社会隔离与抑郁呈双向正相关：T1社会隔离可正向预测T2抑郁（B=0.429，P<0.001），T1抑郁也可正向预测T2社会隔离（B=0.012，P<0.001）。抑郁与认知功能呈双向负相关：T1、T2抑郁均可负向预测T2、T3认知功能（B=-0.043，P<0.001；B=-0.038，P<0.001），T1、T2认知功能也可负向预测T2、T3抑郁（B=-0.089，P<0.05；B=-0.049，P<0.05）。T1社会隔离通过T2抑郁完全中介间接导致T3认知功能下降（B=-0.016，95%CI=-0.029~-0.008），总效应显著（B=-0.099，95%CI=-0.195~-0.010）。结论　在中老年高血压患者中，社会隔离与抑郁、抑郁与认知功能间存在双向恶性循环，且早期社会隔离通过抑郁完全中介导致远期认知功能衰退。早期干预社会隔离和抑郁可打破“认知-情绪”脆弱循环，改善中老年高血压患者的健康状况和生活质量。

Abstract Background Epilepsy is one of the most prevalent and disabling chronic neurological disorders worldwide, affecting approximately 79 million individuals. As a customizable and reversible neuromodulatory intervention, deep brain stimulation (DBS) has revolutionized the clinical management of drug-resistant epilepsy (DRE). Despite its expanding clinical application, there remains a lack of systematic, data-driven integrated research on the global development trajectory and target-specific advances in the field of DBS for epilepsy. This study aims to quantitatively map the 20-year academic landscape of this field and identify current clinical frontier directions. Methods This study represents the first dual-database bibliometric analysis in this domain, cross-validating 1,595 publications from the Web of Science Core Collection (WoSCC) and 1,696 publications from the Scopus database covering the period 2004 to 2024. Knowledge mapping and visualization were performed using VOSviewer (v1.6.20) and CiteSpace (v6.4.R1). To capture recent developments, we additionally screened 502 publications from January 2025 to May 2026 and conducted a focused supplementary analysis of 144 influential recent publications meeting prespecified citation- or journal-based criteria. Results Global publication output demonstrated a sustained upward trend from 2004 to 2024, with annual publications increasing substantially over the study period. The growth trajectory reflected continued expansion of research activity in DBS for epilepsy, accompanied by increasing international collaboration and diversification of clinical targets, with the United States, China and Germany ranking as the top three most productive countries. The academic evolution of the field falls into three distinct phases: an early target exploration phase (2004–2012), a technological iteration and clinical evidence accumulation phase (2013–2018), and a rapid development phase of network modulation and adaptive systems (2019–2024). Frontier literature from 2025 to 2026 identifies five core development directions: ① closed-loop and AI-driven adaptive neuromodulation is progressing toward clinical translation; ② connectome-guided novel targeting strategies are continuously emerging; ③ advances in minimally invasive and non-invasive neuromodulation technologies are providing complementary technical and mechanistic insights for the development of DBS; ④ mechanistic research is increasingly guiding clinical parameter optimization; ⑤ DBS indications are expanding to pediatric populations, with further validation of long-term safety profiles. Conclusions This study systematically delineates the 20-year intellectual landscape of DBS for epilepsy and integrates up-to-date prospective insights. It provides a systematic reference and an updated reference for clinicians and researchers to grasp the evolutionary trajectory of the field and identify priority directions for future investigation.

Research participation is an important component of postgraduate medical training, yet trainees often differ substantially in access to mentorship, protected research time, funding, data, infrastructure, methodological support, and collaboration. Observed scholarly output may therefore reflect not only individual characteristics but also the research-resource environment in which training occurs. We introduce Resource-Attributable Research Loss (RARL-R), a counterfactual framework for quantifying potentially remediable research-opportunity gaps in postgraduate medical education. For trainee i, Rᵢ denotes the observed research-resource profile, R* a prespecified feasible adequacy benchmark, and Rᵢ† = Rᵢ ∨ R* a no-downgrade remediation profile. With μᵢ(r) = E[Yᵢ(r) | Xᵢ], the primary estimand is the resource-attributable expected output gap: Δᵢᴿ = [ μᵢ(Rᵢ†) − μᵢ(Rᵢ) ]₊ When the scholarly outcome has a meaningful zero and ratio-scale interpretation, this gap may additionally be expressed as equivalent research time: τᵢᴿ = T [ 1 − μᵢ(Rᵢ) / μᵢ(Rᵢ†) ]₊ RARL-R does not estimate innate research ability, prescribe how much a trainee should have produced, or provide an adjusted ranking. Instead, it defines an individualized conditional expected counterfactual contrast between observed research resources and a feasible remediation of specified resource deficits. We develop the conceptual and mathematical formulation of RARL-R, specify its measurement and identification requirements, and evaluate estimator recoverability using Monte Carlo simulation. Across 200 replications, a correctly specified g-computation estimator achieved mean RMSEs of 0.209, 0.132, and 0.092 equivalent research years at sample sizes of n = 200, 500, and 1000, respectively. Corresponding mean correlations between true and estimated RARL-R values were 0.938, 0.976, and 0.988. A deliberately crude cohort-reference comparator showed substantially poorer performance. RARL-R provides an opportunity-sensitive framework for studying how modifiable features of postgraduate medical research environments may contribute to differences in expected scholarly development. The simulation demonstrates internal recoverability under a controlled, correctly specified setting, not empirical validity in real trainees. Future evaluation requires prospective multicentre longitudinal validation, prespecified context-sensitive benchmarks, and careful assessment of confounding, positivity, measurement error, model misspecification, and interference.

为探究企业管理者安全履职行为与生产安全事故刑责认定的内在关联，把握司法裁判的量刑规律，本文以2017年6月—2026年5月中国裁判文书网收录的274份生产安全责任事故刑事判决书为样本，采用文本统计、对比分析与相关性分析，将安全履职行为归纳为11类、失职违法行为归纳为10类，考察不同履职状态、违法情形与刑期长短、实缓刑适用及从轻免罚认定的对应关系。生产安全事故刑责认定整体以缓刑为主要方式（缓刑占72.60%）；履职行为存在明显的规模效应，涉案人数越多的履职类型平均刑期越短、缓刑率越高；不具备法定安全条件、安全投入不足、危险物品违规管理、事故瞒报抗拒监管四类违法行为，是重刑判决的核心诱因。样本仅取自中国裁判文书网公开文书，判决书对履职情况的表述一致性较弱，且以描述统计与相关系数分析为主，未控制事故等级、地域与行业等多因素影响，结论外推仍需更多样本验证。常规安全履职不能免除刑事责任，但规范化、全流程的履职可显著降低刑责惩戒力度；企业管理者应重点落实防护警示、安全教育培训与安全责任体系建设，规避重刑风险较高的违法行为。