Spinal Cord Injury–Functional Index/Capacity: Responsiveness to Change Over Time

ObjectiveTo establish responsiveness of 3 Spinal Cord Injury–Functional Index/Capacity (SCI-FI/C) item banks in the first year after spinal cord injury (SCI).DesignLongitudinal patient-reported outcomes assessment replicated through secondary analysis of an independent data set.SettingA total of 8 SCI Model Systems rehabilitation hospitals in the United States.ParticipantsStudy 1 participants included 184 adults with recent (≤4 months) traumatic SCI and 221 community-dwelling adults (>1 year post injury) (N=405). Study 2 participants were 418 individuals with recent SCI (≤4 months) (N=418).InterventionsIn study 1, SCI-FI/C computer adaptive tests were presented in a standardized interview format either in person or by phone call at baseline and 6-month follow-up. Responsiveness was examined by comparing 6-month changes in SCI-FI scores within and across samples (recently injured vs community-dwelling) because only the recent injury sample was expected to exhibit change over time. Effect sizes were also computed. In study 2, the study 1 results were cross-validated in a second sample with recent SCI 1 year after baseline measurement. Study 2 also compared the SCI-FI/C measures’ responsiveness to that of the Self-reported Functional Measure (SRFM) and stratified results by injury diagnosis and completeness.Main Outcome MeasuresThe SCI-FI Basic Mobility/C, Self-care/C and Fine Motor/C item banks (study 1 and study 2); Self-reported Functional Measure SRFM (study 2 only).ResultsIn study 1, changes in SCI-FI/C scores between baseline and 6-month follow-up were statistically significant (P<.01) for recently injured individuals. SCI-FI Basic Mobility/C, Self-care/C, and Fine Motor/C item banks demonstrated small to medium effect sizes in the recently injured sample. In the community-dwelling sample, all SCI-FI/C effects were negligible (ie, effect size<0.08). Study 2 results were similar to study 1. As expected, SCI-FI Basic Mobility/C and Self-care/C were responsive to change for all individuals in study 2, whereas the SCI-FI Fine Motor/C was responsive only for individuals with tetraplegia and incomplete paraplegia. The SRFM demonstrated a medium effect size for responsiveness (effect size=0.65).ConclusionsThe SCI-FI Basic Mobility/C and Self-care/C banks demonstrate adequate sensitivity to change at 6 months and 1 year for all individuals with SCI, while the SCI-FI/C Fine Motor item bank is sensitive to change in individuals with tetraplegia or incomplete paraplegia. All SCI-FI/C banks demonstrate stability in a sample not expected to change. Results provide support for the use of these measures for research or clinical use.     

双环[1.1.1]戊烷衍生物的合成研究进展

双环[1.1.1]戊烷（BCP）是一种具有三维立体结构的桥环骨架，其作为苯环、叔丁基和炔烃的生物电子等排体，已经在药物化学领域得到广泛的应用。随着BCP应用范围的扩大，BCP及其衍生物的合成日益成为研究的热点。本文对BCP衍生物的主要合成策略和方法进行总结，旨在为新药研发人员提供参考。     

TRIM59 通过结合 BCLAF1 调控人皮肤黑色素瘤 SK-MEL-2 细胞的恶 性生物学行为

目的：探究三结构域蛋白59（TRIM59）调控人皮肤黑色素瘤细胞SK-MEL-2增殖、细胞周期、凋亡及迁移侵袭的作用机制，及其与Bcl2相关转录因子1（BCLAF1)之间的关系。方法：qPCR和WB法检测人表皮黑色素细胞HEMn-LP、人皮肤黑色素瘤细胞SK-MEL-2、UACC903、A375及36例邢台市人民医院2019年2月至2021年7月收集的皮肤黑色素瘤组织中TRIM59的mRNA和蛋白表达，使用脂质体将si-con、si-TRIM59转染至SK-MEL-2细胞中，WB法检测干扰TRIM59表达对细胞中周期蛋白D1（CCND1）、细胞周期素依赖性激酶2（CDK2）、肿瘤抑制蛋白基因（TP53）和 BCLAF1 蛋白表达的影响，CCK-8法、流式细胞术、划痕愈合实验、Transwell实验检测对细胞的活性、凋亡、迁移和侵袭的影响，免疫共沉淀（Co-IP）实验检测对细胞中TRIM59蛋白与BCLAF1结合能力的影响。结果：与HEMn-LP细胞相比，SK-MEL-2、UACC903、A375细胞中TRIM59 mRNA和TRIM59、BCLAF1蛋白均呈高表达（均P<0.05），SK-MEL-2细胞中TRIM59表达水平最高。相较于si-con组和Normal组，沉默TRIM59后，SK-MEL-2细胞的活性显著降低，细胞周期阻滞于G2期，CCND1、CDK2的蛋白表达显著降低，TP53蛋白和细胞凋亡率均显著升高，划痕抑制率明显升高，迁移侵袭细胞数明显降低（均P<0.05）。免疫共沉淀实验结果显示，TRIM59与BCLAF1之间存在蛋白结合关系。TRIM59与 BCLAF1 在肿瘤组织中的表达呈显著的正相关（r=0.878，P<0.001）。结论：干扰TRIM59表达能够抑制人皮肤黑色素瘤SK-MEL-2细胞的增殖、迁移和侵袭而促进凋亡，抑制SK-MEL-2细胞的恶性生物学行为，其机制可能与TRIM59结合BCLAF1有关。     

2例胰岛素自身免疫综合征临床病例分析

通过回顾分析我院2例确诊为胰岛素自身免疫综合征(IAS)患者的临床资料,并复习相关文献,总结发病机制及治疗方法,探讨IAS患者的临床特点,提高对低血糖症的诊治水平。     

FDA“治疗等效性评价供企业用指导原则”（草案）介绍

美国食品药品管理局（FDA）于2022年7月发布了"治疗等效性评价供企业用指导原则"（草案）。该指导原则阐明了FDA治疗等效性的标准以及治疗等效性编码系统，目的是准确评价仿制药与参比制剂的治疗等效性并通过治疗等效性代码，在"橙皮书"中迅速检索到治疗等效的仿制药。而中国目前尚无类似的指导原则，详细介绍FDA该指导原则主要内容，期望对中国加强仿制药的治疗等效性评价和加速完善和实施符合国情的治疗等效性编码系统有所帮助。     

基于CNKI的中医药治疗癫痫的知识图谱分析＊

目的 运用科学知识图谱的手段，分析中医药治疗癫痫的研究进程并提炼重点。方法 设置检索时间为1990年至2020年，检索对象为中国知网（CNKI）该领域的相关文献，运用CiteSpace软件科学、准确地分析这些文献的作者信息、研究（发文）机构、关键词情况。结果 共计纳入文献793篇，马融-张喜莲、刘金民、谢炜、王洪图-张丽萍等领导核心作者团队，北京、广州以及广西中医药大学、天津中医药大学第一附属医院、南方医科大学等单位为主要进行相关研究的机构，高频关键词包括大鼠、难治性癫痫、小儿癫痫、海马、脑电图等，作用机制、网络药理学、肠道菌群、氧化应激、分子生物学等为近年来的热点与前沿。结论 通过借用知识图谱的分析能帮助提炼国内中医药治疗癫痫研究领域的重点，全面分析并科学判断近年来该领域的热点及前沿，为未来的研究夯实基础并把握方向。     

The impact of neighborhoods and friendships on interracial anxiety among medical students and residents: A report from the medical student CHANGES study

Objective

To examine the experience of interracial anxiety among health professionals and how it may affect the quality of their interactions with patients from racially marginalized populations. We explored the influence of prior interracial exposure—specifically through childhood neighborhoods, college student bodies, and friend groups—on interracial anxiety among medical students and residents. We also examined whether levels of interracial anxiety change from medical school through residency.

Data Source

Web-based longitudinal survey data from the Medical Student Cognitive Habits and Growth Evaluation Study.

Study Design

We used a retrospective longitudinal design with four observations for each trainee. The study population consisted of non-Black US medical trainees surveyed in their 1st and 4th years of medical school and 2nd and 3rd years of residency. Mixed effects longitudinal models were used to assess predictors of interracial anxiety and assess changes in interracial anxiety scores over time.

Principal Findings

In total, 3155 non-Black medical trainees were followed for 7 years. Seventy-eight percent grew up in predominantly White neighborhoods. Living in predominantly White neighborhoods and having less racially diverse friends were associated with higher levels of interracial anxiety among medical trainees. Trainees' interracial anxiety scores did not substantially change over time; interracial anxiety was highest in the 1st year of medical school, lowest in the 4th year, and increased slightly during residency.

Conclusions

Neighborhood and friend group composition had independent effects on interracial anxiety, indicating that premedical racial socialization may affect medical trainees' preparedness to interact effectively with diverse patient populations. Additionally, the lack of substantial change in interracial anxiety throughout medical training suggests the importance of providing curricular tools and structure (e.g., instituting interracial cooperative learning activities) to foster the development of healthy interracial relationships.     

新型降脂药人前蛋白转化酶枯草溶菌素 9抑制剂与动脉粥样硬化性心血管疾病、静脉血栓栓塞疾病关系的研究进展

随着生活方式的改变，心脑血管疾病逐渐成为全人类死亡的“头号杀手”高于恶性肿瘤、糖尿病等。血脂的升高尤其是低密度脂蛋白胆固醇( LDL-C)的升高与动脉粥样硬化性心血管疾病( ASCVD)的发，生、发展息息相关。现有的专家共识、南提出他汀类药物是降低 LDL-C的一线用药，但仍可能会发生复发性缺血事件。人前蛋白转化酶枯草溶菌素 9(PCSK9)抑制指剂作为一类新型降脂药，有显著降低血 LDL-C水平，同时又可降低脂蛋白( a)的水平，又与 ASCVD与静脉血栓栓塞疾病( VTE)的发病可能相关。本文将系统地阐述新型降脂药 PCSK9抑制剂与 ASCVD、VTE的关系研究进展。     

Characterizing Standardized Functional Data at Inpatient Rehabilitation Facilities

ObjectiveThe Improving Medicare Post-Acute Care Transformation Act of 2014 mandates using standardized patient functional data across post-acute settings. This study characterized similarities and differences in clinician-observed scores of self-care and transfer items for the standardized section GG functional domain and the functional independent measure (FIM) at inpatient rehabilitation facilities.DesignWe conducted secondary analyses of 2017 Uniform Data System for Medical Rehabilitation national data. Patients were assessed by clinicians on both section GG and FIM at admission and discharge. We identified 7 self-care items and 6 transfer items in section GG conceptually equivalent with FIM. Clinician-assessed scores for each pair of items were examined using score distributions, Bland-Altman plot, correlation (Pearson coefficients), and agreement (kappa and weighted kappa) analyses.Setting and ParticipantsIn all, 408,491 patients were admitted to Uniform Data System for Medical Rehabilitation-affiliated inpatient rehabilitation facilities with one of the following impairments: stroke, brain dysfunction, neurologic condition, orthopedic disorders, and debility.MeasuresSection GG and FIM.ResultsPatients were scored as more functionally independent in section GG compared with FIM, but change score distributions and score orders within impairment groups were similar. Total scores in section GG had strong positive correlations (self-care: r = 0.87 and 0.95; transfer: r = 0.82 and 0.90 at admission and discharge, respectively) with total FIM scores. Weak to moderate ranking agreements with total FIM scores were observed (self-care: kappa = 0.49 and 0.60; transfers: kappa = 0.43 and 0.52 at admission and discharge, respectively). Lower agreements were observed for less able patients at admission and for higher ability patients of their change scores.Conclusions and ImplicationsOverall, response patterns were similar in section GG and FIM across impairments. However, variations exist in score distributions and ranking agreement. Future research should examine the use of GG codes to maintain effective care, outcomes, and unbiased reimbursement across post-acute settings.