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关键词： 嵌合抗原受体T细胞   伦理审查   法规  

摘要： 目的 深入分析我国及美国嵌合抗原受体T（chimericantigenreceptorT，CAR-T）细胞疗法伦理审查相关法规政策及伦理审查要点，为进一步完善我国CAR-T细胞疗法伦理审查体系建设提供参考依据。方法在我国与美国政府、协会网站以及中国知网、万方、维普、PubMed等数据库，以“CAR-T细胞疗法”为检索词，检索相关法规、制度及文献，进行深入分析，系统总结相关经验。结果CAR-T细胞疗法进行伦理审查时，需重点关注相关资质（包括研究机构、研究者、第三方实验室等）、知情同意、风险评估与管理、弱势群体等方面。相较于美国，我国尚需进一步加强伦理审查体系建设，设立专门的伦理审查相关法律法规，制定涵盖CAR-T细胞疗法产品从生产到临床应用全生命周期的技术标准或参考规范，完善CAR-T细胞疗法伦理规范，并在国家层面全力支持细胞免疫疗法研究领域的发展，推动CAR-T细胞疗法临床研究快速推进。结论我国目前关于CAR-T细胞疗法伦理审查相关法规发展迅速，但仍需进一步完善细胞免疫疗法伦理规范，保证最小化风险，最大化受益。

关键词： Interleukin-33   Chronic periodontitis   Serum   Plasma   Saliva   Biomarkers   Systematic review  

摘要： Background Activation of the IL-33/ST2 axis leads to the production of proinflammatory cytokines and thus to the triggering of osteoclastogenesis, which is why it plays an important role in the immunopathogenesis of periodontitis. The aim of this study was to compare IL-33 levels in serum, plasma, saliva and gingival crevicular fluid (GCF) of subjects with chronic periodontitis (CP) in comparison with the control group (CG). Methods This systematic review and meta-analysis followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and was registered in the Open Science Framework (OSF): https://***/10.17605/***/YHUWA. Six electronic databases were used for study identification;PubMed, Google Scholar, ScienceDirect, Web of Science, Scopus and Dentistry & Oral Sciences Source from March 10, 2012 to April 30, 2024. The Joanna Briggs Institute (JBI) tool was used to assess the quality of the included cross-sectional articles and clinical trials. Results Of the 949 articles identified, 14 were included according to the inclusion and exclusion criteria. The total number of individuals studied in the included investigations was 814 of whom 445 had CP and 369 were healthy. The reported age range was from 20 to 50 years, with a mean age +/- standard deviation of 40.29 +/- 7.83 years. Four hundred and twenty-six (52%) patients were men and 388 (48%) were women. Meta-analysis revealed that there is an increase in IL-33 levels in plasma, saliva and GCF of subjects with CP compared to CG (p = * < 0.05). Conclusions This study found a significant increase in IL-33 levels in different biological samples (plasma, saliva and GCF) of individuals with CP compared to CG, thus IL-33 has potential to be a biomarker in the diagnosis of periodontitis.

关键词： 嵌合抗原受体T细胞   产业发展现状   监管体系  

摘要： 近年来，基于我国一系列鼓励政策及强大的市场需求，嵌合抗原受体T细胞（chimeric antigen receptor T cells， CAR-T细胞）治疗产业迅猛发展。截至2024年5月，全球共有11种CAR-T细胞技术产品上市，其中我国国家药品监督管理局批准了5种。在CAR-T细胞治疗研发领域，我国在专利申请及临床试验数量方面已跻身全球领先地位。随着经验的不断积累及探索地持续深入，中国监管部门已初步建立了涵盖研发、注册、生产到上市后监管全生命周期的法律、法规及指导原则三级监管体系。然而，与美国、欧盟、日本等国家和地区相比，我国在监管体系建设方面仍存在一定差距。本文分析了我国CAR-T细胞治疗产业发展及监管体系现状，并参考借鉴美国、欧盟、日本等国家和地区的先进经验，以期为我国进一步完善CAR-T细胞治疗监管体系提供参考。

关键词： HIV infection   IL-6   IP-10   MIP-1 beta   PTX-3   immunologic response  

摘要： Despite effective antiretroviral therapy (ART), 15-30% of people with HIV experience poor CD4+ T-cell recovery, termed immunologic non-responders (INR). This study aims to evaluate whether pre-ART plasma levels of interleukin-6 (IL-6), interferon gamma-induced protein-10 (IP-10), macrophage inflammatory protein-1-beta (MIP-1 beta), and/or pentraxin-3 (PTX-3) could predict subsequent immunologic recovery. Seventy-four participants were enrolled and classified as INR and immunologic responders (IR) based on CD4+/CD8+ ratio increase over 24 months after starting ART. The results showed no significant differences in cytokine levels between INR and IR. Therefore, IL-6, IP-10, MIP-1 beta, and PTX-3 were unsuitable as predictive markers of poor immune recovery.

关键词： Osteomyelitis   Inflammation   Inflammatory diseases   Biomarkers   Platelets   Cytokines   Medical implants   Rabbits  

摘要： Infections are a major complication of open fractures and fracture fixation. In this study, an innovative bioactive medical device was used to experimentally treat MRSE-induced osteomyelitis in rabbit tibia. This paper investigates the clinical significance of inflammatory biomarkers (NLR, PLR, MLR and PMR), SII and IL-6 and assesses their role in the development of osteomyelitis. The main objective is to identify the utility of hematological reports derived from neutrophils, leukocytes, monocytes and platelets in the evolution of implant-related osteomyelitis and the estimation of treatment efficiency. In particular, this study compares the response of these inflammatory markers to different treatments in the presence or absence of bioactive materials and/or topical antibiotics over time. The analysis of the threads showed that NLR, PLR and SII had high values in the acute phase of the disease, so that after chronicization, they decrease. The animals treated with vancomycin nano-functionalized peptide-enriched silk fibroin-coated implants showed lower levels of inflammatory biomarkers compared to the other groups (empty implants and peptide-enriched silk fibroin-coated implants). NLR, PLR and SII, complemented by IL-6 can be used as fairly accurate biomarkers for the diagnosis of osteomyelitis.

关键词： Coronary Artery Disease   Mendelian randomization   Lipidome   immune cell   Natural Killer cell  

摘要： Background Coronary artery disease (CAD) imposes a significant global health burden, necessitating a deeper comprehension of its genetic foundations to uncover innovative therapeutic targets. Employing a comprehensive Mendelian randomization (MR) approach, we aimed to explore the genetic associations between lipid profiles, immune cell phenotypes, and CAD *** Utilizing data from recent large-scale genome-wide association studies (GWAS), we scrutinized 179 lipid and 731 immune cell phenotypes to delineate their genetic contributions to CAD pathogenesis, including coronary artery calcification (CAC). Moreover, specific immune cell phenotypes were examined as potential mediators of the lipid-CAD/CAC causal *** Among the 162 lipid species with qualified instrumental variables (IVs) included in the analysis, we identified 36 lipids that exhibit a genetic causal relationship with CAD, with 29 being risk factors and 7 serving as protective factors. Phosphatidylethanolamine (18:0_20:4) with 8 IVs (OR, 95% CI, P-value: 1.04, 1.02-1.06, 1.50E-04) met the Bonferroni-corrected significance threshold (0.05/162 = 3.09E-04). Notably, all 18 shared lipids were determined to be risk factors for both CAD and CAC, including 16 triacylglycerol traits (15 of which had >= 3 IVs), with (50:1) exhibiting the highest risk [OR (95% CI) in CAC: 1.428 (1.129-1.807);OR (95% CI) in CAD: 1.119 (1.046-1.198)], and 2 diacylglycerol traits. Furthermore, we identified HLA DR+ natural killer cells (IVs = 3) as nominally significant with lipids and as potential mediators in the causal pathway between diacylglycerol (16:1_18:1) or various triacylglycerols and CAD (mediated effect: 0.007 to 0.013).Conclusions This study provides preliminary insights into the genetic correlations between lipid metabolism, immune cell dynamics, and CAD susceptibility, highlighting the potential involvement of natural killer cells in the lipid-CAD/CAC causal pathway and suggesting new targets for therap

关键词： 心肌肌钙蛋白I   肌钙蛋白C   单克隆抗体   亲和性  

摘要： 目的：了解不同心肌肌钙蛋白I（cTnI）抗原表位的单克隆抗体（MAb）对cTnI-肌钙蛋白C（cTnI-TnC）抗原的亲和性，筛选新型cTnI特异性抗体用于临床检测试剂盒研发。方法：基于微阵列化学发光免疫分析技术平台，采用cTnI-TnC抗原点样硬基质芯片，以鼠源性cTnI MAb作为待检抗体，HRP-羊抗鼠IgG为检测抗体，对抗原点样液、抗原点样浓度、待检抗体浓度进行实验条件优化；使用竞争法检测不同抗原表位的cTnI MAb对cTnI-TnC的亲和力，实验组为加入梯度浓度的cTnI-TnC，对照组加入等体积的稀释液，检测不同cTnI MAb的反应信号，计算亲和常数。结果：最优实验条件：抗原点样液为P105，抗原点样浓度为0.1mg/mL，待检抗体浓度为80ng/mL；包含TnC抗体的20c6cc和7B9cc MAb亲和性最好，其中20c6cc MAb达3.18×106L/moL；cTnI MAb中位于肽链C端的a.a.r 130-145、169-178和190-196区域的cTnI MAb表现出较好亲和力，其中MAb 625（a.a.r 169-178）为6.37×105L/moL，在cTnI MAb中亲和性最强。结论：cTnI肽链C端a.a.r 130-145、169-178、190-196和TnC区的cTnI MAb与cTnI-TnC抗原的亲和性较好，针对该区域设计新型cTnI补位抗体，可作为解决自身抗体及肽链蛋白水解负性干扰的新思路。

关键词： 咳喘镇定汤   小儿咳嗽变异性哮喘   IL-23/Th17轴   小气道功能   疗效   咳嗽   T淋巴亚群  

摘要： 目的 观察咳喘镇定汤在小儿咳嗽变异性哮喘治疗中的作用及对患儿EOS、IL-23/Th17轴的影响。方法 选取2020.8～2023.2收治的小儿咳嗽变异性哮喘患儿104例，将患儿采用简单随机法分为两组。常规组给予止咳化痰、抗炎、平喘等常规治疗，咳喘镇定汤组在常规组基础上采用咳喘镇定汤辅助治疗。检测组间及组内T淋巴亚群、嗜酸性粒细胞计数（Eosinophil count，EOS）、巨噬细胞炎症蛋白-1α（Macrophage inflammatory protein-1α，MIP-1α）、Clara细胞分泌蛋白16（Clara cell secreted protein 16，CC-16）、嗜酸细胞活化趋化因子（Eotaxin）、白介素-23（Interleukin-23，IL-23）/辅助性T细胞17（Helper T cells17，Th17）轴、小气道功能水平。评估组间及组内咳嗽症状评分、中医症候评分差异。统计组间疗效和不良反应。结果 治疗前T淋巴亚群、CC-16、Eotaxin等无差异（P>0.05）。两组治疗后CD8+、EOS、MIP-1α、Eotaxin降低，CC-16、CD4+、CD4+/CD8+升高，咳喘镇定汤组治疗后CD8+、EOS、MIP-1α、Eotaxin低于常规组，CC-16、CD4+、CD4+/CD8+高于常规组（P＜0.05）。治疗前比较IL-23/Th17轴无差异（P>0.05）。两组治疗后IL-23、Th17、白介素-17（Interleukin-17，IL-17）降低，咳喘镇定汤组治疗后IL-23/Th17轴低于常规组（P＜0.05）。治疗前相关评分无差异（P>0.05）。两组治疗后咳嗽症状评分、中医症候评分降低，咳喘镇定汤组治疗后咳嗽症状评分、中医症候评分低于常规组（P＜0.05）。治疗前小气道功能无差异（P>0.05）。两组治疗后小气道功能升高，咳喘镇定汤组治疗后小气道功能高于常规组（P＜0.05）。咳喘镇定汤组治愈13例，显效和有效共35例，总有效率92.31%高于常规组，有统计学意义（P<0.05）。结论 咳喘镇定汤可通过调控小儿咳嗽变异性哮喘患儿IL-23/Th17轴，改善T淋巴亚群和小气道功能，减轻咳嗽症状，提高疗效。

关键词： Kidneys   Chronic kidney disease   Urinary tract infections   Epidemiology   Kidney stones   Questionnaires   Contract law   Global health  

摘要： Introduction Chronic kidney disease (CKD) has become more common in recent decades, putting significant strain on healthcare systems worldwide. CKD is a global health issue that can lead to severe complications such as kidney failure and *** The purpose of this study was to investigate the actual causes of the alarming increase of kidney failure cases in Saudi Arabia using the supersaturated design analysis and edge design *** and methods A cross-sectional questionnaire was distributed to the general population in the KSA, and data were collected using Google Forms. A total of 401 responses were received. To determine the actual causes of kidney failure, edge and supersaturated designs analysis methods were used, which resulted in statistical significance. All variables were studied from factor h1 to factor h18 related to the causes of kidney *** The supersaturated analysis method revealed that the reasons for the increase in kidney failure cases are as follows: h9(Bad diet), h8(Recurrent urinary tract infection), h1 (Not drinking fluids), h6 (Lack of exercise), h14 (drinking from places not designated for valleys and reefs), h18 (Rheumatic diseases), h10 (Smoking and alcohol consumption), h13 (Direct damage to the kidneys), h2 (take medications), h17 (excessive intake of soft drinks), h12 (Infection), h5 (heart disease), h3 (diabetes), h4 (pressure disease), h15 (Dyes used in X-rays), and h11 (The presence of kidney stones) are all valid. The design analysis method by edges revealed that the following factors contributed to an increase in kidney failure cases: h8 (Recurrent urinary tract infection), h6 (Lack of exercise), h7 (Obesity), and *** The findings showed that there were causes of kidney failure that led to the statistical significance, which is h8 (Recurrent urinary tract infection) and h11 (The presence of kidney stones)