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关键词： 嵌合抗原受体T细胞   细胞治疗产品   扩大产能   风险分析  

摘要： 嵌合抗原受体T细胞免疫治疗(CAR-T)产品在多种血液肿瘤治疗中显示了非常好的临床效果。近年来,我国CAR-T产品研究也呈现蓬勃发展的态势。随着企业品种的适应证不断增加及市场需求的增加,部分生产企业产能需要进一步扩大。文章通过梳理CAR-T产品在扩大产能过程中厂房布局、设备、公用系统、人员及过程控制等方面的影响,分析各要素可能存在的风险,为该类产品质量的持续改进和监管机构的监管提供参考。

关键词： 自身免疫性肝炎   抗可溶性肝抗原抗体   免疫球蛋白G   肝脏病理  

摘要： 目的检测自身免疫性肝炎(AIH)患者血清抗可溶性肝抗原(SLA)抗体水平并分析其在肝脏损伤中的价值。方法回顾性分析南京市第二医院2017年1月至2024年4月确诊的33例抗SLA抗体阳性AIH患者及33例年龄、性别匹配的抗SLA抗体阴性AIH病例数据。收集患者的一般及临床资料,检测抗SLA抗体(蛋白质印迹法)、抗核抗体(间接免疫荧光法)等自身免疫肝病抗体、总胆红素(T-Bil)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、γ-谷氨酰基转移酶(GGT)、碱性磷酸酶(ALP)以及免疫球蛋白IgG水平。分析并比较患者的临床特征、实验室参数以及肝组织病理学特点。结果两组患者性别、年龄、自身免疫肝病抗体(如抗核抗体、抗平滑肌抗体等)及肝功能指标(AST、ALT、GGT、ALP)比较,差异均无统计学意义(P>0.05)。而抗SLA抗体阳性患者的T-Bil、IgG水平显著高于阴性组(P值分别为0.017、0.048)。肝组织病理检查发现,抗SLA阳性组有淋巴细胞-浆细胞浸润表现的患者比例显著高于抗SLA阴性组(χ2=4.243,P<0.05),提示更活跃的免疫反应。结论AIH患者血清抗SLA抗体水平检测有助于反映肝脏损伤程度,具备辅助诊断及监测病情的潜能。

关键词： 高通量血液透析   慢性肾功能衰竭   CRP   TNF-α水平   疗效  

摘要： 探讨高通量血液透析在慢性肾功能衰竭患者治疗中的疗效及对CRP、TNF-α水平的影响。方法 82例慢性肾功能衰竭患选自2022年1月至2023年1月依据随机数字表法分组,各41例;对照组采取常规血液透析治疗,观察组采取高通量血液透析治疗。结果 观察组在治疗后各项肾功能指标所得参数均更低(P<0.05)。观察组在治疗后测得的血磷及甲状旁腺激素参数均更低(P<0.05),血浆白蛋白则更高(P<0.05)。观察组CRP、TNF-α水平及并发症率更低(P<0.05)。结论 高通量血液透析治疗慢性肾功能衰竭患者,对肾功能有明显的改善作用,同时能够有效降低CRP、TNF-α水平,减少患者并发症情况。

关键词： Bupropion   liver injury   myocardial infarction   Sirt1   TLR4  

摘要： BackgroundThe aim of the current study is to identify the possible protective effect of bupropion (BUP) on liver injury in rat model of myocardial infarction (MI). BUP was administered in the presence and absence of *** and methodsThirty-two Wistar adult male rats were randomly arranged into four groups: control, BUP (30 mg/kg/day, intraperitoneal) for 28 days, isoproterenol (ISO) was injected subcutaneous (85 mg/kg) in the 26th and 27th days and BUP/ISO groups. Cardiac and hepatic enzymes were measured, also Hepatic oxidative stress indicators, as well as inflammatory and apoptotic biomarkers, were evaluated. Cardiac and hepatic histopathological examination and hepatic nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) immunohistochemical study were also *** significantly increased cardiac and hepatic enzymes, hepatic oxidative stress, inflammatory, apoptotic, with a histopathological picture of cardiac and hepatic damage and high hepatic NF-kappa B immunoexpression were detected. BUP significantly normalized the upraised oxidative, inflammatory, and apoptotic parameters, with an impressive improvement in the histopathological picture and a reduction in hepatic NF-kappa B *** protects against liver injury on top of MI in rat model via modulation of Sirtuin type 1 (Sirt1)/Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/tumor necrosis factor alpha (TNF alpha);Toll-like receptor 4 (TLR4)/Hepatic myeloid differentiation primary response 88(Myd88)/NF-kappa B signaling pathways.

关键词： AKI   CKD   immunology  

摘要： Background AKI is associated with increased mortality and new or progressive CKD. Inflammatory cells play an important role in acute organ injury. We previously demonstrated that serum IL-17A levels were significantly elevated in critically ill patients with AKI and independently associated with hospital mortality. We hypothesize that IL-17A levels are elevated in hospitalized patients with AKI at diagnosis, and sustained elevation after discharge is associated with subsequent CKD incidence or progression. Methods This was an observational convenience sampling study of hospital survivors of stage 2 or 3 AKI and controls without AKI from the Assessment, Serial Evaluation, and Subsequent Sequelae of AKI study. Patients were classified as progression or nonprogression on the basis of a composite of CKD incidence, progression, or ESKD. IL-17A levels were evaluated with S-Plex assay (Meso Scale Discovery) at 0 (during hospitalization), 3, and 12 months postdischarge and analyzed along with clinical and biomarker data up to 84 months after discharge. Results Among 171 AKI and 175 non-AKI participants, IL-17A levels were elevated in AKI versus non-AKI patients at 0-, 3-, and 12-month time points (P < 0.05 for all comparisons). Furthermore, IL-17A levels were elevated in the progression versus nonprogression group at the 3- and 12-month time points for outcomes occurring at 3-6 and 12-84 months, respectively (P < 0.05 for both). In adjusted multivariable models, IL-17A levels were not independently associated with progression of kidney disease. IL-17A levels were positively correlated with kidney disease and immune activation biomarkers at all time points (P < 0.001). Conclusions IL-17A was higher in patients with AKI versus without AKI during hospitalization and up to 1-year postdischarge. IL-17A was higher in patients with progression of kidney disease after hospitalization, but not independently associated with subsequent progression of kidney disease in fully adjusted m

关键词： Cancer-associated fibroblasts   Gastric cancer   Tumor microenvironment   IL18 receptor accessory protein   Eupafolin  

摘要： Background: Cancer-associated fibroblasts (CAFs) are involved in the progression of gastric cancer (GC) as a critical component of the tumor microenvironment (TME), yet specific interventions remain limited. Natural products hold a promising application prospect in the field of anti-tumor in view of their high activity and ease of binding with biological macromolecules. However, the role of natural products in modulating the cross-talk between CAFs and GC cells has not been fully investigated. Purpose: The aim of this study was to identify a potential therapeutic target in CAFs and then screen for natural small molecule drugs with anti-tumor activity against this target. Methods: Integrating bioinformatics analysis of public databases and experimental validation of human samples and cell lines to identify a candidate target in CAFs. Molecular docking and biolayer interferometry technique were utilized for screening potential natural small molecule drugs. The efficacy and underlying mechanisms of the candidates were explored in vitro and in vivo through techniques such as lentiviral infection, cell spheroids culture, immunoprecipitation and cells-derived xenografts. Results: IL18 receptor accessory protein (IL18RAP) was found to be overexpressed in CAFs derived from GC tissues and facilitated the protumor function of CAFs on GC. Based on virtual screening and experimental validation, we identified a natural product, eupafolin, that interfered with IL18 signaling. Phenotyping studies confirmed that the proliferation, spheroids formation and tumorigenesis of GC cells facilitated by CAFs were greatly attenuated by eupafolin both in vitro and in vivo. Mechanistically, eupafolin impeded the formation of IL18 receptor (IL18R) complex by directly binding to IL18RAP, thus blocking IL18-mediated nuclear factor kappa B (NF-kappa B) activation and reduced the synthesis and secretion of IL6 in CAFs. As a consequence, it inactivated signal transducer and activator of transcriptio

关键词： Diabetic retinopathy   Inflammation   Human leukocyte antigen   Retina   Risk factor  

摘要： Diabetic retinopathy (DR) is a microvascular complication associated with diabetes mellitus (DM). During the course of the disease, high blood glucose levels induce damage to the vasculature of the retina and promote neovascularization. Although numerous environmental risk factors have been associated with the emergence of DR, the role of genetics should not be underestimated. The human leukocyte antigen (HLA) plays a significant role in the regulation of the immune system. DR exhibits significant heterogeneity among patients, with differences in how the disease presents and progresses over time. The HLA gene, characterized by its extensive genetic variation, largely contributes to this diverse spectrum. Differences in HLA allele frequencies among healthy people, diabetic patients without retinopathy, and diabetic patients with different stages of retinopathy highlight the need for proper management of the disease. This comprehensive review outlines the current understanding of the relationship between HLA class I and class II variants and DR, shedding light on their potential significance as early onset indicators, prognostic indicators, and important risk factors for the development of this retinal condition.

关键词： alleles   Brazil   high-throughput nucleotide sequencing   HLA-DP antigens   point mutation  

摘要： Identification of the novel HLA-DPA1*02:141 allele that differs from HLA-DPA1*02:02:02:01 at one position in exon 4.

关键词： cardiomyocytes   EV biogenesis   extracellular vesicles   myocardial infarction   NanoLuc  

摘要： Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the heart under homeostatic and pathological conditions, such as myocardial infarction (MI). However, the basic mechanisms driving cardiomyocyte-derived EV (CM-EV) production following stress are poorly understood. In this study, we generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that express NanoLuc-tetraspanin reporters. These modified hiPSC-CMs allow for quantification of tetraspanin-positive CM-EV secretion from small numbers of cells without the need for time-consuming EV isolation techniques. We subjected these cells to a panel of small molecules to study their effect on CM-EV biogenesis and secretion under basal and stress-associated conditions. We observed that EV biogenesis is context-dependent in hiPSC-CMs. Nutrient starvation decreases CM-EV secretion while hypoxia increases the production of CM-EVs in a nSmase2-dependent manner. Moreover, the inflammatory cytokine TNF-alpha increased CM-EV secretion through a process involving NLRP3 inflammasome activation and mTOR signalling. Here, we detailed for the first time the regulatory mechanisms of EV biogenesis in hiPSC-CMs upon MI-associated stressors.