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关键词： 癌,肝细胞   EB病毒核抗原1结合蛋白2   增殖   侵袭   迁移  

摘要： 目的 探讨EB病毒核抗原1结合蛋白2(EBP2)在肝细胞癌(HCC)组织中的表达水平，并分析EBP2对肝癌细胞增殖、侵袭和迁移能力的影响。 方法 获取来自癌症基因组图谱数据库的HCC患者mRNA表达数据及相应的临床信息，共涵盖371例HCC样本和50例癌旁正常肝组织样本。分析EBP2基因的表达水平。设计针对EBP2的短发夹RNA(shRNA)序列，将他们克隆到慢病毒载体质粒中，作为敲减质粒；同时构建含有非特异性shRNA的阴性对照质粒。将这些质粒分别转染SMMC7721和BEL-7404细胞，用于构建EBP2敲减组细胞(SMMC7721 sh-EBP2 组、BEL-7404 sh-EBP2 组)和各自的阴性对照组细胞(SMMC7221 sh-Ctrl 组、BEL-7404 sh-Ctrl 组)。采用细胞计数实验、平板克隆形成实验、划痕愈合实验等检测EBP2基因敲减对肝癌细胞的影响。 结果 EBP2在HCC肿瘤样本中的表达水平高于正常样本(2.256±0.312比1.362±0.341)，差异具有统计学意义( t ＝7.85， P <0.001)。与SMMC7221 sh-Ctrl 组相比，SMMC7721 sh-EBP2 组肝癌细胞增殖活性(1.28±0.03比2.33±0.05)、形成集落的数量[(86.78±12.69)个比(194.54±14.82)个]、侵袭细胞数[(104.78±12.26)个比(224.18±9.57)个]以及迁移能力[(0.13±0.01)%比(0.24±0.01)%]均降低，差异均具有统计学意义(均 P <0.001)。与BEL-7404 sh-Ctrl 组相比，BEL-7404 sh-EBP2 组肝癌细胞活性(1.08±0.04比1.97±0.06)、形成集落的数量[(90.94±10.49)个比(185.36±11.03)个] 、侵袭细胞数[(94.39±11.25)个比(198.66±10.14)个]以及迁移能力[(0.15±0.01)%比(0.38±0.01)%]均降低，差异均具有统计学意义(均 P <0.001)。 结论 EBP2在HCC癌组织中高表达，EBP2敲减可抑制肝癌细胞的增殖、迁移和侵袭能力。

关键词： 癌,非小细胞肺   血小板   淋巴细胞   D-二聚体   预后  

摘要： 目的 探讨血小板与淋巴细胞比值（PLR）联合D-二聚体（D-Di）在非小细胞肺癌（NSCLC）术后患者预后预测中的价值。 方法 回顾性病例系列研究。回顾性分析2012年1月至2016年12月于福建省肿瘤医院接受手术治疗的283例NSCLC患者资料。收集283例患者人口学资料、病史、吸烟史、饮酒史、病理类型、TNM分期、手术类型及实验室检查结果。采用X-tile软件计算PLR与D-Di的乘积（PLR×D-Di）的临界值为140，以PLR×D-Di值<140为低PLR×D-Di组，≥140为高PLR×D-Di组。随访截止时间为2022年12月，中位随访时间57个月（36个月，71个月）。采用Kaplan-Meier法进行生存分析，并进行log-rank检验。采用Cox比例风险模型分析预后的影响因素。 结果 283例患者中，男性194例，女性89例；中位年龄[ M （ Q 1 ， Q 3 ）]59岁（52岁，65岁）；中位体质量指数（BMI）为22.84 kg/m 2 （20.88 kg/m 2 ，24.85 kg/m 2 ）。低PLR×D-Di组87例，高PLR×D-Di组196例；两组患者性别、年龄、BMI以及不同饮酒史、吸烟史、TNM分期、病理类型、手术类型、是否具有基础疾病、是否有围术期并发症的患者比例比较，差异均无统计学意义（均 P >0.05）。283例患者中位总生存（OS）时间为57个月。低PLR×D-Di组中位随访时间61.0个月（42.0个月，72.0个月），高PLR×D-Di组中位随访时间54.5个月（32.0个月，69.0个月）。低PLR×D-Di组5年OS率为82.4%；高PLR×D-Di组5年OS率为66.7%，两组OS比较差异有统计学意义（ P =0.011）。多因素分析结果显示，腺鳞癌（ HR =7.393，95% CI ：2.974~18.381， P <0.001）、高PLR×D-Di（ HR =1.833，95% CI ：1.020~3.296， P =0.043）、TNM分期Ⅲ~Ⅳ期（ HR =2.811，95% CI ：1.735~4.555， P <0.001）是OS的独立危险因素。 结论 术前PLR×D-Di可能具有预测NSCLC手术患者预后的潜力。

关键词： Cell death   Galvanic current   IL-1β   Inflammation   Macrophage   Percutaneous needle electrolysis  

摘要： Galvanic current has been emerging as a novel therapy to regenerate chronic tissue lesions, including musculoskeletal and dermatological lesions. Recently, the NLRP3 inflammasome and IL-1β release have been identified as a signaling pathway triggered upon galvanic current application. However, the parameters for the clinical application of galvanic current remain subjective to the experience of the facultative in charge. In this study we used an in vitro model of macrophage culture and application of different combinations of the parameters of galvanic current to study IL-1β production and cell death. Increasing electric charge of galvanic current induces the release of IL-1β, but electric charges equal or higher to 144 mC also increase cell death. The release of IL-1β have a substantial variation within different electric charge of galvanic currents, being increased by decreasing the current and increasing the time of current application. Within the range of current intensities studied, the most optimal protocol for maximizing IL-1β release without inducing cell death was identified at electric charges equal to or near 144 mC, applied over a total duration of approximately 25 s. Our findings lay the groundwork for future in vivo studies assessing different electric charge of galvanic current, with the aim of yielding clinically relevant outcomes.

摘要： Central nervous system (CNS) resident memory CD8 T cells (T) that express IFN-γ contribute to neurodegenerative processes, including synapse loss, leading to memory impairment. Here, we show that CCR2 signaling in CD8 T that persist within the hippocampus after recovery from CNS infection with West Nile virus (WNV) significantly prevents the development of memory impairments. Using CCR2-deficient mice, we determined that CCR2 expression is not essential for CNS T cell recruitment or virologic control during acute WNV infection. However, transcriptomic analyses of forebrain CCR2 versus CCR2 CD8 T during WNV recovery reveal that CCR2 signaling significantly regulates hippocampal CD8 T phenotype and function via extrinsic and intrinsic effects, limiting expression of CD103, granzyme A and IFN-γ, respectively, and increasing the percentages of virus-specific CD8 T cells. Consistent with this, WNV-recovered Cd8aCcr2 mice exhibit decreased recognition memory. Overall, these data implicate CCR2 signaling in the regulation of CD8 T phenotype, including antiviral specificity and IFN-γ expression, highlighing a neuroprotective role for CCR2 in limiting CD8 T cell-mediated neuroinflammation and cognitive deficits, providing insights into potential therapeutic targets for CNS infections.

关键词： Chronic Renal Insufficiency   DNA Probları   HLA   polymerase chain reaction-sequence-specific oligonucleotide probing  

摘要： Objective:Chronic kidney disease (CKD) is a prominent public health concern, is defined as functional and structural damage to the kidneys. This study aims to investigate the association between human leukocyte antigen (HLA) alleles individuals with CKD and the different etiological subgroups of diesease. Methods:Genomic DNA was obtained from peripheral blood samples of 1,079 patients with retrospective CKD and 1,111 healthy control individuals. HLA genotyping was conducted using the Luminex based low-resolution method. Allele frequency distributions were calculated with the help of Arlequin v3.11 population genetics statistics program and SPSS v23.0 program, and p<0.05 values were accepted as significant by chi-square tests. Results:HLA A*02 (21.83%), B*35 (18.30%), DRB1*11 (21.41%) alleles were observed most frequently in individuals with CKD, respectively. In our study, B*08, B*49, B*50 alleles in the HLA B locus (p=0.002, p=0.012 p=0.009) and DRB1*03, *04 alleles in the HLA DRB1 locus (p<0.001, p<0.001) were found positively associated with CKD. A*02, A*11, A*74 alleles at the HLA A locus (p=0.003, p<0.001, p=0.009) and B*27, B*39, B* alleles at the HLA B locus 40, B*59 (p<0.001, p<0.001, p<0.001, p=0.009), DRB1*07, *08, *09, *13, *16 (p<0.001, p=0.012, p=0.007, p<0.001, p<0.001) alleles were determined as negatively associated with the disease. Among the etiological groups of CKD, cystic kidney disease (36.8%), hypertension (16.8%) and urological anomalies (16.6%) were negatively associated with the HLA-DR*13 allele. Conclusions:Since CKD shows serious morbidity and mortality, this comprehensive study of HLA subgroups gave an explanatory idea about which alleles associated with the disease in terms of susceptibility and protection.

关键词： HLA-C   IE4   MHC-I   VZV  

摘要： Varicella-zoster virus (VZV) infection downregulates surface major histocompatibility complex class I (MHC-I) expression and retains MHC-I in the Golgi complex of infected cells. However, the underlying mechanism is not fully understood. The VZV IE4 protein is a multifunctional protein that is essential for VZV infection. In this study, the human leucocyte antigen C (HLA-C) protein was identified as a novel cellular factor associated with IE4. Ectopically expressed IE4 co-localizes with HLA-C, sequesters HLA-C to the Golgi complex and downregulates cellular surface MHC-I. VZV, with a mutated Golgi localization signal in IE4, denoted as mutated IE4 (mIE4) VZV, was constructed. In mIE4 VZV-infected cells, the cellular surface MHC-I was restored, and HLA-C was not retained in the Golgi complex. In summary, for the first time, we demonstrate a novel role of VZV IE4 in interfering with the MHC-I presentation pathway, suggesting that it may contribute to the evasion of host antiviral adaptive immunity.

关键词： Airway allergy   Epigenetics   IL-10   Immune regulation   Macrophage   Ubiquitination  

摘要： The pathogenesis of many immune disorders is linked to regulatory macrophage dysfunction. The mechanism underlying it is unclear. The objective of this study is to examine the mechanism by which the PRKN ubiquitin protein ligase (PRKN) inhibits the development of regulatory macrophages (Mreg). In this study, dust mite antigens were used as the specific allergens to establish an airway allergy (AA) mouse model. Flow cytometry cell sorting was used to isolate macrophages from the airway tissues. According to the results, the Prkn gene inhibition led to an increase in the number of Mregs in macrophages. Mregs demonstrated the capacity to suppress Th2 polarization, in which IL-10 played a critical role. Pan macrophages isolated from Prkn-deficient mice were more capable of suppressing the activities of other immune cells. PRKN was required for maintaining the hyperubiquitous status of signal transducer and transcriptional activator-3 (STAT3) in macrophages. Exposure to dust mite antigen increased the expression of PRKN in macrophages. IL-10 suppressed PRKN in macrophages by inducing its promoter hypermethylation. PRKN inhibition mitigated the experimental AA. To sum up, PRKN maintains the hyper ubiquitous status of STAT3 and restricts the expression of IL-10 in macrophages, which compromises their immune suppressive functions. Inhibition of PRKN increases Mreg development and mitigates AA. The data suggest that the regulation of Mreg has translation potential to be used in the treatment of immune disorders such as AA.

摘要： Tralokinumab, an anti-IL-13 antibody, is an effective treatment for patients with atopic dermatitis (AD). However, predictive factors for responders to tralokinumab remain unclear in real-world practice. This study aimed to identify predictive factors for early and late responders to tralokinumab treatment. Early responders were defined as patients achieving investigator's global assessment (IGA) 0/1 at week 12, whereas late responders were defined as those without IGA 0/1 at week 12 but achieving IGA 0/1 at week 24. A prospective study was conducted with 108 Japanese AD patients treated with tralokinumab between October 2023 and August 2024. Patients' background factors and baseline clinical or laboratory indexes were compared between responders and poor responders. Both early and late responders had a higher proportion of systemic therapy-naive patients compared with poor responders. Early responders had higher proportion of females, younger age, shorter disease duration, lower body mass index, and monocyte-to-lymphocyte ratio, whereas late responders had lower immunoglobulin E, thymus and activation-regulated chemokine, platelet-to-lymphocyte ratio, and C-reactive protein compared with poor responders. This study provides valuable insights for optimizing treatment strategies in AD, in selecting patients who may respond to tralokinumab at early or late phases.