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关键词： Tissue typing   Major histocompatibility complex   Human leukocyte antigen   Whole genome sequencing   Transcriptome sequencing   Consensus algorithm   Bioinformatics   Computational Biology  

摘要： BackgroundHuman Leukocyte Antigens (HLA) play central roles in histocompatibility and immune system functions, including antigen presentation. Accurate typing of Class I and II HLA genes is crucial for transplant tissue matching, characterising autoimmune diseases and informing cancer immunotherapy. Clinical serology and PCR-based testing are the gold standards for HLA typing, but offer only single-field resolution (e.g., HLA-A*11). Whole genome sequencing (WGS) and RNA sequencing (RNA-seq) can achieve higher, three-field resolution (e.g., HLA-A & lowast;11:01:01), although some HLA genes can be challenging to type from sequencing data. With the increasing use of germline WGS, tumour WGS and tumour RNA-seq in cancer patient care, there is an opportunity to combine these three dataset types to improve HLA typing accuracy and confidence, and to identify clinically relevant HLA type changes in tumours. To achieve this, we developed consHLA, a tool that employs this consensus HLA typing *** obtained matched germline and tumour WGS and RNA-seq data from 86 high-risk paediatric cancer patients (76 brain cancers, 10 leukaemias) from the ZERO Childhood Cancer precision medicine program. We examined 10 HLA typing packages, selecting HLA-HD to develop our consHLA workflow as HLA-HD can employ all three dataset types, analysing both Class I and II HLA genes at three field resolution. Using consHLA we achieved 97.9% concordance with gold standard HLA test results. We observed 90.5% allele consistency across the three sequencing NGS inputs. Typing inconsistencies in at least one of 12 clinically relevant HLA genes were observed in 29 of the brain tumour cases. 32% of these had clinically relevant explanations. To assist clinically, we implemented consHLA as a fully automated workflow producing a clinician-friendly HLA-typing *** leverage cancer patient germline and tumour WGS and tumour RNA-seq data we developed an automated workflow, consHLA, tha

关键词： type I IFN   signaling   age   children   COVID-19   SARS-CoV-2   STAT1   STAT3   monocytes   T cells   B cells   antibodies   immune response  

摘要：

关键词： 网状内皮组织增生病   Viperin蛋白   相互作用   结构域   IFN  

摘要： 网状内皮组织增殖病病毒（REV）是一种重要的家禽免疫抑制性病原，干扰素诱导内质网关联病毒抑制蛋白（Viperin）是一种由干扰素诱导产生的宿主抗病毒蛋白，目前REV复制与Viperin之间的关系尚不清楚。本试验首先将REV接种DF-1，通过荧光定量PCR（RT-qPCR）探究REV感染对宿主Viperin表达的影响。随后，构建鸡Viperin真核表达质粒，分别通过基因过表达和siRNA干扰技术检测Viperin对REV复制的影响。为探究Viperin影响REV复制的机理，构建了Viperin N、SAM和C结构域的真核表达质粒，并通过RT-qPCR和Western blot检测转染上述质粒对REV复制的影响。最后，通过RT-qPCR检测了Viperin表达与IFN信号通路的关系。结果显示，REV感染上调DF-1中Viperin的转录水平。过表达Viperin在感染早期（12 h-24 h）抑制REV的复制，而在感染后期（36 h-72 h）促进REV复制；Viperin特异性siRNA试验结果与过表达试验结果一致。将pEGFP-Viperin-N、pEGFP-Viperin-SAM、pEGFP-Viperin-C质粒分别转染DF-1细胞，感染后期（36 h-72 h）Viperin的N结构域和SAM结构域抑制REV复制，而Viperin的C结构域促进REV复制。IFN信号通路相关分子的检测结果表明，过表达Viperin后，IFN-α的表达水平在24 h和72 h呈现下调趋势，IFN-β在12-48 h呈现下调趋势，IFN-γ在36-72 h呈现下调趋势。综上所述，REV感染促进Viperin的转录，而Viperin的过表达在REV感染后期可能通过调控IFN信号通路促进REV的复制，其C端结构域是发挥调控作用的关键结构域。本研究揭示了REV感染和宿主Viperin蛋白的相互作用关系，为深入阐明鸡Vieprin调控病毒复制的机制提供了科学数据。

摘要： In the original publication [...].

关键词： 针指震颤行气法   艾灸   神阙穴  

摘要： 探讨针指震颤行气法联合艾灸对慢性盆腔炎患者TNF-α/IL-10平衡及盆腔微循环的影响。方法 纳入222.05-2024.10蒲江县中医医院收治的240例慢性盆腔炎患者为研究对象,按分层随机法分为三组,各80例,A组进行艾灸神阙穴治疗,B组进行针指震颤行气法治疗,C组进行针指震颤行气法联合艾灸神阙穴治疗,对比三组组治疗方法的效果。结果 C组患者的治疗总有效率高于A组、B组(P<0.05)。治疗前三组中医证候评分对比,未见统计差异(P>0.05),治疗后C组分值明显比A组、B组少(P<0.05)。治疗前三组TNF-α/IL-10比值对比,未见统计差异(P>0.05),治疗后C组比值明低于A组、B组(P<0.05)。治疗前三组的子宫动脉RI、PI及盆腔血流量未见对比差异(P>0.05),治疗后C组的子宫动脉RI、PI低于A组、B组,C组的盆腔血流量高于A组、B组(P<0.05)。结论 针指震颤行气法联合艾灸神阙穴治疗应用效果良好,能够促进TNF-α/IL-10平衡,改善盆腔微循环,促进康复可推广使用。

关键词： duplication   HLA   triallelic pattern   unequal crossing-over  

摘要： Background and Objectives Many family investigations of the HLA region are performed in order to identify HLA identical related stem cell donors. In rare cases, deviations from the expected inheritance can be observed. Such a case is shown in this *** and Methods Alleles of the HLA complex have been defined in the members of an Austrian family with atypical segregation of HLA alleles by using the following methods: HLA DNA typing by low-, medium- and high-resolution techniques;genotyping of short tandem repeat (STR) markers in the HLA region;and array-based genome-wide single-nucleotide polymorphism (SNP) *** A duplication of the HLA region encompassing HLA-B, HLA-C and the STR loci D6S2678 and STR-MICA is *** A duplication in the HLA-B/-C region of the HLA system is observed, which results from an unequal crossing-over encompassing a chromosomal region of around 377 kb.

关键词： Cervical Cancer   Head and Neck Cancer   Immunotherapy   Immunosuppression   T cell  

摘要： Background Human papillomavirus type 16 (HPV16) positive cancers have a tumor environment that induces antigen-presenting cells to increase IL-23 expression. Unclear is if HPV16 E6/E7 oncoproteins expressed in these cancers play a role in upregulating interleukin (IL)-23 in the tumor microenvironment (TME), and how this cytokine impacts the antitumor cytotoxic T-cell response in HPV16+ *** CD8 T-cells targeting HPV16+ cancer cells were isolated from C57BL/6 mice bearing HPV16+ C3.43 tumors that were therapeutically vaccinated against HPV16 E6/E7 and incubated with IL-23. These T-cells were then co-incubated with HPV16+ target cells in a cytotoxicity assay to assess their cytolytic capacity. Additionally, carboxyfluorescein succinimidyl ester (CFSE) labeled T-cells were used to track the effect of IL-23 on their proliferation. The effect of IL-23 neutralization on vaccine-induced antitumor immunity during tumor progression was studied in vivo to assess its potential as either a standalone treatment or combined with a vaccine targeting HPV16 E6/E7. HPV16- tumors were engineered to express E6/E7 to find out if these oncoproteins upregulate IL-23. To understand how HPV oncoproteins in the TME affect transcriptional regulation of IL-23 producing cells, we used single-cell Assay for Transposase-Accessible Chromatin (ATAC)+RNA *** Inside macrophages residing in the HPV+ TME, transcription factor enrichment and linkage analysis identified KLF2 as a potential regulator of Il23a. Overexpression of KLF2 in macrophages upregulates IL-23 production. CD8 T-cells that recognize HPV16+ cells incubated with IL-23 are inhibited in both their killing and proliferative capacities. IL-23 neutralization increased the presence of HPV-specific cytotoxic CD8 T-cells inside the HPV16+TME in an IL-17 independent manner. Combination of IL-23 neutralization followed by HPV16 E6/E7 vaccination increases survival by amplifying the anti-tumor immune *** Th

关键词： 厄贝沙坦片   苯磺酸氨氯地平片   难治性高血压   疗效   TNF-α  

摘要： 评价厄贝沙坦片(IRB)联合苯磺酸氨氯地平片(AMB)对于难治性高血压(RH)的治疗有效性。方法 选择70例RH患者,随机数字表均分,实验组选择IRB联合AMB治疗;对照1组选择IRB单一治疗;对照2组选择AMB单一治疗,对比三组的总有效率、血压水平、肿瘤坏死因子-α(TNF-α)水平、动脉粥样硬化指标。结果 实验组的总有效率高于对照1组、对照2组;实验组治疗后的血压水平、TNF-α水平均低于对照1组、对照2组;实验组治疗后的动脉粥样硬化指标优于对照1组、对照2组(P<0.05)。结论 IRB联合AMB能够提高RH患者的总有效率,稳定患者的血压水平,且能减轻炎症反应,预防动脉粥样硬化,具有较高的联合用药优势。

关键词： 系统性血管炎   补体C3   疾病活动度   补体C4   炎症标志物  

摘要： 探讨血清补体C3、C4水平检测在系统性血管炎活动期判断中的临床应用价值。方法 选取2023年7月至2024年8月于我院诊治的80例系统性血管炎患者,根据疾病活动程度评分将患者分为活动期组(45例)和缓解期组(35例)。结果 活动期组患者血清C3、C4水平低于缓解期组,而ESR、CRP、VEGF等炎症指标高于缓解期组(P<0.05)。ROC曲线分析显示,血清C3、C4联合检测对系统性血管炎活动期的诊断效能优于单一指标。多因素Logistic回归分析表明,血清C3、C4水平下降是系统性血管炎活动期的独立危险因素(P<0.005)。结论 血清补体C3、C4水平检测对系统性血管炎活动期判断具有重要的临床价值,可作为疾病活动度评估的重要参考指标,有助于临床医师对系统性血管炎的诊断、治疗方案制定及预后评估。