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关键词： 冠心病   循环单核细胞LincRNA-PACERR   白细胞介素-6   单核细胞趋化蛋白1   单核细胞与高密度脂蛋白胆固醇比值  

摘要： 目的：探讨循环单核细胞LincRNA-PACERR、白细胞介素-6(IL-6)、单核细胞趋化蛋白-1(MCP-1)及单核细胞与高密度脂蛋白胆固醇比值（MHR）对冠心病（CAD）及其严重程度的联合风险评估。方法：回顾性纳入2022年4—10月在武汉大学中南医院行冠状动脉（冠脉）造影检查和冠脉血管内超声检查的306例患者，其中201例符合CAD诊断标准作为CAD组，105例作为对照组。比较两组及CAD不同严重程度患者的循环单核细胞LincRNA-PACERR、IL-6、MCP-1及MHR，采用受试者工作特征曲线（ROC）分析其对CAD及严重程度的诊断。结果：CAD组循环单核细胞LincRNA-PACERR、IL-6、MCP-1及MHR均显著高于对照组（均P<0.05），联合检测上述四项指标对CAD的诊断效能优于单一指标，曲线下面积（AUC）和特异度均较高。重度冠脉病变患者循环单核细胞LincRNA-PACERR、IL-6和MHR显著高于轻度病变患者（均P<0.05），且对CAD严重程度有诊断价值（均P<0.05）。联合检测四项指标对CAD严重程度的诊断效能优于单一指标，且敏感度均较高。结论：CAD患者循环单核细胞LincRNA-PACERR、IL-6、MCP-1及MHR显著升高，联合检测四项指标对CAD及其严重程度具有较高的诊断价值，或可作为筛查CAD严重程度的潜在指标。

关键词： 猪德尔塔冠状病毒   N蛋白   原核表达   单克隆抗体  

摘要： 为了制备猪德尔塔冠状病毒（PDCoV）N蛋白和抗N蛋白的单克隆抗体（mAb），将PDCoV N基因克隆至pGEX-6p-1载体中，转化至BL21（DE3）感受态细胞，诱导纯化后获得可溶性重组N蛋白，约43kDa，大小符合预期。用重组N蛋白对小鼠进行免疫，采用细胞融合技术制备单克隆抗体，共获得5株（2D8、2E2、6A1、9C10、5H10）稳定分泌N蛋白抗体的杂交瘤细胞株。通过免疫印迹和间接免疫荧光试验（IFA）判定5株杂交瘤细胞株均能够特异性地识别N蛋白，其中2株（2D8、6A1）腹水抗体效价均高达1∶1024000。中和试验表明，2株单克隆抗体均具有病毒中和作用。结果表明，成功表达了N蛋白及制备了5株能稳定分泌与PDCoVN蛋白特异性结合的单克隆抗体，为PDCoVN蛋白的功能和 PDCoV检测方法的研究提供了基础，对该疾病的临床诊断、流行病学调查与疫病防控具有重要意义。

摘要： alpha beta T cell receptors (TCR) co-recognise peptide (p) antigens that are presented by major histocompatibility complex (MHC) molecules. While marked variations in TCR-p-MHC docking topologies have been observed from structural studies, the co-recognition paradigm has held fast. Using HLA-DQ2.5-peptide tetramers, here we identify a TRAV12-1+-TRBV5-1+ G9 TCR from human peripheral blood that binds HLA-DQ2.5 in a peptide-agnostic manner. The crystal structures of TCR-HLA-DQ2.5-peptide complexes show that the G9 TCR binds HLA-DQ2.5 in a reversed docking topology without contacting the peptide, with the TCR contacting the beta 1 region of HLA-DQ2.5 and distal from the peptide antigen binding cleft. High-throughput screening of HLA class I and II molecules finds the G9 TCR to be pan-HLA-DQ2 reactive, with leucine-55 of HLA-DQ2.5 being a key determinant underpinning G9 TCR specificity excluding other HLA-II allomorphs. Consistent with the functional assays, the interactions of the G9 TCR and HLA-DQ2.5 precludes CD4 binding, thereby impeding T cell activation. Collectively, we describe a naturally selected alpha beta TCR from human peripheral blood that deviates from the TCR-p-MHC co-recognition paradigm.

关键词： Andrographolide   Inflammation   Nanostructured lipid carrier   Stress   TNF-alpha  

摘要： This study aimed to improve the delivery efficacy of andrographolide (Andro) by encapsulating it in nanostructured lipid carriers (NLCs) and to evaluate its effectiveness in reducing systemic inflammation. These AndroNLCs exhibited homogeneity with a particle size of 131.40 +/- 1.30 nm and approximately 89% encapsulation efficiency. AndroNLCs potentially enhanced oral efficacy by improving gastrointestinal stability, with reduced toxicity and inflammation in SH-SY5Y neuroblastoma cells. Inflammation was induced in sexually active C57BL/6 male mice with five intraperitoneal doses of 63 mu g/kg TNF-alpha every three days. This was accompanied by daily oral administration of 10 mg/kg AndroNLCs, venlafaxine, or 1 mg/kg dexamethasone for 14 days. Mice with TNF-alpha-induced inflammation showed sickness signs and abnormal behaviors, assessed via physical changes, anxiety and depression tests (i.e., open field, elevated-T maze, tail suspension, and forced swimming), and biochemical assays. These changes included weight loss and compensatory responses to inflammation, as indicated by increased immune- and stress-modulated organ weights, elevated serum corticosterone levels, altered liver function markers, and higher levels of hippocampal IL-6 and TNF-alpha. Furthermore, histological analysis showed pyknotic cells, reduced layer thickness, and decreased hippocampal cell survival. Conversely, AndroNLCs significantly improved stress- and inflammation-related markers, alleviated behavioral abnormalities, reduced liver toxicity, and restored hippocampal morphology, showing effects greater than Andro alone and comparable to traditional treatments. These findings suggest that AndroNLCs have therapeutic effects on neuroinflammation but may risk contributing to mood disorders.

关键词： 补肾强督散寒方   面碗灸   肾虚督寒证   强直性脊柱炎   骨髓水肿   关节功能  

摘要： 目的：探讨补肾强督散寒方联合面碗灸对肾虚督寒型强直性脊柱炎骨髓水肿的改善及抗炎因子、关节状态及血清HLA-B27、 Cbfa1的影响。方法：本次研究为前瞻性研究，研究时间在2023年5月至2024年4月期间，采用随机数字表法将90例受试入组的强直性脊柱炎患者分为对照组和研究组，各45例。两组患者同时给予口服柳氮磺吡啶肠溶片进行治疗，对照组患者在口服柳氮磺吡啶肠溶片的基础上实行面碗灸治疗，研究组患者在对照组治疗基础上加用补肾强督散寒方治疗，两组均连续治疗12周。比较两组患者ASAS20疗效情况。比较两组患者治疗前后骨髓水肿程度、免疫球蛋白（IgA、IgM、IgG）、血沉（Erythrocyte Sedimentation Rate，ESR）、C反应蛋白（C-reactive protein，CRP）、关节功能（Joint function，JF）和状态以及血清人白细胞表面抗原B27（Human leukocyte antigen b27，HLA-B27）、核心结合因子（Core Bindingfactor a1，Cbfa1）的变化情况。结果：治疗后，对照组和研究组相较于治疗前的各项肾虚督寒证中医症候评分均有所下降（P<0.05），研究组肾虚督寒证中医症候评分显著低于对照组（P<0.05）；研究组治疗有效率84.44%明显高于对照组64.44%（P<0.05）；治疗后，对照组和研究组相较于治疗前的SPARCC评分均有所下降（P<0.05），研究组SPARCC评分显著低于对照组（P<0.05）；治疗后，对照组和研究组相较于治疗前的血清IgA、IgM、IgG含量均有所下降（P<0.05），研究组血清IgA、IgM、IgG含量显著低于对照组（P<0.05）；治疗后，对照组和研究组相较于治疗前的BASDAI评分和BASFI评分均有所下降（P<0.05），研究组 BASDAI评分和BASFI评分显著低于对照组（P<0.05）；治疗后，对照组和研究组相较于治疗前的血清CRP、ESR、Cbfa1表达水平以及HLA-B27阳性例数均有所下降（P<0.05），研究组血清CRP、ESR、Cbfa1表达水平以及HLA-B27阳性例数显著低于对照组（P<0.05），差异有统计学意义。结论：补肾强督散寒方联合面碗灸对肾虚督寒型强直性脊柱炎的治疗效果较好，有助于减轻骨髓水肿情况，改善关节炎症状态，促进关节功能提高和生活自理能力提高，其作用机制可能与抑制局部病理成骨作用有关。

关键词： 时间分辨荧光免疫层析   新型冠状病毒抗原   小分子螯合剂标记抗体   即时检测  

摘要： 基于时间分辨荧光免疫层析技术,利用稀土小分子螯合剂制备新型冠状病毒抗体标记物,采用时间分辨荧光层析方式用于新型冠状病毒抗原检测.方法线性范围为0.04～100 ng/mL,线性方程为y=0.007 2x+0.033 2,相关系数r=0.999 5,检出限为0.028 ng/mL,批内、批间变异系数小于7%,回收率94.35%～103%.方法具有精准、快速(小于20 min)、成本低、操作简单等优势,具有广阔的应用前景.

关键词： cholangiocarcinoma   CCA   immune checkpoint blockade   ICB   tumor microenvironment   TME   tertiary lymphoid structures   TLSs   BAFF   regulatory T cells   Tregs   Treg fragility  

摘要： Anti-vascular endothelial growth factor (VEGF) treatment has shown clinical activity together with immune checkpoint blockade (ICB), but the exact mechanism is not known. We show that VEGF blockade in combination with anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) + anti-programmed death-ligand 1 (PD-L1) in cholangiocarcinoma (CCA) potentiated a multimodal mechanism dependent on B cell activating factor (BAFF), leading to a proinflammatory B cell response. It led to a BAFF-and interleukin (IL)-12-dependent expansion and rewiring of T regulatory cells (Tregs) toward an anti-tumor T helper-1 (Th-1)-like fragile state. We translated this approach to the clinic and observed immunological changes characterized by Treg cell expansion and rewiring toward fragile and unstable states. We explored the effect of VEGF receptor 2 (VEGFR2) signaling on Treg cell transcriptional programming and established a mouse model ablating VEGFR2 expression on Treg cells. This study reveals the immunological interplay resulting from targeting VEGF together with CTLA-4 and PD-L1 blockade.

关键词： 重症肺炎支原体肺炎   25羟维生素D3   白介素-21   病情程度   预后  

摘要： 目的 分析重症肺炎支原体肺炎(MPP)患儿血清25羟维生素D3[25 (OH) D3]、白介素-21（IL-21）水平与预后的相关性。方法 选取2023年1月至2024年1月安徽医科大学第一附属医院儿科收治的111例重症MPP患儿作为病例组，107例轻症MPP患儿作为对照组，随访3个月后根据预后情况将病例组患儿分为预后不良亚组（n=26）和预后良好亚组（n=85）。比较病例组和对照组患儿入院时血清25 (OH) D3IL-21水平、小儿危重症评分（PCIS）、肺炎严重指数（PSI）评分，并分析血清25 (OH) D3、IL-21水平与PCIS、PSI评分的相关性；比较病例组预后不良亚组和预后良好亚组入院时一般资料、血清常规炎性因子[C-反应蛋白（CRP）、白介素-6（IL-6）]、25 (OH) D3、IL-21水平，分析预后不良影响因素、血清25 (OH) D3、IL-21、CRP、IL-6预测预后不良的价值。结果 病例组入院时血清25 (OH) D3水平、PCIS评分低于对照组，血清IL-21水平、PSI评分高于对照组（P＜0.05）；病例组和对照组入院时血清25 (OH) D3水平与PCIS评分呈正相关，与PSI评分呈负相关（P＜0.05）；血清IL-21水平与PCIS评分呈负相关，与PSI评分呈正相关（P＜0.05）；病例组患病后3个月预后不良率为23.42%；预后不良亚组入院时血清25 (OH) D3水平、PCIS评分低于预后良好亚组，血清IL-21、CRP、IL-6水平、PSI评分高于预后良好亚组（P＜0.05）；入院时血清25 (OH) D3、IL-21、CRP、IL-6水平均为重症MPP患儿预后不良的影响因素（P＜0.05）；病例组入院时血清25 (OH) D3、IL-21、CRP、IL-6单独预测预后不良的曲线下面积（AUC）分别为0.750、0.752、0.735、0.718，25 (OH) D3联合IL-21预测预后不良的AUC为0.876，均＞25 (OH) D3、IL-21、CRP、IL-6单独预测的AUC（P＜0.05）。结论 血清25 (OH) D3、IL-21水平可预测重症MPP患儿预后不良风险，联合检测可为临床识别预后不良高危患儿提供更可靠的临床依据。

关键词： Signaling pathways   elderly patients.   occlusion   stenosis   vertebral artery  

摘要： INTRODUCTION:Vertebral artery stenosis/occlusion leads to ischemic brain cell injury due to partial or complete disruptions of blood flow to the brain. OBJECTIVE:The objective of the present research was to investigate the TNF-α/TLR4/IL-6/NF-κB signaling pathway and ROS/NOX4/p38/MDA signaling pathway in elderly patients with vertebral artery stenosis/occlusion. METHODS:Levels of tumor necrosis factor-alpha (TNF-α), toll-like receptor 4 (TLR4), interleukin 6 (IL-6), nuclear factor kappa-B (NF-κB), reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), p38 mitogen-activated protein kinase (p38) and malondialdehyde (MDA) were evaluated in blood samples from elderly patients with vertebral artery stenosis/ occlusion. RESULTS:Expression levels of TNF-α, TLR4, IL-6, NF-κB, ROS, NOX4, p38, and MDA were significantly higher in the Vertebral Artery Stenosis (VAS) 61-70% group compared with the control group and VAS 50%-60% group, respectively (P<0.01). The expression levels of these markers were significantly higher in the VAS 81-99% group compared with VAS 61-70% group and VAS 71-80% group, respectively (P<0.01), and were further increased in VAS 100% (occlusion) group compared with VAS 71-80% group and VAS 81-99% group, respectively (P<0.01). CONCLUSION:Mutual interactions of TNF-α/TLR4/IL-6/NF-κB and ROS/NOX4/p38/MDA signaling pathways were associated with the pathogenesis of vertebral artery stenosis/occlusion in elderly patients.