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关键词： 蓝舌病毒   VP5蛋白   截短表达   单克隆抗体  

摘要： 参考GenBank中蓝舌病毒血清1型（BTV-1）标准参考株VP5蛋白氨基酸序列，缺失N端1～79位氨基酸，按照大肠杆菌偏嗜性进行基因密码子优化后，合成编码BTV-1 VP5截短蛋白的基因VP5Δ79aa，将其克隆到表达载体pET-28a-sumo上，构建了重组质粒pET-sumo-VP5Δ79aa。将该重组质粒转化到BL21(DE3)感受态细胞中，用0.5 mmol/L IPTG分别在37 ℃和16 ℃条件下进行诱导表达和可溶性分析，经SDS-PAGE检测，重组VP5Δ79aa蛋白主要以包涵体形式表达。用Ni-NTA亲和层析法纯化重组VP5Δ79aa蛋白，得到与预期大小相符的单一目的条带。纯化后的重组VP5Δ79aa蛋白经不同浓度梯度的尿素透析复性后，将其免疫雌性BALB/c小鼠（6～8周龄），取免疫后脾细胞与骨髓瘤细胞融合，获得能稳定分泌单克隆抗体的杂交瘤细胞株。经间接ELISA、免疫荧光和Western-blot分析，筛选得到2株反应性和特异性良好的单克隆抗体4A10和5H11，其不仅能与重组VP5Δ79aa截短蛋白以及重组全长VP5蛋白反应，而且能特异识别BTV-1感染细胞中的天然VP5蛋白，这为深入研究BTV VP5蛋白的生物学功能及其抗原表位鉴定奠定了基础。

关键词： 急性淋巴细胞白血病   异基因造血干细胞移植   髓外复发   乳腺   肝脏  

摘要： 髓外浸润是急性淋巴细胞白血病的表现之一，预后极差。常见髓外浸润部位为中枢神经系统及睾丸，乳腺、肝脏浸润并不常见。同种异体移植后急性淋巴细胞白血病在乳房复发非常罕见，目前可查阅到的文献报道例数仅百例，缺少系统性分析与数据。我们的第一例便报道了移植后2月乳腺浸润，后出现中枢、双侧肾上腺、腹膜淋巴结等多处转移的病例。第二例于异体移植后43月肝脏复发。髓外复发时检测完全供体嵌合。表明骨髓及髓外复发机制并不相同。

摘要： Tumor cell death shapes tumorigenesis and antitumor immunity in complex ways. Recently, Hanggi et al. revealed that necrotic-like death releases interleukin-1 alpha (IL-1 alpha), driving myeloid-mediated immunosuppression. Lamorte et al. demonstrated that medullary sinus macrophage (MSM) efferocytosis of apoptotic tumor cells activates the IL-33-regulatory T cell (Treg) axis, accelerating tumor growth. Blocking these pathways enhances the efficacy of cancer immunotherapy.

摘要： Recent studies have uncovered evidences for pro-tumorigenic activities attributed to IL-11, prompting a renewed focus on therapeutic strategies targeting IL-11 signaling for anti-tumor treatment. Here, we introduce 9MW3811, a monoclonal antibody designed to neutralize IL-11 effectively. By disrupting the IL-11/IL-11R alpha/gp130 complex, 9MW3811 inhibits JAK/STAT3 signaling, significantly reducing tumor growth in diverse mouse models. More importantly, 9MW3811 synergizes with anti-PD-1 therapy, even in PD-1 non-responsive models like CT26. Single-cell RNA-seq analysis reveals that 9MW3811 remodels the tumor microenvironment by enhancing CD8+ T cell infiltration and reversing T cell exhaustion via upregulated XCL1 and downregulated CCL7, boosting anti-tumor cytotoxicity. Furthermore, 9MW3811 counteracts PD-1-induced T cell exhaustion, with anti-PD-1 antibodies effectively mitigating PD-1 upregulation post-9MW3811 treatment. These compelling findings support ongoing clinical trials of 9MW3811, aiming to translate these preclinical insights into therapeutic benefits for cancer patients.

关键词： glioblastoma   MHC   riskscore   immune microenvironment  

摘要： Glioma is the most common primary malignant intracranial tumor with limited treatment options and a dismal prognosis. This study aimed to develop a robust gene expression-based prognostic signature for GBM using the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets. Using WGCNA and LASSO algorithms, we identified four MHC-related genes (TNFSF14, MXRA5, FCGR2B, and TNFRSF9) as prognostic biomarkers for glioma. A risk model based on these genes effectively stratified patients into high- and low-risk groups with distinct survival outcomes across TCGA and CGGA cohorts. This signature correlated with immune pathways and glioma progression mechanisms, showing strong associations with immune function and tumor microenvironment infiltration patterns. The risk score reflected tumor microenvironment remodeling, suggesting its prognostic relevance. We further propose I-BET-762 and Enzastaurin as potential therapeutic candidates for glioma. In conclusion, the four-gene signature we identified and the corresponding risk score model constructed from it provide valuable tools for the prognosis prediction of glioblastoma multiforme (GBM) and may guide personalized treatment strategies. The least absolute shrinkage and selection operator (LASSO) risk score has demonstrated significant prognostic evaluation utility in clinical GBM patients, bringing potential implications for patient stratification and the optimization of treatment regimens.

关键词： 碳酸镧   左卡尼汀   肾功能衰竭   血清细胞因子   肾功能  

摘要： 探讨碳酸镧联合左卡尼汀对肾衰竭患者血清细胞因子及肾功能的改善作用。方法 98例肾衰竭患者随机分为观察组和对照组,各49例。对照组接受常规治疗联合左卡尼汀,观察组加用碳酸镧。对比两组治疗前后血清TNF-α、IL-6水平,肾功能(Scr、BUN、Ccr)及不良反应发生率。结果 观察组治疗后TNF-α、IL-6、Scr、BUN水平低于对照组,Ccr水平高于对照组(P<0.05);不良反应发生率无显著差异(P>0.05)。结论 碳酸镧联合左卡尼汀可有效调节肾衰竭患者血清细胞因子,改善肾功能,安全性良好。

关键词： C-reactive protein (CRP)   interleukin-1 beta (IL-1 beta)   interleukin-6 (IL-6)   ocular inflammation   uveitis   diabetic macular edema  

摘要： Introduction: C-reactive protein (CRP) plays a critical role in the innate immune system and serves as a biomarker for various inflammatory conditions. CRP is a dynamic protein undergoing conformational changes between pentameric (pCRP) and monomeric (mCRP) conformations. pCRP is the well-established systemic marker of inflammation, while mCRP is associated with localized tissue inflammation. Methods: This study aimed to evaluate systemic levels of pCRP, mCRP, interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) in patients with a variety of intraocular inflammatory conditions, including diabetic macular edema (DME) and non-infectious uveitis such as Behcet's disease (BD), Birdshot retinochoroidopathy (BSRC), HLA-B27-associated uveitis, and undifferentiated uveitis (UU). Results: A total of 77 subjects were included. mCRP levels were significantly elevated in BD, DME, and UU compared to controls (p = 0.014, p = 0.036, and p = 0.031, respectively). The mCRP/pCRP ratio was also significantly higher in DME and UU (p = 0.035 and p = 0.011, respectively). In addition, a strong positive correlation was observed between IL-6 and IL-1 beta (rho = 0.638, p <0.0001). No significant differences in serum levels of pCRP, IL-6, or IL-1 beta were observed among the groups. Conclusions: These findings suggest that mCRP, rather than pCRP, may be a more specific systemic biomarker for certain intraocular inflammatory conditions. The involvement of the CRP axis and the strong correlation between IL-6 and IL-1 beta underscore the interaction of these key inflammatory mediators, providing further insight into the targeting of CRP axis for therapeutic purposes.

关键词： 猪源BVDV   分离鉴定   进化分析   淋巴细胞   致病性  

摘要： 为了解致猪腹泻的病原及其分子特征、致病性，本研究基于疑似猪瘟仔猪病料样品进行病毒的MDBK细胞分离培养、牛病毒性腹泻病毒（BVDV）RT-qPCR与IFA检测、5'-UTR和E0基因扩增测序与遗传进化分析，在分离病毒细胞培养物纯净性检测后将其以肌肉注射和滴鼻方式接种实验组仔猪，采用流式细胞术、RT-qPCR、ELISA分别检测感染猪淋巴细胞数量、外周血和主要脏器中BVDV 5'-UTR基因转录、抗体水平。结果显示，分离病毒经细胞盲传15代均未引起细胞病变，RT-qPCR检测出现扩增曲线，IFA检测出现典型的特异性胞浆内黄绿色荧光，与BVDV-1在同一进化分支，其5'-UTR、E0基因与牛源BVDV-1 VEDEVAC疫苗株同源性最高（98.2%、98.7%），命名为BVDV FQ株。FQ株第15代细胞培养物纯净性较好，将其感染猪后，第7 d实验组猪淋巴细胞数量下降至最低值并极显著低于对照组（P<0.01），此时4/5猪外周血检测到FQ株5'-UTR mRNA,3/5猪出现腹泻等临床症状，21 d后可检出BVDV抗体，主要脏器均可检出FQ株5'-UTR mRNA。本研究上述结果表明猪源BVDV FQ株属于BVDV-1基因型，可能起源于牛源BVDV，可明显降低感染猪淋巴细胞数量，对猪具有一定致病性。本研究为深入开展猪源BVDV病原学研究提供了参考。