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关键词： 醋酸阿托西班   盐酸利托君   早产   白细胞介素-6   白细胞介素-8   肿瘤坏死因子-α  

摘要： 目的 探讨醋酸阿托西班联合盐酸利托君在先兆早产患者中的疗效。方法 选择我院产科收治的先兆早产患者为研究对象,随机分为两组,每组46例。对照组采用盐酸利托君治疗,观察组采用盐酸利托君联合醋酸阿托西班治疗。对比两组宫缩抑制有效率、分娩方式及新生儿结局、血清相关指标及不良反应发生情况。结果 观察组宫缩抑制有效率明显高于对照组(P<0.05),早产率明显低于对照组(P<0.05),新生儿体重明显高于对照组(P<0.05),剖宫产率和新生儿评分无明显差异(P>0.05),治疗后,两组血清炎性因子水平明显下降,观察组变化幅度高于对照组(P<0.05),且观察组不良反应发生情况明显低于对照组(P<0.05)。结论 醋酸阿托西班联合盐酸利托君治疗早产,能改善患者的血清炎性因子水平,减轻炎症反应,延长妊娠时间,对改善妊娠结局效果更佳,且孕妇应用安全性好,值得临床推广应用。

关键词： 妥昔单克隆抗体   环磷酰胺   长春地辛   表柔比星   泼尼松   弥漫大B细胞淋巴瘤  

摘要： 评价利妥昔单抗与CHOP化疗方案相结合在治疗弥漫性大B细胞淋巴瘤(DLBCL)过程中的临床治疗反应。方法 在本院选取2023年1月至2024年6月间确诊患有DLBCL的104例患者作为研究样本并将其随机划分为两个治疗组别。观察组接受利妥昔单抗与CHOP方案联合治疗而对照组则仅接受CHOP方案单一治疗。本研究旨在比较两种治疗方案在临床应用中的疗效差异。结果 观察组的总有效率显著高于对照组(P<0.05)。较于对照组,观察组在接受治疗后的血清中的CD3+与CD4+水平呈现上升趋势而CD8+水平则相对较低(P<0.05)。观察组的患者出现不良事件的比率明显低于对照组,但差异不具有统计学意义(P>0.05)。相较于对照组,观察组的生存率显著升高而复发率显著降低(P<0.05)。相较于对照组,观察组在接受治疗后所得到的预后指数评分呈现出降低的趋势(P<0.05)。结论 合并利妥昔单抗与CHOP方案对弥漫性大B细胞淋巴瘤进行治疗展现出显著的治疗效果,不仅提升了总体有效率而且并未导致不良反应的增加,因此该治疗方案具有较高的临床应用价值。

摘要： T cells rely on short peptides presented by highly polymorphic major histocompatibility complexes (MHCs) to selectively initiate adaptive immune responses. Despite its importance, few techniques can systemically evaluate stable peptide presentation across diverse MHC alleles. Here, we describe a yeast display pipeline that can be deployed to rapidly screen proteomic space to identify class I pMHC binders across many alleles. Through this, we capture unique biological phenomena such as interference with peptide presentation via type IV drug-induced hypersensitivity. We apply this approach to multiple pathogen proteomes (Mtb Type 7S substrates, SARS-CoV-2, Dengue, and Zika) to create a high-resolution catalog of potential T cell antigens. Altogether, this platform acts as a flexible tool to generate large unbiased datasets for class I peptide presentation at a speed and scale competitive with the biological systems they represent.

关键词： 中性粒细胞与淋巴细胞比值(NLR)   PD-1抑制剂   晚期胃癌   免疫治疗   临床价值  

摘要： 探讨外周血中性粒细胞与淋巴细胞比值(NLR)在PD-1抑制剂治疗HER2阴性晚期胃癌患者中的临床应用价值。方法 分析2022年1月至2023年6月期间40例接受PD-1抑制剂治疗的HER2阴性晚期胃癌患者的病历。所有患者进行了血常规检测,并通过NLR值(中性粒细胞计数/淋巴细胞计数)评估炎症状况,分为高NLR组(NLR>2.43)和低NLR组(NLR≤2.43),比较两组的临床病理特征和治疗效果。结果 肿瘤分化类型、分期、远处转移和浸润度在两组间有显著差异(P<0.05)。高NLR组和低NLR组的治疗有效率分别为38.89%和80.82%,差异显著(P<0.05)。NLR是影响进展期胃癌免疫治疗效果的独立危险因素。结论 NLR作为反映全身免疫与炎症状况的血液学指标,在HER2阴性晚期胃癌患者免疫治疗中具有重要的临床价值。低NLR组的治疗有效率显著高于高NLR组,提示NLR可作为预测免疫治疗效果的潜在生物标志物。

关键词： Solute carrier family 7 member 11   Interleukin-1 beta   Combined therapy   T cell exhaustion   Oral carcinogenesis  

摘要： Oral squamous cell carcinoma (OSCC), one of the most prevalent and aggressive forms of head and neck squamous cell carcinoma, has a five-year survival rate of about 50% similar to 60%, emphasizing the urgent need for more effective therapeutic strategies. Solute carrier family 7 member 11 (SLC7A11) is overexpressed in various cancers and represents a potential therapeutic target. Sulfasalazine (SAS), a Food and Drug Administration-approved drug, is a potent inhibiter of SLC7A11. However, SAS can also increase the levels of pro-inflammatory cytokines such as IL-1 beta, which may suppress the immune response. Here, we investigate the effect of SAS combined with anti-IL-1 beta monoclonal antibody (anti-IL-1 beta mAb) as a novel treatment strategy for OSCC. In this study, SLC7A11 was markedly increased in OSCC tissues, and high SLC7A11 expression predicted poor prognosis. SAS treatment was shown to suppress OSCC cell proliferation and trigger ferroptosis, as evidenced by elevated reactive oxygen species, reduced glutathione and enhanced lipid peroxidation. SAS also elevated IL-1 beta levels, leading to T cell exhaustion. Combining SAS with anti-IL-1 beta mAb reversed T cell exhaustion and amplified the anti-tumor effects in vitro. In the 4-nitroquinoline-1-oxide-induced oral cancergenisis model, the combination treatment significantly inhibited oral carcinogenesis compared to monotherapy. Our results suggest that combining SAS with anti-IL-1 beta mAb enhances the anti-tumor efficacy against OSCC through tumor growth inhibition and immune modulation, offering a promising therapeutic strategy.

摘要： Background:Co-trimoxazole is a leading global cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Co-trimoxazole-induced SCAR are associated with HLA class I alleles including HLA-B*13:01 and HLA-B*38:02 in Southeast Asian (SEA) populations. However, the global generalizability of these associations is unknown but critical for population-appropriate risk stratification and diagnosis. Objective:To determine HLA risk factors associated with co-trimoxazole-induced SJS/TEN and DRESS in populations from the United States (US) and South Africa (SA). Methods:We performed high-resolution HLA typing on dermatologist-adjudicated co-trimoxazole-induced SCAR patients in the US (n=63) and SA (n=26) compared to population controls. Peptide binding and docking analyses were performed using MHCcluster2.0 and CB-Dock2. Results:In a multiple logistic regression model, HLA-B*44:03 (Pc<0.001, OR: 4.08), HLA-B*38:01 (Pc<0.001, OR: 5.66), and HLA-C*04:01 (Pc=0.003, OR: 2.50) were independently associated with co-trimoxazole-induced SJS/TEN in the US. HLA-B*44:03 was also associated with co-trimoxazole-induced DRESS in SA (Pc=0.019, OR: 10.69). Distinct HLA-B variants with shared peptide binding specificities (SPBS) and HLA-C*04:01 identified 94% and 78% of co-trimoxazole-induced SJS/TEN and DRESS in the US, respectively. The SEA risk allele HLA-B*13:01, with SPBS to HLA-B*44:03, was identified in just 1/63 US SCAR patients. Conclusion:HLA alleles with SPBS to SEA-related risk alleles including HLA-B*44:03 (SPBS with HLA-B*13:01) and HLA-B*38:01 (SPBS with HLA-B*38:02) but also HLA-C*04:01 predisposed to co-trimoxazole-induced SCAR in the US and SA. These findings provide biological plausibility and strategies for global risk prediction and diagnosis of co-trimoxazole-induced SCAR. HIGHLIGHTS BOX:HLA alleles including HLA-B*13:01 and HLA-B*38:02 ar

关键词： Obese asthma   Huatanhuoxue decoction   Network pharmacology   Neutrophils   IL-17A signaling pathway  

摘要： Ethnopharmacological relevance: Huatanhuoxue Decoction (HTHX) is a traditional Chinese formula consisting of nine herbs. It is used to improve obesity-related asthma symptoms and reduce airway inflammation. Aim of the study: To study HTHX effects on airway inflammation in obese asthmatic mice via the IL-17 A signaling pathway. Materials and methods: Network pharmacology was used to predict the bioactive ingredients in HTHX. Subsequently, an obese asthma model was established by high-fat diet feeding and exposure to house dust mite. The effects of HTHX on obesity-related asthma progression were investigated using histopathological examinations, airway hyperresponsiveness determinations, and enzyme-linked immunosorbent assays. The mechanism of action of HTHX was confirmed by Western blots, flow cytometry, immunohistochemistry, and immunofluorescence analyses. Results: HTHX alleviated the development in obese asthma mice by improving the pathological condition of lung tissue, airway hyperresponsiveness, and inflammatory factors. Network pharmacology identified the involvement of the IL-17 signaling pathway. HTHX decreased the production of neutrophils and the expression of NETs in lung tissue. HTHX also reduced group 3 innate lymphoid cells and Th17 cells, which are responsible for producing IL-17 A. The production of IL-17 A-related protein was also suppressed. The results indicate that HTHX inhibited the excessive activation of the IL-17 A signaling pathway. Conclusions: HTHX alleviated airway inflammation by regulating the IL-17 A signaling pathway in obese asthmatic mice.

关键词： IL-4 signaling   dendritic cells   skin allergy  

摘要： IL-13 produced by innate lymphoid cells (ILC2s) is crucial for the steady-state differentiation of dermal CD11b-low type-2 dendritic cells (DC2s), a murine KLF4-dependent DC2 population that is found only in skin and drives enhanced Th2 differentiation. In this study, we examined how CD11b-low DC2s respond to skin inflammation, particularly in the absence of IL-13. We employed a model of MC903-induced atopic dermatitis in which CD11b-low DC2s migrate from skin to the draining lymph node (dLN) in a thymic stromal lymphopoietin receptor (TSLPR)-dependent manner, temporarily depleting the skin CD11b-low population. In C57BL/6J mice, DC2s replenished the empty niche gradually over several days and required IL-4RA-dependent signaling for their differentiation into CD11b-low DC2s. In IL-13 KO mice treated with MC903, IL-4 produced by basophils and CD4+ T cells could compensate for the absence of IL-13 to drive differentiation of skin CD11b-low DC2s. We confirmed this latter finding by showing that IL-4 treatment was sufficient to induce CD11b-low differentiation both in DC cultures and in IL-13 KO mice. Our findings suggest that, in the absence of IL-13, IL-4 produced during type-2 skin inflammation can induce CD11b-low DC2 differentiation, providing insight into how inflammation can drive an environment that supports further allergic sensitization.

关键词： 发酵棉籽蛋白   生长   非特异性免疫   大菱鲆  

摘要： 为了探究希瓦氏菌(Shewanella sp.)发酵棉籽蛋白替代鱼粉对大菱鲆(Scophthalmus maximus L.)生长性能及非特异性免疫的影响。研究以50%鱼粉组为对照组,以发酵棉籽蛋白、棉籽蛋白替代饲料中20%的鱼粉为实验组配制三种等氮等脂的配合饲料(鱼粉组、棉籽蛋白组、发酵棉籽蛋白组)。挑选初始体重为(17.52±0.02) g的大菱鲆,开展为期8周的养殖实验。结果显示:发酵棉籽蛋白组大菱鲆增重率(WGR)、特定生长率(SGR)、蛋白质效率(PER)较棉籽蛋白组均显著升高,饲料系数(FCR)显著降低(P<0.05),且与鱼粉组无显著差异。抗氧化指标显示,发酵棉籽蛋白组大菱鲆肝脏总抗氧化能力(T-AOC)和超氧化物歧化酶(SOD)活性较棉籽蛋白组显著提高,过氧化氢酶(CAT)活性较鱼粉组显著升高,丙二醛(MAD)含量较鱼粉组显著下降(P<0.05)。组织形态方面,发酵棉籽蛋白组肠绒毛高度较棉籽蛋白组显著升高(P<0.05),且与鱼粉组无显著差异。在免疫方面,与棉籽蛋白组相比,发酵棉籽蛋白组大菱鲆肠道促炎因子基因(il-8、ifn-γ、il-1β)和TLR2/NF-κB通路基因(tlr2、myd88、nf-κb p65)表达受到显著抑制(P<0.05),与鱼粉组无显著差异,同时紧密连接蛋白基因(zo-1、occludin、tricelluin)的表达显著上调(P<0.05),其中zo-1和occludin基因表达量显著高于鱼粉组。在本实验条件下,希瓦氏菌发酵棉籽蛋白可显著改善棉籽蛋白替代鱼粉对大菱鲆生长、免疫造成的负面影响,可以替代大菱鲆饲料中20%的鱼粉。

关键词： IL-24   Penta-O-galloyl-β-D-glucose   STAT3   in silico   skin barrier