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关键词： ACR20/50/70   American College of Rheumatology response criteria   bDMARDs   biological Disease-Modifying Anti-Rheumatic drugs   cDAPSA   clinical disease activity index of psoriatic arthritis   DAPSA   disease activity index of psoriatic arthritis   DAS28-CRP   disease activity score based on 28 joints and C-reactive protein concentrations   EQ-5D   EuroQol group questionnaire in 5 dimensions   HR   hazard ratio   i   inhibitor   IL   interleukin   IPW   inverse propensity score-weighted   MASES   Maastricht ankylosing spondylitis enthesitis score   MDA   minimal disease activity   PS   propensity score   PsA   psoriatic arthritis   SCQM   Swiss Clinical Quality Management in Rheumatic Diseases   TC   treatment course   Th17i   inhibitors of the Th17 cell generation or function   TNF   tumor necrosis factor  

摘要： Objective: To compare the effectiveness of Interleukin (IL)-12/23 or IL-17A inhibitors (summarized to inhibitors of the Th17 cell generation or function, Th17i) with tumor necrosis factor inhibitors (TNFi) in patients with TNFi-experienced psoriatic arthritis (PsA). Patients and Methods: We conducted a comparative effectiveness study by taking advantage of prospectively collected patients with PsA data from the Swiss Clinical Quality Management in Rheumatic Diseases register, encompassing the interval from January 1, 2015 to August 1, 2021. Drug retention was the primary outcome in unadjusted and inverse propensity-weighted Cox regression models. Secondary outcomes were a static skin score for psoriasis, the American College of Rheumatology (ACR) 20, 50, and 70 response rates, and the disease activity in PsA score. Results: At baseline, Th17i (n=341) were initiated in patients with more severe skin disease, but with comparable disease activity as TNFi (n=503) in all other disease domains. In the unadjusted analysis, Th17i were later discontinued than TNFi (median 828 vs 445 days, P<.001), but the hazard ratio for discontinuation was significantly lower for Th17i than for TNFi only in women (0.57 [0.37-0.87], P=.01). Furthermore, differences in static skin scores between the groups at baseline were equalized at follow-up. However, improvements in the disease activity in PsA were similar in both groups, and ACR20 (33% [29%] vs 14% [13%];P=.03) and ACR50 response rates (24% [21%] vs 7% [6%];P=.02) were even higher for TNFi in unadjusted and (LUNDEX-adjusted) analyses. Conclusion: After TNFi failure, more profound skin improvement and longer drug retention in women argue in favor of switching to Th17i in certain patient populations. However, TNFi may at least be equivalent in improving locomotor system manifestations and remain a viable option in the first and in the later treatment line of PsA. © 2025 The Authors

关键词： Atypicaldiverse phenotype   Gene therapy   IL2RG   Self-inactivating lentiviral vector   X-linked severe combined immunodeficiency disease  

摘要： X-linked severe combined immunodeficiency disease(X-SCID)is a rare inheriteddisease caused by mutations in the interleukin 2 receptor subunit gamma gene(IL2RG),whichencodes the common g chain protein,a subunit of the receptor for lymphocytes.X-SCID ischaracterized by profound defects in T-cell,B-cell,and natural killer cell ***,we report a Chinese cohort of nine X-SCID patients with six novel IL2RG ***,the two adolescent patients with an atypical immunotype were confirmed by furtheranalyzing IL-2-JAK-STAT5 signaling,T cell proliferation,and T cell receptor excision circles(Trecs).Interestingly,Bacillus Calmette-Guerin(BCG)disease occurred commonly in *** allogeneic hematopoietic stem-cell transplantation is curative for the disease,it is not available to all patients due to the lack of suitable matched *** therapy using a self-inactivating lentiviral vector(SIN-LV)technology has provided analternative therapy for such mono-genetic ***,we performed the pre-clinicalstudies to assess our SIN-LV carrying IL2RG on human ED7R cells deficient in IL2RG andCD34^(+)stem cells derived from the bone marrow of a healthy donor and a patient with *** work is done complied with the established“Good Manufacturing Practice”(GMP)used inthe clinical *** addition,a safety study is performed using the transduced CD34^(+)cells implanted into the axilla of nude mice in ***,our studies have demonstrated the efficiency and safety of SIN-IL2RG-LV,which paves the way for conducting X-SCID gene therapyclinical trials in China in the near future.

关键词： Breast cancer   IL27RA,   Tumor immune microenvironment   Single-cell RNA sequencing,   Immunotherapy response  

摘要： BackgroundInterleukin-27 receptor alpha (IL27RA), a key subunit of the interleukin-27 receptor, plays an essential role in T cell-mediated immunity. However, its relevance in breast cancer and response to immunotherapy remains *** integrated bulk and single-cell RNA sequencing data from TCGA, GEO, and scRNA-seq datasets to analyze IL27RA expression, prognosis, immune infiltration, and treatment response. TIDE and immune checkpoint-treated clinical cohorts were used to assess immunotherapy responsiveness. Chemotherapy sensitivity was predicted using GDSC data, and IL27RA protein expression was validated by Western ***27RA was downregulated in breast cancer but high expression correlated with favorable survival. It was primarily expressed in T cells, particularly CD8(+) subsets, and associated with enriched immune infiltration and elevated checkpoint gene expression. IL27RA high-expression patients showed lower TIDE scores, better outcomes in ICI-treated cohorts, and higher sensitivity to multiple chemotherapeutic ***27RA is a potential immune biomarker that reflects an inflamed tumor microenvironment and predicts benefit from immunotherapy and chemotherapy in breast cancer. These findings provide novel insights into immune-based stratification using single-cell transcriptomic data.

关键词： 小鼠结肠癌C26   恶病质   肌肉   脂肪   细胞因子   血细胞变化  

摘要： 目的建立小鼠结肠癌C26恶病质模型,并观察其血象和炎症因子的时程变化。方法将C26小鼠保种瘤液接种到BALB/c小鼠右侧背部皮下,待肿瘤生长至直径10 mm左右时处死小鼠取肿瘤,匀浆后按照1:60稀释,皮下注射200μL细胞液,然后称体重,量瘤径。接种肿瘤12 d和18 d后处死动物,当天取血、棕色脂肪、附睾白色脂肪、股四头肌、腓肠肌、脾脏、胸腺和瘤块。取血浆样品进行细胞因子的检测;取血细胞进行血象和CD4^(+)/CD8^(+)淋巴细胞的分类分析;并对脂肪组织进行病理切片和HE染色。结果C26瘤液接种到BALB/c小鼠皮下后,肿瘤组小鼠体重在12d和18 d明显下降,棕色脂肪组织的重量均明显下降,脂滴明显变小,胞浆含量增加;附睾白色脂肪在接种肿瘤后12 d时和对照相比基本无变化,而18 d时重量明显减轻,脂滴变小,并出现白色脂肪棕色化现象;肿瘤组股四头肌和腓肠肌的重量减轻;肿瘤组动物的脾脏体积变大,脾重也明显增加;胸腺重量降低。流式细胞术检测发现,小鼠血液中CD4^(+)/CD8^(+)淋巴细胞比例无显著差别;接种12 d后,血浆中IL-6的含量显著增加,接种18 d后,IFN-γ的浓度显著降低,IL-1β、TNF-α、IL-6含量均显著增加;接种肿瘤12 d后,肿瘤组中红细胞、血红蛋白、红细胞压积、平均红细胞血红蛋白含量、血小板数目和血小板压积均较对照组明显降低,单核细胞百分比较对照组明显升高;接种肿瘤18 d后,红细胞、血红蛋白、红细胞压积、碱性粒细胞百分比、淋巴细胞百分比较对照组均明显降低,红细胞体积分布宽度、白细胞、淋巴细胞、单核细胞、单核细胞百分比、中性粒细胞数量和中性粒细胞百分比显著增加。结论成功构建了C26恶病质小鼠模型,该模型具有体重下降、肌肉和脂肪减少、白色脂肪褐变、脾脏肿大、胸腺萎缩、血细胞计数明显变化等特征,早期血浆IL-6的变化值得关注。该模型的建立与验证为研究癌症恶病质提供了可靠的依据和参考。

关键词： 血白细胞介素-17A   难治性肺炎支原体肺炎   预测   诊断及治疗   儿童  

摘要： 目的:探讨血白细胞介素(IL)-17A对难治性肺炎支原体肺炎(RMPP)诊断预测价值及指导治疗意义。方法:选取2023年2月—2024年2月石河子大学第一附属医院儿科收治的肺炎支原体肺炎(MPP)患儿及RMPP患儿各40例作为研究对象。抽取空腹外周静脉血,酶联免疫吸附法(ELISA)检测IL-17A,同时收集相关临床资料。结果:RMPP组患儿肺实变、胸腔积液、大叶性改变的比例明显高于MPP组,差异均有统计学意义(χ^(2)=14.066、16.970、16.200,P<0.05);RMPP组患儿选择非大环内酯类药物抗肺炎支原体、糖皮质激素的比例明显高于MPP组,差异均有统计学意义(χ^(2)=19.948、24.2321,P<0.05);RMPP组患儿的IL-6、IL-17A、降钙素原(PCT)、乳酸脱氢酶(LDH)水平均高于MPP组,差异均有统计学意义(Z=3.305、4.754、2.308、3.975,P<0.05);Spearman相关分析发现,IL-17A与PCT、IL-6呈正相关(r=0.777、0.598,P<0.001);LDH、IL-6和IL-17A的受试者工作特征(ROC)曲线下面积(AUC)分别为0.74、0.71、0.81;非大环内酯类药物治疗组患儿的IL-6、IL-17A、C反应蛋白(CRP)、LDH水平均高于大环内酯类药物治疗组,差异均有统计学意义(z=2.541、2.973、2.148、2.127,P<0.05);IL-17A作为独立预测因素在指导RMPP用药的AUG为0.73。结论:IL-17A>54.60 pg/mL能相对准确的预测儿童RMPP,IL-17A指导RMPP用药的AUC为0.73,提示为有中等程度的预测价值,截断值为115.0 pg/mL。

关键词： 多囊卵巢综合征   补肾助排汤   胰岛素抵抗   IL-6/PI3K/AKT信号通路   大鼠  

摘要： 目的基于IL-6/PI3K/AKT信号通路探讨补肾助排汤对多囊卵巢综合征伴胰岛素抵抗大鼠的干预机制。方法采用高脂饲料喂养联合来曲唑灌胃构建多囊卵巢综合征伴胰岛素抵抗大鼠模型,空白组予普通饲料喂养,将成模大鼠随机分为模型组、二甲双胍组和补肾助排汤低、中、高剂量组,并予相应干预,连续28 d。检测大鼠空腹血糖(FBG)含量,计算稳态模型评估胰岛素抵抗指数(HOMA-IR),ELISA测定血清空腹胰岛素(FINS)、睾酮(T)、雌二醇(E_(2))、黄体生成素(LH)、卵泡刺激素(FSH)含量,HE染色观察卵巢组织形态,免疫组化测定卵巢组织白细胞介素(IL)-6、p-磷脂酰肌醇-3-激酶(PI3K)、p-蛋白激酶B(AKT)、葡萄糖转运蛋白(GLUT)4表达,Western blot检测卵巢组织IL-6、PI3K、p-PI3K、AKT、p-AKT、GLUT4蛋白表达,RT-PCR检测IL-6、PI3K、AKT、GLUT4 mRNA表达。结果与空白组比较,模型组大鼠体质量、FBG、FINS和血清T、LH含量明显升高(P<0.01),血清E_(2)、FSH含量明显降低(P<0.01);卵巢组织呈多囊样改变,颗粒细胞层数减少、排列松散,卵巢组织IL-6蛋白和mRNA表达明显升高(P<0.01),p-PI3K、p-AKT、GLUT4蛋白表达明显降低(P<0.01),PI3K、AKT、GLUT4 mRNA表达明显降低(P<0.01)。与模型组比较,各给药组大鼠体质量减少,FBG、FINS和血清T、LH含量降低(P<0.01,P<0.05),E_(2)、FSH含量升高;卵巢组织多囊样变减轻,成熟卵泡增多,颗粒细胞排列紧密,卵巢组织IL-6蛋白和mRNA表达降低,p-PI3K、p-AKT、GLUT4蛋白及PI3K、AKT、GLUT4 mRNA表达升高,其中补肾助排汤高剂量组差异均有统计学意义(P<0.01)。结论补肾助排汤可改善多囊卵巢综合征伴胰岛素抵抗大鼠生殖、代谢紊乱,其机制可能与抑制IL-6表达,激活PI3K/AKT信号通路,减轻胰岛素抵抗状态有关。

关键词： 骨质疏松症   正五聚蛋白3   膜联蛋白A2   白细胞介素-33   老年   骨折  

摘要： 目的:探究血清正五聚蛋白3(PTX3)、膜联蛋白A2(ANXA2)、白细胞介素-33(IL-33)在老年骨质疏松症患者中的表达变化及其预测并发骨折价值。方法:将老年骨质疏松症患者207例和骨密度(BMD)正常者207例分别作为观察组与对照组。比较两组血清PTX3、ANXA2、IL-33水平及BMD,分析血清PTX3、ANXA2、IL-33水平与BMD的相关性。随访2年,根据老年骨质疏松症患者是否发生骨折分为发生亚组与未发生亚组,比较发生与未发生亚组患者临床资料、BMD、骨质疏松标志物[Ⅰ型胶原交联羧基末端肽(CTX)、骨碱性磷酸酶(BALP)、全段甲状腺旁激素(iPTH)]及血清PTX3、ANXA2、IL-33水平,分析血清PTX3、ANXA2、IL-33水平与骨质疏松标志物及老年骨质疏松症患者骨折的关系。绘制受试者工作特征(ROC)曲线评价血清PTX3、ANXA2、IL-33预测老年骨质疏松症患者骨折的价值。结果:观察组血清PTX3、ANXA2水平高于对照组,血清IL-33水平及BMD低于对照组(均P<0.05)。骨质疏松症患者血清PTX3、ANXA2水平与BMD呈负相关,血清IL-33与BMD呈正相关(均P<0.05)。207例老年骨质疏松症患者随访2年,失访7例,其中88例发生骨折(发生亚组),112例未发生骨折(未发生亚组)。发生亚组女性比例、年龄及血清CTX、BLAP、iPTH、PTX3、ANXA2水平高于未发生亚组,血清IL-33水平及BMD低于未发生亚组(均P<0.05)。老年骨质疏松症患者血清PTX3、ANXA2水平与骨质疏松标志物CTX、BLAP、iPTH呈正相关,血清IL-33水平与骨质疏松标志物CTX、BLAP、iPTH呈负相关(均P<0.05)。Logistic回归分析显示,校正其他混杂因素后,血清PTX3、ANXA2、IL-33仍为老年骨质疏松症患者骨折的独立影响因素(均P<0.05)。血清PTX3、ANXA2、IL-33联合预测老年骨质疏松症患者骨折的曲线下面积(AUC)最大,为0.918,预测价值明显优于血清PTX3、ANXA2、IL-33单项(均P<0.05)。结论:老年骨质疏松症患者血清PTX3、ANXA2水平升高,IL-33水平下降,与骨折风险有关,三项联合对骨折风险的预测价值较高。

关键词： 甲基苯丙胺(METH)   巨噬细胞   多巴胺D3受体(D3R)   ERK1/2   IL-6   IL-10  

摘要： 目的研究甲基苯丙胺(methamphetamine,METH)对脂多糖(lipopolysaccharide,LPS)刺激的巨噬细胞产生细胞因子的影响,并探究可能机制。方法研究METH对LPS刺激RAW264.7细胞产生细胞因子的实验分为空白对照组、LPS刺激组、不同浓度METH(20、100、200μmol/L)干预组(即METH/LPS组)。研究多巴胺D3受体(dopamine D3 receptor,D3R)在该过程中的作用,应用D3R拮抗剂NGB2904处理,实验分为空白对照组、LPS刺激组、METH/LPS组、NGB2904/LPS组、NGB2904/METH/LPS组。采用MTT法检测细胞活性,ELISA法检测培养上清中IL-6、IL-10和TNF-α水平,Western blotting检测p-ERK1/2、ERK1/2蛋白表达。结果相对于空白对照组,LPS刺激组、METH/LPS处理组RAW264.7细胞活性、IL-6、IL-10及TNF-α水平均明显升高(P<0.05)、ERK1/2磷酸化水平明显升高(P<0.05);相对于LPS刺激组,METH/LPS处理组细胞活性无明显变化(P>0.05),IL-6、IL-10水平、ERK1/2磷酸化水平均明显降低(P<0.05),且METH的抑制作用呈现剂量依赖性,在200μmol/L时抑制效应最强;进一步采用D3R拮抗剂干预的结果显示:相对于LPS刺激组,METH/LPS组、NGB2904/LPS组细胞活性无明显变化(P>0.05),但IL-6、IL-10水平、ERK1/2磷酸化水平均明显降低(P<0.05);NGB2904/METH/LPS组的IL-6、IL-10水平、ERK1/2磷酸化水平相对于METH/LPS组、NGB2904/LPS组进一步降低(P<0.05)。结论METH可能通过抑制LPS刺激的RAW264.7细胞内ERK1/2磷酸化,降低RAW264.7细胞产生IL-6和IL-10;METH的免疫抑制效应类似于D3R被拮抗的免疫效应。

关键词： 疾病诊断   移植抗原   造血干细胞移植   药物治疗  

摘要： 一说起骨髓配型,想必读者朋友们首先映入脑海的就是白血病患者寻找合适的捐献者并进行造血干细胞移植,或者一些患者在进行器官移植前需要相关检查,这里的“配型”配的就是俗称为“移植抗原”的人类白细胞抗原(human leukocyte antigen, HLA)。编码HLA的基因群有一个读起来有点拗口的名称“主要组织相容性复合体”(major histocompatibility complex,MHC),位于人类6号染色体短臂上。HLA的配型结果对于移植后的免疫排斥反应和移植物生存率均有重要影响,因而一直都是研究的热门。HLA按照其分布和功能可分为Ⅰ类抗原、Ⅱ类抗原和Ⅲ类抗原,经典的HLAⅠ类抗原包括HLA-A、HLA-B、HLA-C,Ⅱ类抗原包括HLA-DR、HLA-DQ、HLA-DP,Ⅲ类抗原为C4a、C4b、C2、Bf等。那么,除了移植之外,HLA是不是与我们的日常生活关联不大呢?其实不然,今天就向大家介绍一下HLA在疾病诊断与药物治疗这两方面的作用。

关键词： 子宫肌瘤   腹腔镜子宫切除术   C反应蛋白/白蛋白   癌胚抗原   预后  

摘要： 目的检测子宫肌瘤患者腹腔镜全子宫切除术后C反应蛋白与白蛋白比值(CRP/ALB)、癌胚抗原(CEA)水平变化,探讨二者与术后不良反应发生的关系及预后价值。方法选取2022年1月至2024年1月于安徽医科大学附属宿州医院妇科收治的100例因子宫肌瘤行腹腔镜下全子宫切除术的患者,根据术后首次复查时是否发生不良反应将患者分为预后良好组(n=72)与预后不良组(n=28)。比较两组患者的一般资料和手术相关指标;通过溴甲酚绿法、免疫比浊法和化学发光免疫分析法测定术前及术后24 h血清CRP/ALB、CEA水平;采用Logistic回归分析影响患者预后的危险因素;ROC曲线评估预测价值。结果术后24 h患者的CRP/ALB水平显著高于术前,CEA水平显著低于术前(P<0.05),且预后不良组患者血清CRP/ALB、CEA水平显著高于预后良好的患者(P<0.05);Logistic回归分析发现,高水平的CRP/ALB、CEA是子宫肌瘤患者腹腔镜下全子宫切除术预后的影响因素(P<0.05);ROC曲线结果显示,术后血清CRP/ALB、CEA高水平表达对子宫肌瘤患者预后不良预测的AUC分别为0.894、0.851。二者联合预测的AUC为0.949。结论腹腔镜下全子宫切除术后24 h血清CRP/ALB、CEA水平高表达与术后不良反应发生关系密切,二者联合检测有一定的预后价值。