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关键词： 脑卒中后抑郁   重复经颅磁刺激   艾司西酞普兰   神经递质   炎性因子  

摘要： 目的探讨高压氧(HBO)联合重复经颅磁刺激(rTMS)技术对脑卒中后抑郁(PSD)患者细胞因子和神经递质的影响。方法选取2022年1月至2023年12月江阴博医家康复医院46例PSD患者作为研究对象。通过随机数字表划分为对照组与研究组,每组各23例。两组均予脑卒中常规治疗,口服艾司西酞普兰10 mg,1次/d。高压氧方案:间断面罩吸纯氧1 h,之后改成呼吸舱内空气,20 min后便可出舱,1次/d,10次为1个疗程,每个疗程有3~5 d间隔期,治疗4个疗程。研究组在上述治疗基础上联合rTMS治疗,20 min/次,1次/d,5次/周,10次为1个疗程,治疗前后检测两组血清神经递质水平及细胞因子水平变化。结果入院时,两组血清氨基酸类神经递质、炎症因子水平差异无统计学意义(P>0.05)。治疗4个疗程后,研究组血清神经递质谷氨酸(GLu)(12.17±1.31)mg/dL水平显著低于对照组(18.28±2.31)mg/dL,差异有统计学意义(P<0.05),甘氨酸(GLy)(2.86±0.43)mg/dL水平显著高于对照组(2.19±0.24)mg/dL,差异有统计学意义(P<0.05);血清炎性因子肿瘤坏死因子-α(TNF-α)、白介素-8(IL-8)、白介素-6(IL-6)水平均显著低于对照组(P<0.05)。结论对PSD患者在脑卒中常规治疗及抗抑郁剂治疗的同时,联合HBO与rTMS治疗具有协同增效作用,能有效调节神经递质平衡,降低炎性因子水平,改善或缓解抑郁症状,有利于促进患者神经功能的康复。

关键词： 电针   百会(GV20)   大椎(GV14)   缺血性脑卒中   小胶质细胞   HIF-1α   VEGF   IL-1β   TNF-α   神经功能   大鼠  

摘要： 【目的】探讨电针百会和大椎对缺血性脑卒中大鼠的长期和短期治疗作用及机制。【方法】将30只大鼠随机分为假手术组、模型组和电针组,每组10只。模型组和电针组大鼠采用改良的Longa方法建立大脑中动脉阻塞(MCAO)模型。电针组电针百会(GV20)和大椎(GV14)1周,每日1次。于MCAO术后14、21和28 d,进行粘贴去除试验和前肢放置试验评估长期神经恢复情况。MCAO术后第2天,透射电子显微镜观察脑皮层组织病理变化,采用免疫荧光法检测脑皮层组织Iba-1的表达,Western Blot法检测脑皮层组织缺氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)、白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的表达。【结果】(1)与假手术组同时间点比较,模型组MCAO术后14、21、28 d拆除胶带的时间延长,前肢踏步次数增加(P<0.05);与模型组同时间点比较,电针组大鼠MCAO术后14、21、28 d胶带去除时间显著缩短,前肢踏步次数减少(P<0.05)。MCAO术后28 d内,胶带去除时间逐渐缩短、前肢步数逐渐减少。(2)MCAO术后第2天:与假手术组比较,模型组脑皮层缺血半暗带小胶质细胞变性和坏死,线粒体损伤,脑皮层组织Iba-1的表达水平升高,HIF-1α、VEGF及IL-1β和TNF-α的表达水平升高,差异均有统计学意义(P<0.05);与模型组比较,电针组脑皮层缺血半暗带小胶质细胞损伤得到改善,脑皮层组织Iba-1的表达水平降低,HIF-1α、VEGF及IL-1β和TNF-α的表达水平降低,差异均有统计学意义(P<0.05)。【结论】电针百会和大椎可长期改善缺血性脑卒中大鼠症状,短期改善脑皮层缺血半暗带小胶质细胞的变性和坏死,其机制可能与下调脑皮层组织HIF-1α、VEGF、IL-1β和TNF-α表达,并抑制小胶质细胞向M1表型的转化有关。

关键词： 甲型流感   T淋巴细胞   免疫功能  

摘要： 目的:探讨甲型流感患者外周血免疫细胞水平的变化。方法:选取2023年1月—2024年3月在九江市第三人民医院首诊收治的甲型流感核酸/抗原检测阳性的甲流患者123例,按疾病严重程度分为轻症组(n=80)和重症/危重症组(n=43),另选取同期本院体检中心年龄匹配的健康人群50例为对照组,检测并比较三组外周血淋巴细胞计数(LYM)、T淋巴细胞亚群及调节性T细胞(Treg)分泌的细胞因子[白细胞介素-4(IL-4)、白细胞介素-10(IL-10)、转化生长因子β(TGF-β)]水平。结果:重症/危重症组LYM及CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平均低于轻症组和对照组,CD8^(+)水平高于轻症组和对照组,差异均有统计学意义(P<0.05)。重症/危重症组IL-4、IL-10、TGF-β水平均低于轻症组和对照组,差异均有统计学意义(P<0.05)。结论:T淋巴细胞介导的细胞免疫参与甲型流感发生发展过程,外周血LYM、T淋巴细胞亚群及Treg分泌的细胞因子可作为患者病情评估的潜在指标。

关键词： 结缔组织病   间质性肺疾病   IL-36   IL-38  

摘要： 目的:通过检测原发性干燥综合征、系统性硬化症以及类风湿关节炎(rheumatoid arthritis, RA)等结缔组织病相关间质性肺疾病(connective tissue disease associated interstitial lung disease, CTD-ILD)患者血清中白细胞介素-36 (interleukin-36, IL-36) (包括IL-36α,IL-36β,IL-36γ,IL-36Ra和IL-38)的表达水平,评估IL-36作为CTD-ILD潜在生物标志物的价值,为CTD-ILD的早期筛查、分层管理及靶向治疗提供新型生物标志物筛选策略和探索发病机制提供理论支撑。方法:本研究纳入2024年5~12月湖北民族大学附属民大医院风湿免疫科确诊的111例CTD患者,依据是否合并间质性肺疾病(interstitial lung disease, ILD),将患者分为CTD-ILD组(56例)和结缔组织病未合并间质性肺疾病(connective tissue disease-non interstitial lung disease, CTD-NILD)组(55例);同时纳入55名同期健康体检者作为健康对照组。采用酶联免疫吸附试验检测各组的血清IL-36表达水平,并收集所有研究对象的一般临床资料,以及CTD患者的实验室检验结果和肺高分辨率计算机断层扫描结果。采用IBM SPSS Statistics 27.0统计软件对所有数据进行统计分析。结果:(1) IL-36α、IL-36β、IL-36γ、IL-38在CTD患者血清中的表达水平均高于健康人群,差异均具有统计学意义(P P β、IL-36γ、IL-38在CTD-ILD患者血清中的表达水平均高于CTD-NILD患者,差异均有统计学意义(P P β、IL-38、IL-36β + IL-38从CTD中识别出ILD的曲线下面积分别为0.780、0.734、0.855,特异度分别为96.4%、92.7%、76.4%,敏感度分别为48.2%、44.6%、85.7%。(3) CTD-ILD患者的血清IL-36Ra表达水平与血沉呈负相关(r = −0.352, P = 0.008);结论:(1) 血清IL-36β、IL-38可能是诊断CTD-ILD的潜在生物标志物,且二者联合诊断可明显提高敏感度。(2) IL-36激动剂和受体拮抗剂的失衡可能在CTD及其相关ILD的病理生理过程中发挥调控作用。Objective: By measuring serum levels of interleukin-36 (IL-36) isoforms (including IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38) in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD)—specifically primary Sjögren’s syndrome, systemic sclerosis, and rheumatoid arthritis (RA)—this study aims to evaluate the value of IL-36 as a potential biomarker, thereby providing novel screening strategies for early detection, stratified management, and targeted therapy of CTD-ILD, while also advancing mechanistic insights into its pathogenesis. Methods: This study enrolled 111 patients with CTD diagnosed in the Department of Rheumatology and Immunology at Minda Hospital of Hubei Minzu University between May and December 2024. Participants were stratified into two groups based on interstitial lung disease (ILD) comorbidity status: the CTD-ILD group (56 cases) and the connective tissue disease-non interstitial lung disease (CTD

关键词： 牛CD4   单克隆抗体   原核表达  

摘要： 目的制备抗牛CD4的单克隆抗体,并对其进行基本生物学特性鉴定。方法通过构建牛CD4基因原核质粒,成功表达并纯化出重组牛CD4(rHis-BoCD4和rGST-BoCD4)。利用杂交瘤技术制备抗牛CD4单克隆抗体,通过ELISA对单克隆抗体亚型和效价进行鉴定和分析,使用间接免疫荧光实验、Western blot法分析其特异性。结果成功获得了四株稳定分泌BoCD4单克隆抗体的杂交瘤细胞株,命名为1H4、6A10、3F9和4G10。亚类鉴定单克隆抗体亚类6A10为IgG2b,其余单克隆抗体均为IgM型。Western blot结果显示,4株牛CD4单克隆抗体均可与体外表达的牛CD4蛋白发生特异性结合。间接免疫荧光实验表明4株单克隆抗体均能够特异性识别天然牛CD4蛋白。流式细胞术检测结果显示,3F9识别牛天然CD4分子的能力最强。结论成功制备了4株特异性强且能识别天然牛CD4蛋白的单克隆抗体,为后续研究牛CD4分子的功能、牛T淋巴细胞疾病的诊断及治疗方法的建立奠定基础。

关键词： 白术内酯Ⅲ   IL-6/STAT3信号通路   结直肠癌细胞   奥沙利铂   耐药性   药理实验  

摘要： 目的观察白术内酯Ⅲ(AT-Ⅲ)调节白细胞介素6(IL-6)/信号转导和转录激活因子3(STAT3)信号通路对结直肠癌(CRC)细胞奥沙利铂耐药性的影响。方法将25μmol/L奥沙利铂处理的奥沙利铂耐药CRC细胞(SW480/R)分为对照组、AT-Ⅲ组(40μmol/L AT-Ⅲ处理SW480/R细胞)、IL-6组(25 ng/mL的IL-6重组蛋白处理SW480/R细胞)、AT-Ⅲ+IL-6组(40μmol/L AT-Ⅲ和25 ng/mL的IL-6重组蛋白处理SW480/R细胞)。四甲基偶氮唑盐(MTT)法检测各组SW480/R细胞活性;流式细胞术检测各组SW480/R细胞凋亡情况;Transwell法检测SW480/R细胞迁移、侵袭情况;蛋白免疫印迹法(Western blot)检测凋亡蛋白B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、裂解的半胱氨酸天冬氨酸蛋白酶(cleaved-Caspase-3)及IL-6/STAT3信号通路相关蛋白IL-6、STAT3表达。结果与SW480细胞比较,SW480/R细胞活力、半抑制浓度(IC50)显著升高(P<0.05),筛选出较适浓度25μmol/L奥沙利铂用于后续实验。与对照组比较,AT-Ⅲ组SW480/R细胞A_(570 nm)值、细胞迁移数量以及侵袭数量、Bcl-2、IL-6、STAT3蛋白水平均显著下降(P<0.05),凋亡率、Bax、cleaved-Caspase-3蛋白水平显著上升(P<0.05),IL-6组SW480/R细胞A_(570 nm)值、细胞迁移数量以及侵袭数量、Bcl-2、IL-6、STAT3蛋白水平均显著升高(P<0.05),凋亡率、Bax、cleaved-Caspase-3蛋白水平显著降低(P<0.05);IL-6重组蛋白减弱了AT-Ⅲ对SW480/R细胞的有利影响。结论AT-Ⅲ可能通过抑制IL-6/STAT3信号通路调节CRC细胞的奥沙利铂耐药性。

关键词： HLA   HLA-C*05:37   novel allele   sequence-based typing   Taiwanese  

摘要： One nucleotide substitution in codon 186 of HLA-C*05:01:01:01 results in a novel allele, HLA-C*05:37.

关键词： cerebellum   obesity   Purkinje cell   TNF-alpha   topiramate   volume  

摘要： The rising incidence of obesity underscores the necessity for alternative obesity treatments. Patients commonly prefer medication aiding in weight reduction. Topiramate, an antiepileptic drug, is gaining popularity among obese patients for its weight loss benefits. This study aims to explore Topiramate's impact on the cerebella of obese female rats. In the experiment, 24 female rats (200-250 g) were divided into four groups: non-obese control (NOC), obese control (OC), non-obese topiramate (NOT) and obese topiramate (OT). The non-obese rats were given a standard diet, while the obese rats received a high-fat diet (40% fat). After 9 weeks, topiramate was administered intraperitoneally daily for 6 weeks. Following this, the rats were euthanised, and their cerebella were removed. The volume of the cerebellum and mean numerical density of the molecular neurons, granular neurons and Purkinje cells were estimated using stereological methods, and the link between obesity-caused cerebellum damage and TNF-alpha was assessed through immunohistochemical and bioinformatic techniques. Additionally, histopathological evaluations of the tissues were conducted. The cerebellar volume in the OC group was decreased compared to the NOC group. The topiramate groups exhibited a decrease in molecular or/and granular neuron numbers in the NOT and OT groups. Notably, neurons with dark cytoplasm were observed in the topiramate-treated groups, alongside neuronal degeneration was seen in the obese groups. The connection between TNF-alpha and obesity or obesity-caused cerebellum damage was confirmed through both immunohistochemical and bioinformatics analyses. These findings suggest that topiramate might have a degenerative effect on the cerebellum, especially following obesity.

关键词： xerostomia   mesenchymal stromal cell   interferon gamma  

摘要： Background & Aim The Phase I Dose-Escalation Trial of Mesenchymal Stromal Cells in Patients with Xerostomia After Radiation Therapy for Head and Neck Cancer (NCT05820711) is a first-in-human clinical trial manufactured by the University of Wisconsin Program for Advanced Cell Therapy (UW PACT) in partnership with UW Health hospital. Xerostomia, dry mouth, is a common side effect of radiation for head and neck cancer when cells necessary for saliva production are destroyed. Patients suffering from xerostomia experience decreased quality of life including difficulty eating and drinking. Current treatment options are generally palliative in nature. We have demonstrated the tolerability of bone marrow aspiration, feasibility of MSC expansion, safety and tolerability of injection into the submandibular glands and maximum tolerated dose of IFNγ-stimulated MSCs. Methodology A total of 9 subjects were enrolled in a dose escalation cohort. Patients on Dose Level 0 received one injection of 10 × 10 6 MSCs in each submandibular gland and patients on Dose Level 1 received 20 × 10 6 MSCs. The expansion cohort is currently enrolling up to 12 patients. MSCs are isolated from bone marrow by Ficoll method in a GMP cleanroom facility. Cells are cultured in platelet lysate-based media and incubated at 37°C with 5% CO 2 . After approximately two weeks, expanded cells are stimulated with IFNγ and cryopreserved. Prior to administration, MSCs are thawed and culture-rescued overnight. MSC harvest, drug product formulation, and release testing are performed on the day of administration. Results Due to insufficient quality of starting material, one manufacturing batch was terminated prior to completion. The 10 other successful manufacturing runs were analyzed by flow cytometry to determine the following potency markers: MHC I, PD-L1, MHC II, ICAM and IDO (Figure 1). Results were calculated by comparison of median fluorescent intensity (MFI) between IFNγ-stimulated and unstimulated MSCs and re