Bystanders or not?Microglia and lymphocytes in aging and stroke

As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.

T lymphocyte proportion in Alzheimer’s disease prognosis

Bai et al investigate the predictive value of T lymphocyte proportion in Alzheimer's disease(AD)prognosis.Through a retrospective study involving 62 AD patients,they found that a decrease in T lymphocyte proportion correlated with a poorer prognosis,as indicated by higher modified Rankin scale scores.While the study highlights the potential of T lymphocyte proportion as a prognostic marker,it suggests the need for larger,multicenter studies to enhance generalizability and validity.Additionally,future research could use cognitive exams when evaluating prognosis and delve into immune mechanisms underlying AD progression.Despite limitations inherent in retrospective designs,Bai et al's work contributes to understanding the immune system's role in AD prognosis,paving the way for further exploration in this under-researched area.

Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.

Tumor-infiltrating T-Lymphocyte immunity-related immune tolerance and anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy for advanced hepatocellular carcinoma

Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.

Correlation Study Between T Lymphocyte Subsets and Rheumatoid Arthritis

Objective:To study the effect of Helicobacter pylori infection on rheumatoid arthritis and T-lymphocyte subpopulations in patients with rheumatoid arthritis and to provide a new method for the treatment of rheumatoid arthritis by removing Helicobacter pylori from patients.Methods:60 patients with rheumatoid arthritis admitted to the hospital from May 2022 to May 2023 were selected for the study,and all patients underwent a 13-carbon urea breath test to detect gastric H.pylori and the test results showed that 20 cases were negative and 40 cases were positive.The 40 positive patients were divided into the treatment group(n=20)and non-treatment group(n=20)by random number table method and the treatment group was given anti-Helicobacter pylori treatment,and the non-treatment group was given maintenance rheumatoid basic treatment,comparing the anti-cyclic citrulline peptide(CCP),DS28 score,peripheral blood T-lymphocyte subsets(CD4^(+)T-lymphocytes,CD8^(+)T-lymphocytes,CD4^(+)/CD8^(+)ratio)before and after the treatment of patients by 13-carbon urea respiration test(pylori-negative group,20 patients)and those who were positive for the treatment of H pylori(pylori-positive group,40 patients).Besides,the correlation of peripheral blood T-lymphocyte subsets and disease activity between treatment and non-treatment groups in the pylori-positive group was identified together with the correlation of DS28 scores,TNF-αlevels,sedimentation and immunoglobulin,lymphocyte subsets in the pylori-positive treatment group and positive non-treatment group as well as the level of globulin,lymphocyte subsets,and peripheral blood lymphocytes before and after treatment.Results:Before treatment,CCP,DS28 score,CD8^(+)T lymphocyte level of the pylori-negative group were lower than that of the positive group,and CD4^(+)T lymphocyte and CD4^(+)/CD8^(+)ratio were higher than that of the positive group(P<0.05);after treatment,the indexes of the pylori-positive group improved,and there was no significant difference in the comparison of the indexes with those of the pylori-negative group(P>0.05);the positive treatment group had a DS28(3.19±1.02)points,positive non-treatment group DS28(5.36±1.85)points,non-treatment group DS28 score and CD4^(+)T lymphocytes,CD4^(+)/CD8^(+)negative correlation with CD8^(+)T lymphocytes showed a positive correlation(P<0.05);before the treatment,pylori-positive treatment group and non-treatment group DS28 scores,TNF-αlevels,peripheral blood T lymphocyte subpopulation levels were not significantly different(P>0.05);after treatment,DS28 score,TNF-αlevel,CD8^(+)T of the treatment group were lower than those of the non-treatment group,and CD4^(+)T lymphocytes and CD4^(+)/CD8^(+)ratio were higher than those of the non-treatment group(P<0.05).Conclusion:H.pylori affects the level of T lymphocyte subsets in patients with rheumatoid arthritis,and there is a certain correlation between the two.Removal of H.pylori can improve the level of T lymphocyte subsets,which is important for the treatment of patients with rheumatoid arthritis.

Analysis of the Peripheral Blood Helper T-Cell 17- Cell Level and Monocyte/Lymphocyte Ratio for Colorectal Cancer Prognosis Prediction

Objective: To investigate the value of peripheral blood helper T cell 17 cell level and monocyte/lymphocyte ratio to predict the prognosis of colorectal cancer patients. Methods: 74 colorectal cancer patients who attended Hospital 960 from January 2021 to January 2022 were retrospectively analyzed. Clinical data of the patients were collected, including gender, age, and histologic type. Immunohistochemical indexes such as Th17 cell level and monocyte/ lymphocyte ratio in the peripheral blood of patients were also collected. The prognosis of patients after treatment, as well as peripheral blood Th17 and MLR levels, were observed and analyzed. Results: After follow-up after treatment, in the final 74 patients, the prognosis was good in 32 patients, accounting for 43.24%, and the prognosis was bad in 42 patients, accounting for 56.76%. There were no significant differences between the average age and tumor diameters of the good prognosis and poor prognosis groups (P > 0.05). However, the TNM staging, intervention taken, differentiation degree, presence of distant metastasis, presence of lymph node metastasis, Th17 level, and MLR level are significantly different between the two groups (P < 0.05). Conclusion: Peripheral blood Th17 and MLR have predictive value for the prognosis of colorectal cancer patients, and high levels of peripheral blood Th17 and MLR imply poor prognosis. The detection of peripheral blood Th17 and MLR levels is simple and convenient and can be used as indicators to provide a reference for the prognostic assessment of colorectal cancer patients.

黄芪对甲状腺功能正常的桥本甲状腺炎患者外周血T淋巴细胞亚群表达的影响

目的·探讨黄芪对甲状腺功能正常的桥本甲状腺炎患者T淋巴细胞亚群及细胞因子表达的影响。方法·选择2020年1月—12月在上海市第六人民医院金山分院接受治疗且资料完整的甲状腺功能正常的桥本甲状腺炎患者120例,采用随机数字表将患者为干预组及对照组,每组各60例。对照组治疗方案为碘适宜状态饮食,干预组在对照组治疗方案基础上联合黄芪药液口服(150 mL/次,2次/d)治疗。连续治疗6个月,比较2组治疗前后外周血清T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)),细胞因子[包括白细胞介素2(interleukin-2,IL-2)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、IL-6、IL-10],超敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP),红细胞沉降率(erythrocyte sedimentation rate,ESR),以及甲状腺功能及自身抗体、肝肾功能等指标的变化。观察黄芪治疗期间不良反应。应用多因素线性回归分析甲状腺过氧化物酶抗体(thyroid peroxidase antibody,TPOAb)变化幅度的影响因素。结果·最终纳入118例患者,每组各59例。治疗6个月后,干预组CD4^(+)T细胞比例,CD4^(+)/CD8^(+)比值,IL-2、TNF-α、IL-6、IL-10、hs-CRP、ESR、TPOAb和甲状腺球蛋白抗体(thyroglobulin antibody,TGAb)水平均较治疗前及其同期对照组显著改善,差异均有统计学意义(均P<0.05)。对照组治疗后上述指标与治疗前比较,差异均无统计学意义(P>0.05)。治疗后干预组未见严重不良反应。多因素线性回归分析结果显示,应用黄芪、CD4^(+)T细胞、CD4^(+)/CD8^(+)比值升高幅度及hs-CRP下降幅度均是TPOAb下降幅度的独立影响因素(β=−0.393,P=0.029;β=−0.513,P=0.010;β=−0.351,P=0.035;β=0.434,P=0.023)。结论·黄芪可改善甲状腺功能正常的桥本甲状腺炎患者CD4^(+)T细胞、IL-2、TNF-α、IL-6、IL-10水平及CD4^(+)/CD8^(+)比值,且安全性佳。

Th1/Th2细胞因子谱在不同感染程度病人水平变化及其对脓毒症病人预后的评估价值

目的:探讨外周血1型或2型辅助型T淋巴细胞(Th1/Th2)细胞因子谱对不同感染程度病人的临床应用及其对脓毒症病人短期预后的评估价值。方法:选取78例脓毒症病人(脓毒症组),64例局部感染病人(普通感染组)以及42例非感染病人(非感染组),收集3组病人的临床资料,比较入科后各组病人细胞因子浓度,使用Spearman等级相关分析其与感染严重程度的关系;依据随访结果,将脓毒症病人分成存活组(31例)和死亡组(47例),比较2组Th1/Th2细胞因子谱的差异,采用logistic回归分析筛选影响脓毒症病人预后的独立危险因素,对脓毒症病人28 d生存率进行亚组分析,并绘制Kaplan-Meier生存曲线,分析病人28 d累积生存情况。结果:随着感染严重程度的增加,IL-4水平逐渐降低,IL-6、IL-8及IL-10水平逐渐升高;普通感染组和脓毒症组病人IL-5水平低于非感染组(P<0.05~P<0.01)。Spearman等级相关分析显示,IL-4与感染严重程度呈负相关(P<0.01);IL-6、IL-8、IL-10与感染严重程度呈显著正相关(P<0.01)。随访28 d,脓毒症病人死亡率60.26%。死亡组病人IL-5、IL-6、IL-8、IL-10浓度均大于存活组(P<0.05~P<0.01);logistic回归分析显示,IL-5和IL-8是脓毒症病人28 d死亡的独立危险因素(P<0.05);根据最佳截断值对IL-5、IL-8进行亚分组,结果提示IL-5、IL-8升高,增加了脓毒症病人28 d死亡的风险。Kaplan-Meier生存分析进一步证实了IL-5≥0.55 pg/mL组病人的28 d累积生存率明显低于IL-5<0.55 pg/mL组病人(P<0.05);IL-8≥54.61 pg/mL组病人的28 d累积生存率明显低于IL-8<54.61 pg/mL组病人(P<0.01)。结论:Th1/Th2细胞因子谱与感染严重程度呈现出显著的相关关系,且IL-5及IL-8对脓毒症病人28 d生存情况具有良好的预测价值。

Experimental Study on Double Blocking of T Lymphocytes Apoptosis Induced by Fas/FasL

Objective： To block the apoptosis of T lymphocytes induced by Fas/FasL in order to establish a method of the large-scale preparation of large amounts of tumor-specific cytoxic T-lymphocytes （CTL）. Methods： Liver cancer cells and tumor infiltrating lymphocytes （TIL） were isolated from FasL positive fresh specimens, and co-cultured. Specific CTL were activated and prepared in the presence of the co-stimulation of monoclonal antibody CD28. Then the blocking and activation of apoptosis of T lymphocytes was activated by soluble Fas receptor, which was detected by cytometry and DNA ladder test simultaneously. The apoptosis-blocking effect was compared with the control group. Furthermore, the changes of T cell proliferation and killing activity were detected by the method of ^3H thymidine incorporation and ^51Cr release test. Results： There was a significant increase in apoptosis rate in unblocking group compared with blocking group and quiescent group, with the unblocking group of 47.82%±0.13%, quiescent group of 3.76%±0.25%, and the blocking group of 8.22%±0.26% respectively （P〈0.01）. T cell-ladder appeared in unblocking group by DNA ladder test. Both the killing ability and proliferation rate of T cells were significantly increased after blocking. There was significant difference among blocking group, unblocking group and quiescent group （P〈0.01）. Conclusion： With this method we obtained large amounts of tumor-specific T lymphocytes, which was able to kill liver cancer cells effectively.

不同剂量异烟肼治疗肺结核的临床效果及对患者肺功能和T淋巴细胞亚群的影响

目的 探讨不同剂量异烟肼治疗肺结核的临床效果及对患者肺功能、T淋巴细胞亚群的影响。方法 选取2020年6月至2022年6月河北省胸科医院收治的肺结核患者90例为研究对象,按照随机数字表法分为对照组和观察组,各45例。对照组在常规抗结核药物基础上予0.3 g/d异烟肼治疗,观察组在常规抗结核药物基础上予0.5 g/d异烟肼治疗,2组疗程均为6个月。比较2组临床疗效,评估患者肺功能及T淋巴细胞亚群变化情况。结果 观察组总有效率高于对照组(P<0.05)。治疗后,2组最大呼气流量、第1秒用力呼气容积均高于治疗前,且观察组均高于对照组[(7.8±1.4)L/s比(6.3±1.2)L/s、(1.48±0.28)L比(1.15±0.23)L](均P<0.05)。治疗后,2组血清CD+3、CD+4、CD+4/CD+8比值均高于治疗前,且观察组均高于对照组,CD+8均低于治疗前,且观察组低于对照组(均P<0.05)。2组不良反应发生率比较差异无统计学意义(P>0.05)。结论 不同剂量异烟肼治疗肺结核的临床效果不同,增加异烟肼剂量至0.5 g/d能够提升疗效,促进肺结核患者肺功能改善,提高免疫功能,且安全性较好。

外周血CD8+CD28-CD57+T淋巴细胞对老年脓毒症患者预后的预测价值

目的 探讨外周血CD8+CD28-CD57+T淋巴细胞对老年脓毒症患者预后的预测价值。方法 采用回顾性队列研究,选取2015年2月—2016年8月西安交通大学第二附属医院重症医学科住院的年龄≥60岁的脓毒症患者75例,依据ICU结局分为存活组(n=54)及死亡组(n=21)。收集患者一般资料,诊断脓毒症当天进行急性生理和慢性健康评分Ⅱ(APACHEⅡ)评分及序贯器官衰竭(SOFA)评分,检测外周血液标本TNF-a、IL-10及CD8+CD28-CD57+T淋巴细胞。结果 死亡组平均年龄大于存活组(P<0.05)。死亡组较存活组有更高的APACHEⅡ评分、SOFA评分及休克比例,差异均有统计学意义(P<0.05)。死亡组外周血CD8+CD28-CD57+T淋巴细胞、TNF-a、IL-10较存活组更高(P<0.05)。存活组的耐药菌感染比例低于死亡组,但差异无统计学意义(P>0.05)。无论单因素还是对一系列协变量进行调整的多因素Logistic回归分析均显示,较高的外周血CD8+CD28-CD57+T淋巴细胞比例与高的ICU死亡率相关(OR, 1.21;95%CI, 1.10~1.33)(OR, 1.30;95%CI, 1.07~1.58);APACHEⅡ评分预后预测的AUC为0.78(95%CI 0.67~0.90),将最适诊断界点22.5分作为预测死亡可能的临界点,敏感性和特异性分别为61.9%和75.2%。SOFA评分预后预测的AUC为0.80(95%CI,0.68~0.92),将最适诊断界点9.5分作为预测死亡可能的临界点,敏感性和特异性分别为71.4%和77.8%。外周血CD8+CD28-CD57+T淋巴细胞预后预测的AUC为0.91(95%CI,0.83~0.99),将最适诊断界点60.2%作为预测死亡可能的临界点,敏感性和特异性分别为81.0%和92.6%。结论 老年脓毒症患者外周血高CD8+CD28-CD57+T淋巴细胞比例与ICU死亡率增加相关,一定程度上可用于评估此类人群的病情严重程度及预测预后。

白细胞介素-38对乳腺癌患者CD8^(+)T淋巴细胞功能的影响

目的探讨白细胞介素-38(IL-38)在乳腺癌患者中的表达及其对CD8^(+)T细胞功能的调控作用。方法纳入2020年7月—2022年9月在新乡医学院第一附属医院就诊的44例乳腺癌患者、25例乳腺良性肿瘤患者和20例对照者。分离所有受试者的血浆和外周血单个核细胞,分离乳腺癌患者肿瘤组织中的肿瘤浸润淋巴细胞,纯化CD8^(+)T细胞。应用酶联免疫吸附试验(ELISA)检测血浆IL-38蛋白水平,应用实时定量PCR检测组织IL-38 mRNA相对表达量。使用重组人IL-38刺激乳腺癌患者外周血和肿瘤组织分离的CD8^(+)T细胞,建立CD8^(+)T细胞与乳腺癌细胞系MCF-7的共培养系统,通过测定乳酸脱氢酶水平计算靶细胞死亡比例,ELISA法检测培养上清中穿孔素、颗粒酶B、干扰素-γ和肿瘤坏死因子-α(TNF-α)水平,流式细胞术检测CD8^(+)T细胞的免疫检查点分子表达。结果乳腺癌患者血浆IL-38水平(74.23±19.88 pg/mL)高于乳腺良性肿瘤患者(62.87±16.27 pg/mL,P=0.018)和对照者(61.77±12.75 pg/mL,P=0.013)。乳腺癌患者肿瘤组织中IL-38 mRNA相对表达量显著高于癌旁组织(1.57±0.22 vs.1.00±0.18,P<0.001)。外周血和肿瘤浸润CD8^(+)T细胞诱导靶细胞死亡比例、穿孔素和颗粒酶B分泌在直接接触共培养组中的水平高于间接接触共培养组(P<0.05),但干扰素-γ和TNF-α分泌水平在直接接触共培养组和间接接触共培养组之间的差异无统计学意义(P>0.05)。在直接接触共培养组内,靶细胞死亡比例、穿孔素、颗粒酶B、干扰素-γ、TNF-α在IL-38刺激组中的水平低于无刺激组(P<0.05)。在间接接触共培养组内,靶细胞死亡比例、干扰素-γ、TNF-α在IL-38刺激组中的水平亦低于无刺激组(P<0.05),但穿孔素和颗粒酶B水平在间接接触共培养组内的IL-38刺激组和无刺激组之间的差异无统计学意义(P>0.05)。CD8^(+)T细胞中免疫检查点分子表达水平在无刺激组和IL-38刺激组之间的差异均无统计学意义(P>0.05)。结论乳腺癌患者中高表达的IL-38可能参与诱导CD8^(+)T细胞功能衰竭。

(1-3)-β-D葡聚糖联合降钙素原、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究

目的探讨(1-3)-β-D葡聚糖联合降钙素原(procalcitonin,PCT)、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究。方法回顾性选取我院2020年1月—2022年6月住院的120例艾滋病患者为研究对象。依据实验室结果,将其分为马尔尼菲篮状菌感染确诊组(血或组织液培育养出马尔尼菲篮状菌),简称A组(62例),及马尔尼菲篮状菌感染临床诊断组[根据临床症状、体征、血常规及(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞多指标诊断],简称B组(58例)。检测患者(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞的表达水平,采用受试者工作特征(receiver-operating characteristic,ROC)曲线下面积(area under the curve,AUC)评估上述指标联合检测对艾滋病患者感染马尔尼菲篮状菌的诊断效能。结果A组的(1-3)-β-D葡聚糖和PCT水平均高于B组,CD4^(+)T淋巴细胞个数低于B组(P<0.05);(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞联合检测的AUC为0.933,(1-3)-β-D葡聚糖单独检测的AUC是0.812,PCT单独检测的AUC为0.883,CD4^(+)T淋巴细胞单独检测的AUC是0.810,(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的AUC皆优于三项单独检测,表明(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的诊断价值皆优于单一指标诊断,且联合检测的特异度、约登指数分别为92.43%和0.580,均高于三项单独检测。结论(1-3)-β-D葡聚糖联合PCT和CD4^(+)T淋巴细胞多指标对艾滋病马尔尼菲篮状菌感染具有非常高的临床诊断价值,能够帮助医生分析出高危风险患者,及时制定治疗方案,同时也承担预后效果的判断依据,对治疗艾滋病马尔尼菲篮状菌感染具有非常重要的研究价值。

PD-1检测联合T淋巴细胞亚群分析对脓毒症患者预后评估的临床研究

目的 检测PD-1表达量联合T淋巴细胞亚群和部分细胞因子分析,评估脓毒症患者的免疫状态及预后。方法 选取符合2016年美国重症医学会/欧洲重症医学会(SCCM/ESICM)脓毒症及脓毒症休克定义Sepsis-3诊断标准,并且符合入组条件的68例患者,根据病情分为脓毒症组和脓毒症休克组,其中脓毒症组30例,脓毒症休克组38例,记录患者一般临床资料,通过ELISA法检测PD-1,抽取外周血送检,检查项目包括血常规、淋巴细胞亚群测定(T辅助淋巴细胞CD4^(+)与T抑制淋巴细胞CD8^(+))、降钙素原、白介素-6、超敏C反应蛋白。结果 2组患者一般资料比较差异无统计学意义(P>0.05),但2组患者急性生理与慢性健康评分和序贯器官衰竭的评分比较差异有统计学意义(P<0.05);脓毒症休克组的PD-1较脓毒症组表达水平高,差异有统计学意义(P<0.05),但淋巴细胞计数、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)较脓毒症组低(P<0.05);2组患者的感染指标降钙素原及炎症指标白介素-6和超敏C反应蛋白比较差异有统计学意义(P<0.05),脓毒症休克组较脓毒症组检测值更高(P<0.05);总T淋巴细胞相比,2组患者差异无统计学意义(P>0.05);脓毒症休克组患者的住ICU时间、14天病死率、28天病死率均较脓毒症组明显升高(P<0.05);PD-1表达水平、CD4^(+)T细胞是影响脓毒症患者死亡的独立危险因素。结论 脓毒症和脓毒症休克患者早期即出现免疫抑制,脓毒症休克组患者免疫抑制更严重,预后更差。

Periostin、Notch1、维生素D与自身免疫性甲状腺炎淋巴细胞浸润程度、Treg/Th17的相关性研究

目的探讨骨外膜素(Periostin)、Notch跨膜受体-1(Notch1)m RNA、维生素D(VitD)与自身免疫性甲状腺炎(AIT)淋巴细胞浸润程度、调节性T细胞/辅助性T细胞17(Treg/Th17)的相关性。方法选取2021年7月至2023年12月郑州大学第一附属医院收治的92例AIT患者纳入AIT组,另选取同期50例无甲状腺疾病的健康人群纳入对照组。比较两组受检者的淋巴细胞浸润程度及抗体水平,采用Spearman、Pearson相关系数分析淋巴细胞浸润程度、Treg/Th17与甲状腺功能、抗体水平的相关性,比较两组受检者的Periostin、Notch1 m RNA、VitD及Treg/Th17,采用Pearson相关系数分析Periostin、Notch1 mRNA、VitD与淋巴细胞浸润程度及Treg/Th17的相关性。结果AIT组患者的CD3^(+)、CD3^(+)CD4^(+)、CD4^(+)CD25^(+)CD127^(-)、TgAb、TPOAb、TRAb水平及甲亢/亚临床甲亢、甲减/亚临床甲减患者占比明显高于对照组,差异均有统计学意义(P<0.05);Pearson相关系数分析结果显示,CD3^(+)(r=0.579、0.602、0.563)、CD3^(+)CD4^(+)(r=0.612、0.637、0.606)、CD~4+CD25^(+)CD127^(-)(r=0.655、0.643、0.687)与TgAb、TPOAb、TRAb呈正相关(P<0.05);AIT组患者的Periostin、Notch1 m RNA分别为(4.27±1.40)μg/L、1.73±0.56,明显高于对照组的(2.86±0.49)μg/L、1.02±0.14,VitD、Treg/Th17分别为(17.82±5.09)ng/mL、2.82±0.97,明显低于对照组的(22.30±3.76)ng/mL、12.36±2.03,差异均有统计学意义(P<0.05);Pearson相关系数分析结果显示,Periostin(r=0.792、0.811、0.737)、Notch1 mRNA(r=0.812、0.775、0.792)与CD3^(+)、CD3^(+)CD4^(+)、CD4^(+)CD25+CD127-呈正相关(P<0.05),VitD(r=-0.687、-0.753、-0.799)与之呈负相关(P<0.05),且Periostin(r=-0.823)、Notch1 m RNA(r=-0.772)与Treg/Th17呈负相关(P<0.05),VitD(r=0.745)与之呈正相关(P<0.05)。结论Periostin、Notch1 mRNA在AIT患者血清中表达上调,VitD表达下调,各指标与AIT淋巴细胞浸润程度及Treg/Th17均具有一定相关性,可为临床判断病情提供参考,并对后续临床治疗具有一定指导价值。

楮芍凉血汤加减治疗寻常型银屑病的效果及对免疫功能、辅助性T淋巴细胞17相关因子的影响

目的观察楮芍凉血汤加减治疗寻常型银屑病的临床疗效和对免疫功能、辅助性T淋巴细胞17(Th17)相关因子的影响。方法选取2020年2月至2021年12月在本院接受治疗64例进行期PV患者,采用随机数字表法将患者分为对照组和观察组各32例。对照组患者接受常规西药治疗,观察组接受楮芍凉血汤加减治疗,治疗周期为6周。所有研究对象均检测外周血T淋巴细胞亚群、分离单个核细胞(PBMC)情况,分析PBMC中Thl7细胞相关因子白细胞介素17(IL-17)、IL-22、维甲酸相关孤儿受体γ(ROR-γ)mRNA、干扰素γ(INF-γ)mRNA相对表达量,并对比临床总疗效。结果治疗6周后,观察组总有效治疗30例(93.75%),对照组总有效治疗24例(75.00%),2组总疗效差异具有统计学意义(P<0.05)。治疗6周后,2组患者T淋巴细胞指标CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平均升高,CD8^(+)及Th17相关因子IL-17、IL-22、RORC mRNA、INF-γmRNA相对表达量均降低,组内不同时点和组间同时点比较差异均具有统计学意义(P<0.05)。结论楮芍凉血汤可有效治疗寻常型银屑病,且作用机制与T淋巴细胞亚群分布及Thl7细胞相关因子有关,可以提高机体免疫功能,以此减少不良症状,提高临床疗效。

GPC3刺激对DC-CTL靶向杀伤肝细胞癌的影响

目的本研究将磷脂酰肌醇蛋白聚糖3(GPC3)作为肝细胞癌(LIHC)的靶分子,研究其在激活树突状细胞(DC)-细胞毒性T淋巴细胞(CTL)和增强肿瘤杀伤能力中的作用。方法为更系统、更全面地鉴定GPC3在多种恶性肿瘤中的意义,对GPC3在泛癌中的基因表达水平进行评估,并从LIHC与临床特征的相关性角度进一步研究GPC3。分别通过生存预后分析(Kaplan-Meier图)和受试者工作特征(ROC)曲线分析评估GPC3在LIHC中的预后价值和诊断价值。重组GPC3蛋白用于刺激DC,然后与CTL细胞共培养,经酶联免疫吸附试验(ELISA)分析以检测DC-CTL细胞中细胞因子的表达。通过CCK8测定法测定在Huh7细胞上用GPC3培养刺激的DC-CTL细胞的细胞毒性。结果GPC3的基因表达水平在大多数癌症中显著不同,并且在LIHC中与正常组织相比更高。GPC3在血清中与年龄和甲胎蛋白(AFP)水平相关(均P<0.001),而与LIHC的TNM分期、病理分期和组织学分级无关。ROC曲线分析表明,GPC3可用于准确预测LIHC。GPC3的表达水平与LIHC的总生存期无关。联合治疗显著上调了IFN-γ和TNF-α的分泌。用150 ng/ml和200 ng/ml GPC3刺激的DC-CTL细胞杀死Huh7细胞的能力强于不使用GPC3刺激的DC-CTL细胞(均P<0.05)。结论用GPC3刺激DC-CTL细胞通过促进细胞毒性在体外抑制肿瘤生长。GPC3可能是一种潜在的肿瘤标志物,可用于提高DC-CTL细胞的治疗效率。

T淋巴细胞、炎症细胞因子与卵巢子宫内膜异位症的相关性及诊断价值

目的探讨外周血中T淋巴细胞、炎症细胞因子与卵巢子宫内膜异位症(OMs)的相关性及诊断价值。方法选取2020年10月—2022年6月我院收治行开腹或腹腔镜手术经病理确诊OMs患者72例为观察组,根据修正子宫内膜异位症分期(r-AFS)分为I~II期37例,III~IV期35例,另选取同期术后诊断为单纯性卵巢囊肿或良性畸胎瘤的患者72例为对照组。利用流式细胞检测法检测外周血中T淋巴细胞(CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、炎症细胞因子(IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ和TNF-α含量),收集相关临床资料进行单因素及Logistic多因素回归分析讨论OMs影响因素,I~II、III~IV期EMs患者中比较外周血独立影响指标CD4^(+)、TNF-α表达差异。ROC曲线评估CD4^(+)、CD8^(+)和TNF-α3项指标单独及联合对OMs的诊断效能。结果CD8^(+)、IL-2、IL6、IL-10、TNF-α、月经初潮年龄<13岁,经期天数>6天、痛经、人流手术或宫腔操作史和剖宫产史为OMs危险因素,CD4^(+)及CD4^(+)/CD8^(+)为OMs保护因素;CD8^(+)、TNF-α、经期天数>6天、痛经和人流手术或宫腔操作史为OMs独立危险因素,CD4^(+)为OMs独立保护因素;I~II、III~IV期OMs CD4^(+)、CD8^(+)和TNF-α差异有统计学意义(P<0.05);CD4^(+)、CD8^(+)与TNF-α联合检测可提高OMs诊断效能。结论外周血T淋巴细胞亚群、炎症细胞因子在OMs发生中发挥着一定作用,CD4^(+)、CD8^(+)和TNF-α参与疾病进展且3者联合检测在OMs诊断方面可能具有较高应用价值。

温针灸四关穴对中晚期宫颈癌癌性疼痛患者T淋巴细胞亚群调节作用研究

目的 探讨温针灸四关穴治疗气滞血瘀证中晚期宫颈癌癌性疼痛的疗效及对T淋巴细胞亚群的调节作用。方法 选定沧州市中心医院2021年10月至2023年10月就诊的84例气滞血瘀证中晚期宫颈癌癌性疼痛患者,按随机数字表法分为温针灸组、西药组,各42例。西药组给予三级止痛治疗,温针灸组在西药组基础上给予温针灸四关穴治疗,比较两组患者临床疗效、卡氏评分量表(Karnofsky,KPS)评分、视觉模拟评分量表(visual analogue scale,VAS)评分、一般自我效能感量表(general self-efficacy scale-schwarzer,GSES)评分、疼痛应激指标[5-羟色胺(5-hydroxytryptamine,5-HT)、β内啡肽(β-endorphin,β-EP)、P物质(substance P,SP)]、T淋巴细胞亚群指标、生活质量综合评定问卷量表(generic quality of life inventory-74,GQOLI-74)评分。结果 温针灸组总有效率(95.24%)高于西药组(76.19%)(P<0.05)。两组治疗后KPS评分、GSES评分、GQOLI-74评分、血清β-EP水平、CD3+、CD4+、CD4+/CD8+均较治疗前更高(P<0.05),两组治疗后VAS评分、血清5-HT水平、SP水平、CD8+均较治疗前更低(P<0.05)。温针灸组治疗后KPS评分、GSES评分、GQOLI-74评分、血清β-EP水平、CD3+、CD4+、CD4+/CD8+均较西药组更高(P<0.05,P<0.01),VAS评分、血清5-HT水平、SP水平、CD8+均较西药组更低(P<0.01)。结论 在三级止痛的基础上联合温针灸四关穴可有效缓解气滞血瘀证中晚期宫颈癌癌性疼痛患者疼痛症状,改善身体状况、免疫功能,调节疼痛应激物质释放,提高生存质量,效果显著。

慢性淋巴细胞白血病患者Tfh细胞及其亚群水平的变化和临床意义研究

目的 初步探讨Tfh细胞及其亚群在慢性淋巴细胞白血病(CLL)患者中的变化特点,并分析其临床意义。方法 选取2021年1月-2023年9月新疆医科大学第一附属医院收治的70例初诊CLL患者为CLL组,另选取该院体检健康人员50例为对照组。应用流式细胞术检测Tfh、Tfh1、Tfh2、Tfh17细胞比例,并分析Tfh细胞PD-1和ICOS的表达水平;实时荧光定量聚合酶链反应检测BCL-6、Blimp-1、IL-21基因表达;Western blotting检测BCL-6、Blimp-1蛋白表达;酶联免疫吸附试验检测血清细胞因子IL-21的水平。结果 CLL组外周血Tfh、Tfh1、PD-1+Tfh、ICOS+Tfh和PD-1+ICOS+Tfh细胞比例较对照组增加(P <0.05),亚群比值Tfh1/(Tfh2+Tfh17)比值也升高(P <0.05)。与对照组相比,CLL组BCL-6、Blimp-1、IL-21基因和蛋白相对表达量均升高(P <0.05),BCL-6/Blimp-1比值也升高(P <0.05)。Pearson相关性分析结果显示,BCL-6基因和蛋白表达、BCL-6/Blimp-1比值、IL-21水平与Tfh、Tfh1/(Tfh2+Tfh17)均呈正相关(P <0.05)。临床指标分析结果显示,随着IPI评分分组越靠后,Tfh细胞比例、Tfh1/(Tfh2+Tfh17)比值越高,并且与骨髓中B淋巴细胞呈正相关(P <0.05),与免疫球蛋白呈负相关(P <0.05)。结论 CLL患者外周血Tfh细胞参与疾病发病机制,并且Tfh细胞亚群存在偏向于Tfh1细胞的失衡,Tfh细胞的异常分化可能参与CLL的发病和体液免疫紊乱机制。