纳武利尤单抗联合DP方案超选择性支气管动脉栓塞灌注治疗晚期非小细胞肺癌的临床研究

目的 探讨纳武利尤单抗联合DP方案超选择性支气管动脉栓塞灌注治疗晚期非小细胞肺癌（NSCLC）患者的临床疗效。方法 选取2018年12月—2020年12月在成都医学院第一附属医院呼吸与危重症医学科收治的晚期NSCLC患者187例,将患者按照治疗方法分为对照组（92例）和观察组（95例）。对照组使用超选择支气管动脉栓塞灌注化疗治疗,输注2 000 mL 0.9%氯化钠溶液或糖盐水水化,0.9%氯化钠溶液100 mL分别稀释多西他赛注射液及顺铂注射液,37.5 mg/m²,先缓慢注入稀释后多西他赛,间隔30 min再注入稀释后顺铂。灌注化疗间隔3周,共4个疗程。观察组患者在对照组的基础上静脉输注纳武利尤单抗注射液,3 mg/kg,每2周用药1次,直至患者不耐受或病情进展。观察两组患者临床疗效,比较治疗前后Karnofsky功能状态评分（KPS）、肿瘤标志物和T淋巴细胞亚群变化以及化疗期间不良反应情况。结果 治疗后,观察组的总有效率为65.26%,显著高于对照组的40.22%,两组比较差异具有统计学意义（P<0.05）。治疗后,两组患者KPS评分较化疗前均增加（P<0.05）,且观察组KPS评分增加程度明显较对照组大（P<0.05）。治疗后,两组患者血清癌抗原125（CA125）、癌胚抗原（CEA）、CYFRA21-1水平较化疗前降低（P<0.05）;且观察组肿瘤标志物水平显著低于对照组（P<0.05）。治疗后,对照组患者CD3⁺、CD4⁺和CD4⁺/CD8⁺均显著降低（P<0.05）,而观察组患者显著升高（P<0.05）;观察组免疫功能指标显著优于对照组（P<0.05）。两组患者化疗期间不良反应发生率比较差异无统计学意义。结论 纳武利尤单抗联合DP方案超选择性支气管动脉栓塞灌注治疗对晚期NSCLC患者近期疗效良好,且可以改善患者生存资料和免疫功能,降低肿瘤标志物水平,不良反应轻,患者耐受性较好。     

他克莫司治疗特应性皮炎的效果及对患者免疫功能的影响

目的探讨他克莫司治疗特应性皮炎的临床效果及对患者免疫功能的影响。方法选取辽宁省某医院2016年12月-2019年3月收治的120例特应性皮炎患者为研究对象,采用随机数字表法分为对照组和观察组,每组60例。对照组患者给予盐酸左西替利嗪口服液治疗,观察组患者在对照组基础上给予0.03%他克莫司软膏治疗,比较2组患者临床疗效、不良反应发生情况,治疗前后T淋巴细胞亚群中CD4+、CD8+,自然杀伤(NK)细胞水平及CD4+/CD8+水平。结果治疗前,2组患者血清CD4+,CD8+,NK细胞水平及CD4+/CD8+水平比较,差异无统计学意义(P>0.05);治疗后,2组患者血清CD4+,CD4+/CD8+水平均高于治疗前,NK细胞水平低于治疗前,且观察组患者CD4+细胞水平及CD4+/CD8+水平均高于对照组,NK细胞水平低于对照组,差异均有统计学意义(P<0.05)。观察组患者治疗总有效率为96.67%(58/60),高于对照组的83.33%(50/60),差异有统计学意义(P<0.05)。2组患者治疗期间均无明显不良反应发生,差异无统计学意义(P>0.05)。结论他克莫司治疗特应性皮炎效果较好,可有效改善患者免疫功能,安全性较好,值得推广。     

术前淋巴细胞与C反应蛋白比值在预测胆囊癌术后复发中的应用及其临床价值

背景与目的：系统性炎症与大多数恶性肿瘤的发生发展密切相关,炎症相关评分的研究为改善癌症患者风险分层和患者预后提供了有效的预测信息。但目前尚缺乏关于炎症评分与胆囊癌（GBC）患者术后复发风险关系的研究。因此,本研究探讨术前淋巴细胞计数与C反应蛋白（CRP）比值（LCR）与胆囊癌患者术后复发的关系,并建立预测GBC术后复发风险的列线图模型。方法：回顾性分析中国人民解放军联勤保障部队第九〇〇医院2009年5月—2021年12月接受手术治疗的103例GBC患者的临床资料,绘制LCR预测术后复发的受试者工作特征曲线（ROC）,确定最佳临床临界值。根据临界值将GBC患者分为高LCR组和低LCR组,分析两组患者临床病理特征的差异及影响患者术后复发的危险因素,并根据危险因素的回归系数绘制相应的GBC患者术后复发的列线图预测模型,并通过校准曲线及一致性曲线进行验证。Kaplan-Meier法绘制生存曲线,并用Log-rank检验比较两组患者的总生存时间（OS）和无复发生存时间（RFS）的差异。结果：术前LCR预测GBC患者术后复发的ROC曲线下面积为0.681 (95%CI=0.560～0.802,P&...     

脑外伤合并不同程度获得性肺炎患者外周血T细胞亚群表达水平观察

 目的 观察脑外伤(traumatic brain injury,TBI)合并不同程度获得性肺炎(hospital acquired pneumonia ,HAP)患者外周血T细胞亚群表达水平。方法 连续选择2013-01至2015-06神经外科住院的合并HAP患者31例,另选择同期住院确诊TBI但无HAP患者19例(TBI组),另有同期参加我院体检结论健康者为对照组(23例)。3组对象接受了外周血T细胞亚群(CD3⁺、CD4⁺、CD8⁺、CD4⁺/ CD8⁺)指标检测。结果 TBI合并HAP患者外周血CD3⁺、CD4⁺表达水平[(52.71±5.24)%和(29.30±3.15)%]及CD4⁺/CD8⁺(0.89±0.17)比值明显低于TBI组及对照组(P均<0.05)。同时,TBI合并重度HAP患者外周血CD3⁺、CD4⁺表达水平[(49.64±4.81)%和(28.76±3.04)%]以及CD4⁺/CD8⁺(0.85±0.13)比值明显低于TBI合并轻度HAP患者(P均<0.05)。结论 TBI合并HAP患者存在明确的外周血T细胞亚群表达异常,且随病情加重趋于显著。     

托里消毒散对手术前后肝癌患者细胞免疫功能的影响

目的探讨托里消毒散对调节肝癌患者细胞免疫功能的作用.方法选择可手术切除的肝癌患者38例,随机分两组.Ⅰ组20例,在肝癌切除术前和术后第7天服用中药托里消毒散,服药前后检测T淋巴细胞亚群(CD3、CD4、CD8)和肝功能[谷草转氨酶(AST)、谷丙转氨酶(ALT)、直接胆红素(DBIL)、间接胆红素(IBIL)];Ⅱ组18例,不服用托里消毒散,在与Ⅰ组相应的时期检测T淋巴细胞亚群和肝功能.T淋巴细胞亚群的测定采用单克隆抗体标记直接免疫花环法.结果Ⅰ组患者CD3、CD4、CD4/CD8显著升高,术后AST、ALT、DBIL、IBIL降低;Ⅱ组无明显变化.结论肝癌切除术前和术后服用托里消毒散均可提高患者的细胞免疫功能,术后服用还可明显改善患者的肝功能.     

In vitro adsorption of colon cancer sera over staphylococcus protein a: lymphocyte stimulation by leakage of adsorbance

Summary Serum factors may be responsible for reduced host-anti-tumor defence. Although there is still confusion about their origin, attempts have been made to immobilize serum components by Protein A columns as a therapeutic modality. In our study the in vitro adsorption of 90% of the IgG from cancer sera on immobilized protein A did not influence the inhibitory serum activity as measured in a mixed lymphocyte culture. Therefore, IgG or immune complexes do not seem to be the suppressive serum factor in patients with advanced colorectal carcinoma. There is evidence for leakage of small amounts of protein A from the columns which have immunostimulatory activity. Perhaps this may explain necrosis after a therapeutic immunoadsorption.Abbreviations CEA Carcinoembryonal antigen - C Effluent Unadsorbed fraction - C Eluate Adsorbed fraction - CP Cancer plasma - CPG Controlled pore glass beads - CPM Counts per minute - C Sera Sera from patients with metastatic colorectal cancer - HSA Human serum albumin - ³H-Tdr ³H-thymidine - MLC Mixed lymphocyte culture - NP Control plasma - N Sera Sera from healthy persons - PBMNC Peripheral blood mononuclear cells - PBS Phosphate-buffered saline - PI Untreated plasma probes - RPMI 1640 Culture medium (Ross Park Memorial Institute) - SAC Staphylococcus aureus Cowan I - SAW Staphylococcus aureus Wood - SpA Purified staphylococcal protein A Supported by the BMFT, project no. 03/8410/0     

P-glycoprotein expression in the cells of the immune system during aging

P-glycoprotein (P-gp) is a member of adenosine triphosphate (ATP)-binding cassette transporter superfamily that is expressed in a variety of hematopoietic cells. Although a role of P-gp in multidrug resistance in cancer is well-established, its physiological role in immune cells remains unclear. A role for P-gp in the secretion of cytokines and in cytotoxic effector functions has been suggested; however, knock out experiments suggest that P-gp may not be required for cytokine secretion or effector functions. There is no linear correlation between the expression of P-gp and hyporesponsiveness to antigens in aging. A recently discovered role of P-gp in T-cell survival has been discussed in the context of the aging process. A functional role for P-gp in the context of aging of memory subsets of CD4+ and CD8+ T-cells remains to be investigated. The use of a combination of P-gp expression and efflux of substrate dyes in the presence or absence of modulators of P-gp function to determine the structure-functional relationship and some of the limitations in the use of efflux of fluorescent dyes alone as a measure of the expression of P-gp have been reviewed.     

Measurement of antigen specific lymphocyte proliferation using 5-bromo-deoxyuridine incorporation An easy and low cost alternative to radioactive thymidine incorporation

The classical in vitro assay for the determination of cell mediated immune responses is the lymphocyte transformation test (LTT) in which cell proliferation is measured by incorporation of radioactive labeled thymidine (³H-TdR). The LTT assay using ³H-TdR is less suited for modestly equipped laboratories as it is costly, laborious and involves the need to handle radioactive isotopes and specialized equipment.

Here we describe an improved alternative LTT method which is capable of detecting specific cellular immune reactions (CMI) against (mycobacterial) antigens in vitro. This assay, the bromodeoxyuridine-ELISA LTT test, is simple, less expensive, reproducible and is as sensitive as the ³H-TdR test. The specific advantages of the test are a simple denaturation step and the fact that no radioactive isotopes are needed. The test is specifically suited for research laboratories in tropical countries which study CMI in those human infectious diseases where this arm of the immune response plays a pivotal role in the generation of immunity, e.g., in tubercolosis, leprosy and leishmaniasis.     

胸腺摘除对重症肌无力患者T细胞亚群变化的影响

采用免疫荧光染色技术，经流式细胞仪分析，观察了重症肌无力（ＭＧ）患者胸腺摘除前、后外周血Ｔ细胞亚群变化，并研究了淋巴细胞经植物血凝素（ＰＨＡ）激活后Ｔ淋巴细胞亚群的变化。结果显示：１．未经治疗的患者存在明显Ｔ细胞亚群异常，表现为ＣＤ３~＋、ＣＤ４~＋ＣＤ８~－和ＣＤ２９~＋ＣＤ４~＋百分率高，ＣＤ４~－ＣＤ８~＋和ＣＤ１６， ５６~＋百分率低下；２．胸腺摘除后，ＣＤ３~＋、ＣＤ４~＋ＣＤ８~－、ＣＤ２９~＋ＣＤ４~＋百分率降低，ＣＤ４~－ＣＤ８~＋百分率增高；３．ＰＨＡ对外周血中ＣＤ３~＋和ＣＤ２９~＋ＣＤ４~＋有明显下调作用；ＣＤ４~＋ＣＤ８~＋亚群在２４小时呈现上调，４８－７２小时呈现下调；４．ＰＨＡ作用７２小时，正常人ＣＤ４~＋ＣＤ８~－亚群无明显变化，对ＣＤ４~－ＣＤ８~＋亚群呈下调作用；对摘除胸腺的患者ＣＤ４~＋ＣＤ８~－亚群呈现明显下调，对ＣＤ４~－ＣＤ８~＋亚群则呈轻度下调作用。本研究结果表明：摘除胸腺后，ＣＤ４~＋ＣＤ８~－亚群减少，ＣＤ４~－ＣＤ８~＋亚群占优势。     

Immune disorders in women with premature ovarian failure in initial period

PROBLEM: Premature ovarian failure (POF) may be considered as an autoimmune endocrine disease. Autoantibodies and lymphocyte subset changes are associated with premature ovarian failure. Immune cell parameters were studied in relation with anticardiolipin antibodies (ACAB) classes M and G in the initial period of POF. METHODS: Two-color flow cytometry was used to determine lymphocyte subsets and enzyme-linked immunosorbent assay (ELISA) was used to detect ACAB and hormones in the peripheral blood of 68 POF patients, 32 women with normal menopause (NM) and 13 healthy women as a normal control (NC). RESULTS: Patients in the initial period of POF had decreased levels of CD3+, CD19+, CD3+8+, and CD8+57+ lymphocytes and a high percentage of CD5 positive in CD19+ cell population compared to the control; frequencies of IgM ACAB in POF patients were significantly higher than both IgG ACAB and IgM ACAB in NC; correlation between lymphocyte subsets and hormone levels was absent. Women with early NM showed a low number of CD3+, CD3+4+, and CD3+8+ lymphocytes, a high number of CD3 + DR, and elevation of the percentage of CD5 positive in CD19+ lymphocytes compared with the control. The frequencies of both IgM and IgG ACAB were high; the levels of lymphocyte subsets had correlations with progesterone and estradiol concentrations. CONCLUSIONS: An increase of autoantibody producing B cells (CD5+19+) and a low number of effector suppressor/cytotoxic lymphocytes (CD8+57+) with active production of anticardiolipin autoantibodies class M were found. This suggested a primary autoimmune process in the initial period of POF. Autoimmune defeat of the ovary could be the primary cause of POF, whereas in NM autoimmunity is a result of hormone dysfunction.