自发性脑出血（SICH）是脑卒中的一种常见形式,其预后通常较差,因此早期评估和调节患者出血后的免疫状态至关重要。免疫检查点是评估T淋巴细胞活跃性和增殖状态的关键指标,监测这些检查点有助于预测脑出血患者的预后。程序性死亡蛋白1（PD-1）和细胞分化抗原28（CD28）作为两个典型的免疫检查点,它们在脑出血预后评估中的应用正逐渐成为研究的热点。该文综述了脑出血后机体免疫状态的变化,以及PD-1和CD28在脑出血后评估和治疗中的研究进展。

Spontaneous intracerebral hemorrhage（SICH）is a common cause of stroke,with specific outcomes often being poor．Therefore,early assessment and modulation of the immune status after hemorrhage are of critical importance．Immune checkpoints serve as key indicators for assessing the activation and proliferation of T cells,and monitoring these checkpoints can help to predict the outcomes of patients with intracerebral hemorrhage．PD-1（programmed death 1）and CD28（Cluster of Differentiation 28）are two representative immune checkpoints,and their use in prognostic assessment after intracerebral hemorrhage is becoming a focus of research．This article reviews the changes in the immune state of the body after intracerebral hemorrhage,as well as the research progress on the use of PD-1 and CD28 in the evaluation and treatment following intracerebral hemorrhage．

目的 探讨表皮生长因子受体酪氨酸酶抑制剂（EGFR-TKIs）一线治疗耐药后,二线化学治疗（化疗）联合程序性死亡蛋白1及其配体（PD-1/L1）免疫检查点抑制剂方案对晚期非小细胞肺癌（NSCLC）的疗效。方法 选取2018年 6月—2022年10月期间就诊于南通大学附属肿瘤医院院的80例有完整临床资料、应用EGFR-TKIs耐药后晚期NSCLC患者进行回顾性分析,依照不同治疗方式将患者分为观察组与对照组,均为40例。对照组一线EGFR-TKIs治疗耐药后进行二线化疗,观察组一线EGFR-TKIs治疗耐药后进行二线化疗联合PD-1/L1免疫检查点抑制剂治疗。对比两组临床疗效及无进展生存期（PFS）,化疗前后血清中人细胞角蛋白21-1片段（Cyfra21-1）、糖类抗原125（CA125）、碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）水平变化,不良反应发生率及生存质量。结果 观察组客观缓解率与疾病控制率高于对照组（P<0.05）,对照组PFS为10（2.38,24.13）个月,观察组PFS为14（5.27~,5.27）个月,观察组高于对照组（χ²=4.536,P=0.041）;化疗后两组bFGF、VEGF,CA125、Cyfra21-1肿瘤标志物水平均比化疗前降低,且观察组[（17.85±3.32）ng/L、（310.51±88.37）ng/L、（51.62±13.66）U/mL、（10.26±3.37）ng/mL]低于对照组[（19.62±3.24）ng/L、（366.26±49.42）ng/L、（59.26±9.35）U/mL、（12.62±2.73）ng/mL],对比差异有统计学意义（t₁=2.413,P₁=0.018;t₂=3.482,P₂<0.001;t₃=2.919,P₃=0.005;t₄=3.442,P₄<0.001）;两组不良反应发生率对比差异无统计学意义（P>0.05）;化疗后两组世界卫生组织生存质量量表简表评分均升高,观察组[（98.62±8.24）、（101.53±12.62）、（95.28±11.15）、（97.79±10.47）分]高于对照组[（84.25±7.32）、（93.58±15.75）、（82.24±9.34）、（83.47±8.38）]分,对比差异有统计学意义（t₁=8.246,P₁<0.001;t₂=2.491,P₂=0.015;t₃=5.670,P₃<0.001;t₄=6.753,P₄<0.001）。结论 对EGFR-TKIs耐药后晚期非小细胞肺癌患者采取二线化疗联合PD-1/L1免疫检查点抑制剂可提升其临床疗效及生存期,改善血清相关肿瘤标志物表达水平,提升患者生存质量。

Objective To explore the therapeutic effect of second-line chemotherapy combined with PD-1/L1 immune checkpoint inhibitor regimen on advanced non-small cell lung cancer（NSCLC） after epidermal growth factor receptor-tyrosine kinase inhibitors（EGFR-TKIs）resistance in first-line chemotherapy．Methods Retrospectively selected 80 patients with advanced NSCLC EGFR TKIs resistance,who were admitted to the Affiliated Cancer Hospital of Nantong University from June 2018 to October 2022．Patients were divided into an observation group and a control group according to different treatment methods,with 40 cases in each group．The control group received second-line chemotherapy after first-line EGFR-TKIs therapy resistance,while the observation group received second-line chemotherapy and PD-1/L1 inhibitor after first-line EGFR-TKIs therapy reactions and quality of live．Clinical efficacy and PFS,changes in serum levels of human Cyfra21-1,CA125,bFGF,VEGF,incidence of adverse chemotherapy of two groups were compared．Results The ORR and DCR of the observation group were significantly higher than those of the control group（P<0.05）．The mean PFS of the control group was 10（2.38-24.13）months,while the mean PFS of the observation group was 14（5.27-35.27）months．The observation group was higher than the control group（χ²=4.536,P=0.041）．After chemotherapy,levels of bFGF,VEGF,CA125 and Cyfra21-1 tumor markers decreased in both groups,and the observation group [（17.85±3.32）ng/L,（310.51±88.37）ng/L,（51.62±13.66）U/mL,（10.26±3.37）ng/mL] was lower than the control group [（19.62±3.24）ng/L,（366.26±49.42）ng/L,（59.26±9.35）U/mL,（12.62±2.73）ng/mL],which showed statistically significant difference in the comparison（t₁=2.413,P₁=0.018;t₂=3.482,P₂<0.001;t₃=2.919,P₃=0.005;t₄=3.442,P₄<0.001）．There was no significant difference in the incidence of adverse reactions between the two groups（P>0.05）．After treatment,the WHO QOL-BREF scores increased in both patient groups and the observation group scores[（98.62±8.24）,（101.53±12.62）,（95.28±11.15）,（97.79±10.47）] were higher than the control group scores[（84.25±7.32）,（93.58±15.75）,（82.24±9.34）,（83.47±8.38）],which showed statistically significant difference．（t₁=8.246,P₁<0.001;t₂=2.491,P₂=0.015;t₃=5.670,P₃<0.001;t₄=6.753,P₄<0.001）．Conclusions The combination of second-line chemotherapy with PD-1/L1 immune checkpoint inhibitors can improve the clinical efficacy and survival of advanced NSCLC patients who are resistant to EGFR-TKIs,improve the expression levels of serum related tumor markers,and enhance the quality of life of patients．

目的 观察脓毒症患者血清胆碱酯酶(S-ChE)和T细胞程序性死亡分子-1(PD-1)以及炎症因子水平,并分析其与患者预后关系。方法 选取2018年8月—2021年5月在我院接受治疗的脓毒症患者为研究对象,同时选取同期在我院接受体检的健康人群为对照组。根据脓毒症患者的预后分为存活组和死亡组。比较脓毒症组和对照组、脓毒症存活组和死亡组患者S-ChE、PD-1水平和炎症因子水平的差异,并分析与患者预后的关系。结果 脓毒症患者的S-ChE水平低于对照组,PD-1水平高于对照组(P＜0.05)。脓毒症患者的CRP、PCT水平高于对照组,CD3⁺T、CD3⁺CD4⁺T和CD4⁺CD8⁺T水平低于对照组(P＜0.05)。死亡组患者的S-ChE水平低于存活组,PD-1水平高于存活组(P＜0.05)。死亡组患者的CRP、PCT水平高于存活组,CD3⁺T、CD3⁺CD4⁺T和CD4⁺CD8⁺T水平低于存活组(P＜0.05)。脓毒症患者S-ChE、PD-1水平呈负相关,(P＜0.05)。脓毒症患者的S-ChE与 CRP、PCT水平负相关,与CD3⁺T、CD3⁺CD4⁺T、CD4⁺CD8⁺T水平正相关(P＜0.05)。脓毒症患者的PD-1与 CRP、PCT水平正相关,与CD3⁺T、CD3⁺CD4⁺T、CD4⁺CD8⁺T水平负相关(P＜0.05)。S-ChE、PD-1预测脓毒症患者预后的AUC值为0.725(95%CI:0.605~0.825)、0.706(95%CI:0.585~0.809),P＜0.05。结论 脓毒症患者的S-ChE水平较低,PD-1水平较高,且与炎症因子水平和患者的预后相关。

Objective To analyze the levels of serum cholinesterase (S-ChE), programmed death 1 (PD-1) and inflammatory factors in patients with sepsis, and analyze the relationship between them and the prognosis of patients. Methods Patients with sepsis treated in our hospital from August 2018 to May 2021 were selected as the research subjects, and healthy people who received physical examinations in our hospital during the same period were selected as the control subjects.The differences in the levels of S-ChE, PD-1 and inflammatory factors between the sepsis group and the control group, the sepsis survival group and the death group were compared, and their relationship with the prognosis of the patients were analyzed. Results The level of S-ChE in patients with sepsis was lower than that of the control group, and the level of PD-1 was higher than that of the control group (P<0.05).The CRP and PCT levels of sepsis patients were higher than those of the control subjects, and the levels of CD3⁺T, CD3⁺CD4⁺T and CD4⁺CD8⁺T were lower (P<0.05).The S-ChE level of the death group was lower than that of the survival group, and the PD-1 level was higher than that of the survival group (P<0.05).The levels of CRP and PCT in the death group were higher than those in the survival group, and the levels of CD3⁺T, CD3⁺CD4⁺T and CD4⁺CD8⁺T were lower than those in the survival group (P<0.05).The levels of S-ChE and PD-1 in sepsis patients were negatively correlated (P< 0.05).S-ChE level in patients with sepsis was negatively correlated with CRP and PCT levels, and positively correlated with CD3⁺T, CD3⁺CD4⁺T, and CD4⁺CD8⁺T levels (P<0.05).PD-1 level in patients with sepsis was positively correlated with CRP and PCT levels, and negatively correlated with CD3⁺T, CD3⁺CD4⁺T, and CD4⁺CD8⁺T levels (P<0.05).The AUC values of S-ChE and PD-1 predicting the prognosis of patients with sepsis were 0.725 (95% CI: 0.605~0.825), 0.706 (95% CI: 0.585~0.809), P＜0.05. Conclusions Patients with sepsis had lower level of S-ChE and higher level of PD-1, which were related to the levels of inflammatory factors and the prognosis of patients.

目的 观察程序性死亡受体1（PD-1）联合细胞毒性T淋巴细胞相关蛋白4（CTLA-4）双免疫疗法对改善晚期乳腺癌近期疗效及远期预后的影响。方法 选择2020年5月—2022年5月商丘市第一人民医院收治的124例晚期乳腺癌患者为研究对象,经随机数字表法将其分为对照组（60例）和观察组（64例）,对照组予以常规PD-1单抗免疫疗法治疗,观察组采用PD-1联合CTLA-4双免疫疗法治疗,比较2组患者治疗前后肿瘤标志物水平、治疗后病灶缓解情况,对所有患者开展为期1年随访,统计并对比2组的不良反应发生情况及远期生存情况。结果 治疗前,2组患者的肿瘤标志物水平比较差异均无统计学意义（均P>0.05）;治疗后,观察组的癌胚抗原为（3.36±0.17）ng/mL,糖类抗原15-3为（25.33±5.28）U/mL,糖类抗原19-9为（38.77±5.62）U/mL,均低于对照组[（5.27±1.36）ng/mL、（28.44±5.18）U/mL、（41.25±5.46）U/mL,均P<0.05]。治疗后,观察组的完全缓解率为21.88%（14/64）,部分缓解率为31.25%（20/64）,病情稳定率为37.50%（24/64）,均高于对照组[8.33%（5/60）、13.33%（8/60）、23.33%（14/60）],肿瘤生长率为（30.27±5.18）%,肿瘤超进展率为6.25%（4/64）,均低于对照组[（33.49±5.32）%、18.33%（11/60）,均P<0.05]。治疗后,观察组的不良反应发生率为34.38%（22/64）,略高于对照组33.33%（20/60）,组间比较差异无统计学意义（P>0.05）;观察组的中位无进展生存期为（9.33±2.25）月,中位总生存期为（10.76±3.32）月,均高于对照组[（7.25±2.31）月、（7.41±1.62）月,均P<0.05]。结论 PD-1联合CTLA-4双免疫疗法能有效改善晚期乳腺癌的近期疗效及远期预后,此疗法未明显增加不良反应发生风险,安全性高。

Objective To observe the effect of programmed cell death protein-1（PD-1）combined with cytotoxic T lymphocyte-associated antigen-4（CTLA-4）dual immunotherapy on the short-term efficacy and long-term prognosis of advanced breast cancer．Methods A total of 124 patients with advanced breast cancer who were admitted to the First People's Hospital of Shangqiu City from May 2020 to May 2022 were selected as the research objects．They were randomly divided into the control group（60 cases）and the observation group（64 cases）by the method of random number table．The control group was treated with conventional PD-1 monoclonal antibody immunotherapy,and the observation group was treated with PD-1 combined with CTLA-4 double immunotherapy．The levels of tumor markers before and after treatment and the focal remission after treatment were compared between the two groups．All patients were followed up for one year,the incidence of adverse reactions and long-term survival between the two groups were compared．Results Before treatment,there was no statistically significant difference in the levels of tumor markers between two groups（all P>0.05）．After treatment,the carcino-embryonic antigen content of the observation group was（3.36±0.17）ng/mL,CA153 was（25.33±5.28）U/mL,and CA199 was（38.77±5.62）U/mL,which were lower than those of the control group [（5.27±1.36）ng/mL,（28.44±5.18）U/mL,（41.25±5.46）U/mL,all P<0.05]．After treatment,the complete remission rate of the observation group was 21.88%（14/64）,partial remission rate was 31.25%（20/64）,and stable disease rate was 37.50%（24/64）,all higher than those of the control group [8.33%（5/60）,13.33%（8/60）,23.33%（14/60）];tumor growth rate of the observation group was（30.27±5.18）%,hyper progressive disease rate was 6.25%（4/64）,both lower than those of the control group [（33.49±5.32）%,18.33%（11/60）,both P<0.05]．After treatment,the incidence of adverse reactions in the observation group was 34.38%（22/64）,slightly higher than that in the control group 33.33%（20/60）（P>0.05）．The median progression free survival of the observation group was（9.33±2.25）months,and the median overall survival was（10.76±3.32）months,both higher than those of the control group [（7.25±2.31）months and（7.41±1.62）months]（P<0.05）．Conclusions PD-1 combined with CTLA-4 dual immunotherapy can effectively improve the short-term efficacy and long-term prognosis of advanced breast cancer．This therapy does not significantly increase the risk of side effects,which is safe．

       自发性脑出血（SICH）是脑卒中的一种常见形式，其预后通常较差，因此早期评估和调节患者出血后的免疫状态至关重要。免疫检查点是评估T淋巴细胞活跃性和增殖状态的关键指标，监测这些检查点有助于预测脑出血患者的预后。程序性死亡蛋白1（PD-1）和细胞分化抗原28（CD28）作为两个典型的免疫检查点，它们在脑出血预后评估中的应用正逐渐成为研究的热点。该文综述了脑出血后机体免疫状态的变化，以及PD-1和CD28在脑出血后评估和治疗中的研究进展。

       Spontaneous intracerebral hemorrhage（SICH）is a common cause of stroke，with  specific outcomes often being poor．Therefore，early assessment and modulation of the immune status after hemorrhage are of critical importance．Immune checkpoints serve as key indicators for assessing the activation and proliferation of T cells，and monitoring these checkpoints can help to predict the outcomes of patients with intracerebral hemorrhage．PD-1（programmed death 1）and CD28（Cluster of Differentiation 28）are two representative immune checkpoints，and their use in prognostic assessment after intracerebral hemorrhage is becoming a focus of research．This article reviews the changes in the immune state of the body after intracerebral hemorrhage，as well as the research progress on the use of PD-1 and CD28 in the evaluation and treatment following intracerebral hemorrhage．