目的 研究SOCS6/STAT6通路在前列腺细胞炎性增殖作用中的调控作用。方法 使用人前列腺细胞株RWPE-1建立炎症模型,将细胞分为对照（CON）组和炎症刺激（INF）组,后者通过添加脂多糖（LPS）模拟炎症环境。采用ELISA检测白细胞介素-1β（IL-1β）-1β、白细胞介素-6（IL-6）和白细胞介素-8（IL-8）表达水平,蛋白免疫印迹法检测细胞因子信号抑制物-6（SOCS6）、信号转导和转录激活因子-6（STAT6）及磷酸化STAT6蛋白的表达水平。结果 经过LPS处理后,RWPE-1细胞中的SOCS6蛋白表达水平显著下降（P<0.01）,而磷酸化STAT6表达水平上升（P<0.01）。结论 SOCS6/STAT6通路可能通过调节炎症环境下STAT6的磷酸化水平,参与调节前列腺细胞的炎性增殖作用。

Objective To explore the regulatory role of SOCS6/STAT6 pathway in the inflammatory proliferation of prostate cells．Methods The human prostate cell line RWPE-1 was used to establish an inflammation model．Cells were divided into a control（CON）group and an inflammation-stimulated（INF）group,with the latter subjected to lipopolysaccharide（LPS）treatment to simulate an inflammatory environment．The expression levels of interleukin（IL）-1β、IL-6 and IL-8 were detected by ELISA,and the expression levels of suppressor of cytokine signaling 6（SOCS6）,signal transducer and activator oftranscription-6,（STAT6）,and phosphorylated STAT6 proteins were detected by Western blot．Results The results showed that after LPS treatment,the expression of SOCS6 protein in RWPE-1 cells significantly decreased,while the expression of phosphorylated STAT6 increased．Conclusions The SOCS6/STAT6 pathway may be involved in regulating the inflammatory proliferation of prostate cells by modulating the phosphorylation level of STAT6 under inflammatory conditions．

慢性炎症是心血管疾病的常见发病机制,它主要通过损伤内皮细胞、氧化应激和刺激血栓形成影响疾病发展。全身免疫炎症指数（SII）作为一种新型炎症指标,最早用于肿瘤患者的预后评估,现已在多学科领域广泛使用,它由中性粒细胞、血小板、淋巴细胞计算得到,更加全面地反映机体炎症状态。SII已经在多项研究中被证实具有良好的预测价值,该文对SII的优势和在心血管疾病的临床研究进展进行综述,为研究的进一步开展提供参考。

Chronic inflammation is a common pathogenesis of cardiovascular disease,which mainly affects disease progression by damaging endothelial cells,oxidative stress and stimulating thrombosis．As a new type of inflammatory index,the systemic immune inflammatory index（SII）was first used to evaluate the prognosis of cancer patients,and has been widely used in multidisciplinary fields．SII has been confirmed to have good predictive value in a number of studies,and this article reviews the advantages of SII and the progress of clinical research in cardiovascular diseases,so as to provide reference for further research development．

目的 探讨链霉菌抗生物素蛋白-过氧化物酶（SP）免疫组化染色检测胰岛素样生长因子-1（IGF-1）及组织P53蛋白的表达在结直肠腺癌中意义。方法 选取乌鲁木齐市中医医院2020年1月—2023年12月收治的169例结直肠腺癌患者为恶性组,另选取我院同期收治的169例良性结直肠肿瘤患者为良性组。取手术或活检病理组织应用SP免疫组化染色检测2组肿瘤组织IGF-1及P53蛋白表达水平,对比良性组与恶性组间差异,分析不同临床分期、淋巴结转移情况及组织分化程度患者的IGF-1水平、IGF-1mRNA及P53蛋白阳性率。结果 SP免疫组化染色检测IGF-1阳性率、P53蛋白阳性率,恶性组（72.78%、47.93%）均高于良性组（14.79%、6.51%）,对比差异有统计学意义（χ²=115.440、χ²=73.180,P<0.05）;Ⅳ期患者IGF-1阳性率（96.77%）及P53蛋白阳性率（77.42%）高于Ⅲ期（85.11%、63.83%）、Ⅱ期（62.69%、31.34%）及Ⅰ期患者（45.83%、25.00%）,对比差异有统计学意义（χ²=24.860,χ²=28.000,P<0.05）,各亚组两两比较差异无统计学意义（IGF-1阳性与阴性,Ⅰ期 vs Ⅲ期,χ²=12.110,P<0.001;Ⅰ期 vs Ⅳ期,χ²=16.060,P<0.001;Ⅱ期 vs Ⅲ期,χ²=6.880,P=0.009;P53蛋白阳性与阴性Ⅰ期 vs Ⅲ期,χ²=9.580,P<0.002;Ⅰ期 vs Ⅳ期,χ²=14.9990,P<0.001;Ⅱ期 vs Ⅲ期,χ²=11.790,P=0.001;）;有淋巴结转移患者IGF-1阳性率（85.71%）及P53蛋白阳性率（71.43%）高于无淋巴结转移患者（14.79%、40.94%）,对比差异有统计学意义（χ²=4.720、11.740,P<0.05）;低分化患者IGF-1阳性率（93.48%）及P53蛋白阳性率（71.74%）高于中分化患者（81.18%、54.12%）、高分化患者（52.63%、31.58%）,对比差异有统计学意义（χ²=21.250、13.510,P<0.05）。结论 SP免疫组化染色检测提示结直肠腺癌患者IGF-1、P53蛋白阳性率高于良性肿瘤患者,且临床分期高、淋巴结转移与肿瘤组织低分化者的IGF-1、P53蛋白阳性率高,因此IGF-1、P53有望成为结直肠腺癌诊治的重要检测指标。

Objective Exploring the significance of immunohistochemical staining with streptavidin-perosidase（SP）to detect the expression of insulin-like growth factor-1（IGF-1）and tissue P53 in colorectal adenocarcinoma．Methods A total of 169 patients with colorectal adenocarcinoma admitted to a hospital from January 2020 to December 2023 were selected and divided into the malignant group．Other 169 patients with benign colorectal tumors admitted to a hospital during the same period were selected and divided into the benign group．SP immunohistochemistry staining was used to detect and compare the expression levels of IGF-1 and P53 proteins in two groups of tumor tissues obtained in surgery or biopsy．And the IGF-1 levels,IGF-1 mRNA,and P53 positivity rates in patients with different clinical stages,lymph node metastasis,and tissue differentiation levels were compared．Results There was a significant difference in the positive rates of IGF-1mRNA and P53 detected by SP immunohistochemistry staining,and malignant group（72.78%,47.93%）were higher than the benign group（14.79%,6.51%）,which were statistically significant（χ²=115.440,73.180,P<0.05）．The positive rates of IGF-1 and P53 were 96.77% and 77.42% in stage IV,which were higher than those in Stage III（85.11%,63.83%）,II（62.69%,31.34%）and I（45.83%,25.00%）,the differences were statistically significant（χ²=24.860,28.000,P<0.05）．The expression levels of IGF-1 and P53 in colorectal adenocarcinoma patients with different lymph node metastases showed significant differences,the positive rates of IGF-1（85.71%）and P53（71.43%）in patients with lymph node metastasis were higher than those without lymph node metastasis（14.79%,40.94%）,and the differences were statistically significant（χ²=4.720,11.740,P<0.05）．There were significant differences in the expression levels of IGF-1 and P53 among patients with colorectal adenocarcinoma of different degrees of differentiation,the positive rates of IGF-1（93.48%）and P53（71.74%）were significantly higher than those of moderately differentiated（81.18%,54.12%）and well differentiated（52.63%,31.58%）,and the differences were statistically significant（χ²=21.250,13.510,P<0.05）．Conclusion sThrough SP immunohistochemical staining,it was found that the positivity rates of IGF-1 and P53 in colorectal adenocarcinoma patients were higher than those in benign tumor patients,and those with high the clinical stage,lymph node metastasis,and low differentiation of tumor tissue,had higher the positivity rates of IGF-1 and P53．Therefore,IGF-1 and P53 are expected to become important monitoring indicators for the diagnosis and treatment of colorectal adenocarcinoma．

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．

N⁶-甲基腺苷(N⁶-methyladenosine, m⁶A)修饰是真核生物信使 RNA中最丰富的表观遗传修饰,其失调会导致mRNA异常生物学行为如翻译和降解紊乱,从而调控肿瘤发生发展。近期研究表明m⁶A在免疫调控过程中可发挥重要作用,其不仅可调节免疫细胞的活化,还在肿瘤微环境中免疫应答发挥重要调控作用,从而影响免疫治疗效果。越来越多的证据表明m⁶A修饰可能是肿瘤免疫治疗的重要潜在干预靶点。本文阐述了免疫细胞中m⁶A修饰调控及其在肿瘤免疫微环境中相关调节作用,并进一步探讨了靶向m⁶A调控蛋白在肿瘤免疫治疗中的干预策略及潜在治疗价值。

N⁶-methyladenosine (m⁶A) modification is the most abundant epigenetic modification in eukaryotic messenger RNA (messenger RNA). Its dysregulation drives abnormal transcription and translation processes, which promotes the occurrence and development of tumors. Studies have shown that m⁶A modification can regulate the activation of immune cells and their infiltration into the tumor microenvironment (TME), which may affect the efficiency of immunotherapy. Therefore, m⁶A modification may be a potential target for tumor immunotherapy. This paper describes the modification of m⁶A in immune cells and the antitumor immune response associated with TME, and explores the potential therapeutic value of targeting m⁶A regulators in tumor immunotherapy.

自身免疫性肝炎（AIH）是由不明原因免疫异常引起的急性或慢性肝脏炎症性疾病,不分年龄或性别,影响所有种族群体。AIH如果没有得到及时的治疗,可能会发展为肝硬化、肝衰竭,甚至导致死亡。目前一些诊断评分系统和肝活组织病理检查已成为诊断的标准,然而由于疾病表现的高度异质性,AIH诊断仍很有挑战性。大多数患者最初对一线治疗（糖皮质激素与硫唑嘌呤的联合治疗）有应答,然而,应答欠佳和因不良反应引起的不耐受也不少见,需要二线和（或）三线治疗。本文总结阐述诊断困难、一线药物治疗应答欠佳或不耐受的疑难AIH诊断和管理的最新进展,并归纳了目前国内外关于AIH治疗的新方法,为AIH的临床诊疗提供参考。

Autoimmune hepatitis（AIH）is an acute or chronic inflammatory disease of liver caused by unclear immune response that affects people from all ethnic groups irrespective of age or sex．If left untreated,AIH will lead to cirrhosis,liver failure,or death．A number of diagnostic scoring systems and histopathological examination of liver biopsies are now the standard for diagnosis．However,due to the high heterogeneity of the disease presentation,AIH diagnosing remains challenging．Most patients initially respond to first-line treatment,which is corticosteroids combined with azathioprine．However,insufficient response and intolerance due to side effects are also common,so some patients requires second-and/or third-line therapies．Here we summarized the latest progress in diagnosis and management of AIH with difficult diagnosis,poor response to first-line drug treatment or intolerance,as well as the new methods of AIH treatment worldwide,to provide reference for the clinical diagnosis and treatment of AIH．

目的 探讨基于心肺运动试验（CPET）的康复运动应用于维持性血液透析（MHD）患者免疫功能及疲劳程度的影响。方法 选取2020年1月—2022年6月我院200例MHD患者作为研究对象,随机将其分入研究组（n=100）和对照组（n=100）。对照组患者采用常规运动模式进行管理,研究组患者采用基于CPET的康复运动。比较2组的疲劳程度、炎症反应、免疫功能以及心功能。结果 干预3个月后,2组患者透析后的疲劳程度均优于干预前,且研究组优于对照组（均P<0.05）。干预3个月后,2组C-反应蛋白均低于干预前,且研究组低于对照组,免疫球蛋白G（IgG）、IgA、IgM、CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺均高于干预前,且研究组高于对照组（均P<0.05）。干预3个月后,2组左室射血分数、6 min步行距离均高于干预前,且研究组高于对照组（均P<0.05）。干预3个月后,2组左室舒张末期内径、左室收缩末期内径比较差异均无统计学意义（均P>0.05）。结论 基于CPET的康复运动应用于MHD患者中可缓解炎症反应及透析后疲劳程度,提升免疫功能及心功能。

目的 分析早、中期肝细胞癌（HCC）切除术后早期（≤2年）复发的危险因素并探讨术前系统免疫炎症指数（SII）对早、中期HCC术后早期复发的预测价值。方法 回顾性研究2017年10月—2020年10月于我院接受肝癌根治性切除术的238例早中期HCC患者,收集基线资料,通过1∶1倾向性评分匹配（PSM）均衡组间协变量获取早期复发组及未复发组各69例;单因素和多因素Logistic回归分析影响术后早期HCC复发的相关因素,构建列线图模型,临床决策曲线（DCA）评估列线图预测模型在临床的应用效果;受试者操作特征（ROC）曲线评价预测效能,根据最高约登指数确定截断点。结果 单因素及多因素Logistic回归分析结果均提示微血管侵犯（MVI）及术前系统免疫炎症指数（SII）高水平是术后早期复发的独立危险因素;列线图模型有较好的预测效能;ROC曲线计算出SII最佳临界值为696.85×10⁹／L。结论 术前高水平SII可能对预测HCC患者术后早期复发具有潜在价值。

严重烧伤后患者免疫功能的失调,易导致创面感染、全身炎症反应综合征、脓毒症、感染性休克等并发症,增加患者病死率。免疫细胞功能适度的活化将有助于烧伤患者抵御外界病原体的侵袭、促进创面的愈合,但功能过度激活或者功能低下,则会引发一系列严重的后果。本文旨在归纳严重烧伤后中性粒细胞、单核/巨噬细胞、肥大细胞、NK细胞及T淋巴细胞等免疫细胞的功能变化与炎症反应之间的关系,为完善烧伤患者诊疗、减少并发症、改善预后提供新的思路。

The imbalance of immune function in severely burned patients can easily lead to wound infection,systemic inflammatory response syndrome,sepsis,septic shock and other complications,which increase the mortality of patients. Moderate activation of immune cell function will help burned patients to resist the invasion of external pathogens and promote wound healing,but excessive activation or low function can lead to a series of serious consequences. The purpose of this paper is to summarize the relationship between the functional changes of immune cells such as neutrophils,monocytes/macrophages,mast cells,NK cells,T lymphocytes and inflammatory reaction after severe burns,and to provide new ideas for improving the diagnosis and treatment of burned patients,reducing complications and improving the prognosis.

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．