动脉粥样硬化（AS）是一种起始于炎症介导的内皮损伤的慢性血管疾病，其本质是免疫炎症驱动的病理过程，是众多心血管疾病的病理基础。CD4⁺  T细胞亚群［包括辅助性T细胞1型（T helper 1 cell，Th1）、Th2、Th17、调节性T细胞等］通过分泌特异性细胞因子参与AS的炎症反应，其中促炎性CD4+  T细胞与抗炎性CD4⁺  T细胞的抗炎功能失衡是推动斑块进展的关键环节，在AS斑块形成与发展中起关键作用。近年来，多项研究表明某些中药单体、经典复方及其有效成分，具有多靶点、多层次机制调控CD4⁺  T细胞分化及功能，这些作用共同减轻血管内皮炎症反应、抑制巨噬细胞泡沫化及平滑肌细胞迁移等，延缓AS斑块形成与发展，为AS防治提供了新思路，展现了中医药在该领域的研究展现出独特优势与广阔前景，本文综述了中医药通过干预CD4⁺  T细胞亚群平衡防治AS的最新研究进展，及其影响相关细胞因子网络及关键信号通路的作用机制，为开发具有多靶点协同优势的创新中药与中西医结合治疗方案提供了关键理论依据与实践方向。

       Atherosclerosis（AS）is a chronic vascular disease that originates from inflammation mediated endothelial 

damage．Its essence is a pathological process driven by immune inflammation，and it is the pathological basis of many cardiovascular diseases．CD4⁺  T cell subsets（including Th1，Th2，Th17，Treg，etc.）participate in the inflammatory response of AS by secreting specific cytokines．The imbalance of anti-inflammatory function between pro-inflammatory CD4⁺  T cells and anti-inflammatory CD4⁺T cells is a key link in promoting plaque progression and playing a crucial role in the formation and development of AS plaques．In recent years，a number of studies have shown that the monomers，classic prescriptions and their effective ingredients of Chinese herbs have the effect of multi-target，multi-level mechanism to regulate the differentiation and function of CD4⁺  T cells．These effects together reduce the inflammatory reaction of vascular endothelium，inhibit the foam formation of macrophages and smooth muscle cell migration，delay the formation and development of AS plaque，provide new ideas for the prevention and treatment of AS，and make the research of Chinese medicine show unique advantages and broad prospects in this field．This article  reviews the latest  research progress of Chinese medicine in the prevention and treatment of AS by intervening in the balance of CD4⁺  T cell subsets，as well as the mechanism of its effects on related cytokine networks and key signal pathways．This provides a key theoretical basis and practical direction for the development of innovative traditional Chinese medicine and integrated traditional Chinese and Western medicine treatment plans with multi-target synergistic advantages．

       目的   探讨慢性阻塞性肺疾病急性加重期血嗜酸性粒细胞（EOS）、血清白细胞介素-5（IL-5）水平与第一秒用力呼气容积（FEV1）、第一秒用力呼气容积与用力肺活量的比值（FEV1/FVC）、用力肺活量（FVC）的相关性。方法   纳入2023年3月—2024年3月于佛山市顺德区第五人民医院住院的73例慢性阻塞性肺疾病急性加重期患者，以2%作为外周血EOS比例（EOS%）截断值分为两组，研究组（EOS%≥2%）34例，对照组（EOS%＜2%）39例，收集两组患者_{的一般临床资料、实验室检查结果、肺功能检查结果（FEV1}、FVC、FEV₁/FVC），比较组间差异，分析指标间的相关性。结果   对照组与实验组患者EOS%分别为0.5（0.1，0.9）%、5.15（2.60，10.05）%，两组患者EOS%差异有统计学意义（P＜0.05）。对照组与实验组患者IL-5水平分别为0.98（0.56，1.78）ng/L、3.6（1.73，6.77）ng/L，两组IL-5水平差异有统计学意义（P＜0.05）。对照组FEV₁（L）、FVC（L）、FEV₁/FVC水平分别为1.32（1.18，1.58）、2.07（1.92，2.62）、0.62（0.57，0.67）；实验组分别为1.24（1.00，1.52）、2.22（1.94，2.56）、0.58（0.47，0.67），两组FEV₁、FVC、FEV₁/FVC水平差异均无统计学意义（P＞0.05）。Spearman等级相关检验结果显示，EOS%与IL-5水平呈正相关（rs=0.870，P＜0.001）；按组别进行分层后结果显示，对照组、试验组EOS%与IL-5水平均呈正相关（r_s=0.820，P＜0.001；r_s=0.938，P＜0.001）。EOS%、IL-5水平与FEV₁、FEV₁/FVC呈负相关（P＜0.05），与FVC不相关（r_s=0.039，P＞0.05）。对照组EOS%、IL-5水平与FEV₁、FEV₁/FVC、FVC不相关（P＞0.05）；实验组EOS%、IL-5水平与FEV₁、FEV₁/FVC呈负相关（P＜0.05），与FVC不相关（P＞0.05）。结论 慢性阻塞性肺疾病急性加重期血EOS%与血清IL-5水平呈正相关，外周血EOS%≥2%时血EOS%、血清IL-5与FEV₁、FEV₁/FVC呈负相关，与FVC无关。

       Objective  To explore the correlation among blood eosinophil levels，serum interleukin-5（IL-5）levels，and forced expiratory volume in one second（FEV₁），the ratio of forced expiratory volume in one second to forced vital capacity（FEV₁/FVC），and forced vital capacity（FVC）during the acute exacerbation of chronic obstructive pulmonary disease（AECOPD）．Methods  From March 2023 to March 2024，73 patients hospitalized for AECOPD at Shunde District Fifth People’s Hospital of Foshan City were included，and divided into two groups based on a cutoff value of 2% for peripheral blood eosinophil（EOS%）．The experimental group（EOS%≥2%）included 34 patients，while the control group（EOS%＜2%）included 39 patients．General clinical data，laboratory test results，and pulmonary function test results（FEV₁，FVC，FEV₁/FVC）were collected from both groups．Results  The median quartiles of EOS% for the control group and experimental group were 0.5（0.10.9）% and 5.15（2.60，10.05）%，respectively．There was a statistically significant difference between the EOS% of two groups（P＜0.05）．The median quartiles of IL-5 levels for the control group and experimental group were 0.98（0.56，1.78）ng/L and 3.6（1.73，6.77）ng/L，respectively．There was also a statistically significant difference in IL-5 levels between the two groups（P＜0.05）．For the control group，the median quartiles of FEV₁，FVC，and FEV₁/FVC were 1.32（1.18，1.58），2.07（1.92，2.62）and 0.62（0.57，0.67），respectively．For the experimental group，they were 1.24（1.00，1.52），2.22（1.94，2.56）and 0.58（0.47，0.67）respectively．There was no statistically significant difference between the two groups in FEV₁，FVC and FEV₁/FVC levels（P＜0.05）．Spearman rank correlation analysis showed a positive correlation between EOS% and IL-5 level （r_s=0.870，P＜0.001）．Stratified by group，both the control and experimental groups showed a positive correlation between EOS% and IL-5 level （r_s=0.820，P＜0.001；r_s=0.938，P＜0.001）．There was a negative correlation between EOS%，IL-5 level，and FEV₁，FEV1/FVC（P＜0.05），but no correlation with FVC（P＞0.05）．In the control group，there was no correlation between EOS%，IL-5 level，and FEV₁，FEV1/FVC，or FVC（P＞0.05）．In the experimental group，there was a negative correlation between EOS%，IL-5 level，and FEV₁，FEV₁/FVC（P＜0.05），but no correlation with FVC（P＞0.05）．Conclusions  During AECOPD，blood EOS% is positivelycorrelated with serum IL-5 levels．When peripheral blood eosinophils are ≥2%，blood EOS%，serum IL-5，and FEV₁，FEV₁/FVC are negatively correlated，while there is no correlation with FVC．

      目的   通过生物信息学手段筛选非小细胞肺癌（NSCLC）中的关键靶点基因，识别预后标志物NDC80，并探讨其在NSCLC中的表达意义，进而分析NDC80作为NSCLC基因治疗靶点的可行性。方法   采用癌症基因组图谱（TCGA）TCGA数据库检索NSCLC相关数据，进行加权基因共表达网络分析（WGCNA）以识别关键基因，并进行差异表达分析、相关性分析和蛋白互作网络构建。对筛选出的关键基因进行功能分析。利用免疫组化染色法检测癌组织及癌旁组织中NDC80蛋白的表达水平，并进一步探究其与临床病理特征的关系。采用Kaplan-Meier法分析NDC80表达与NSCLC患者无进展生存时间（PFS）的关系。结果   共筛选出20个与NSCLC高度关联的关键基因，包括CDC20、CDK1、MCM4、CDC6、MCM2、PLK1、NDC80、CCNB1、CDC45、AURKA、MCM8、BUB1、CDT1、ORC1、CCNA2、CASC5、MAD2L1、BUB1B、CENPA、AURKB。免疫组化验证显示，NDC80蛋白在NSCLC组织中高表达，其在NSCLC组（阳性表达率88.6%）显著高于癌旁组（50.0%）（P＜0.05）。NDC80蛋白的阳性表达率在TNM分期（Ⅲ期+Ⅳ期）、低分化、淋巴结转移的NSCLC组高于TNM分期（Ⅰ期+Ⅱ期）、高分化及中分化以及未发生淋巴结转移的NSCLC组（P＜0.05）。NDC80蛋白的阳性表达率在不同性别、年龄、病灶大小分类的NSCLC组织中无显著差异（P＞0.05）。Kaplan-Meier分析显示，NDC80蛋白高表达组的PFS中位数为（9.00±0.27）个月，明显低于低表达组（11.00±0.79）个月（P＜0.05）。结论   本研究发现的关键基因在NSCLC干细胞的维持中发挥重要作用。免疫组化结果显示，NDC80蛋白在NSCLC组织中高表达，且与肿瘤分化、TNM分期及淋巴结转移密切相关。NDC80蛋白高表达组的PFS明显低于低表达组，提示NDC80可能成为NSCLC筛查、治疗和预后评估的潜在生物标志物。

      Objective  To screen the key target genes in non-small cell lung cancer（NSCLC）by bioinformatics，identify the prognostic marker NDC80，and explore its expression significance in NSCLC，so as to analyze the feasibility of NDC80 as a gene therapy target for NSCLC．Methods  TCGA database was used to retrieve NSCLC-related data，and weighted gene co-expression network analysis（WGCNA）was used to identify key genes，and differential expression analysis，correlation analysis and protein-protein interaction network construction were carried out．The function of the selected key genes was analyzed．Immunohistochemical staining was used to detect the expression level of NDC80 protein in cancer tissues and adjacent tissues，and to further explore its relationship with clinicopathological features．Kaplan-Meier method was used to analyze the relationship between NDC80 expression and progression-free survival （PFS）of NSCLC patients．Results  A total of 20 key genes highly associated with NSCLC were screened out，which were CDC20，CDK1，MCM4，CDC6，MCM2，PLK1，NDC80，CCNB1，CDC45，AURKA，MCM8，BUB1，CDT1，ORC1，CCNA2，CASC5，MAD2L1，BUB1B and CENPA．Immunohistochemical  verification  showed that NDC80 protein was highly expressed in NSCLC tissue，and its positive expression rate in NSCLC group（88.6%）was significantly higher than that in adjacent cancer group（50.0%，P＜0.05）．The positive expression rate of NDC80 protein in NSCLC with TNM staging（Ⅲ+Ⅳ），low differentiation and lymph node metastasis was higher than that in NSCLC with TNM staging（Ⅰ+Ⅱ），high differentiation and moderate differentiation and no lymph node metastasis（P＜0.05）．There was no significant difference in the positive expression rate of NDC80 protein among NSCLC tissues with different gender，age and lesion size（P＞0.05）．Kaplan-Meier analysis showed that the median PFS of high expression group of NDC80 protein was（9.00±0.27）months，which was significantly lower than that of low expression group（11.00±0.79）months（P＜0.05）．Conclusions  The key genes found in this study play an important role in the maintenance of NSCLC stem cells．Immunohistochemical results showed that NDC80 protein was highly expressed in NSCLC，and it was closely related to tumor differentiation，TNM staging and lymph node metastasis．The PFS of high expression group of NDC80 protein was significantly lower than that of low expression group，suggesting that NDC80 may become a potential biomarker for screening，treatment and prognosis evaluation of NSCLC．

       目的   开发一种多功能纳米颗粒输送系统来刺激骨再生和血管形成，用于逆转骨质疏松症。方法   通过制备基于外消旋聚乳酸 Poly（D，L-lactide）即PLA的纳米颗粒来封装淫羊藿苷。随后，通过红细胞膜包被这些纳米颗粒以增强生物相容性。为了提高靶向特异性，进一步合成了由阿仑膦酸盐修饰的聚乙二醇-磷脂酰乙醇胺（PEG-DSPE） 组成的骨靶向聚合物脂质，并将其掺入细胞膜涂层中。结果   多功能纳米颗粒输送系统可通过调节骨髓间充质干细胞 （BMSC）功能，从而增强成骨和血管生成能力。结论   本研究结果表明，多功能纳米颗粒输送系统可以在体外刺激骨形成和血管形成，表明其有成为骨质疏松症先进治疗策略的潜力。

       Objective  To developed a multifunctional nanoparticle system to stimulate bone regeneration and vascularization as a therapeutics strategy for osteopovost．Methods  Poly（D，L-lactide）（PLA）-based nanoparticles were fabricated to encapsulate the icariin，which is renowned for its osteogenic potential．These nanoparticles were then coated with  red blood cell membranes to enhance biocompatibility．To further improve targeting specificity，a bone-targeted polymer-lipid consisting of alendronate-modified PEG-DSPE was synthesized and incorporated into the cell membrane coating．Results  The delivery system was designed to modulate the function of bone marrow mesenchymal stem cells，thereby enhancing both osteogenesis and angiogenesis．Conclusions  Our findings demonstrated that the therapeutic system could enhance bone formation and vascularization in vitro，indicating its potential as an advanced treatment strategy for osteoporosis．

       帕金森病是全球第二大神经退行性疾病，其根本病理特征为中脑黑质多巴胺能神经元的退变死亡。目前临床一线治疗主要采用左旋多巴替代疗法，然而疗效有限且副作用显著。以补充多巴胺能神经元为基础的细胞替代疗法，能够从根本上解决神经元丢失的问题，具有长远的临床意义。细胞替代治疗的细胞最早来自于胎儿腹侧中脑组织，随着重编程技术的不断发展，已逐步转向人类胚胎干细胞和诱导多能干细胞体外分化的前体细胞。同时，直接在体内重编程，将胶质细胞转分化为多巴胺能神经元，也是一种具有应用潜力的策略。本文系统总结了近年来帕金森病细胞替代疗法的进展和面临的挑战，旨在为该疾病治疗新策略的研究提供参考和启示。

       Parkinson’s disease（PD）is the second most prevalent neurodegenerative disorder worldwide，characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta．Traditional treatments，primarily involving levodopa for dopamine replacement，offer limited efficacy and associated with significant side effects．Cell  replacement therapies aimed at replenishing dopaminergic neurons provide a promising long-term solution to neuronal loss，with  substantial clinical significance．The initial successful cellular source for transplantation in PD research was fetal ventral mesencephalic tissue．Nevertheless，advancements in  reprogramming technologies have increasingly favored the use of human embryonic stem cells and induced pluripotent stem cells．Additionally，direct in vivo reprogramming，converting glial cells into dopaminergic neurons，has emerged as an alternative strategy for cell replacement therapy．This  review  systematically  summarizes the  recent advances and challenges in cell replacement therapies for PD，with the aim of providing insights and guidance for the development of novel therapeutic strategies for the PD．

目的 明确亚甲基四氢叶酸还原酶（MTHFR）C677T、A1298C基因多态性与成人患者使用大剂量甲氨蝶呤（MTX）治疗急性淋巴细胞白血病（ALL）毒性反应和24、48、72 h MTX血药浓度关系。方法 收集2014年6月—2020年6月就诊于新疆医科大学第一附属医院成人急性淋巴细胞白血病75例患者血样检测MTHFR C677T及A1298C基因多态性, 根据抗癌药物常见毒性反应分级标准对毒性反应进行分级,采用非条件Logistic回归分析MTHFR C677T、A1298C基因多态性与HD-MTX毒性反应及血药浓度的关系。结果 MTHFR 677TT型发生贫血风险显著高于CC型（P=0.027, OR=4.694, 95%CI：1.195~18.438）; 未发现MTHFR C677T与白细胞减少、血小板计数减少、中性粒细胞计数减少、淋巴粒细胞计数减少、骨髓抑制、谷丙转氨酶升高、谷草转氨酶升高、肝功能损伤、急性肾损伤及黏膜损伤、24 h、48 h及72 h MTX血药浓度有相关性（P>0.05）; 未发现MTHFR A1298C与HD-MTX毒性反应及血药浓度有相关性（P>0.05）。结论 MTHFR C677T基因多态性与成人急性淋巴细胞白血病患者大剂量MTX化学治疗后血液毒性存在相关性。

Objective To determine the relationship among C677T and A1298C gene polymorphisms of methyltetrahydrofolate reductase（MTHFR）and adult acute lymphocytic leukemia（ALL）, the relationship between the toxicity of high-dose methotrexate（HD-MTX）after chemotherapy and the MTX blood concentration of 24 h, 48 h and 72 h in patients with ALL．Methods Blood samples were collected from 75 adult patients with ALL who were treated at the First Affiliated Hospital of Xinjiang Medical University from June 2014 to June 2020．The samples were used to detect the genetic polymorphisms of MTHFR C677T and A1298C, and the toxic reactions were graded according to the common toxic reaction classification criteria of anti-cancer drugs．Unconditional Logistic regression was used to analyze the relationship between MTHFR C677T and A1298C gene polymorphisms and HD-MTX toxic reactions and blood drug concentration．Results The risk of anemia in MTHFR 677TT was significantly higher than that in CC type（P=0.027, OR=4.694, 95% CI：1.195-18.438）．No correlation was found between MTHFR C677T and leukopenia, thrombocytopenia, neutropenia, lymphogranulocytopenia, bone marrow suppression, elevated alanine aminotransferase, elevated aspartate aminotransferase, liver function injury, acute kidney injury and mucosal injury, 24 h, 48 h and 72 h MTX plasma concentrations（>0.05）．No correlation was found among MTHFR A1298C and HD-MTX toxicity and blood concentration（P>0.05）．Conclusions MTHFR C677T gene polymorphism is associated with hematotoxicity after HD-MTX chemotherapy in adult patients with ALL．

目的 观察辅助性T17细胞（Th17）与调节性T细胞（Treg）比值与2型糖尿病（T2DM）患者胰岛素抵抗及胰岛β细胞功能的关系。方法 纳入2022年4月—2023年4月在贵州医科大学第二附属医院内分泌科住院及健康体检人群各100例, 分为糖耐量正常组（NGT组, n=100）和T2DM组（n=100）, 分别测定糖化血红蛋白（HbA1c）、空腹血糖（FPG）、甘油三酯（TG）等生化指标, 电化学发光法测定空腹胰岛素（FINS）, 稳态模型计算胰岛β细胞功能指数（HOMA-β）、胰岛素抵抗指数（HOMA-IR）及胰岛素敏感指数（HOMA-ISI）。流式细胞术检测Th17、Treg水平。HOMA-IR、HOMA-β和HOMA-ISI的影响因素采用多元线性回归分析。结果 与NGT组相比, T2DM组BMI、FPG、HbA1c、LDL-C 、TG、TC、FINS、HOMA-IR、Th17及Th17/Treg水平均升高（P<0.01）, HDL-C、HOMA-β、HOMA-ISI、Treg水平均降低, 且差异有统计学意义（P<0.01）。Th17与BMI（r=0.251, P<0.001）及HOMA-IR（r=0.305, P<0.001）呈正相关; 与HOMA-β（r=-0.204, P<0.001）及HOMA-ISI（r=-0.359, P<0.001）呈负相关。Treg与HOMA-ISI之间呈正相关（r=0.170, P=0.008）, 而与HOMA-IR呈负相关（r=-0.153, P=0.017）; Th17/Treg与BMI（r=0.332, P<0.001）及HOMA-IR（r=0.374, P<0.001）;与HOMA-β（r=-0.249, P<0.001）及HOMA-ISI（r=-0.427, P<0.001）呈负相关。多元线性回归分析显示, Th17/Treg是HOMA-IR（β=5.915）升高及HOMA-ISI（β=-2.557）下降的影响因素（P<0.01）。结论 Th17/Treg可能通过影响胰岛素抵抗、降低胰岛素敏感性参与T2DM的发生。

Objective To explore the relationship among the proportion of helper T17 cells（Th17）to regulatory T cells（Treg）, insulin resistance, and the function of islet beta cells．Methods One hundred cases of hospitalized patients and 100 cases of health check-ups people in the Department of Endocrinology of the Second Affiliated Hospital of Guizhou Medical University from April 2022 to April 2023 were included．Patients were divided into normal glucose tolerance group（NGT group, n=100）and type 2 diabetes mellitus group（T2DM group, n=100）．The biochemical indexes of HbA1c, fasting blood glucose（FPG）, triglyceride（TG）and fasting insulin（FINS）were determined by electrochemiluminescence．Islet beta cell function index（HOMA-β）, insulin resistance index（HOMA-IR）and insulin sensitivity index（HOMA-ISI）were calculated in homeostasis model．The levels of Th17 and Treg were detected by flow cytometry．Spearman was used to analyze the correlation between indicators, and multiple linear regression analysis was used to analyze the influencing factors of HOMA-IR, HOMA-β and HOMA-ISI．Results In contrast to the NGT group, the T2DM group exhibited elevated levels of BMI, FPG, HbA1c, LDL-C, TG, TC, FINS, HOMA-IR, Th17 and Th17/Treg, with these variances being signifincantly different（P<0.01）．There was a notable reduction in the levels of HDL-C,HOMA-β,HOMA-ISI,Treg,with those changes being significantly different（P<0.01）．Th17 was positively correlated with BMI（r=0.251, P<0.001）and HOMA-IR（r=0.305, P<0.001）, it was negatively correlated with HOMA-β（r=-0.204, P<0.001）and HOMA-ISI（r=-0.359, P<0.001）．Treg was positively correlated with HOMA-ISI（r=0.170, P=0.008）, while it was negatively correlated with HOMA-IR（r=-0.153, P=0.017）．The ratio of Th17/Treg was positively correlated with BMI（r=0.332, P<0.001）and HOMA-IR（r=0.374, P<0.001）, it was negatively correlated with HOMA-β（r=-0.249, P<0.001）and HOMA-ISI（r=-0.427, P<0.001）．Multiple linear regression analysis showed that Th17/Treg was an influential factor in the increase of HOMA-IR（β=5.915）and the decrease of HOMA-ISI（β=-2.557）（P<0.01）．Conclusions Th17/Treg may be involved in the development of T2DM by affecting insulin resistance and reducing insulin sensitivity．

目的 探讨卵巢癌化学治疗（化疗）耐药与焦孔素E（GSDME）基因的甲基化是否有关, 以及地西他滨是否可以通过去甲基化使GSDME蛋白表达水平升高从而逆转卵巢癌化疗耐药。方法 顺铂逆浓度梯度构建SKOV-3卵巢癌耐顺铂细胞株（SKOV-3/DDP）; CCK8法检测耐药前后细胞株的半抑制浓度（IC₅₀）; 实时荧光定量甲基化特异性PCR法检测两组细胞中GSDME基因的甲基化水平; Wetern Blot检测两组细胞中GSDME的表达水平。将耐药细胞株用不同质量浓度的地西他滨处理,重复上述实验, 检测地西他滨处理前后细胞的IC₅₀、GSDME基因的甲基化水平及GSDME蛋白的表达程度。结果 与SKOV-3细胞相比, SKOV-3/DDP中GSDME基因的甲基化水平升高（P<0.01）, 同时GSDME蛋白的表达水平降低（P<0.001）; 随着地西他滨作用浓度的升高, 耐药细胞中GSDME基因的甲基化程度逐渐降低, 蛋白的表达水平逐渐升高, 细胞的IC₅₀逐渐降低：在用0.5 μg/mL地西他滨处理耐药细胞后GSDME基因的甲基化水平虽然降低（P<0.01）, 但是此时蛋白的表达水平及耐药细胞的IC₅₀均无明显改变（P>0.05）; 当地西他滨的浓度增加到1.0 μg/mL时蛋白的表达水平才明显升高（P<0.05）, 而此时细胞的IC₅₀仍未见明显降低（P>0.05）; 待药物浓度达到1.5 μg/mL时, 细胞的IC₅₀才表现出明显的下降趋势（P<0.05）。结论 GSDME的表达与卵巢癌的化疗耐药密切相关, GSDME的高甲基化水平致使其低表达可促进卵巢癌的化疗耐药。但地西他滨可以通过去甲基化使卵巢癌耐药细胞中GSDME的表达水平升高, 从而增加卵巢癌细胞对化疗药物的敏感性, 进而逆转卵巢癌化疗耐药。

Objective To explore whether drug resistance in ovarian cancer is associated with gasdermin E（GSDME） methylation, and to explore whether decitabine can reverse ovarian cancer chemoresistance by increasing GSDME protein expression levels through demethylation．Methods The cisplatin-resistant cell line（SKOV-3/DDP）was constructed by inverse concentration gradient of cisplatin．Semi-inhibitory concentration（IC₅₀）of cell lines after drug resistance was detected using the CCK8 assay．Real-time fluorescence quantitative methylation-specific PCR was used to detect the methylation level of GSDME gene in the two groups of cells．Wetern Blot was used to detect the expression level of GSDME in the two groups of cells．Drug-resistant cell lines were treated with different concentrations of the demethylating drug decitabine．Experiments above were repeated to detect the methylation degree of IC₅₀ and GSDME genes and the expression level of GSDME protein in drug-resistant cells before and after decitabine treatment．Results Compared with SKOV-3 cells, the methylation level of GSDME gene in SKOV-3/DDP was significantly increased（P<0.01）, while the expression level of GSDME protein was significantly decreased（P<0.001）．With the increase of decitabine concentration, the methylation degree of GSDME gene in drug-resistant cells was gradually decreased, the expression level of protein was gradually increased, and the IC₅₀ of cells was gradually decreased：the methylation level of GSDME gene was decreased after 0.05 μg/mL decitabine treatment（P<0.01）, but there were no significant changes in protein expression level and IC₅₀ of drug-resistant cells（P>0.05）．The protein expression level was significantly increased when the concentration of local citabine was increased to 0.10 μg/mL（P<0.05）, while the IC50 of the cells was not significantly decreased（P>0.05）．When the drug concentration reached 0.15 μg/mL, he IC₅₀ of the cells showed a significant downward trend（P<0.05）．Conclusions The expression of GSDME is closely related to chemoresistance in ovarian cancer, and the low expression of GSDME due to its high methylation level can promote chemoresistance in ovarian cancer．However, decitabine can increase the expression level of GSDME in drug-resistant ovarian cancer cells through demethylation,thereby increasing the sensitivity of ovarian cancer cells to chemotherapeutic drugs, and then reversing the chemoresistance of ovarian cancer．

目的 研究靶向NKG2A抑制剂抗头颈部鳞状细胞癌（HNSCC）的作用。方法 应用GEO和TCGA数据库分析NKG2A及其配体HLA-E单细胞表达情况、与患者预后以及免疫微环境的相关性。构建HNSCC皮下抑制瘤模型,流式细胞技术检测化学治疗（化疗）对免疫检测点NKG2A表达的影响。动物实验验证NKG2A抑制剂以及NKG2A抑制剂联合多西他赛化疗的抗肿瘤作用。结果 NKG2A（KLRC1）主要表达在NK细胞,少量表达在T淋巴细胞。HNSCC肿瘤高表达NKG2A/HLA-E（P<0.01）,与患者不良预后密切相关;肿瘤微环境中NKG2A/HLA-E与多个免疫细胞浸润以及免疫检测点表达密切相关（P<0.01）。动物实验显示化疗能上调T、B淋巴细胞表达免疫检查点NKG2A的表达水平（P<0.01）;化疗的基础上联合NKG2A抑制剂能更有效地介导抗肿瘤作用（P=0.013）。结论 化疗基础上联合NKG2A抑制剂能更有效地介导抗肿瘤作用,为探索HNSCC临床新策略提供实验和理论基础。

Objective To investigate the anti-tumor effects of NKG2A inhibitor on head and neck squamous cell carcinoma（HNSCC）．Methods The single-cell expression of NKG2A ,its ligand HLA-E and their correlations with patient prognosis and immune microenvironment were analyzed in GEO and TCGA databases．The subcutaneous tumor model of HNSCC was constructed,and the effects of chemotherapy on the expression of NKG2A on T and B lymphocytes were detected by flow cytometry．Animal experiments were used to confirmed the anti-tumor effects of NKG2A inhibitor and NKG2A inhibitors combined with docetaxel．Results NKG2A（KLRC1）was mainly expressed in NK cells,and a small amount was expressed in T lymphocytes．The high expression of NKG2A/HLA-E in HNSCC tumors（P<0.01）were closely related to poor prognosis．NKG2A/HLA-E in tumor microenvironment were closely related to the infiltration of multiple immune cells and the expression of immune checkpoints（P<0.01）．Animal experiments showed that chemotherapy could up-regulate the expression of NKG2A in T and B lymphocytes（P<0.01）．Chemotherapy in combination with NKG2A inhibitor could mediate more effective antitumor effects in HNSCC（P=0.013）．Conclusions Combined with NKG2A inhibitor on the basis of chemotherapy can mediate more effective anti-tumor effects,and this study may provide experimental and theoretical basis for exploring new clinical strategies of HNSCC．

目的 探讨多梳蛋白SUZ12对肝细胞肝癌（HCC）细胞增殖、血管生成拟态形成和人脐静脉内皮细胞（HUVECs）血管生成的影响。方法 分别利用MTT比色法及体外血管生成实验检测SUZ12表达水平改变对HCC细胞SMMC-7721、Hep3B增殖、血管生成拟态形成和HUVECs血管生成的影响。结果 MTT结果显示,在HCC细胞中分别敲低或过表达SUZ12均对HCC细胞的增殖能力无明显影响。将SUZ12低表达HCC细胞与HUVECs共培养后,HCC细胞的血管生成拟态管样结构形成增多。此外,将SUZ12敲低组HCC细胞的培养上清用于培养HUVECs后,HUVECs的血管生成拟态管样结构形成也明显增多。结论 SUZ12对HCC细胞的增殖无影响,其在HCC中可抑制HCC细胞和HUVECs的血管生成拟态管样结构形成。上述结果提示SUZ12可能通过调控HCC细胞及HUVECs的血管生成发挥抑癌作用。

Objective To investigate the effects of SUZ12 on cell proliferation of hepatocellular carcinoma（HCC）,vasculogenic mimicry formation and human umbilical vein endothelial cells（HUVECs）angiogenesis．Methods MTT assay was performed to detect the proliferation of SMMC-7721 and Hep3B cells．The effects of SUZ12 on the angiogenesis of HCC cells and HUVECs cells were studied by in vitro angiogenesis experiment．Results The result of MTT assay showed that SUZ12 knockdown or overexpression in HCC cells had no significant effect on the proliferation of HCC cells．We found that when HCC cells with low SUZ12 expression were co-cultured with HUVECs cells,the formation of vasculogenic mimicry tubular structures in HCC cells increased．In addition,we also found that after the culture supernatant of HCC cells in the SUZ12 knockdown group was used to culture HUVECs cells,the formation of vasculogenic mimicry tubular structures in HUVECs cells also increased significantly．Conclusions SUZ12 has no effect on the proliferation of HCC cells,but it can inhibit the formation of vasculogenic mimicry tubular structures in HCC cells and HUVECs cells．These results suggest that SUZ12 plays a role in cancer inhibition by regulating the angiogenesis of HCC cells and HUVECs cells．