表皮生长因子受体家族特点及与肿瘤关系的研究进展

人类表皮生长因子受体(human epidermal growth factor receptor,HER)家族属于酪氨酸激酶Ⅰ亚族的跨膜蛋白受体家族，包括4个成员，分别是HER1(EGFR/ErbB1)、HER2(ErbB2)、HER3(ErbB3)和HER4(ErbB4)，由erb基因编码，在细胞生长、增殖及凋亡等活动中起到重要的调节作用。同时，作为原癌基因家族，HER家族在许多人类肿瘤中异常激活及过度表达，是这些肿瘤发生和发展的关键因素，与多种肿瘤的临床病理特征及肿瘤患者的不良预后密切相关。HER家族一直是肿瘤领域基础实验研究和临床诊治研究的热点之一，以其为靶点的综合抗肿瘤治疗方案获得了良好的临床疗效。本文通过查阅对有关HER家族及其与肿瘤关系的相关文献，总结人表皮生长因子受体家族特点及其在肿瘤发生发展、生物靶向诊治方面的最新研究进展。相信随着HER家族临床研究成果的不断丰富及分子生物学技术的快速发展可为肿瘤临床诊治提供新的思路和帮助。     

Interleukin-36 alpha levels are elevated in the serum and cerebrospinal fluid of patients with neuromyelitis optica spectrum disorder and correlate with disease activity

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory neurological disease characterized by longitudinally extensive transverse myelitis (LETM) and optic neuritis. Interleukin (IL)-36 is a novel cytokine of the IL-1 family that is involved in the development of inflammatory diseases. The aim of this study was to investigate the role of IL-36α in NMOSD. We retrospectively collected 73 patients, who fulfilled the 2015 criteria for NMOSD diagnosis and were admitted to the Department of Neurology of the First Hospital of Jilin University from 2015 to 2016. Fifty age and gender matched patients with non-inflammatory neurological disorders (ONNDs) were collected in the same period and served as controls. Neurological function was evaluated by the expanded disability status scale (EDSS). All participants were assessed for the annual relapse rate (ARR). Blood and cerebrospinal fluid (CSF) samples were obtained and the levels of IL-36α in the serum and CSF were analyzed by enzyme-linked immunosorbent assay (ELISA). IL-36α levels in serum and CSF were found to be significantly increased in patients with NMOSD compared to those in the controls. Furthermore, IL-36α levels in both serum and CSF were positively correlated with the EDSS score. CSF IL-36α levels were positively correlated with CSF leukocyte counts, protein concentration and immunoglobulin IgG. Our results suggest that IL-36α may be a novel biomarker for monitoring disease severity in NMOSD.     

白头翁汤灌肠联合口服美沙拉嗪对溃疡性结肠炎的疗效及其机制的研究

目的 研究白头翁汤灌肠联合口服美沙拉嗪对溃疡性结肠炎的疗效及其机制。方法 将110例溃疡性结肠炎患者随机分为观察组和对照组,均为55例,对照组口服美沙拉嗪,观察组白头翁汤灌肠联合口服美沙拉嗪,观察2组患者的疗效以及治疗前后的炎症因子(TNF-α、IL-6、IL-8、IL-10)以及CD4+CD25+Treg细胞占CD4比例的变化。结果 治疗后观察组的临床有效率为96.36%,显著高于对照组的78.18%(P<0.05);治疗后2组患者血清中TNF-α、IL-6、IL-8水平均低于治疗前(P<0.05),且治疗后观察组TNF-α、 IL-6、 IL-8降低明显优于对照组(P<0.05);治疗后2组患者IL-10、CD4+CD25+Treg/CD4较治疗前均明显升高,差异有统计学意义( P<0.05),且观察组IL-10、CD4+CD25+Treg/CD4升高明显优于对照组(P<0.05)。结论 采用白头翁汤联合口服美沙拉嗪治疗溃疡性结肠炎有显著的疗效,其作用机制可能是降低血清中TNF-α、IL-6、IL-8,提高IL-10,提高CD4+CD25+Treg细胞的比例,从而维持机体内免疫平衡,有效降低肠道炎症反应。     

钠离子通道相关基因突变致儿童癫痫 17例的临床特征及致病基因谱

目的 探讨钠离子通道相关基因突变致儿童癫痫的临床特征及致病基因谱.方法 收集2017年6月至2019年10月徐州医科大学附属医院靶向捕获二代测序发现钠离子通道相关基因可疑致病性突变,并经Sanger测序验证基因突变来源的儿童癫痫17例,进行回顾性总结和分析.结果 共检测到5种不同类型突变,其中SCN1A 8例(47.06％),SCN2A 5例(29.41％),SCN1B 1例(5.88％),SCN8A 1例(5.88％),SCN9A 2例(11.77％);涉及多种突变类型,其中错义突变14例(82.36％),非编码区突变1例(5.88％),剪接位点突变1例(5.88％),移码突变1例(5.88％);3种已报道的致病突变,14种新发现的突变;9例携带遗传性突变,8例新生突变;涉及多种癫痫综合征,对药物的反应也不同.结论 癫痫的发生与编码电压门控钠离子通道的基因突变密切相关,轻者表型如热性惊厥,预后较好,重者表型如Dravet综合征等癫痫性脑病可导致病儿死亡.钠离子通道基因突变以SCN1A基因突变多见,突变类型以错义突变为主.     

铁死亡相关蛋白SLC7A11与miRNA-375在子宫内膜癌组织中的表达及其临床意义

目的:探究子宫内膜癌组织中溶质载体家族7成员11（solute carrier family 7,member 11,SLC7A11）、微小RNA-375（microRNA-375,miRNA-375）的表达水平及其临床意义。方法:选取2017年01月至2019年01月徐州市中心医院40例子宫内膜癌患者肿瘤组织、30例子宫肌瘤患者增殖期正常子宫内膜组织作为研究对象。采用实时荧光定量PCR（real-time fluorescence quantitative PCR,qRT-PCR）技术检测组织中miRNA-375、SLC7A11 mRNA表达水平,采用免疫组织化学染色法检测组织中SLC7A11蛋白表达水平,分析两者在子宫内膜癌组织中表达的相关性与子宫内膜癌患者临床病理学特征的关系及其对患者预后的影响。结果:子宫内膜癌组织中miRNA-375表达水平明显低于正常子宫内膜组织（P＜0.05）,子宫内膜癌组织中SLC7A11 mRNA表达水平及SLC7A11蛋白阳性表达率均明显高于正常子宫内膜组织（P＜0.05）。子宫内膜癌组织中miRNA-375表达水平的降低与FIGO分期升高、淋巴结转移、肌层浸润程度加深及HE4、NLR、SII升高有关（P＜0.05）,SLC7A11蛋白表达的升高与BMI增加、FIGO分期增加、肌层浸润程度加深及CA125、HE4升高有关（P＜0.05）。子宫内膜癌组织中miRNA-375与SLC7A11蛋白、SLC7A11 mRNA表达水平均呈负相关（P＜0.05）。子宫内膜癌组织中miRNA-375低表达患者5年累积生存率低于miRNA-375高表达患者（P＜0.05）,子宫内膜癌组织中SLC7A11蛋白阳性表达患者5年累积生存率低于SLC7A11蛋白阴性表达患者（P＜0.05）。子宫内膜癌组织中miRNA-375、SLC7A11 mRNA表达水平单独及联合检测对子宫内膜癌患者不良预后诊断的曲线下面积分别为0.764、0.859、0.875,敏感性分别为0.767、0.700、0.833,特异性分别为0.775、0.950、0.900,单项指标miRNA-375敏感性最高,SLC7A11 mRNA特异性最高,二者联合时特异性和敏感性均较高。结论:子宫内膜癌组织中miRNA-375表达下调、SLC7A11蛋白表达上调,两者表达呈负相关,且与患者不良预后相关;二者可能与EC的发生发展有关,对EC的诊疗及预后评估具有一定价值。     

转移病灶再活检对乳腺癌患者的临床意义

目的 比较雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER-2）在乳腺癌原发灶及转移灶中的表达差异,探讨这种差异对乳腺癌患者预后的影响。方法 回顾性分析2012年1月—2018年12月就诊于徐州医科大学附属医院的188例乳腺癌转移灶再活检患者的病历资料。分别分析ER、PR和HER-2在原发灶及对应转移灶中的表达情况、转移部位的变化分布及其表达差异对预后的影响。结果 ER、PR和HER-2表达在原发灶和转移灶中的变化率分别为21.8%、33.5%和24.5%,其中PR和HER-2表达的差异均有统计学意义（P<0.05）,ER表达的差异无统计学意义（P=0.117）。原发灶和转移灶中ER、PR表达不一致患者与表达一致患者的无进展生存期（PFS）比较,差异均有统计学意义（P<0.05）,原发灶和转移灶中HER-2表达不一致患者与表达一致患者的PFS比较,差异无统计学意义（P=0.236）。结论 乳腺癌患者原发灶和转移灶中ER、PR和HER-2表达存在差异,且激素受体的表达变化能够影响患者的预后。检测乳腺癌转移灶中ER、PR和HER-2的表达,对个体化治疗策略的制定以及预后判断有重要的临床意义。     

Medication-Related Acute Care Admission and Inappropriate Polypharmacy of Nursing Home Residents

ObjectivesTo evaluate the prevalence of medication-related admissions (MRAs) and their association with potentially inappropriate medications (PIMs) used by nursing home residents admitted to the geriatric center of a tertiary hospital.DesignCross-sectional study.Setting and ParticipantsOlder patients admitted from nursing homes to the geriatric center of the Seoul National University Bundang Hospital who had undergone comprehensive geriatric assessment from January 1, 2016, to December 31, 2020.MethodsMRAs were determined and verified using a previously described MRA adjudication guide. The PIMs in the preadmission medication lists were identified according to each of the following criteria (as well as the combined criteria), the Beers, NORGEP-NH, STOPP/START-NH, and STOPPFrail criteria. Medication use factors associated with MRAs were analyzed using multivariate logistic regression.ResultsAmong the 304 acute care admissions, 32.2% were MRAs. The main cause of MRAs was acute kidney injury related with use of renin-angiotensin system inhibitors. Approximately 81% of the patients used at least 1 PIM according to the combined criteria. The use of 1 or more PIMs, renin-angiotensin system inhibitors, diuretics, nonsteroidal anti-inflammatory drugs, and benzodiazepines was significantly associated with MRAs. The combined criteria were able to predict MRAs better than the individual criteria.Conclusions and ImplicationsApproximately one-third of acute admissions of nursing home residents may be MRAs. Interventions for the optimal use of medication among nursing home residents are needed.