简介:摘要老年男性右肺上叶3.5 cm×2.5 cm大小肿块,显微镜下示肿瘤由2种成分构成,主要以小到中等、蓝圆细胞片巢状分布为主,胞质较少,核呈泡状,核仁明显,另一部分肿瘤细胞透亮,2部分可见过渡,均异型性显著,核分裂象易见。免疫组织化学显示INI1(SMARCB1)缺失,BRG1(SMARCA4)未缺失,广谱细胞角蛋白(CKpan)、p40、细胞角蛋白(CK)5/6、p63、突触素均阳性,甲状腺转录因子1灶区阳性,CK7少量阳性,生长抑素受体2个别细胞阳性,CD56个别细胞阳性,Ki-67阳性指数50%。基因检测示INI1(SMARCB1)拷贝数异常以及EGFR、DIS3、BRIP1、HMCN1、PLCG2、RAD21、TSC2基因突变,病理诊断为INI1(SMARCB1)缺失低分化癌伴有鳞、腺及神经内分泌免疫表型。INI1(SMARCB1)蛋白是染色体重塑相关多聚体蛋白SWI/SNF的一个亚单位,SWI/SNF复合体缺失的未分化癌对传统化疗药物不敏感、预后差,但组蛋白甲基转移酶抑制剂治疗可能有效,而本例极易与低分化鳞癌、腺鳞癌混淆,故将INI1(SMARCB1)缺失的肿瘤识别出来十分必要。
简介:摘要颅内黏液样间叶性肿瘤是一种罕见的肿瘤,分子遗传学伴EWSR1与CREB家族基因融合。本文报道1例9岁男性患儿,小脑占位性病变,肿瘤结节状生长,界限清楚,肿瘤细胞椭圆形、梭形或星芒状,疏密不等,大部分呈条索状或疏松网状分布于黏液性间质中,间质内可见“石棉样”纤维,局灶细胞较丰富,呈片状排列。免疫组织化学结果:波形蛋白阳性,结蛋白及CD68部分阳性,上皮细胞膜抗原及CD99弱阳性,胶质纤维酸性蛋白、Olig2、S-100蛋白、平滑肌肌动蛋白、p63、CD34等均阴性,p53野生型表达,热点区Ki-67阳性指数约20%。分子表型:荧光原位杂交检测到EWSR1基因分离,二代测序检测出EWSR1-CREB1及SELENOW-EWSR1融合基因。病理诊断为伴EWSR1-CREB1融合的颅内黏液样间叶性肿瘤。术后7个月,患者状态良好,无复发及转移。诊断时应与脑膜瘤、胶质瘤、伴EWSR1-CREB家族基因融合的其他肿瘤及骨外黏液样软骨肉瘤等形态相似的肿瘤鉴别。
简介:摘要患儿 男,3岁9月龄,以“排稀便10个月、间断抽搐4个月”就诊,经乳糜泻抗体、人类白细胞抗原(HLA)-DQ基因检测、十二指肠病理活检明确诊断为乳糜泻,予去麦麸类饮食以及对症营养治疗后好转。随访过程中出现多饮多尿,查血糖明显升高,尿糖、尿酮体阳性,诊断为乳糜泻合并1型糖尿病,给予对症补充胰岛素治疗。随访6年患儿血糖控制平稳,生长发育正常。
简介:AbstractBackground:Emerging evidence indicates that the sineoculis homeobox homolog 1-eyes absent homolog 1 (SIX1-EYA1) transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the expression of genes involved in different biological processes, such as cell-cycle progression and metastasis. However, the roles of the SIX1-EYA1 transcriptional complex and its targets in colorectal cancer (CRC) are still being investigated. This study aimed to investigate the roles of SIX1-EYA1 in the pathogenesis of CRC, to screen inhibitors disrupting the SIX1-EYA1 interaction and to evaluate the efficiency of small molecules in the inhibition of CRC cell growth.Methods:Real-time quantitative polymerase chain reaction and western blotting were performed to examine gene and protein levels in CRC cells and clinical tissues (collected from CRC patients who underwent surgery in the Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, between 2016 and 2018, n = 24). In vivo immunoprecipitation and in vitro pulldown assays were carried out to determine SIX1-EYA1 interaction. Cell proliferation, cell survival, and cell invasion were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clonogenic assay, and Boyden chamber assay, respectively. The Amplified Luminescent Proximity Homogeneous Assay Screen (AlphaScreen) method was used to obtain small molecules that specifically disrupted SIX1-EYA1 interaction. CRC cells harboring different levels of SIX1/EYA1 were injected into nude mice to establish tumor xenografts, and small molecules were also injected into mice to evaluate their efficiency to inhibit tumor growth.Results:Both SIX1 and EYA1 were overexpressed in CRC cancerous tissues (for SIX1, 7.47 ± 3.54 vs.1.88 ± 0.35, t = 4.92, P = 0.008; for EYA1, 7.61 ± 2.03 vs. 2.22 ± 0.45, t = 6.73, P = 0.005). The SIX1/EYA1 complex could mediate the expression of two important genes including cyclin A1 (CCNA1) and transforming growth factor beta 1 (TGFB1) by binding to the myocyte enhancer factor 3 consensus. Knockdown of both SIX1 and EYA1 could decrease cell proliferation, cell invasion, tumor growth, and in vivo tumor growth (all P < 0.01). Two small molecules, NSC0191 and NSC0933, were obtained using AlphaScreen and they could significantly inhibit the SIX1-EYA1 interaction with a half-maximal inhibitory concentration (IC50) of 12.60 ± 1.15 μmol/L and 83.43 ± 7.24 μmol/L, respectively. Administration of these two compounds could significantly repress the expression of CCNA1 and TGFB1 and inhibit the growth of CRC cells in vitro and in vivo.Conclusions:Overexpression of the SIX1/EYA1 complex transactivated the expression of CCNA1 and TGFB1, causing the pathogenesis of CRC. Pharmacological inhibition of the SIX1-EYA1 interaction with NSC0191 and NSC0933 significantly inhibited CRC cell growth by affecting cell-cycle progression and metastasis.
简介:摘要帕金森病(PD)是世界上第二常见的神经退行性疾病,它的发病机制与线粒体功能障碍、氧化应激反应以及钙稳态失衡有关。近年来,PD与Ca2+的关系成为研究热点,钙稳态失衡可通过不同的途径导致PD。细胞内Ca2+水平取决于钙库操纵性钙内流(SOCE),而SOCE由钙释放激活钙通道调节分子1(Orai1)、基质相互作用分子1(STIM1)及瞬时受体电位通道1(TRPC1)相互作用组成的功能复合体调节。常见的PD神经毒素可通过降低Orai1-STIM1-TRPC1复合体功能,损伤SOCE及其下游的信号通路选择性损伤多巴胺能神经元,并且Orai1-STIM1-TRPC1复合体可能通过作用于小胶质细胞以及内质网调控神经炎症、自噬现象以影响PD的发生发展。因此恢复Orai1-STIM1-TRPC1复合体表达及功能,维持钙稳态可能成为PD的有效治疗靶点。
简介:摘要患儿男性,11个月。生后5个月出现发育倒退,随后出现四肢无力和对响声的异常惊吓反应,求医2个月诊断不明,转诊至首都医科大学附属北京儿童医院,发现患儿双眼眼底黄斑樱桃红斑,以此为线索进一步基因分析显示GLB基因出现复合杂合子突变,酶学检查结果显示酸性β-半乳糖苷酶明显低于正常值,确诊GM1型神经节苷脂沉积症。
简介:AbstractBackground:PD-1 and PD-L1 inhibitors have emerged as promising treatments for patients with head and neck squamous cell carcinoma (HNSCC).Methods:Systematic review and meta-analysis of PD-1 and PD-L1 inhibitors in HNSCC. Outcomes: median overall survival (mOS), median progression-free survival (mPFS), Response Evaluation Criteria in Solid Tumors (RECIST) and treatment-related adverse events (TRAEs).Results:Eleven trials reported data on 1088 patients (mean age: 59.9 years, range: 18-90). The total mOS was 7.97 months (range: 6.0-16.5). Mean mPFS for all studies was 2.84 months (range: 1.9-6.5). PD-1 inhibitors had a lower rate of RECIST Progressive Disease than PD-L1 inhibitors (42.61%, 95% confidence interval [CI]: 36.29-49.06 vs. 56.79%, 95% CI: 49.18-64.19, P < 0.001). The rate of TRAEs of any grade (62.7%, 95% CI: 59.8-65.6) did not differ.Conclusions:Meta-analysis shows the efficacy of PD-1 and PD-L1 inhibitors in HNSCC and suggests a possible difference in certain RECIST criterion between PD-1 and PD-L1 inhibitors. Future work to investigate the clinical significance of these findings is warranted.
简介:摘要目的比较H1N1流感病毒疫苗株在MDCK和MDCK-G1细胞中的最佳培养条件、产毒量、病毒滴度和细胞代谢情况。方法通过棋盘法摸索两种细胞的最佳种毒条件,然后比较2株细胞在最佳条件种毒后的血凝滴度、半数组织感染剂量(TCID50)、葡萄糖和乳酸的代谢情况。结果MDCK-G1细胞以感染复数(MOI)=0.001、1 μg/ml TPCK胰酶接种H1N1流感病毒后,72 h时血凝滴度达到峰值(1∶512),病毒滴度为107.4TCID50/ml;MDCK细胞以MOI=0.000 1、1 μg/ml TPCK胰酶接种H1N1流感病毒后,72 h时血凝滴度达到峰值(1∶256),病毒滴度为106.6TCID50/ml。结论MDCK-G1比MDCK细胞更适合流感病毒的增殖。本研究为细胞基质流感疫苗的研究提供了参考数据。
简介:摘要目的探讨恶性胸膜间皮瘤(MPM)组织的Ⅰ型胶原蛋白α1链(COL1A1)和Ⅰ型胶原蛋白α2链(COL1A2)基因的表达水平及临床意义。方法于2020年1月,收集26例MPM患者的MPM组织及相邻的正常胸膜组织,采用定量反转录PCR测定组织中COL1A1和COL1A2基因表达水平,并采用受试者工作特征(ROC)曲线评估两者诊断MPM的效能。通过肿瘤基因组图谱(TCGA)数据库分析COL1A1和COL1A2基因表达与临床病理特征的关系,采用基因表达谱动态分析两者表达水平与MPM患者总生存率(OS)和无疾病进展生存率(DFS)的关系,通过Cox比例风险回归模型探讨影响MPM患者预后的因素。采用TIMER 2.0平台探讨COL1A1和COL1A2基因在MPM中的表达与肿瘤免疫浸润性细胞的关系。结果与正常胸膜组织比较,MPM组织中COL1A1和COL1A2基因表达量明显增加(P<0.01),且两者表达呈正相关(P<0.001);ROC曲线显示,COL1A1和COL1A2表达水平诊断MPM的曲线下面积分别为0.900和0.897。COL1A1基因表达量与MPM患者肿瘤类型有关(P<0.05),COL1A2基因表达量与MPM患者T分期有关(P<0.05)。COL1A1和COL1A2基因表达量与MPM患者OS均有关联(Logrank P<0.05),与DFS的关联均无统计学意义(Logrank P>0.05)。Cox多因素分析结果显示,COL1A1和COL1A2基因高表达及双相混合型MPM患者的死亡风险较高(P<0.05)。TIMER 2.0平台分析结果显示,COL1A1和COL1A2基因在MPM中的表达与巨噬细胞均呈正相关,COL1A2基因在MPM中的表达与中性粒细胞呈负相关(P<0.05)。结论COL1A1和COL1A2基因在MPM组织中高表达,对MPM的诊断、病情预测和预后评估有一定的价值,两者可能共同促进了MPM的发生发展。
简介:摘要目的通过对上海市城、郊区社区卫生服务中心老年就诊居民"1+1+1"签约影响因素的比较分析,为提高签约率及完善"1+1+1"签约政策提供参考。方法本研究采用以中心城区、郊区分层抽样为原则的多中心横断面问卷调查法,于2017年9—11月抽取上海市复旦大学附属中山医院全科定点带教的6家社区卫生服务中心,城区、郊区各3家,对其中574例60岁以上的老年就诊居民进行问卷调查。调查问卷是在课题定性访谈结果的基础上进行设计,包括居民基本情况、健康状况、对"1+1+1"签约知晓及签约情况等。结果574份回收问卷中有效问卷564份,有效率98.25%。其中,城区292例,167例(57.2%)已签约;郊区272例,133例(48.9%)已签约。单因素分析结果显示,自评健康状况、中心就诊次数、中心满意程度、健康知识关注状况、长期服药、首诊意愿、转诊意愿、签约知晓与否对城区居民签约的影响有统计学意义(χ2值分别为13.05、8.51、13.89、10.76、6.26、12.98、24.73、76.77,均P<0.05);年龄、自评健康状况、此次至中心目的、体检情况、患慢性病种类、长期服药、首诊意愿、转诊意愿、签约知晓与否对郊区居民签约的影响有统计学意义(χ2值分别为9.56、14.26、13.83、18.30、18.65、11.96、5.99、5.46、83.44,均P<0.05)。多因素分析结果显示,自评健康状况、"1+1+1"签约知晓情况对城区居民签约的影响有统计学意义(P<0.05);"1+1+1"签约知晓情况、此次至中心目的、体检频率对郊区居民签约的影响有统计学意义(P<0.05)。结论城区居民因关注自身健康和对签约知晓率较高,"1+1+1"签约率高于郊区,建议政府重视郊区社区卫生服务机构"1+1+1"签约制度的建设。
简介:摘要本文报道1例妊娠合并强直性肌营养不良(myotonic dystrophy,DM)1型患者的诊治经过。患者早孕期因偶发心前区钝痛伴盗汗查心肌酶轻度升高,口服药物改善症状后未规律复查。晚孕期出现心肌酶、肝酶及尿蛋白明显异常,心脏、腹部超声提示心脏、脾脏等多发器质性病变。孕36周+5因心力衰竭行剖宫产术,新生儿女,Apgar评分1、5 min均为10分。患者术后出现急性呼吸衰竭、室性二联律及腹泻等症状。神经内科会诊发现双眼埋睫不全、鼓腮力弱和上肢末端肌力减弱。肌肉活检证实DM,基因检测示染色体19q13.3肌营养不良蛋白激酶基因非编码区[CTG]n异常扩增而诊断DM1型。产后随访9个月身体恢复尚可,建议进一步行家系及子代的遗传学分析。