长链非编码RNA反义RNA 1靶向微小RNA-501-3p对食管癌细胞恶性生物学行为影响的实验研究

目的探讨长链非编码RNA(lncRNA)胸腺生成素反义RNA 1(TMPO-AS1)对食管癌细胞恶性生物学行为的影响及其机制。方法2016年6月至2019年12月,实时荧光定量聚合酶链反应(RT-qPCR)检测20例食管癌组织和癌旁组织中lncRNA TMPO-AS1和微小RNA(miR)-501-3p的水平,食管癌Eca109细胞分为lncRNA TMPO-AS1干扰组(转染si-NC和si-TMPO-AS1);miR-501-3p过表达组(转染miR-NC和miR-501-3p);lncRNA TMPO-AS1过表达组(转染pcDNA和pcDNA-TMPO-AS1);lncRNA TMPO-AS1和miR-501-3p共抑制组(转染si-TMPO-AS1+anti-miR-NC和si-TMPO-AS1+anti-miR-501-3p)。噻唑蓝(MTT)法、流式细胞术和Transwell实验分别检测食管癌Eca109细胞增殖、凋亡率、细胞迁移和侵袭能力,蛋白质印迹法(Western blot)检测相关蛋白水平,双荧光素酶报告系统验证lncRNA TMPO-AS1与miR-501-3p的调控关系。两组间比较采用独立样本t检验,多组间比较采用单因素方差进行分析。结果食管癌组织组中的lncRNA TMPO-AS1水平(2.64±0.26)高于癌旁组织(1.00±0.09,t=26.657,P<0.05),miR-501-3p水平(0.44±0.04)低于癌旁组织(1.00±0.07,t=31.063,P<0.05);干扰lncRNA TMPO-AS1的Eca109细胞24 h增殖(0.36±0.03)低于si-NC组(0.39±0.03,t=2.121,P<0.05),48 h增殖(0.45±0.04)低于si-NC组(0.75±0.07,t=11.163,P<0.05),72 h增殖(0.57±0.05)低于si-NC组(1.16±0.09,t=17.191,P<0.05),迁移细胞数[(54.14±5.65)个]低于si-NC组[(113.02±9.87)个,t=15.531,P<0.05],侵袭细胞数[(47.69±5.01)个]低于si-NC组[(96.32±9.88)个,t=13.169,P<0.05],细胞凋亡率[(22.15±2.22)%]高于si-NC组[(6.98±0.69)%,t=19.576,P<0.05];过表达miR-501-3p的Eca109细胞48 h增殖(0.51±0.05)低于miR-NC组(0.77±0.07,t=9.067,P<0.05),72 h增殖(0.65±0.06)低于miR-NC组(1.15±0.09,t=13.867,P<0.05),迁移细胞数[(61.23±6.33)个]低于miR-NC组[(115.25±9.25)个,t=14.458,P<0.05],侵袭细胞数[(53.14±5.33)]低于miR-NC组[(98.32±8.47)个,t=13.543,P<0.05],细胞凋亡[(19.58±1.74)%]高于miR-NC组[(7.23±0.77)%,t=19.471,P<0.05],差异均有统计学意义。结论lncRNA TMPO-AS1通过靶向miR-501-3p促进食管癌细胞的恶性生物学行为,可被视为食管癌患者的潜在治疗靶标。     

呼气末正压对不同血容量状态猪颅高压模型颅内压和脑氧代谢影响的实验研究

目的观察不同血容量状态下颅高压的急性呼吸窘迫综合征(ARDS)猪模型,增加呼气末正压(PEEP)后,其血流动力学状态、颅内压(ICP)及脑氧分压(PtiO2)的变化。方法选取雄性14~16月龄巴马小型猪12头,随机数字表法随机分成低血容量组和正常血容量组。建立ARDS和颅高压模型。自5 cmH2O(1 cmH2O=0.098 kPa)水平逐步增加PEEP 5 cmH2O,直至25 cmH2O。采用重复测量的方差分析,并应用Sidak法进行多重比较和P值的校正。结果随着PEEP逐渐增加,正常血容量组ICP逐渐升高,而低血容量组ICP逐渐下降;当PEEP在5、10、15 cmH2O时,两组间ICP值分别为(25.83±1.47)mmHg(1 mmHg=0.133 kPa)比(27.00±1.63)mmHg、(27.33±1.75)mmHg比(27.67±2.21)mmHg、(28.83±1.72)mmHg比(27.5±2.06)mmHg,差异均无统计学意义(t=0.793、0.227、0.906,P值均>0.05);当PEEP在20、25 cmH2O时,两组间ICP值分别为(31.33±2.07)mmHg比(26.5±3.35)mmHg、(31.67±2.94)mmHg比(25.83±3.67)mmHg,差异均有统计学意义(t=3.284、3.964,P值均<0.01)。随着PEEP逐渐增加,两组PtiO2均逐渐下降,其中低血容量组下降更明显;在各PEEP水平时,两组间PtiO2值分别为(19.83±2.64)mmHg比(14.33±3.50)mmHg、(18.67±2.50)mmHg比(12.33±3.88)mmHg、(17.67±3.88)mmHg比(10.67±3.88)mmHg、(15.33±2.34)mmHg比(9.17±3.54)mmHg、(13.67±3.61)mmHg比(6.67±2.73)mmHg,差异均有统计学意义(t=2.333、3.319、3.668、3.231、3.668,P值均<0.05)。结论PEEP对血流动力学、颅内压、脑代谢作用受不同容量状态的影响。低血容量状态下,PEEP逐渐上升,其心输出量、血压和PtiO2下降更明显。     

TLR9 Deficiency in B Cells Promotes Immune Tolerance via Interleukin-10 in a Type 1 Diabetes Mouse Model

Toll-like receptor 9 (TLR9) is highly expressed in B cells, and B cells are important in the pathogenesis of type 1 diabetes (T1D) development. However, the intrinsic effect of TLR9 in B cells on β-cell autoimmunity is not known. To fill this knowledge gap, we generated NOD mice with a B-cell–specific deficiency of TLR9 (TLR9^fl/fl/CD19-Cre+ NOD). The B-cell–specific deletion of TLR9 resulted in near-complete protection from T1D development. Diabetes protection was accompanied by an increased proportion of interleukin-10 (IL-10)–producing B cells. We also found that TLR9-deficient B cells were hyporesponsive to both innate and adaptive immune stimuli. This suggested that TLR9 in B cells modulates T1D susceptibility in NOD mice by changing the frequency and function of IL-10–producing B cells. Molecular analysis revealed a network of TLR9 with matrix metalloproteinases, tissue inhibitor of metalloproteinase-1, and CD40, all of which are interconnected with IL-10. Our study has highlighted an important connection of an innate immune molecule in B cells to the immunopathogenesis of T1D. Thus, targeting the TLR9 pathway, specifically in B cells, may provide a novel therapeutic strategy for T1D treatment.     

Annual review of Chinese Journal of Traumatology 2020

The year 2020 is an extremely unusual year.The world lost more than one million lives due to the attack of COVID-19.Economic production has been greatly reduced,and daily activities are largely restricted.Luckily the work of Chinese Journal of Traumatology(CJTEE)has not been adversely affected.2020 is a harvest year for the journal,which(1)was included in the high-quality academic journals by China Association for Science and Technology;(2)cover of each issue is newly designed;(3)submission increased by about 60%with more countries and regions covered;(4)usage in the ScienceDirect database exceeded a million;(5)the CiteScore rises to more than 2.0 the first time.This study reviewed the articles published in the year 2020 by CJTEE.     

进展期胃癌病人发生腹腔脱落细胞学阳性的危险因素分析及风险预测评分模型建立

目的探讨影响进展期胃癌病人腹腔脱落细胞学阳性的危险因素,建立腹腔脱落细胞学阳性的风险预测评分模型。方法收集分析河北医科大学第四医院2012年2月至2018年12月期间开展的一项前瞻性、多中心、开放、随机对照Ⅲ期临床试验(NCT01516944)中的225例进展期胃癌病人临床病理资料,所有病人术中均行腹腔镜探查及腹腔脱落细胞学检查(500 mL生理盐水冲洗),检测腹腔脱落癌细胞的阳性率,分析影响进展期胃癌病人腹腔脱落细胞学阳性的临床病理因素。结果225例胃癌病人腹腔冲洗液中脱落细胞学阳性者32例,阳性率为14.22%。单因素分析结果显示,病人的年龄、肿瘤直径,浸润深度(cT分期)、组织学类型、肿瘤部位、淋巴结转移情况(cN分期)以及血清中肿瘤标志物癌胚抗原(CEA)、癌抗原72-4(CA72-4)、癌抗原19-9(CA19-9)的表达情况均是发生腹腔脱落细胞学阳性的危险因素(P<0.05);多因素分析显示,影响进展期胃癌病人发生腹腔脱落细胞学阳性的独立危险因素为:肿瘤浸润深度为cT4a~cT4b期[OR=20.954,95%置信区间(CI):(1.610,12.651),P=0.020];CEA表达阳性[OR=7.695,95%CI(1.307,8.669),P=0.001];CA72-4表达阳性[OR=7.551,95%CI(2.255,25.283),P=0.001];CA19-9表达阳性[OR=3.317,95%CI(1.011,10.883),P=0.048]。根据多因素Logistic回归结果建立风险预测方程:logit(p)=-7.088+3.042×X1(肿瘤浸润深度)+2.041×X2(CEA)+1.199×X3(CA19-9)+2.022×X4(CA72-4),采用Hosmer-Lemeshow检验检测回归方程的拟合优度(P=0.614)。采用受试者工作特征(ROC)曲线评价回归方程的区分度,曲线下面积为0.844[95%CI(0.751,0.936),P=0.000]。病人术前肿瘤浸润深度为cT4a~cT4b期、血清中肿瘤标志物CEA、CA72-4、CA19-9表达阳性其发生腹腔脱落细胞学阳性风险评分分别为3、2、2、1分,病人发生腹腔脱落细胞学阳性的概率:评分≥4分者为19.44%,评分<4分者为4.94%。结论进展期胃癌病人CEA、CA72-4、CA19-9水平升高以及浸润程度为cT4a~cT4b期则提示可能存在腹腔脱落细胞学阳性。同时联合上述指标建立风险评分模型,能够有效预测进展期胃癌病例中发生腹腔脱落细胞学阳性的高风险病人。     

紫外线致皮肤光老化及光癌变机制的研究进展

日光的累计照射可加速皮肤老化与癌变,使皮肤的生物学及临床反应发生改变,包括急性损伤(日晒伤)和慢性损伤(光老化、光癌变或色素沉着等)。文章概述了近年来紫外线对皮肤光老化及光癌变影响的研究进展,揭示光老化和光致癌机制是通过紫外线照射产生活性氧和DNA损伤,以及由此引起的细胞损伤、炎症、免疫抑制、细胞外基质重塑及血管生成改变所致,为临床防治光老化和光癌变提供帮助。     

Systematic review of outcomes and meta-analysis of risk factors for prognosis after liver resection for hepatocellular carcinoma without cirrhosis

Long-term overall survival (OS) after liver resection for non-cirrhotic hepatocellular carcinoma (NCHCC) has been reported recently. The aim of this study was to review outcomes systematically and analyze risk factors for survival after surgical resection for HCC without cirrhosis. A literature search was performed of the PubMed and Embase databases for papers published between January 1995 and October 2012, which focused on hepatic resection for HCC without underlying cirrhosis. Cochrane systematic review methodology was used for this review. Outcomes were OS, operative mortality and disease-free survival (DFS). Pooled hazard ratios (HR) were calculated using the random effects model for parameters considered as potential prognostic factors. Totally, 26 retrospective case series were eligible for inclusion. The 1-, 3- and 5-year OS rate after surgical resection of NCHCC ranged from 62% to 100%, 46.3%–78.0%, and 30%–64%, respectively. The corresponding DFS rates ranged from 48.7% to 84%, 31.0%–66.0%, and 24.0%–58.0%, respectively. Five variables were related to poor survival: multiple tumors (HR 1.68, 95%CI 1.25–2.11); larger tumor size (HR 2.66, 95%CI 1.69–3.63); non-clear resection margin (R0 resection) (HR 3.52, 95%CI 1.63–5.42); poor tumor stage (HR 2.61, 95%CI 1.64–3.58); and invasion of the lymphatic vessels (HR 4.85, 95%CI 2.67–7.02). In sum, hepatic resection provides excellent OS rates for patients with NCHCC, and results have tended to improve recently. Risk factors for poor prognosis comprise multiple tumors, lager tumor size, non-R0 resection and invasion of the lymphatic vessels.