睡眠呼吸障碍与自发性早产的巢式病例对照研究

目的:探讨妊娠晚期睡眠呼吸障碍是否为自发性早产的危险因素。方法:采用巢式病例对照研究,纳入从2018年10月-2019年5月在北京市大兴区人民医院住院妊娠晚期孕妇为研究对象。收集孕妇的相关资料,包括人口学信息、病史信息以及柏林问卷(Berlin Questionnaire,BQ)、匹兹堡睡眠质量指数(Pittsburgh Sleep Quality Index,PSQI)和艾普沃斯嗜睡量表(Epworth Sleepiness Scale,ESS)。依据我国早产临床诊断与治疗指南(2014)诊断为自发性早产者为自发性早产组(46例),无早产等合并症的足月产孕妇为足月产组(407例)。比较2组孕妇的一般情况、睡眠呼吸障碍问卷评分等相关因素,并分析可能影响自发性早产的独立危险因素。结果:自发性早产组孕妇的年龄、孕前BMI、既往流产次数及早产史均高于足月分娩组,受教育程度低于足月分娩组,差异均有统计学意义(均P<0.05)。自发性早产组PSQI总分和BQ阳性率高于足月分娩组,差异均有统计学意义(均P<0.05)。Logistic回归分析显示在校正可能影响自发性早产的混杂因素后,BQ阳性孕妇发生自发性早产的风险约是BQ阴性孕妇的2.61倍(OR=2.61,95%CI:1.21~5.64,P=0.015)。结论:妊娠晚期具有阻塞性睡眠呼吸暂停高风险的孕妇发生自发性早产的可能性较高。     

白芍对酒精性肝损伤肝阴虚证的保护功效和机制

目的研究白芍对小鼠酒精性肝损伤肝阴虚证的保护功效和机制。方法将ICR小鼠随机分为空白组、模型组、一贯煎组、白芍组,每组10只,除空白组外,用Lieber-DeCarli酒精液体饲料加甲状腺激素灌胃制备小鼠酒精性肝损伤肝阴虚证模型。造模期第1天开始给药,一贯煎组灌胃一贯煎水提液9.07 g/kg,白芍组灌胃白芍水提液4.3 g/kg,空白组和模型组灌胃等量生理盐水。28 d后观察各组小鼠状态,测定体重、体温、心率,测定血清及肝组织转氨酶活性、细胞因子水平、乙醇及脂肪代谢相关酶活性、抗氧化酶活性并取肝脏进行冰冻油红、HE病理切片检查。结果与空白组相比,模型组小鼠体重明显减轻,体温升高,心率加快,且出现毛发无光泽、疲倦易困、烦躁易怒等症状;血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)、总胆固醇(TC)、环磷酸腺苷(cAMP)水平及肝组织丙二醛(MDA)、细胞色素P450同工酶E1(CYP2E1)、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)水平明显升高;血清中环磷酸鸟苷(cGMP)水平及肝组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、乙醇脱氢酶(ADH)、乙醛脱氢酶2(ALDH2)、白细胞介素10(IL-10)、白细胞介素1Ra(IL-1Ra)水平明显降低;肝脏出现脂质沉积及肝细胞坏死情况。与模型组相比,白芍组小鼠血清中ALT、AST、TG、TC、cAMP水平均明显降低(P<0.05),cGMP水平明显升高(P<0.05);肝组织中CYP2E1、TNF-α、IL-1β、IL-6水平明显降低(P<0.05),SOD、CAT、ADH、ALDH2、IL-10、IL-1Ra水平明显升高(P<0.05);肝组织脂质占比显著降低(P<0.05),肝细胞坏死程度改善。结论白芍具有明显的保护酒精性肝损伤肝阴虚证的作用,其机制与调节cAMP/cGMP水平及细胞因子水平、使肝细胞功能与代谢恢复平衡、增强肝组织中乙醇代谢关键酶及抗氧化酶活性、同时抑制脂质过氧化反应、减少脂质沉积有关。     

基于黄酮类成分含量构成特征和体外抗病毒活性的不同产地黄芩的质-效评价研究

目的:评价黄芩道地药材与非道地药材中主要黄酮类成分含量构成特征及其抗病毒活性,以探讨黄芩药材的质-效关系及药效物质基础。方法:制备8批不同产地黄芩(S1~S8)的水提物冻干粉,采用超高效液相色谱法测定水提物中黄芩苷、汉黄芩苷、黄芩素、汉黄芩素等4种黄酮类成分的含量并计算其含量构成比。按不同产地黄芩的黄酮类成分含量构成比,制备上述4种成分混合物作为对应的黄酮类成分模拟样品(E1~E8)。以利巴韦林为阳性对照,采用MTT法和细胞病变程度法,考察8批黄芩水提物样品及其对应的模拟样品对人喉癌细胞Hep-2的半数有毒浓度(TD50)和对呼吸道合胞病毒(RSV)的半数抑制浓度(IC50),并计算治疗指数(TI)。采用SPSS 17.0软件对黄芩苷、汉黄芩苷、黄芩素、汉黄芩素含量与其抗RSV活性(IC50值)进行Pearson相关性分析。结果:样品S4(产地为河北承德)的黄芩苷、汉黄芩苷含量最高,样品S6(产地为内蒙古-2)的黄芩素、汉黄芩素含量最高;上述4种成分含量最低的分别为样品S6、S6、S7(产地为北京)、S4。样品S4中黄酮苷类成分含量较高,相应的苷元类成分含量较低,其黄芩苷、汉黄芩苷、黄芩素、汉黄芩素的含量构成比为1∶0.224∶0.111∶0.013;样品S6中黄酮苷类成分含量较低,相应的苷元类成分含量较高,上述4种成分的含量构成比为1∶0.241∶0.713∶0.106。不同产地黄芩水提物对Hep-2细胞的TC50均高于50μg/mL,对RSV的IC50为11.11~51.74μg/m L,TI为1.86~5.20;其对应的黄酮类成分模拟样品的TC50为23.11~52.23μg/mL,对RSV的IC50为4.87~14.61μg/mL,TI为1.85~4.75。道地产区(河北承德)黄芩(S4)的水提物及其对应模拟样品(E4)的抗RSV作用最强。相关性分析显示,4种黄酮类成分的含量与其抗病毒活性的相关系数均小于0.5,两者无显著相关性。结论:当黄芩中4种主要黄酮类成分的含量构成比为1∶0.224∶0.111∶0.013时,其对RSV的抑制作用较强。道地产区黄芩样品具有较优的黄酮类成分构成特征,该特征可能是道地药材发挥最佳抗病毒疗效的重要物质基础。     

SMYD3 promotes implant metastasis of ovarian cancer via H3K4 trimethylation of integrin promoters

Detachment of cancer cells from the primary tumor and formation of spheroids in ascites is required for implantation metastasis in epithelial ovarian cancer (EOC), but the underlying mechanism of this process has not been thoroughly elucidated. To mimic this process, ovarian cancer cells were grown in 3D and 2D culture. Hey and OVCA433 spheroids exhibited decreased cell proliferation and enhanced adhesion and invasion. SMYD3 expression was elevated in ovarian carcinoma spheroids in association with increased H3K4 methylation. Depletion of SMYD3 by transient siRNA, stable shRNA knockdown and the SMYD3 inhibitor BCI-121 all decreased spheroid invasion and adhesion. Gene expression arrays revealed downregulation of integrin family members. Inhibition assays confirmed that invasion and adhesion of spheroids are mediated by ITGB6 and ITGAM. SMYD3-deficient cells regained the ability to invade and adhere after forced overexpression of SMYD3, ITGB6 and ITGAM. However, this biological ability was not restored by forced overexpression of SMYD3 in ITGB6- and/or ITGAM-deficient cancer cells. SMYD3 and H3K4me3 binding at the ITGB6 and ITGAM promoters was increased in spheroids compared to that in monolayer cells, and the binding was decreased when SMYD3 expression was inhibited, consistent with the expression changes in integrins. SMYD3 expression and integrin-mediated adhesion were also activated in an intraperitoneal xenograft model and in EOC patient spheroids. In vivo, SMYD3 knockdown inhibited tumor metastasis and reduced ascites volume in both the intraperitoneal xenograft model and a PDX model. Overall, our results suggest that the SMYD3-H3K4me3-integrin pathway plays a crucial role in ovarian cancer metastasis to the peritoneal surface.     

Relationship between tRNA-derived fragments and human cancers

tRNA-derived fragments, a class of small noncoding RNAs (sncRNAs), have been identified in numerous studies in recent years. tRNA-derived fragments are classified into two main groups, including tRNA halves (tiRNAs) and tRNA-derived small RNA fragments (tRFs), according to different cleavage positions of the precursor or mature tRNAs. Instead of random tRNA degradation debris, a growing body of evidence has shown that tRNA-derived fragments are precise products of specific tRNA modifications and play important roles in biological activities, such as regulating protein translation, affecting gene expression, and altering immune signaling. Recently, the relations between tRNA-derived fragments and the occurrence of human diseases, especially cancers, have generated wide interest. It has been demonstrated that tRNA-derived fragments are involved in cancer cell proliferation, metastasis, progression and survival. In this review, we will describe the biogenesis of tRNA-derived fragments, the distinct expression and function of tRNA-derived fragments in the development of cancers, and their emerging roles as diagnostic and prognostic biomarkers and precise targets of future treatments.     

Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: An ancillary analysis of the POPLAR and OAK studies

This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447–0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death-ligand 1 expression and blood-based tumor-mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood-based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.     

分析蓝光照射、白蛋白治疗新生儿黄疸效果

目的探讨蓝光照射联合白蛋白治疗新生儿黄疸的临床效果。方法选取2018年1月—2018年12月医院收治的136例新生儿黄疸患儿,按随机数字表法分为A组(68例)和B组(68例),A组采取蓝光照射进行治疗,B组在此基础上联合白蛋白进行治疗,并比较不同组患儿治疗疗效。结果B组患儿治疗有效率较A组明显增加(P<0.05);B组患儿治疗前间接胆红素(IBIL)、总胆红素(TBIL)、γ-谷氨酰基转移酶(γ-GT)、游离脂肪酸(FFA)和超敏C反应蛋白(hsCRP)水平比较差异无统计学意义(P>0.05),治疗后B组患儿IBIL、TBIL、γ-GT、FFA和hs-CRP水平明显小于A组(P<0.05)。结论蓝光照射联合白蛋白静滴治疗新生儿黄疸临床疗效较好,有助于减轻胆红素水平以及改善临床症状。     

基于病因病机分析各省市新型冠状病毒肺炎的中医药防治

新型冠状病毒肺炎属于中医学“疫病”范畴。疫情爆发以来,全国各省市卫生行政管理部门坚持中西医结合原则,陆续制定了各省市的中医药防治方案,三因制宜,分期分型辨证并不断完善。笔者全面收集并整理相关信息,基于病因病机分析了各省市中医药防治方案,认为此次疫病是外感疫气,病位主要在肺卫,病邪主要表现为“毒、湿、热、虚、寒”。此“毒”即为疫气,武汉遇暖冬,非其时而有其气而发疫,一气一病,播散流行,治疫必先治毒;“湿”邪之地在南北方各占一半,东西部均有,在南方源于季节和地域,在北方可由寒挟杂,治疗均应祛湿;“热”主要见于南方,为南方常见的病邪,亦可因湿毒入里,湿郁化热,而在北方热与湿同现,主要是因湿毒入里,湿郁化热,治热均以清为主;“虚”则主要在北方,北方冬季多寒,易伤正致虚,或邪正交争激烈,伤阳伤阴致虚,宜祛邪为标,扶正为本;“寒”见于北方和南方山区,寒气过甚,易伤阳伤正,故尤其要注重预防,且以补正气为主。中医防疫治疫应三因制宜,重视预防,与时俱进。