葡萄糖-6-磷酸脱氢酶在糖尿病及其并发症中的作用及机制

葡萄糖-6-磷酸脱氢酶(G6PD)是磷酸戊糖途径的限速酶,对维持细胞内还原型烟酰胺腺嘌呤二核苷酸磷酸和氧化还原反应的平衡起着重要作用。G6PD缺乏症是人类最常见的遗传性细胞酶病,以往的研究多集中在溶血、贫血等方面。然而,近年来的研究发现G6PD在机体发育、多种疾病的发生和发展等方面也具有重要作用。     

替格瑞洛在老年STEMI患者急诊PCI中的疗效与安全性分析

目的观察替格瑞洛在老年急性ST段抬高型心肌梗死(ST-segment elevated myocardial infarction,STEMI)患者急诊经皮冠状动脉介入治疗术(percutaneous coronary artery intervention,PCI)中的疗效和安全性。方法 2013年4月至2014年10月行急诊PCI术的60岁以上STEMI患者113例,采用数字表法随机分为负荷量替格瑞洛组(57例)和氯吡格雷组(56例),分别给予300 mg阿司匹林和180 mg替格瑞洛嚼服及300 mg阿司匹林和600 mg氯吡格雷嚼服。观察并比较2组患者急诊PCI术后无复流情况及术后1个月内主要心脏不良事件(major adverse cardiovascular events,MACE)发生率及出血、呼吸困难及恶性心律失常的发生率。结果替格瑞洛组无复流发生率以及术后1个月MACE的发生率均低于氯吡格雷组(P<0.05);而2组主要出血、恶性心律失常的发生率差异无统计学意义(P>0.05)。结论在老年STEMI患者的急诊PCI治疗中,应用替格瑞洛抗栓疗效显著,且安全性较好。     

直肠癌新辅助治疗后不同等待时间对术后病理和预后的影响

目的探讨中低位直肠癌术前新辅助治疗后不同等待时间对术后病理及预后的影响。 方法回顾性分析2013年1月~2018年12月期间于江苏省人民医院行新辅助放化疗的77例进展期中低位直肠癌患者临床资料,按照新辅助治疗后术前等待时间分为Ⅰ组43例（6~8周）和Ⅱ组34例（9~12周）,比较两组术后病理及预后情况。 结果两组患者新辅助前的一般资料如性別、年龄、cTNM分期及CEA水平等比较差异均无统计学意义（P>0.05）。术后病理结果提示：Ⅱ组术后病理淋巴结阳性率显著低于Ⅰ组（20.6% vs. 46.5%,P=0.018）。Ⅰ组和Ⅱ组pCR率分别为18.6%和17.6%,二者差异无统计学意义（χ²=0.012,P=0.914）。Ⅰ组共有14例患者（32.6%,14/43）肿瘤消退明显,仅剩下少量镜下癌灶或无肿瘤残留,Ⅱ组共有13例患者（38.2%,13/34）肿瘤消退明显,两组比较差异无统计学意义（Z=-0.702,P=0.483）。两组术后并发症发生率及远期肿瘤复发及转移差异无统计学意义（P>0.05）。 结论延长新辅助放化疗至手术的时间间隔至9~12周较6~8周能进一步降低淋巴结的阳性率,但对pCR率及肿瘤消退分级评分并无影响。对术后短期并发症发生情况以及长期复发及转移等情况也未产生较大影响。延期手术对患者来说利弊共存,因此应根据患者病情制定个体化治疗策略。     

Effect of a Family Intervention on Psychological Outcomes of Children Affected by Parental HIV

This study assesses intervention outcomes in children’s self-esteem, perceived parental care, and problem behavior and their potential connections to intervention outcomes in depressive symptoms and family functioning reported by parents living with HIV (PLH) and family members. A total of 79 families were recruited from Anhui province, China. The intervention was delivered at the individual, family and community levels. Face-to-face interviews were administered at baseline, 3 and 6 months. A mixed-effects regression model was used to assess the intervention effect on the improvement of children’s reported self-esteem, parental care, and problem behavior. To further investigate the association between the parental measures and their children’s outcomes, we added parental measure as a time-varying covariate to explore whether the intervention effect on children was influenced by the parental measures. We observed some intervention effects related to children’s psychological measures accompanied by the improvement in mental health of PLH and family members. Our study findings highlight the importance of empowering families as a whole to confront HIV related challenges and the need to develop child-adequate and age-specific intervention strategies.     

ABCB4 mutations underlie hormonal cholestasis but not pediatric idiopathic gallstones

AIM:To investigate the contribution of ABCB4 mutations to pediatric idiopathic gallstone disease and the potential of hormonal contraceptives to prompt clinical manifestations of multidrug resistance protein 3 deficiency.METHODS:Mutational analysis of ABCB4,screening for copy number variations by multiplex ligation-dependent probe amplification,genotyping for low expression allele c.1331T>C of ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with cholesterol gallstones in adults was performed in 35 pediatric subjects with idiopathic gallstones who fulfilled the clinical criteria for low phospholipid-associated cholelithiasis syndrome(LPAC,OMIM#600803)and in 5young females with suspected LPAC and their families(5 probands,15 additional family members).The probands came to medical attention for contraceptiveassociated intrahepatic cholestasis.RESULTS:A possibly pathogenic variant of ABCB4was found only in one of the 35 pediatric subjects with idiopathic cholesterol gallstones whereas 15 members of the studied 5 LPAC kindreds were confirmed and another one was highly suspected to carry predictably pathogenic mutations in ABCB4.Among these 16,however,none developed gallstones in childhood.In 5index patients,all young females carrying at least one pathogenic mutation in one allele of ABCB4,manifestation of LPAC as intrahepatic cholestasis with elevated serum activity of gamma-glutamyltransferase was induced by hormonal contraceptives.Variants ABCB11c.1331T>C and ABCG8 c.55G>C were not significantly overrepresented in the 35 examined patients with suspect LPAC.CONCLUSION:Clinical criteria for LPAC syndrome caused by mutations in ABCB4 cannot be applied topediatric patients with idiopathic gallstones.Sexual immaturity even prevents manifestation of LPAC.     

Disentangling the lifespans of hepatitis C virus‐infected cells and intracellular vRNA replication‐complexes during direct‐acting anti‐viral therapy

The decay rate of hepatitis C virus (HCV)‐infected cells during therapy has been used to determine the duration of treatment needed to attain a sustained virologic response, but with direct‐acting anti‐virals (DAA), this rate has been difficult to estimate. Here, we show that it is possible to estimate it, by simultaneously analysing the viral load and alanine aminotransferase (ALT) kinetics during combination DAA therapy. We modelled the HCV RNA and ALT serum kinetics in 26 patients with chronic HCV genotype 1b infection, under four different sofosbuvir‐based combination treatments. In all patients, ALT decayed exponentially to a set point in the normal range by 1‐3 weeks after initiation of therapy. The model indicates that the ALT decay rate during the first few weeks after initiation of therapy reflects the death rate of infected cells, with an estimated median half‐life of 2.5 days in this patient population. This information allows independent estimation of the rate of loss of intracellular replication complexes during therapy. Our model also predicts that the final ALT set point is not related to the release of ALT by dying HCV‐infected cells. Using ALT data, one can separately obtain information about the rate of ‘cure’ of HCV‐infected cells versus their rate of death, something not possible when analysing only HCV RNA data. This information can be used to compare the effects of different DAA combinations and to rationally evaluate their anti‐viral effects.