Evaluation of relationship between KEAP1 gene and genetic susceptibility of deep vein thrombosis after orthopedic surgery in Han Chinese population

Journal of Thrombosis and Thrombolysis - Deep vein thrombosis (DVT) is the blood clot formed in a vein deep in body, mostly occurred in the lower leg or thigh. Early studies indicate that DVT is a...     

Early electrocardiographic indices for predicting chronic doxorubicin-induced cardiotoxicity

BackgroundDealing with chemotherapy-related cardiac dysfunction (CTRCD) remains a significant problem complicated by the difficulty in early detection of cardiotoxicity. Electrocardiogram (ECG) is expected to be the most realistic methodology due to lower cost-performance and non-invasiveness. We investigated the long-term visual fluctuations in the ECG waveforms in patients with chronic doxorubicin (DOX)-induced cardiotoxicity to identify ECG indices for the early detection of cardiotoxicity.MethodsWe conducted a retrospective case series study by reviewing the medical records of 470 consecutive patients with malignant lymphoma who were treated with DOX at our institute between January 2010 and December 2017. Of them, 23 (4.9%) patients developed left ventricular dysfunction and were diagnosed with CTRCD using echocardiography. We assessed the ECG indices on 12-lead ECG recordings before and after treatment in 15 patients; eight patients were excluded due to conduction disturbances or atrial fibrillation.ResultsCTRCD was detected at a median of 475 (interquartile range, IQR: 341–1333) days after initiating chemotherapy. The evaluation of ECG indices preceding CTRCD development was performed 93 (IQR: 52–232) days before the detection of CTRCD. In the stage of CTRCD, the most significant ECG change was T-wave flattening in leads V3–V6 (12 patients, 80%). Additionally, QTa prolongation was observed in leads I and aVL (n = 10, 66%), leads II, III, and aVF (n = 9, 60%), and leads V3–V6 (n = 10, 73%). These ECG changes were not observed before the treatment but were detected mildly in the pre-CTRCD stage, which subsequently worsened in the CTRCD stage.ConclusionsThis study indicated that T-wave changes and QTa prolongation may be useful as an early indicator before the onset of CTRCD in patients with DOX-induced cardiotoxicity.     

Silencing of H19 alleviates oxygen–glucose deprivation/reoxygenation-triggered injury through the regulation of the miR-1306-5p/BCL2L13 axis

Cerebral ischemia/reperfusion (I/R) injury remains a leading cause of death and disability. Long noncoding RNAs (lncRNAs) exert key functions in cerebral I/R injury. Here, we sought to elucidate the mechanism underlying the regulation of H19 in cerebral I/R cell injury. An in vitro model of cerebral I/R injury was created using oxygen–glucose deprivation/reoxygenation (OGD/R). The levels of H19, miR-1306-5p and B cell lymphoma-2 (Bcl-2)-like 13 (BCL2L13) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell viability and apoptosis were determined by the Cell Counting-8 Kit (CCK-8) assay and flow cytometry, respectively. The levels of lactate dehydrogenase (LDH) and cytokines were evaluated by enzyme-linked immunosorbent assays (ELISA). Direct relationships among H19, miR-1306-5p and BCL2L13 were verified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pulldown assays. Our data showed that H19 and BCL2L13 were highly expressed in the cerebral I/R injury rats and OGD/R-triggered SK-N-SH and IMR-32 cells. The knockdown of H19 or BLC2L13 alleviated OGD/R-triggered injury in SK-N-SH and IMR-32 cells. Moreover, H19 silencing protected against OGD/R-triggered cell injury by down-regulating BCL2L13. H19 acted as a sponge of miR-1306-5p and BCL2L13 was a direct target of miR-1306-5p. H19 mediated BCL2L13 expression by sequestering miR-1306-5p. Furthermore, miR-1306-5p was a molecular mediator of H19 function. These results suggested that H19 silencing alleviated OGD/R-triggered I/R injury at least partially depending on the regulation of the miR-1306-5p/BCL2L13 axis.

     

Exacerbation of Ulcerative Colitis with Tocilizumab: A Report of Two Cases,One with Takayasu Arteritis and the Other with Relapsing Polychondritis

Tocilizumab (TCZ), a biologic that blocks the signal transduction of interleukin-6, has been used for the treatment of various autoimmune diseases. Many of these cases are sometimes complicated by ulcerative colitis (UC). However, the effect of TCZ on UC is unclear. We experienced two cases with concomitant UC that were treated with TCZ, one for Takayasu arteritis (TAK) and the other for relapsing polychondritis (RP). TCZ did not improve UC in either of these cases. TCZ might have adverse effects on the intestinal tract, since interleukin-6 signaling plays an important role in intestinal epithelium maintenance. Treatment with TCZ should therefore be carefully provided in patients complicated with UC.     

异丙酚在人肝微粒体中酶促动力学研究

目的 研究异丙酚在人肝微粒体中的代谢。方法 采用高效液相方法测定孵育液中异丙酚的浓度。研究异丙酚的酶促动力学,推导出药物米氏常数(Km)和最大反应速度(Vmax);并计算体外酶对药物的清除率(CLint)。同时观察不同种类的CYP酶特异性抑制剂对异丙酚代谢的影响。结果 异丙酚在人肝微粒体中Km和Vmax分别为777.43μuM和172.413μM?h ?1?mg ?1?protein,Clint为0.22h?1?mg?1?protein。CYP2B6特异性抑制剂氯吡格雷能够显著抑制异丙酚的代谢,而CYP2C9和CYP2C19特异性抑制剂对异丙酚代谢无显著影响CYP2B6抑制剂能够减少异丙酚的代谢。结论 CYP2B6主要参与异丙酚的代谢, CYP2B6酶抑制剂可能会抑制异丙酚的代谢,造成药物药效或毒性的增加。     

circPUM1通过调控miR-524-5p表达对结肠癌细胞恶性生物学行为的影响

目的探讨环状RNA PUM1(circPUM1)对结肠癌细胞增殖、凋亡、迁移、侵袭的影响及其分子机制。方法实时荧光定量聚合酶链反应(qRT-PCR)检测结肠癌组织、癌旁组织中circPUM1、微小RNA-524-5p(miR-524-5p)的表达量。体外培养人结肠癌细胞株SW620,分别将si-NC、si-circPUM1、miR-NC、miR-524-5p mimics、si-circPUM1与anti-miR-NC、si-circPUM1与anti-miR-524-5p转染至SW620细胞。甲基噻唑基四唑(MTT)检测细胞增殖;Transwell小室实验检测细胞迁移、侵袭能力;流式细胞术检测细胞凋亡率;双荧光素酶报告实验验证circPUM1是否能够结合miR-524-5p;蛋白免疫印迹法(Western blotting)检测细胞周期蛋白1(Cyclin D1)、p21、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、B淋巴细胞瘤-2(Bcl-2)、B淋巴细胞瘤-2相关蛋白(Bax)表达量。结果结肠癌组织circPUM1的表达水平显著高于癌旁组织(P<0.05),miR-524-5p的表达水平显著降低(P<0.05);干扰circPUM1表达或miR-524-5p过表达后,细胞活力显著降低(P<0.05),迁移细胞数与侵袭细胞数显著减少(P<0.05),细胞凋亡率显著升高(P<0.05),Cyclin D1、MMP-2、MMP-9、Bcl-2蛋白表达显著降低(P<0.05),p21、Bax蛋白表达显著升高(P<0.05);双荧光素酶报告实验证实circPUM1可靶向结合miR-524-5p的作用位点;抑制miR-524-5p表达可减弱干扰circPUM1表达对SW620细胞增殖、凋亡、迁移、侵袭的作用。结论circPUM1可通过海绵吸附miR-524-5p促进结肠癌细胞增殖、迁移、侵袭,抑制细胞凋亡。     

2018—2019年赤道几内亚Bioko岛恶性疟原虫抗药性基因多态性分析

目的　调查赤道几内亚Bioko岛恶性疟原虫多药耐药蛋白1（Plasmodium falciparum multidrug resistance protein 1, PfMDR1）、氯喹抗性转运蛋白基因（P. falciparum chloroquine resistant transporter, PfCRT）和Kelch 13基因（P. falciparum Kelch 13, PfK13）多态性,为当地疟疾防控策略制定提供参考。方法　采集2018—2019年赤道几内亚Bioko岛恶性疟原虫感染者外周血样本85份,提取基因组DNA。采用巢式PCR技术扩增PfMDR1、PfCRT和 PfK13基因,对扩增产物进行DNA测序,并对基因序列进行比对。结果　赤道几内亚Bioko岛恶性疟原虫PfK13基因不存在已知与青蒿素抗性相关的突变;PfMDR1基因和PfCRT基因均存在不同比例抗药性突变,其中PfMDR1_N86Y、PfMDR1_Y184F和PfCRT_K76T突变率分别为35.29%（30/85）、72.94%（62/85）和24.71%（21/85）。结论　赤道几内亚Bioko岛恶性疟原虫PfMDR1、PfCRT基因和 PfK13基因均存在不同程度突变。     

医源性多药耐药菌感染的动态及耐药性分析

目的了解医院多药耐药现状及病原菌耐药性,为预防与控制医院感染提供必要的病原学依据。方法 2012年9月-2013年5月临床住院患者送检的1517份各类标本,采用法国生物梅里埃公司VITEK-32全自动细菌分析系统进行细菌鉴定,药敏试验使用K-B纸片扩散法,以WHONET5.4软件分析数据。结果共分离出1 132株病原菌,标本来源以痰液、分泌物、脓液为主,分别占40.92%、16.40%、12.52%;共检出多药耐药菌567株,其中产ESBLs大肠埃希菌378株占66.67%;产ESBLs克雷伯菌属96株占16.93%;产ESBLs大肠埃希菌对氨苄西林、头孢曲松、头孢呋辛、头孢唑林、哌拉西林耐药率均>97.62%,产ESBLs克雷伯菌属对头孢呋辛、氨苄西林/舒巴坦、阿莫西林/克拉维酸、氨曲南耐药率均为100.00%,耐甲氧西林金黄色葡萄球菌对苯唑西林、头孢唑林、头孢呋辛、环丙沙星、红霉素具有较高的耐药性,多药耐药铜绿假单胞菌、鲍氏不动杆菌对多种抗菌药物显著耐药,而对亚胺培南、美罗培南敏感。结论多药耐药菌医院感染现象日趋严重,应加强病原菌检测和耐药性监测,依据药敏试验结果选用抗菌药物,从而降低医院感染率。     

四川省西部山区农村寄宿制学校食育干预效果评价

目的通过对四川省西部山区农村寄宿制学校学生进行食育干预,提高学生的营养健康知识和技能,培养其科学的饮食习惯。方法整群抽取四川省蒲江县长秋山区农村寄宿制学校3所,并随机分为食育教育模式干预学校、普通营养教育对照学校及空白对照学校,研究对象为3所学校的2~8年级全部学生。结果经过1年时间的干预,食育干预学校学生营养健康知识知晓率有明显改善,"清楚知道《中国居民膳食宝塔》每层食物的"的知晓率上升最明显,相比基线调查上升了59.1%,高于对照组;在态度方面,食育干预学校学生喜欢吃含糖饮料的下降了19.0%;在行为方面,"学生购买食物前经常看营养标签"的上升了22.8%,"最近1周每天吃早餐"的上升了22.8%,均高于对照组。结论食育干预对学生的营养健康态度、食物喜好改变,还是饮食及健康相关行为方面的改善效果明显,而且食育干预效果优于普通营养教育对照学校。     

Insomnia symptoms are associated with an increased risk of type 2 diabetes mellitus among adults aged 50 and older

Purpose

To evaluate the association of the different degrees of insomnia symptoms with subsequent incidence of type 2 diabetes mellitus (T2DM).

Methods

The data were extracted from Health and Retirement Study 2006–2014 waves. The association of insomnia symptoms with T2DM incidence was evaluated by the competing risk model with cumulative incidence function (death was considered a competing event) and Cox proportional hazard model with the Kaplan–Meier method. Population attributable fraction (PAF) was calculated. All analyses related to our study were conducted between November 2020 and January 2021.

Results

A total of 14,112 patients were included in this study, with an average follow-up of 6.4 years, and the incidence density was 17.9 per 1000 person-years. Insomnia symptoms were positively associated with T2DM incidence compared with those with no insomnia symptoms, regardless of competing risk model (≥?1 symptoms: sub-distribution hazard ratio (SHR) 1.13; 95% confidence interval (CI) 1.02–1.26; P-trend?=?0.012) and Cox proportional hazard model (≥?1 symptoms: hazard ratio (HR) 1.13; 95% CI 1.02–1.26; P-trend?=?0.013). The cumulative incidence function (Gray’s test, p?<?0.001) and Kaplan–Meier estimate (log-rank test, p?<?0.001) also presented this positive relationship. This positive association was more apparent in women and participants with ages from 50 to 65 years. The PAF was 4.1% with 95% CI (0.7–7.9%).

Conclusions

Insomnia symptoms may be an important risk factor for the development of T2DM, which is unbiased by the death competing risk. These findings suggest that management of sleep problems may be an important part of strategies to prevent T2DM.