Newer second-line glucose-lowering drugs versus thiazolidinediones on cirrhosis risk among older US adult patients with type 2 diabetes

AimsType 2 diabetes (T2D) accelerates progression of chronic liver disease to cirrhosis, yet the effects of most glucose-lowering drugs (GLDs) on cirrhosis risk in T2D are unknown. To address this gap, we compared cirrhosis risk following initiation of newer second-line GLDs vs. thiazolidinediones (TZDs), which improve histology in non-alcoholic fatty liver disease.Materials and methodsUsing the US Medicare Fee-for-Service database (2007–2015) and an active comparator, new-user design, we estimated crude incidence rates (IRs) and propensity-score adjusted hazard ratios (aHR) for incident cirrhosis, comparing newer GLDs (dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1RA), and sodium-glucose co-transporter 2 inhibitors (SGLT2i)) vs. TZDs.ResultsAmong 239,549 total initiators, we observed 318, 151, and < 30 cirrhosis events when comparing DPP4i vs. TZD, GLP1RA vs. TZD, and SGLT2i vs. TZD, respectively. IRs ranged from 1.7 [95% CI, 0.8–3.6] to 3.6 [2.5–5.2] events per 1000 person-years. Point aHR estimates for cirrhosis were elevated among newer GLD initiators vs. TZD (DPP4i: 1.15 [0.89–1.50]; GLP1RA: 1.34 [0.82–2.20]; SGLT2i: 1.16, [0.44–3.08]), although estimates were imprecise due to short durations of drug exposure.ConclusionsWe observed mildly elevated cirrhosis risk with newer GLDs vs. TZD; however, uncertainty remains due to imprecise and statistically non-significant effect estimates.     

Fabrication and Adsorption Optimization of Novel Magnetic Core-shell Chitosan/Graphene Oxide/β-cyclodextrin Composite Materials for Bisphenols in Aqueous Solutions

A novel magnetic composite material, Fe₃O₄@SiO₂/chitosan/graphene oxide/β-cyclodextrin (MCGC), was prepared by multi-step methods. Various methods were used to systematically characterize the morphology, composition, structure, and magnetic properties of MCGC. The results obtained show that the composite material has good morphology and crystal structure and can be separated quickly by an external magnetic field. The operation is relatively easy, and the raw materials used to prepare this material are economical, easy to obtain, and environmentally friendly. The performance and adsorption mechanism for using this material as an adsorbent to remove bisphenol A (BPA) and bisphenol F (BPF) from water were studied. The adsorption parameters were optimized. Under optimal conditions, MCGC was found to remove more than 90% of BPA and BPF in a mixed solution (20 mg/L, 50 mL); the adsorption process for BPA and BPF on MCGC was found to follow a Redlich–Peterson isotherm model and Pseudo-second-order kinetic model. The adsorption mechanism for MCGC may involve a combination of various forces. Recycling experiments showed that after five uses, MCGC retained a more than 80% removal effect for BPA and BPF, and through real sample verification, MCGC can be used for wastewater treatment. Therefore, MCGC is economical, environmentally friendly, and easy to separate and collect, and has suitable stability and broad application prospects.     

Different metabolic profiles of K1 serotype and non-serotype K1 and K2 Klebsiella pneumoniae isolates in oral infection mice model

K1 or K2 serotype Klebsiella pneumoniae isolate caused clinical pyogenic liver abscess (KLA) infection is prevalent in many areas. It has been identified that K1 or K2 serotype K. pneumoniae isolates caused KLA infection in mice by oral inoculation. In our study, K1 serotype K. pneumoniae isolate Kp1002 with hypermucoviscosity (HV)-positive phenotype caused KLA infection in C57BL/6 mice by oral inoculation. Simultaneously, non-serotype K1 and K2 isolate Kp1014 with HV-negative phenotype failed to cause KLA infection in the same manner. It seems that gastrointestinal tract translocation is the pathway by which K1 or K2 serotype K. pneumoniae caused KLA infection. Liquid chromatography-tandem mass spectrometry was used to further analyze metabolic profile changes in mice with KLA infection. Data showed that after Kp1002 or Kp1014 oral inoculation, serum Phosphatidylcholine (PC) and Lysophosphatidylcholine (LPC) levels significantly changed in mice. Some PC and LPC molecules showed changes both in the Kp1002 KLA group and the Kp1014 no-KLA group compared with the control group. The level of 18:1/18:2-PC significantly changed in the Kp1002 KLA group compared with the control group, but showed no change between the Kp1014 no-KLA group and the control group. The level of 18:1/18:2-PC might have been particularly affected by KLA infection caused by K1 serotype K. pneumoniae Kp1002. It may be a potential biomarker for KLA infection.     

Improved sectioned images and surface models of the whole dog body

The objective of this research was to produce high-quality sectioned images of a whole dog which can be used to create sectional anatomy atlases and three-dimensional (3D) models. A year old female beagle was sacrificed by potassium chloride injection and frozen. The frozen dog was then serially ground using a cryomacrotome. Sectioned surfaces were photographed using a digital camera to create 3555 sectioned images of whole dog body (intervals, 0.2 mm; pixel size, 0.1 mm; 48 bit color). In a sectioned image, structures of dimension greater than 0.1 mm could be identified in detail. Photoshop was used to make segmented images of 16 structures. Sectioned and segmented images were stored in browsing software to allow easy access. Segmented images were reconstructed to make surface models of 16 structures using Mimics software and stored in portable document format (PDF) using Adobe 3D Reviewer software. In this research, state-of-art sectioned images and surface models were produced for the dog. The authors hope that the sectioned images produced will become a useful source of software for basic and clinical veterinary medicine, and therefore, are distributing the sectioned images and surface models through browsing software and PDF file available free of charge.     

RNA、lnc-EGFR对肝细胞癌免疫逃避调节的相关性

目的探讨RNA、表皮生长因子受体长链非编码RNA(lnc-EGFR)对肝细胞癌(HCC)免疫逃避调节的相关性。方法通过医院病理档案室随机选择保定市第一中心病医院2017年1月至2019年1月收集的HCC标本30份和癌旁正常组织30份,采用RT-PCR法检测各组织中RNA、lnc-EGFR表达水平;蛋白质印迹法检测HCC组织中化学因子和细胞免疫因子表达情况,并分析RNA、lnc-EGFR与其相关性;将HCC细胞株随机分为两组,分别为RNA、lnc-EGFR抑制组(n=15)与空白对照组(n=15),MTT法检测细胞增殖情况,流式细胞仪检测细胞凋亡情况与细胞周期分布情况。结果癌旁正常组织中RNA、lnc-EGFR表达水平分别为(0.46±0.12)和(0.62±0.15)低于HCC组织(0.22±0.06)和(0.14±0.05)(P<0.05)。HCC组织中CXCL12-CXCR4表达水平低于癌旁正常组织(P<0.05);HCC组织中CCL20-CCR6、CX3CLI-CX3CR1高于癌旁正常组织(P<0.05);HCC组织中细胞免疫因子IL-6、IL-10、TGF-β、TNF-α表达水平高于癌旁正常组织(P<0.05);RNA、lnc-EGFR表达水平与CXCL12-CXCR4呈显著负相关(P<0.05),与CCL20-CCR6、CX3CLI-CX3CR1、IL-6、IL-10、TGF-β、TNF-α呈显著正相关关系(P<0.05);HCC、癌旁正常组织中细胞相对吸光度、细胞凋亡率、细胞周期占比均具有统计学差异(P<0.05)。结论RNA、lnc-EGFR在HCC组织中呈高表达水平,可通过上调组织中化学因子和细胞免疫因子水平来提高癌细胞免疫逃避调节水平,与HCC免疫逃避调节具有显著相关性。     

脓毒血症患者乳酸清除率、红细胞分布宽度 和血乳酸水平及与预后的关系

目的 探讨脓毒血症患者乳酸清除率（LCR）、红细胞分布宽度（RDW）和血乳酸（Lac）水平 及与临床预后的关系。方法 选取2016 年5 月—2018 年9 月保定市第一中心医院收治的脓毒血症患者92 例 作为观察组,同期该院92 例健康体检者作为对照组。将观察组患者按照病情严重程度分为脓毒症亚组46 例、 严重脓毒症亚组29 例和脓毒性休克亚组17 例。检测两组治疗前血清RDW、Lac 水平。检测观察组治疗后 血清RDW、Lac,并计算LCR。比较两组治疗前RDW、Lac 水平,比较观察组中各亚组患者治疗前后血清 LCR、RDW 及Lac 水平。采用Pearson 法分析LCR、RDW、Lac 与脓毒血症患者病情严重程度的相关性, 生存曲线分析血清RDW、Lac 与脓毒血症患者预后的关系。结果 观察组患者治疗前RDW、Lac 水平高于 对照组（P <0.05）。严重脓毒症亚组、脓毒性休克亚组患者治疗前后血清RDW、Lac 水平高于脓毒症亚组 （P <0.05）;而LCR 低于脓毒症亚组（P <0.05）。各亚组患者治疗后血清RDW、Lac 水平低于同组治疗前 （P <0.05）。Pearson 相关性分析显示,RDW、Lac 与脓毒血症患者病情严重程度呈正相关（r =0.776 和0.817, P <0.05）;而LCR 与脓毒血症患者病情严重程度呈负相关（r =-0.851,P <0.05）。低Lac 患者中位生存时间 长于高Lac 患者（36 d VS 28 d）（P <0.05）。低RDW 患者中位生存时间长于高RDW 患者（38 d VS 30 d） （P <0.05）。结论 LCR、RDW、Lac 水平能有效反映脓毒血症患者的病情严重程度,RDW 和Lac 水平能有 效评估脓毒血症患者预后。     

益生菌联合整蛋白型肠内营养辅助治疗脓毒血症的疗效及对肠道和免疫功能的影响*

目的?探讨益生菌联合整蛋白型肠内营养辅助治疗脓毒血症的疗效及对肠道功能、炎症因子和免疫功能的影响。方法?选取2015年6月—2018年6月保定市第一中心医院西院收治的脓毒血症患者134例。随机分为观察组和对照组。对照组根据患者病情予以抗感染、液体复苏、清创引流、机械通气等治疗。在此基础上,观察组另加用双歧杆菌四联活菌片联合整蛋白型肠道营养进行支持治疗。分别观察两组治疗前和治疗3?d、10?d后APACHE-Ⅱ评分、SOFA评分、肠道功能、炎症因子水平和外周血T淋巴细胞亚群水平。结果?观察组治愈率较对照组高（P?<0.05）,病死率较对照组低（P?<0.05）。两组APACHE-Ⅱ评分、SOFA评分在不同时间、不同组间不变化趋势上有差异（P?<0.05）。观察组治疗后肠道功能评分较对照组低（P?<0.05）。两组PCT、IL-6、CRP及SAA水平在不同时间、不同组间不变化趋势上有差异（P?<0.05）。两组CD3+、CD4+和CD4+/CD8+水平在不同时间、不同组间不变化趋势上有差异（P?<0.05）。结论?益生菌联合整蛋白型肠内营养支持治疗脓毒血症,能提高疗效,改善肠道功能,并对炎症因子水平、免疫力的改善有积极作用,有效降低病死率。     

虾青素对2型糖尿病大鼠视网膜病变的干预作用及机制研究

探讨虾青素对2型糖尿病大鼠视网膜病变的保护作用及机制。将40只大鼠随机分为4组:正常组、模型组、低剂量实验组(虾青素15 mg/kg)、高剂量实验组(虾青素30 mg/kg),每组各10只。除正常组外,其它各组采用腹腔注射链脲佐菌素(STZ 30 mg/kg)并持续高糖高脂饲料饲养构建2型糖尿病大鼠模型;采用HE染色观察大鼠视网膜组织病理变化;免疫沉淀法检测大鼠视网膜组织中活性氧(ROS)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)水平;蛋白质免疫印迹法检测大鼠视网膜组织中色素上皮衍生因子(PEDF)和血管内皮生长因子(VEGF)水平。结果显示,与模型组比较,低、高剂量实验组大鼠视网膜组织中ROS、VEGF水平降低,CAT、SOD和PEDF水平升高,差异均有统计学意义(P＜0.05)。高剂量实验组大鼠视网膜组织中CAT、SOD和PEDF水平高于低剂量实验组(P＜0.05),ROS、VEGF水平低于低剂量实验组(P＜0.05)。该结果表明虾青素对2型糖尿病大鼠视网膜病变有一定保护作用,其机制可能与调控氧化应激、PEDF和VEGF有关。     

加味茵陈蒿汤抑制人肝癌裸鼠皮下移植瘤生长的机制

目的:观察加味茵陈蒿汤对人肝癌裸鼠皮下移植瘤的影响。方法:建立人肝癌裸鼠皮下移植模型,随机分为生理盐水组、加味茵陈蒿汤组各8只,比较各组裸鼠瘤质量情况,流式细胞学技术检测各组瘤体细胞凋亡的分布、线粒体膜电位的分布、Caspase-3和Caspase-9的分布;透射电镜检测各组瘤体细胞形态;蛋白印迹法检测各组瘤体线粒体凋亡相关蛋白的表达。结果:加味茵陈蒿汤组的平均瘤质量均低于生理盐水组,差异有统计学意义(P<0.05)。流式细胞学技术检测显示:加味茵陈蒿汤组干预的皮下移植瘤的凋亡率高于生理盐水组、加味茵陈蒿汤组发生线粒体膜电位的比率高于生理盐水组、加味茵陈蒿汤组的Caspase-3和Caspase-9的活性均高于生理盐水组,差异均有统计学意义(P<0.05)。透射电镜显示:加味茵陈蒿汤组皮下移植瘤细胞出现细胞浆肿胀、凋亡。Western blot检测分析显示:加味茵陈蒿汤干预后的肿瘤组织中Caspase-3、Caspase-9和Bax蛋白的表达水平明显上升,Bcl-2和Bcl-x蛋白的表达水平明显降低,差异均有统计学意义(P<0.05)。结论:加味茵陈蒿汤可抑制人肝癌裸鼠皮下移植瘤生长,其作用机制可能通过活化线粒体途径诱导肿瘤细胞凋亡而实现。     

金水宝胶囊联合舒洛地特治疗早期糖尿病肾病的临床研究

目的探讨金水宝胶囊联合舒洛地特治疗早期糖尿病肾病的临床效果。方法选取2015年1月—2018年1月河北大学附属医院收治的早期糖尿病肾病患者80例,随机分成对照组(40例)和治疗组(40例)。对照组口服舒洛地特软胶囊,1粒/次,2次/d。治疗组在对照组基础上口服金水宝胶囊,6粒/次,3次/d。两组患者均连续治疗4个月。观察两组患者临床疗效,同时比较治疗前后两组患者尿白蛋白排泄率(UAE)、24 h尿蛋白定量(24 h-UTP)值、血清肌酐(Cr)和尿素氮(BUN)水平、血脂、内皮功能、炎症及氧化应激指标和肾动脉血流参数。结果治疗后,对照组的总有效率为75.0%,显著低于治疗组的92.5%,两组比较差异具有统计学意义(P0.05)。治疗后,两组UAE、24 h-UTP值及血清Cr、BUN水平均显著降低(P0.05),且治疗组患者UAE、24h-UTP值及血清Cr、BUN水平明显低于对照组(P0.05)。治疗后,两组血清三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、内皮素(ET)-1、C反应蛋白(CRP)浓度及外周血中性粒细胞与淋巴细胞比值(NLR)较治疗前均显著降低(P0.05),血清降钙素基因相关肽(CGRP)、超氧化物歧化酶(SOD)水平则均显著升高(P0.05),且治疗组患者上述血脂、内皮功能、炎症及氧化应激指标水平明显好于对照组(P0.05)。治疗后,两组患者肾动脉血流参数RI和PI值均显著降低(P0.05),且治疗组患者RI和PI值明显低于对照组(P0.05)。结论金水宝胶囊联合舒洛地特治疗早期糖尿病肾病能有效减少患者尿蛋白排泄,保护肾功能,纠正脂质代谢紊乱,改善微循环及肾脏血流动力学。