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91.
Yaobin Ouyang Gongmeizi Liu Wenting Xu Zhen Yang Nianshuang Li Chuan Xie Chun Zhou Jiang Chen Yin Zhu Junbo Hong Nonghua Lu 《Oncology Letters》2021,21(2)
Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development. 相似文献
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93.
随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。 相似文献
94.
目的探讨3D打印模型在儿童先天性脊柱侧凸治疗中的应用疗效。方法回顾性分析2015年12月至2016年12月于首都医科大学附属北京儿童医院接受手术治疗的83例先天性脊柱侧凸患儿临床及影像学资料,根据是否使用3D打印模型分为试验组(n=44)和对照组(n=39),比较两组手术时间、术中透视次数、置钉准确性、矫形效果及并发症情况。结果本研究共纳入83例先天性脊柱侧凸患儿,其中男童47例,女童36例,平均手术年龄5.98 (1.5~13)岁。行半椎体切除术40例,Ponte截骨术31例,经椎弓根截骨术8例,全脊椎切除术4例。随访时间24~35个月。试验组患儿手术时间短于对照组[(180.92±16.74) min (201.51±27.60) min],差异有统计学意义(t=2.798,P<0.05),试验组术中出血量[(340.23±89.52) mL vs.(392.64±100.41) mL]及术中透视次数(4.36±0.89 6.05±1.28)明显少于对照组,差异有统计学意义(P<0.05);试验组置钉准确率高于对照组(93.55%vs 79.91%)(X^2=218.00,P<0.05),平均置钉时间明显短于对照组[(4.24±1.05) min vs.(8.35±2.29) min],差异有统计学意义(t=10.71,P<0.05)。两组患儿矫形率无明显差异(t=-1.135,P=0.272)。试验组与对照组患儿术后胸膜损伤、硬膜损伤发生率无明显差异(P>0.05)。结论 3D打印模型能清晰、直观显示先天性脊柱侧凸患儿的脊柱结构及形态,为制定手术计划及手术置钉提供帮助,从而提高置钉准确率,减少术中透视次数,缩短手术时间,减少术中出血量。 相似文献
95.
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97.
Roberto V.P. Ribeiro Mitesh V. Badiwala Danny Ramzy Laura C. Tumiati Vivek Rao 《The Journal of thoracic and cardiovascular surgery》2019,157(2):615-625.e1
Objective
Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.Methods
Heart transplants were performed after 6 hours of cold ischemic storage. Recipient pigs were randomized to treatment with or without HTS (7.5% NaCl) before cardiopulmonary bypass (CPB). Using a myograft apparatus, coronary artery endothelial-dependent (Edep) and -independent (Eind) relaxation was assessed. LV performance was determined using pressure-volume loop analysis. Pulmonary interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α expression was measured.Results
Weaning from CPB and LV performance after transplantation were improved in HTS-treated animals. Successful weaning from CPB was greater in the HTS-treated hearts (8 of 8 vs 2 of 8; P < .05). Mean LV functional recovery was improved in the HTS-treated animals, as assessed by preload recruitable stroke work (65 ± 10% vs 27 ± 10%; P < .001) and end-systolic elastance (55 ± 7% vs 37 ± 4%; P < .001). Treatment with HTS resulted in improved Edep (mean maximum elastance [Emax], 56 ± 5% vs 37 ± 7%; P < .001) and Eind (mean Emax%, 77 ± 6% vs 52 ± 4%; P < .001) vasorelaxation compared with control. Pulmonary expression of IL-2, IL-6, and TNF-α increased following transplantation, whereas HTS therapy attenuated IL production (P < .001). Transplantation increased plasma TNF-α levels and LV TNF-α expression, whereas HTS prevented this up-regulation (P < .001).Conclusions
Recipient HTS pretreatment preserves allograft vasomotor and LV function, and HTS therapy limits CPB-induced injury. HTS may be a novel recipient intervention to prevent graft dysfunction. 相似文献98.
目的:建立液相色谱-串联质谱法(UPLC-MS/MS)同时测定人血浆中头孢哌酮与舒巴坦的浓度,分析头孢哌酮/舒巴坦血药浓度监测结果,为临床合理用药提供参考。方法:以氯唑沙宗为内标,采用Waters BEHC18柱(2.1 mm×100 mm,1.7 μm)进行分离,通过串联质谱仪,负离子检测模式下,以多反应监测(MRM)方式进行定量测定。对某院2018年以不同给药方案进行治疗的73例住院患者测定的头孢哌酮/舒巴坦血药浓度结果进行分析。结果:头孢哌酮与舒巴坦在测定条件下1~200 mg·L-1范围内线性关系良好,两者日内精密度RSD均<10%,基质效应分别为(72.77±0.99)%与(75.72±0.11)%,提取回收率均>90%。73例患者共监测血药浓度96次,其中不同给药方案2 g,q8 h(43例次);2 g,q12 h(26例次);2 g,q6 h(27例次),各组头孢哌酮血药浓度的中位数分别为34.12 mg·L-1(4.12~177.79 mg·L-1)、31.23 mg·L-1(1.89~251.8 mg·L-1)、59.96 mg·L-1(1.77~140.58 mg·L-1),舒巴坦血药浓度的中位数分别为6.3 mg·L-1(0.61~136.01 mg·L-1)、28.83 mg·L-1(0.5~133.69 mg·L-1)、11.17 mg·L-1(0.73~143.53 mg·L-1)。Mann-Whitney U检验显示,头孢哌酮血药浓度结果无统计学差异(P>0.05),舒巴坦有统计学差异(P<0.05)。结论:本检测方法操作简便、快速、重复性好,可满足临床头孢哌酮与舒巴坦浓度的检测;头孢哌酮/舒巴坦在不同给药方案下血药浓度结果与个体差异相关,有必要开展血药浓度监测并依据结果适时调整用药方案,提高治疗效果减少耐药率的发生。 相似文献
99.
《Drug metabolism and pharmacokinetics》2019,34(1):87-94
The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with Ki values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with Km values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CLR) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CLR (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CLR of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates. 相似文献
100.
《Clinical Lymphoma, Myeloma & Leukemia》2020,20(8):509-518
BackgroundIn the phase III CASTOR study in relapsed or refractory multiple myeloma, daratumumab, bortezomib, and dexamethasone (D-Vd) demonstrated significant clinical benefit versus Vd alone. Outcomes after 40.0 months of median follow-up are discussed.Patients and MethodsEligible patients had received ≥ 1 line of treatment and were administered bortezomib (1.3 mg/m2) and dexamethasone (20 mg) for 8 cycles with or without daratumumab (16 mg/kg) until disease progression.ResultsOf 498 patients in the intent-to-treat (ITT) population (D-Vd, n = 251; Vd, n = 247), 47% had 1 prior line of treatment (1PL; D-Vd, n = 122; Vd, n = 113). Median progression-free survival (PFS) was significantly prolonged with D-Vd versus Vd in the ITT population (16.7 vs. 7.1 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.25-0.40; P < .0001) and the 1PL subgroup (27.0 vs. 7.9 months; HR, 0.22; 95% CI, 0.15-0.32; P < .0001). In lenalidomide-refractory patients, the median PFS was 7.8 versus 4.9 months (HR, 0.44; 95% CI, 0.28-0.68; P = .0002) for D-Vd (n = 60) versus Vd (n = 81). Minimal residual disease (MRD)–negativity rates (10−5) were greater with D-Vd versus Vd (ITT: 14% vs. 2%; 1PL: 20% vs. 3%; both P < .0001). PFS2 was significantly prolonged with D-Vd versus Vd (ITT: HR, 0.48; 95% CI, 0.38-0.61; 1PL: HR, 0.35; 95% CI, 0.24-0.51; P < .0001). No new safety concerns were observed.ConclusionAfter 3 years, D-Vd maintained significant benefits in patients with relapsed or refractory multiple myeloma with a consistent safety profile. D-Vd provided the greatest benefit at first relapse and increased MRD-negativity rates. 相似文献