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101.
There are approximately 350 million hepatitis B virus (HBV) carriers worldwide. Chronic HBV infection increases the risk of liver cirrhosis and hepatocellular carcinoma. To date, two classes of antiviral drugs have been approved by the Food and Drug Administration for the treatment of hepatitis B, immunomodulators (interferon [IFN]‐α and pegylated‐interferon [PEG‐IFN]‐α) and nucleos(t)ide analogs (lamivudine, telbivudine, adefovir, tenofovir [TDF], and entecavir [ETV]). Of these, ETV, TDF, and PEG‐IFN‐α are the most effective and are currently recommended for anti‐HBV therapy. However, these therapies are less than optimal because of their low rate of viral DNA and surface antigen clearance; thus, there exists a significant unmet medical need for safe and efficacious new anti‐HBV drugs. Covering diverse chemical structures and mechanisms of action, non‐nucleos(t)ide compounds offer great promise in the search for new anti‐HBV drugs. This review summarizes the currently approved anti‐HBV drugs and highlights advances in the identification and characterization of novel small molecule HBV inhibitors. We discuss the sources, structures, anti‐HBV effects, mechanisms of action, and potential toxicities of these novel inhibitors. 相似文献
102.
Xia Cao Qin Zhu Qi-Long Wang Michael Adu-Frimpong Chun-Mei Wei Wen Weng Rui Bao Ya-Ping Wang Jiang-Nan Yu Xi Ming Xu 《Journal of pharmaceutical sciences》2021,110(7):2718-2727
This study sought to prepare a self-microemulsion drug delivery system containing zingerone (Z-SMEDDS) to improve the low oral bioavailability of zingerone and anti-tumor effect. Z-SMEDDS was characterized by particle size, zeta potential and encapsulation efficiency, while its pharmacokinetics and anti-tumor effects were also evaluated. Z-SMEDDS had stable physicochemical properties, including average particle size of 17.29 ± 0.07 nm, the zeta potential of -22.81 ± 0.29 mV, and the encapsulation efficiency of 97.96% ± 0.02%. In vitro release studies have shown the release of zingerone released by Z-SMEDDS was significantly higher than free zingerone in different release media. The relative oral bioavailability of Z-SMEDDS was 7.63 times compared with free drug. Meanwhile, the half inhibitory concentration (IC50)of Z-SMEDDS and free zingerone was 8.45 μg/mL and 13.30 μg/mL, respectively on HepG2. This study may provide a preliminary basis for further clinical research and application of Z-SMEDDS. 相似文献
103.
The interleukin (IL)-17 superfamily, a relatively new family of cytokines, consists of six ligands (from IL-17A to IL-17F), which bind to five receptor subtypes (from IL-17RA to IL-17RE) and induce downstream signaling. IL-17A, a prototype member of this family, has been reported to be involved in the pathogenesis of allergies, autoimmune diseases, allograft transplantations, and malignancies. Unlike IL-17A, which is mainly produced by T helper 17 cells, IL-17B is widely expressed in various tissues. Recently, the biological function of IL-17B in diseases, particularly tumors, has attracted the attention of researchers. We previously reported that the expression of IL-17RB increased in gastric cancer tissues and demonstrated that IL-17B/IL-17RB signaling plays a critical role in gastric tumor progression. However, studies on IL-17B are scant. In this review, we detail the structural characteristics, expression patterns, and biological activities of IL-17B and its potential role in the pathogenesis of diseases. 相似文献
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105.
目的:通过观察定量脑电图(QEEG)在低频重复经颅磁刺激(r TMS)干预亚急性期运动性失语患者前后的变化,进一步探讨其机制。方法:将30例脑卒中后亚急性期运动性失语患者随机分为r TMS组与假刺激组各15例。两组患者均给予常规药物治疗及言语训练,r TMS组在右侧大脑半球Broca镜像区给予低频r TMS治疗,连续治疗3周。最终两组各脱落2例。于治疗前和治疗3周后(治疗后)行定量脑电图检查,比较各个频段上(δ+θ)/(α+β)值的差异,并采用西方失语成套测验(WAB)评定治疗前后的言语功能。结果:治疗后,两组患者在FP1、F3、F7、T3、C3频段(δ+θ)/(α+β)值下降,差异有显著性意义(P0.01);r TMS组在F3频段(δ+θ)/(α+β)值下降较假刺激组明显,差异有显著性意义(P0.01);r TMS组治疗前后自发言语、复述、命名以及失语商(AQ)分的差值较假刺激组大,差异有显著性意义(P0.05);相关分析显示r TMS组在FP1、F3、F7、T3、C3频段上,治疗前后的(δ+θ)/(α+β)差值与AQ差值呈负相关,差异有显著性意义(P0.05)。结论:低频r TMS刺激右侧大脑半球Broca镜像区能改善亚急性期运动性失语患者的言语功能,定量脑电图的变化提示了低频r TMS能促进左侧大脑皮质神经电活动变化。 相似文献
106.
107.
《Current problems in cardiology》2022,47(12):101354
Cognitive impairment is a frequent condition in patients with heart failure (HF). This meta-analysis aimed to evaluate the prognostic impact of cognitive impairment on all-cause mortality and readmission among HF patients. We systematically searched articles indexing in PubMed and Embase databases until August 5, 2022. Original studies investigating the association of cognitive impairment with mortality and/or readmission for more than 3-month follow-up in patients with HF were selected. Twelve studies including 9556 patients were eligible. The prevalence of cognitive impairment ranged from 13.5% to 63.4% in HF patients. For patients with cognitive impairment vs those without, the pooled adjusted risk ratio (RR) was 1.88 (95% confidence intervals [CI] 1.42-2.48) for all-cause mortality, 1.48 (95% CI 1.19-1.84) for readmission, and 1.53 (95% CI 1.35-1.73) for combined endpoints of all-cause mortality/readmission, respectively. Cognitive impairment is a significant predictor of all-cause mortality/readmission in patients with HF, even after adjustment for the conventional confounding. Evaluation of cognitive function may help to improve risk classification of HF patients. 相似文献
108.
Xiaofen Liu Yuancheng Chen Haijing Yang Jian Li Jicheng Yu Zhenwei Yu Guoying Cao Xiaojie Wu Yu Wang Hailan Wu Yaxin Fan Jingjing Wang Jufang Wu Yi Jin Beining Guo Jiali Hu Xingchen Bian Xin Li Jing Zhang 《The Journal of infection》2021,82(2):207-215
ObjectivesPolymyxin B is a last-line antibiotic for multidrug-resistant gram-negative bacterial infections. However, limited safety and pharmacokinetic information is available. We investigated the safety and pharmacokinetics of intravenous polymyxin B in healthy subjects.MethodsAn open-label, single-dose clinical trial was conducted in healthy Chinese subjects. Polymyxin B (sulphate) was administered intravenously at 0.75 or 1.5 mg/kg (n = 10 per dose, 5 males and 5 females) to examine the safety and pharmacokinetics.ResultsOne female subject in the 1.5-mg/kg group discontinued due to abdominal pain during administration. The most frequently reported adverse events were perioral paraesthesia, dizziness, and numbness of extremities (7/10 subjects in the 0.75-mg/kg group, all subjects in the 1.5-mg/kg group). All neurotoxicity-related events dissipated without treatment within a maximum of 23 h. Notably, abdominal pain (3/5) and vulvar pruritus (2/5), colpitis (2/5) or abnormal uterine bleeding (1/5) were reported in female subjects receiving the 1.5-mg/kg dose. In the 0.75-mg/kg group, the total clearance, volume of distribution and half-life of polymyxin B were 0.028±0.002 L/h/kg, 0.219±0.023 L/kg and 5.44±0.741 h, respectively; similar values were observed in the 1.5-mg/kg group. Urinary recovery was 3.7 ± 1.1% and 8.1 ± 1.3% in the 0.75- and 1.5-mg/kg groups, respectively. Population pharmacokinetics of polymyxin B was consistent with a three-compartment model. The clearance and distribution of the central compartment were 0.027 L/h/kg and 0.071 L/kg, respectively.ConclusionsThis study is the first to examine the safety and pharmacokinetics of polymyxin B in healthy subjects. Our results highlight that acute toxicity is a dose-limiting factor for intravenous polymyxin B. 相似文献
109.
目的探讨骨原发性巨细胞血管母细胞瘤(giant cell angioblastoma,GCAB)的临床特点、影像学表现、病理学形态、免疫表型及其鉴别诊断。方法对3例骨原发性GCAB的临床资料、影像学表现、病理学形态和免疫表型进行回顾性分析。结果2例为成年女性,1例为男童。病变分别位于第2腰椎、左股骨远端和左手第3~5掌骨。患者均以局部骨疼痛就诊,其中2例伴活动受限,2例伴周围软组织肿胀。影像学显示为骨质破坏,2例累及邻近软组织。低倍镜下见组织由丛状增生的不规则形血管瘤样结节组成,结节之间为纤维结缔组织。高倍镜下,血管瘤样结节由增生的小血管和周围的胖梭形周皮细胞组成,后者可呈同心圆状围绕小血管,结节内可见散在的破骨样巨细胞。免疫表型:结节内小血管内皮细胞表达CD31和CD34,其周围的周皮细胞表达α-SMA和vimentin,破骨样巨细胞表达KP-1。结论 GCAB属于局部侵袭性的中间型血管内皮瘤。除周围软组织外,少数病例可原发于骨内,并可发生于成人。GCAB需与慢性肉芽肿性炎症、丛状纤维组织细胞瘤、簇状血管瘤和卡波西型血管内皮瘤等鉴别。 相似文献
110.