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1.
Background and aimsSkin autofluorescence (SAF) can non-invasively assess the accumulation of tissue AGEs. We investigated the association between SAF and kidney dysfunction in participants with T2D.MethodsOf 4030 participants consecutively measured SAF at baseline, 3725 participants free of end-stage kidney disease (ESKD) were included in the analyses. The association of SAF with incident ESKD or ≥30% reduction in estimated glomerular filtration rate (eGFR) was examined with Cox regression, linear mixed-effects model for the association with annual eGFR decline, and mediation analyses for the mediating roles of renal markers.ResultsDuring a median (IQR) 1.8 (1.1–3.1) years of follow-up, 411 participants developed the outcome. SAF was associated with progression of kidney disease (hazard ratio 1.15 per SD, 95% confidence interval [CI] [1.04, 1.28]) and annual decline in eGFR (β ?0.39 per SD, 95% CI [?0.71, ?0.07]) after adjustment for risk factors, including baseline eGFR and urinary albumin-creatinine ratio (UACR). Decreased eGFR (12.9%) and increased UACR (25.8%) accounted for 38.7% of the effect of SAF on renal outcome.ConclusionsSAF is independently associated with progression of kidney disease. More than half of its effect is independent of renal markers. SAF is of potential to be a prognostic marker for kidney dysfunction.  相似文献   
2.
目的 探讨纠正低蛋白血症对减少抗结核药物性肝损伤(DILI)发生的作用。方法 2019 年3月~2021 年3 月汕头市中心医院感染病科收治的56例肺结核合并低蛋白血症患者被分为两组,每组28例。给予两组2HRZE/4HR抗结核治疗,另给予观察组输注人血白蛋白纠正低蛋白血症,对照组仅接受抗结核治疗,两组治疗时间均为6个月。使用全自动生化分析仪检测血清白蛋白(ALB)、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)和总胆红素(TBIL)水平,采用化学发光法检测血清总胆汁酸(TBA)水平。在DILI发生时,给予护肝治疗。在治疗结束时,评定临床转归,进行痰培养和肺部CT检查。结果 观察组结核治愈有效率为92.9%,显著高于对照组的71.4%(P<0.05);观察组痰菌转阴率为91.3%,显著高于对照组的(66.7%,P<0.05),肺部病变吸收率为89.3%,显著高于对照组的64.3%(P<0.05);在治疗期间,观察组DILI发生率为25.0%,显著低于对照组的53.6%(P<0.05);在DILI发生时,7例观察组血清ALB水平为(35.2±4.9)g/L,显著高,15例对照组【(29.6±4.9)g/L g/L,P<0.05】,而血清TBIL水平为(33.6±5.2)μmol/L,显著低于对照组【(45.7±16.6)μmol/L,P<0.05】;在护肝治疗后,观察组血清AST、ALT、ALP、TBIL和TBA水平分别为(39.4±9.8)U/L、(35.1±10.8)U/L、(98.6±16.2)U/L、(17.4±4.6)μmol/L和(81.3±13.7)μmol/L,均显著低于对照组【分别为(64.8±9.9)U/L、(78.0±13.8)U/L、(133.7±22.9)U/L、(26.5±6.8)μmol/L和(96.9±16.4)μmol/L,P<0.05】。结论 补充人血白蛋白及时纠正低蛋白血症,对于肺结核合并低蛋白血症患者能够提高结核治愈率,降低药物性肝损害发生率,值得进一步研究。  相似文献   
3.
BackgroundAbout 50% of Americans and 70% of US military service members (SMs) regularly use dietary supplements (DSs) and some are associated with adverse effects (AEs). SMs are more likely to use unsafe DSs than civilians.ObjectiveThe aim of this investigation was to examine the prevalence of, and factors associated with, AEs.DesignCross-sectional.ParticipantsA stratified random sample of 200,000 US SMs from the Air Force, Army, Marine Corps, and Navy were obtained from military workforce records. Eighteen percent (n = 26,681) of successfully contacted SMs (n = 146,365) volunteered to participate between December 2018 and August 2019. Participants completed a detailed online questionnaire on demographic characteristics, lifestyle factors, and AEs associated with DS use.Main outcome measurePrevalence of, and factors associated with, AEs among DS users.Statistical analysisPrevalence of AEs was calculated by DS categories. Linear trends, χ2 statistics, and multivariable logistic regression examined associations between AEs and demographic characteristics, lifestyle factors, and number DSs consumed.ResultsProportion of DS users (≥ 1 time /week) reporting ≥1 AE was 18% overall, 20% for combination products (ie, weight loss, muscle building, and before/after workout supplements), 8% for purported prohormones, 6% for protein/amino acid products, 6% for multivitamin/multiminerals, 6% for individual vitamins/minerals, 4% for herbal products, and 2% for joint health products. Combination products are very popular in military personnel with nearly half of SMs regularly taking them. In multivariable analysis, reporting AEs were independently associated with female gender, younger age, higher body mass index, smoking, higher alcohol intake, service in the Army, Navy, or Marine Corps (compared with Air Force), and consumption of a greater number of DSs.ConclusionsA large proportion of SMs report experiencing AEs, especially users of combination products and purported prohormone supplements. This study presents contemporary data collected from a very large at-risk population on potentially hazardous categories of DSs.  相似文献   
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5.
《Drug discovery today》2022,27(1):82-101
WNT/β-catenin signaling orchestrates various physiological processes, including embryonic development, growth, tissue homeostasis, and regeneration. Abnormal WNT/β-catenin signaling is associated with various cancers and its inhibition has shown effective antitumor responses. In this review, we discuss the pathway, potential targets for the development of WNT/β-catenin inhibitors, available inhibitors, and their specific molecular interactions with the target proteins. We also discuss inhibitors that are in clinical trials and describe potential new avenues for therapeutically targeting the WNT/β-catenin pathway. Furthermore, we introduce emerging strategies, including artificial intelligence (AI)-assisted tools and technology-based actionable approaches, to translate WNT/β-catenin inhibitors to the clinic for cancer therapy.  相似文献   
6.
Arguably, the two most important causes of pathological healing in the skin are diabetes and ageing. While these factors have historically been considered independent modifiers of the healing process, recent studies suggest that they may be mechanistically linked. The primary contributor to diabetic pathology is hyperglycaemia, which accelerates the production of advanced glycation end products, a characteristic of ageing tissue. Indeed, advanced age also leads to mild hyperglycaemia. Here, we discuss emerging literature that reveals a hitherto unappreciated link between cellular senescence, diabetes and wound repair. Senescent cells cause widespread destruction of normal tissue architecture in ageing and have been shown to be increased in chronic wounds. However, the role of senescence remains controversial, with several studies reporting beneficial effects for transiently induced senescence in wound healing. We recently highlighted a direct role for senescence in diabetic healing pathology, mediated by the senescence receptor, CXCR2. These findings suggest that targeting local tissue senescence may provide a therapeutic strategy applicable to a broad range of chronic wound types.  相似文献   
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目的:研究下调晚期糖基化终末产物受体(RAGE)对乳腺癌细胞增殖、凋亡、侵袭、迁移能力的影响。 方法:培养乳腺癌BT474 细胞,分为对照组( 不做任何处理的乳腺癌BT474 细胞)、上调组( 乳腺癌BT474 细 胞+RAGE阴性对照)、下调组( 乳腺癌BT474 细胞+RAGE siRNA)。用四甲基偶氮唑盐法检测乳腺癌细胞增 殖、凋亡水平;用Transwell 法检测乳腺癌细胞迁移、侵袭水平;用免疫印迹法检测细胞PI3K/Akt 信号通路蛋白 PI3K、p-PI3K、Akt、p-Akt、caspase 3、Bcl-2、Bax 表达量。结果:下调组细胞不同时间点增殖率均显著低于 上调组、对照组。下调组细胞不同时间点凋亡率均显著高于上调组、对照组。下调组细胞迁移、侵袭数均显著 低于上调组、对照组。下调组p-PI3K、PI3K、Akt、p-Akt、Bcl-2 蛋白表达量低于上调组、对照组,caspase 3、 Bax 蛋白表达量高于上调组、对照组。结论:经下调RAGE作用于PI3K/Akt 信号通路,其可抑制p-PI3K、PI3K、 Akt、p-Akt、Bcl-2 表达,促进caspase 3、Bax 表达,致乳腺癌细胞凋亡,抑制乳腺癌细胞增殖、侵袭、迁移。  相似文献   
9.
采用液相色谱-质谱(LC-MS)联用技术研究他克莫司的有关物质。采用Agilent Eclipse Plus-C18(150 mm × 4.6 mm,3.5 μm)色谱柱,以0.01%甲酸水溶液-乙腈-甲基叔丁基醚为流动相体系,对他克莫司及其强制降解试验样品中的有关物质进行梯度洗脱分离;电喷雾正离子化-四极杆-飞行时间串联质谱法(ESI-Q-TOF/MS)测定各有关物质的母离子及碎片离子的准确质荷比和元素组成,并解析鉴定有关物质的结构。在所建立的条件下,他克莫司与其有关物质分离良好,检测并鉴定出35个主要有关物质,其中2个分别为他克莫司的互变异构体Ⅰ和Ⅱ(他克莫司的有效成分),3个为美国药典收载的已知杂质,其余30个为新鉴定的未知有关物质。研究结果可为他克莫司发酵生产过程的质量控制提供参考依据。  相似文献   
10.
随着科技的高速发展,基于核物理的诊断技术和放疗技术在医学中得到广泛应用,但同时也会给人体造成不同程度的损伤。因此,研究和开发能够预防以及治疗辐射损伤的药物意义重大。综述抗辐射天然产物如多糖、黄酮、酚酸、皂苷等的研究进展,并对其研究前景进行展望,为其进一步开发提供参考。  相似文献   
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