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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.
The main aim of the paper is to discuss current knowledge on how Age Related Macular Degeneration (AMD) affects Dark Adaptation (DA). The paper is divided into three parts. Firstly, we outline some of the molecular mechanisms that control DA. Secondly, we review the psychophysical issues and the corresponding analytical techniques. Finally, we characterise the link between slowed DA and the morphological abnormalities in early AMD.Historically, DA has been regarded as too cumbersome for widespread clinical application. Yet the technique is extremely useful; it is widely accepted that the psychophysically obtained slope of the second rod-mediated phase of the dark adaptation function is an accurate assay of photoreceptor pigment regeneration kinetics. Technological developments have prompted new ways of generating the DA curve, but analytical problems remain. A simple potential solution to these, based on the application of a novel fast mathematical algorithm, is presented. This allows the calculation of the parameters of the DA curve in real time.Improving current management of AMD will depend on identifying a satisfactory endpoint for evaluating future therapeutic strategies. This must be implemented before the onset of severe disease. Morphological changes progress too slowly to act as a satisfactory endpoint for new therapies whereas functional changes, such as those seen in DA, may have more potential in this regard. It is important to recognise, however, that the functional changes are not confined to rods and that building a mathematical model of the DA curve enables the separation of rod and cone dysfunction and allows more versatility in terms of the range of disease severity that can be monitored. Examples are presented that show how analysing the DA curve into its constituent components can improve our understanding of the morphological changes in early AMD.  相似文献   
4.
AIM: To determine whether the prevalence of treated hypertension is higher among males or females with early/intermediate (e/i) age-related macular degeneration (AMD) with and without bilateral reticular pseudodrusen (RPD). METHODS: Retrospective review of the records of patients with e/iAMD who were recruited into the University of Colorado AMD registry between July 2014 and November 2019. Images were classified using the Beckman Initiative criteria and presence/absence of RPD. Patients were categorized into three groups: 1) e/iAMD with RPD; 2) e/iAMD without RPD; 3) control patients who did not have AMD. Multinomial logistic regression analysis was used for adjusted analysis with odds ratios (OR) and confidence intervals (CI). RESULTS: There were 260 patients with e/iAMD of which 101 had bilateral RPD and 159 had no RPD, and 221 controls. Overall, 62% of patients were female and the three groups did not differ by gender. When stratified by gender, the female e/iAMD/RPD group had a higher prevalence of hypertension, 64.1% vs 45.2% for controls, OR=2.2 (95%CI: 1.2-4.0). The frequency of hypertension in the e/iAMD/no RPD group was 54.1% and did not significantly differ from the control group. Among males, prevalence rates of treated hypertension did not differ. There is a significant interaction of hypertension and gender for the e/iAMD/RPD group such that women with e/iAMD who had RPD were significantly more likely to have hypertension (P=0.042). This relationship was not significant in the e/iAMD/no RPD group (P=0.269). CONCLUSION: Among females treated hypertension is significantly higher among e/iAMD/RPD patients, whereas for males there is no significant association.  相似文献   
5.
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   
6.
7.
《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   
8.
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   
9.
BackgroundPatients hospitalized for COVID-19-related pneumonia often need several degrees of ventilatory support, which are performed between Respiratory Intermediate Care Units (RICUs) and Intensive Care Units (ICUs), and which depend on the severity of acute respiratory distress syndrome. There is no firm consensus on transfer predictors from the RICU to the ICU.MethodsIn this retrospective observational single center study, we evaluated 96 COVID-19 patients referred to the RICU for acute respiratory failure (ARF) according to their transferal to the ICU or their stay at the RICU. We compared demographic data, baseline laboratory profile, and final clinical outcomes to identify early risk factors for transfer.ResultsThe best predictors for transfer to the ICU were elevated C-reactive protein and lymphopenia. The mortality rate was lower in the RICU than in the ICU, where transferred patients who died were mostly younger men and with less comorbidities than those in the RICU.ConclusionsFew inflammatory markers can predict the need for transfer from the RICU to the ICU. Due to the ongoing COVID-19 pandemic, we urge better clinical stratification by early and meaningful profiles in patients admitted to the RICU who are at risk of transferal to the ICU.  相似文献   
10.
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