丹蛭降糖胶囊通过mTOR/S6K1信号通路对糖尿病肾病大鼠的干预作用研究

目的研究丹蛭降糖胶囊对糖尿病肾病大鼠的肾脏病理改变和足细胞自噬水平的影响,初步探讨其相应的作用机制。方法选取GK大鼠40只,采用醋酸脱氧皮质酮-盐皮下注射联合高脂饲料喂养诱导糖尿病肾病模型。造模成功后随机分为模型组、丹蛭降糖胶囊低剂量组[0.54 g/(kg·d)]、高剂量组[1.08 g/(kg·d)]、缬沙坦组[10 mg/(kg·d)],每组10只。另选取10只同周龄正常Wistar大鼠作为正常组。模型组和正常组给予等容积生理盐水。连续灌胃10周后检测空腹血糖(FBG)、血肌酐(SCr)、尿素氮(BUN)和尿微量蛋白(U-mAlb)。Western Blot检测肾小球p-mTOR、p-S6K1、Beclin-1、LC3和Nephrin蛋白的表达,HE染色和PAS染色后于光镜下观察肾脏病理变化,电镜下观察各组亚细胞形态结构变化。结果与正常组比较,模型组FBG、SCr、BUN、U-mAlb水平升高(P<0.01);与模型组比较,丹蛭降糖胶囊低、高剂量组和缬沙坦组U-mAlb水平降低(P<0.01)。模型组可见肾小球基底膜增厚,系膜基质沉积,足细胞损伤,各用药组均有不同程度改善,丹蛭降糖胶囊高剂量组足细胞内有较多自噬体形成。与正常组比较,模型组p-mTOR、p-S6K1的表达增高,Nephrin、Beclin-1和LC3的表达水平降低(P<0.01);与模型组比较,各用药组p-mTOR、p-S6K1的表达下降,Nephrin、Beclin-1和LC3的表达增高(P<0.01)。丹蛭降糖胶囊高剂量组和缬沙坦组Beclin1、LC3Ⅱ/LC3Ⅰ水平较丹蛭降糖胶囊低剂量组升高(P<0.05)。结论丹蛭降糖胶囊具有减轻糖尿病肾病大鼠U-mAIb、足细胞损伤及相关肾脏病理改变的作用,其机制可能与抑制mTOR/S6K1信号通路进而提高足细胞的自噬活性有关。     

Clinical implications,diagnosis,and management of diabetes in patients with chronic liver diseases

Diabetes mellitus(DM) negatively affects the development and progression of chronic liver diseases(CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma(HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.     

Exercise and Lifestyle Education program for Brazilians living with prediabetes and diabetes: A pilot randomized trial

AimsTo test the Diabetes College Brazil Study feasibility, the acceptability of study interventions and their preliminary effectiveness, and describe the study protocol modifications due to the COVID-19 pandemic.MethodsSingle-center, double-blinded pilot randomized trial with two parallel groups, Exercise and Lifestyle Education (ExLE; 12-week exercise and educational interventions) and Exercise (Ex; 12-week exercise intervention only) involving patients with prediabetes or diabetes. Feasibility (eligibility, recruitment, retention, completeness of variables measures and participation rates), acceptability (satisfaction), and preliminary effectiveness of interventions (variables: functional capacity, physical activity (PA), exercise self-efficacy, diabetes knowledge, health literacy, adherence to Mediterranean food pattern, glycated hemoglobin (HbA1c), anthropometric measures, cardiac autonomic control, depression, and quality of life (QofL)).ResultsEligibility, recruitment, retention, participation in exercise sessions, and education classes rates were 17%, 93%,82%, 76%, and 71%, respectively. Missing data in the post-intervention assessment (PA, HbA1c, cardiac autonomic control, anthropometric measures, depression, and QofL) were mainly related to research procedure modifications. The interventions were highly acceptable, and most variables improved farther in the ExLE, with moderate effect sizes for PA, diabetes knowledge, health literacy, cardiac autonomic control, and QofL.ConclusionsThe Diabetes College Brazil Study is feasible, and the ExLE may benefit Brazilians living with prediabetes and diabetes.     

SGLT2 inhibitors for the treatment of diabetes: a patent review (2013-2018)

Introduction: The sodium-glucose co-transporter 2 (SGLT2) is ascribed to target renal tubular glucose re-absorption, and its inhibition has been proved to induce glucosuria which improves the glycemic index. Accordingly, SGLT2 inhibitors have found to be the promising class of antidiabetic agents for the management of type 2 diabetes mellitus. A large number of SGLT2 inhibitors have developed through structural modification and investigated for their ability to selectivity inhibit SGLT2 transporters with better bioavailability.

Areas covered: This review comprises a summary of patent applications (2013–2018) of SGLT2 inhibitors with focus on chemical structural advancement and therapeutic potentials in the management of diabetes and related disorders.

Expert opinion: SGLT2 inhibitors exert multiple metabolic benefits, including reduced glycated hemoglobin (HbA1c), improved glycemic control (fasting and postprandial), reduced body weight, reduced systolic and diastolic blood pressure and improved HDL cholesterol. Due to the virtue of no interference with insulin action and secretion, their efficacy remains the same even in presence of progressive β cell failure in type 2 diabetes. Additionally, few members of this class have been reported to exhibit cardioprotective, renoprotective, and anticancer activity. However, more study on the long-term outcomes in patients taking SGLT2 inhibitors is warranted.     

基于SOCS通路探讨糖尿病足溃疡治疗中中药“去腐生新”作用的研究进展

糖尿病足溃疡（DFUs）是糖尿病严重的并发症之一，发病率和截肢率高，目前具体发病机制仍未完全明确。相关研究表明，炎症、感染和营养障碍等多种因素共同影响DFUs的转归及预后。抑制相关炎症通路和细胞因子表达，可促使坏死组织脱落促进愈合。此外，细胞因子信号传导抑制因子家族蛋白（SOCS）可通过激活蛋白酪氨酸激酶（JAK）/信号转导和转录活化因子（STAT）信号通路参与细胞因子信号转导，参与DFUs创面炎症反应以及愈合过程。近年来，大量研究发现具有“去腐生新”功效的单味中药及其活性成分、中药复方对DFUs具有很好的疗效，研究中药治疗DFUs的具体机制已成为近些年来研究的热点之一。文章查阅近年文献，就SOCS通路与DFUs的关系及中医药治疗DFUs作用机制进行综述。     

Potential roles of chromium on inflammatory biomarkers in diabetes: A Systematic

Diabetes, as a low‐grade chronic inflammatory disease, causes disruption in proper function of immune and metabolic system. Chromium is an important element required for normal lipid and glucose metabolism. Chromium deficiency is correlated with elevation in cardiometabolic risk, which results from increased inflammation. This systematic review was conducted to discover the potential roles of chromium on inflammatory biomarkers. Eligible studies were all in vitro, animal and human studies published in English‐language journals from inception until October 2018. PubMed, Scopus, Embase, ProQuest and Google Scholar databases were searched to fined interventional studies from the effects of chromium on inflammatory biomarkers such as tumour necrosis factor a (TNF‐a), C‐reactive protein (CRP), interleukins, monocyte chemoattractant protein–1 (MCP‐1), intercellular adhesion molecule‐1 (ICAM‐1) and adipocytokines in hyperglycaemia and diabetes. Out of 647 articles found in the search, only 14 articles were eligible for analysis, three in vitro studies, eight animal studies and three human studies. Twelve of the 14 studies included in this review, chromium significantly decreased inflammatory factors. The findings of this review indicate, based on in vitro and in vivo studies, that chromium might have potential anti‐inflammatory properties, but some of the studies did not show anti‐inflammatory effects for chromium (two studies). There are only three studies in humans with controversial results. Therefore, more consistent randomized double‐blind controlled trials are needed to reach relevant clinical recommendations, as well as to determine the precise mechanism, of chromium on inflammation in diabetes.     

84例产褥感染的临床特点及常见致病微生物耐药性分析

目的 研究产褥感染的危险因素及常见致病微生物耐药情况，为临床治疗提供参考。方法 回顾性分析我院2017 年1 月～2019 年12 月发生的84 例产褥感染病例的临床资料，与同时期未发生产褥感染的200 例产妇进行对照研究，分析产褥感染的影响因素，并对分离获得的致病微生物进行耐药性分析。结果 感染组妊娠糖尿病、产钳助产、宫口开全后中转剖宫产患者的分布率高于对照组，差异有统计学意义（P＜0.05）；经多因素Logistic 回归分析，妊娠糖尿病是产褥感染的独立影响因素（P＜0.05）。本研究中共检出致病微生物40 株，其中革兰阴性菌13 株（占32.50%），革兰阳性菌10 株（占25.00%），支原体16 株（占40.00%），衣原体1 株（占2.50%），革兰阴性菌中以大肠埃希菌最常见，对二代头孢菌素类抗生素耐药率20%。革兰阳性菌以金黄色葡萄球菌最常见，对青霉素及头孢菌素耐药率高，未发现对亚胺培南及万古霉素耐药。结论 产钳助产、妊娠糖尿病、宫口开全后中转剖宫产是产褥感染可能的危险因素，其中，妊娠糖尿病是产褥感染的独立危险因素。目前临床常见致病微生物谱及耐药率未发生明显变化。     

绝经后女性2型糖尿病伴骨质疏松患者骨密度与骨代谢指标的相关性分析

目的分析研究绝经后女性2型糖尿病伴骨质疏松症患者骨密度与骨代谢指标的相关性。方法选取2013年10月至2017年05月于重庆医科大学附属第一医院内分泌内科住院的绝经后女性2型糖尿病患者385名。搜集其基本资料、骨代谢指标及骨密度等。根据T值将这些患者分为骨质疏松组(233例)、骨量减少组(101例)和骨量正常组(51例),比较三组间骨代谢指标的变化,并对骨密度(bone mineral density,BMD)与各项骨代谢指标进行相关性分析。结果 1型前胶原氨基末端前肽(Type I procollagen N-terminal propeptide,P1NP)、骨钙素(bone Gla protein,BGP)在骨质疏松组显著高于骨量减少组、骨量正常组(P0.05);随着骨密度的降低,1型胶原羧基端肽β特殊序列(β-Carboxyl terminal peptide,β-CTX)逐渐升高,骨质疏松组、骨量减少组与骨量正常组相比较差异有统计学意义(P0.05);Spearman等级相关分析示P1NP、BGP、β-CTX与骨密度呈负相关,25(OH)D_3与骨密度呈现正相关。结论绝经后女性2型糖尿病伴骨质疏松症患者骨密度与骨代谢指标有一定的相关性,有助于预测骨折风险并及时抗骨质疏松治疗。     

Perioperative,short-, and long-term outcomes of gastric cancer surgery: Propensity score-matched analysis of patients with or without prior solid organ transplantation

BackgroundDetails of perioperative outcomes and survival after gastric cancer surgery in prior transplant recipients have received minimal research attention.MethodsWe performed an observational cohort study using the database of 20,147 gastric cancer patients who underwent gastrectomy at a single gastric cancer center in Korea. Forty-one solid organ recipients [kidney (n = 35), liver (n = 5), or heart (n = 1)] were matched with 205 controls using propensity score matching.ResultsOperation time, blood loss, and postoperative pain were similar between groups. Short-term complication rates were similar between transplantation and control groups (22.0% vs. 20.1%, P = 0.777). Transplantation group patients with stage 1 gastric cancer experienced no recurrence, while those with stage 2/3 cancer had significantly higher recurrence risk compared to the controls (P = 0.049). For patients with stage 1 cancer, the transplantation group had a significantly higher rate of non-gastric cancer-related deaths compared to the controls (19.2% vs. 1.4%, P = 0.001). For those with stage 2/3 cancer, significantly lower proportion of the transplantation group received adjuvant chemotherapy compared to the control group (26.7% vs. 80.3%, P < 0.001). The transplantation group had a higher (albeit not statistically significant) rate of gastric cancer-related deaths compared to the controls (40.0% vs. 18.0%, P = 0.087).ConclusionTransplant recipients and non-transplant recipients exhibited similar perioperative and short-term outcomes after gastric cancer surgery. From long-term outcome analyses, we suggest active surveillance for non-gastric cancer-related deaths in patients with early gastric cancer, as well as strict oncologic care in patients with advanced cancer, as effective strategies for transplant recipients.