The efficacy and safety of glucokinase activators for the treatment of type-2 diabetes mellitus: A protocol for systematic review and meta-analysis

Background:Glucokinase activators are a novel family of glucose-lowering agents used for the treatment of type-2 diabetes mellitus (T2DM). Glucokinase activators blind to GK activate the enzyme allosterically. Treatment with different GKAs has been shown to reduce fasting and postprandial glucose in patients with type 2 diabetes. We compared the efficacy/safety of glucokinase activators in T2DM patients through a meta-analysis.Methods:We searched PubMed, Excerpt Medica Database, and Cochrane Central Register of Controlled Trials databases for articles published before December 30, 2020. Two independent reviewers extracted the information from article. The quality of articles were assessed by 2 independent reviewers using the 5 items of scale proposed by Jadad. We computed the weighted mean difference and 95% confidence interval (CI) for a change from baseline to the study endpoint for glucokinase activators vs placebo. Egger test and Begg test were used to assess the possible publication bias caused by the tendency of published studies to be positive.Results:The present meta-analysis will compare the efficacy and safety of glucokinase activators and placebo for the treatment of T2DM.Conclusions:This meta-analysis will provide advanced evidence on the efficacy and safety of glucokinase activators for the treatment of T2DM.Ethics and dissemination:Ethical approval and patient consent are not required because this study is a literature-based study. This systematic review and meta-analysis will be published in a peer-reviewed journalPROSPERO registration number:CRD42021220364.     

Anesthetic effect of ultrasound-guided multiple-nerve blockade in modified radical mastectomy in patients with breast cancer

Introduction:Routine anesthesia modality for modified radical mastectomy (MRM) includes general anesthesia (GA), epidural blockade-combined GA and nerve blockade-combined GA. However, GA has been associated with postoperative adverse effects such as vertigo, postoperative nausea and vomiting and requirement for postoperative analgesia, which hinders recovery and prognosis. Moreover, combined blockade of thoracic paravertebral nerves or intercostal nerves and adjuvant basic sedation for massive lumpectomy provided perfect anesthesia and reduced opioid consumption, whereas the excision coverage did not attain the target of MRM. Regional anesthesia strategies involving supplementation of analgesics in ultrasound-guided multiple nerve blocks have garnered interests of clinicians. Nevertheless, the precise effects of intercostal nerves, brachial plexus and supraclavicular nerves in MRM in patients with breast cancer remain obscure.Methods:Eighty female patients with breast cancer scheduled for MRM were recruited in the present trial between May, 2019 and Dec., 2019 in our hospital. The patients ranged from 30 to 65 years of age and 18∼30 kg/m² in body-mass index, with the American Society of Anesthesiologists I or II. The patients were randomized to ultrasound-guided multiple nerve blocks group and GA group. The patients in multiple nerve blocks group underwent ultrasound guided multiple intercostal nerve blocks, interscalene brachial plexus and supraclavicular nerve blocks, (local anesthesia with 0.3% ropivacaine: 5 ml for each intercostal nerve block, 8 ml for brachial plexus block, 7 mL for supraclavicular nerve block) and basic sedation and intraoperative mask oxygen inhalation. The variations of hemodynamic parameters such as mean arterial pressure, heart rate (HR) and pulse oxygen saturation were monitored. The visual analog scale scores were recorded at postoperative 0 hour, 3 hour, 6 hour, 12 hour and 24 hour in resting state. The postoperative adverse effects, including vertigo, postoperative nausea, and vomiting, pruritus, and urinary retention and so on, as well as the analgesic consumption were recorded.Conclusions:The ultrasound guided multiple intercostal nerve blocks, brachial plexus and supraclavicular nerve blocks could provide favorable anesthesia and analgesia, with noninferiority to GA and the reduced incidence of adverse effects and consumption of postoperative analgesics.     

Clinical significance of apelin in the treatment of type 2 diabetic peripheral neuropathy

Background:Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes. As apelin is an adipocytokine closely associated with diabetes, this study explored the clinical significance of serum apelin levels in patients with type 2 DPN before and after treatment.Methods:In total, 44 patients with T2DM without DPN (non-DPN group), 41 patients with DPN who received antihyperglycemic treatment (DPN-A group), 44 patients with DPN who received antihyperglycemic treatment combined with nutritional neurotherapy (DPN-B group), and 40 healthy control individuals (NC group) were selected continuously enrolled in the present study. Enzyme-linked immunosorbent assays (ELISA) were performed to determine serum levels of apelin and tumor necrosis factor-α (TNF-α). Related apelin, fasting blood glucose (FBG), glycosylated hemoglobin A1c, TNF-α, body mass index, fasting C peptide, and nerve conduction velocity (NCV) were recorded in each group before and after treatment.Results:Serum levels of apelin and TNF-α were higher in patients with diabetes than those in the NC group, as well as in the DPN group as compared to the non-DPN group; furthermore, some NCV values were significantly reduced in the DPN group. After treatment, the serum levels of apelin, TNF-α, and FBG reduced in patients with diabetes; moreover, apelin levels were found significantly lower in the DPN-B group as compared to the DPN-A group, while some NCV values significantly increased in the DPN-B group. Apelin was negatively correlated with part of NCV values and positively correlated with TNF-α and FBG (P < .01).Conclusion:Our results show that the increase in serum apelin levels is an important clinical reference index for DPN, while a decrease indicates that the DPN treatment is effective.     

Orexin A Suppresses the Expression of Exosomal PD-L1 in Colon Cancer and Promotes T Cell Activity by Inhibiting JAK2/STAT3 Signaling Pathway

Digestive Diseases and Sciences - Colon cancer, ranked third in cancer related mortality, is the most common malignant cancer of digestive tract. Though immune checkpoint inhibitors show promising...     

恶性肿瘤的姑息治疗

现代社会,恶性肿瘤患者越来越多,大多数患者确诊已属中晚期,并且出现各种并发症,所以姑息治疗在恶性肿瘤综合治疗中至关重要。姑息治疗主要是通过姑息性手术和药物治疗改善患者的伴随症状,提高患者及家属的生活质量。     

The role of anti-ribosomal P autoantibodies in the prediction of neuropsychiatric damage in systemic lupus erythematosus based on CSTAR cohort (XIV)

Clinical Rheumatology - To identify the predictive value of anti-ribosomal P protein (anti-RibP) antibodies on the accrual of neuropsychiatric damage in systemic lupus erythematosus (SLE) patients...     

Enhanced tryptophan-kynurenine metabolism via indoleamine 2,3-dioxygenase 1 induction in dermatomyositis

Clinical Rheumatology - Extrahepatic tryptophan (Trp)-kynurenine (Kyn) metabolism via indoleamine 2,3-dioxygenase 1 (IDO1) induction was found to be associated with intrinsic immune regulation....     

血管内超声指导药物洗脱支架置入对合并慢性肾脏病患者长期预后的影响:ULTIMATE CKD亚组分析

目的评估血管内超声(IVUS)指导药物洗脱支架(DES)置入对慢性肾脏病(CKD)患者长期临床结局的影响。方法研究对象来源于ULTIMATE研究,该研究是一项前瞻性、多中心、随机对照研究,从2014年8月到2017年5月在国内8家中心入选1448例置入DES的冠心病患者,按1∶1的比例随机分为两组(接受IVUS或冠状动脉造影指导支架置入)。本研究选取ULTIMATE研究中有基线血肌酐值的患者1443例,分为CKD组和非CKD组。CKD的定义为Cockcroft-Gault(CG)公式得出的估算的肾小球滤过率(eGFR)<60 ml·min^-1·1.73 m^-2至少3个月。主要终点是术后3年靶血管失败(TVF),包含心原性死亡、靶血管心肌梗死和临床症状驱动的靶血管血运重建。采用Kaplan-Meier法进行生存分析,通过log-rank检验比较各组的终点事件发生情况,并采用Cox风险比例模型计算HR及其95%CI,同时检验交互作用。采用多因素Cox回归分析TVF的独立影响因素。结果本研究共入选1443例置入DES的冠心病患者,其中CKD组349例(24.2%),非CKD组1094例。CKD组中采用IVUS指导支架置入者180例,造影指导支架置入者169例;非CKD组中采用IVUS指导支架置入者543例,造影指导支架置入者551例。3年临床随访率为98.3%(1418/1443)。术后3年时,CKD组的TVF发生率为12.0%(42/349),高于非CKD组的7.4%(81/1094)(P=0.01),其差异主要来源于CKD组更高的心原性死亡率[4.6%(16/349)比1.5%(16/1094),P<0.001]。CKD组中IVUS指导下置入支架者的TVF发生率低于造影指导下置入支架者[8.3%(15/180)比16.0%(27/169),P=0.03]。而非CKD组共81例发生TVF,其中IVUS指导下置入支架者的TVF发生率与造影指导下置入支架者差异无统计学意义[5.9%(32/543)比8.9%(49/551),P=0.06],不存在交互作用(P=0.47)。多因素Cox回归分析结果显示,IVUS指导(HR=0.56,95%CI 0.39~0.81,P=0.002)、CKD(HR=1.83,95%CI 1.17~2.87,P=0.010)和支架长度(每增加10 mm)(HR=1.11,95%CI 1.04~1.19,P=0.002)是置入DES术后3年发生TVF的独立影响因素。结论对于置入DES的冠心病患者,合并CKD者术后3年的TVF发生风险高于非CKD患者;相比于冠状动脉造影,IVUS指导DES置入可以降低CKD患者的TVF风险。     

Efficacy and safety of app-based remote warfarin management during COVID-19-related lockdown: a retrospective cohort study

Journal of Thrombosis and Thrombolysis - Patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) are at increased risk for thrombotic and bleeding...