Decreased microRNA miR-181c expression in peripheral blood mononuclear cells correlates with elevated serum levels of IL-7 and IL-17 in patients with myasthenia gravis

miR-181c is a newly identified negative regulator of immune cell activation. In this study, we aimed to investigate the expression and functional role of miR-181c in myasthenia gravis (MG). miR-181c showed significant downregulation in peripheral blood mononuclear cells (PBMCs) from MG patients compared with healthy controls, with lower expression in generalized patients than in ocular ones. MG patients also had increased serum IL-7 and IL-17 levels. Additionally, serum IL-7 level presents a positive correlation with the serum IL-17 level. miR-181c levels were negatively correlated with serum levels of IL-7 and IL-17 in either generalized patients or ocular patients. A luciferase reporter assay revealed that miR-181c could directly bind to the 3′-UTR of interleukin-7. Forced expression of miR-181c led to decreased IL-7 and IL-17 release in cultured PBMCs, while depletion of miR-181c increased the secretion of these two proinflammatory cytokines. The results from our study suggested for the first time that miR-181c was able to negatively regulate the production of proinflammatory cytokines IL-7 and IL-17 in MG patients, and it is a novel potential therapeutic target for MG.     

黄芪甲苷对慢性心力衰竭大鼠的心脏保护作用

目的 从不同角度研究黄芪甲苷对慢性心力衰竭(CHF)大鼠心脏的保护作用。方法 对基线情况无统计学差异的60只雄性SD大鼠采用腹主动脉缩窄法建立慢性心力衰竭模型,术后6周行大鼠心脏超声判断建模是否成功。建模成功后随机分为模型组、低剂量及高剂量黄芪甲苷组;另建立假手术组,每组20只大鼠。低剂量和高剂量黄芪甲苷组分别给予30μg·g-1·d-1、70μg·g-1·d-1的黄芪甲苷灌胃,假手术组及模型组给予相同体积的0.9%Na Cl溶液灌胃。干预8周后行大鼠心脏超声测定大鼠心脏结构及功能指标,然后行大鼠左室插管收集血流动力学参数,留取心脏测定左室质量指数及右室质量指数,并对心肌组织行苏木素-伊红(HE)染色、Masson染色观察心肌细胞形态学变化,从心脏结构、功能、血流动力学、心室重构情况及形态学方面多角度研究黄芪甲苷对CHF大鼠的心脏保护作用。结果 与假手术组比较,模型组大鼠的左室后壁厚度(LVPWD)、左室质量指数(LVMI)、胶原容积分数(CVF)均增高(P0.05)。黄芪甲苷干预后,低剂量及高剂量黄芪甲苷组左室后壁厚度、左室质量指数、胶原容积分数较模型组均下降(P0.05)。结论 黄芪甲苷可以通过抑制CHF大鼠心肌纤维化、降低左室厚度、改善血流动力学等方面发挥保护心脏的作用。     

The Chinese version of the Addiction Severity Index (ASI-C): Reliability,validity, and responsiveness in Chinese patients with alcohol dependence

We evaluated the reliability, validity, and responsiveness of the Chinese version of the 5th edition Addiction Severity Index (ASI-C-5) in Chinese male alcohol-dependent inpatients. Three hundred and fifty-four inpatients with alcohol dependence from five regions of China were interviewed in person by five trained interviewers using the ASI-C-5. Responses were then analyzed for internal consistency reliability, discriminant validity, criterion validity, and responsiveness. Forty subjects were re-interviewed 7 days later to assess test–retest reliability. The ASI-C-5 had good internal consistency, with an overall standardized Cronbach's alpha of 0.79. The Cronbach's alpha values for internal consistency of domain CSs ranged from 0.48 to 0.95, and were above 0.60 for six domains. The 7 day test–retest reliability was acceptable as evidenced by high Pearson correlation coefficients (0.75–0.92, p < 0.01) for 6 of 7 domain CSs. Correlation coefficients between the seven domain CSs ranged from 0.007 to 0.390 (p < 0.05 or 0.01 two-sided), indicating strong discriminant validity. The correlation coefficient between the alcohol dependence composite score of ASI-C-5 and the Alcohol Use Disorders Identification Test (AUDIT) was 0.69 (p < 0.01), indicating good criterion validity. The frequency of extreme scores was low, except for significant floor effects in the “Drugs” and “Legal Status” domains. Collectively, these findings suggest that the ASI-C-5 exhibited strong reliability, validity, and responsiveness in Chinese male alcohol-dependent inpatients.     

脑血管淀粉样变性相关脑出血的手术疗效分析

目的 探讨脑血管淀粉样变性相关脑出血（CAA-ICH）手术治疗的临床效果。方法 回顾性分析2014年3月～2019年3月手术治疗的33例CAA-ICH的临床资料。结果 33例中,年龄<70岁15例（低龄组）,年龄≥70岁18例（高龄组）。小骨窗手术5例,标准骨瓣开颅手术28例（骨瓣回置20例,去骨瓣减压8例）。术后24 h复查头部CT显示血肿清除率在60～95%,平均（80.5±4.2）%。低龄组血肿清除率[（81.6±4.3）%]与高龄组[（79.4±5.1）%]无统计学差异（P>0.05）。低龄组术后发生再出血发生率（6.67%）、肺部感染发生率（40.00%）、下肢静脉血栓发生率（13.33%）与高龄组（分别为11.11%、55.56%、33.33%）无统计学差异（P>0.05）。术后随访1年,按GOS评分：死亡5例,植物生存5例,重残9例,中残10例,恢复良好4例。低龄组预后良好率（60.00%;GOS评分4～5分）明显高于高龄组（27.78%;P<0.05）。结论 CAA-ICH术后并发症发生率高,总体预后不理想。相对年轻的CAA-ICH病人,显微手术...     

Conversion to Belatacept in kidney transplant recipients with chronic antibody-mediated rejection (CAMR)

BackgroundThe costimulatory inhibitor Belatacept (Bela) has been shown to be an effective alternative in several clinical situations, including chronic antibody-mediated rejection, calcineurin toxicity, and de novo alloantibody formation. To further explore the usefulness of Belatacept under various clinical scenarios, we performed a retrospective analysis of a prospective database of all recipients who had a BPAR diagnosis of CAMR and were converted to a Belatacept maintenance immunosuppression regimen after kidney transplantation.Material and methodWe conducted a retrospective analysis of a prospectively collected database of all kidney transplants adult patients at SUNY Upstate Medical Hospital from 1 January 2013 to 31 December 2021. Our inclusion criteria were the patients who have been diagnosed with CAMR according to their renal biopsy based on the 2013 Banff criteria. The primary objective was to compare the kidney viability and function using GFR between the two interest groups and finally compare the outcomes.ResultsA total of 48 patients met our inclusion criteria based on the kidney biopsy result, which showed chronic antibody-mediated graft rejection (CAMR). Nineteen patients (39.6%) were converted to the Belatacept, and we continued the previous immunosuppression regimen in 29 patients (60.4%). The mean time from the transplant date to the diagnosis of CAMR was 1385 days in the Belatacept group and 914 days for the non-Belatacept group (P = 0.15). The mean GFR comparison at each time point between the groups did not show a significant difference, and Belatacept did not show superiority compared to the standard immunosuppression regimen in terms of kidney function preservation. 1 (5.2%) patient from the Belatacept group and 1 (3.4%) patient from the non-Belatacept group had a biopsy-proven acute rejection (BPAR) after CAMR confirmation, and it was comparable (P = 0.76). De novo synthesis of the DSA rate was 12.5% in the Belatacept group and 15% In the non-Belatacept group, which was comparable. (P = 0.90). The patient survival rate was 100% in both groups.ConclusionsWe conclude that compared to the standard Tacrolimus/MMF/Prednisone regimen, Belatacept did not significantly benefit in preserving the GFR in long-term follow-ups and stabilizing the DSA production, which is one of the main factors resulting in chronic graft failure.