Multiomics analyses reveal a critical role of selenium in controlling T cell differentiation in Crohn’s disease

1. Download : Download high-res image (195KB)
2. Download : Download full-size image

     

肝脏原发性未分化多形性肉瘤的CT及MRI表现

目的 观察肝脏原发性未分化多形性肉瘤（UPS）的CT与MRI表现。方法 回顾性分析8例经病理证实的肝脏原发性UPS患者的影像学资料。结果 6例肿瘤位于肝右叶,1例位于肝左叶,1例位于尾状叶。6例病灶呈不规则形,边界模糊;2例呈类圆形,边界尚清。7例呈混杂密度,1例密度较均匀。8例肿瘤增强扫描动脉期均呈轻度不均匀强化,静脉期肿瘤强化程度、范围均进一步增加;6例肿瘤延迟期持续强化。4例肿瘤并发下腔静脉或门静脉癌栓。结论 肝脏UPS的CT及MRI表现具有一定特征性,有助于诊断。     

Acute toxicity is a dose-limiting factor for intravenous polymyxin B: A safety and pharmacokinetic study in healthy Chinese subjects

ObjectivesPolymyxin B is a last-line antibiotic for multidrug-resistant gram-negative bacterial infections. However, limited safety and pharmacokinetic information is available. We investigated the safety and pharmacokinetics of intravenous polymyxin B in healthy subjects.MethodsAn open-label, single-dose clinical trial was conducted in healthy Chinese subjects. Polymyxin B (sulphate) was administered intravenously at 0.75 or 1.5 mg/kg (n = 10 per dose, 5 males and 5 females) to examine the safety and pharmacokinetics.ResultsOne female subject in the 1.5-mg/kg group discontinued due to abdominal pain during administration. The most frequently reported adverse events were perioral paraesthesia, dizziness, and numbness of extremities (7/10 subjects in the 0.75-mg/kg group, all subjects in the 1.5-mg/kg group). All neurotoxicity-related events dissipated without treatment within a maximum of 23 h. Notably, abdominal pain (3/5) and vulvar pruritus (2/5), colpitis (2/5) or abnormal uterine bleeding (1/5) were reported in female subjects receiving the 1.5-mg/kg dose. In the 0.75-mg/kg group, the total clearance, volume of distribution and half-life of polymyxin B were 0.028±0.002 L/h/kg, 0.219±0.023 L/kg and 5.44±0.741 h, respectively; similar values were observed in the 1.5-mg/kg group. Urinary recovery was 3.7 ± 1.1% and 8.1 ± 1.3% in the 0.75- and 1.5-mg/kg groups, respectively. Population pharmacokinetics of polymyxin B was consistent with a three-compartment model. The clearance and distribution of the central compartment were 0.027 L/h/kg and 0.071 L/kg, respectively.ConclusionsThis study is the first to examine the safety and pharmacokinetics of polymyxin B in healthy subjects. Our results highlight that acute toxicity is a dose-limiting factor for intravenous polymyxin B.     

鞭节舌虫病：附一例报告

报告１例鞭节舌虫病。据文献检索此系世界上第一例鞭节舌虫寄生于人体内并引起发病。该病临床特点为长期高热、腹痛、腹泻、肝脾肿大、轻度贫血；骨髓及周围血嗜酸性白细胞增高；全结肠多发性息肉样赘生物；肝细胞变性坏死和大量嗜酸性白细胞浸润。该病需与引起肝脾肿大，长期高热，腹痛腹泻等各种疾病相鉴别。该病的流行病学、发病机制、病理、自然病史，临床表现、诊断与鉴别诊断及治疗等都有待进一步研究     

Association of mental health with the risk of coronary artery disease in patients with diabetes: A mendelian randomization study

Background and aimsObservational studies have shown an association between mental health and coronary artery disease (CAD) in patients with diabetes. Nevertheless, whether these associations are causal is still unknown. In this two-sample Mendelian randomization (MR) study, we aimed to assess the causality between mental health and CAD in patients with diabetes.Methods and resultsSingle-nucleotide polymorphisms (SNPs) associated with: depression (807,553 individuals), anxiety (83,556 individuals) and neuroticism (329,821 individuals) were identified from the largest genome-wide association studies (GWAS). Summary-level data for CAD were extracted from the recently published GWAS of 15,666 diabetic patients (3968 CAD cases and 11,696 controls). The inverse-variance weighted (IVW) method was used for the main analysis. Sensitivity analyses included weighted median, maximum likelihood, and the MR-Egger method. Genetic liability to depression was significantly associated with a higher risk of CAD in patients with diabetes (odds ratio [OR], 1.286; 95%CI,1.018–1.621;p = 0.035). For anxiety and neuroticism, no causal association with CAD in patients with diabetes was observed. Consistent results were obtained in most sensitivity analyses.ConclusionsThis MR study provides genetic evidence that depression is a potential risk factor for CAD in patients with diabetes. However, anxiety and neuroticism were not causally associated with CAD in patients with diabetes. Mental health treatments should be enhanced to prevent CAD in patients with diabetes.     

Augmentation in patients with restless legs syndrome receiving pramipexole therapy: a retrospective study in a single center from China

Sleep and Breathing - Augmentation is a major complication of long-term pramipexole treatment of restless legs syndrome (RLS). However, there have been no studies on augmentation in Chinese...     

老年心肌缺血者QTc和QTcd变化及临床意义

测定了６４例老年心肌缺血（ＭＩＳ）患者和２１例心肌梗塞（ＭＩ）患者心电图的ＱＴｃ间期和ＱＴｃ离散度（ＱＴｃｄ），并与心血管神经官能症（ＣＶＮ）及正常老年人进行比较；探讨ＱＴｃ、ＱＴｃｄ与致命性室性心律失常（ＦＶＡ）、心原性猝死（ＣＳＤ）的关系；分析ＭＩ不同部位的ＱＴｃｄ变化以及稳定性心绞痛（ＳＡＰ）和不稳定性心绞痛（ＵＳＡＰ）的ＱＴｃｄ差异。结果：老年女性患者ＱＴｃ较男性长（Ｐ＜０．０５），而ＱＴｃｄ两者无差异；老年ＭＩＳ患者ＱＴｃ和ＱＴｃｄ较正常组明显延长（Ｐ＜０．０１）；ＭＩ前壁、下壁和后壁３组ＱＴｃｄ无明显差异（Ｐ＞０．０５）；ＵＳＡＰ患者ＱＴｃｄ较ＳＡＰ长（Ｐ＜０．０５）。     

CD4+CD25+调节性T细胞与1型糖尿病

CD4^＋CD25^＋调节性T细胞是调节性T细胞亚群中的重要组成成分，可组成性表达许多细胞表面分子，包括CD25、细胞毒性T淋巴细胞相关抗原-4（CTLA-4）、糖皮质激素诱导肿瘤坏死因子受体（GITR）、CD122、CD103和转录因子FOXp3，并具有免疫无能性和免疫抑制性两大特性。1型糖尿病的发病与调节性T细胞的数目、功能以及调节性T细胞与效应性T细胞的比例失衡有关。多项实验表明，在体内诱生或过继调节性T细胞能预防1型糖尿病的发生和发展。     

Effects of a Chinese Medicinal Plant Radix Astragali on the Ovariectomized Female Rats

Perimenopausal syndrome occurs during the transition to menopause. Complementary and alternative medicine, especially Chinese medicinal plants, has manifested significant effects in alleviating perimenopausal symptoms. However, little research has been focused on the effects of Chinese medicinal plant on the immune function of the perimenopausal women. The present study aimed to explore the effects of Radix Astragali (RA) on the sex hormone levels and the interleukins of the ovariectomized female rats. 24 female Sprague-Dawley (SD) rats were randomly divided into model control group (MOD group), sham-operation group (SHAM group), RA group and estrogen group (EST group). After all the treatment ended, the serum levels of estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), interleukin-2 (IL-2), and interleukin-8 (IL-8) were measured using enzyme-linked immune-sorbent assay (ELISA) and the uterus was removed and weighed after blood exsanguinations immediately. In the MOD group, the serum levels of E2 were significantly lower, and the serum levels of FSH and LH were markedly higher than those of the RA group, EST group and SHAM group (P<0.05). In the RA group, the serum levels of E2 were significantly lower, and the serum levels of FSH were markedly higher than those of the SHAM group and EST group, respectively. In the MOD group, the serum levels of IL-2 and IL-8 were significantly lower than those of the RA group, EST group and SHAM group (P<0.05), and no marked differences existed among RA group, EST group and SHAM group in the serum levels of IL-2 and IL-8 (P>0.05). The uterine weight of the rats in the RA group, EST group and SHAM group were significantly higher than those of the rats in MOD group (P<0.05). There were no marked differences among the rats from RA group, EST group and SHAM group on the uterine weight (P>0.05). It is concluded that RA can significantly improve the immune functions of the ovariectomized female rats, although it cannot change the sex hormones levels as significantly as estrogen.     

The inhibitor effect of RKIP on inflammasome activation and inflammasome-dependent diseases

Aberrant inflammasome activation contributes to the pathogenesis of various human diseases, including atherosclerosis, gout, and metabolic disorders. Elucidation of the underlying mechanism involved in the negative regulation of the inflammasome is important for developing new therapeutic targets for these diseases. Here, we showed that Raf kinase inhibitor protein (RKIP) negatively regulates the activation of the NLRP1, NLRP3, and NLRC4 inflammasomes. RKIP deficiency enhanced caspase-1 activation and IL-1β secretion via NLRP1, NLRP3, and NLRC4 inflammasome activation in primary macrophages. The overexpression of RKIP in THP-1 cells inhibited NLRP1, NLRP3, and NLRC4 inflammasome activation. RKIP-deficient mice showed increased sensitivity to Alum-induced peritonitis and Salmonella typhimurium-induced inflammation, indicating that RKIP inhibits NLRP3 and NLRC4 inflammasome activation in vivo. Mechanistically, RKIP directly binds to apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and competes with NLRP1, NLRP3, or NLRC4 to interact with ASC, thus interrupting inflammasome assembly and activation. The depletion of RKIP aggravated inflammasome-related diseases such as monosodium urate (MSU)-induced gouty arthritis and high-fat diet (HFD)-induced metabolic disorders. Furthermore, the expression of RKIP was substantially downregulated in patients with gouty arthritis or type 2 diabetes (T2D) compared to healthy controls. Collectively, our findings suggest that RKIP negatively regulates NLRP1, NLRP3, and NLRC4 inflammasome activation and is a potential therapeutic target for the treatment of inflammasome-related diseases.