目的 探讨醋酸泼尼松+环磷酰胺治疗甲亢合并突眼的临床疗效及血清促甲状腺激素受体抗体(TRAb)、白细胞介素-1(IL-1)变化研究.方法 前瞻性选取2016年5月至2019年12月北京医院收治的64例甲亢合并突眼患者,采用随机数字表法将其分为2组:对照组(n=30)予以常规甲亢治疗,研究组(n=34)在常规治疗基础上应用醋酸泼尼松+环磷酰胺治疗.观察2组患者甲亢指标、突眼疗效及血清TRAb、IL-1水平变化.结果 治疗后8周2组患者游离三碘甲状腺原氨酸(FT3)、游离甲状腺激素(FT4)、总三碘甲状腺原氨酸(TT3)和总甲状腺素(TT4)水平均较治疗前明显降低(P<0.05),而促甲状腺激素(TSH)水平显著增高(P<0.05);治疗后8周研究组FT3、FT4、TT3、TT4水平均明显低于对照组(P<0.05),TSH水平明显高于对照组(P<0.05);研究组临床总有效率为91.18％,明显高于对照组(76.67％),组间比较差异有统计学意义(P<0.05);治疗后8周2组患者血清TRAb、IL-1水平均显著降低(P<0.05),且治疗后8周研究组TRAb、IL-1水平均明显低于对照组,差异有统计学意义(P<0.05).结论 醋酸泼尼松+环磷酰胺可改善甲亢合并突眼患者甲状腺功能和突眼症状,下调TRAb、IL-1水平,可作为甲亢合并突眼的有效治疗方法.

BACKGROUND:The association of gut microbiota and diseases of the central nervous system (CNS), including multiple sclerosis (MS), has attracted much attention. Although a previous analysis of MS gut microbiota revealed a reduction in species producing short-chain fatty acids (SCFAs), the influence of these metabolites on demyelination and remyelination, the critical factors of MS pathogenesis, remains unclear. METHODS:To investigate the relationship between demyelination and gut microbiota, we administered a mixture of non-absorbing antibiotics or SCFAs to mice with cuprizone-induced demyelination and evaluated demyelination and the accumulation of microglia. To analyze the direct effect of SCFAs on demyelination or remyelination, we induced demyelination in an organotypic cerebellar slice culture using lysolecithin and analyzed the demyelination and maturation of oligodendrocyte precursor cells with or without SCFA treatment. RESULTS:The oral administration of antibiotics significantly enhanced cuprizone-induced demyelination. The oral administration of butyrate significantly ameliorated demyelination, even though the accumulation of microglia into demyelinated lesions was not affected. Furthermore, we showed that butyrate treatment significantly suppressed lysolecithin-induced demyelination and enhanced remyelination in an organotypic slice culture in the presence or absence of microglia, suggesting that butyrate may affect oligodendrocytes directly. Butyrate treatment facilitated the differentiation of immature oligodendrocytes. CONCLUSIONS:We revealed that treatment with butyrate suppressed demyelination and enhanced remyelination in an organotypic slice culture in association with facilitating oligodendrocyte differentiation. Our findings shed light on a novel mechanism of interaction between the metabolites of gut microbiota and the CNS and may provide a strategy to control demyelination and remyelination in MS.

This meta-analysis aims to evaluate whether the CD40 rs1883832 polymorphism is associated with Graves' disease (GD) risk in different populations. We performed a systematic literature search in China National Knowledge Infrastructure (CNKI), Web of Science, and Pubmed databases to identify case-control association studies on the association between rs1883832 and GD risk. For each study we calculated the odds ratios (OR) and 95 % confidence intervals (CI) assuming dominant, recessive and homozygote models. We then calculated pooled ORs and 95 % CIs. After applying inclusion and exclusion criteria, 17 studies involving 4707 cases and 4215 controls were included in the meta-analysis. The results showed that rs1883832 was associated with GD risk in Asians under dominant (CT + TT vs CC, OR=0.67, 95 % CI: 0.56-0.81, P<0.001), recessive (TT vs CT + CC, OR=0.58, 95 % CI: 0.47-0.72, P<0.001), and homozygote (TT vs CC, OR=0.49, 95 % CI: 0.37-0.64, P<0.001) models. In Caucasians, rs1883832 was associated with GD risk under the dominant model (CT + TT vs CC, OR=0.82, 95 % CI: 0.68-0.99, P=0.042). Besides GD, we evaluated the relation of rs1883832 with Graves' ophthalmopathy (GO), finding that rs1883832 was associated with GO under the dominant model (CT + TT vs CC, OR=0.82, 95 % CI: 0.69-0.98, P=0.031). The findings of our meta-analysis suggest that the CD40 rs1883832 polymorphism is protective against GD and GO in Asians and Caucasians.

BACKGROUND:The interleukin-2 receptor alpha (IL2RA) gene polymorphisms may be implicated in the genetic susceptibility to multiple sclerosis (MS). This meta-analysis aims to evaluate the relationship of the IL2RA polymorphisms rs2104286 and rs12722489 with MS risk in different populations.METHODS:Eligible association studies were identified through search in Pubmed, Medline, Web of Science, and Scopus (end of search: August 2017). Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models. All statistical analyses were two-sided.RESULTS:Eleven studies including 8608 cases and 9061 controls evaluated rs2104286. The results demonstrated that the A allele of rs2104286 was associated with increased risk of MS in Caucasians (OR = 1.19, 95%CI: 1.13-1.25, p < 0.001) and Asians (OR = 1.25, 95%CI: 1.01-1.55, p = 0.041), respectively. Concerning rs12722489, six studies with 4259 cases and 5420 controls were eligible. We found that the C allele of rs12722489 was associated with elevated MS risk in Caucasians (OR = 1.20, 95% CI: 1.12-1.29, p < 0.001) but not in Asians (OR = 1.10, 95%CI: 0.75-1.63, p = 0.629). Statistical evidence from the Egger and Begg tests showed absence of publication bias. Sensitivity analysis showed that the results were stable.CONCLUSION:Our meta-analysis suggests that the rs2104286 A allele is associated with increased MS risk in both Caucasians and Asians, whereas the rs12722489 C allele is associated with elevated MS risk in Caucasians but not in Asians.

Background/Aim: Thyroid-associated ophthalmopathy (TAO) is a chronic autoimmune disorder characterized by an increased volume of adipose/connective tissue. This study aims to explore whether steroidogenic factor 1 (SF1) is implicated in development of TAO through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. Methods: Initially, we extracted orbital preadipocytes from 10 TAO patients for culture and identification. After differentiation, cells were inoculated with plasmids with overexpressed SF1, and plasmids with siRNA against SF1, respectively. Then fat content and PGE(2) secretion were measured by using ELISA. The levels of SF1, Bax, Bcl-2, Caspase3, Pref-1, PPAR gamma, Leptin, Adiponectin, p-AMPK alpha(Thr172), p-mTOR(ser2448), and p-S6K(Thr389) were detected by RT-qPCR and western blot analysis. Cell proliferation and apoptosis were measured by EdU and flow cytometry. Results: TAO patients showed reduced SF1 expression in orbital preadipocytes. Overexpression of SF1 led to inhibited expression of Bcl-2, PPAR gamma, Leptin, Adiponectin and p-AMPK alpha(Thr172), fat content, cell proliferation and differentiation, but increased levels of Bax, Caspase3, Pref-1, p-mTOR(ser2448) and p-S6K(Thr389), PGE(2) secretion and apoptosis rate. Conclusion: Our result showed up-regulated SF1 may relieve TAO through suppressing cell proliferation and differentiation, but accelerating cell apoptosis by inhibiting the activation of the AMPK/mTOR signaling pathway.