艾拉莫德联合甲氨蝶呤治疗类风湿性关节炎的临床疗效及对患者骨代谢的影响

目的 探讨艾拉莫德联合甲氨蝶呤治疗类风湿性关节炎(RA)的临床效果及对患者骨代谢的影响。方法 将我院收治的86例RA患者随机分为两组各43例。对照组采用甲氨蝶呤治疗,观察组采用艾拉莫德联合甲氨蝶呤治疗。比较两组的临床疗效、骨代谢指标(β-CTX、 TPINP、 N-MID)及不良反应发生情况。结果 观察组治疗总有效率为95.35%,明显高于对照组的81.40%(P<0.05)。治疗后,两组的β-CTX水平降低, TPINP、 N-MID水平升高(P<0.05);观察组的β-CTX水平明显低于对照组, TPINP、 N-MID水平高于对照组(P<0.05)。两组的不良反应发生率(9.30%vs. 6.98%)比较差异无统计学意义(P>0.05)。结论 艾拉莫德联合甲氨蝶呤治疗RA效果显著,可有效改善患者的骨代谢,且安全性较高。     

脑出血继发损伤中沉默信息调节因子2的表达和炎症反应*

目的：探讨脑出血对酵母沉默信息调节因子2（Sirt2）和炎症的影响。方法：将胶原酶Ⅳ注入SD大鼠右侧 纹状体中建立脑出血模型，通过免疫印迹和ELISA 等方法测定大鼠脑出血后48 h 的Sirt2 的表达及炎症变化。利 用Hemin 诱导PC12 细胞损伤模拟体外脑出血模型，并检测Sirt2 及炎症变化；采用短发夹RNA（shRNA）-Sirt2 沉 默Sirt2 在PC12 细胞中的表达及对炎症的影响。结果：手术后48 h 脑出血行为学评分最低。脑出血组Sirt2 的表达 显著高于假手术组。脑出血组IL-6、IL-1β 表达显著升高。结论：脑出血可以促进Sirt2 的表达和炎症反应，降低 Sirt2 的表达可减缓炎症反应。 关键词 脑出血；沉默信息调节     

肥胖型PCOS患者的生物学特征和临床特征

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是一种内分泌代谢紊乱综合征,临床表现高度异质性。肥胖是PCOS异质性临床表现之一,超过50%的PCOS患者超重或肥胖。肥胖型PCOS主要表现为高雄激素血症、中心型肥胖和糖脂代谢紊乱,非肥胖型PCOS主要表现为黄体生成激素（luteinizing hormone,LH）水平异常升高。尽管肥胖型和非肥胖型PCOS均存在内分泌代谢异常,然而肥胖可加重PCOS糖脂代谢紊乱;肥胖型PCOS还表现脂肪代谢的异常。综述肥胖型PCOS患者的临床特征、性激素水平、糖脂代谢特征,旨在为肥胖型和非肥胖型PCOS患者新的分型诊治提供参考。     

胰腺切除患者围术期血糖管理的最佳证据总结

背景血糖紊乱是胰腺切除患者围术期常见问题。然而，目前国内开展的胰腺切除患者围术期血糖管理实践多以经验为指导，缺乏循证依据。目的总结胰腺切除患者围术期血糖管理的最佳证据。方法系统检索BMJ最佳临床实践、Up to Date、国际指南协作组、国际糖尿病联盟（IDF）、世界卫生组织（WHO）、美国国立指南数据库（NGC）、美国糖尿病协会、英国国家临床优化研究所（NICE）、新西兰指南研究组、加拿大糖尿病协会、澳大利亚糖尿病协会、苏格兰校际指南网络（SIGN）、PubMed、Web of Science、EMBase、CINHAL数据库、Cochrane图书馆、乔安娜布里格斯研究所（JBI）循证卫生保健中心、医脉通、万方数据知识服务平台、中国知网（CNKI）、生物医学数据库（CBM），筛选关于胰腺切除患者围术期血糖管理的文献。检索时间为建库至2020年12月。指南的质量评价采用国际AGREE协作组织2009年更新的AGREE Ⅱ量表。专家共识的质量评价采用澳大利亚JBI循证卫生保健中心专家共识评价标准2017版。随机对照试验的评价采用Jadad评分量表。结果通过初步检索筛选出文献6 637篇，最终纳入文献13篇，其中7篇为临床实践指南，4篇为专家共识，2篇为随机对照试验。评价结果显示，7篇临床实践指南中3篇总体质量评价为A级，剩下4篇为B级；4篇专家共识的质量评价在"观点与其他文献不一致的地方是否有合理解释？"条目的评价结果为"不清楚"，其余条目的评价结果均为"是"。2篇随机对照试验均为高质量文献。共汇总了62条最佳证据，主要涉及围术期组织管理、入院评估及处理、血糖控制目标、血糖监测、术前血糖管理策略、术中血糖管理策略、术后血糖管理策略、危急状况处理以及出院指导9个方面。结论临床医务人员应根据总结的9个方面最佳证据（包括围术期组织管理、入院评估及处理、血糖控制目标、血糖监测、术前血糖管理策略、术中血糖管理策略、术后血糖管理策略、危急状况处理以及出院指导）为胰腺切除患者制定个体化、全程化的围术期血糖管理方案。     

ArgD of Mycobacterium tuberculosis is a functional N-acetylornithine aminotransferase with moonlighting function as an effective immune modulator

Mycobacterium tuberculosis (M. tuberculosis) encodes an essential enzyme acetyl ornithine aminotransferase ArgD (Rv1655) of arginine biosynthetic pathway which plays crucial role in M. tuberculosis growth and survival. ArgD catalyzes the reversible conversion of N-acetylornithine and 2 oxoglutarate into glutamate-5-semialdehyde and L-glutamate. It also possesses succinyl diaminopimelate aminotransferase activity and can thus carry out the corresponding step in lysine biosynthesis. These essential roles played by ArgD in amino acid biosynthetic pathways highlight it as an important metabolic chokepoint thus an important drug target. We showed that M. tuberculosis ArgD rescues the growth of ΔargD E. coli grown in minimal media validating its functional importance. Phylogenetic analysis of M. tuberculosis ArgD showed homology with proteins in gram positive bacteria, pathogenic and non-pathogenic mycobacteria suggesting the essentiality of this protein. ArgD is a secretory protein that could be utilized by M. tuberculosis to modulate host innate immunity as its moonlighting function. In-silico analysis predicted it to be a highly antigenic protein. The recombinant ArgD protein when exposed to macrophage cells induced enhanced production of pro-inflammatory cytokines TNF, IL6 and IL12 in a dose dependent manner. ArgD also induced the increased production of innate immune effector molecule NOS2 and NO in macrophages. We also demonstrated ArgD mediated activation of the canonical NFkB pathway. Notably, we also show that ArgD is a specific TLR4 agonist involved in the activation of pro-inflammatory signaling for sustained production of effector cytokines. Intriguingly, ArgD protein treatment activated macrophages to acquire the M1 phenotype through the increased surface expression of MHCII and costimulatory molecules CD80 and CD86. ArgD induced robust B-cell response in immunized mice, validating its antigenicity potential as predicted by the in-silico analysis. These properties of M. tuberculosis ArgD signify its functional plasticity that could be exploited as a possible drug target to combat tuberculosis.     

Impact of the one-carbon metabolism on oocyte maturation,fertilization, embryo quality,and subsequent pregnancy

PurposeTo investigate impact of the one‐carbon metabolism (OCM) on oocyte maturity and embryo development.MethodsThis prospective study analyzed 18 women who agreed to participate. We measured the OCM biomarkers’ concentrations including Vitamin B12 (VB12), folic acid (FA), and homocysteine (Hcy) in serum and follicular fluid (FF), and assessed their correlation. We also evaluated the influence of such OCM biomarker concentrations in mono‐FF on oocyte maturation, fertilization, embryo quality, and consequent pregnancy after embryo transfers.ResultsAll biomarkers showed a high concentration variability in different follicles of each woman, but their mean levels correlated with the serum levels. Among the 106 collected oocytes, 92 were mature, 59 were fertilized, and 16 yielded good‐quality embryos. We performed 26 single embryo transfers, and 7 patients achieved clinical pregnancies. VB12 concentration (FF) was significantly lower in fertilized than unfertilized oocytes by univariate analysis. In multivariate logistic analysis, a significant correlation was found between FA concentration (FF) <14.25 ng/mL and good‐quality embryos and between Hcy concentration (FF) <4.9 nmol/mL and clinical pregnancy.ConclusionOCM in FF may affect fertilization, embryo quality, and clinical pregnancy.     

续筋接骨方治疗骨折临床观察

目的研究续筋接骨方治疗骨折的临床疗效。方法选取2018年1月—2018年6月在辽宁中医药大学附属第三医院就诊的骨折患者60例,所有患者按照随机数字表法分为对照组与观察组,每组30例。观察组口服续筋接骨方联合正骨后小夹板固定治疗,对照组患者采用正骨后小夹板固定治疗。分析2组患者干预3个月后的血清骨代谢指标、骨密度、生活质量改善情况以及疗效判定。结果干预前,2组的血清Ⅰ型前胶原羧基端肽β特殊序列(β-CTX)、血清Ⅰ型前胶原氨端肽原(PINP)、骨特异性碱性磷酸酶(ALP)水平、钙、磷及骨密度比较,差异无统计学意义(P>0.05);干预后,2组的β-CTX、PINP、骨特异性ALP水平、钙、磷及骨密度较干预前改善,观察组的改善效果优于对照组,差异均有统计学意义(P<0.05)。干预前,2组的物质生活、社会功能、躯体健康以及心理健康评分比较,差异无统计学意义(P>0.05);干预后,2组的物质生活、社会功能、躯体健康以及心理健康评分较干预前升高,观察组的各项生活质量评分高于对照组,差异均有统计学意义(P<0.05)。观察组的治疗恢复率高于对照组,差异有统计学意义(P<0.05)。结论续筋接骨方可以改善骨折患者骨代谢功能及生活质量。     

Abnormal glucose tolerance in a pediatric cystic fibrosis cohort: Trends in clinical outcomes and associated factors in the preceding years

Background and aimsDeterioration of anthropometric and lung function parameters was shown to precede the onset of cystic fibrosis-related diabetes (CFRD) in adults. In children, studies have been conducted in small cohorts with relatively short observation period. Study objectives were to document the longitudinal trends of anthropometric, pulmonary, nutritional and metabolic parameters from cystic fibrosis (CF) diagnosis to the ascertainment of abnormal glucose tolerance and identify parameters associated with the incidence of such abnormalities in a pediatric CF cohort.Methods and resultsRetrospective cohort study of 281 children with CF. Longitudinal trends of anthropometric, lung function, nutritional and metabolic data were generated from CF diagnosis to the ascertainment of abnormal glucose tolerance defined as the presence of either impaired glucose tolerance (IGT), unconfirmed CFRD or CFRD. Cox models and Kaplan–Meier curves were used to identify factors associated with developing abnormal glucose tolerance.Forty-five percent of cohort had normal glucose tolerance (NGT), 27% IGT, 10% unconfirmed CFRD and 18% CFRD. Children who developed CFRD displayed lower height z-scores from a very early age. Conversely, HbA1c levels began to rise closer to CFRD ascertainment. Height z-scores (HR: 0.45; CI 95% [0.29–0.69]) and HbA1c (HR: 2.43; CI 95% [1.86–3.18]) in years preceding ascertainment were associated with the risk of developing CFRD.ConclusionChildren who developed CFRD display distinctive trends for height z-scores from a very early age, whereas HbA1c appears as a marker of established glucose metabolism derangements.