不同肥胖表型者中医体质特点分析研究

背景　有研究表明肥胖者和代谢紊乱者的中医体质类型存在一定的相似性,但是不同肥胖者发生代谢紊乱的风险不完全相同,是否中医体质为其内在原因？目前尚不可知。目的　探究不同肥胖表型者中医体质特点。方法　从2012年6月-2014年1月北京同仁医院、安徽中医药大学第一附属医院以及广东省中医院珠海医院治未病中心健康体检人群1 814例数据库中,排除年龄<18岁者、分析变量存在缺失值及体质量过轻和超重者,纳入1 267例体质量正常和肥胖样本进行分析。根据代谢正常/异常及体质量正常/肥胖组合形成4种代谢肥胖表型,即代谢正常体质量正常表型（MHNW）、代谢异常体质量正常表型（MUNW）、代谢正常肥胖表型（MHO）、代谢异常肥胖表型（MUO）。采用中医体质量表评价中医体质,采用最小二乘回归法（控制社会人口学因素及行为习惯因素）计算不同肥胖表型者9种中医体质（平和质、气虚质、阳虚质、阴虚质、痰湿质、湿热质、血瘀质、气郁质、特禀质）得分。结果　1 267例调查对象中,MHNW 584例（46.1%）,MUNW 207例（16.3%）,MHO 174例（13.7%）,MUO 302例（23.9%）。不同肥胖表型者平和质、阳虚质、痰湿质得分比较,差异均有统计学意义（P<0.05）;其中MUO者平和质得分高于MHNW和MUNW者,阳虚质得分低于MHNW和MUNW者;MHO和MUO者痰湿质得分高于MHNW和MUNW者（P<0.05）。男性不同肥胖表型者平和质、阳虚质、痰湿质得分比较,差异均有统计学意义（P<0.05）;其中MUO者平和质得分高于MHNW和MUNW者,阳虚质得分低于MHNW和MUNW者;MUNW、MHO和MUO者痰湿质得分高于MHNW者（P<0.05）。女性不同肥胖表型者阳虚质、痰湿质得分比较,差异均有统计学意义（P<0.05）;其中MUO者阳虚质得分低于MHNW者,MHO者痰湿质得分高于MHNW和MUNW者,MUO者痰湿质得分高于MUNW者（P<0.05）。结论　代谢状况相近的情况下,肥胖者痰湿质、平和质倾向更高,阳虚质倾向更低;体质量相近的情况下,不同代谢状况者未表现出明显的体质差异。但男性和女性情况有所不同,男性肥胖者和代谢异常者均表现为较高的痰湿质倾向;女性仅有肥胖者表现为较高的痰湿质倾向,而代谢异常者未发现较高的痰湿质倾向。     

虚拟实验在临床微生物学检验技术中的应用研究

临床微生物学检验技术实验是临床微生物学检验技术教学的重要组成部分。在临床微生物学检验技术实验教学中,将虚拟仿真技术与传统教学结合,充分发挥虚拟实验平台的优势。有些传统教学无法开展的实验项目和一些重要的实验项目,学生可以在虚拟实验平台上进行学习,并在学习完成后,参加相应的考核。两者的完美结合,可解决目前实验课实验成本过高和实验内容有限的问题,弥补传统教学的不足,实现教学资源共享,强化学生实验操作技能,提升学习兴趣;也有利于应用型医学检验技术专业人才的培养。     

不同密度胸腺囊肿CT表现差异及其病理基础

目的：探讨不同密度胸腺囊肿CT表现差异及其病理基础。方法：回顾分析手术病理证实的45例实性密度胸腺囊肿和23例液性密度胸腺囊肿CT表现及其病理改变。结果：胸腺囊肿密度与囊肿大小有相关性（P＜0.01）。实性密度囊肿形态多较规则,液性密度囊肿以不规则、沿大血管间隙塑形多见,组间分布差异有统计学意义（P＜0.01）。泪滴状及三角状在2组均可见,组间分布差异无统计学意义（P＞0.05）。实性密度囊肿多不膨隆于胸腺轮廓,与液性密度相比差异有统计学意义（P＜0.01）。实性密度胸腺囊肿病理表现为有分泌功能的假复层纤毛柱状上皮或纤毛柱状上皮覆盖,囊壁上皮细胞排列较密实,囊液多浑浊;液性密度胸腺囊肿被覆表面为无分泌功能扁平或柱状上皮为主,排列稀疏甚至缺失,基层薄弱,囊液往往较清亮。囊肿密度与被覆上皮类型有相关性（P＜0.05）。结论：胸腺实性密度囊肿与液性密度囊肿影像学表现有差异,病理基础对理解不同表现胸腺囊肿有帮助。     

Bacterial expression of mutant argininosuccinate lyase reveals imperfect correlation of in-vitro enzyme activity with clinical phenotype in argininosuccinic aciduria

Background

The urea cycle defect argininosuccinate lyase (ASL) deficiency has a large spectrum of presentations from highly severe to asymptomatic. Enzyme activity assays in red blood cells or fibroblasts, although diagnostic of the deficiency, fail to discriminate between severe, mild or asymptomatic cases. Mutation/phenotype correlation studies are needed to characterize the effects of individual mutations on the activity of the enzyme.

Methods

Bacterial in-vitro expression studies allowed the enzyme analysis of purified mutant ASL proteins p.I100T (c.299?T?>?C), p.V178M (c.532?G?>?A), p.E189G (c.566A?>?G), p.Q286R (c.857A?>?G), p.K315E (c.943A?>?G), p.R379C (c.1135?C?>?T) and p.R385C (c.1153?C?>?T) in comparison to the wildtype protein.

Results

In the bacterial in-vitro expression system, ASL wild-type protein was successfully expressed. The known classical p.Q286R, the novel classical p.K315E and the known mutations p.I100T, p.E189G and p.R385C, which all have been linked to a mild phenotype, showed no significant residual activity. There was some enzyme activity detected with the p.V178M (5 % of wild-type) and p.R379C (10 % of wild-type) mutations in which K_m values for argininosuccinic acid differed significantly from the wild-type ASL protein.

Conclusion

The bacterially expressed enzymes proved that the mutations found in patients and studied here indeed are detrimental. However, as in the case of red cell ASL activity assays, some mutations found in genetically homozygous patients with mild presentations resulted in virtual loss of enzyme activity in the bacterial system, suggesting a more protective environment for the mutant enzyme in the liver than in the heterologous expression system and/or in the highly dilute assays utilized here.     

Metabonomics analysis of serum from rats given long-term and low-level cadmium by ultra-performance liquid chromatography–mass spectrometry

1. This study evaluated the toxicity of chronic exposure to low-level cadmium (Cd) in rats using ultra-performance liquid chromatography–mass spectrometry (UPLC–MS). Forty male Sprague–Dawley rats were randomly assigned to four groups, namely, the control group, low-dose group (0.13?mg/kg·bw), middle-dose group (0.8?mg/kg·bw) and high-dose group (4.89?mg/kg·bw). The rats continuously received CdCl₂ via drinking water for 24?weeks. Serum samples were collected for metabonomics analysis. The data generated from the UPLC–MS was analysed using principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). PLS-DA model with satisfactory explanatory and predictive ability is capable of discriminating the treatment groups from the control group.

2. Finally, the 10 metabolites were identified and showed significant changes in some treatment groups compared with that in the control group (p?p?3. Results suggest that exposure to Cd can cause disturbances in the lipid metabolism, amino acid metabolism, nervous system, antioxidant defence system, liver and kidney function.     

Evaluating biapenem dosage regimens in intensive care unit patients with Pseudomonas aeruginosa infections: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation

This study was conducted to identify optimal dosage regimens and estimate pharmacokinetic/pharmacodynamic (PK/PD) characteristics of short-infusion (SI) versus extended-infusion (EI) biapenem against Pseudomonas aeruginosa infections in Chinese intensive care unit (ICU) patients. A total of 85 strains of P. aeruginosa were collected, and the minimum inhibitory concentration (MIC) of biapenem was measured by the serial two-fold agar dilution method. We designed four frequently used clinical regimens: biapenem 300?mg I.V. q12h, q8h, and q6h, and 600?mg q12h. The Monte Carlo Simulation (MCS) was performed using previously published pharmacokinetic data to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of these regimens as an SI (0.5?h) and an EI (1?h, 2?h, 3?h, and 4?h).For a target of 40%fT_>MIC (serum drug concentration remains above the MIC for a dosing period), none of the regimens achieved any CFRs>90% for P. aeruginosa, multidrug–resistant P. aeruginosa (MDR-PA) and even non–MDR-PA. The traditional biapenem SI regimens most commonly seen in clinical practice were insufficient in treating both MDR and non-MDR P. aeruginosa in ICU patients. However, biapenem 600?mg q12h over 2–4?h EI regimens could achieve CFR>90% with 20%fT_>MIC. Clinical trials should aim to validate the potentially greater PK/PD index with higher, more frequent doses and longer extended infusions.     

Enzymatic glycosylation of oleanane-type triterpenoids

Abstract

Glycosylation is an effective approach to improve the druggability of natural products by increasing their water solubility. In this work, we report the glycosylation of oleanane-type triterpenoids by a recombinant microbial glycosyltransferase YjiC1. A preliminary screening test indicated YjiC1 exhibited robust capabilities for O-glycosylation of triterpenoids, based on LC/MS analysis. Among the products, two new compounds (2a and 3a), together with a known one (1a), were isolated and characterized. These products exhibited improved water solubility, and 3a showed moderate anti-HIV activities at 100 μM. This reaction provides a facile and efficient approach to synthesize the glucosides of triterpenoids.     

Effective intracellular delivery and Th1 immune response induced by ovalbumin loaded in pH-responsive polyphosphazene polymersomes

A polymersome system for delivering protein antigen ovalbumin (OVA) based on amphiphilic polyphosphazene grafting with N,N-diisopropylethylenediamine (DPA) and poly(ethylene glycol) (PEG) groups (poly[(DPA)_m (PEG)_n phosphazene], PEDP) was designed and constructed. The 200-240?nm-size OVA-loaded polymersomes displayed high stability at physiological pH, slow internalization through clathrin-mediated endocytosis pathway, and then a pH-triggered sustained OVA release in acidic environment, leading to extensive antigen access to cytosol. Prime-boost vaccine kept high antibody titers for 8?weeks and the subcutaneous vaccine of OVA polymersomes biased the immune response towards a type 1?T helper (Th1) response. Animal experiment results showed that the antigen-specific prophylactic vaccination by PEDP polymersomes delivery was much more rapid and efficient in depressing tumor growth and progress when compared with the therapeutic vaccination. These results suggested that PEDP-based polymersomes are very promising in controlled cytosolic delivery of protein antigens, and enhanced Th1 specific immune response.     

喉癌组织中SEMA3F与NRP2的表达及临床价值

探讨喉癌组织中神经轴突导向因子(SEMA3F)、神经菌毛蛋白2（NRP2）的表达及临床意义。方法 选取2016年3月～2018年3月我院收治的82例喉癌患者为研究对象,用实时定量PCR法检测癌及癌旁组织中SEMA3F、NRP2 mRNA的表达。以癌组织中SEMA3F、NRP2 mRNA表达的平均数为界,将研究对象分别分为SEMA3F高、低表达组及NRP2高、低表达组。分析SEMA3F、NRP2的表达与临床病理特征关系。Pearson线性相关分析SEMA3F与NRP2表达的相关性。Kaplan-Meier生存分析（Log-Rank检验）癌组织不同SEMA3F、NRP2表达与喉癌患者的生存预后差异。多因素COX回归分析影响喉癌患者生存预后的危险因素。结果 与癌旁组织相比,癌组织SEMA3F mRNA表达明显降低,NRP2 mRNA表达明显升高（均P＜0.05）。喉癌组织中SEMA3F与NRP2的表达呈显著负相关（r=-0.561,P＜0.001）。SEMA3F、NRP2 mRNA的表达与肿瘤临床分期及淋巴结转移有关（均P＜0.05）。生存分析结果表明,喉癌组织中SEMA3F低表达、NRP2高表达喉癌患者3年总体生存率明显较差（均P＜0.05）。多因素COX回归分析结果喉癌组织中SEMA3F低表达、NRP2高表达、肿瘤Ⅲ～Ⅳ期及淋巴结转移是喉癌患者不良预后的危险因素。结论 喉癌中SEMA3F表达降低,NRP2表达增高,均与肿瘤分期及淋巴结转移有关,可能是喉癌预后新的标志物。     

半夏泻心汤联合美沙拉嗪治疗轻度活动期克罗恩病疗效研究

目的:探讨半夏泻心汤联合美沙拉嗪治疗轻度活动期克罗恩病的临床疗效。方法:选择82例克罗恩病患者,随机分为两组,各41例。对照组接受美沙拉嗪治疗,观察组联合应用半夏泻心汤治疗,疗程均为8周。结果:治疗后,观察组中医证候临床缓解率、总有效率高于对照组,差异有统计学意义(均P<0.05)。治疗后,两组克罗恩疾病活动指数(CDAI)评分均降低,炎症性肠病生活质量问卷(IBDQ)评分均升高,且观察组优于对照组,差异有统计学意义(均P<0.05)。治疗后两组ESR、血清TNF-α、IL-6水平均降低,且观察组水平均低于对照组,差异有统计学意义(均P<0.05)。结论:半夏泻心汤联合美沙拉嗪治疗轻度活动期克罗恩病患者可以有效缓解临床症状,抑制炎症反应,提高临床疗效,改善患者生活质量。