Multiplex cytokine profiling in patients with sepsis

A major goal for the clinical research in sepsis is mapping the various mediators driving the systemic manifestations of infection. Identifying relevant mediators responsible for the physiological alterations during sepsis may offer diagnostic and therapeutic opportunities. We aimed to explore the novel approach of simultaneously measuring several biomolecules using the multiplex technique and to study its relevance in diagnosing and monitoring septic patients. In 30 patients fulfilling American College of Chest Physicians and the Society of Critical Care Medicine sepsis criteria, we simultaneously measured 17 cytokines during the first 7 days after admission. We analysed the results with respect to the presence of septic shock and survival. Five patients died during the study. We found a significant positive correlation between the monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1β and interleukin (IL)-8 levels in the first 3 days and Sepsis-related Organ Failure Assessment score on day 1. Most cytokines showed no significant difference between patients with mild or severe sepsis. The initial levels of MIP-1β and granulocyte macrophage colony-stimulating factor were lower in patients with septic shock than in patients without shock. IL-8 and MCP-1 early after admission were higher in the non-survivors (p < 0.05). In the multivariate logistical regression, the initial levels of IL-8 were the most predictive for fatal outcome. Moreover, IL-1β, IL-6, IL-8, IL-12, interferon-γ, granulocyte colony-stimulating factor and tumour necrosis factor-α exhibited persistent increases in non-survivors. The simultaneous evaluation of multiple cytokines in sepsis may identify complex cytokine patterns that reflect the systemic response associated with shock and mortality.     

Evolutionary evidence of the effect of rare variants on disease etiology

Gorlov IP, Gorlova OY, Frazier ML, Spitz MR, Amos CI. Evolutionary evidence of the effect of rare variants on disease etiology. The common disease/common variant hypothesis has been popular for describing the genetic architecture of common human diseases for several years. According to the originally stated hypothesis, one or a few common genetic variants with a large effect size control the risk of common diseases. A growing body of evidence, however, suggests that rare single‐nucleotide polymorphisms (SNPs), i.e. those with a minor allele frequency of less than 5%, are also an important component of the genetic architecture of common human diseases. In this study, we analyzed the relevance of rare SNPs to the risk of common diseases from an evolutionary perspective and found that rare SNPs are more likely than common SNPs to be functional and tend to have a stronger effect size than do common SNPs. This observation, and the fact that most of the SNPs in the human genome are rare, suggests that rare SNPs are a crucial element of the genetic architecture of common human diseases. We propose that the next generation of genomic studies should focus on analyzing rare SNPs. Further, targeting patients with a family history of the disease, an extreme phenotype, or early disease onset may facilitate the detection of risk‐associated rare SNPs.     

Low serum endothelial cell-selective adhesion molecule predicts increase in albuminuria in type 2 diabetes patients

Purpose

The newly discovered endothelial cell-selective adhesion molecule (ESAM) stabilizes the interendothelial tight junction; it circulates in serum as a soluble fraction. In experimental diabetes, reduced ESAM expression in the kidney is associated with albuminuria. We investigated, for the first time, serum ESAM as a predictor of progression of kidney disease in type 2 diabetes (T2D).

Methods

T2D non-nephrotic patients with glomerular filtration rate (GFR) > 30 ml/min were included. History, medication and laboratory evaluation were assessed at inclusion and the end of study; ESAM was determined at baseline.

Results

Eighty-eight patients—mean age 63 ± 10.84 years, 49 (55.68 %) males—were prospectively followed up for 20 months. Baseline GFR was 76.37 ± 29.56 ml/min, and urinary albumin/creatinine ratio (UACR) 21.63(7.08–94.52) mg/g; ESAM was 12.85(6.13–19.83) ng/ml. Difference (Δ) in UACR between end of study and baseline was inversely related to serum albumin (r = ?0.27, p = 0.017) and ESAM (r = ?0.21, p = 0.047); ΔGFR correlated to glycated hemoglobin (r = 0.22, p = 0.05). In multiple regression, introducing variables susceptible to influence progression of kidney disease, ΔUACR was significantly related to log ESAM (p = 0.005) and ΔGFR to glycated hemoglobin (p = 0.016).

Conclusion

Serum ESAM is a predictor of worsening of albuminuria in T2D patients without advanced kidney disease.     

毛细管电泳非环糊精体系拆分手性药物的研究进展

据统计 ,目前所用药物 ,5 2 3种天然及半合成药物中手性药物有 5 17种 ,132 7种全合成药物中手性药物有 5 2 8种。人体中的受体和酶一般皆呈手征性 ,多有其立体选择性 ,与手性药物异构体的作用可能区别很大 ,从而导致手性药物对映异构体之间不同的药理、毒理作用及药物动力学过程。目前 ,部分国家的药物审批部门 ,虽允许以外消旋体形式申请新药上市 ,但要求分离对映体 ,分别进行毒理、药理实验。可以预见 ,以单一对映体形式上市将是手性药物的发展趋势。手性新药研制工作中 ,对映异构体之间药理学、毒理学、药效学及药动学差异的研究是极为…     

Use of online sources of information by dental practitioners: findings from The Dental Practice‐Based Research Network

Objective: Estimate the proportion of dental practitioners who use online sources of information for practice guidance. Methods: From a survey of 657 dental practitioners in The Dental Practice‐Based Research Network, four indicators of online use for practice guidance were calculated: read journals online, obtained continuing education (CDE) through online sources, rated an online source as most influential, and reported frequently using an online source for guidance. Demographics, journals read, and use of various sources of information for practice guidance in terms of frequency and influence were ascertained for each. Results: Overall, 21 percent (n = 138) were classified into one of the four indicators of online use: 14 percent (n = 89) rated an online source as most influential and 13 percent (n = 87) reported frequently using an online source for guidance; few practitioners (5 percent, n = 34) read journals online, fewer (3 percent, n = 17) obtained CDE through online sources. Use of online information sources varied considerably by region and practice characteristics. In general, the four indicators represented practitioners with as many differences as similarities to each other and to offline users. Conclusion: A relatively small proportion of dental practitioners use information from online sources for practice guidance. Variation exists regarding practitioners' use of online source resources and how they rate the value of offline information sources for practice guidance.     

西藏日喀则地区口腔颌面间隙感染90例临床分析

目的 探讨西藏日喀则地区口腔颌面间隙感染患者的发病特点。方法 回顾2015年1月—2018年2月在日喀则市人民医院口腔科住院的90例颌面间隙感染患者的病例资料,分析发病年龄、职业、感染原因、好发部位等。结果 90例患者中,儿童、学生及农牧民为好发人群;牙源性感染为首要致病原因,以第一、二恒磨牙为主要病灶牙;单间隙感染71例,占78.89%;多间隙感染19例,占21.11%;下颌下间隙受累最多。结论 日喀则地区口腔颌面间隙感染发病年龄较早,应及早对儿童及父母开展口腔卫生宣教,提高医疗保健意识,并加强基层医疗队伍建设。     

山核桃叶总黄酮对小鼠抗心肌缺血及心肌细胞缺氧损伤保护作用研究

目的探究山核桃叶总黄酮对小鼠心肌缺血及心肌细胞（H9c2）缺氧损伤的保护作用及机制。方法1. 建立皮下注射盐酸异丙肾上腺素造成小鼠急性心肌缺血模型,心脏切片HE染色,并测定小鼠血清中肌酸激酶（CK）、乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）、丙二醛（MDA）含量。2. 建立心肌细胞过氧化氢缺氧损伤模型,观察细胞形态,测定细胞存活率并检测细胞培养液中CK、SOD、MDA含量。结果与模型组相比,山核桃叶总黄酮高中低剂量组的心肌组织完整,炎症因子较少,血清中CK、LDH、MDA的活性显著降低,SOD活性显著升高;山核桃叶总黄酮各剂量组均能显著提高过氧化氢损伤心肌细胞的存活率,抑制LDH的释放,减少MDA的生成,提高SOD活性。结论山核桃叶总黄酮对小鼠心肌缺血及心肌细胞缺氧损伤具有保护作用。     

宫颈上皮内瘤变自然史转移概率的研究

[目的]探讨1级宫颈上皮内瘤变(CIN1)进展、退化或保持不变的转移概率,为使用基于转移概率为基本参数的Markov模型进行卫生经济学评价提供参数。[方法]利用前瞻性的宫颈癌自然史随访6年队列(SPOCCS-I)的宫颈癌自然史的数据,使用指数分布模型和微积分方法对CIN1进展和退化的年转移概率进行了估计。[结果]SPOCCS-I人群中CIN1患者的疾病保持不变的、发生进展和退化的年转移概率分别为0.658、0.020和0.322,相应的6年累积转移概率分别为0.081、0.054和0.865。[结论]SPOCCS-I人群中CIN1的患者在1年内发生进展的可能性为2%,该人群中有32.2%的CIN1患者会在1年内发生退化。根据中国宫颈癌自然史队列SPOCCS-I计算出的CIN1的转移概率符合卫生经济学评价中使用的Markov模型需要的参数,可以为之提供参数的参考依据。