The Association between Gut Microbiota and Osteoarthritis: Does the Disease Begin in the Gut?

Some say that all diseases begin in the gut. Interestingly, this concept is actually quite old, since it is attributed to the Ancient Greek physician Hippocrates, who proposed the hypothesis nearly 2500 years ago. The continuous breakthroughs in modern medicine have transformed our classic understanding of the gastrointestinal tract (GIT) and human health. Although the gut microbiota (GMB) has proven to be a core component of human health under standard metabolic conditions, there is now also a strong link connecting the composition and function of the GMB to the development of numerous diseases, especially the ones of musculoskeletal nature. The symbiotic microbes that reside in the gastrointestinal tract are very sensitive to biochemical stimuli and may respond in many different ways depending on the nature of these biological signals. Certain variables such as nutrition and physical modulation can either enhance or disrupt the equilibrium between the various species of gut microbes. In fact, fat-rich diets can cause dysbiosis, which decreases the number of protective bacteria and compromises the integrity of the epithelial barrier in the GIT. Overgrowth of pathogenic microbes then release higher quantities of toxic metabolites into the circulatory system, especially the pro-inflammatory cytokines detected in osteoarthritis (OA), thereby promoting inflammation and the initiation of many disease processes throughout the body. Although many studies link OA with GMB perturbations, further research is still needed.     

Clinical Utility of a Unique Genome-Wide DNA Methylation Signature for KMT2A-Related Syndrome

Wiedemann–Steiner syndrome (WDSTS) is a Mendelian syndromic intellectual disability (ID) condition associated with hypertrichosis cubiti, short stature, and characteristic facies caused by pathogenic variants in the KMT2A gene. Clinical features can be inconclusive in mild and unusual WDSTS presentations with variable ID (mild to severe), facies (typical or not) and other associated malformations (bone, cerebral, renal, cardiac and ophthalmological anomalies). Interpretation and classification of rare KMT2A variants can be challenging. A genome-wide DNA methylation episignature for KMT2A-related syndrome could allow functional classification of variants and provide insights into the pathophysiology of WDSTS. Therefore, we assessed genome-wide DNA methylation profiles in a cohort of 60 patients with clinical diagnosis for WDSTS or Kabuki and identified a unique highly sensitive and specific DNA methylation episignature as a molecular biomarker of WDSTS. WDSTS episignature enabled classification of variants of uncertain significance in the KMT2A gene as well as confirmation of diagnosis in patients with clinical presentation of WDSTS without known genetic variants. The changes in the methylation profile resulting from KMT2A mutations involve global reduction in methylation in various genes, including homeobox gene promoters. These findings provide novel insights into the molecular etiology of WDSTS and explain the broad phenotypic spectrum of the disease.     

Fractality of tics as a quantitative assessment tool for Tourette syndrome

Tics manifest as brief, purposeless and unintentional movements or noises that, for many individuals, can be suppressed temporarily with effort. Previous work has hypothesized that the chaotic temporal nature of tics could possess an inherent fractality, that is, have neighbour-to-neighbour correlation at all levels of timescale. However, demonstrating this phenomenon has eluded researchers for more than two decades, primarily because of the challenges associated with estimating the scale-invariant, power law exponent—called the fractal dimension D_f—from fractional Brownian noise. Here, we confirm this hypothesis and establish the fractality of tics by examining two tic time series datasets collected 6–12 months apart in children with tics, using random walk models and directional statistics. We find that D_f is correlated with tic severity as measured by the YGTTS total tic score, and that D_f is a sensitive parameter in examining the effect of several tic suppression conditions on the tic time series. Our findings pave the way for using the fractal nature of tics as a robust quantitative tool for estimating tic severity and treatment effectiveness, as well as a possible marker for differentiating typical from functional tics.     

Gangliosides in Podocyte Biology and Disease

Gangliosides constitute a subgroup of glycosphingolipids characterized by the presence of sialic acid residues in their structure. As constituents of cellular membranes, in particular of raft microdomains, they exert multiple functions, some of them capital in cell homeostasis. Their presence in cells is tightly regulated by a balanced expression and function of the enzymes responsible for their biosynthesis, ganglioside synthases, and their degradation, glycosidases. The dysregulation of their abundance results in rare and common diseases. In this review, we make a point on the relevance of gangliosides and some of their metabolic precursors, such as ceramides, in the function of podocytes, the main cellular component of the glomerular filtration barrier, as well as their implications in podocytopathies. The results presented in this review suggest the pertinence of clinical lipidomic studies targeting these metabolites.     

不同年份对虾白斑综合征病毒基因组差异的微阵列分析

根据对虾白斑综合征病毒(white spot syndrome virus,WSSV)全基因组序列的分析与应用,设计了190对引物,覆盖全基因组绝大多数可预测的开放读框(ORF).扩增相应基因片段,在尼龙膜上点样,制备成为DNA微阵列.收集了1996年和2002年感染阳性对虾,分别提取纯病毒基因组DNA,用地高辛标记后与DNA微阵列杂交.与1996年病毒株相比较,2002年病毒株缺失了wsv479、wsv482、wsv489和wsv493.运用PCR技术验证了DNA微阵列杂交结果的可靠性.     

黄芪注射液对儿童原发性肾病综合征高凝状态的影响简

目的：探讨黄芪注射液对儿童原发性肾病综合征（primary nephrotic syndrome,PNS）高凝状态的影响。方法将41例PNS患儿随机分为治疗组21例、对照组20例。2组均给予泼尼松片1．5～2 mg·kg-1·d-1口服治疗,在常规激素治疗基础上治疗组给予黄芪注射液1 mL · kg^-1· d^-1静脉滴注治疗,对照组给予阿司匹林1～3 mg· kg^-1· d^-1口服治疗。15 d 为1个疗程,2组均治疗2个疗程。结果2组治疗后血生化指标血尿素氮（BUN）、肌酐清除率（Ccr）、血肌酐（Scr）、血浆清蛋白（A1b）、总胆固醇（TC）、三酰甘油（TG）,24 h尿蛋白定量及血液高凝状态指标血纤维蛋白原降解产物（FDP）、血浆纤维蛋白原（FIB）浓度、血 D-二聚体（D-D）较治疗前均显著改善（P＜0．01）,且治疗组改善效果明显优于对照组,差异有统计学意义（P＜0．05）;2组凝血酶原时间（PT）指标治疗前后比较差异无统计学意义（P＞0．05）。结论黄芪注射液对PNS患儿高凝状态有显著疗效,同时可降低蛋白尿,保护肾功能。     

连续性血液滤过在治疗以第三间隙液体潴留为主的腹腔高压中的应用

目的：探讨连续性血液滤过（CBP）治疗以第三间隙液体潴留为主的腹腔高压及腹腔间隙综合征（ACS）的疗效。方法37例诊断为以第三间隙液体潴留为主的腹腔高压或腹腔间隙综合征的患者按是否进行血液滤过分为治疗组（21例）和对照组（16例）,对照组采用胃肠减压、镇痛等常规治疗,治疗组采用在常规治疗基础上给予连续性血液滤过治疗,1次·d^-1,5次。记录比较治疗前后腹内压、氧合指数、平均动脉压、APACHEⅡ评分、生化指标以及 TNF-α、IL-6,和 C-反应蛋白（CRP）的水平。观察治疗前、治疗后患者一般情况及生化指标、炎症介质的变化,计算死亡率。结果治疗组14例腹腔高压好转,3例死亡,4例自动出院,好转率66．6％;对照组腹腔高压好转3例,死亡9例,自动出院4例,好转率18．7％。治疗组肾功能指标、乳酸、HCO-3、肌钙蛋白 I（cTnI）及炎症介质CRP、TNF-α、IL-6改善明显优于对照组,病死率明显低于对照组（P ＜0．05）。结论CBP 可明显改善以第三间隙液体潴留为主的腹腔高压或腹腔间隙综合征的症状,降低腹内压,改善预后,降低死亡率。     

阻塞性睡眠呼吸暂停综合征合并高血压与红细胞分布宽度的关系

目的：探讨阻塞性睡眠呼吸暂停综合征（OSAS）合并高血压与红细胞分布宽度（RDW）的关系。方法选择2011年1月至2013年8月在中国人民解放军第九四医院呼吸内科门诊及住院的 OSAS 合并高血压患者（OSAS合并高血压组）44例和体检中心体检的原发性高血压患者（高血压组）57例、健康体检者（正常对照组）52例。各组清晨空腹抽取肘静脉血2 mL,用全自动五分类血细胞分析仪检测红细胞（RBC）计数、血红蛋白（Hb）、RDW 及白细胞（WBC）计数,比较各组 RDW 的差异,并进行相关性分析。结果高血压组 RBC 计数、Hb、RDW 和 WBC 计数与正常对照组比较差异均无统计学意义（均 P ＞0．05）;OSAS 合并高血压组 BMI、DBP、RBC 计数、Hb 和 RDW 均明显高于正常对照组、高血压组,SBP 明显高于正常对照组、明显低于高血压组（均 P ＜0．05）;高血压组 SBP、DBP均明显高于正常对照组（均 P ＜0．05）。相关性分析结果显示,OSAS 合并高血压组 RDW 与睡眠呼吸暂停低通气指数（AHI）呈正相关（r＝0．426,P ＜0．05）,与最低氧饱和度呈负相关（r＝－0．509,P ＜0．05）。结论高血压患者RDW 无明显改变,RDW 增高可能是 OSAS 合并高血压患者心脑血管事件的标志物。     

Long-Term Measures of Dyslipidemia,Inflammation, and Oxidative Stress in Rats Fed a High-Fat/High-Fructose Diet

Inflammation and oxidative stress are thought to be involved in, or associated with, the development of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. This work was designed to determine the evolution of inflammation and oxidative stress during onset and progression of hepatic steatosis and glucose intolerance. Seventy-five male Wistar rats were divided to control and high-fat high-fructose (HFHFr) groups. A subgroup of each group was sacrificed at 4, 8, 12, 16, and 20 weeks. HFHFr-fed rats exhibited overweight, glucose intolerance, and hepatic steatosis with increased contents of hepatic diacylglycerols and ceramides. The HFHFr diet increased hepatic interleukin 6 (IL-6) protein and adipose tissue CCL5 gene expression and hepatic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity but not mitochondrial reactive oxygen species (ROS) production. The HFHFr diet decreased plasma and liver levels of isoprostanoid metabolites as well as plasma thiobarbituric acid-reactive substance (TBARS) levels. Hepatic glutathione content was decreased with a moderate decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) with the HFHFr diet. Overall, HFHFr diet led to hepatic lipid accumulation and glucose intolerance, which were accompanied by only moderate inflammation and oxidative stress. Most of these changes occurred at the same time and as early as 8 or 12 weeks of diet treatment. This implies that oxidative stress may be the result, not the cause, of these metabolic alterations, and suggests that marked hepatic oxidative stress should probably occur at the end of the steatotic stage to result in frank insulin resistance and steatohepatitis. These findings need to be further evaluated in other animal species as well as in human studies.