Matters of size: Roles of hyaluronan in CNS aging and disease

Involvement of extracellular matrix (ECM) components in aging and age-related neurodegeneration is not well understood. The role of hyaluronan (HA), a major extracellular matrix glycosaminoglycan, in malignancy and inflammation is gaining new understanding. In particular, the differential biological effects of high molecular weight (HMW-HA) and low molecular weight hyaluronan (LMW-HA), and the mechanism behind such differences are being uncovered. Tightly regulated in the brain, HA can have diverse effects on cellular development, growth and degeneration. In this review, we summarize the homeostasis and signaling of HA in healthy tissue, discuss its distribution and ontogeny in the central nervous system (CNS), summarize evidence for its involvement in age-related neurodegeneration and Alzheimer Disease (AD), and assess the potential of HA as a therapeutic target in the CNS.     

Novel variants in aromatic L-amino acid decarboxylase deficiency: Case report of sisters with mild phenotype

BackgroundAromatic L-amino acid decarboxylase (AADC) deficiency, caused by a pathogenic variant in the dopa decarboxylase (DDC) gene, is a rare neurometabolic disorder in which catecholamine and serotonin are not synthesized. From a large number of reports, it has been recognized that most affected patients show severe developmental delay in a bedridden state and are unable to speak. On the other hand, patients with a mild phenotype with AADC deficiency have been reported, but they number only a few cases. Therefore, the variation of phenotypes of the disease appears to be broad, and it may be challenging to diagnose an atypical phenotype as AADC deficiency.Case reportWe report novel compound heterozygous variants in DDC (c.202G > A and c.254C > T) in two sisters, whose main complaint was mild developmental delay, by whole-exome sequencing (WES). Additionally, we describe their clinical features and provide an image that shows the variants located at different sites responsible for the catalysis of AADC in a three-dimensional structure. The patients were prescribed a Monoamine oxidase (MAO) inhibitor after diagnosis.InterpretationOur cases indicate that a comprehensive genomic approach helps to diagnose AADC deficiency with atypical features, and underscore the significance of understanding the variations of this disorder for diagnosis and appropriate treatment.     

单味中药降尿酸作用机制概述※

降尿酸是治疗痛风和高尿酸血症的基本方法，目前降尿酸作用途径主要是通过抑制黄嘌呤氧化酶、腺苷脱氨酶等合成酶的活性，或（且）影响肾脏尿酸转运蛋白（OAT1、OAT3、URAT1、GLUT9）等的表达，进而降低尿酸的水平。由于中药治疗高尿酸血症及痛风的作用机制尚不明确，因此本文通过检索中国知网、维普、万方、pubMed、Embase等数据库，对相关文献进行筛选，总结了具有明确降尿酸作用机制的单味中药，并进行功效归类，有助于对其作用机制进一步研究，为防治痛风和高尿酸血症提供更可靠、更安全的中医治疗依据。     

基于Apriori算法与网络药理学的藏医治疗肝胆疾病用药规律及机制分析＊

目的 挖掘藏医治疗肝胆疾病的用药规律，寻找核心药组，并预测核心药组的潜在靶点，以探讨核心药组治疗肝胆疾病的作用机制。方法 收集藏医药典籍中治疗肝胆疾病处方，采用SPSS软件进行Apriori算法关联规则分析得到藏医治疗肝胆疾病的核心药组。检索中药系统药理学分析平台（TCMSP）、Therapeutic Target Database （TTD）、Genecards、Metascape等数据库进行基因本体（GO）和KEGG富集分析。结果 共纳入607首方剂，数据挖掘得到藏医治疗肝胆疾病的核心药组为蒂达-洪连-波棱瓜子。收集到核心药组56个活性成分，作用于47个关键靶点，预测出1194条生物过程、49个细胞组成、54个分子功能以及226条信号通路。结论 藏医在治疗肝胆疾病中主要以“清赤巴热”为核心，所使用方剂中的药物多以苦味为主；核心药组治疗肝胆疾病可能是通过缓解体内氧化应激、降低炎症表达以及调节胆汁酸肝肠循环等作用机制。     

Gene annotation of nuclear receptor superfamily genes in the kissing bug Rhodnius prolixus and the effects of 20-hydroxyecdysone on lipid metabolism

The hormone 20-hydroxyecdysone is fundamental for regulating moulting and metamorphosis in immature insects, and it plays a role in physiological regulation in adult insects. This hormone acts by binding and activating a receptor, the ecdysone receptor, which is part of the nuclear receptor gene superfamily. Here, we analyse the genome of the kissing bug Rhodnius prolixus to annotate the nuclear receptor superfamily genes. The R. prolixus genome displays a possible duplication of the HNF4 gene. All the analysed insect organs express most nuclear receptor genes as shown by RT-PCR. The quantitative PCR analysis showed that the RpEcR and RpUSP genes are highly expressed in the testis, while the RpHNF4-1 and RpHNF4-2 genes are more active in the fat body and ovaries and in the anterior midgut, respectively. Feeding does not induce detectable changes in the expression of these genes in the fat body. However, the expression of the RpHNF4-2 gene is always higher than that of RpHNF4-1. Treating adult females with 20-hydroxyecdysone increased the amount of triacylglycerol stored in the fat bodies by increasing their lipogenic capacity. These results indicate that 20-hydroxyecdysone acts on the lipid metabolism of adult insects, although the underlying mechanism is not clear.     

Unmasking antibiotic-associated neurological disorders: The underminer in Intensive Care Unit

Psychosis is a common and intractable disorder of hospitalization, especially in patients hospitalized in Intensive Care Unit (ICU). Along with the widely use of multiple antibiotics in community-acquired infection and hospital-acquired infection, the occurrence of antibiotic-associated neurological disorders has become more frequently. However, antibiotic neurotoxicity is often overlooked or misinterpreted. In this review, we summarized the neurological disorders caused by antibacterial agent usage and firstly systematically formulated the pathogenesis of antibiotic-associated neurotoxic reactions. Precautions of the complications are critical in preventing serious clinical outcome as the inducement is curable. Regular neurological physical examination, electroencephalogram (EEG) examination, lumbar puncture and therapeutic drug monitoring closely are essential for early diagnosis and differential diagnosis.     

PA-aO2、PaCO2和Lac水平与急性百草枯中毒患者的预后的相关性

目的探究肺泡-动脉氧分压差(PA-aO2)、动脉血二氧化碳分压(PaCO2)和血乳酸(Lac)水平与急性百草枯中毒(APP)患者的预后的相关性。方法选取2018年8月至2020年8月就诊于本院的126例APP患者,根据3个月随访情况,分为存活组57例和死亡组69例,另选取同期于本院进行健康体检的健康人群45例作为对照组,检测3组PA-aO2、PaCO2和Lac水平。结果与对照组比较,APP患者PA-aO2和Lac水平显著升高,PaCO2水平显著降低,且死亡组变化幅度显著大于存活组,差异有统计学意义(P<0.05);PA-aO2和Lac与存活组呈负相关,与死亡组呈正相关,PaCO2与存活组呈正相关,与死亡组呈负相关(P<0.05);PA-aO2、PaCO2和Lac联合检测对APP患者预后的预测价值显著高于单一指标,差异有统计学意义(P<0.05)。结论PA-aO2、PaCO2和Lac水平与APP患者预后密切相关,值得临床参考。