霉酚酸酯对IgA肾病患者血清和尿液TGF-β1表达的影响

目的 探讨IgA肾病(IgAN)患者血清、尿液TGF-β1表达以及霉酚酸酯(mycophenolate mofetil,MMF)对其表达的影响,揭示MMF治疗IgAN可能的机制.方法 用ELISA法检测健康对照组19例(Ⅰ组)、与MMF组匹配初诊未治疗IgAN 39例(Ⅱ组)、MMF治疗组48例(Ⅲ组)血清、尿液TGF-β1的水平,并比较各组表达差异性.结果 血清中TGF-β1的表达,Ⅱ组较Ⅰ组表达增加(P＜0.05);Ⅲ组较Ⅱ组表达下降(P ＜0.0001).尿液中TGF-β1的表达,Ⅱ组、Ⅲ组均较Ⅰ组表达增加(P＜0.05);Ⅲ组较Ⅱ组表达下降(P＜0.05).IgAN患者血清TGF-β1的表达与病理级别、尿蛋白排泄呈正相关(P=0.044、0.001),尿液TGF-β1的表达与GFR呈负相关(P=0.012),与病理级别、血肌酐、尿蛋白排泄呈正相关(P=0.01、0.013、＜0.0001).血清TGF-β1与尿液TGF-β1的表达呈正相关(P=0.001).IgAN LEE分级≤3级与＞3级的患者相比,后者血清、尿液TGF-β1表达增加,差别有统计学意义(P =0.049,0.028).MMF治疗组疗程3～6个月与≥6个月的患者相比,后者血清、尿液TGF-β1表达下降,差别有统计学意义(P=0.001,0.026).结论 IgAN患者血清、尿液TGF-β1表达显著增加,并且其表达水平与肾功能进展及严重程度等密切相关,MMF可显著下调IgAN患者血清、尿液中TGF-β1表达.因此,血清、尿液TGF-β1可作为预测IgAN疾病进展及评估MMF疗效的重要指标.     

心脏手术中抗纤溶药物的临床应用进展

心脏手术中过度失血仍是心脏手术面临的的主要挑战之一,抗纤溶药物的临床应用为解决这一难题带来希望。由于抑肽酶可增加肾损伤、增加术后死亡率,赖氨酸类似物成为心脏手术中主要抗纤溶用药,其中氨甲环酸的应用最为广泛。无论是在体外循环心脏手术还是在非体外循环冠状动脉搭桥手术中,氨甲环酸的有效性经多项研究证实。而如今,不同出血风险的心脏手术中氨甲环酸的应用剂量仍未明确。在氨甲环酸广泛应用的同时,其安全性也引起大家质疑,其与术后谵妄的关系也引起大家高度注意,而有专家呼吁抑肽酶有必要再次进入临床。将来,抑肽酶是否会成为高危出血心脏手术中的主要抗纤溶用药,氨甲环酸的合理应用剂量最终怎样界定,对这些问题我们拭目以待。     

AISF update on the diagnosis and management of adult-onset lysosomal storage diseases with hepatic involvement

Lysosomal storage diseases (LSDs) are a heterogeneous group of inherited disorders caused by loss-of-function mutations in genes encoding for lysosomal enzymes/proteins. The consequence is a progressive accumulation of substrates in these intracellular organelles, resulting in cellular and tissue damage. The overall incidence is about 1/8000 live births, but is likely underestimated. LSDs are chronic progressive multi-systemic disorders, generally presenting with visceromegaly, and involvement of the central nervous system, eyes, the skeleton, and the respiratory and cardiovascular systems. The age at onset and phenotypic expression are highly variable, according to the specific enzymatic defect and tissues involved, the residual activity, and the disease-causing genotype. Enzyme-replacement therapies and substrate-reduction therapies have recently become available, leading to the improvement in symptoms, disease progression and quality of life of affected individuals. Liver involvement and hepatosplenomegaly are frequent features of LSDs and a hallmark of adult-onset forms, frequently leading to medical attention. LSDs should therefore be considered in the differential diagnosis of liver disease with organomegaly. The present document will provide a short overview of adult-onset LSDs with hepatic involvement, highlighting the specificities and systemic manifestations of the ones most frequently encountered in clinical practice, which may hint at the correct diagnosis and the appropriate treatment.     

Methylenetetrahydrofolate Reductase 677 Genotype-Specific Reference Values for Plasma Homocysteine and Serum Folate Concentrations in Korean Population Aged 45 to 74 Years: The Namwon Study

The reference interval for plasma total homocysteine (tHcy) and serum folate concentrations were estimated. Total of 3,154 reference individuals (1,029 men and 2,125 women) were selected based on stringent exclusion criteria. For plasma tHcy concentration (µM/L), reference values (median [5-95 percentile]) were 7.72 (5.03 to 13.80) and 6.09 (3.95-10.19) in men and women, respectively. For serum folate concentration (nM/L), reference values were 23.71 (11.73-38.44) and 28.95 (15.23-40.44) in men and women, respectively. The tHcy levels of both genders in the present study were lower than those in previous reports from other countries and Korea.

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老年人抗γ氨基丁酸B型受体脑炎的临床特点

目的探讨老年人抗γ氨基丁酸B型(GABA-B)受体脑炎的临床特点。方法回顾性分析10例老年抗GABA-B受体脑炎患者临床资料,采用改良的Rankin量表(mRS)评分进行预后评估。结果10例患者主要临床表现包括痫性发作(100%)、精神行为异常(100%),认知障碍(100%),意识障碍(80%)。头颅MRI异常7例,以累及颞叶、海马、岛叶、杏仁体及扣带回等边缘系统,其中3例同时累及非边缘系统(包括额叶、放射冠)。胸部CT示肺部占位性病变3例。10例均给予免疫调节治疗。出院6个月后电话随访,死亡2例,预后不良4例,预后良好4例。结论老年抗GABA-B受体脑炎患者以痫性发作、精神行为异常、认知障碍为主要表现;头颅MRI以边缘系统异常信号多见;易合并有肿瘤,需注意肿瘤筛查及定期跟踪随访;免疫调节及抗肿瘤为主要治疗方法,预后较差。     

Pinellia Total Alkaloids Modulate the GABAergic System in Hippocampal Formation on Pilocarpine-Induced Epileptic Rats

Objective: To investigate the neuromodulatory effect of pinellia total alkaloids(PTA) on the gamma-aminobutyric acidergic(GABAergic) system in epileptic rats, and preliminarily evaluate the anti-epileptic effect of PTA. Methods: Ninety-one male Sprague-Dawley rats were randomized to a control group(n=17) or an epileptic group(n=74) using computer-generated random numbers. Status epilepticus(SE) was induced with pilocarpine in the epileptic group. Epileptic rats that survived SE were randomly divided into 4 groups, namely an epilepsy group(n=13), a topiramate(TPM, 60 mg/kg) group(n=12), a high-dose PTA(800 mg/kg) group(n=12), and a low-dose PTA(400 mg/kg) group(n=10). Treatments were given intragastrically once daily for 14 days. The control group and epilepsy group received normal saline. Spontaneous recurrent seizures(SRSs) were monitored 8-h daily for 7 days after treatment. Then, the hippocampal formation tissues were collected. GABA level was measured using enzyme-linked immunosorbent assay. Protein and mRNA expression levels of glutamate decarboxylase 65(GAD65), GABA transporter-1(GAT-1), GABA transaminase(GABA-T), and GABAA receptor(GABAAR) α4, α5, γ2 and δ subunits were measured using Western-blotting analysis and quantitative polymerase chain reaction. Results: PTA lowered the incidence and frequency of SRS(both doses vs. the TPM group, P0.05). Compared with the epilepsy group, PTA increased the levels of GABA(both doses P0.01) and GAD65(mRNA, 800 mg/kg, P0.01), and suppressed the levels of GAT-1(mRNA, 800 mg/kg, P0.01; 400 mg/kg, P0.05), GABA-T(mRNA, both doses P0.01), and GABAAR δ subunit(protein, 800 mg/kg, P0.05) and γ2 subunit(protein, both doses P0.01). PTA upregulated the low-expressed mRNA levels of GABAAR α5 subunit(400 mg/kg, P0.01), δ subunit(800 mg/kg, P0.05), and γ2 subunit(400 mg/kg, P0.05). Conclusions: PTA regulated the GABAergic system through modulating GABA levels and the expression levels of GAD65, GAT-1, GABA-T, and GABAAR α4, α5, γ2 and δ subunits. PTA may exert antiepileptic effects on the pilocarpine-induced epilepsy model.     

注射用丹参多酚酸治疗急性脑梗死疗效观察

目的 探讨注射用丹参多酚酸治疗急性脑梗死的临床疗效、安全性。方法 将80例急性脑梗死患者随机分为观察组（40例）和对照组（40例）,对照组采用常规治疗方法,阿司匹林肠溶片100 mg,每日1次,口服,瑞舒伐他汀钙片10mg,每晚1次,口服,依达拉奉30 mg,每日2次,静脉滴注;观察组在对照组基础上加用注射用丹参多酚酸100 mg,每日1次,静脉滴注,疗程14 d。两组分别在治疗前、后,对患者进行美国国立卫生院神经功能缺损程度评分（NHISS）,日常生活活动能力量表评分（Barthel指数）,检测血清C反应蛋白水平。结果 观察组总有效率为87.5%,对照组总有效率为57.5%,两组治疗临床效果比较差异显著（P<0.05）;治疗后,两组患者NIHSS评分、C反应蛋白水平明显降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组显著低于对照组,差异有统计学意义（P<0.05）。治疗后,两组患者Barthel指数明显升高,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组显著高于对照组,差异有统计学意义（P<0.05）。观察组仅1例出现短暂性面红情况,减慢静滴速度后消失。两组肝功及心肌酶均在正常范围。结论 注射用丹参多酚酸治疗急性脑梗死疗效显著、安全性好。     

百癣夏塔热片联合夫西地酸乳膏治疗寻常痤疮的临床研究

目的探讨百癣夏塔热片联合夫西地酸乳膏治疗寻常痤疮的临床疗效。方法选取2017年6月—2018年6月在监利县人民医院治疗的寻常痤疮患者98例,根据用药的不同分为对照组(49例)和治疗组(49例)。对照组患者取适量夫西地酸乳膏涂于患处,3次/d;治疗组在对照组基础上口服百癣夏塔热片,1.55 g/次,3次/d。两组患者均治疗4周。观察两组患者临床疗效,同时比较治疗前后两组患者红斑、色素沉着、Acne-QOL和SF-36评分及血清白细胞介素-8(IL-8)、可溶性白细胞介素-2受体(sIL-2R)、肿瘤坏死因子-α(TNF-α)、IL-10和γ干扰素(IFN-γ)水平。结果治疗后,对照组临床有效率为81.63%,显著低于治疗组的97.96%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者红斑、色素沉着评分显著降低(P0.05),Acne-QOL和SF-36评分显著升高(P0.05),且治疗组红斑、色素沉着、Acne-QOL和SF-36评分明显优于对照组(P0.05)。治疗后,两组患者血清IL-8、s IL-2R和TNF-α水平均显著降低(P0.05),IL-10和IFN-γ水平显著升高(P0.05),且治疗组上述炎症因子水平明显好于对照组(P0.05)。结论百癣夏塔热片联合夫西地酸乳膏治疗寻常痤疮可有效改善患者临床症状,促进皮损修复,降低机体炎症反应,提高患者生活质量。     

Resting-state glutamate level in the anterior cingulate predicts blood-oxygen level-dependent response to cognitive control

The dorsal anterior cingulate cortex (dACC) is a core structure for the governing of cognitive control, and recent studies have shown that interindividual differences in dACC anatomy are associated with corresponding differences in the ability for cognitive control. However, individuals differ not only in anatomical features of dACC, but also exhibit substantial variability regarding the biochemical characteristics of the dACC. In this study, we combined magnetic resonance spectroscopy ((1)H-MRS) and functional magnetic resonance imaging (fMRI), finding that interindividual differences of glutamate levels in the dACC during resting-state predict the strength of the blood-oxygen level-dependent (BOLD) response to a task requiring cognitive control. This relationship was observed in the retrosplenial cortex, the orbitofrontal cortex, the inferior parietal lobe, and the basal ganglia. More specifically, individuals with low resting-state glutamate levels in the dACC showed an increased BOLD response when the task demands were high, whereas high-glutamate individuals showed the opposite pattern of an increased BOLD response when the task demands were low. Thus, we show here that individual variability of glutamate levels is directly related to how the brain implements cognitive control.