Molecular epidemiology of norovirus associated with gastroenteritis and emergence of norovirus GII.4 variant 2012 in Japanese pediatric patients

In late 2012, an outbreak of acute gastroenteritis due to norovirus variant Sydney_2012 occurred and have been reported from many counties. In this study, we described surveillance study of the incidence of norovirus infections among Japanese pediatric patients in association with gastroenteritis and investigated the antigenic change of the new variant Sydney_2012 circulated in Japanese populations. A total of 2381 fecal specimens collected from children with acute gastroenteritis in Hokkaido, Tokyo, Shizuoka, Kyoto, Osaka, and Saga from 2009 to 2013 were examined for norovirus and further analyzed molecularly. A high proportion (39.3%) of norovirus positive samples and several genotypes were detected. Norovirus GII.4 dominated over other genotypes (71.4%). The Den_Haag_2006b (43.2%) was detected as the predominant variant and co-circulated with New_Orleans_2009 (17.8%) until March 2012. Subsequently, they were displaced by Sydney_2012. The Sydney_2012 variant has been responsible for the majority of norovirus infections in 2012–2013 (85.7%). Although Sydney_2012 variant has a common ancestor with New_Orleans_2009 variant, analysis of P2 sub-domain showed a high level of diversity in comparison with other variants in four amino acid changes at the antigenic sites. The change in particular residue 393 of new variant may affect HBGA recognition. Analysis of noroviruses circulating in the past 4 years revealed a change of predominant variant of norovirus GII.4 in each epidemic season. The change of amino acid in putative epitopes may have led the virus escape from the existing herd immunity and explain the increase of new variant outbreaks.     

Unusual hyperpigmented patches,an undeveloped breast and a cataract in a female with incontinentia pigmenti

A 19‐year‐old female and her mother visited our department with a history of unusual reticular brown‐black patches on their trunks and limbs since infancy. Besides the obviously fulsome hyperpigmentation, the daughter also showed other unusual clinical manifestations such as generalized hypohidrosis, especially on the hyperpigmented patches, cicatricial alopecia, a cataract on her right eye, abnormal teeth and a right dysplastic breast. The mother had a median diastema between her maxillary central incisors, hypoplasia of the enamel, hypohidrosis and hyperpigmented patches on her left thoracic region. Analysis of the NEMO (NF‐κB essential modulator) gene in the patient and her mother revealed a deletion of exons 4–10. Their EDA and EDAR genes were normal.     

初诊糖尿病预后评估表形成的分析

现今对糖尿病的各种研究有很多,关于糖尿病的致残率和病死率的报道也有不少,但如何评估糖尿病的预后,一直未被重视。而对于预后又是每个病人都非常关心的问题。要确定某一因素对糖尿病预后的影响有多大,甚至能"打多少分",确实非常困难。要搞清各种因素对糖尿病预后的综合影响,可能需要相当长的时间。笔者根据文献报道的对糖尿病预后的影响因素综     

Paraneoplastic syndrome mimicking progressive supranuclear palsy

Paraneoplastic syndrome presenting with progressive supranuclear palsy (PSP) phenotype is extremely rare. We report a patient who presented with features of rapidly progressive parkinsonism similar to PSP and was found to have small cell carcinoma of the lung along with seropositivity for onconeural antigen. The patient was treated with immunomodulation and was given chemotherapy for the malignancy and subsequently improved.     

Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world,multi-center,cohort study

BackgroundThere is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia.ObjectiveTo define the characteristics of phenotypic and genetic HoFH probands from mainland China.MethodsWe collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test.ResultsA total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH.ConclusionsThis report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.     

恩替卡韦治疗乙型肝炎患者血清铁蛋白的检测与临床意义

目的:检测慢性乙型肝炎患者血清铁蛋白(SF)的水平及恩替卡韦抗病毒治疗前后的变化。方法:采用化学发光法检测102例慢性乙型肝炎患者SF水平,并检测ALT、HBV DNA、基因型等指标。结果:轻度、中度至重度患者SF水平依次递增,均高于健康对照组,SF与ALT水平呈正相关,不同基因型之间SF水平差异无统计学意义(P>0.05)。抗病毒治疗48周后,ALT复常组及HBV DNA阴性组患者SF水平均明显下降。结论:检测SF水平可以在一定程度上反映肝脏炎性反应程度。定期监测SF的变化,对判断恩替卡韦抗病毒疗效及疾病预后有一定意义。     

L-1416, a novel MDR reversing agent with possible reduced calcium antagonism

BackgroundMultidrug efflux transporter P-glycoprotein (P-gp) is highly expressed on membrane of tumor cells and supposed to be implicated in the resistance to tumor chemotherapy. However, currently none of P-gp inhibitors has been approved by Food and Drug Administration not only due to toxicity but also lack of efficacy in clinical trials.MethodsTo solve the problem, our lab synthesized a novel compound named 1416 [1-(2,6-dimethylphenoxy)-3,4-dimethoxyphenylethylamino) propane hydrochloride] with the hope of high P-gp inhibition and low side effects. Caco-2 cell monolayer and tumor bearing mice were used to evaluate the P-gp inhibition of 1416 in vitro and in vivo, respectively. One of its potential side effects, calcium antagonism was also evaluated.ResultsResults showed that 1416 showed a similar P-gp inhibition as verapamil in Caco-2 cell monolayer. No significant difference was observed in antitumor enhancement when the optical isomers of 1416 (D-1416 and L-1416) were co-administered with vinblastine. In calcium antagonism, L-1416 showed less calcium inhibition than both D-1416 and verapamil.ConclusionThe novel compound 1416 could significantly increase the antitumor effects of cytotoxic drugs and one of its optical isomers, L-1416, might be more promising due to its potential low calcium antagonism.     

结构方程在肺源性心脏病中医证候分类中的临床研究

目的：通过对肺源性心脏病患者中医四诊信息的收集调查，对肺源性心脏病进行证候分类研究。方法：采用结构方程模型方法对肺源性心脏病进行证候分类。结果：结构方程模型拟合参数（GFI）为0.932，拟合度高，具有统计学意义。结论：咳嗽、胸闷、咯痰、倚息、夜间多尿、形寒怕冷、气短为结构方程的基础信息，符合肺心病的临床表现和病理特征。     

Visual afference mediates head and trunk stability in vestibular hypofunction

Humans must maintain head and trunk stability while walking. The purpose of this study was to compare the kinematics of healthy controls and patients with vestibular hypofunction (VH) when walking and making head rotations of different frequencies in both light and dark conditions. We recruited eight individuals with VH and nine healthy control subjects to perform four tasks at their preferred gait speed, being normal walk, walking and making yaw head rotations at 1.5 Hz and 2 Hz, and walking in the dark and making yaw head rotations at 1.5 Hz. Linear kinematics as well as head, trunk, and pelvis angular velocities were captured using the Vicon motion analysis system (Vicon Motion Systems, Oxford, UK). We found no difference in walking velocities for any of the four walking conditions across groups. The lateral displacement of the center of mass was increased in VH patients. In the dark, patients had more head instability in pitch (larger amplitudes and velocities) even though they were walking and making active yaw head rotations. Patients also had a smaller relative phase angle (mean 3.50 ± standard deviation 2.13°) than controls (mean 10.31 ± standard deviation 2.70°) (p < 0.01). Our data suggest that patients with VH have difficulty walking with a straight trajectory when turning their head. Additionally, patients with VH have an abnormal excursion of spontaneous pitch head rotation while walking and making active yaw head turns, which is dependent on vision. Rehabilitation for these patients should consider applying unique head rotation frequencies when training gait with head turns as well as alternating their exposure to light.     

陶瓷-陶瓷全髋关节假体的初步临床应用结果

目的综合评价陶瓷-陶瓷全髋关节假体的初步临床应用结果。方法 1999年1月~2010年6月进行了28例28髋高纯度氧化铝陶瓷-陶瓷全髋关节置换术,均使用意大利Lima公司的＂三明治型＂高纯度氧化铝陶瓷-陶瓷全髋关节。其中,24例24髋得到随访,平均年龄56.4岁（39~68岁）,平均随访时间18.6个月（12~48个月）。对临床结果采用改良Har ris系统评分评价疗效,术前及术后均拍摄X线片进行临床随访和观察,主要评价了患者术后的临床疗效,并对假体的磨损及陶瓷部件的碎裂作了影像学评估。结果术后Harris评分平均97.5分（92~100分）,无患侧髋关节周围异常杂音,无陶瓷假体碎裂,无其他严重并发症。影像学结果提示假体位置满意,无磨损、松动征象,无明显骨溶解及感染表现。3例发生股骨近段纵向劈裂骨折并发症。结论高纯度氧化铝陶瓷-陶瓷全髋关节的短期疗效令人满意,尤其适合用于年轻、活跃的患者。