氨溴索治疗戈谢病相关肝硬化门静脉高压症1例报告

戈谢病(Gaucher disease,GD)是一种罕见的常染色体隐性遗传病,该病是因葡糖脑苷脂酶(glycocerebrosidase,GBA)活性缺乏引起底物葡糖脑苷脂聚集于巨噬细胞溶酶体中而发病[1]。GD是一种慢性进展性和多器官系统可受累的疾病,多数Ⅰ型戈谢病(GD-1)肝肿大与这些病理性巨噬细胞(戈谢细胞)浸润相关,仅少数病例进展为肝纤维化、门静脉高压症[1-3]。     

成年女性Ⅰ型戈谢病1例并文献复习

<正>戈谢病(Gaucher disease,GD)是最常见的溶酶体贮积病(lysosomal storage disease,LSD),属常染色体隐性遗传病,1882年由法国医生Gaucher首先报道而得名。该病由于基因突变导致机体葡萄糖脑苷脂酶(glucocerebrosidase,GBA),又称酸性β-葡萄糖苷酶,acidβ-glucosidase)活性缺乏,造成其底物葡萄     

戈谢病局灶性肝损伤疑似肝细胞癌1例报告

戈谢病(Gaucher disease,GD)是一种罕见的常染色体隐性遗传病,该病由于葡糖脑苷脂酶(glucerebrosidase,GBA)缺乏引起底物葡糖脑苷脂聚集于巨噬细胞溶酶体中而发病。脂质过载的巨噬细胞,即戈谢细胞主要浸润脾、肝脏和骨髓。临床表现为贫血、血小板少、脾大、肝大以及骨骼受累,然而不同患者其临床表现差异显著[1-3]。近年来,GD患者局灶性肝损伤影像学多样性,引起人们关注[4-6]。     

戈谢病治疗进展

戈谢病(Gaucher disease,GD)是基因突变导致患者巨噬细胞内溶酶体缺乏β-葡萄糖脑苷脂酶,致使葡糖脑苷脂在巨噬细胞内大量聚积,从而引起肝脾肿大和骨骼表现,进而出现血液学异常、肝纤维化和门静脉高压的一种溶酶体贮积症.治疗上采用酶替代方法,价格昂贵并且不能纠正中枢神经系统病变.异基因造血干细胞移植是治疗GD的...     

胱硫醚β合酶基因T833C突变与脑梗死发生的相关性研究

目的探讨脑梗死患者同型半胱氨酸(Hcy)代谢相关酶胱硫醚β合酶(CBS)基因T833C位碱基突变与脑梗死发病的相关性。方法对67例经头部CT或MR I证实为脑梗死的患者(脑梗死组)和31名健康对照者(对照组),应用聚合酶链反应(PCR)扩增法检测CBS基因T833C多态性,采用高效液相色谱法测定血清Hcy水平。结果在脑梗死组有9例CBS基因纯合子突变,28例为杂合子突变;对照组3名为纯合子突变,5名为杂合子突变。两组基因型频率分布差异亦有显著意义,2χ=11.429,P<0.01;脑梗死组C等位基因频率为34.33%,T等位基因频率为65.67%,与对照组比较差异有显著意义,2χ=8.978,P<0.01。CBS基因杂合突变者血清Hcy浓度显著高于正常基因者(t=4.612,P<0.01)。脑梗死组患者血清Hcy浓度为(23±7)nmol/m l,显著高于对照组(13±4)nmol/m l,两组比较差异有显著性(t=8.826,P<0.01)。结论Hcy血症是脑梗死的独立危险因素,而CBS基因T833C点突变可能是其发病的重要遗传因素。     

胆固醇酯转运蛋白基因突变患者低密度脂蛋白亚组分颗粒直径增大

为探讨胆固醇酯转运蛋白基因突变对低密度脂蛋白亚组分颗粒大小的影响,采用聚合酶链反应片段长度多态性技术检测２００例冠心病患者胆固醇酯转运蛋白基因１５外显子Ｄ４４２Ｇ错义突变,并分析低密度脂蛋白颗粒直径及图形。共检测出６例杂合子和１例纯合子突变,冠心病患者该基因突变率为３．５％。突变患者（７例）低粒走私及图形。共检测出６例杂合子和１例纯合子突变,冠心病患者该基因突变率为３．５％。突变患者（７例）低密度     

中国汉族人群中艾滋病相关的CCR2-64I和CCR5-C927T等位基因的多态性分析

目的 调查中国汉族人群中艾滋病相关的CCR2-64I和CCR5-C927T等位基因突变频率和多态性特点。方法 用试剂盒提取中国889例汉族人外周血单个核细胞的基因组DNA,随之进行聚合酶链反应/限制性片段长度多态性(PCR/RFLP)技术和DNA直接测序法分析,并对有关的数据进行统计学分析。结果 在检测的889例个体中,野生型CCR2-64I等位基因纯合子(基因型64V/64V)有570例,杂合子(64V/64I)298例,突变纯合子(64I/64I)21例,所占百分比分别是64.1％、33.5％和2.36％,CCR2-64I等位基因突变频率为0.1913。在889份基因样品中,有93例经过CCR5-C927T基因突变检测,结果显示野生型CCR5-C927T纯合子(基因型C/C)为63例,占67.7％;杂合子(C/T)为26例,占28.0％;突变纯合子基因型(T/T)为4例,占4.3％;CCR5-C927T等位基因频率为0.183。统计分析表明在我国汉族人群中,上述两种等位基因多态性呈Hardy-Weinberg平衡分布。结论 本研究首次阐明了土生土长的中国汉族人群中CCR2-64I和CCR5-C927T等位基因突变频率和多态性特点,这一结果将有助于综合评估中国人群对HIV-1感染的遗传易感性,同时为深入研究HIV-1抗性基因在艾滋病发病机制中的作用奠定了基础。     

戈谢病Ⅲ型诊疗进展

戈谢病(GD)是一种常染色体隐性遗传病, 由葡萄糖脑苷脂酶基因突变引起, 并具有不同表型。神经病变型GD(nGD)是较严重的疾病形式, 临床表型包括急性神经病变型GD(GD Ⅱ型)和亚急性神经病变型GD(GD Ⅲ型)。随访常发现GDⅠ型至Ⅲ型转变的病例。GD Ⅲ型除出现内脏损伤、骨破坏等外, 亦会出现逐渐加重的神经系统损伤, 区分不同的GD类型具有重要的治疗意义。本文系统总结了GD Ⅲ型的神经病变特征及相关治疗进展, 为GD Ⅲ型早诊断、早治疗提供临床参考。     

线粒体tRNALeu（UUR）基因A3243G突变糖尿病患者的临床特征

目的探讨线粒体tRNALeu(UUR)基因A3243G突变糖尿病患者的临床特征。方法选取临床症状疑似线粒体基因突变糖尿病患者12例,采外周血提取DNA,检测mtDNA 3243A→G点突变情况。结果共4例携带mtDNA 3243A→G点突变,均存在线粒体基因突变糖尿病的典型临床表现,即起病年龄早、体型消瘦、伴严重双耳听力损害、胰岛β细胞分泌功能降低及无明显母系遗传史。在测定骨密度的3例患者中,2例骨质疏松,1例骨密度降低。结论线粒体基因突变糖尿病患者存在一定的隐匿性,对消瘦、耳聋的年轻患者进行线粒体基因突变筛查及骨代谢评估,有利于及时诊治线粒体基因突变糖尿病患者,防止并发症发生。     

线粒体tRNA~(Leu(UUR))基因A3243G突变糖尿病患者的临床特征

目的探讨线粒体tRNALeu(UUR)基因A3243G突变糖尿病患者的临床特征。方法选取临床症状疑似线粒体基因突变糖尿病患者12例,采外周血提取DNA,检测mtDNA 3243A→G点突变情况。结果共4例携带mtDNA 3243A→G点突变,均存在线粒体基因突变糖尿病的典型临床表现,即起病年龄早、体型消瘦、伴严重双耳听力损害、胰岛β细胞分泌功能降低及无明显母系遗传史。在测定骨密度的3例患者中,2例骨质疏松,1例骨密度降低。结论线粒体基因突变糖尿病患者存在一定的隐匿性,对消瘦、耳聋的年轻患者进行线粒体基因突变筛查及骨代谢评估,有利于及时诊治线粒体基因突变糖尿病患者,防止并发症发生。     

Prevalence,awareness, treatment,and control of hypertension in Bissau,Western Africa

Hypertension is the leading preventable risk factor for cardiovascular diseases. In Guinea–Bissau there are no previous population‐based hypertension surveys. Therefore, the authors aimed to estimate the prevalence, awareness, treatment, and control of high blood pressure among adults living in Bissau. A sample (n = 973) of dwellers in Bissau, aged 18–69 years, was assembled through stratified and cluster sampling. Patients underwent face‐to‐face interviews and blood pressure measurements following the World Health Organization Stepwise Approach to Chronic Disease Risk Factor Surveillance. The prevalence of hypertension was 26.9%, and 51.4% of hypertensive individuals were aware of their condition, of whom 51.8% reported having received pharmacological treatment in the previous 2 weeks. Among the latter, 49.9% had blood pressure values below 140/90 mm Hg. These findings show that hypertension has become a major public health problem in Guinea‐Bissau, emphasizing the urgent need to develop and implement national strategies for the prevention and management of hypertension.     

Viruses, autophagy genes, and Crohn's disease

The etiology of the intestinal disease Crohn's disease involves genetic factors as well as ill-defined environmental agents. Several genetic variants linked to this disease are associated with autophagy, a process that is critical for proper responses to viral infections. While a role for viruses in this disease remains speculative, accumulating evidence indicate that this possibility requires serious consideration. In this review, we will examine the three-way relationship between viruses, autophagy genes, and Crohn's disease and discuss how host-pathogen interactions can mediate complex inflammatory disorders.     

临床病例评析——关节炎发热喘憋

目的 探索类风湿关节炎(RA)患者合并发热和肺部病变的诊断和鉴别诊断方法的要领。方法 对1例55岁,出现关节炎、发热和喘憋的男性患者进行详尽的临床诊治分析。结果 患者的关节表现符合RA,经过肺高分辨率CT进行肺部空洞的鉴别诊断,并经过试验性抗真菌治疗的验证,最后确定诊断为RA合并肺间质病变和真菌感染。结论 RA患者出现发热和肺部空洞性病变要考虑到肺真菌感染的可能性。     

Diagnosing ascites: Value of ascitic fluid total protein, albumin, cholesterol, their ratios, serum-ascites albumin and cholesterol gradient

Abstract Ascitic fluid total protein, albumin, cholesterol, their ascites/serum ratios, serum-ascites albumin and cholesterol gradients were measured for their ability to differentiate cirrhotic, malignant and tuberculous ascites in 76 patients. The mean ± s.d. ascitic fluid total protein, albumin, cholesterol, their respective ascitic fluid/serum ratios in cirrhotic ascites were lower than malignant and tuberculous groups ( P < 0.001 for each). The difference between malignant and tuberculous groups was significant for ascitic fluid/serum total protein ( P < 0.05) and ascitic fluid/serum albumin ( P < 0.01) only. Mean serum-ascites albumin gradient in cirrhotics was higher than in the malignant and tuberculous groups ( P < 0.001 for each). The difference between malignant and tuberculous groups was significant ( P < 0.01). Mean ± s.d. serum-ascites cholesterol gradient in cirrhotics was higher than that in malignant and tuberculous groups ( P < 0.001 for each). The difference between malignant and tuberculous groups was also significant ( P < 0.01). Both serum/ascitic fluid total protein less than 0.5 and ascitic fluid cholesterol less than 55 mg/dL had 94% diagnostic accuracy for differentiating cirrhotic from malignant and tuberculous ascites. Serum ascitic fluid albumin gradient greater than 1.1 g/dL, ascitic fluid/serum albumin less than 0.65 and ascitic fluid albumin less than 2 g/dL had diagnostic accuracy of 92, 92 and 91%, respectively. Ascitic fluid total protein had diagnostic accuracy of 88%. None of the tests was able to differentiate between malignant and tuberculous ascites. Measurement of ascitic fluid cholesterol concentration is a simple method of differentiating cirrhotic from non-cirrhotic ascites.     

重庆綦江赶水地区库蠓及其胃血血源分子鉴定

目的 利用物种线粒体CO Ⅰ基因对吸血库蠓胃血来源进行检测,研究库蠓的吸血习性。方法 采用诱蚊灯法于重庆綦江赶水地区不同生境采集吸血库蠓,并调查该地区吸血库蠓种类组成;同时根据周边环境中库蠓可能的吸血对象的线粒体CO Ⅰ基因序列差异,设计物种特异性引物,采用PCR技术对吸血库蠓胃内血粉进行线粒体CO Ⅰ基因扩增,通过将扩增产物与不同物种所对应的目的条带大小进行匹配,检测吸血库蠓胃内血粉种属来源。结果 鸡舍、羊舍和鸡鸭混合圈舍主要以荒川库蠓为主,分别占93.36%、75.26%和94.29%,猪舍以洋岛库蠓为主,占69.44%。通过随机抽样,对6种主要吸血库蠓的190份饱血库蠓胃血进行PCR检测,结果显示上述种类都存在兼性吸血的现象,可同时吸食4~6种动物的血液,其中琉球库蠓和荒川库蠓兼具吸食人血,两者吸食人血比例分别为56.52%和1.39%。结论 本研究初步证实物种线粒体CO Ⅰ基因序列可应用于吸血库蠓胃血来源的检测,同时发现6种吸血库蠓都为兼性吸血,具有吸血习性多样、对象广泛的特点。     

The gastric microbial community,Helicobacter pylori colonization,and disease

Long thought to be a sterile habitat, the stomach contains a diverse and unique community of bacteria. One particular inhabitant, Helicobacter pylori, colonizes half of the world’s human population and establishes a decades-long infection that can be asymptomatic, pathogenic, or even beneficial for the host. Many host and bacterial factors are known to influence an individual’s risk of gastric disease, but another potentially important determinant has recently come to light: the host microbiota. Although it is unclear to what extent H. pylori infection perturbs the established gastric microbial community, and H. pylori colonization seems generally resistant to disturbances in the host microbiota, it can modulate H. pylori pathogenicity. Interactions between H. pylori and bacteria at non-gastric sites are likely indirect—via programming of the pro-inflammatory vs. regulatory T lymphocytes—which may have a significant impact on human health.     

Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk

We propose a model wherein chronic stress results in glucocorticoid receptor resistance (GCR) that, in turn, results in failure to down-regulate inflammatory response. Here we test the model in two viral-challenge studies. In study 1, we assessed stressful life events, GCR, and control variables including baseline antibody to the challenge virus, age, body mass index (BMI), season, race, sex, education, and virus type in 276 healthy adult volunteers. The volunteers were subsequently quarantined, exposed to one of two rhinoviruses, and followed for 5 d with nasal washes for viral isolation and assessment of signs/symptoms of a common cold. In study 2, we assessed the same control variables and GCR in 79 subjects who were subsequently exposed to a rhinovirus and monitored at baseline and for 5 d after viral challenge for the production of local (in nasal secretions) proinflammatory cytokines (IL-1β, TNF-α, and IL-6). Study 1: After covarying the control variables, those with recent exposure to a long-term threatening stressful experience demonstrated GCR; and those with GCR were at higher risk of subsequently developing a cold. Study 2: With the same controls used in study 1, greater GCR predicted the production of more local proinflammatory cytokines among infected subjects. These data provide support for a model suggesting that prolonged stressors result in GCR, which, in turn, interferes with appropriate regulation of inflammation. Because inflammation plays an important role in the onset and progression of a wide range of diseases, this model may have broad implications for understanding the role of stress in health.     

Inflammasome,the Constitutive Heterochromatin Machinery,and Replication of an Oncogenic Herpesvirus

The success of long-term host–virus partnerships is predicated on the ability of the host to limit the destructive potential of the virus and the virus’s skill in manipulating its host to persist undetected yet replicate efficiently when needed. By mastering such skills, herpesviruses persist silently in their hosts, though perturbations in this host–virus equilibrium can result in disease. The heterochromatin machinery that tightly regulates endogenous retroviral elements and pericentromeric repeats also silences invading genomes of alpha-, beta-, and gammaherpesviruses. That said, how these viruses disrupt this constitutive heterochromatin machinery to replicate and spread, particularly in response to disparate lytic triggers, is unclear. Here, we review how the cancer-causing gammaherpesvirus Epstein–Barr virus (EBV) uses the inflammasome as a security system to alert itself of threats to its cellular home as well as to flip the virus-encoded lytic switch, allowing it to replicate and escape in response to a variety of lytic triggers. EBV provides the first example of an infectious agent able to actively exploit the inflammasome to spark its replication. Revealing an unexpected link between the inflammasome and the epigenome, this further brings insights into how the heterochromatin machinery uses differential strategies to maintain the integrity of the cellular genome whilst guarding against invading pathogens. These recent insights into EBV biology and host–viral epigenetic regulation ultimately point to the NLRP3 inflammasome as an attractive target to thwart herpesvirus reactivation.     

Evidence for an increase in the intensity of inter‐seasonal influenza,Queensland, Australia, 2009‐2019

BackgroundInter‐seasonal influenza cases have been increasing in Australia. Studies of influenza seasonality typically focus on seasonal transmission in temperate regions, leaving our understanding of inter‐seasonal epidemiology limited. We aimed to improve understanding of influenza epidemiology during inter‐seasonal periods across climate zones, and explored influenza intensity and strain dominance patterns over time.MethodsQueensland state‐wide laboratory‐confirmed influenza notifications and public laboratory influenza test data from 2009‐2019 were described by demographics, time period, region and strain type. We compared influenza intensity over time using the WHO Average Curve method to provide thresholds for seasonal and inter‐seasonal periods.ResultsAmong the 243 830 influenza notifications and 490 772 laboratory tests reported in Queensland between 2009 and 2019, 15% of notifications and 40% of tests occurred during inter‐seasonal periods, with 6.3% of inter‐seasonal tests positive. Inter‐seasonal notifications and tests substantially increased over time and increases in weekly proportions positive and intensity classifications suggested gradual increases in virus activity. Tropical inter‐seasonal activity was higher with periods of marked increase. Influenza A was dominant, although influenza B represented up to 72% and 42% of notifications during some seasonal and inter‐seasonal periods, respectively.ConclusionsUsing notification and testing data, we have demonstrated a gradual increase in inter‐seasonal influenza over time. Our findings suggest this increase results from an interplay between testing, activity and intensity, and strain circulation. Seasonal intensity and strain circulation appeared to modify subsequent period intensity. Routine year‐round surveillance data would provide a better understanding of influenza epidemiology during this infrequently studied inter‐seasonal time period.