The 185delAG BRCA1 mutation originated before the dispersion of Jews in the diaspora and is not limited to Ashkenazim

The 185delAG mutation in BRCA1 is detected in Ashkenazi Jews both in familial breast and ovarian cancer and in the general population. All tested Ashkenazi mutation carriers share the same allelic pattern at the BRCA1 locus. Our previous study showed that this 'Ashkenazi' mutation also occurs in Iraqi Jews with a similar allelic pattern. We extended our analysis to other non-Ashkenazi subsets: 354 of Moroccan origin, 200 Yemenites and 150 Iranian Jews. Heteroduplex analysis complemented by direct DNA sequencing of abnormally migrating bands were employed. Four of Moroccan origin (1. 1%) and none of the Yemenites or Iranians was a carrier of the 185delAG mutation. BRCA1 allelic patterns were determined for four of these individuals and for 12 additional non-Ashkenazi 185delAG mutation carriers who had breast/ovarian cancer. Six non-Ashkenazi individuals shared the common 'Ashkenazi haplotype', four had a closely related pattern, and the rest ( n = 6) displayed a distinct BRCA1 allelic pattern. We conclude that the 185delAG BRCA1 mutation occurs in some non-Ashkenazi populations at rates comparable with that of Ashkenazim. The majority of Jewish 185delAG mutation carriers have a common allelic pattern, supporting the founder effect notion, but dating the mutation's origin to an earlier date than currently estimated. However, the different allelic pattern at the BRCA1 locus even in some Jewish mutation carriers, might suggest that the mutation arose independently.      

Rhino-orbital-cerebral mucormycosis as a complication of coronavirus disease 2019

Coronavirus disease 2019 is a highly contagious respiratory disease caused by severe acute respiratory syndrome coronavirus 2. This disease as well as its various treatments like steroids, antivirals, and antibacterials can alter the immune state of the affected individuals and result in secondary infections such as mucormycosis. Mucormycosis is a well-known opportunistic fungal infection that affects immunocompromised subjects, particularly those with diabetes mellitus, prolonged antibiotic or steroid use, and patients with organ trans-plantation, neutropenia, and hematological malignancies. Rhino-orbital-cerebral mucormycosis is an aggressive disease owing to its ability to invade the blood vessels by fungal hyphae, leading to necrosis of the involved structures. Large cases were reported from India, indicating that this clinical entity shows a geographical variation. The affected patients are suffering on a clinical spectrum depending on the stage of the disease. Radiological assessment, including computerized tomography and magnetic resonance imaging, is necessary to evaluate the stage of the disease and choose the appropriate surgical treatment. A multidisciplinary approach is required to treat rhino-orbital-cerebral mucor-mycosis and includes local or intravenous antifungal drugs, debridement of the dead tissues, and appropriate management of any predisposing conditions. The disease has a very poor prognosis with a death rate of 50%. This review aimed to sum-marize the demographic and clinical risk factors, investigations, treatments, and outcomes of coronavirus disease 2019 patients with rhino-orbital-cerebral mucormycosis.     

Liver dysfunction-related COVID-19: A narrative review

The coronavirus 2019 disease (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2. This disease was designated by the World Health Organization as a pandemic on March 11, 2020, which is not seen before. There are no classical features among the cases of the disease owing to the involvement of nearly all body tissues by the virus. Hepatic involvement is one of the characteristics of the COVID-19 course. There are six possible mechanisms of such involvement: Direct virus injury, drug-induced effect, inflammatory cytokine storm, hypoxia-ischemic destruction, abnormalities in liver function tests, and pre-existing chronic liver diseases. Liver abnormalities are seen commonly in the severe or critical stage of COVID-19. Therefore, these abnormalities determine the COVID-19 severity and carry a high rate of morbidity and mortality. The elderly and patients with comorbidities like diabetes mellitus and hypertension are more vulnerable to liver involvement. Another issue that needs to be disclosed is the liver manifestations following the COVID-19 vaccination, such as autoimmune hepatitis. Of note, complete vaccination with third and fourth booster doses is necessary for patients with previous chronic liver diseases or those who have been subjected to liver transplantation. This review aims to explore the various aspects of liver dysfunction during the COVID-19 course regarding the epidemiological features, predisposing factors, pathophysiological mechanisms, hepatic manifestations due to COVID-19 or following vaccination, role of liver function tests in the assessment of COVID-19 severity, adverse effects of the therapeutic agents for the disease, and prognosis.     

应用心脏综合信息检测仪进行心率变异性时域和频域分析

目的:应用心脏综合信息检测仪对健康大学生运动前后和不同年龄及健康状态教工进行心率变异性时域和频域分析,拟为短时间心率变异性测试评价健康人、患者自主神经系统的功能状态和躯体性亚健康状态提供客观依据。方法:于2003-01/2005-12选择大连大学的受试者254人,其中男142人,女112人;健康20～39岁175人次,健康40～60岁57人次;其中年龄20～25岁无亚健康状态大学生100人次,运动后疲劳状态大学生64人次,40～60岁躯体性亚健康状态教工22人次。实验方法:用MCA-3C心脏综合信息检测仪的心率变异性程序软件对以上受试者进行512次心率的心率变异性采集分析,检测心率变异性。在跑步机上进行3min固定程序8～10级跑步运动,达到力竭状态。休息5min后进行心率变异性检测。实验评估:R-R间期与平均R-R间期之差>50ms的个数占总数的百分比;全频范围内的总功率;低、中频段功率与高频段功率的比值;高频段和低、中频段的功率。结果:①健康人不同性别和不同年龄之间心率变异性差异无显著性。②大学生运动后疲劳状态与亚健康状态的心率变异性的下降有所不同。结论:认为应用心脏综合信息检测仪的心率变异性程序软件对受试者测验的结果是准确可靠的,建议利用心率变异性指标在全民健身运动中对健康状况进行评估。     

延边朝鲜族新生儿血红蛋白Gγ/(Gγ+Aγ)比值测定

目的:血红蛋白γ链包括Gγ和Aγ,基因图谱分析发现新生儿常有γ链基因的异常。实验测定延边朝鲜族新生儿血红蛋白Gγ/(Gγ Aγ)比值,对于研究人类遗传变异和基因调节具有重要意义。方法:实验于2005-12/2007-04在延边大学医学部基础医学院生物化学与分子生物学教研室完成。①材料来源:97例朝鲜族新生儿脐带血由延边大学医院妇产科产室提供,产妇均签署知情同意书。②实验方法:新生儿脐带血取样后立即冷冻于液氮之中,EDTA-Na2抗凝,进行血红蛋白解链,每500μL脐带血与0.9%的NaCl溶液1000μL相混合稀释,离心去上清,分离血红蛋白。用酸性聚丙烯酰胺以凝胶电泳法分离血红蛋白中的Gγ和Aγ肽链,电压200V,电泳50min,电泳方向为正极到负极。电泳后凝胶用丽春红2R染色,乙酸脱色致本底无色。用UVP扫描凝胶成像分析系统对凝胶板上的Gγ和Aγ肽链进行扫描定量,测定血红蛋白中Gγ/(Gγ Aγ)比值。结果:朝鲜族新生儿脐带血中的血红蛋白Gγ/(Gγ Aγ)比值分布情况:1例处于30%～48%低Gγ区,占总例数的1.03%,平均值27.60%;96例处于50%～79%中间区,占总例数的98.97%,平均值(68.40±2.90)%,明显低于相关文献报道的新疆维吾尔族、广西壮族、北京市汉族、西藏藏族新生儿Gγ/(Gγ Aγ)的整体均值(75.4±2.50)%,差异有显著性意义(P<0.05);未发现>80%高Gγ区者。结论:延边朝鲜族新生儿血红蛋白Gγ/(Gγ Aγ)比值多分布于50%～79%中间区,其平均值与其他民族比较相对较低。     

人成釉蛋白抗体的制备及组织表达特异性

目的:制备抗人成釉蛋白抗体,观察成釉蛋白在各组织中的表达。方法:实验于2002-03在解放军第四军医大学基础部生物化学与分子生物学教研室完成。以重组、纯化的成釉蛋白C端肽为抗原,混入完全/不完全弗氏佐剂,免疫新西兰大白兔,经5次免疫后,颈动脉取血,分离血清并用饱和硫酸铵纯化,制备兔抗人成釉蛋白多克隆抗体,用双向免疫扩散试验和ELISA检测抗体的效价。用WesternBlot检测人成釉蛋白的组织表达特异性。结果:①ELISA检测结果:表明兔抗人成釉蛋白多克隆抗体效价达到1∶10000。②WesternBlot显示:成釉蛋白在人牙胚组织总蛋白中有特异性表达,相对分子质量约为65000,在脑、心、肝、脾、肺、肾、胰腺、胸腺、骨骼肌等组织中未见表达条带。结论:制备了抗人成釉蛋白抗体,为研究成釉蛋白在人牙胚中的组织表达以及利用抗体纯化蛋白提供了基础,从蛋白水平证实成釉蛋白为牙胚组织特异性蛋白,并证实人牙胚组织中的成釉蛋白相对分子质量约为65000。     

Serum ammonia does not guide management and is overutilised in patients with cirrhosis in hospital settings

Background

Hepatic encephalopathy is a confusional state associated with cirrhosis. Serum ammonia levels are neither sensitive nor specific for the diagnosis.

Aims

We audited the ordering location and hospital unit whilst assessing the impact on management at a major Australian tertiary centre.

Methods

We conducted a single-centre retrospective chart review of the ordering of serum ammonia levels between 1 March 2019 and 29 February 2020 at The Royal Melbourne Hospital, a tertiary-referral centre in Melbourne, Victoria. Demographic, medication and pathology results, including serum ammonia measurements, were collected. The main outcomes assessed were ordering location, sensitivity, specificity and impact on management.

Results

A total of 1007 serum ammonia tests were ordered in 425 patients. Nearly all ammonia ordering was by non-gastroenterologists, 24.2% by the intensive care unit, 23.1% by general medicine and 19.5% by the emergency department (ED). Only 21.6% of patients had a history of cirrhosis, with hepatic encephalopathy diagnosed in 13.6%. On subgroup analysis, 217 ammonia tests were performed in 92 patients with cirrhosis. Cirrhotic patients were older (64 vs 59 years, P = 0.012) and had higher median ammonia levels (64.46 vs 59 μmol/L, P < 0.001) compared with non-cirrhotic patients. In cirrhotic patients, the sensitivity and specificity for serum ammonia and diagnosis of hepatic encephalopathy were 75% and 52.3% respectively.

Conclusion

We affirm the poor utility of serum ammonia levels for guiding management of hepatic encephalopathy within the Australian context. ED and general medical units account for the majority of test ordering within the hospital. Understanding where ordering occurs provides a target for targeted education.     

胰腺癌的当代治疗

胰腺癌是消化系统常见肿瘤,在西欧和美国,胰腺癌位居恶性肿瘤死亡的第四位.在我国胰腺癌的发病率原来很低,近年来逐年增多,据上海、天津统计,胰腺癌的死亡率在15 a前占第10位,近年来升到第5位.几乎所有患者在诊断明确的同时已是晚期或有转移.胰腺癌的特点是病程短,进展快,死亡率高.文献报道该病五年生存率＜4%,中位或平均生存期4mo～6 mo[1].