A nonsynonymous SNP in human cytosolic sialidase in a small Asian population results in reduced enzyme activity: potential link with severe adverse reactions to oseltamivir

oseltamivir 的使用，广泛地是的 stockpiled 为在可能的鸟的流行性感冒的使用的药之一流行，被报导了与 neuropsychiatricdisorders 和严重皮肤反应被联系，首先在日本。这里，我们在 dbSNP 数据库识别了非同义的 SNP (单个核苷酸多型性) ， R41Q 在 humancytosolic sialidase 的酶的活跃地点附近，是 oseltamivir 的目标的病毒 neuraminidase 的一个相当或相同事物。在欧洲、非洲的美国人口的 9.29% 亚洲人口和没有的这 SNPoccurred。Ourstructural 分析和 Ki 大小使用试管内 sialidase 试金显示这 SNPcould 增加人的 sialidase 的非计划中的有约束力的亲密关系到 oseltamivir 羧化物， oseltamivir 的活跃形式，因此减少 sialidase 活动。另外，这 SNP 自己与一项内在地更低的 sialidase 活动导致酶，由它的增加的 Km 证明 Vmax 珍视并且减少。理论上，到有这 SNP 的人的 oseltamivir 的管理可能进一步减少他们的 sialidase 活动。我们注意 oseltamivir 的 reportedneuropsychiatric 副酌和人的 sialidase-relateddisorders 的已知的症状的类似。我们建议这个充实亚洲人的 sialidase 变化由 SNP 引起了，在同型结合的形式可能，可以与对 oseltamivir 的某些严重不利反应被联系。

Retrospective observation of therapeutic effects of adult auxiliary partial living donor liver transplantation on postpartum acute liver failure: A case report

We present a female patient with preterm labor, severe viral hepatitis B of acute phase, hepatic encephalopathy stage Ⅲ and coma.After delivery, the illness was exacerbated and the patient presented with clinical signs of vital organ dysfunctions such as acute respiratory distress syndrome, cerebral edema and hypoxemia that needed mechanical ventilation.Emergency liver transplantation was recommended after multidisciplinary panel consultations.The donor, her mother, consented to donate her right liver.Auxiliary partial orthotopic living donor liver transplantion(APOLDLT) was performed.After operation, the patient was on triple medication of tacrolimus plus mofetil mycophenolate and prednisone for immunosuppression.The combination of antihepatitis B virus(HBV) immunoglobulin and entecavir was initiated for anti-HBV therapy.Both the patient and the donor recovered well without any complications.The patient was followed up regularly.Her liver function, clinical signs and symptoms improved significantly.Until now, the recipient has been living for more than 78 mo free of any complications.The APOLDLT is a life-saving modality for rescuing patients with high-risk acute liver failure following HBV infection without available donor and hence is recommended under standardized antiviral therapy coverage as stated above.

Anticoagulation therapy prevents portal-splenic vein thrombosis after splenectomy with gastroesophageal devascularization

AIM:To compare the incidence of early portal or splenic vein thrombosis(PSVT) in patients treated with irregular and regular anticoagulantion after splenectomy with gastroesophageal devascularization.METHODS:We retrospectively analyzed 301 patients who underwent splenectomy with gastroesophageal devascularization for portal hypertension due to cirrhosis between April 2004 and July 2010.Patients were categorized into group A with irregular anticoagulation and group B with regular anticoagulation,respectively.Group A(153 patients) received anticoagulant monotherapy for an undesignated time period or with aspirin or warfarin without low-molecular-weight heparin(LMWH) irregularly.Group B(148 patients) received subcutaneous injection of LMWH routinely within the first 5 d after surgery,followed by oral warfarin and aspirin for one month regularly.The target prothrombin time/international normalized ratio(PT/INR) was 1.25-1.50.Platelet and PT/INR were monitored.Color Doppler imaging was performed to monitor PSVT as well as the effectiveness of thrombolytic therapy.RESULTS:The patients' data were collected and analyzed retrospectively.Among the patients,94 developed early postoperative mural PSVT,including 63 patients in group A(63/153,41.17%) and 31 patients in group B(31/148,20.94%).There were 50(32.67%) patients in group A and 27(18.24%) in group B with mural PSVT in the main trunk of portal vein.After the administration of thrombolytic,anticoagulant and antiaggregation therapy,complete or partial thrombus dissolution achieved in 50(79.37%) in group A and 26(83.87%) in group B.CONCLUSION:Regular anticoagulation therapy can reduce the incidence of PSVT in patients who undergo splenectomy with gastroesophageal devascularization,and regular anticoagulant therapy is safer and more effective than irregular anticoagulant therapy.Early and timely thrombolytic therapy is imperative and feasible for the prevention of PSVT.

CHDbase:A Comprehensive Knowledgebase for Congenital Heart Disease-related Genes and Clinical Manifestations

Congenital heart disease(CHD)is one of the most common causes of major birth defects,with a prevalence of 1%.Although an increasing number of studies have reported the etiology of CHD,the findings scattered throughout the literature are difficult to retrieve and utilize in research and clinical practice.We therefore developed CHDbase,an evidence-based knowledgebase of CHD-related genes and clinical manifestations manually curated from 1114 publications,linking 1124 susceptibility genes and 3591 variations to more than 300 CHD types and related syndromes.Metadata such as the information of each publication and the selected population and samples,the strategy of studies,and the major findings of studies were integrated with each item of the research record.We also integrated functional annotations through parsing50 databases/tools to facilitate the interpretation of these genes and variations in disease pathogenicity.We further prioritized the significance of these CHD-related genes with a gene interaction network approach and extracted a core CHD sub-network with 163 genes.The clear genetic landscape of CHD enables the phenotype classification based on the shared genetic origin.Overall,CHDbase provides a comprehensive and freely available resource to study CHD susceptibilities,supporting a wide range of users in the scientific and medical communities.CHDbase is accessible at http://chddb.fwgenetics.org.