Metformin therapy in COVID-19: inhibition of NETosis

Journal of Thrombosis and Thrombolysis -     

Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

贵州省"5+3"模式订单定向医学毕业生的离职意愿及影响因素研究

背景 我国基层全科医生的离职意愿较高，调查其离职意愿并分析影响因素，可以为减少基层卫生人才流失提供思路。目前，完成"5+3"模式（5年临床医学本科教育+3年住院医师规范化培训）培养的订单定向医学毕业生逐步履约进入基层工作，而针对该部分全科医生离职意向的研究相对较少。 目的 调查贵州省"5+3"模式订单定向医学毕业生回归基层工作后的离职意愿及影响因素，为完善吸引卫生人才留任、建设基层全科医生队伍相关政策提供依据。 方法 以贵州省截至2020年底已完成"5+3"模式培养并履约到基层医疗卫生机构工作的2015—2017级订单定向医学毕业生为研究对象。于2021-01-20至2021-02-10对其开展电子问卷调查，内容包括毕业生的一般情况、职业满意度、离职意愿、服务期满后职业方向。共回收问卷347份，其中有效问卷311份，问卷有效回收率为89.6%。采用单因素分析及多元逐步线性回归分析全科医生离职意愿的影响因素。 结果 贵州省"5+3"订单定向医学毕业生的整体离职意愿得分为（3.98±0.98）分，具有离职倾向者229例（73.6%）。不同性别、单位地理位置、每日工作量者的离职意愿得分比较，差异有统计学意义（P<0.05）。多元逐步线性回归分析显示，单位负责人对待下属的方式、在工作中获得的成就感、对当前收入满意程度、家人对工作的支持程度、当地激励政策执行程度是"5+3"订单定向医学毕业生离职意愿的影响因素（P<0.05）。服务期满后，计划留任原基层医疗卫生机构者12例（3.9%），计划去其他基层医疗卫生机构者21例（6.7%），计划离开基层去上级医院工作者196例（63.0%），计划攻读全日制硕士学位者60例（19.3%）。 结论 贵州省"5+3"模式订单定向医学毕业生的离职意愿较高，预计服务期满后基层全科人才流失较多，需从提高收入、重视全科医生心理需求、优化全科医生培养与使用、发展基层医疗卫生机构、加强全科宣传等方面着手改善。     

An assessment of cerebral venous thrombosis risk factors and associated clinical outcomes in Jazan region,Saudi Arabia

Objectives:To assess cerebral venous thrombosis risk factors, and associated clinical outcomes in Jazan region, Kingdom of Saudi Arabia.Methods:This study is a retrospective review of the medical records of patients diagnosed with cerebral venous thrombosis and admitted to King Fahad Central Hospital in Jazan between 2010 and 2019. Data concerning socio-demographics, clinical features, risk factors, laboratory, and imaging investigations were retrieved. Furthermore, data about cases management, and outcomes, including death, were collected and analysed.Results:A total of 51 medical records were identified. The majority of the patients were females (68.6%), and the mean age of the patients was 33.3 years, of which three patients were under 18 years old. The most frequently recorded symptom was headache (76.5%), followed by seizure (45.1%). The most commonly recorded risk factor was protein S deficiency (57%), followed by anaemia (51%). Venous infarction and haemorrhage were the most common acute complications (13.7%). The majority of the patients had a favourable prognosis where only 27.5% recovered with disability and only one patient died due to the disease.Conclusion:Clinical presentation of cerebral venous thrombosis in Jazan region is similar to other local and international studies. However, anaemia was recorded as a main risk factor for the disease, which might require further investigation to assess the possible association between prevalence of anaemia in Jazan region and the incidence of cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular disease in comparison with arterial stroke. CVT cases represent approximately 0.5-1% of all types of stroke which mainly occur in young and middle-aged adults.1 The data concerning the global epidemiology of CVT is currently limited.2 However, the incidence of CVT has been reported to vary between countries where the incidence might be higher as in Asian and the Middle Eastern countries in comparison to Australia and European countries.3According to a recent study conducted in Australia, the incidence of CVT was reported to reach 15.7 per 1,000,000 persons on a yearly basis. The incidence was higher among women and among those between 31-50 years old.4 In the Middle East, an Iranian study looked at the frequency of CVT between 2001 and 2004, and the annual frequency of CVT was 12.3 per one million.5 An older study, conducted in the city of Riyadh in Saudi Arabia between 1985 and 1994, identified 40 cases of CVT. Those identified were aged between 16 and 40.6 In addition, in a more recent study conducted in Jeddah and Al-Baha between 1990 and 2010, the number of detected cases of CVT was 111 where 19 of these were detected among children.7The CVT occurs when a thrombus develops as a result of a disturbance of the balance between the process of prothrombosis and thrombolysis.8,9 Risk factors for CVT can be categorised into transient and permanent risk factors. Permanent risk factors are hereditary thrombophilia, systemic diseases or miscellaneous factors, such as obesity. Transient risk factors can be subcategorised into sex-specific, iatrogenic, or miscellaneous risk factors, such as infection, head trauma or anaemia.8 The prevalence of CVT risk factors differs between countries. Infection, pregnancy, post-partum period, and dehydration have been reported to be more common in Asia and the Middle Eastern countries in comparison to European countries.8Patients with CVT exhibit variable clinical manifestations and complications, some of which can be life threatening. The most common clinical presentation is a headache, while some patients exhibit other signs and symptoms, such as seizure, decreased level of consciousness, vomiting, focal neurological deficit, or visual symptoms.8-10 Venous infarction and haemorrhage are frequently reported complications of CVT.11 Late presentation of CVT patients can increase the risk of disability and death. The mortality rate among CVT patients has been reported to vary between 4.3% and 6.8%.12Since CVT risk factors and vulnerable groups can vary between different populations, assessment of the distribution of risk factors among local populations can be clinically valuable. Studies assessing CVT prevalence and associated risk factors and clinical outcomes in Saudi populations are currently limited. Furthermore, data about CVT in Jazan region is currently lacking. This investigation aims to identify cases diagnosed with CVT in Jazan region and to evaluate the risk factors and associated clinical outcomes.     

儿童可逆性后部脑病综合征的研究现状与进展

可逆性后部脑病综合征(PRES)是一组异质性疾病,需要结合临床及神经影像学共同诊断。其病因复杂,发病机制不甚明确,高血压和钙调神经蛋白抑制剂是公认的危险因素。但对于儿童来说,其本身的基础疾病可能对此症的发生起决定性作用。PRES的临床表现与病变位置有关,头颅磁共振成像是首选的检查。其治疗的关键是迅速诊断,如诊治不及时,部分患者将发生不可逆的神经系统损害而遗留后遗症,甚至导致死亡。     

Metabolic reprogramming in childhood acute lymphoblastic leukemia

The first observations of altered metabolism in malignant cells were made nearly 100 years ago and therapeutic strategies targeting cell metabolism have been in clinical use for several decades.  In this review, we summarize our current understanding of cell metabolism dysregulation in childhood acute lymphoblastic leukemia (cALL). Reprogramming of cellular bioenergetic processes can be expected in the three distinct stages of cALL: at diagnosis, during standard chemotherapy, and in cases of relapse. Upregulation of glycolysis, dependency on anaplerotic energy sources, and activation of the electron transport chain have all been observed in cALL. While the current treatment strategies are tackling some of these aberrations, cALL cells are likely to be able to rewire their metabolism in order to escape therapy, which may contribute to a refractory disease and relapse. Finally, here we focus on novel therapeutic approaches emerging from our evolving understanding of the alterations of different metabolic networks in lymphoblasts.     

The effect of nadroparine on coagulation mechanisms: ultrastructural analysis.

Low molecular weight heparins are widely used in the prophylaxis and treatment of thrombotic disorders. The effect of low molecular weight heparins on coagulation was examined ultrastructurally in an animal model. A test and a control group was formed, each consisting of five rabbits. Nadroparine (225 Institute of Chaoy Unit/kg twice daily) was applied to the test group for 10 days. The control group received 1 ml saline solution subcutaneously. Blood and vascular tissue samples collected at the end of the 10th day were evaluated under a JEM 100 B electron microscope. Platelet degranulation and agglutination was observed in the control group. Fibrin materials were detected in the cytoplasms and surroundings of degranulated platelets. Erythrocyte accumulation was remarkable on the vascular endothelium with intact coagulation periods. In the test group, outer membranes of platelets, hyalomere, and granular structures in the granulomeres were detected to be nearly intact. There were rare erythrocytes in the large vascular lumens. The aggregation phase had occurred but no agglutination was detected. Nadroparine seems to preserve consistency of lipoprotein membranes of platelets and granular structures containing enzymes, which contribute to the coagulation mechanisms.