Identification of potential drugs for Parkinson's disease based on a sub-pathway method

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in ageing individuals. Current therapeutic regimen suffers from general side effects and a poor efficiency for PD symptoms. The need for development new therapeutic agents for PD is urgent. Here, we aimed to explore the metabolic mechanism of PD and identified potential novel agents for PD by a sub-pathway-based method. By using the GSE7621 microarray data from the GEO database, we first identified the 1226 differentially expressed genes (DEGs) between PD and normal samples. Then we identified 19 significant enriched metabolic sub-pathways, which may involve in development of PD. Finally, by an integrated analysis of PD-involved sub-pathways and drug-affected sub-pathways, we identified 49 novel small molecular drugs capable to target the PD-involved sub-pathways. Our method could not only identify existing drug (apomorphine) for PD, but also predict potentially novel agents (ketoconazole and astemizole), which might have therapeutic effects via targeting some key enzymes in arachidonic acid metabolism. These candidate agents identified by our approach may provide insights into a novel therapy approach for PD.     

Evaluation of three methods for measurement of hemoglobin and calculated hemoglobin parameters with the Sysmex KX-21 and ADVIA 120 in Beagle dogs and Sprague Dawley (SD) rats

The Sysmex KX-21 uses a novel cyanide-free colorimetric method to detect hemoglobin (HGB) concentration. This measurement has not been compared with the cyanmethemoglobin method on the ADVIA 120 which is recommended as the reference method by the International Committee for Standardization in Hematology. Additionally, ADVIA 120 uses flow cytometric method to detect cellular HGB concentration. The aim of this study was to compare the three methods of HGB analysis on the two analyzers. Fresh K₃EDTA blood samples from 32 dogs and 27 rats were included. A complete blood count (CBC) was performed on each sample using the Sysmex KX-21 and ADVIA 120. Colorimetric and cellular HGB concentrations and all calculated variables based on HGB measurement were compared using linear regression, Passing–Bablok regression, and Bland–Altman plots, using the cyanmethemoglobin method as the reference method. In samples from both species, an excellent correlation was found between the HGB results measured with the cyanide-free method and the cyanide-based method (r?=?0.97); however, a slight mean proportional bias of 3.8 % (dogs) and 1.9 % (rats) was observed. The correlation of flow cytometric cellular HGB concentration and extracellular total HGB concentration on the ADVIA 120 was excellent (r?=?0.97), and no significant bias was observed. Additionally, excellent to fair agreement was evident for all calculated erythrocyte and HGB variables. Thus, the cyanide-free HGB method and flow cytometric method could be used with blood samples from dogs and rats; however, the proportional bias should be considered.     

Characterization of viral genomic mutations in novel influenza A (H7N9)-infected patients: the association between oseltamivir-resistant variants and viral shedding duration

Since February 2013, human infections with the novel influenza A H7N9 virus have occurred in eastern China. It is important to detect mutations in viral genes and analyze the clinical features of patients and viral shedding duration related to neuraminidase inhibitor (NAI) resistance. We collected clinical specimens from 31 hospitalized H7N9 patients and sequenced NA, PB2, HA, and M gene fragments. Of the 31 identified patients, 7 (22.6%) carried the R292K substitution in NA, 30 (96.8%), 3 (9.7%), and 5 (16.1%) carried E627K, Q591K, and D701N mutations in PB2, respectively, and 2 (6.5%) carried both E627K and D701N mutations in PB2. All 26 identified patients harbored Q226L mutations and possessed only a single arginine (R) at cleavage sites in the HA and a S31N mutation in M2. Among 7 NA-R292K mutated patients, 3 died and 4 were discharged. There was no significant difference in the days that patients started oseltamivir treatment after symptom onset between NA-R292K mutant and NA-R292 wild-type patients (median days, 7 vs 6, P?=?0.374). NA-R292K mutant patients had a significantly longer duration of viral shedding than NA-R292 wild-type patients after oseltamivir treatment (median days, 10 vs 5, P?=?0.022). The mutation of R292K in NA conferring the potential ability of oseltamivir resistance resulted in prolonged viral duration and poor outcome and should be taken into consideration in the clinical management of infected patients.

     

Prenatal diagnosis of pulmonary artery sling associated with tracheal agenesis: A case report

Pulmonary artery sling (PAS) and tracheal agenesis (TA) are rare diseases, and most cases of PAS are associated with tracheal bronchial malformations. However, PAS associated with TA is yet to be reported. We report a case of PAS with TA diagnosed prenatally. Due to the extremely low incidence, physicians do not have sufficient understanding of these diseases and it is challenging to diagnose these diseases by prenatal ultrasound, with high rates of misdiagnosis. Prenatal examination of the pulmonary artery branches, trachea, and esophagus is useful; therefore, improving the accuracy of prenatal diagnosis will help in perinatal management and counseling.     

The eighth American college of chest physicians guidelines on venous thromboembolism prevention: implications for hospital prophylaxis strategies

Venous thromboembolism (VTE) is the most common potentially preventable form of hospital-related mortality. It presents as a major healthcare burden, affecting both medical and surgical patients. The prevention of VTE has been identified as one of the most important in-hospital safety practices in the US. VTE guideline recommendations provide a framework for clinical practice and guide VTE prophylaxis policies. Guidelines produced by the American College of Chest Physicians (ACCP) are considered to be the ‘gold standard’ in VTE prevention, diagnosis and management, and have been updated. A number of differences exist between the new 2008 ACCP guidelines on VTE prevention and the previous version published in 2004. There are variations regarding VTE prevention, including new and stronger evidence-based recommendations for several indications and agents. The updated guidelines give a strong recommendation that every hospital develop a VTE prevention policy, which is particularly important given the current international drive to reduce the incidence of VTE. A formal hospital policy should help improve compliance with appropriate VTE prophylaxis strategies. The ACCP guidelines form a basis for improving patient safety at a time of public reporting of quality of care, hospital accreditation, national standards of care, and pay for performance initiatives. In this review, changes in recommendations for VTE prevention in the 2008 ACCP guidelines compared with the previous edition in 2004 are outlined. In addition, outstanding areas of debate are discussed and the role of the 2008 ACCP guidelines in the context of the new VTE performance measures analyzed.     

MiR-876-5p acts as an inhibitor in hepatocellular carcinoma progression by targeting DNMT3A

Hepatocellular carcinoma (HCC) is one of the biggest challenges that human beings faced with in 21st century. Previous researches have revealed that miRNAs can serve as regulators in various cancers. MiR-876-5p, a member of miRNA family, has been studied in lung cancer for its anti-oncogenic function. However, the exact function of it is not reported in HCC. Our study aims to find out the effects of miR-876-5p expression on HCC progression. Two HCC cells were chosen to do functional assays after miR-876-5p expression was detected in cell lines by qRT-PCR. HepG2 cell was transfected with miR-876-5p mimics, whereas LM3 cell was transfected with miR-876-5p inhibitors. Next, cell activities of these two indicated cells were analyzed by means of MTT assay, colony forming assay, transwell migration assay and western blot analysis. Consequently, we found that miR-876-5p could inhibit both cell proliferation and metastasis. Moreover, we found out a target gene (DNMT3A) of miR-876-5p by performing bioinformatics analysis, dual luciferase reporter assay and biotin-avidin pull-down assay. Finally, rescue assays were carried out in HepG2 cells. We found that DNMT3A could reverse miR-876-5p mimics-induced inhibition. Therefore, we concluded that miR-876-5p suppressed hepatocellular carcinoma progression by targeting DNMT3A.     

Report of 457 sporotrichosis cases from Jilin province,northeast China,a serious endemic region

Background Most reported sporotrichosis cases came from South American countries, the USA, India and Japan. This mycosis is also endemic in Northeast China. However, the situation is not clear for international researchers due to lack of large series reported in English. Objectives To report and analyse 457 sporotrichosis cases. Methods Retrospective study of 457 cases of sporotrichosis diagnosed by fungal culture at the First Hospital of Jilin University from 1 January 2007 to 31 December 2009. Results In this series, the male: female ratio was 1:1.42. Mean age was 41.2 years. Cases from age group 51–60 years accounted for most of the cases (22.54%). A total of 434 patients lived in rural areas (94.97%). The onset of symptoms in 67.61% cases happened in cold seasons (winter and spring). History of trauma presented in 133 cases (29.1%). The mean duration of the symptoms before the presentation was 6.41 months. A total of 190 (41.58%) showed lymphocutaneous form, 252 patients (55.14%) showed fixed form, 8 patients (1.75%) showed disseminated cutaneous sporotrichosis and the clinical form of 7 patients (1.53%) could not be defined. Extremities and nodules were the most frequently involved sites and founded manifestation. Main histopathology findings were suppurative granuloma, tuberculoid granuloma and mixed inflammatory granuloma. A total of 75 cases (19.74%) had fungal elements revealed by Periodic Acid‐Schiff staining. Patients responded well to potassium iodide (KI), itraconazole, terbinafine and combinations of these agents with a mean course of 2.17 months to resolve. Conclusion As the first report of a large series of sporotrichosis cases from China to be published in English literature, our study indicated a serious sporotrichosis endemic situation in Jilin province, Northeast China, with epidemiological and clinical characteristics similar to those of previous Chinese reports, but different from those in other countries. KI, itraconazole and terbinafine are effective for the treatment.     

The epidemiology of hyperuricaemia and gout in Taiwan aborigines

To determine the prevalence of hyperuricaemia, gout and gout-related factors in Central Taiwan Atayal aborigines, 342 subjects over 18 yr old were interviewed and examined. A questionnaire was designed to screen for signs and symptoms of gout and gout-related risk factors. Serum uric acid, triglyceride and creatinine were measured in all subjects. The prevalence of hyperuricaemia was 41.4% and that of gout 11.7% in aborigines. The uric acid level was 7.9+/-1.7 mg/dl in males and 5.7+/-1.5 in females, and differed significantly under age 70 yr (P < 0.001). Significantly increased triglyceride, creatinine and alcoholism was found in gouty patients compared with non-gouty patients. In 40 cases with gout, 54% had tophi and 35% of their first- degree relatives had gout. The high prevalence of hyperuricaemia and gout in Taiwan Atayal aborigines, a significant family predisposition, increased creatinine level and alcoholism suggest multiple factors affecting the hyperuricaemia.