ObjectiveTo evaluate the neuroprotective effect and possible mechanisms of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) in neonatal Harlequin (Hq) mutant mice brain after hypoxia-ischemia brain injury(HIBD) insult.MethodsThe nine-day-old male Hq mutant mouse pups were assigned randomly either edaravone (n=16) and vehicle (n=17) treatment group. The Hq mice were subjected to left common carotid artery occlusion combined with inhalation 100 mL/L oxygen for 45 minutes. The mice were injected intraperitoneally either with edaravone (10 mg/kg) or equivalent volume of saline immediately after artery occlusion and after hypoxia. Nitrotyrosine and lipid peroxidation formation were evaluated at 3 h and 24 h after hypoxia-ischemia(HI) by using immunohistochemistry staining. Nitrotyrosine formation and caspases activation were evaluated either by immunoblotting or fluorogenic activity measurement at 24 h after HI. Brain injury was evaluated at 72 h by neuropathological score and calculating the infarct volume.ResultsBrain injury encompassed cortex, hippocampus, striatum and thalamus. Edaravone treatment reduced brain injury significantly in all the brain regions. The total infarct volume was reduced 52.8% in edaravone treatment group compared with vehicle group (P<0.001). The edaravone treatment reduced nitrotyrosine formation as well as lipid peroxidation formation significantly, but without obviously effect on caspases activation.ConclusionEdaravone affords neuroprotection after neonatal HI insult, which correlated with the reduction of free radical formation.

Objective To evaluate the neuroprotective effect and possible mechanisms of edaravone(3-methyl-1-phenyl-2-pyrazolin-5-one) in neonatal Harlequin(Hq) mutant mice brain after hypoxia-ischemia brain injury(HIBD) insult.Methods The nine-day-old male Hq mutant mouse pups were assigned randomly either edaravone(n=16) and vehicle(n=17) treatment group.The Hq mice were subjected to left common carotid artery occlusion combined with inhalation 100 mL/L oxygen for 45 minutes.The mice were injected intraperitoneally either with edaravone(10 mg/kg) or equivalent volume of saline immediately after artery occlusion and after hypoxia.Nitrotyrosine and lipid peroxidation formation were evaluated at 3 h and 24 h after hypoxia-ischemia(HI) by using immunohistochemistry staining.Nitrotyrosine formation and caspases activation were evaluated either by immunoblotting or fluorogenic activity measurement at 24 h after HI.Brain injury was evaluated at 72 h by neuropathological score and calculating the infarct volume.Results Brain injury encompassed cortex,hippocampus,striatum and thalamus.Edaravone treatment reduced brain injury significantly in all the brain regions.The total infarct volume was reduced 52.8% in edaravone treatment group compared with vehicle group(P

Background: The interaction of the non-deletional α+-thalassaemia mutations Haemoglobin Constant Spring and Haemoglobin Quong Sze with the Southeast Asian double α-globin gene deletion results in non-deletional Haemoglobin H disease. Accurate detection of non-deletional Haemoglobin H disease, which is associated with severe phenotypes, is necessary as these mutations have been confirmed in the Malaysian population. Methods: DNA from two families with Haemoglobin H disease was extracted from EDTAanticoagulated whole blood and subjected to molecular analysis for α-thalassaemia. A duplex polymerase chain reaction was used to detect the Southeast Asian α-globin gene deletion. Polymerase chain reaction-restriction fragment length polymorphism analysis was then carried out to determine the presence of Haemoglobin Constant Spring and Haemoglobin Quong Sze. A combine- amplification refractory mutation system protocol was optimised and implemented for the rapid and specific molecular characterisation of Haemoglobin Constant Spring and Haemoglobin Quong Sze in a single polymerase chain reaction. Results and Conclusions: The combine- amplification refractory mutation system for Haemoglobin Constant Spring and Haemoglobin Quong Sze, together with the duplex polymerase chain reaction, provides accurate pre- and postnatal diagnosis of non-deletional Haemoglobin H disease and allows detailed genotype analyses using minimal quantities of DNA.

Objective To assess and compare the difference in image quality and exposure dose between single-sided reading image plate(IP)and dual-sided reading IP.Methods A contrast-detail phantom CDRAD 2.0 was exposed by single-sided and dual-sided reading IP with different mAs sets.The entrance surface doses were recorded for all images.Images were then presented to two radiologists on a high resolution monitor of diagnosis workstation.The image quality figure(IQF)was measured for each image. Statistical analysis was performed using Spearman's correlation test and Wilcoxon signed-rank test to compare the difference in image quality and exposure dose between single-sided IP and dual-sided reading IP. Results With different tube current dosage of 5.6,12.0,20.0,25.0,and 40.0 mAs,IQF values of single-sided reading IP were 47.95,37.68,34.31,28.61,and 24.65,respectively,while those of dual- sided reading IP were 38.83,29.81,29.65,25.16,and 21.43,respectively.The IQF difference between them showed statistical significance(P

PURPOSE: The American Joint Committee on Cancer 8th edition (AJCC8) prognostic stage (PS) was implemented January 1, 2018, but it is complex due to multiple permutations. A North American group proposed a simpler system using the anatomic stage with a risk score system (RSS) of 1 point each for grade 3 tumor and human epithelial growth factor receptor 2 (HER2) and estrogen receptor (ER) negativity. Here we aimed to evaluate this risk score system with our database of Asian breast cancer patients and compare it against the AJCC8 PS. METHODS: Patients diagnosed with breast cancer stage I–IV in 2006–2012 were identified in the SingHealth Joint Breast Cancer Registry. Five-year breast cancer-specific survival (CSS) and overall survival (OS) were calculated for each anatomic stage according to the risk score and compared with the AJCC8 PS. RESULTS: A total of 6,656 patients were analyzed. The median follow-up was 61 (interquartile range, 37–90) months. There was a high receipt of endocrine therapy (84.6% of ER+ patients), chemotherapy (84.3% of node-positive patients), and trastuzumab (86.0% of HER2+ patients). Within each anatomic stage, there were significant differences in survival in all sub-stages except IIIB. On multivariate analysis, the hazard ratio for negative ER was 1.74 (1.48–2.06), for negative HER2 was 1.49 (1.26–1.74), and for grade 3 was 1.84 (1.55–2.19). On multivariate analysis controlled for age, ethnicity, and receipt of chemotherapy, the RSS (Akaike information criterion [AIC] = 10,649.45; Harrell's Concordance Index [C] = 0.85) was not inferior to the AJCC8 PS (AIC = 10,726.65; C = 0.84) for CSS, nor was the RSS (AIC = 14,714.4; C = 0.82) inferior to the AJCC8 PS (AIC = 14,784.69; C = 0.81) for OS. CONCLUSION: The RSS is comparable to the AJCC8 PS for a patient population receiving chemotherapy as well as endocrine- and HER2-targeted therapy and further stratifies stage IV patients.
Asian Continental Ancestry Group ; Biomarkers ; Breast Neoplasms ; Breast ; Drug Therapy ; Estrogens ; Follow-Up Studies ; Humans ; Joints ; Multivariate Analysis ; Trastuzumab

Objective To study the effect of administration of transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine (CPZ) into the nucleus accumbens (NAc) on the regulation of body weight and fat accumulation in rats, and evaluate the therapeutic effect of CPZ on neuropathic obesity. Methods Forty rats were randomly divided into 5 groups (n=8), namely, control group (without giving any treatment),group A (performed intra-NAc injection of 1 nmol/mL CPZ),group B (performed intra-NAc injection of 10 nmol/mL CPZ),group C (performed injection of 10 nmol/mL CPZ via the areas adjacent to NAc) and group D (performed injection of 10 nmol/mL CPZ via the dorsal striatum); rats of the later 4 groups were given 1 μL CPZ daily for a consecutive 3 d.The body weight of rats from different treatment groups 1 and 3 weeks after the injection was measured and compared them to that of the control group.Then,the animals were sacrificed,the body fat content of each group was evaluated. Results The body weight in rats of group A 1 week after the injection increased (126.31± 10.25)％ as compared with their original weight, and that in rats of control group increased (148.78±6.98)％ as compared with their original weight, which showed significant difference between the 2 increment (P＜0.05); the body weight in rats of group B 1 week after the injection increased (115.87± 13.90)％ as compared with their original weight, which showed significant decrease as compared with that in the control group (P＜0.05); The body weight in rats of group B 3 week after the injection increased (132.82±15.8)％ as compared with their original weight, and that in rats of control group increased (164.86±6.34)％ as compared with their original weight,which showed significant difference between the 2 increment (P＜0.05).Furthermore,the body fat content in group B was significantly lower than that of other groups (P＜0.05). Conclusion Blockade of NAc TRPV1 receptor by CPZ has significant inhibitory central adjusting effect on body weight and fat content in rats; and TRPV1 antagonist may potentially serve as a specific drug for neuropathic obesity.

OBJECTIVETo investigate the effects of simvastatin on the proliferation, cell cycle and expression of cyclin-dependent kinase inhibitor p21 protein in human hepatocellular carcinoma (HepG2) cells in vitro.

METHODSHepG2 cells were administrated with simvastatin. Proliferation of the cells was detected by MTT assay, cell cycle was measured by flowcytometry and the cyclin-dependent kinase inhibitor p21 protein expression was detected by immunocytochemistry. The results were evaluated by factorial design and one-way analysis of variance.

RESULTSSimvastatin inhibited HepG2 cells growth in vitro (F(concentration) = 1264, P value less than 0.001; F(time) = 17.466, P value less than 0.001; F(concentration*time) = 35.053, P value less than 0.001) and could arrest HepG2 cells in G0/G1 phase of cell cycle. However, apoptosis of HepG2 cells was not obvious. Simvastatin could also increase cyclin-dependent kinase inhibitor p21 protein expression (F = 512.133, P value less than 0.001).

CONCLUSIONSimvastatin can inhibit the growth of HepG2 cells in vitro, which may be explained by its effects of enhancing cyclin-dependent kinase inhibitor p21 protein expression and arresting HepG2 cells at G0/G1 phase of cell cycle.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Hep G2 Cells ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Simvastatin ; pharmacology

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare neurodegenerative multisystem disorder inherited in an autosomal recessive manner and characterized clinically by gastrointestinal dysmotility, cachexia, ophthalmoparesis and/or ptosis, peripheral neuropathy and leukoencephalopathy. Heterogenous causative mutations in the thymidine phosphorylase (TP) gene located on chromosome 22q13 have been identifi ed. This is the fi rst reported case of a 25-year-old Malaysian patient, of indigenous Bajau ethnicity who presented with recurrent abdominal pain before developing other clinical features of classical MNGIE. Biochemical correlates include elevated plasma levels of thymidine, deoxyuridine and lactate. The brain MRI showed diffuse leucoencephalopathy while nerve conduction studies were consistent with demyelinating polyneuropathy. Direct DNA sequencing of the nine coding exons of the TP gene showed both a novel and a previously described mutation. The former is a point mutation in exon 5 (NG_011860.1:g.7387C>T) at amino acid position 179, resulting in a stop codon and premature truncation of thymidine phosphorylase(TP) protein while the latter mutation occurred at exon 10 (NG_011860.1:g.9279C>T) resulting in a missense homozygous mutation at amino acid position 471. Defi nite diagnosis was based on clinical features, plasma and urinary nucleosides and the identifi cation of mutations in the TP gene. This case report adds to the knowledge of genotype-phenotype relationship of TP mutations and its occurrence among ethnic groups worldwide.

Objective To explore the experience of developing evidence-based nursing (EBN) course in postgraduate nursing program in order to improve the quality of course.Methods A comprehensive project on developing EBN course for postgraduate nursing students was initiated in School of Nursing Fudan University.59 postgraduate nursing students in school of nursing, Fudan University were conveniently classified into EBN teaching group (n = 33) and control group (n = 26).The students in the EBN teaching group received 54 credit hours evidence-based nursing education.The teaching and learning experience were reflected through faculty interview and student interview. The teaching and learning outcome were evaluated by self-designed questionnaires.Results Students considered EBN course as a challenge.They experienced both positive and negative feelings during learning EBN.The critical appraisal, data extraction, Meta analysis and evidences utilization were seen as bigger challenges. However, they valued the experience of learning EBN as the opportunity for them to integrate knowledge and skill of literature searching, clinical epidemiology, health statistics, and nursing research into the learning of EBN course. Students in EBN teaching group had significantly higher score on evidence-based nursing knowledge than control group (z = 3.582, P < 0.01).Students in EBN teaching group had significantly higher scores on critical appraisal at post-course than at pre-course(t = 3.674,P < 0.01).Most of the students in EBN teaching group were satisfied with course content, teaching materials and teaching methods.In addition, they proposed constructive suggestions on credit hours and teaching arrangement for further implementing of evidence-based nursing course.Conclusions It is suggested that EBN can be developed as a course in postgraduate nursing program.The knowledge and skills on critical appraisal of literature and conducting systematic review can be improved by learning a comprehensive EBN course.However,the course content and teaching methods need further explore.

Objective To evaluate the outcome of the comprehensive evidence-based nursing course on Postgraduate training courses students. Methods Postgraduate training courses students in school of nursing of Fudan University were conveniently assigned to experimental group ( n =22) and control group ( n = 26). The students in the experimental group received 36 hours evidence-based nursing education. The teaching and learning outcome were evaluated by self-designed questionnaires. Results After 36 hours teaching and learning, Students in experimental group got significantly higher score on evidence-based nursing knowledge and literature criticism than control group(Z =3. 582,P<0. 01; t =3. 674,P<0. 01) ; There was no statistical difference on evidence-based nursing attitude score of students in experimental group and control group after evidence-based nursing course(t = 0. 310,P >0. 05); The results of course feedback questionnaire suggested that most of the students in experimental group were satisfied with course content, teaching materials and teaching methods. Interview results showed that students can develop system evaluation and practice Evidence-based nursing. In addition, they proposed constructive suggestions on credit hours and teaching arrangement for further implementing of evidence-based nursing course. Conclusions The knowledge and skill of EBN could be significantly improved by learning a comprehensive evidence-based nursing course for nurses studied in postgraduate nursing Program. Further study is needed to explore the effect of EBN course on students' attitude to evidence-based nursing.