Objective This research approaches the methods of intensifying the medical clinical skills training to develop students’medical abilities in clinical practice.Methods We chose 129 seven-year medical students.They were devided into two groups in random.The con-trol group entered the clinical practice directly,while the experimental group accepted the clini-cal skill training before they entered the clinical practice.Results The examination record and qualification number of experimental group were higher than the control group obviously.After the clinical skill training,the examination record became higher than before.Conclusion The experiment shows that receiving clinical skill training before entering clinical practice is the ef-fective method of elevating medical students’clinical abilities and practical skill level.

Objective:To explore the pathogenesis of multiple organ dysfunction syndrome(MODS)with respect to the bal- ance of Th1/Th2.Methods:Eighteen healthy male minipigs,weighing 22-30 kg,were randomly divided into two groups: MODS group and control group.Double-hit method including hemorrhagic shock and endotoxiemia was used to establish the porcine MODS model.The peripheral vein blood samples were collected at different time-points(before bloodletting,before en- dotoxin injection,1 h,24 h,48 h and 72 h after endotoxin injection)in the two groups.The spleen samples were collected after death of the animals.Plasma levels of IFN-?and IL-4 were detected by enzyme-linked immunosorbent assay(ELISA).Real- time PCR was used to detect the expression of IFN-?,IL-4,T-bet and GATA-3 mRNA(The latter 2 were the key transcription factors associated with Th1/Th2 response)in the spleen samples.Results:The plasma levels of IFN-?and IL-4 quickly reached the peak values 1 h after the endotoxin injection,then the level of IFN-?decreased quickly.The ratio of IFN-?/IL-4 was signifi- cantly lower than the baseline value 72 h after endotoxin injection(P=0.000).The ratio of IFN-?/IL-4 mRNA in MODS group was obviously lower than that in the control group(P=0.020);the ratio of T-bet/GATA-3 was also lower in MODS group (P=0.038).Conclusion:The shift from Th1 to Th2 occurs in the progress of MODS.

0.05).CART vaccine at 10?g significantly depressed the analgesic effect of morphine analgesia (P

BACKGROUNDNeurofibromatosis type 1 (NF1) is the most common genetic syndrome predisposing patients to various tumors due to dysregulation of the Ras signaling pathway. Recent research has shown NF1 patients also suffer a spectrum of bone pathologies. The pathogenesis of NF1 bone diseases is largely unknown. There is no current treatment. By Nf1 heterozygote (Nf1+/-) mice and Nf1 conditional knockout mice, we and other groups demonstrated abnormal osteoblast and osteoclast function due to dysregulation of Ras signaling. However, the specific downstream effector pathways linked to NF1 abnormal osteoblastogenesis and osteoclastogenesis have not been defined. In this study, we investigated the Ras downstream effector related with NF1 bone disease.

METHODSWe used Nf1+/+ and Nf1+/- mice as normal and NF1 models. Bone stromal cells extracted from Nf1+/+ and Nf1+/- mice were induced osteoclasts. The osteoclast cell was stained by tartrate resistant acid phosphatase staining. The osteoclast cell number was counted and the surface area of osteoclast cells was calculated under the microscope. The mRNA of mammalian target of rapamycin (mTOR) was determined by quantitative reverse-transcription-polymerase chain reaction. The presence of ribosomal protein S6 kinase was determined by Western blotting.

RESULTSCompared with Nf1+/+ mice, Nf1+/- mice had about 20% more of osteoclast cells. These osteoclast cells were larger in size with more nuclei. Hyperactive mTOR was detected in Nf1+/- osteoclast cells. Inhibition of mTOR signaling by rapamycin in Nf1+/- osteoclasts abrogated abnormalities in cellular size and number.

CONCLUSIONmTOR pathway inhibition may represent a viable therapy for NF1 bone diseases.

Animals ; Male ; Mice ; Neurofibromatosis 1 ; drug therapy ; Osteoclasts ; drug effects ; physiology ; Osteogenesis ; drug effects ; Sirolimus ; pharmacology ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; physiology

Objective To investigate the expression and significance of major histocompatibility complex classⅡgene in multiple organ dysfunction syndrome.Methods Two-hit porcine model of MODS was duplicated in 18 swine that were randomly assigned into experimental group(Group M,n=9) and control group(Group C,n=9).The Group M was given compound factors including hemorrhagic shock,reperfusion injury and endotoxemia,and the Group C only underwent anesthesia and arterious/ve- nous eannula.After seven days,the animals were killed to remove splenic tissues fro extracting total RNA by Trizol method.The primer of SLA-DQA(MHC classⅡgene of swine)was designed to construct cD- NA by reverse transcription and the quantity of SLA-DQA mRNA detected with real time fluorescent quan- titative polymerase chain reaction(real time FQ-PCR).The standard curve was described by UVP com- puter image analysis system.Results The mortality of Group M was 78%(7/9),and the incidence rate of MODS was 89%(8/9).The expressing quantity of Group M was(1.376?1.006)?10~3,signifi- cantly lower than(5.330?3.053)?10~3 of Group C(P＜0.01).Conclusion Duplication of por- cine MODS model is satisfactory.Down-regulation of MHC classⅡgene may be due to control of classⅡtransactivator(CⅡTA)and release of multiple eytokine,such as TNF-?and IL-10.

BACKGROUNDHistone deacetylase (HDAC) inhibitors are a group of small chemical molecules that inhibit histone deacetylase. At cell level, HDAC inhibitors have multiple biological effects such as cell cycle arrest, apoptosis, cell differentiation and auotophagy. At molecular level, HDAC inhibitors cause histone and nonhistone acetylation and induce gene expression. HDAC inhibitors are widely used in cancer therapy because of its function of inducing apoptosis. However, the mechanisms of apoptosis effect are not fully understood. TSA is a classical HDAC inhibitor and widely used in epigenetic and anti-cancer research. In this study, we selected Trichostatin A (TSA) to investigate the mechanisms of HDAC inhibitors apoptotic effect on cancer cells.

METHODSCervical cancer cell lines such as Hela, Caski and normal human keratinocyte line HaCaT were treated with various concentrations of TSA. Crystal violent assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed to determine cell number. PARP cleavage and FITC-AnexinV were performed to determine apoptosis. DNA-methyltransferase (DNMT)1, DNMT3A and DNMT3B were determined by regular PCR, qPCR and Western Blotting. Small interfering RNA (SiRNAi) was used to knock down DNMT3B.

RESULTSHDAC inhibitors only induce cervical cancer cell apoptosis. At 1 µmol/L of TSA, 86% of Hela cell and 76% of Caski went apoptosis. For normal cells, HDAC inhibitors have no cytotoxic effect at therapeutic dosage, (90.0 ± 8.4)% of normal cell survive after treated with 1 µmol/L of TSA. We compared 1 µmol/L group with untreated control with t-test. There was no significance between 1 µmol/L group and untreated control for normal cell (P > 0.05). HDAC inhibitors decreased DNMT3B in cancer cell but not in normal cell. Manually knock-down of DNMT3B induced Hela and Caski cell apoptosis. More than 99% of Hela and Caski cell went apoptosis after deprived of DNMT3B.

CONCLUSIONSDNMT3B was essential to cervical cancer cell survival. Down-regulated DNMT3B by HDAC inhibitors may play an important role in the toxicity of HDAC inhibitors on cervical cancer cells.

Apoptosis ; drug effects ; genetics ; Cell Line ; Cell Line, Tumor ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; metabolism ; Female ; HeLa Cells ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Hydroxamic Acids ; pharmacology ; Uterine Cervical Neoplasms ; enzymology ; genetics

OBJECTIVETo evaluate the expression of ezrin and CD44-v6 in esophageal squamous cell carcinoma, and to evaluate its relationship with lymph node metastasis (LNM) and histological grading.

METHODSThe expression of ezrin and CD44-v6 in 71 patients with esophageal squamous cell carcinoma was studied using immunohistochemical (SP) method. The correlation of their expression with relevant clinical data was statistically analyzed.

RESULTSIn normal esophageal squamous epithelia, the expression of ezrin was found in 33 cases among 71 cases and the expression of CD44-v6 in 18 cases among 71 cases. In esophageal squamous cell carcinoma, the expression of ezrin was found in 64 cases among 71 cases and CD44-v6 in 58 cases among 71 cases. The expression of ezrin was closely related to LNM. The positive rate of ezrin expression in LNM cases was significantly higher than that in cases without LNM. The expression of CD44-v6 had a close relation to tumor differentiation and LNM. The positive rate of CD44-v6 expression in LNM cases was significantly higher than that in patients without LNM. The expression of ezrin in CD44-v6 positive cases was significantly higher than that of CD44-v6 negative cases. The LNM rate was 60.0% in 48 patients with positive expression of both ezrin and CD44-v6, while none of lymph node metastasis was found in the 6 patients with both negative.

CONCLUSIONThe test of CD44-v6 and ezrin expression may have significant prognostic value for assessing the degree of malignancy and potential LNM probability of ESCC. Ezrin may become a new target in evaluation of tumor prognosis.

Carcinoma, Squamous Cell ; metabolism ; pathology ; Cytoskeletal Proteins ; metabolism ; Esophageal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging

Tic disorders(TD), a complex chronic neuropsychiatric disorder characterized by rapid, involuntary, non rhythmic, single or multiple muscle movements or vocal twitches, usually occurs in children aged from 2 to 15 years.TD has various clinical manifestations, which are usually related to various psychopathology or behavioral comorbidities, including attention deficit hyperactivity disorder, anxiety, depression and obsessive-compulsive disorder.The etiology and pathogenesis of TD are still not completely clear.Immune, genetic, neurobiochemical and environmental factors are generally recognized as factors related to the pathogenesis of TD.In recent years, the research on TD and genetic factors has gradually increased, but so far there is no clear conclusion on the pathogenic genes of TD.This paper only discusses the genes related to TD.

Lissencephaly(LIS)is a group of abnormal cerebral cortical dysplasias caused by the defective migration of neurons and it is characterized by thickening of the cerebral cortex, widening of the gyri and disappearance or shallowness of the sulci.Clinically, the patients often have manifestations such as epilepsy, mental retardation, and developmental delay.At present, there is no specific treatment and most patients have poor prognosis.There is currently no specific treatment, and most patients have a poor prognosis.Recently, with the widespreading clinical application of genetic testing, many disease-causing genes related to the lissencephaly have been discovered, so it is important for us to study its pathogenesis and the mode of inheritance.In this study, we reviewed the recent literature on genes associated with lissencephaly.

OBJECTIVETo study the features of DUOX2 mutations and genotype-phenotype relationship in children with congenital hypothyroidism (CH), in order to provide evidence for gene diagnosis and gene treatment of CH.

METHODSBlood samples were collected from 10 CH children with thyromegaly. Genomic DNA was extracted from peripheral blood leukocytes. All exons of DUOX2 gene were analyzed using PCR and direct sequencing.

RESULTSG3632A mutation in the exon 28 of DUOX2 that may result in arginine to histidine substitution at codon 1211 was found in one patient. T2033C mutation in the exon 17 of DUOX2 that may result in histidine to arginine substitution at codon 678 was found in three patients. They were all heterozygous mutations.

CONCLUSIONSHeterozygous mutations in DUOX2 may affect protein function and cause CH. The relationship between DUOX2 genotypes and clinical phenotypes is unclear and needs further studies.

Child ; Child, Preschool ; Computational Biology ; Congenital Hypothyroidism ; genetics ; Dual Oxidases ; Female ; Humans ; Male ; Mutation ; NADPH Oxidases ; genetics ; Sequence Analysis, DNA