OBJECTIVETo investigate the effects of host-derived p38 mitogen-activated protein kinase subunit 38 (p38MAPK) and the hepatitis B virus X antigen (HbxAg) on cell proliferation and apoptosis in human hepatocellular carcinoma (HCC), and to study the mechanism underlying hepatocarcinogenesis.

METHODSLiver tissues were biopsied from healthy individuals and patients with chronic hepatitis B (CHB), liver cirrhosis, paratumor cirrhosis, and HCC. Immunohistochemical staining was used to detect expressions of HBxAg, p38MAPK, cell cycle G2/M phase-related factors (cdc25B, p34cdc2, cyclin B1), and cell proliferation factor ki-67.The terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method (known as TUNEL) was used to detect apoptosis.

RESULTSThe highest rates of HBxAg were detected in CHB (65.0%) and HCC (44.4%) liver samples, and the antigen was mainly expressed in nuclei. Increasingly higher rates of p38MAPK, cdc25B, cyclin B1, and p34cdc2 expression were detected with increases in disease severity: normal liver (40.0%, 20.0%, 20.0%, and 30.0%, respectively), chronic hepatitis B (60.0%, 65.0%, 40.0%, and 50.0%, respectively), liver cirrhosis (65.0%, 75.0%, 70.0%, and 55.0%, respectively), paratumor cirrhosis (66.7%, 75.0%, 75.0%, and 63.9%, respectively), and HCC (77.8%, 80.6%, 80.6%, and 72.2%, respectively). In addition, the intracellular location of p38MAPK expression was different under different disease conditions, showing nuclear expression in CHB and liver cirrhosis samples and cytoplasmic expression in paratumor cirrhosis and HCC samples (x2 = 1.11, P more than 0.05). The proliferation index (PI) and the apoptosis index (AI) were both increased along with disease severity (normal more than CHB more than paratumor cirrhosis more than HCC) (PI: 0.0000+/-0.000, 0.0502+/-0.011, 0.0411+/-0.009, 0.0762+/-0.017; AI: 0.0351+/-0.024, 0.0607+/-0.022, 0.0562+/-0.013, 0.0716+/-0.011), with the notable exception for liver cirrhosis (PI: 0.1810+/-0.036 and AI: 0.1200+/-0.018). PI in poorly-differentiated HCC (0.2285+/-0.062) was significantly higher than in well-differentiated HCC (0.1216+/-0.032, t = 2.082, P = 0.044). AI in well-differentiated HCC (0.152+/-0.026) was significantly higher than in poorly-differentiated HCC (0.081+/-0.022, t = 2.129, P = 0.041).

CONCLUSIONSIn the process of hepatocarcinogenesis, HBxAg may cause a series of abnormal changes in cell cycle, proliferation and apoptosis by affecting the expression of p38MAPK.

Apoptosis ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Cycle ; Cell Division ; Cell Proliferation ; Hepatitis B, Chronic ; pathology ; Humans ; Liver Cirrhosis ; pathology ; Liver Neoplasms ; metabolism ; pathology ; Trans-Activators ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

Adolescent idiopathic scoliosis(AIS)is a complex three-dimensional spinal deformity,characterized by lateral curvature and vertebral rotation.The medical imaging techniques are essential for determination of severity of scoliotic spine, prediction of progression and assistance in the decision-making process of treatment for scoliosis, including radiograph, stereoradiography, computed tomography, magnetic resonance imaging and ultrasound.This paper reviewed their application from the view of measure parameters,reliability and va-lidity,as well as merits and demerits.It is possible to assess the three-dimensional nature of scoliosis in the future.

Objective To explore if reduced number of circulating endothelial progenitor cells (EPCs) is a risk factor for patients with coronary slow flow (CSF).Methods Thirty patients with CSF and 30 age and gender matched control subjects with normal coronary angiography were included in the study.Mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation and plated on fibronectin-coated culture dishes.EPCs were characterized as adherent cells double positive for DiI-AcLDLuptake and lectin-binding by converted fluorescence microscope (× 200).Results Smoking,diabetes mellitus,hypertension and the levels of plasma lipoprotein profile were similar between the two groups (all P ＞ 0.05).The number of EPCs was significantly lower in patients with CSF compared with control subjects (35.7 ± 5.9 vs.53.2 ± 5.9,P ＜ 0.01).TIMI frame counts was correlated with circulating EPCs number (OR =0.424,95％ CI 0.358-0.621,P ＜ 0.01) and not associated with gender,age,smoking,diabetes mellitus,hypertension and the levels of plasma lipoprotein profile.Conclusion Decreased circulating EPCs is an independent risk factor for CSF.

OBJECTIVETo investigate the effect of vasoactive intestinal peptide (VIP) on angiogenesis after focal cerebral ischemia.

METHODSFocal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 120 min in adult SD rats with intracerebroventricular VIP administration at the beginning of reperfusion. Immunohistochemistry was performed to assay BrdU immunoreactive endothelial cells, expressions of VEGF, flt-1 and flk-1 in the ischemic zone, and the protein expressions of vascular endothelial growth factor (VEGF) in the brain was measured using Western blotting.

RESULTSImmunohistochemical staining revealed significantly increased BrdU immunoreactive endothelial cells on the margins of the ischemic lesion in rats treated with VIP as compared with that in the control rats (P<0.05). VIP significantly increased the number of VEGF immunoreactive cells and flt-1- and flk-1-positive endothelial cells in comparison with the control group (P<0.01). Western blotting showed that VIP treatment resulted in significantly increased VEGF protein level in the ipsilateral hemisphere (P<0.05).

CONCLUSIONSVIP enhances angiogenesis in the ischemic brain by increasing the expressions of VEGF in the brain tissue and its receptors flt-1 and flk-1 in the endothelial cells.

Animals ; Brain ; drug effects ; metabolism ; Brain Ischemia ; immunology ; metabolism ; pathology ; physiopathology ; Endothelial Cells ; drug effects ; metabolism ; Gene Expression Regulation ; drug effects ; Male ; Neovascularization, Physiologic ; drug effects ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Vasoactive Intestinal Peptide ; pharmacology

OBJECTIVETo reassess the natural history of polycythemia vera (PV) in Chinese and evaluate the relationship between the incidence of thrombosis, post-polycythaemic myelofibrosis with myeloid metaplasia( PPMM) , leukemia transformation and the therapeutic outcome and prognostic factors.

METHODSThe clinical manifestations, laboratory parameters and treatment were retrospectively analyzed in 287 patients with PV. Univariate analysis of prognostic factors was performed using Log-rank model and multivariate analysis using COX model in term of the incidence of thrombosis, PPMM, hematologic or non hematologic cancers and mortality.

RESULTSOf the 287 patients, the median follow-up time was 46 (8-360) months. 208 thromboses were recorded in 115 patients. Twice or more thrombotic events occurred on 59 patients (51.34%). Most of these episodes occurred either at presentation or in the 2 years before diagnosis. Elder patients, prior thrombosis, poor response to therapy were associated with poor prognosis. With these three adverse prognostic factors, the patients could be separated into different risk groups. The incidence of thrombosis was higher in high risk group. 36 patients progressed to PPMM, the median time to PPMM was 80 (7-190) months. Higher WBC count, splenomegaly and treatment with alkylating agent and hydroxy-carbamide (HU) were associated with poor prognosis. 2 cases progressed to AML. 1 to lymphoma and 1 to nonhematologic cancer. 13 patients died, the cause of death was fatal thrombosis in 9 and AML in 2.

CONCLUSIONThe incidence of thromboembolism is higher and the time to myelofibrosis was shorter in Chinese PV patients than in western PV patients. The main factors that influence the survival of PV patients are thromboembolism and leukemia transformation.

Acute Disease ; Female ; Follow-Up Studies ; Humans ; Leukemia ; etiology ; Male ; Polycythemia Vera ; complications ; Primary Myelofibrosis ; etiology ; Prognosis ; Risk Factors ; Thromboembolism ; etiology

OBJECTIVETo explore the neuroprotective effect of vasoactive intestinal peptide (VIP) in rat ischemic brain injury.

METHODSVIP was administered via intracerebroventricular injection in SD rats prior to focal cerebral ischemia by intraluminal occlusion of the middle cerebral artery. The infarct volume was assessed with TTC staining, and immunohistochemistry was performed to analyze the S100beta expression in the cerebral tissue, with the serum concentrations of S100beta detected by double-antibody sandwich enzyme-linked immunosorbent assay.

RESULTSAfter VIP injection, the relative infarct volume in the rats with cerebral ischemia was significantly reduced by 32.3% as compared with the volume in the control group on day 1 (P<0.05), and the number of S100beta-positive cells was significantly decreased in the cerebral tissue (P<0.05). The injection also resulted in significantly decreased serum S100beta concentrations in the rats (P<0.05).

CONCLUSIONVIP injection can reduce the infarct volume in rats with focal cerebral ischemia, suggesting the neuroprotective effect of VIP in brain ischemia possibly by reducing S100beta overexpression.

Animals ; Brain Ischemia ; drug therapy ; Cerebral Infarction ; prevention & control ; Nerve Growth Factors ; blood ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; blood ; Vasoactive Intestinal Peptide ; pharmacology

OBJECTIVETo analyze polysomnogram characteristics of children with suspected obstructive sleep apnea hypopnea syndrome (OSAHS) and to explore the role of obstructive apnea index (OAI), apnea hypopnea index (AHI) and arousal index for pediatric OSAHS diagnosis.

METHODSSixty one suspected pediatric OSAHS cases had overnight polysomnography for at least 8 h in a quiet, dark room. Sleep studies were interpreted according to diagnostic criteria of Guangzhou Children's Hospital (Obstructive apnea was defined as cessation of nose and mouth airflow, while the respiratory effort continues for any duration. Hypopnea was defined as reduction of oronasal flow > 50% accompanied by a desaturation of 0. 04 or greater) and Urumqi diagnostic criteria (Obstructive apnea was defined as cessation of airflow at the nose and the mouth, while the respiratory effort continues for at least two breaths. Hypopnea was defined as reduction of oronasal flow > 50% accompanied by a desaturation of more than 0.03, or/and by an arousal) respectively. The OAI, AHI and arousal index were recorded and analyzed according to the two different diagnostic criteria respectively.

RESULTS(1) Forty - one children (67.2%) had 206 obstructive apneas. Fifty - four children (88.5%) had 2249 obstructive hypopneas. Apnea - hypopnea events mainly occurred during rapid eye movement sleep. (2) OAI and AHI were analyzed by diagnostic criteria of Guangzhou Children's Hospital and Urumqi diagnostic criteria respectively. OAI < 1 was observed in 68. 9% and 75.4% children respectively and AHI < 5 occurred in 34.4% and 24.6% children respectively. (3) Statistically significant difference found between spontaneous arousal index and respiratory - related arousal index (z = -5.787, P = 0.000).

CONCLUSIONSAs the criteria of pediatric OSAHS, arbitrary OAI number should be determined on the basis of large sample investigation, the significance of spontaneous arousal index still needs further investigation.

Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Polysomnography ; Sleep Apnea, Obstructive ; diagnosis ; physiopathology

Objective To observe the symptoms of inattention,hyperactivity among obstructive sleep apnea hypopnea syndrome(OSAHS) children,also to investigate the effects of surgery(tonsillectomy and adenoidectomy or adenoidectomy alone)on the changes of sleep architecture and inattention-hyperactivity score(HIS). Methods Between June 2004 and may 2007,eighty children diagnosed as OSAHS with overnight polysomnography(PSG) were included in this study,only sixteen children had complete pre-op and post-op PSG data. Thirty children with vocal cord nodules were selected as control group. DSM-Ⅳ-derived HIS was evaluated by neurologist. All OSAHS children accepted surgery(tonsillectomy and adenoidectomy or adenoidectomy alone) and HIS evaluation. The pre-op and post-op sleep architecture and than that it in control group(0.89 vs 0.17)and the difference was significant(Z=-4.276,P＜0.05).OSAHS children had pre-op HIS greater than 1.25 and nine had post-op HIS greater than 1.25,while only three children in control group had HIS greater than 1.25. The difference was statistically significant(x2=data,a decrease in the percentage of phase 1 sleep and an increase in the percentage of phase 2 sleep,slow wave sleep(SWS) and rapid eye movement(REM) sleep were observed in six months after surgery and the difference was significant(t=12.2,-5.4,-6.3,-8.1 respectively,P＜0.001). After surgery,apneahypopnea index(AHI) decreased from 13.9 times/h to 1.5 times/h while lowest saturation of blood oxygen (LSaO2) increased from 0.855 to 0.940(t=5.3,-3.7 respectively,P＜0.01). REM sleep percentage and LSaO2 was still lower than that of control group six months after surgery. Conclusions Children with OSAHS showed significantly impaired attention and hyperactivity as compared with control group.Improvement of behavior and sleep architecture were observed after dnoidectomy and tonsillectomy.

Objective To investigate the causes and treatments of severe complications after laparoscopic surgery. Methods Clinical data of 7 cases with severe complications after laparoscopic surgery in the Third People’s Hospital of Shenzhen from January 2008 to January 2013 were analyzed retrospectively. The informed consents of all patients were obtained and local ethical committee approval had been received. There were 3 males and 4 females with the age ranging from 6 to 67 years old and median of 40 years old. The diagnosis, treatments clinical data of the patients were collected, and the causes, treatments and prevention measures of the complications were summarized. Results Five cases underwent laparoscopic cholesystectomy (LC), 4 of which suffered bile duct injury for severe abdominal adhesion and unclear anatomy of the Calot triangle and 1 case suffered strangulated intestinal obstruction after operation because the hepatic falciform ligament was ruptured when puncturing below the xiphoid. One case underwent laparoscopic high ligation of hernial sac for indirect inguinal hernia and suffered strangulated intestinal obstruction after operation because part of the small intestine ran out of the peritoneum through the port site below the umbilicus. One case underwent laparoscopic tension-free repair for indirect inguinal hernia and suffered ischemic necrosis of the left testis possibly because of testicular torsion when stretching the tissue. The 4 cases with bile duct injury received primary drainage, 3 of which underwent secondary Roux-en-Y cholangiojejunostomy for severe biliary stricture and all recovered well after operation, and the other case underwent endoscopic biliary stent implantation 3 months after operation. The 2 cases with strangulated intestinal obstruction underwent emergent partial resection and end-to-end anastomosis of small intestine and recovered well after operation. The case with necrosis of testis underwent testicular excision. Conclusions The main causes of severe complications after laparoscopic surgery probably are the unclear local anatomy and failing to convert surgical procedure timely, etc. Early diagnosis, comprehensive evaluation and proper surgical interventions are the important measures for improving the prognosis of these patients.

PURPOSE: The purpose of this study was to investigate the function of Zinc finger protein 488 (ZNF488) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: The endogenous expression of ZNF488 in NPC tissues, normal nasopharyngeal epithelium tissues and NPC cell lines were detected by quantitative reverse transcription polymerase chain reaction. ZNF488 over-expressing and knock-down NPC cell line models were established through retroviral vector pMSCV mediated over-expression and small interfering RNA (siRNA) mediated knock-down. The invasion and migration capacities were evaluated by wound healing and transwell invasion assays in ZNF488 over-expressing and control cell lines. Soft-agar colony formation and a xenograft experiment were performed to study tumorigenic ability in vitro and in vivo. Immunofluorescence and western blotting analysis were used to examine protein changes followed by ZNF488 over-expression. Microarray analysis was performed to explore gene expression profilings, while luciferase reporter assay to evaluate the transcriptive activity of Tcf/Lef. RESULTS: ZNF488 was over-expressed in NPC tissues compared with normal tissues, especially higher in 5-8F and S18, which are well-established high metastatic NPC clones. Functional studies indicate that over-expression of ZNF488 provokes invasion, whereas knock-down of ZNF488 alleviates invasive capability. Moreover, over-expression of ZNF488 promotes NPC tumor growth both in vitro and in vivo. Our data further show that over-expression of ZNF488 induces epithelial mesenchymal transition (EMT) by activating the WNT/beta-catenin signaling pathway. CONCLUSION: Our data strongly suggest that ZNF488 acts as an oncogene, promoting invasion and tumorigenesis by activating the Wnt/beta-catenin pathway to induce EMT in NPC.
Blotting, Western ; Carcinogenesis* ; Cell Line ; Clone Cells ; Epithelial-Mesenchymal Transition* ; Epithelium ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Heterografts ; Luciferases ; Microarray Analysis ; Oncogenes ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Small Interfering ; Wnt Signaling Pathway* ; Wound Healing ; Zidovudine ; Zinc Fingers