ObjectiveTo investigate the expression of heme oxygenase-1 (HO-1) in lung tissue of mice with acute paraquat poisoning, and discuss its pathological mechanism.Methods Fifty-eight healthy male mice were randomly divided into control group (n = 8) and poisoned group (n = 50). The mice in poisoned group were lavaged with 20% paraquat (50 mg/kg), and those in control group with equal amount of normal saline. The mice were sacrificed on the day of experiment in control group, and those in poisoned group at 6 hours and 1, 3, 7, 14 days after poisoning. The lung tissue was harvested to observe the changes in pathology of lung with hematoxylin and eosin (HE) staining. The positive expression of HO-1 was determined with immunohistochemistry, and the protein expression of HO-1 was determined with Western Blot. The contents of superoxide dismutase (SOD) and malonaldehyde (MDA) were determined.Results The mice showed shortness of breath and signs of exhaustion 1 hour after poisoning, getting worse on 3-5 days, but returned to normal 14 days after poisoning. Under the light microscope, it showed that the control group had no significant pathological changes in lung tissue. One day after the ingestion, pulmonary alveolar structure disorder, obvious hemorrhage, edema and infiltration of inflammatory cells were found. At 3 days, the pathological changes in the lung tissue were more pronounced. They were less pronounced on 7 days, and inflammatory changes disappeared on 14th day, but alveolar structure disorder remained. Immunohistochemical test showed that HO-1 was seldom expressed in the lung tissue, and a little amount was expressed in the mucosal epithelial cells of the airway in control group. It was shown that inflammatory cell and endothelial were mainly distributed in the mucosal epithelial cells of airway 1 day after poisoning followed by a gradually decrease tendence, and came to normal level of control group 7 days after poisoning. It was shown by Western Blot that HO-1 (gray value) in lung tissue increased 6 hours after poisoning (2.438±0.467 vs. 0.475±0.167,P< 0.01), peaked at 1 day (9.200±0.940 vs. 0.475±0.167,P< 0.01), continued to increase till 7 days after poisoning, and it lowered to normal level thereafter (0.825±0.260 vs. 0.475±0.167,P> 0.05). The SOD activity (μU/L) in lung tissue was lowered 6 hours after poisoning, and it was significantly lower than that of control group (649.681±13.951 vs. 1 167.051±15.744,P< 0.01), and it continued to decrease up to 14 days after poisoning (859.733±121.079 vs. 1 167.051±14.744,P< 0.01). MDA content (μmol/L) in the lung tissue homogenate was elevated 6 hours after poisoning with significant difference compared with that of the control group (4.542±0.266 vs. 3.705±0.176,P< 0.01). It peaked on day 1 (5.956±0.281 vs. 3.705±0.176,P< 0.01), then it declined and reached normal level 3 days after poisoning (4.134±0.168 vs. 3.705±0.176,P> 0.05).Conclusion HO-1 expression was increased significantly in lung tissue of mice with acute paraquat poisoning, which may be considered as an important protection mechanism against paraquat poisoning.

Objective Artificial atrial septum defect combining pulmonary artery banding to create a model of congenital heart defect with decreased pulmonary blood flow to explore the morphological changes of immature pulmonary vascular. Methods Choose twenty piglets with about one to two-month-old, which are exclusively for experiment used. The piglets were randomly divided into three groups: normal control group (group C, n = 6), Small incisions on the right chest, produced a transient reduction in pulmonary blood; low-medium pulmonary artery stenosis groups ( group T1, n = 7 ) : Did artificial room septostomy creation by self-dilators which were delivered into the surface of the right atrium and controlled Systolic trans pulmonary artery banding pressure (Trans-PABP) at pressure of 20 - 30 mmHg; severe pulmonary artery stenosis groups ( group T2, n = 7): T2 were the same surgical procedures with group T1 ,and controlled Trans-PABP ≥ 30 -50 mmHg. Monitored ultrasound after operation , carried out 64-slice computed tomography scanning after one month, to measure the proximal vessel diameter and TransPABP , after two month surgical exploration on the left chest. When the animals were sacrificed, the heart and lung tissue was cut to measure atrial septal defect, pulmonary artery and the banding diameter. By weihgt elastic fiber and van Cieson staining to observe the morphological pathological changes, three groups took lung tissue with right middle lobe lateral segment about 1.0 cm × 0.8 cm × 0.8cm at the end of surgery and 2-months after operation respectively. Results The models were all successfully in the survival animal of the two test groups. One pig died from tracheal intubation accident in the C group, there was one case died due to bowel obstruction in the T1 group, And there were two cases died result from acute right heart failure and chronic heart failure respectively in T2 group. 64-slice CT angiography showed that BD was significantly lower than the AOD in the two test groups, the proximal pulmonary vascular expansion result from stenosis, distal pulmonary vascular scarce. Histopathology showed that the pulmonary artery inside diameter of T1 and T2 was significantly higher than group C(P ＜0. 05,P ＜ 0.01), and the NAPSC of two experimental groups were significantly lower than group C 2-month after operation( P ＜0.01).Conclusion This type of Piglet model is closer to clinical pathological and physiological ,64-slice spiral CT combined with lung histopathology observed for the evaluation of pulmonary vascular hypoplasia is a reliable method. Tunica media of pulmonary arterioles hypoplasia with the number reducing, with pulmonary artery banding increased,the degree of pulmonary arterioles hypoplasia gradually increased.

A.niger M1, the initial strain, was treated by UV and a mutant with 30% higher xylanase activity was obtained. Zymogram for detecting xylanase showed there are three different xylanases in the mutant mature culture, while two xylanases in initial strain. After orthogonal experiment, the optimum fermentation conditions of the mutant were obtained as follows: concentration of the major carbon resource 4 %, ratio between bran and corncob 5:5, concentration of glucose 0.1%, concentration of ammonium oxalate as supplemental nitrogen resource 2.0%, the initial pH of liquid medium 5.0, 100mL/250mL flask.

Objective To investigate the effect of proteasome inhibitor MG132 on the proliferation of human lens epithelial cells SRA01/04. Methods The SRA01/04 cells were treated with MG132 by different concentrations (0, 0. 1, 0. 5, 1. 0, 2. 5, 5.0, 10. 0μmol/L) for 36 hours. The cell viability in all groups was determined using methylthiazoltetrazolium (MTT) test. The effect of MG132 on the apoptosis and regulation of cell cycle about SRA01/04 cells were detected by flow cytometry (FCM). The SRA01/04 cells treated with MG132 were observed after Annexin V/FITC-PI staining by fluorescence microscope. Results The inhibitory effect of MG132 on SRA01/04 cells proliferation was enhanced with the increase of MG132 concentration. The 50% inhibiting concentration ( IC50 ) of MG132 was 2. 50μmol/L after SRA01/04 cells were treated with MG132 for 36 hours. The apoptosis index of the cells treated by MG132 at 2. 5μmol/L and 5 μmol/L for 36 hours was 6. 55 ± 0. 35% and 13.75 ± 3.18%, and 0. 75 ± 0. 21% for 5.0μmol/L for 36 hours in control group. After cells were treated with MG132 for 48h, the percentages of cells at G0/G1 phase were (42. 57 ± 0. 64) %, (73.42 ± 3.10) %, ( 80. 95 ± 3.83 ) % 0, 2. 5,5.0 μmol/Lgroups respectively, and those at S phase were (49. 44±1.36)%, ( 17. 40 ± 1.50)%, ( 19. 57 ± 1.29)%.Annexin V/FITC-PI staining was used, and MG132 was found to result to apoptosis. Conclusions MG132 could inhibit the proliferation of SRA01/04 cells by the effect of inducing apoptosis and regulation of cell cycle. The proteasome inhibitor-might play a key role in the prevention of posterior capsular opacification.

Objective To understand the correlations between HIV-1 subtypes and changes in CD4+T cell count over time in patients with different subtypes of HIV-1 infection.Methods A total of 94 patients who were diagnosed with HIV-1 infection in Nanjing and received at least twice CD4+T cell counting test before antiretroviral therapy (ART) were recruited in this study.Descriptive analysis was used to present the rates of CD4+T cell decline for different HIV-1 subtypes.Logistic regression analysis and nonparametric test were conducted to investigate the factors responsible for CD4+T cell decline and to analyze the correlations between the rates of CD4+T cell decline and HIV-1 subtypes.Results The median monthly rate of CD4+T cell decline was-2.20 [interquartile range (IQR):-11.36-2.13] cell/μl.Of all patients,25.5% (24/94) had a significant decline (≥30%) in CD4+T cell count.Compared with the patients infected with CRF01_AE,those infected with CRF07_BC (OR=0.28,95%CI: 1.7-6.5) or other subtypes (OR=0.16,95%CI: 1.0-2.9) had a lower risk of significant decline in CD4+T cell count.In addition,results of the nonparametric test showed that the patients infected with CRF01_AE (M=-21.54,IQR:-30.97——11.92 cell/μl) had a faster CD4+T cell loss than those infected with CRF07_BC (M=-11.26,IQR:-14.06——5.63 cell/μl) (P=0.033).Conclusion HIV-1 subtype is associated with the rate of CD4+T cell decline.It is important to monitor the changes in CD4+T cell count in patients infected with CRF01_AE and to carry out timely ART.

OBJECTIVETo examine the effect of ONO-AE3-208, an EP4 antagonist, on the formation of bone metastasis from prostate cancer in mice.

METHODSThirty-four 6-week old nude mice were divided into an experimental and a control group of equal number to be treated by intraperitoneal injection of ONO-AE3-208 and double distilled water, respectively. Then PC3/LUC cells were constructed by stably transfecting luciferin to prostate cancer PC3 cells and inoculated into the left ventricle of the mice to establish an animal model of systemic bone metastasis. The time of metastasis formation, photon tumor burdens, and changes of the survival curves after modeling were compared between the two groups of mice.

RESULTSAt 30 days after modeling, bioluminescence imaging analysis showed that the photon tumor burdens were significantly increased in a time-dependent manner in the control group in comparison with those in the experimental group (P < 0.01). The rate of metastasis formation was significantly higher in the former than in the latter (93.3% vs 33.3%, P < 0.001). The median time of metastasis formation was 29 d (95% CI 26.547 - 35.262) in the experimental animals as compared with 21 d (95% CI 17.213 -24.787) in the controls (P < 0.001).

CONCLUSIONEP4 antagonist ONO-AE3-208 can inhibit the formation of bone metastasis from prostate cancer in mice.

Animals ; Bone Neoplasms ; prevention & control ; secondary ; Cell Line, Tumor ; Disease Models, Animal ; Humans ; Male ; Mice ; Mice, Nude ; Naphthalenes ; pharmacology ; Neoplasms, Experimental ; prevention & control ; Phenylbutyrates ; pharmacology ; Prostatic Neoplasms ; pathology

OBJECTIVETo compare robot-assisted laparoscopic radical prostatectomy (RALRP) with laparoscopic radical prostatectomy (LRP) in the treatment of prostate cancer and investigate the clinical application value of RLRP.

METHODSWe retrospectively analyzed 70 cases of prostate cancer treated by RALRP and another 32 cases treated by LRP. We compared the operation time, intraoperative blood loss and transfusion, catheter-indwelling time, postoperative hospital stay, incisal margin positive rate, biochemical recurrence, and normal postoperative urinary continence and penile erectile function between the two groups of patients.

RESULTSAll the operations were successfully accomplished. RALRP exhibited a significant superiority over LRP in intraoperative blood loss and transfusion, catheter-indwelling time, and postoperative hospital stay, urinary continence and erectile function (P < 0.05).

CONCLUSIONRobot-assisted laparoscopic radical prostatectomy, with its advantages of few postoperative complications and well-preserved urinary continence and penile erectile function, is an effective, safe and minimally invasive surgical option for prostate cancer.

Blood Loss, Surgical ; Humans ; Laparoscopy ; Length of Stay ; Male ; Operative Time ; Penile Erection ; Postoperative Complications ; Postoperative Period ; Prostatectomy ; methods ; Prostatic Neoplasms ; surgery ; Retrospective Studies ; Robotic Surgical Procedures ; methods

Objective To investigate the potential association of Ghrelin(GHRL)gene polymorphisms susceptible to schizophrenia by case-control study.Methods Six hundred and thirty-four patients,six hundred and six healthy control subjects were recruited.Four SNPs rs696217,rs26802,rs27647 and rs26311 were detected by the polymerase chain reaction-based-restriction fragment length polymorphism analysis.Results No significant differences in genotype or allele frequencies of the four SNPs were observed between schizophrenic patients and healthy controls (Pvalues of genotype frequencies were 0.649,0.944,0.410,0.826;P values of allele frequencies were 0.773,0.992,0.301,0.723).However,seven haplotypes(GAAG,GAGC,GAGG,GCGC,GCGG,TAGC,TAGG)showed significant differences in frequency between schizophrenic and control groups(P values were 0.011,0.001,1.76×10-6,9.84×10-10,1.38×10-9,2.12×10-5,2.57×10-6).Conclusion These data suggest that the GHRL gene may not be associated with susceptibility to schizophrenia in the Chinese Han population.However,the haplotype of GA may be the susceptive factor of schizophrenia.

BACKGROUNDbeta-amyloid peptide (Abeta) is considered responsible for the pathogenesis of Alzheimer's disease (AD). Possible mechanisms underlying Abeta-induced neuronal cytotoxicity include excessive production of reactive oxidative species (ROS) and apoptosis. Cyclophilin A (CypA), exhibits antioxidant properties and protects neurons against oxidative stress induced injury. This study was conducted to demonstrate whether CyPA added to cultured PC12 cells could alleviate Abeta-induced oxidative stress and protect them from apoptosis.

METHODSPC12 cells were pre-incubated for 30 minutes with recombinant human cyclophilin A (rhCyPA) in 0.1 nmol/L, 1.0 nmol/L, 10 nmol/L and 100 nmol/L and then incubated with 10 micromol/L Abeta(25-35). In every group, cell viability, apoptotic morphology, apoptotic rate, intracellular ROS accumulation, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of PC12 cells and mitochondrial transmembrane potential were detected. Subsequently, the expression of the active form of caspase-3 was determined by Western blotting.

RESULTSIt was shown that cultures treated with 1.0 nmol/L, 10 nmol/L or 100 nmol/L rhCyPA + Abeta(25-35) had significantly higher cell viability and a lower rate of apoptosis compared with the cultures exposed only to Abeta(25-35). In addition, rhCyPA attenuated Abeta(25-35)-induced overproduction of intracellular ROS and Abeta(25-35)-induced a decrease in activity of the key antioxidant enzymes SOD and GSH-Px. Furthermore, rhCyPA also attenuated Abeta(25-35)-induced mitochondrial dysfunction and the activation of caspase-3.

CONCLUSIONCyPA may act as an ROS scavenger, and prevent Abeta(25-35)-induced neurotoxicity through attenuating oxidative stress induced by Abeta(25-35).

Amyloid beta-Peptides ; pharmacology ; Animals ; Caspase 3 ; metabolism ; Cyclophilin A ; pharmacology ; Glutathione Peroxidase ; metabolism ; Humans ; Oxidative Stress ; drug effects ; PC12 Cells ; Peptide Fragments ; pharmacology ; Rats ; Superoxide Dismutase ; metabolism

Objective To explore the effect of cyclophilin A (CyPA) on apoptosis of PC 12 cells induced by Aβ25-35 and its potential mechanism. Methods PC 12 cells were divided into normal control group (0 μmol/L Aβ25-35), Aβ25-35 inducement group (10 μmol/L Aβ25-35) and drug protection groups (0.1, 1,10 and 100 nmol/L CyPA+10 μmol/L Aβ25-35). Cells in the drug protection groups were pretreated by CyPA of different concentrations for 30 min, and then co-cultured with Aβ25-35 We evaluated the survival rate of PC12 cells with MTT assay, analyzed the apoptosis of PC12 cells with Hoechst33258 staining, and detected the mRNA expressions of Bcl-2 and Bax with PT-PCR and the protein levels of Bcl-2 and Bax with Western blotting. Results Cells pretreated wth CyPA of 1, 10 and 100 nmol/L enjoyed an obvious elevation of survival rate of PC 12 cells, a significant reduction of apoptosis induced by Aβ25-35,an obvious increase of mRNA expression of Bcl-2 and protein level of Bcl-2, and a statistical decrease of mRNA expression of Bax and protein level of Bax as compared with those cells of the Aβ25-35 inducement group (P<0.05);and these effects were dose-dependent. Conclusion CyPA could resist the toxic role of Aβ25-35 on PC 12 cells and reduce the apoptosis in a dose-dependent manner by up-regulation of anti-apoptosis gene Bcl-2 and down-regulation of apoptosis gene Bax.