Objective To explore the clinical significance of second transurethral resection (TUR) in patients with T1 urothelial cell carcinoma of the bladder.Methods The 142 cases with urothelial carcinoma were recruited.All patients underwent transurethral resection of bladder tumor (TURBT) and were diagnosed as stage T1 urothelial carcinoma of the bladder.The 68 of 142 cases underwent second TUR after the initial surgery.Tumor recurrence rate,progression rate and recurrence-free survival were compared.Results There were no statistical differences in age,gender,follow-up time,number of tumors,size of tumors or grade of tumors between patients with and without second TUR.Of the 68 cases that underwent second TUR,25 cases (36.8%) had residual tumor and 6 of them (8.8%) had muscle-invasive bladder cancer.After an average observation for 26.8 months,patients who underwent second TUR showed lower recurrence rate,higher recurrence-free rate and longer recurrence-free survival than patients without second TUR [37.1% vs.58.1%,x2=5.962,P=0.015;41% vs.35.1%,x2=8.502,P=0.004;21 months vs.12 months,U= 1584,P= 0.002].While the progression rate showed no statistical difference between them (14.5% vs.25.7%,x2 =2.570,P=0.109).Conclusions Second TUR provides an effective way to completely excise tumor.Second TUR is beneficial to the decrease of recurrence rate and improvement of recurrence-free survival.However,its effect on tumor progression needs further discussion.

In this study, we propose that diprophylline exerts bidirectional modulation (BM) on the isolated rat jejunal segment depending on its contractile state. The results supported the hypothesis. Diprophylline (20 microM) exerted stimulatory effects on the contractility of jejunal segment in six low contractile states while inhibitory effects in six high contractile states, showing the characteristics of BM. Diprophylline-induced stimulatory effect was significantly blocked by atropine, indicating the correlation with cholinergic activation. Diprophylline-induced inhibitory effect was partially blocked by phentolamine, propranolol, and L-N-Nitro-Arginine respectively, indicating their correlation with sympathetic activation and nitric oxide-mediated relaxing mechanisms. Diprophylline-induced BM was abolished by tetrodotoxin or in a Ca2+ free condition or pretreated with tyrosine kinase inhibitor imatinib, suggesting that diprophylline-induced BM is Ca2+ dependent, and that it requires the presence of enteric nervous system as well as pacemaker activity of interstitial cells of Cajal. Diprophylline significantly increased the reduced MLCK expression and myosin extent in constipation-prominent rats and significantly decreased the increased MLCK expression and myosin extent in diarrhea-prominent rats, suggesting that the change of MLCK expression may also be involved in diprophylline-induced BM on rat jejunal contractility. In summary, diprophylline-exerted BM depends on the contractile states of the jejunal segments, requires the presence of Ca2+, enteric nervous system, pacemaker activity of interstitial cells of Cajal, and MLCK-correlated myosin phosphorylation. The results suggest the potential implication of diprophylline in relieving alternative hypo/hyper intestinal motility.
Animals ; Atropine ; Dyphylline ; Enteric Nervous System ; Gastrointestinal Motility ; Interstitial Cells of Cajal ; Myosins ; Phentolamine ; Phosphorylation ; Propranolol ; Protein-Tyrosine Kinases ; Rats* ; Tetrodotoxin ; Imatinib Mesylate

MicroRNAs (miRNAs) are important diagnostic markers and therapeutic targets for many diseases. However, the miRNAs that control the pathogenesis of idiopathic pulmonary fibrosis (IPF) and act as potential therapeutic targets for the disease are rarely studied. In the present study, we analyzed the function and regulatory mechanism of microRNA-708-3p (miR-708-3p) and evaluated this marker’s potential as a therapeutic target in IPF. The clinical and biological relevance of fibrogenesis for miR-708-3p was assessed in vivo and in vitro, specifically in matching plasma and tissue samples from 78 patients with IPF. The data showed that the miR-708-3p levels decreased during fibrosis and inversely correlated with IPF. The experiments showed that the decreased miR-708 promoter activity and primer-miR-708(pri-miR-708) expression were the potential causes. By computational analysis, a dual luciferase reporter system, rescue experiments and a Cignal Finder 45-Pathway system with siADAM17 and a miR-708-3p mimic, we identified that miR-708-3p directly regulates its target gene, a disintegrin and metalloproteinase 17 (ADAM17), through a binding site in the 3′ untranslated region, which depends on the GATA/STAT3 signaling pathway. Finally, an miR-708-3p agomir was designed and used to test the therapeutic effects of the miR-708-3p in an animal model. Small-animal imaging technology and other experiments showed that the dynamic image distribution of the miR-708-3p agomir was mainly concentrated in the lungs and could block fibrogenesis. In conclusion, the miR-708-3p–ADAM17 axis aggravates IPF, and miR-708-3p can serve as a potential therapeutic target for IPF.

OBJECTIVETo investigate the properties of screw-bone interface of expansive pedicle screw (EPS) in osteoporotic sheep by micro-CT and histological observation.

METHODSSix female sheep with bilateral ovariectomy-induced osteoporosis were employed in this experiment. After EPS insertion in each femoral condyle, the sheep were randomly divided into two groups: 3 sheep were bred for 3 months (Group A), while the other 3 were bred for 6 months (Group B). After the animals being killed, the femoral condyles with EPS were obtained, which were three-dimensionally-imaged and reconstructed by micro-CT. Histological evaluation was made thereafter.

RESULTSThe trabecular microstructure was denser at the screw-bone interface than in the distant parts in expansive section, especially within the spiral marking. In the non-expansive section, however, there was no significant difference between the interface and the distant parts. The regions of interest (ROI) adjacent to EPS were reconstructed and analyzed by micro-CT with the same thresholds. The three-dimensional (3-D) parameters, including tissue mineral density (TMD), bone volume fraction (BVF, BV/TV), bone surface/bone volume (BS/BV) ratio, trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp), were significantly better in expansive sections than non-expansive sections (P less than 0.05). Histologically, newly-formed bony trabeculae crawled along the expansive fissures and into the center of EPS. The newly-formed bones, as well as the bones at the bone-screw interface, closely contacted with the EPS and constructed four compartments.

CONCLUSIONSThe findings of the current study, based on micro-CT and histological evaluation, suggest that EPS can significantly provide stabilization in osteoporotic cancellous bones.

Animals ; Bone Screws ; Bone and Bones ; diagnostic imaging ; pathology ; Female ; Osteoporosis ; diagnostic imaging ; pathology ; Sheep ; Tomography, X-Ray Computed

OBJECTIVETo investigate the effect of short hairpin RNA (shRNA) targeting hypoxia-inducible factor-1 alpha (HIF-1 alpha) on the human breast carcinoma MCF-7 cell line.

METHODSThe hypoxia environment was achieved by treating cells with cobalt chloride. The shRNA eukaryotic expression vector targeting HIF-1 alpha was constructed, and transfected into MCF-7 cells through lipofectamine 2000. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to study the expression of vascular endothelial growth factor (VEGF). The mRNA and protein level of HIF-1 alpha were detected by real-time PCR and Western blot. Sub-G1 apoptotic population analysis, Annexin V/PI binding assay, and DNA ladder analysis were applied to investigate the cell apoptosis. The cell cycle was detected by flow cytometry.

RESULTSThe mRNA and protein level of HIF-1 alpha increased after exposure of MCF-7 cells to hypoxia (P < 0.01). However, apoptosis was lower in hypoxia compared with normoxia (P < 0.05). The HIF-1 level of MCF-7 transfected with HIF-1 alpha shRNA decreased approximately 91.63% (P < 0.01). When the cells were treated with or without apoptosis inducer Ara-C, the apoptosis of MCF-7 cells transfected with HIF-1 alpha shRNA increased by 1.75 times (P < 0.01) and 61. 31 times (P < 0.01), respectively. The expression of VEGF in MCF-7 cells transfected with HIF-1 alpha shRNA decreased 66.8% compared with untransfected cells (P < 0.05). Cell cycle progression was inhibited when the MCF-7 cells were transfected with HIF-1 alpha shRNA.

CONCLUSIONSHIF-1 alpha plays an anti-apoptotic role in human breast carcinoma MCF-7 cell line. The shRNA we designed targeting HIF-1 alpha in MCF-7 can promote cell apoptosis, inhibit the expression of VEGF, and delay cell cycle progression.

Apoptosis ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Cell Cycle ; Cell Line, Tumor ; Down-Regulation ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; RNA Interference ; RNA, Messenger ; genetics ; RNA, Small Interfering ; genetics ; Transfection ; Vascular Endothelial Growth Factor A ; metabolism

Objective To study the outcomes of AIDS intervention programs and to provide scientific evidence for developing pertinent strategy on intervention among men who have sex with men (MSM).Methods MSM were recruited through snowballing and investigated by face to face interview in 2006 and 2007 respectively.SPSS 12.0 was used to compare the change of cognition about AIDS,sexual behavior,prevalence rates of HIV and Syphilis before and after the intervention program among the population under study.Results The cognition about AIDS among MSM was obviously improved after the intervention with the rate increased from 74.3% to 82.4% (P=0.01).The rate of last time condom use among MSM increased from 56.4% to 65.5% (P=0.00).The rate of consistent condom use during six months among MSM increased from 31.8% to 41.9% (P=0.00).The rates of both condom use during commercial sex with men and with women did not change much among MSM.The prevalence rates of HIV in 2006 and 2007 were 10.4% and 10.8% and of syphilis in 2006 and 2007 were 9.3% and 7.3% respectively which were not significantly different between before and after the intervention.Conclusion The cognition about AIDS among MSM was improved obviously.However,the rate of consistent condom use was still low,reflecting the segregation phenomenon between their behavior and cognition.All our findings implied that it was crucial to carry out AIDS prevention and control programs.

OBJECTIVETo observe the effect of Dendrobium officinale granule (DOG) on symptoms, blood pressure and serum biochemical indexes of long-term-alcohol-induced hypertension rats.

METHODThe alcohol-induced hypertension rat model was established by feeding alcohol drink to normal rats (the alcohol volume fraction increases from 5% to 22%). Since the 4th week, DOG was administered for 32 weeks, once everyday. During the experiment, body weight, kinematic parameters (locomotor activities, grip strength, duration of vertigo) and blood pressures (systolic blood pressure, diastolic blood pressure and mean blood pressure) were detected regularly. On the 28th and 32nd weeks, blood samples were collected to determine serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), uric acid (UA), creatinine (Cr), cholesterol (CH) and triglycerides (TG).

RESULT(1) Sign: The DOG-administered group showed reduction in the duration of vertigo and increase in appetite, body weight, locomotor activities and grip strength. (2) Blood pressure: The DOG-administered group showed significant decrease in blood pressure since the 8th week. (3) Biochemical indexes: The DOG-administered group showed notable decrease in serum ALT, AST, ALP, Cr, UA, TG level, but without significant change in TC level.

CONCLUSIONThe long-term administration of DOG can relieve alcohol-induced hypertension, while alleviating general signs, liver and kidney injuries and abnormal blood fat biochemical indexes.

Animals ; Blood Pressure ; drug effects ; Body Weight ; drug effects ; Cholesterol ; metabolism ; Dendrobium ; chemistry ; Drugs, Chinese Herbal ; administration & dosage ; Ethanol ; adverse effects ; Humans ; Hypertension ; drug therapy ; etiology ; metabolism ; physiopathology ; Lipid Metabolism ; drug effects ; Male ; Motor Activity ; drug effects ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; metabolism

Toxicologic pathology plays an important role in the safety evaluation of drugs.The results of toxicologic pathology can answer the basic problems of pathological lesions such as location,severity grading,nature and prognosis,etc.Necropsy and gross pathology examination are important aspects of toxicologic pathology assessment.Procedures typically include preparation for the necropsy,euthanasia procedures,identification and recording all gross lesions,collection of tissues listed in the study protocol,determination of organ weight,as well as tissue fixation so as to be ready for the subsequent tissue processing and histopathology examination.All the procedures must be done in a consistent manner and in accordance with standard operating procedures (SOPs).The present paper briefly introduced the principles of necropsy and gross pathology examination for toxicologic pathology in order to standardize the procedures and to lay foundation for the improvement of the histopathology examination in the field of preclinical safety evaluation of drugs of China.

Examination and assessment of target organ toxicity in toxicologic pathology of preclinical safety evaluation of drugs should combine the results of the gross pathology,histopathology and clinical pathology examination data in a well-considered,stepwise approach.In addition,the nomenclature and diagnostic criteria recommended by INHAND should be used to avoid subjective and inappropriate diagnosis.In this paper,we briefly introduced the basic principles for the examination of organ toxicity in toxicology studies,gross pathology,histopathology,diagnostic approach,procedures,and considerations,international harmonization of diagnostic term and criteria,clinical pathology parameters analysis,results of a well-concerted combination of anatomical and clinical pathology data so as to provide some reference for the examination and assessment of target organ toxicity in toxicologic pathology in the field ofpreclinical safety evaluation of drugs in China.

OBJECTIVETo investigate the effect of premature rupture of the membrane (PROM) on neonatal complications in premature infants.

METHODSThe registration information of 7684 preterm infants with gestational age <37 weeks were collected from the cooperative units in the task group between January 1, 2014 to December 31, 2014. Specially trained personnel from each cooperative units filled in the unified form in a standardized format to record the gender, gestational age, birth weight, PROM, placental abruption, antenatal corticosteroid, Apgar score, amniotic fluid pollution, and complications of the infants. The data were analyzed comparatively between the cases with PROM and those without (control).

RESULTSThe preterm mortality rate was significantly lower but the incidences of ICH, NEC, ROP and BPD were significantly higher in PROM group than in the control group (P<0.05). The 95% confidence interval of the OR value was <1 for mortality, and was >1 for ICH, NEC, ROP and BPD. After adjustment for gestational age, birth weight, gender, mode of delivery, placental abruption, placenta previa, prenatal hormones, gestational diabetes mellitus (GDM), gestational period hypertension and 5-min Apgar score <7, the incidences of NEC, ROP and BPD were significantly different between the two groups (P<0.05) with 95% confidence interval of OR value >1, but the mortality rate and incidence of ICH were not significantly different between the two groups (P>0.05).

CONCLUSIONPROM is a risk factor for NEC, ROP and BPD in preterm infants, and adequate intervention of PROM can reduce the incidences of such complications as NEC, ROP and BPD in the infants.

Apgar Score ; Birth Weight ; Female ; Fetal Membranes, Premature Rupture ; pathology ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Infant, Newborn, Diseases ; etiology ; Infant, Premature ; Pregnancy ; Risk Factors