Objective To investigate the methylation status of the CpG island of tumor suppressor gene PCDH 8 and its clinical significance in bladder cancer tissues .Methods 79 cases of primary bladder transitional cell carcinoma and 20 cases of normal blad-der mucosa tissue were collected ,and then the promoter methylation status of PCDH8 gene was examined by methylation specific PCR (MSP) ,and correlated with clinical pathological data for statistical analysis .Results We found that no PCDH8 gene methyla-tion was detected in 20 normal bladder mucous tissues ,while PCDH8 promoter methylation was found in 44 cases of total 79 prima-ry bladder transitional cell carcinoma tissues ,the methylation rate was 55 .7% ,and the difference was statistical significant between normal bladder mucous group and bladder cancer group (P<0 .01) .The promoter methylation of PCDH8 gene in bladder transi-tional cell carcinoma tissues did not correlate with patient′s age ,gender ,tumor number (P>0 .05) ,the methylation rate of PCDH8 gene in tumors whose diameter more than 3 cm was 72 .7% ,while the methylation rate of PCDH8 gene in tumors whose diameter less than 3 cm was 43 .5% ,and the difference was significant(P< 0 .05) .The methylation rate of PCDH8 gene in the papillary tumor was 48 .2% ,while the methylation rate of PCDH8 gene in the unpapillary tumor was 73 .9% ,and the difference was signifi-cant(P<0 .05) .The methylation rate of PCDH8 gene in recurrent tumors was 71 .1% ,while the methylation rate of PCDH8 gene in primary tumors was 35 .3% ,and the difference was significant(P<0 .05) .The methylation rate of PCDH8 gene in tumors with G1 ,G2 phase was 43 .4% ,while the methylation rate of PCDH8 gene in tumors with G3 was 80 .8% ,and the difference was signifi-cant(P<0 .05) .The methylation rate of PCDH8 gene in the tumors with Ta T1 phase was 43 .7% ,while the methylation rate of PCDH8 gene in tumors with T2 T4 was 74 .2% ,and the difference was significant(P<0 .05) .Our result suggested that PCDH8 gene methylation was associated with tumor growth ,morphology ,recurrence ,poor differentiation and tumor invasion (P<0 .05) . Conclusion The promoter methylation of tumor suppressor gene PCDH8 is closely correlated with the occurrence and development of primary bladder transitional cell carcinoma .The promoter methylation of PCDH8 gene could be used as molecular markers of ear-ly diagnosis ,monitoring and prognosis biomarker in bladder cancer .

OBJECTIVE: To explore the effects of Salvia miltiorrhiza on renal morphology and renal function of rats with streptozotocin diabetes. METHODS: Thirty male Wistar rats were randomly divided into three groups, which were normal control group, untreated group and Salvia miltiorrhiza-treated group. Diabetic nephropathy was induced in rats of the last two groups by intraperitoneal injection of streptozotocin after unilateral nephrectomy. Then the rats in the normal control and untreated groups were fed with normal saline while those in the Salvia miltiorrhiza-treated group were fed Salvia miltiorrhiza preparation for 8 weeks. The glomerular volume (VG), kidney-to-body weight ratio (KW/BW), urinary albumin excretion rate (UAER) and creatinine clearance (Ccr) were observed. The expression levels of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), fibronectin (FN) and plasminogen activator inhibitor-1 (PAI-1) were detected by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) at the end of the experiment. RESULTS: UAER, Ccr, VG and KW/BW ratio were significantly higher in the untreated group than those in the normal control group (P<0.05). The expression levels of TGF-beta1, CTGF, PAI-1 and FN in the untreated group were also significantly higher as compared with those in the normal control group (P<0.05). UAER, Ccr, VG, KW/BW ratio and the levels of TGF-beta1, CTGF, PAI-1 and FN in the Salvia miltiorrhiza-treated group were obviously lower than those in the untreated group (P<0.05). CONCLUSION: Salvia miltiorrhiza can protect rats with streptozotocin diabetes from diabetic nephropathy by suppressing the over-expressions of TGF-beta1, CTGF, PAI-1 and FN in renal cortex.

Objective To explore the effects of human umbilical cord mesenchymal stem cells (HUC?MSCs) on podocytic apoptosis and injury induced by high glucose (HG) and the underlying mechanisms. Methods Podocytes were divided into six groups according to treatment: ⑴ normal glucose group (NG);⑵high glucose group (HG);⑶mannitol control group (NG+Ma);⑷HUC?MSC co?culture group (HUC?MSCs); ⑸ recombinant human hepatocyte growth factor treatment group (rhHGF);⑹ neutralizing antibody group(HGF?NtAb). Cytometry and Hoechst staining were used to detect the apoptosis rates. Western blot was used to measure the ratio of active PARP to total PARP and the level of Bcl?2. Immunofluorescence was used to study podocytic apoptosis and injury. Neutralizing antibody (NtAb) was used to block its function and the recombinant cytokine was added to induce its function. Results High glucose induced podocytic apoptosis in a time?dependent manner, HUC?MSCs co?culture decreased the podocytic apoptosis rate and the expression of PARP (all P﹤0.05), increased the expression of Bcl?2, prevented the reduced expression and maintained the normal arrangement of podocytic podoplanin. The rhHGF prevented podocytic apoptosis and injury similarly to HUC?MSCs, the beneficial effect of HUC?MSC decreased when blockade of HGF. Conclusions HUC?MSCs co?culture ameliorates podocytic apoptosis and injure induced by HG, probably through secreting soluble HGF.

Objective To discuss microvessel density (MVD) and expression of vascular endothelial growth factor(VEGF), androgen receptor(AR) in the prostates of men who received re-operation after TURP. Methods Fifty cases were performed re-TURP (re-TURP group) and the remaining 50 cases served as controls. 150 specimens were collected. Sections were stained for CD34 and VEGF, AR by immuno-histo-chemistry(S-P). Statistical analysis of the results was performed using t-test or Pearson Chi-Square test Results The expression of VEGF, AR and MVD were significantly higher in the re-TURP group compared to controls(P<0. 05),but in re-TURP group, difference in VEGF and AR expression as well as MVD were not found to be significantly different between the first and the second TURP(P>0.05). Conclusion Over expression of VEGF and AR as well as high MVD in prostatic tissue might play an important role in the pathological process of BPH after TURP.

OBJECTIVETo observe the inhibitory effect of Tongxinluo (TXL) on coronary vaso spasm in small swine in vivo, and to investigate its possible acting mechanism.

METHODSThe model of coronary atherosclerosis in 16 male small swines was established by left thoracotomy after anesthesia, isolated the sections of left anterio-descending branch and proximal end of rotator branch with similar outer diameter, and encapsulated them with paper-towel holding 2.5 microg interleukin-1beta. Two weeks later, the condition of coronary vasospasm induced by catheter intra-coronary injection of 5-hydroxytryptamine (5-HT, 10 microg/kg) was observed through coronary artery contrast examination. The 12 swines with successfully formed coronary vaso spasm were randomly divided into 2 groups, the TXL group and the control group. They were fed with special diet, but TXL 1 g/(kg d) was administered additionally to the TXL group for 4 weeks. The observation on coronary vasospasm was repeated 1 week after discontinuation of TXL treatment, then the animals were sacrificed, their vascular sections enclosed with IL-1beta was taken to conduct the pathologic examination and to detect the expressions of Rho kinase mRNA and its substrate myosin- binding subunit phosphorylation (MBS-P) by RT-PCR and Western blot method.

RESULTSCoronary artery contrast showed that local coronary stenosis occurred in the 12 model swines to different extents (20% - 30%, and vascular spasm on them could be induced by 5-HT. At the time of repeating examination, 11 vascular sections in the control group still maintain their positive spasm reaction to 5-HT, but only 2 in the TXL group did so, the reaction turned to negative in 1 and 10 in the two groups respectively. Pathological examination showed that different degrees of macrophage aggregation could be found in both groups. The degree of lumen stricture and endometrial hyperplasia in the TXL group was obviously attenuated than those in the control group. The expressions of Rho kinase mRNA and MBS-P in the control group were up-regulated obviously. As compared with those in the control group, they were inhibited significantly in the TXL group, as (71.5 +/- 2.4) vs (98.2 +/- 7.7)% and 16,633 +/- 1,390 vs 25,818 +/- 4,745, respectively (all P < 0.05).

CONCLUSIONTXL could obviously inhibit the coronary intimal hyperplasia mediated by IL-1beta and coronary vasospasm induced by 5-HT, one of its mechanisms is possibly the inhibition on the intracellular Rho kinase mRNA expression in the IL-1beta enclosed vascular section to decrease the level of MBS-P.

Animals ; Coronary Vasospasm ; chemically induced ; drug therapy ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Gene Expression ; drug effects ; Humans ; Interleukin-1beta ; genetics ; metabolism ; Male ; Random Allocation ; Serotonin ; adverse effects ; Swine ; rho-Associated Kinases ; genetics ; metabolism

OBJECTIVEVasoconstriction and vascular hypersensitivity to serotonin were previously shown in animal models of adventitia injury. We investigated the contribution of angiotensin II (AngII)/AngII receptors and oxidative stress to vascular contractility and reactivity in this model.

METHODSWistar Kyoto rats were divided into 3 groups: normal (n = 6, no any intervention, only for measuring the serum AngII concentration), vehicle (n = 12, collared), and valsartan (n = 12, collared + valsartan 30 mg×kg(-1)×d(-1)). After one week of treatment, adventitia injury was induced by positioning a silicone collar around the right carotid artery for one week. Blood flow and vascular reactivity to serotonin were determined one week after injury, the blood from left ventricle was taken to measure the serum AngII concentration by ELISA, and carotids were harvested for morphometry and Western blot analysis.

RESULTSAdventitia injury induced lumen cross-sectional area reduction (-44% vs. -5%), media diameter increase (62% vs. 10%), blood flow reduction [(2.79 ± 0.22) vs. (4.33 ± 0.84) ml/min] were significantly attenuated by valsartan. The increased vascular reactivity sensitivity to serotonin in vehicle group was also significantly reduced in valsartan group. Serum AngII concentration was significantly increased in vehicle group [(45.21 ± 4.52) pg/ml vs. (19.83 ± 0.5) pg/ml in normal rats, P = 0.0148] and the expression of AngII type 1 (AT(1)) receptor, AngII type 2 (AT(2)) receptor, as well as p22(phox) in collared arteries were significantly upregulated. Valsartan did not affect the AT(1) receptor expression but further increased serum AngII concentration [(89.73 ± 20.44) pg/ml vs. (45.21 ± 4.52) pg/ml, P = 0.001], and AT(2) receptor expression, while downregulated p22(phox) expressions.

CONCLUSIONSCollar-induced adventitia injury resulted in chronic vasoconstriction and vascular hypersensitivity to serotonin via increased serum AngII level, upregulated AngII receptors expression in the vascular well, and activated local oxidative stress. These changes could be blocked by valsartan suggesting a crucial role of AngII/AngII receptors on vascular contractility and reactivity changes in this model.

Angiotensin II ; metabolism ; Animals ; Carotid Arteries ; drug effects ; metabolism ; pathology ; Connective Tissue ; pathology ; Male ; Oxidative Stress ; Rats ; Rats, Inbred WKY ; Receptors, Angiotensin ; metabolism ; Tetrazoles ; pharmacology ; Valine ; analogs & derivatives ; pharmacology ; Valsartan ; Vasoconstriction ; drug effects

Parkinson disease(PD)is characterized by the loss of dopaminergic neurons in the substantia nigra and deposition of cytosolic inclusions in surviving neurons (Lewy bodies), resulting in motor deficits and non-motor symptoms.Although Levodopa remains the gold standard treatment for PD,side effects like dyskinesia followed by long-term use could notbe ignored.Consequently,there is a need for devel-opment new drugs. Baicalein is a flavonoid isolated from traditional Chinese herb, Scutellaria baicalensis Georgi.Our laboratory discovered that baicalein could effectively attenuate neurotoxicity of 6-hydroxy-dopamine(6-OHDA)and promote the differentiation of PC12 cells through high throughput drug screen-ing at the cellularlevel. In vivo studies have shown that baicalein exerts significant therapeutic effect, particularly in the attenuation of muscle tremor in 6-OHDA-lesioned rats.Based on the result from the so far acquired knowledge and previous findings from our laboratory, we could consider neuroprotec-tive mechanism of baicalein focus on the activities ofanti-oxidation and anti-inflammation. Baicalein could prevent oxidative stress and apoptosis through maintaining the mitochondrial function, inhibition of collapse of mitochondrial membrane potential, increase the activity of antioxidant enzymes and restraint of lipid peroxidation via several pathways such as Keap1/Nrf2/HO-1.Anti-inflammatory activity of baicalein exert by attenuating activation of astrocyte and microglia, as well as the production of cathepsin B and cytokines. Additionally, promoting the degradation of α-synuclein contributes to the neuroprotective effect of baicalein against Lewy bodies toxicity.Furthermore,baicalein also modulates the metabolic balance between glutamate(GLu)and gamma-aminobutyric acid(GABA).Overall,baica-lein could protect nervous systemby inhibiting oxidative damage and neuroinflammation caused by environmental and genetic factors.This article reviewed the developments of studies on pharmacody-namics and mechanism of baicalein in PD therapy and provideda reference for further exploration.

OBJECTIVETo investigate the pathohistological characteristics of the prostate tissues in patients who receive a second TURP and to evaluate their clinical significance.

METHODSWe collected surgical specimens from 50 cases of TURP (the control group) and another 50 cases of re-TURP (the re-TURP group), detected the expressions of CD34, vascular endothelial growth factor (VEGF) and androgen receptor (AR) in the prostate tissues by immunohistochemistry (S-P), and determined microvessel density (MVD) and the expressions of VEGF and AR. We performed statistical analyses on the results obtained from the specimens of the control group as well as from those of the first and second operations of the re-TURP group.

RESULTSVEGF and AR expressed in all the specimens. The expressions of VEGF and AR and MVD were significantly higher in the re-TURP group than in the controls (P < 0.05), but showed no significant differences between the first and second operations in the re-TURP group (P > 0.05). Positive correlations were found between the expressions of AR and VEGF, VEGF and MVD, and AR and MVD (r = 0.650, 0.705 and 0.525, P < 0.05).

CONCLUSIONIncreased AR, VEGF and MVD in the prostatic tissues may be one of the important causes of recurrence of BPH after TURP, and could be considered as the risk factors for postoperative recurrence and targeted indicators for preventive measures.

Humans ; Male ; Prostatic Hyperplasia ; metabolism ; pathology ; surgery ; Receptors, Androgen ; metabolism ; Reoperation ; Transurethral Resection of Prostate ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVEPhosphorylation of myosin light chain (MLC) is one of the most important steps for vascular smooth muscle contraction and Rho-kinase is involved in this process. We investigated the role of Rho-kinase in a porcine coronary artery spasm model with interleukin-1beta.

METHODSSegments of left coronary artery adventitia were surrounded by normal saline (n = 8) or IL-1beta agarose microne (n = 8) for 2 weeks. Vasospastic responses to intracoronary serotonin or histamine then studied at the saline or IL-1beta-treated site. The Rho-kinase mRNA expression in the treated site was measured by reverse transcription-polymerase chain reaction analysis (RT-PCR). The extent of phosphorylation of myosin-binding subunit of myosin phosphates (MBS, one of the major substrates of Rho-kinase) were quantified by Western blot analysis.

RESULTSIntracoronary serotonin or histamine repeatedly induced coronary artery spasm and coronary arterial stenosis was evidenced at IL-1beta-treated site. Expression of Rho-kinase mRNA in IL-1beta-treated site was significantly increased compared to saline treated site (98.20% +/- 7.66% vs. 63.70% +/- 4.26%, P < 0.05). Western blot analysis showed that during the serotonin-induced contractions the extent of phosphorylation of MBS was also significantly increased in the spastic site (25,485 +/- 4745 vs. 6510 +/- 779, P < 0.05).

CONCLUSIONRho-kinase upregulation at the spastic site and increased phosphorylation of myosin-binding subunit of myosin phosphates are key players in inducing vascular smooth muscle hypercontraction in this porcine model.

Animals ; Coronary Vasospasm ; metabolism ; pathology ; Disease Models, Animal ; Interleukin-1beta ; adverse effects ; metabolism ; Male ; Myosin Light Chains ; metabolism ; Phosphorylation ; RNA, Messenger ; metabolism ; Swine ; rho-Associated Kinases ; metabolism

OBJECTIVETo summarize lessons learned from an outbreak of severe acute respiratory syndrome (SARS) in China during the spring of 2004.

METHODSData of SARS cases were officially reported by Beijing Municipal Center for Disease Control and Prevention (BCDC) and Anhui Provincial Center for Disease Control and Prevention (APCDC) and results of epidemiological investigations were collected and analyzed.

RESULTSThree generations of 11 cases of SARS were identified during the outbreak. Initial two cases were most likely to be infected in Diarrhea Virus Laboratory of National Institute of Virology, China Centers for Disease Control and Prevention and main mode of transmission was direct contact with SARS patients. Delay in detecting initial case resulted in spread of the illness at hospitals and communities with two generations of secondary cases.

CONCLUSIONSSARS outbreak in 2004 has yielded following lessons for public health globally. (1) Lab bio-safety programs should be made and should be strictly abided by. Studies in highly pathogenic viruses such as SARS coronavirus should be utmost cautious. (2) Management systems of occupational exposure to virus and disease surveillance need to be strengthened to take all risk factors into account so as to detect potential patients with infectious disease as early as possible.

China ; epidemiology ; Disease Outbreaks ; Female ; Humans ; Male ; Occupational Exposure ; prevention & control ; Occupational Health ; Retrospective Studies ; Severe Acute Respiratory Syndrome ; epidemiology ; prevention & control ; transmission