OBJECTIVETo investigate the effect of dihydrotestosterone (DHT) on the gene transcriptions and expressions of Smad3 and Smad4 in androgen dependent prostate cancer cell line LNCaP, and whether this effect can be suppressed by the androgen receptor inhibitor flutamide.

METHODSThe androgen dependent prostate cancer cell line LNCaP was cultured in RPMI 1640 medium and treated with different concentrations of DHT(2, 10, 50 nmol/L) and flutamide (100 nmol/L). Quantitative reverse transcription PCR (RT-PCR) was used to detect the mRNAs of Smad3 and Smad4. The expressions of Smad3 and Smad4 protein were detected by Western blot assay.

RESULTSCompared with the control group without any DHT or flutamide, higher concentration(10, 50 nmol/L) of DHT enhanced the transcription of Smad3 mRNA (P <0.05). Serial concentrations of DHT increased the expression of Smad3 protein(P < 0.05). Flutamide inhibited the up-regulation of both Smad3 mRNA transcription and expression significantly (P <0.05). 10 nmol/L DHT significantly suppressed the transcription of Smad4 (P <0.05). There was considerable suppressions of Smad4 expression at the presence of DHT in different concentrations (P < 0.05). And the degree of this suppression was more significant than that of DHT on Smad4 mRNA transcription. Flutamide inhibited the suppressive effects of DHT on both Smad4 mRNA transcription and expression.

CONCLUSIONDHT can enhance the transcription and expression of Smad3, while it decreases the transcription and expression of Smad4 in LNCaP cell line. There is a possible crosstalk between the AR signal and TGF-beta signal passways at the level of Smads.

Androgens ; physiology ; Cell Line, Tumor ; Dihydrotestosterone ; pharmacology ; Flutamide ; pharmacology ; Humans ; Male ; Neoplasms, Hormone-Dependent ; metabolism ; Prostatic Neoplasms ; metabolism ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects ; Smad3 Protein ; biosynthesis ; genetics ; Smad4 Protein ; biosynthesis ; genetics ; Transcription, Genetic

OBJECTIVETo observe the effects of three fluid resuscitation methods on apoptosis of visceral organs in rats with hemorrhagic shock.

METHODSA model of rat with severe hemorrhagic shock and active bleeding was established in 32 SD (Sprague-Dawley) rats. The rats were randomly divided into control group, no fluid resuscitation group (NF group), controlled fluid resuscitation group (NS40 group) and rapid large scale fluid resuscitation group (NS80 group). Each group contained 8 rats. The curative effects were compared. At the same time, the apoptosis in liver, kidney, lung and small intestinal mucosa of survivors after hemorrhage and resuscitation was detected by light microscopy in HE (hematoxylin and eosin) stained tissue sections, flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL).

RESULTSThe survival rate of early fluid resuscitation (14/16) was markedly higher than that of NF group (3/8). There was some apoptosis in liver, kidney, lung and small intestinal mucosa of all survivors. Compared with NF and NS40 groups, the apoptosis of liver, kidney and small intestinal mucosa of NS80 group was obviously increased.

CONCLUSIONSAmong three fluid resuscitation methods, controlled fluid resuscitation can obviously improve the early survival rate and the apoptosis of liver, kidney and small intestinal mucosa in rats with severe and uncontrolled hemorrhagic shock, and may benefit improvement of prognosis.

Animals ; Apoptosis ; Blood Pressure ; Flow Cytometry ; Fluid Therapy ; methods ; In Situ Nick-End Labeling ; Intestine, Small ; pathology ; Kidney ; pathology ; Lactic Acid ; blood ; Liver ; pathology ; Lung ; pathology ; Male ; Organ Specificity ; Rats ; Rats, Sprague-Dawley ; Resuscitation ; methods ; Shock, Hemorrhagic ; pathology ; physiopathology ; therapy

Animals ; Apoptosis ; Blood Pressure ; Disease Models, Animal ; Flow Cytometry ; Fluid Therapy ; In Situ Nick-End Labeling ; Intestinal Mucosa ; pathology ; Lactic Acid ; blood ; Male ; Rats ; Rats, Sprague-Dawley ; Resuscitation ; Shock, Hemorrhagic ; mortality ; pathology ; therapy ; Survival Rate

OBJECTIVETo observe the effects of antisense RNA of connective tissue growth factor (CTGF) on rat liver fibrosis.

METHODSGene recombinant techniques were used to construct a rat antisense RNA of CTGF recombinant plasmid which could be expressed in eukaryotic cells. The recombinant plasmids were encapsulated with lipofectamine and then transducted into a carbon tetrachloride (CCl4) induced rat liver fibrosis model. Expression of CTGF was assessed by RT-PCR, Western blot and immunohistochemistry. Immunohistochemistry was used to identify type I and III collagens. HE stained liver slides were used for pathological study.

RESULTSThe mRNA and protein expression of CTGF in the fibrotic liver transfected with antisense-CTGF were significantly decreased compared with those of the controls (P<0.01). The depositions of type I and type III collagens were also decreased (P<0.05). Antisense-CTGF also minimized the pathological fibrosis in the rat livers (P<0.01).

CONCLUSIONThe results demonstrate that the antisense RNA of CTGF recombinant plasmid has certain effects in preventing liver fibrosis and makes it a possible candidate for use in future gene therapy.

Animals ; Connective Tissue Growth Factor ; genetics ; Genetic Therapy ; Liver ; pathology ; Liver Cirrhosis, Experimental ; pathology ; Male ; Plasmids ; RNA, Antisense ; genetics ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Transfection

Objective To explore the association between metabolic syndromes (MS) and carotid atherosclerosis and to estimate the predictive effects of MS under 3 different definitions.Methods A cross-sectional study was conducted in 2 community-based populations in Beijing,in 2008.1266 subjects (598 men,668 women),aged 45-69,were included in the analyses.MS was defined by the criteria of International Diabetes Federation (IDF),the revised NCEPATPm (ATP Ⅲ-R) and "The Guidelines of Dyslipidemia Control for Chinese Adult" ( "Guidelines" ) in 2007.Results The prevalence rates of MS by the 3 criteria were 39.0%,43.3% and 30.9% respectively.The Kappa value for the measure of the agreement between each pair of the 3 definitions were 0.911,0.719 and 0.730 respectively.The intima-media thickness in common carotid artery (CCA-IMT) was significantly higher (P＜0.001) in all MS groups than in non-MS groups,diagnosed with the 3 criteria independent of age,gender,LDL-C,and current smoking status.After adjustment of age,gender,LDL-C,and current smoking status,the classification of MS significantly increased the risk of prevalence of carotid atberosclerotic plaques,compared to the non-MS group.OR value were 1.499 (95% CI:1.157-1.942) for IDF,1.696 (95% CI:1.314-2.189) for NCEP-R,1.763 (95% CI:1.344-2.312) for "Guideline" respectively.Conclusion Our research findings indicated that,when MS were defined with the 3 definitions,prediction on the risk of sub-clinical atberosclerosis would work beyond some of the conventional cardiovascular risk factors such as smoking,LDL-C.There might exist some differences in gender issue on the strength of association between MS when diagnosed by different criteria and carotid plaque.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; China/epidemiology* ; Heart Valve Prosthesis Implantation ; Humans ; Severity of Illness Index ; Treatment Outcome