Androgen deprivation therapy can effectively suppress the progression of prostate cancer, but accumulating evidence for the relationship of testosterone with prostate cancer challenges the conventional wisdom. High levels of testosterone are not risk factors for prostate cancer, nor promote its development. On the contrary, a low testosterone level indicates a worse pathological stage. So far there has been no strong evidence to prove the role of testosterone in the occurrence and progression of prostate cancer. Therefore, the relationship between testosterone and prostate cancer is quite complicated and deserves further investigation.
Humans ; Male ; Prostatic Neoplasms ; Testosterone

Adolescent ; Child ; Female ; Humans ; Parotid Diseases ; pathology ; Parotid Gland ; pathology ; Recurrence

Objective: To prepare sustained-release polylactic acid microspheres containing bupivacaine (BUP-PLA-MS) and to measure its dissolution in vitro. Methods: BUP-PLA-MS was prepared with polylactic acid (PLA) as carriers using the water-in-oil-in-water (W/O/W) emulsion solvent evaporation method. The powder particle characteristics of BUP-PLA-MS were evaluated comprehensively, and its dissolution characteristics in vitro were studied. Results: It was indicated that bupivacaine formed molecular dispersion within PLA matrix by differential thermal analysis(DTA). The in vitro release behavior of bupivacaine could be best described by Higuchi equation, with t 1/2 =22.76 h. Conclusion: Release of bupivacaine from microspheres is sustained in vitro.

Transforming growth factor-?(TGF-?) is a kind of multifunctional cytokine that regulates cell growth,differentiation,cellular senescence,apoptosis,wound healing and embryo development.As a tumor suppressor,deregulated or aberrant TGF-? signaling has been strongly implicated in human solid tumors,as well as in normal and malignant hematopoiesis.TGF? exerts an inhibitory role during the whole procedure of hematopoiesis.As a cell cycle inhibitor,it maintains cells in a quiescent state and can downregulate expression of hematopoiesis activators and oncoproteins.In malignant hematopoiesis,altered expression of coactivators or corepressors involve in TGF-?-induced transcriptional responses and loss/disruption of TGF-? target gene expression.Then malignant cells grow and differentiate abnormally.In acute promyelocytic leukemia,PML-RAR? may inhibit TGF-? signaling through inhibition of cPML and nPML.Degradation of PML-RAR? by ATRA restores this signaling pathway.

AIM: To quantitatively investigate transforming growth factor-β(TGF-β) and its receptors in normal bulbar conjunctival tissues and pterygium tissues. METHODS: Thirty cases of pterygium patients were randomly selected to undergo surgical resection of pterygium lesion, and the normal margin of bulbar con-junctival tissues were collected as control. Gene expres-sion was detected quantitatively by the method of quantitative real-time PCR (QRT-PCR) analysis. RESULTS: The expression level of TGF-β1 and TGF-β2 was 4.26×10-7±1.45×10-7 and 1.08×10-10±0.68×10-10 in normal bulbar conjunctival tissues, while 10.67×10-7±7.47×10-7 and 8.23×10-11±6.63×10-11 in pterygium tissues. The expression level of TGF-βRⅠand TGF-βRⅡwas 0.003015±0.0036 and 5.33×10-5±5.05×10-5in normal bulbar conjunctival tissues, while 0.000379±0.000281 and 1.002×10-5±9.04×10-6 in pterygium tissues. The expression level of TGF-β1 and TGF-β2 in pterygium was elevated (P<0.01). TGF-β1 expression level in pterygium increase 2.9±2.8 times than in normal conjunctiva. TGF-β2 expression level in pterygium increase 7.5±1.4 times than in normal conjunctiva. The expression level of TGF-βRⅠin pterygium was significantly lower (P<0.05). The expression level of TGF-βRII in pterygium was significantly lower (P<0.01). CONCLUSION: QRT-PCR is an effective method to quantitatively detect gene expression in eye. The upregulation of TGF-β1 and TGF-β2 and downregulation of their receptors expression may play an important role in the pathogenesis of pterygium, which is noteworthy further investigation in diagnosis and treatment of pterygium.real-time PCR; gene expression

Background Congenital heart disease (CHD) is a diverse group of diseases determined by genetic and environmental factors.Considerable research has been done on genes associated with the development of the heart.Recently,focus is on the role of transcription factor NFATc1 in the development of proper valve and septa.As part of a larger study,high density single nucleotide polymorphism (SNP) scanning was used to explore the relationship between NFATc1 gene polymorphism and susceptibility to ventricular septal defect (VSD) in the Chinese Han population.Methods One hundred and ninety-two pediatric patients with congenital VSD and 192 matching healthy control subjects were studied.The haplotype reconstructions were calculated by PHASE2.0 software.Haploview software was used to perform linkage disequilibrium assessment and define haplotype blocks.The algorithm used for defining the blocks was the confidence interval method.Results The NFATc1 gene region can be divided into 11 haplotype blocks.Strong linkage disequilibrium existed within blocks 6,8,9,and 11.Three SNPs (rs7240256,rs11665469,and rs754505) within the NFATc1 gene had significant correlation with VSD by single marker association analysis.In addition,two haplotypes correlated with VSD.Conclusions NFATc1 is associated with the occurrence of VSD and it may be a predisposing gene to CHD in Han Chinese.This finding has set a direction for further genetic and functional studies.

OBJECTIVETo evaluate the efficacy and safety of testosterone undecanoate (TU) in the treatment of late-onset hypogonadism (LOH) by meta-analysis.

METHODSWe searched Pubmed (until April 1, 2014), Embase (until March 28, 2014), Cochrane Library (until April 17, 2014), CBM (from January 1, 2001 to February 2, 2014), CNKI (from January 1, 2001 to February 2, 2014), Wanfang Database (from January 1, 2000 to February 2, 2014), and VIP Database (from January 1, 2000 to Febru ary 2, 2014) for randomized controlled trials of TU for the treatment of LOH. We evaluated the quality of the identified literature and performed meta-analysis on the included studies using the Rveman5. 2 software.

RESULTSTotally, 14 studies were included after screening, which involved 1 686 cases. Compared with the placebo and blank control groups, TU treatment significantly increased the levels of serum total testosterone (SMD = 6.22, 95% CI 3.99 to 8.45, P < 0.05) and serum free testosterone (SMD = 4.35, 95% CI 1.86 to 6. 85, P < 0.05) but decreased the contents of luteinizing hormone (WMD = -2.23, 95% CI -4.03 to -0.42, P < 0.05), sex hormone binding globulin (WMD = 2.00, 95% CI 1.38 to 2.63, P < 0.05). TU also remarkably reduced the scores of Partial Androgen Deficiency of the Aging Males (WMD = -9.49, 95% CI -12.96 to -6.03, P < 0.05) and Aging Males Symptoms rating scale (WMD = -2.76, 95% CI -4.85 to -0.66, P <0.05) but increased the hemoglobin level (SMD = 2.35, 95% CI 0.29 to 4.41, P < 0.05) and packed-cell volume (SMD = 4.35, 95% CI 1.36 to 7.33, P < 0.05). However, no significant changes were shown in aspertate aminotransferase, alanine transaminase, prostate-specific antigen, or prostate volume after TU treatment (P > 0.05).

CONCLUSIONTU could significantly increase the serum testosterone level and improve the clinical symptoms of LOH patients without inducing serious adverse reactions. However, due to the limited number and relatively low quality of the included studies, the above conclusion could be cautiously applied to clinical practice.

Androgens ; therapeutic use ; Hemoglobin A ; metabolism ; Humans ; Hypogonadism ; blood ; drug therapy ; Luteinizing Hormone ; blood ; Male ; Prostate-Specific Antigen ; Randomized Controlled Trials as Topic ; Sex Hormone-Binding Globulin ; metabolism ; Testosterone ; adverse effects ; analogs & derivatives ; blood ; pharmacology

A series of isoindoline derivatives were designed, synthesized, and evaluated for their double inhibitory activities. All of them were new compounds, and their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological tests showed that all compounds exhibited 5-HT or NE reuptake inhibition activity. Among the tested compounds, compound I-3 exhibited potent inhibitory activity against 5-HT and NE reuptake in vitro, and exhibited potent antidepressant activity in vivo. These compounds designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.
Antidepressive Agents ; chemical synthesis ; chemistry ; Biological Transport ; Drug Design ; Isoindoles ; chemical synthesis ; chemistry ; Serotonin Uptake Inhibitors ; chemical synthesis ; chemistry ; Structure-Activity Relationship

BACKGROUND: Autologous blood transfusion device has been widely used in the clinic, reduces al ogeneic blood transfusion, and avoids the occurrence of blood transfusion complications, and effectively improves the patient’s blood safety, but the application of autologous blood transfusion after total hip arthroplasty has been seldom reported. OBJECTIVE: To discuss the safety and effectiveness of autologous blood transfusion after total hip arthroplasty. METHODS: 200 patients were treated by primary unilateral total hip arthroplasty from March 2013 to March 2015. They were randomly divided into two groups. 127 patients in the autologous blood transfusion group received autologous blood transfusion by a drainage tube. 73 patients in the negative pressure drainage bal group received a negative pressure drainage tube. The standard for al ogeneic blood transfusion after replacement was hemoglobin < 80 g/L. The changes in hemoglobin were compared before and 1 and 7 days after replacement between the two groups. Total drainage volume and al ogeneic blood transfusion were compared within 6 hours after replacement between the two groups. RESULTS AND CONCLUSION: There were no statistical differences in hemoglobin levels at 7 days before and after replacement, in drainage volume within 6 hours and the total drainage volume between the two groups (P >0.05). Hemoglobin levels were significantly higher in the autologous blood transfusion group than in the negative pressure drainage bal group at 1 day after replacement (P < 0.05). In the autologous blood transfusion group, autologous blood transfusion volume was averagely 324.2 mL. Al ogeneic blood transfusion volume was averagely 146.7 mL in 31 patients. No reaction was found after autologous blood transfusion. In the negative pressure drainage bal group, 49 patients received al ogeneic blood transfusion (averagely 261 mL). The volume and proportion of al ogeneic blood transfusion were significantly lower in the autologous blood transfusion group than in the negative pressure drainage bal group (P < 0.05). Among patients receiving al ogeneic blood transfusion, seven patients affected pyrogenetic reaction during blood transfusion. These findings suggested that autologous blood transfusion is simple and effective, can effectively reduce the volume and reaction of al ogeneic blood transfusion after total hip arthroplasty and avoid blood-borne diseases, with good prospects.

Objective To establish RNase L gene knockout HEK 293 cell lines using CRISPR/Cas9 system.Methods Small guide RNA ( sgRNA) sequences of human RNase L were designed and sgRNAs were inserted into pCas-Guide and pCas-guide RNA(gRNA) vectors were obtained.The donor DNA sequences of the homologous arm were designed for RNase L knockout .In the presence of the right homologous arm , the resistance gene of hygromycin B and the left homologous arm as templates of homology-directed repair , the donor DNA template was amplified by overlopping PCR and cloned into the pBackZero-T expression vector and pBackZero-T-RNase LK vector was obtained .The pCas-gRNA vector and pBackZero-T-RNase LK vector were co-transfected into HEK293 cells to establish the stable expression cell line of RNase L gene knockout .Cells were cultured with hygromycin B , while Western blotting and DNA sequencing were used to analyze the gene of RNase L knockout from genome .Results and Conclusion The pCas-gRNA vector and pBackZero-T-RNase LK vector were successfully constructed.Five RNase L gene knockout HEK293 cell lines were generated,contributing to the study of the biological function and molecular mechanism of RNase L .