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

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

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.

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: Bupivacaine is widely used to alleviate post-operation pain and cure acute and chronic pain caused by inflammation or cancer.Its analgesic time cannot meet the request that drug is released slowly to prolong the analgesic time in clinic.OBJECTIVE: To detect the alleviating effect of bupivacaine polylactic acid microspheres taking high molecular polymer-polylactic acid as vector in rabbits with high performance liquid chromatograph (HPLC) and traditional skin test method.DESIGN: A completely randomized controlled animal experimental study.SETTING: School of Pharmacy, Second Military Medical University of Chinese PLAMATERIALS: Sixteen New Zealand rabbits, weighing (2.58±0.17)kg were used in this experiment.INTERVENTIONS: The experiment was carried out at the Department of pharmaceutics, School of Pharmacy, Second Military Medical University of Chinese PLA between September and November 2002. ① Animal models were established according to traditional skin test method. ② Totally 16 New Zealand rabbits were randomly divided into 2 groups: Group A and Group B, with 8 in each one. 5 mg/kg bupivacaine parenteral solution was injected subcutaneously in Group A, 5 mg/kg bupivacaine polylactic acid microspheres were implanted between subcutaneous tissue and sarcolemma in Group B. We took 1.5 mL blood from ear border vein at 5, 10, 20, 30,45 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours after administration of bupivacaine parenteral solution respectively in Group A and another 1.5 mL at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 3 6, 48 and 60 hours after admistration of bupivacaine microsphere powder for index detection. ③ HPLC method was used to detect the concentration and releasing effect of bupivacaine in blood serum.MAIN OUTCOME MEASURES: Concentration change of bupivacaine in blood serum and efficacy diameter of local anesthetic.RESULTS:All the 16 rabbits entered the stage of result analysis. ①Change of bupivacaine concentration: Plasma bupivacaine concentration in Group A reached the peaked quickly after subutaneous injection with the high concentration of 2.466 4 mg/L, then declined quickly. Plasma bupivacaine concentration in Group B was relative stable, reached a peak much slowly after subcutaneous implantation, with peak concentration of 0.778 1 mg/L, and the plasma bupivacaine concentration maintained a relative low level, the mean retention time was obviously prolonged (P ＜ 0.05).② Alleviating effect of bupivacaine: The analgesic time was significantly longer in the bupivacaine microsphere group than in the bupivacaine parenteral solution group (P ＜ 0.05).CONCLUSION:Bupivacaine polylactic acid microspheres have sustained release effects in rabbits.

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 .

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

Objective To observe the clinical curative effect of modified Qiwei Baizhu Powder for mesenteric lymphadenitis in children with spleen deficiency and dampness retention. Methods A multi-center randomized and controlled trial was carried out in 150 cases of mesenteric lymphadenitis in children with spleen deficiency and dampness retention. The patients were randomized into Chinese medicine group, western medicine group and combination group, 50 cases in each group. Chinese medicine group was treated with modified Qiwei Baizhu Powder, western medicine group was treated with Cefaclor for Oral Suspension, and the combination group was treated with modified Qiwei Baizhu Powder plus Cefaclor for Oral Suspension. Before treatment and after treatment for 7 days, one month and 3 months, changes in syndrome manifestations and the size of abdominal mesenteric lymph nodes were monitored. The total effective rate and cure rate of the three groups were compared, and the safety of the regimen was also evaluated. Results (1) In Chinese medicine group, 5 patients dropped out, and a total of 45 cases completed the trial; in western medicine group, 3 patients dropped out, and a total of 47 cases completed the trial; in the combination group, 7 patients dropped out, and a total of 43 casescompleted the trial.(2) The total effective rate of Chinese medicine group and combination group after treatment for 7 days, one month and 3 months was significantly higher than that of western medicine group (P < 0.05), and the cure rate after treatment for one month and 3 months was also significantly higher than that of western medicine group (P<0.01). The differences of total effective rate and cure rate were insignificant between Chinese medicine group and combination group(P>0.05) at various time points.(3) After treatment for 7 days, one month and 3 months, the transverse and longitudinal diameters of mesenteric lymph nodes in Chinese medicine group and combination group were shorter than those of western medicine group (P < 0.05) , but the difference was insignificant between Chinese medicine group and combination group (P>0.05). (4) Except for the drop-out cases, all of the children finished the trial. During the treatment, no obvious adverse reaction was found. Conclusion Modified Qiwei Baizhu Powder exerts certain efficacy for the treatment of mesenteric lymphadenitis in children with spleen deficiency and dampness retention.