Serum deprivation inhibits cardiomyocyte proliferation, promotes apoptosis and affects P53 and Wnt/β-catenin signaling pathways / 第二军医大学学报

Objective To explore the effect of serum deprivation on proliferation and apoptosis of cardiomyocytes and its mechanisms. Methods Human cardiomyocytes AC16 were randomly divided into serum-deprivation group (the cells were cultured in DMEM medium without fetal bovine serum for 48 h) and control group (the cells were cultured in DMEM medium containing 10% fetal bovine serum for 48 h). CCK-8 assay was performed to test the proliferation ability, and EdU imaging was conducted to detect the DNA synthesis level. Flow cytometry was performed to analyze the apoptosis level and mitochondrial membrane potential. Western blotting was conducted to detect the protein expression levels of caspase-9, Bcl-2, P53, proliferating cell nuclear antigen (PCNA), cyclin D1, β-catenin, Wnt5a, Axis inhibition protein 1 (Axin1), dishevelled 2 (Dvl2), dishevelled 3 (Dvl3) and low-density lipoprotein receptor-related protein 6 (LRP6). Results CCK-8 assay showed that the optical density value of the control group was 1.93±0.01 and that of the serum-deprivation group was 1.08±0.08, which was 55.8% of the control group, and there was significant difference between the two groups (P0.05). Western blotting analysis showed that serum deprivation could upregulate the protein expression of caspase-9 and downregulate the protein expression of Bcl-2, P53, PCNA and cyclin D1. Serum deprivation could inhibit the protein expression of β-catenin, Wnt5a, Axin1, Dvl2, Dvl3 and LRP6 in cardiomyocytes. Conclusion Serum deprivation can inhibit proliferation and induce apoptosis of cardiomyocytes, which may be mediated by inhibition of Wnt/β-catenin signaling pathway.

Indirect comparison of different adjuvant chemotherapies for stage II-III gastric cancer after D2 gastrectomy in Asian patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare efficacy of different adjuvant chemotherapy regimens for stage II-III gastric cancer after D2 gastrectomy in Asian patients.</p><p><b>METHODS</b>Associated literatures were searched through electronic databases and hand-searching. Prospective randomized clinical trials (RCTs) comparing adjuvant chemotherapy after D2 gastrectomy with surgery alone were included in the study. Overall survival and disease-free survival were chosen as the endpoints. Relative hazard was analyzed by Bucher adjusted indirect comparison.</p><p><b>RESULTS</b>Two RCTs were selected, including comparison between S-1 versus surgery alone and comparison between XELOX versus surgery alone. There was no statistical difference in overall survival between the two regimens (HR=0.94, 95%CI:0.62-1.44, P=0.79). The recurrence risk of S-1 was slightly higher as compared to XELOX, but no statistical difference was found (HR=1.11, 95%CI:0.80-1.53, P=0.54).</p><p><b>CONCLUSION</b>The adjuvant chemotherapy with S-1 is similar to XELOX for stage II-III gastric cancer after D2 gastrectomy in Asian patients.</p>

Chronic prostatitis with non-neurogenic detrusor sphincter dyssynergia: diagnosis and treatment / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the features of chronic prostatitis with non-neurogenic detrusor sphincter dyssynergia (NNDSD) and the effects of pelvic floor biofeedback in the treatment of the disease.</p><p><b>METHODS</b>We included in this study 113 male patients, aged 15 - 48 (mean 36) years and diagnosed as having chronic prostatitis for 1 -2 (mean 1.2) years based on such typical symptoms as frequent micturition, urgent micturition, voiding pain, difficult void, etc, that lasted over 3 months, and the score > or = 1 on the first and second parts of NIH-CPSI. Urethritis, interstitial cystitis, urethral stricture and neurogenic bladder were excluded. All the patients underwent urodynamic examinations for the uroflow curve, Q(max), Pdet. max and MUCP. Biofeedback was carried out for those with non-neurogenic detrusor sphincter dyssynergia, and the effects were evaluated at 10 weeks.</p><p><b>RESULTS</b>Twenty-one (18.6%) of the 113 cases were found to be NNDSD. Biofeedback treatment achieved obvious decreases in Q(max) (8.2 +/- 4.1), Pdet. max (125.1 +/- 75.3), MUP (124.3 +/- 23.3) and MUCP (101.5 +/- 43.6), as compared with 15.1 +/- 7.3, 86.3 +/- 54.2, 65.4 +/- 23.0 and 43.5 +/- 16.7 before the treatment (P < 0.05). Statistically significant differences were observed between pre- and post-treatment scores on voiding pain (4.0 +/- 2.0 vs 2.2 +/- 1.7), urination (7.9 +/- 2.1 vs 2.2 +/- 1.9), life impact (9.6 +/- 2.7 vs 2.9 +/- 2.6) and total scores (21.7 +/- 4.8 vs 8.4 +/- 4.6) (P < 0.05).</p><p><b>CONCLUSION</b>Chronic prostatitis patients with LUTS may have NNDSD, which is urodynamically characterized by low Q(max), high intra-bladder pressure and increased urethral pressure in some patients. Urodynamic examinations may contribute to definite diagnosis and appropriate choice of treatment. Pelvic floor biofeedback has satisfactory short-term effects in the treatment of these patients.</p>

Clinical features and minimally invasive treatment of prostatic utricle cyst / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics, diagnostic methods and minimally invasive treatment of prostatic utricle cyst.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 9 cases of prostatic utricle cyst, of whom 5 presented with frequent or urgent micturition, 3 with difficult urination or thinning urinary stream, and the other 1 with hemospermia. All the cases underwent ultrasonography and MRI. Transurethral cyst deroofing was performed for 3 of the patients with smaller cysts close to the prostatic urethra, and laparoscopic excision of the prostatic utricle was conducted for the other 6 with bigger cysts behind the prostatic urethra.</p><p><b>RESULTS</b>The duration of transurethral cyst deroofing ranged from 30 to 50 min and intraoperative bleeding was 20 -70 ml; the mean time of laparoscopic excision of the prostatic utricle was 100 - 150 min and intraoperative bleeding was 30 -50 ml. All the patients were followed up for 3 - 12 months, which revealed normal penile erection and ejaculation, and no urinary tract irritation or difficult urination.</p><p><b>CONCLUSION</b>Ultrasonography and MRI are excellent imaging modalities for accurate depiction of prostatic utricle cyst. Transurethral cyst deroofing is valuable for prostatic utricle cyst close to the prostatic urethra. Laparoscopic excision of the prostatic utricle, owing to its safety, effectiveness, minimal invasiveness, fewer complications and rapid recovery, can be used as the first option for the treatment of prostatic utricle cyst.</p>

Effects of different immunodepressants on the sperm parameters of kidney transplant recipients / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the effects of different immunodepressants on the sperm parameters of kidney transplant recipients.</p><p><b>METHODS</b>In 15 healthy fertile men and 37 kidney transplant recipients, ejaculates were aseptically obtained by masturbation. Thirty-seven patients were divided into two groups, 20 patients were treated with Prograf (FK506) combination with mycophenolate mofetil (MMF) and prednisone; 17 patients were treated with cyclosporine (CsA) combination with azathioprine with prednisone. The sperm viability, mobility parameters such as prorsad percentage motility, straight line velocity (VSL), curve line velocity (VCL), velocity of average path (VAP) and morph were estimated with a computer-assisted sperm analyzer (CASA) provided with a multiple-exposure photography system.</p><p><b>RESULTS</b>There were no significant difference in sperm viability rate [(81.7 +/- 5.7)%, (79.4 +/- 6.8)% and (83.8 +/- 6.0)%], VCL [(24.1 +/- 8.6)%, (23.9 +/- 4.4)%, (24.8 +/- 4.2)% ] and VAP [(19.7 +/- 6.6)%, (18.6 +/- 2.9)%, (21.0 +/- 4.0)%] among groups of FK506, CsA and control, respectively (P > 0.05). The rate of anomaly [(67.8 +/- 5.7)%], the prorsad percentage motility [(46.4 +/- 8.1)%] and VSL [(15.4 +/- 4.6)%] in the group of FK506 were respectively significantly lower and higher than those in the group of CsA [(80.1 +/- 5.6%, (33.3 +/- 6.4)%, (10.2 +/- 2.4)%] (P < 0.05).</p><p><b>CONCLUSION</b>The application of FK506 combined with MMF could help recover the mobility and morphology of the sperm in kidney transplantation recipients.</p>

Effects of small interfering RNA magnetic nanoparticles combination with external magnetic fields on survivin gene expression of bladder cancer cells and apoptosis / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of the small interfering RNA plasmid-dextran magnetic nanoparticles (siRNA-DMN) combination with external magnetic fields on silencing survivin gene expression of bladder cancer cells and apoptosis when DMN used as gene carrier to transfer siRNA-survivin recombinant plasmid in vivo.</p><p><b>METHODS</b>The siRNA-survivin recombinant plasmid specific targeted survivin was synthesized in previous experiment. DMN were prepared by chemical coprecipitation method and used as gene carrier. The siRNA-DMN were constructed by static electricity of polylysine and transferred into human bladder cancer BIU-87 cells with the help of external magnetic fields. The growth inhibiting rate (IR) of BIU-87 cells was observed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide's test and the apoptosis index (AI) was detected by transferase-mediated dUTP nick end labeling method. The relatively transcription levels of survivin mRNA and protein expression were respectively detected by semi-quantitive reverse transcription polymerase chain reaction and Western Blotting techniques.</p><p><b>RESULTS</b>The diameter, effective diameter and saturation magnetization of DMN-siRNA were about 10 - 12 nm, 94.8 nm and 0.19 emu/g, respectively. The IR (39.60%) and AI (28.72%), the relative expression of survivin mRNA and protein of siRNA-DMN combination with external magnetic fields on BIU-87 cells were significantly higher and lower than those in the control group and single siRNA-DMN group, respectively (P < 0.05).</p><p><b>CONCLUSIONS</b>The siRNA-survivin plasmid-DMN combination with external magnetic fields could effectively inhibit survivin expression and induce BIU-87 cells apoptosis which provided experimental basis for the magnetic targeting gene therapy of bladder tumor.</p>

Prostate androgen-regulated gene: a novel potential target for androgen-independent prostate cancer therapy / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To investigate the involvement of the prostate androgen-regulated (PAR) gene in the androgen receptor (AR) signaling pathway and the malignant phenotype of androgen-independent prostate cancer (PCa) cells.</p><p><b>METHODS</b>The difference in PAR expression between LNCaP and PC3 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR). Androgen and anti-androgen effects on PAR expression were evaluated by RT-PCR in LNCaP, PC3 cells and PC3 cells stably transfected with vector containing wild-type AR. To determine the importance of PAR in the malignant proliferation of androgen-independent PCa cells, we used small interfering RNA (siRNA) transfection to knock down the expression of the gene in PC3 cells. The changes in the malignant phenotype of PCa cells after transfection were analyzed by cell count, colony formation in soft agar and flow cytometry.</p><p><b>RESULTS</b>PAR expression was 3-fold higher in PC3 cells than that in LNCaP cells. Dihydrotestosterone (DHT) regulated PAR mRNA expression in LNCaP cells and the effect was inhibited by the AR antagonist, flutamide. By contrast, DHT did not affect PAR expression in PC3 cells. The reintroduction of AR into PC3 cells by stable transfection restored the androgen effect on PAR upregulation. After the knockdown of the PAR gene by siRNA, PC3 cells exhibited a reversal of the malignant phenotype.</p><p><b>CONCLUSION</b>Because of the possibility that PAR is downstream from the AR, and because of its contribution to malignant proliferation in androgen-independent PCa cells, the gene could be a potential therapeutic target for androgen-independent PCa with AR signaling pathway alteration.</p>

Effect of photodynamic therapy with metalloporphyrin compound on human prostate cancer PC-3 cells in vitro / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effect of the photodynamic therapy (PDT) with the new water-soluble metalloporphyrin compound on human prostate cancer PC-3 cells in vitro and the anticancer mechanism of PDT.</p><p><b>METHODS</b>The new water-soluble manganese, 5,10,15, 20-tetra (N-methyl4-pyridyl) porphinato (2-) tetraiodide salt, was synthesized. The PC-3 cells were treated with the compound of serial concentrations(0, 0.1, 1, 1.0 micromol/L) followed by irradiation of different dosages of visible light. The techniques of MTT and Annexin-V/propidium iodide double-labeled flow cytometry (FCM) were applied to measuring the inhibitory effect of the compound on the growth activity and apoptosis of the cells.</p><p><b>RESULTS</b>When the metalloporphyrin compound concentration was within 10 micromol/L and the irradiation time was within 30 min, the water-soluble metalloporphyrin compound had a significant inhibitory effect on the proliferation of PC-3 cells and induced PC-3 cell apoptosis, and the effects depended greatly on metalloporphyrin concentration and illumination dosages. Higher concentrations and dosages induced the death of the majority of PC-3 cells.</p><p><b>CONCLUSION</b>The PDT of the water-soluble metalloporphyrin compound followed by light irradiation has a distinctive killing effect on PC-3 cells in vitro, and the rates of proliferation inhibition and cell apoptosis are correlated with metalloporphyrin concentration and the dosages of light irradiation. The results suggest that the mechanism of metalloporphyrin PDT may be involved with the induction of apoptosis in human prostate cancer cells.</p>

Chronic prostatitis related sexual dysfunction and its psychologic treatment / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the relationship between sexual dysfunction and chronic prostatitis and investigate the effect of psychologic treatment.</p><p><b>METHODS</b>A total number of 346 patients with chronic prostatitis complicated by sexual dysfunction were randomized into two groups, one treated with routine medication (antibiotic, indomethacin, alpha1 receptor blocker and Chinese traditional medicine), and the other with both routine medication and psychologic treatment. Results were analyzed by comparing NIH-CPSI and IIEF-5 between pre- and post-treatment groups.</p><p><b>RESULTS</b>The prostatitis symptoms and sexual dysfunction were improved obviously after treatment in the two groups, but compared with the control, more marked improvement was observed in the combined psychologic treatment group (P <0.01). The degree of chronic prostatitis related sexual dysfunction was not correlated with that of prostatitis symptoms.</p><p><b>CONCLUSION</b>Psychology plays a very important role in chronic prostatitis related sexual dysfunction. Psychologic treatment not only works on the sexual dysfunction, but also improves prostatitis symptoms.</p>

An experimental study of effect of different extracts of Alisma orientalis on urinary calcium oxalate stones formation in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of different extracts of Alisma orientalis on urinary calcium oxalate stone formation in rats and to identify the effective constituents.</p><p><b>METHOD</b>Different extracts were administered through a stomach tube to rats of different groups with renal calcium oxalate stones induced by ethylene glycol (EG) and ammonium chloride (AC).</p><p><b>RESULT</b>In the rats administered with ethyl acetate elution of ethyl acetate extract, blood Cr, BUN, renal tissue calcium content, urinary calcium excretion and crystals deposition in renal tissue were significantly lower than those of the stone formation group.</p><p><b>CONCLUSION</b>The ethyl acetate elution of ethyl acetate fraction extract of Alisma orientalis can significantly inhibit urinary calcium oxalate stone formation in rats and be the most effective constituent of Alisma orientalis.</p>

Effects of hyperbaric oxygenation on rabbits 'testes with varicocele / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the mechanism of male infertility caused by varicocele by evaluating the effects of hyperbaric oxygenation (HBO) therapy on the testicular tissue morphology and function of rabbit model with varicocele(VC).</p><p><b>METHODS</b>Twenty-four mature male rabbits were randomly divided into three groups: pseudo-operation, VC model and VC model administered by HBO. Experimental varicocele was induced by partial ligation of the left "lumbotesticular" trunk vein in rabbits. HBO was administered to one of the two groups of VC model rabbits after the operation. Weight and volume of both testes, parameters of seminal fluid, histological changes of testicular tissues, MTDs, TFI, and Sertoli cell index (SI) of seminiferous tubules were studied.</p><p><b>RESULTS</b>The average weight and volume of the left testes significantly increased in the rabbits treated by HBO. The semen quality was improved, and MTDs increased significantly compared with VC group(P < 0.0001). The testicular tissue morphology became nearly normal in VC + HBO group.</p><p><b>CONCLUSIONS</b>1. Both the structure and spermatogenetic function of testes can be damaged by the presence of varicocele; 2. Chronic ischemia, anoxia and microcircular dysfunction may be the key process and essential factor that make varicocele contributive to testicular damage and spermatogenetic dysfunction; 3. HBO can effectively alleviate, even eliminate, chronic ischemia, anoxia and microcircular dysfunction in testicular tissues with varicocele, and thus protect the structure and functions of testes.</p>

Tumor infiltrating dendritic cells and Mucin1 gene expression in benign prostatic hyperplasia and prostate cancer / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the expression of Mucin1 gene and tumor infiltrating dendritic cells(TIDC) in the tissues of benign prostatic hyperplasia (BPH) and prostate cancer.</p><p><b>METHODS</b>Mucin1 and TIDC were detected in 20 specimens of BPH and 30 specimens of prostate cancer by immunohistochemistry SP method.</p><p><b>RESULTS</b>MUC1 expressed in both prostate cancer and BPH. The staining patterns were significantly associated with tumor pathological grade (P < 0.001). The number of TIDC was negatively correlated with tumor pathological grade, the higher the grade, the smaller the number of TIDC (P < 0.001).</p><p><b>CONCLUSIONS</b>The expression pattern of MUC1 and the number of TIDC could be considered as useful markers to evaluate the malignant degree and prognosis of prostate cancer. The decrease of TIDC plays an important role in tumor immune evasion and immune tolerance. Highly expressed MUC1 could lead to the failure of hormonal treatment for prostate cancer, and contribute much to tumor infiltration and metastasis.</p>

NF-kappa B and prostatic adenocarcinoma / 中华男科学杂志

Nuclear factor of kappa B (NF-kappa B) is a multipolar nuclear transcription factor, and adjusts many gene expressions concerned with immunization, apoptosis, inflammation, neoplasia and metastasis. Recently, NF-kappa B has become a kind of hot spot in the studies of neoplasia, infiltration, metastasis and drug resistance. NF-kappa B can serve as an ideal target molecular approach to the promising gene therapy. This article reviews recent advances in studies on the structure and function of NF-kappa B, and the relationship between NF-kappa B and prostatic adenocarcinoma infiltration, metastasis and tactics of gene therapy.

Study on the correlation between Mta-1 expression and ER,u-PA/PAI-1,MVD in bladder transitional cell carcinoma / 中华泌尿外科杂志

Objective To investigate the expression of Mta-1 in bladder transitional cell carcinoma (BTCC)and to analyze its correlation with the clinical staging,pathologic grading,metastasis and recur- rence,and to explore the possible molecular mechanisms.Methods Samples of 42 cases of BTCC and 12 normal bladder mueosa tissues were examined with immunohistochemical analysis for the expression of Mta- 1,ER,u-PA and PAI-1.Endothelial cells were stained by anti-CD34,and microvascular density(MVD)of carcinoma tissue was calculated.The correlation of Mta-1 expression with the invasion,metastasis,angiogene- sis and recurrence of BTCCs was analyzed;and the correlation of Mta-1 expression with ER,u-PA,PAI-1,and MVD was also analyzed.Results The positive rate of Mta-1 expression in BTCCs was 73.8%(31/42) , while it was 0.0% in normal bladder mucosa tissues(P＜0.01).The expression level of Mta-l increased with the higher clinical stages and pathologic grades of BTCCs;it was higher in recurrence group(100.0% , 15/15)than in non-recurrence group(59.3%,16/27),and high in metastasis group(100.0%,14/14) than in non-metastasis group(60.7%,17/28)(P＜0.05).The expression level of ER increased with the lower clinical stages and pathologic grades of BTCCs;the positive rate of ER expression was 0.0% in 14 ca- ses with metastasis and was 53.6% in 13 of 28 cases without metastasis(P＜0.05);and the rate was 6.7% in 1 of 15 cases with recurrence and 44.4% in 12 of 27 cases without recurrence(P＜0.05).Negative cor- relation was found between Mta-1 and ER expression(r=-0.739,P＜0.01).The positive rate of u-PA ex- pression(59.5%,25/42)was significantly higher in BTCCs than that in normal bladder mucosa tissues (16.7%,2/12)(P＜0.05).Positive correlation was found between u-PA and Mta-1 expression(r= 0.875),while negative correlation was found between u-PA and PAI-1 expression(r=-0.535).The posi- tive rate of PAI-1 expression in normal bladder mucosa tissues(50.0%,6/12)was significantly higher than that in BTCCs(19.0%,8/42)(P＜0.05).In addition,negative correlation was found between PAI-1 and Mta-1 expression(r=-0.706).And positive correlation was found between MVD in BTCCs marked by an- ti-CD34 and Mta-1 expression(r=0.683).Conclusions Mta-1 is highly expressed in BTCCs,and it correlates closely with tumor pathologic grades,clinical stages,recurrence and metastasis.Mta-1 up-regulates the expression of u-PA and down-regulates that of PAI-1,which is associated with invasion and metastasis and acts as an angiogenic mediator in BTCCs.A negative correlation is found between Mta-1 and ER in inva- sion and metastasis of BTCCs.

Proliferation and identification of dendritic cells from peripheral blood of patients with bladder cancer in vitro / 中华泌尿外科杂志

Objective To investigate the proliferation and identification of dendritic cells(DC)de- rived from peripheral blood of patients with bladder cancer in vitro.Methods The mononuclear cells were prepared from peripheral blood of patients with bladder cancer by Ficoll-Hypaque centrifugation method,and were induced by the recombinant cytokines hGM-CSF(50 ng/ml),hlL-4(10 ng/ml)and hTNF-?(50 ng/ ml)for 2 weeks.The growth and morphology of DC were observed through the phase contrast or electron mi- croscope,and their pheuotypes were determined by flow cytometry.The capacity of DC to activate T cell-de- pendent anti-tumor immune responses was tested by MTT method.Results The DC cultured in vitro turned into suspensive growth from adhesive situation on the 6th day,then the number of DC increased con- tinuously and the cells showed the irregular morphologic appearance of DC with veiled edges on the 8th day. Flow cytometry showed that the mature DC expressed high levels of specific markers such as CD_(1a),CD_(83), CD_(86)and HLA-DR.T cells activated by DC showed strong cytotoxicity to bladder cancer cell line BIU87 with a killing rate of(48.8?3.7)%,while the killing rate of T cells which were not activated by DC was(25.7?1.5)%;the difference of the rate between them was significant(P＜0.01). Conclusions The DC can be cultured from peripheral blood of patients with bladder cancer by induction of rhGM-CSF,rhIL-4 and hT- NF-?in vitro.This may lay an experimental foundation for further research on DC vaccine.