Hui-qing Wang

Ursolic acid induces PC-3 cell apoptosis via activation of JNK and inhibition of Akt pathways in vitro

Ursolic acid (UA), a pentacyclic triterpenoid compound, has been demonstrated to have an antiproliferative effect in various tumors. We investigated the cell killing effects of UA in the human hormone refractory prostate cancer cell line, PC‐3 cells. Also, the molecular mechanisms underlying its antigrowth effect were explored. We found that UA treatment in vitro can effectively inhibit PC‐3 cell viability in a dose‐dependent manner by inducing apoptosis, demonstrated by annexin V‐FITC/propidium iodide staining. Both extrinsic and intrinsic apoptotic pathways appear to be triggered by UA treatment, because inhibiting activation of both caspase‐8 and ‐9 could prevent UA‐induced apoptosis in PC‐3 cells. The c‐Jun N‐terminal kinase (JNK) was found to be activated, followed by Bcl‐2 phosphorylation and activation of caspase‐9. On the other hand, UA inhibited the Akt pathway, subsequently upregulating the expression of Fas ligand (FasL), which initiates death receptor‐mediated apoptosis in PC‐3 cells. Importantly, experimentally lowering FasL expression by siRNA significantly inhibited UA‐induced caspase‐8 activation and at least partly attenuated the consequent apoptosis, suggesting an involvement of FasL and its regulating pathway in the cell killing effect of UA. UA also inhibited cell invasion by downregulating matrix metalloproteinase‐9 via inhibition of Akt in PC‐3 cells. Although further evaluation of the UA effects in vivo is needed, the present results suggest the potential utility of UA as a novel therapeutic agent in advanced prostate cancer.

Phosphorylation of Bcl-2 and activation of caspase-3 via the c-Jun N-terminal kinase pathway in ursolic acid-induced DU145 cells apoptosis

There is currently no successful therapy for androgen-independent prostate cancer. Ursolic acid (UA), a pentacyclic triterpenoid compound, has been shown to have an anti-proliferative effect on various tumors. We investigated the effect of UA on cell viability in the human hormone-refractory prostate cancer cell line DU145, as well as the molecular mechanisms underlying its growth inhibiting effect. We demonstrated that UA induces apoptosis and the activation of caspase-3 in DU145 cells. UA also causes the activation of c-Jun N-terminal kinase (JNK), but has no effect on extracellular signal-regulated protein kinases (ERK1/2) and p38 MAP kinases (p38). UA-induced JNK activation could result in Bcl-2 phosphorylation (Ser70) and degradation in DU145 cells, which may be one of the molecular mechanisms by which it induces apoptosis. Although further evaluation, such as in vivo testing, is clearly needed, the present results suggest the potential utility of UA as a novel therapeutic agent in advanced prostate cancer.

A novel urinary long non-coding RNA transcript improves diagnostic accuracy in patients undergoing prostate biopsy

Long non‐coding RNA (LncRNA) PCA3 has been a well‐established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up‐regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE).

Are the Aging Male's Symptoms (AMS) scale and the Androgen Deficiency in the Aging Male (ADAM) questionnaire suitable for the screening of late-onset hypogonadism in aging Chinese men?

Abstract The Aging Male’s Symptoms (AMS) scale and the Androgen Deficiency in the Aging Male (ADAM) questionnaire have been widely used for screening men suspected of late-onset hypogonadism (LOH). We evaluated the consistency of the two questionnaires with sex hormone levels. A total of 985 men completed the two questionnaires, as well as an analysis of the serum levels of total testosterone (TT), bioavailable testosterone (BT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL) and sex hormone-binding globulin (SHBG). No correlation was observed between any hormone level and the psychological or somatic section of the AMS score, whereas the sexual section was correlated with the levels of FT, LH, FSH, SHBG and BT. Significant correlations were observed between the result of the two questionnaires and these hormone levels. When LOH was defined as TT < 300 ng/dl and FT < 5 ng/dl, the sensitivity and specificity of the AMS scale were 54.0% and 41.2% compared with 78.7% and 14.8% for the ADAM questionnaire. Several sex hormone levels correlated with the two questionnaires, but neither of these questionnaires had sufficient sensitivity and specificity. It is necessary to provide a new questionnaire applicable to the Chinese population to screening LOH.

Relationship between serum sex hormones levels and degree of benign prostate hyperplasia in Chinese aging men

Benign prostatic hyperplasia (BPH) is one of the most common medical conditions in middle aged and older men. This study investigated the relationship between serum levels of sex hormones and measures of BPH in the aging male population of China. Prostate symptoms were assessed as part of a free health screening program for men ≥ 40 years of age. The examination included digital rectal examination, determination of serum prostate-specific antigen levels, International Prostate Symptom Score (IPSS) and transrectal ultrasonography. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), free testosterone (FT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL) and estradiol (E(2)) were evaluated. The men also completed a health and demographics questionnaire and received a detailed physical examination. The final study population consisted of 949 men with a mean age of 58.9 years. Pearson correlation analysis indicated that there were significant correlations between age and levels of all sex hormones except TT, and between age and prostate volume (PV; r=0.243; P<0.01) or IPSS (r=0.263; P<0.01). Additional significant correlations were found between IPSS and serum levels of LH (r=0.112; P<0.01) and FSH (r=0.074; P<0.05), but there were no significant correlations between sex hormone levels and PV. Multivariate linear regression analysis showed significant correlations between age and body mass index (BMI) with PV (P<0.0001). In addition, there was a significant correlation between age and PV with IPSS (P<0.0001). Serum sex hormone levels did not correlate with PV or IPSS. The effects of endocrine changes on measures of BPH in aging men require further investigation in longitudinal and multicenter studies that include patients with all severities of BPH.

A specialized course of basic skills training for single-port laparoscopic surgery

BACKGROUND Single-port laparoscopy (SPL) requires specialized skills; however, there are currently no specialized training courses for SPL. The aim of this study is to present an effective specialized training course of basic skills for SPL. METHODS We designed a specialized training course for single-port laparoscopic basic skills. The study included 10 male urology residents. The trainees practiced the traditional training course for laparoscopy basic skills for 5 days. Basic skills were assessed on day 6 and a self-efficacy confidence index was measured. On day 7, all trainees performed a traditional laparoscopic nephrectomy and single-port laparoscopic nephrectomy. The participants were then randomized into 2 groups: 5 trainees performed the specialized training course and the other 5 trainees continued to practice the traditional training course. Both groups were trained for 5 days. After completion, the trainees were tested on completing a porcine single-port laparoscopic nephrectomy. Operative performance was measured by 2 experts who were blinded to which training the student had received, using an altered global rating. In addition, participants completed a general self-efficacy instrument after performing surgeries. RESULTS The overall operative performance score for single-port laparoscopic surgery was significantly better in the specialized training group. A significant difference in confidence index was seen between the traditional laparoscopy training and specialized single-port training groups (18.40 ± 2.70 vs 29.4 ± 3.51, respectively; P = .001.). Four relative instrument locations which avoided the problem of crowding were also noted in the specialized training group. CONCLUSION The specialized training course is effective for developing SPL skills.

A novel training model for laparoscopic partial nephrectomy using porcine kidney.

PURPOSE The purpose of this study was to create a simple model for teaching laparoscopic partial nephrectomy (LPN) for duplicating the blood supply setting and main technical points of the procedure. MATERIALS AND METHODS A fresh porcine kidney was placed on an unfolded metallic box to help trainees observe, practice, and develop LPN skills in both tumor incision and suturing. The metallic box was specially designed not only for fixing and positioning the kidney but also for storing the outflow of the kidney while its artery was kept artificially infused. A spherical renal parenchyma excision about 2 cm in diameter was initially made and the suture-repairing work followed. This model was used by trainees who had fair laparoscopic competency after completing dry laboratory training programs. During a 20-day training period the trainees were assessed with respect to the time needed to complete LPN. A mentor-trainee fellowship program was planned to guarantee the success of the operations and the quality of LPN. RESULTS There was a good reduction in the total operative time from the fourth to the last attempt. There was also increasing improvement in the quality of the incision suturing during the attempts. By the end of 10 attempts all trainees were more confident in completing a good quality LPN in a mean time of 28.4 minutes. CONCLUSION This model not only offers trainees the opportunities to acquire the skills necessary for LPN but also provides for more economical practice by using easily available porcine kidney.

Identification of late-onset hypogonadism in middle-aged and elderly men from a community of China.

In this study, we investigated the essential criteria for late-onset hypogonadism (LOH) syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total testosterone (TT) and sex hormone-binding globulin (SHBG) were performed, and the aging male symptoms (AMS) questionnaire was conducted in a randomly selected cohort composed of 944 Chinese men aged 40 to 79 years from nine urban communities. Three sexual symptoms (decreased ability/frequency of sexual activity, decreased number of morning erections, and decreased libido) were confirmed to be related to the total and free testosterone levels. The thresholds for TT were approximately 12.55 nmol l−1 for a decreased ability/frequency to perform sex, 12.55 nmol l−1 for decreased frequency of morning erections, and 14.35 nmol l−1 for decreased sexual desire. The calculated free testosterone (CFT) thresholds for these three sexual symptoms were 281.14, 264.90, and 287.21 pmol l−1 , respectively. TT <13.21 nmol l−1 (OR = 1.4, 95%CI: 1.0-1.9, P = 0.037) or CFT <268.89 pmol l−1 (OR = 1.5, 95%CI: 1.1-20, P = 0.020) was associated with an increase in the aforementioned three sexual symptoms. The prevalence of LOH was 9.1% under the criteria, including all three sexual symptoms with TT levels <13.21 nmol l−1 and CFT levels <268.89 pmol l−1 . Our results may improve the diagnostic accuracy of LOH in older men.

Clinical utility of a novel urine-based gene fusion TTTY15-USP9Y in predicting prostate biopsy outcome.

OBJECTIVE In recent years, great effort has been made to explore new biomarkers for early detection of prostate cancer. Our previous study has demonstrated the high prevalence of TTTY15-USP9Y in prostate cancer samples from a Chinese population. Our aim was to evaluate the clinical utility of TTTY15-USP9Y in predicting the prostate biopsy outcome. MATERIALS AND METHODS We retrospectively examined the expression of TTTY15-USP9Y in 226 qualified urine sediment samples. Total RNA was extracted from the urine sediment by using TRIzol reagent, and complementary DNA was synthesized using TransPlex Complete Whole Transcriptome Amplification Kit (WTA2). Real-time quantitative polymerase chain reaction was performed to evaluate the expression of TTTY15-USP9Y and the prostate cancer-specific antigen (PSA) level. The TTTY15-USP9Y score was calculated as 2(Ct(PSA)-Ct(TTTY15-USP9Y))× 1,000. RESULTS The TTTY15-USP9Y score was statistically significantly higher in men with positive biopsy outcome than in men with negative biopsy outcome (P<0.001). The area under the curve was 0.828 for the TTTY15-USP9Y score in the entire patient cohort. The TTTY15-USP9Y score׳s cutoff of 90.28 provided the optimal balance between sensitivity (84.0%) and specificity (77.5%). The combination of PSA level and the TTTY15-USP9Y score significantly improved the diagnostic performance of PSA level (P = 0.001). The TTTY15-USP9Y score alone was superior to PSA level, percent free PSA, and PSA density (serum PSA/prostate volume) in the subgroup of clinical interest (PSA level: 4-10ng/ml, gray zone). Univariable and multivariable logistic analyses indicated that TTTY15-USP9Y score, PSA level, age, and prostate volume were independent predictors of PCa. Adding the TTTY15-USP9Y score in the clinical base model (PSA level, age, and prostate volume) could bring a higher net benefit and reduce more unnecessary biopsies in the defined range of interest (10%-40% threshold probability). CONCLUSION In conclusion, our study explored the potential utility of measuring the TTTY15-USP9Y score in post-digital rectal examination urine samples to predict biopsy outcome and provided the basis for the utility of this novel gene fusion in multicenter and large cohort studies.

New Practical Course for Laparoscopy Training: Anatomizing the Orange

Purpose: The aim of this study was to evaluate whether anatomizing the orange reliably improves laparoscopic skills and can therefore be used as a course in laparoscopic surgical training. Materials and Methods: 12 trainees were required to practice baseline laparoscopic skills for 10 days and were then randomized into groups: 6 people who anatomized the orange for 1 h daily for 5 days and 6 in a control group who continued to practice the baseline laparoscopic skills. The trainees were tested on completing porcine laparoscopic nephrectomy. Operative performance was measured using a global assessment scale of surgical skill. Results: The total score of global rating scale was 23.4 ± 4.1 for the group who anatomized the orange and 18.3 ± 2.7 for the control group (p < 0.05). Operative performance significantly improved in the group anatomizing the orange. Conclusion: Anatomizing the orange resulted in improving laparoscopic skills and can be incorporated into the laparoscopic training course. This could be beneficial for those who wish to develop the advanced skills required for various laparoscopic surgery procedures.