Renal denervation ameliorates cardiac metabolic remodeling in diabetic cardiomyopathy rats by suppressing renal SGLT2 expression.

This study aimed to investigate the effects of renal denervation (RDN) on diabetic cardiomyopathy (DCM) and explore the related mechanisms. Male Sprague-Dawley rats were fed high-fat chow and injected with low-dose streptozotocin to establish a DCM model. Six rats served as controls. The surviving rats were divided into three groups: control group, DCM group and DCM + RDN group. RDN surgery was performed in the fifth week. At the end of the experiment, all rats were subjected to 18F-FDG PET/CT and metabolic cage studies. Cardiac function and structure were evaluated by echocardiography and histology. Myocardial substrate metabolism and mitochondrial function were assessed by multiple methods. In the 13th week, the DCM rats exhibited cardiac hypertrophy and interstitial fibrosis accompanied by diastolic dysfunction. RDN ameliorated DCM-induced cardiac dysfunction (E/A ratio: RDN 1.07 ± 0.18 vs. DCM 0.93 ± 0.12, P < 0.05; E/E' ratio: RDN 10.74 ± 2.48 vs. DCM 13.25 ± 1.99, P < 0.05) and pathological remodeling (collagen volume fraction: RDN 5.05 ± 2.05% vs. DCM 10.62 ± 2.68%, P < 0.05). Abnormal myocardial metabolism in DCM rats was characterized by suppressed glucose metabolism and elevated lipid metabolism. RDN increased myocardial glucose uptake and oxidation while reducing the absorption and utilization of fatty acids. Meanwhile, DCM decreased mitochondrial ATP content, depolarized the membrane potential and inhibited the activity of respiratory chain complexes, but RDN attenuated this mitochondrial damage (ATP: RDN 30.98 ± 7.33 µmol/gprot vs. DCM 22.89 ± 5.90 µmol/gprot, P < 0.05; complexes I, III and IV activity: RDN vs. DCM, P < 0.05). Furthermore, both SGLT2 inhibitor and the combination treatment produced similar effects as RDN alone. Thus, RDN prevented DCM-induced cardiac dysfunction and pathological remodeling, which is related to the improvement of metabolic disorders and mitochondrial dysfunction.

The relationship between urologic cancer outcomes and national Human Development Index: trend in recent years.

OBJECTIVES: To describe the influence of the socioeconomic development on worldwide age-standardized incidence and mortality rates, as well as mortality-to-incidence ratio (MIR) and 5-year net survival of urologic cancer patients in recent years. METHODS: The Human Development Index (HDI) values were obtained from the United Nations Development Programme, data on age-standardized incidence/mortality rates of prostate, bladder and kidney cancer were retrieved from the GLOBOCAN database, 5-year net survival was provided by the CONCORD-3 program. We then evaluated the association between incidence/MIR/survival and HDI, with a focus on geographic variability as well as temporal patterns during the last 6 years. RESULTS: Urologic cancer incidence rates were positively correlated with HDIs, and MIRs were negatively correlated with HDIs. Prostate cancer survival also correlated positively with HDIs, solidly confirming the interrelation among cancer indicators and socioeconomic factors. Most countries experienced incidence decline over the most recent 6 years, and a substantial reduction in MIR was observed. Survival rates of prostate cancer have simultaneously improved. CONCLUSION: Development has a prominent influence on urologic cancer outcomes. HDI values are significantly correlated with cancer incidence, MIR and survival rates. HDI values have risen along with increased incidence and improved outcomes of urologic caner in recent years.

Thymol inhibits bladder cancer cell proliferation via inducing cell cycle arrest and apoptosis.

Thymol is a phenolic compound with various pharmacological activities such as anti-inflammatory, anti-bacterial and anti-tumor effects. However, the effect of thymol on bladder cancer cell growth is still elusive. The purpose of this study is to investigate the efficacy of thymol in bladder cancer cells and its underlying mechanism. Thymol inhibited bladder cancer cell proliferation in a dose and time-dependent manner. We also observed cell cycle arrest at the G2/M phase after the treatment of thymol. Moreover, thymol could induce apoptosis in bladder cancer cells via the intrinsic pathway along with caspase-3/9 activation, release of cytochrome c and down-regulation of anti-apoptotic Bcl-2 family proteins. The activation of JNK and p38 was also critical for thymol-induced apoptosis since it was abrogated by the treatment of JNK inhibitor (SP600125), and p38 inhibitor (SB203580) but not ERK inhibitor (SCH772984). Furthermore, the generation of ROS (reactive oxygen species) was detected after the treatment of thymol. ROS scavenger NAC (N-acetyl cysteine) could block the thymol-triggered apoptosis and activation of MAPKs. These findings offer a novel therapeutic approach for bladder cancer.

[Low-dose tadalafil combined with Shuganyiyang capsules for mild-to-moderate erectile dysfunction].

OBJECTIVE: To observe the clinical effect of low-dose once-daily tadalafil combined with Shuganyiyang Capsules in the treatment of mild-to-moderate erectile dysfunction (ED). METHODS: Ninety patients with mild-to-moderate ED were equally randomized to groups A, B and C to receive Shuganyiyang Capsules, tadalafil, and tadalafil + Shuganyiyang Capsules, respectively. The scores of the patients on IIEF-5 and SF-PAIRS (15-Item Short Form of Psychological Interpersonal Relationship Scales) were recorded before and at 1 and 3 months after treatment. RESULTS: The IIEF-5 scores of groups A, B and C were 10.13 +/- 1.55, 11.00 + 1.60 and 10.73 +/- 1.91 before treatment, and 13.77 +/- 2.11, 17.77 +/- 2.13 and 17.17 +/- 3.84 at 1 month after treatment, significantly higher in B and C than in A (P <0. 001) , but with no remarkable difference between B and C (P =0. 411). At 3 months after treatment, the IIEF-5 scores were 15.77 +/- 2.05, 18.07 +/- 2.24 and 19.37 +/- 3.76 in the three groups, dramatically higher in B and C than in A (P <0.001) as well as in C than in B (P<0.05). The scores on sexual self-confidence, sexual spontaneity and time concerns in SF-PAIRS were 3.90 +/-0.80, 8.67 +/- 1.94 and 14.43 +/- 1.92 before medication, 5.83 +/- 1.02, 9.90 +/- 1.75 and 11.17 +/- 1.68 at 1 month and 6.73 +/- 0.98, 11.07 +/- 2.08 and 10.67 +/-1.60 at 3 months after medication in group A; 4.17 +/- 0.87, 9.37 +/-1.43 and 14.47 +/-1.57 before medication, 6.47 +/-0.78, 10.83 +/- 2.18 and 10.20 +/-1.56 at 1 month and 6.83 +/-0.91, 11.30 +/- 1.88 and 9.47 +/- 1.57 at 3 months in group B; and 4.23 +/-0. 94, 9.50 +/- 1.89 and 14.67 +/- 2.91 before medication, 8.03 +/- 1.67, 13.43 +/-1.10 and 9.70 +/-1.21 at 1 month and 8.93 +/- 1.78, 14.70 +/- 1.26 and 8. 87 +/- 0. 97 at 3 months in group C. Compared with the baseline, the SF-PAIRS scores of the three groups were all significantly improved after treatment (P <0. 05) , and markedly higher in C than in the other two groups (P <0.05). CONCLUSION: Low-dose once-daily tadalafil combined with Shuganyiyang Capsules is obviously effective in the treatment of mild-to-moderate ED, which not only improves the patients'erectile function, sexual self-confidence and sexual spontaneity, but also reduces their time concerns.

[Salidroside inhibits hypoxia-induced phenotypic modulation of corpus cavernosum smooth muscle cells in vitro].

OBJECTIVE: To explore the effects of salidroside on the phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMC) in hypoxic SD rats. METHODS: CCSMCs were cultured in vitro and identified by immunohistochemistry. The cells were divided into six groups: normal control (21% O2), hypoxia (1% O2), hypoxia + salidroside 1 mg/L, hypoxia + salidroside 3 mg/L, hypoxia + salidroside 5 mg/L and hypoxia + PGE1 0.4 microg/L, and then cultured for 48 hours. The relative expressions of alpha-actin and osteopontin (OPN) in each group were determined by RT-PCR. RESULTS: The in vitro cultured CCSMCs grew well, with anti-alpha-smooth muscle actin monoclonal antibodies immunohistochemically positive. The relative expression of alpha-actin was markedly decreased while that of OPN remarkably increased in the hypoxia group as compared with the normal control group (P < 0.01). The hypoxia + salidroside 5 mg/L group showed a significantly higher expression of alpha-actin and lower expression of OPN than the hypoxia group (P < 0.01), but exhibited no significant differences from the hypoxia + PGE group (P > 0.05). CONCLUSION: Hypoxia can reduce the relative expression level of alpha-actin and increase that of OPN in the CCSMCs of SD rats, namely, induce their phenotypic modulation from the contraction to the non-contraction type. Salidroside can restrain hypoxia-induced phenotypic modulation of CCSMCs, and its inhibitory effect at 5 mg/L is similar to that of PGE1.

[Hypoxia induces fibrosis of corpus cavernosum smooth muscle in SD rats].

OBJECTIVE: To explore the effect of hypoxia on the fibrosis of corpus cavernosum smooth muscle cells (CCSMC) in SD rats. METHODS: CCSMCs were cultured in vitro, identified by immunohistochemistry, and then exposed to hypoxia at the concentration of 1% O2 for 12, 24, 48 and 72 hours. Those exposed to normal oxygen concentration for the corresponding lengths of time were used as the control. The relative expressions of TGF-131, type I collagen and type DI collagen were determined by RT-PCR. RESULTS: The in vitro cultured CCSMCs grew well, and the anti-a-smooth muscle actin monoclonal antibodies were positive on immunohistochemical staining. The relative expression levels of TGF-beta1, type I collagen and type mI collagen were positively correlated with the time of hypoxia interference within 48 hours, and did not increase further with prolonged exposure. CONCLUSION: When exposed to hypoxia, the relative expressions of TGF-beta1, type I collagen and type mI collagen in the CCSMCs of SD rats increased with the length of time, and reached the peak at 48 hours. Hypoxia can cause fibrosis of CCSMCs in SD rats.

A Potential Predictive Biomarker for Miller/Payne Grading: PD-L1 Expression before Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the value of programmed death ligand 1 (PD-L1) expression as a predictive biomarker for Miller/Payne grading before neoadjuvant chemotherapy (NACT) in breast cancer. PATIENTS AND METHODS: The expression of PD-L1 in pretreatment biopsies of breast cancer was assessed by immunohistochemistry in tissue microarrays. The results were analyzed using SPSS 22.0 statistical software. RESULTS: Of 53 female patients, 10 (18.9%) patients had a grade 5 (G5) response, and 12 (22.6%) patients showed PD-L1 expression, including 7 (13.2%) patients with staining in tumor cells (TCs) and 8 (15.1%) patients with staining in peritumoral lymphocytes (PTLCs). Logistic regression analysis revealed that G5 response to NACT was significantly associated with TCs or PTLCs PD-L1 positivity, whether with univariate analysis (TCs PD-L1: p = 0.00, OR 20.50, 95% CI 3.11-134.94; PTLCs PD-L1: p = 0.02, OR 6.50, 95% CI 1.27-33.20) or with multivariate analysis (TCs PD-L1: p = 0.00, OR 42.23, 95% CI 3.36-530.90; PTLCs PD-L1: p = 0.02, OR 9.07, 95% CI 1.37-60.02). The same trend was found in the luminal subgroup analysis (TCs PD-L1: p = 0.02, OR 23.43, 95% CI 1.66-331.58; PTLCs PD-L1: p = 0.01, OR 47.89, 95% CI 2.47-927.41). CONCLUSION: G5 response to NACT in breast cancer was significantly associated with TCs or PTLCs PD-L1-positive expression in pretreatment biopsies; it can be expected that PD-L1 will become a new independent biomarker of response to NACT in breast cancer.

The Prognostic Value of Deficient Mismatch Repair in Stage II-IVa Nasopharyngeal Carcinoma in the Era of IMRT.

In the era of intensity-modulated radiotherapy (IMRT), it is important to analyse the prognostic value of deficient mismatch repair (dMMR) in nasopharyngeal carcinoma (NPC). In this study, in pretreatment biopsies of 69 patients with stage II-IVa NPC, the expression levels of MMR proteins, including MLH1, MSH2, MSH6 and PMS2, were assessed by immunohistochemistry (IHC). The median follow-up time was 37.5 months (3.1-87.4 months). 50.7% of cases (35/69) showed preserved expression of all 4 MMR proteins, which was interpreted as proficient mismatch repair (pMMR). Only 1.5% of cases (1/69) lost expression of all 4 MMR proteins, 26.1% of cases (18/69) have PMS2 loss alone and 21.7% of cases (15/69) lost expression of both PMS2 and MLH1. Thus, 49.3% of cases (34/69) lost expression of one or more MMR proteins, which was interpreted as dMMR. There was no significant difference (P > 0.05) in terms of sex, age, clinical stage, T category, N category or therapy regimens between the dMMR and pMMR groups. The multivariate Cox regression analysis revealed that dMMR was an independent significant prognostic factor for distant metastasis-free survival (DMFS) (dMMR vs pMMR: P = 0.01, HR = 0.25, 95% CI: 0.09~0.75). Therefore, NPC patients with dMMR had significantly superior DMFS compared with patients with pMMR. It can be expected that dMMR will become a new independent prognostic factor for NPC.

[Hypoxia promotes corpus cavernosum smooth muscle cell apoptosis in SD rats].

OBJECTIVE: To explore the relationship between hypoxia and the apoptosis of corpus cavernosum smooth muscle cells (CCSMC) in SD rats. METHODS: CCSMCs were cultured in vitro and identified by immunohistochemistry, and then underwent hypoxia interference at the concentration of 1% O2 for 12, 24, 48 and 72 hours, with normal oxygen concentration as the control. Flow cytometry was used to determine the cycles and apoptosis of the cells. RESULTS: The cultured CCSMCs grew well, positive for anti-smooth muscle alpha-actin monoclonal antibody immunohistochemical staining. Flow cytometry showed that the number of CCSMCs in G0/G1 was gradually increased within 48 hours and then decreased, just opposite to the proportion of the S phase cells. But no regular change was found in the proportion of the cells in the G2/M phase. CONCLUSION: Hypoxia promotes the apoptosis of CCSMCs in a time-dependent manner, to the maximum at 48 hours, and then cell lysis may occur, but with no further apoptosis.

[Prevention of urethral stricture after transurethral vaporesection of prostate by adjustable urethral tractor].

OBJECTIVE: To reduce the complication by transurethral vaporesection of prostate (TUVP) using adjustable urethral tractor. METHODS: One hundred and six cases with benign prostate hypertrophy underwent TUVP and catheter traction after operation by an adjustable tractor. The results by catheter traction were compared with those by rubberized cloth paste and carbasus compression. RESULT: The urethral stricture occurred in 2.7%, 6.7%, 30.4% of cases by the catheter traction, rubberized cloth paste and carbasus compression respectively, which had statistical significance (P <0.01). CONCLUSION: The incidence of urethral stricture can be reduced by catheter traction after TUVP.

Disposable circumcision suture device: clinical effect and patient satisfaction.

In our experience patients undergoing circumcision are mostly concerned about pain and penile appearances. We conducted a prospective randomized trial to assess the benefits of a new disposable circumcision suture device (DCSD). A total of 942 patients were equally divided into three groups (conventional circumcision, Shang ring and disposable suture device group). Patients in the DCSD group were anesthetized with compound 5% lidocaine cream, the others with a 2% lidocaine penile block. Operation time, intra-operative blood loss, incision healing time, intra-operative and post-operative pain, the penile appearance and overall satisfaction degree were measured. Operation time and intra-operative blood loss were significantly lower in the Shang ring and suture device groups compared to the conventional group (P < 0.001). Intra-operative pain was less in the suture device group compared with the other two groups (P < 0.001); whereas post-operative pain was higher in the conventional group compared to the other two groups (P < 0.001). Patients in the suture device (80.57%) and Shang ring (73.57%) groups were more satisfied with penile appearances compared with the conventional circumcision group (20.06%, P < 0.05). Patients in suture device group also healed markedly faster than the conventional group (P < 0.01). The overall satisfaction rate was better in the suture device group (78.66%) compared with the conventional (47.13%) and Shang ring (50.00%) groups (P < 0.05). The combination of DCSD and lidocaine cream resulted in shorter operation and incision healing times, reduced intra-operative and post-operative pain and improved patient satisfaction with the cosmetic appearances.