Dongliang Xu

Autophagy plays key roles in the development of acute pancreatitis (AP) and the regulation of impaired autophagy has therapeutic potential. The objective of the present study was to investigate whether pharmacological inhibition of autophagy could ameliorate AP in mice and examine the underlying mechanisms. In current study, by imaging-based high-throughput screening, a novel spautin-1 derivative spautin-A41 was identified as a potent autophagy inhibitor. Mice treated with spautin-A41 were resistant to the cerulein-induced elevation of serum pancreatic enzyme activities and pancreatic apoptosis. Mechanistically, spautin-A41 effectively reduced the expression levels of Class III phosphatidylinositol 3 (PI3) kinase complexes and subsequently ameliorated pancreatitis by inhibiting the formation of autophagosome. Therefore, pharmacological inhibition of autophagy by spautin-A41 may serve as new target for treating or lessening the severity of AP.

This research aims to observe and compare the wound healing process of urethral bladder after transurethral holmium laser resection of bladder tumor (HoLRBT) and transurethral resection of bladder tumor (TURBT) and explore the possible mechanism of wound healing and bladder re-epithelialization after HoLRBT. An animal model of canine achieving HoLRBT and TURBT was established. Cystoscopy was performed at different time points (3 days and 1, 2, 3, and 4 weeks) after operation to observe the wound healing and re-epithelialization of bladder epithelium. Bladder mucosa specimens were obtained and histopathological changes of the bladder epithelium were observed under light microscope after HE staining. Immunochemistry was used to determine the cell expression ofCK5, CK14, EGF, EGFR; microRNA expressions of CK5, CK14, EGF, and EGFR were measured by qRT-PCR. The changes of urinary EGF concentration were detected by ELISA. The bladder epithelial wound was repaired and re-epithelialized at 1 week after HoLRBT. At the 4th week, the bladder wound was basically completed and re-epithelialized; repair of bladder epithelial wounds recapitulates the wounds with the proliferation and migration of residual epithelial cells under the wound and the bladder epithelium that proliferates alongside the wound surface to complete re-epithelialization. The process begins at 1 week after surgery and basically completes at 4 weeks after surgery. CK5 and CK14 positive cells were detected in the basal cells of the bladder epithelium after HoLRBT, and the expression of CK5 and CK14 mRNA in the basal cells of the bladder epithelium under hyperplasia was significantly higher than that of the normal bladder epithelial basal cells. Bladder epithelial wound repair of TURBT group was performed by the proliferative differentiation of the peri-bladder epithelium adjacent to the wound edge and crawled to the wound surface to complete the re-epithelialization process. The wound repair and re-epithelialization were significantly slower than HoLRBT group. The CK5 and CK14 positive cells can also be detected in the basal cells of marginal hyperplasia of basal margin, and the expression of CK5 and CK14 mRNA in the basal cells of the peri-bladder hyperplasia is obviously higher than that of the normal bladder epithelial basal cells. The expression of EGF in bladder regenerating epithelium gradually increased with time after HoLRBT. Bladder basal cells and bladder regenerating epithelium express high levels of EGFR after HoLRBT. The concentration of EGF in urine after HoLRBT and TURBT increased significantly after surgery, and peaked at 3 days after operation. The urinary EGF concentration in HoLRBT group was higher than that in TURBT group at 3 and 4 weeks after operation. The re-epithelialization process can be seen 1 week after the cystectomy with holmium laser cystectomy, and the epithelialization rate is faster than the traditional transection surgery. This is because the residual bladder epithelial stem cells and wound marginal epithelial cells are involved in the process of wound repair and re-epithelialization following HoLRBT. But only the marginal epithelial tissue participates in the re-epithelialization process after TURBT, so the repair rate of TURBT is slower. The repair of bladder epithelium after HoLRBT is related to the stimulation of tissue factor EGF. The regenerated bladder epithelium also participates in the wound repair process by means of autocrine of EGF.

Bladder cancer is currently considered the most common malignancy of the urinary tract. Thulium laser en bloc resection of bladder tumor (TmLRBT) and plasmakinetic transurethral resection of bladder tumor (PK-TURBT) are two alternative common procedures used in our department to manage patients with primary non-muscle invasive bladder cancer (NMIBC) over the past decade. In this work, the safety and efficacy of TmLRBT were retrospectively compared to those of PK-TURBT in patients with primary NMIBC. From January 2013 to December 2015, 256 patients diagnosed with primary NMIBC were selected for this retrospective study. A total of 136 consecutive patients diagnosed with primary NMIBC were enrolled in the TmLRBT group. A similar historical cohort of 120 consecutive patients who underwent PK-TURBT was used to compare the two procedures. Clinical data, including age, gender, tumor characteristics, operation duration, hospitalization, irrigation, catheterization, and intraoperative and postoperative complications, were recorded. There were no significant differences in age, gender, mean tumor size, mean tumor number, tumor location, or risk between the TmLRBT and PK-TURBT groups. The TmLRBT group was associated with a significantly shorter operation duration (25.96 ± 21.19 min vs 37.18 ± 25.77 min, P = 0.018) and a shorter hospitalization time (3.11 ± 1.05 days vs 5.24 ± 2.06 days, P = 0.036). The postoperative irrigation time (6.33 ± 4.05 h vs 14.76 ± 6.28 h, P = 0.027) and catheterization time (2.03 ± 1.61 days vs 4.27 ± 1.17 days, P = 0.035) in the TmLRBT group were lower than those in the PK-TURBT group. No significant differences in fever and rebleeding were found in the TmLRBT and PK-TURBT groups. There were no significant differences in the overall, low-risk, intermediate-risk, and high-risk recurrence-free rates between the two groups (P = 0.43, P = 0.68, P = 0.71, and P = 0.24, respectively). The proportion of bladder detrusor muscle (BDM) identified in pathologic specimens of the TmLRBT group was higher than that in the PK-TURBT group (P = 0.006). TmLRBT may reduce operation duration time, hospitalization time, postoperative irrigation time, and catheterization time. TmLRBT is considered safer and more effective in treating primary NMIBC. Recurrence-free rates did not differ between groups.

Significant amount of bone mass is lost during the process of aging due to an imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption in bone marrow microenvironment, which leads to net bone loss in the aging population, resulting in the pathogenesis of osteoporosis. Firstly, differences in proliferative capacity of adipocyte or adipogenic differentiation in mouse mesenchymal stem cells (MMSCs) and senile mouse model-derived bone marrow mesenchymal stem cells (SMMSCs), as well as mRNA expression of OGN and PPARγ2 were observed. Secondly, osteogenic abilities of MMSCs and SMMSCs treated with rosiglitazone (a PPARγ2 agonist) to induce osteogenic changes were observed, and negative correlation of PPARγ2 with OGN was evaluated. Thirdly, the role of SMMSCs in promoting osteogenesis was examined through enhancing expression of OGN; besides, the related mechanism was investigated by means of expression of related adipocyte and osteoblast specific genes. Forced OGN expression by OGN-infected lentivirus could increase expression of Wnt5b, RUNX2, OCN, ALP and Colla1, as well as bone formation, while decreases expression of adipogenesis marker PPARγ2. It resulted in expression inhibition of adipocyte genes such as adipocytic differentiation related genes adipocyte binding protein 2 (aP2) and osteoclast differentiation factor Rankl in bone marrow, giving rise to increased bone mass. OGN may plays a significant role in osteoporosis, which may also provide a potential target for therapeutic intervention of senile osteoporosis characterized by altered differentiation of BMSCs into osteoblasts and adipocytes.

Objective To compare intra-arterial chemotherapy combined with intravesical chemotherapy with intravesical chemotherapy alone in the treatment of high-risk non-muscle invasive bladder cancer (HRBC) after thulium laser resection of a bladder tumor (TmLRBT).

To investigate the feasibility and effectiveness of three-dimensional laparoscopic partial nephrectomy with selective segmental artery clamping (3D-LPNSSAC) comparing with the conventional two-dimensional laparoscopic partial nephrectomy (2D-LPN). Between November 2012 and March 2014, 90 patients with cT1 renal tumor at Shanghai General Hospital were enrolled in our study, which were randomly divided into two groups: the 3D-LPNSSAC group (n = 45) and 2D-LPN group (n = 45). The perioperative variables, including operative time, dissecting time, suturing time, blood loss, warm ischemia time (WIT), preoperative and postoperative renal functions, were recorded and analyzed. In addition, the oncological outcomes and complications were also evaluated. All the LPNs were performed successfully without conversion to radical nephrectomy or open surgery, only three cases were converted to total renal artery clamping during 3D-LPNSSAC. There were no significant differences in operative time and dissecting time between the groups, while the suturing time was shorter during 3D-LPNSSAC (P < 0.01). The technique was associated with higher blood loss (P < 0.01). The technique of 3D-LPNSSAC significantly reduced WIT (P = 0.04), and better postoperative ipsilateral renal function could be obtained during 3D-LPNSSAC (P < 0.01). During a mean follow-up time of 16.8 months (range 5.5–22.5 months), the complication rate was 8.8 % (8/90) and no tumor reoccurrence was detected. 3D-LPNSSAC is a feasible and safe technique for treating selective renal tumors, presenting with the beneficial clinical outcomes of reduced suturing time, shorter WIT and better postoperative ipsilateral renal function.

To assess the efficacy and safety of thulium laser versus standard transurethral resection of the prostate (TURP) for treating patients with benign prostatic obstruction. A systematic search of the electronic databases, including Medline, Embase, Web of Science, and The Cochrane Library, was performed up to February 1, 2014. The pooled estimates of demographic and clinical baseline characteristics, perioperative variables, complications, and postoperative efficacy including International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), and postvoid residual (PVR) were calculated. Seven trials assessing thulium laser versus standard TURP were considered suitable for meta-analysis including four randomized controlled trials (RCTs) and three non-RCTs. Compared with TURP, although thulium laser prostatectomy (TmLRP) needed a longer operative time [weighted mean difference (WMD) 8.18 min; 95 % confidence interval (CI) 1.60–14.75; P = 0.01], patients having TmLRP might benefit from significantly less serum sodium decreased (−3.73 mmol/L; 95 % CI −4.41 to −3.05; P < 0.001), shorter time of catheterization (WMD −1.29 days; 95 % CI −1.95 to −0.63; P < 0.001), shorter length of hospital stay (WMD −1.83 days; 95 % CI −3.10 to −0.57; P = 0.005), and less transfusion (odds ratio 0.09; 95 % CI 0.02–0.41; P = 0.002). During the 1, 3, and, 12 months of postoperative follow-up, the procedures did not demonstrate a significant difference in IPSS, QoL, Qmax, and PVR. TmLRP had a similar efficacy to standard TURP in terms of IPSS, QoL, Qmax, and PVR, and offered several advantages over TURP in terms of blood transfusion, serum sodium decreased, catheterization time, and hospital stay, while TURP was superior in terms of operation duration. Well-designed multicentric/international RCTs with long-term follow-up are still needed.

The purpose of the study was to evaluate the efficacy of circumcision combined with antibiotic, anti-inflammatory, and α-blocker therapy for the treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Subjects assigned to the circumcision group were given antibiotic, anti-inflammatory, and α-blocker medications and scheduled for surgery the same period in each site by study clinicians. Subjects assigned to the control group were asked to only take the same medications and remain uncircumcised until the end of the 3-month study period. The primary outcome was a reduction of at least four points on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). A total of 774 eligible participants underwent randomization, and the ratio of men with a decrease of at least four points on the total NIH-CPSI score from baseline to 12 weeks was 84.6 % in the circumcision group and 68.5 % in the control group (P < 0.001). Of the 713 men who completed the trial, the median total NIH-CPSI score decreased significantly from 21.0 ± 7.0 to 12.0 ± 8.0 (P < 0.001) in the circumcision group, and in the control group, the change was from 21.0 ± 8.0 to 15.0 ± 7.0 (P < 0.001). Comparison of the changes in the total and three subdomain NIH-CPSI scores over time revealed significant differences between the circumcision and control groups (P < 0.001). Our findings show that circumcision plus antibiotic, anti-inflammatory, and α-blocker therapy for CP/CPPS patients resulted in improved NIH-CPSI scores compared with medication therapy only.

Osteopontin (OPN) is highly correlated with cyclosporine A (CsA) nephrotoxicity. As epithelial‐to‐mesenchymal transition (EMT) of renal tubular epithelial cells plays an important role in CsA nephropathy, we investigated whether OPN mediated EMT of renal tubular epithelial cells upon CsA stimulation. OPN knockdown suppresses CsA induced EMT on NRK52E cells, and it also attenuates downregulation of E‐cadherin and upregulation of α‐smooth muscle actin (α‐SMA) and fibronectin (FN) that are induced by CsA. OPN alone can induce EMT on NRK52E cells, which also results in upregulation of TGF‐β1. Thus, OPN is a causative factor in mediating CsA induced EMT on NRK52E cells.