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Abstract In the adult pancreas, the presence of progenitor or stem cells and their potential involvement in homeostasis and regeneration remains unclear. Here, we identify that SET domain-containing protein 4 (SETD4), a histone lysine methyltransferase, is expressed in a small cell population in the adult mouse pancreas. Genetic lineage tracing shows that during pancreatic development, descendants of SETD4+ cells make up over 70% of pancreatic cells and then contribute to each pancreatic lineage during pancreatic homeostasis. SETD4+ cells generate newborn acinar cells in response to cerulein-induced pancreatitis in acinar compartments. Ablation of SETD4+ cells compromises regeneration of acinar cells, in contrast to controls. Our findings provide a new cellular narrative for pancreatic development, homeostasis and response to injury via a small SETD4+ cell population. Potential applications may act to preserve pancreatic function in case of pancreatic disease and/or damage.

To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0–10.0 ng ml−1, 10.1–20.0 ng ml−1, and >20.0 ng ml−1, the ideal PZ-PSAD cut-off value for predicting clinically significant PCa was 0.019 ng ml−2, 0.297 ng ml−2, and 1.180 ng ml−2, respectively (sensitivity >90%). Compared with PSA, PSAD, and TZ-PSAD, the efficiency of PZ-PSAD for predicting PCa is the highest, leading to fewer missed diagnoses and unnecessary biopsies. [ABSTRACT FROM AUTHOR]

To cope with harsh environments, the Artemia shrimp produces gastrula embryos in diapause, a state of obligate dormancy, having cellular quiescence and suppressed metabolism. The mechanism behind these cellular events remains largely unknown. Here, we study the regulation of cell quiescence using diapause embryos of Artemia. We found that Artemia DEK (Ar-DEK), a nuclear factor protein, was down-regulated in the quiescent cells of diapause embryos and enriched in the activated cells of post-diapause embryos. Knockdown of Ar-DEK induced the production of diapause embryos whereas the control Artemia released free-swimming nuaplii. Our results indicate that Ar-DEK correlated with the termination of cellular quiescence via the increase in euchromatin and decrease in heterochromatin. The phenomena of quiescence have many implications beyond shrimp ecology. In cancer cells, for example, knockdown of DEK also induced a short period of cellular quiescence and increased resistance to environmental stress in MCF-7 and MKN45 cancer cell lines. Analysis of RNA sequences in Artemia and in MCF-7 revealed that the Wnt and AURKA signaling pathways were all down-regulated and the p53 signaling pathway was up-regulated upon inhibition of DEK expression. Our results provide insight into the functions of Ar-DEK in the activation of cellular quiescence during diapause formation in Artemia. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of a novel transurethral thulium laser vapoenucleation of the prostate with low-power conventional pulse mode (LP-ThuVEP) on sexual function in patients with benign prostatic hyperplasia (BPH)., Methods: 89 BPH patients admitted to Department of Urology, Jintan People's Hospital, Affiliated to Jiangsu University, from January 2022 to June 2023 were selected and randomly divided into the LP-ThuLEP group (45 cases) and the transurethral plasma kinetic resection of the prostate (TUPKRP) group (44 cases). Perioperative indicators were recorded, and the IPSS, Qmax, Qavg, PVR, and QoL of the two groups of patients before surgery and 3 months and 6 months after surgery were comparatively analyzed. The effect of surgery on male sexual function was evaluated through the International Index of Erectile Function-5 (IIEF-5) score and the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD) score., Results: Compared with the TUPKRP group, the LP-ThuVEP group had no statistically significant difference in operation time (P>0.05), but there were statistical differences in bladder irrigation time and indwelling urinary catheter time (P<0.05) and significant statistical differences in the decrease in hemoglobin on the day of surgery and the disappearance time of gross hematuria induced by defecation after surgery (P<0.001). The perioperative complications of the two groups were comparable. Among the urinary tract symptom indicators, the LP-ThuVEP group had statistically significant differences in IPSS score, QoL score, and PVR compared with the TUPKRP group 3 months after surgery (P<0.05). In terms of male sexual function, there was a statistical difference in IIEF-5 scores between the two groups at 3 months and 6 months after surgery (P<0.05); Except that there was no statistical difference in the ejaculation-related satisfaction scores between the two groups at 3 months after surgery (P>0.05), there had all significant statistical differences in ejaculation function and satisfaction scores between and within the groups at 3 months and 6 months after surgery (P<0.001)., Conclusion: Compared with TUPKRP, the LP-ThuVEP can also effectively relieve urinary tract obstruction caused by BPH and has the advantages of less damage and faster recovery of erectile function and ejaculatory function of patients.

To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml -1 , 10.1-20.0 ng ml -1 , and >20.0 ng ml -1 , the ideal PZ-PSAD cut-off value for predicting clinically significant PCa was 0.019 ng ml -2 , 0.297 ng ml -2 , and 1.180 ng ml -2 , respectively (sensitivity >90%). Compared with PSA, PSAD, and TZ-PSAD, the efficiency of PZ-PSAD for predicting PCa is the highest, leading to fewer missed diagnoses and unnecessary biopsies., Competing Interests: None

Benign prostatic hyperplasia (BPH) patients experience complications after surgery. We studied oxidative stress scavenging by porous Se@SiO 2 nanospheres in prostatic urethra wound healing after transurethral resection of the prostate (TURP). Beagle dogs were randomly distributed into two groups after establishing TURP models. Wound recovery and oxidative stress levels were evaluated. Re-epithelialization and the macrophage distribution at the wound site were assessed by histology. The mechanism by which porous Se@SiO 2 nanospheres regulated macrophage polarization was investigated by qRT-PCR, western blotting, flow cytometry, immunofluorescence and dual luciferase reporter gene assays. Our results demonstrated that Porous Se@SiO 2 nanosphere-coated catheters advance re-epithelization of the prostatic urethra, accelerating wound healing in beagle dogs after TURP, and improve the antioxidant capacity to inhibit oxidative stress and induced an M2 phenotype transition of macrophages at the wound. By restraining the function of reactive oxygen species (ROS), porous Se@SiO 2 nanospheres downregulated Ikk, IκB and p65 phosphorylation to block the downstream NF-κB pathway in macrophages in vitro. Since activation of NF-κB signaling cascades drives macrophage polarization, porous Se@SiO 2 nanospheres promoted macrophage phenotype conversion from M1 to M2. Our findings suggest that porous Se@SiO 2 nanosphere-coated catheters promote postoperative wound recovery in the prostatic urethra by promoting macrophage polarization toward the M2 phenotype through suppression of the ROS-NF-κB pathway, attenuating the inflammatory response. STATEMENT OF SIGNIFICANCE: The inability to effectively control post-operative inflammatory responses after surgical treatment of benign prostatic hyperplasia (BPH) remains a challenge to researchers and surgeons, as it can lead to indirect cell death and ultimately delay wound healing. Macrophages at the wound site work as pivotal regulators of local inflammatory response. Here, we designed and produced a new type of catheter with a coating of porous Se@SiO 2 nanosphere and demonstrated its role in promoting prostatic urethra wound repair by shifting macrophage polarization toward the anti-inflammatory M2 phenotype via suppressing ROS-NF-κB pathway. These results indicate that the use of porous Se@SiO 2 nanosphere-coated catheter may provide a therapeutic strategy for postoperative complications during prostatic urethra wound healing to improve patient quality of life., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the effect of creatine phosphate sodium (sodium phosphocreatine) on miRNA378, miRNA378 * and calumenin mRNA in adriamycin-injured suckling mouse myocardium., Methods: The suckling mouse myocardium of primary culture were randomly divided into control group, adriamycin group and treatment group. To identify the suckling mouse myocardium, Smooth muscle actin-α (α-SMA) was monitored by immunohistochemical method. Cardiac function was evaluated by transthoracic echocardiography. The mRNA change of miRNA378, miRNA378 * and calumenin mRNA were detected by quantitative real-time PCR. The expression of calumenin and GRP78 were identified by western blot., Results: Mitochondrial damage and vacuolization were found in adriamycin-induced suckling mouse myocardium compared with control group, while creatine phosphate sodium could reduce this phenomenon. Compared with the control group, the mRNA of miRNA378, miRNA378 * and calumenin in adriamycin group was reduced, while creatine phosphate sodium could increase this phenomenon. The expression of calumenin and GRP78 were decreased after adriamycin treatment in suckling mouse myocardiums, creatine phosphate sodium increased the expression of calumenin and GRP78., Conclusions: The results of this experiment might be closely related to the effects of that creatine phosphate sodium reduced the pathological mechanism of suckling mouse myocardium with myocarditis caused by adriamycin.

Objective: To explore the expression patterns of cadherins (N-cadherin and E-cadherin) in urothelial carcinomas and understand the values of N-E cadherin switch in the predictions of postoperative recurrence and prognosis., Methods: The expressions of N-cadherin and E-cadherin were measured by immunohistochemistry in 64 transurethral bladder tumor resection (TURBT) or partial cystectomy samples (48 cases) in 2005 by the method of streptavidin-biotin peroxidase., Results: A positive expression of N-cadherin and a negative expression of E-cadherin were noted in 27 (42.2%) and 16 (25.0%) specimens respectively. Patients with more poorly differentiated bladder cancer were accompanied with a higher expression of N-cadherin and a lower expression of E-cadherin (both P < 0.05). A positive expression of N-cadherin decreased the recurrence-free and cancer-related survival rates while a negative expression of E-cadherin was correlated with a lower cancer-related survival rate (all P < 0.05). No significant association was found between the expression of E-cadherin and the recurrence-free survival rate. Furthermore, the N-E cadherin switch (a negative expression of E-cadherin and a positive expression of N-cadherin) showed a higher predictive power in both recurrence-free and cancer-related survival according to multivariate analysis (HR = 0.428, 95%CI: 0.217 - 0.845, HR = 0.098, 95%CI: 0.013 - 0.767). No significant association was found between the expressions of two cadherins and postoperative progression., Conclusion: Although the expressions of E-cadherin and N-cadherin appear to be correlated with survival outcomes in bladder cancer, N-E cadherin switch may be a better predicator for postoperative recurrence and cancer-related survival.

Objective: To investigate the long-term efficacy of ureteral reconstruction with tubularized peritoneal free grafts for the treatment of avulsion of ureteral mucosa in animal models., Methods: The model of avulsion of ureteral mucosa was established in 12 adult dogs. Then they were divided into Group A (n = 6, length of avulsed mucosa at 4 cm) and Group B (n = 6, length of avulsed mucosa at 6 cm). And the tubularized peritoneal free grafts and ureteral stents were implanted into the injured ureters. The curative effect was observed by intravenous urethrogram (IVU) and histological examination at Week 24 post-operation., Results: Severe stenosis was observed by IVU in 1 dogs in Groups A and B respectively. In the remaining 10 dogs, IVU showed normal size and morphology of kidneys. There was no hydronephrosis. And no obvious stricture of ureteral part was observed for mucosa substitutes made of peritoneal free grafts. In all 10 dogs without stenosis of both groups, peritoneal membrane was replaced by integrated transitional epithelium. And there was no obvious stricture. Collagen fibers were arranged parallel to mucosal surface., Conclusion: For avulsion of ureteral mucosa under 6 cm, reconstruction with tubularized peritoneal free grafts as mucosa substitutes is an effective method. And its long-term efficacy is satisfactory.

Objective: To investigate the clinical and pathological features, diagnosis and treatment of cystic lymphangioma of the spermatic cord., Methods: One case of cystic lymphangioma of the spermatic cord in a 71-year-old patient was retrospectively analyzed and the relevant literature was reviewed., Results: The patient, presented with spermatic cord hydrocele, was treated by local excision of the tumor, which was pathologically diagnosed as cystic lymphangioma. No relapse was found during a 3-month follow-up after the operation., Conclusion: Lymphangioma of the spermatic cord is a benign tumor. Preoperation ultrasonography and CT are important for determining the location and nature of lymphangioma. Surgical excision is an effective option for the treatment of cystic lymphangioma of the spermatic cord.

Objective: To investigate the curative effects of different reconstruction methods in the treatment of avulsion of ureteral mucosa., Methods: Twenty adult dogs were randomly divided into 4 equal groups: Group III (control group in which the ureter was incised and a ureteral stent was placed therein), Group II (the ureter was incised and a ureteral mucosal avulsion about 5 cm in length was created and the avulsed mucosa was replaced to the original position and a ureteral stent was placed in addition), Group III (a piece of bladder mucosa was incised and grafted to the avulsed ureter mucosa and a ureteral stent was placed in addition), and Group IV (a tubularized peritoneal free graft and a ureteral stent were placed in the avulsed ureter). Ten weeks later intravenous pyelography (IVP) was conducted to observe the images of ureter. Then the dogs were killed and pathological examination of the reconstructed ureter was conducted., Results: IVP showed atresia and stenosis in all control group dogs. No obvious stenosis was observed in Groups II and IV. Pathological examination showed that the newly grown mucosa was similar to the normal ureter structure in Groups II and IV. In Group III one dog died, slight distension of ureter superior to the reconstructed part was found in 2 dogs, and no obvious stenosis was observed in 3 dogs., Conclusion: Orthotopic replacement and tabularized peritoneal free grafting with placement of ureter stent are effective in treatment of avulsion of ureter mucosa. Bladder mucosa can be used as selectable material.