A nomogram for predicting risk factors of testicular salvage after testicular torsion in children.

OBJECTIVES: This study aimed to establish a nomogram for predicting the probability of testicular salvage after testicular torsion in children. METHODS: We retrospectively collected data of children with testicular torsion who were treated at Shenzhen Children's Hospital between September 2005 and August 2022. Of the training cohort, 113 patients who underwent orchiectomy and five with testicular atrophy after orchiopexy were included in the failed testicular salvage group. Additionally, 37 patients who underwent orchiopexy without postoperative testicular atrophy were included in the successful testicular salvage group. The predictive factors affecting testicular salvage were determined using univariate and multivariate logistic regression analyses; a nomogram was constructed. The nomogram was verified using data from the validation group. RESULTS: Using multivariate logistic regression analysis, the independent risk factors of testicular salvage after testicular torsion were symptom duration (p = 0.034), intratesticular blood flow (p = 0.003), spermatic cord torsion degree (p = 0.037), and monocyte count (odds ratio: 0.012, p = 0.036). A nomogram was established based on these four risk factors. In the training cohort, the area under the receiver operating characteristic curve was 0.969. The area under the receiver operating characteristic curve of the verification cohort was 0.965, indicating good discrimination ability of the nomogram. Increased symptom duration without intratesticular blood flow increased the monocyte count and spermatic cord torsion degree and decreased the success rate of testicular salvage. CONCLUSION: This prediction model could obtain the corresponding probability of testicular salvage according to the clinical characteristics of different patients with testicular torsion, providing reference for clinicians and parents.

SAVE Testis-sparing score: a multicenter retrospective study of a novel predictive tool for quantifying testicular tumors.

BACKGROUND: Testis-sparing surgery (TSS) is a safe treatment for patients with benign testicular tumors. Presently, assessments for evaluating the suitability of TSS are poorly standardized, partially because testicular anatomical elements cannot be quantitatively described. MATERIALS AND METHODS: The authors developed a scoring method known as the SAVE testis-sparing score based on four critical and accessible anatomical features of a testicular tumor. The SAVE score ranges from 0 to 8 and is divided into four risk classes ( low , medium , high , and extremely high ) to evaluate the feasibility of TSS, wherein low-risk indicates high feasibility and vice versa. This study included 444 testicular tumor patients from eight centers. Among them, 216 patients (model group: 151 patients, validation group: 65 patients) were included in the modeling analysis, and the other 228 patients from children's centers were included in the proportion analysis. Using retrospective data, patient characteristics associated with surgical methods were identified. Furthermore, a multivariate logistic regression model was built quantify the associations between these characteristics and the surgery method. The receiver operator characteristic curve was used to evaluate the classification efficiency of SAVE. RESULTS: The SAVE testis-sparing score includes size (tumor size as maximal diameter), available testicular tissue volume, volume ratio of the tumor to the testis, and the exophytic / endophytic properties of the tumor. The SAVE scoring system accurately classified the suitability of TSS based on the complexity of benign testicular tumors. CONCLUSION: The SAVE score is a reproducible and robust tool for quantitatively describing the anatomical characteristics of benign testicular tumors and guide the preoperative evaluation of TSS.

Predictive value of hematological parameters in testicular salvage: A 12-year retrospective review.

Purpose: This study aimed to evaluate the predictive value of preoperative hematological parameters for testicular salvage in patients with testicular torsion. Methods: Clinical data of patients with testicular torsion treated at Shenzhen Children's Hospital from January 2010 to December 2021 were analyzed retrospectively. The data collected included age, symptom duration, degree of spermatic cord torsion, the surgical approach adopted, hematological parameters, and ultrasound results during postoperative follow-up. Results: The study participants were classified into three groups as follows: the successful testicular salvage group (n = 43), failed testicular salvage group (n = 124), and control group (n = 100). Univariate analysis showed that testicular salvage was related to patient age, duration of symptoms, spermatic cord torsion degree, white blood cell count, lymphocyte count, monocyte count, platelet-lymphocyte ratio, and neutrophil-lymphocyte ratio. However, multivariate analysis revealed that symptom duration (OR = 0.948, P < 0.001), degree of spermatic cord torsion (OR = 0.994, P < 0.001), and monocyte count (OR = 0.020, P = 0.011) were independent risk factors for testicular torsion salvage. The monocyte count in the failed salvage group was significantly higher than in the successful salvage and control groups (P < 0.01). Conclusion: Monocyte count is an independent predictor of testicular salvage. Therefore, clinicians can predict the success rate of testicular salvage in patients with testicular torsion based on the monocyte count.

Diagnosis and treatment of cryptorchid testicular torsion in children: A 12-year retrospective study.

Purpose: To investigate the clinical characteristics, treatment, and prognosis of cryptorchid testicular torsion in children. Methods: The clinical data of 25 children who received treatment for cryptorchid testicular torsion between January 2010 and December 2021 were retrospectively reviewed. The median age of the patients was 64.5 months (range: 2 months to 15 years). All patients had unilateral torsion, and the duration of symptoms ranged from 3 to 192 h. Results: Among the 25 patients, five underwent orchidopexy, while the remaining 20 underwent orchiectomy. After 6 months to 8 years of follow up, the 20 patients who had undergone orchiectomy had a well-developed testis on the healthy side. Four of the five patients who had undergone orchidopexy of the affected testis had well-developed testes bilaterally, while one experienced testicular atrophy. Conclusion: Cryptorchid testicular torsion is a rare urological emergency that displays a delayed presentation and is often misdiagnosed. Clinicians need to carefully review the patient's medical history and ultrasound findings and perform a thorough physical examination to make a correct diagnosis. Active testicular exploration is required for patients suspected to have cryptorchid testicular torsion, and the decision to perform orchidopexy or orchiectomy depends on the intraoperative situation.

Single-port laparoscopic percutaneous extraperitoneal internal ring closure for paediatric inguinal hernia using a needle grasper.

BACKGROUND: Single-site laparoscopic percutaneous extraperitoneal closure has been widely used for the repair of paediatric inguinal hernia. In this study, we aimed to introduce the usage of a needle grasper in single-port laparoscopic herniorrhaphy in children. METHODS: In our study, 447 children with inguinal hernia underwent single-port laparoscopic percutaneous extraperitoneal closure between October 2018 and October 2021 in Shenzhen Children' hospital were retrospectively reviewed. RESULTS: Among 447 patients, there were 396 males and 51 females with a mean age of 2.24 ± 0.36 years. A contralateral patent processus vaginalis was present in 165 unilateral hernia patients. All patients underwent laparoscopic percutaneous extraperitoneal closure successfully without converting to open operation. The mean operating time in unilateral and bilateral hernia patients were 10.23 ± 2.25 mine and 14.54 ± 2.81 mine respectively. One patient had subcutaneous emphysema, two male patients had inguinal hernia recurrence and none had complications such as hydrocele and testicular atrophy. Additional 0.3 cm port was done in 4 cases. The mean follow-up time was 22.36 ± 4.56 months. CONCLUSIONS: Single-port laparoscopic percutaneous extraperitoneal closure of paediatric inguinal hernia using a needle grasper is a feasible and safe procedure. It has the advantages of fewer skin surgical incisions, short operating time, low complication and low recurrence rate.

Association between winter season and desmopressin treatment efficiency in children with monosymptomatic nocturnal enuresis: a pilot study

ABSTRACT Objectives: The purpose of our study was to assess the association between the winter season and desmopressin treatment failure in South Chinese children with monosymptomatic nocturnal enuresis (MNE). Materials and Methods: A retrospective study was conducted to analyze the clinical data of children with monosymptomatic nocturnal enuresis who have visited our urology clinic from January to December 2019. All patients received desmopressin treatment. Final treatment outcomes were categorized as successful (complete response) or failed (absent and partial response). The relationship between winter season and treatment response to desmopressin was evaluated. Additionally, associated risk factors were investigated with both univariate and multivariate regression analysis. Results: In total, 393 patients diagnosed with MNE were included in the present study. There were no statistically significant differences in pretreatment variables at first visit between patients who visited the clinic in winter and those who did so in other seasons. However, the treatment failure rate of MNE in the winter season was higher than that of other seasons (77.50% vs. 52.74%). Multivariate logistic regression analysis demonstrated that the severity of symptoms and an initial clinic visit in the winter season were significantly related to desmopressin treatment failure in MNE patients. Conclusion: Winter season and severity of symptoms are two risk factors associated with desmopressin treatment failure in MNE patients.

Association between winter season and desmopressin treatment efficiency in children with monosymptomatic nocturnal enuresis: a pilot study.

OBJECTIVES: The purpose of our study was to assess the association between the winter season and desmopressin treatment failure in South Chinese children with monosymptomatic nocturnal enuresis (MNE). MATERIALS AND METHODS: A retrospective study was conducted to analyze the clinical data of children with monosymptomatic nocturnal enuresis who have visited our urology clinic from January to December 2019. All patients received desmopressin treatment. Final treatment outcomes were categorized as successful (complete response) or failed (absent and partial response). The relationship between winter season and treatment response to desmopressin was evaluated. Additionally, associated risk factors were investigated with both univariate and multivariate regression analysis. RESULTS: In total, 393 patients diagnosed with MNE were included in the present study. There were no statistically significant differences in pretreatment variables at first visit between patients who visited the clinic in winter and those who did so in other seasons. However, the treatment failure rate of MNE in the winter season was higher than that of other seasons (77.50% vs. 52.74%). Multivariate logistic regression analysis demonstrated that the severity of symptoms and an initial clinic visit in the winter season were significantly related to desmopressin treatment failure in MNE patients. CONCLUSION: Winter season and severity of symptoms are two risk factors associated with desmopressin treatment failure in MNE patients.

MicroRNA-302b mitigates renal fibrosis via inhibiting TGF-ß/Smad pathway activation.

Renal fibrosis is one of the most significant pathological changes after ureteral obstruction. Transforming growth factor-ß (TGF-ß) signaling pathway plays essential roles in kidney fibrosis regulation. The aims of the present study were to investigate effects of microRNA-302b (miR-302b) on renal fibrosis, and interaction between miR-302b and TGF-ß signaling pathway in murine unilateral ureteral obstruction (UUO) model. Microarray dataset GSE42716 was downloaded by retrieving Gene Expression Omnibus database. In accordance with bioinformatics analysis results, miR-302b was significantly down-regulated in UUO mouse kidney tissue and TGF-ß1-treated HK-2 cells. Masson's trichrome staining showed that miR-302b mimics decreased renal fibrosis induced by UUO. The increased mRNA expression of collagen I and α-smooth muscle actin (α-SMA) and decreased expression of E-cadherin were reversed by miR-302b mimics. In addition, miR-302b up-regulation also inhibited TGF-ß1-induced epithelial mesenchymal transition (EMT) of HK-2 cells by restoring E-cadherin expression and decreasing α-SMA expression. miR-302b mimics suppressed both luciferase activity and protein expression of TGF-ßR2. However, miR-302b inhibitor increased TGF-ßR2 luciferase activity and protein expression. Meanwhile, miR-302b mimics inhibited TGF-ßR2 mRNA expression and decreased Smad2 and Smad3 phosphorylation in vivo and in vitro. Furthermore, over-expression of TGF-ßR2 restored the miR-302b-induced decrease of collagen I and α-SMA expression. In conclusion, this study demonstrated that miR-302b attenuated renal fibrosis by targeting TGF-ßR2 to suppress TGF-ß/Smad signaling activation. Our findings showed that elevating renal miR-302b levels may be a novel therapeutic strategy for preventing renal fibrosis.

MicroRNA-302b mitigates renal fibrosis via inhibiting TGF-ß/Smad pathway activation

Renal fibrosis is one of the most significant pathological changes after ureteral obstruction. Transforming growth factor-β (TGF-β) signaling pathway plays essential roles in kidney fibrosis regulation. The aims of the present study were to investigate effects of microRNA-302b (miR-302b) on renal fibrosis, and interaction between miR-302b and TGF-β signaling pathway in murine unilateral ureteral obstruction (UUO) model. Microarray dataset GSE42716 was downloaded by retrieving Gene Expression Omnibus database. In accordance with bioinformatics analysis results, miR-302b was significantly down-regulated in UUO mouse kidney tissue and TGF-β1-treated HK-2 cells. Masson's trichrome staining showed that miR-302b mimics decreased renal fibrosis induced by UUO. The increased mRNA expression of collagen I and α-smooth muscle actin (α-SMA) and decreased expression of E-cadherin were reversed by miR-302b mimics. In addition, miR-302b up-regulation also inhibited TGF-β1-induced epithelial mesenchymal transition (EMT) of HK-2 cells by restoring E-cadherin expression and decreasing α-SMA expression. miR-302b mimics suppressed both luciferase activity and protein expression of TGF-βR2. However, miR-302b inhibitor increased TGF-βR2 luciferase activity and protein expression. Meanwhile, miR-302b mimics inhibited TGF-βR2 mRNA expression and decreased Smad2 and Smad3 phosphorylation in vivo and in vitro. Furthermore, over-expression of TGF-βR2 restored the miR-302b-induced decrease of collagen I and α-SMA expression. In conclusion, this study demonstrated that miR-302b attenuated renal fibrosis by targeting TGF-βR2 to suppress TGF-β/Smad signaling activation. Our findings showed that elevating renal miR-302b levels may be a novel therapeutic strategy for preventing renal fibrosis.

Epigenetic inactivation of the candidate tumor suppressor gene ASC/TMS1 in human renal cell carcinoma and its role as a potential therapeutic target.

This study investigated the epigenetic alteration and biological function of the pro-apoptotic gene ASC/TMS1 in renal cell carcinoma. ASC/TMS1 was downregulated in five out of six RCC cell lines. A significant downregulation was also detected in sixty-seven paired renal tumors compared with adjacent non-cancerous tissues. The downregulation of ASC/TMS1 was correlated with promoter hypermethylation and could be restored with demethylation treatment. Re-expression of ASC/TMS1 in silenced RCC cell lines inhibited cell viability, colony formation, arrested cell cycle, induced apoptosis, suppressed cell invasion and repressed tumorigenicity in SCID mice. The antitumorigenic function of ASC/TMS1 in renal cancer was partially regulated by activation of p53 and p21 signaling. In addition, restoration of ASC/TMS1 sensitizes RCC cells to DNA damaging agents. Knockdown of ASC/TMS1 reduced DNA damaging agents-induced p53 activation and cell apoptosis. Moreover, ASC/TMS1 hypermethylation was further detected in 41.1% (83/202) of RCC tumors, but only 12% in adjacent non-cancerous tissues. ASC/TMS1 methylation was significantly correlated with higher tumor nuclear grade. In conclusion, ASC/TMS1 is a novel functional tumor suppressor in renal carcinogenesis. ASC/TMS1 tumor specific methylation may be a useful biomarker for designing improved diagnostic and therapeutic strategies for RCC.

Frequent epigenetic suppression of tumor suppressor gene glutathione peroxidase 3 by promoter hypermethylation and its clinical implication in clear cell renal cell carcinoma.

The goal of this study is to identify novel tumor suppressor genes silenced by promoter methylation in clear cell renal cell carcinoma (ccRCC) and discover new epigenetic biomarkers for early cancer detection. Reactive oxygen species (ROS) is a major cause of DNA damage that correlates with cancer initiation and progression. Glutathione peroxidase 3 (GPX3), the only known extracellular glycosylated enzyme of GPXs, is a major scavenger of ROS. GPX3 has been identified as a tumor suppressor in many cancers. However, the role of GPX3 in ccRCC remains unclear. This study aimed to investigate its epigenetic alteration in ccRCC and possible clinicopathological association. In our study, GPX3 methylation and down-regulation were detected in 5 out of 6 ccRCC cell lines and the GPX3 mRNA and protein expression level in ccRCC tumors was significantly lower than in adjacent non-malignant renal tissues (p<0.0001). Treatment with 5-Aza-2'-deoxycytidine restored GPX3 expression in ccRCC cells. Aberrant methylation was further detected in 77.1% (162/210) of RCC primary tumors, but only 14.6% (7/48) in adjacent non-malignant renal tissues. GPX3 methylation status was significantly associated with higher tumor nuclear grade (p=0.014). Thus, our results showing frequent GPX3 inactivation by promoter hypermethylation in ccRCC may reveal the failure in the cellular antioxidant system in ccRCC and may be associated with renal tumorigenesis. GPX3 tumor specific methylation may serve as a biomarker for early detection and prognosis prediction of ccRCC.

Urothelial carcinoma of the bladder in patients aged 30 years or younger: clinicopathological analysis and expression of fibroblast growth factor receptor 3 (FGFR3) of 45 cases.

The aim of this study was to demonstrate the clinicopathological features, prognostic outcomes and fibroblast growth factor receptor 3 (FGFR3) protein expression status of a large series (n = 45) of urothelial carcinoma of bladder patients aged 30 or younger, retrospectively. We identified an age gradient (an age of 25, 26 and 27 years), classified patients as ≤ 25 or >25, ≤ 26 or >26, ≤ 27 or >27 years, respectively, and compared variables including recurrence events and FGFR3 expression patterns between different groups. Patients aged 25 years or younger were less likely to experience tumor recurrence (p = 0.046), were more likely to develop smaller size tumors (p = 0.040) and expressed more proportion of negative pattern of FGFR3 protein (p = 0.036). Patients aged 25 years or younger were less likely to develop tumor recurrence and revealed more proportion of negative pattern of FGFR3 expression than those aged 26-30 years did. We identified patients aged 25 years or younger as the true "young" urothelial carcinoma patients, carrying distinct clinical outcomes and molecular tumorigenesis.

Low intraprostatic DHT promotes the infiltration of CD8+ T cells in BPH tissues via modulation of CCL5 secretion.

Clinical studies suggested thatandrogen might be associated with infiltrating T cells in prostate of benign prostatic hyperplasia (BPH) patients, but detail of T-cell subset and mechanism still remained unclear. The present study tested the hypothesis that intraprostatic 5 α -dihydrotestosterone (DHT) exerts effects on T cells recruitment by BPH epithelial cells. Prostate tissues from 64 cases of BPH patients after transurethral resection of prostate (TURP) were divided into 2 groups: (1) no medication history; (2) administration of 5 α -reductase type II inhibitor-finasteride 5 mg daily for at least 6 months before surgery. Group 2 presented significantly higher CD8+ T cells infiltration than group 1, but no changes in CD4+ T cells (immunohistochemistry and flow cytometry). In vitro study more CD8+ T cell migrated to the prostate tissue lysates from group 2 and BPH-1 cells in low DHT condition. Transcription of chemokine (C-C motif) Ligand 5 (CCL5) mRNA in BPH-1 cells and chemokine (C-C motif) receptor 5 (CCR5) mRNA in CD8+ T cells were upregulated in low DHT condition (q-PCR). CCL5 expression was also identified to be higher in group 2 prostate tissues by IHC. This study suggested that intraprostatic DHT may participate in regulating inflammatory response which was induced by human prostatic epithelial cell, via modulating CCL5 secretion.

Saturated fatty acids up-regulate COX-2 expression in prostate epithelial cells via toll-like receptor 4/NF-κB signaling.

Cyclooxygenase-2 (COX-2) has been implicated in prostate carcinogenesis, and recently it has been confirmed to be a molecular target of saturated fatty acids (SFAs). In the present study, we investigated the effect of stearic acid (SA) and palmitic acid (PA), two of the most abundant SFAs contained in dietary fat, on COX-2 expression in prostate epithelial cells and the signaling transduction pathway involved. First, we demonstrated that both SA and PA increased the mRNA and protein expression of COX-2, and consistently induced the activation of NF-κB in RWPE-1, BPH-1 and PC-3 prostate epithelial cell lines. The effect of SA and PA on COX-2 over-expression and NF-κB activation was in a dose-dependent manner, and PA was more potent than SA at the same concentration. Then, we demonstrated inhibition of NF-κB using its specific inhibitor strikingly attenuated PA-induced COX-2 expression. Toll-like receptor 4 (TLR4) was revealed to be expressed on RWPE-1, BPH-1 and PC-3 cell lines by PCR and immunofluorescence staining, and blocking its signaling significantly inhibited PA induced COX-2 over-expression and NF-κB activation. Taken together, we demonstrated that SFAs can up-regulate COX-2 expression in prostate epithelial cells, and this effect was mediated mainly through the TLR4/NF-κB signaling pathway.