TR4 worsen urosepsis by regulating GSDMD.

BACKGROUND: Urosepsis is a life-threatening organ disease in which pathogenic microorganisms in the urine enter the blood through the vessels, causing an imbalance in the immune response to infection. The aim of this study was to elucidate the role of testicular orphan receptor 4 (TR4) in urosepsis. METHODS: The role of TR4 in the progression and prognosis of urosepsis was confirmed by analyzing data from online databases and clinical human samples. To mimic urosepsis, we injected E. coli bacteria into the renal pelvis of mice to create a urosepsis model. Hematoxylin and eosin staining was used to observe histopathological changes in urosepsis. The effects of the upregulation or downregulation of TR4 on macrophage pyroptosis were verified in vitro. Chromatin immunoprecipitation assay was used to verify the effect of TR4 on Gasdermin D (GSDMD) transcription. RESULTS: TR4 was more highly expressed in the nonsurviving group than in the surviving group. Furthermore, overexpressing TR4 promoted inflammatory cytokine expression, and knocking down TR4 attenuated inflammatory cytokine expression. Mechanistically, TR4 promoted pyroptosis by regulating the expression of GSDMD in urosepsis. Furthermore, we also found that TR4 knockdown protected mice from urosepsis induced by the E. coli. CONCLUSIONS: TR4 functions as a key regulator of urosepsis by mediating pyroptosis, which regulates GSDMD expression. Targeting TR4 may be a potential strategy for urosepsis treatment.

Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2.

Testicular nuclear receptor 4 (TR4) is a member of the nuclear hormone receptor family and acts as a ligand-activated transcription factor and functions in many biological processes, such as development, cellular differentiation, and homeostasis. Recent studies have shown that TR4 plays an important role in prostate cancer, renal cell carcinoma, and hepatocellular carcinoma; however, its potential link to bladder cancer (BC) remains unknown. This study found that bladder cancer exhibited a higher expression of TR4 compared to normal tissues. Overexpressed TR4 promoted the bladder cancer cell proliferation, and knocked down TR4 with TR4-siRNA suppressed the bladder cancer cell proliferation. Mechanistic studies reveal that TR4 functions by altering the expression of Bcl-2 to regulate apoptosis in bladder cancer cells. Furthermore, knocking down Bcl-2 reversed the BC proliferation induced by TR4. In vivo, we also confirmed that TR4 knockdown mice (TR4+/-) showed slower bladder cancer growth than wild-type mice (TR4+/+) induced by the carcinogenic chemicals. Moreover, TR4+/- mice showed a lower grade of histopathology than the control group. In conclusion, these results indicate that TR4 plays a key role in bladder cancer proliferation, and targeting TR4 would probably be a potential strategy for bladder cancer treatment.

Proteomic Signature of Urosepsis: From Discovery in a Rabbit Model to Validation in Humans.

Urosepsis after upper urinary tract endoscopic lithotripsy (UUTEL) may cause uroseptic shock with high mortality, which can be prevented if early diagnosis and timely intervention are implemented with help of a diagnostic protein panel. The plasma of five rabbits of uroseptic shock and five controls was subjected to exploratory proteomics to search biomarker candidates from proteomic profiles related to uroseptic shock. Then, plasma from 21 nonsepsis and 20 urosepsis patients according to European diagnostic criteria of sepsis was enrolled in the validation study via targeted proteomics. Changes in a massive number of plasma proteins, mainly enriched in immune regulation, coagulation, structural repair, and transport activity, were observed in the rabbit model of septic shock. Fifteen proteins were identified as differential expression proteins between sepsis and nonsepsis patients. A diagnostic model composed of three proteins lipopolysaccharide-binding protein (LBP), clusterin (CLU), and vascular cell adhesion protein 1 (VCAM1) was developed for the early detection (2 hours postoperatively) of urosepsis after UUTEL, with a high area under the receiver operating characteristic (ROC) curve of 0.921. In conclusion, changes in the proteomic profile may reflect the underlying biological mechanisms during the development of urosepsis and produce diagnostic biomarkers for the early detection of urosepsis after UUTEL.

Complete urethral injury in the penile fracture: a case report and literature review.

Penile fracture is described as a traumatic rupture of the tunica albuginea caused by blunt injury to the erect penis. It usually occurs as a single rupture of the tunica albuginea in one of two corpora cavernosa; a rupture with urethral injury is an extremely rare condition. Although its diagnosis is usually clinical, ultrasound plays an important role in confirming diagnosis and identifying the site of the injury. Here, we presented a case of penile fracture with complete urethral injury. A 43-year-old male was admitted to the hospital because of trauma to the genital and dysuria following sexual intercourse. After admission, the patient was diagnosed with double penile fracture and complete urethral injury after the physical and B-ultrasound examinations. Emergency surgery to remove the hematoma and repair the urethra was performed. The patient recovered smoothly and was discharged on the third day after operation. After two months' follow-up, the patient urinated smoothly and achieved an adequate erection without other complications. In this case, consistent with previous studies, emergency surgery for penile fracture is necessary and can preserve the urethral function and sexual function. In addition, there are two lesions in tunica albuginea in this case, so careful search for the penile shaft during the surgery is important to avoid the missed injuries. This report provides evidence of an uncommon and underreported clinical case.

Inadvertent insertion of nephrostomy tube into the renal vein following percutaneous nephrolithotomy: A case report and literature review.

Percutaneous nephrolithotomy (PCNL) is an effective and well accepted procedure for the treatment of large and complex renal calculi. We encountered a patient with a misplaced percutaneous nephrostomy drainage tube (PNDT) into the contralateral renal vein resulting thrombus formation after undergoing right side PCNL. We placed a temporary filter to prevent embolism and started anti-coagulation therapy immediately and finally the PNDT was removed without bleeding.

Laparoscopic nephrectomy outside gerota fascia and en bloc ligation of the renal hilum for management of inflammatory renal diseases

ABSTRACT Objectives This study aims to improve laparoscopic nephrectomy techniques for inflammatory renal diseases (IRD) and to reduce complications. Materials and Methods Thirty-three patients underwent laparoscopic nephrectomy for IRD, with a method of outside Gerota fascia dissection and en-bloc ligation and division of the renal pedicle. Operative time, blood loss, complications, analgesia requirement, post-operative recovery of intestinal function and hospital stay were recorded. The degrees of perinephric adhesion were classified based on the observation during operation and post-operative dissection of the specimen, and the association of different types of adhesion with the difficulty of the procedures was examined. Results Among 33 cases, three were converted to hand-assisted laparoscopy, and one was converted to open surgery. Mean operative time was 99.6±29.2min, and blood loss was 75.2±83.5 mL. Postoperative recovery time of intestinal function was 1.6±0.7 days and average hospital stay was 4.8±1.4 days. By classification and comparison of the perinephric adhesions, whether inflammation extending beyond Gerota fascia or involving renal hilum was found to be not only an important factor influencing the operative time and blood loss, but also the main reason for conversion to hand-assisted laparoscopy or open surgery. Conclusions In laparoscopic nephrectomy, outside Gerota fascia dissection of the kidney and en-bloc ligation of the renal pedicle using EndoGIA could reduce the difficulty of procedure and operative time, with satisfactory safety and reliability. Inflammation and adhesion extending beyond Gerota fascia or involving renal hilum is an important predictor of the difficulty related to laparoscopic nephrectomy for IRD.

A five-gene signature may predict sunitinib sensitivity and serve as prognostic biomarkers for renal cell carcinoma.

Sunitinib resistance is, nowadays, the major challenge for advanced renal cell carcinoma patients. Illuminating the potential mechanisms and exploring effective strategies to overcome sunitinib resistance are highly desired. We constructed a reliable gene signature which may function as biomarkers for prediction of sunitinib sensitivity and clinical prognosis. The gene expression profiles were obtained from The Cancer Genome Atlas database. By performing GEO2R analysis, numerous differentially expressed genes (DEGs) were found to be associated with sunitinib resistance. To acquire more precise DEGs, we integrated three different microarray datasets. Functional analysis revealed that these DEGs were mainly involved in Rap1 signaling pathway, p53 signaling pathway and Ras signaling pathway. Then, top five hub genes, BIRC5, CD44, MUC1, TF, CCL5, were identified from protein-protein interaction (PPI) network. Sub-network analysis carried out by MCODE plugin revealed that key DEGs were related with PI3K-Akt signaling pathway, Rap1 signaling pathway and VEGF signaling pathway. Next, we established sunitinib-resistant OS-RC-2 and 786-O cell lines and validated the expression of five hub genes in cell lines. To further evaluate the potentials of five-gene signature for predicting clinical prognosis, we analyzed RCC patients with gene expressions and overall survival information from two independent patient datasets. The Kaplan-Meier estimated the OS of RCC patients in the low- and high-risk groups according to gene expression signature. Multivariate Cox regression analysis indicated that the prognostic power of five-gene signature was independent of clinical features. In conclusion, we developed a five-gene signature which can predict sunitinib sensitivity and OS for advanced RCC patients, providing novel insights into understanding of sunitinib-resistant mechanisms and identification of RCC patients with poor prognosis.

Laparoscopic nephrectomy outside gerota fascia and En bloc ligation of the renal hilum for management of inflammatory renal diseases.

OBJECTIVES: This study aims to improve laparoscopic nephrectomy techniques for inflammatory renal diseases (IRD) and to reduce complications. MATERIALS AND METHODS: Thirty-three patients underwent laparoscopic nephrectomy for IRD, with a method of outside Gerota fascia dissection and en-bloc ligation and division of the renal pedicle. Operative time, blood loss, complications, analgesia requirement, post-operative recovery of intestinal function and hospital stay were recorded. The degrees of perinephric adhesion were classified based on the observation during operation and post-operative dissection of the specimen, and the association of different types of adhesion with the difficulty of the procedures was examined. RESULTS: Among 33 cases, three were converted to hand-assisted laparoscopy, and one was converted to open surgery. Mean operative time was 99.6±29.2min, and blood loss was 75.2±83.5 mL. Postoperative recovery time of intestinal function was 1.6±0.7 days and average hospital stay was 4.8±1.4 days. By classification and comparison of the perinephric adhesions, whether inflammation extending beyond Gerota fascia or involving renal hilum was found to be not only an important factor influencing the operative time and blood loss, but also the main reason for conversion to hand-assisted laparoscopy or open surgery. CONCLUSIONS: In laparoscopic nephrectomy, outside Gerota fascia dissection of the kidney and en-bloc ligation of the renal pedicle using EndoGIA could reduce the difficulty of procedure and operative time, with satisfactory safety and reliability. Inflammation and adhesion extending beyond Gerota fascia or involving renal hilum is an important predictor of the difficulty related to laparoscopic nephrectomy for IRD.

Laparoscopic colonic anastomosis using a degradable stent in a porcine model.

AIM: To explore the feasibility and safety of laparoscopic colonic anastomosis using a degradable stent in a porcine model. METHODS: Twenty Bama mini-pigs were randomly assigned to a stent group (n = 10) and control group (hand-sewn anastomosis, n = 10). The anastomotic completion and operation times were recorded, along with histological examination, postoperative general condition, complications, mortality, bursting pressure, and the average anastomotic circumference (AC). RESULTS: All pigs survived postoperatively except for one in the stent group that died from ileus at 11 wk postoperatively. The operation and anastomotic completion times of the stent group were significantly shorter than those of the control group (P = 0.004 and P = 0.001, respectively). There were no significant differences in bursting pressure between the groups (P = 0.751). No obvious difference was found between the AC and normal circumference in the stent group, but AC was significantly less than normal circumference in the control group (P = 0.047, P < 0.05). No intestinal leakage and luminal stenosis occurred in the stent group. Histological examination revealed that the stent group presented with lower general inflammation and better healing. CONCLUSION: Laparoscopic colonic anastomosis with a degradable stent is a simple, rapid, and safe procedure in this porcine model.