Research prospects for kidney xenotransplantation: a bibliometric analysis.

BACKGROUND: Xenograft kidney transplantation has been receiving increasing attention. The purpose of this study is to use bibliometric analysis to identify papers in this research field and explore their current status and development trends. METHODS: Using the data in the Web of Science core database from Clarivate Analytics as the object of study, we used 'TS = Kidney OR Renal AND xenotransplantation' as the search term to find all literature from 1980 to 2 November 2022. RESULTS: In total, 1005 articles were included. The United States has the highest number of publications and has made significant contributions in this field. Harvard University was at the forefront of this study. Professor Cooper has published 114 articles in this field. Xenotransplantation has the largest number of relevant articles. Transplantation was the most cited journal. High-frequency keywords illustrated the current state of development and future trends in xenotransplantation. The use of transgenic pigs and the development of coordinated co-stimulatory blockers have greatly facilitated progress in xenotransplantation research. We found that 'co-stimulation blockade', 'xenograft survival', 'pluripotent stem cell', 'translational research', and 'genetic engineering' were likely to be the focus of attention in the coming years. CONCLUSIONS: This study screened global publications related to xenogeneic kidney transplantation; analyzed their literature metrology characteristics; identified the most cited articles in the research field; understood the current situation, hot spots, and trends of global research; and provided future development directions for researchers and practitioners.

Transurethral Hem-o-lok Clip Ligation of the Distal Ureter in Retroperitoneal Laparoscopic Radical Nephroureterectomy.

BACKGROUND AND OBJECTIVE: Distal ureter management is an essential part of radical nephroureterectomy (RNU). However, there is no agreement on the optimal surgical treatment for ureter and bladder cuff excision. The classical "pluck" technique following transurethral resection of the intramural ureter increases the risk of extravesical and intravesical tumor cell spillage. We aimed to provide a simple transurethral technique with the Hem-o-lok clip ligation for the management of the distal ureter during retroperitoneal laparoscopic RNU. METHODS: Transurethral resection of the bladder cuff was performed using a bipolar ß electrode mounted on resectoscope. Subsequently, a Super Scope (S-scope) with a 5.6-mm diameter working channel was used with a clip applier to deliver the 5-mm Hem-o-lok clips, which consequently ligated the ureteral stump and avoided urine spillage from the upper tract. Traditional retroperitoneal laparoscopic surgery was used to treat the renal and upper ureter. The resected distal ureter and the Hem-o-lok clip were gently pulled out of the bladder by the "pluck" technique. RESULTS: A total of 14 upper tract urothelial carcinoma patients were analyzed, including 10 men and 4 women. The Hem-o-lok clip ligation took less than 20 s. In each patient, the clip was clearly visible and attached tightly to the ureter, and a clear distal ureter was observed in all patients. Histopathology results showed pT2 in 8 and pT3 in 6 patients. A median follow-up of 15 months revealed no extravesicular or intravesicular recurrences. CONCLUSIONS: Transurethral Hem-o-lok clip ligation technique provides a simple and safe option for distal ureter management in retroperitoneal laparoscopic RNU. This novel approach enables construction of a watertight system of the upper urinary tract, preventing the spread of tumor cells effectively and minimizing local tumor implantation risk.

Transurethral Resection of Bladder Tumor: Novel Techniques in a New Era.

Transurethral resection of bladder tumor (TURBT) serves both diagnostic and therapeutic purposes in the management of bladder cancer. Attaining a high-quality TURBT is not always guaranteed due to various factors. En-bloc resection of bladder tumors (ERBT) holds promise to be a primary technique for removing bladder tumors in most non-muscle invasive bladder cancers. However, so far, no conclusive evidence indicates the superiority of any specific energy source used for ERBT. While laser energy can prevent the activation of obturator nerve reflex during ERBT, it poses challenges such as thermal injury and imprecise controllability. Needle-shaped electrodes offer high-level precision and controllability, without causing tissue deterioration or vaporization. The primary limitation of ERBT at present is the extraction/harvesting of large en-bloc specimens. Effective tools have been developed to overcome this limitation. Enhanced cystoscopy improves the detection of flat and small bladder tumors, allowing for better removal of cancerous tissues and significantly reducing recurrence rates. Advances in medical technology have brought forth a multitude of strategies to address the shortcomings of traditional TURBT. Appliances with large operating channel provide a platform for conducting laparoscopic procedures within the context of pneumocystoscopy, facilitating the execution of super TURBT and conferring comparable advantages to en-bloc resection. Moreover, the utilization of pneumocystoscopy enables the safe and effective performance of transurethral partial cystectomy for localized muscle-invasive bladder cancer. Novel techniques significantly improve the precision of the transurethral surgery and lower the risk of complications.

Short-term and long-term outcomes of intracorporeal "V-O manner" ureter-ileal anastomosis in robotic-assisted laparoscopic radical cystectomy with urinary diversion: a retrospective cohort study.

Background: There are several ways to perform ureter-ileal anastomosis (UIA), but there is currently no universally recognized standard approach. Unfortunately, these approaches may increase the risk of urine leakage or stricture. The aim of this study is we to describe an intracorporeal "V-O manner" UIA in robotic-assisted laparoscopic radical cystectomy (RARC) with urinary diversion, and to evaluate the short- and long-term patient outcomes. Methods: Between May 2012 and September 2018, 28 patients of bladder urothelial carcinomas (clinical stage T2-4aN0M0) who underwent RARC with intracorporeal urinary diversion (IUD) were included. All the patients received regular postoperative follow-up for 6-76 months. During the procedure of intracorporeal diversion, a "V-O manner" of UIA imitating the pyeloplasty in ureteropelvic junction (UPJ) obstruction was used to perform a mucosa-to-mucosa anastomosis. We observed short-term outcomes (operative time, blood loss, transfusion rate, length of hospital stay, 90-day mortality, and surgical complications) as well as long-term outcomes including kidney function and urinary diversion. Results: Intracorporeal orthotopic ileal neobladder (OIN) was performed in 23 patients whereas intracorporeal ileal conduit (ICD) was performed in 5 patients. The "V-O manner" UIA was applied in all the cases. The average duration of bilateral UIA was about 40 min. The median pelvic lymph node yield was 26 (range, 14-43). All patients ambulated on postoperative 2 to 3 days, and bowel function recovered on postoperative day 3 to 4. The median length of hospital stay was 14 days [interquartile range (IQR), 9-18 days]. A total of 9 patients experienced complications. Postoperative images confirmed satisfying drainage of bilateral ureters without urine leakage or stricture. During the follow up (median 29 months), all participants showed normal renal functions with satisfactory urinary diversion without hydronephrosis. Conclusions: We describe a feasible intracorporeal "V-O manner" UIA in RARC with urinary diversion, which provides improved outcomes in avoiding urine leakage or stricture and preventing the occurrence of hydronephrosis. Larger randomized controlled trials and longer duration of follow-up needs to be required in the future.

Light delivery device modelling for homogenous irradiation distribution in photodynamic therapy of non-spherical hollow organs.

SIGNIFICANCE: Photodynamic therapy (PDT) is a useful treatment for select cancers. Homogeneous illumination is a key factor in the successful application of PDT treatment of tumours in hollow organs. Over illumination may damage normal tissue while under illumination may not ablate the target. BACKGROUND: There have been many approaches to provide homogeneous irradiation for PDT treatment of hollow organs, including light-scattering medium and isotropic emitter to diffuse light, a balloon filled with solution to expand the organ wall, and shaped fibres. In most studies, the organ is assumed to be spherical. However, many hollow organs treated by PDT are non-spherical, and the uniformity of azimuthal irradiation remains an unsolved problem for cylindrical light sources. OBJECTIVE: Find a design principle for homogeneous irradiation in a non-spherical cavity for PDT treatment. METHOD: A PDT light delivery device is modeled by a series of sub light sources placed along the longitudinal axis of an ellipsoid. In order to achieve a homogeneous azimuthal irradiation distribution on the elliptical arc, a cost function is solved by adding modulation coefficient to the emission profile. The coefficient of variation of uniformity (Ucov) describes the statistical dispersion of the variation in irradiation over the ellipsoid to the average value. Ucov is used to evaluate the homogeneity of the azimuthal irradiation distribution. RESULT: By minimizing the cost function, we found that the truncated Gaussian function can be chosen as the emission profile to generate homogeneous irradiation profile within an ellipsoid cavity model. The emission profile can be tailored to generate Ucov of 96.7 %. Further discussion shows that the light distribution could be generated practically by a side-emitting optical fibre, a LED array, or moving an isotropic emitter successively. The impact of emission angle of light sub-source is analysed and the irradiation profile from discrete longitudinal emissions is calculated. CONCLUSION: Theory analysis and simulation indicate that a cylindrical emitter with a non-uniform longitudinal emission profile (truncated Gaussian functions) results in an approximate homogeneous irradiance profile within an ellipsoidal cavity.

Robot-assisted radical cystectomy with intracorporeal Mainz â ¡ rectosigmoid pouch for muscle-invasive bladder cancer.

BACKGROUND: To report the surgical techniques and results of robot-assisted radical cystectomy (RARC) with intracorporeal Mainz Ⅱ rectosigmoid pouch at our centre. METHODS: Two female patients were treated with this procedure. Construction of the pouch was divided into four main steps: incision of the rectum and sigmoid colon, closure of the posterior wall of the pouch, reimplantation of the ureters at the bottom of pouch in an anti-reflux manner, and closure of the anterior wall. Surgical results and perioperative complications were assessed. RESULTS: The operations were performed completely intracorporeally. No perioperative complications were observed. Postoperatively, high-grade invasive urothelial carcinoma was detected. On postoperative day 60, no bilateral ureteral dilation was detected. Two patients demonstrated total continence. Clinical recurrence was not observed during the follow-up period. CONCLUSIONS: With careful patient selection, robot-assisted intracorporeal Mainz Ⅱ rectosigmoid pouch might be a simple minimally invasive surgical technique to be evaluated in repeated applications.

A potential panel of five mRNAs in urinary extracellular vesicles for the detection of bladder cancer.

BACKGROUND: Extracellular vesicles (EVs) have showed promising potential in liquid biopsy of cancer. In present study, we evaluate the feasibility to diagnose bladder cancer using EVs RNA markers identified from public tissue RNA sequencing data. METHODS: We used urine samples from a cohort of population with suspected bladder cancer. Disease status (i.e., primary or recurrent bladder cancer) was diagnosed by cystoscopy. A prediction model including the expression of multiple RNAs in urinary EVs were developed in training cohort (n=368, 126 bladder cancer and 242 negative controls). The performance of optimal model (ExoPanel) consists of five mRNAs (MYBL2, TK1, UBE2C, KRT7, S100A2) was further assessed by a validation cohort (n=155, 56 bladder cancer and 99 negative controls). RESULTS: The performance of ExoPanel in training cohort was AUC 0.7759 (95% CI: 0.7259-0.8260), NPV 90.34% (95% CI: 84.04-94.42%), SN 88.89% (95% CI: 81.75-93.57%), and SP 54.13% (95% CI: 47.63-60.50%) respectively. In the validation cohort, the performance of this model was AUC 0.8402 (95% CI: 0.7690-0.9114), NPV 90.91% (95% CI: 79.29-96.60%), SN 91.07% (95% CI: 79.63-96.67%), and SP 50.51% (95% CI: 40.34-60.63%). Using this model, it is possible to rule out a significant number of non cancer patients, thus reduce the unnecessary operation of cystoscopy. CONCLUSIONS: We discovered a panel of five mRNAs, and evaluated its potential to facilitate bladder cancer diagnosis by analyzing their expression in urinary EVs.

Robot-assisted laparoendoscopic single-site surgery for the simultaneous management of multiple urinary tract calculi: a case report and experience sharing.

BACKGROUND: Urolithiasis is a clinically common benign disease in urology. Surgical treatments that are widely used in urolithiasis are percutaneous nephrolithotomy, rigid/flexible ureteroscopy, laparoscopic surgery, and endoscopic combined intrarenal surgery. The da Vinci surgical system is rarely used in the treatment of urolithiasis. In the current study, we report a case of multiple urinary tract calculi treated by robot-assisted laparoendoscopic single-site (RA-LESS) surgery. CASE PRESENTATION: A 49-year-old male patient was admitted to our hospital and diagnosed with multiple urinary tract calculi. He previously underwent right ureterolithotomy, laparoscopic cholecystectomy, and extracorporeal shockwave lithotripsy. Computed tomography (CT) scan and three-dimensional reconstruction CT image showed that multiple calculi were located in the right kidney, right upper ureter, and bladder. The preoperative glomerular filtration rate (GFR) were 17.81 ml/min (right kidney) and 53.11 ml/min (left kidney). We utilized the da Vinci system docking with a single-site port to perform pyelolithotomy, ureterolithotomy, and cystolithotomy, simultaneously. The operative time was 135 min and estimated blood loss was 30 ml. The postoperative hospital stay was 5 days. Three months after surgery, the serum creatinine and urea nitrogen levels dropped to a normal range, and no residual fragments were found in the CT scan. The postoperative GFR were 26.33 ml/min (right kidney) and 55.25 ml/min (left kidney). CONCLUSIONS: RA-LESS surgery is a safe and effective surgical procedure in the treatment of multiple urinary tract calculi; however, further investigation is needed to validate its long-term therapeutic effect.

Expression of serum microRNA-378 and its clinical significance in renal cell carcinoma.

Studies have demonstrated that miRNA-378 is expressed in various malignant tumors. In the present study, we aimed to explore the expression of serum miRNA-378 and its clinical significance in renal cell carcinoma (RCC) patients. A total of 75 RCC patients, 63 renal cysts (RC) patients and 75 healthy controls were selected. The miRNA-378 level in RCC and RC groups was significantly higher than in healthy control group, with RCC group having the highest level. The miRNA-378 levels were significantly decreased within the same group after surgery. When compared with healthy controls, RC group had higher levels but not significantly (p > 0.05) while levels in RCC group were significantly higher (p < 0.05). miRNA-378 expression was correlated with clinical stage and differentiation degree, but not correlated with patient's age, gender, surgical strategy and tumor diameter. The AUC of miRNA-378 was 0.896, 95% confidence interval was 0.847 to 0.945, and AUC hypothesis testing was statistically significant (p < 0.001, RCC vs healthy control). miRNA-378 shows potential in the diagnosis and prediction of postoperative curative effect of renal cell carcinoma, but further studies with lager samples are needed.

Expression of serum microRNA-378 and its clinical significance in renal cell carcinoma

Abstract Studies have demonstrated that miRNA-378 is expressed in various malignant tumors. In the present study, we aimed to explore the expression of serum miRNA-378 and its clinical significance in renal cell carcinoma (RCC) patients. A total of 75 RCC patients, 63 renal cysts (RC) patients and 75 healthy controls were selected. The miRNA-378 level in RCC and RC groups was significantly higher than in healthy control group, with RCC group having the highest level. The miRNA-378 levels were significantly decreased within the same group after surgery. When compared with healthy controls, RC group had higher levels but not significantly (p > 0.05) while levels in RCC group were significantly higher (p < 0.05). miRNA-378 expression was correlated with clinical stage and differentiation degree, but not correlated with patient's age, gender, surgical strategy and tumor diameter. The AUC of miRNA-378 was 0.896, 95% confidence interval was 0.847 to 0.945, and AUC hypothesis testing was statistically significant (p < 0.001, RCC vs healthy control). miRNA-378 shows potential in the diagnosis and prediction of postoperative curative effect of renal cell carcinoma, but further studies with lager samples are needed.

Overexpression of a novel candidate oncogene KIF14 correlates with tumor progression and poor prognosis in prostate cancer.

Prostate cancer (PCa) is the second leading cause of death from cancer in men. The mechanism underlying tumorigenesis and development of PCa is largely unknown. Here, we identified Kinesin family member 14 (KIF14) as a novel candidate oncogene in PCa. We found that KIF14 was overexpressed in multiple PCa cell lines and primary PCa tissues. Knockdown of KIF14 in DU145 and PC3 prostate cancer cells suppressed cell proliferation, induced cell cycle arrest and apoptosis. Transcriptome analysis by RNA-sequencing demonstrated that KIF4 suppression led to transcriptional changes of genes involved in p53 and TGF-beta signaling pathway. In addition, upregulated expression of GADD45A, GADD45B, p21, PIDD and Shisa5, which contribute to growth arrest and apoptosis induction, and downregulated CCNB1 that promotes cell cycle progression were confirmed by quantitative real-time PCR after KIF4 knockdown. We further found that KIF14 protein level was positively correlated with T stage and Gleason Score. Patients with higher KIF14 expression had shorter overall survival time than those with lower KIF14 expression. Thus, our data indicate that KIF14 could act as a potential oncogene that contributes to tumor progression and poor prognosis in PCa, which may represent a novel and useful prognostic biomarker for PCa.

Retroperitoneal Laparoscopic Partial Nephrectomy for Tumors Larger than 7 cm in Renal Cell Carcinoma: Initial Experience of Single-Institution.

BACKGROUND: To report our initial experience dealing with retroperitoneal laparoscopic partial nephrectomy (LPN) for tumors larger than 7 cm in renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 15 patients with malignant tumors larger than 7 cm underwent retroperitoneal LPN at our institution. Patient baseline demographics, perioperative outcomes, pathological characteristics, and estimated glomerular filtration rate (eGFR) were analyzed retrospectively in our collected database. RESULTS: The tumor size is 7.5 (7.1-9.0) cm. Nine (60.00%) patients, 4 (26.67%) patients, and 2 (13.33%) patients suffered from preoperative chronic kidney disease (CKD) at stage I, II, and III, respectively. The median operating time was 121 (90-330) minutes and the warm ischemia time (WIT) was 29 (12-45) minutes, with the estimated blood loss of 50 (10-1200) mL. The preoperative eGFR was 81.26 mL/min per 1.73 m2 (ranging from 56.15 to 140.47), eGFR on 1 and 30 days postoperative was 70.49 mL/min per 1.73 m2 (ranging from 50.32 to 137.73) and 75.13 mL/min per 1.73 m2 (ranging from 54.07 to 142.99), respectively. At last follow-up, the eGFR was 72.78 mL/min per 1.73 m2 (ranging from 51.28 to 137.86); no stage migration for CKD was observed. Major complications included 2 patients requiring blood transfusions and 1 patient performing renal vein suture as well as single leak. CONCLUSIONS: Our initial experience suggests that retroperitoneal LPN maybe a feasible, safe, and effective procedure for selected tumors larger than 7 cm in RCC, with the advantage of renal function preservation and acceptable major surgical complications. Tumor size might not be the contraindication of LPN in the treatment of selected tumors.

Ubiquitin specific peptidase 21 regulates interleukin-8 expression, stem-cell like property of human renal cell carcinoma.

USP family proteins play essential roles in cancer cell proliferation and apoptosis and represent as candidate targets for cancer therapeutics. However, the effects and underlying mechanism of USP21 on renal cell carcinomas (RCC) remain unclear. In the present study, we investigate the effects of USP21 on proliferation, invasion and cancer stem cells (CSCs) property of RCC cell lines. As a result, siRNA-mediated depletion of USP21 inhibits cell proliferation, invasion ability and decreases the CSCs percentage of RCC cell lines. Complementarily, forced expression of USP21 leads to increase of tumorigenic properties. In addition, CSCs properties assessed by sphere formation assays demonstrated that depletion of USP21 impair the self-renewal capability of CSCs. Furthermore, decrease USP21 levels is associated with repression of interleukin 8 (IL-8), a chemokine that regulates CSCs characteristics in RCC. Mechanistically, USP21 binds to the promoter region of IL-8 and mediates transcriptional initiation. These data suggest that USP21/IL-8 could be a pair of the critical molecular targets for the development of therapeutic strategies for RCC.

Genomic profiling screens small molecules of metastatic prostate carcinoma.

The aim of the present study was to investigate the pathogenesis of metastatic prostate carcinoma, to find the metabolic pathways changed in the disease and to screen out the potential therapeutic drugs. GSE38241 was downloaded from Gene Expression Omnibus; the Geoquery package was applied to preprocessed expression profiling, and the differentially-expressed genes (DEGs) were selected with limma (linear regression model packages). Next, WikiPathways cluster analysis was performed for DEGs on a Gene Set Analysis Toolkit V2 platform, and DEGs with hypergeometric algorithms were calculated through gene set enrichment analysis. A total of 1,126 DEGs were identified between the normal prostate and metastatic prostate carcinoma. In addition, KPNA4, SYT1, PLCB1, SPRED1, MBNL2, RNF165, MEF2C, MBNL1, ZFP36L1 and CELF2, were found to be likely to play significant roles in the process of metastatic prostate carcinoma. The small molecules STOCK1N-35874 and 5182598 could simulate the state of normal cells well, while the small molecules MS-275 and quinostatin could simulate the state of metastatic prostate carcinoma cells. In conclusions, the small molecules STOCK1N-35874 and 5182598 were identified to be good potential therapeutic drugs for the treatment of metastatic prostate carcinoma, while the two small molecules MS-275 and quinostatin could cause metastatic prostate carcinoma.

Investigation on lower urinary tract symptoms (LUTS) in elderly patients with prostate cancer (PC) received endocrine therapy.

This study was designed to investigate the LUTS after endocrine therapy and their effects on the quality of life in elderly patients with PC. The elderly patients with PC who had no progression after receiving endocrine therapy and had data of total prostate volume (TPV) before receiving endocrine therapy were asked to complete the questionnaire of International Prostate Symptom Score (IPSS) questionnaire with quality-of-life (QOL) assessment. Transrectal ultrasound assessment was performed in all patients to measure prospectively the TPV, maximum flow rate (Qmax) and residual urine volume (RUV) after endocrine therapy. A total of 42 patients aged 76-98 (87.8 ± 5.6) years finished the investigation, with duration of endocrine therapy ranged 1-17 (6.5 ± 4.2) years, including orchidectomy in 18 patients, medical castration with luteinizing hormone-releasing hormone analog in 24 patients. The TPV [28-53 (34.9 ± 14.7)ml] after endocrine therapy was significantly decreased compared to that before endocrine therapy [28-53 (34.9 ± 14.7)ml]. The Qmax was 8.7 ± 3.8 ml/s, RUV measured by B-Ultrasound was 37.5 ± 14.9 ml. However, all patients presented LUTS with various severities, and had an IPSS score of 23.7 ± 4 that was consisted by a score of 15.5 ± 2.8 for storage symptoms, 8.2 ± 2.2 for voiding symptoms, and had QOL score of 4.2 ± 1.8. The Spearman rank correlation test showed a positive correlation between IPSS score, score of storage symptoms and QOL (r1=0.83, P<0.01 and r2=0.81, P<0.01); but no such correlation was detected between score of voiding symptoms and QOL (r3=0.43, P=0.49). The more important is that the storage symptoms contribute significantly more effects on QOL than the voiding symptoms (P=0.0032). Based on these results, it was proposed in our study that aging bladder associated with the storage symptoms might be the key reason for the LUTS sustained during the endocrine therapy in elderly patients with PC, especially in LUTS patients who mainly present as storage symptoms and could not be controlled by repeated treatments.

Celastrol stimulates hypoxia-inducible factor-1 activity in tumor cells by initiating the ROS/Akt/p70S6K signaling pathway and enhancing hypoxia-inducible factor-1α protein synthesis.

Celastrol, a tripterine derived from the traditional Chinese medicine plant Tripterygium wilfordii Hook F. ("Thunder of God Vine"), has been reported to have multiple effects, such as anti-inflammation, suppression of tumor angiogenesis, inhibition of tumor growth, induction of apoptosis and protection of cells against human neurodegenerative diseases. However, the mechanisms that underlie these functions are not well defined. In this study, we reported for the first time that Celastrol could induce HIF-1α protein accumulation in multiple cancer cell lines in an oxygen-independent manner and that the enhanced HIF-1α protein entered the nucleus and promoted the transcription of the HIF-1 target genes VEGF and Glut-1. Celastrol did not influence HIF-1α transcription. Instead, Celastrol induced the accumulation of the HIF-1α protein by inducing ROS and activating Akt/p70S6K signaling to promote HIF-1α translation. In addition, we found that the activation of Akt by Celastrol was transient. With increased exposure time, inhibition of Hsp90 chaperone function by Celastrol led to the subsequent depletion of the Akt protein and thus to the suppression of Akt activity. Moreover, in HepG2 cells, the accumulation of HIF-1α increased the expression of BNIP3, which induced autophagy. However, HIF-1α and BNIP3 did not influence the cytotoxicity of Celastrol because the main mechanism by which Celastrol kills cancer cells is through stimulating ROS-mediated JNK activation and inducing apoptosis. Furthermore, our data showed that the dose required for Celastrol to induce HIF-1α protein accumulation and enhance HIF-1α transcriptional activation was below its cytotoxic threshold. A cytotoxic dose of Celastrol for cancer cells did not display cytotoxicity in LO2 normal human liver cells, which indicated that the novel functions of Celastrol in regulating HIF-1 signaling and inducing autophagy might be used in new applications, such as in anti-inflammation and protection of cells against human neurodegenerative diseases. Future studies regarding these applications are required.

Screening candidate genes associated with bladder cancer using DNA microarray.

The aim of the present study was to screen candidate genes that are closely associated with bladder cancer and to select the most distinct candidate target genes in order to provide theoretical evidence and direction for improved treatment of bladder cancer. The gene microarray dataset GSE45184 was downloaded from the Gene Expression Omnibus database. There were a total of six expression prolife microarrays from three pairs of freshly frozen bladder cancer tissues and corresponding normal adjacent tissues. Differentially expressed genes (DEGs) were identified using the limma package in R software and then subjected to further biological information analysis, including hierarchical clustering analysis and gene ontology enrichment analysis. Co­expression networks and functional interaction networks were established using the up­ and downregulated genes. Pathway enrichment analysis was then performed for the genes in the functional interaction networks. A total of 522 DEGs were identified, including 223 upregulated and 299 downregulated genes. Functional enrichment analysis of the target genes indicated that downregulated genes were associated with the regulation of biological processes, while the upregulated genes participated in the processes involved in the cell cycle. The functional network of the upregulated genes comprised 1,518 connections and 92 gene nodes that were associated with 10 closely­related functions, while the network of the downregulated genes consisted of 129 connections and 24 gene nodes involving 11 significantly related functions. Pathway enrichment analysis revealed that the downregulated genes were mainly involved in the mitogen­activated protein kinase signaling pathway, while the upregulated genes were closely associated with the cell cycle. These DEGs and the relevant cell cycle pathways have the potential to be used as targets for the treatment of bladder cancer.

A novel approach to locate renal artery during retroperitoneal laparoendoscopic single-site radical nephrectomy.

OBJECTIVE: To verify the feasibility and safety of retroperitoneal laparoendoscopic single-site radical nephrectomy and assess the value of our proposed approach to search for renal artery. METHODS: A total of 60 cases of retroperitoneal laparoendoscopic single-site radical nephrectomy were performed using our homemade single-port multi-channel device. An incision of 5-6 cm was cut forward from the posterior axillary line under the lower margin of the 12th rib, and a single-port multi-channel device comprised of two control rings and a No. 7 glove was placed into the incision. Retroperitoneal laparoendoscopic single-site radical nephrectomy was then performed via locating renal artery through muscle and ligament on the posterior abdominal. RESULTS: The 60 cases were all successful. None of the 60 patients developed surgical complications. CONCLUSION: The application of homemade device is safe and feasible. Our proposed method is of greater practical significance for the relatively narrow operating space in retroperitoneal laparoendoscopic single-site surgery.

CC chemokine ligand 18 and IGF-binding protein 6 as potential serum biomarkers for prostate cancer.

Prostate cancer (PCa) is the second leading cause of cancer-related death in men globally. However, there are few sensitive biomarkers for PCa, especially those which can distinguish PCa and benign prostate hyperplasia (BPH). Antibody microarrays allow for high-throughput and high-sensitivity detection of multiple proteins simultaneously, providing a powerful tool for biomarker screening. Here, we selected 46 patients with PCa and 42 controls with BPH, and compared the serum levels of different cytokines in PCa and BPH patients using antibody microarrays. The results indicated that serum levels of macrophage colony-stimulating factor (M-CSF) and CC chemokine ligand 18 (CCL-18) were remarkably higher in PCa patients than those in BPH patients, while serum levels of insulin-like growth factor-binding protein 6 (IGFBP-6) and Fas receptor (Fas), also called tumor necrosis factor receptor superfamily member 6 (TNFRSF6), were significantly lower. M-CSF and Fas/TNFRSF6 have been reported to be associated with PCa pathogenesis, and thus were used as positive controls in the present study. CCL-18 is a chemokine primarily involved in recruitment of the adaptive immune system, while IGFBP-6 has been reported to inhibit proliferation of PCa cells. Serum levels of these four cytokines could distinguish PCa from BPH with high sensitivity and high specificity. Furthermore, the area under the ROC curve (AUC) was above 0.925 and 0.835 for CCL-18 and IGFBP-6, respectively, implying their high diagnostic value. In conclusion, we have identified CCL-18 and IGFBP-6 as new potential serum biomarkers for PCa.