Constructing a novel gene signature derived from oxidative stress specific subtypes for predicting survival in stomach adenocarcinoma.

Oxidative stress (OS) response is crucial in oncogenesis and progression of tumor. But the potential prognostic importance of OS-related genes (OSRGs) in stomach adenocarcinoma (STAD) lacked comprehensive study. STAD clinical information and transcriptome data were retrieved from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The prognostic OSRGs were filtered via the univariate Cox analysis and OSRG-based molecular subtypes of STAD were developed using consensus clustering. Weighted gene co-expression network analysis (WGCNA) was subsequently conducted to filter molecular subtype-associated gene modules. The prognosis-related genes were screened via univariate and least absolute shrinkage and selection operator Cox regression analysis were used to construct a prognostic risk signature. Finally, a decision tree model and nomogram were developed by integrating risk signature and clinicopathological characteristics to analyze individual STAD patient's survival. Four OSRG-based molecular subtypes with significant diversity were developed based on 36 prognostic OSRGs for STAD, and an OSRGs-based subtype-specific risk signature with eight genes for prognostic prediction of STAD was built. Survival analysis revealed a strong prognostic performance of the risk signature exhibited in predicting STAD survival. There were significant differences in mutation patterns, chemotherapy sensitivity, clinicopathological characteristics, response to immunotherapy, biological functions, immune microenvironment, immune cell infiltration among different molecular subtypes and risk groups. The risk score and age were verified as independent risk factors for STAD, and a nomogram integrating risk score and age was established, which showed superior predictive performance for STAD prognosis. We developed an OSRG-based molecular subtype and identified a novel risk signature for prognosis prediction, providing a useful tool to facilitate individual treatment for patients with STAD.

Identification of ISCA1 as novel immunological and prognostic biomarker for bladder cancer.

Background: Iron-sulfur cluster assembly 1 (ISCA1) has a significant effect on respiratory complexes and energy metabolism. Although there is some evidence that ISCA1 gene expression impacts energy metabolism and consequently has a role in tumorigenesis and cancer metastasis in different types of malignancies, no systematic pan-cancer study of the ISCA1 has been conducted. As a result, we sought to investigate ISCA1's predictive value in 33 cancer types as well as its possible immunological function. Methods: We included the pan-cancer expression profile dataset and clinical data from the public database. Firstly, the single-sample Gene Set Enrichment Analysis (ssGSEa) approach was employed for analyzing the immune link in pan-cancer, while the limma package was utilized for analyzing the differential expression in cancer species. Subsequently, ciberport, MCP-counter, TIMER2, quanTIseq, and xCELL were employed for analyzing bladder cancer (BLCA)'s immune infiltration. Least absolute shrinkage and selection operator (Lasso) were employed for choosing the best gene to develop the immune risk scoring model. Results: ISCA1 gene expression was positively related to four immune signatures (chemokine, immunostimulator, MHC, and receptor) in BLCA. Samples of BLCA were sorted into two groups by the best cut-off of ISCA1 expression degree. The group with a high level of ISCA1 expression had a higher risk, suggesting that the ISCA1 gene was a risk factor in BLCA, and its high expression resulted in a poorer prognosis. Additionally, it was noted that ISCA1 was positively linked with these immune checkpoints. Moreover, there was a considerable positive link between ISCA1 and different immune properties in subgroups with different immune checkpoint inhibiting responses. Finally, an immune risk scoring model was made and it showed a better score in comparison to that of TIDE. Conclusion: ISCA1 can be a prognostic marker for a variety of cancers, particularly BLCA. Its high level of expression has a deleterious impact on the prognosis of BLCA patients. This strongly shows that ISCA1 is a significant prognostic factor for BLCA and that it could be used as a new prognostic detection target and treatment approach.

Gene Expression Analysis Reveals Prognostic Biomarkers of the Tyrosine Metabolism Reprogramming Pathway for Prostate Cancer.

Background: Tyrosine metabolism pathway-related genes were related to prostate cancer progression, which may be used as potential prognostic markers. Aims: To dissect the dysregulation of tyrosine metabolism in prostate cancer and build a prognostic signature based on tyrosine metabolism-related genes for prostate cancer. Materials and Method. Cross-platform gene expression data of prostate cancer cohorts were collected from both The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Based on the expression of tyrosine metabolism-related enzymes (TMREs), an unsupervised consensus clustering method was used to classify prostate cancer patients into different molecular subtypes. We employed the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to evaluate prognostic characteristics based on TMREs to obtain a prognostic effect. The nomogram model was established and used to synthesize molecular subtypes, prognostic characteristics, and clinicopathological features. Kaplan-Meier plots and logrank analysis were used to clarify survival differences between subtypes. Results: Based on the hierarchical clustering method and the expression profiles of TMREs, prostate cancer samples were assigned into two subgroups (S1, subgroup 1; S2, subgroup 2), and the Kaplan-Meier plot and logrank analysis showed distinct survival outcomes between S1 and S2 subgroups. We further established a four-gene-based prognostic signature, and both in-group testing dataset and out-group testing dataset indicated the robustness of this model. By combining the four gene-based signatures and clinicopathological features, the nomogram model achieved better survival outcomes than any single classifier. Interestingly, we found that immune-related pathways were significantly concentrated on S1-upregulated genes, and the abundance of memory B cells, CD4+ resting memory T cells, M0 macrophages, resting dendritic cells, and resting mast cells were significantly different between S1 and S2 subgroups. Conclusions: Our results indicate the prognostic value of genes related to tyrosine metabolism in prostate cancer and provide inspiration for treatment and prevention strategies.

Hsa_circ_0074032 promotes prostate cancer progression through elevating homeobox A1 expression by serving as a microRNA-198 decoy.

It has been reported that circular RNA hsa_circ_0074032 (circ_0074032) has a higher level in prostate cancer (PCa) tissues. However, the role and regulatory mechanism of circ_0074032 in PCa are still unknown. Circ_0074032 was overexpressed in PCa, and high circ_0074032 level was associated with worse PCa-related prognosis. Functionally, circ_0074032 silencing decreased xenograft tumour growth in vivo and induced cell apoptosis, curbed cell proliferation, migration and invasion in PCa cells in vitro. Furthermore, circ_0074032 was identified as a miR-198 decoy, and miR-198 inhibition abolished circ_0074032 silencing-mediated effects on PCa cell proliferation, apoptosis, migration and invasion. In addition, miR-198 directly targeted homeobox A1 (HOXA1), and HOXA1 weakened miR-198 mimic-mediated impacts on PCa cell malignant phenotypes. Importantly, circ_0074032 regulated HOXA1 expression by sponging miR-198. Our findings uncovered a novel mechanism by which circ_0074032 promoted PCa progression via elevating HOXA1 expression through acting as a miR-198 sponge, providing a mechanism for circ_0074032 to affect the development of PCa.

Down-regulated LINC00115 inhibits prostate cancer cell proliferation and invasion via targeting miR-212-5p/FZD5/Wnt/ß-catenin axis.

Prostate cancer is the second most frequent malignancy in men worldwide, and its incidence is increasing. Therefore, it is urgently required to clarify the underlying mechanisms of prostate cancer. Although the long non-coding RNA LINC00115 was identified as an oncogene in several cancers, the expression and function of LINC00115 in prostate cancer have not been explored. Our results showed that LINC00115 was significantly up-regulated in prostate cancer tissues, which was significantly associated with a poor prognosis for prostate cancer patients. Functional studies showed that knockdown LINC00115 inhibited cell proliferation and invasion. In addition, LINC00115 served as a competing endogenous RNA (ceRNA) through sponging miR-212-5p to release Frizzled Family Receptor 5 (FZD5) expression. The expression of miR-212-5p was noticeably low in tumour tissues, and FZD5 expression level was down-regulated with the knockdown of LINC00115. Knockdown LINC00115 inhibited the Wnt/ß-catenin signalling pathway by inhibiting the expression of FZD5. Rescue experiments further showed that LINC00115 inhibits prostate cancer cell proliferation and invasion via targeting miR-212-5p/ FZD5/ Wnt/ß-catenin axis. The present study provided clues that LINC00115 may be a promising novel therapeutic target for prostate cancer patients.

Downregulation of METTL7B Inhibits Proliferation of Human Clear Cell Renal Cancer Cells In Vivo and In Vitro.

Clear cell renal cell carcinoma (ccRCC) is the most aggressive urologic tumor, and its incidence and diagonosis have been continuously increasing. Identifying novel molecular biomarker for inhibiting the progression of ccRCC will facilitate developing new treatment strategies. Although methyltransferase-like 7B (METTL7B) was identified as a Golgi-associated methyltransferase, the function and mechanism of METTL7B in ccRCC development and progression has not been explored. METTL7B expression were significantly upregulated in ccRCC tissues (n = 60), which significantly associated with TNM classification, tumor size, lymph node metastasis, and poor prognosis for ccRCC patients. Functional studies showed downregulation of METTL7B inhibited cell proliferation, migration in vitro, and xenograft tumor formation in vivo. In addition, METTL7B knockdown promoted cell cycle arrest at G0/G1phase and induced cellular apoptosis. Taken together, downregulation of METTL7B inhibits ccRCC cell proliferation and tumorigenesis in vivo and in vitro. These findings provide a rationale for using METTL7B as a potential therapeutic target in ccRCC patients.

A Modified Endoscopic Primary Realignment of Severe Bulbar Urethral Injury.

Purpose: Male urethral injury is a common urologic emergency in developing countries. Whether early or late treatment of urethral injuries is often multifactorial and controversial. The goal of this study is to determine whether early realignment can reduce postsurgical complications and evaluate the clinical feasibility of emergency endoscopic urethroplasty using single rigid ureteroscopy in the treatment of bulbar urethral severe injury. Patients and Methods: Between September 2013 and March 2019, 15 male adult patients (mean age 35 years; from 21 to 62 years) with severe bulbar urethral injury were enrolled into the current study. The patients mainly presented with dysuria or painful urination (15/15, 100%), urethral bleeding (13/15, 86.7%), and urinary retention (11/15, 73.3%). Six of them had swelling of perineal or scrotal soft tissue, while four had testicular contusion. No pelvic fracture was found in all cases with CT scanning of the pelvic cavity. The bulbar urethral at grade IV was confirmed to be completely ruptured in all cases by endoscopy during operation. The modified endoscopic primary realignment was performed. Results: This new urethral repair technique was effectively performed in all patients and none converted to open operation. Mean operation time was 42.3 ± 11.5 minutes (28-52 minutes) and the mean Foley catheter indwelling time was 34.5 ± 6.9 days (28-42 days). During a follow-up of 41.3 ± 22.8 months (12-64 months), mild urethral strictures (grade I) (19.7 ± 9.5 weeks, 10-27 weeks postsurgery) developed in 8 patients (53.3%) and then were all improved 2.1 ± 0.8 months (1.3-2.9 months) after periodic dilatations of the urethra (4-10 times). Erectile dysfunction (ED) occurred in three patients (20%) after surgery, who recovered from mild ED to normal by administration with oral sildenafil (100 mg, three times a week) for 12 weeks. The International Index of Erectile Function-5 (IIEF-5) score was significantly improved after surgery (M ± SD, 25 ± 3) compared with before (16.4 ± 3.5) (p < 0.05). No incontinence and other complications occurred in all cases. Conclusions: Early endoscopic realignment via suprapubic puncture cystostomy by single rigid ureteroscopy provides an effective, feasible, and safe procedure for severe bulbar urethral injury.

Challenges in the diagnosis of testicular infarction in the presence of prolonged epididymitis: Three cases report and literature review.

INTRODUCTION: Testicular infarction is a rare complication of prolonged epididymitis and may be misdiagnosed as testicular torsion. In this study, we present three cases of testicular infarction and discuss their clinical characteristics, imaging features and clinical management. PATIENTS AND METHODS: Three adult males with prolonged epididymitis presented with chronic unilateral testicular pain, tenderness, and palpable swelling, including left varicocele in one case and hydrocele in the other two cases. Patient's symptoms were not relieved after antibiotic therapy. We analyzed the diagnosis, management, and outcome of these three cases of testicular infarction resulting from prolonged epididymitis. This includes the clinical characteristics, features of color doppler ultrasound imaging for diagnosis, and treatment strategy for testicular infarction from prolonged epididymitis. RESULTS: Complete blood count (CBC) indicated a small leukocytosis (10.6±0.4×109/L; normal arrange 3.5-9.5 WBC×109/L). Color doppler images demonstrated appropriate blood flow to areas of interest at patient's initial visit. At follow up visit several months later, the increased blood flow was detected at the edges of the involved testes with no blood flow to the center. The sizes of the involved testis (27±4 ml) was significantly larger compared to the non affected side (17±2 ml) (p < 0.05). Unilateral simple orchiectomy was performed on the involved testis in all three cases. Grossly, abscess cavities with caseous necrosis were found at the center of the testicle and epididymis in two patients. Histopathologic examination showed chronic inflammation with lymphocytic and macrophage infiltration of the involved testicle in two cases. The third case stained positive for acid fast bacteria. Left varicocele disappeared postoperatively in one patient. No pain, wound infection or other discomfort were noted 12 months after surgery. COMMENTS: This series revealed that testicular infarction may result from inappropriately treated prolonged epididymitis. Epididymal tuberculosis should be considered in cases with epididymitis not responding to broad spectrum antibiotics. Testicular infarction induced by prolonged epididymitis is easily missed due to a lack of symptom changes. Color doppler images are helpful in the diagnosis. This usually presents as a decrease in blood flow at the center of the testis with the increased flow at the periphery differentiating this from testicular torsion.

Challenges in the diagnosis of severe renal trauma in child: A case report and literature review.

INTRODUCTION: To report the management and outcome of one case of pediatric patient sustaining high-grade blunt renal trauma. We present and discuss the clinical characteristics and radiologic features of the patient. PATIENTS AND METHODS: A 10 years old child was admitted for serious blunt renal trauma formed a huge urinoma in the right renal after injury gradually in 2018. We treated the patient with synchronous percutaneous nephrostomy drainage and retrograde ureteral catheterization. A retrospective review was performed of this case, including the clinical features, imaging studies and short-term follow-up. A literature review was also performed to highlight the principals of diagnosis and treatment of severe blunt renal trauma in children. RESULTS: After drainage, the symptoms of abdominal distension gradually disappeared, and the physical examination shows that the abdomen gradually reduced to normal. The huge urinoma was cured by synchronous drainge. No complications occurred in short-term follow-up. COMMENTS: The choice of surgical treatment is based on the degree and location of renal trauma. Grade IV injuries are a heterogeneous group and management should be tailored to the patient, especially among pediatric patients. Persistent urinary extravasation and/or symptomatic urinoma is a common complication of high-grade renal trauma, which will be amenable to ureteral stent placement or percutaneous drainage. For huge urinoma, synchronous percutaneous nephrostomy drainage and retrograde ureteral catheterization can relieve symptoms quickly.

Minimally invasive management of acute ureteral obstruction and severe infection caused by upper urinary tract calculi.

PURPOSETo evaluate therapeutic efficacy of two minimally invasive surgical methods in managing acute ureteral obstruction and severe infection caused by upper urinary tract calculi (UUTC).PATIENTS AND METHODSData of 47 patients diagnosed with acute upper urinary tract obstruction and severe infection caused by ureteral calculus using X-ray CT between September 2014 and January 2019 were retrospectively analyzed. All patients were treated with immediate renal drainage and, after infection and ureteral obstruction were relieved, UUTC removal. Renal drainage was performed by ultrasound-guided percutaneous nephrostomy and retrograde ureteral catheterization was performed using cystoscopy. Kidney and ureteral stones were removed; renal function and the urinary tract were examined by X-ray during follow-up.RESULTSPercutaneous nephrostomy was performed in 29 patients in a critical condition including intolerance to surgery, high-grade hydronephrosis, or failure of retrograde ureteric stent placement. In other 18 patients diagnosed with small stones (≤10 mm) and low-grade hydronephrosis, indwelling double-J ureteral stents were temporally installed by a cystoscope. Acute infection and ureteral obstruction were relieved; white blood cell counts returned to normal values within 3 to 7 days after drainage in all patients. In the second-stage treatment, percutaneous nephrolithotomy (PCNL), ureteroscopic lithotripsy, extracorporeal shock wave lithotripsy and nephrectomy were performed in 24, 10, 8 and 5 patients, respectively. No patients developed severe complication after stone removal surgery. All patients were followed up for 3 months to 4.5 years. Renal function was significantly recovered; 17/29 (59%) patients with elevated serum creatinine returned to normal and serum creatinine in 12/29 (41%) patients improved significantly after drainage, with a pre-operation level of 285±169µM vs 203±91µM post-operation (P = 0.014). Five patients were lost during follow-up.CONCLUSIONThis study demonstrated an optimal approach for relieving upper urinary tract obstruction and acute infection in which percutaneous nephrostomy drainage is preferred for patients with severe pyonephrosis, large stones (>10 mm) with high-grade hydronephrosis, steinstrasse, or failure in retrograde ureteric stent placement, while retrograde ureteral catheterization using cystoscopy is suitable for patients diagnosed with small stones (≤10 mm) and low-grade hydronephrosis.

Challenges in the diagnosis of calyceal diverticulum: A report of two cases and review of the literature.

BACKGROUND: Calyceal diverticula outpouchings that occur rarely in the upper collecting system of the kidney and is often difficult to detect. In this study, we present two cases of calyceal diverticula and discuss their clinical characteristics and radiologic features. PATIENTS AND METHODS: In the presented two cases, we applied several imaging examinations, including delayed intravenous pyelography, retrograde pyelography and axial computerized tomographic (CT) scanning of the kidneys with and without contrast. Serum creatinine levels in fluid withdrawn from the diverticula were found to be significantly higher than the simultaneous serum creatinine levels. Intravenous injection of methylene blue through a ureteral catheter was also aided in the diagnosis. Calyceal diverticulum neck dilatation was performed through a percutaneous nephroscope.ResultsThe two cases were diagnosed preoperatively and the operation was successful performed. The nephrostomy tube was removed seven days after surgery without complications. CT scans of the kidney after six months showed that the size of the calyceal diverticulum of two patients were considerably smaller than pre-surgery. There were no reports of pain in the lumbar region or other discomfort. COMMENTS: Diagnosis of calyceal diverticulum mainly depend on a variety of imaging examinations, including the delayed intravenous pyelography, retrograde pyelography, and kidney CT plain scan plus enhanced scan. If the patient cannot be diagnosed by above methods, cyst fluid can be aspirated percutaneously to measure the preoperative creatinine level. If it is significantly higher than the serum creatinine level, the cyst fluid is considered urine, which can assist in the diagnosis of calyceal diverticulum. A ureteral catheter should also be inserted before operation namely, intravenous injection of methylene blue through a ureteral catheter is helpful for diagnosis. The choice of surgical treatment is based on the size and location of calyceal diverticulum and clinical manifestations.

Diagnosis value of multi-slice spiral CT in renal trauma.

Computed tomography (CT) is most commonly used as a noninvasive approach in diagnosis of internal organ injures. Use of multi-slice spiral CT becomes more popular in diagnosis of trauma because of its ability to generate 3D volumetric information. This study evaluated the diagnostic value of multi-slice spiral computed tomography (MSCT) with enhanced scanning in renal trauma. In total, 126 patients with kidney injury underwent MSCT scanning from a single hospital in the southern of China between January 2012 and February 2016. According to kidney injury grading standards of American Association for the Surgery of Trauma (AAST), 30 were diagnosed and classified in level I, 26 in level II, 42 in level III, 17 in level IV, 11 in level V. The outcomes of MSCT enhanced scanning achieve a 100% diagnostic accuracy rate, which was confirmed by surgical findings. We concluded that the enhanced MSCT scan permits reliable detection of renal trauma and the associated organ or tissue injuries, providing important clinical value for the diagnosis and classification of renal trauma or internal organ injures.

Retroperitoneal laparoscopic versus open dismembered pyeloplasty for ureteropelvic junction obstruction.

OBJECTIVE: To compare classical open pyeloplasty with retroperitoneal laparoscopic pyeloplasty in effectiveness, potential advantages and complications. MATERIALS AND METHODS: Between March 2006 and April 2010, 113 patients with ureteropelvic junction obstruction underwent retroperitoneal laparoscopic dismembered pyeloplasty were retrospectively compared with those of 59 patients who underwent open dismemberse pyeloplasty through a retroperitoneal flank approach. The Chi-square test was used for statistical analysis of qualitative data and the Student t-test for analysis of quantitative data. P < 0.05 was considered significant. RESULTS: Operative time was shorter in the retroperitoneal laparoscopic group (mean 125 min) compared to the open pyeloplasty group (mean 142 min, P < 0.05). Mean hospital stay was shorter in the retroperitoneal laparoscopic group (mean 6 days, compared to 9 days, open). Complication rates, including anastomotic urinary leakage, stenosis and infection, were 4.42% in retroperitoneoscopic compared to 6.78% open surgery. Anastomotic leakage was 3 cases in the retroperitoneoscopic group versus 1 case in the open group. Success, defined as improved ultrasonic or renographic parameters, with resolution of symptoms where discernable, was noted in 98.0% of the open group and 98.1% of the retroperitoneoscopic group with a mean follow up of 38.4 and 32.7 months, respectively. CONCLUSIONS: Retroperitoneal laparoscopic dismembered pyeloplasty in treatment of ureteropelvic junction obstruction is a minimally invasive, safe and effective therapy with short procedure time, less complications, and shorter convalescence.