Proteomic Identification of Small Extracellular Vesicle Proteins LAMB1 and Histone H4 for Prostate Cancer Diagnosis and Risk Stratification.

Diagnosis and stratification of prostate cancer (PCa) patients using the prostate-specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label-free LC-MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared to low-risk PCa patients and control subjects. These two sEV proteins demonstrate higher specificity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratification.

Establishment and validation of a nomogram for predicting overall survival of upper-tract urothelial carcinoma with bone metastasis: a population-based study.

BACKGROUND: Bone metastasis (BM) carries a poor prognosis for patients with upper-tract urothelial carcinoma (UTUC). This study aims to identify survival predictors and develop a prognostic nomogram for overall survival (OS) in UTUC patients with BM. METHODS: The Surveillance, Epidemiology, and End Results database was used to select patients with UTUC between 2010 and 2019. The chi-square test was used to assess the baseline differences between the groups. Kaplan-Meier analysis was employed to assess OS. Univariate and multivariate analyses were conducted to identify prognostic factors for nomogram establishment. An independent cohort was used for external validation of the nomogram. The discrimination and calibration of the nomogram were evaluated using concordance index (C-index), area under receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). All statistical analyses were performed using SPSS 23.0 and R software 4.2.2. RESULTS: The mean OS for UTUC patients with BM was 10 months (95% CI: 8.17 to 11.84), with 6-month OS, 1-year OS, and 3-year OS rates of 41%, 21%, and 3%, respectively. Multi-organ metastases (HR = 2.21, 95% CI: 1.66 to 2.95, P < 0.001), surgery (HR = 0.72, 95% CI: 0.56 to 0.91, P = 0.007), and chemotherapy (HR = 0.37, 95% CI: 0.3 to 0.46, P < 0.001) were identified as independent prognostic factors. The C-index was 0.725 for the training cohort and 0.854 for the validation cohort, and all AUC values were > 0.679. The calibration curve and DCA curve showed the accuracy and practicality of the nomogram. CONCLUSIONS: The OS of UTUC patients with BM was poor. Multi-organ metastases was a risk factor for OS, while surgery and chemotherapy were protective factors. Our nomogram was developed and validated to assist clinicians in evaluating the OS of UTUC patients with BM.

Early differential diagnosis of pancytopenia related diseases based on serum surface-enhanced Raman spectroscopy.

Pancytopenia is a common blood disorder defined as the decrease of red blood cells, white blood cells and platelets in the peripheral blood. Its genesis mechanism is typically complex and a variety of diseases have been found to be capable of causing pancytopenia, some of which are featured by their high mortality rates. Early judgement on the cause of pancytopenia can benefit timely and appropriate treatment to improve patient survival significantly. In this study, a serum surface-enhanced Raman spectroscopy (SERS) method was explored for the early differential diagnosis of three pancytopenia related diseases, i.e., aplastic anemia (AA), myelodysplastic syndrome (MDS) and spontaneous remission of pancytopenia (SRP), in which the patients with those pancytopenia related diseases at initial stage exhibited same pancytopenia symptom but cannot be conclusively diagnosed through conventional clinical examinations. The SERS spectral analysis results suggested that certain amino acids, protein substances and nucleic acids are expected to be potential biomarkers for their early differential diagnosis. In addition, a diagnostic model was established based on the joint use of partial least squares analysis and linear discriminant analysis (PLS-LDA), and an overall accuracy of 86.67 % was achieved to differentiate those pancytopenia related diseases, even at the time that confirmed diagnosis cannot be made by routine clinical examinations. Therefore, the proposed method has demonstrated great potential for the early differential diagnosis of pancytopenia related diseases, thus it has significant clinical importance for the timely and rational guidance on subsequent treatment to improve patient survival.

Distinguishable Colorimetric Biosensor for Diagnosis of Prostate Cancer Bone Metastases.

Castration-resistant prostate cancer (PCa) causes severe bone metastasis (BM), which significantly increases mortality in men with PCa. Imaging tests and radiometric scanning require long analysis times, expensive equipment, specialized personnel, and a slow turnaround. New visualization technologies are expected to solve the above problems. Nonetheless, existing visualization techniques barely meet the urgency for precise diagnosis because the human eyes cannot recognize and capture even slight variations in visual information. By using dye differentiated superposition enhancement colorimetric biosensors, an effective method to diagnose prostate cancer bone metastases (PCa-BM) with excellent accuracy for naked-eye quantitative detection of alkaline phosphatase (ALP) is developed. The biomarker ALP specific hydrolytic product ascorbic acid can be detected by rhodamine derivatives (Rd) as gold nanobipyramids (Au NBPs) are deposited and grown. Color-recombining enhancement effects between Rd and Au NBPs significantly improved abundance. The 150 U L-1 threshold between normal and abnormal can be identified by color. And with color enhancement effect and double signal response, the ALP index is visually measured to diagnose PCa-BM and provide handy treatment recommendations. Additionally, the proposed colorimetric sensing strategy can be used to diagnose other diseases.

Eph receptor B6 shapes a cold immune microenvironment, inhibiting anti-cancer immunity and immunotherapy response in bladder cancer.

Background: The role of Eph receptors and related ephrin (EFN) ligands (as the largest family of transmembrane-bound RTKs) in immunomodulation in many types of cancer, especially bladder cancer (BLCA), is scarcely known. Methods: A pan-cancer dataset was retrieved from The Cancer Genome Atlas (TCGA) to explore the relation between Eph receptor/EFN ligand family genes and immunomodulators and tumor-infiltrated immune cells (TIICs). Local BLCA, GSE32894, and GSE31684 cohorts were applied to validate. The IMvigor210 cohort was employed to explore the relationship between EPHB6 and immunotherapy response. Moreover, association between EPHB6 and molecular subtype was investigated to explore potential therapeutic strategies. Immunohistochemical staining of CD8 and CD68 was performed to validate the correlation between EPHB6 and TIICs. Results: The pan-cancer analysis revealed variations in the immunological effects of Eph receptor/EFN ligand family genes across different types of cancer. EPHB6 expression negatively correlated with the expression of the majority of immunomodulators (including HLA and immune checkpoints), and CD8 T cells and macrophages in both the TCGA-BLCA and validation BLCA cohorts, shaping a cold immune microenvironment with inhibited immunity. In the IMvigor210 cohort, patients with high-EPHB6 highly correlated with a non-inflamed, low PD-L1 expression immune phenotype, and correspondingly, with less responders to immunotherapy. The high-EPHB6 group, enriched with the basal subtype, presented significantly fewer TP53 and more FGFR3 genomic alterations. Finally, a novel EPHB6-related Genes signature, with reliable and robust ability in prognosis prediction, was constructed. Conclusions: This study comprehensively investigated the immunological effects of Eph receptor/EFN ligand family genes pan-cancer, and specially identified the immunosuppressive role of EPHB6 in BLCA. Furthermore, EPHB6 may predict the molecular subtype and prognosis of BLCA, and serve as a novel therapeutic target to improve the sensitivity of immunotherapy.

Dual enzyme induced colorimetric sensor for simultaneous identifying multiple pathogens.

Rapid and accurate identification of foodborne pathogens improves public health. Currently employed methods are time-consuming, sensitive to environmental factors, and complex. This study develops a colorimetric sensor for detecting multiple bacteria with one probe using double-enzyme-induced colorimetry. Based on alkaline phosphatase (ALP) in bacteria decomposes L-ascorbic acid 2-magnesium phosphate salt hydrate into ascorbic acid (AA). Manganese dioxide flowers (MnO2 NFs) can oxidize TMB to etch gold nanorods (Au NRs), which can be inhibited by AA reduction to produce rich colors. Bacteria with varying ALP levels can be identified based on color changes and plasmon resonance wavelength signals produced from Au NRs. Furthermore, the conversion of RGB signals to digital signals and the use of linear discriminant analysis (LDA) allowed 99.57% accuracy in identifying multiple bacteria. It can simultaneously identify five foodborne pathogens across diverse environments (shrimp, meat, milk, etc.). This method may be useful for the rapid and simple identification of foodborne illnesses.

Adverse Childhood Experiences Are Associated With Adult Dream Content: A Cross-Sectional Survey.

Background: Dreams can be affected by recent life events and long-term life experiences. Previous evidence has shown that childhood adverse experiences are associated with sleep quality and dream experiences. Objective: The aim of this study was to explore the relationship between childhood adverse experiences and dream content in adults. Participants and Setting: A total of 163 participants without current or past physical or mental disorders aged between 18 and 35 were screened in the hospital. Among them, 120 subjects who completed a dream content record at home and whose anxiety and depression levels and sleep quality were within the normal range were included in the data analysis. Methods: A cross-sectional survey was conducted from June 2017 to December 2019. Dream content for 10 consecutive days was recorded by the participants and coded by the Hall and Van de Castle coding system. Childhood adversity was assessed by the Childhood Trauma Questionnaire (CTQ). In the end, 719 dreams out of 626 nights for 120 participants (44 female) were included in the data analysis, gender differences between groups were analyzed using t-tests or U tests, and Spearman's partial correlation and multiple linear regression were used to investigate the relationship between childhood trauma and dream content. Results: Childhood adversity was associated with characters, friendly interactions, and objects in dream content. Regression models of childhood adversity predicting characters and objects in dream content were constructed. There were no gender differences in general demographic data, sleep quality, emotional state, childhood adversity, dream recall frequency, or dream content. Conclusion: Childhood adversity is associated with adult dream content.

Acute pulmonary embolism and severe post thrombolysis renal bleeding, two deadly complications following mini-percutaneous nephrolithotomy: a rare case report.

BACKGROUND: Acute pulmonary embolism and severe renal bleeding are two lethal postoperative complications, but there has been no report that involves both of them after mini-percutaneous nephrolithotomy. CASE PRESENTATION: A 62-year-old woman was admitted to our hospital with extremely severe hydronephrosis and multiple right renal calculi. After thorough examination, she received prone-position mini-percutaneous nephrolithotomy under spinal anaesthesia. Three days postoperatively, the patient complained of chest pain and dyspnea. Computed tomography pulmonary angiogram (CTPA) showed multiple embolisms in the left pulmonary artery and its branches. Symptoms were relieved after anticoagulant and thrombolysis therapy. On the 6th postoperative day, the patient developed shortness of breath, computed tomography angiography (CTA) showed massive hemorrhage in the right kidney, diffused contrast medium in the middle and lower part of the right kidney was seen during digital substraction angiography (DSA). Superselective right renal artery embolization (SRAE) was then applied using coil to occlude the responsible artery. The patient generally recovered under conscientious care and was approved to be discharged 26 days postoperatively. CONCLUSIONS: This is the first case that involved both acute pulmonary embolism and severe post thrombolysis renal bleeding. The importance of D-dimer in the prediction and early detection of pulmonary embolism should be noted. For post thrombolysis renal bleeding, SRAE is considered as a reliable treatment.

Gelatin-grafted tubular asymmetric scaffolds promote ureteral regeneration via activation of the integrin/Erk signaling pathway.

Introduction: The repair of a diseased ureter is an urgent clinical issue that needs to be solved. A tissue-engineered scaffold for ureteral replacement is currently insufficient due to its incompetent bioactivity, especially in long-segment abnormalities. The primary reason is the failure of urothelialization on scaffolds. Methods: In this work, we investigated the ability of gelatin-grafted tubular scaffold in ureteral repairment and its related biological mechanism. We designed various porous asymmetric poly (L-lactic acid) (PLLA)/poly (L-lactide-co-e-caprolactone) (PLCL) tubes with a thermally induced phase separation (TIPS) method via a change in the ratio of solvents (named PP). To regulate the phenotype of urothelial cells and ureteral reconstruction, gelatin was grafted onto the tubular scaffold using ammonolysis and glutaraldehyde crosslinking (named PP-gel). The in vitro and in vivo experiments were performed to test the biological function and the mechanism of the scaffolds. Results and Discussion: The hydrophilicity of the scaffold significantly increased after gelatin grafting, which promoted the adhesion and proliferation of urothelial cells. Through subcutaneous implantation in rats, PP-gel scaffolds demonstrated good biocompatibility. The in vivo replacement showed that PP-gel could improve urothelium regeneration and maintain renal function after the ureter was replaced with an ∼4 cm-long PP-gel tube using New Zealand rabbits as the experimental animals. The related biologic mechanism of ureteral reconstruction was detected in detail. The gelatin-grafted scaffold upgraded the integrin α6/ß4 on the urothelial cell membrane, which phosphorylates the focal adhesion kinase (FAK) and enhances urothelialization via the MAPK/Erk signaling pathway. Conclusion: All these results confirmed that the PP46-gel scaffold is a promising candidate for the constitution of an engineered ureter and to repair long-segment ureteral defects.

Bilateral hematoma after tubeless percutaneous nephrolithotomy for unilateral horseshoe kidney stones: A case report.

BACKGROUND: Bilateral perirenal hematoma is rarely reported in endoscopic management of horseshoe kidney stones, and there are few studies reporting the formation of bilateral hematoma following tubeless percutaneous nephrolithotomy (PCNL) for unilateral horseshoe kidney calculi. CASE SUMMARY: A 32-year-old man was admitted to our hospital because of repeated intermittent hematuria for 10 years. Plain abdominal computed tomography (CT) scan revealed calculi in the horseshoe kidney; the largest being 2 cm in diameter. Tubeless PCNL was performed to remove the stones. Three days after the operation, the patient was discharged in a stable situation. Three days after discharge, the patient presented to our emergency department because of right low back pain and vomiting. Emergent CT scan revealed subcapsular and perirenal hematocele and exudates in both kidneys. Ultrasound-guided puncture and drainage of perirenal effusion were performed. After the temperature stabilized, the patient received low-pressure injection of urokinase 100000 U for 3 d. His routine blood indexes and the renal function returned to normal in 3 wk. CT re-examination 3 mo after lithotripsy showed that the subcapsular and perirenal hematoma and exudates in both kidneys were significantly absorbed as compared with those before. The patient was followed up for 1 year, during which no flank pain or hematuria recurred. CONCLUSION: This is the first case report on the formation of bilateral hematoma following tubeless PCNL for unilateral horseshoe kidney calculi.

The Use of High-Intensity Focused Ultrasound (HIFU) Plus 150mg Bicalutamide as First Line Salvage Therapy for Local Recurrent Prostate Cancer.

Patients with localized prostate cancer (PCa) are often treated with radical prostatectomy (RP). However, more than 30% of such patients have high risk of recurrence. Salvage radiotherapy (SRT), androgen deprivation therapy (ADT) and combination of radiotherapy and ADT are the standard care for recurrent PCa. Recently, high intensity focused ultrasound (HIFU) has gradually applied in the treatment of recurrent PCa. Here, we proposed a hypothesis that combined HIFU and bicalutamide 150mg as first line salvage therapy to treat patients with local recurrent PCa with visible lesions due to the following advantages: (1) HIFU is effective in reducing local tumor load, and bicalutamide 150mg is a feasible and safety option to combine with HIFU. (2) Compared with radiotherapy, HIFU plus 150mg bicalutamide is minimal invasiveness with fewer adverse effects and better quality of life(QOL); (3) Radiotherapy can be preserved as the second-line salvage method in the cases who are failure to HIFU and 150mg bicalutamide combination. More clinical trials are warranted to confirm this hypothesis in treatment with recurrent PCa.

Atypical granular cell tumor of the urinary bladder: A case report.

BACKGROUND: Granular cell tumor (GCT) is a neurogenic tumor mainly occurring in the head and neck. GCT in the genitourinary system is extremely rare and only sporadic cases of urinary bladder GCT have been reported. Most urinary bladder GCT cases are benign and only two malignant cases have been reported. Due to its rarity, no consensus criteria for the treatment of urinary bladder GCT are available at present. CASE SUMMARY: A 62-year-old Chinese woman was found to have a urinary bladder tumor without any clinical manifestations on physical examination. Cystoscopy revealed a semispherical shaped lesion measuring approximately 4.0 cm in diameter at the junction of the left wall and roof of the bladder, which was covered with normal bladder mucosa. Computed tomography scan demonstrated a high-density lesion on the left wall of the bladder, measuring approximately 2.9 cm × 2.4 cm with clear boundaries. Contrast-enhanced pelvic magnetic resonance imaging revealed a space-occupying lesion on the left wall of the bladder (non-mucosal origin/ external pressure), which was preliminarily suspected to be a desmoplastic fibroma or leiomyoma. In the context of the above findings, a pre-operative diagnosis of bladder leiomyoma was made. The patient consequently underwent a laparoscopic partial cystectomy. The resected bladder mass looked yellowish and well-demarcated, measuring 4.0 cm × 3.5 cm and infiltrated the muscular layer. The diagnosis of urinary bladder GCT was finally made by postoperative pathology, with positive immunohistochemical S-100 staining and negative pancytokeratin. The patient has been followed for 6 mo so far, with no tumor recurrence detected. CONCLUSION: This case highlights the biological feature and differential diagnosis of urinary bladder GCT at the pathological and molecular levels. Transurethral resection of the bladder tumor and partial cystectomy are recommended in most urinary bladder GCT cases, while radical cystectomy is recommended in malignant cases.

Identification of novel biomarkers in Hunner's interstitial cystitis using the CIBERSORT, an algorithm based on machine learning.

BACKGROUND:  Hunner's interstitial cystitis (HIC) is a complex disorder characterized by pelvic pain, disrupted urine storage, and Hunner lesions seen on cystoscopy. There are few effective diagnostic biomarkers. In the present study, we used the novel machine learning tool CIBERSORT to measure immune cell subset infiltration and potential novel diagnostic biomarkers for HIC. METHODS: The GSE11783 and GSE57560 datasets were downloaded from the Gene Expression Omnibus for analysis. Ten HIC and six healthy samples from GSE11783 were analyzed using the CIBERSORT algorithm. Gene Set Enrichment Analysis (GSEA) was performed to identify biological processes that occur during HIC pathogenesis. Finally, expression levels of 11 T cell follicular helper cell (Tfh) markers were compared between three healthy individuals and four patients from GSE57560. RESULTS: Six types of immune cells in HIC from GSE11783 showed significant differences, including resting mast cells, CD4+ memory-activated T cells (CD3+ CD4+ HLA-DR+ cells), M0 and M2 macrophages, Tfh cells, and activated natural killer cells. Except for plasma cells, there were no significant differences between Hunner's lesion and non-Hunner's lesion areas in HIC. The GSEA revealed significantly altered biological processes, including antigen-antibody reactions, autoimmune diseases, and infections of viruses, bacteria, and parasites. There were 11 Tfh cell markers with elevated expression in patients from GSE57560. CONCLUSION: This was the first demonstration of Tfh cells and CD3+ CD4+ HLA-DR+ cells with elevated expression in HIC. These cells might serve as novel diagnostic biomarkers.

From "feeling" to "seeing": modification of the percutaneous peritoneal dialysis catheter insertion with an optical puncture system.

PURPOSE: Blind insertion limits the application of percutaneous peritoneal dialysis (PD) catheter placement. In this study, we first described the use of an optical puncture system in the PD catheter insertion, and investigated the feasibility and advantages of this modified technique. METHODS: This retrospective study included 65 patients with chronic kidney disease stage 5 (CKD5) who received ultrasound-guided percutaneous PD catheter insertion with or without optical puncture system assistance between June 2018 and July 2019. The patients' characteristics as well as the surgical outcomes and complications were compared between the modified group and the routine percutaneous insertion group. RESULTS: Twenty-five patients underwent optical puncture system assistant insertion, whereas 40 patients received routine percutaneous insertion. More patients had previous abdominal surgical histories in the modified group than those in the routine group (24.0% vs. 5.0%, p = 0.047). The time of accessing to the abdominal cavity was significantly shorter in the modified group (median [IQR]; 1.1 min [0.8-1.3] vs. 5.0 min [4.0-6.0]; p < 0.001). Meanwhile, the time of the whole procedure was also significantly shorter in the modified group (median [IQR]; 26.0 min [25.0-29.0] vs. 33.0 min [29.0-35.0]; p < 0.001). None of the patient in the modified group, while two patients (5.0%) in the routine group converted to open procedure. There were no significant differences in the short and long postoperative complications between the two groups. CONCLUSIONS: The operation of ultrasound-guided PD catheter placement with the optical puncture system is easy, safe, fast and accurate, whereby the PD catheter can be implanted percutaneously and visually under local anesthesia with minimal procedure-related complications. The visible puncture of the optical puncture system may facilitate ultrasound-guided percutaneous PD catheter insertion in patients with obesity and previous abdominal surgeries.

Effect of silver diamine fluoride on plaque microbiome in children.

OBJECTIVE: To investigate the microbiome profile and relative abundance changes of the plaque on silver diamine fluoride (SDF)-treated caries in children with early childhood caries. METHODS: A single trained examiner assessed the caries as being arrested or active and then collected plaque samples from the caries lesions from fourteen 5-year-old children immediately before, 2 weeks after, and 12 weeks after a one-off application of 38 % SDF. We assigned 16S rRNA gene sequences to operational taxonomic units (OTUs) using a 98.5 % identity cut-off. We also used a variety of taxonomy- and phylogeny-based statistical approaches to compare the biodiversity and relative abundance among different groups. RESULTS: The caries arrest rate were 90 % and 83 % after 2 and 12 weeks, respectively. We studied 46 plaque samples and identified 388 OTUs (254 identified at the species level, 129 identified at the genus level, and 76 identified at the family level). There was no significant change in the diversity in the arrested caries before and 12 weeks after SDF treatment (p = 0.71). The diversity in active caries reduced significantly 12 weeks after SDF treatment (p = 0.006). The relative abundance of certain caries-related species (e.g., Streptococcus mutans and Lactobacillus sp.) was reduced in arrested caries but was increased in active caries after SDF treatment. CONCLUSION: There was no overall microbiome changes in the caries arrested by SDF. The relative abundance of some caries-related species is reduced in arrested caries, while increased in active caries. CLINICAL SIGNIFICANCE: This study provides information on microbiome changes on SDF-treated caries of children.

The in vitro effects of trimethyltin on the androgen biosynthesis of rat immature Leydig cells.

Trimethyltin (TMT) is widely used in industry and agriculture. The present study aims to clarify the effects of in vitro TMT exposure on androgen biosynthesis and metabolism in immature Leydig cells (ILCs), and to unveil the underlying mechanism. It was found that 1-10µM TMT decreased ILC androgen productions under basal conditions. TMT at 10µM decreased luteinizing hormone (LH) or 8-Br-cAMP (8BR)-stimulated androgen productions from ILCs. TMT at 10µM decreased 22R-hydroxycholesterol (22R) and androstenedione (D4)-mediated androgen productions from ILCs. TMT at 0.1-10µM down-regulated the mRNA or protein expression levels of STAR, CYP11A1, 17ß-HSD3, or NR5A1. TMT at 10µM directly inhibited the enzyme activities of CYP11A1 and 17ß-HSD3. In conclusion, the present study demonstrated that in vitro TMT exposure decreased ILC function of androgen production, via exerting negative effects on the mRNA/protein expression levels, or enzyme activities of STAR, CYP11A1, 17ß-HSD3, or NR5A1.

Long non-coding RNA MIR4435-1HG promotes cancer growth in clear cell renal cell carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in cancer development, yet their roles in renal carcinoma remain unclear. OBJECTIVE: We performed this study in order to investigate the expression and roles of lncRNAs in renal cell carcinoma. METHODS: In this study, we investigated the expression of lncRNAs in renal cell carcinoma through microarray analysis. Quantitative real-time PCR was performed to measure the expression of lncRNAs. Gain- or loss-of-function experiments were performed to investigate the roles of lncRNAs in cell proliferation and apoptosis. RNA pull-down and western blotting were performed to explore the underlying mechanism. RESULTS: The microarray analysis identified an upregulated lncRNA MIR4435-1HG in renal carcinoma. The expression level of MIR4435-1HG was correlated with TNM stage, tumor size, and Fuhrman grade. High expression of MIR4435-1HG indicated poor prognosis. MIR4435-1HG knockdown inhibited cell proliferation, and suppressed the migrating and invasive capacity of renal carcinoma cells. RNA pull-down followed by mass spectrometry revealed an interaction between MIR4435-1HG and pyruvate carboxylase, which was later corroborated by western blotting. CONCLUSIONS: MIR4435-1HG plays a critical role in the oncogenesis of renal cell carcinoma and may serve as a potential biomarker for renal cell carcinoma.

Safety and efficacy of en bloc transurethral resection versus conventional transurethral resection for primary nonmuscle-invasive bladder cancer: a meta-analysis.

BACKGROUND: The purpose of this meta-analysis is to compare the safety and efficacy of en bloc transurethral resection of bladder tumor (EBRT) versus conventional transurethral resection of bladder tumor (CTURBT). METHODS: We performed a meta-analysis of relevant articles through November 2019 using PubMed, Embase, and Cochrane Central Register to compare the safety and efficacy of EBRT versus CTURBT. The main endpoint included the operation time (OT), hospitalization time (HT), catheterization time (AT), perioperative period complications, bladder detrusor muscle found in the specimen, the residual tumor on the base, the ratio of the same site recurrence, and 12/24/36-month recurrence rate. Cochrane Collaboration's Revman software, version 5.3, was used for statistical analysis. RESULTS: A total of 19 studies with 2651 patients were included, 1369 underwent EBRT and 1282 underwent CTURBT. Patients treated with EBRT had a significantly lower AT, HT, obturator nerve reflex, bladder perforation, bladder irritation, postoperative complications, and 24-month recurrence rate than those who underwent CTURBT. While no significant difference was found in terms of OT, the ratio of bladder detrusor muscle found in the specimen, the residual tumor on the base, 12-month recurrence rate, 36-month recurrence rate, and the ratio of the same site recurrence. In mitomycin subgroup, EBRT was superior to CTURBT in terms of 12/24-month recurrence rate. Similarly, in the prospective subgroup and retrospective subgroup, EBRT had a lower 24-month recurrence rate than CTURBT. However, no significant difference was found in the low, intermediate, and high-risk group in the light of 12-36-month recurrence rate. CONCLUSIONS: Based on the included 19 articles, EBRT had a significantly lower AT, HT, intraoperative and postoperative complications, and 24-month recurrence rate than those treated with CTURBT. Well-designed randomized controlled trials were needed to reevaluate these outcomes. TRIAL REGISTRATION: This meta-analysis was reported in agreement with the PRISMA statement and was registered on PROSPERO 2019 CRD42019121673.

Sinularin exerts anti-tumor effects against human renal cancer cells relies on the generation of ROS.

Sinularin, a soft corals-derived natural product, exerts anti-tumorigenic activity in various types of human cancer cells. However, the action of Sinularin and its mechanism in renal carcinoma is not well understood. In the current study, we demonstrated that Sinularin inhibited the viability of human renal cancer cells 786-O and ACHN in a dose- and time-dependent manner, but did not show significant toxicity against non-malignant HRCEpic cells. Cell cycle analysis revealed that Sinularin induced G2/M arrest significantly. In addition, Sinularin could induce apoptosis in cells along with caspase-3/-9 activation, release of mitochondrial proteins, up-regulation of pro-apoptotic Bcl-2 family proteins and inhibition of anti-apoptotic Bcl-2 family proteins. Sinularin could also repress the activation of PI3K/Akt/mTOR signaling pathway. Moreover, Sinularin triggered the activation of MAPKs and p38 activation was essential for the anti-tumor effect of Sinularin. The generation of ROS (reactive oxygen species) was critical for Sinularin-induced apoptosis since ROS scavenger NAC (N-acetyl cysteine) could block the Sinularin-triggered apoptosis. In conclusion, all the results indicated that Sinularin may be applied as a therapeutic natural agent for human renal cancer.