Comparing the diagnostic value of 68Ga-prostate-specific membrane antigen PET/CT and multiparametric MRI in pelvic lymph node metastasis of locally advanced prostate cancer.

Background: Multiparametric magnetic resonance imaging (mpMRI) is a commonly used method to diagnose pelvic lymph node metastasis (PLNM) in prostate cancer (PCa) patients, but there are few comparative studies on mpMRI and 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in locally advanced PCa (LAPC) patients. Therefore, we designed a retrospective study to compare the diagnostic value of 68Ga-PSMA PET/CT and mpMRI for PLNM of LAPC. Methods: A retrospective study was performed on 50 patients with LAPC who underwent radical prostatectomy (RP) in Tongji Hospital from 2021 to 2023. All patients underwent PET/CT and mpMRI examination, and were diagnosed as LAPC before surgery, followed by robot-assisted laparoscopic prostatectomy or laparoscopic RP and extended pelvic lymph node dissection (ePLND). Routine postoperative pathological examination was performed. According to the results, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT and mpMRI for the diagnosis of PLNM of LAPC were compared. Results: Among the 50 patients, the mean age was 65.5±10.3 years, the preoperative total serum prostate-specific antigen (PSA) was 30.7±12.3 ng/mL, and the Gleason score was 7 [7, 8]. The difference in diagnostic efficacy between 68Ga-PSMA PET/CT and mpMRI in the preoperative diagnosis of PLNM of PCa was determined by postoperative pathological results. Based on the number of patients who developed PLNM, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were as follows: 93.75%, 100.00%, 100.00%, 97.14%, and 68.75%, 97.06%, 91.67%, 86.84% for mpMRI, respectively. Based on the number of pelvic metastatic lymph nodes, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were 95.24%, 100.00%, 100.00%, 99.48%, and 65.08%, 99.13%, 89.13%, 96.30% for mpMRI, respectively. It turned out that PET/CT was more sensitive than mpMRI in detecting PLNM of PCa, and the difference was statistically significant. Conclusions: 68Ga-PSMA PET/CT is more sensitive than mpMRI in the detection of PLNM in patients with LAPC. It is a promising method in the diagnosis and preoperative assessment of PLNM in LAPC.

Molecular characterization, expression and immune functional analysis of cystatin 10 in turbot.

BACKGROUND: Cystatin is a protease inhibitor that also regulates genes expression linked to inflammation and plays a role in defense and regulation. METHODS AND RESULTS: Cystatin 10 (Smcys10) was cloned from Scophthalmus maximus and encodes a 145 amino acid polypeptide. The results of qRT-PCR showed that Smcys10 exhibited tissue-specific expression patterns, and its expression was significantly higher in the skin than in other tissues. The expression level of Smcys10 was significantly different in the skin, gill, head kidney, spleen and macrophages after Vibrio anguillarum infection, indicating that Smcys10 may play an important role in resistance to V. anguillarum infection. The recombinant Smcys10 protein showed binding and agglutinating activity in a Ca2+-dependent manner against bacteria. rSmcys10 treatment upregulated the expression of IL-10, TNF-α and TGF-ß in macrophages of turbot and hindered the release of lactate dehydrogenase (LDH) from macrophages after V. anguillarum infection, which confirmed that rSmcys10 reduced the damage to macrophages by V. anguillarum. The NF-κB pathway was suppressed by Smcys10, as demonstrated by dual-luciferase analysis. CONCLUSIONS: These results indicated that Smcys10 is involved in the host antibacterial immune response.

C-type lectin 12B/4E of black rockfish (Sebastes schlegelii) macrophages as pattern recognition receptors in the antibacterial mechanism of exploration.

As lower vertebrates, fish have both innate and adaptive immune systems, but the role of the adaptive immune system is limited, and the innate immune system plays an important role in the resistance to pathogen infection. C-type lectins (CLRs) are one of the major pattern recognition receptors (PRRs) of the innate immune system. CLRs can combine with pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) to trigger NF-κB signaling pathway and exert immune efficacy. In this study, Ssclec12b and Ssclec4e of the C-type lectins, were found to be significantly up-regulated in the transcripts of Sebastes schlegelii macrophages stimulated by bacteria. The identification, expression and function of these lectins were studied. In addition, the recombinant proteins of the above two CLRs were obtained by prokaryotic expression. We found that rSsCLEC12B and rSsCLEC4E could bind to a variety of bacteria in a Ca2+-dependent manner, and promoted the agglutination of bacteria and blood cells. rSsCLEC12B and rSsCLEC4E assisted macrophages to recognize PAMPs and activate the NF-κB signaling pathway, thereby promoting the expression of inflammatory factors (TNF-α, IL-1ß, IL-6, IL-8) and regulating the early immune inflammation of macrophages. These results suggested that SsCLEC12B and SsCLEC4E could serve as PRRs in S. schlegelii macrophages to recognize pathogens and participate in the host antimicrobial immune process, and provided a valuable reference for the study of CLRs involved in fish innate immunity.

Initial Experience with Hybrid Partial Nephrectomy with Ultrasound-guided Balloon Catheter Occlusion of the Renal Artery for Recurrent Renal Tumors.

Repeat partial nephrectomy (PN) is an effective treatment in improving the prognosis for patients with recurrent renal cancer after initial PN. However, salvage PN (sPN) is inevitably associated with a higher rate of complications, largely because of intraperitoneal adhesions and fibrosis. Here we describe three initial cases for which recurrent renal tumors were treated with a novel minimally invasive approach, namely Ultrasound-guided Renal Artery Balloon catheter Occluded Hybrid Partial Nephrectomy (UBo-HPN).With laparoscopic ultrasound (LUS) guiding a Fogarty catheter to occlude the arterial blood supply, dissection of the renal hilum and most of the abdominal cavity can be avoided. UBo-HPN was successfully performed in three patients. One case of postoperative fever (Clavien-Dindo grade II) occurred, with no other complications. The mean operative time was 106 min, with a mean warm ischemia time of 21 min. UBo-HPN may be considered a safe and effective alternative for sPN, with a minimally invasive surgical footprint and better surgical outcomes.

[Corrigendum] MicroRNA­10b promotes migration and invasion through KLF4 and HOXD10 in human bladder cancer.

Following the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 2 on p. 1835, which was designed to show how miR­10b promotes the migration and invasion of human bladder cancer cell lines in vitro, there appeared to be several overlapping panels such that certain of the data may have been derived from the same original sources, even though they were intended to show the results obtained under different experimental conditions. The authors have re­examined their original data, and have realized that the errors arose as a consequence of inadvertently misfiling and mishandling the data. The corrected version of Fig. 2 is shown below. Note that these errors did not affect the overall conclusions reported in the study. All the authors agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish it; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [the original article was published in Oncology Reports 31: 1832­1838, 2014; DOI: 10.3892/or.2014.3048].

Erratum: Inhibition of SMYD2 suppresses tumor progression by down-regulating microRNA-125b and attenuates multi-drug resistance in renal cell carcinoma: Erratum.

[This corrects the article DOI: 10.7150/thno.37628.].

CD46 splice variant enhances translation of specific mRNAs linked to an aggressive tumor cell phenotype in bladder cancer.

CD46 is well known to be involved in diverse biological processes. Although several splice variants of CD46 have been identified, little is known about the contribution of alternative splicing to its tumorigenic functions. In this study, we found that exclusion of CD46 exon 13 is significantly increased in bladder cancer (BCa) samples. In BCa cell lines, enforced expression of CD46-CYT2 (exon 13-skipping isoform) promoted, and CD46-CYT1 (exon 13-containing isoform) attenuated, cell growth, migration, and tumorigenicity in a xenograft model. We also applied interaction proteomics to identify exhaustively the complexes containing the CYT1 or CYT2 domain in EJ-1 cells. 320 proteins were identified that interact with the CYT1 and/or CYT2 domain, and most of them are new interactors. Using an internal ribosome entry site (IRES)-dependent reporter system, we established that CD46 could regulate mRNA translation through an interaction with the translation machinery. We also identified heterogeneous nuclear ribonucleoprotein (hnRNP)A1 as a novel CYT2 binding partner, and this interaction facilitates the interaction of hnRNPA1 with IRES RNA to promote IRES-dependent translation of HIF1a and c-Myc. Strikingly, the splicing factor SRSF1 is highly correlated with CD46 exon 13 exclusion in clinical BCa samples. Taken together, our findings contribute to understanding the role of CD46 in BCa development.

Junction plakoglobin regulates and destabilizes HIF2α to inhibit tumorigenesis of renal cell carcinoma.

BACKGROUND: Increased hypoxia-inducible factor 2α (HIF2α) activation is a common event in clear cell renal cell carcinoma (ccRCC) progression. However, the function and underlying mechanism of HIF2α in ccRCC remains uninvestigated. We conducted this study to access the potential link between junction plakoglobin (JUP) and HIF2α in ccRCC. METHODS: Affinity purification and mass spectrometry (AP-MS) screening, glutathione-s-transferase (GST) pull-down and co-immunoprecipitation (Co-IP) assays were performed to detect the interacting proteins of HIF2α. Quantitative PCR (qPCR) and Western blotting were used to detect the expression of JUP in human ccRCC samples. Luciferase reporter assays, chromatin immunoprecipitation (ChIP), cycloheximide chase assays, and ubiquitination assays were conducted to explore the regulation of JUP on the activity of HIF2α. Cell Counting Kit-8 (CCK-8) assays, colony formation assays, transwell assays, and xenograft tumor assays were performed to investigate the effect of JUP knockdown or overexpression on the tumorigenicity of renal cancer cells. RESULTS: We identified JUP as a novel HIF2α-binding partner and revealed an important role of JUP in recruiting von Hippel-Lindau (VHL) and histone deacetylases 1/2 (HDAC1/2) to HIF2α to regulate its stability and transactivation. JUP knockdown promoted and overexpression suppressed the tumorigenicity of renal cell carcinoma in vitro and in vivo. Importantly, the low expression of JUP was found in clinical ccRCC samples and correlated with enhanced hypoxia scores and poor treatment outcomes. CONCLUSION: Taken together, these data support a role of JUP in modulating HIF2α signaling during ccRCC progression and identify JUP as a potential therapeutic target.

Optimize the management of urological tube-related emergencies during the coronavirus disease 2019 (COVID-19) pandemic.

BACKGROUND: To introduce and determine the value of optimized strategies for the management of urological tube-related emergencies with increased incidence, complexity and operational risk during the global spread of coronavirus disease 2019 (COVID-19). METHODS: All emergent urological patients at Tongji Hospital, Wuhan, during the period of January 23 (the beginning of lockdown in Wuhan) to March 23, 2020, and the corresponding period in 2019 were recruited to form this study's COVID-19 group and control group, respectively. Tongji Hospital has the most concentrated and strongest Chinese medical teams to treat the largest number of severe COVID-19 patients. Patients in the control group were routinely treated, while patients in the COVID-19 group were managed following the optimized principles and strategies. The case incidence for each type of tube-related emergency was recorded. Baseline characteristics and management outcomes (surgery time, secondary complex operation rate, readmission rate, COVID-19 infection rate) were analyzed and compared across the control and COVID-19 periods. RESULTS: The total emergent urological patients during the COVID-19 period was 42, whereas during the control period, it was 124. The incidence of tube-related emergencies increased from 53% to 88% (P<0.001) during the COVID-19 period. In particular, the incidence of nephrostomy tube-related (31% vs. 15%, P=0.027) and single-J stent-related problems (19% vs. 6%, P=0.009) increased significantly. The mean surgery times across the two periods were comparable. The number of secondary complex operations increased from 12 (18%) to 14 (38%) (P=0.028) during the COVID 19-period. The number of 2-week postoperative readmission decreased from 10 (15%) to 1 (3%) (P=0.049). No participants contracted during the COVID-19 period. CONCLUSIONS: Urological tube-related emergencies have been found to have a higher incidence and require more complicated and dangerous operations during the COVID-19 pandemic. However, the optimized management strategies introduced in this study are efficient, and safe for both urologists and patients.

No detection of SARS-CoV-2 from urine, expressed prostatic secretions, and semen in 74 recovered COVID-19 male patients: A perspective and urogenital evaluation.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been spreading all over the world since December 2019. However, medical information regarding the urogenital involvement in recovered COVID-19 patients is limited or unknown. OBJECTIVES: To comprehensively evaluate urogenital involvement in recovered COVID-19 patients. MATERIALS AND METHODS: Men aged between 20 years and 50 years who were diagnosed with SARS-CoV-2 infection and recovered when the study was conducted were enrolled in our study. Demographic and clinical characteristics, and history of hospitalization were collected and analyzed. Urine, expressed prostatic secretions (EPSs), and semen samples were collected for SARS-CoV-2 RNA detection. Semen quality and hormonal profiles were analyzed. RESULTS: Among 74 male recovered COVID-19 patients, 11 (14.9%) were asymptomatic, classified into mild type, and 31 (41.9%) were classified into moderate type. The remaining patients (32/74, 43.2%) had severe pneumonia. No critically ill recovered COVID-19 patient was recruited in our cohort. The median interval between last positive pharyngeal swab RT-PCR test and semen samples collection was 80 days (IQR, 64-93). The median age was 31 years (IQR, 27-36; range, 21-49), and the median body mass index (BMI) was 24.40 (IQR, 22.55-27.30). Forty-five (61.6%) men were married, and 28 (38.4%) were unmarried. Fifty-three (72.6%) patients denied cigarette smoking, 18 (24.7%) were active smokers, and 2 of them were past smokers. The majority of our participants (53/74, 72.6%) did not consume alcohol. Fever occurred in most of the patients (75.3%), and 63 of them had abnormal chest CT images. Only one patient complained of scrotal discomfort during the course of COVID-19, which was ruled out orchitis by MRI (data not shown). A total of 205 samples were collected for SARS-CoV-2 detection (74 urine samples, 70 semen samples, and 61 EPS samples). However, viral nucleic acid was not detected in body fluids from the urogenital system. In terms of hormonal profiles, the levels of FSH, LH, testosterone, and estradiol were 5.20 [4.23] mIU/mL, 3.95 [1.63] mIU/mL, 3.65 [1.19] ng/mL, and 39.48 [12.51] pg/mL, respectively. And these values were within the normal limits. The overall semen quality of recovered COVID-19 patients was above the lower reference limit released by the WHO. While compared with healthy control, sperm concentration, total sperm count, and total motility were significantly declined. In addition, different clinical types of COVID-19 have no significant difference in semen parameters, but total sperm count showed a descending trend. Interestingly, subjects with a longer recovery time showed worse data for sperm quality. Small sample size and lacking semen parameters before the infection are the major limitations of our study. DISCUSSION AND CONCLUSIONS: To the best of our knowledge, it is the largest cohort study with longest follow-up for urogenital evaluation comprehensively so far. Direct urogenital involvement was not found in the recovered COVID-19 male patients. SARS-CoV-2 RNA was undetectable in the urogenital secretions, and semen quality declined slightly, while hormonal profiles remained normal. Moreover, patients with a long time (≥90 days) since recovery had lower total sperm count. Great attention and further study should be conducted and follow-up on the reproductive function in the following months.

Hsa_circ_0088233 Alleviates Proliferation, Migration, and Invasion of Prostate Cancer by Targeting hsa-miR-185-3p.

Prostate cancer is the most common malignant tumor of the urinary system. The mechanisms of the initiation and progression of prostate cancer have not been fully elucidated. Increasing evidence suggests that circular RNAs (circRNAs) are involved in cancer pathogenesis. In this study, we aimed to identify differentially expressed circRNAs in prostate cancer tissues and explored the role of circRNAs in the pathogenesis of prostate cancer. By screening a circRNA microarray assay, we found that circ_0088233 was upregulated in prostate cancer tissues compared to adjacent normal tissues, and this upregulation can be verified in 46 pairs of prostate cancer and adjacent normal tissues examined using quantitative reverse transcription-PCR. The level of circ_0088233 correlated with the TNM stage. Knockdown of circ_0088233 reduced cell proliferation, migration, invasion, and induced G1 phase arrest and apoptosis. In addition, miR-185-3p was identified as the downstream target of circ_0088233 using luciferase reporter assays and a biotinylated circ_0088233 probe pull-down assay. The miR-185-3p level showed a negative correlation with the circ_0088233 level in prostate cancer tissues. Overexpression of circ_0088233 blocked the effects of miR-185-3p on cell proliferation, migration, invasion, cell cycle, and apoptosis. In conclusion, circ_0088233 may function as an oncogene and play an oncogenic role by sponging hsa-miR-185-3p. This study increases the understanding of circRNAs in the progression of prostate cancer. These results implicate circ_0088233 as a potential therapeutic target for prostate cancer.

[Mir-29c-3p targeting TUG1 affects migration and invasion of bladder cancer cells by regulating CAPN7 expression].

OBJECTIVE: To investigate the mechanism by which long non-coding RNA TUG1 affects bladder cancer cell migration and invasion. METHODS: The expressions of TUG1 and miR-29c-3p were examined by quantitative RT-PCR (qRT-PCR) in 10 bladder cancer tissues and 5 bladder cancer cell lines. Trans-well assay was used to detect the changes in migration and invasion abilities of bladder cancer T24 cells after TUG1 knockdown using RNA interference technique, and the alteration in the expression of CAPN7 was also detected. The expression of CAPN7 was examined in T24 cells overexpressing mir-29c-3p by Western blotting, and luciferase reporter assay was performed to confirm the targeting of miR-29c-3p to TUG1 and CAPN7. The effects of CAPN7 overexpression and sh-TUG1 on the migration and invasion of T24 cells were investigated. RESULTS: The expression of TUG1 was up-regulated and mir-29c-3p was down-regulated significantly in bladder cancer tissue with a negative correlation between their expressions. TUG1 knockdown significantly inhibited the migration and invasion of T24 cells (P < 0.01). Overexpression of mir-29c-3p in T24 cells obviously down-regulated the expression of CAPN7 protein, whose expression was positively correlated with TUG1 expression (r=0.4081, P=0.0139). The results of luciferase reporter assay confirmed both TUG1 and CAPN7 as the targets of mir-29c-3p. CAPN7 overexpression could partially reverse the tumor suppressing effect of sh-TUG1 in T24 cells. CONCLUSIONS: Mir-29c-3p targeting TUG1 affects the migration and invasion of bladder cancer cells by regulating the expression of CAPN7.

Three-dimensional printing - Assisted planning for complete and safe resection of retroperitoneal tumor.

BACKGROUND: Surgery is usually recommended to treat retroperitoneal tumors. However, complete surgical resections often remain challenging. OBJECTIVE: To assess the assistant role of three-dimensional (3D) imaging and printing model in retroperitoneal tumor resection, as well as compare the difference between 3D printing and computed tomography (CT) in preoperative planning and confidence building. METHODS: We admitted a patient with retroperitoneal mass (13.0×6.4×14.8 cm) adjacent to important abdominal blood vessels whose surgery was thought to be difficult. 3D printing and CT was arranged. A novel questionnaire and scoring system consisting of surgery difficulty and safety were designed to compare doctors understanding and confidence for surgery based on 3D printing and CT. Twenty-four doctors completed the scoring table based on CT and then 3D imaging, respectively. Paired t-test was applied for statistics analysis. RESULTS: Preoperative evaluation based on 3D printing indicated that the tumor could be removed completely. The operation lasted 120 minutes to successfully remove the tumor and the estimated blood loss was less than 100 ml. Scores based on 3D printing is significantly higher than CT in difficulty and safety of surgery (p < 0.001). Interestingly, the junior doctors seem to benefit more from 3D printing than the senior doctors. CONCLUSIONS: 3D imaging and printing model provides greater help for preoperative planning and confidence building than using CT in resection of retroperitoneal tumor, especially for the junior doctors.

Rs145204276 and rs4759314 affect the prognosis of prostate cancer by modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.

Non-coding RNAs play an important role in the pathogenesis of prostate cancer (PC). This study aims to characterize the role of GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms in the pathogenesis of PC. Both INS allele of GAS5 rs145204276 and A allele of HOTAIR rs4759314 were identified to increase the survival of PC patients. And patients carrying DEL/DEL + AG genotypes tend to present higher levels of HMGB1, GAS5, HOTAIR and lower levels of miR-1284 and miR-22. In addition, the transcription activity of GAS5 promoter was increased by the deletion allele of rs145204276 polymorphism, while the G allele of rs4759314 polymorphism increased the transcription activity of HOTAIR promoter. GAS5 and HOTAIR could bind to miR-1284 and miR-22, respectively, while miR-1284 and miR-22 could bind to the 3'UTR of HMGB1. Compared with the control group, the expressions of miR-1284 or miR-22 were decreased with the presence of GAS5 or HOTAIR, and the expression of HMGB1 was the highest in the GAS5 + HOTAIR group. In summary, the findings of this study demonstrated that both GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms could affect the prognosis of PC by modulating the expression of HMGB1 via modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.

Silencing of tumor-suppressive NR_023387 in renal cell carcinoma via promoter hypermethylation and HNF4A deficiency.

Dysregulation of the epigenetic status of long noncoding RNAs (lncRNAs) has been linked to diverse human diseases including human cancers. However, the landscape of the whole-genome methylation profile of lncRNAs and the precise roles of these lncRNAs remain elusive in renal cell carcinoma (RCC). We first examined lncRNA expression profiles in RCC tissues and corresponding adjacent normal tissues (NTs) to identify the lncRNA signature of RCC, then lncRNA Promoter Microarray was performed to depict the whole-genome methylation profile of lncRNAs in RCC. Combined analysis of the lncRNAs expression profiles and lncRNAs Promoter Microarray identified a series of downregulated lncRNAs with hypermethylated promoter regions, including NR_023387. Quantitative real-time polymerase chain reaction (RT-PCR) implied that NR_023387 was significantly downregulated in RCC tissues and cell lines, and lower expression of NR_023387 was correlated with shorter overall survival. Methylation-specific PCR, MassARRAY, and demethylation drug treatment indicated that hypermethylation in the NR_023387 promoter contributed to its silencing in RCC. Besides, HNF4A regulated the expression of NR_023387 via transcriptional activation. Functional experiments demonstrated NR_023387 exerted tumor-suppressive roles in RCC via suppressing the proliferation, migration, invasion, tumor growth, and metastasis of RCC. Furthermore, we identified MGP as a putative downstream molecule of NR_023387, which promoted the epithelial-mesenchymal transition of RCC cells. Our study provides the first whole-genome lncRNA methylation profile in RCC. Our combined analysis identifies a tumor-suppressive and prognosis-related lncRNA NR_023387, which is silenced in RCC via promoter hypermethylation and HNF4A deficiency, and may exert its tumor-suppressive roles by downregulating the oncogenic MGP.

Inhibition of SMYD2 suppresses tumor progression by down-regulating microRNA-125b and attenuates multi-drug resistance in renal cell carcinoma.

SMYD2 is a histone methyltransferase that has been reported to be an important epigenetic regulator. This study aims to investigate SMYD2 as a prognostic indicator of clear cell renal cell carcinoma (ccRCC) and explore its role in tumorigenesis and multi-drug resistance. Methods: Tumor specimens, clinicopathologic information, and prognostic outcomes of 186 ccRCC patients from three hospitals in China were collected for SMYD2 immunohistochemistry staining, Kaplan-Meier analysis, and Cox proportional hazards-regression analysis. MicroRNA (miRNA)-microarray profiling identified differentially expressed miRNAs in renal cancer cells subjected to SMYD2 knockdown or treatment with the SMYD2 inhibitor AZ505. The effects of SMYD2 and candidate SMYD2-mediated miRNAs on renal cancer cell proliferation, migration, clonogenicity, and tumorigenicity were determined via cell-function assays and murine xenograft experiments. The half-inhibitory concentrations (IC50) of five antineoplastic drugs (cisplatin, doxorubicin, fluorouracil, docetaxel, and sunitinib) in AZ505-treated and control cells were calculated, and the effects of SMYD2 inhibition on P-glycoprotein (P-gP) expression and multiple-drug resistance were verified. Results: SMYD2 was overexpressed and acted as an oncogene in ccRCC. High SMYD2 expression correlated with a high TNM stage (P = 0.007) and early tumor relapse (P = 0.032). SMYD2 independently predicted a worse overall survival (P = 0.022) and disease-free survival (P = 0.048). AZ505 inhibited the binding of SMYD2 to the miR-125b promoter region (based on chromatin immunoprecipitation assays) and suppressed ccRCC cell migration and invasion by inhibiting the SMYD2/miR-125b/DKK3 pathway. SMYD2 and miR-125b inhibition acted synergistically with anticancer drugs via P-gP suppression in vitro and in vivo. Conclusions: These findings suggested that SMYD2 plays an important role in ccRCC development and could be a potential biomarker for the treatment and prognosis of RCC.

Pan-cancer analysis of clinical relevance of alternative splicing events in 31 human cancers.

Alternative splicing represents a critical posttranscriptional regulation of gene expression, which contributes to the protein complexity and mRNA processing. Defects of alternative splicing including genetic alteration and/or altered expression of both pre-mRNA and trans-acting factors give rise to many cancers. By integrally analyzing clinical data and splicing data from TCGA and SpliceSeq databases, a number of splicing events were found clinically relevant in tumor samples. Alternative splicing of KLK2 (KLK2_51239) was found as a potential inducement of nonsense-mediated mRNA decay and associated with poor survival in prostate cancer. Consensus K-means clustering analysis indicated that alternative splicing events could be potentially used for molecular subtype classification of cancers. By random forest survival algorithm, prognostic prediction signatures with well performances were constructed for 31 cancers by using survival-associated alternative splicing events. Furthermore, an online tool for visualization of Kaplan-Meier plots of splicing events in 31 cancers was explored. Briefly, alternative splicing was found of significant clinical relevance with cancers.

Does Postoperative Rehabilitation for Radical Cystectomy Call for Enhanced Recovery after Surgery? A Systematic Review and Meta-analysis.

The aim of this review was to systematically compare the outcomes of enhanced recovery after surgery (ERAS) with standard care (SC) after radical cystectomy. We performed a systematic search of PubMed, Ovid, Web of Science, and the Cochrane Library to identify studies published until September 2017 which involved a comparison of ERAS and SC. A meta-analysis was performed to assess the outcomes of ERAS versus SC. Sixteen studies including 8 prospective and 8 retrospective trials met the eligibility criteria. A total of 2100 participants were assigned to ERAS (1258 cases) or SC (842 cases). The time to first flatus passage {WMD=-0.95 days, 95% CI (-1.50,-0.41), P=0.0006}, time until return to a regular diet {WMD=-2.15 days, 95% CI (-2.86,-1.45), P<0.00001} and the length of hospital stay {WMD=-3.75 days, 95% CI (-5.13,-2.36), P<0.00001} were significantly shorter, and the incidence of postoperative complications {OR=0.60, 95% CI (0.44, 0.83), P=0.002}, especially postoperative paralytic ileus {OR=0.43, 95% CI (0.30, 0.62), P<0.00001} and cardiovascular complications {OR=0.28, 95% CI (0.09, 0.90), P=0.03} was significantly lower in the ERAS group than those in the SC group. This meta-analysis demonstrated that ERAS was associated with a shorter time to first flatus passage, return of bowel function, and the length of hospital stay than SC in patients undergoing radical cystectomy, as well as a lower rate of postoperative complications, especially paralytic ileus and cardiovascular complications.