Salivary Extracellular MicroRNAs for Early Detection and Prognostication of Esophageal Cancer: A Clinical Study.

BACKGROUND & AIMS: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a microRNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication. METHODS: Salivary EVP miRNA expression was profiled in a pilot cohort (n = 54) using microarray. Area under the receiver operator characteristic curve (AUROC) and least absolute shrinkage and selector operation regression analyses were used to prioritize miRNAs that discriminated patients with ESCC from controls. Using quantitative reverse transcription polymerase chain reaction, the candidates were measured in a discovery cohort (n = 72) and cell lines. The prediction models for the biomarkers were derived from a training cohort (n = 342) and validated in an internal cohort (n = 207) and an external cohort (n = 226). RESULTS: The microarray analysis identified 7 miRNAs for distinguishing patients with ESCC from control subjects. Because 1 was not always detectable in the discovery cohort and cell lines, the other 6 miRNAs formed a panel. A signature of this panel accurately identified patients with all-stage ESCC in the training cohort (AUROC = 0.968) and was successfully validated in 2 independent cohorts. Importantly, this signature could distinguish patients with early-stage (stage Ⅰ/Ⅱ) ESCC from control subjects in the training cohort (AUROC = 0.969, sensitivity = 92.00%, specificity = 89.17%) and internal (sensitivity = 90.32%, specificity = 91.04%) and external (sensitivity = 91.07%, specificity = 88.06%) validation cohorts. Moreover, a prognostic signature based on the panel was established and efficiently predicted the high-risk cases with poor progression-free survival and overall survival. CONCLUSIONS: The salivary EVP-based 6-miRNA signature can serve as noninvasive biomarkers for early detection and risk stratification of ESCC. Chinese Clinical Trial Registry, ChiCTR2000031507.

LIMK2 acts as an oncogene in bladder cancer and its functional SNP in the microRNA-135a binding site affects bladder cancer risk.

LIM kinases modulate multiple aspects of cancer development, including cell proliferation and survival. As the mechanisms of LIMK-associated tumorigenesis are still unclear, we analyzed the tumorigenic functions of LIM kinase 2 (LIMK2) in human bladder cancer (BC) and explored whether the newly identified LIMK2 3´-UTR SNP rs2073859 (G-to-A allele) is correlated with clinical features. Expression levels of LIMK2 in 38 human BC tissues and eight cell lines were examined using quantitative real-time PCR and immunohistochemistry. LIMK2 was overexpressed in most BC tissues (27/38, 71%) and BC-derived cell lines (6/8), and was more frequently overexpessed in high-grade than low-grade BC (80% vs. 47%). The effects of LIMK2 on BC cell proliferation, survival and migration, were studied by overexpression and RNA interference approaches in vitro and in vivo. LIMK2 overexpression promoted proliferation, migration and invasion of BC cells, while LIMK2 depletion inhibited cell invasion and viability and induced growth arrest in vitro and in vivo. PCR-Restriction Fragment Length Polymorphism (RFLP) was used to genotype LIMK2 SNP rs2073859 and multivariate logistic regression applied to assess the relationship between allele frequency and clinical features in 139 BC patients. Functional analyses localized SNP rs2073859 within the microRNA-135a seed-binding region and revealed significantly lower LIMK2 G allele expression. The frequency of A genotypes (AG + AA) was higher in the BC group than normal controls and correlated with risks of high-grade and high-stage BC. In conclusion, LIMK2 may function as an oncogene in human BC, while allele-specific regulation by microRNA-135a may influence disease risk.

Targeting Ezh2 could overcome docetaxel resistance in prostate cancer cells.

BACKGROUND: Docetaxel was used to treat metastatic CRPC patients. However, Doc resistance in prostate cancer (PCa) hinders its clinical application. OBJECTIVE: To understand the underlying mechanisms by which Doc resistance is developed and to find novel therapeutic target to cure Doc resistant PCa has clinical importance. METHODS: We established Doc resistant cell lines and explored the role of Ezh2 in the development of Doc resistance by overexpressing its cDNA or using its inhibitor. RESULTS: We found that Ezh2 was induced in our established Doc resistant (DocR) cells, which was attributable to the silenced expression of miR-101-3p and miR-138-5p. Blockage of Ezh2 activity by either inhibitor or miRNA mimics could overcome Doc resistance by suppressing Doc-induced cancer stem cells populations. Mechanistically, Ezh2 activity was required for the induced expression of Nanog, Sox2 and CD44 upon Doc treatment. CONCLUSIONS: Targeting Ezh2 could overcome Doc resistance.

Characterization of rabbit urine-derived stem cells for potential application in lower urinary tract tissue regeneration.

Tissue-engineered urethra with autologous cells seeded on biodegradable scaffolds offers an alternative for lower urinary tract reconstruction. Rabbit is most commonly used as an animal model in urethra and bladder tissue repair. The goal of this study is to characterize rabbit urine-derived stem cells (rUSC) and induce these cells to differentiate into urothelial and smooth muscle cells as an autologous cell source for potential use in lower urinary tract tissue regeneration in a rabbit model. We successfully cultured rUSC from 12 urine samples and 13 bladder wash samples of six rabbits. rUSC colonies appeared more in the bladder wash solution (2-4/15 ml) than those in the urine samples (1-2 clones/15 ml urine). The cells displayed rice grain-like in morphology. Mean population doubling of rUSC was 48.5 ± 6.2 and average doubling time was 25.7 ± 8.4 h, indicating that a single of rUSC clone generated about 4 × 1014 cells in 50 days. The rUSC were positive for CD29, CD90 and CD105 but negative for CD31, CD34 and CD45 in flow cytometry. When exposed to PDGF-BB and TGF-ß1, these cells could differentiate into spindle-like cells, expressing smooth muscle-specific proteins, including α-smooth muscle action, desmin and myosin. Urothelially differentiated rUSC expressed urothelial-specific proteins, i.e., AE1/AE3 and E-cadherin when exposed to epidermal growth factor (EGF). Osteogenic-differentiated rUSC expressed osteogenic marker, i.e., alkaline phosphatase when exposed to serum containing DMEM low-glucose medium with osteogenic supplements. In conclusion, rUSC can be isolated from bladder wash or urine samples and cultured in vitro. There stem cells possess strong proliferative ability and are capable of differentiating in urothelial, myogenic and osteogenic lineages. Thus, rUSC are a potential alternative autologous cell source for lower urinary tract repair with tissue engineering technology in a rabbit model.

[One-puncture one-needle TRUS-guided prostate biopsy for prevention of postoperative infections].

OBJECTIVE: To explore the feasibility and effectiveness of "one-puncture one-needle" transrectal ultrasound (TRUS)-guided prostate biopsy in the prevention of postoperative infections. METHODS: We retrospectively analyzed the clinical data about "one-puncture one-needle" (the observation group) and "one-person one-needle" (the control group) TRUS-guided prostate biopsy performed in the Second People's Hospital of Guangdong Province from January 2005 to December 2015, and compared the incidence rates of puncture-related infection between the two strategies. By "one-puncture one-needle", one needle was used for one biopsy puncture, while by "one-person one-needle", one needle was used for all biopsy punctures in one patient and the needle was sterilized with iodophor after each puncture. RESULTS: Totally, 120 patients received 6+1-core or 12+1-core "one-person one-needle" and 466 underwent 12+1-core "one-puncture one-needle" TRUS-guided prostate biopsy. There were no statistically significant differences between the two groups of patients in age, the prostate volume, the serum PSA level, or the detection rate of prostate cancer (P >0.05). Compared with the control group, the observation group showed remarkably lower incidence rates of puncture-related urinary tract infection (7.5% vs 0.9%, P <0.05), fever (5.0% vs 1.1%, P <0.05), bacteriuria (2.5% vs 0.2%, P <0.05), and total infections (16.7% vs 2.6%, P<0.05) postoperatively. Two cases of bacteremia or sepsis were found in each of the groups, with no significant difference between the two. CONCLUSIONS: "One-puncture one-needle" TRUS-guided prostate biopsy can effectively prevent puncture-related infections.

Nomogram including renal pelvic pressure to predict the occurrence of urosepsis following percutaneous nephrolithotomy: a dual center retrospective study of 1,448 patients.

Background: Urosepsis is a serious complication after percutaneous nephrolithotomy (PCNL). This study aimed to develop and validate a nomogram model that can effectively predict urosepsis following PCNL. Methods: A total of 839 patients who underwent PCNL at General Hospital of Southern Theater Command from January 2018 to January 2023 and a total of 609 patients who underwent PCNL at Guangdong Second Provincial General Hospital from January 2020 to January 2023 were retrospectively analyzed in this study. The center with 839 patients was used to develop the model, and another center with 609 patients was used as an external validation group. Multivariate analysis was used to determine the optimal variables. The validation of the nomogram was assessed using the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA). Results: Urosepsis was observed in 47 (5.6%) and 33 (5.4%) patients in the two centers. Four variables were selected to establish the nomogram through multivariate analysis, including operative time [P<0.001, odds ratio (OR): 1.035, 95% confidence interval (CI): 1.019-1.051], accumulated time of renal pelvic pressure ≥30 mmHg (0 vs. 0-60 s, P=0.011, OR: 3.180, 95% CI: 1.300-7.780; 0-60 vs. ≥60 s, P<0.001, OR: 6.389, 95% CI: 2.603-15.685), bladder urine culture (P<0.001, OR: 6.045, 95% CI: 2.454-14.891) and hydronephrosis (none or light vs. moderate, P=0.003, OR: 3.403, 95% CI: 1.509-7.674; moderate vs. several, P=0.002, OR: 4.704, 95% CI: 1.786-12.391). The calibration results showed that the model was well calibrated and ROC curve demonstrated excellent discrimination of the nomogram. In addition, the DCA showed that the nomogram had a positive net benefit. Conclusions: A prediction nomogram was developed and validated to assist clinicians in assessing the probability of urosepsis after PCNL.

Characterization of a G2M checkpoint-related gene model and subtypes associated with immunotherapy response for clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) presents challenges in early diagnosis and effective treatment. In this study, we aimed to establish a prognostic model based on G2M checkpoint-related genes and identify associated clusters in ccRCC through clinical bioinformatic analysis and experimental validation. Utilizing a single-cell RNA dataset (GSE159115) and bulk-sequencing data from The Cancer Genome Atlas (TCGA) database, we analyzed the G2M checkpoint pathway in ccRCC. Differential expression analysis identified 45 genes associated with the G2M checkpoint, leading to the construction of a predictive model with four key genes (E2F2, GTSE1, RAD54L, and UBE2C). The model demonstrated reliable predictive ability for 1-, 3-, and 5-year overall survival, with AUC values of 0.794, 0.790, and 0.794, respectively. Patients in the high-risk group exhibited a worse prognosis, accompanied by significant differences in immune cell infiltration, immune function, TIDE and IPS scores, and drug sensitivities. Two clusters of ccRCC were identified using the "ConsensusClusterPlus" package, cluster 1 exhibited a worse survival rate and was resistant to chemotherapeutic drugs of Axitinib, Erlotinib, Pazopanib, Sunitinib, and Temsirolimus, but not Sorafenib. Targeted experiments on RAD54L, a gene involved in DNA repair processes, revealed its crucial role in inhibiting proliferation, invasion, and migration in 786-O cells. In conclusion, our study offers valuable insights into the molecular mechanisms underlying ccRCC, identifying potential prognostic genes and molecular subtypes associated with the G2M checkpoint. These findings hold promise for guiding personalized treatment strategies in the management of ccRCC.

Foreign body penetrating duodenum into kidney: A case report.

The case of penetrating injury of the kidney caused by a foreign body mistakenly swallowing through the duodenum is rare. A 22-year-old male patient found that a strip of the foreign body penetrated the descending duodenum - the lower pole of the right kidney through an abdominal CT examination. After Multi-Disciplinary treatment, the patient underwent extracorporeal ultrasound-assisted endoscopic foreign body removal and hemostatic clamp suture. Extracorporeal ultrasound monitoring and intravenous pyelography showed that there was no leakage of contrast medium around the right kidney. No hematuria and urinary tract infection were found during the follow-up.

PTPRO suppresses lymph node metastasis of esophageal carcinoma by dephosphorylating MET.

Protein tyrosine phosphatase receptor-type O (PTPRO) is a membrane-bound tyrosine phosphatase. Notably, epigenetically silenced PTPRO due to promoter hypermethylation is frequently linked to malignancies. In this study, we used cellular and animal models, and patient samples to demonstrate that PTPRO can suppress the metastasis of esophageal squamous cell carcinoma (ESCC). Mechanistically, PTPRO can inhibit MET-mediated metastasis by dephosphorylating Y1234/1235 in the kinase activation loop of MET. Patients with PTPROlow/p-METhigh had significantly poor prognosis, suggesting that PTPROlow/p-METhigh can serve as an independent prognostic factor for patients with ESCC.

Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment.

Chemotherapy-related cognitive impairment (CRCI) or "chemo brain" is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro-/- female mice with doxorubicin (DOX) because Ptpro-/- female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are highly phosphorylated/activated in the hippocampi of Ptpro-/- female mice, with increased sensitivity to DOX-induced CRCI. On the other hand, restoration of PTPRO in the hippocampal CA3 region significantly ameliorate CRCI in Ptpro-/- female mice. In addition, we found that the plant alkaloid berberine (BBR) is capable of ameliorating CRCI in aged female mice by upregulating hippocampal PTPRO. Mechanistically, BBR upregulates PTPRO by downregulating miR-25-3p, which directly targeted PTPRO. These findings collectively demonstrate the protective role of hippocampal PTPRO against CRCI.

CD8A as a Prognostic and Immunotherapy Predictive Biomarker Can Be Evaluated by MRI Radiomics Features in Bladder Cancer.

As an important member of T cytotoxic pathway-related genes, CD8a molecule (CD8A) may be a useful biomarker of immunotherapeutic response and immune cell infiltration. We aimed to investigate the clinical predictive value of CD8A in prognosis and tumor microenvironment (TME) and preoperatively predict the expression of CD8A using radiogenomics in bladder cancer (BCa). Among 12 T cytotoxic pathway-related genes, CD8A was a novel protective gene and had the highest correlations with T cells and Macrophages M1 in BCa. In advanced cancer patients treated with immunotherapy, low CD8A expression was associated with immunotherapeutic failure and poor survival outcomes. CD8A expression was highly related to tumor mutation burden, critical immune checkpoint genes and several types of tumor-infiltrating immune cells, predicting effective response to immunotherapy. The preoperative MRI radiomics features and RNA-sequence data of 111 BCa samples were used to develop a radiomics signature that achieved good performance in the prediction of CD8A expression in both the training (area under curve (AUC): 0.857) and validation sets (AUC: 0.844). CD8A is a novel indicator for predicting the prognosis and immunotherapeutic response in BCa. A radiomics signature has the potential to preoperatively predict the expression of CD8A in BCa patients.

The CSRNP Gene Family Serves as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma.

The cysteine-serine-rich nuclear protein (CSRNP) family has prognostic value for various cancers. However, the association between this proteins and prognosis of clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to determine the prognostic value of the CSRNP family for patients with ccRCC. Therefore, the gene expression profiling interactive analysis database was used to analyze the mRNA expression of CSRNP family members (CSRNPs) in relation with survival. Combined and independent prognostic values of CSRNPs were evaluated using SurvExpress and multivariate Cox regression analyses, respectively. Potential signaling pathways impacted by CSRNPs were evaluated using Metascape. Associations between the CSRNP family and immunocyte infiltration were determined from single-sample gene set enrichment analysis. Both cBioPortal and MethSurv were used to explore whether genomic and epidemic alterations might influence prognosis. We found that when both CSRNP1 and CSRNP3 had a low expression, patients with ccRCC had a worse overall survival (OS). Therefore, a prognostic signature was constructed as follows: risk score = -0.224 × expmRNA of CSRNP1 + 0.820 × expmRNA of CSRNP2 - 1.428 × expmRNA of CSRNP3 . We found that OS was worse in patients from the high- than from the low-risk groups (AUC = 0.69). Moreover, this signature was an independent predictor after adjusting for clinical features. Functional enrichment analysis positively associated CSRNPs with the acute inflammatory response and humoral immune response pathways. This was validated by correlating each CSRNP with 28 types of immunocytes in tumor and normal tissues. A higher expression of CSRNP1 and CSRNP3 was associated with a better prognosis in both the high- and low-mutant burden groups. Cg19538674, cg07772537, and cg07811002 of CSRNP1, CSRNP2, and CSRNP3, respectively, were the predominant DNA methylation sites affecting OS. The CSRNP gene family signature may serve as a prognostic biomarker for predicting OS in patients with ccRCC. The association between CSRNPs and immune infiltration might offer future clinical treatment options.

Targeting c-MET to Enhance the Efficacy of Olaparib in Prostate Cancer.

PURPOSE: Prostate cancer is the second leading cause of cancer death in men worldwide. Olaparib is clinically approved for the treatment prostate cancer, but cytotoxicity and off-target effects including DNA damage limit its clinical applications. In the current study, new strategies to improve the therapeutic efficacy of olaparib for the treatment of prostate cancer were investigated. METHODS: Two prostate cancer cell lines were exposed to the c-MET inhibitor PHA665752 and/or the PARP inhibitor olaparib. Cell counting kit-8, colony formation assays, and transwell assays were conducted to evaluate the cytotoxicity of olaparib alone or in combination with PHA665752 in prostate cancer cell lines. Western blotting, immunofluorescence staining, and the comet assay were used to assess the effects of PHA665752 on olaparib-induced DNA damage. RESULTS: Combined inhibition of c-MET and PARP resulted in effective and synergistic blocking of the growth of prostate cancer cell lines. Invasion and migration were significantly suppressed when the agents were combined. Mechanistically, dual blocking of PARP and c-MET in prostate cancer cell lines was associated with an impaired DNA damage response. Interestingly, immunofluorescence staining analysis of RAD51 protein indicated that the c-MET inhibitor PHA665752 significantly impaired homologous repair via downregulated translocation of RAD51 into the nucleus in prostate cancer cells. CONCLUSION: The combination of the c-MET inhibitor PHA665752 and the PARP inhibitor olaparib may be a promising therapeutic strategy in patients with prostate cancer.

[Effectiveness and significance of prostatic ischemia in rabbit].

OBJECTIVE: To evaluate the effect of prostatic ischemia in rabbit and approach the significance of ischemia in the development of benign prostatic hyperplasia. METHODS: Male rabbits underwent surgical prostatic ischemia for durations of 1, 2, 4, 8 and 12 weeks and sham-operated rabbits served as controls. The weight of prostate was examined and a histological examination conducted. Ki67 immunohistochemical stain for the generation of prostatic cells and TUNEL test for the apoptosis of prostatic cells were used. RESULTS: In sham-operated rabbits, the mean (SD) weight of prostate were 0.831(0.127) g, the mean (SD) positive Ki67 staining prostatic epithelial cells 2.1(0.8) in 100 prostatic epithelial cells and stromal cells 2.6(1.1) in 100, mean (SD) positive TUNEL test prostatic epithelial cells 2.0(1.0) in 100 and stromal cells 2.5(0.7) in 100. In operated rabbits, the generation of prostatic stromal cells increased and the apoptosis of prostatic stromal cells decreased over 1 - 12 weeks. The generation of prostatic epithelial cells increased and the apoptosis of prostatic epithelial cells decreased over 2 - 12 weeks, but in the first week, there were no significantly difference between operated and sham-operated rabbits in the generation and apoptosis of prostatic epithelial cells. The weight of prostate in operated animals increased at Weeks 4, 8 and 12, were significantly heavier than sham-operated rabbits, 1 week post-op and 2 weeks post-op rabbits, there were no significantly difference between the latter 3 groups. CONCLUSION: Ischemia can induce the gain of prostatic weight by improving the generation and inhibiting the apoptosis of prostatic cells. And the effect of ischemia to prostate is correlated with ischemic time. Ischemia may play an important role in the development of benign prostatic hyperplasia. The first response to ischemia is the change of prostatic stromal cells.

TR4 nuclear receptor promotes clear cell renal cell carcinoma (ccRCC) vasculogenic mimicry (VM) formation and metastasis via altering the miR490-3p/vimentin signals.

While TR4 nuclear receptor plays key roles to promote prostate cancer progression, its roles to alter the progression of clear cell renal cell carcinoma (ccRCC), remains unclear. Here, we demonstrate that TR4 can promote the ccRCC cell vasculogenic mimicry (VM) formation and its associated metastasis via modulating the miR490-3p/vimentin (VIM) signals. Mechanism dissection revealed that TR4 might increase the oncogene VIM expression via decreasing the miR-490-3p expression through direct binding to the TR4-response-elements (TR4REs) on the promoter region of miR-490-3p, which might then directly target the 3' UTR of VIM-mRNA to increase its protein expression. Preclinical studies using the in vivo mouse model with xenografted RCC Caki-1 cells into the sub-renal capsule of nude mice also found that TR4 could promote the ccRCC VM and its associated metastasis via modulating the miR490-3p/VIM signals. Together, results from preclinical studies using multiple RCC cell lines and the in vivo mouse model all conclude that TR4 may play a key role to promote ccRCC VM formation and metastasis and targeting the newly identified TR4/miR-490-3p/VIM signals with small molecules may help us to develop a new therapeutic approach to better suppress the ccRCC metastasis.

[Transrectal high-intensity focused ultrasound with the Sonablate 500 for the treatment of prostate cancer].

OBJECTIVE: To evaluate the clinical effect of transrectal high-intensity focused ultrasound (HIFU) in the treatment of prostate cancer (PCa). METHODS: A total of 57 PCa patients, 27 localized and 30 advanced, underwent transrectal HIFU with the Sonab- late 500, the localized group treated by transrectal HIFU only, while the advanced group by transrectal HIFU combined with androgen ablation. RESULTS: For the HIFU treatment, the mean operating time, hospital stay and follow-up were 111 mm (ranging from 86 to 153 mm), 3.2 days (ranging from 2 to 18 days) and 18 months (ranging from 6 to 30 months), respectively. The biochemical disease-free rates at 1, 2 and 3 years in the localized group were 86%, 81% and 79%, respectively. While in the advanced group, the serum prostate specific antigen (PSA) was < 4.0 microg/L in 26 cases ( < 0.51 microg/L in 20) and the prostate volume decreased more than 50% in 21 cases after treated for an average of 8 months (ranging from 3 to 24 months). After transrectal HIFU prostate ablation, the prostate volume reduced, serum PSA lowered, Qmax raised and IPSS improved significantly (P < 0.05). No serious complications occurred including severe urethrorectal fistula and incontinence. CONCLUSION: Transrectal HIFU is a safe, effective and minimally invasive therapy for patients with prostate cancer.

The safety and efficacy of front-firing green-light laser endoscopic en bloc photoselective vapo-enucleation of non-muscle-invasive bladder cancer.

PURPOSE: Laser therapy provides an alternative option for treating non-muscle-invasive bladder cancer (NMIBC). However, the clinical evidence for potassium-titanyl-phosphate (KTP) laser en bloc resection is still limited. Here, we investigated the efficacy and safety of the 120-W front-firing KTP laser for the treatment of NMIBC. METHODS: A total of 64 patients with NMIBC treated with either a 120-W front-firing KTP-photoselective vapo-enucleation of the bladder tumor (PVEBT, n=34) or transurethral resection of the bladder tumor (TURBT, n=30) were included. En bloc resection was applied to the patients in PVEBT group. RESULTS: There was no significant difference in rinsing time (P=0.292), indwelling catheter (P=0.080), pathologic type, and T stage (P=0.870) between the two groups. Compared with the TURBT group, patients treated with PVEBT had a shorter hospitalization stay (P=0.044), a shorter operation time (P=0.008), and a lower muscle miss rate (P=0.044). PVEBT is superior to TURBT in terms of the rate of 1-year recurrence (P=0.015) and tumor grade progression rate (P=0.019). CONCLUSION: The 120-W front-firing KTP laser en bloc enucleation technique is a safe and feasible procedure for treating patients with NMIBC. Further external validation in larger cohorts with a long follow-up period is warranted.

Upregulation of FBXW7 Suppresses Renal Cancer Metastasis and Epithelial Mesenchymal Transition.

BACKGROUND AND OBJECTIVE: FBXW7, known as a general tumor suppressor, is commonly lowly expressed in metastatic malignancies. We aim to investigate the potential influence of FBXW7 overexpression on renal cell carcinoma (RCC) metastasis. METHODS: We employed quantitative real-time PCR (qRT-PCR) and Western blotting (WB) to quantify the FBXW7 expression in RCC cell lines. Upregulation of FBXW7 was performed in vitro on RCC cells using the lentivirus covering coding region FBXW7 cDNA sequence, and functional tests were performed to verify FBXW7 overexpression on migration and invasion of RCC cells. Moreover, WB was employed to determine the expressions of MMP-2, MMP-9, and MMP-13, as well as EMT markers in the transfected RCC cells. RESULTS: FBXW7 was significantly downregulated in RCC cell lines, dominated by 786-O and ACHN, when compared to normal renal cell line HK-2. Moreover, upregulation of FBXW7 in 786-O and ACHN cell lines significantly inhibited cell migration and invasion, as well as EMT. Present study also showed that FBXW7 was involved in the migration and invasion of RCC cells via regulating the expressions of MMP-2, MMP-9, and MMP-13. CONCLUSION: Our findings demonstrate that upregulation of FBXW7 inhibits RCC metastasis and EMT. FBXW7 is a potential therapeutic target for RCC patients.

[Effects of antibiotic and anti-inflammatory treatment on serum PSA and free PSA levels in patients with chronic prostatitis IIIA].

OBJECTIVE: To investigate the effect of antibiotics and a nonsteroidal anti-inflammatory agent on the level of total prostate specific antigen (PSA) and free PSA ratio (F-PSAR) in patients with chronic prostatitis IIIA. METHODS: A total of 228 outpatients diagnosed as with chronic prostatitis III A received 4-week antibiotic and anti-inflammatory treatment. The PSA level and F-PSAR were determined before and after the treatment, and the changes analyzed. RESULTS: Significant variations were observed in the median PSA concentrations (3.51 microg/L and 2.75 microg/L) and F-PSAR (0.25% and 0.27%) 4 weeks after the treatment. Sixty-five of the patients (28.5%) presented with serum PSA greater than 4 ng/ml, the mean PSA decreased by 32.9%, from 6.24 microg/L before the treatment to 4.58 microg/L 4 weeks after the treatment (P < 0.05), and the serum PSA was normalized in 18 of the 65 patients (27.7%). The median variation of F-PSAR (0.16% and 0.22%) was greater than that of PSA. The variation indexes obtained 4 weeks after the treatment showed no statistical difference from those observed 8 weeks after the treatment. CONCLUSION: Chronic prostatitis IIIA appears to contribute to increased serum PSA levels in some men. Antibiotic and anti-inflammatory treatment could significantly reduce the PSA level and increase F-PSAR.

[Seminal parameter analysis in noninflammatory chronic prostatitis/chronic pelvic pain syndrome].

OBJECTIVE: To investigate seminal parameters in noninflammatory chronic prostatitis/chronic pelvic pain syndrome (CAP III B). METHODS: A total of 74 consecutive cases of patients who had been diagnosed as CAP III B and 46 cases of controls were included in the study. Severity of symptoms in men with CAP III B was defined according to the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). All of them underwent a 'four glass-test' including leukocyte determination in expressed prostatic secretions (EPS), voided urine after prostatic massage (VB3) and ejaculate semen followed by analysis according to WHO. The analysis included seminal volume, pH, duration of liquefaction, sperm density, vitality, motility(a + b) and morphology. Correlations between the duration or the severity of symptoms and spermiogram results in patients with CAP III B were assessed respectively. RESULTS: The CAP III B group and the control group differed significantly in ejaculate volume, duration of liquefaction and motility, while the remaining parameters did not differ significantly. The duration of chronic pelvic pain showed apparently positive correlationship with liquefaction time, while the symptom duration negatively correlated with sperm motility. The NIH-CPSI score had no significant relationship with seminal volume, duration of liquefaction and sperm motility. CONCLUSION: Our results indicate that CAP III B can have a significant negative impact on sperm volume, liquefaction and motility. Our data also supports the results that the longer the duration of symptoms, the more influences on semen liquefaction and motility might be.