A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer.

Bladder cancer (BLCA) is a common malignant tumor in urinary system all over the world. However, due to its high recurrence rate and complex causes, clinicians often have limited options for surgical and drug treatments. Recent researchs on the molecular mechanism of BLCA have reveals its biological progress and potential for early diagnosis. Serine hydroxymethyltransferase 1/2 (SHMT1/2) is a crucial enzyme in the one-carbon metabolism of tumor cells, and the expression levels of these isozymes have been found to be associated with the biological progression of various malignant tumors. However, the impact of SHMT1/2 on the biological progression of bladder cancer and its molecular regulation mechanism remain unclear. In this research utilizes BLCA clinical sample data, the TCGA database, and in vitro cell experiments to predict the expression levels of SHMT1/2 in BLCA. The findings indicate that SHMT1 remained unchanged, while SHMT2 expression is increased in BLCA, which was related to poor prognosis. Additionally, SHMT2 affects the growth, migration, and apoptosis of bladder cancer cells in vitro. It also influences the expression levels of E-cadherin and N-cadherin, ultimately impacting the malignant biological progression of bladder tumors. These results establish a correlation between SHMT2 and the malignant biological progression of BLCA, providing a theoretical basis for the early diagnosis and treatment of bladder cancer.

The effect of perioperative pelvic floor muscle exercise on urinary incontinence after radical prostatectomy: a meta-analysis

ABSTRACT Background: Pelvic floor muscle exercise (PFME) is the most common conservative management for urinary incontinence (UI) after radical prostatectomy (RP). We performed this meta-analysis to investigate whether PFME during the entire perioperative period, including before and after RP, can significantly improve the recovery of postoperative UI. Methods: We systematically reviewed randomized controlled trials (RCT) from PubMed, Medline, web of science, Cochrane library, and clinicalitrials.com prior to October 2022. Efficacy data were pooled and analyzed using Review Manager Version 5.3. Pooled analyses of urinary incontinence rates 1, 3, 6, and 12 months postoperatively were conducted, using odds ratio (OR) and 95% confidence intervals (CIs). Results: We included a total of 15 RCT studies involving 2178 patients received RP. Postoperative UI could be improved after 1 month, 3 months and 6 months, and the OR were 0.26 (95%CI:0.15-0.46) 0.30 (95%CI: 0.11-0.80) 0.20 (95%CI: 0.07- 0.56) in postoperative PFME group compared to no PFME group. However, there was no significant difference between the two groups in 12 months after surgery, and the OR was 0.85(95%CI: 0.48,1.51). There were similar results in perioperative PFME group compared to no PFME group with the OR of 0.35 (95%CI: 0.12, 0.98) and 0.40 (95%CI: 0.21, 0.75) in 1 and 3 months after surgery. Our results indicated no significant difference between perioperative PFME group and postoperative PFME group. The OR was 0.58 (95%CI: 0.20-1.71) 0.58 (95%CI:0.20-0.71) and 0.66 (95%CI: 0.32-1.38) in 1, 3 and 6 months after surgery. Conclusion: Application of PFME after RP significantly reduced the incidence of early postoperative UI, and additional preoperative PFME had no significant improvement on the recovery of UI.

The effect of perioperative pelvic floor muscle exercise on urinary incontinence after radical prostatectomy: a meta-analysis.

BACKGROUND: Pelvic floor muscle exercise (PFME) is the most common conservative management for urinary incontinence (UI) after radical prostatectomy (RP). We performed this meta-analysis to investigate whether PFME during the entire perioperative period, including before and after RP, can significantly improve the recovery of postoperative UI. METHODS: We systematically reviewed randomized controlled trials (RCT) from PubMed, Medline, web of science, Cochrane library, and clinicalitrials.com prior to October 2022. Efficacy data were pooled and analyzed using Review Manager Version 5.3. Pooled analyses of urinary incontinence rates 1, 3, 6, and 12 months postoperatively were conducted, using odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: We included a total of 15 RCT studies involving 2178 patients received RP. Postoperative UI could be improved after 1 month, 3 months and 6 months, and the OR were 0.26 (95%CI:0.15-0.46) 0.30 (95%CI: 0.11-0.80) 0.20 (95%CI: 0.07- 0.56) in postoperative PFME group compared to no PFME group. However, there was no significant difference between the two groups in 12 months after surgery, and the OR was 0.85(95%CI: 0.48,1.51). There were similar results in perioperative PFME group compared to no PFME group with the OR of 0.35 (95%CI: 0.12, 0.98) and 0.40 (95%CI: 0.21, 0.75) in 1 and 3 months after surgery. Our results indicated no significant difference between perioperative PFME group and postoperative PFME group. The OR was 0.58 (95%CI: 0.20-1.71) 0.58 (95%CI:0.20-0.71) and 0.66 (95%CI: 0.32-1.38) in 1, 3 and 6 months after surgery. CONCLUSION: Application of PFME after RP significantly reduced the incidence of early postoperative UI, and additional preoperative PFME had no significant improvement on the recovery of UI.

Effects of Multi-Pass Turning on Stress Corrosion Cracking of AISI 304 Austenitic Stainless Steel.

Austenitic stainless steels are extensively used in mechanical engineering. The machined surface integrity has an essential influence on the stress corrosion cracking (SCC) performance of stainless steels. In this paper, the effects of multi-pass turning on the SCC susceptibility of AISI 304 austenitic stainless steel were investigated by correlating the SCC crack density to the machining-induced surface characteristics in terms of roughness, micro-hardness, and residual stress. In the multi-pass turning, the surface roughness and residual stress were the least after the double pass turning, and the surface micro-hardness was the maximum after the triple-pass turning. The SCC susceptibility was evaluated after SCC tests in boiling MgCl2 solution. The results showed that the weakest SCC sensitivity was observed in double-pass turning 304 stainless steel, while the most susceptible SCC was found in triple-pass turning. Compared with the double-pass turning, the increase in SCC sensitivity of triple-pass turning was attributed to the larger roughness, higher micro-hardness and greater residual tensile stresses.

Adjuvant Transarterial Chemoembolization for Patients with Intrahepatic Cholangiocarcinoma after Surgical Resection: A Systematic Review and Meta-analysis.

AIM: To investigate the efficacy of postoperative adjuvant transarterial chemoembolization (TACE) in patients with intrahepatic cholangiocarcinoma (ICC) after resection. METHODS: Studies were systematically searched until August 2021 in the following databases: MEDLINE, EMBASE, PUBMED, Web of Science, Cochrane Library, Science Direct, and Springer Link. Overall survival (OS) and recurrence-free survival (RFS) were considered as the main outcomes. Pooled hazard ratio (HR) with 95% confidence interval (95%CI) was reported as results for the survival data. Subgroup analysis was conducted on the outcomes stratified by early-stage ICC and intra-arterial chemotherapeutic regimen. RESULTS: Eleven studies with 2,757 patients were finally included in the study. The pooled HR of OS was 0.68 (95%CI: 0.50-0.87, I 2 =83.7%). The pooled HR of RFS was 1.00 (95%CI: 0.69-1.31, I 2 =88%). Receipt of postoperative adjuvant TACE improved the OS in the early-stage ICC subgroup (HR=0.68, 95%CI: 0.50-0.86, I 2 =54%). Addition of carboplatin could slightly improve the OS (HR=0.6, 95%CI: 0.35-0.85, I 2 =48%). But receipt of postoperative adjuvant TACE (HR=1.06, 95%CI: 0.83-1.29, I 2 =41.2%) or use of carboplatin (HR=1.30, 95%CI: 0.93-1.67, I 2 =0%) caused no significant improvement in the RFS in the early-stage ICC subgroup. CONCLUSIONS: Postoperative adjuvant TACE could improve the OS in ICC patients after hepatectomy but could not prevent late recurrence. Survival benefit was also found in early-stage ICC patients undergoing postoperative adjuvant TACE after hepatectomy. Addition or non-addition of carboplatin in chemoembolization showed a similar OS outcome.

Effect of Cu2+ on Corrosion Behavior of A106B Carbon Steel and 304L Stainless Steels in Seawater.

The corrosion behaviors of A106B carbon steel and 304L stainless steel (SS) in seawater with different Cu2+ concentrations were studied by the immersion test and the potentiodynamic polarization test. The results showed that with the increasing Cu2+ concentration, the mass lot rates of A106B and 304L SS all increased in the immersion test, and compared with A106B, the mass lot rates of 304L SS were all smaller. In the potentiodynamic polarization test, following the concentration of Cu2+ increased, the corrosion potential of A106B firstly shifted negatively; then, when Cu2+ increased to 100 ppm, the polarization curve moved to the upper right direction; namely, both the corrosion potential and corrosion electrical density increased. The corrosion potential of 304L SS increased with the increasing Cu2+, and the passive region was reduced; the pitting sensitivity improved.

Microstructure and Properties of ER50-6 Steel Fabricated by Wire Arc Additive Manufacturing.

In this paper, ER50-6 steel was fabricated by wire arc additive manufacturing (WAAM) with an A-W GTAW system. The microstructure, mechanical properties, and corrosion behaviors of ER50-6 steel by WAAM were studied. The results showed that, with the GMAW current increased, from the bottom to the top of the sample, the microstructure was fine ferrite and granular pearlite, ferrite equiaxed grains with fine grains at grain boundaries, and columnar ferrite, respectively. The average hardness in the vertical direction of samples 1# and 2# was 146 and 153 HV, respectively. The hardness of sample 2# increased because of the refinement of grain. The pores in the sample increased as the bypass current increased. The higher bypass current also has a deterioration effect on the corrosion behavior of ER50-6 steel.

Integrative nomogram of intratumoral, peritumoral, and lymph node radiomic features for prediction of lymph node metastasis in cT1N0M0 lung adenocarcinomas.

Radiomics studies to predict lymph node (LN) metastasis has only focused on either primary tumor or LN alone. However, combining radiomics features from multiple sources may reflect multiple characteristic of the lesion thereby increasing the discriminative performance of the radiomic model. Therefore, the present study intends to evaluate the efficiency of integrative nomogram, created by combining clinical parameters and radiomics features extracted from gross tumor volume (GTV), peritumoral volume (PTV) and LN, for the preoperative prediction of LN metastasis in clinical cT1N0M0 adenocarcinoma. A primary cohort of 163 patients (training cohort, 113; and internal validation cohort, 50) and an external validation cohort of 53 patients with clinical stage cT1N0M0 were retrospectively included. Features were extracted from three regions of interests (ROIs): GTV; PTV (5.0 mm around the tumor) and LN on pre-operative contrast enhanced computed tomography (CT). LASSO logistic regression method was used to build radiomic signatures. Multivariable regression analysis was used to build a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. The discriminative performance of nomogram was validated both internally and externally. The radiomic signatures using the features of GTV, PTV and LN showed a good ability in predicting LN metastasis with an area under the curve (AUC) of 0.74 (95% CI 0.60-0.88), 0.72 (95% CI 0.57-0.87) and 0.64 (95% CI 0.48-0.80) respectively in external validation cohort. The integration of different signature together further increases the discriminatory ability: GTV + PTV (GPTV): AUC 0.75 (95% CI 0.61-0.89) and GPTV + LN: AUC 0.76 (95% CI 0.61-0.91) in external validation cohort. An integrative nomogram of clinical parameters and radiomic features demonstrated further increase in discriminatory ability with AUC of 0.79 (95% CI 0.66-0.93) in external validation cohort. The nomogram showed good calibration. Decision curve analysis demonstrated that the radiomic nomogram was clinically useful. The integration of information from clinical parameters along with CT radiomics information from GTV, PTV and LN was feasible and increases the predictive performance of the nomogram in predicting LN status in cT1N0M0 adenocarcinoma patients suggesting merit of information integration from multiple sources in building prediction model.

Efficacy of ureterocalicostomy in treating secondary long-segment upper ureteral stricture.

OBJECTIVE: To evaluate the efficacy and safety of ureterocalicostomy for long-segment upper ureteral stricture. METHODS: A total of 13 patients underwent ureterocalicostomy for long-segment upper ureteral stricture, and a long-term follow-up was carried out to observe postoperative results, complications and renal function at 6 months after surgery. RESULTS: Among the 13 patients undergoing ureterocalicostomy, 12 achieved successful results with surgery. Nine of the 12 received open surgery and 3 patients received laparoscopic surgery. During the perioperative period, 3 patients developed fever while 2 patients had hematuria and irritation in lower urinary tract, and all improved after symptomatic treatment. The 12 patients with successful surgeries achieved remission of hydronephrosis without anastomotic stricture. At 6 months after surgery, the 12 patients had significantly decreased serum creatinine and cystatin C levels and markedly increased estimated glomerular filtration rate, as compared with those before surgery (P<0.05). CONCLUSION: Ureterocalicostomy is an effective, safe, optional treatment strategy for secondary long-segment upper ureteral stricture.

Effect of Iron Ion on Corrosion Behavior of Inconel 625 in High-Temperature Water.

The corrosion behavior of an ultralow iron nickel-based alloy Inconel 625 under high-temperature water has been evaluated. The results show that surface oxidation and pitting were the principal corrosion mechanisms of Inconel 625 during the initial immersion period. The surface layer of the oxide film is first Ni-enriched and then Fe-enriched as immersion time increases. The iron ions dissolved from the autoclave could lead to the formation of NiFe2O4 and have a great influence on the oxidation behavior of Inconel 625. The oxides nucleated by solid-state reactions with selective dissolution of Fe and Ni and then grew up through precipitation of cations from solution.

Second-line treatment strategy for urothelial cancer patients who progress or are unfit for cisplatin therapy: a network meta-analysis.

BACKGROUND: Second-line treatment for urothelial carcinoma (UC) patients is used if progression or failure after platinum-based chemotherapy occurs or if patients are cisplatin-unfit. However, there is still no widely accepted treatment strategy. We aimed to analyze the effectiveness and safety of second-line treatment strategies for UC patients. METHODS: The PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) that included UC patients who were cisplatin-ineligible or unfit up to April 19, 2019. The primary outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). RESULTS: Thirteen trials that assessed 3502 UC patients were included. This study divided the network comparisons into three parts. The first part contained studies comparing taxanes and other interventions; the second part assessed investigator's choice chemotherapy (ICC)-related comparisons; and the third part assessed best support care (BSC). In the OS results of the first part, pembrolizumab (87.5%), ramucirumab plus docetaxel (74.6%), and atezolizumab (71.1%) had a relative advantage. Pembrolizumab also had advantages in ORR and severe adverse effect (SAE) results. Vinflunine and ramucirumab plus docetaxel had a relatively high surface under the cumulative ranking curve (SUCRA) rank by exploratory cluster analysis. CONCLUSIONS: This study concluded that atezolizumab and pembrolizumab are superior to other treatments, mainly in OS results, but no treatment confers a significant advantage in PFS. Pembrolizumab still has relative advantages in ORR and SAE results compared to ICC. Due to limitations, more studies are necessary to confirm the conclusions.

Effects of repetitive magnetic stimulation on the growth of primarily cultured hippocampus neurons in vitro and their expression of iron-containing enzymes.

Background: The mechanism of action of repetitive transcranial magnetic stimulation (rTMS) involves the generation of neuronal and action potentials utilizing induced currents in time-varying magnetic fields. However, the long-lasting and effective biological impact of magnetic stimulation does not appear to be completely explained by the transient magnetic field pulses. In this context, we hypothesized magnetic stimulation may affect the expression of iron-containing enzymes in neurons, mediating the long-lasting biological effects associated with this stimulus. Methods: Primarily cultured hippocampus neurons from SD rats were used as the cell model in this study. These were randomly divided into control, sham, and magnetic stimulation groups to probe into the effect of the magnetic field directly. The latter group received 40%, 60%, and 100% maximal stimulator output Tesla (1.68, 2.52, and 4.2 T) with low-frequency rTMS (1 Hz). The expression of iron-containing enzymes (catalase and aconitase) and non-ferrous enzymes (protein kinase A) was measured with Western blotting and ELISA. Results: The survival rates of neurons in the 40%T and 60%T groups were significantly increased in comparison to the controls (P<0.05), while those in the 100%T group showed cell damage, with slightly disturbed neurite connections and decreased survival rate. Furthermore, catalase and aconitase expression was higher in all of the stimulated groups in comparison to controls (P<0.05). On the other hand, the expression of the iron-containing enzymes decreased in the 100%T group in comparison with the 40%T and 60%T groups (P<0.05). Meanwhile, the expression of protein kinase A was not significantly increased in the groups which underwent magnetic stimulation. Conclusion: rTMS may increase the expression of ferrous enzymes but does not have a strong effect on non-ferrous enzymes. Excessive intensity of magnetic stimulation may reduce neuronal survival rate and affect the expression of iron-containing enzymes. The mechanism underlying the lasting effect of rTMS may be related to the increase of ferriferous expression induced by magnetic stimulation, with a clear correlation with stimulation intensity.

Prelamin A overexpression promotes detrusor calcification/aging in urinary incontinence via prelamin A accumulation.

Urinary incontinence (UI) is known as a distressing condition particularly among older adults, and negatively associated with health-related quality of life in both males and females. Prelamin A accumulation has been found in all progeroid laminopathies and is obviously linked to cell and organism aging. Therefore, this study was expected to investigate the effect of prelamin A on detrusor on UI. Prelamin A expression in clinical and animal samples was detected. To investigate the degree of prelamin A accumulation and detrusor calcification/aging, the detrusor cells were subcultured separately into low and high passage. The low-passage subculture cells were treated with transfection of overexpressed prelamin A plasmid, and transfection of overexpressed prelamin A plasmid and application of farnesyl transferase inhibitor (FTIs) H-9279, respectively. Zmpste24, Icmt and lamin A/C expression were detected to explore how prelamin A affected detrusor calcification/aging. Prelamin A was overexpressed in aged detrusor cells, indicating prelamin A expression was positively related to the age of subjects. The degree of prelamin A accumulation and detrusor calcification/aging was higher in aged rats and high passage subculture cells. Zmpste24, Icmt and lamin A/C were poorly expressed in cells transfected with overexpressed prelamin A, as well as cell proliferation activity decreased and calcium deposition and apoptotic rate increased. Furthermore, we also found that the effect of overexpressed prelamin A was lost when cells were treated with H-9279. These findings provide evidence that prelamin A overexpression impairs degradation of its farnesylated form, thus causing prelamin A accumulation which induces detrusor calcification/aging in UI.

640-slice DVCT multi-dimensionally and dynamically presents changes in bladder volume and urine flow rate.

The present study aimed to explore the application of 640-slice dynamic volume computed tomography (DVCT) to excretory cystography and urethrography. A total of 70 healthy subjects were included in the study. Excretory cystography and urethrography using 640-slice DVCT was conducted to continuously record the motions of the bladder and the proximal female and male urethra. The patients' voiding process was divided into early, early to middle, middle, middle to late, and late voiding phases. The subjects were analyzed using DVCT and conventional CT. The cross-sectional areas of various sections of the male and female urethra were evaluated, and the average urine flow rate was calculated. The 640-slice DVCT technique was used to dynamically observe the urine flow rate and changes in bladder volume at all voiding phases. The urine volume detected by 640-slice DVCT exhibited no significant difference compared with the actual volume, and no significant difference compared with that determined using conventional CT. Furthermore, no significant difference in the volume of the bladder at each phase of the voiding process was detected between 640-slice DVCT and conventional CT. The results indicate that 640-slice DVCT can accurately evaluate the status of the male posterior urethra and female urethra. In conclusion, 640-slice DVCT is able to multi-dimensionally and dynamically present changes in bladder volume and urine flow rate, and could obtain similar results to conventional CT in detecting urine volume, as well as the status of the male posterior urethra and female urethra.

Network meta-analysis of the efficacy and adverse effects of several treatments for advanced/metastatic prostate cancer.

This network meta-analysis was conducted to compare the efficacy and adverse effects of several treatments for advanced/metastatic prostate cancer (PC). The PubMed and Cochrane Library databases were searched for randomized controlled trials of treatments for advanced/metastatic PC. Eighteen studies covering 6,340 patients were included in this analysis. The calculated were odds ratios, 95% confidence intervals, and the surface under the cumulative ranking (SUCRA) curve. Pairwise meta-analysis showed that overall survival rates achieved with radiotherapy or endocrine therapy were lower than obtained with radiotherapy + endocrine therapy. The endocrine therapy includes estrogen therapy, luteinizing hormone-releasing hormone agonist (LHRH-A), anti-androgen therapy (ADT), ADT + LHRH-A and estrogen therapy + LHRH-A, and its SUCRA values indicated that for overall response rate, estrogen therapy + LHRH-A ranked the highest (92.6%); for overall survival rate, ADT ranked the highest (75.2%); for anemia, estrogen therapy ranked the highest (88.2%); and for diarrhea and hot flushes, ADT ranked the highest (diarrhea, 87.4%; hot flushes, 89.3%). Cluster analysis on the endocrine therapy showed that ADT + LHRH-A achieved the highest overall survival and overall response rates in the treatment of advanced/metastatic PC. Estrogen therapy and ADT had the lowest incidences of diarrhea and anemia. Thus, combined radiotherapy + endocrine therapy had higher overall survival rate, and among the endocrine therapy, in terms of overall response rate and overall survival rate, ADT + LHRH-A may be a better regimen in the treatment of advanced or metastatic PC.

MicroRNA-214 Affects Fibroblast Differentiation of Adipose-Derived Mesenchymal Stem Cells by Targeting Mitofusin-2 during Pelvic Floor Dysfunction in SD Rats with Birth Trauma.

BACKGROUND/AIMS: This study investigated whether microRNA-214 (miR-214) targets mitofusin-2 (Mfn2) in the process of fibroblast differentiation of adipose-derived mesenchymal stem cells (ADMSCs) during pelvic floor dysfunction (PFD) in Sprague Dawley (SD) rats with birth trauma. METHODS: The ADMSCs were isolated from 4-6 week male SD rats (n = 20) and were cultured and divided into the blank, miR-214 mimic negative control (NC), miR-214 mimic, miR-214 inhibitor NC, miR-214 inhibitor, empty vector, Mfn2 over-expression and miR-214 + Mfn2 over-expression groups. Fibroblast differentiation of ADMSCs was measured with immunocytochemistry and immunofluorescence methods. The expression of miR-214 and the mRNA and protein expression of Mfn2, FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ and Runx2 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. A dual-luciferase reporter assay was performed to confirm whether Mfn2 was the target gene of miR-214. RESULTS: During ADMSC differentiation into fibroblasts, miR-214 expression was up-regulated, but the expression of Mfn2 was down-regulated. Fibroblast differentiation of ADMSCs was promoted in the miR-214 mimic group but was inhibited in the miR-214 inhibitor and Mfn2 over-expression groups. The expression of Mfn2 was decreased, but the expression of FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ or Runx2 was increased in the miR-214 mimic group; the miR-214 inhibitor group and Mfn2 over-expression group exhibited the opposite results. Mfn2 was the target gene of miR-214. CONCLUSIONS: The study provided strong evidence that miR-214 could promote fibroblast differentiation of ADMSCs by down-regulating Mfn2 to improve PFD in SD rats with birth trauma.

The significance of De Ritis (aspartate transaminase/alanine transaminase) ratio in predicting pathological outcomes and prognosis in localized prostate cancer patients.

PURPOSE: To illustrate whether De Ritis (aspartate transaminase-AST/alanine transaminase-ALT) ratio is useful in risk stratification of localized prostate cancer and propose an easy predictive model for biochemical recurrence-free survival (BCRFS). METHODS: In total, 438 patients who underwent radical prostatectomy were included in this study. Blood samples including AST and ALT were collected 1-7 days before surgery. An elevated AST and ALT value was defined as over 40 or 56 IU/L. RESULTS: The median AST and ALT value was 18.5 (16-22) and 14 (11-18) IU/L. In total, 15 patients (3.4%) and 9 patients (2.1%) exhibited elevated AST value and ALT value. The median De Ritis ratio was 1.33 (1.11-1.60), and ROC curve indicated the best cutoff of 1.325 in predicting the occurrence of biochemical recurrence. Higher De Ritis ratio was found to be related to older age (p < 0.001), higher tumor stages (p < 0.001) and Gleason Score (p < 0.001), presence of seminal invasion (p < 0.001), positive surgical margin (p < 0.001) and lymph node metastasis (p = 0.003). Multivariate logistic regression confirmed that De Ritis ratio was an independent predictor for final Gleason Score (p < 0.001), and multivariate Cox regression demonstrated De Ritis ratio as an independent risk factor for BCRFS. A simple predictive model which incorporated De Ritis ratio, pathological tumor stage and final Gleason Score could help risk stratification for BCRFS. CONCLUSION: Higher De Ritis ratio could be predictive for worse pathological outcomes and higher BCR in localized prostate cancer patients. A predictive model which incorporates De Ritis ratio, Gleason Score and pathological tumor stage could help risk stratification for BCRFS.

IL-6 Inhibits the Targeted Modulation of PDCD4 by miR-21 in Prostate Cancer.

Prostate cancer is the most common cancer among men in the Unites States. The cytokine IL-6 activates several prostate cancer pathways, but its upstream trans-signaling pathway remains poorly understood. In this study, we evaluated the role of IL-6 in PDCD4 gene expression and how the microRNA miR-21 regulates this process in prostate cancer cell lines PC-3 and LNCaP. The expression pattern of PDCD4 from samples from human prostate cancer, precancerous lesions, and benign prostatic hyperplasia was investigated by immunohistochemistry. PDCD4 transcription and translation were detected by quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. The targeted modulation of PDCD4 by miR-21 was analyzed in PC-3 and LNCaP cells, and the effect of IL-6 on the expression of PDCD4 was studied in vitro. PDCD4 expression in samples from the 3 tissue types progressively increased, and the expression levels of PDCD4 and prostate-specific antigen were negatively correlated. The levels of PDCD4 mRNA and protein in PC-3 and LNCaP cells transfected with anti-miR-21 constructs were lower than those in control cells. The expression of PDCD4 was inhibited by IL-6, but this effect was weakened in cell lines with low expression of miR-21. Our study demonstrates that the regulation of PDCD4 by miR-21 is targeted and IL-6 inhibits expression of the PDCD4 gene in PC-3 and LNCaP cells through the targeted function of miR-21 on PDCD4. These findings support the feasibility of future efforts for diagnosis and gene therapy for prostate cancer that are based on IL-6, miR-21, and PDCD4.