Ameliorated PGC demodulation technique based on the ODR algorithm with insensitivity to phase modulation depth.

For the optical fiber sensing system using phase generated carrier (PGC) technology, it is very important to eliminate the nonlinear effect of phase modulation depth (C) fluctuation on the demodulation results in the actual environment. In this paper, an ameliorated phase generated carrier demodulation technique is presented to calculate the C value and suppress its nonlinear influence on the demodulation results. The value of C is calculated out by the fundamental and third harmonic components with the equation fitted by the orthogonal distance regression algorithm. Then the Bessel recursive formula is used to convert the coefficients of each order of Bessel function contained in demodulation result into C values. Finally, the coefficients in demodulation result are removed by the calculated C values. In the experiment, when the C ranges from 1.0 rad to 3.5 rad, the minimum total harmonic distortion and maximum phase amplitude fluctuation of the ameliorated algorithm are 0.09% and 3.58%, which are far superior to the demodulation results of the traditional arctangent algorithm. The experimental results demonstrate that the proposed method can effectively eliminate the error caused by the fluctuation of the C value, which provides a reference for signal processing in practical applications of fiber-optic interferometric sensors.

A New Signature That Predicts Progression-Free Survival of Clear Cell Renal Cell Carcinoma with Anti-PD-1 Therapy.

Immunotherapy has greatly improved the survival time and quality of life of patients with renal cell carcinoma, but the benefits are limited to a small portion of patients. There are too few new biomarkers that can be used to identify molecular subtypes of renal clear cell carcinoma and predict survival time with anti-PD-1 treatment. Single-cell RNA data of clear cell renal cell carcinoma (ccRCC) treated with anti-PD-1 were obtained from public databases, then 27,707 high-quality CD4 + T and CD8 + T cells were obtained for subsequent analysis. Firstly, genes set variation analysis and CellChat algorithm were used to explore potential molecular pathway differences and intercellular communication between the responder and non-responder groups. Additionally, differentially expressed genes (DEGs) between the responder and non-responder groups were obtained using the "edgeR" package, and ccRCC samples from TCGA-KIRC (n = 533) and ICGA-KIRC (n = 91) were analyzed by the unsupervised clustering algorithm to recognize molecular subtypes with different immune characteristics. Finally, using univariate Cox analysis, least absolute shrinkage and selection operator (Lasso) regression, and multivariate Cox regression, the prognosis model of immunotherapy was established and verified to predict the progression-free survival of ccRCC patients treated with anti-PD-1. At the single cell level, there are different signal pathways and cell communication between the immunotherapy responder and non-responder groups. In addition, our research also confirms that the expression level of PDCD1/PD-1 is not an effective marker for predicting the response to immune checkpoint inhibitors (ICIs). The new prognostic immune signature (PIS) enabled the classification of ccRCC patients with anti-PD-1 therapy into high- and low-risk groups, and the progression-free survival times (PFS) and immunotherapy responses were significantly different between these two groups. In the training group, the area under the ROC curve (AUC) for predicting 1-, 2- and 3-year progression-free survival was 0.940 (95% CI: 0.894-0.985), 0.981 (95% CI: 0.960-1.000), and 0.969 (95% CI: 0.937-1.000), respectively. Validation sets confirm the robustness of the signature. This study revealed the heterogeneity between the anti-PD-1 responder and non-responder groups from different angles and established a robust PIS to predict the progression-free survival of ccRCC patients receiving immune checkpoint inhibitors.

Identification and validation of a lipid metabolism gene signature for predicting biochemical recurrence of prostate cancer after radical prostatectomy.

Background: Pro5state cancer is one of the most commonly diagnosed cancers in men worldwide and biochemical recurrence occurs in approximately 25% of patients after radical prostatectomy. Current decisions regarding biochemical recurrence after radical prostatectomy are largely dependent on clinicopathological parameters, which are less accurate. A growing body of research suggests that lipid metabolism influences tumor development and treatment, and that prostate cancer is not only a malignancy but also a lipid metabolism disease. Therefore, this study aimed to identify the prognostic value of lipid metabolism-related gene signaling disease to better predict biochemical recurrence and contribute to clinical decision-making. Methods: Expression data and corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA) database and the MSKCC database. Candidate modules closely associated with BCR were screened by univariate and LASSOcox regression analyses, and multivariate Cox regression analyses were performed to construct gene signatures. Kaplan-Meier (KM) survival analysis, time-dependent subject operating curves (ROC), independent prognostic analysis, and Nomogram were also used to assess the prognostic value of the signatures. In addition, Gene Ontology Analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore potential biological pathways. Results: A 6-gene lipid metabolism-related gene signature was successfully constructed and validated to predict biochemical recurrence in prostate cancer patients. In addition, we identified the 6-gene signature as an independent risk factor. Functional analysis showed that lipid metabolism-related genes were closely associated with arachidonic acid metabolism, PPAR transduction signaling pathway, fatty acid metabolism, peroxisome, and glycerophospholipid metabolism. Prognostic models were associated with immune cell infiltration. Conclusion: We have successfully developed a novel lipid metabolism-related gene signature that is highly effective in predicting BCR in patients with limited prostate cancer after RP and created a prognostic Nomogram. Furthermore, the signature may help clinicians to select high-risk subpopulations, predict patient survival, and facilitate more personalized treatment than traditional clinical factors.

Highly sensitive temperature and strain sensor based on an antiresonant hollow core fiber probe with the Vernier effect.

A highly sensitive temperature and strain sensor based on an antiresonant hollow core fiber (ARHCF) probe with the Vernier effect is proposed and experimentally demonstrated. The ARHCF probe is used as a reference interferometer by sandwiching an ARHCF, which is insensitive to temperature, strain, and refractive index, between a single-mode fiber (SMF) and a polarization-maintaining fiber (PMF). The polarization mode interferometer (PMI), fabricated by splicing a section of PMF with a fiber polarizer at a 45-degree angle, works as a sensing interferometer. The Vernier effect is introduced by connecting the reference interferometer and the PMI in parallel. The experimental results show that by introducing the Vernier effect, the temperature sensitivity is improved from -1.68 to -15.7nm/∘C and the strain sensitivity is improved from 5.09 to 47.65 pm/µÎµ. The magnification is consistent with the theoretical results. The reference segment of the proposed sensor is not affected by ambient factors, which provides a new strategy and idea for the development of multiparameter sensors based on the Vernier effect.

COVID-19 inhibits spermatogenesis in the testes by inducing cellular senescence.

Introduction: COVID-19 (SARS-CoV-2) has been linked to organ damage in humans since its worldwide outbreak. It can also induce severe sperm damage, according to research conducted at numerous clinical institutions. However, the exact mechanism of damage is still unknown. Methods: In this study, testicular bulk-RNA-seq Data were downloaded from three COVID-19 patients and three uninfected controls from GEO to evaluate the effect of COVID-19 infection on spermatogenesis. Relative expression of each pathway and the correlation between genes or pathways were analyzed by bioinformatic methods. Results: By detecting the relative expression of each pathway and the correlation between genes or pathways, we found that COVID-19 could induce testicular cell senescence through MAPK signaling pathway. Cellular senescence was synergistic with MAPK pathway, which further affected the normal synthesis of cholesterol and androgen, inhibited the normal synthesis of lactate and pyruvate, and ultimately affected spermatogenesis. The medications targeting MAPK signaling pathway, especially MAPK1 and MAPK14, are expected to be effective therapeutic medications for reducing COVID-19 damage to spermatogenesis. Conclusion: These results give us a new understanding of how COVID-19 inhibits spermatogenesis and provide a possible solution to alleviate this damage.

Novel biomarkers predict prognosis and drug-induced neuroendocrine differentiation in patients with prostate cancer.

Background: A huge focus is being placed on the development of novel signatures in the form of new combinatorial regimens to distinguish the neuroendocrine (NE) characteristics from castration resistant prostate cancer (CRPC) timely and accurately, as well as predict the disease-free survival (DFS) and progression-free survival (PFS) of prostate cancer (PCa) patients. Methods: Single cell data of 4 normal samples, 3 CRPC samples and 3 CRPC-NE samples were obtained from GEO database, and CellChatDB was used for potential intercellular communication, Secondly, using the "limma" package (v3.52.0), we obtained the differential expressed genes between CRPC and CRPC-NE both in single-cell RNA seq and bulk RNA seq samples, and discovered 12 differential genes characterized by CRPC-NE. Then, on the one hand, the diagnosis model of CRPC-NE is developed by random forest algorithm and artificial neural network (ANN) through Cbioportal database; On the other hand, using the data in Cbioportal and GEO database, the DFS and PFS prognostic model of PCa was established and verified through univariate Cox analysis, least absolute shrinkage and selection operator (Lasso) regression and multivariate Cox regression in R software. Finally, somatic mutation and immune infiltration were also discussed. Results: Our research shows that there exists specific intercellular communication in classified clusters. Secondly, a CRPC-NE diagnostic model of six genes (HMGN2, MLLT11, SOX4, PCSK1N, RGS16 and PTMA) has been established and verified, the area under the ROC curve (AUC) is as high as 0.952 (95% CI: 0.882-0.994). The mutation landscape shows that these six genes are rarely mutated in the CRPC and NEPC samples. In addition, NE-DFS signature (STMN1 and PCSK1N) and NE-PFS signature (STMN1, UBE2S and HMGN2) are good predictors of DFS and PFS in PCa patients and better than other clinical features. Lastly, the infiltration levels of plasma cells, T cells CD4 naive, Eosinophils and Monocytes were significantly different between the CRPC and NEPC groups. Conclusions: This study revealed the heterogeneity between CRPC and CRPC-NE from different perspectives, and developed a reliable diagnostic model of CRPC-NE and robust prognostic models for PCa.

MiR-629-5p Promotes Prostate Cancer Development and Metastasis by Targeting AKAP13.

Prostate cancer (PCa) has become the most frequently occurring cancer among western men according to the latest report, and patients' prognosis is often poor in the event of tumor progression, therefore, many researches are devoted to exploring the molecular mechanism of PCa metastasis. MicroRNAs (miRNA) have proved to play an important role in this process. In present study, by combining clinical samples with public databases, we found that miR-629-5p increased to varying degrees in primary localized PCa tissues and metastatic PCa tissues compared with adjacent normal tissues, and bioinformatics analysis suggested that high level of miR-629-5p was related to poor prognosis. Functionally, miR-629-5p drove PCa cell proliferation, migration and invasion in vitro, and promoted growth of PCa cells in vivo. Moreover, A-kinase Anchor Protein 13 (AKAP13) was screened as a direct target of miR-629-5p, that expression was negatively correlated with the malignant phenotype of tumor cells. In the end, through verification in clinical specimens, we found that AKAP13 could be independently used as a clinical prognostic indicator. Overall, the present study indicates that miR-629-5p plays an oncogenic role in PCa by targeting AKAP13, which provides a new idea for clinical diagnosis and treatment of complex refractory PCa.

miR-199b-5p-DDR1-ERK signalling axis suppresses prostate cancer metastasis via inhibiting epithelial-mesenchymal transition.

BACKGROUND: The investigation of underlying mechanism and the exploitation of novel therapies for metastatic prostate cancer (PCa) are still urgently needed. miR-199b-5p has been suggested to function as tumour suppressor in various human cancers. However, the clinical significance and role of miR-199b-5p in PCa remain unclear. METHODS: The current study sought to investigate the expression status of miR-199b-5p in PCa and the involved molecular mechanisms in PCa metastasis by using bioinformatics analyses, loss-and gain-of-functions and rescue experiments in vitro and in vivo. RESULTS: We demonstrated that miR-199b-5p was significantly downregulated in metastatic PCa tissues and cells when compared with the normal prostate tissue, the localised disease, the weakly metastatic and androgen-dependent PCa cell and the normal prostate epithelial cell. We also found that miR-199b-5p drastically suppressed PCa cell proliferation, migration and invasion in vitro and inhibited xenografts tumour growth and metastasis in vivo. Mechanistically, our results showed that miR-199b-5p could inhibit discoidin domain receptor tyrosine kinase 1 (DDR1) expression by directly targeting its 3'-UTR, thereby hindering epithelial-mesenchymal transition (EMT)-associated traits, which were induced by DDR1 activating ERK signalling pathway. Moreover, PCa patients with low miR-199b-5p expression level had a remarkably shorter overall survival than those with high miR-199b-5p level, indicating an association of miR-199b-5p loss with poor prognosis in patients with PCa. Furthermore, DDR1 was upregulated in PCa, and significantly correlated with high Gleason score, advanced pathological stage, tumour metastasis and shorter overall survival. CONCLUSIONS: Our study, for the first time, provide evidence of a tumour-suppressive function of miR-199b-5p in the invasion and metastasis of PCa, supporting the translational exploitation of miR-199b-5p-based therapeutic approaches for PCa metastases. Also, the miR-199b-5p-DDR1-ERK signalling axis identified in this study represents a novel mechanism of regulating EMT in PCa metastases.

Low intensity extracorporeal shockwave therapy shifts PDE5i nonresponders to responders

ABSTRACT To evaluate the efficiency of an energy density of 0.05mj/mm2 of low intensity extracorporeal shockwave therapy (Li-ESWT) on erectile dysfunction (ED) patients.A total of 45 ED patients met the inclusion criteria, including 7 PDE5i responders and 38 nonresponders. All the patients have already been delivered 10000 shockwaves of total seven treatment points twice a week for 4 weeks. Simultaneously, questionnaires of International Index of Erectile Function-Erectile Function (IIEF-EF), Erectile Hard Score (EHS) and Minimal Clinical Important Differences (MCID) were evaluated for the efficiency and safety at 8th and 16th weeks.The changes in the IIEF-EF score by MCID suggested that Li-ESWT treatment was effective in 22 PDE5i nonresponders patients (58%) at 8th week. Then at 16th week the number of patients who were effectively treated increased to 27 (71%). Among PDE5i responders, 5 patients (71%) were effective base on MCID at 16th week. Among PDE5i nonresponders 22 patients (58%) achieved erection hard enough for vaginal penetration and increased to 27 (71%) patients at 16th week (EHS ≥3). Moreover, even 3 patients achieved EHS 4 in PDE5i nonresponders at 16th week. Among PDE5i responders, 4 of 7 patients reached EHS of 4 from EHS 3 at 16th week. Apart from this, Li-ESWT treatment was also effective in 9 patients (24%) in PDE5i nonresponders without follow-up PDE5i.Energy flux density (EFD) of 0.05 of Li-ESWT could improve the erectile function of ED patients with PDE5i response. In addition, EFD of 0.05 of Li-ESWT treatment could turn PDE5i nonresponders to responders.

MiRNA-671-5p Promotes prostate cancer development and metastasis by targeting NFIA/CRYAB axis.

Prostate cancer (PCa) is the second cause of death due to malignancy among men, and metastasis is the leading cause of mortality in patients with PCa. MicroRNAs (miRNAs) play important regulatory roles in tumor development and metastasis. Here, we identified 13 miRNAs related to PCa metastasis by bioinformatics analysis. Moreover, we found that miR-671-5p was increased in metastatic PCa tissues, and its high expression indicated poor prognosis of PCa. MiR-671-5p could facilitate PCa cells proliferation, migration, and invasion in vitro and vivo. We confirmed that miR-671-5p directly bound to the 3' untranslated regions of NFIA mRNA, and NFIA directly bound to the CRYAB promoter. High expression of NFIA and CRYAB negatively correlated with the advanced clinicopathological characteristics and metastasis status of PCa patients. Our study demonstrated that miR-671-5p promoted PCa development and metastasis by suppressing NFIA/ CRYAB axis.

The Correlation between PSCA Expression and Neuroendocrine Differentiation in Prostate Cancer.

The prostate stem cell antigen (PSCA), as a predominantly prostate-specific marker, is overexpressed in most prostate cancer specimens, is positively correlated with prostate cancer androgen independence, and has the potential to be treated with castration-resistant prostate cancer (CRPC) as a gene therapy target. Using the typical androgen deprivation therapy, most tumors will progress to CRPC, as well as develop into neuroendocrine prostate cancer (NEPC) characterized by the expression of neuroendocrine markers such as enolase 2 (NSE). Our study was aimed at investigating the expressions of PSCA and NSE and the relationship between the two markers, as well as the correlation between the PSCA and NSE expressions and the clinicopathological parameters in prostate cancer specimens from 118 patients by using immunohistochemistry. Our results demonstrated that the PSCA and NSE protein expressions did not correlate with the prostate cancer patients' age or the hormone therapy but showed a significant correlation with the pathological tumor stage of prostate cancer, the Gleason score, and the presence of metastasis. There is a positive association between PSCA and NSE but a negative one between the prostate-specific antigen (PSA) and PSCA or between PSA and NSE. High PSCA and NSE expressions correlated with a poor prognosis in prostate cancer patients. PSCA may play an important role in the progression of neuroendocrine prostate cancer (NEPC).

Significant Increase of Sexual Dysfunction in Patients With Renal Failure Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: It has been shown that sexual dysfunction (SD) is highly prevalent among patients with chronic renal failure (CRF), and starting renal replacement therapy may even increase it. However, SD is an infrequently reported problem in these treated patients. AIM: To investigate the prevalence of SD among patients with CRF undergoing renal replacement therapy, by a meta-analysis method. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for all studies assessing sexual function in patients with CRF receiving renal replacement therapy from January 2000 to April 2020. Relative risk (RR) with 95% CIs was used for analysis to assess the risk of SD in patients with CRF receiving renal replacement therapy. The cross-sectional study quality methodology checklist was used for the cross-sectional study. The methodologic quality of the case-control and cohort studies was assessed with the Newcastle-Ottawa Scale. Data were pooled for the random-effect model. Sensitivity analyses were conducted to assess potential bias. The Begg and Egger tests were used for publication bias analysis. OUTCOMES: The prevalence of SD among patients with CRF receiving renal replacement therapy was summarized using pooled RR and 95% CI. RESULTS: This meta-analysis included 3,725 participants from 10 studies. Of these, 737 were patients with CRF receiving renal replacement therapy. The mean age of participants ranged from 32.75 to 56.1 years. Based on the random-effect model, synthesis of results demonstrated that the prevalence of SD was significantly increased among patients with CRF receiving renal replacement therapy in women (RR = 2.07, 95% CI: 1.47-2.91, P = .000; heterogeneity: I2 = 78.7%, P = .000) and in men (RR = 2.95, 95% CI: 2.16-4.02, P = .000; heterogeneity: I2 = 86.1%, P = .000). Estimates of the total effects were generally consistent in the sensitivity analysis. No evidence of publication bias was observed. CLINICAL IMPLICATIONS: Patients with CRF receiving renal replacement therapy had a significantly increased risk of SD, which suggests that clinicians should evaluate sexual function, when managing patients with CRF receiving renal replacement therapy. STRENGTHS AND LIMITATIONS: This is the first study to explore the prevalence of SD among patients with CRF undergoing renal replacement therapy based on all available epidemiologic studies. However, all included studies were an observational design, which may downgrade this evidence. CONCLUSION: The prevalence of SD is significantly increased among patients with CRF receiving renal replacement therapy. More research studies are warranted to clarify the relationship. Luo L, Xiao C, Xiang Q, et al. Significant Increase of Sexual Dysfunction in Patients With Renal Failure Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis. J Sex Med 2020;17:2382-2393.

Low intensity extracorporeal shockwave Therapy shifts PDE5i nonresponders to responders.

To evaluate the efficiency of an energy density of 0.05mj/mm2 of low intensity extracorporeal shockwave therapy (Li-ESWT) on erectile dysfunction (ED) patients. A total of 45 ED patients met the inclusion criteria, including 7 PDE5i responders and 38 nonresponders. All the patients have already been delivered 10000 shockwaves of total seven treatment points twice a week for 4 weeks. Simultaneously, questionnaires of International Index of Erectile Function-Erectile Function (IIEF-EF), Erectile Hard Score (EHS) and Minimal Clinical Important Differences (MCID) were evaluated for the efficiency and safety at 8th and 16th weeks. The changes in the IIEF-EF score by MCID suggested that Li-ESWT treatment was effective in 22 PDE5i nonresponders patients (58%) at 8th week. Then at 16th week the number of patients who were effectively treated increased to 27 (71%). Among PDE5i responders, 5 patients (71%) were effective base on MCID at 16th week. Among PDE5i nonresponders 22 patients (58%) achieved erection hard enough for vaginal penetration and increased to 27 (71%) patients at 16th week (EHS ≥3). Moreover, even 3 patients achieved EHS 4 in PDE5i nonresponders at 16th week. Among PDE5i responders, 4 of 7 patients reached EHS of 4 from EHS 3 at 16th week. Apart from this, Li-ESWT treatment was also effective in 9 patients (24%) in PDE5i nonresponders without follow-up PDE5i. Energy flux density (EFD) of 0.05 of Li-ESWT could improve the erectile function of ED patients with PDE5i response. In addition, EFD of 0.05 of Li-ESWT treatment could turn PDE5i nonresponders to responders.

The m6A methylation regulator-based signature for predicting the prognosis of prostate cancer.

Aim: To construct a survival prediction signature for prostate cancer (PC) based on the RNA N6-methyladenosine (m6A) methylation regulator. Materials & methods: This paper explores the interaction network of differentially expressed m6A RNA methylation regulators in PC by Pearson correlation analysis. Univariate Cox risk regression and LASSO regression analysis were used to construct a predictive signature of PC. Kaplan-Meier survival analysis compared the overall survival of the high- and low-risk groups. Results & Conclusion: We first constructed a prognostic two gene signature for PC based on the m6A RNA methylation regulators MRTTL14 and YTHDF2. The interaction network of m6A RNA methylation regulators in PC was also established.

Identifying the key genes and microRNAs in prostate cancer bone metastasis by bioinformatics analysis.

Prostate adenocarcinoma (PCa) is the most common cause of death due to malignancy among men, and bone metastasis is the leading cause of mortality in patients with PCa. Therefore, identifying the causes and molecular mechanism of bone metastasis is important for early detection, diagnosis and personalized therapy. In this study, we systematically analyzed molecular correlates of bone metastasis by bioinformatics analysis. A total of 12 differentially expressed microRNAs (miRNAs) and 102 differentially expressed genes were identified. Five miRNAs had prognostic significance in biochemical recurrence-free survival (miR-636, miR-491-5p, miR-199b-5p, miR-199b-3p, miR-28-3p). The differentially expressed genes were significantly enriched in extracellular matrix, cell-substrate adhesion, collagen and integrin. Seven hub genes (VCAN, COL3A1, COL1A1, APOE, COL1A2, SDC1, THY1) with worse biochemical recurrence-free survival and one hub gene (MMP9) with worse overall survival were detected. miR-636, a novel oncogene, was found to be up-regulated in bone metastatic PCa tissues and also predominately up-regulated in human PCa cell lines. miR-636 promoted cellular invasion and migration, and may promote bone metastasis via targeting MBNL2, TNS1 and STAB1. In conclusion, we have successfully defined molecular signatures of bone metastasis in PCa.

Association between chronic obstructive pulmonary disease and risk of erectile dysfunction: a systematic review and meta-analysis.

Chronic obstructive pulmonary disease (COPD) is a common chronic disease. Mounting evidence shows that male patients with COPD have an increased risk of developing erectile dysfunction (ED). The aim of this meta-analysis was to assess the relationship between COPD and the risk of ED. To identify relevant studies, the PubMed, Cochrane Library and Embase databases, Chinese Biomedical Literature (CBM), China National Knowledge Infrastructure (CNKI) were systematically searched up to September 2018. Relative risks (RR) and corresponding 95% confidence intervals (CI) were used to estimate the strength of association between COPD and the risk of ED by using random-effects models. Finally, four studies (three cross-sectional, one cohort study) involving 58,307 participants were included. Synthesis results demonstrated that patients with COPD was not significantly associated with an increased overall prevalence of ED (RR = 1.31, 95% CI: 0.95-1.81, P = 0.099) compared to the healthy controls. However, the subgroup analyses showed that the prevalence of moderate ED (RR = 2.44, 95% CI: 1.29-4.59, P = 0.006) and severe ED (RR = 2.77, 95% CI: 1.57-4.94, P = 0.001) were significantly higher in patients with COPD. Evidence from this meta-analysis revealed that patients with COPD had a significantly increased susceptibility to moderate and severe ED, which should remind both clinicians and patients to be aware of the potential hazardous effect of COPD for developing ED.

Association between 5α-reductase inhibitors therapy and incidence, cancer-specific mortality, and progression of prostate cancer: evidence from a meta-analysis.

5α-reductase inhibitors (5-ARI) are widely employed for the treatment of benign prostatic hyperplasia. It has been noted that 5-ARI exhibit the potential to attenuate the risk of prostate cancer, but consistent agreement has not been achieved. Moreover, the effect of 5-ARI on cancer-specific mortality and progression of prostate cancer remains unclear. Therefore, the goal of the current meta-analysis was to elucidate the impact of 5-ARI on the incidence and progression of prostate cancer. We searched for all studies assessing the effect of 5-ARI on risk of prostate cancer in PubMed, Embase, Medline, and Cochrane Library databases. Pooled relative risk (RR) and corresponding 95% confidence intervals (CIs) were accepted to evaluate the association between 5-ARI and the risk of prostate cancer. Synthetic results implied that subjects who accepted 5-ARI compared with the placebo group experienced a distinctly weakened overall incidence of prostate cancer (RR = 0.74; 95% CI: 0.66-0.82; P < 0.001). Subgroup analyses further revealed that 5-ARI reduction of the incidence of prostate cancer was limited to low-grade (Gleason score 2-6; RR = 0.68; 95% CI: 0.57-0.81; P < 0.001) and intermediate-grade tumors (Gleason score 7; RR = 0.81; 95% CI: 0.67-0.97; P = 0.023), but not high-grade tumors (Gleason score >7; RR = 1.19; 95% CI: 0.98-1.43; P = 0.069). The results also showed that 5-ARI treatment did not significantly alter prostate cancer-specific mortality (RR = 1.0; 95% CI: 0.95-1.05; P = 0.916). In addition, it was worth noting that 5-ARI treatment acted in a protective role that presented a dramatic benefit to delay the progression of low-risk tumors (RR = 0.58; 95% CI: 0.43-0.78; P < 0.001).

Application of nomograms in the prediction of overall survival and cancer-specific survival in patients with T1 high-grade bladder cancer.

To predict survival outcomes for individual patients with clinical T1 high-grade (T1HG) bladder cancer (BC), data from the Surveillance Epidemiology and End Results (SEER) database were analyzed in the present study. The data of 6,980 cases of T1HG BC between 2004 and 2014 were obtained from the SEER database. Uni- and multivariate Cox analyses were performed to identify significant prognostic factors. Subsequently, prognostic nomograms for predicting 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates were constructed based on the SEER database. Clinical information from the SEER database was divided into internal and external groups and used to validate the nomograms. In addition, calibration plot diagrams and concordance indices (C-indices) were used to verify the predictive performance of the nomogram. A total of 6,980 patients were randomly allocated to the training cohort (n=4,886) or the validation cohort (n=2094). Univariate and multivariate Cox analyses indicated that age, ethnicity, tumor size, marital status, radiation and surgical status were independent prognostic factors. These characteristics were used to establish nomograms. The C-indices for OS and CSS rate predictions for the training cohort were 0.707 (95% CI, 0.693-0.721) and 0.700 (95% CI, 0.679-0.721), respectively. Internal and external calibration plot diagrams exhibited an excellent consistency between actual survival rates and nomogram predictions, particularly for 3- and 5-year OS and CSS. The significant prognostic factors in patients with T1HG BC were age, ethnicity, marital status, tumor size, status of surgery and use of radiation. In the present study, a nomogram was developed that may serve as an effective and convenient evaluation tool to help surgeons perform individualized survival evaluations and mortality risk determination for patients with T1HG BC.

Shengjing Capsule Improves Spermatogenesis through Upregulating Integrin α6/ß1 in the NOA Rats.

OBJECTIVE: To evaluate the therapeutic effect of Shengjing capsules on nonobstructive azoospermia (NOA) in the rat model. METHODS: Twenty-five male Sprague-Dawley rats were randomly divided into five groups as follows (n=5 per group): normal group, NOA group, and three Shengjing capsule treatment groups (low-dose, medium-dose, and high-dose groups, respectively). HE staining and semen smear were performed to assess sperm quality. The expression levels of PI3K/AKT and integrin α6/ß1 were measured by qRT-PCR and western blot analyses. RESULTS: In the NOA group, almost all of the seminiferous tubules were vacuolated with a thin layer of basal compartment containing some spermatogonial stem cells. The counts of sperms in the NOA group were strongly lower than those of the normal group (P=0.0001). The expression of PI3K/AKT and integrin α6/ß1 was scarcely expressed in the NOA group. All indexes mentioned above were significantly different from those of the medium- and high-dose groups (P=0.001, all). The sperm count of rats treated with Shengjing capsules was significantly higher than that of the NOA group (P=0.0001). The rats of Shengjing capsule groups had more layers of spermatogonial stem cells and spermatocytes, and some had intracavitary sperms. CONCLUSIONS: Shengjing capsules may be a promising therapeutic medicine for NOA. The underlying mechanisms might involve activating SSCs by upregulating the integrin α6/ß1 expression via the PI3K/AKT pathway.