From Waterloo to the Great Wall: A retrospective, multicenter study on the clinical practice and cultural attitudes in the management of premature ejaculation, in China.

Premature ejaculation (PE), despite its wide prevalence, is largely underdiagnosed and undertreated. Being a multifactorial dysfunction with strong cultural characteristics, PE requires skillful attitudes in the psychosexological support, necessary to manage the patient's and the couple's expectations, as well as in the medical treatment. Dapoxetine is a short-acting selective serotonin reuptake inhibitor approved for use in lifelong and acquired PE in a number of countries. Opinions, not always generated by the evidence-based medicine, impacted the attitudes of Western andrologists, as a nocebo effect which produced a drug's Waterloo, characterized by low prescription rates much more built on the patients' and doctors' expectations than on costs, side effects, and efficacy. In the present study, we retrospectively reviewed real-life data from eight Andrology and Sexual Medicine Public Centers in China to assess the prevalence of PE among attending patients, its association with erectile dysfunction, its subtype, and the proposed treatments. In 2019, among 156,486 patients coming to the centers, 32,667 visits having PE as the chief complaint were performed (20.9%). Almost all patients received treatment prescriptions (32,641 patients, 99.92%); 23,273 patients came back for a follow-up visit in the subsequent 12 months (71.2% of those who initially received treatment). Dapoxetine, either alone or in combination with another therapy, was the most prevalent treatment, prescribed to 22,767 patients (69.7% of treated patients), followed by traditional Chinese medicine (TCM) (39.4%). At follow-up, 8174 patients were unsatisfied with treatment, and a new treatment was proposed (35.12%). Dapoxetine was the best treatment, with an overall 27.1% switching rate when used either alone or in combination: Although the switching rate for Dapoxetine alone was 44.2%, the association of the same drug with psychotherapy resulted in much lower rates (19.5%) and reached a minimum of 12% when also combined with TCM demonstrating how cultural aspects and medical attitudes may dramatically impact on the therapy of a multifaceted, complex, and culture-grounded sexual symptom such as PE. In conclusion, taking switching rates as surrogate markers of treatment failure, this real-life study-the largest in the field-shows that in a more patient-oriented (as in Chinese medical culture), and less symptom-oriented (as in Western medical attitudes), Dapoxetine is a successful treatment for PE patients, with higher reliability when used alone or as part of combined and integrated therapies.

FBP1 /miR-24-1/enhancer axis activation blocks renal cell carcinoma progression via Warburg effect.

Warburg effect is a pivotal hallmark of cancers and appears prevalently in renal cell carcinoma (RCC). FBP1 plays a negative role in Warburg effect as a rate-limiting enzyme in gluconeogenesis, yet its mechanism in RCC remains to be further characterized. Herein, we revealed that FBP1 was downregulated in RCC tissue samples and was related to the poor survival rate of RCC. Strikingly, miR-24-1 whose DNA locus is overlapped with enhancer region chr9:95084940-95087024 was closely linked with the depletion of FBP1 in RCC. Of note, miRNAs like miR-24-1 whose DNA loci are enriched with H3K27ac and H3K4me1 modifications are belonging to nuclear activating miRNAs (NamiRNAs), which surprisingly upregulate target genes in RCC through enhancer beyond the conventional role of repressing target gene expression. Moreover, miR-24-1 reactivated the expression of FBP1 to suppress Warburg effect in RCC cells, and subsequently inhibited proliferation and metastasis of RCC cells. In mechanism, the activating role of miR-24-1 was dependent on enhancer integrity by dual luciferase reporter assay and CRISPR/Cas9 system. Ultimately, animal assay in vivo validated the suppressive function of FBP1 on 786-O and ACHN cells. Collectively, the current study highlighted that activation of FBP1 by enhancer-overlapped miR-24-1 is capable of contributing to Warburg effect repression through which RCC progression is robustly blocked, providing an alternative mechanism for RCC development and as well implying a potential clue for RCC treatment strategy.

A Prospectively Validated Nomogram for Predicting the Risk of PHQ-9 Score ≥15 in Patients With Erectile Dysfunction: A Multi-Center Study.

Background: Although erectile dysfunction (ED) often occurs simultaneously with depression, not all patients with ED suffer major depression (MD), with a PHQ-9 score ≥15 indicating MD. Because the PHQ-9 questionnaire includes phrases such as "I think I am a loser" and "I want to commit suicide," the psychological burdens of ED patients are likely to increase inevitably after using the PHQ-9, which, in turn, may affect ED therapeutic effects. Accordingly, we endeavored to develop a nomogram to predict individual risk of PHQ-9 score ≥15 in these patients. Methods: The data of 1,142 patients with ED diagnosed in Xijing Hospital and Northwest Women and Children's Hospital from January 2017 to May 2020 were analyzed. While the Least Absolute Shrinkage and Selection Operator regression was employed to screen PHQ-9 score ≥15 related risk factors, multivariate logistic regression analysis was performed to verify these factors and construct the nomogram. The training cohort and an independent cohort that comprised 877 prospectively enrolled patients were used to demonstrate the efficacy of the nomogram. Results: The IIEF-5 score, PEDT score, physical pain score, frequent urination, and feeling of endless urination were found to be independent factors of PHQ-9 score ≥15 in patients with ED. The nomogram developed by these five factors showed good calibration and discrimination in internal and external validation, with a predictive accuracy of 0.757 and 0.722, respectively. The sensitivity and specificity of the nomogram in the training cohort were 0.86 and 0.52, respectively. Besides, the sensitivity and specificity of the nomogram in the validation cohort were 0.73 and 0.62, respectively. Moreover, based on the nomogram, the sample was divided into low-risk and high-risk groups. Conclusion: This study established a nomogram to predict individual risk of PHQ-9 score ≥15 in patients with ED. It is deemed that the nomogram may be employed initially to avoid those with a low risk of MD completing questionnaires unnecessarily.

Nomogram for stratifying patients with lifelong premature ejaculation before using the PHQ-9: An observational study.

OBJECTIVE: A PHQ-9 score ≥ 15, represented as PHQ-9+ , indicates major depressive disorder (MDD). On using PHQ-9, the psychological burden of several patients with lifelong premature ejaculation (LPE) gets aggravated, which may lead to LPE development. We aim to construct a nomogram for predicting the individual risk of PHQ-9+ in patients with LPE and discerning those with low risks, who should avoid the PHQ-9. METHODS: The nomogram was constructed by analysing data of 802 patients from Xijing Hospital and Northwest Women's & Children's Hospital. The LASSO and multivariable logistic regressions were used to identify independent predictors of PHQ-9+ , used for developing the nomogram. The discrimination, calibration and clinical usefulness of the nomogram were assessed in the derivation cohort and an independent validation cohort, which was composed of 505 prospectively enrolled patients from Daxing Hospital and Xijing Hospital. RESULTS: The duration of PE, IELT, a history of PE exacerbation, IIEF-5 score, urinary frequency and physical pain score were identified as independent predictors. The nomogram showed excellent calibration, discrimination and clinical usefulness in the derivation and validation cohorts, with a predictive accuracy of 0.781 and 0.763, respectively. Based on this nomogram, patients were divided into not recommended, recommended and strongly recommended PHQ-9 filling groups, with PHQ-9+ rates of 3.5%, 9.3% and 30.7%, respectively. CONCLUSION: A nomogram to discern LPE patients with low risks of PHQ-9+ was established. This tool can increase the positivity of MDD screening and may improve the therapeutic outcomes of those in the low-risk group.

Construction and internal validation of a prediction nomogram for acquired premature ejaculation (APE) in PE patients.

BACKGROUND: A predictive model for acquired premature ejaculation (APE) in PE patients has not yet been established. OBJECTIVES: This study was aimed at determining which factors were independently associated with the possibility of predicting APE in PE patients, and whether an effective pre-treatment nomogram for predicting their individual chances of being APE in PE patients can be developed. MATERIALS AND METHODS: We analyzed the medical histories of 915 PE patients diagnosed at Xijing Hospital (Xi'an, China) and Northwest Women's and Children's Hospital (Xi'an, China) between May 2019 and May 2020. The diagnostic nomogram was developed using a multivariate logistic regression model by integrating selected significant variables determined through univariate analysis. Receiver operating characteristic curves were used to measure the predictive accuracy of the nomogram and its constituted variables, and calibrations were performed by making a comparison of nomogram-predicted probability with actual rate of APE. RESULTS: The independent predictors for APE that were identified include Age, Intra-vaginal Ejaculation Latency Time (IELT), Frequency of sexual desire (FSD), and Eysenck Personality Questionnaire-Revised Short Scale for Chinese (psychoticism) [EPQ-RSC(P)] scores. The predictive accuracy of the nomogram was 0.782 (95% CI: 0.723-0.841). Also, excellent agreement was demonstrated between the nomogram-predicted probability and the actual rate of APE. DISCUSSION AND CONCLUSION: We identified 4 independent predictors for APE and demonstrated the potential significant differences in psychoticism between LPE and APE patients. This was the first internally validated predictive APE nomogram where good discrimination and calibration were applied, and it offers a promising role in clinical practice. More studies are necessary for verification of its universal applicability.

Novel survival nomograms for patients with lung metastatic clear cell renal cell carcinoma: A population-based study.

ABSTRACT: Survival heterogeneity is observed among renal cell carcinoma (RCC) patients with metastases in different organs. Moreover, almost all previous prognostic nomograms based on data from metastatic RCC patients did not take competing events, such as death from cerebrovascular and heart diseases, into account. We aimed to construct novel prognostic nomograms for patients with lung metastatic clear cell RCC (LMCCRCC).Data of 712 non-Hispanic white LMCCRCC patients registered in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. Nomograms for predicting overall survival (OS) and disease-specific survival (DSS) were established using the Cox approach and Fine and Gray approach, respectively, and their performances were assessed using the concordance index (C-index), calibration plots, and an independent cohort comprising 181 Hispanic patients.Sex, tumor grade, T stage, N stage, presence or absence of bone metastases, and presence or absence of brain metastases were independent predictors for both OS and DSS. Additionally, presence or absence of liver metastases was an independent predictor only for DSS. Meanwhile, age at diagnosis was independently associated with OS. The C-indexes of the nomograms were 0.702 for OS and 0.723 for DSS in internal validation. In external validation, the C-indexes were 0.700 for OS and 0.708 for DSS. Both internal and external calibration plots showed excellent consistency between the prediction and the observation.The current study developed a novel nomogram for predicting individual OS in LMCCRCC patients. Moreover, we constructed an effective competing risk nomogram for predicting their individual DSS for the first time.

An Internally Validated Nomogram for Predicting the Likelihood of Improvement of Clinical Global Impression in Patients With Lifelong Premature Ejaculation Treated With Dapoxetine.

BACKGROUND: Although the introduction of dapoxetine has ushered in a new era in the treatment of premature ejaculation, many patients with lifelong premature ejaculation (LPE) exhibit an unimproved clinical global impression even after treatment with dapoxetine. AIM: To investigate independent predictors of the improvement of Clinical Global Impression (iCGI) in patients with LPE treated with dapoxetine and develop a nomogram to predict a patient's likelihood of achieving iCGI. METHODS: Data of 243 patients with LPE diagnosed at Xijing Hospital (Xi'an, China) and Northwest Women's and Children's Hospital (Xi'an, China) from January 2019 to May 2020 were analyzed. Independent predictors of iCGI were identified, and a nomogram was developed using R software based on a multivariate logistic regression model. The predictive accuracy of the nomogram was measured using the area under the receiver operating characteristic curve. The nomogram was calibrated by comparing predictions with observations. MAIN OUTCOME MEASURES: The primary outcome was the patient-rated Clinical Global Impression of Change scale score after a 4-week course of dapoxetine treatment, which was collected via an online questionnaire. A Clinical Global Impression of Change score of ≥1 was defined as iCGI in this study. RESULTS: Patients with LPE with at least a bachelor's degree, a self-reported intravaginal ejaculation latency time of >1 minute, and an International Index of Erectile Function question 5 score of ≥3 were independent factors associated with achieving iCGI, whereas a Premature Ejaculation Diagnostic Tool question 1 score of ≥2 was an independent factor negatively associated with achieving iCGI. The predictive accuracy of the nomogram, which was developed by integrating all variables with independent predictive significance, was 0.710 (95% confidence interval: 0.702-0.718). In addition, the calibration plot demonstrated excellent agreement between predictions and observations. CLINICAL IMPLICATIONS: If the predictive performance of our nomogram is further proven in multiple external validations, it can be used to select suitable patients for dapoxetine treatment, thereby reducing the number of patients discontinuing treatment. STRENGTHS & LIMITATIONS: This study developed the first nomogram for predicting the likelihood of achieving iCGI in patients with LPE treated with dapoxetine. However, our nomogram was not externally validated using independent cohorts from other institutions. CONCLUSION: This study identified several independent predictors of iCGI in patients with LPE treated with dapoxetine. An effective nomogram was developed to predict their likelihood of achieving iCGI. External validations using data of Western patients with LPE are required to test the broader applicability of this Chinese patient-based tool. Hou G, Gao M, Zhang L, et al. An Internally Validated Nomogram for Predicting the Likelihood of Improvement of Clinical Global Impression in Patients With Lifelong Premature Ejaculation Treated With Dapoxetine. J Sex Med 2020;17:2341-2350.

A novel nomogram predicting the risk of positive biopsy for patients in the diagnostic gray area of prostate cancer.

The roles played by several inflammatory factors in screening for prostate cancer (PCa) among gray area patients, namely those with serum prostate-specific antigen (PSA) levels between 4 and 10 ng/ml, have not been completely identified, and few effective diagnostic nomograms have been developed exclusively for these patients. We aimed to investigate new independent predictors of positive biopsy (PB) results and develop a novel diagnostic nomogram for this group of patients. The independent predictors of PB results were identified, and a nomogram was constructed using multivariate logistic regression analysis based on a cohort comprising 401 Gy area patients diagnosed at Xijing Hospital (Xi'an, China) between January 2016 and December 2019. The predictive accuracy of the nomogram was assessed using the receiver operating characteristic curve, and the nomogram was calibrated by comparing the prediction with the observation. The performance of the nomogram was further validated using an independent cohort. Finally, lymphocyte-to-monocyte ratio (LMR) > 4.11 and red blood cell distribution width (RDW)-standard deviation (SD) > 42.9 fl were identified as independent protective predictors of PB results, whereas PSA density (PSAD) > 0.141 was identified as an independent risk predictor. The nomogram established using PSAD, LMR, and RDW-SD was perfectly calibrated, and its predictive accuracy was superior to that of PSAD in both internal and external validations (0.827 vs 0.769 and 0.765 vs 0.713, respectively). This study is the first to report the importance of LMR and RDW-SD in screening for PCa among gray area patients and to construct an exclusive nomogram to predict the individual risk of positive 13-core biopsy results in this group of patients. With superior performance over PSAD, our nomogram will help increase the accuracy of PCa screening, thereby avoiding unnecessary biopsy.

The near-infrared fluorescent dye IR-780 was coupled with cabazitaxel for castration-resistant prostate cancer imaging and therapy.

A new drug, Caba-780, was synthesized by chemical coupling of the heptamethyl phthalocyanine near-infrared fluorescent (NIRF) dye IR-780 and the paclitaxel-based chemotherapeutic drug cabazitaxel. Then, the potential value of Caba-780 in the diagnosis and treatment of castration-resistant prostate cancer (CRPC) was evaluated. The CRPC cell lines DU145 and PC-3, as well as the normal human prostate stromal cell line WPMY-1, were used to evaluate the uptake of Caba-780 and its antitumor effect in vitro. The distribution, antitumor effect, and safety of Caba-780 were also evaluated in tumor-bearing mouse xenograft models. Our results showed that Caba-780 was efficiently absorbed by DU145 and PC-3 cells and that the cytotoxicity of Caba-780 was significantly stronger than that of IR-780 and cabazitaxel. In addition, Caba-780 inhibited the migration and invasion of DU145 and PC-3 cells and promoted apoptosis by prolonging the G2 phase of the cell cycle. Further analysis indicated that Caba-780 could be used to effectively image tumor xenografts. At the same time, this drug inhibited the growth of tumors in vivo. Therefore, the new synthetic drug Caba-780 has potential applications in the diagnosis and treatment of CRPC.