Identification of ferroptotic genes and phenotypes in idiopathic nonobstructive azoospermia.

Effective treatments for nonobstructive azoospermia (NOA), which affects 1% of all men globally, are limited by undefined pathogenic mechanisms, especially in idiopathic NOA (iNOA). Here, we tried to identify the functional ferroptosis-related genes and phenotypes involved in iNOA. Differentially expressed ferroptotic genes were identified from iNOA mRNA microarray datasets by bioinformatic analyses, and these ferroptotic genes were subsequently filtered by various algorithms. Then, receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic ability of the abovementioned genes for iNOA. Generally, 11 differentially expressed ferroptotic genes were downregulated, and five genes were upregulated in iNOA samples. Four genes, including DUSP1, GPX4, HSD17B11, and SLC2A8, were technically selected and determined to be potential biomarkers for iNOA. Subsequently, similar expression levels were validated at both the RNA and protein levels in the iNOA specimens. Finally, morphologic and biochemical assays were applied to define the ferroptotic phenotypes in testes. The ferroptotic features, like shrunken mitochondria with electron-dense membranes and a reduction in cristae were observed across various cell types within iNOA patients, accompanied by the overload of ferrous ions and increased lipid peroxidation production. Our findings demonstrated that these ferroptosis genes could be involved in the underlying pathogenesis mechanisms of iNOA by regulating ferroptosis and serve as potential diagnostic biomarkers. Also, the ferroptotic phenotypes were identified in iNOA patients.

Construction and Validation of a Nomogram for Predicting Progression- Free Survival in Patients with Early-Stage Testicular Germ Cell Tumor.

BACKGROUND: Testicular Germ Cell Tumor (TGCT) is the most common malignant tumor in young men, but there is a lack of a prediction model to evaluate the prognosis of patients with TGCT. OBJECTIVE: To explore the prognostic factors for Progression-Free Survival (PFS) and construct a nomogram model for patients with early-stage TGCT after radical orchiectomy. METHODS: Patients with TGCT from The Cancer Genome Atlas (TCGA) database were used as the training cohort; univariate and multivariate cox analysis was performed. A nomogram was constructed based on the independent prognostic factors. Patients from the Nanfang Hospital affiliated with Southern Medical University were used as the cohort to validate the predictive ability using the nomogram model. Harrell's concordance index (C-index) and calibration plots were used to evaluate the nomogram. RESULTS: A total of 110 and 62 patients with TGCT were included in the training cohort and validation cohort, respectively. Lymphatic Vascular Invasion (LVI), American Joint Committee on Cancer (AJCC) stage and adjuvant therapy were independent prognostic factors in multivariate regression analyses and were included to establish a nomogram. The C-index in the training cohort for 1- , 3-, and 5-year PFS were 0.768, 0.74, and 0.689, respectively. While the C-index for 1-, 3-, and 5- year PFS in the external validation cohort were 0.853, 0.663 and 0.609, respectively. The calibration plots for 1-, 3-, and 5-year PFS in the training and validation cohort showed satisfactory consistency between predicted and actual outcomes. The nomogram revealed a better predictive ability for PFS than AJCC staging system. CONCLUSION: The nomogram as a simple and visual tool to predict individual PFS in patients with TGCT could guide clinicians and clinical pharmacists in therapeutic strategy.

Effect of Different Modes of Exercise on Sarcopenia in Older Adults: A Meta-analysis / 中国康复理论与实践

Objective:To evaluate the effectiveness of single modal and multimodal exercise interventions on sarcopenia in the elderly. Methods:Randomized controlled trials about the effects of single modal and multimodal exercises on the improvement of sarcopenia in the elderly were retrieved from seven databases (PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP and Wanfang data) from the establishment of the databases to July, 2021. Two researchers selected the literatures independently, and evaluated the quality of methodology. The meta-analysis was performed with RevMan 5.3. Results:A total of 15 studies were incorporated, including 816 cases of sarcopenia. Compared to the blank control group, the skeletal muscle mass index improved little with single (MD = -0.05, 95%CI -0.14 to 0.04, P > 0.05) and multiple (MD = 0.15, 95%CI -0.01 to 0.31, P > 0.05) exercises. The maximum grip force improved with both single (MD = 2.06, 95%CI 0.25 to 3.87, P < 0.05) and multiple (MD = 2.36, 95%CI 1.10 to 3.63, P < 0.001) exercises. The knee extensors strength (SMD = 0.49, 95%CI 0.26 to 0.73, P < 0.001) and the walking speed (MD = 0.24, 95% CI 0.19 to 0.29, P < 0.001) improved with multimodal exercises. Conclusion:Single modal exercise may improve maximal grip strength in the elderly with sarcopenia, and multimodal exercise may be effective on maximal grip strength, knee extensors strength and walking speed.

[Surgical intervention in adult varicocele: An update].

Varicocele is one of the common causes of infertility in adult males. Surgical intervention can improve the semen quality of some of the patients and significantly increase the pregnancy rate, but fails to benefit them all. Therefore, it is of great practical significance to identify the patients who can significantly benefit from surgical interventions to maximize the effectiveness of surgery and avoid medical waste. This article summarizes the recent progress in surgical indications and strategies for varicocele in adult males, and provides some reference for the management of the disease.

[Vascular damage-related risk factors for erectile dysfunction in patients with type 2 diabetes mellitus: Analysis based on a nomogram model].

OBJECTIVE: To analyze vascular damage-related risk factors for ED in patients with type 2 diabetes mellitus (DM) and develop a nomogram for the prediction of the factors. METHODS: A total of 181 patients with type 2 DM were included for sexual function assessment, and the clinical data on vascular damage were retrieved from the patients system. After preprocessing, the data were described by the number and percentage of different types of cases and subjected to statistical analysis with the R software. The Lasso regression model was used to optimize feature selection. On the premise of the sample size required for logistic regression analysis according to the number of events per variable, multivariable logistic regression analysis was performed on the selected variables and a nomogram was developed for diabetes-induced erectile dysfunction (DIED). Then, the performance of the nomogram was evaluated with respect to its calibration, discrimination and clinical utility using Harrell's concordance index (C-index), the calibration plot and decision curve analysis, as well as bootstrapping for internal validation. RESULTS: ED was diagnosed in 90 (49.7%) of the 181 patients. The risk factors subjected to logistic regression analysis included the duration of DM (OR = 4.440, 95% CI: 1.594－13.105; OR = 7.667, 95% CI: 1.444－48.733), status of carotid intima-media thickness (c-IMT) (OR = 3.767, 95% CI: 1.194－12.691), diabetic retinopathy (DR) (OR = 5.382, 95% CI: 1.373－28.301), diabetic kidney disease (DKD) (OR = 4.959, 95% CI: 1.156－27.728), low-density lipoprotein cholesterol (LDL-C) (OR = 8.210, 95% CI: 2.027－43.507), red blood cell distribution width (RDW) (OR = 2.418, 95% CI: 1.021－5.826), and plasma fibrinogen (Fbg) (OR = 4.649, 95% CI: 2.001－11.339). The C-index of the DIED model was 0.911 (95% CI: 0.869－0.954). The curve representing the performance of the nomogram fit in well with that representing a perfect prediction by the calibration plot. Decision curve analysis indicated that the nomogram was clinically useful for predicting DIED in the type 2 DM patients at the possibility threshold of 6% to 93%. CONCLUSIONS: A nomogram was preliminarily developed for predicting the risk of DIED in type 2 DM patients with respect to the seven independent influencing factors, including the duration of DM, status of c-IMT, DR, DKD, LDL-C, RDW, and Fbg.