Bibliometric and Visualization Analysis of Stem Cell Therapy for Erectile Dysfunction.

Purpose: As a common male disease, erectile dysfunction (ED) seriously affects the physical and mental health of patients. In recent years, studies have continued to point out the great potential of stem cell therapy (SCT) in the treatment of ED. The purpose of this study is to comprehensively analyze the research of SCT for ED and understand the development trends and research frontiers in this field. Methods: Publications regarding SCT and ED were retrieved and collected from the Web of Science Core Collection. CiteSpace and VOSviewer software were then utilized for bibliometric and visualization analysis. Results: A total of 524 publications were eventually included in this study. The annual number of publications in this field was increasing year by year. China and the USA were the two most productive countries. Lin GT, Lue TF and Lin CS, and the University of California San Francisco where they worked were the most productive research group and institution, respectively. The journal with the largest number of publications was The Journal of Sexual Medicine, and the following were mostly professional journals of urology and andrology. Diabetes mellitus-induced ED and cavernous nerve injury-related ED were the two most commonly constructed models of ED in studies. Concerning the types of stem cells, mesenchymal stem cells derived from adipose and bone marrow were most frequently used. Moreover, future research would mainly focus on exosomes, tissue engineering technology, extracorporeal shockwave therapy, and clinical translation. Conclusion: The research of SCT for ED will receive increasing global attention in the future. Our study provided bibliometric and visualization analysis of published literature, helping researchers understand the global landscape and frontiers in this field. More preclinical and clinical studies should be conducted to more deeply explore the underlying mechanisms of treatment and promote clinical translation.

Improvement of the Thermal Stability and Aqueous Solubility of Three Matrine Salts Assembled by the Similar Structure Salt Formers.

Matrine (MAT), a natural Chinese herbal medicine, has a unique advantage in the treatment of various chronic diseases. However, its low melting point, low bioavailability, and high dosage restrict its subsequent development into new drugs. In this study, three kinds of MAT salts, namely, MAT-2,5-dihydroxybenzoic acid (MAT-25DHB), MAT-2,6-dihydroxybenzoic acid (MAT-26DHB), and MAT-salicylic acid-hydrate (MAT-SAL-H2O), were designed and synthesized to improve the drugability of MAT. The three salts were characterized by using various analytical techniques, including single-crystal X-ray diffractometry, powder X-ray diffractometry, differential scanning calorimetry, thermogravimetry, and infrared spectroscopy. The results of the thermal stability evaluation showed that the formation of salts improved the stability of MAT; MAT-25DHB is the most stable salt reported at present. The results of aqueous solubility showed that the solubility of MAT-25DHB was higher than that of MAT, while that of MAT-26DHB and MAT-SAL-H2O were less. Given that the MAT-25DHB salt further improved the solubility of MAT, it is expected to be subjected to further research as an optimized salt. Lattice energy and solvation free energy are important factors affecting the solubility of salts; the reasons for the changes of solubility and stability of three kinds of salts are explained by calculating them.

Exploring potential genes and mechanisms linking erectile dysfunction and depression.

Background: The clinical correlation between erectile dysfunction (ED) and depression has been revealed in cumulative studies. However, the evidence of shared mechanisms between them was insufficient. This study aimed to explore common transcriptomic alterations associated with ED and depression. Materials and methods: The gene sets associated with ED and depression were collected from the Gene Expression Omnibus (GEO) database. Comparative analysis was conducted to obtain common genes. Using R software and other appropriate tools, we conducted a range of analyses, including function enrichment, interactive network creation, gene cluster analysis, and transcriptional and post-transcriptional signature profiling. Candidate hub crosslinks between ED and depression were selected after external validation and molecular experiments. Furthermore, subpopulation location and disease association of hub genes were explored. Results: A total of 85 common genes were identified between ED and depression. These genes strongly correlate with cell adhesion, redox homeostasis, reactive oxygen species metabolic process, and neuronal cell body. An interactive network consisting of 80 proteins and 216 interactions was thereby developed. Analysis of the proteomic signature of common genes highlighted eight major shared genes: CLDN5, COL7A1, LDHA, MAP2K2, RETSAT, SEMA3A, TAGLN, and TBC1D1. These genes were involved in blood vessel morphogenesis and muscle cell activity. A subsequent transcription factor (TF)-miRNA network showed 47 TFs and 88 miRNAs relevant to shared genes. Finally, CLDN5 and TBC1D1 were well-validated and identified as the hub crosslinks between ED and depression. These genes had specific subpopulation locations in the corpus cavernosum and brain tissue, respectively. Conclusion: Our study is the first to investigate common transcriptomic alterations and the shared biological roles of ED and depression. The findings of this study provide insights into the referential molecular mechanisms underlying the co-existence between depression and ED.

Comprehensive analysis of biological landscape of oxidative stress-related genes in diabetic erectile dysfunction.

Oxidative stress plays a pivotal role in the pathogenesis of diabetic erectile dysfunction, while specific mechanisms have not been illuminated. The study aims to reveal the genetic expression patterns of oxidative stress in diabetic erectile dysfunction. Transcriptome data of diabetic erectile dysfunction and oxidative stress-related genes (OSRGs) in the Gene Expression Omnibus database were downloaded and analyzed based on differential expression. Functional enrichment analyses were conducted to clarify the biological functions. A protein interaction framework was established, and significant gene profiles were validated in the cavernous endothelial cells, clinical patients, and rat models. A miRNA-OSRGs network was predicted and validated. The results were analyzed using Student's t-test. The analysis screened 203 differentially expressed OSRGs (p < 0.05), which had a close association with oxidoreductase activities, glutathione metabolism, and autophagy. A four-gene signature comprised of EPS8L2 (p = 0.044), GSTA3 (p = 0.015), LOX (p < 0.001) and MGST1 (p = 0.002) was well validated and regarded as the hub OSRGs. Compared with the control group, notable increases and decreases were observed in the expressions of GSTA3 (3.683 ± 0.636 vs. 0.416 ± 0.507) and LOX (2.104 ± 1.895 vs. 18.804 ± 2.751) in the validated diabetic erectile dysfunction group. The hub OSRGs-related miRNAs participated in smooth muscle cell proliferation. Besides, miR-125a-3p (p = 0.034) and miR-138-2-3p (p = 0.012) were validated as promising oxidative stress-related miRNA biomarkers. Our findings revealed the genetic alternations of oxidative stress in diabetic erectile dysfunction. These results will be instructive to explore the molecular landscape and the potential treatment for diabetic erectile dysfunction.

Identification of hub genes and biological mechanisms underlying the pathogenesis of asthenozoospermia and chronic epididymitis.

Objective: Asthenozoospermia (AZS) is one of the most common causes of male fertility, affecting family wellbeing and population growth. Chronic epididymitis (CE) is a common and lingering inflammatory disease in the scrotum. Inflammation in the epididymis has a severe impact on sperm motility. This study aimed to explore the genetic profile and critical pathways involved in the pathological mechanisms of AZS and CE, and discover potential biomarkers. Methods: Genomic datasets of AZS and CE were obtained from the Gene Expression Omnibus (GEO) database, and relevant differentially expressed genes (DEGs) were identified. GO and pathway enrichment analyses, construction of a protein-protein interaction network, and receiver operator characteristic curve analysis were conducted. The expression profile of hub genes was validated in immunohistochemical data and testicular cell data. Immune infiltration, miRNA-hub gene interactions, and gene-disease interactions were explored. The mRNA levels of hub genes were further measured by qRT-PCR. Results: A total of 109 DEGs were identified between the AZS/CE and healthy control groups. Pathways of the immune system, neutrophil degranulation, and interleukin-4 and interleukin-13 signaling were enriched in AZS and CE. Five hub genes (CD300LB, CMKLR1, CCR4, B3GALT5, and CTSK) were selected, and their diagnostic values were validated in AZS, CE, and independent validation sets (area under the curve >0.7). Furthermore, the five-hub gene signature was well characterized in testicular immunohistochemical staining and testicular cells from healthy controls. Immune infiltration analysis showed that infiltration of CD8+ cells and T helper cells was significantly related to the expression level of five hub genes. In addition, a miRNA-hub gene network and interaction of other diseases were displayed. The mRNA levels of hub genes (CD300LB, CMKLR1, CCR4, and B3GALT5) were significantly elevated in the patient group. The mRNA level of CTSK also showed a similar trend. Conclusion: Our study uncovered the genetic profile involved in AZS and CE, and elucidated enriched pathways and molecular associations between hub genes and immune infiltration. This finding provides novel insight into the common pathogenesis of both diseases as well as the potential biomarkers for CE-associated AZS.

Exploration of the common genetic landscape of COVID-19 and male infertility.

Background: COVID-19 has spread widely across continents since 2019, causing serious damage to human health. Accumulative research uncovered that SARS-CoV-2 poses a great threat to male fertility, and male infertility (MI) is a common comorbidity for the COVID-19 pandemic. The aim of the study was to explore the cross-talk molecular mechanisms between COVID-19 and MI. Materials and methods: A total of four transcriptome data regarding COVID-19 and MI were downloaded from the Gene Expression Omnibus (GEO) repository, and were divided for two purposes (initial analysis and external validation). Differentially expressed genes (DEGs) analysis, GO and pathway annotation, protein-protein interaction (PPI) network, connectivity ranking, ROC analysis, immune infiltration, and translational and post-translational interaction were performed to gain hub COVID-19-related DEGs (CORGs). Moreover, we recorded medical information of COVID-19 patients with MI and matched healthy controls, and harvested their sperm samples in the university hospital. Expressions of hub CORGs were detected through the qRT-PCR technique. Results: We identified 460 overlapped CORGs in both the COVID-19 DEGs and MI DEGs. CORGs were significantly enriched in DNA damage and repair-associated, cell cycle-associated, ubiquitination-associated, and coronavirus-associated signaling. Module assessment of PPI network revealed that enriched GO functions were closely related to cell cycle and DNA metabolism processes. Pharmacologic agent prediction displayed protein-drug interactions of ascorbic acid, biotin, caffeine, and L-cysteine with CORGs. After connectivity ranking and external validation, three hub CORGs (ENTPD6, CIB1, and EIF3B) showed good diagnostic performance (area under the curve > 0.75). Subsequently, three types of immune cells (CD8+ T cells, monocytes, and macrophages M0) were dominantly enriched, and 24 transcription factor-CORGs interactions and 13 miRNA-CORGs interactions were constructed in the network. Finally, qRT-PCR analysis confirmed that there were significant differences in the expression of hub CORGs (CIB1 and EIF3B) between the patient and control groups. Conclusion: The present study identified and validated hub CORGs in COVID-19 and MI, and systematically explored molecular interactions and regulatory features in various biological processes. Our data provide new insights into the novel biomarkers and potential therapeutic targets of COVID-19-associated MI.

Constructing a seventeen-gene signature model for non-obstructive azoospermia based on integrated transcriptome analyses and WGCNA.

BACKGROUND: Non-obstructive azoospermia (NOA) affects approximately 1% of the male population worldwide. The underlying mechanism and gene transcription remain unclear. This study aims to explore the potential pathogenesis for the detection and management of NOA. METHODS: Based on four microarray datasets from the Gene Expression Omnibus database, integrated analysis and weighted correlation network analysis (WGCNA) were used to obtain the intersected common differentially expressed genes (DESs). Differential signaling pathways were identified via GO and GSVA-KEGG analyses. We constructed a seventeen-gene signature model using least absolute shrinkage and selection operation (LASSO) regression, and validated its efficacy in another two GEO datasets. Three patients with NOA and three patients with obstructive azoospermia were recruited. The mRNA levels of seven key genes were measured in testicular samples, and the gene expression profile was evaluated in the Human Protein Atlas (HPA) database. RESULTS: In total, 388 upregulated and 795 downregulated common DEGs were identified between the NOA and control groups. ATPase activity, tubulin binding, microtubule binding, and metabolism- and immune-associated signaling pathways were significantly enriched. A seventeen-gene signature predictive model was constructed, and receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) values were 1.000 (training group), 0.901 (testing group), and 0.940 (validation set). The AUCs of seven key genes (REC8, CPS1, DHX57, RRS1, GSTA4, SI, and COX7B) were all > 0.8 in both the testing group and the validation set. The qRT-PCR results showed that consistent with the sequencing data, the mRNA levels of RRS1, GSTA4, and COX7B were upregulated, while CPS1, DHX57, and SI were downregulated in NOA. Four genes (CPS1, DHX57, RRS1, and SI) showed significant differences. Expression data from the HPA database showed the localization characteristics and trajectories of seven key genes in spermatogenic cells, Sertoli cells, and Leydig cells. CONCLUSIONS: Our findings suggest a novel seventeen-gene signature model with a favorable predictive power, and identify seven key genes with potential as NOA-associated marker genes. Our study provides a new perspective for exploring the underlying pathological mechanism in male infertility.

Uncovering the genetic links of diabetic erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome.

Background: Clinical associations between erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been noticed, but the common pathogenic mechanisms between them remain elusive. The aim of the study was to mine shared genetic alterations between ED and chronic prostatitis/chronic pelvic pain syndrome. Method: Transcriptome data of ED and chronic prostatitis/chronic pelvic pain syndrome-related genes (CPRGs) were retrieved from relevant databases and differentially expressed analysis was used to obtain significant CPRGs. Then function enrichment and interaction analyses were performed to show shared transcriptional signature, including gene ontology and pathway enrichment, the construction of protein-protein interaction (PPI) network, cluster analysis, and co-expression analysis. Hub CPRGs and key cross-link were selected by validating these genes in clinical samples, chronic prostatitis/chronic pelvic pain syndrome and ED-related datasets. Then the miRNA-OSRGs co-regulatory network was predicted and validated. Subpopulation distribution and disease association of hub CPRGs were further identified. Result: Differentially expressed analysis revealed 363 significant CPRGs between ED and chronic prostatitis/chronic pelvic pain syndrome, functioning in inflammatory reaction, oxidative stress, apoptosis, smooth muscle cell proliferation, and extracellular matrix organization. A PPI network containing 245 nodes and 504 interactions was constructed. Module analysis depicted that multicellular organismal process and immune metabolic process were enriched. 17 genes were screened in PPI via topological algorithms, and reactive oxygen species as well as interleukin-1 metabolism were regarded as the bridging interactive mechanism. After screening and validation, a hub-CPRG signature consisting of COL1A1, MAPK6, LPL, NFE2L2 and NQO1 were identified and associated miRNA were verified. These miRNAs played an important role in immune and inflammatory response likewise. Finally, NQO1 was identified as a key genetic link between ED and chronic prostatitis/chronic pelvic pain syndrome. It was predominately enriched in corpus cavernosum endothelial cell, and correlated with other male urogenital and immune system diseases tightly. Conclusion: We identified the genetic profiles as well as corresponding regulatory network underlying interaction between ED and chronic prostatitis/chronic pelvic pain syndrome via multi-omics analysis. These findings expanded a new understanding for the molecular mechanism of ED with chronic prostatitis/chronic pelvic pain syndrome.

Identifying potential cross-talk signatures for the occurrence of atherosclerosis in diabetic erectile dysfunction.

BACKGROUND: Erectile dysfunction and atherosclerosis are common cardiovascular complications in diseases. Clinical associations between erectile dysfunction and atherosclerosis have been noticed, but the specific mechanisms are not illustrated adequately. OBJECTIVES: The aim of the study was to further mine associated pathological mechanisms and genetic alterations of atherosclerosis in diabetes mellitus-related erectile dysfunction. MATERIALS AND METHODS: Significant atherosclerosis-related genes were identified from transcriptome data of diabetes mellitus-related erectile dysfunction and atherosclerosis-related gene sets from DisGeNET and GeneCard databases. Functional enrichment and immune infiltration analyses were performed to clarify the biological roles and pathways as well as immune responses of significant atherosclerosis-related gene sets. A protein-protein interaction network was constructed, and gene clusters were performed. Then, data of diabetic plaques and high-glucose cavernosum endothelial cells were analyzed for validation. And hub atherosclerosis-related gene sets were identified. Finally, expressed pattern of hub atherosclerosis-related gene sets were explored by single-cell profiling and immune analysis. RESULTS: In total, 202 significant atherosclerosis-related gene sets including 100 upregulated and 102 downregulated genes were identified. These genes were related to endothelial cell migration, inflammatory response, regulation of oxidative stress, and immune response. In immune infiltration, immature dendritic cells and monocytes showed differential expression between the diabetes mellitus-related erectile dysfunction and control groups, A protein-protein interaction network containing 135 nodes was constructed. A hub atherosclerosis-related gene set signature consisting of HBEGF, LOX, NQO1, and VLDLR was obtained by multi-omics validation. In addition, Functional enrichment analysis revealed that hub atherosclerosis-related gene sets were involved in oxidoreductase activity and extracellular matrix organization. DISCUSSION AND CONCLUSION: We explored atherosclerosis-related genetic changes and signaling pathways in diabetes mellitus-related erectile dysfunction. HBEGF, LOX, NQO1, and VLDLR were identified as hub atherosclerosis-related gene sets. These may serve as potential biomarkers for the clinical management of atherosclerosis and preventing further cardiovascular risks in diabetes mellitus-related erectile dysfunction.

Insight into the Formation of Cocrystal and Salt of Tenoxicam from the Isomer and Conformation.

Tenoxicam (TNX) is a new non-steroidal anti-inflammatory drug that shows a superior anti-inflammatory effect and has the advantages of a long half-life period, a fast onset of action, a small dose, complete metabolism, and good tolerance. Some compounds often have tautomerism, and different tautomers exist in different crystalline forms. TNX is such a compound and has three tautomers. TNX always exists as the zwitterionic form in cocrystals. When the salt is formed, TNX exists in the enol form, which exhibits two conformations depending on whether a proton is gained or lost. Currently, the crystal structure of the keto form is not in the Cambridge Structural Database (CSD). Based on the analysis of existing crystal structures, we derived a simple rule for what form of TNX exists according to the pKa value of the cocrystal coformer (CCF) and carried out validation tests using three CCFs with different pKa values, including p-aminosalicylic acid (PAS), 3,5-dinitrobenzoic acid (DNB), and 2,6-dihydroxybenzoic acid (DHB). The molecular surface electrostatic potential (MEPS) was combined with the pKa rule to predict the interaction sites. Finally, two new cocrystals (TNX-PAS and TNX-DNB) and one salt (TNX-DHB) of TNX were obtained as expected. The differences between the cocrystals and salt were distinguished by X-ray diffraction, vibration spectra, thermal analysis, and dissolution measurements. To further understand the intermolecular interactions in these cocrystals and salt, the lattice energy and energy decomposition analysis (EDA) were used to explain them from the perspective of energy. The results suggest that the melting point of the CCF determines that of the cocrystal or salt, the solubility of the CCF itself plays an important role, and the improvement of the solubility after salt formation is not necessarily better than that of API or its cocrystals.

Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways.

BACKGROUND: The population with diabetes mellitus-induced erectile dysfunction is increasing rapidly, but current drugs are not effective in treating erectile dysfunction. Studies of the traditional Chinese medicine extract berberine on diabetes and its complications provide us with new ideas. OBJECTIVES: To evaluate the therapeutic effect and potential mechanism of berberine on the erectile function of diabetic rats. MATERIALS AND METHODS: Fifty male Sprague-Dawley rats were randomly grouped, and 42 rats were injected intraperitoneally with streptozotocin to establish a diabetes model. Erectile dysfunction rats were screened out through the apomorphine test and randomly divided into the diabetes mellitus and berberine groups, and these animals were administered berberine (200 mg/kg/day) and normal saline by gavage for 4 weeks. Primary corpus cavernous smooth muscle cells from healthy rats were cultured and treated with berberine. RESULTS: Fasting blood glucose in the diabetes mellitus group was significantly increased, while berberine showed no significant effect on glucose. Erectile function was obviously impaired in the diabetes mellitus group, and berberine administration partially rescued this impairment. The expression of sphingosine kinase 1, S1PR2, and sphingosine-1-phosphate in the diabetes mellitus group was increased. Berberine partially inhibited the expression of sphingosine kinase 1 and S1PR2, but the decrease in sphingosine-1-phosphate was not significant. Moreover, mitogen-activated protein kinase pathway factor expression was upregulated and eNOS activity was decreased in the diabetes mellitus group. Berberine treatment could partially reverse these alterations. Severe fibrosis and apoptosis were detected in diabetic rats, accompanied by higher expression of TGFß1, collagen I/IV, Bax/Bcl-2, and caspase 3 than in the other groups. However, supplementation with berberine inhibited the expression of these proteins and attenuated fibrosis and apoptosis. CONCLUSIONS: Berberine ameliorated erectile dysfunction in rats with diabetes mellitus, possibly by improving endothelial function and inhibiting apoptosis and fibrosis by suppressing the sphingosine kinase 1/sphingosine-1-phosphate/S1PR2 and mitogen-activated protein kinase pathways.

Phosphorylation of the androgen receptor at Ser81 is co-sustained by CDK1 and CDK9 and leads to AR-mediated transactivation in prostate cancer.

Androgen receptor (AR) is the principal molecule in prostate cancer (PCa) etiology and therapy. AR re-activation still remains a major challenge during treatment of castration-resistant prostate cancer (CRPC) tumors that relapse after castration therapies. Recent reports have indicated the enrichment of Ser81-phosphorylated AR (pS81) in the nucleus of CRPC cells, and CDK1 and CDK9 as the kinases phosphorylating AR at S81. In the current study we showed that pS81 is preferentially localized in the nucleus in both rapid biopsy metastatic CRPC samples and PCa xenografts, and nuclear pS81 localization is correlated with AR transactivation in tumor xenografts. Chromatin immunoprecipitation (ChIP) analysis demonstrated an alignment of S81 phosphorylation and AR-mediated transactivation with the chromatin locus openness. Moreover, pS81-specific ChIP-Seq showed a disproportional occupancy of pS81 on AR-activated promoters, while 3C-ChIP assays further indicated an enrichment of pS81 at the PSA enhancer-promoter loop, a known AR activating hub. In the latter, CDK9 was shown to modulate the transactivation of the AR and RNA Pol II. Indeed, ChIP and re-ChIP assays also confirmed that AR-dependent activation of the PSA enhancer and promoter mediated by pS81 was coupled with activation of Pol II and the pTEFb complex. Mechanistically, we determined that CDK1 and CDK9 sustained the pS81 AR modification in the soluble and chromatin-bound fractions of PCa cells, respectively. Finally, we demonstrated that CDK1 activity was maintained throughout the cell cycle, and that CDK1 inhibitors restored androgen sensitivity in CRPC tumor cells. Based on these findings, CDK1 and CDK9 could be targeted as pS81 kinases in patients with CRPC, either alone or in conjunction with direct AR antagonists.

Identification of RNA-binding protein SNRPA1 for prognosis in prostate cancer.

Prostate cancer is one of the deadliest cancers in men. RNA-binding proteins play a critical role in human cancers; however, whether they have a significant effect on the prognosis of prostate cancer has yet to be elucidated. In the present study, we performed a comprehensive analysis of RNA sequencing and clinical data from the Cancer Genome Atlas dataset and obtained differentially expressed RNA-binding proteins between prostate cancer and benign tissues. We constructed a protein-protein interaction network and Cox regression analyses were conducted to identify prognostic hub RNA-binding proteins. SNRPA1 was associated with the highest risk of poor prognosis and was therefore selected for further analysis. SNRPA1 expression was positively correlated with Gleason score and pathological TNM stage in prostate cancer patients. Furthermore, the expression profile of SNRPA1 was validated using the Oncomine, Human Protein Atlas, and Cancer Cell Line Encyclopedia databases. Meanwhile, the prognostic profile of SNRPA1 was successfully verified in GSE70769. Additionally, the results of molecular experiments revealed the proliferative role of SNRPA1 in prostate cancer cells. In summary, our findings evidenced a relationship between RNA-binding proteins and prostate cancer and indicated the prognostic significance of SNRPA1 in prostate cancer.

The role of adrenal venous sampling and computed tomography in the management of primary aldosteronism.

BACKGROUND: The role of adrenal venous sampling (AVS) has been challenged by some recent evidence. This study aimed to compare the role of AVS and computed tomography (CT) in the management of primary aldosteronism. METHODS: Patients who underwent unilateral adrenalectomy for primary aldosteronism at a single center between January 2015 and December 2018 were included, and postoperative outcomes of the patients who underwent surgery based on CT (n = 195) or AVS (n = 40) were compared. The data of all the patients who underwent AVS successfully (n = 75) during this period were also collected and analyzed. RESULTS: There were no significant differences between the CT-guided and AVS-guided adrenalectomies in most of the postoperative outcomes, and the proportion of patients achieving cure of hypokalemia (CT vs. AVS, 98.3 vs. 96.4%) and alleviation of hypertension (89.2 vs. 92.9%) were similar between the two groups. However, since the baseline characteristics of the two groups were not identical, the AVS-guided group showed greater improvement in postoperative hypokalemia and greater reduction in the number of antihypertensive medications than the CT-guided group. In addition, for the 75 patients who underwent AVS successfully, the concordance rate between CT abnormalities and AVS lateralization was 60.0% in total, and 22.7% patients changed treatment plans according to the AVS results. CONCLUSION: Although the clinical outcomes were not significantly different between the CT-guided and AVS-guided group, the AVS-guided group seemed to benefit more from the surgery, and a considerable number of patients with primary aldosteronism would have received inappropriate treatment if they did not undergo AVS.

Systematic Review and Meta-Analysis of the Association between Vitamin D Status and Lower Urinary Tract Symptoms.

PURPOSE: Cumulative studies have shown that vitamin D may be associated with lower urinary tract symptoms but the findings have been inconsistent. The aim of this study was to systematically evaluate the relationship between vitamin D and lower urinary tract symptoms. MATERIALS AND METHODS: The PubMed®, Scopus® and Embase™ databases were searched for articles up to June 2020. A meta-analysis was conducted to evaluate the effects of vitamin D insufficiency or intake on lower urinary tract symptoms. A qualitative description summarized vitamin D intervention for treating lower urinary tract symptoms. Sensitivity analysis was conducted to examine heterogeneity and the robustness of the results. RESULTS: A total of 23 studies including 86,332 participants were analyzed in our study. Vitamin D insufficiency was associated with a 1.37-fold to 2.06-fold increased likelihood of having lower urinary tract symptoms, and patients with lower urinary tract symptoms had significantly lower levels of vitamin D. Furthermore, vitamin D intake was significantly associated with an 11% reduction in the risk of lower urinary tract symptoms. In the subgroup analysis, the effects of vitamin D insufficiency on the risk of lower urinary tract symptoms were notably observed in nonAsians, females and patients with urinary incontinence. CONCLUSIONS: Consistent results indicated that vitamin D insufficiency was a crucial risk factor for lower urinary tract symptoms and that vitamin D supplementation showed promising effects on these symptoms. It would be of great guiding significance to consider vitamin D status when treating lower urinary tract symptoms.

Prognostic Value of Androgen Receptor Splice Variant 7 in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: The prognostic value of androgen receptor splice variant 7 (AR-V7) for the treatment response of metastatic castration-resistant prostate cancer (mCRPC) remains unclear. In this study, we aimed to synthesize relevant studies that assessed the prognostic value of AR-V7 status for the treatment response of mCRPC patients treated with androgen receptor signalling inhibitors (ARSis) and chemotherapy. METHODS: We searched the PubMed, Embase, and MEDLINE databases by using the keywords AR-V7 and prostate cancer to identify relevant studies published before 25 September 2019. The main outcomes were prostate-specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS). Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: A total of 1,545 patients from 21 studies were included. For the mCRPC patients treated with ARSis, AR-V7-positive patients had a lower PSA response rate (OR 6.01, 95% CI 2.88-12.51; P < 0.001), shorter PFS (HR 2.56, 95% CI 1.80-3.64; P < 0.001) and shorter OS (HR 4.28, 95% CI 2.92-6.27; P < 0.001) than AR-V7-negative patients. Although AR-V7-positive patients treated with chemotherapy also had a lower PSA response rate (OR 2.23, 95% CI 1.38-3.62; P = 0.001) and shorter OS than AR-V7-negative patients (HR 1.60, 95% CI 1.02-2.53; P = 0.043), there was no significant difference in PFS (HR 1.05, 95% CI 0.74-1.49; P = 0.796) between these groups. Furthermore, AR-V7-positive patients receiving ARSis had a shorter median OS than those receiving chemotherapy (HR 3.50, 95% CI 1.98-6.20; P < 0.001); There was no significant difference among AR-V7-negative patients (HR 1.30, 95% CI 0.64-2.62; P = 0.47). CONCLUSIONS: AR-V7 is a potential biomarker of treatment resistance in mCRPC patients. AR-V7-positive mCRPC patients had poorer treatment outcomes than AR-V7-nagetive patients when treated with ARSis. AR-V7-positive patients have better outcomes when treated with taxane than ARSis. Furthermore, the ability of AR-V7 status to predict treatment outcomes varies from different detection methods. The detection of AR-V7 before treatment is important for the selection of treatment modalities for mCRPC patients.

Characterization of a New Solvatomorph of Drospirenone by Thermogravimetry-Mass Spectrometry Combined with Other Solid-State Analysis Methods.

Drospirenone (DE) is a fourth-generation progesterone that has been widely used in oral contraceptives for women because of its safety and few side effects in terms of pharmacological activity. A new solvatomorph (crystal form C) of DE with dimethyl sulfoxide was identified and characterized for the first time through a thermogravimetry-mass spectrometry (TG-MS) coupling system. The thermodynamic property of the new solvatomorph of DE was different from those of most pharmaceutical solvatomorphs, and it was revealed via the skimmer-type interfaced TG-MS system and differential scanning calorimetry. This new solvatomorph and a polymorph of DE obtained without solvent (crystal form A) were well characterized by X-ray crystallography and vibrational spectroscopic analysis. Computational studies based on their single-crystal structures, such as Hirshfeld surface analyses, were used to determine the intermolecular interactions in the crystal network. The single-crystal structure of crystal form C of DE was determined and reported for the first time.

Liraglutide Ameliorates Erectile Dysfunction via Regulating Oxidative Stress, the RhoA/ROCK Pathway and Autophagy in Diabetes Mellitus.

BACKGROUND: Erectile dysfunction (ED) occurs more frequently and causes a worse response to the first-line therapies in diabetics compared with nondiabetic men. Corpus cavernosum vascular dysfunction plays a pivotal role in the occurrence of diabetes mellitus ED (DMED). The aim of this study was to investigate the protective effects of glucagon-like peptide-1 (GLP-1) analog liraglutide on ED and explore the underlying mechanisms in vivo and in vitro. METHODS: Type 1 diabetes was induced in rats by streptozotocin, and the apomorphine test was for screening the DMED model in diabetic rats. Then they were randomly treated with subcutaneous injections of liraglutide (0.3 mg/kg/12 h) for 4 weeks. Erectile function was assessed by cavernous nerve electrostimulation. The corpus cavernosum was used for further study. In vitro, effects of liraglutide were evaluated by primary corpus cavernosum smooth muscle cells (CCSMCs) exposed to low or high glucose (HG)-containing medium with or without liraglutide and GLP-1 receptor (GLP-1R) inhibitor. Western blotting, fluorescent probe, immunohistochemistry, and relevant assay kits were performed to measure the levels of target proteins. RESULTS: Administration of liraglutide did not significantly affect plasma glucose and body weights in diabetic rats, but improved erectile function, reduced levels of NADPH oxidases and ROS production, downregulated expression of Ras homolog gene family (RhoA) and Rho-associated protein kinase (ROCK) 2 in the DMED group dramatically. The liraglutide treatment promoted autophagy further and restored expression of GLP-1R in the DMED group. Besides, cultured CCSMCs with liraglutide exhibited a lower level of oxidative stress accompanied by inhibition of the RhoA/ROCK pathway and a higher level of autophagy compared with HG treatment. These beneficial effects of liraglutide effectively reversed by GLP-1R inhibitor. CONCLUSION: Liraglutide exerts protective effects on ED associated with the regulation of smooth muscle dysfunction, oxidative stress and autophagy, independently of a glucose- lowering effect. It provides new insight into the extrapancreatic actions of liraglutide and preclinical evidence for a potential treatment for DMED.

A four-gene signature associated with clinical features can better predict prognosis in prostate cancer.

Prostate cancer (PCa) is one of the most deadly urinary tumors in men globally, and the 5-year over survival is poor due to metastasis of tumor. It is significant to explore potential biomarkers for early diagnosis and personalized therapy of PCa. In the present study, we performed an integrated analysis based on multiple microarrays in the Gene Expression Omnibus (GEO) dataset and obtained differentially expressed genes (DEGs) between 510 PCa and 259 benign issues. The weighted correlation network analysis indicated that prognostic profile was the most relevant to DEGs. Then, univariate and multivariate COX regression analyses were conducted and four prognostic genes were obtained to establish a four-gene prognostic model. And the predictive effect and expression profiles of the four genes were well validated in another GEO dataset, The Cancer Genome Atlas and the Human Protein Atlas datasets. Furthermore, combination of four-gene model and clinical features was analyzed systematically to guide the prognosis of patients with PCa to a largest extent. In summary, our findings indicate that four genes had important prognostic significance in PCa and combination of four-gene model and clinical features could achieve a better prediction to guide the prognosis of patients with PCa.