The bibliometric analysis of extended reality in surgical training: Global and Chinese perspective.

Objectives: The prospect of extended reality (XR) being integrated with surgical training curriculum has attracted scholars. However, there is a lack of bibliometric analysis to help them better understand this field. Our aim is to analyze relevant literature focusing on development trajectory and research directions since the 21st century to provide valuable insights. Methods: Papers were retrieved from the Web of Science Core Collection. Microsoft Excel, VOSviewer, and CiteSpace were used for bibliometric analysis. Results: Of the 3337 papers published worldwide, China contributed 204, ranking fifth. The world's enthusiasm for this field has been growing since 2000, whereas China has been gradually entering since 2001. Although China had a late start, its growth has accelerated since around 2016 due to the reform of the medical postgraduate education system and the rapid development of Chinese information technology, despite no research explosive period has been yet noted. International institutions, notably the University of Toronto, worked closely with others, while Chinese institutions lacked of international and domestic cooperation. Sixteen stable cooperation clusters of international scholars were formed, while the collaboration between Chinese scholars was not yet stable. XR has been primarily applied in orthopedic surgery, cataract surgery, laparoscopic training and intraoperative use in neurosurgery worldwide. Conclusions: There is strong enthusiasm and cooperation in the international research on the XR-based surgical training. Chinese scholars are making steady progress and have great potential in this area. There has not been noted an explosive research phase yet in the Chinese pace. The research on several surgical specialties has been summarized at the very first time. AR will gradually to be more involved and take important role of the research.

Inflammation-related indicators have a potential to increase overall quality of the prostate cancer management: a narrative review.

Background and Objective: Increasing evidence suggests that inflammation plays an essential role in cancer development and progression. The levels of inflammation-related indicators are correlated with prognosis across a wide variety of tumor types, including prostate cancer (PCa), but its diagnostic and prognostic value in PCa remains controversial. In the present review, the diagnostic and prognostic value of inflammation-related indicators in PCa patients is investigated. Methods: A literature review was performed using the PubMed database, screening articles from English and Chinese journals published mainly from 2015 to 2022. Key Content and Findings: Inflammation-related indicators based on haematological tests have some diagnostic and prognostic value not only when used alone but also in combination with common clinical indicators such as prostate-specific antigen (PSA), and can significantly improve the accuracy of diagnostic results. Elevated neutrophil-to-lymphocyte-count ratio (NLR) is strongly associated with the detection of PCa in men with PSA levels of 4-10 ng/mL. Preoperative NLR levels in localized PCa patients affect their overall survival (OS), cancer-specific survival (CSS), and biochemical recurrence-free survival (BCRFS) after radical prostatectomy (RP). In patients with castration-resistant prostate cancer (CRPC), a high NLR is associated with poorer OS, progression-free survival (PFS), CSS, and radiographic PFS. Platelet-to-lymphocyte-count ratio (PLR) appears to have the greatest accuracy in predicting an initial diagnosis of clinically significant PCa. The PLR also has the potential to predict the Gleason score. Patients with higher PLR levels have a higher risk of death compared to those with a lower PLR. Elevated procalcitonin (PCT) is correlated with the development of PCa and may be useful in improving the diagnostic accuracy of PCa. Elevated C-reactive protein (CRP) levels are an independent predictor of poorer OS in metastatic PCa. Conclusions: Numerous studies have been conducted on the value of inflammation-related indicators in guiding the diagnosis and treatment of PCa. The value of inflammation-related indicators in predicting the diagnosis and prognosis of PCa patients is now becoming clear.

Extracellular vesicles from bone marrow mesenchymal stem cells alleviate acute rejection injury after liver transplantation by carrying miR-22-3p and inducing M2 polarization of Kupffer cells.

BACKGROUND: Acute rejection (AR) is a major problem following liver transplantation. Extracellular vesicles (EVs) are involved in various pathological processes including liver disease. The present study investigated the effect of EVs derived from bone marrow mesenchymal stem cells (BMSCs) on AR injury after orthotopic liver transplantation (OLT) in mice. METHODS: BMSCs and EVs were isolated and identified. The OLT mouse model was established using Kamada's two-cuff method and injection with EVs, followed by liver function detection and measurement of inflammatory cytokines (interleukin-10, interferon-γ, and tumor necrosis factor-α), M1 and M2 markers (tumor necrosis factor-α, inducible nitric oxide synthase, resistin like alpha, and Arg1) were detected. Kupffer cells (KCs) were cultured and treated with lipopolysaccharides. miR-22-3p expression was detected. The effect of EVs-shuttled miR-22-3p on Kupffer cell polarization was studied. Binding relation of miR-22-3p and interferon regulatory factor 8 (IRF8) was verified. The effect of IRF8 on KC polarization was verified. RESULTS: BMSC-EV treatment enhanced liver function of OLT mice and alleviated AR and apoptosis, which were annulled after removing KCs. EVs induced KC M2 polarization. Mechanically, EVs carried miR-22-3p into KCs, upregulated miR-22-3p in KCs, and inhibited IRF8 expression. Upregulation of IRF8 in KCs inhibited EV-induced KC M2 polarization. CONCLUSIONS: BMSCs-EVs carry miR-22-3p into KCs and upregulate miR-22-3p, inhibit IRF8 expression, induce KC M2 polarization, and attenuate AR injury after liver transplantation.

Cancer-derived exosomal miR-375 targets DIP2C and promotes osteoblastic metastasis and prostate cancer progression by regulating the Wnt signaling pathway.

Bone metastasis is the most common complication responsible for most deaths in the advanced stages of prostate cancer (PCa). However, the exact mechanism of bone metastasis in PCa remains unelucidated. Herein, we explored the function and potential underlying mechanism of exosomal miR-375 in bone metastasis and tumor progression in PCa. This study revealed that miR-375 expression was markedly upregulated in advanced PCa with bone metastasis and metastatic PCa cell lines. Moreover, miR-375 showed high expression in PCa-derived exosomes and could be delivered to human mesenchymal stem cells (hMSCs) via exosomes. Mechanistically, miR-375 directly targeted DIP2C and upregulated the Wnt signaling pathway, thereby promoting osteoblastic differentiation in hMSCs. Furthermore, miR-375 promoted the proliferation, invasion, and migration of PCa cells in vitro and enhanced tumor progression and osteoblastic metastasis in vivo. Notably, the expression of miR-375, TCF-1, LEF-1, and ß-catenin in was higher in PCa tissues with bone metastasis than in PCa tissues without bone metastasis and showed a continuous increase, whereas DIP2C, cyclin D1, and Axin2 showed an opposite expression pattern. In conclusion, our study suggests that cancer-derived exosomal miR-375 targets DIP2C, activates the Wnt signaling pathway, and promotes osteoblastic metastasis and PCa progression.

Tim3scFv-Transforming Lactobacillus Inhibits Transplanted Tumor of Renal-Cell Carcinoma.

INTRODUCTION: T-cell immunoglobulin-3 (Tim-3) antibody drugs can treat malignant renal tumors but are expensive. To overcome this limitation, Lactococcus lactis host bacteria were used to express Tim-3 single-chain antibodies. METHODS: The pLAN-CTB-Tim3scFv plasmid was constructed using molecular cloning technology and transformed into Lactococcus lactis. Expression and immune activity of proteins in the transformed bacteria were analyzed using Western blotting and enzyme-linked immunosorbent assay in vitro. A mouse subcutaneously transplanted tumor model of renal adenocarcinoma was constructed. The promoting effect of transformed bacteria on mouse spleen lymphocyte activation and their inhibitory effect on transplanted tumors were analyzed. RESULTS: Transformed L. lactis NZ-CTB-Tim3scFv and NZ-Tim3scFv were successfully constructed. CTB-Tim3scFv secreted by NZ-CTB-Tim3scFv showed immunological activity. Compared with the NZ-Tim3scFv and NZ-Vector groups, the subgroups of splenic lymphocytes in the NZ-CTB-Tim3scFv group had a higher proportion of CD3+CD4+, CD3+CD8a+, and CD3+CD69+ cells. Ki67 and CD31 expression in the NZ-CTB-Tim3scFv group was significantly reduced. Tumor volume in the NZ-CTB-Tim3scFv group increased the least. DISCUSSION/CONCLUSION: Secretion of CTB-Tim3scFv promoted the proliferation and activation of spleen lymphocytes and inhibited growth, cell proliferation, and angiogenesis of tumors. The proposed method is low cost and convenient with potential to become a new immunotherapy approach for renal-cell carcinoma.

Construction and Characterization of n6-Methyladenosine-Related lncRNA Prognostic Signature and Immune Cell Infiltration in Kidney Renal Clear Cell Carcinoma.

Background: Kidney renal clear cell carcinoma (KIRC) lacks effective prognostic biomarkers and the role and mechanism of N6-methyladenosine (m6A) modification of long noncoding RNAs (lncRNAs) in KIRC remain unclear. Methods: We extracted standard mRNA-sequencing and clinical data from the TCGA database. The prognostic risk model was obtained by Lasso regression and Cox regression. We randomly divided the samples into training and test sets, each taking half of the cases. Based on Lasso regression and Cox regression for training set, the prognostic risk signature was constructed; risk scores were calculated with the R package "glmnet." Based on the median value of the prognostic risk score, risk scores were calculated for each patient and we divided all KIRC samples into high-risk and low-risk groups. Then, high- and low-risk subtypes were established and their prognosis, clinical features, and immune infiltration microenvironment were evaluated in test set and the entire sampled data set. The reliability of the prognostic model was confirmed by receiver operating characteristic curve analysis. Results: We found 28 prognostic m6A-related lncRNAs and established a m6A-related lncRNAs prognostic signature. Risk score=AC015813.1∗(0.0086)+EMX2OS∗(-0.0101)+LINC00173∗(0.0309)+PWAR5∗(-0.0146)+SNHG1∗(0.0043). The signature showed a better predictive ability than other clinical indicators, including tumor node metastasis classification (TNM), histological, and pathological stages. In the high-risk group, M0 macrophages, CD8+ T cells, and regulatory T cells had significantly higher scores. Contrarily, in the low-risk group, activated dendritic cells, M1 macrophages, mast resting cells, and monocytes had significantly higher scores. In the high-risk group, LSECtin was overexpressed. In the low-risk group, PD-L1 was overexpressed. Moreover, high-risk patients may benefit more from AZ628. Conclusions: In conclusion, prognosis prediction of patients with KIRC and new insights for immunotherapy are provided by the m6A-related lncRNA prognostic signature.

Urinary Exosomal miRNAs as biomarkers of bladder Cancer and experimental verification of mechanism of miR-93-5p in bladder Cancer.

BACKGROUND: Bladder cancer (BC) is one of the most common malignancies globally. Early diagnosis of it can significantly improve patients' survival and quality of life. Urinary exosomes (UEs)-derived miRNAs might be a promising biomarker for BC detection. METHOD: A total of 12 patients with BC and 4 non-cancerous participants (as healthy control) were recruited from a single center between March 2018 and December 2019 as the discovery set. Midstream urine samples from each participants were collected and high-throughput sequencing and differentially expression analysis were conducted. Combined with miRNA expression profile of BC tissue from The Cancer Genome Atlas (TCGA), miRNAs biomarkers for BC were determined. Candidate miRNAs as biomarkers were selected followed by verification with a quantitative reverse-transcription polymerase chain reaction assay in an independent validation cohort consisting of 53 BC patients and 51 healthy controls. The receiver-operating characteristic (ROC) curve was established to evaluate the diagnostic performance of UE-derived miRNAs. The possible mechanism of miRNAs were revealed by bioinformatic analysis and explored in vitro experiments. RESULTS: We identified that miR-93-5p, miR-516a-5p were simultaneously significantly increased both in UEs from BC compared with healthy control and BC tissue compared with normal tissue, which were verified by RT-qPCR in the validation cohort. Subsequently, the performance to discover BC of the miR-93-5p, miR-516a-5p was further verified with an area under ROC curve (AUC) of 0.838 and 0.790, respectively, which was significantly higher than that of urine cytology (AUC = 0.630). Moreover, miR-93-5p was significantly increased in muscle-invasive BC compared with non-muscle-invasive BC with an AUC of 0.769. Bioinformatic analysis revealed that B-cell translocation gene 2(BTG2) gene may be the hub target gene of miR-93-5p. In vitro experiments verified that miR-93-5p suppressed BTG2 expression and promoted BC cells proliferation, invasion and migration. CONCLUSION: Urine derived exosomes have a distinct miRNA profile in BC patients, and urinary exosomal miRNAs could be used as a promising non-invasive tool to detect BC. In vitro experiments suggested that miR-93-5p overexpression may contribute to BC progression via suppressing BTG2 expression.

Erectile Dysfunction in Type-2 Diabetes Mellitus Patients: Predictors of Early Detection and Treatment.

PURPOSE: To identify risk factors and potential predictors of erectile dysfunction (ED) in type-2 diabetes mellitus (T2DM) patients for early detection and treatment. METHODS: A retrospective cohort was used to assess the clinical data of 105 diabetic patients with ED from May 2019 to April 2020 age-matched to 105 diabetic patients without ED. Potential risk factors that could contribute to ED were compared between the groups. Erectile function was evaluated using the International Index of Erectile Function-5 questionnaire. RESULTS: There were higher rates of diabetic peripheral neuropathy (p = 0.036) and retinopathy (p < 0.001), longer duration of diabetes (p < 0.001), lower estimated glomerular filtration rate (p = 0.010) values, and higher uric acid (p < 0.001) and C-reactive protein (p = 0.001) levels in the ED group compared to the non-ED group. Multivariate logistic analysis identified uric acid, diabetic retinopathy, and T2DM course as independent predictors of diabetic ED. Diabetics with retinopathy and T2DM for ≥49 months were 3.028 and 3.860 times more likely to have ED, respectively. Uric acid values ≥392.5 µmol/L were associated with 18.638 times greater risk of having ED, though the values were within normal range. CONCLUSION: In T2DM patients, higher uric acid (≥392.5 µmol/L), longer diabetes duration (≥49 months), and the presence of diabetic retinopathy were important and reliable predictors for diabetic ED. For patients who have high risk factors for developing ED, diligent screening and early treatment are necessary.

Diagnostic Value of Portal Vein Velocity for Portal Hypertension in Patients with Hepatitis B Virus-related Cirrhosis.

BACKGROUND: Portal vein velocity (PVV) has shown a reasonable correlation with the presence of portal hypertension in patients with cirrhosis. This study aims to evaluate the value of PVV for diagnosing clinically significant portal hypertension (CSPH) and predicting the risk of variceal hemorrhage (VH) in patients with hepatitis B virus (HBV)-related cirrhosis. MATERIALS AND METHODS: A cohort of 166 consecutive adult patients with HBV-related cirrhosis was recruited in this retrospective study from two high-volume liver centers in China between April 2015 and April 2017. The performance of PVV and other non-invasive parameters for diagnosing CSPH and predicting the risk of VH was studied. RESULTS: PVV demonstrated the best performance for diagnosing CSPH (defined as an HVPG ≥10 mmHg) in patients with HBV-related cirrhosis among the included non-invasive predictors with the area under the receiver operating characteristic curve (AUC), specificity, and sensitivity of 0.745, 50%, and 93.5%, respectively. Other non-invasive markers, including APRI, AAR, LS, FIB-4, and diameter of the portal vein, did not show sufficient performance with the AUCs of 0.565, 0.560, 0.544, 0.529, and 0.474, respectively. With regard to predicting the risk of VH (defined as an HVPG ≥12 mmHg), PPV also exhibited a moderate performance with an AUC of 0.762, which was superior to that of the aforementioned markers. By using two cutoff values of PVV to rule-out (11.65 cm/s) and rule-in (20.20 cm/s) CSPH, 30 (33.7%) patients showed definite results categories, with 23 (76.7%) patients were well classified and 7 (23.3%) were misclassified. Fifty-nine (66.3%) patients were with indeterminate results. By using PVV values of 13.10 cm/s and 21.40 cm/s to rule-out and rule-in HVPG ≥ 12mmHg, 34 (38.2%) patients has definite results, among whom 26 (76.5%) were well classified and 8 (23.5%) were misclassified. And 55 (61.8%) patients required further evaluation. CONCLUSION: PPV is insufficient to serve as a non-invasive parameter for identifying CSPH and predicting the risk of VH in patients with HBV-related cirrhosis.

A bibliometric analysis of international publication trends in premature ejaculation research (2008-2018).

The incidence of premature ejaculation (PE) has been on the rise over the years. Thus, significant research efforts have been directed toward understanding the pathogenesis and hence treatment of PE. Here, we performed a comprehensive analysis of the worldwide trends in research outputs in the field of PE. This study investigated the universal findings of previous PE studies and the trending issues surrounding the condition. We employed the Web of Science Core Collection for data collection. The Excel (2016) and CiteSpace IV were used for information analysis. The information was categorized using journal names, institutions, research frontiers, citation reports, regions/countries, and authors. A sum of 886 publications concerning PE between 2008 and 2018 were identified as of July 6, 2019. The highest number of publications was identified in the Journal of Sexual Medicine published. The United States of America (USA) had the highest number of publications and H-index value. The highest co-citations were from Waldinger MD. The most common keyword was 'drug treatment'. A steady pattern was observed for PE publications done between the period of 2008-2018. Thus, the USA is at the forefront of research on PE research. The interesting advanced research frontiers were drug treatment, circumcision, and sertraline.

Effects of "metabolic memory" on erectile function in diabetic men: A retrospective case-control study.

OBJECTIVE: This study was performed to explore the effects of metabolic memory on diabetic erectile dysfunction (ED), especially the severity and response to treatment. METHODS: Through medical records and follow-up by telephone, 67 patients meeting the criteria with a clinical diagnosis of ED and a diabetic history of more than 5 years were enrolled for erectile function analysis. They were divided into a glycemic control group, a glycemic non-control group and a metabolic memory group according to glycemic levels and treatments for diabetes in the past 5 years, and they were treated with phosphodiesterase type 5 (PDE5) inhibitors for 4 weeks. Erectile function and efficacy were assessed by the International Index for Erectile Function (IIEF), the Erection Hardness Score (EHS), and the Sexual Encounter Profile (SEP). RESULTS: The patients in the glycemic control group performed better in erectile function than those in the other groups. The patients in the glycemic control group received a significantly greater score on both the EHS and the five domains of the IIEF than did the patients in the glycemic non-control group and the metabolic memory group (all P < .001). There were also statistically significant differences favoring the glycemic control group (P < .05) in SEP2 and SEP3 success rates. However, there were no significant differences between the metabolic memory group and the glycemic non-control group in these erectile function assessments (P > .05). Significant negative correlations were seen between HbA1c levels at the time of consultation and the scores on the IIEF-EF and the EHS (Pearson r-values of -0.338 with P = .005 and -0.273 with P = .025, respectively). HbA1c levels at the first diagnosis of diabetes mellitus (DM) were also significantly negatively correlated with scores on the IIEF-EF and the EHS with greater Pearson correlation coefficients (Pearson r-values of -0.478 with P < .001 and -0.392 with P = .001, respectively). Significant improvements on each of the erectile function assessments were observed among diabetic patients with ED, but no significant difference in efficacy was observed between each group. CONCLUSIONS: The phenomenon of metabolic memory did have a significant influence on ED in men with diabetes, associated with the severity of ED but not the response to medical treatment. Early hyperglycemia exposure would have long-term disadvantageous effects on erectile function in diabetic patients with ED, which would be sustained even after the patients achieve better glycemic control. PATIENTS SUMMARY: In this report, we looked at the erectile functions of 67 patients with a clinical diagnosis of ED and a diabetic history of more than 5 years. We found that early hyperglycemia exposure would have long-term disadvantageous effects on erectile function in diabetic patients with ED, which would be sustained even after the patients achieve better glycemic control. We further found that the effects were associated with the severity of ED but not the response to medical treatment in men with diabetes.

The pancancer landscape of Wnt family expression reveals potential biomarkers in urinary system tumors.

Immunotherapy and targeted therapy have been particularly effective in treating tumors of the urinary system; however, the mechanisms of the Wnt family of proteins in the tumorigenesis, development, and immune response of urinary system tumors are not fully understood. Here, we show that the Wnt family was extensively upregulated in and impacted the prognosis of patients with prostate adenocarcinoma (PRAD) and bladder urothelial carcinoma (BLCA). Moreover, the Wnt family correlated with the levels of infiltrating immune cells, including B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells. The expression levels of Wnt family members were closely related to neoantigens, the mismatch repair system (MMRS) and DNA methyltransferases, and the mutation rate was generally low. Wnt family members are potential biomarkers for precision immunotherapy of urinary system tumors.

Screening and identification of critical biomarkers in erectile dysfunction: evidence from bioinformatic analysis.

PURPOSE: Erectile dysfunction (ED) is one of the most common male-disease globally. Despite efforts to explain its pathogenesis, the molecular mechanisms of ED are still not well understood. METHODS: The microarray dataset GSE10804 was downloaded from the Gene Expression Omnibus (GEO) to find candidate genes in ED progression. After differentially expressed genes (DEGs) were identified, functional enrichment analysis was performed. In addition, a protein-protein interaction network (PPI) was established and module analysis was performed through the STRING and Cytoscape. RESULTS AND CONCLUSIONS: A total of 618 DEGs were identified in all, containing 430 downregulated genes and 188 upregulated genes. The enriched functions and pathways of the DEGs include transcription from RNA polymerase II promoter, cell adhesion, calcium ion binding, receptor binding, Akt signaling pathway, receptor interaction, protein digestion, and absorption. We picked out twenty-five hub genes, with biological process (BP) analyses revealing that the genes were principally associated with cellular responses to amino acid stimuli, extracellular matrix structural constituent, collagen trimer, protein digestion and absorption, ECM-receptor interaction and PI3K-Akt signaling pathway. To sum up, DEGs and hub genes distinguished in this study not only help us understand the molecular mechanisms behind the carcinogenesis and progression of ED, but also play a part in the diagnosis and treatment of ED by providing candidate targets.

Association of short-term exposure to sulfur dioxide and hospitalization for ischemic and hemorrhagic stroke in Guangzhou, China.

BACKGROUND: In developing countries, ambient sulfur dioxide (SO2) is a serious air pollutant concern, but there is no enough and consistent epidemiological evidence about its health effects on stroke hospitalization. METHODS: We collected the daily air pollution data, meteorological data and number of daily hospital admissions for ischemic and hemorrhagic stroke, in Guangzhou from January 1st 2009 to December 31st 2014. Then we applied generalized additive model with a quasi-Poisson link to assess the relationship between short-term SO2 exposure and the total number of hospital admissions for ischemic and hemorrhagic stroke. In addition, we evaluated the effect of ambient SO2 by age (< 65 years and ≥ 65 years). RESULTS: During the study period, a 24-h mean concentration of ambient SO2 of 27.82 µg/m3, a total of 58,473 ischemic stroke and 9167 hemorrhagic stroke hospital admissions hospital were recorded. Ambient SO2 was found to increase the risk for both ischemic and hemorrhagic stroke hospital admission in single pollutant model. The maximum value of percentage changes for ischemic and hemorrhagic stroke occurred in lag 0 day and lag 1 day, per 10 µg/m3 increase in SO2 concentrations was corresponded to a 1.27% (95% confidence interval (CI), 0.42-2.12%) and 1.55% (95%CI, 0.02-3.11%) increased risk, respectively. The association between SO2 and ischemic stroke hospitalization was robust to two pollutant model, but for hemorrhagic stroke it's partially weakened after adjusting for co-pollutants. The effect of ambient SO2 on ischemic stroke appeared to be greater for people < 65 years old, but null effect on hemorrhagic stroke was identified for both age groups. CONCLUSIONS: We found short-term exposure to ambient SO2 may significantly increase the risks of hospitalization for ischemic stroke. The findings may contribute to a better understanding of the health effects of low-levels of SO2.

Trends in erectile dysfunction research from 2008 to 2018: a bibliometric analysis.

Insufficient penile erection to facilitate vaginal penetration is a medical condition referred to as erectile dysfunction (ED). By the year 2025, the number of ED cases across the world is expected to reach 322 million. There are numerous publications and studies in the field of ED over the past decades. Our aim is to comprehensively analyze the global scientific outputs of ED research and show the trends and hotspots in ED research. Data of publications were downloaded from the Web of Science Core Collection. We used CiteSpace IV and Excel 2016 to analyze literature information, including journals, countries/regions, institutes, authors, citation reports, and research frontiers. Until October 26, 2018, a total of 8880 papers in ED research were identified as published between 2008 and 2018. Journal of Sexual Medicine published the most articles. The United States contributed the most publications and occupied leading positions in H-index value and the number of ESI top papers. Maggi M owned the highest co-citations. The keyword "Oxidative stress" ranked first in the research front-line. The amount of articles published in ED research has been stable from 2008 to 2018. The United States showed enormous progress in ED research, and is still the dominant country. Oxidative stress, vardenafil, and late-onset hypogonadism were the latest research frontiers and should be paid more attention.

Correction to: Trends in erectile dysfunction research from 2008 to 2018: a bibliometric analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

[Exogenous hydrogen sulfide improves erectile dysfunction by inhibiting apoptosis of corpus cavernosum smooth muscle cells in rats with cavernous nerve injury].

OBJECTIVE: To explore the effects of exogenous hydrogen sulfide (H2S) on apoptosis of corpus cavernosum smooth muscle cells (CCSMCs) and erectile dysfunction (ED) in rats with bilateral cavernous nerve injury (BCNI). METHODS: Twentyfour male SD rats were randomly divided into 3 groups (n=8):sham operation group, bilateral cavernous nerve injury group (BCNI group) and H2S intervention group (BCNI+NaHS group). In BCNI and BCNI+NaHS groups, BCNI was induced by clamp injury of the bilateral cavernous nerves, and the rats were subjected to daily intraperitoneal injection of normal saline and 100 µmol/kg NaHS solution for 4 weeks, respectively. After the treatment, the intracavernous pressure (ICP) and mean arterial pressure (MAP), ) of the rats were measured. Western blotting was used to detect the expressions of cystathionine ß synthetase (CBS), cystathionine γ lyase (CSE), α-SMA, collagen-I, caspase-3, Bax and Bcl-2 in the penile cavernous tissue, and the expressions of CBS and CSE were also detected immunohistochemically. The ratio of cavernous smooth muscle to collagen was detected using Masson's Trichrome staining. The apoptosis level of CCSMC was detected by TUNEL + α-SMA immunofluorescence double staining. RESULTS: After 4 weeks of treatment, the rats in BCNI+NaHS group showed a significantly higher ICP/MAP ratio than those in BCNI group (P < 0.05). The results of Masson's Trichrome staining showed that the ratio of cavernous smooth muscle/collagen was significantly higher in BCNI + NaHS group than in BCNI group (P < 0.05). Western blotting showed a significantly higher expression of α-SMA protein but a lower expression of collagen-I protein in BCNI + NaHS group than in BCNI group (P < 0.05). TUNEL+α-SMA immunofluorescence double staining revealed a significantly lower number of apoptotic CCSMCs in BCNI+NaHS group than in BCNI group (P < 0.05). Compared with those in BCNI group, the rats in BCNI+NaHS group had significantly decreased expressions of caspase-3 and Bax proteins (P < 0.05) with significantly enhanced Bcl-2 protein expression and an increased Bcl-2/Bax ratio (P < 0.05). The expressions of CBS and CSE were significantly lower in BCNI group than in the other two groups (P < 0.05). CONCLUSIONS: Exogenous H2S enhance the expression of the classic apoptotic protein Bcl-2 and reduces apoptosis of CCSMC to improve the erectile function in rats with BCNI.

Virtual Hepatic Venous Pressure Gradient with CT Angiography (CHESS 1601): A Prospective Multicenter Study for the Noninvasive Diagnosis of Portal Hypertension.

Purpose To develop and validate a computational model for estimating hepatic venous pressure gradient (HVPG) based on CT angiographic images, termed virtual HVPG, to enable the noninvasive diagnosis of portal hypertension in patients with cirrhosis. Materials and Methods In this prospective multicenter diagnostic trial (ClinicalTrials.gov identifier: NCT02842697), 102 consecutive eligible participants (mean age, 47 years [range, 21-75 years]; 68 men with a mean age of 44 years [range, 21-73 years] and 34 women with a mean age of 52 years [range, 24-75 years]) were recruited from three high-volume liver centers between August 2016 and April 2017. All participants with cirrhosis of various causes underwent transjugular HVPG measurement, Doppler US, and CT angiography. Virtual HVPG was developed with a three-dimensional reconstructed model and computational fluid dynamics. Results In the training cohort (n = 29), the area under the receiver operating characteristic curve (AUC) of virtual HVPG in the prediction of clinically significant portal hypertension (CSPH) was 0.83 (95% confidence interval [CI]: 0.58, 1.00). The diagnostic performance was prospectively confirmed in the validation cohort (n = 73), with an AUC of 0.89 (95% CI: 0.81, 0.96). Inter- and intraobserver agreement was 0.88 and 0.96, respectively, suggesting the good reproducibility of virtual HVPG measurements. There was good correlation between virtual HVPG and invasive HVPG (R = 0.61, P < .001), with a satisfactory performance to rule out (7.3 mm Hg) and rule in (13.0 mm Hg) CSPH. Conclusion The accuracy of a computational model of virtual hepatic venous pressure gradient (HVPG) shows significant correlation with invasive HVPG. The virtual HVPG also showed a good performance in the noninvasive diagnosis of clinically significant portal hypertension in cirrhosis. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Malayeri in this issue.

Implications of alpha-synuclein nitration at tyrosine 39 in methamphetamine-induced neurotoxicity in vitro and in vivo.

Methamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson's disease. However, its specific mechanism of action is still unclear. In the present study, we established a Parkinson's disease pathology model by exposing SH-SY5Y cells and C57BL/6J mice to methamphetamine. In vitro experiments were performed with 0, 0.5, 1.0, 1.5, 2.0 or 2.5 mM methamphetamine for 24 hours or 2.0 mM methamphetamine for 0-, 2-, 4-, 8-, 16-, and 24-hour culture of SH-SY5Y cells. Additional experimental groups of SH-SY5Y cells were administered a nitric oxide inhibitor, 0.1 mM N-nitro-L-arginine, 1 hour before exposure to 2.0 mM methamphetamine for 24 hours. In vivo experiments: C57BL/6J mice were intraperitoneally injected with N-nitro-L-arginine (8 mg/kg), eight times, at intervals of 12 hours. Methamphetamine 15 mg/kg was intraperitoneally injected eight times, at intervals of 12 hours, but 0.5-hour after each N-nitro-L-arginine injection in the combined group. Western blot assay was used to determine the expression of nitric oxide synthase, α-synuclein (α-Syn), 5G4, nitrated α-synuclein at the residue Tyr39 (nT39 α-Syn), cleaved caspase-3, and cleaved poly ADP-ribose polymerase (PARP) in cells and mouse brain tissue. Immunofluorescence staining was conducted to measure the positive reaction of NeuN, nT39 α-Syn and 5G4. Enzyme linked immunosorbent assay was performed to determine the dopamine levels in the mouse brain. After methamphetamine exposure, α-Syn expression increased; the aggregation of α-Syn 5G4 increased; nT39 α-Syn, nitric oxide synthase, cleaved caspase-3, and cleaved PARP expression increased in the cultures of SH-SY5Y cells and in the brains of C57BL/6J mice; and dopamine levels were reduced in the mouse brain. These changes were markedly reduced when N-nitro-L-arginine was administered with methamphetamine in both SH-SY5Y cells and C57BL/6J mice. These results suggest that nT39 α-Syn aggregation is involved in methamphetamine neurotoxicity.

SUMOylation of Alpha-Synuclein Influences on Alpha-Synuclein Aggregation Induced by Methamphetamine.

Methamphetamine (METH) is an illegal and widely abused psychoactive stimulant. METH abusers are at high risk of neurodegenerative disorders, including Parkinson's disease (PD). Previous studies have demonstrated that METH causes alpha-synuclein (α-syn) aggregation in the both laboratory animal and human. In this study, exposure to high METH doses increased the expression of α-syn and the small ubiquitin-related modifier 1 (SUMO-1). Therefore, we hypothesized that SUMOylation of α-syn is involved in high-dose METH-induced α-syn aggregation. We measured the levels of α-syn SUMOylation and these enzymes involved in the SUMOylation cycle in SH-SY5Y human neuroblastoma cells (SH-SY5Y cells), in cultures of C57 BL/6 primary mouse neurons and in brain tissues of mice exposure to METH. We also demonstrated the effect of α-syn SUMOylation on α-syn aggregation after METH exposure by overexpressing the key enzyme of the SUMOylation cycle or silencing SUMO-1 expression in vitro. Then, we make introduced mutations in the major SUMOylation acceptor sites of α-syn by transfecting a lentivirus containing the sequence of WT α-syn or K96/102R α-syn into SH-SY5Y cells and injecting an adenovirus containing the sequence of WT α-syn or K96/102R α-syn into the mouse striatum. Levels of the ubiquitin-proteasome system (UPS)-related makers ubiquitin (Ub) and UbE1, as well as the autophagy-lysosome pathway (ALP)-related markers LC3, P62 and lysosomal associated membrane protein 2A (LAMP2A), were also measured in SH-SY5Y cells transfected with lentivirus and mice injected with adenovirus. The results showed that METH exposure decreases the SUMOylation level of α-syn, although the expression of α-syn and SUMO-1 are increased. One possible cause is the reduction of UBC9 level. The increase in α-syn SUMOylation by UBC9 overexpression relieves METH-induced α-syn overexpression and aggregation, whereas the decrease in α-syn SUMOylation by SUMO-1 silencing exacerbates the same pathology. Furthermore, mutations in the major SUMOylation acceptor sites of α-syn also aggravate α-syn overexpression and aggregation by impairing degradation through the UPS and the ALP in vitro and in vivo. These results suggest that SUMOylation of α-syn plays a fundamental part in α-syn overexpression and aggregation induced by METH and could be a suitable target for the treatment of neurodegenerative diseases.