qSOFA predicted pneumonia mortality better than minor criteria and worse than CURB-65 with robust elements and higher convergence.

BACKGROUND: Limited data are available on the discriminatory capacity of quick sequential [sepsis-related] organ failure assessment (qSOFA) versus IDSA/ATS minor criteria for predicting mortality in patients with community-acquired pneumonia (CAP). METHODS: An observational prospective cohort study of 2116 patients with CAP was performed. Construct validity was determined using Cronbach α. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI). RESULTS: Overall in-hospital mortality was 6.43%. Mortality was 25.96% for patients with a qSOFA score of 2 or higher versus 3.05% for those with a qSOFA score less than 2 (odds ratio for mortality 6.57, P < 0.0001), and 13.85% for patients with at least 3 minor criteria versus 2.03% for those with 2 or fewer minor criteria (odds ratio for mortality 2.27, P < 0.0001). qSOFA had a higher correlation with mortality than minor criteria, as well as higher internal consistency (Cronbach alpha 0.43 versus 0.14) and diagnostic values of individual elements (larger AUROCs and higher Youden's indices). qSOFA ≥2 was less sensitive but more specific for predicting mortality than ≥3 minor criteria (qSOFA sensitivity 59.6%, specificity 88.3% and positive likelihood ratio 5.11 versus ≥3 minor criteria sensitivity 80.1%, specificity 65.8% and positive likelihood ratio 2.34). The predictive validity of qSOFA was good for mortality (AUROC = 0.868), was statistically greater than minor criteria, was equal to pneumonia severity index, and was inferior compared with CURB-65 (AUROC, 0.824, 0.902, 0.919; NRI, 0.088, -0.068, -0.103; respectively). CONCLUSIONS: The qSOFA predicted mortality in CAP better than IDSA/ATS minor criteria and worse than CURB-65 with robust elements and higher convergence. qSOFA as a bedside prompt might be positioned as a proxy for minor criteria and increase the recognition and thus merit more appropriate management of CAP patients likely to fare poorly, which might have implications for more accurate clinical triage decisions.

[Influence of epididymitis history on the results of vasoepididyostomy in patients with epididymal obstruction].

OBJECTIVE: To evaluate the influence of epididymitis history on the results of microsurgical vasoepididymostomy and spontaneous pregnancy in patients with epididymal obstruction. METHODS: Totally 205 patients with epididymal obstruction underwent microsurgical two-suture longitudinal intussusception vasoepididymostomy from January 2014 to December 2016. After surgery, we evaluated the semen quality of the patients every 3 months till conception and compared the rates of patency and spontaneous pregnancy between the patients with and those without an epididymitis history. RESULTS: The patients ranged in age from 22 to 46 (mean 31) years, 37 (22.2%) with and 126 (77.8%) without an epididymitis history among the 163 patients for whom a 25.4-month follow-up (from 7 to 42 months) was completed. No statistically significant differences were observed postoperatively between the patients with and those without an epididymitis history in the patency rate (73.0% vs 81.7%, P = 0.243), sperm concentration (18 ï¼»1.3－33.6ï¼½ vs 15.2 ï¼»0.8－33.4ï¼½ ×106/ml, P = 0.710), percentage of progressively motile sperm (27.5 ï¼»0－46.1ï¼½% vs 19.3 ï¼»0－41ï¼½% (P = 0.592) or rate of spontaneous pregnancy (24.3% vs 38.9%, P = 0.104). CONCLUSION: Microsurgical vasoepididymostomy is an effective method for the treatment of epididymal obstruction, and epididymitis history does not affect the results of the strategy.

Diagnostic Value of Galactomannan in Bronchoalveolar Lavage Fluid for Chronic Respiratory Disease with Pulmonary Aspergillosis.

The objective of this study was to explore the diagnostic value of the bronchoalveolar lavage fluid galactomannan (BALF GM) test for chronic respiratory disease with pulmonary aspergillosis and to establish the optimal cutoff value. Samples from a total of 309 chronic respiratory disease patients seen at the respiratory medicine department of Peking University Shenzhen Hospital from September 2016 to September 2019 were analyzed. According to the diagnostic criteria, we divided the patients into a case group (n = 79, comprising 25 proven cases and 54 probable cases) and a control group (n = 230). Bronchoalveolar lavage fluid was collected, and the BALF GM test results were analyzed. A nonparametric rank sum test showed that the mean rank of the case group was 255.30, which was higher than that of the control group (120.55). The Z-value was -11.567 (P = 0.000), indicating that the general distributions of BALF GM differed between the two groups. A BALF GM cutoff value of 0.88 showed the highest diagnostic efficacy for pulmonary aspergillosis. The sensitivity, specificity, positive predictive value, and negative predictive value were 77.2%, 93%, 79.2%, and 92.2%, respectively. As the cutoff value increased, the specificity and sensitivity of the BALF GM test increased and decreased, respectively. The BALF GM test can be used confirm the diagnosis of patients with pulmonary aspergillosis and chronic respiratory disease. The optimum BALF GM cutoff value is 0.88.

Weighted Epworth sleepiness scale predicted the apnea-hypopnea index better.

BACKGROUND: The relationship between the Epworth sleepiness scale (ESS) and the apnea-hypopnea index (AHI) is uncertain and even poor. The major problem associated with the ESS might be a lack of consideration of weight in prediction in clinical practice. Would awarding different item-scores to the four scales of ESS items to develop a weighted ESS scoring system improve the accuracy of the AHI prediction? It is warranted to explore the intriguing hypotheses. METHODS: Seven hundred fifty-six adult patients with suspicion of obstructive sleep apnoea syndrome (OSAS) were prospectively recruited to a derivation cohort. This was tested against a prospective validation cohort of 810 adult patients with suspected OSAS. Each ESS item's increased odds ratio for the corresponding AHI was calculated using univariate logistic regression. The receiver operating characteristic curves were created and the areas under the curves (AUCs) were calculated to illustrate and compare the accuracy of the indices. RESULTS: The higher the ESS item-score, the closer the relationship with the corresponding AHI. The odds ratios decreased as a result of the increased AHI. The ESS items were of unequal weight in predicting the corresponding AHI and a weighted ESS was developed. The coincidence rates with the corresponding AHI, body mass indices, and neck circumferences rose as the scores increased, whereas nocturnal nadir oxygen saturations decreased, and the weighted ESS was more strongly associated with these indices, compared with the ESS. The capability in predicting the patients without OSAS or with severe OSAS was strong, especially the latter, and the weighted ESS orchestrated manifest improvement in screening the patients with simple snoring. The patterns of sensitivities, specificities, and Youden's indices of the four ranks of weighted ESS for predicting the corresponding AHI were better than those of the ESS, and the AUCs of weighted ESS were greater than the corresponding areas of ESS in the two cohorts. CONCLUSIONS: The weighted ESS orchestrated significant improvement in predicting the AHI, indicating that the capability in predicting the patients without OSAS or with severe OSAS was strong, which might have implications for clinical triage decisions to prioritize patients for polysomnography.

Cold-inducible RNA-binding protein might determine the severity and the presences of major/minor criteria for severe community-acquired pneumonia and best predicted mortality.

BACKGROUND: Severity of community-acquired pneumonia (CAP) depends on microbial pathogenicity, load and virulence, and immune responses. The Infectious Disease Society of America and the American Thoracic Society (IDSA/ATS) minor criteria responsible for clinical triage of patients with CAP are of unequal weight in predicting mortality. It is unclear whether the IDSA/ATS major/minor criteria might be strongly and positively associated with the immune responses. It is warranted to explore this intriguing hypothesis. METHODS: A prospective cohort study of 404 CAP patients was performed. Cold-inducible RNA-binding protein (CIRP) levels were measured using a sandwich-based enzyme-linked immunosorbent assay. The receiver operating characteristic curves were created and the areas under the curves were calculated to illustrate and compare the accuracy of the indices. RESULTS: Severe CAP patients meeting the major criteria had the highest plasma concentrations of CIRP. The more the number of most predictive minor criteria strongly associated to mortality, i.e. arterial oxygen pressure/fraction inspired oxygen ≤ 250 mmHg, confusion, and uremia, present, the higher the CIRP level. Interestingly, the patients with non-severe CAP meeting the most predictive minor criteria demonstrated unexpectedly higher CIRP level compared with the patients with severe CAP not fulfilling the criteria. Procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP), sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores, and mortality confirmed similar intriguing patterns. CIRP was strongly linked to PCT, IL-6, CRP, minor criteria, SOFA and PSI scores, and mortality (increased odds ratio 3.433). The pattern of sensitivity, specificity, positive predictive value, and Youden's index of CIRP ≥ 3.50 ng/mL for predicting mortality was the optimal. The area under the receiver operating characteristic curve of CIRP was the highest among the indices. CONCLUSIONS: CIRP levels were strongly correlated with the IDSA/ATS major/minor criteria. CIRP might determine the severity and the presences of major/minor criteria and best predicted mortality, and a CIRP of ≥ 3.50 ng/mL might be more valuable cut-off value for severe CAP, suggesting that CIRP might be a novel and intriguing biomarker for pneumonia to monitor host response and predict mortality, which might have implications for more accurate clinical triage decisions.

Correction to: Scored minor criteria for severe community-acquired pneumonia predicted better.

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Scored minor criteria for severe community-acquired pneumonia predicted better.

BACKGROUND: Infectious Disease Society of America/American Thoracic Society (IDSA/ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight in predicting mortality, but the major problem associated with IDSA/ATS minor criteria might be a lack of consideration of weight in prediction in clinical practice. Would awarding different points to the presences of the minor criteria improve the accuracy of the scoring system? It is warranted to explore this intriguing hypothesis. METHODS: A total of 1230 CAP patients were recruited to a retrospective cohort study. This was tested against a prospective two-center cohort of 1749 adults with CAP. 2 points were assigned for the presence of PaO2/FiO2 ≤ 250 mmHg, confusion, or uremia on admission and 1 point for each of the others. RESULTS: The mortality rates, and sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores increased significantly with the numbers of IDSA/ATS minor criteria present and minor criteria scores. The correlations of the minor criteria scores with the mortality rates were higher than those of the numbers of IDSA/ATS minor criteria present. As were the correlations of the minor criteria scores with SOFA and PSI scores, compared with the numbers of IDSA/ATS minor criteria present. The pattern of sensitivity, specificity, positive predictive value, and Youden's index of scored minor criteria of ≥2 scores or the presence of 2 or more IDSA/ATS minor criteria for prediction of mortality was the best in the retrospective cohort, and the former was better than the latter. The validation cohort confirmed a similar pattern. The area under the receiver operating characteristic curve of scored minor criteria was higher than that of IDSA/ATS minor criteria in the retrospective cohort, implying higher accuracy of scored version for predicting mortality. The validation cohort confirmed a similar paradigm. CONCLUSIONS: Scored minor criteria orchestrated improvements in predicting mortality and severity in patients with CAP, and scored minor criteria of ≥2 scores or the presence of 2 or more IDSA/ATS minor criteria might be more valuable cut-off value for severe CAP, which might have implications for more accurate clinical triage decisions.

Contributions of individual qSOFA elements to assessment of severity and for prediction of mortality.

BACKGROUND: The quick sequential [sepsis-related] organ failure assessment (qSOFA) acts as a prompt to consider possible sepsis. The contributions of individual qSOFA elements to assessment of severity and for prediction of mortality remain unknown. METHODS: A total of 3974 patients with community-acquired pneumonia were recruited to an observational prospective cohort study. The area under the receiver operating characteristic curve (AUROC), odds ratio, relative risk and Youden's index were employed to assess discrimination. RESULTS: Respiratory rate ≥22/min demonstrated the most superior diagnostic value, indicated by largest odds ratio, relative risk and AUROC, and maximum Youden's index for mortality. However, the indices for altered mentation and systolic blood pressure (SBP) ≤100 mm Hg decreased notably in turn. The predictive validities of respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg were good, adequate and poor for mortality, indicated by AUROC (0.837, 0.734 and 0.671, respectively). Respiratory rate ≥22/min showed the strongest associations with SOFA scores, pneumonia severity index, hospital length of stay and costs. However, SBP ≤100 mm Hg was most weakly correlated with the indices. CONCLUSIONS: Respiratory rate ≥22/min made the greatest contribution to parsimonious qSOFA to assess severity and predict mortality. However, the contributions of altered mentation and SBP ≤100 mm Hg decreased strikingly in turn. It is the first known prospective evidence of the contributions of individual qSOFA elements to assessment of severity and for prediction of mortality, which might have implications for more accurate clinical triage decisions.

Respiratory rate ≥22/min demonstrated the most superior diagnostic value.Respiratory rate ≥22/min showed the strongest association with severity.Respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg predicted mortality well, adequately and poorly, respectively.

[Efficacy of microsurgical vasectomy reversal on patients after vasectomy].

OBJECTIVE: To evaluate the efficacy of microsurgical vasectomy reversal on patients after vasectomy. METHODS: In the study, 41 patients after vasectomy were admitted for microsurgical vasectomy reversal. The mean (range) age was 45 (29 to 66) years for the men. The mean duration of obstruction was 12 years. All the patients were seen by the surgeon for a complete history and physical examination. Semen analyses proved azoopermia, and their serum levels of sexual hormone were normal. They were all offered scrotal exploration. Microvasovasostomy was performed if the sperm was found in the material coming from the proximal vas lumen. The decision for microvasoepididymostomy was made during surgery, if the fluid was creamy, containing only debris or there was no fluid whatsoever when the vas was milked toward the cut end. Microvasovasostomy was performed in 40 patients, of whom 6 were with lateral microvasoepididymostomy and 1 with bilateral microvasoepididymostomy. The initial semen analysis was then done after usually 3 months postoperatively. Patency was arbitrarily defined as>10 000 sperm/mL in ejaculate in at least one semen analysis after surgery. Postoperative patency rate and postoperative impregnation rate were followed. RESULTS: The 41 patients were followed up for 3 to 72 months, and 5 cases were lost. In the 28 patients who had obstructions for less than 15 years, 3 were lost. Sperm was found by semen analysis in 21 patients. Their sperm density was 2×10(6) to 46×10(6) sperms/mL and motility was 0% to 60%. The semen analysis revealed azoospermia in 2 patients after 12 months, who were advised to undergo intracytoplasmic sperm injection. Natural conception occurred in 6 patients followed for more than 12 months. The overall patency rate was 84% (21/25). Among the patients with a follow-up of >6 months, the natural paternity rate was 29% (6/21). In the 13 patients who had obstructions for more than 15 years, 2 were lost. The patency and pregnancy rates were 64% (7/11) and 14% (1/7) respectively. Their sperm density was 0.02×10(6) to 30× 10(6) sperms/mL and motility was 0% to 43%. CONCLUSION: Microsurgical vasectomy reversal is an effective method to treat vasal obstruction due to vasectomy. The patency and pregnancy rates are related to the time of vasectomy. The patency and pregnancy rates are higher in patients with obstruction for less than 15 years than those for more than 15 years.

[Daily low-dose tadalafil for erectile dysfunction induced by pelvic fracture urethral disruption].

OBJECTIVE: To evaluate the effect of daily low-dose tadalafil on erectile dysfunction (ED) induced by pelvic fracture urethral disruption (PFUD). METHODS: This study included 46 cases of PFUD-induced ED treated from Jan 2008 to Dec 2011. The patients were aged 33.9 +/- 7.2 years (range 25 -51 yr), and the interval between injury and treatment was 19.6 +/- 12.7 months (range 3 - 72 mo), all with normal erectile function before PFUD. Based on the nocturnal penile tumescence and rigidity (NPTR) recorded by erectometry without medication of phosphodiesterase type 5 inhibitor (PDE-5I), the patients were divided into an abnormal nocturnal erection group and a non-nocturnal erection group, and treated with tadalafil 10 mg once daily for 3 months. The therapeutic effect was evaluated by IIEF-5 scores and the rate of yes responses to questions 2 and 3 of the Sexual Encounter Profile (SEP). RESULTS: Totally 38 (82.6%) of the patients accomplished the treatment and follow-up, 26 (68.4%) in the abnormal nocturnal erection group and 12 (31.6%) in the non-nocturnal erection group. After 3 months of daily tadalafil treatment at 10 mg, the IIEF-5 scores were significantly improved in the abnormal nocturnal erection group than in the non-nocturnal erection group (P < 0.05), and the rate of yes responses to SEP2 and SEP3 was remarkably higher in the former than in the latter (76.9% vs 41.7% and 65.4% vs 25.0%, P < 0.05). CONCLUSIONS: Daily low-dose tadalafil can effectively improve the erectile function of PFUD-induced ED patients, particularly in those with nocturnal erection.

LncRNA TUG1 promotes pulmonary fibrosis progression via up-regulating CDC27 and activating PI3K/Akt/mTOR pathway.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with an unclear pathogenesis. This study aimed to elucidate the function and potential mechanisms of TUG1 in IPF progression. Cell viability and migration were detected by CCK-8 and transwell assays. Autophagy, fibrosis, or EMT-related proteins were measured by Western blotting. Pro-inflammatory cytokine levels were assessed by ELISA kits. The subcellular localization of TUG1 was observed by FISH assay. RIP assay detected the interaction between TUG1 and CDC27. TUG1 and CDC27 was up-regulated in TGF-ß1-induced RLE-6TN cells. TUG1 depletion suppressed pulmonary fibrosis via attenuating inflammation, EMT, inducing autophagy and inactivating PI3K/Akt/mTOR pathway in vitro and in vivo. TUG1 knockdown prevented CDC27 expression. TUG1 silencing ameliorated pulmonary fibrosis by reducing CDC27 expression and inhibiting PI3K/Akt/mTOR pathway.

Transcriptome analysis highlights the role of ferroptosis in palmitic acid-induced endothelial dysfunction.

Background: Palmitic acid (PA) has a lipotoxic effect on blood vessels, leading to endothelial dysfunction and cell death. The underlying mechanisms are not yet fully understood. Aim: We sought to investigate the effects of PA on endothelial cells, with an emphasis on ferroptosis. Methods: Rat corpus cavernosum endothelial cells (RCCECs) and human umbilical vein endothelial cells (HUVECs) were treated with PA to induce a pattern of cell death, as evidenced by the evaluation of cell viability. The differentially expressed genes were measured via RNA sequencing to reveal potential mechanisms. The intracellular levels of glutathione (GSH), malondialdehyde (MDA), ferrous ion (Fe2+), and reactive oxygen species (ROS) were evaluated using commercial kits. Western blot was performed to determine the expressions of relative proteins. Outcomes: At the end of the study period, the evaluated outcomes were cell viability, transcriptome profiles, the expressions of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), as well as levels of GSH, MDA, Fe2+, and ROS. Results: PA-induced cell death of RCCECs and HUVECs was demonstrated in a dose- and time-dependent manner. Based on the findings of RNA-sequencing (RNA-seq), enrichment of many biological processes associated with cell cycle and response to stimulus occurred. More importantly, ferroptosis was highlighted in the bioinformatic analysis of both endothelial cells. The levels of intracellular Fe2+, MDA, and ROS were significantly increased following PA exposure while GSH was decreased, suggesting excessive iron accumulation, development of lipid peroxidation, and imbalanced redox homeostasis. Mechanistically, PA decreased the protein expression levels of GPX4 and SLC7A11 in endothelial cells, both of which played crucial roles in ferroptotic cell death. Clinical Translation: This study suggests that ferroptosis may be a useful target for novel therapeutic interventions for endothelial dysfunction and cell death in vascular diseases such as erectile dysfunction. Strengths and Limitations: In this study, we found that ferroptosis could participate in PA-induced endothelial dysfunction and cell death. A limitation of the study is that it did not shed light on the overall mechanisms of this process. Therefore, further research on the intricate networks of regulating ferroptosis is needed. Conclusion: Overall, the occurrence of ferroptosis was demonstrated in the PA-treated HUVECs and RCCECs in this study.

Updating cut-off values of severity scoring systems for community-acquired pneumonia to orchestrate more predictive accuracy.

Background: The assessment of severity is crucial in the management of community-acquired pneumonia (CAP). It remains unknown whether updating cut-off values of severity scoring systems orchestrate improvement in predictive accuracy.Methods: 3,212 patients with CAP were recruited to two observational prospective cohort studies. Three bettered scoring systems were derived from the corresponding well-established and extensively used pneumonia-specific severity scoring systems, i.e. pneumonia severity index, minor criteria and CURB-65 (confusion, urea >7 mmol/L, respiratory rate ≥30/min, low blood pressure, and age ≥65 years) score, with the updating cut-off values for tachypnea and low blood pressure. Cronbach α was employed to determine construct validity. Discrimination was valued by calculating the area under the receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI).Results: Respiratory rate ≥22/min and systolic blood pressure ≤100 mm Hg were performed better than respiratory rate ≥30/min and hypotension for predicting mortality in the derivation cohort, respectively (AUROC, 0.823 vs 0.519, 0.688 vs 0.622; NRI, 0.61, 0.13). Bettered scoring systems orchestrated higher convergences, indicated by greater Cronbach α and more decrease in Cronbach α if the updating cut-off values were deleted. The six scoring systems agreed well with one another. Bettered- pneumonia severity index, minor criteria and CURB-65 score showed higher associations with severity and mortality rates and demonstrated greater predictive accuracies for mortality compared with the corresponding original systems (AUROC, 0.939 vs 0.883, 0.909 vs 0.871, 0.913 vs 0.859; NRI, 0.113, 0.076, 0.108; respectively). The validation cohort confirmed a similar pattern.Conclusions: Updating cut-off values of severity scoring systems for CAP orchestrate improvement in predictive accuracy, suggesting that it may facilitate the rationalization of clinical triage decision-making and further reduce mortality. The current studies provide the first known prospective evidence of potential benefit of the updating cut-off values of severity scoring systems for CAP in predictive accuracy.Key messagesUpdating cut-off values were performed better for predicting mortality.Bettered scoring systems orchestrated higher convergences.Bettered scoring systems demonstrated greater predictive accuracies for mortality.

Icariside â ¡ Attenuates Palmitic Acid-Induced Endothelial Dysfunction Through SRPK1-Akt-eNOS Signaling Pathway.

Background: Endothelial dysfunction is commonly accompanied by a reduced capacity for nitric oxide (NO) production and decreased NO sensitivity, playing a central role in numerous vascular diseases. Saturated free fatty acids are known to reduce NO production and then induce endothelial dysfunction. Alternative splicing participates in the regulation of cellular and tissular homeostasis and is highly regulated by serine-arginine protein kinase (SRPK1). The role of SRPK1 in the biology of endothelial cells remains elusive. Icariside Ⅱ (ICA Ⅱ) has been reported to have protective effects on endothelial function. However, the specific molecular mechanisms are still unknown. The purpose of this study is to explore the role of SRPK1 in the biology of endothelial cells and the underlying mechanism of ICA Ⅱ on palmitic acid (PA) induced endothelial dysfunction. Methods: Endothelial dysfunction was induced using PA in human umbilical vein endothelial cells (HUVECs). The expression and phosphorylation of related proteins in the SRPK1-Akt-eNOS signaling pathway were detected by Western Blot. Cell Counting Kit-8 assay and Ki-67 immunofluorescence were used to estimate cell viability. Endothelial cell function was assessed by detecting NO production using DAF-FM DA. Interaction between ICA Ⅱ and SRPK1 was demonstrated by a biotinylated protein interaction pull-down assay. Results: The expressions of eNOS, Akt, and SRPK1 were down-regulated in the endothelial dysfunction stimulated by PA. SRPK1 inhibitor SPHINX31 restrained endothelial cell viability in a dose-dependent manner. Moreover, inhibition of SRPK1 using SPHINX31 and knockdown of SRPK1 by shRNA also showed a down-regulation of the proteins associated with the SRPK1-Akt-eNOS signaling pathway. Biotinylated protein interaction pull-down assay revealed that ICA Ⅱ could be directly bound with SRPK1. On the other hand, ICA Ⅱ could attenuate the PA-induced endothelial dysfunction and restore cell viability through the SRPK1-Akt-eNOS pathway. Conclusions: ICA Ⅱ, bound with SRPK1, could attenuate the endothelial dysfunction induced by the PA in HUVECs via the SRPK1-Akt-eNOS signaling pathway.

Proteomic analysis and miRNA profiling of human testicular endothelial cell-derived exosomes: the potential effects on spermatogenesis.

Testicular endothelial cells have been found to play an important role in spermatogenesis and fertility, but their mechanism is obscure. Exosomes released by various cells are recognized as cell-cell communication mediators during the initiation and progression of many diseases. Therefore, the current study aimed to investigate the protein and miRNA components of human testicular endothelial cell-derived exosomes (HTEC-Exos) and to explore their potential effects on spermatogenesis. In this study, HTEC-Exos were first isolated by the ultracentrifugation method, and then identified by nanoparticle tracking analysis, transmission electron microscopy (TEM), and western blotting. The characteristics of HTEC-Exos were examined by liquid chromatography-mass spectrometry and microRNA (miRNA) chip analysis. Bioinformatics analysis was performed to explore the potential role of the exosomal content on spermatogenesis. A total of 945 proteins were identified, 11 of which were closely related to spermatogenesis. A total of 2578 miRNAs were identified. Among them, 30 miRNAs demonstrated potential associations with male reproductive disorders, such as azoospermia, and spermatogenesis disorders. In particular, 11 out of these 30 miRNAs have been proven to be involved in spermatogenesis based on available evidence. This study provides a global view of the proteins and miRNAs from HTEC-Exos, suggesting that HTEC-Exos may function as potential effectors during the process of spermatogenesis.

Single-Cell RNA Sequencing of Human Corpus Cavernosum Reveals Cellular Heterogeneity Landscapes in Erectile Dysfunction.

Purpose: To assess the diverse cell populations of human corpus cavernosum in patients with severe erectile dysfunction (ED) at the single-cell level. Methods: Penile tissues collected from three patients were subjected to single-cell RNA sequencing using the BD Rhapsody™ platform. Common bioinformatics tools were used to analyze cellular heterogeneity and gene expression profiles from generated raw data, including the packages Seurat, Monocle, and CellPhoneDB. Results: Disease-related heterogeneity of cell types was determined in the cavernous tissue such as endothelial cells (ECs), smooth muscle cells, fibroblasts, and immune cells. Reclustering analysis of ECs identified an arteriole ECs subcluster and another one with gene signatures of fibroblasts. The proportion of fibroblasts was higher than the other cell populations and had the most significant cellular heterogeneity, in which a distinct subcluster co-expressed endothelial markers. The transition trajectory of differentiation from smooth muscle cells into fibroblasts was depicted using the pseudotime analysis, suggesting that the expansion of corpus cavernosum is possibly compromised as a result of fibrosis. Cell-cell communications among ECs, smooth muscle cells, fibroblasts, and macrophages were robust, which indicated that inflammation may also have a crucial role in the development of ED. Conclusions: Our study has demonstrated a comprehensive single-cell atlas of cellular components in human corpus cavernosum of ED, providing in-depth insights into the pathogenesis. Future research is warranted to explore disease-specific alterations for individualized treatment of ED.

[Factors affecting the results of microsurgical vasoepididymostomy].

OBJECTIVE: To evaluate the intraoperative factors affecting the patency of microsurgical vasoepididymostomy. METHODS: From January 2009 to July 2010, 73 men with obstructive azoospermia had undergone longitudinal intussusception vasoepididymostomy (LIVE). The mean age (range) was 31 years (23 to 48) for the patients and their mean infertility was 50.9 months (2 to 180). All the patients were included in three groups by the clinical variables in surgery: anastomosis number, anastomosis sites, epididymal fluid analysis. Bilateral and lateral anastomosis was in 50 and 23 cases, respectively. The anastomosis on caput, corpus and caudal was in 19, 46, and 8 cases respectively. Motile sperm in the epididymal fuild continuing flowage could be found in 55 patients. By contrast, immotile sperm could be found in 18 patients. Semen analysis was done at the end of 3 months, and patency was arbitrarily defined as >10 000 sperm/mL in ejaculate in at least one semen analysis after surgery. RESULTS: Of all the patients, 53 were followed up. Sperm was present in the ejaculate in 38 patients postoperatively. The overall patency rate was 71.7% (38/53). Patency rates of bilateral surgery and of lateral surgery achieved 80.7% and 27.6%; of caput anastomosis 38.5%, of corpus anastomosis 78.8%, of caudal anastomosis 100%, of motile sperm with epididymal fluid continuing flowage 83.7% and of immotile sperm 40%, respectively. In the study, 17 patients (33.3%, 17/53) reported spontaneous pregnancy. CONCLUSION: Except for microsurgical technology, bilateral anastomosis, corpus or caudal anastomosis, and motile sperm with epididymal fluid continuing flowage may improve patency rate postoperatively.

[Clinical characteristics of patients with erectile dysfunction-no sexual life].

OBJECTIVE: To collect clinical data of patients with erectile dysfunction-no sexual life (ED-NS), and investigate its characteristics with a simple evaluating questionnaire. METHODS: Sixty-one patients who complained erectile dysfunction without sexual life for more than six months and 57 normal controls were enrolled in our study. The mean age of the ED-NS patients was 26.2 ± 4.3 years, compared with 24.9 ± 4.1 years of normal controls, without significant difference (P>0.05). The erectile function was assessed with a simple questionnaire including 16 questions, such as sexual libido, general erectile function, nocturnal penile erection, erectile function during foreplay without sexual life, erectile function during audio-video sexual stimulation, confidence, depressions, etc. The patients filled "yes" or "no" in the blank of the questionnaire according to their erectile function. The frequency distributions of each question between the two groups were analyzed with chi-square test of four-fold table. RESULTS: Compared with normal control group, the frequency distributions of 13 questions in ED-NS group were significantly different, such as sexual libido (χ²=35.891, P<0.05), confidence of erection (χ²=75.608, P<0.05), general erectile function(χ²=54.433, P<0.05), nocturnal penile erection(χ²=29.815, P<0.05), erectile function during foreplay without sexual life(χ²=21.211, P<0.05), confidence of erection during foreplay without sexual life(χ²=70.445, P<0.05), erectile function during audio-video sexual stimulation(χ²=34.422, P<0.05), etc. But in both groups, some patients didn't have masturbation so that they couldn't answer the masturbation questions. CONCLUSION: We have created a new conception about the patients without sexual life, erectile dysfunction-no sexual life, which defines it as the inability to have enough erection hardness and duration so as to have enough confidence in attempting sexual intercourse for more than six months. We will establish a special index of the ED-NS questionnaire to assess erectile function of ED-NS. Further study is needed.

[The association of non-specific chronic inflammation with dendritic cells in a rat model of chronic obstructive pulmonary disease].

OBJECTIVE: To evaluate the changes in the number and maturation of lung tissue dendritic cells (DCs) and to assess the chronic inflammation in a cigarette smoke-induced COPD model in rats. METHODS: Thirty male F344 rats were randomly divided into 3 groups (n = 10): a control group, a smoke-exposure group and a smoking cessation group. Rat lung pathomorphological changes were observed by hematoxylin-eosin (HE) stain. Lung tissue CD(11c)(+) DCs, CD(86)(+) DCs and CD(8)(+) T cell numbers were observed by immunohistochemistry method. Flow cytometry was used for detection of CD(11c)(+)/CD(86)(+) DCs and CD(11c)(+)/MHCII(+) DCs proportions. RESULTS: The airway inflammatory pathological score and the mean linear intercept (MLI) obtained from he smoke-exposure group and the smoking cessation group (390 ± 33, 324 ± 28) and [(68 ± 11) µm, (58 ± 9) µm] were higher than those in the control group (56 ± 13) and (36 ± 6) µm (F = 459.85 and 34.03, all P < 0.05). In the smoke-exposure group and the smoking cessation group, the positive rate of CD(11c)(+) DCs [(1.47 ± 0.12)%, (1.30 ± 0.17)%], and the positive rate of CD(86)(+) DCs [(1.26 ± 0.18)%, (1.02 ± 0.08)%] were higher than those in the control group [(0.96 ± 0.08)%, (0.65 ± 0.03)%] (F = 6.55 and 30.26, all P < 0.05), but there was no significant difference between the smoke-exposure group and the smoking cessation group (t = 1.10 and 1.47, all P>0.05). In the smoke-exposure group and the smoking cessation group, CD(8)(+) T positive rate [(2.72 ± 0.15)%, (2.35 ± 0.23)%] was higher than that in the control group [(1.39 ± 0.11)%] (F = 16.07, P < 0.05). CD(11c)(+)/CD(86)(+) DCs and CD(11c)(+)/MHCII(+)DCs percentages [(5.5 ± 0.4)%, (4.8 ± 0.4)%], [(4.2 ± 0.4)%, (3.3 ± 0.3)%] decreased in the smoke-exposure group and the smoking cessation group as compared to the control group [(8.0 ± 0.5)%, (6.1 ± 0.5)%] (F = 14.34 and 12.82, all P < 0.05). There was no significant difference between all the above index from the smoke-exposure group and the smoking cessation group (t = 1.10 and 2.11, all P > 0.05). CONCLUSIONS: Cigarette smoke exposure induced increased DCs transmigrated and influenced the maturation of DCs in COPD rats. Even after smoking cessation, non-specific chronic inflammation was still present, suggesting that DCs number and maturation abnormality may be involved in the chronic inflammation of COPD.

Enhanced Strength and Plasticity of CoCrNiAl0.1Si0.1 Medium Entropy Alloy via Deformation Twinning and Microband at Cryogenic Temperature.

The synthesis of lightweight yet strong-ductile materials has been an imperative challenge in alloy design. In this study, the CoCrNi-based medium-entropy alloys (MEAs) with added Al and Si were manufactured by vacuum arc melting furnace subsequently followed by cool rolling and anneal process. The mechanical responses of CoCrNiAl0.1Si0.1 MEAs under quasi-static (1 × 10-3 s-1) tensile strength showed that MEAs had an outstanding balance of yield strength, ultimate tensile strength, and elongation. The yield strength, ultimate tensile strength, and elongation were increased from 480 MPa, 900 MPa, and 58% at 298 K to 700 MPa, 1250 MPa, and 72% at 77 K, respectively. Temperature dependencies of the yield strength and strain hardening were investigated to understand the excellent mechanical performance, considering the contribution of lattice distortions, deformation twins, and microbands. Severe lattice distortions were determined to play a predominant role in the temperature-dependent yield stress. The Peierls barrier height increased with decreasing temperature, owing to thermal vibrations causing the effective width of a dislocation core to decrease. Through the thermodynamic formula, the stacking fault energies were calculated to be 14.12 mJ/m2 and 8.32 mJ/m2 at 298 K and 77 K, respectively. In conclusion, the enhanced strength and ductility at cryogenic temperature can be attributed to multiple deformation mechanisms including dislocations, extensive deformation twins, and microbands. The synergistic effect of multiple deformation mechanisms lead to the outstanding mechanical properties of the alloy at room and cryogenic temperature.