Serum folic acid levels and erectile dysfunction: A meta-analysis and systematic review.

The aim of this study was to assess the relationship between serum folic acid (FA) levels and erectile dysfunction (ED) through a meta-analysis. A research was conducted in MEDLINE via PubMed, Cochrane Library, EMBASE and Web of Science up to 22 November 2020 to identify studies related to FA and ED. Two authors independently screened the literature, evaluated methodological quality and extracted the data. We used RevMan5.3 and STATA 14.0 for meta-analysis. A total of six studies including 1,842 participants were included, and the results showed that the FA levels in the non-ED group were significantly higher than those in the ED group (MD = 3.37, 95% CI 1.49-5.52, p = 0.004). Subgroup analysis indicated that with the increase in ED severity, the difference in FA levels between groups was more obvious (MD: 1.99 vs. 4.63 vs. 5.63). The differences in FA levels between groups seem more significant in the younger group (MD = 4.87, 95% CI 2.58-6.89, p < 0.001) than in the older group (MD = 3.15, 95% CI 2.21-4.08, p < 0.001). In conclusion, FA deficiency is closely related to ED, and the degree of FA deficiency may reflect the severity of ED. In addition, the association seems to be more pronounced in the younger group.

Association between folic acid, homocysteine, vitamin B12 and erectile dysfunction-A cross-sectional study.

To evaluate the relationship between serum levels of folic acid (FA), homocysteine (HCY), vitamin B12 (B12) and erectile dysfunction (ED) and to explore their internal relationships. The study included 134 ED patients and 50 healthy controls. ED was assessed using IIEF-5 scores. ED group had lower median FA (6.08 versus 10.21; p < .001) and B12 (256.0 versus 337.5; p < .001) levels, and higher median HCY (11.4 versus 7.95; p < .001) levels, and these differences seemed to be more pronounced in the younger participants (age < 35 yr). FA decreased with the severity of ED (7.52 versus 6.15 versus 5.49 versus 3.97; p < .001), while HCY increased (10.35 versus 11.8 versus 12.9 versus 15; p < .001). Smoking and shift work were associated with lower FA levels. Multivariate analysis showed that serum FA and HCY revealed significant relation with ED. ROC analysis showed that FA ≤ 8.84 and HCY ≥ 10.35 were the best cut-off values for ED diagnosis. Both FA (r = -0.703, p < .001) and B12 (r = -0.576, p < .001) were negatively correlated with HCY. In conclusion, low FA levels and high HCY levels might be independent risk factors for ED. Low serum FA and B12 levels might co-cause high HCY levels and lead to ED.

Risk Factors of Infectious Complications following Ureteroscopy: A Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate the potential risk factors of infectious complications following ureteroscopy (URS). MATERIALS AND METHODS: Studies reporting risk factors of infectious complications following URS were searched via PubMed, EMBASE, Cochrane Library, and Web of Science databases up to August 30, 2019. OR or mean difference (MD) with 95% CI was calculated to assess the potential risk factors. RESULTS: A total of 14 studies containing 9,532 patients were included. Positive preoperative urine culture was the most significant risk factor (OR 2.95, 95% CI 1.96-4.43, p < 0.01), followed by female gender (OR 1.95, 95% CI 1.48-2.57, p < 0.01), diabetes mellitus (OR 1.55, 95% CI 1.13-2.13, p < 0.01), pre- and postoperative stent (OR 1.53, 95% CI 1.11-2.11, p = 0.01, OR 1.44, 95% CI 1.01-2.03, p = 0.04, relatively), and extended operative time (MD -11.54, 95% CI -16.10 to 6.98, p < 0.01). Age (MD -2.59, 95% CI -5.36 to 0.18, p = 0.07), cumulative stone diameter (MD -1.54; 95% CI -4.63 to 1.55, p = 0.33), and renal insufficiency (OR 1.22, 95% CI 0.80-1.88, p = 0.36) were not the potential risk factors. CONCLUSION: The prevalence of infectious complications following URS was correlated with female gender, diabetes mellitus, preoperative urine culture, pre- and postoperative stent insertion, and extended operative time. Publication bias and high heterogeneity were observed in some risk factors. Further studies are warranted for a valid conclusion.

Efficacy and Safety of Transurethral Laser Surgery Versus Transurethral Resection for Non-Muscle-Invasive Bladder Cancer: A Meta-Analysis and Systematic Review.

OBJECTIVE: To compare the efficacy and safety of transurethral laser surgery and transurethral resection of a bladder tumor (TURBT) for non-muscle-invasive bladder cancer (NMIBC). MATERIAL AND METHODS: A research was carried out in Medline via PubMed, EMBASE, the Cochrane Library, and Web of Science up to October 20, 2019, to identify articles related to transurethral laser surgery and TURBT for NMIBC. All analyses were done using RevMan5.3 and Stata14. RESULTS: A total of 17 studies involving 2,439 participants were included. The analysis showed no significant difference in operation times (mean difference = -0.2; 95% CI -2.29 to 1.89; p = 0.85) or occurrences of urethral stricture (OR = 0.7; 95% CI 0.24-2.06; p = 0.52). Transurethral laser surgery was associated with a lower incidence of obturator nerve reflex (OR = 0.04; 95% CI 0.02-0.09; p < 0.00001) and bladder perforation (OR = 0.09; 95% CI 0.04-0.23; p < 0.00001), a higher rate of detrusor muscle acquisition (OR = 5.28; 95% CI 2.42-11.49; p < 0.0001), shorter catheterization (mean difference = -1.05; 95% CI -1.41 to -0.68; p < 0.00001) and hospitalization times (mean difference = -0.96; 95% CI -1.59 to -0.33; p = 0.003), and lower rates of bladder irrigation (OR = 0.21; 95% CI 0.13-0.35; p < 0.00001) and recurrence both at 12 months (OR = 0.66; 95% CI 0.48-0.9, p = 0.008) and at 24 months (OR = 0.6; 95% CI 0.41-0.86; p = 0.005). CONCLUSIONS: Transurethral laser surgery for NMIBC, as compared to TURBT, is associated with a lower incidence of complications, a lower recurrence rate, and faster postoperative recovery.

STAT1 activation represses IL-22 gene expression and psoriasis pathogenesis.

IL-22 plays an important role in tissue repair and inflammatory responses, and is implicated in the pathogenesis of psoriasis, ulcerative colitis, as well as liver and pancreas damage. The molecular mechanisms of its regulation have been actively studied. Here, we show that the differential regulation of IL-22 expression in CD4+ T cells by IL-6 and IL-27 was detected rapidly after stimulation. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays demonstrated that both STAT1 and STAT3 directly bind to the STAT responsive elements (SRE) of the IL-22 promoter, and the balance between activated STAT3 and STAT1 determines IL-22 promoter activities. We further show that the heterozygous mutation of the STAT1 gene results in elevated levels of IL-22 production and induces much severer skin inflammation in an imiquimod (IMQ)-induced murine psoriasis model. Together, our results reveal a novel regulatory mechanism of IL-22 expression by STAT1 through directly antagonizing STAT3, and the importance of the balance between STAT3 and STAT1 in IL-22 regulation and psoriasis pathogenesis.

Regulatory T cell migration during an immune response.

CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells migrate into both inflammatory sites and draining lymph nodes (LNs) during an immune response, and have unique and overlaping functions in each location. Current studies suggest that Treg cells in draining LNs and inflamatory sites may not simply be a division of labor, but rather Treg cells migrate in a coordinated fashion between peripheral tissues and draining LNs. Trafficking between inflammatory sites and draining LNs is not only crucial for Treg cells to act, but also for them to acquire optimal immune regulatory activities. Furthermore, recent work has revealed that T helper (Th)1, Th2 and Th17 cell master transcription factors control Treg cell function by regulating genes important for Treg cell migration and suppression, and consequently affect disease pathogenesis.

Regulatory T cell induction, migration, and function in transplantation.

Regulatory T cells (Treg) are important in maintaining immune homeostasis and in regulating a variety of immune responses, making them attractive targets for modulating immune-related diseases. Success in using induction or transfer of Treg in mice to mediate transplant tolerance suggests Treg-based therapies as mechanisms of long-term drug-free transplant tolerance in human patients. Although more work is needed, critical analyses suggest that key factors in Treg induction, migration, and function are important areas to concentrate investigative efforts and therapeutic development. Elucidation of basic biology will aid in translating data gleaned from mice to humans so that Treg therapies become a reality for patients.

Functional specialization of islet dendritic cell subsets.

Dendritic cells (DC) play important roles in both tolerance and immunity to ß cells in type 1 diabetes. How and why DC can have diverse and opposing functions in islets remains elusive. To answer these questions, islet DC subsets and their specialized functions were characterized. Under both homeostatic and inflammatory conditions, there were two main tissue-resident DC subsets in islets, defined as CD11b(lo/-)CD103(+)CX3CR1(-) (CD103(+) DC), the majority of which were derived from fms-like tyrosine kinase 3-dependent pre-DC, and CD11b(+)CD103(-)CX3CR1(+) (CD11b(+) DC), the majority of which were derived from monocytes. CD103(+) DC were the major migratory DC and cross-presented islet-derived Ag in the pancreatic draining lymph node, although this DC subset displayed limited phagocytic activity. CD11b(+) DC were numerically the predominant subset (60-80%) but poorly migrated to the draining lymph node. Although CD11b(+) DC had greater phagocytic activity, they poorly presented Ag to T cells. CD11b(+) DC increased in numbers and percentage during T cell-mediated insulitis, suggesting that this subset might be involved in the pathogenesis of diabetes. These data elucidate the phenotype and function of homeostatic and inflammatory islet DC, suggesting differential roles in islet immunity.

Impact of perioperative blood transfusion on prognosis after nephrectomy in patients with renal cell carcinoma: A meta-analysis and systematic review.

BACKGROUND: Perioperative blood transfusion (PBT) has been associated with worse prognosis in several malignancies. For renal cell carcinoma (RCC), the effect of PBT is still debated. OBJECTIVE: To evaluate the impact of PBT on prognosis after nephrectomy in patients with RCC. METHODS: This study is A systematic review and meta-analysis of published article data (PRISMA protocol) for literature related to PBT and RCC through extensive search of EMBASE, Medline via PubMed, Web of Science and Cochrane Library, language limited to English, with no time constraint until May 20, 2022. We pooled the results of multivariable cox regression analyses from each study, with subgroup analyses by dose and timing of transfusion. All analyses were done using Stata14. RESULTS: A total of 12 studies involving 27,683 participants were included. Our meta-analysis pooled the results of multivariable cox regression analysis in each study, showing that PBT is associated with higher overall Mortality (OM; hazard ratio [HR] = 1.34, 1.23-1.44), cancer-specific mortality (CSM; HR = 1.35, 1.20-1.51), and disease recurrence (HR = 1.54, 1.18-1.89). when only patients with nonmetastatic RCC were included, PBT was still associated with higher OM (HR = 1.29, 1.11-1.47) and disease recurrence (HR = 1.58, 1.18-1.98), but the association with CSM (HR = 1.26, 0.99-1.52) was not statistically significant. In subgroup analysis by transfusion dose, small (1-2) units of PBT were not associated with CSM (HR = 1.84, 0.95-2.73), but large (≥3) units were associated with higher CSM (HR = 2.98, 1.74-4.22) and disease recurrence (HR = 1.99, 1.31-2.67). Each additional unit of PBT resulted in a higher CSM (HR = 1.07, 1.04-1.10). In subgroup analysis by transfusion timing, intraoperative transfusion was associated with higher CSM and disease recurrence, but postoperative transfusion was not. CONCLUSIONS: PBT is associated with higher OM, CSM and disease recurrence. This adverse effect seems to be particularly significant in high-dose intraoperative transfusion. It is necessary to limit the overuse of PBT, especially high-dose intraoperative transfusion, in order to improve the prognosis of patients undergoing nephrectomy for RCC.

Association of reproductive lifespan and age at menopause with depression: Data from NHANES 2005-2018.

BACKGROUND: The association between reproductive lifespan and depression in older women is unclear. We conducted this analysis to explore whether a shorter reproductive lifespan is associated with higher odds of depression, while also considering the age at menarche and age at menopause. METHODS: This observational study used data from the National Health and Nutrition Examination Survey (NHANES), which was conducted between 2005 and 2018. Reproductive lifespan was defined as years from age at menarche to age at menopause. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression models were used to explore the relationship between the association of reproductive life span, age at menarche and age at menopause with the incidence of depression. RESULTS: Totally, 2947 patients aged 60 and above were enrolled in the trial, with 241 individuals (8.18 %) diagnosed with depression. Higher odds of depression were found to be significantly correlated with a shorter reproductive lifespan [Odds Ratio (OR) = 0.95, 95 % Confidence interval (CI) = 0.92-0.98] or an earlier ager at menopause (OR = 0.95, 95 % CI = 0.92-0.99), according to the results of multivariable logistic regression analysis after full adjustment. Subgroup analysis and interaction tests indicated a similar association. LIMITATIONS: The cross-sectional study could not yield any conclusions regarding causality. CONCLUSION: In this large cross-sectional study, our result suggested that populations with a shorter reproductive lifespan or an earlier age at menopause were significantly more likely to have depressive symptoms in older U.S. women. Further large-scale prospective studies are warranted for a comprehensive analysis of the role of the reproductive lifespan and age at menopause in depression.

Stat4 is critical for the balance between Th17 cells and regulatory T cells in colitis.

Th17 play a central role in autoimmune inflammatory responses. Th1 are also necessary for autoimmune disease development. The interplay of Th1 signals and how they coordinate with Th17 during inflammatory disease pathogenesis are incompletely understood. In this study, by adding Stat4 deficiency to Stat6/T-bet double knockout, we further dissected the role of Stat4 in Th1 development and colitis induction. We showed that in the absence of the strong Th2 mediator Stat6, neither Stat4 nor T-bet is required for IFN-γ production and Th1 development. However, addition of Stat4 deficiency abolished colitis induced by Stat6/T-bet double-knockout cells, despite Th1 and Th17 responses. The failure of colitis induction by Stat4/Stat6/T-bet triple-knockout cells is largely due to elevated Foxp3(+) regulatory T cell (Treg) development. These results highlight the critical role of Stat4 Th1 signals in autoimmune responses in suppressing Foxp3(+) Treg responses and altering the balance between Th17 and Tregs to favor autoimmune disease.

Association between erectile dysfunction and Helicobacter pylori, folic acid, vitamin B12, and homocysteine: a cross-sectional study.

Background: Previous studies have shown that Helicobacter pylori (Hp) infection is associated with erectile dysfunction (ED), but the mechanism is unclear. Aim: To assess the relationship between ED and Hp, folic acid (FA), vitamin B12 (B12), and homocysteine (HCY). Methods: This study included 84 patients with ED and 42 healthy men. We adopted an IIEF-5 score <21 (5-item International Index of Erectile Function) as the diagnostic criterion for ED, and the RigiScan monitoring device was used to preliminarily screen for and rule out psychogenic ED. Outcomes: Levels of Hp immunoglobulin G (Hp-IgG) titer, FA, B12, and HCY were compared between the ED group and the non-ED group, and the correlation between the indicators was evaluated. Results: The median Hp-IgG titer was higher in the ED group than the control group (32.34 vs 20.88, P < .001). The ED group had lower median levels of B12 (195 vs 338, P < .001) and FA (4.66 vs 10.31, P < .001) and a higher median level of HCY (12.7 vs 8.1, P < .001). Multivariate logistic regression analysis showed that the level of FA (odds ratio, 0.111; 95% CI, 0.031-0.399; P < .001) was an independent risk factor for ED. Specifically, FA level was significantly higher in the moderate ED group than the severe ED group, which had a higher median Hp-IgG titer and lower level of B12; although not significant, this was still a clinical trend. Hp-IgG titer was negatively correlated with levels of FA (r = -0.601, P < .001) and B12 (r = -0.434, P < .001) and with the IIEF-5 score (r = -0.382, P < .001) and positively correlated with HCY (r = 0.69, P < .001). Clinical Implications: The ED group had higher levels of Hp-IgG titer and HCY and lower levels of B12 and FA. Strengths and Limitations: This study is the first to link Hp infection, FA, B12, and HCY and further explain the relationship between these indicators and the underlying pathologic mechanisms that jointly cause ED. The limitation is that our study was based on Hp-IgG titers, which do not necessarily represent the full extent of Hp infection, despite the avoidance of invasive testing. Conclusion: Hp infection might lead to decreased FA and B12 and then increased HCY, which might be a mechanism leading to ED. Hp eradication or FA and B12 supplementation might have certain clinical value in the treatment of vascular ED.

Identify AGAP2 as prognostic biomarker in clear cell renal cell carcinoma based on bioinformatics and IHC staining.

Background: Arf GTPase-activating proteins are aberrantly expressed in a variety of tumors, but their role in clear cell renal cell carcinoma (ccRCC) was unclear. Exploring the biological role of Arf GAP with GTP binding protein like domain, Ankyrin repeat and PH domain 2 (AGAP2) in ccRCC could improve our understanding on the aggressiveness and immune relevance of ccRCC. Methods: The expression of AGAP2 was analyzed based on the Cancer Genome Atlas (TCGA) database and verified in ccRCC samples using immunohistochemistry. The association between AGAP2 and clinical cancer stages was explored by TCGA dataset and UALCAN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to analyze the biological functions of AGAP2-related genes. Moreover, the relationship between AGAP2 and immune cell infiltration was investigated with TIME and TCGA dataset. Results: Compared to normal tissues, AGAP2 was upregulated in ccRCC tissues. Higher expression of AGAP2 was associated with clinical cancer stages, TNM stages, pathologic stages, and status. Prognostic analysis on AGAP2 showed that AGAP2 overexpression was associated with KIRC overall survival (OS) reduction (P = 0.019). However, higher expression of AGAP2 may improve the OS of CESC (P = 0.002), THYM (P = 0.006) and UCEC (P = 0.049). GO and KEGG analysis showed that AGAP2-related genes was related to T cell activation, immune activity and PD-L1 expression and PD-1 checkpoint pathway. Furthermore, our study showed that AGAP2 were significantly associated with T cells, Cytotoxic cells, Treg, Th1 cells, CD8 T cells, T helper cells. And AGAP2 expression level affected the abundance of immune cells infiltration. The infiltrating level of immune cells was different between the AGAP2 high-expression and low-expression groups. Conclusion: The expression of AGAP2 in ccRCC was higher than that in normal kidney tissues. It was significantly associated with clinical stage, poor prognosis, and immune cell infiltration. Therefore, AGAP2 may become an important component for ccRCC patients who receive precision cancer therapy and may be a promising prognostic biomarker.

Development and external validation of a novel nomogram to predict prostate cancer in biopsy-naïve patients with PSA <10 ng/ml and PI-RADS v2.1 = 3 lesions.

OBJECTIVE: To develop and externally validate a novel nomogram in biopsy-naïve patients with prostate-specific antigen (PSA) <10 ng/ml and PI-RADS v2.1 = 3 lesions. METHODS: We retrospectively collected 307 men that underwent initial biopsy from October 2015 to January 2022 in Cohort 1 (The First Affiliated Hospital of Soochow University). External cohort (Cohort 2, Kunshan Hospital) included 109 men that met our criteria from July 2016 to June 2021. By Slicer-3D Software, the volume of all lesions was divided into two subgroups (PI-RADS v2.1 = 3a and 3b). Logistic regression analysis was performed to screen for variables and construct nomogram by analyzing clinical data from Cohort 1. Receiver operating characteristics curve analysis, calibration plot and decision curve analysis (DCA) were plotted to validate the nomogram in external cohort. RESULTS: A total of 70 (22.8%) patients was diagnosed with prostate cancer in Institution 1. Among them, 34 (11.1%) had clinically significant prostate cancer (csPCa). Age, prostate-specific antigen density, digital rectal examination, PI-RADS v2.1 = 3 subgroups (3a and 3b) and apparent diffusion coefficient (ADC, <750 mm2 /s) were predictive factors for prostate cancer (PCa) and csPCa. High area under the curve of the nomogram was found in Cohort 1 and Cohort 2 for PCa (0.857 vs. 0.850) and for csPCa (0.896 vs. 0.893). Calibration curves showed excellent agreement between the predicted probability and actual risk for the models in internal and external validation. The DCA demonstrated net benefit of our nomogram. CONCLUSION: Until now, this is the first nomogram that predicts PCa and csPCa in biopsy-naïve patients with PSA <10 ng/ml and PI-RADS v2.1 = 3 lesions. Furthermore, PI-RADS v2.1 = 3 subgroups were considered to be an independent risk factor in our model. Our nomogram may assist urologists in biopsy decision making for these so-called "double gray zone" patients.

Isolation of a potential probiotic strain Bacillus amyloliquefaciensLPB-18 and identification of antimicrobial compounds responsible for inhibition of food-borne pathogens.

This study was carried out to screen a potential probiotic microbe with broad-spectrum antagonistic activity against food-borne pathogens and identify the antimicrobial compounds. Based on morphological and molecular analysis, a new Bacillus strain with the ability to produce effective antimicrobial agents was isolated from the breeding soil of earthworms and identified as having a close evolutionary footprint to Bacillus amyloliquefaciens. The antimicrobial substances produced by B. amyloliquefaciens show effective inhibition of Aspergillus flavus and Fusarium oxysporum in an agar diffusion assay. Antimicrobial agents were identified as a series of fengycin and its isoforms (fengycin A and fengycin B) after being submitted to RT-HPLC and MALDI-TOF MS analyses. To evaluate the probiotic activity of the B. amyloliquefaciens, antibiotic safety and viability of the isolated strain in a simulated gastrointestinal environment were carried out. The safety test result revealed that strain LPB-18 is susceptible to multiple common antibiotics. Moreover, acidic condition and bile salts assay were carried out, and the results revealed that it couble be a potential probiotic microbe B. amyloliquefaciens LPB-18 is good choice for biological strains in agricultural commodities and animal feedstuffs.

Can a reresection be avoided after initial en bloc resection for high-risk nonmuscle invasive bladder cancer? A systematic review and meta-analysis.

Background: This study aims to evaluate the effectiveness of en bloc resection for patients with nonmuscle invasive bladder cancer (NMIBC) and explore whether a reresection can be avoided after initial en bloc resection. Material and methods: We conducted research in PubMed, EMBASE, Cochrane Library, and Web of Science up to October 12, 2021, to identify studies on the second resection after initial en bloc resection of bladder tumor (ERBT). R software and the double arcsine method were used for data conversion and combined calculation of the incidence rate. Results: A total of 8 studies involving 414 participants were included. The rate of detrusor muscle in the ERBT specimens was 100% (95%CI: 100%-100%), the rate of tumor residual in reresection specimens was 3.2% (95%CI: 1.4%-5.5%), and the rate of tumor upstaging was 0.3% (95%CI: 0%-1.5%). Two articles compared the prognostic data of the reresection and non-reresection groups after the initial ERBT. We found no significant difference in the 1-year recurrence-free survival (RFS) rate (OR = 1.44, 95%CI: 0.67-3.09, P = 0.35) between the two groups nor in the rate of tumor recurrence (OR = 0.72, 95%CI: 0.44-1.18, P = 0.2) or progression (OR = 0.98, 95%CI: 0.33-2.89, P = 0.97) at the final follow-up. Conclusions: ERBT can almost completely remove the detrusor muscle of the tumor bed with a very low postoperative tumor residue and upstaging rate. For high-risk NMIBC patients, an attempt to appropriately reduce the use of reresection after ERBT seems to be possible.

A Modified Disposable Circumcision Suture Device with Application of Plastic Sheet to Avoid Severe Bleeding After Circumcision.

PURPOSE: To evaluate the effectiveness of a modified disposable circumcision suture device (DCSD) with application of plastic sheet to avoid severe bleeding after circumcision and compare the surgical effects and other postoperative complications of two DCSDs. MATERIALS AND METHODS: A total of 943 excess foreskin patients from January 2018 to January 2020 who underwent circumcision using two different DCSDs were recruited. Preoperative characteristics (patient age, height and weight), main surgical outcomes (surgical time, intraoperative blood loss, incision healing time) and postoperative complications (postoperative hemorrhage and hematoma rate, edema rate, incision infection rate, residual staples rate) were collected and analyzed. Patients' "satisfaction" or "dissatisfaction" was also investigated. RESULTS: Preoperative characteristics showed no significant statistical difference. The modified DCSD group has a lower intraoperative bleeding, postoperative hemorrhage or hematoma rate and residual staples rate compared with the conventional group. Incision healing time and incision infection rate between the two groups were similar. Nevertheless, conventional group has a shorter surgical time, a lower edema rate and a higher satisfaction rate. CONCLUSION: The modified DCSD with application of plastic sheet can avoid severe bleeding after circumcision effectively and can be served as a new choice for circumcision.

H1N1 influenza virus dose dependent induction of dysregulated innate immune responses and STAT1/3 activation are associated with pulmonary immunopathological damage.

Influenza A virus (IAV) infection poses a substantial challenge and causes high morbidity and mortality. Exacerbated pulmonary inflammatory responses are the major causes of extensive diffuse alveolar immunopathological damage. However, the relationship between the extent of cytokine storm, neutrophils/macrophages infiltration, and different IAV infection dose and time still needs to be further elucidated, and it is still unclear whether the signal transduction and transcriptional activator 1/3 (STAT1/3) signalling pathway plays a beneficial or detrimental role. Here, we established a mouse model of high- and low-dose pH1N1 infection. We found that pH1N1 infection induced robust and early pathological damage and cytokine storm in an infection dose- and time-dependent manner. High-dose pH1N1 infection induced massive and sustained recruitment of neutrophils as well as a higher ratio of M1:M2, which may contribute to severe lung immunopathological damage. pH1N1 infection activated dose- and time-dependent STAT1 and STAT3. Inhibition of STAT1 and/or STAT3 aggravated low-dose pH1N1 infection, induced lung damage, and decreased survival rate. Appropriate activation of STAT1/3 provided survival benefits and pathological improvement during low-dose pH1N1 infection. These results demonstrate that high-dose pH1N1 infection induces robust and sustained neutrophil infiltration, imbalanced macrophage polarization, excessive and earlier cytokine storm, and STAT1/3 activation, which are associated with pulmonary dysregulated proinflammatory responses and progress of acute lung injury. The severe innate immune responses may be the threshold at which protective functions give way to immunopathology, and assessing the magnitude of host innate immune responses is necessary in adjunctive immunomodulatory therapy for alleviating influenza-induced pneumonia.

c-Maf regulates IL-10 expression during Th17 polarization.

IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. Gene array analysis on Stat6 and T-bet double-deficient Th17 cells identified the Th2 transcription factor c-Maf to be synergistically up-regulated by IL-6 plus TGFbeta and associated with Th17 IL-10 production. Both c-Maf and IL-10 induction during Th17 polarization depended on Stat3, but not Stat6 or Stat1, and mechanistically differed from IL-10 regulation by Th2 or IL-27 signals. TGFbeta was also synergistic with IL-27 to induce c-Maf, and it induced Stat1-independent IL-10 expression in contrast to IL-27 alone. Retroviral transduction of c-Maf was able to induce IL-10 expression in Stat6-deficient CD4 and CD8 T cells, and c-Maf directly transactivated IL-10 gene expression through binding to a MARE (Maf recognition element) motif in the IL-10 promoter. Taken together, these data reveal a novel role for c-Maf in regulating T effector development, and they suggest that TGFbeta may antagonize Th17 immunity by IL-10 production through c-Maf induction.

Comparison of Retzius-Sparing Robot-Assisted Radical Prostatectomy vs. Conventional Robot-Assisted Radical Prostatectomy: An Up-to-Date Meta-Analysis.

Background: The Retzius space-sparing robot-assisted radical prostatectomy (RS-RARP) has shown better results in urinary continence, but its efficacy and safety compared to conventional robot-assisted radical prostatectomy (c-RARP) remain controversial. Material and Methods: A research was conducted in Medline via PubMed, Cochrane Library, EMBASE, and Web of Science up to January 4, 2021, to identify studies comparing RS-RARP to c-RARP. We used RevMan 5.3 and STATA 14.0 for meta-analysis. Results: A total of 14 studies involving 3,129 participants were included. Meta-analysis showed no significant difference in positive surgical margins (PSMs), but the RS-RARP group had significantly higher PSM rates in the anterior site [odds ratio (OR) = 2.25, 95% CI: 1.22-4.16, P = 0.01]. Postoperative continence in RS-RARP group at 1 month (OR = 5.72, 95% CI: 3.56-9.19, P < 0.01), 3 months (OR = 6.44, 95% CI: 4.50-9.22, P < 0.01), 6 months (OR = 8.68, 95% CI: 4.01-18.82, P < 0.01), and 12 months (OR = 2.37, 95% CI: 1.20-4.70, P = 0.01) was significantly better than that in the c-RARP group. In addition, the RS-RARP group had a shorter console time (mean difference = -16.28, 95% CI: -27.04 to -5.53, P = 0.003) and a lower incidence of hernia (OR = 0.35, 95% CI: 0.19-0.67, P = 0.001). However, there were no significant differences in estimated blood loss, pelvic lymph node dissection rate, postoperative complications, 1-year-biochemical recurrence rate, and postoperative sexual function. Conclusions: Compared with c-RARP, RS-RARP showed better recovery of continence, shorter console time, and lower incidence of hernia. Although there was no significant difference in overall PSM, we suggest that the surgeon should be more careful if the lesion is in the anterior prostate.