Identification of differentially expressed genes, transcription factors, microRNAs and pathways in neutrophils of sepsis patients through bioinformatics analysis.

Sepsis has been recognized to be a life-threatening organ dysfunction caused by the dysregulation of the host response to infections. Our work aims to screen key biomarkers related to neutrophils in sepsis using bioinformatics analysis. For this purpose, the microarray datasets related to neutrophils in sepsis patients were downloaded from the Gene Expression Omnibus (GEO) database. According to the Bayesian test, the Limma package in R was used to screen differentially expressed genes (DEGs). Then, DEGs were uploaded to the DAVID online diagnostic tool for subsequent Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment on the selected DEGs. Next, protein-protein interaction (PPI) network was established based on the selected DEGs using the STRING website and the Cytoscape software. Furthermore, according to the function of the iRegulon plug-in in Cytoscape, our study further predicts and established regulatory networks related to transcription factors and regulatory genes. In addition, the miRWalk2.0 database was used to search for miRNA-DEG pairs, associated with the conduction of intersections of miRNAs predicted by TargetScan, Miranda, miRDB and RNA22 databases. Then, these miRNA-DEG pairs were also displayed in the form of a regulatory network through Cytoscape. Finally, two datasets were selected to verify the screened genes, regulatory factors, and miRNAs, to plot receiver operating characteristics (ROC) curves and compute the area under the curve (AUC) values. The results showed that AKT1, MMP9, ARG1, ETS1 targeting AKT1, and has-miR-124-3p targeting RPS6KA5 may have diagnostic value for patients with sepsis and septic shock. While further experimental studies are required to confirm their role in septic neutrophils.

Protective effects of P2X7R antagonist in sepsis-induced acute lung injury in mice via regulation of circ_0001679 and circ_0001212 and downstream Pln, Cdh2, and Nprl3 expression.

BACKGROUND: Sepsis induces pulmonary P2X7 receptor (P2X7 R) expression and P2X7 R-knockout reduced lung inflammation in mice. The present study investigated the expression of circular RNA (circRNA) and mRNA in sepsis-induced acute lung injury (ALI) treated with a P2X7 R antagonist. METHODS: Sepsis was induced by tracheal administration of lipopolysaccharide (LPS), and the mice were then divided into two groups: without [sepsis + dimethyl sulfoxide (DMSO)] or with P2X7 R antagonist treatment (sepsis + P2X7 A). Sham mice were administrated sterile normal saline. Serum levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, pathological changes, cell apoptosis and P2X7 R expression in lung were assessed, followed by RNA sequencing (RNA-seq) and bioinformatics analyses. A quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) was used to validate circRNAs and mRNAs. RESULTS: Compared to the sham group, LPS-induced sepsis produced obvious pathological changes in lung tissue, as well as increased apoptotic lung cells, serum TNF-α and IL-1ß levels, and P2X7 R expression; P2X7 R antagonism significantly ameliorated these changes. RNA-seq identified many dysregulated circRNAs and mRNAs during sepsis, whereas this changed with P2X7 R antagonism. RT-qPCR confirmed that Mus musculus (mmu)_circ_0001679, mmu_circ_0001212, phospholamban (Pln), cadherin-2 (Cdh2) and nitrogen permease regulator 3-like (Nprl3) expression were significantly increased in the sepsis + DMSO group compared to that in the sham group but were decreased in the sepsis + P2X7 A group compared to that in the sepsis + DMSO group. The circRNA-microRNA-mRNA coexpression network indicated that mmu_circ_0001679 may regulate Nprl3 and that mmu_circ_0001212 may similarly regulate Pln, Cdh2 and Nprl3 as a competing endogenous RNA. CONCLUSIONS: P2X7 R antagonism attenuates sepsis-induced ALI by inhibiting dysregulated expression of circRNA (circ_0001679, circ_0001212) and mRNA (Pln, Cdh2 and Nprl3).

Early post-operative serum albumin level predicts survival after curative nephrectomy for kidney cancer: a retrospective study.

BACKGROUND: Previous studies have shown that albumin-related systemic inflammation is associated with the long-term prognosis of cancer, but the clinical significance of an early (≤ 7 days) post-operative serum albumin level has not been well-documented as a prognostic factor in patients with renal cell cancer. METHODS: We retrospectively included patients hospitalized for kidney cancer from January 2009 to May 2014. First, the receiver operating characteristic analysis was used to define the best cut-off of an early post-operative serum albumin level in determining the prognosis, from which survival analysis was performed. RESULTS: A total of 329 patients were included. The median duration of follow-up was 54.8 months. Patients with an early post-operative serum albumin level < 32 g/L had a significantly shorter median recurrence-free survival (RFS; 49.1 versus 56.5 months, P = 0.001) and median overall survival (OS; 52.2 versus 57.0 months, P = 0.049) than patients with an early post-operative serum albumin level ≥ 32 g/L. After adjusting for age, BMI, tumor stage, post-operative hemoglobin concentration, and pre-operative albumin, globulin, and hemoglobin levels, multivariate Cox regression showed that an early post-operative serum albumin level < 32 g/L was an independent prognostic factor associated with a decreased RFS (HR = 3.60; 95% CI,1.05-12.42 [months], P = 0.042) and decreased OS (HR = 9.95; 95% CI, 1.81-54.80 [months], P = 0.008). CONCLUSION: An early post-operative serum albumin level < 32 g/L is an independent prognostic factor leading to an unfavorable RFS and OS. Prospective trials and further studies involving additional patients are warranted.

Significance of MRI/Transrectal Ultrasound Fusion Three-Dimensional Model-Guided, Targeted Biopsy Based on Transrectal Ultrasound-Guided Systematic Biopsy in Prostate Cancer Detection: A Systematic Review and Meta-Analysis.

PURPOSE: To assess MRI/Transrectal Ultrasound (TRUS) fusion three-dimensional model-guided targeted biopsy (3D-Tb) versus TRUS-guided systematic biopsy (Sb) in detecting overall and high-Gleason-score (≥7) prostate cancer (PCa). METHODS: Pubmed and Web of science were searched. Studies with men having a suspicious lesion on MRI were included, which were divided into initial biopsy, previous negative biopsy, and mixed groups in meta-analysis. RESULTS: Totally 13 cohorts in 12 studies, with 3,225 men were included. In total population, 3D-Tb and Sb did not differ significantly in the PCa detection rate (43.1 vs. 42.6%, p = 0.36), but after excluding initial biopsy group, the superiority of 3D-Tb became significant (p = 0.01); 3D-Tb had a significantly higher detection rate of high-Gleason-score PCa compared to Sb (30.0 vs. 24.1%, p < 0.05); 3D-Tb plus Sb significantly improved the PCa detection rate based on Sb alone (52.7 vs. 42.6%, p < 0.05). CONCLUSIONS: In men with increased serum PSA and/or abnormal DRE and suspicious lesion on MRI but non-previous evidence of PCa, 3D-Tb plus Sb improves the PCa detection rate based on Sb alone. 3D-Tb alone has better performance in detecting high-Gleason-score PCa, and tends to have a higher PCa detection rate in population with previous negative biopsy compared to Sb.

Short-term efficacy and safety of low-intensity extracorporeal shock wave therapy in erectile dysfunction: a systematic review and meta-analysis.

AIM: The role of low-intensity extracorporeal shock wave therapy (LI-ESWT) in erectile dysfunction (ED) is not clearly determined. The purpose of this study is to investigate the short-term efficacy and safety of LI-ESWT for ED patients. MATERIALS AND METHODS: Relevant studies were searched in Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WANFANG and VIP databases. Effective rate in terms of International Index of Erectile Function-Erectile Function Domain (IIEF-EF) and Erectile Hardness Score (EHS) at about 1month after LI-ESWT was extracted from eligible studies for meta-analysis to calculate risk ratio (RR) of effective treatment in ED patients treated by LI-ESWT compared to those receiving sham-treatment. RESULTS: Overall fifteen studies were included in the review, of which four randomized controlled trials (RCTs) were for meta-analysis. Effective treatment was 8.31 [95% confidence interval (CI): 3.88-17.78] times more effective in the LI-ESWT group (n=176) than in the sham-treatment group (n=101) at about 1 month after the intervention in terms of EHS, while it was 2.50 (95% CI: 0.74-8.45) times more in the treatment group (n=121) than in the control group (n=89) in terms of IIEF-EF. Nine-week protocol with energy density of 0.09mJ/mm2 and 1500 pluses seemed to have better therapeutic effect than five-week protocol. No significant adverse event was reported. CONCLUSION: LI-ESWT, as a noninvasive treatment, has potential short-term therapeutic effect on patients with organic ED irrespective of sensitivity to PDE5is. Owing to the limited number and quality of the studies, more large-scale, well-designed and long-term follow-up time studies are needed to confirm our analysis.

[Low-intensity extracorporeal shockwave therapy for erectile dysfunction: An update].

Low-intensity extracorporeal shockwave therapy (LI-ESWT) is a novel treatment for erectile dysfunction (ED). With the property of angiogenesis, LI-ESWT acts on vasculogenic ED by improving penile hemodynamics and endothelial function. LI-ESWT is proved to be safe and effective in the treatment of vasculogenic ED in various prospective clinical studies, including randomized, double-blind, and sham-controlled trails. With more multi-centered larger-sample randomized controlled trials, LI-ESWT will play a valuable role in the treatment of ED.

The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial.

INTRODUCTION: Severe sepsis is associated with a high mortality rate despite implementation of guideline recommendations. Adjunctive treatment may be efficient and require further investigation. In light of the crucial role of immunologic derangement in severe sepsis, thymosin alpha 1 (Tα1) is considered as a promising beneficial immunomodulatory drug. The trial is to evaluate whether Tα1 improves 28-day all-cause mortality rates and immunofunction in patients with severe sepsis. METHODS: We performed a multicenter randomized controlled trial in six tertiary, teaching hospitals in China between May 12, 2008 and Dec 22, 2010. Eligible patients admitted in ICU with severe sepsis were randomly allocated by a central randomization center to the control group or Tα1 group (1:1 ratio). The primary outcome was death from any cause and was assessed 28 days after enrollment. Secondary outcomes included dynamic changes of Sequential Organ Failure Assessment (SOFA) and monocyte human leukocyte antigen-DR (mHLA-DR) on day 0, 3, 7 in both groups. All analyses were done on an intention-to-treat basis. RESULTS: A total of 361 patients were allocated to either the control group (n = 180) or Tα1 (n = 181) group. The mortalities from any cause within 28 days in the Tα1 group and control group were 26.0% and 35.0% respectively with a marginal P value (nonstratified analysis, P = 0.062; log rank, P = 0.049); the relative risk of death in the Tα1 group as compared to the control group was 0.74 (95% CI 0.54 to 1.02). Greater improvement of mHLA-DR was observed in the Tα1 group on day 3 (mean difference in mHLA-DR changes between the two groups was 3.9%, 95% CI 0.2 to 7.6%, P = 0.037) and day 7 (mean difference in mHLA-DR changes between the two groups was 5.8%, 95% CI 1.0 to 10.5%, P = 0.017) than in the control group. No serious drug-related adverse event was recorded. CONCLUSIONS: The use of Tα1 therapy in combination with conventional medical therapies may be effective in improving clinical outcomes in a targeted population of severe sepsis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00711620.

Diagnostic and prognostic value of autophagy-related key genes in sepsis and potential correlation with immune cell signatures.

Background: Autophagy is involved in the pathophysiological process of sepsis. This study was designed to identify autophagy-related key genes in sepsis, analyze their correlation with immune cell signatures, and search for new diagnostic and prognostic biomarkers. Methods: Whole blood RNA datasets GSE65682, GSE134347, and GSE134358 were downloaded and processed. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify autophagy-related key genes in sepsis. Then, key genes were analyzed by functional enrichment, protein-protein interaction (PPI), transcription factor (TF)-gene and competing endogenous RNA (ceRNA) network analysis. Subsequently, key genes with diagnostic efficiency and prognostic value were identified by receiver operating characteristic (ROC) curves and survival analysis respectively. The signatures of immune cells were estimated using CIBERSORT algorithm. The correlation between significantly different immune cell signatures and key genes was assessed by correlation analysis. Finally, key genes with both diagnostic and prognostic value were verified by RT-qPCR. Results: 14 autophagy-related key genes were identified and their TF-gene and ceRNA regulatory networks were constructed. Among the key genes, 11 genes (ATIC, BCL2, EEF2, EIF2AK3, HSPA8, IKBKB, NLRC4, PARP1, PRKCQ, SH3GLB1, and WIPI1) had diagnostic efficiency (AUC > 0.90) and 5 genes (CAPN2, IKBKB, PRKCQ, SH3GLB1 and WIPI1) were associated with survival prognosis (p-value < 0.05). IKBKB, PRKCQ, SH3GLB1 and WIPI1 had both diagnostic and prognostic value, and their expression were verified by RT-qPCR. Analysis of immune cell signatures showed that the abundance of neutrophil, monocyte, M0 macrophage, gamma delta T cell, activated mast cell and M1 macrophage subtypes increased in the sepsis group, while the abundance of resting NK cell, resting memory CD4+ T cell, CD8+ T cell, naive B cell and resting dendritic cell subtypes decreased. Most of the key genes correlated with the predicted frequencies of CD8+ T cells, resting memory CD4+ T cells, M1 macrophages and naive B cells. Conclusion: We identified autophagy-related key genes with diagnostic and prognostic value in sepsis and discovered associations between key genes and immune cell signatures. This work may provide new directions for the discovery of promising biomarkers for sepsis.

High level of neutrophil to lymphocyte ratio increases the risk of deep venous thrombosis in intensive care unit patients after oral cancer surgery: a retrospective study.

Background: The incidence of deep venous thrombosis (DVT) is higher in surgical patients, but there have been few studies on the risk factors of DVT in intensive care unit (ICU) patients after oral cancer surgery, particularly in relation to the inflammatory and nutritional scores, and intervene with these risk factors early may decrease the occurrence of DVT. Methods: We performed a retrospective study of adult patients who were admitted to ICU after undergoing radical resection of oral cancer and performed ultrasound detection for DVT within 1 week after surgery from April 2019 to July 2021. DVT was diagnosed by venous ultrasonography of the lower extremities. Preoperative inflammatory and nutritional scores, including neutrophil to lymphocyte ratio (NLR), plate to lymphocyte ratio (PLR), prognostic nutritional index (PNI) were retrospectively calculated according to test results before surgery. Clinical characteristics, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Caprini Risk Score (CRS), Charlson comorbidity index, anticoagulation therapy, and mechanical ventilation time (MVT) after admitted to ICU were obtained. The risk factors affecting DVT occurrence were analyzed by logistic regression, and the receiver operating characteristic (ROC) curve was used to analyze the value of the relevant indicators in evaluating DVT. Results: Among the 128 patients, 43 patients (33.6%) developed DVT. Compared with the non-DVT group, the preoperative glucose (GLU), postoperative D-dimer (P<0.05), and postoperative NLR (P<0.001) were higher in the DVT group than in the non-DVT group. In multivariate logistic analysis, NLR (P=0.001), postoperative D-dimer >5.57 µg/mL (P=0.002), GLU >5.15 mmol/L (P=0.025) was associated with DVT, and the areas under the curve (AUCs) of NLR in predicting DVT was 0.729. We also found that the DVT group had longer MVT and length of stay (LOS) than the non-DVT group, and correlation analysis indicated that NLR level was positively related with MVT (r=0.36; P<0.0001) and LOS (r=0.452; P<0.0001). Conclusions: A high level of NLR, indicative of a poor immunity and nutrition status, increases the risk of DVT in patients after oral cancer surgery, and improvement of immunity and nutrition status may help decrease the occurrence of postoperative DVT.

The effects of external diaphragmatic pacing on diaphragm function and weaning outcomes of critically ill patients with mechanical ventilation: a prospective randomized study.

Background: Diaphragmatic pacing can improve diaphragm function, which is beneficial for the prognosis of patients treated with prolonged mechanical ventilation (MV). While most previous studies have focused on the role of implanted diaphragm pacing (IDP), our study is the first to examine the effects of external diaphragmatic pacing (EDP) in mechanically ventilated patients. Specifically, the effect of EDP on diaphragm function, the success rate of weaning, the duration of MV (DMV), and the intensive care unit (ICU) length of stay (ILOS) were assessed. Methods: From September 2019 to December 2020, a total of 51 mechanically ventilated patients in the ICU of the Sun Yat-sen Memorial Hospital, Sun Yat-sen University were enrolled and randomly divided into an EDP group of 27 patients and a control group of 24 patients. The control group received routine treatment, and the EDP group received EDP treatment in addition to routine treatment. The diaphragm excursion (DE), diaphragm thickening fraction (DTF), DMV, ILOS, and average survival time were recorded to evaluate efficacy. Results: Patients treated with EDP had increased DE [exp(B) =1.86, 95% CI: 1.39 to 2.50, P<0.001] and DTF [exp(B) =1.35, 95% CI: 1.05 to 1.76, P=0.022], shortened weaning time (P=0.026) and prolonged average survival time (P<0.001) compared to patients who did not receive EDP therapy. Especially in cases with difficult weaning, the improvement of DE and DTF in the EDP treatment group was more obvious than that in the control group (P=0.013 and P=0.032). Moreover, the DTF upon attempted spontaneous breathing trial (SBT) was negatively correlated with the fraction of inspired oxygen (FiO2) [r=-0.54; 95% confidence interval (CI): -0.77 to -0.19; P=0.004], the arterial partial pressure of oxygen (PaO2) (r=-0.58; 95% CI: -0.79 to -0.25; P=0.001), the PaO2/FiO2 ratio (r=-0.52; 95% CI: -0.75 to -0.16; P=0.006), and the serum lactate concentration (Lac) (r=-0.39; 95% CI: -0.68 to 0.003; P=0.046). Conclusions: EDP treatment can effectively reduce the DMV and prolong the average survival time of mechanically ventilated patients. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900024096.

[Impact of hypophosphatemia on weaning from mechanical ventilation].

OBJECTIVE: To explore the influence of hypophosphatemia on weaning from mechanical ventilation. METHODS: An observational study was conducted. The medical records of 30 mechanical ventilated patients with hypophosphatemia admitted to intensive care unit of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to August 2020 were analyzed; another 60 mechanical ventilated patients with normophosphatemia around the same time were enrolled as controls by 1:2 case-control matching based on gender, age, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score. And then the duration of invasive mechanical ventilation, times of spontaneous breathing trial (SBT), the diaphragmatic ultrasonography movement indexes, and outcome of weaning and prognosis during hospitalization were compared between the two groups. Receiver operator characteristic curve (ROC curve) was plotted to calculate the areas under ROC curve (AUC) and cut-off values of serum phosphorus for successful weaning and hospital survival. The correlations between the diaphragmatic ultrasonography movement indexes and serum phosphorus were analyzed by Pearson partial correlation analysis. RESULTS: Compared with normophosphatemic group, the duration of invasive mechanical ventilation in hypophosphatemia group was significantly longer [days: 13.0 (7.0, 22.0) vs. 10.0 (5.5, 14.0), P < 0.05], and SBT attempts were more often [times: 3 (0, 5) vs. 1 (1, 2), P < 0.01], while the rate of successful weaning was lower (53.3% vs. 91.7%, P < 0.01), and the hospital mortality was higher (20.0% vs. 1.7%, P < 0.01). ROC curve analysis showed that serum phosphorus could predict successful weaning of mechanical ventilated patients, the AUC was 0.795, and the optimum cut-off value of serum phosphorus was 0.85 mmol/L with sensitivity of 73.2% and specificity of 84.2%. Serum phosphorus could predict hospital survival of mechanical ventilated patients, the AUC was 0.782, and the optimum cut-off value of serum phosphorus was 0.48 mmol/L with sensitivity of 81.9% and specificity of 85.7%. Compared with normophosphatemic group, diaphragm thickness at the end of inspiration (DTei), diaphragm thickness at the end of expiration (DTee), diaphragm thickening fraction (DTF), diaphragm excursion (DE) in hypophosphatemia group were all significantly decreased [DTei (cm): 0.19±0.07 vs. 0.27±0.08, DTee (cm): 0.14±0.05 vs. 0.19±0.06, DTF: (33.55±16.17)% vs. (45.04±18.66)%, DE (cm): 1.17±0.49 vs. 2.28±0.69, all P < 0.01]. Pearson partial correlation analysis showed that linear correlations were found between serum phosphorus and DTei, DTee, DTF, DE (r values were 0.442, 0.351, 0.293, 0.628 respectively, all P < 0.01). CONCLUSIONS: Serum phosphorus may have correlation with the diaphragmatic ultrasonography movement indexes. Hypophosphatemia may impair the contractile properties of diaphragm, induce more SBT attempts and longer duration of invasive mechanical ventilation, and affect outcome of weaning and prognosis.

Caspofungin pharmacokinetics and probability of target attainment in ICU patients in China.

OBJECTIVES: Effective antifungal therapy is important to reduce mortality in patients with invasive fungal infections (IFIs). Numerous factors affect pharmacokinetic/pharmacodynamic (PK/PD) parameters in critically-ill patients. To guide individualised administration in critically-ill patients, it is of great significance to determine the population pharmacokinetics of caspofungin. METHODS: A prospective study in 42 ICU patients with IFIs was conducted in China. A population pharmacokinetic model of caspofungin was established using a non-linear mixed-effects model, which was utilised to investigate the effects of demographic indices, liver function and kidney function on pharmacokinetics. Additionally, appropriate dosages of caspofungin under various scenarios were determined based on MICs and probability of target attainment (PTA) at specific dosages. RESULTS: In critically-ill Chinese patients, clearance (CL), volume of distribution (V) and area under the curve at steady-state (AUCss) of caspofungin were 0.32 L/h, 6.77 L and 135.47 mg•h/L, respectively. Blood albumin and total bilirubin levels were factors affecting CL, while body weight was the only factor affecting V among Chinese people with relatively low weight compared with other populations. A maintenance dose of 50 mg caspofungin achieved a high PTA for treating IFIs caused by Candida albicans (MIC ≤ 0.06 mg/L) and Candida glabrata (MIC ≤ 0.125 mg/L). The maintenance dose of caspofungin should be adjusted to 70-200 mg for IFIs caused by C. albicans (MIC, 0.06-0.125 mg/L). For IFIs caused by Candida parapsilosis, an MIC > 0.03 mg/L is associated with a very low PTA, but higher doses of caspofungin or alternative antifungals need to be further studied. CONCLUSION: The population pharmacokinetic model established here described well the PK/PD characteristics of caspofungin in critically-ill Chinese patients. These results could guide the formulation of individualised caspofungin dosing regimens for critically-ill patients.

Silencing of LncRNA-PVT1 ameliorates lipopolysaccharide-induced inflammation in THP-1-derived macrophages via inhibition of the p38 MAPK signaling pathway.

BACKGROUND: Sepsis is common in intensive care units and has a high mortality rate; yet, its pathogenesis and treatment remain unclear. Recent studies have shown that long non-coding RNA plasmacytoma variant translocation 1 (lncRNA-PVT1) plays a pro-inflammatory role in immune-related inflammatory diseases. Therefore, we investigated whether lncRNA-PVT1 plays an important pro-inflammatory effect in the inflammatory response of sepsis. METHODS: Quantitative real-time PCR (RT-qPCR) was employed for the detection of lncRNA-PVT1, interleukin 1ß (IL-1ß), and tumor necrosis factor α (TNF-α) mRNA, and the correlations between their expressions were analyzed. After lncRNA-PVT1 knockdown by lncRNA Smart Silencer, abnormal expressions of lncRNA-PVT1, and IL-1ß and TNF-α mRNA were detected. The expressions of total and phosphorylated protein of p38 were detected by western blotting. The effect of silencing lncRNA-PVT1 on p38 mitogen-activated protein kinase (MAPK) signaling pathway during lipopolysaccharide (LPS)-induced inflammation was subsequently analyzed. The MAPK selective inhibitor, SB202190, was used to block this signaling pathway, and the expressions of lncRNA-PVT1 and TNF-α were detected by RT-qPCR. Furthermore, the effect of partial blockade of the p38 MAPK signaling pathway by SB202190 on the levels of lncRNA-PVT1 was explored. RESULTS: Following treatment of THP-1-derived macrophages with different concentrations of LPS, the levels of lncRNA-PVT1 and IL-1ß, TNF-α mRNA were increased in a dose-dependent manner. Silencing of lncRNA-PVT1 reduced the expressions of IL-1ß and TNF-α mRNA via inhibition of the p38 MAPK signaling pathway. Specifically, inhibiting the p38 MAPK pathway significantly decreased the LPS-induced lncRNA-PVT1 elevation. CONCLUSIONS: Our observations suggest that lncRNA-PVT1 can be silenced to ameliorate LPS-induced inflammation in macrophages via inhibition of the p38 MAPK pathway. Further, the p38 MAPK pathway can regulate the expression of lncRNA-PVT1 via a positive feedback loop.

Clinical significance of prognostic nutritional index in renal cell carcinomas.

ABSTRACT: Prognostic nutritional index (PNI) could reflect the nutrition and inflammation status in cancer patients. This study aims to identify the prognostic significance of PNI in patients with renal cell carcinoma (RCC).A total of 694 RCC patients from our institution were included in this study. The prognostic correlation between PNI and overall survival (OS) and recurrence-free survival (RFS) was analyzed respectively using Kaplan-Meier method and univariate and multivariate Cox model. Studies about the association between pretreatment or preoperative PNI and prognosis of RCC were systemically reviewed and a meta-analysis method was performed to further evaluate the pooled prognostic value of PNI in RCC.267 (38.47%) RCC patients had low PNI according to the cut off value (49.08). Low PNI was associated with poor OS (P < .001) and RFS (P < .001), respectively. In the multivariate Cox analysis, PNI was identified to be an independent prognostic factor for OS (hazard ratio [HR] = 2.13, 95%CI: 1.25-3.62, P = .005). Compared to other nutritional indexes, this risk correlation of PNI is better than that of geriatric nutritional risk index (GNRI; HR = 1.19; P = .531), while is no better than that of neutrophil-lymphocyte ratio (NLR; 1/HR = 2.56; P < .001) and platelet-lymphocyte ratio (PLR; 1/HR = 2.85; P < .001) respectively. Meanwhile, additional 4785 patients from 6 studies were included into pooled analysis. For RCC patients who underwent surgery, low preoperative PNI was significantly associated with worse OS (pooled HR = 1.57, 95%CI: 1.37-1.80, P < .001) and worse RFS (pooled HR = 1.69, 95%CI: 1.45-1.96, P < .001). Furthermore, low PNI (<41-51) was also significantly associated with poor OS (HR = 1.78, 95%CI: 1.26-2.53 P < .05) and poor RFS (HR = 2.03, 95%CI: 1.40-2.95, P < .05) in advanced cases treated with targeted therapies.The present evidences show that PNI is an independent prognostic factor in RCC. Low PNI is significant associated with poor prognosis of RCC patients.

Mutation analysis of the cystic fibrosis transmembrane conductance regulator gene in Chinese congenital absence of vas deferens patients.

To find the variant spectrum of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and evaluate its frequent variants in Chinese congenital absence of vas deferens (CAVD) patients. A total of 276 patients with azoospermia and CAVD (aged from 21 to 44 years old) were investigated from May 2013 to September 2019 in the Third Affiliated Hospital of Sun Yat-sen University. Additionally, 50 healthy, unrelated volunteers were recruited as controls (aged from 21 to 46 years old). The 5'-UTR, exons and their flanking side of the CFTR gene were sequenced by high-throughput sequencing technology. The results were compared with those retrieved from the Ensembl Genome Browser. In addition, all 13 novel variants were further confirmed independently by Sanger sequencing and evaluated in the bioinformatics web servers. A schematic of the variant spectrum of the CFTR gene, including 13 novel variants (12 in CAVD patients, one in the control group), is shown, and the frequent variants in Chinese CAVD patients were 5 T (27.54%), c.-8G > C (7.25%), p.Q1352H (5.98%), and p.I556V (3.08%). 5 T was found to be the most frequent variant. p.Q1352H had a significantly high allelic frequency in CAVD patients (P < 0.05). c.-8G > C and p.I556V had high allelic frequencies but showed no difference between patients and controls (P > 0.05). p.Q1352H is the most common and important missense variant in Chinese patients with CAVD, while the pathological effects of C.-8G > C and p.I556V may be weak after evaluation.

Consecutive nightly measurements are needed for accurate evaluation of nocturnal erectile capacity when the first-night laboratory recording is abnormal.

Multiple measurements of nocturnal penile tumescence and rigidity (NPTR) are widely accepted as a method to differentiate psychogenic erectile dysfunction (ED) from organic ED. However, direct evidence remains limited regarding the first-night effect on NPTR measurement using the RigiScan. Here, we evaluated the first-night effect on the results of NPTR measurement to validate the necessity of NPTR measurement for two consecutive nights, particularly when abnormal first-night measurements are recorded in a laboratory setting. We retrospectively reviewed 105 patients with a complaint of ED, who underwent NPTR measurement using the RigiScan in the Department of Infertility and Sexual Medicine, the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China), for two consecutive nights, during the period from November 2015 to May 2016. NPTR parameters were collected and analyzed. We found that more effective nocturnal erections were detected during the second night than during the first night (P <0.001). Twenty percent of all patients had no effective erection during the first night, but exhibited at least one effective erection during the second night. The negative predictive value of NPTR measurement during the first night was 43.2%; this was significantly lower than that on the second night (84.2%; P = 0.003). Most NPTR parameters were better on the second night than on the first night. The first-night effect might be greater among patients younger than 40 years of age. In conclusion, two consecutive nightly measurements of NPTR can avoid a false-abnormal result caused by the first-night effect; moreover, these measurements more accurately reflect erectile capacity, especially when the first-night record is abnormal in a laboratory setting.

[Exploration of the effect of inhibitor of matrix metalloproteinase-9 on blood brain barrier in cardiopulmonary resuscitation in rats].

OBJECTIVE: To explore the effect of inhibitor of matrix metalloproteinase-9 (MMP-9, SB-3CT) on blood brain barrier (BBB) after cardiopulmonary resuscitation (CPR) in rats. METHODS: Rats were randomly divided into three groups: the sham-operated group, the resuscitation control group, and the resuscitation treatment group. Cardiac arrest was produced by clamping the endotracheal intubation, and CPR was executed 1 minute later. In the resuscitation treatment group, SB-3CT (25 mg/kg) was injected intraperitoneally after the restoration of spontaneous circulation (ROSC). The rats were executed immediately, and 0, 3, 9, 24 and 48 hours after the treatment. BBB was examined, and the expression of MMP-9 protein and MMP-9 mRNA in brain tissue were detected, and the ultrastructure of brain tissue was studied with electron microscopy. RESULTS: In the sham-operated group, the water content, Evans blue content, MMP-9 protein, and MMP-9 mRNA did not change significantly, and there was no obvious change in microstructure of brain tissue. The expression of MMP-9 protein and MMP-9 mRNA in the resuscitation control group were obviously up-regulated at 3 hours after CPR, peaking at 24 hours. There was also significant change in BBB. The differences were significant statistically compared with sham-operated group. The changes in the resuscitation treatment group were similar to the resuscitation control group, but the levels were lower than those of the resuscitation control group (P<0.05 or P<0.01). CONCLUSION: The specific inhibitor of MMP-9 (SB-3CT) could decreased the expression of MMP-9, the injury of BBB, and cerebral edema in the cerebral ischemia model with CPR rats, and the protection of cerebral ischemia/reperfusion (I/R) injury after CPR is obvious.

The Role of Nocturnal Penile Tumescence and Rigidity (NPTR) Monitoring in the Diagnosis of Psychogenic Erectile Dysfunction: A Review.

INTRODUCTION: Nocturnal penile tumescence and rigidity (NPTR) monitoring with RigiScan was considered one of the most reliable methods to differentiate psychogenic erectile dysfunction (pED) from organic ED. However, its reliability has been questioned because of some limitations in the practice. AIM: To present contemporary views on the role of NPTR monitoring in the diagnosis of pED. METHOD: We performed a comprehensive review of English-language literature on NPTR and pED by a PubMed search. MAIN OUTCOME MEASURES: Studies were included if the mechanisms of pED and nocturnal erection and the practice of NPTR monitoring in ED were the main research contents. RESULTS: The pED results from not only psychosocial factors but also physiological changes containing central nervous abnormality. NPTR monitoring with RigiScan is still considered a useful method for the diagnosis of pED. A normal NPTR recording in a man with ED complaints probably suggests pED, whereas an abnormal recording may represent organic ED. Radial rigidity of no more than 60% is correlated well with axial rigidity, but, when it is more than 60%, the correlation between them is questioned. The consistency between NPTR and sex-stimulated erection is questionable, and the correlation of NPTR with different patient-reported outcome scoring systems is different. A normal NPTR recording in patients with ED does not necessarily mean pED, especially in patients with spinal cord injury. NPTR recordings can be influenced by depression, smoking, aging, negative dream content, and sleep disorders. CONCLUSION: NPTR monitoring with the RigiScan is still considered a useful diagnostic tool for pED at the present stage. However, there are some disputes regarding the correlation between penile radial rigidity and axial rigidity and between NPTR and sex-related erection, as well as normative evaluation criteria for ED and the possibility of a false NPTR result, that need to be further studied. Zou Z, Lin H, Zhang Y, et al. The Role of Nocturnal Penile Tumescence and Rigidity (NPTR) Monitoring in the Diagnosis of Psychogenic Erectile Dysfunction: A Review. Sex Med Rev 2019;7:442-454.

Knockdown of ribosomal protein S15A inhibits human kidney cancer cell growth in vitro and in vivo.

Ribosomal protein S15A (RPS15A), a member of the ribosomal protein gene family, was demonstrated to be closely associated with tumorigenesis in multiple human malignancies. Nevertheless, the role of RPS15A in the progression of renal cell carcinoma (RCC) remains unknown. In the present study, by comparing the publicly available data from RCC tissues and reverse transcription­quantitative polymerase chain reaction results, it was identified that RPS15A was upregulated in RCC tissues and cell lines (P<0.001). Notably, knockdown of RPS15A suppressed 786­O cell proliferation (P<0.001) and promoted its apoptosis/necrotic (P=0.0001) in vitro. Additionally, tumour formation and growth of transfected 786­O cells were observed to be restrained in a mouse model (P<0.05). Subsequent to analysing the microarray data, 747 genes were differentially expressed in the RPS15A­knockdown 786­O cells. The enriched canonical pathways, diseases and functions of differentially expressed genes, and the interactive network of RPS15A in RCC were successfully constructed by ingenuity pathway analysis. Overall, the present results provided a preliminary experimental basis for RPS15A as a novel oncogene and potential therapeutic target in RCC.