Key genes involved in nonalcoholic steatohepatitis improvement after bariatric surgery.

Background: Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), one of the most prevalent chronic liver diseases. The effectiveness of bariatric surgery in treating NASH and preventing or even reversing liver fibrosis has been demonstrated in numerous clinical studies, but the underlying mechanisms and crucial variables remain unknown. Methods: Using the GSE135251 dataset, we examined the gene expression levels of NASH and healthy livers. Then, the differentially expressed genes (DEGs) of patients with NASH, at baseline and one year after bariatric surgery, were identified in GSE83452. We overlapped the hub genes performed by protein-protein interaction (PPI) networks and DEGs with different expression trends in both datasets to obtain key genes. Genomic enrichment analysis (GSEA) and genomic variation analysis (GSVA) were performed to search for signaling pathways of key genes. Meanwhile, key molecules that regulate the key genes are found through the construction of the ceRNA network. NASH mice were induced by a high-fat diet (HFD) and underwent sleeve gastrectomy (SG). We then cross-linked the DEGs in clinical and animal samples using quantitative polymerase chain reaction (qPCR) and validated the key genes. Results: Seven key genes (FASN, SCD, CD68, HMGCS1, SQLE, CXCL10, IGF1) with different expression trends in GSE135251 and GSE83452 were obtained with the top 30 hub genes selected by PPI. The expression of seven key genes in mice after SG was validated by qPCR. Combined with the qPCR results from NASH mice, the four genes FASN, SCD, HMGCS1, and CXCL10 are consistent with the biological analysis. The GSEA results showed that the 'cholesterol homeostasis' pathway was enriched in the FASN, SCD, HMGCS1, and SQLE high-expression groups. The high-expression groups of CD68 and CXCL10 were extremely enriched in inflammation-related pathways. The construction of the ceRNA network obtained microRNAs and ceRNAs that can regulate seven key genes expression. Conclusion: In summary, this study contributes to our understanding of the mechanisms by which bariatric surgery improves NASH, and to the development of potential biomarkers for the treatment of NASH.

Ubiquitination, SUMOylation, and NEDDylation related genes serve as prognostic and therapeutic biomarkers for oral squamous cell carcinoma.

BACKGROUND: Ubiquitination, small ubiquitin-related modifiers, and NEDDylation are now found to function in cancer biology; however, its role in the oral cancer patients remains unclear. METHODS: A set of bioinformatic tools was integrated to analyze the expression and prognostic significance of ubiquitin and ubiquitin-like (UB/UBL) genes. A UB/UBL-related risk score was developed via correlation analyses, univariate Cox regression, and multivariate Cox regression. Nomogram analysis evaluates the model's prediction performance. The drug sensitivity analysis, immune profiles of UB/UBL-classified oral squamous cell carcinoma (OSCC) patients, and their related function pathway were investigated, and the role of UB/UBL-related genes in drug therapy was analyzed. RESULTS: A total of six prognostic UB/UBL-related genes were obtained. PSMD3, PCGF2, and H2BC10 were significantly downregulated in OSCC tissue and associated with longer survival time. OSCC patients in the high-risk group showed a significantly lower overall survival and enriched in cancer-related pathways. The prognostic potential of genes associated with UB/UBL was discovered, and patients with high-risk scores showed an increase of protumor immune infiltrates and a high expression of immune checkpoints. Moreover, the area under the curve of the annual survival rate was 0.616, 0.671, and 0.673, respectively. Besides, patients in the high-risk group are more sensitive to docetaxel, doxorubicin, and methotrexate therapy. CONCLUSIONS: We construct a prognosis model for OSCC patients with UB/UBL-related genes and try to find a new approach to treating oral cancer patients. The UB/UBL-related signature is helpful in developing new tumor markers, prognostic prediction, and in guiding treatment for OSCC patients.

Integrative analysis of lysine acetylation-related genes and identification of a novel prognostic model for oral squamous cell carcinoma.

Introduction: Oral squamous cell carcinoma (OSCC), which accounts for a high proportion of oral cancers, is characterized by high aggressiveness and rising incidence. Lysine acetylation is associated with cancer pathogenesis. Lysine acetylation-related genes (LARGs) are therapeutic targets and potential prognostic indicators in various tumors, including oral squamous cell carcinoma. However, systematic bioinformatics analysis of the Lysine acetylation-related genes in Oral squamous cell carcinoma is still unexplored. Methods: We analyzed the expression of 33 Lysine acetylation-related genes in oral squamous cell carcinoma and the effects of their somatic mutations on oral squamous cell carcinoma prognosis. Consistent clustering analysis identified two lysine acetylation patterns and the differences between the two patterns were further evaluated. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to develop a lysine acetylation-related prognostic model using TCGA oral squamous cell carcinoma datasets, which was then validated using gene expression omnibus (GEO) dataset GSE41613. Results: Patients with lower risk scores had better prognoses, in both the overall cohort and within the subgroups These patients also had "hot" immune microenvironments and were more sensitive to immunotherapy. Disscussion: Our findings offer a new model for classifying oral squamous cell carcinoma and determining its prognosis and offer novel insights into oral squamous cell carcinoma diagnosis and treatment.

Redefining the Incidence and Profile of Fluoropyrimidine-Associated Cardiotoxicity in Cancer Patients: A Systematic Review and Meta-Analysis.

AIM: The cardiac toxicity that occurs during administration of anti-tumor agents has attracted increasing concern. Fluoropyrimidines have been used for more than half a century, but their cardiotoxicity has not been well clarified. In this study, we aimed to assess the incidence and profile of fluoropyrimidine-associated cardiotoxicity (FAC) comprehensively based on literature data. METHODS: A systematic literature search was performed using PubMed, Embase, Medline, Web of Science, and Cochrane library databases and clinical trials on studies investigating FAC. The main outcome was a pooled incidence of FAC, and the secondary outcome was specific treatment-related cardiac AEs. Random or fixed effects modeling was used for pooled meta-analyses according to the heterogeneity assessment. PROSPERO registration number: (CRD42021282155). RESULTS: A total of 211 studies involving 63,186 patients were included, covering 31 countries or regions in the world. The pooled incidence of FAC, by meta-analytic, was 5.04% for all grades and 1.5% for grade 3 or higher. A total of 0.29% of patients died due to severe cardiotoxicities. More than 38 cardiac AEs were identified, with cardiac ischemia (2.24%) and arrhythmia (1.85%) being the most frequent. We further performed the subgroup analyses and meta-regression to explore the source of heterogeneity, and compare the cardiotoxicity among different study-level characteristics, finding that the incidence of FAC varied significantly among different publication decades, country/regions, and genders. Patients with esophagus cancer had the highest risk of FAC (10.53%), while breast cancer patients had the lowest (3.66%). The treatment attribute, regimen, and dosage were significantly related to FAC. When compared with chemotherapeutic drugs or targeted agents, such a risk was remarkably increased (χ2 = 10.15, p < 0.01; χ2 = 10.77, p < 0.01). The continuous 5-FU infusion for 3-5 consecutive days with a high dosage produced the highest FAC incidence (7.3%) compared with other low-dose administration patterns. CONCLUSIONS: Our study provides comprehensive global data on the incidence and profile of FAC. Different cancer types and treatment appear to have varying cardiotoxicities. Combination therapy, high cumulative dose, addition of anthracyclines, and pre-existing heart disease potentially increase the risk of FAC.

Cuproptosis-Mediated Patterns Characterized by Distinct Tumor Microenvironment and Predicted the Immunotherapy Response for Gastric Cancer.

Cuproptosis is a newly discovered programmed cell death process, and several cuproptosis-related genes have been reported to regulate cancer cell proliferation and progression. The association between cuproptosis and tumor microenvironment in gastric cancer (GC) remains unclear. This study aimed to explore multiomics characteristics of cuproptosis-related genes regulating tumor microenvironment and provide strategies for prognosis and prediction of immunotherapy response in GC patients. We collected 1401 GC patients from the TCGA and 5 GEO data sets and identified three different cuproptosis-mediated patterns, each of which shared a distinct tumor microenvironment and different overall survival. The GC patients with high cuproptosis levels were enriched in CD8+ T cells and had a better prognosis. Whereas, the low cuproptosis level patients were associated with inhibitory immune cell infiltration and had the worst prognosis. In addition, we constructed a 3-gene (AHCYL2, ANKRD6 and FDGFRB) cuproptosis-related prognosis signature (CuPS) via Lasso-Cox and multivariate Cox regression analysis. The GC patients in the low-CuPS subgroup had higher TMB levels, MSI-H fractions, and PD-L1 expression, which suggests a better immunotherapy response. Therefore, the CuPS might have the potential value for predicting prognosis and immunotherapy sensitivity in GC patients.

Effect of extreme temperatures on asthma hospital visits: Modification by event characteristics and healthy behaviors.

Although ambient temperature has been linked to asthma exacerbation, impacts associated with extreme temperature events remain unclear. This study aims to identify the events characteristics that elevate risk of asthma hospital visits, and to assess whether healthy behavior changes due to the COVID-19 prevention and control policy may modify the relationships. Data of asthma hospital visits from all medical facilities in Shenzhen, China during 2016-2020 were assessed in relation to extreme temperature events using a distributed lag model. Stratified analysis was conducted by gender, age and hospital department to identify susceptible populations. Through events defined by various duration days and temperature thresholds, we explored the modification by events intensity, length, occurrence time and healthy behaviors. The cumulative relative risk of asthma during heat waves compared to other days was 1.06 (95%CI: 1.00-1.13) and for cold spells was 1.17 (95%CI: 1.05-1.30), and that of males and school-aged children were generally higher than other sub-groups. There were significant effects of heat waves and cold spells on asthma hospital visits when the mean temperature was above 90th percentile (30 °C) and below 10th percentile (14 °C) respectively, and the relative risks were higher when events lasted longer, became stronger, occurred in daytime and in early summer or winter. During the healthy behaviors maintaining period, the risk of heat waves increased whilst the risk of cold spells reduced. Extreme temperatures may pose considerable impact on asthma and the health effect can be modified by the event characteristics and anti-epidemic healthy behaviors. Strategies of asthma control should consider the heightened threats of the intense and frequent extreme temperature events in the context of climate change.

Asthma triggered by extreme temperatures: From epidemiological evidence to biological plausibility.

BACKGROUND: There is rapidly growing evidence indicating that extreme temperature is a crucial trigger and potential activator of asthma; however, the effects of extreme temperature on asthma are inconsistently reported and the its potential mechanisms remain undefined. OBJECTIVES: This review aims to estimate the impacts of extreme heat, extreme cold, and temperature variations on asthma by systematically summarizing the existing studies from epidemiological evidence to biological plausibility. METHODS: We conducted a systematic search in PubMed, Embase, and Web of Science from inception to June 30, 2022, and we retrieved articles of epidemiology and biological studies which assessed associations between extreme temperatures and asthma. This protocol was registered with PROSPERO (CRD42021273613). RESULTS: From 12,435 identified records, 111 eligible studies were included in the qualitative synthesis, and 37 articles were included in the meta-analysis (20 for extreme heat, 16 for extreme cold, and 15 for temperature variations). For epidemiological evidence, we found that the synergistic effects of extreme temperatures, indoor/outdoor environments, and individual vulnerabilities are important triggers for asthma attacks, especially when there is extreme heat or cold. Meta-analysis further confirmed the associations, and the pooled relative risks for asthma attacks in extreme heat and extreme cold were 1.07 (95%CI: 1.03-1.12) and 1.20 (95%CI: 1.12-1.29), respectively. Additionally, this review discussed the potential inflammatory mechanisms behind the associations between extreme temperatures and asthma exacerbation, and highlighted the regulatory role of immunological pathways and transient receptor potential ion channels in asthma triggered by extreme temperatures. CONCLUSIONS: We concluded that both extreme heat and cold could significantly increase the risk of asthma. Additionally, we proposed a potential mechanistic framework, which is important for understanding the disease pathogenesis that uncovers the complex mechanisms of asthma triggered by extreme temperatures and protects the sensitive individuals from impacts of extreme weather events and climate change.

Construction of m6A-based prognosis signature and prediction for immune and anti-angiogenic response.

Background: Increasing evidence illustrated that m6A regulator-mediated modification plays a crucial role in regulating tumor immune and angiogenesis microenvironment. And the combination of immune checkpoint inhibitor and anti-angiogenic therapy has been approved as new first-line therapy for advanced HCC. This study constructed a novel prognosis signature base on m6A-mediated modification and explored the related mechanism in predicting immune and anti-angiogenic responses. Methods: Gene expression profiles and clinical information were collected from TCGA and GEO. The ssGSEA, MCPCOUNT, and TIMER 2.0 algorithm was used to Estimation of immune cell infiltration. The IC50 of anti-angiogenic drugs in GDSC was calculated by the "pRRophetic" package. IMvigor210 cohort and Liu et al. cohort were used to validate the capability of immunotherapy response. Hepatocellular carcinoma single immune cells sequencing datasets GSE140228 were collected to present the expression landscapes of 5 hub genes in different sites and immune cell subpopulations of HCC patients. Results: Three m6A clusters with distinct immune and angiogenesis microenvironments were identified by consistent cluster analysis based on the expression of m6A regulators. We further constructed a 5-gene prognosis signature (termed as m6Asig-Score) which could predict both immune and anti-angiogenic responses. We illustrated that high m6Asig-Score is associated with poor prognosis, advanced TNM stage, and high TP53 mutation frequency. Besides, the m6Asig-Score was negatively associated with immune checkpoint inhibitors and anti-angiogenic drug response. We further found that two of the five m6Asig-Score inner genes, B2M and SMOX, were associated with immune cell infiltration, immune response, and the sensitivity to sorafenib, which were validated in two independent immunotherapy cohorts and the Genomics of Drug Sensitivity in Cancer (GDSC) database. Conclusion: We constructed a novel prognosis signature and identified B2M and SMOX for predicting immune and anti-angiogenic efficacy in HCC, which may guide the combined treatment strategies of immunotherapy and anti-angiogenic therapy in HCC.

A novel cuproptosis-related prognostic signature and potential value in HCC immunotherapy.

Background: Copper metabolism plays an important role in the tumor microenvironment, and cuproptosis is the last discovered programmed cell death process. However, the potential mechanism of cuproptosis in regulating the immune microenvironment of HCC remains unclear. Methods: A total of 716 HCC patients with complete mRNA expression and survival information were collected from three public HCC cohorts (TCGA-LIHC cohort, n = 370; GSE76427 cohort, n = 115; ICGC-LIRI cohort, n = 231). The unsupervised clustering analysis (NMF) was performed to identify three different cuproptosis-related subtypes. The univariate-Cox, lasso-Cox and multivariate-Cox regression analyses were performed to screen the cuproptosis related and construct the cuproptosis-related prognosis signature (Cu-PS). The immune cell infiltration was estimated by both CIBERSORT and MCPcounter algorithms. Results: This study identified three distinct cuproptosis-related metabolic patterns, which presented different pathway enrichment and immune cell infiltration. The Cu-PS, a 5-genes (C7, MAGEA6, HK2, CYP26B1 and EPO) signature, was significantly associated with TNM stage, tumor mutational burden (TMB), drugs sensitivity, and immunotherapies response. Conclusion: This study performed a multi-genetic analysis of cuproptosis-related genes and further explored the regulatory mechanism of cuproptosis in HCC. The Cu-PS might be a useful biomarker for predicting immunotherapy response and enhancing the diagnosis and treatment of HCC.

Exploration of the Tumor Immune Landscape and Identification of Two Novel Immunotherapy-Related Genes for Epstein-Barr virus-associated Gastric Carcinoma via Integrated Bioinformatics Analysis.

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a specific molecular subtype of gastric carcinoma with a high proportion of tumor-infiltrating lymphocytes. It is a highly immunogenic tumor that may benefit from immunotherapy. Hence, it is imperative to analyze the immune landscape and identify immunotherapy biomarkers for EBVaGC. In our study, we investigated the immune landscape and identified 10 hub genes for EBVaGC via integrated bioinformatics analysis. We found that EBVaGC expressed more immune-related genes, including common immune checkpoints and human leukocyte antigen (HLA) genes than EBV-negative gastric carcinoma (EBVnGC). The immune score in EBVaGC was higher, which means EBVaGC has greater immune cell infiltration. Ten hub genes (CD4, STAT1, FCGR3A, IL10, C1QA, CXCL9, CXCL10, CXCR6, PD-L1, and CCL18) were detected as candidate biomarkers for EBVaGC. Two hub genes, CXCL9 and CXCR6, were identified as novel immunotherapy-related genes. Taken together, the results of our comprehensive analysis of the immune microenvironment of EBVaGC revealed its unique immune landscape, demonstrating that it is a highly immunogenic tumor. Moreover, we identified hub genes that may serve as potential immunotherapy biomarkers for EBVaGC.

Treatment-Related Coronary Disorders of Fluoropyrimidine Administration: A Systematic Review and Meta-Analysis.

Background: Coronary disorders are recognized as the most common manifestation of fluoropyrimidine-related cardiotoxicity in clinical practice. However, there are limited and conflicting data on the incidence and profiles of fluoropyrimidine-related coronary disorders. In this meta-analysis, we aimed to systematically assess the incidence of all-grade and grade 3 or higher fluoropyrimidine-related coronary disorders, and further explore the factors that influence its occurrence. Methods: Studies reporting the fluoropyrimidine-related coronary disorders were retrieved from a systematic search of English literature in the PubMed, Web of Science, Medline, and Cochrane database from 1 Jan 2001, to 1 Jan 2022. The NIH assessment tool was used to evaluate the quality of each study. The data of basic study characteristics, treatment details, and results of coronary toxicities were extracted. According to the results of the heterogeneity test (I2 and p-value statistic), a random-effect model or fixed-effect model was selected for the pooled analysis of the incidence of adverse coronary events. Subgroup analysis was conducted to further explore the risks influencing the occurrence of fluoropyrimidine-related coronary disorders. The stability and publication bias of our results were evaluated by sensitivity analysis and Egger test, respectively. Results: A total of 63 studies were finally included in our pooled analysis, involving 25,577 patients. The pooled cumulative incidence of all-grade and grade 3 or higher coronary disorders was 2.75% (95% CI 1.89%-3.76%) and 1.00% (95% CI 0.62%-1.47%), respectively. The coronary disorders were most reported as myocardial ischemia (1.28%, 95% CI 0.42%-2.49%) and angina/chest pain (1.1%, 95% CI 0.54%-1.81%). Subgroup analysis revealed that studies in the female-only population seemed to have a lower incidence of fluoropyrimidine-related coronary disorders. The occurrence of adverse coronary events varied among different tumor types. Patients with esophageal cancer have the highest coronary toxicity (6.32%), while those with breast cancer have a relatively lower incidence (0.5%). Coronary disorders induced by 5-FU monotherapy are more frequent than that induced by capecitabine (3.31% vs. 1.21%, p < 0.01). Fluoropyrimidine combination therapy, whether combined with other chemotherapy drugs, targeted therapy drugs, or radiotherapy, significantly increased the incidence of coronary complications (p < 0.01). Conclusion: This meta-analysis has defined the incidence of fluoropyrimidine-related coronary disorders and depicted its epidemiological profiles for the first time, which may provide a reference for clinical practice in cancer management.

Immune Gene Signatures and Immunotypes in Immune Microenvironment Are Associated With Glioma Prognose.

Glioma is the most common primary malignant brain tumor in adults with very poor prognosis. The limited new therapeutic strategies for glioma patients can be partially attributed to the complex tumor microenvironment. However, knowledge about the glioma immune microenvironment and the associated regulatory mechanisms is still lacking. In this study, we found that, different immune subtypes have a significant impact on patient survival. Glioma patients with a high immune response subtype had a shorter survival compared with patients with a low immune response subtype. Moreover, the number of B cell, T cell, NK cell, and in particular, the macrophage in the immune microenvironment of patients with a high immune response subtype were significantly enhanced. In addition, 132 genes were found to be related to glioma immunity. The functional analysis and verification of seven core genes showed that their expression levels were significantly correlated with the prognosis of glioma patients, and the results were consistent at tissue levels. These findings indicated that the glioma immune microenvironment was significantly correlated with the prognosis of glioma patients and multiple genes were involved in regulating the progression of glioma. The identified genes could be used to stratify glioma patients based on immune subgroup analysis, which may guide their clinical treatment regimen.

Climate change, air pollution, and allergic respiratory diseases: a call to action for health professionals.

Rising emissions of greenhouse gases in the atmosphere have warmed the planet substantially and are also accompanied by poor air quality. The increased prevalence of allergic airway disease worldwide can be partially attributed to those global environmental changes. Climate change and air pollution pose adverse impacts on respiratory allergies, and that the mechanisms are complex and interactive. Adverse weather conditions, such as extreme temperatures, can act directly on the respiratory tract to induce allergic respiratory illnesses. Thunderstorms and floods can alter the production and distribution of aeroallergens while wildfires and dust storms increase air pollution, and therefore indirectly enhance health risks. Concentrations of particulate matter and ozone in the air have been projected to increase with climate warming and air stagnation, and the rising temperatures and CO2 increase pollen, molds, and spores, which escalate the risk of allergic respiratory diseases. The synergistic effects of extreme heat and aeroallergens intensify the toxic effect of air pollutants, which in turn augment the allergenicity of aeroallergens. With the Earth's climate change, migration of humans and plants shift the living environments and allergens of susceptible people. Urban residents are exposed to multiple factors while children are sensitive to environmental exposure. Since climate change may pose many unexpected and persistent effects on allergic respiratory diseases, health professionals should advocate for effective mitigation and adaptation strategies to minimize its respiratory health effects.

Short-term associations between ambient air pollution and stroke hospitalisations: time-series study in Shenzhen, China.

OBJECTIVE: To investigate the association between ambient air pollution and stroke morbidity in different subgroups and seasons. METHODS: We performed a time-series analysis based on generalised linear models to study the short-term exposure-response relationships between air pollution and stroke hospitalisations, and conducted subgroup analyses to identify possible sensitive populations. RESULTS: For every 10 µg/m3 increase in the concentration of air pollutants, across lag 0-3 days, the relative risk of stroke hospitalisation was 1.029 (95% CI 1.013 to 1.045) for PM2.5, 1.054 (95% CI 1.031 to 1.077) for NO2 and 1.012 (95% CI 1.002 to 1.022) for O3. Subgroup analyses showed that statistically significant associations were found in both men and women, middle-aged and older populations, and both cerebral infarction and intracerebral haemorrhage. The seasonal analyses showed that statistically significant associations were found only in the winter. CONCLUSIONS: Our study indicates that short-term exposure to PM2.5, NO2 and O3 may induce stroke morbidity, and the government should take actions to mitigate air pollution and protect sensitive populations.

Geographical disparities in the impacts of heat on diabetes mortality and the protective role of greenness in Thailand: A nationwide case-crossover analysis.

Diabetes is a major public health problem globally, and heat exposure may be a potential risk factor for death among diabetes. This study examines the association between heat and diabetes mortality in different regions of Thailand and investigates whether heat effects are modified by regional greenness. Daily temperature and daily diabetes deaths data were obtained for 60 provinces of Thailand during 2000-2008. A case-crossover analysis was conducted to quantify the odds of heat-related death among diabetes. Meta-regression was then used to examine potential modification effects of regional greenness (as represented by the Normalized Difference Vegetation Index) on heat-related mortality. A strong association between heat and diabetes mortality was found in Thailand, with important regional variations. Nationally, the pooled odds ratio of diabetes mortality was 1.10 (95% confidence interval (CI): 1.06-1.14) for heat (90th percentile of temperature) and 1.20 (95% CI: 1.10-1.30) for extreme heat (99th percentile of temperature) compared with the minimum mortality temperature, across lag 0-1 days. Central and northeast Thailand were the most vulnerable regions. Regional greenness modified the effects of heat, with lower mortality impacts in areas of higher levels of greenness. In conclusion, heat exposure increases mortality risk in diabetes, with large geographical variations in risk suggesting the need for region-specific public health strategies. Increasing greenness levels may help to reduce the burden of heat on diabetes in Thailand against the backdrop of a warming climate.

Epidemiology, microbiology and treatment implications in adult patients hospitalized with pneumonia in different regions of China: a retrospective study.

BACKGROUND: Data describing epidemiology, clinical outcomes and treatment patterns, of hospitalised patients with pneumonia in China are limited. We aimed to describe such information among adult pneumonia patients in southern and northern China. METHODS: We retrospectively reviewed electronic medical records of pneumonia patients aged ≥18 years, hospitalized between 2008 and 2013 at Guangdong Provincial Hospital of Chinese Medicine (n=3,636), southern China, and between 2010 and 2014 at Peking University People's Hospital, Beijing (n=1,689), northern China, in order to collect data on patient demographics, microbiology, clinical outcomes and treatment and resistance patterns. RESULTS: The mean (SD) age of patients was 60.0 (21.4) and 64.4 (18.4) years in Guangdong and Beijing, respectively. Mean length of hospital stay was 12.1 and 20.8 days, and overall mortality was 2.9% and 8.0%, respectively. Gram-negative bacilli were most frequently isolated, predominantly Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Infection with these bacteria was associated with unfavourable clinical outcomes, and the antibiotic resistance among these bacteria increased between 2008-2010 and 2011-2013 in both regions of China. The treatment and choice of antibiotics slightly varied between the two regions based on the susceptible pathogens identified among their populations. CONCLUSIONS: Of the pathogens identified, Staphylococcus aureus infection (particularly the methicillin-resistant S. aureus) was associated with poor clinical outcomes; however antibiotic resistance among S. aureus generally decreased during the study data collection periods. Also, disease severity was greater in Beijing as compared with Guangdong, and this may be associated with higher microbiological diagnosis rate and higher frequency of initial antibiotic modification among Beijing populations.

Effects of Anthocyanins on Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Numerous clinical trials have examined the role of anthocyanins on cardiometabolic health, but their effects have not been quantitatively synthesized and systematically evaluated. The aim of our study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of anthocyanins on glycemic regulation and lipid profiles in both healthy populations and those with cardiometabolic diseases. The MEDLINE, EMBASE, Cochrane database, OVID EBM Reviews, and clinicaltrials.gov databases were searched until February 2017. RCTs with a duration of ≥2 wk that evaluated the effects of anthocyanins on glycemic control, insulin sensitivity, and lipids as either primary or secondary outcomes were included. The Cochrane Risk of Bias tool was used to assess the study quality. Standardized mean differences (SMDs) were determined by random-effects models. Meta-regression, sensitivity, and subgroup analyses were performed to explore the influence of covariates on the overall effects. Thirty-two RCTs (1491 participants) were eligible for meta-analysis. Anthocyanins significantly reduced fasting glucose (SMD: -0.31; 95% CI: -0.59, -0.04; I2 = 80.7%), 2-h postprandial glucose (SMD: -0.82; 95% CI: -1.49, -0.15; I2 = 77.7), glycated hemoglobin (SMD: -0.65; 95% CI: -1.00, -0.29; I2 = 72.7%), total cholesterol (SMD: -0.33; 95% CI: -0.62, -0.03; I2 = 86.9%), and LDL (SMD: -0.35; 95% CI: -0.66, -0.05; I2 = 85.2%). Sensitivity analyses showed that the overall effects remained similar by excluding the trials with a high or unclear risk of bias. The significant improvements in glycemic control and lipids support the benefits of anthocyanins in the prevention and management of cardiometabolic disease. Further well-designed RCTs are needed to evaluate the long-term effects of anthocyanins on metabolic profiles and to explore the optimal formula and dosage. The protocol for this review was registered at https://www.crd.york.ac.uk/PROSPERO/#index.php as CRD42016033210.

[Synthesis and experimental study of a novel polymer/gene compound drug controlled release system for the treatment of erectile dysfunction].

OBJECTIVE: To overcome the deficiency in the current therapies for erectile dysfunction (ED), we designed and synthesized a novel high-efficiency polymer/gene compound drug controlled release system and discussed the feasibility of pH and temperature dually sensitive injectable hydrogel in ED gene therapy. METHODS: We synthesized optimal siRNA gene nanoparticles by characterizing the zeta potential of polylysine (PLL)/siRNA gene compounds, and established a pH and temperature dually sensitive injectable gene compound drug controlled release system via Schiffs reaction between glycol chitosan (GC) and benzaldehyde capped OHC-PEO-PPO-PEO-CHO. Then we demonstrated the sustained release of the system at different temperatures. RESULTS: When the mass ratio of PLL to siRNA was 20:1, the zeta potential of the PLL/siRNA gene compound reached the peak (+23.5 mV) and the siRNA was encapsulated by PLL in the maximal degree. GC and OHC-PEO-PPO-PEO-CHO was crosslinked via benzoicimine reaction when environmental pH was changed from 5.5 to 7.4. The reslease of the siRNA encapsulated in this system kept at a low rate at 37 degrees C, significantly enhanced with the increase of the temperature to 60 degrees C, rising to (122.5 +/- 5.3) microg at 1 000 minutes as compared with (23.8 +/- 6.0) microg at 37 degrees C (P < 0.05). CONCLUSION: The polymer/gene compound drug controlled release system was successfully synthesized, which improved the stability and capacity of gene carriers and achieved siRNA release at different temperatures, promising to be a new approach to the gene therapy of ED.

[Animal models in sexual dysfunction].

Animal models in sexual dysfunction were reviewed to further improve the modeling methods and to promote the effectiveness of drug evaluation translation from animal models to humans. A MEDLINE search was performed to retrieve articles relating to animal models in sexual dysfunction. Researches on a variety of animal models in sexual dysfunction, with their own merits, has to a certain extent contributed to the understanding of sexual function. However, no models could give a fully accurate assessment of sexual function. The existing sexual function studies on animal models of interpretive function, the development mechanisms, the effects of drugs on sexual function and the clinical translation still have some deficiencies, but with their basic principles and ideas for the improvement of the models and the preservation of the valuable data of drugs and clinical trials.

[Androgen regulates penile erection at the peripheral level].

Androgen has been claimed for so long as a pivotal hormone in regulating male sexual function, acting both at the central and peripheral level. We believe that androgen is indeed the main synchronizer of sexual activity regulating libido and enzymes as nitric oxide synthase (NOS) and phosphodiesterase type 5 ( PDE5) , which are crucial for the erectile process. The main action of androgen is to timely adjust the erectile process as a function manifestation of sexual desire, therefore finalizing erection to sex.