Uncovering the potential molecular mechanism of liraglutide to alleviate the effects of high glucose on myoblasts based on high-throughput transcriptome sequencing technique.

BACKGROUND: Myoblasts play an important role in muscle growth and repair, but the high glucose environment severely affects their function. The purpose of this study is to explore the potential molecular mechanism of liraglutide in alleviating the effects of high glucose environments on myoblasts. METHODS: MTT, western blot, and ELISA methods were used to investigate the role of liraglutide on C2C12 myoblasts induced by high glucose. The high-throughput transcriptome sequencing technique was used to sequence C2C12 myoblasts from different treated groups. The DESeq2 package was used to identify differentially expressed-mRNAs (DE-mRNAs). Then, functional annotations and alternative splicing (AS) were performed. The Cytoscape-CytoHubba plug-in was used to identify multicentric DE-mRNAs. RESULTS: The MTT assay results showed that liraglutide can alleviate the decrease of myoblasts viability caused by high glucose. Western blot and ELISA tests showed that liraglutide can promote the expression of AMPKα and inhibit the expression of MAFbx, MuRF1 and 3-MH in myoblasts. A total of 15 multicentric DE-mRNAs were identified based on the Cytoscape-CytoHubba plug-in. Among them, Top2a had A3SS type AS. Functional annotation identifies multiple signaling pathways such as metabolic pathways, cytokine-cytokine receptor interaction, cAMP signaling pathway and cell cycle. CONCLUSION: Liraglutide can alleviate the decrease of cell viability and degradation of muscle protein caused by high glucose, and improves cell metabolism and mitochondrial activity. The molecular mechanism of liraglutide to alleviate the effect of high glucose on myoblasts is complex. This study provides a theoretical basis for the clinical effectiveness of liraglutide in the treatment of skeletal muscle lesions in diabetes.

MyoFold: Joint myocardial tissue composition and wall motion quantification via a highly folded sequence.

PURPOSE: This study aims to develop and evaluate a novel cardiovascular MR sequence, MyoFold, designed for the simultaneous quantifications of myocardial tissue composition and wall motion. METHODS: MyoFold is designed as a 2D single breathing-holding sequence, integrating joint T1/T2 mapping and cine imaging. The sequence uses a 2-fold accelerated balanced SSFP (bSSFP) for data readout and incorporates electrocardiogram synchronization to align with the cardiac cycle. MyoFold initially acquires six single-shot inversion-recovery images, completed during the diastole of six successive heartbeats. T2 preparation (T2-prep) is applied to introduce T2 weightings for the last three images. Subsequently, over the following six heartbeats, segmented bSSFP is performed for the movie of the entire cardiac cycle, synchronized with an electrocardiogram. A neural network trained using numerical simulations of MyoFold is used for T1 and T2 calculations. MyoFold was validated through phantom and in vivo experiments, with comparisons made against MOLLI, SASHA, T2-prep bSSFP, and the conventional cine. RESULTS: In phantom studies, MyoFold exhibited a 10% overestimation in T1 measurements, whereas T2 measurements demonstrated high accuracy. In vivo experiments revealed that MyoFold T1 had comparable accuracy to SASHA and precision similar to MOLLI. MyoFold demonstrated good agreement with T2-prep bSSFP in myocardial T2 measurements. No significant differences were observed in the quantification of left-ventricle wall thickness and function between MyoFold and the conventional cine. CONCLUSION: MyoFold presents as a rapid, simple, and multitasking approach for quantitative cardiovascular MR examinations, offering simultaneous assessment of tissue composition and wall motion. The sequence's multitasking capabilities make it a promising tool for comprehensive cardiac evaluations in clinical settings.

The influence of minimally invasive esophagectomy on wound infection in patients undergoing esophageal cancer surgery: A meta-analysis.

The impacts of minimally invasive esophagectomy (MIE) in comparison with open esophagectomy (OE) on postoperative complications, wound infections and hospital length of stay in patients with esophageal carcinoma (ESCA) using meta-analysis to provide reliable evidence for clinical practice. A search strategy was developed and computer searches were performed on Embase, Web of Science, PubMed, Cochrane Library, Wanfang, China Biomedical Literature Database and China National Knowledge Infrastructure databases for clinical studies that reported the effects of MIE in comparison with OE in patients with ESCA. The retrieval time was from their inception to October 2023. Two authors independently performed literature screening, and data extraction and literature quality evaluation were performed separately for the included studies. Meta-analysis was performed using Stata 17.0 software. Overall, 26 studies with 2427 ESCA patients were included in this study, of which 1203 were in the MIE group and 1224 were in the OE group. The results showed that, compared with OE, ESCA patients who underwent MIE were less likely to develop postoperative wound infections (odds ratio [OR] = 0.31, 95% confidence intervals [CIs]: 0.20-0.49, p < 0.001) and complications (OR = 0.23, 95% CI: 0.18-0.30, p < 0.001) and have a shorter hospital stay (standardized mean difference = -1.93, 95% CI: -2.38 to -1.48, p < 0.001). MIE has advantages over OE in terms of shorter hospital stay and reduced incidence of postoperative wound infections and complications.

Three-dimensional High-Resolution Dark-Blood Late Gadolinium Enhancement Imaging for Improved Atrial Scar Evaluation.

Background Radiofrequency ablation (RFA) is a widely used treatment for atrial fibrillation, reducing the risk of cardiac arrhythmia. Detailed visualization and quantification of atrial scarring has the potential to improve preprocedural decision-making and postprocedural prognosis. Conventional bright-blood late gadolinium enhancement (LGE) MRI can help detect atrial scars; however, its suboptimal myocardium to blood contrast inhibits accurate scar estimation. Purpose To develop and test a free-breathing LGE cardiac MRI approach that simultaneously provides high-spatial-resolution dark-blood and bright-blood images for improved atrial scar detection and quantification. Materials and Methods A free-breathing, independent navigator-gated, dark-blood phase-sensitive inversion recovery (PSIR) sequence with whole-heart coverage was developed. Two coregistered high-spatial-resolution (1.25 × 1.25 × 3 mm3) three-dimensional (3D) volumes were acquired in an interleaved manner. The first volume combined inversion recovery and T2 preparation to achieve dark-blood imaging. The second volume functioned as the reference for phase-sensitive reconstruction with built-in T2 preparation for improved bright-blood contrast. The proposed sequence was tested in prospectively enrolled participants who had undergone RFA for atrial fibrillation (mean time since RFA, 89 days ± 26 [SD]) from October 2019 to October 2021. Image contrast was compared with conventional 3D bright-blood PSIR images using the relative signal intensity difference. Furthermore, native scar area quantification obtained from both imaging approaches was compared with measurements obtained with electroanatomic mapping (EAM) as the reference standard. Results A total of 20 participants (mean age, 62 years ± 9; 16 male) who underwent RFA for atrial fibrillation were included. The proposed PSIR sequence successfully acquired 3D high-spatial-resolution volumes in all participants, with a mean scan time of 8.3 minutes ± 2.4. The developed PSIR sequence improved scar to blood contrast compared with conventional PSIR sequence (mean contrast, 0.60 arbitrary units [au] ± 0.18 vs 0.20 au ± 0.19, respectively; P < .01) and correlated with EAM regarding scar area quantification (r = 0.66 [P < .01] vs r = 0.13 [P = .63]). Conclusion In participants who had undergone RFA for atrial fibrillation, an independent navigator-gated dark-blood PSIR sequence produced high-spatial-resolution dark-blood and bright-blood images with improved image contrast and native scar quantification compared with conventional bright-blood images. © RSNA, 2023 Supplemental material is available for this article.

Global Burden and Its Association with Socioeconomic Development Status of Meningitis Caused by Specific Pathogens over the Past 30 years: A Population-Based Study.

BACKGROUND: Meningitis is a severe and fatal neurological disease and causes lots of disease burden. The purpose of this study was to assess the global, regional, and national burdens and trends of meningitis by age, sex, and etiology. METHODS: Data on the burden of meningitis were collected from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. R and Joinpoint were used for statistical analysis and charting. RESULTS: In 2019, meningitis caused 236,222 deaths and 15,649,865 years of life lost (YLL) worldwide. The age-standardized death rate and age-standardized YLL rate of meningitis were 3.29 and 225, which decreased steadily. Burden change was mainly driven by epidemiological changes. Regionally, meningitis burden was the highest in Sub-Saharan Africa. Burden of disease increasingly concentrated in low sociodemographic index countries, and this was most pronounced in meningitis caused by N. meningitidis. Countries such as Mali, Nigeria, Sierra Leone, etc., especially need to enhance the rational allocation of public health resources to reduce the disease burden. Children and men were more likely to be affected by meningitis. PM2.5 was found to be an important risk factor. CONCLUSIONS: This study provides the first comprehensive understanding of the global disease burden of meningitis caused by specific pathogens and highlights policy priorities to protect human health worldwide, with particular attention to vulnerable regions, susceptible populations, environmental factors, and specific pathogens.

Epidemiology of healthcare-associated infections and outcomes among open and robotic pancreatoduodenectomy: A retrospective study from 2013 to 2022.

BACKGROUND AND AIM: Healthcare-associated infections (HAIs) after pancreaticoduodenectomy (PD) are one of the common postoperative complications. This study aims to investigate the epidemiology of postoperative HAIs in patients with open pancreaticoduodenectomy (OPD) and robotic pancreaticoduodenectomy (RPD). METHODS: This retrospective cohort study described the trend of HAIs in patients undergoing PD from January 2013 to December 2022 at a tertiary hospital. Patients were divided into OPD and RPD, and the HAIs and outcomes were compared. RESULTS: Among 2632 patients who underwent PD, 230 (8.7%, 95% confidence interval [CI] 7.7-9.9%) were diagnosed with HAIs, with a decreasing trend from 2013 to 2022 (P < 0.001 for trend). The incidence of postoperative HAIs was significantly higher in patients with OPD than RPD (9.6% vs 5.8%; P = 0.003). The incidence of HAIs for patients with OPD showed a decreasing trend (P = 0.001 for trend), and the trend for RPD was not significant (P = 0.554 for trend). Logistic regression showed that RPD was significantly associated with postoperative HAIs after adjusting for covariates (adjusted odds ratio = 0.654; 95% CI 0.443-0.965; P = 0.032), especially in the subgroup of patients without preoperative biliary drainage (adjusted odds ratio = 0.486; 95% CI 0.292-0.809; P = 0.006). Regarding clinical outcomes, RPD has a shorter length of stay and a more expensive charge than OPD (all P < 0.05). CONCLUSION: Postoperative HAIs in patients with PD showed a decreasing trend in recent years, especially in OPD. RPD was significantly associated with reduced postoperative HAIs and length of stay, although the charge is more expensive. Attention should be paid to postoperative HAIs in OPD, and it is imperative to continue reducing the costs of RPD.

Identification of biomarkers associated with immune-propionate metabolism in nonalcoholic fatty liver disease.

The mechanisms of the effect of propionate metabolism and immunity on nonalcoholic fatty liver disease (NAFLD) have not been adequately studied. Firstly, differentially expressed-propionate metabolism-related genes (DE-PMRGs) were selected by overlapping PMRGs and differentially expressed genes (DEGs) between the simple steatosis (SS) and health control (HC) groups. Then, common genes were selected by overlapping DE-PMRGs and key module genes obtained from weighted gene co-expression network analysis (WGCNA). Subsequently, the biomarkers were screened out by machine learning algorithms. The expression of the biomarkers was validated by quantitative Real-time PCR. In total, 5 biomarkers (JUN, LDLR, CXCR4, NNMT, and ANXA1) were acquired. The nomogram constructed based on 5 biomarkers had good predictive power for the risk of SS. Next, 5 biomarkers, 11 miRNAs, and 149 lncRNAs were encompassed in the ceRNA regulatory network. The expression of biomarkers was significantly higher in the HC group than in the SS group, which was consistent with the results in the GSE89632 and GSE126848 datasets. In this study, 5 immune and propionate metabolism-related biomarkers (JUN, LDLR, CXCR4, NNMT, and ANXA1) were screened out to provide a basis for exploring the prediction of diagnosis of NAFLD.

What Matters in Radiological Image Segmentation? Effect of Segmentation Errors on the Diagnostic Related Features.

Segmentation is a crucial step in extracting the medical image features for clinical diagnosis. Though multiple metrics have been proposed to evaluate the segmentation performance, there is no clear study on how or to what extent the segmentation errors will affect the diagnostic related features used in clinical practice. Therefore, we proposed a segmentation robustness plot (SRP) to build the link between segmentation errors and clinical acceptance, where relative area under the curve (R-AUC) was designed to help clinicians to identify the robust diagnostic related image features. In experiments, we first selected representative radiological series from time series (cardiac first-pass perfusion) and spatial series (T2 weighted images on brain tumors) of magnetic resonance images, respectively. Then, dice similarity coefficient (DSC) and Hausdorff distance (HD), as the widely used evaluation metrics, were used to systematically control the degree of the segmentation errors. Finally, the differences between diagnostic related image features extracted from the ground truth and the derived segmentation were analyzed, using the statistical method large sample size T-test to calculate the corresponding p values. The results are denoted in the SRP, where the x-axis indicates the segmentation performance using the aforementioned evaluation metric, and the y-axis shows the severity of the corresponding feature changes, which are expressed in either the p values for a single case or the proportion of patients without significant change. The experimental results in SRP show that when DSC is above 0.95 and HD is below 3 mm, the segmentation errors will not change the features significantly in most cases. However, when segmentation gets worse, additional metrics are required for further analysis. In this way, the proposed SRP indicates the impact of the segmentation errors on the severity of the corresponding feature changes. By using SRP, one could easily define the acceptable segmentation errors in a challenge. Additionally, the R-AUC calculated from SRP provides an objective reference to help the selection of reliable features in image analysis.

Irisin as a predictor of bone metabolism in Han Chinese Young Men with pre-diabetic individuals.

BACKGROUND: Irisin is a novel myokine both in mice and humans, and it can also be secreted by adipose tissue and the liver in a small amounts. There are few studies on irisin and bone metabolism. The aim of this study was to assess the relationship between serum irisin levels and bone metabolism and analyze its related factors in Han young male with pre-diabetic individuals. METHODS: This cross-sectional study included 41 pre-diabetes and 45 normal glucose tolerance (NGT). Anthropometric measurements, including height, weight, waist circumference (WC), and bone mineral content (BMC), were performed. All patients underwent an oral glucose tolerance test (OGTT) after 8 h of fasting, and the levels of glucose, insulin, lipids, serum irisin and bone turnover markers were measured. RESULTS: The levels of serum irisin (4.4 ± 1.4 vs. 6.3 ± 1.5 µg/mL), P1NP and OC were significantly lower and CTX was significantly higher in the pre-diabetes group (P < 0.05). BMC did not differ in the two groups (P > 0.05). Serum irisin levels negatively correlated with BMI (r =-0.325), FPG (r =-0.329), TG (r =-0.339) (P < 0.05) in NGT individuals. Serum irisin levels positively correlated with P1NP (r = 0.398), OC (r = 0.351), HDL-C (r = 0.432) and negatively correlated with FPG (r = -0.725), 2 h-PG (r = -0.360) (P < 0.05) in pre-diabetic individuals. Multiple regression analysis revealed that Serum irisin (ß = 9.768, P = 0.025) and WC (ß = -2.355, P = 0.002) were significant independent predictors for P1NP. CONCLUSION: Bone turnover markers were changed rather than bone mineral content in young men with pre-diabetes. In pre-diabetes individuals, serum irisin levels were reduced and close relationship with P1NP. Falling irisin levels may be a predictor of decreased bone formation in Han young men with pre-diabetes individuals.

Lung adenocarcinoma-related TNF-α-dependent inflammation upregulates MHC-II on alveolar type II cells through CXCR-2 to contribute to Treg expansion.

MHC-II on alveolar type-II (AT-II) cells is associated with immune tolerance in an inflammatory microenvironment. Recently, we found TNF-α upregulated MHC-II in AT-II in vitro. In this study, we explored whether TNF-α-mediated inflammation upregulates MHC-II on AT-II cells to trigger Treg expansion in inflammation-driven lung adenocarcinoma (IDLA). Using urethane-induced mice IDLA model, we found that IDLA cells mainly arise from AT-II cells, which are the major source of MHC-II. Blocking urethane-induced inflammation by TNF-α neutralization inhibited tumorigenesis and reversed MHC-II upregulation on tumor cells of AT-II cellular origin in IDLA. MHC-II-dependent AT-II cells were isolated from IDLA-induced Treg expansion. In human LA samples, we found high expression of MHC-II in tumor cells of AT-II cellular origin, which was correlated with increased Foxp3+ T cells infiltration as well as CXCR-2 expression. CXCR-2 and MHC-II colocalization was observed in inflamed lung tissue and IDLA cells of AT-II cellular origin. Furthermore, at the pro-IDLA inflammatory stage, TNF-α-neutralization or CXCR-2 deficiency inhibited the upregulation of MHC-II on AT-II cells in inflamed lung tissue. Thus, tumor cells of AT-II cellular origin contribute to Treg expansion in an MHC-II-dependent manner in TNF-α-mediated IDLA. At the pro-tumor inflammatory stage, TNF-α-dependent lung inflammation plays an important role in MHC-II upregulation on AT-II cells.

Dynamic 18F-FDG PET imaging of liver lesions: evaluation of a two-tissue compartment model with dual blood input function.

BACKGROUND: Dynamic PET with kinetic modeling was reported to be potentially helpful in the assessment of hepatic malignancy. In this study, a kinetic modeling analysis was performed on hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) from dynamic FDG positron emission tomography/computer tomography (PET/CT) scans. METHODS: A reversible two-tissue compartment model with dual blood input function, which takes into consideration the blood supply from both hepatic artery and portal vein, was used for accurate kinetic modeling of liver dynamic 18F-FDG PET imaging. The blood input functions were directly measured as the mean values over the VOIs on descending aorta and portal vein respectively. And the contribution of hepatic artery to the blood input function was optimization-derived in the process of model fitting. The kinetic model was evaluated using dynamic PET data acquired on 24 patients with identified hepatobiliary malignancy. 38 HCC or ICC identified lesions and 24 healthy liver regions were analyzed. RESULTS: Results showed significant differences in kinetic parameters [Formula: see text], blood supplying fraction [Formula: see text], and metabolic rate constant [Formula: see text] between malignant lesions and healthy liver tissue. And significant differences were also observed in [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] between HCC and ICC lesions. Further investigations of the effect of SUV measurements on the derived kinetic parameters were conducted. And results showed comparable effectiveness of the kinetic modeling using either SUVmean or SUVmax measurements. CONCLUSIONS: Dynamic 18F-FDG PET imaging with optimization-derived hepatic artery blood supply fraction dual-blood input function kinetic modeling can effectively distinguish malignant lesions from healthy liver tissue, as well as HCC and ICC lesions.

[Advancement of imaging technology for coronary microcirculation dysfunction assessment].

Coronary microcirculation dysfunction (CMVD) is an important risk factor for the prognosis of re-perfused ischemic heart. Recent studies showed that the evaluation of CMVD has significant impact on both the early diagnosis of heart diseases relevant to blood supply and prognosis after myocardial reperfusion. In this review, the definition of CMVD from the perspective of pathophysiology was clarified, the principles and features of the state-of-the-art imaging technologies for CMVD assessment were reviewed from the perspective of engineering and the further research direction was promoted.

Multicenter surveillance study of surgical site infection and its risk factors in radical resection of colon or rectal carcinoma.

BACKGROUND: Colorectal surgery is associated with high rates of surgical site infection (SSI). We investigated SSI in radical resection of colon or rectal carcinoma and its epidemiological distribution in 26 hospitals in China. METHODS: We conducted prospective surveillance of patients who underwent radical resection of colon or rectal carcinoma in 26 selected hospitals from January 2015 to June 2016.An information system monitored all of the surgical inpatients. Infection control professionals observed the inpatients with suspected SSI who had been screened by the system at the bedside. The infection status of the incisions was followed up by telephone 1 month after the operation. RESULTS: In total, 5729 patients were enrolled for the two operations; SSIs occurred in 206 patients, and the infection rate was 3.60%. The incidence of SSI after radical resection of rectal carcinoma (5.12%; 119/2323) was 2.1 times higher than that after radical resection of colon carcinoma (2.55%; 87/3406) (P < 0.0001). Additionally, in the colon versus rectal groups, the rate of superficial incisional SSI was 0.94% versus 2.28% (P < 0.0001), the rate of deep incisional SSI was 0.56% versus 1.11% (P = 0.018), and the rate of organ space SSI was 1.06% versus 1.72% (P = 0.031), respectively. The most common pathogens causing SSIs after radical resection of colon carcinoma were Escherichia coli (21/38) and Pseudomonas aeruginosa (5/38). Escherichia coli (24/65) and Enterococcus spp. (14/65) were the two most common pathogens in the rectal group. The multivariate logistic regression analysis showed that only the operating time and number of hospital beds were common independent risk factors for SSIs after the two types of surgery. CONCLUSION: This multicenter study showed that there were significant differences in the incidence of SSIs, three types of SSIs, and some risk factors between radical resection of colon carcinoma and rectal carcinoma.

Serum ferritin, an early marker of cardiovascular risk: a study in Chinese men of first-degree relatives with family history of type 2 diabetes.

BACKGROUND: Ferritin is one of the key proteins that regulate iron homeostasis and is widely available clinical biomarker of iron status. This study aimed to discuss the influence of serum ferritin (SF) on cardiovascular risk factors in the first-degree relatives with family history of type 2 diabetes (FHD). METHODS: This cross-sectional study included 232 men. Anthropometric measurements and blood samples were analyzed. The people were divided into four groups according to median SF (102.8 ng/ml) and people with or without FHD. Group A (FHD-and low SF), group B (FHD-and high SF), group C (FHD+ and low SF), and group D (FHD+ and high SF). RESULTS: The subjects in different categories of SF concentrations showed significant differences in BMI (SF main effect: P = 0.010), WC (P = 0.030), SBP (P < 0.001), FPG (P < 0.001), PPG-2 h (P < 0.001), FINS (P < 0.001), and HOMA-IR (P = 0.015; all: 2-way ANOVA). There was a significant difference in SBP (FHD main effect: P = 0.003), DBP (P = 0.006), and FINS (P = 0.013, all: 2-way ANOVA) between the groups with or without FHD. The interaction term between SF and FHD was significant for SBP (P = 0.011), DBP (P = 0.012), and PPG-2 h (P = 0.022). Logistic analysis showed that accumulation of CVD risk factors, which were ≥ 2 items and ≥ 3 items in group D were 7.546 and 3.343 times higher compared with group A (P < 0.05). CONCLUSIONS: The increased SF levels increased the risk of cardiovascular risk factors and the occurrence of insulin resistance in first-degree relatives with FHD.

Impact of energy taxation on economy, environmental and public health quality.

This paper argues computable general equilibrium model and assess impact of energy taxation on economy, environmental and public health quality in Tianjin. In order to investigate different energy taxation based on medical cost and labor loss, the computable general equilibrium model integrating with input-output table and social accounting matrix (SAM) was constructed. The medical expense caused by air pollution of Tianjin in 2007 is 396 million yuan and death for 18104 people, which accounted for the total GDP and population 0.754‰ and 1.6‰, respectively. The results show that the enery taxes levy can improve the GDP, but it is only slightly. The energy taxes have adverse impact on energy sector because that the energy cost is increased. The scale of production is reduced, and the capital and labor resources are transferred to low energy consumption low emissions sector. The energy tax levy can reduce air pollutants concentration and improve air environmental quality. The PM10, SO2 and NO2 concentration in the energy taxes 5%-30% was reduced by 0.24%-0.24%, 0.09-0.52% and 0.29%-0.52% respectively. The medical expense has little impact on GDP, but labor loss has a certain effect on GDP. For higher energy taxes rate, the health effects on GDP can reach 0.06%-0.16%. This simultaneous economic and environmental improvement and health effect would thus have positive implications regarding energy taxes of the country.

Activation of Stimulator of Interferon Genes in Hepatocytes Suppresses the Replication of Hepatitis B Virus.

Induction of interferon and proinflammatory cytokines is a hallmark of the infection of many different viruses. However, hepatitis B virus (HBV) does not elicit a detectable cytokine response in infected hepatocytes. In order to investigate the molecular mechanism underlying the innate immune evasion, a functional cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway was reconstituted in a human hepatoma cell line supporting tetracycline-inducible HBV replication. It was demonstrated that induction of HBV replication neither activated nor inhibited this cytosolic DNA sensing pathway. However, human hepatoma cells, as well as immortalized mouse hepatocytes, express low levels of STING, which upon activation by cGAMP, the natural ligand of STING, led to induction of a proinflammatory cytokine response. Treatment of immortalized mouse hepatocytes supporting HBV replication with either cGAMP or a small molecule pharmacologic STING agonist significantly reduced viral DNA in a STING- and Janus kinase 1-dependent manner. Moreover, cGAMP treatment was able to induce inflammatory cytokine gene expression and inhibit the transcription of covalently closed circular DNA in HBV-infected human hepatoma cells expressing sodium taurocholate cotransporting polypeptide, an essential receptor for HBV infection of hepatocytes. The studies reported here and previously (F. Guo et al., Antimicrob Agents Chemother 59:1273-1281, 2015, https://doi.org/10.1128/AAC.04321-14) thus support the notion that pharmacological activation of STING in macrophages and hepatocytes induces host innate responses that can efficiently control HBV replication. Hence, despite not playing a significant role in host innate immune response to HBV infection of hepatocytes, STING is potentially a valuable target for immunotherapy of chronic hepatitis B.

The Levels of Serum Irisin as a Predictor of Insulin Resistance in Han Chinese Adults with Metabolically Healthy Obesity.

BACKGROUND: The aim of this study was to evaluate serum irisin levels and analyze its related factors in Han adults with metabolically healthy obesity. METHODS: This cross-sectional study included 75 metabolically healthy, non-obese adults and 51 metabolically healthy, obese adults. Anthropometric measurements, including height, weight, waist circumference (WC), and blood pressure, were performed. All patients underwent an oral glucose tolerance test (OGTT) after 8 hours of fasting, and the levels of glucose, insulin, lipids, and serum irisin were measured. RESULTS: The levels of serum irisin (5.40 ± 1.69 vs. 6.46 ± 1.37 µg/mL) were significantly lower in the metabolically healthy obese group (p < 0.05). Irisin correlated positively with high density lipoprotein cholesterol (HDL-C) (r = 0.303) and correlated negatively with body mass index (BMI) (r = -0.389), WC (r = -0.324), fasting plasma glucose (FPG) (r = -0.441), HOMA-IR (r = -0.429), triglycerides (TG) (r = -0.185), total cholesterol (TC) (r = -0.209), low density lipoprotein cholesterol (LDL-C) (r = -0.157) (p < 0.05). Multiple regression analysis revealed that FPG (ß = -1.720, p = 0.001) and HOMA-IR (ß = -0.399, p = 0.006) were still significantly associated with irisin. Serum irisin (ß = -0.246, p = 0.005) and BMI (ß = 0.078, p = 0.043) were significant independent predictors for HOMAIR. CONCLUSIONS: Serum irisin levels were reduced in metabolically healthy, obese Han adults. Irisin reduction appears to be associated with elevated FPG and insulin resistance but not obesity. In additional, falling irisin may increase the occurrence of insulin resistance in metabolically healthy Han adults and should be examined in future studies.

cAMP and cGMP Play an Essential Role in Galvanotaxis of Cell Fragments.

Cell fragments devoid of the nucleus and major organelles are found in physiology and pathology, for example platelets derived from megakaryocytes, and cell fragments from white blood cells and glioma cells. Platelets exhibit active chemotaxis. Fragments from white blood cells display chemotaxis, phagocytosis, and bactericidal functions. Signaling mechanisms underlying migration of cell fragments are poorly understood. Here we used fish keratocyte fragments and demonstrated striking differences in signal transduction in migration of cell fragments and parental cells in a weak electric field. cAMP or cGMP agonists completely abolished directional migration of fragments, but had no effect on parental cells. The inhibition effects were prevented by pre-incubating with cAMP and cGMP antagonists. Blocking cAMP and cGMP downstream signaling by inhibition of PKA and PKG also recovered fragment galvanotaxis. Both perturbations confirmed that the inhibitory effect was mediated by cAMP or cGMP signaling. Inhibition of cathode signaling with PI3K inhibitor LY294002 also prevented the effects of cAMP or cGMP agonists. Our results suggest that cAMP and cGMP are essential for galvanotaxis of cell fragments, in contrast to the signaling mechanisms in parental cells.

Real-time automatic hospital-wide surveillance of nosocomial infections and outbreaks in a large Chinese tertiary hospital.

BACKGROUND: We aimed to develop a real-time nosocomial infection surveillance system (RT-NISS) to monitor all nosocomial infections (NIs) and outbreaks in a Chinese comprehensive hospital to better prevent and control NIs. METHODS: The screening algorithm used in RT-NISS included microbiological reports, antibiotic usage, serological and molecular testing, imaging reports, and fever history. The system could, in real-time, identify new NIs, record data, and produce time-series reports to align NI cases. RESULTS: Compared with a manual survey of NIs (the gold standard), the sensitivity and specificity of RT-NISS was 98.8% (84/85) and 93.0% (827/889), with time-saving efficiencies of about 200 times. RT-NISS obtained the highest hospital-wide monthly NI rate of 2.62%, while physician and medical record reviews reported rates of 1.52% and 2.35% respectively. It took about two hours for one infection control practitioner (ICP) to deal with 70 new suspicious NI cases; there were 3,500 inpatients each day in the study hospital. The system could also provide various updated data (i.e. the daily NI rate, surgical site infection (SSI) rate) for each ward, or the entire hospital. Within 3 years of implementing RT-NISS, the ICPs monitored and successfully controlled about 30 NI clusters and 4 outbreaks at the study hospital. CONCLUSIONS: Just like the "ICPs' eyes", RT-NISS was an essential and efficient tool for the day-to-day monitoring of all NIs and outbreak within the hospital; a task that would not have been accomplished through manual process.

Relationships Between the Apolipoprotein Levels and Sarcopenia in Inpatients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Background: Apolipoprotein (Apo) may be associated with sarcopenia in elderly inpatients with type 2 diabetes mellitus (T2DM), but fewer studies are available. In this study, we explored the association of ApoA1, ApoB, and ApoB/ApoA1 with sarcopenia and compared the predictive role of Apo indicators for sarcopenia in an elderly T2DM. Objective: To investigate the relationships between the Apo and sarcopenia in elderly inpatients with T2DM. Methods: This study included 253 inpatients with T2DM (mean age of 70.11±5.44 years, 32.8% male). The inpatients were divided into the sarcopenic group (n = 100) and non-sarcopenic group (n = 153). The associations among the Apo and sarcopenia were assessed using multivariate analyses. Results: Inpatients in the sarcopenia group showed lower ApoA1 levels than those in the non-sarcopenia group (1.25±0.21 vs 1.36±0.20 g/L, P < 0.05) and showed higher ApoB/ApoA1 and ApoB levels than those in the non-sarcopenia group (0.82±0.27 vs 0.69±0.19 g/L, P < 0.05;1.00±0.32 vs 0.93±0.24 g/L, P < 0.05, respectively). After adjusting for age and BMI, the logistic regression model indicated that ApoA1 was a protective factor for elderly inpatients with T2DM sarcopenia.(OR =0.079,95% CI: 0.021~0.306, P < 0.05);ApoB and AopB/AopA1 were risk factors for elderly inpatients with T2DM sarcopenia.(OR =3.578,95% CI:1.318~9.715, P < 0.05;OR =16.440,95% CI:4.437~60.427, P < 0.05, respectively). AopB/AopA1 provided an AUC value of 0.765 in elderly men.(95% CI: 0.665~0.866, P<0.05). Conclusion: ApoA1, AopB, and AopB/AopA1 are associated with sarcopenia in elderly inpatients with T2DM, and AopB/AopA1 may be a potential predictor of sarcopenia in elderly men with T2DM.