Causal relationship between chronic obstructive pulmonary disease and heart failure: A Mendelian randomization study.

BACKGROUND: Causal association between chronic obstructive pulmonary disease (COPD) and heart failure (HF) has been controversial. This study used Mendelian Randomization (MR) analysis to clarify the potential causal connection between these two conditions. OBJECTIVES: The purpose of the study was to investigate the causal relationship between COPD and HF based on the hypothesis that the genetic predisposition to COPD could lead to an increased risk of developing HF METHODS: A two-sample MR analysis of genetic data was performed for COPD and HF. This study was based on genome-wide association study (GWAS) data, including 6,915 patients with confirmed COPD and 186,723 controls. The odds ratios (ORs) and their 95 % confidence intervals (95 %CIs) were estimated using a fixed effects inverse variance weighting (IVW) method. Several supplementary statistical methods, including MR-Egger, weighted median, maximum likelihood, penalized weighted median, and random effects IVW, were applied to enhance the robustness of findings. Moreover, MR-PRESSO was employed as an alternative method for statistical detection. RESULTS: Pooled data for HF were obtained from different GWASs, including 4,7309 confirmed HF patients and 930,014 controls. The MR analysis, based on the IVW model, revealed that COPD was significantly associated with an increased risk of HF. Specifically, the obtained findings showed that COPD patients had a higher risk of developing HF (Model 1: OR = 1.068, 95 %CI: 1.006-1.134, p = 0.031; Model 2: OR = 1.038, 95 %CI: 1.006-1.071, p = 0.020), indicating a causal relationship between COPD and HF. No evidence was found to suggest a reverse causal effect of HF on COPD incidence. CONCLUSION: The MR analysis substantiates a causal link between COPD and HF, with no evidence supporting a reverse causation from HF to COPD. These findings underscore the importance of proactive COPD management as a potential strategy to prevent the development of HF, highlighting the need for targeted interventions in patients with COPD to mitigate their risk of HF.

An improvement method for pancreas CT segmentation using superpixel-based active contour.

Pancreas is one of the most challenging organs for CT image automatic segmentation due to its complex shapes and fuzzy edges. It is simple and universal to use the traditional segmentation method as a post-processor of deep learning method for segmentation accuracy improvement. As the most suitable traditional segmentation method for pancreatic segmentation, the active contour model(ACM), still suffers from the problems of weak boundary leakage and slow contour evolution speed. Therefore, a convenient post-processor for any deep learning methods using superpixel-based active contour model(SbACM) is proposed to improve the segmentation accuracy. Firstly, the superpixels with strong adhesion to edges are used to guide the design of narrowband and energy function. A multi-scale evolution strategy is also proposed to reduce the weak boundary leakage and comprehensively improve the evolution speed. Secondly, using the original image and the coarse segmentation results obtained from deep learning methods as inputs, the proposed SbACM method is used as a post-processor for fine segmentation. Finally, the pancreatic segmentation public dataset TCIA from the National Institutes of Health(NIH, USA) is used for evaluation, and the Wilcoxon Test confirmed that the improvement of proposed method is statistically significant. The results show that: (1) The superpixel-based narrowband shape and dynamic edge energy of the proposed SbACM work for boundary leakage reduction, as well as the multi-scale evolution strategy and dynamic narrowband width for the evolution speed improvement; (2)As a post-processor, SbACM can increase the Dice similarity coefficients(DSC) of five typical UNet-based models, including UNet, SS-UNet, PBR UNet, ResDSN, and nnUNet, 2.35% in average and 9.04% in maximum. (3)Based on the best backbone nnUNet, the proposed post-processor performs better than either adding edge awareness or adding edge loss in segmentation enhancement without increasing the complexity and training time of deep learning models.

[Study on chemical components of Hypericum himalaicum and mechanism of anti-inflammatory based on network pharmacology and molecular docking technology].

The chemical constituents of ethyl acetate from Hypericum himalaicum were isolated by silica gel column chromatography, gel column chromatography, and high-performance liquid chromatography. The structure of the isolated compounds was identified by modern spectral techniques(NMR, MS, IR, and UV), and the potential anti-inflammatory targets and action pathways were analyzed and predicted by network pharmacology and molecular docking methods.Ten compounds were isolated from H. himalaicum and identified as 5,9,11-trihydroxy-3,3-dimethyl-3H,8H-benzo[6,7][1,4]dioxepino[2,3-f]chromen-8-one(1), betulinic acid(2), demethyltorosaflavone C(3), kaempferol(4), quercetin(5), hyperwightin B(6), toxyloxanthone B(7), 1,7-dihydroxy-xanthone(8), emodin(9), and 1,7-dihydroxy-4-methoxy-xanthone(10). Among them, compound 1 was a new compound, and compounds 2-10 were isolated from H. himalaicum for the first time. Network pharmacology screened 60 key anti-inflammatory targets. By acting on TNF, AKT1, CASP3, and other key targets, involving PI3K-AKT signaling pathway, IL-17 signaling pathway, VEGF signaling pathway, MAPK signaling pathway, and other signaling pathways, and phosphorylation, cell migration and movement, protein tyrosine kinase, and other biological processes were regulated to achieve anti-inflammatory effects. The results of molecular docking show that the above components have good binding properties with the core targets.

Structure searches and superconductor discovery in XB2 (X = Sc, Ti, V, Cr, and Tc).

With extensive structure searches for XB2 (X = Sc, Ti, V, Cr, and Tc) under pressures up to 100 GPa, we uncovered that the crystal structures of these compounds with the lowest enthalpy have the same space group (P6/mmm) as MgB2 at ambient pressure. Among them, ScB2, TiB2 and VB2 are dynamically stable at ambient pressure, but they do not superconduct. CrB2 becomes dynamically stable at 108 GPa and shows superconductivity with a transition temperature (Tc) of 26.0 K. TcB2 is not dynamically stable until 9 GPa. At 20 GPa, it has a Tc of 23.5 K. Further calculations indicate that CrB2 and TcB2 are also thermodynamically stable, suggesting that it is highly likely that they can be synthesized successfully in the laboratory. We found that transition metal atoms (Cr/Tc) dominate soft phonon vibrations and make significant contributions to the electron-phonon coupling (EPC) and superconductivity in CrB2/TcB2, which is in strong contrast to the case of MgB2, where high-frequency B vibrations dominate the EPC and superconductivity. Our work enriches the understanding of superconductivity in transition metal borides.

Ketamine induces insomnia-like symptom of zebrafish at environmentally relevant concentrations by mediating GABAergic synapse.

Although the stimulative effects on the normal behaviors of fish posed by ketamine (KET) were well-studied, the adverse effects on the behavioral functions induced by KET at nighttime were unknown. Here, we used zebrafish larvae as a model exposed to KET (10, 50, 100, and 250 ng/L) at environmental levels for 21 days. The behavioral functions at nighttime, morphological changes during exposure stage, and alterations on the associated genes transcriptional levels of fish were determined. The difficultly initiating sleep was found in the fish exposed to KET, while the sleep duration of the animals was at the normal levels in exposure groups. The significant suppressions of the developmentally relevant genes, including bmp2, bmp4, and pth2ra were consistent with the developmental abnormalities of fish found in exposure groups. Moreover, the expression of γ-aminobutyric acid (GABA) receptor increased and melatonin (MTN) receptor decreased while the levels of GABA and MTN remained unchanged after exposure, by gene expression analysis and molecular docking. In addition, the transcriptional expression of apoptotic genes, including tp53, aifm1, and casp6, was significantly upregulated by KET. After a 7-day recovery, the insomnia-like behaviors (shorter sleep duration) were observed in zebrafish from the 250 ng/L-KET group. Accordingly, the adverse outcome pathway framework of KET was constructed by prognostic assessment of zebrafish larvae. This study suggested that the adverse outcomes of KET on the sleep health of organisms at environmentally relevant concentrations should be concerned.

Surface profile measurement and parameter analysis of silicon wafers in the upright state.

A novel approach, to the best of our knowledge, is presented for assessing silicon wafer surface profiles using an interferometer and vertically rotatable wafer holder. This approach significantly enhances precision and reduces costs, and outperforms traditional techniques in measurement consistency and accuracy. It effectively reduces sample distortion and positional shifts owing to the removal and reinstallation of the wafers. Using this method, a global backsurface-referenced ideal range of 0.385 µm, warp of 0.193 µm, and other parameters were obtained, demonstrating its practicality in efficiently capturing key surface profile metrics for silicon wafers. This innovation promises substantial improvements in high-volume wafer surface profile testing, overcoming prevalent technological challenges in this industry.

Proteinase­3­antineutrophil cytoplasmic antibody­associated vasculitis secondary to subacute infective endocarditis: A case report.

A 58-year-old male patient was admitted to Peking University First Hospital (Beijing, China) due to recurrent hematuria, proteinuria and kidney dysfunction. The patient was positive for proteinase-3 (PR3)-antineutrophil cytoplasmic antibody (ANCA). Pathology of the kidney showed focal proliferative necrotizing glomerulonephritis with crescent formation and immune complex-mediated glomerulonephritis. The patient was diagnosed with PR3-ANCA-associated vasculitis (AAV), received intensive immunosuppressive therapy and experienced two relapses within 1 year. After admission, aortic valve vegetation was observed via echocardiography. The patient subsequently received antibiotic treatment and valve replacement, and achieved complete remission of kidney and cardiac function. The present case emphasized the importance of identifying secondary reasons for ANCA formation, especially infective endocarditis in patients with PR3-AAV.

Establishment of a model of LPS-induced inflammatory injury in human aortic endothelial cells.

PURPOSE: We aim to establish an LPS-induced human aortic endothelial cells (HAECs) inflammatory injury model and explore the optimal conditions for inducing its injury. We expect to provide modeling references for the related experiments of vascular inflammatory diseases. METHODS: HAECs were cultured in vitro and treated with different concentrations of lipopolysaccharide (LPS) (0.1, 1, 10, 50, 100 µg/mL) for 6, 12, and 24 h to establish the HAECs inflammatory injury model. The cell viability was determined by CCK-8 assay; the expression levels of inflammatory cytokines in the cells were detected by RT-PCR；the apoptosis rate of the cells was detected by flow cytometry. RESULTS: ① Within 24 h of LPS treatment, the cell viability of the 0.1 and 1 µg/mL groups showed an overall increasing trend with time, while the cell viability of the 10, 50, and 100 µg/mL groups increased first and then decreased with time, and the cell viability of 50 and 100 µg/mL groups was significantly lower than the normal control group at 24 h (P<0.01). ② RT-PCR results showed that after 50 and 100 µg/mL LPS for 24 h, the inflammatory cytokines all showed an apparent upward trend compared with the normal control group (P<0.05), which was more significant in the 100 µg/mL group. ③ After 100 µg/mL LPS for 24 h, the apoptotic necrosis rate of HAECs was higher than the normal control group (P<0.01). CONCLUSIONS: This experiment successfully established a HAECs injury model, indicating that the optimal conditions for inducing injury are an LPS concentration of 100 µg/mL and a treatment time of 24 h.

Diagnostic Accuracy of Computerized Bowel Sound Analysis with Non-Invasive Devices for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.

Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome (IBS) with a systematic review and meta-analysis. Methods We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science, and IEEE Xplore databases until September 2023. Cross-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were identified. We estimated the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio with a 95% confidence interval (CI), and plotted a summary receiver operating characteristic curve and evaluated the area under the curve. Results Four studies were included. The pooled diagnostic sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.94 (95% CI, 0.87－0.97), 0.89 (95% CI, 0.81－0.94), 8.43 (95% CI, 4.81－14.78), 0.07 (95% CI, 0.03－0.15), and 118.86 (95% CI, 44.18－319.75), respectively, with an area under the curve of 0.97 (95% CI, 0.95－0.98). Conclusions Computerized bowel sound analysis is a promising tool for IBS. However, limited high-quality data make the results' validity and applicability questionable. There is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis.

Higher serum alanine aminotransferase levels and the incidence of hypertension: The Kailuan cohort study.

Objective: The association between serum alanine aminotransferase (ALT) concentrations and the incidence of hypertension remains unclear. To explore the association between serum ALT levels and the risk of incident hypertension based on the Kailuan cohort study. Methods: People who had participated in health check-ups in 2006-2007 without hypertension, cardiovascular, or liver diseases were enrolled and received follow-ups every two years until December 2017. Hypertension was defined as systolic blood pressure/diastolic blood pressure ≥140/90 mmHg or using anti-hypertensive medication. A multivariable-adjusted Cox regression model was used to estimate the hazard ratio (HR) and its corresponding 95 % confidence intervals (95 % CIs). Results: During 10.5 years of follow-up, 24,023 (50.7 %) participants were diagnosed with hypertension. The HR of incident hypertension was 1.02 (95 % CI=1.01-1.03) for each 10 U/L increment of ALT concentrations. Participants with elevated ALT levels (>40 U/L) had an increased incidence of hypertension by 7 % (HR =1.07; 95 % CI=1.01-1.13). Besides, the HR was 1.10 (95 % CI=1.06-1.15), 1.13 (95 % CI=1.08-1.18), and 1.22 (95 % CI=1.16-1.30) (P for trend <0.001) in (10-20], (20-30], and (30-40] groups, compared with ≤10 U/L group. In addition, participants whose ALT levels decreased to the normal range at the first follow-up had a 23 % lower incidence of hypertension than those with elevated ALT levels at baseline and the first follow-up. Conclusion: People with higher serum ALT levels may have an increased risk of incident hypertension and thus may benefit from heightened surveillance for hypertension and lifestyle interventions to reduce the risk of hypertension.

Enhancing soil health and strawberry disease resistance: the impact of calcium cyanamide treatment on soil microbiota and physicochemical properties.

Introduction: Continuous strawberry cropping often causes soil-borne diseases, with 20 calcium cyanamide being an effective soil fumigant, pig manure can often be used as soil organic fertilizer. Its impact on soil microorganisms structure, however, remains unclear. Methods: This study investigated the effectiveness of calcium cyanamide and pig manure in treating strawberry soil, specifically against strawberry anthracnose. We examined the physical and chemical properties of the soil and the rhizosphere microbiome and performed a network analysis. Results: Results showed that calcium cyanamide treatment significantly reduces the mortality rate of strawberry in seedling stage by reducing pathogen abundance, while increasing actinomycetes and Alphaproteobacteria during the harvest period. This treatment also enhanced bacterial network connectivity, measured by the average connectivity of each Operational Taxonomic Unit (OTU), surpassing other treatments. Moreover, calcium cyanamide notably raised the levels of organic matter, available potassium, and phosphorus in the soil-key factors for strawberry disease resistance and yield. Discussion: Overall, applying calcium cyanamide to soil used for continuous strawberry cultivation can effectively decrease anthracnose incidence. It may be by changing soil physical and chemical properties and enhancing bacterial network stability, thereby reducing the copy of anthracnose. This study highlights the dual benefit of calcium cyanamide in both disease control and soil nutrient enhancement, suggesting its potential as a valuable tool in sustainable strawberry farming.

Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Fructose induces hepatic steatosis in adolescent mice linked to the disorders of lipid metabolism, bile acid metabolism, and autophagy.

The effects of excessive fructose intake on the development and progression of metabolic disorders have received widespread attention. However, the deleterious effects of fructose on the development of hepatic metabolic disease in adolescents and its potential mechanisms are not fully understood. In this study, we investigated the effects of isocaloric fructose-rich diets on the liver of adolescent mice. The results showed that fructose-rich diets had no effect on the development of obesity in the adolescent mice, but did induce hepatic lipid accumulation. Besides, we found that fructose-rich diets promoted hepatic inflammatory responses and oxidative stress in adolescent mice, which may be associated with activation of the NLRP3 inflammasome and inhibition of the Nrf2 pathway. Furthermore, our results showed that fructose-rich diets caused disturbances in hepatic lipid metabolism and bile acid metabolism, as well as endoplasmic reticulum stress and autophagy dysfunction. Finally, we found that the intestinal barrier function was impaired in the mice fed fructose-rich diets. In conclusion, our study demonstrates that dietary high fructose induces hepatic metabolic disorders in adolescent mice. These findings provide a theoretical foundation for fully understanding the effects of high fructose intake on the development of hepatic metabolic diseases during adolescence.

Establishing national reference materials for genetic testing of cytochrome P450.

OBJECTIVES: Reference materials for in-vitro diagnostic reagents play a critical role in determining the quality of reagents and ensuring the accuracy of clinical test results. This study aimed to establish a national reference material (NRM) for detecting cytochrome P450 (CYP) genes related to drug metabolism by screening databases on the Chinese population to identify CYP gene polymorphism characteristics. METHODS: To prepare the NRM, we used DNA extracted from healthy human immortalized B lymphoblastoid cell lines as the raw material. Samples of these cell lines were obtained from the Chinese Population PGx Gene Polymorphism Biobank. Further, we used Sanger sequencing, next-generation sequencing, and commercial assay kits to validate the polymorphic genotypes. RESULTS: Among the CYP superfamily genes, we confirmed 24 riboswitch loci related to drug metabolism, with evidence levels of 1A, 2A, 3, and 4. We confirmed the polymorphic loci and validated their genotypes using various sequencing techniques. Our results were consistent with the polymorphism information of samples obtained from the biobank, thus demonstrating high precision and stability of the established NRM. CONCLUSION: An NRM (360 056-202 201) for CYP genetic testing covering 24 loci related to drug metabolism was established and approved to assess in-vitro diagnostic reagents containing CYP family gene polymorphisms and perform clinical inter-room quality evaluations.

Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization.

Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients with isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterize a Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxic niche cues to acquire a hypoxia response signature. Hypoxia-TAM destabilizes endothelial adherens junctions by activating adrenomedullin paracrine signaling, thereby stimulating a hyperpermeable neovasculature that hampers drug delivery in glioblastoma xenografts. Accordingly, genetic ablation or pharmacological blockade of adrenomedullin produced by Hypoxia-TAM restores vascular integrity, improves intratumoral concentration of the anti-tumor agent dabrafenib, and achieves combinatorial therapeutic benefits. Increased proportion of Hypoxia-TAM or adrenomedullin expression is predictive of tumor vessel hyperpermeability and a worse prognosis of glioblastoma. Our findings highlight Mo-TAM diversity and spatial niche-steered Mo-TAM reprogramming in diffuse gliomas and indicate potential therapeutics targeting Hypoxia-TAM to normalize tumor vasculature.

Structure and biological activity in vitro of Flagellin and its mutants from Escherichia coli Nissle 1917.

Bacterial flagellin is a potent immunomodulatory agent. Previously, we successfully obtained flagellin from Escherichia coli Nissle 1917 (FliCEcN) and constructed two mutants with varying degrees of deletion in its highly variable regions (HVRs). We found that there was a difference in immune stimulation levels between the two mutants, with the mutant lacking the D2-D3 domain pair of FliCEcN having a better adjuvant effect. Therefore, this study further analyzed the structural characteristics of the aforementioned FliCEcN and its two mutants and measured their levels of Caco-2 cell stimulation to explore the impact of different domains in the HVRs of FliCEcN on its structure and immune efficacy. This study utilized AlphaFold2, SERS (Surface-enhanced Raman spectroscopy), and CD (circular dichroism) techniques to analyze the structural characteristics of FliCEcN and its mutants, FliCΔ174-506 and FliCΔ274-406, and tested their immune effects by stimulating Caco-2 cells in vitro. The results indicate that the D2 and D3 domains of FliCEcN have more complex interactions compared to the D1-D2 domain pair., and these domains also play a role in molecular docking with TLR5 (Toll-like receptor 5). Furthermore, FliCΔ274-406 has more missing side chain and characteristic amino acid peaks than FliCΔ174-506. The FliCEcN group was found to stimulate higher levels of IL-10 (interleukin 10) secretion, while the FliCΔ174-506 and FliCΔ274-406 groups had higher levels of IL-6 (interleukin 6) and TNF-α (tumor necrosis factor-α) secretion. In summary, the deletion of different domains in the HVRs of FliCEcN affects its structural characteristics, its interaction with TLR5, and the secretion of immune factors by Caco-2 cells.

Study on the pharmacokinetics, tissue distribution and excretion of Penthorum chinense Pursh in normal and acute alcoholic liver injury rats using validated UPLC-MS/MS method.

Penthorum chinense Pursh (PCP), as a traditional medicine of Miao nationality in China, is often used for the treatment of various liver diseases. At present, information regarding the in vivo process of PCP is lacking. Herein, a sensitive and robust ultra-performance liquid chromatography tandem with mass spectrometry (UPLC-MS/MS) was developed and validated for the quantification of several components to study their pharmacokinetics, tissues distribution and excretion in normal and acute alcoholic liver injury (ALI) rats. Prepared samples were separated on a Thermo C18 column (4.6 mm × 50 mm, 2.4 µm) using water containing 0.1 % formic acid (A) and acetonitrile (B) as the mobile phase for gradient elution. Negative electrospray ionization was performed using multiple reaction monitoring (MRM) mode for each component. The validated UPLC-MS/MS assay gave good linearity, accuracy, precision, recovery rate, matrix effect and stability. This method was successfully applied to the pharmacokinetics, tissue distribution and excretion in normal and acute ALI rats. There were differences in pharmacokinetic process, tissue distribution and excretion characteristics, indicating that ALI had a significant influence on the in vivo process of PCP in rats. The research provided an experimental basis for the study of PCP quality control and further application in the clinic.

Porcine epidemic diarrhea virus E protein induces formation of stress granules and attenuates protein translation through activation of the PERK/eIF2α signaling pathway.

Porcine epidemic diarrhea virus (PEDV) envelope protein (E) has been characterized as an important structural protein that plays critical roles in the interplay with its host to affect the virus life cycle. Stress granules (SGs) are host translationally silent ribonucleoproteins, which are mainly induced by the phosphorylation of eIF2α in the PERK/eIF2α signaling pathway. Our previous study found that PEDV E protein caused endoplasmic reticulum stress response (ERS)-mediated suppression of antiviral proteins' translation. However, the link and the underlying mechanism by which PEDV induces SGs formation and suppresses host translation remain elusive. In this study, our results showed that PEDV E protein significantly elevated the expression of GRP78, CANX, and phosphorylation of PERK and eIF2α, indicating that the PERK/eIF2α branch of ERS was activated. PEDV E protein localized to the ER and aggregated into puncta to reconstruct ER structure, and further induced SGs formation, which has been caused through upregulating the G3BP1 expression level. In addition, a significant global translational stall and endogenous protein translation attenuation were detected in the presence of E protein overexpression, but the global mRNA transcriptional level remained unchanged, suggesting that the shutoff of protein translation was associated with the translation, not with the transcription process. Collectively, this study demonstrates that PERK/eIF2α activation is required for SGs formation and protein translation stall. This study is beneficial for us to better understand the mechanism by which PEDV E suppresses host protein synthesis, and provides us a new insight into the host translation regulation during virus infection.

Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: A multicenter real-world study in China.

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.