ObjectiveTo observe the protective effect of Erchentang （ECT） on SiO₂-induced lung injury in rats and to explore its underlying mechanism. MethodsA rat model of lung injury was established by a single intratracheal instillation of 50 mg·mL^-1 SiO₂ suspension. Thirty male Sprague-Dawley （SD） rats were randomly assigned to five groups： control， model， low and high-dose （4.5 g·kg^-1·d^-1 and 9 g·kg^-1·d^-1， respectively） ECT， and dexamethasone （0.2 mg·kg^-1·d^-1）. All the groups were treated for 4 consecutive weeks. Histopathological alterations in the lung tissue were examined by hematoxylin and eosin （HE） staining. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px） in the lung tissue were measured through biochemical assays. The expression of key molecules in the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway was determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， Western blot， and immunofluorescence assay. The primary active components of ECT were identified by ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and their binding affinity to Nrf2/HO-1 was assessed by molecular docking. Untargeted metabolomics of the lung tissue was performed based on UPLC-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and correlation analysis was performed to identify differential metabolites and parameters closely associated with the Nrf2/HO-1 pathway. ResultsCompared with the control group， the model group exhibited a reduction in body weight gain， an increase in lung index， increased MDA content， weakened SOD and GSH-Px activities in the lung tissue， down-regulated mRNA and protein levels of Nrf2 and protein levels of HO-1 and GPX4， and an up-regulated protein level of Keap1 （P<0.05， P<0.01）. Treatment with ECT attenuated the SiO₂-induced decline in body weight （P<0.05）， alleviated inflammatory cell infiltration and silicotic nodule formation in alveoli， and reduced the MDA content and enhanced the SOD and GSH-Px activities in the lung tissue （P<0.05， P<0.01）. UPLC-MS/MS and molecular docking revealed that core components of ECT， such as hesperidin and glycyrrhizic acid， displayed strong binding affinity to Nrf2/HO-1. Molecular biological experiments demonstrated that ECT promoted nuclear translocation of Nrf2， up-regulated the mRNA and protein levels of HO-1 and GPX4， and down-regulated Keap1 expression （P<0.05， P<0.01）. Metabolomic analysis indicated that ECT reversed the SiO₂-induced aberrant expression of metabolites， including linoleic acid and glutamine （P<0.05， P<0.01）. Correlation analysis showed that Nrf2 and HO-1 were positively correlated with SOD and GSH-Px （P<0.05， P<0.01）， but negatively correlated with glutamine and serine （P<0.05， P<0.01）. ConclusionECT may activate the Nrf2/HO-1 pathway through its core active components， thereby regulating oxidative stress and metabolic disorders to ameliorate SiO₂-induced lung injury in rats. This study provides experimental evidence for ECT in the prevention and treatment of occupational lung injury.

Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Objective To assess the effectiveness of the Regulations on Medical Dispute Prevention and Resolution(hereafter referred to as the Regulations)and to provide evidence-based recommendations for enhancing the legal governance sys-tem of medical dispute management.Methods A cross-sectional study was conducted involving physicians,nurses,techni-cians,clinical department directors,and head nurses.The investigation was conducted through literature review,questionnaire surveys,and expert interviews.Factor analysis and chi-square tests were employed for statistical analysis.Results Significant differences(P＜0.01)were observed among healthcare practitioners in Guangxi concerning their understanding of the Regula-tions,preferences for dispute resolution methods,implementation of informed consent,and risk intervention practices.However,no significant differences emerged in medical quality and safety evaluations or recommendations for surgical accident insurance.Conclusion This study suggests it is a need to refine the legal framework for medical dispute prevention and resolution.It is rec-ommended to strengthen medical personnel's compliance with informed consent obligations and deepen their understanding of rel-evant laws and regulations.Efforts should be intensified to promote third-party mediation mechanisms such as the Medical Dispute Mediation Committee(MedMC)and medical accident insurance coverage.Additionally,pre-dispute risk assessments should be enhanced,and a risk early intervention model integrating artificial intelligence,healthcare practices,and legal regulations should be established.

Objective To analyze the quality of medical record home pages for discharged patients in a tertiary hospital in Guangzhou in 2023 based on the dual dimensions of Diagnosis-Related Groups(DRG)and Disease Intervention Program(DIP),and to provide a basis for improving the refinement of medical record home page quality management.Methods Dis-charge medical records from a tertiary general hospital in 2023 were selected.All medical records were grouped using DRG,while medical records under Guangzhou medical insurance and cross-province medical insurance implemented under DIP were simulated for DIP grouping.The writing defects in the discharge medical records were analyzed,as well as the DRG grouping,RW,and DIP standard scores of medical records with home page filling defects.Results Among 172 230 discharge medical records,171 786 were grouped into DRG,91 768 were grouped into DIP,and 91 604 were grouped into both DRG and DIP.A significant positive correlation was found between RW and DIP standard scores(r2=0.681,P＜0.001).Among the 91 604 medical records grouped into both DRG and DIP,1 942(2.12％)had writing defects,including 837(0.91％)with home page defects.DRG groups with more home page defect records included NC15,HK2,EJ13,EB15,HJ13,and RE19.Conclusion Quality defects in medical record home pages impact the accuracy of DRG and DIP grouping.Systematic measures such as strengthening medical record writing training and establishing scientific reward and punishment mechanisms should be implemented to provide data sup-port for the further advancement of DRG/DIP payment reform.

Objective: To compare the transcriptomic profiles between three distinct metabolic dysfunction⁃associat⁃mal murine model that more closely resembles human MASH progression . Methods: Forty 8 ⁃week⁃old male C57BL/6J mice were randomly assigned to either a control group fed normal chow diet ( NCD) or one of three MASH model groups receiving high⁃fat high⁃cholesterol diet (HFHCD) , choline⁃deficient high⁃fat diet (CDHFD) ,from three randomly selected mice per group were collected for mRNA sequencing ( mRNA⁃seq) analysis . Mean⁃bases . Overlap of functional profiles was analyzed by gene set enrichment analysis (GSEA) profiles to compare the mouse transcriptome with that of human patients at different stages of the disease . Additionally , Pearson ′s correla⁃tion analysis was used to explore the correlation between gene expression of murine models and human MASH . Results: Seven commonly up⁃regulated genes (Col1a1 , Smoc2 , Col6a1 , Gpx3 , Col16a1 , Spp1 and Crtap) were de⁃ways involving steatosis , hepatocellular injury and fibrosis were detected in the three MASH models at the pathway level . HFHCD and MCD might share more common traits . In comparing gene expression and pathway profiles be⁃tween different murine models and patients with different stages of MASH , all three murine MASH models showed a closer resemblance to the human progressive stages of MASH . Notably , the transcriptomic features of the CDHFD model were more consistent with those of human MASH . Conclusion There are certain similarities and differences among the transcriptional profiles of the three MASH models . The MASH models are more similar to the advanced stage of MASH in human patients . Compared to the other two models , the CDHFD model ′ s transcriptome profile more closely resembles human MASH .

The study aims to investigate the impacts of prolyl oligopeptidase (POP) on the replication of foot-and-mouth disease virus (FMDV) in BHK-21 cells. Firstly, the effects of FMDV replication on POP expression in BHK-21 cells were analyzed by Western blotting and Real-time reverse transcription polymerase chain reaction (RT-qPCR). Secondly, a eukaryotic expression plasmid for POP was constructed, and the effects of POP overexpression on the replication of two different serotypes of FMDV were assessed by Western blotting, RT-qPCR, and virus titer assays. Thirdly, specific small interfering RNAs (siRNAs) targeting POP were synthesized, and their efficiency in interfering with endogenous POP expression was identified by RT-qPCR. The impacts of downregulating endogenous POP expression on FMDV replication were further evaluated by Western blotting, RT-qPCR, and virus titer assays. The results indicated that FMDV infection did not significantly affect POP expression in BHK-21 cells. Overexpression of POP dose-dependently enhanced the replication of both FMDV/O and FMDV/A serotypes. Conversely, siRNA-mediated downregulation of endogenous POP expression markedly suppressed FMDV/O replication. This study is the first to demonstrated that the role of the host POP protein in promoting FMDV replication in BHK-21 cells, thereby providing a critical theoretical foundation and potential molecular targets for developing efficient candidate cell strains for foot-and-mouth disease inactivated vaccines.
Foot-and-Mouth Disease Virus/genetics* ; Virus Replication/genetics* ; Prolyl Oligopeptidases ; Serine Endopeptidases/physiology* ; Animals ; Cell Line ; RNA, Small Interfering/genetics* ; Foot-and-Mouth Disease/virology* ; Cricetinae

Chronic pain, frequently comorbid with neuropsychiatric disorders, significantly impairs patients' quality of life and functional capacity. Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key players in chronic pain pathogenesis. This review examines the regulatory mechanisms of the CCL2/CCR2 axis in chronic pain processing at three hierarchical levels: (1) Peripheral Sensitization: CCL2/CCR2 modulates TRPV1, Nav1.8, and HCN2 channels to increase neuronal excitability and CGRP signaling and calcium-dependent exocytosis in peripheral nociceptors to transmit pain. (2) Spinal Cord Central Sensitization: CCL2/CCR2 contributes to NMDAR-dependent plasticity, glial activation, GABAergic disinhibition, and opioid receptor desensitization. (3) Supraspinal Central Networks: CCL2/CCR2 signaling axis mediates the comorbidity mechanisms of pain with anxiety and cognitive impairment within brain regions, including the ACC, CeA, NAc, and hippocampus, and it also increases pain sensitization through the descending facilitation system. Current CCL2/CCR2-targeted therapeutic strategies and their development status are discussed, highlighting novel avenues for chronic pain management.
Humans ; Chronic Pain/physiopathology* ; Animals ; Neuroglia/metabolism* ; Chemokine CCL2/metabolism* ; Receptors, CCR2/metabolism*

Objective To analyze the quality of medical record home pages for discharged patients in a tertiary hospital in Guangzhou in 2023 based on the dual dimensions of Diagnosis-Related Groups(DRG)and Disease Intervention Program(DIP),and to provide a basis for improving the refinement of medical record home page quality management.Methods Dis-charge medical records from a tertiary general hospital in 2023 were selected.All medical records were grouped using DRG,while medical records under Guangzhou medical insurance and cross-province medical insurance implemented under DIP were simulated for DIP grouping.The writing defects in the discharge medical records were analyzed,as well as the DRG grouping,RW,and DIP standard scores of medical records with home page filling defects.Results Among 172 230 discharge medical records,171 786 were grouped into DRG,91 768 were grouped into DIP,and 91 604 were grouped into both DRG and DIP.A significant positive correlation was found between RW and DIP standard scores(r2=0.681,P＜0.001).Among the 91 604 medical records grouped into both DRG and DIP,1 942(2.12％)had writing defects,including 837(0.91％)with home page defects.DRG groups with more home page defect records included NC15,HK2,EJ13,EB15,HJ13,and RE19.Conclusion Quality defects in medical record home pages impact the accuracy of DRG and DIP grouping.Systematic measures such as strengthening medical record writing training and establishing scientific reward and punishment mechanisms should be implemented to provide data sup-port for the further advancement of DRG/DIP payment reform.

Objective To evaluate the current status of knowledge,attitudes,and practices(KAP)regarding home bathing among ostomy patients and analyze the influencing factors,aiming to provide targeted improvement suggestions for clinical nursing practice.Methods A convenient sampling method was used to select 435 ostomy patients who were followed up at specialized ostomy care clinics in 16 tertiary hospitals across 1 1 prefecture-level cities in Zhejiang Province from July to October 2023.Data were collected using a general information survey and a questionnaire assessing KAP of home bathing for ostomy patients.Univariate analysis and multiple linear regression analysis were conducted to explore the influencing factors.Results A total of 418 valid questionnaires were recovered,with an effective recovery rate of 96.09％.The scores on the Ostomy Patients'Home Bathing KAP Assessment Questionnaire ranged from 40 to 104 points(72.32±12.95),with a passing score of 72 points.221 patients passed,achieving a pass rate of 52.87％.Multiple linear regression analysis showed that educational level,type of caregivers,postoperative time,and changes in postoperative bathing methods and frequency were significant influencing factors for the current status of home bathing among ostomy patients(P＜0.05).Conclusion Ostomy patients have a moderate level of knowledge about home bathing,a relatively negative attitude,and behaviors that need improvement.It is recommended that clinical nursing staff timely assess the bathing abilities and needs of patients,develop personalized bathing guidance and follow-up plans based on specific circumstances,promote self-care awareness,assist in the early recovery of bathing habits,and thereby enhance the knowledge,attitudes,and practices of home bathing in patients with ostomy to meet their hygiene needs.

Objective To evaluate the current status of knowledge,attitudes,and practices(KAP)regarding home bathing among ostomy patients and analyze the influencing factors,aiming to provide targeted improvement suggestions for clinical nursing practice.Methods A convenient sampling method was used to select 435 ostomy patients who were followed up at specialized ostomy care clinics in 16 tertiary hospitals across 1 1 prefecture-level cities in Zhejiang Province from July to October 2023.Data were collected using a general information survey and a questionnaire assessing KAP of home bathing for ostomy patients.Univariate analysis and multiple linear regression analysis were conducted to explore the influencing factors.Results A total of 418 valid questionnaires were recovered,with an effective recovery rate of 96.09％.The scores on the Ostomy Patients'Home Bathing KAP Assessment Questionnaire ranged from 40 to 104 points(72.32±12.95),with a passing score of 72 points.221 patients passed,achieving a pass rate of 52.87％.Multiple linear regression analysis showed that educational level,type of caregivers,postoperative time,and changes in postoperative bathing methods and frequency were significant influencing factors for the current status of home bathing among ostomy patients(P＜0.05).Conclusion Ostomy patients have a moderate level of knowledge about home bathing,a relatively negative attitude,and behaviors that need improvement.It is recommended that clinical nursing staff timely assess the bathing abilities and needs of patients,develop personalized bathing guidance and follow-up plans based on specific circumstances,promote self-care awareness,assist in the early recovery of bathing habits,and thereby enhance the knowledge,attitudes,and practices of home bathing in patients with ostomy to meet their hygiene needs.