Objective To establish a stable and reliable sepsis model of rat after liver transplantation (LT) for clinical translational research and analyze its characteristics. Methods The "two-sleeve method" was used to establish the in situ LT model of SD rats, and the sepsis model was constructed through cecal ligation and puncture (CLP) at 3 d after the operation. SD rats were randomly divided into 3 groups: sham operation group (Sham group), LT group, and LT + CLP group, with 6 rats in each group. The changes in body weight, rectal temperature and survival rate were compared, and the sepsis score was used for evaluation. The levels of blood biochemical indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Urea), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH)] and inflammatory factors [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α] in each group were detected, and the pathological changes and cell apoptosis in different organs were observed. Results Compared with the Sham group, the body weight of the LT group and LT + CLP group decreased (all P<0.05). The rectal temperature of the LT + CLP group showed a continuous downward trend after the operation, the sepsis score increased sharply after the operation, and the survival rate dropped to 16.7%, and the differences between the Sham group, LT group and LT + CLP group were statistically significant (all P<0.05). The levels of ALT, AST, Urea, Cr, CK, LDH, and serum IL-1β, IL-6, IL-10 and TNF-α in the LT + CLP group were higher than those in the Sham group and LT group rats within 72 hours after the operation(all P<0.05). The pathological examination of the LT + CLP group showed severe tissue structure destruction, necrosis and infiltration of inflammatory cells in multiple organs, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed an increased level of cell apoptosis in multiple organs. Conclusions Using liver transplantation combined with CLP, a stable animal model of liver transplantation infection is successfully established, which exhibits a high mortality rate, significant multi-organ damage and intense inflammatory response, providing an ideal animal model for transplantation infection research.

Background/Aims: The pathophysiology of refractory gastroesophageal reflux disease (RGERD), which differs from proton pump inhibitor dependent gastroesophageal reflux disease (DGERD), remains incompletely elucidated. This study aims to compare esophageal motility patterns, transdiaphragmatic pressure gradients (TPG), and reflux profiles between RGERD and DGERD patients, and to delineate dynamic pressure gradient-esophagogastric junction (EGJ) interactions in these patients. Methods: In this retrospective study, 274 patients who underwent 24-hour impedance-pH monitoring and high-resolution manometry, along with an assessment of proton pump inhibitor responsiveness, were classified as RGERD (32.5%), DGERD (54.4%), or non-GERD (13.1%). Clinical characteristics, TPG, esophageal motility, and reflux metrics were compared between RGERD and DGERD patients. Subgroup analysis excluding hiatal hernia (HH) was conducted to investigate the pathophysiology of RGERD. Results: The RGERD group exhibited a significantly higher proportion of chest pain compared to the DGERD group. Regarding reflux profiles, RGERD patients without HH (RGERDHH- group) experienced increased weakly acidic reflux (P < 0.001) and prolonged bolus exposure (P = 0.006) compared to their counterparts (DGERDHH- group). Mechanistically, the RGERDHH- group showed reduced lower esophageal sphincter basal pressure (P = 0.010) and EGJ contractile integral (P = 0.005). Notably, following a wet-swallow, the RGERDHH- group experienced the significant elevation in gastric pressure and TPG. Correlation analyses revealed weakly acidic reflux and bolus exposure were positively correlated with gastric pressure variation, and inversely correlated with lower esophageal sphincter basal pressure. Conclusions Transient gastric pressure elevation and compromised EGJ barrier function drive weakly acidic reflux and esophageal bolus exposure. This pressure gradient-barrier mismatch underpins the refractoriness of RGERD.

Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective To analyze the status of willingness to participate in health science popularization (HSP) and its influencing factors among medical workers in Guangdong Province. Methods A total of 462 medical workers in Guangdong Province were recruited as the study subjects using a stratified convenience sampling method. The Questionnaire on Influencing Factors of Willingness to Participate in Health Science Popularization, developed by the research team, was used to investigate their willingness to participate in HSP and related variables, including previous communication experience, attitude, moral belief, descriptive norm, injunctive norm, self-efficacy, and social support. Hierarchical regression analysis was used to identify the influencing factors of willingness to participate in HSP. Results The median and 25^th and 75^th percentiles score of willingness to participate in HSP was 4.0 (3.8, 4.5), indicating a moderately high level of willingness. The HSP participation willingness score was positively correlated with scores for previous communication experience, attitude, moral belief, descriptive norm, injunctive norm, self-efficacy, and social support (Spearman correlation coefficients were 0.513, 0.384, 0.507, 0.533, 0.463, 0.556, and 0.435, respectively; all P<0.01). Hierarchical regression analysis showed that previous communication experience, moral belief, descriptive norm and self-efficacy positively predicted willingness to participate in HSP (all P<0.05). Medical workers in the non-Pearl River Delta region had lower willingness than those in the Pearl River Delta region for HSP participation (P<0.05). Conclusion There is still room for improving willingness for HSP participation among healthcare professionals in Guangdong Province. It is recommended to enhance self-efficacy through communication skills training, strengthen professional ethics education, foster a positive peer engagement atmosphere, and intensify resource support and capacity building for HSP in the non-Pearl River Delta region, to improve HSP participation willingness among medical workers in Guangdong Province.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

Objective To compare the early clinical efficacy and safety of transapical transcatheter aortic valve implantation (TA-TAVI) with surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS). Methods A retrospective study was conducted on patients with severe AS admitted to the Department of Cardiovascular Surgery, The First Affiliated Hospital of University of Science and Technology of China from January 2020 to March 2024. According to the surgical method, patients were divided into a SAVR group and a TA-TAVI group, and the clinical data of the two groups were compared. Results A total of 71 patients were included, with 45 in the SAVR group, including 33 males and 12 females, aged 16-75 (60.89±10.88) years; 26 in the TA-TAVI group, including 15 males and 11 females, aged 61-83 (72.85±5.53) years. The results showed that postoperative aortic valve transvalvular flow velocity [(2.31±0.38) m/s vs. (2.60±0.50) m/s, P=0.019] and transvalvular pressure gradient [(21.09±6.03) mm Hg vs. (28.20±10.79) mm Hg, P=0.001] in the TA-TAVI group were lower than those in the SAVR group. In terms of left ventricular end-diastolic diameter, both preoperative [(56.73±7.74) mm vs. (52.36±7.00) mm, P=0.017] and postoperative [(52.61±7.18) mm vs. (48.04±4.78) mm, P=0.010] values in the TA-TAVI group were larger than those in the SAVR group. In terms of left ventricular ejection fraction, the preoperative value in the TA-TAVI group was lower than that in the SAVR group (58.00%±13.84% vs. 64.87%±7.63%, P=0.026), but there was no statistical difference between the two groups after surgery (P=0.670). The operation time and drainage volume on the first day after surgery in the TA-TAVI group were shorter or lower than those in the SAVR group (P<0.05). There was no statistical difference between the two groups in the postoperative hospital stay, ICU stay, or postoperative mechanical ventilation time (P>0.05). In addition, no serious complications occurred in patients after SAVR, while perivalvular leakage (2 patients), third-degree atrioventricular block (1 patient), and death (3 patients) occurred in the TA-TAVI group. Conclusion For elderly patients with severe AS and poor cardiac function, TA-TAVI technology has minimal surgical trauma, high safety and effectiveness, and is a safe and effective treatment option besides traditional surgical operations.

Objective To develop and validate a scoring system to predict the possibility of laparoscopic cholecystectomy (LC) conversion to laparotomy based on preoperative clinical data, and to establish a grading management model of surgery. Methods A retrospective analysis was conducted on the clinical data of 9 414 patients who underwent LC at Renhe Hospital and Huashan Hospital from June 2013 to June 2018. The patients were divided into two groups: the LC group (9 246 patients who successfully underwent LC) and the conversion to laparotomy group (168 patients who required conversion to open surgery). The data of two groups were compared, and the risk factors affecting conversion to laparotomy were screened out by single factor analysis of Chi-square test. Then, the risk factors were analyzed by multiple Logistic regression, and the pre-coefficient of each variable of the risk factors was assigned according to the established conversion to laparotomy possibility function. After calculating the score of each case, the difference in the actual conversion rate of each group was compared. The area under receiver operating characteristic (ROC) curve was calculated to evaluate the performance of the scoring system. According to the scoring system, LC surgical grading management model was created and verified. Results The following factors were identified as significant risk factors for conversion to laparotomy (P < 0.001): body temperature ≥ 38.5℃, frequency of acute cholecystitis ≥3 times, maximum thickness of gallbladder wall ≥ 5 mm, gallbladder neck stone incarceration, diameter of common bile duct ≥8 mm, and surgical experience ≤50 cases were the risk factors for conversion to laparotomy (P < 0.001). A score >3 points was associated with a high risk of conversion to laparotomy. Conclusions The LC scoring system and surgical grading management are reliable and effective tools for predicting and reducing the conversion rate of LC to laparotomy.

Objective:To investigate the clinical features and prognostic factors of newly-treated elderly acute myeloid leukemia (AML) patients with intermediate-risk karyotype.Methods:A retrospective case series study was conducted. A total of 87 newly-treated elderly AML patients with intermediate-risk karyotype in the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2013 to December 2023 were selected. The clinical characteristics were summarized. The Kaplan-Meier method was used for survival analysis and Cox proportional hazards model was used to make univariate and multivariate analyses of prognostic factors.Results:The median age [ M ( Q1, Q3)] of 87 patients was 69 (60, 87) years. The patients with normal karyotype and abnormal karyotype accounted for 77.1% (67/87), 22.9% (20/87), respectively. A total of 74 patients (85.1%) had 1 or more gene mutations, of which FLT3-ITD, NPM1 mutation, CEBPA mutation and WT1 high expression accounted for 29.9% (26/87), 26.4% (23/87), 19.5% (17/87), and 65.5% (57/87), respectively; additionally, 44.7% (39/87) of patients had 2 or more gene mutations. The objective response rate of patients after induction therapy was 47.7% (41/87), while the relapse rate was 73.2% (30/41). The median progression-free survival (PFS) time was 7.8 months, and the median overall survival (OS) time was 12.1 months. Univariate analysis result revealed that age, FLT3-ITD, hypomethylating agents, and minimal residual disease complete remission (MDR-CR) were factors influencing the OS of newly-treated elderly AML patients with intermediate-risk karyotype (all P < 0.05). Multivariate analysis indicated that MDR-CR was an independent risk factor for OS (yes vs. no: HR = 0.27, 95% CI: 0.14-0.51, P < 0.001). Conclusions:Newly-treated elderly AML patients with intermediate-risk karyotype have a high relapse rate and poor prognosis, and MDR-CR is identified as an independent influencing factor for the prognosis of these patients.

Autoimmune diseases, cancers, and viral infections pose significant global health threats, characterized by chronic pathology, unregulated cellular proliferation, and rapid transmission, respectively, requiring urgent early warning and treatment strategies. Antibodies, primarily classified into autoantibodies and therapeutic antibodies based on their clinical roles, provide essential information and show considerable value in the precise diagnosis and treatment of these serious diseases. Among the technologies utilized in bioanalysis, electrochemical biosensors, with their unique advantages of rapid response, high sensitivity, miniaturization, cost-effectiveness and user-friendly operation, have been developed as a trending technology for precise diagnostic and therapeutic drug monitoring. This review systematically summarizes the relationships and roles of clinically relevant antibodies in autoimmune diseases, cancers, and viral infections, while detailing the composition, strategies, development, and application trends of relevant electrochemical biosensors. Furthermore, it highlights the remaining challenges and opportunities for the advancement and prospects of electrochemical sensors in the context of clinically relevant antibodies.