ObjectiveProtein-protein interactions (PPIs) are fundamental to the execution of biological functions within living cells. However, traditional biochemical methods, such as co-immunoprecipitation (Co-IP), often fail to capture transient, weak, or membrane-associated interactions due to the stringent detergent requirements for cell lysis. Proximity labeling (PL) has emerged in recent years as a transformative technology for mapping the proteomes of specific subcellular compartments and identifying dynamic interactomes in situ. Golgi protein 73 (GP73, also known as GOLPH2), a resident type II Golgi transmembrane protein, is a well-recognized clinical biomarker for liver diseases, including hepatocellular carcinoma (HCC). Despite its clinical significance, the comprehensive physiological and pathological functions of GP73 remain partially understood. This study aims to establish an APEX2-mediated proximity labeling system specifically targeting GP73 to map its interactome in a living cellular environment, thereby providing new insights into its molecular roles and regulatory mechanisms. MethodsTo achieve spatial specificity, we first constructed a stable cell line expressing a fusion protein consisting of GP73 and the engineered soybean peroxidase APEX2. The localization of the GP73-APEX2 fusion protein was validated to ensure it correctly targeted the Golgi apparatus. The proximity labeling reaction was initiated by incubating the cells with biotin-phenol (BP) for 30 min, followed by a brief (1 min) treatment with1 mmol/L hydrogen peroxide (H₂O₂). This catalytic reaction converts BP into highly reactive, short-lived biotin-phenoxyl radicals that covalently attach to endogenous proteins within a small labeling radius of the GP73-APEX2 enzyme. Subsequently, the cells were quenched, and biotinylated proteins were enriched using high-affinity streptavidin-coated magnetic beads. The captured “neighbor” proteins were subjected to on-bead digestion and analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) for high-throughput identification. Rigorous bioinformatics analysis, including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction network mapping, was performed to interpret the biological significance of the identified candidates. ResultsOur results demonstrate the successful establishment of a robust and sensitive APEX2-based proximity labeling system for GP73. We identified a total of 95 high-confidence interacting proteins that were significantly enriched in the GP73 proximity proteome compared to control groups. Bioinformatics analysis revealed that these interactors were predominantly associated with biological processes such as vesicular transport, protein localization, and, most notably, molecular functions related to “ribosome binding” and “translation regulation”. This suggested an unexpected role for the Golgi-resident GP73 in the cellular translation machinery. To validate these findings, we performed targeted biochemical assays which confirmed a direct interaction between GP73 and the subunits of the eukaryotic translation initiation factor 3 (eIF3) complex, specifically EIF3G and EIF3I. Furthermore, functional validation using the surface sensing of translation (SUnSET) assay—a non-radioactive method to monitor protein synthesis—revealed that the overexpression of GP73 significantly promoted global protein translation levels in the cell, whereas its depletion or inhibition resulted in reduced translation efficiency. ConclusionThis study successfully utilized APEX2-mediated proximity labeling to provide the first systematic map of GP73 interactome in living cells. Our findings uncover a novel, unconventional function of GP73 as a regulator of cellular protein translation, likely mediated through its interaction with the eIF3 complex. This discovery significantly broadens our understanding of the biological roles of GP73 beyond its traditional function in the Golgi apparatus and suggests that it may act as a bridge between Golgi-related trafficking and the protein synthesis machinery. Furthermore, the technical framework established in this study provides a valuable template for investigating other complex organelle-associated protein networks and resolving transient macromolecular interactions in various physiological and pathological contexts.

Cellular death in the body can occur through different processes,including apoptosis,pyroptosis and necrotic apoptosis,etc.PANoptosis is a newly discovered form of inflammatory cell death in recent years.It can be triggered by various stimulating factors and integrates multiple components that can induce cell death to assemble into various types of macromolecular complexes-PANoptosome,which then mediates cell death.Given the impact of PANoptosis on the entire disease spectrum,promoting or inhibiting its occurrence process may prevent the development of various diseases.The review summarizes the research progress on the occurrence mechanism of PANoptosis and its role in some diseases,and explores the crosstalk among multiple programmed cell death pathways,aiming to provide new ideas for the treatment of related diseases.

AIM To optimize the extraction process for total polyphenols from Conioselinum vaginatu(Spreng.)Thell.,make component analysis,and evaluate their anti-oxidant,hypoglycemic activities.METHODS The effects of ultrasound,enzymatic hydrolysis,acid hydrolysis,alcohol extraction and hydrolysis processes on the extraction quantity of total polyphenols were investigated,respectively.With extraction temperature,extraction time,ethanol concetration and liquid-solid ratio as influencing factors,extraction quantity of total polyphenols as an evaluation index,the extraction process was optimized by response surface method.HPLC was adopted in the identification of polyphenolic composition and determination of their contents.Subsequently,total polyphenols' scavenging capacities on DPPH,ABTS,OH free radicals,total reducing power and inhibitory capacity on α-glucosidase were determined.RESULTS The highest extraction quantity of total polyphenols was observable when extraction process was employed.The optimal conditions were determined to be 62 ℃ for extraction temperature,54 min for extraction time,69％for ethanol concentration,and 50∶1 for liquid-solid ratio,the extraction quantity of total polyphenols was(9.51±0.2)mg GAE/g.Seven constituents existed in C.vaginatu,among which ferulic acid demonstrated the highest content,followed by that of myricetin,while D-tryptophan content was the lowest.At the concentration of 7.61 mg/L,total polyphenols displayed the scavenging rates on DPPH,ABTS,OH free radicals of 80.70％,85.97％,28.60％,total reducing power of 0.22,and inhibition rate on α-glucosidase of 77.23％,respectively.CONCLUSION This stable and reliable method can be used for the extraction of total polyphenols from C.vaginatum with strong anti-oxidant,hypoglycemic activities.

Objective:To evaluate the clinical features of dystonia in patients with different types of atypical Parkinson syndrome (APS).Methods:A total of 104 patients with APS admitted in the Department of Neurology, Beijing Hospital from January 2015 to June 2023 were enrolled in the study, including 57 cases of multiple system atrophy (MSA), 38 cases of progressive supranuclear palsy (PSP) and 9 cases of corticobasal degeneration (CBD). Among 104 cases there were 63 males (60.6%), the mean age of patients was (62.3±8.9) years (54 to 73 years). The sex, age at onset, disease duration, first symptom, clinical features of dystonia and other neurological signs, response to levodopa therapy, numbers of Hoehn & Yahr scale≥3 after 3 years of disease, and MRI findings were documented in patients with different type APS.Results:The overall frequency of dystonia in this series was 45.2%(47/104), and 33.3% (19/57) for MSA group, 50.0% (19/38) for PSP group, 9/9 for CBD group. The types of dystonia were anterocollis, retrocollis, blepharospasm, oromandibular, foot/limb dystonia, Pisa syndrome and myoclonus. In all 47 cases presenting dydtonia, dystonia was not the first complaint and it did not respond to levodopa therapy.Conclusion:In this series of atypical Parkinson syndrome, dystonia is a common feature of the disease, while it is not the first symptom at disease onset, and usually does not respond to levodopa therapy.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

AIM To study the chemical constituents from the roots of Siraitia grosvenorii(Swingle)C.Jeffrey and their α-glucosidase inhibitory activities.METHODS The 95％ethanol extract was isolated and purified by silica gel,MCI,ODS and HSCCC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The α-glucosidase inhibitory activities were evaluated by PNPG method,after which molecular docking was performed.RESULTS Twenty-one compounds were isolated and identified as vanillin(1),siraitic acid B(2),cucurbitacin B(3),salicylic acid(4),ferulic acid(5),p-hydroxybenzaldehyde(6),(+)-lariciresinol(7),(+)-isolariciresinol(8),liballinol(9),3-(hydroxyacetyl)indole(10),2E-4-hydroxy-nonenoic acid(11),vomifolilol(12),vanillic acid(13),indole-3-carboxylic acid(14),ω-hydroxypropioguaiacone(15),p-hydroxybenzoic acid(16),p-coumaric acid(17),dehydrodipinocarpine(18),secoisolariciresinol(19),sesquimarocanol A(20),threo-guaiacylglycerol-β-O-4-lariciresinol ether(21).IC50 values of compounds 4,10,18 and 21 were(0.42±0.060)-(0.89±0.037)mg/mL.CONCLUSION Compounds 4,10-12,15,16,18,and 21 are isolated from the roots of this plant for the first time.Compounds 4,10,18,21 have α-glucosidase inhibitory activities,and 18 has the strongest activity.

Objective To comprehensively evaluate the multidimensional impact of the"Tianjin Experience"of Chest Pain Center(CPC)development on in-hospital mortality,optimization of treatment workflows,and regional coordination of care for patients with acute myocardial infarction(AMI),with the aim of providing scientific evidence to further improve the model and enhance AMI treatment outcomes.Methods This study analyzed data from the"Cardiovascular and Cerebrovascular Acute Events Surveillance System"maintained by the Tianjin Center for Disease Control and Prevention from 2013 to 2024.A segmented regression model was applied to assess the long-term trends in in-hospital mortality from acute myocardial infarction(AMI),with a particular focus on evaluating the impact of the chest pain center program on treatment outcomes.Additionally,supplementary analyses were conducted using surveillance data from the Tianjin Chest Pain Center Quality Control Team between 2017 and 2024.To verify the effectiveness of treatment process optimization,temporal trends in key time-based process indicators were assessed,including Door-in-Door-out(DIDO)time at non-PCI hospitals,Door-to-Wire(D-to-W)time,and First Medical Contact to Wire(FMC-to-W)to wire time.Results According to the data from the Tianjin Center for Disease Control and Prevention,the average 28-day AMI mortality rate in the overall patient population was 9.85％.Between 01/2013 and 12/2014,the mortality rate showed a significant upward trend(P＜0.01),followed by a downward trend from 01/2015 to 12/2024,although the latter did not reach statistical significance(P＞0.05).From 2013 to 2024,a total of 27 633 AMI cases with complete clinical records were collected from Tianjin Chest Hospital,with an average 28-day mortality rate of 4.55％.The mortality rate exhibited a decreasing trend from 01/2013 to 12/2016,with an annual percent change(APC)of-7.56(P＜0.05).From 01/2017 to 12/2024,the trend stabilized,with an APC of 0.39(P＞0.05).Conclusions The development of the CPC system in Tianjin significantly reduced key treatment times and improved the overall efficiency of AMI management.While population-level AMI mortality rates began to decline after 2015,the rate of improvement has slowed,indicating a continued need for optimizing the regional coordinated care system to further enhance patient outcomes.

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.