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.

Based on the theory of blood collateral， postoperative recurrence and metastasis of bladder cancer are considered to arise primarily from the binding of stasis and toxin， which accumulate and hide within the blood collaterals. Accordingly， treatment should focus on clearing and resolving the deeply concealed stasis toxin retained in the blood collaterals. The paired use of insect and vine medicinals may exert synergistic effects by simultaneously searching out and eliminating pathogenic factors， guiding the action of herbs to the channels， and unblocking the collaterals. Drawing on clinical practice， the stasis-toxin pathogenesis of postoperative recurrence and metastasis of bladder cancer can be divided into four stages including stagnation and astringent of collateral qi， formation of fixed stasis nests， transformation of persistent stasis into toxin， and deficiency of healthy qi with lingering toxin. Accordingly， four herb pairs are proposed for each stage based on conventional treatment， which are Dilong （Pheretima）-Daxueteng （Caulis Sargentodoxae）， Shuizhi （Hirudo）-Jixueteng （Caulis Spatholobi）， Wugong （Scolopendra）-Luoshiteng （Caulis Trachelospermi）， and Quanxie （Scorpio）-Qianjinteng （stephania）. Their potential modern pharmacological mechanisms are further discussed.

ObjectiveTo investigate the expression of prefrontal cortical neurons， methyltransferase-like 3 （METTL3）， fat mass and obesity-associated gene （FTO）， and AlkB homolog 5 （ALKBH5） proteins in a mouse model of post-traumatic stress disorder （PTSD）. MethodsA PTSD mouse model was established using a single prolonged stress and foot shock stimulation （SPSS） method. The despair， anxiety， and learning and memory functions of PTSD mice were assessed through the open field test， Y-maze test， and forced swimming test. Neuronal damage was detected via HE and Nissl staining. The expression levels of METTL3， FTO， ALKBH5， and neuronal nuclear protein （NEUN） were assessed by Western blot and immunofluorescence staining. ResultsCompared to control group， PTSD mice subjected to SPSS exhibited signs of despair， anxiety， and impaired learning and memory. HE and Nissl staining results showed neuronal damage in the prefrontal cortex of PTSD mice. Western blot and immunofluorescence staining results showed that the expression of the m6A-related proteins METTL3 and FTO decreased， while the expression of ALKBH5 increased in the prefrontal cortex. Additionally， NEUN protein levels showed a declining trend. ConclusionThe pathogenesis of PTSD may be associated with neuronal damage in the prefrontal cortex and alterations in m6A methylation proteins.

ObjectiveTo investigate the effect of Zishen Huoxue Formula （ZSXHF） on molecular-targeted therapy-associated proteinuria in patients with primary liver cancer （PLC）， to assess the efficacy of ZSXHF in the treatment of molecular-targeted therapy-associated proteinuria， and to provide a basis for clinical medication. MethodsA retrospective cohort study was conducted among the PLC patients with molecular-targeted therapy-associated proteinuria who were diagnosed and treated in The Department of Hepatology of Chinese PLA General Hospital， from January 1， 2022 to July 1， 2025. With ZSXHF treatment as the exposure factor， the patients with a cumulative treatment duration of ≥9 weeks were enrolled as traditional Chinese medicine （TCM） group， while those without TCM treatment were enrolled as control group. Propensity score matching was performed for the two groups at a ratio of 1∶1 based on sex， age， 24-hour urinary protein， blood urea nitrogen， and serum creatinine. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for promoting the improvement of targeted-therapy-associated proteinuria. ResultsA total of 137 PLC patients with targeted-therapy-associated proteinuria were enrolled， with 34 patients in the TCM group and 103 in the control group. After follow-up for 6 months， the TCM group had a significant improvement in urinary protein grade compared with the control group （χ²=9.261， P=0.016）. There were 25 patients in each group after propensity score matching， and after follow-up for 6 months， there were significant differences between the two groups in urinary protein grade （χ²=15.689， P<0.001） and 24-hour urinary protein （Z=-3.075， P=0.002）. After cumulative treatment with ZSXHF for ≥9 weeks， the TCM group had a significantly greater change in 24-hour urinary protein from baseline compared with the control group （t=-2.514， P=0.016）， while there were no significant differences in the changes in liver and renal function after ZSXHF intervention between the two groups （all P>0.05）. The multivariate Logistic regression analysis showed that ZSXHF treatment （odds ratio=2.901， 95% confidence interval： 1.135 — 7.417， P=0.026） was an independent influencing factor for improvement in molecular-targeted therapy-associated proteinuria. ConclusionZSHXF can effectively alleviate molecular-targeted therapy-associated proteinuria in PLC patients with a favorable safety profile， which provides a new reference for TCM prevention and treatment of molecular-targeted therapy-associated adverse reactions in PLC patients.

Objective: To understand classroom environmental conditions and their association with spinal curvature abnormalities among students of primary and secondary schools in Guizhou Province, so as to provide a basis for formulating school health policies and scientific prevention and control measures for abnormal spinal curvature in students. Methods: Using a stratified random sampling method, 471 schools (2 811 classrooms) were selected annually across the province from 2022 to 2024 in order to monitor and evaluate classroom environment according to national standards. Spinal examinations were conducted for 196 606 (2022), 194 876 (2023), and 195 048 (2024) students, and χ 2 test was used to analyze the correlation of desk and chair compliance with student spinal curvature abnormalities. Results: The qualified rates of classroom blackboard illuminance uniformity ( 85.41 %) and the blackboard size (82.24%) were the highest in primary and secondary schools in Guizhou Province, while the average blackboard surface illumination qualified rate (20.10%) was the lowest. The average desk illumination (50.11%-58.63%), desk illumination uniformity (61.92%-72.27%) and qualified noise rate (50.04%-51.94%) increased significantly in 3 years; in addition, the compliance rate of desks and chairs decreased from 25.00% to 13.52%, and the differences were all statistically significant ( χ 2=42.48, 80.93, 46.09, 129.72, all P <0.05). Middle school classrooms outperformed primary schools in terms of per capita area, average blackboard illuminance, blackboard illuminance uniformity, average desktop illuminance, desktop illuminance uniformity, and noise compliance ( χ 2=311.55, 12.41, 20.64, 40.76, 10.25, 52.47), but had lower compliance for blackboard size and reflectance ( χ 2=537.29, 7.59) (all P <0.01). Urban schools had higher compliance than suburban schools for per capita area, average blackboard illuminance, average desktop illuminance, and desktop illuminance uniformity ( χ 2=73.71, 17.68, 29.30 , 36.03), but lower compliance for desk-chair suitability, blackboard size, and blackboard reflectance ( χ 2=4.72, 26.02, 5.43 ) (all P <0.05). The spinal curvature abnormality detection rate was 0.83%. A significant association was found between abnormality detection and desk-chair non compliance ( χ 2=223.85, P <0.01). Conclusions Classroom environment hygiene in Guizhou schools is suboptimal. Strengthening school environmental hygiene infrastructure and greater attention to its impact on student s health are essential.

Objective: To understand the epidemiological characteristics of abnormalities spinal curvature among children and adolescents in Karst landform in Guizhou Province, so as to provide a scientific basis for targeted comprehensive intervention. Methods: From September to December 2023, 194 875 children and adolescents aged 6-18 were selected from all countieldistricts of 9 cities (prefectures) in Guizhou Province by stratified random cluster sampling method according to the proportion of Karst landform area in Guizhou Province for carrying out spinal curvature abnormality screening, and a questionnaire survey was conducted on 139 449 students in the fourth grade and above of primary school. Binary Logistic regression was used for multivariate analysis. Results: The detection rate of abnormal spinal curvature among children and adolescents aged 6-18 in Guizhou Province was 1.13%. The detection rates of abnormal spinal curvature in areas with a high proportion of Karst landform, areas with a low proportion of Karst landform, intercalation areas, and nonKarst landform areas were 1.10%, 2.00%, 0.90%, and 0.60%, respectively. Among them, the detection rates of abnormal spinal curvature in female students (2.40%, 1.60%, 0.90%) in areas with a low proportion of Karst landform, intercalation areas and nonKarst landform were higher than those in male students (1.60%, 0.10%, 0.30) (χ2=12.66, 112.69, 30.22, all P<0.05). The detection rates of abnormal spinal curvature among senior high school students (2.00%, 4.30%, 1.40%, 1.30%) in different Karst landform distributions were successively higher than those among junior high school students (1.40%, 3.20%, 1.00%, 0.60%) and primary school students (0.70%, 0.80%, 0.60%, 0.30%) (χ2=306.11, 175.80, 14.24, 39.57, all P<0.05). The results of multivariate Logistic regression analysis showed that the detection rates of abnormal spinal curvature in both highproportion and lowproportion Karst landform areas were higher than those in nonKarst landform areas [OR(95%CI)=1.84(1.05-2.25), 1.60(1.23-2.09), both P<0.05]. Conclusion The detection rate of abnormal spinal curvature in children and adolescents aged 6-18 in Guizhou Province is related to the distribution of Karst landform, so it is necessary to strengthen screening and appropriate comprehensive interventions.

Objective To explore the value of oral contrast-enhanced ultrasonography (OCEUS) combined with contrast-enhanced CT in predicting preoperative T staging in patients with gastric cancer. Methods A retrospective analysis was conducted on 80 patients with gastric cancer confirmed via endoscopic biopsy or postoperative pathology at the First People’s Hospital of Jining from January 2021 to November 2024. The cohort included 56 males and 24 females, aged 38-79 years, with a median age of 55.9 years. All patients underwent both OCEUS and contrast-enhanced CT within one week prior to surgery. T staging of gastric cancer was determined using OCEUS, contrast-enhanced CT, or their combination. The results were compared with pathological T staging, and statistical differences in accuracy were analyzed. Results Pathological T staging identified T1 in 9 cases, T2 in 16 cases, T3 in 42 cases, and T4 in 13 cases. OCEUS indicated T1 in 6 cases, T2 in 14 cases, T3 in 50 cases, and T4 in 10 cases, with an accuracy rate of 80.0%. Contrast-enhanced CT indicated T1 in 4 cases, T2 in 12 cases, T3 in 52 cases, and T4 in 12 cases, with an accuracy rate of 75.0%. The combination of OCEUS and contrast-enhanced CT indicated T1 in 6 cases, T2 in 15 cases, T3 in 47 cases, and T4 in 12 cases, with an accuracy rate of 87.5%. The combined approach demonstrated significantly higher accuracy in preoperative T staging compared to either method alone (P < 0.05). Conclusion The combination of OCEUS and contrast-enhanced CT improves the accuracy of preoperative T staging in gastric cancer patients, providing valuable support for their diagnosis and treatment.

Objective To evaluate cardiac involvement in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) using echocardiography combined with electrocardiography. Methods A retrospective analysis was performed on the detailed medical records of AAV patients treated in Jining First People’s Hospital between January 2020 and December 2024. Eighty patients were enrolled in the AAV group, and the risk of heart disease was compared between the AAV group and a control group with 80 subjects matched for age, sex, and cardiovascular disease risk factors. Results Electrocardiographic abnormalities were observed in 78.75% of patients in the AAV group, while significant electrocardiographic abnormalities only occurred in symptomatic patients in the control group. There were no differences in left atrial enlargement or interventricular septal thickening between the AAV group and the control group. The overall left ventricular systolic function in the AAV group was lower than that in the control group (8.75% vs. 0). The incidence of reduced diastolic function in the AAV group was significantly higher than that in the control group (37.5% vs. 15%). The incidence rates of tricuspid regurgitation, mitral regurgitation, aortic regurgitation, and pericardial effusion in the AAV group were significantly higher than those in the control group. Pericardial thickening, aortic stenosis, pulmonary hypertension, and rare periaortic granulomas were found in the AAV group, but not in the control group. Conclusion Echocardiography and electrocardiography are important examination methods for evaluating cardiac involvement in AAV. These methods have key roles in disease screening, diagnosis and treatment, follow-up, and prognosis judgment.

Urticarial vasculitis is a skin disease with urticaria-like lesions and a histopathological pattern of leukocytoclastic vasculitis. It is considered a "hidden rash" in traditional Chinese medicine. Xuanfu is the portal that regulates qi, blood, fluid, and the ascending, descending, exiting, and entering of nutrition qi and defensive qi. Collaterals are the pathways for the circulation of qi and blood. The two accompany each other, connecting zang-fu organs, reaching the surfaces of the skin, hair, and external body, circulating qi and fluid, and moistening and protecting the skin. Based on the theory of Xuanfu-collateral, this study aimed to clarify the etiology, pathogenesis, and treatment method of urticarial vasculitis. External assault by wind and Xuanfu blockage are believed to be the initiating factors of this disease. The malnutrition of Xuanfu and collaterals and accumulated dampness-heat are important links in the occurrence and development of urticarial vasculitis. It spreads from Xuanfu to the collaterals, and blockage of the collaterals is the immanent trend of this disease. Clinically, by closely adhering to the core pathogenesis of blockage of Xuanfu-collateral, treatment method such as using wind medicinals to open Xuanfu with pungent and dispersing properties, using the method of supplement deficiency and removing the blockage, and using medicinals to promote blood circulation and remove blood stasis to unblock the blocked collaterals. The herbs are flexibly added or subtracted to unblock Xuanfu and collaterals, harmonize qi and blood, thus all symptoms can be relieved. We hope that this study will provide new ideas for the treatment of urticarial vasculitis with traditional Chinese medicine.

OBJECTIVE To evaluate the cost-utility of enfortumab vedotin combined with pembrolizumab （PemEV） versus gemcitabine combined with cisplatin or carboplatin （GP） in the first-line treatment of advanced urothelial carcinoma （aUC）. METHODS From the perspective of China’s health system， a dynamic Markov model was established based on the pan-Asian subgroup data from the EV-302 trial. The study timeframe was set at 20 years， with a cycle length of 21 days and a discount rate of 5%. Using total direct medical costs and quality-adjusted life years （QALYs） as outcome measures， the incremental cost- effectiveness ratio （ICER） of the PemEV regimen compared to the GP regimen was calculated. The robustness of the model was validated through sensitivity analysis and scenario analysis， and the price thresholds for enfortumab vedotin and pembrolizumab were estimated under conditions where the PemEV regimen was more cost-effective compared to the GP regimen. RESULTS Cost- utility analysis indicated that compared to the GP regimen， PemEV regimen could generate an additional 2.602 QALYs in aUC patients， but the treatment cost increased by 3 339 703.56 yuan， with an ICER of 1 283 554.39 yuan/QALY. This figure significantly exceeded the willingness-to-pay （WTP） threshold （3 times China’s gross domestic product per capita in 2024， 287 247 yuan/QALY）. The rate parameter of the exponential distribution fitted to the overall survival curve in the PemEV regimen had the greatest impact on ICER， according to the one-way sensitivity analysis. Probabilistic sensitivity analysis suggested that the PemEV regimen had no chance of being more cost-effective than the GP regimen at the current WTP threshold. Scenario analysis revealed that the PemEV regimen consistently lacked cost-utility advantage over the GP regimen， regardless of whether the study model was changed to a partitioned survival model， the study timeframe was set to 5， 10 or 20 years， or the prices of enfortumab vedotin and/or pembrolizumab were reduced by 60%. The prices of enfortumab vedotin and pembrolizumab should be simultaneously reduced by 78.65% （55.71 yuan/mg and 38.26 yuan/mg， respectively） when the PemEV regimen had a cost-utility advantage over the GP regimen. CONCLUSIONS From the perspective of China’s healthcare system， PemEV regimen does not demonstrate a cost-utility advantage over GP regimen in the first-line treatment of aUC.