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.

ObjectiveTo observe the clinical efficacy and safety of Yuyin Lidan granules （YYLD） in preventing the recurrence of common bile duct stones （CBDS） in patients with liver and gallbladder dampness-heat syndrome following endoscopic retrograde cholangiopancreatography （ERCP）. MethodsThis randomized， parallel， controlled trial enrolled postoperative CBDS-ERCP patients who met the inclusion and exclusion criteria. Sixty-four patients were randomly assigned to an observation group or a control group， with 32 cases in each. Both groups received conventional Western medical treatment after ERCP， while the observation group additionally received YYLD for 8 weeks. The follow-up period lasted for 1 year. The efficacy indicators included bile bilirubin levels， traditional Chinese medicine （TCM） syndrome scores， clinical efficacy rate， pancreatitis and inflammation markers， postoperative liver function， and CBDS recurrence rate at 1-year follow-up， which were used to jointly evaluate the clinical efficacy and safety of both groups. ResultsA total of 56 patients completed the study and were included in the final analysis， i.e.， 29 in the observation group and 27 in the control group. Baseline characteristics were comparable between the two groups. Compared with pre-treatment and with the control group after treatment， the bile bilirubin level in the observation group significantly decreased （P<0.05）. After treatment， the clinical cure and marked improvement rates were higher in the observation group than in the control group， showing a statistically significant difference in overall clinical efficacy （P<0.05）. Compared with pre-treatment， the primary and secondary symptoms in the observation group， as well as the primary symptom and the secondary symptom of nausea and vomiting in the control group （weeks 4 and 8）， were significantly reduced （P<0.05）. Compared with the control group after treatment， the observation group showed significant reductions in the primary symptom of loose stools/constipation （day 5 and week 4） and in three secondary symptoms， i.e.， bitter taste and sticky dry mouth， abdominal distension and poor appetite （throughout the treatment period）， and general heaviness and fatigue （day 5 and week 4）， with statistical differences （P<0.05）. Compared with pre-treatment， both groups showed decreased lipase and urinary amylase levels （P<0.05）. However， no significant between-group differences were observed in pancreatitis or inflammation-related indices after treatment. Compared with pre-treatment， all liver function indicators in the observation group and alanine aminotransferase （ ALT ）， γ-glutamyl transferase （ γ-GT ）， alkaline phosphatase （ALP）， and conjugated bilirubin in the control group significantly decreased at weeks 4 and 8 （P<0.05）. Compared with the control group after treatment， only serum total bilirubin and unconjugated bilirubin were significantly reduced in the observation group during the treatment period （P<0.05）. ConclusionYYLD combined with conventional Western medical treatment can effectively regulate bilirubin metabolism （in bile and serum）， improve TCM clinical symptoms， and prevent CBDS recurrence after ERCP in patients with liver and gallbladder dampness-heat syndrome. This regimen is safe and effective and is worthy of further clinical research and promotion.

Objective:To analyze the clinical efficacy and learning curve for robot-assisted cortical bone trajectory (CBT) screw fixation performed by surgeons with different seniority in the treatment of lumbar degenerative disease.Methods:The clinical data of 91 lumbar degenerative disease patients underwent robot-assisted CBT screw fixation from August 2020 to December 2022 in Beijing Shijitan Hospital, Capital Medical University were retrospectively analyzed. Among them, 48 patients underwent surgery performed by the same senior surgeon (senior group), with a total of 234 CBT screws were placed; while 43 patients underwent surgery performed by the same junior surgeon (junior group), with a total of 206 CBT screws were placed. The surgical related indexes, functional improvement score, lower back pain and lower limb radiation pain scores, acceptable nail insertion rate, non invasion rate of facet joints and incidence of postoperative complications were compared between two groups. The functional improvement score was evaluated using the Japanese Orthopaedic Association (JOA) score, the pain score was evaluated using visual analog score (VAS). The cumulative sum (CUSUM) method was used to depict the learning curve with "single screw placement time" as the observation index.Results:There were no statistical difference in incision length, operation time, intraoperative blood loss and postoperative hospital stay between two groups ( P>0.05). The least squares means of JOA scores 1, 3 and 6 months after surgery in both groups increased significantly compared to baseline, while the least squares means of lower back pain VAS and lower limb radiation pain VAS decreased significantly compared to baseline; there were no statistical differences between two groups ( P>0.05). There were no statistical difference in acceptable nail insertion rate, non invasion rate of facet joints and incidence of postoperative complications between two group ( P>0.05). The CUSUM learning curves were fitting well and the inflection point for senior surgeon corresponded to 18 cases, while it was reached after performing surgery on 21 cases for junior surgeon. Conclusions:Robot-assisted CBT screw fixation performed by surgeons with different seniority could achieve similar clinical outcomes for treating lumbar degenerative disease. The senior surgeons are able to complete the initial learning stage faster than the junior surgeons, but there is not much difference in the number of surgeries performed the learning curve.

Objective:To investigate the effect of a new method of utilizing frontalis sling with polypropylene non-absorbable sutures for the treatment of senile ptosis.Methods:A retrospective analysis was conducted on the clinical data of senile patients with blepharoptosis who were treated with frontalis sling surgery with polypropylene non-absorbable sutures at the Department of Plastic Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine between January 2022 and December 2023. The palpebral fissure height and margin reflex distance (MRD1) of the upper eyelid margin were measured and recorded before and after the operation, and the operation time and postoperative detumescence time were recorded. Postoperative complications and recurrence of ptosis were followed up. Patients’ satisfaction with the postoperative effect was investigated and divided into three levels: very satisfied, satisfied, and dissatisfied. Normal distribution measurement data were expressed as Mean±SD; counting data were expressed as frequency.Results:A total of 8 patients were enrolled, including 3 males and 5 females, with an age of (68.8±6.1) years. Six patients underwent bilateral ptosis correction surgery, and two underwent unilateral ptosis correction surgery. The ptosis was graded as follows: 1 case was mild, 2 cases were moderate, and 5 cases were severe. There were 2 cases of aponeurotic ptosis, 3 cases of congenital ptosis and 3 cases of traumatic ptosis (1 of which was prosthetic eye). The operative time of 8 patients (14 eyes) with unilateral ptosis was (43.9±4.9) min. The swelling resolved in (9.4±1.7) days. One patient still had symptoms of lagophthalmos and corneal irritation 7 days after the operation. The symptoms gradually relieved after wearing corneal protective goggles and applying eye ointment. The postoperative follow-up lasted from 2 to 15 months (mean 6.3 months). Palpebral cleft height [(9.8±0.6) mm vs. (3.3±1.2) mm] and MRD1[(4.1±0.5) mm vs. (-1.1±0.8) mm] in 8 patients (14 eyes) after surgery were significantly higher than those before the operation( P<0.01). There was no recurrence of ptosis after the operation. There were 2 cases of upper eyelid hysteresis, of which 1 case was mild upper eyelid hysteresis, and the other case had relatively obvious upper eyelid hysteresis on prosthetic side. Satisfaction survey showed that 7 patients were very satisfied with the result of the operation, and 1 patient was satisfied. Conclusion:Frontal muscle suspension with polypropylene non-absorbable suture is a feasible method for the treatment of ptosis in elderly patients with simple operation, little tissue damage, positive effect, rapid postoperative recovery and acceptable complications.

Background and Aims:Autoimmune thyroid disease(AITD)are closely associated with metabolic dysregulation,but the causal role of specific metabolites remains unclear.This study aimed to systematically evaluate the causal relationships between approximately 1 400 blood metabolites and two major AITD subtypes-Graves'disease(GD)and Hashimoto's thyroiditis(HT)-using a two-sample Mendelian randomization(MR)approach,to identify potential risk or protective metabolites and provide genetic evidence for mechanistic studies and targeted metabolic interventions.Methods:Summary-level genome-wide association study(GWAS)data for blood metabolites and AITDs were analyzed using inverse-variance weighted MR as the primary method,supplemented by MR-Egger,weighted median,and mode-based methods.Heterogeneity,pleiotropy,and robustness were assessed through Cochran's Q test,horizontal pleiotropy test,and leave-one-out analyses.Results:Forty-nine metabolites showed significant causal associations with GD and 89 with HT.Hexanoylglutamine and ceramide(d18∶1/16∶0)were identified as GD risk factors,while N2,N2-dimethylguanosine and β-hydroxyisovalerylcarnitine were protective.Pregnanediol sulfate and theobromine were associated with increased HT risk,whereas dihomo-linolenate(20:3n3 or n6)and caprylate appeared protective.The α-ketoglutarate/succinate ratio was positively associated with both diseases,suggesting a shared metabolic risk pathway.Conclusion:This MR study provides genetic evidence supporting causal links between multiple blood metabolites and GD or HT.Several metabolites may serve as predictive or protective biomarkers,offering novel insights into the pathophysiology,early screening,and personalized metabolic intervention strategies for AITDs.

AIM To evaluate the quality of Tibetan medicine"Sangdi"based on HPLC fingerprints combined with chemometrics.METHODS The analysis was performed on a 30 ℃ thermostatic Welch Ultimate AQ-C18 column(250 mm × 4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2％phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 245 nm,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were performed,the contents of gentiopicroside,sweroside,mangiferin,isoorientin,8-hydroxy-1,3,5-trimethoxyxanthone(R2)and 1,8-dihydroxy-3,7-dimethoxyxanthone(R3)were determined.RESULTS There were 18 common peaks in the fingerprints for 15 batches of samples with the similarities of more than 0.90.Six constituents showed good linear relationships within their own ranges(R 2 ≥ 0.999 2),whose average recoveries were 96.93％-103.58％with the RSDs of 0.82％-2.9％.Various batches of samples were clustered into 2 categories,4 principal components demonstrated the accumulative variance contribution rate of 86.404％,mangiferin,gentiopicroside and isoorientin were taken as quality difference markers.CONCLUSION This stable,reliable and reproducibe method can provide a reference for the comprehensive quality evaluation of"Sangdi".

Objective:To understand the potential characteristics of decision-making preparation in outpatient hypertensive patients based on latent profile analysis, to identify the influencing factors of different categories of decision-making preparation levels, and to explore the performance of different decision-making preparation types in facilitation of patients involvement in treatment decision-making.Methods:Through a cross-sectional study, 350 hypertensive patients attending outpatient clinics in five different types of healthcare institutions (general hospitals, specialised hospitals and community hospitals) in Tianjin during January to May 2024 who met the inclusion and exclusion criteria were selected by the convenience sampling method as study subjects. General Information Questionnaires, Preparation for Decision Making Scale, and Facilitation of Patient Involvement Scale were used for investigation.Results:Totally 350 valid questionnaires [178 males and 172 females aged 25-89(57.24 ± 13.39)years old] were collected. The decision-making preparation score of outpatient hypertensive patients was (64.19 ± 18.69). The latent profile analysis results showed that the decision-making preparation of outpatient hypertensive patients could be divided into three potential categories: decision-making information scarcity type accounted for 20.0%(70/350), decision-making balance negotiation type accounted for 39.7%(139/350), and decision-making preparation adequacy type accounted for 40.3%(141/350). The results of multiple Logistic regression analysis showed that age, medical insurance type, occupation, and children′s condition were the influencing factors for the potential categories of decision-making preparation in outpatient hypertensive patients (all P<0.05). Age [less than 35 years old: OR(95% CI)=0.127(0.020-0.796)], occupation [on the job: OR(95% CI)=2.010 (1.034-3.906)], were the influencing factors of decision-making balance negotiation group (all P<0.05). Medical insurance type [basic medical insurance for urban employees: OR(95% CI)=0.372(0.193-0.720)], occupation [on the job: OR(95% CI)=2.500(1.270-4.920)], children′s condition[junior and senior high school: OR(95% CI)=0.391(0.190-0.802)] were the influencing factors of decision-making preparation adequacy group (all P<0.05). Conclusions:The level of promoting patient participation among outpatients with hypertension is relatively high, and there are differences in the perceived degree of promoting patient participation among patients with different types of decision preparation.It is recommended that medical staff provide decision-making related information based on the characteristics of different decision-making preparation categories of patients, encourage patients to actively participate in decision-making, and construct targeted decision support plans.

OBJECTIVE To explore the risk factors for polymyxin-and carbapenem-resistant Klebsiella pneumoni-ae(PR-CRKP)infection and establish the prediction model.METHODS The clinical data were retrospectively col-lected from the patients with CRKP infection who were treated in the First Affiliated Hospital of Xi'an Jiaotong University from Jan.2023 to Mar.2024.The enrolled patients were divided into the CRKP group and the PR-CRKP group according to the result of drug susceptibility testing for polymyxin B.Totally 203 patients who were treated from Jan.2023 to Dec.2023 were assigned as the modeling group,and 91 patients who were treated from Jan.2024 to Mar.2024 were assigned as the validation group.Multivariate logistic regression analysis was per-formed for the risk factors for PR-CRKP infection,nomogram was built up for prediction of PR-CRKP infection by R software,and the predictive efficacy of the model was evaluated by means of receiver operating characteristic(ROC)curves.RESULTS The result of univariate analysis showed that the proportions of patients who received fi-berobronchoscopy,endotracheal intubation/tracheotomy,were complicated with other carbapenem-resistant or-ganisms(CROs)infections,bloodstream infections,were treated in intensive care unit(ICU)and had the history of exposure to polymyxins and carbapenems 3 months before the admission were higher in the PR-CRKP group than in the CRKP group(P＜0.05);the length of hospital stay and duration of use of polymyxins and carbapene-ms were longer in the PR-CRKP group than in the CRKP group(P＜0.05).Multivariate logistic regression analy-sis indicated that complication with other CROs infections,history of exposure to polymyxins and carbapenems 3 months before the admission,duration of use of polymyxins and ICU stay were the risk factors for the PR-CRKP infection(P＜0.05).The area under the curve(AUC)of the predictive model was 0.898 in the modeling group,with the sensitivity 80.33％,the specificity 84.51％.ROC curve analysis showed that the AUC was 0.901 in the validation group,with the sensitivity 75.00％,the specificity 92.73％.CONCLUSION The prediction model that is established based on the result of multivariate analysis has high value in prediction of PR-CRKP infection.

Neurodegenerative disorders(NDDs)are prevalent chronic conditions characterized by progressive synaptic loss and pathological protein alterations.Increasing evidence suggested that mitochondrial quality control(MQC)serves as the key cellular process responsible for clearing misfolded proteins and impaired mitochondria.Herein,we provided a comprehensive analysis of the mechanisms through which MQC mediates the onset and progression of NDDs,emphasizing mitochondrial dynamic stability,the clearance of damaged mitochondria,and the generation of new mitochondria.In addition,traditional Chinese medicines(TCMs)and their active monomers targeting MQC in NDD treatment have been demonstrated.Consequently,we compiled the TCMs that show great potential in the treatment of NDDs by targeting MQC,aiming to offer novel insights and a scientific foundation for the use of MQC stabilizers in NDD prevention and treatment.

Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.