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.

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.

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

Objective:To study the inhibitory effect of phillyrin(PN)on myocardial fibrosis in diabetes mellitus(DM)rats and its mechanism.Methods:Sixty SD rats were randomly assigned:control group,DM group,low-dose PN group(10 mg/kg),high-dose PN group(30 mg/kg)and LY294002 group(PN 30 mg/kg+PI3K inhibitor 100 mg/kg),with 12 rats in each group,DM model was constructed by streptozotocin.After 8 weeks of drug intervention,FBG was measured with a blood glucose meter,the LVFS,LVEF,LVPWT and E/A were measured by echocardiography;HE staining and Masson staining were used to changes of myocardium,and the CVF was measured;ELISA was used to detect the Vaspin,TNF-α,IL-1β and IL-6 in myocardium;Western blot was used to detect the expressions of α-SMA,FSP-1,CD31,COL1,PI3K,p-PI3K,AKT,p-AKT,eNOS and p-eNOS in myocardium.Results:Compared with the control group,the myocardial cells in DM group were swollen,gaps were enlarged,and collagen fibers were in-creased,the levels of FBG,CVF,Vaspin,TNF-α,IL-1β,IL-6,α-SMA,FSP-1 and COL1 were increased obviously,the levels of LVFS,LVEF,LVPWT,E/A,CD31,p-PI3K/PI3K,p-AKT/AKT,p-eNOS/eNOS were reduced obviously(P<0.05).Compared with the DM group,the swelling of myocardial cells,the normal gap,and the decrease of collagen fibers in the low-dose and high-dose PN groups were reduced,the levels of FBG,CVF,Vaspin,TNF-α,IL-1β,IL-6,α-SMA,FSP-1 and COL1 were decreased obviously,the LVFS,LVEF,LVPWT,E/A,CD31,levels of p-PI3K/PI3K,p-AKT/AKT,p-eNOS/eNOS were increased obviously(P<0.05).LY294002,AKT/eNOS pathway inhibitor,obviously weakened the relieving effect of PN on myocardial fibrosis in DM rats.Conclu-sion:PN may improve cardiac function,reduce myocardial fibrosis and inhibit endothelial mesenchymal transdifferentiation(EndMT)in DM rats by activating PI3K/AKT/eNOS pathway.

OBJECTIVE To analyze the characteristics of 57 acquired immune deficiency syndrome(AIDS)patients complicated with cryptococcal meningitis and observe the treatment outcomes.METHODS Totally 57 AIDS pa-tients with complicated cryptococcal meningitis who were treated in Guiyang Public Health Treatment Center from Jan.2019 to Jun.2023 were continuously assigned as the cryptococcal meningitis group,meanwhile,57 patients with simple AIDS were chosen as the simple AIDS group based on a 1∶1 ratio matching case-control study.Both groups received standardized therapies on basis of the criteria.The clinical characteristics,T lymphocyte subsets,biochemical indexes and treatment outcomes were observed and compared between the two groups.RESULTS There were no significant differences in gastrointestinal reactions,fever and eye discomfort between the two groups;the incidence of neurological symptoms of the cryptococcal meningitis group was higher than that of the simple AIDS group(P＜0.05).There was significant difference in the peripheral blood T lymphocyte subsets be-tween the cryptococcal meningitis group and the simple AIDS group(P＜0.05).The levels of whole blood CD4+,CD4+/CD8+and CD8+of the cryptococcal meningitis group were lower than those of the simple AIDS group;the serum glucose(GLU)level of the cryptococcal meningitis group was lower than that of the simple AIDS group;the serum adenosine deaminase(ADA)level of the cryptococcal meningitis group was higher than that of the sim-ple AIDS group;the serum immunoglobulin A(IgA)level of the cryptococcal meningitis group was higher than that of the simple AIDS group(P＜0.05).There were no significant differences in the immunological failure,vir-ological failure and immunological failure plus virological failure between the two groups after the treatment for 6 months.CONCLUSIONS The incidence of neurological symptoms is higher among the patients with AIDS com-plicated with cryptococcal meningitis than among the patients with simple AIDS.The patients have poor treatment outcomes and more severe damage of T lymphocyte subset functions,and the levels of biochemical indexes vary a-mong the patients,which may provide bases for diagnosis of diseases and assessment of curative effect and prog-nosis.

Mesoporous carbon nanoparticles (MCNs) have received considerable attention for biomedical applications due to their unique structural features, including high specific surface area, adjustable pore size, and remarkable biocompatibility. These properties have addressed key challenges such as inefficiencies in drug loading and release, minimizing the side effects associated with conventional treatments. In this review, the classification and the research progress of MCNs are summarized firstly, the preparation and modification techniques to enhance their functionality and properties are further reviewed, the main physicochemical properties are introduced as well, highlighting their contributions to MCNs in applications. In addition, the biomedical applications of MCNs are emphasized, including tumor therapy, tumor theranostics, antibacterial, delivery of active molecules and biological detection. Finally, the prospects and challenges of clinical application based on MCNs are analyzed to provide an effective reference and lay the foundation for further research.

Objective:To investigate the clinical efficacy of transcranial alternating current stimulation (tACS) combined with drug treatment in patients with bipolar Ⅰ disorder (BD Ⅰ).Methods:Forty-two patients with BD Ⅰ who were admitted to the Mental Health Center Affiliated to Anhui Medical University from March 2022 to June 2023 were included in this randomized double-blind study. These patients were randomly divided into a control group and an observation group using an Excel spreadsheet. In the control group, patients received 10 sessions of sham stimulation in addition to drug treatment, while the observation group received 10 sessions of tACS along with drug treatment. All patients were treated for 2 weeks. Each patient received stimulation for 15 minutes on each of the right and left prefrontal lobes once every working day. The Montreal Cognitive Assessment (MoCA) scores and Bech-Rafaelsen Mania Scale (BRMS) scores were compared between the two groups before and after treatment. Eighteen patients from the observation group and nineteen patients from the control group were included in the final analysis.Results:Two weeks after treatment, the MoCA score in the observation group was higher than that in the control group [(27.39 ± 1.88) vs. (24.63 ± 2.39)], and the BRMS score in the observation group was lower than that in the control group [(15.89 ± 3.18) vs. (19.00 ± 3.32)]. These differences were statistically significant ( t = -3.89, 2.91, both P < 0.05). After treatment, the MoCA score in the observation group increased, while the BRMS score decreased ( t = 5.04, -4.14, both P < 0.05). Pearson correlation analysis indicated the change in MoCA score was negatively correlated with BRMS score in both groups ( r = -0.433, P < 0.05). Conclusions:Drug treatment combined with tACS greatly improved clinical cognitive symptoms and reduced manic symptoms in patients with BD Ⅰ. The combined therapy exhibited better efficacy than monotherapy.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective:To study the inhibitory effect of phillyrin(PN)on myocardial fibrosis in diabetes mellitus(DM)rats and its mechanism.Methods:Sixty SD rats were randomly assigned:control group,DM group,low-dose PN group(10 mg/kg),high-dose PN group(30 mg/kg)and LY294002 group(PN 30 mg/kg+PI3K inhibitor 100 mg/kg),with 12 rats in each group,DM model was constructed by streptozotocin.After 8 weeks of drug intervention,FBG was measured with a blood glucose meter,the LVFS,LVEF,LVPWT and E/A were measured by echocardiography;HE staining and Masson staining were used to changes of myocardium,and the CVF was measured;ELISA was used to detect the Vaspin,TNF-α,IL-1β and IL-6 in myocardium;Western blot was used to detect the expressions of α-SMA,FSP-1,CD31,COL1,PI3K,p-PI3K,AKT,p-AKT,eNOS and p-eNOS in myocardium.Results:Compared with the control group,the myocardial cells in DM group were swollen,gaps were enlarged,and collagen fibers were in-creased,the levels of FBG,CVF,Vaspin,TNF-α,IL-1β,IL-6,α-SMA,FSP-1 and COL1 were increased obviously,the levels of LVFS,LVEF,LVPWT,E/A,CD31,p-PI3K/PI3K,p-AKT/AKT,p-eNOS/eNOS were reduced obviously(P<0.05).Compared with the DM group,the swelling of myocardial cells,the normal gap,and the decrease of collagen fibers in the low-dose and high-dose PN groups were reduced,the levels of FBG,CVF,Vaspin,TNF-α,IL-1β,IL-6,α-SMA,FSP-1 and COL1 were decreased obviously,the LVFS,LVEF,LVPWT,E/A,CD31,levels of p-PI3K/PI3K,p-AKT/AKT,p-eNOS/eNOS were increased obviously(P<0.05).LY294002,AKT/eNOS pathway inhibitor,obviously weakened the relieving effect of PN on myocardial fibrosis in DM rats.Conclu-sion:PN may improve cardiac function,reduce myocardial fibrosis and inhibit endothelial mesenchymal transdifferentiation(EndMT)in DM rats by activating PI3K/AKT/eNOS pathway.

Objective:To investigate the clinical efficacy of transcranial alternating current stimulation (tACS) combined with drug treatment in patients with bipolar Ⅰ disorder (BD Ⅰ).Methods:Forty-two patients with BD Ⅰ who were admitted to the Mental Health Center Affiliated to Anhui Medical University from March 2022 to June 2023 were included in this randomized double-blind study. These patients were randomly divided into a control group and an observation group using an Excel spreadsheet. In the control group, patients received 10 sessions of sham stimulation in addition to drug treatment, while the observation group received 10 sessions of tACS along with drug treatment. All patients were treated for 2 weeks. Each patient received stimulation for 15 minutes on each of the right and left prefrontal lobes once every working day. The Montreal Cognitive Assessment (MoCA) scores and Bech-Rafaelsen Mania Scale (BRMS) scores were compared between the two groups before and after treatment. Eighteen patients from the observation group and nineteen patients from the control group were included in the final analysis.Results:Two weeks after treatment, the MoCA score in the observation group was higher than that in the control group [(27.39 ± 1.88) vs. (24.63 ± 2.39)], and the BRMS score in the observation group was lower than that in the control group [(15.89 ± 3.18) vs. (19.00 ± 3.32)]. These differences were statistically significant ( t = -3.89, 2.91, both P < 0.05). After treatment, the MoCA score in the observation group increased, while the BRMS score decreased ( t = 5.04, -4.14, both P < 0.05). Pearson correlation analysis indicated the change in MoCA score was negatively correlated with BRMS score in both groups ( r = -0.433, P < 0.05). Conclusions:Drug treatment combined with tACS greatly improved clinical cognitive symptoms and reduced manic symptoms in patients with BD Ⅰ. The combined therapy exhibited better efficacy than monotherapy.