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 newly reported HIV-1 infection in several prefectures of Hubei Province，and analyze its influencing factors. Methods The limiting antigen avidity enzyme immunoassay(LAg-avidity EIA,LAg) was conducted on HIV-1 positive samples confirmed by Western blot of Hubei in 2017-2022. The demographic characteristics of the newly infected samples were analyzed by χ2 test.Logistic regression model was used to analyze influencing factors of new infection rate and predict the factors associated with the HIV-1 recent infection. Results There were 403 new cases of HIV-1 from 2017 to 2022 in several prefectures of Hubei Province, of which 77 were newly infected sorted by LAg,with a new infection rate of 19.11%. The newly confirmed HIV-1 persons of whom aged ≤24 years (40.00% new infection ratio), unmarried (29.41%), college or above (31.37%), and from Voluntary counseling and testing testing(VCT) clinics (40.00%) had a higher proportion of new infections, and the difference was statistically significant. Multivariate Logistic regression analysis showed that age ≤24 years old (aOR=4.346,95%CI: 1.342-14.075) and screening from the VCT clinic (aOR=6.761,95%CI: 1.460-31.319) were more likely to be newly infected. Conclusion The proportion of new HIV infection in several prefectures of Hubei province is relatively low in recent years.Further effective publicity and intervention measures for young students and the construction of VCT clinic should be continuously promoted to achieve early diagnosis and treatment.

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.

ObjectiveThis study proposes a novel single-cell protein localization method based on a class perception graph convolutional network (CP-GCN) to overcome several critical challenges in protein microscopic image analysis, including the scarcity of cell-level annotations, inadequate feature extraction, and the difficulty in achieving precise protein localization within individual cells. The methodology involves multiple innovative components designed to enhance both feature extraction and localization accuracy. MethodsFirst, a class perception module (CPM) is developed to effectively capture and distinguish semantic features across different subcellular categories, enabling more discriminative feature representation. Building upon this, the CP-GCN network is designed to explore global features of subcellular proteins in multicellular environments. This network incorporates a category feature-aware module to extract protein semantic features aligned with label dimensions and establishes a subcellular relationship mining module to model correlations between different subcellular structures. By doing so, it generates co-occurrence embedding features that encode spatial and contextual relationships among subcellular locations, thereby improving feature representation. To further refine localization, a multi-scale feature analysis approach is employed using the K-means clustering algorithm, which classifies multi-scale features within each subcellular category and generates multi-cell class activation maps (CAMs). These CAMs highlight discriminative regions associated with specific subcellular locations, facilitating more accurate protein localization. Additionally, a pseudo-label generation strategy is introduced to address the lack of annotated single-cell data. This strategy segments multicellular images into single-cell images and assigns reliable pseudo-labels based on the CAM-predicted regions, ensuring high-quality training data for single-cell analysis. Under a transfer learning framework, the model is trained to achieve precise single-cell-level protein localization, leveraging both the extracted features and pseudo-labels for robust performance. ResultsExperimental validation on multiple single-cell test datasets demonstrates that the proposed method significantly outperforms existing approaches in terms of robustness and localization accuracy. Specifically, on the Kaggle 2021 dataset, the method achieves superior mean average precision (mAP) metrics across 18 subcellular categories, highlighting its effectiveness in diverse protein localization tasks. Visualization of the generated CAM results further confirms the model’s capability to accurately localize subcellular proteins within individual cells, even in complex multicellular environments. ConclusionThe integration of the CP-GCN network with a pseudo-labeling strategy enables the proposed method to effectively capture heterogeneous cellular features in protein images and achieve precise single-cell protein localization. This advancement not only addresses key limitations in current protein image analysis but also provides a scalable and accurate solution for subcellular protein studies, with potential applications in biomedical research and diagnostic imaging. The success of this method underscores the importance of combining advanced deep learning architectures with innovative training strategies to overcome data scarcity and improve localization performance in biological image analysis. Future work could explore the extension of this framework to other types of microscopic imaging and its application in large-scale protein interaction studies.

Objective:To explore the effects three of anesthetics(tribromoethanol,isoflurane,and pentobarbital so-dium)on the outcome of mice with post-stroke dysphagia(PSD)induced by photothrombosis(PT)method,and to e-valuate which anesthetic is more suitable for the preparation of this model.Methods:Sixty-six male C57BL/6J mice were divided into Tribromoethanol group,Isoflurane group,Pentobarbital sodium group and Sham group.The post-stroke dysphagia model was established by PT.Before and 5 min after modeling,a laser speckle imager was used to measure the regional cerebral blood flow(rCBF)decrease rate of mice and record the wake-up time of mice.Forty-eight hours after modeling,the mortality rate of PSD mice in three groups was recorded and the rCBF decrease rate was meas-ured again.The neurological function of mice was evaluated using the neurological deficit score,the water intake of mice was recorded using the 4-min drinking test,the infarct volume ratio was measured using the TTC staining method,and the swallowing counts induced by water administration was recorded using the multichannel physiological recorder MP160 and the myoelectric area of the swallowing muscle was calculated.Results:There was no statistical difference in the percentage of decrease in rCBF,infarct volume ratio,neurological deficit score,water intake,swallowing counts,and myoelectric area of swallowing muscle among the three groups of PSD mice 48 h after modeling(P＞0.05).Com-pared with the Tribromoethanol group and the Pentobarbital sodium group,the rCBF of the mice in the Isoflurane group decreased rapidly within 5 min(P＜0.05),and the mortality rate of the mice was lower and the awakening time was shorter.(P＜0.05).Conclusion:The use of different anesthesia will affect the mortality rate,wake-up time and the downward trend of rCBF within 48 h after modeling of PSD mice.Among the three anesthetics,isoflurane is more suit-able as an anesthetic for the PSD mouse model.

Deficiencies remain in the early identification and screening method for type 2 diabetes mellitus(T2DM).Relying solely on blood glucose indicators as diagnostic criteria fails to capture the systematic evolution of glucose metabolism destabilization and does not allow for the identification of the critical transition period preceding the onset of T2DM.In the complex system of the human body,structural and state variables correspond to the traditional Chinese medicine concepts of"zang"and"xiang."These variables determine the landscape of the systemic state changes over time.The pathogenesis of T2DM is characterized by a shift from compensatory insulin secretion to β-cell dysfunction,driven by negative-positive feedback dynamics,ultimately resulting in a marked increase in blood glucose levels.A critical transition exists between glycemic homeostasis and the establishment of T2DM disease homeostasis.Using theoretical approaches such as critical slowing and dynamic network markers in dynamical systems theory,various clinical case data-including four-diagnosis information,multiple biological samples,and histological analysis method-can be leveraged to identify the critical transition key stage from pre-disease to disease of T2DM,facilitating early intervention.This paper aims to develop a dynamic model describing the transition from"glucose homeostasis-glycemic state of instability-steady state of T2DM"by analyzing the mechanism of the complex human system and the dynamic characteristics underlying T2DM onset.This framework aims to enhance early identification method.Establishing this holistic approach offers a novel perspective for the prevention and treatment of T2DM.

Barrett's esophagus(BE),a precancerous state of esophageal adenocarcinoma,poses a major challenge for prevention and treatment owing to its complex mechanism of inflammation-cancer transformation and the lack of effective clinical treatment and torsion strategies.Building upon the"preventing disease progression"theory,this study aimed to address the critical clinical challenge of intercepting the pathological progression during the inflammation-cancer transformation of BE by proposing an innovative"two critical nodes-three stages"pathomechanism framework.The pathogenesis of BE originates from liver depression and qi stagnation.The pathological progression evolves through two critical nodes:liver depression transforming into heat and heat transforming into blood stasis,representing a three-stage evolutionary pattern of qi stagnation,heat transformation,and blood stasis formation.Acidic bile salts,acting as a pathogenic toxin,permeate the entire process and catalyze carcinogenesis.Based on this understanding,the therapeutic principles of"treatment from the liver"and"truncation and torsion"were established,emphasizing stage-specific interventions.For the qi stagnation stage,treatment focuses on soothing the liver and regulating qi,as well as moistening,harmonizing,and descending the qi.This is achieved by combining modified Chaihu Shugan Powder with Xuanfu Daizhe Decoction,while using pungent and drying herbs cautiously and supplementing them with light and floral herbs.In the heat transformation stage,the strategy aims to clear the liver and drain heat while protecting yin and harmonizing the stomach,employing modified Huaganjian combined with Yiguanjian and supplemented with Jinlingzi Powder to clear depressed fire.For the blood stasis formation stage,treatment involves activating blood and resolving stasis,combined with supporting healthy qi and removing toxins.This is achieved using a modified Gexia Zhuyu Decoction,supplemented with Liujunzi Decoction,and additions such as Radix Salviae Miltiorrhizae and turtle carapace to disperse nodules and reduce masses.This theoretical framework establishes a diagnostic and therapeutic model characterized by the integration of disease mechanisms with pathology and the mutual reference of macro-level signs with micro-level indicators.It provides a comprehensive clinical practice pathway,complete with principles,methods,formulas,and herbs,for the stage-specific interception of inflammation-cancer transformation in BE using traditional Chinese medicine.

Objective:To investigate the application effect of aleximumab combined with ivabradine in patients with STEMI after PCI.Methods:A retrospective analysis was conducted on 90 STEMI patients admitted to Jiamusi Central Hospital for PCI treatment from October 2023 to October 2024.The patients were divided into two groups based on whether they were treated with aleximumab in the early stages of admission.The 45 patients treated with aleximumab combined with ivabradine were assigned to the experimental group,and the 45 patients treated with ivabradine were assigned to the matched group.Compare two groups of blood lipid metabolism indicators[Low density lipoprotein cholesterol(LDL-C),triglycerides,total cholesterol],inflammatory factors[interleukin-6(IL-6),matrix metalloproteinase-9(MMP-9),hypersensitive C-reactive protein(Hs CRP)],ventricular remodeling[Left ventricular mass index(LVMI),end diastolic interventricular thickness(LVST)],and carotid plaques[plaque score,plaque area,carotid intima-media thickness(CarST)].otid intima-media thickness(IMT)was observed,and patients were followed up by telephone and outpatient follow-up for 6 months to record the incidence of cardiovascular adverse events(MACE).Results:Post-treatment,the level of lipid metabolism in both groups was lower than that pretherapy,and the level of lipid metabolism in the test group was lower than that in the matched group(P＜0.05);Post-treatment,the levels of inflammatory factors in both groups were lower than that pretherapy,and the test group was lower than that in the matched group(P＜0.05);Post-treatment,t-test showed that LVMI LVST,The plaque score,plaque area,and TMT level were all lower than pretherapy,and the experimental group was lower than the matched group(P＜0.05);All patients were followed up for 6 months after surgery.Through follow-up,it was found that the total incidence of MACE in the experimental group was 8.89％,while that in the matched group was 26.67％.According to the chi square test,the total incidence of MACE in the experimental group was lower than that in the matched group(P＜0.05).Conclusion:The combination of aleximumab and ivabradine treatment after PCI in STEMI patients can further improve the patient's lipid metabolism,reduce the body's inflammatory response,reverse some carotid plaques,improve ventricular remodeling,and thus further reduce the risk of long-term cardiovascular adverse events in patients.

Head and neck squamous cell carcinoma(HNSCC)is an immunosuppressive tumor with high morbidity and mortal-ity,and easy to develop treatment tolerance.In recent years,it has been found that the tumor microenvironment,especially the chemo-kine-chemokine receptor network,plays an important role in the occurrence,development,prognosis and treatment tolerance of HN-SCC.In this review,the research progress on the relationship between chemokine-chemokine receptor network and HNSCC is summa-rized,focusing on the regulatory role and mechanism of HNSCC progression,so as to provide new ideas for the diagnosis and treatment of HNSCC.

Poly-(adenosine diphosphate-ribose)-polymerase(PARP)inhibitors are a novel group of small molecule targeted therapeutic drugs.It has become an effective treatment for ovarian cancer,prostate cancer and breast cancer carrying BRCA1/2 mutations.Studies have demonstrated that PARP inhibitors(PARPi)can improve treatment outcomes by targeting genetic defects in tumors with syner-gistic effects with standard therapies for glioma treatment,such as increasing radiation sensitivity and overcoming temozolomide resistance.Howev-er,the limited blood-brain barrier permeability,the adverse reactions of drug combination and the oc-currence of drug resistance are the key factors af-fecting the therapeutic effect.This article reviews the mechanism of action and research progress of PARP inhibitors involved in the treatment of brain glioma,and analyzes the challenges to be faced in clinical practice,in order to provide references for future research in this field.