BACKGROUND:Arthroscopic anchor repair has become the main treatment method for rotator cuff tears at present.Among them,the insertion status of the anchor is a key factor in the success or failure of the operation.However,currently,the impact of the insertion depth of the anchor on the stress of the bone tunnel and the anchor under different bone density conditions remains unclear.OBJECTIVE:To explore the stress distribution of the bone tunnel and the anchor when the insertion depth of the anchor varies under different bone density conditions by using three-dimensional finite element analysis technology.METHODS:The CT image data of the humerus of volunteers were collected,and the models of the humerus and the anchor were constructed by using Mimics,3-Matic,and Solidworks software.In 3-Matic,holes with distances of 0,2,4,6,and 8 mm from the surface of the humerus were respectively created at the same position of the humerus and assembled with the anchor.In Mimics,values were assigned based on the CT gray value to obtain a model with normal bone mass(T value ≥-1.0).The parameters were changed to construct models with reduced bone mass(-2.5＜T value＜-1.0)and osteoporosis(T value＜-2.5).In each model,a 70 N pulling force was applied to the anchor along the direction tangent to the inner edge of the bone tunnel.The stress distribution and magnitude of the bone tunnel and the anchor when inserted at different depths under different bone density conditions were observed.RESULTS AND CONCLUSION:(1)When the insertion depth was the same,as the bone density decreased,the maximum equivalent stress of the anchor increased,while the maximum equivalent stress of the bone tunnel decreased.(2)When the bone density was the same,as the insertion depth of the anchor increased,the maximum equivalent stress of the anchor decreased.When the insertion depth was 4 mm,the stress of the bone tunnel was the smallest and the distribution was relatively uniform.The stress of the anchor was mainly distributed around the lower anchor hole and the proximal thread,and the stress of the bone tunnel was mainly at the part in contact with the proximal thread.The increase in the insertion depth would change the uniformity and pattern of the stress distribution,while the bone density had a relatively small impact on the stress distribution pattern.(3)It is concluded that the bone density of the humerus is crucial for the anchor repair of rotator cuff tears.It is recommended that clinicians measure the bone density of the greater tuberosity of the humerus before the operation.Excessive insertion depth of the anchor does not significantly increase its stability.Clinicians can conduct personalized preoperative assessments by using the finite element analysis method in combination with the actual situation of patients to achieve the best surgical results.

BACKGROUND:Arthroscopic anchor repair has become the main treatment method for rotator cuff tears at present.Among them,the insertion status of the anchor is a key factor in the success or failure of the operation.However,currently,the impact of the insertion depth of the anchor on the stress of the bone tunnel and the anchor under different bone density conditions remains unclear.OBJECTIVE:To explore the stress distribution of the bone tunnel and the anchor when the insertion depth of the anchor varies under different bone density conditions by using three-dimensional finite element analysis technology.METHODS:The CT image data of the humerus of volunteers were collected,and the models of the humerus and the anchor were constructed by using Mimics,3-Matic,and Solidworks software.In 3-Matic,holes with distances of 0,2,4,6,and 8 mm from the surface of the humerus were respectively created at the same position of the humerus and assembled with the anchor.In Mimics,values were assigned based on the CT gray value to obtain a model with normal bone mass(T value ≥-1.0).The parameters were changed to construct models with reduced bone mass(-2.5＜T value＜-1.0)and osteoporosis(T value＜-2.5).In each model,a 70 N pulling force was applied to the anchor along the direction tangent to the inner edge of the bone tunnel.The stress distribution and magnitude of the bone tunnel and the anchor when inserted at different depths under different bone density conditions were observed.RESULTS AND CONCLUSION:(1)When the insertion depth was the same,as the bone density decreased,the maximum equivalent stress of the anchor increased,while the maximum equivalent stress of the bone tunnel decreased.(2)When the bone density was the same,as the insertion depth of the anchor increased,the maximum equivalent stress of the anchor decreased.When the insertion depth was 4 mm,the stress of the bone tunnel was the smallest and the distribution was relatively uniform.The stress of the anchor was mainly distributed around the lower anchor hole and the proximal thread,and the stress of the bone tunnel was mainly at the part in contact with the proximal thread.The increase in the insertion depth would change the uniformity and pattern of the stress distribution,while the bone density had a relatively small impact on the stress distribution pattern.(3)It is concluded that the bone density of the humerus is crucial for the anchor repair of rotator cuff tears.It is recommended that clinicians measure the bone density of the greater tuberosity of the humerus before the operation.Excessive insertion depth of the anchor does not significantly increase its stability.Clinicians can conduct personalized preoperative assessments by using the finite element analysis method in combination with the actual situation of patients to achieve the best surgical results.

ObjectiveTo investigate the effects and underlying mechanisms of Xiaozheng Zhitong Paste （XZP） on bone cancer pain （BCP）. MethodsThirty female BALB/c mice were randomly divided into five groups： a Sham group， a BCP group， a BCP+low-dose XZP group， a BCP+high-dose XZP group， and a BCP+high-dose XZP + protease-activated receptor 2 （PAR2） agonist GB-110 group. BCP mice model was constructed by injecting Lewis lung carcinoma cells into the femoral cavity of the right leg， which was followed by being treated with XZP for 21 d. After 21 d， the mice were sacrificed. Nissl staining was used to evaluate the survival of spinal cord neurons. Immunofluorescence staining was conducted to localize ionized calcium-binding adapter molecule 1 （Iba1） and neuronal nuclear antigen （NeuN） in spinal cord tissue， thereby assessing microglial activation and neuronal survival. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， transforming growth factor-β （TGF-β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in spinal cord tissue. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels associated with M1/M2 polarization of microglia. Western blot analysis was performed to examine the expression of proteins related to microglial polarization as well as those involved in the PAR2/nuclear factor kappa B （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway in the spinal cord. ResultsCompared with the Sham group， the spinal cord neurons were damaged， the number of Nissl-positive spinal cord neurons in the spinal cord tissue was significantly reduced （P<0.01）， and the rate of NeuN-positive cells was significantly decreased （P<0.01）. The spinal cord microglia were activated， the inflammatory level of the spinal cord tissue was enhanced， and Iba1 staining was significantly enhanced （P<0.01）. The levels of IL-1β， TNF-α， IL-6， TGF-β， IL-4 and IL-10 were significantly increased （P<0.01）. The mRNA expressions of IL-1β， TNF-α and inducible nitric oxide synthase （iNOS） were significantly increased （P<0.01）， and the expression of PAR2， NLRP3， ASC and NF-κB p65 proteins in the spinal cord tissue of the BCP mice was significantly enhanced （P<0.01）. Compared with the BCP group， high-dose XZP treatment significantly increased the number of Nissl-positive spinal cord neurons in the BCP mice （P<0.01）， significantly enhanced the rate of NeuN-positive cells in the spinal cord tissue， and significantly weakened Iba1 staining （P<0.01）. In addition， the levels of IL-1β， TNF-α， and IL-6 were significantly decreased， while the levels of TGF-β， IL-4， and IL-10 were significantly increased （P<0.05， P<0.01）. The mRNA expression levels of IL-1β， TNF-α， and iNOS were decreased， whereas those of cluster of differentiation 206 （CD206）， arginase-1 （Arg-1）， and YM1/2 were significantly increased （P<0.05， P<0.01）. Low-dose and high-dose XZP treatment significantly decreased the expression of PAR2， NLRP3， ASC， and NF-κB p65 proteins in the spinal cord tissue （P<0.05， P<0.01）. These effects could all be significantly eliminated by the PAR2 agonist GB-110. ConclusionXZP can mitigate BCP in mice， which may be achieved through blocking the activated PAR2/NF-κB/NLRP3 pathway.

Pain， as one of the most common symptoms in cancer patients， seriously affects the survival quality of patients. The three-step pain relief program currently used in clinical practice cannot completely relieve pain in cancer patients and is accompanied by many problems. From the perspective of Jueyin syndrome in traditional Chinese medicine （TCM）， this paper believed that the core pathogenesis of cancer pain was declined healthy Qi and cold and heat in complexity， and used Wumeiwan as the main formula with modification according to syndrome for clearing the upper， warming the lower part of the body， and harmonizing the cold and heat. It can regulate the pathological environment of deficiency， cold， stasis， toxicity， and heat， and restore the physiological function of Yang transforming Qi while Yin constituting form， so as to prevent， relieve， and even eliminate cancer pain， having achieved good clinical efficacy. It can not only help cancer patients relieve pain， but also control tumor and eliminate tumor， achieving a dual benefit of pain relief and tumor suppression. It gives full play to the characteristics and advantages of syndrome differentiation and treatment in TCM， and expands the scope of ZHANG Zhongjing's treatment for Jueyin syndrome， which provides ideas for the clinical diagnosis and treatment of cancer pain from the perspective of deficiency-excess in complexity and cold and heat in complexity.

ObjectiveTo analyze the characteristics of 150 patients with spinal cord injury complicated with spasticity. MethodsA cross-sectional survey was conducted on 150 patients with spinal cord injury accompanied by spasticity from September, 2019 to December, 2024. Their age, gender, cause of injury, injury site, severity of injury, spasticity severity and other indicators were recorded. The relationships between different characteristics were analyzed, and a correlation analysis of disease duration, spasticity grade, injury level, injury severity and age were conducted. ResultsThere was no significant difference in age distribution between patients with tetraplegia and paraplegia (Z = 0.806, P = 0.420). The proportions of trauma (χ² = 3.982, P = 0.046) and tetraplegia (χ² = 10.559, P = 0.010) were higher in males than in females. Trauma was the main cause of injury in both tetraplegia and paraplegia patients; the proportion of tetraplegia was higher than paraplegia in trauma patients, while paraplegia was higher than tetraplegia in non-trauma patients (χ² = 11.885, P < 0.001). Patients with tetraplegia was dominated by incomplete injury, whereas patients with paraplegia was dominated by complete injury (χ² = 10.885, P = 0.012). Grade A injury was predominant in trauma patients (P = 0.003). Spasticity grade showed a very weak positive correlation with disease duration (r = 0.175, P = 0.032) and age (r = 0.168, P = 0.040). Injury severity showed a very weak positive correlation with age (r = 0.183, P = 0.025). ConclusionCharacteristics of patients with spinal cord injury complicated with spasticity is different with gender, cause of injury, injury level, injury severity.

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.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

OBJECTIVE To analyze the clinical characteristics of the patients with severe infections who were treated with polymyxin B and compare the plasma concentration of polymyxin B among the patients with severe infections with different creatinine clearance rates(Ccr).METHODS The clinical data were collected from 152 patients with severe infections who were treated with intravenous polymyxin B in intensive care unit(ICU)of Zhongda Hospital Affiliated to Southeast University from Jan.2021 to Mar.2023.The trough concentration(Cmin),median concen-tration(C1/2t)and peak concentration(Cmax)of polymyxin B were determined after 5 doses were completed.Based of the area under the curve(AUC)of drug concentration of polymyxin B(AUC0～24h)combined with the Ccr level[the ≤30 to＜60 ml/min group(n=40),the 60 to＜130ml/min group(n=79),and the ≥ 130ml/min group(n=33)],the AUC0～24h of polymyxin B were calculated,and the influence of Ccr on the plasma concentration was observed.RESULTS Among the 152 patients with severe infections,118 were male,and 34 were female,with the age ranging between 20 and 90 years old;the patients with high blood pressure accounted for 14.47％(22/152),the patients with diabetes mellitus 7.24％(11/152).Polymyxin B is primarily used in clinical settings for the treatment of pulmonary infections and bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae.The median initial dose and the median maintenance dose were 1.35(1.00,1.67)mg/kg q12 h and 1.07(0.83,1.25)mg/kg q12 h,respectively.The median AUC0～24h of polymyxin B was 76.57(54.65,106.47)μg·h/ml among the 152 patients,and the patients with AUC0～24 h ranging between 50 and 100 μg·h/ml accounted for 53.95％(82/152).Although the median AUC0～24h of polymyxin B of all the three groups ranged between 50 and 100)μg·h/ml,there were significant differences in Cmin,C1/2t,Cmax and AUC0～24h among the three groups(P＜0.05).In addition,there were significant differences in the AUC0～24h of polymyxin B less than 50 μg·h/ml,ranging between 50 and 100 μg·h/ml and more than 100 μg·h/ml among the three groups of patients(x2=21.632,P＜0.001).CONCLUSION Therapeutic drug monitoring(TDM)is nec-essary for the patients with severe infection who receive the polymyxin B for treatment,especially for the patients with Ccr ≤30 to＜60 ml/min and Ccr ≥130 ml/min.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective To develop a virtual reality rehabilitation support system and evaluate its effects on improving discharge readiness in caregivers of laryngectomy patients.Methods The system is equipped with a virtual reality-based home nursing skills guidance module for post-laryngectomy patients and an evidence-based artificial intelligence Q&A module.A convenience sampling method was adopted to select 64 caregivers of patients who underwent laryngectomy for the first time in the otorhinolaryngology head and neck surgery department of a tertiary A hospital in Beijing from July 2024 to January 2025 for a systematic study on application effects.To avoid cross-contamination between an experimental group and a control group,ward-based grouping was applied.A coin toss was used to assign Ward 1 to an experimental group and Ward 2 to a control group,with 32 cases in each group.The experimental group received discharge guidance based on the virtual reality technology,while the control group was provided with conventional verbal and written discharge instructions.The readiness for hospital discharge and the quality of discharge teaching scores of caregivers were compared between the 2 groups after the intervention.Results No sample detachment.After the intervention,the patient caregivers in the experimental group scored significantly higher than those in the control group in terms of discharge readiness and quality of discharge guidance,with a statistically significant difference(P＜0.001).Conclusion This study developed the virtual reality rehabilitation system for laryngeal cancer patients demonstrated good feasibility and effectiveness.The application of this system for discharge education significantly improved discharge readiness of caregivers and quality of discharge guidance for post-laryngectomy patients.It also helped with the optimization of health education models,enhancement of nursing resource utilization efficiency,and improvement of transitional care.