ObjectiveTo investigate the effects of targeted silencing of Runt-related Transcription Factor 3 （RUNX3） on the proliferation and migration of Mouse Hepatic Stellate Cells （HSCs）， as well as subsequent collagen deposition. MethodsMouse hepatic stellate cell line （JS-1） was selected and then morphologically observed and identified under a microscope. After the cells had fully adhered， they were treated with 5 ng/mL of transforming growth factor beta 1 （TGF-β₁） for 24 hours to induce hepatic stellate cell activation. Furthermore， a RUNX3 silencing model was established using RUNX3 lentiviral infection. The experiment was divided into four groups： Control group， TGF-β₁ group， TGF-β₁+siRNA-NC group， and TGF-β₁+siRNA-RUNX3 group. Protein expression changes of RUNX3， alpha-smooth muscle actin （α-SMA）， and Alpha 1 type I collagen （Collagen I） were detected using Western blot method. Cellular immunofluorescence assays were employed to investigate the deposition changes of α-SMA and RUNX3 in hepatic stellate cells. RT-qPCR was utilized to examine the mRNA expression changes of RUNX3， α-SMA， and Collagen I. The proliferative capacity of hepatic stellate cells was assessed using Edu staining. The migratory ability of hepatic stellate cells was evaluated through wound healing assays and Transwell migration experiments. ResultsCompared with Control group， a significant elevation in RUNX3 was observed in the TGF-β₁-induced activated HSCs （P<0.01）. Meanwhile， the protein and mRNA levels of fibrosis-related markers and α-SMA and Collagen I were significantly upregulated （P<0.001）. Additionally， the proliferation and migration capabilities of HSCs were significantly enhanced （P<0.001）. In contrast， when compared to TGF-β₁+siRNA-NC group， TGF-β₁+siRNA-RUNX3 group exhibited a notable decrease in RUNX3 and other related indicators， such as the protein and mRNA levels of α-SMA and Collagen I （P<0.05）. Concurrently， the proliferation and migration capabilities of HSCs were significantly inhibited in TGF-β₁+siRNA-RUNX3 group （P<0.01）. ConclusionSilencing RUNX3 can inhibit the deposition of collagen and the proliferation and migration of hepatic stellate cells. Conversely， RUNX3 promotes the proliferation and migration capabilities of HSCs， thereby facilitating the activation of HSC.

Kirsten rat sarcoma viral oncogene homolog (KRAS) protein inhibitors are a promising class of therapeutics, but research on molecules that effectively penetrate the blood-brain barrier (BBB) remains limited, which is crucial for treating central nervous system (CNS) malignancies. Although molecular generation models have recently advanced drug discovery, they often overlook the complexity of biological and chemical factors, leaving room for improvement. In this study, we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug efficacy and drug absorption properties. Our approach utilizes a variational autoencoder (VAE) generative model integrated with reinforcement learning for multi-objective optimization. This method specifically aims to enhance BBB permeability (BBBp) while maintaining high-affinity substructures of KRAS inhibitors. To support this, we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models. Additionally, we introduce two novel metrics, the knowledge-integrated reproduction score (KIRS) and the composite diversity score (CDS), to assess structural performance and biological relevance. Retrospective validation with KRAS inhibitors, AMG510 and MRTX849, demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications. This study provides a robust framework for accelerating the structural enhancement of lead compounds, advancing the drug development process across diverse targets.

Kirsten rat sarcoma viral oncogene homolog(KRAS)protein inhibitors are a promising class of thera-peutics,but research on molecules that effectively penetrate the blood-brain barrier(BBB)remains limited,which is crucial for treating central nervous system(CNS)malignancies.Although molecular generation models have recently advanced drug discovery,they often overlook the complexity of bio-logical and chemical factors,leaving room for improvement.In this study,we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug effi-cacy and drug absorption properties.Our approach utilizes a variational autoencoder(VAE)generative model integrated with reinforcement learning for multi-objective optimization.This method specifically aims to enhance BBB permeability(BBBp)while maintaining high-affinity substructures of KRAS in-hibitors.To support this,we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models.Additionally,we introduce two novel metrics,the knowledge-integrated reproduction score(KIRS)and the composite diversity score(CDS),to assess structural performance and biological relevance.Retrospective validation with KRAS inhibitors,AMG510 and MRTX849,demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications.This study provides a robust framework for accelerating the structural enhancement of lead compounds,advancing the drug development process across diverse targets.

Objective:To explore the factors influencing the incidence and duration of delirium in ICU patients, so as to provide a reference for early identification and prevention of delirium in these patients.Methods:A retrospective analysis was conducted on the medical records of 1, 500 patients admitted to the ICU of the Affiliated Jiangning Hospital of Nanjing Medical University from January 2020 to December 2024. The data collected included gender, age, anesthesia method, surgical duration, infection duration, extubation time, duration of mechanical ventilation and hypoxia, Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) score, Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score, duration of sedative medication, and ICU length of stay. Binary Logistic regression and multiple linear regression analysis were employed to investigate the factors influencing the incidence and duration of delirium in ICU patients.Results:The incidence of delirium among 1 500 ICU patients was 38.4% (576/1 500), with a duration of 1.10 (1.00, 3.20) d. Binary Logistic regression analysis revealed that infection duration, APACHEⅡ score, mechanical ventilation duration, and sedative medication duration were statistically significant factors influencing delirium incidence in ICU patients ( P<0.05). Multiple linear regression analysis revealed that delirium type, duration of hypoxia, use of sedative medications, and length of ICU stay were statistically significant factors influencing the duration of delirium in ICU patients ( P<0.05) . Conclusions:ICU patients have a relatively high incidence of delirium, and numerous factors influence the incidence and duration of delirium. Clinical nursing professionals should identify risk factors early and develop corresponding intervention measures to reduce the incidence of delirium in ICU patients and promote their recovery.

Objective:To explore the factors influencing the incidence and duration of delirium in ICU patients, so as to provide a reference for early identification and prevention of delirium in these patients.Methods:A retrospective analysis was conducted on the medical records of 1, 500 patients admitted to the ICU of the Affiliated Jiangning Hospital of Nanjing Medical University from January 2020 to December 2024. The data collected included gender, age, anesthesia method, surgical duration, infection duration, extubation time, duration of mechanical ventilation and hypoxia, Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) score, Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score, duration of sedative medication, and ICU length of stay. Binary Logistic regression and multiple linear regression analysis were employed to investigate the factors influencing the incidence and duration of delirium in ICU patients.Results:The incidence of delirium among 1 500 ICU patients was 38.4% (576/1 500), with a duration of 1.10 (1.00, 3.20) d. Binary Logistic regression analysis revealed that infection duration, APACHEⅡ score, mechanical ventilation duration, and sedative medication duration were statistically significant factors influencing delirium incidence in ICU patients ( P<0.05). Multiple linear regression analysis revealed that delirium type, duration of hypoxia, use of sedative medications, and length of ICU stay were statistically significant factors influencing the duration of delirium in ICU patients ( P<0.05) . Conclusions:ICU patients have a relatively high incidence of delirium, and numerous factors influence the incidence and duration of delirium. Clinical nursing professionals should identify risk factors early and develop corresponding intervention measures to reduce the incidence of delirium in ICU patients and promote their recovery.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To investigate the anti-tumor effects and mechanisms of sonodynamic therapy (SDT) combined with anlotinib on non-small cell lung cancer (NSCLC). Methods:A549 and H1299 cells were used as the research models and the following groups were estab-lished:control,anlotinib,SDT,and SDT-anlotinib. Cell viability and migration ability were assessed using the CCK-8 and cell scratch assays. Additionally,flow cytometry was employed to determine reactive oxygen species (ROS)levels,apoptosis,and cell cycle;Western blot was performed to detect Caspase-3 and Cyclin D1 expression;and ROS elimination experiments were conducted to explore the mechanisms of co-mbined SDT and anlotinib treatment. Results:In comparison to the anlotinib group,the SDT-anlotinib group demonstrated a notable inhibi-tion in the proliferation of lung cancer cells[cell viability:A549:(49.96±4.82)％ vs. (86.79±2.64)％,P<0.01;H1299:(31.91±4.87)％ vs. (88.04±2.16)％,P<0.001]and migration[healing rate:A549:(4.23±0.17)％ vs. (14.28±0.05)％,P<0.05;H1299:(13.68±2.16)％ vs. (42.81±8.11)％,P<0.001]. Furthermore,the combination therapy group exhibited a notable induction of apoptosis[apoptosis rate:(12.58±0.815)％ vs. (8.43±0.56)％,P<0.05]. Mechanistic studies have demonstrated that anlotinib resistance is associated with ROS levels. Treatment with the ROS scavenger N-acetylcysteine (NAC) has been shown to decrease intracellular ROS content,increase the IC50 of anlotinib,and reduce sens-itivity. Intracellular ROS levels in tumor cells were significantly higher in SDT-anlotinib group compared to that in the anlotinib group[(934.14±2.01) vs. (166.75±1.45),P<0.001]. Additionally,Caspase-3 activation was observed,accompanied by a reduction in Cyclin D1 ex-pression. Conclusions:The combination of SDT and anlotinib exerted a pronounced anti-tumor effect. Activation of the ROS pathway led to the activation of Caspase-3 and the downregulation of Cyclin D1,resulting in the inhibition of lung cancer cell proliferation and the induction of apoptosis.

Objective:To investigate the clinicopathological features and molecular characteristics of β-catenin-deficient colorectal cancer.Methods:The clinical, pathological and molecular features of 11 colorectal cancers with β-catenin protein loss diagnosed at the 960th Hospital of People′s Liberation Army of China, from January 2012 to November 2022 were analyzed.Results:Among the 11 patients, 3 were males and 8 were females. Their age ranged from 43 to 74 years, with the median age of 59 years. Six were in the left colon and 5 were in the right colon. One of the 11 cases had lymph node metastasis, 10 cases were well and moderately differentiated adenocarcinoma, and 1 was mucinous adenocarcinoma. Eight cases were of TNM stage T4, 2 of T1 stage and 1 of Tis stage. β-catenin protein was not detected using immunohistochemistry. Sanger sequencing revealed the presence of fragment-deletion mutation in exon 3 of CTNNB1 gene, resulting in loss of β-catenin protein expression.Conclusion:β-catenin deficiency is present in a small number of colorectal cancers and may be associated with exon 3 mutations of CTNNB1 gene.

Objective To investigate the unmet needs for assistive technology for people with physical disabilities in Chengdu,and analyze the related factors. Methods From November,2023 to March,2024,the persons with physical disabilities in Chengdu were selected from Sichuan Individuation service platform,and investigated using World Health Organization rapid Assistive Tech-nology Assessment. Results A total of 558 questionnaires were set up,and 527 effective questionnaires retured.26.8%of them reported un-met needs for aids,with the highest need for mobility aids(66.0%).Lack of support(54.9%),high price(26.3%)and lack of knowledge about aids(20.3%)were the main reasons for not obtaining the aids they needed.Loss of spouse(OR=3.615),serious mobility impairment(OR＞2.926)and serious self-care impairment(OR＞2.781)were the risks of unmet needs for aids. Conclusion It is important to popularize policies and products of aids,pay attention to personal adaptation for people with different barriers,and strengthen the service system,to meet the needs of people with disabilities.

Objective:To investigate the anti-tumor effects and mechanisms of sonodynamic therapy (SDT) combined with anlotinib on non-small cell lung cancer (NSCLC). Methods:A549 and H1299 cells were used as the research models and the following groups were estab-lished:control,anlotinib,SDT,and SDT-anlotinib. Cell viability and migration ability were assessed using the CCK-8 and cell scratch assays. Additionally,flow cytometry was employed to determine reactive oxygen species (ROS)levels,apoptosis,and cell cycle;Western blot was performed to detect Caspase-3 and Cyclin D1 expression;and ROS elimination experiments were conducted to explore the mechanisms of co-mbined SDT and anlotinib treatment. Results:In comparison to the anlotinib group,the SDT-anlotinib group demonstrated a notable inhibi-tion in the proliferation of lung cancer cells[cell viability:A549:(49.96±4.82)％ vs. (86.79±2.64)％,P<0.01;H1299:(31.91±4.87)％ vs. (88.04±2.16)％,P<0.001]and migration[healing rate:A549:(4.23±0.17)％ vs. (14.28±0.05)％,P<0.05;H1299:(13.68±2.16)％ vs. (42.81±8.11)％,P<0.001]. Furthermore,the combination therapy group exhibited a notable induction of apoptosis[apoptosis rate:(12.58±0.815)％ vs. (8.43±0.56)％,P<0.05]. Mechanistic studies have demonstrated that anlotinib resistance is associated with ROS levels. Treatment with the ROS scavenger N-acetylcysteine (NAC) has been shown to decrease intracellular ROS content,increase the IC50 of anlotinib,and reduce sens-itivity. Intracellular ROS levels in tumor cells were significantly higher in SDT-anlotinib group compared to that in the anlotinib group[(934.14±2.01) vs. (166.75±1.45),P<0.001]. Additionally,Caspase-3 activation was observed,accompanied by a reduction in Cyclin D1 ex-pression. Conclusions:The combination of SDT and anlotinib exerted a pronounced anti-tumor effect. Activation of the ROS pathway led to the activation of Caspase-3 and the downregulation of Cyclin D1,resulting in the inhibition of lung cancer cell proliferation and the induction of apoptosis.