Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

ObjectiveTo observe the clinical efficacy and radiographic outcomes of manipulative reduction combined with small splint fixation in the treatment of distal radius fractures. MethodsThe clinical data of 1051 patients with distal radius fractures were retrospectively collected from five hospitals included in the Jiangsu Diagnosis and Treatment Data Platform for Traditional Chinese Medicine（TCM） Dominant Diseases. Propensity score matching at a 1∶4 ratio was applied， resulting in 580 cases selected for final analysis， which comprised 448 patients in the TCM group（manipulative reduction plus small splint fixation） and 132 in the surgical treatment group（open reduction and internal fixation）. Each group was further stratified into type A， B， and C subgroups based on AO fracture classification. Radiographic indicators including palmar tilt， radial inclination， and radial height were compared between groups before treatment and 1 day， 1 week， and 4-6 weeks after treatment， and pain visual analog scale（VAS） scores before treatment and 1 week and 4-6 weeks after treatment were also compared. Wrist joint function was assessed 12 weeks after treatment， using the Dienst wrist function score and the Gartland and Werley（G-W） wrist function score. Additionally， the radiographic indicators at different timepoints and the 12-week wrist function levels were compared between groups across different fracture types. ResultsNo statistically significant difference was observed in radiographic indicators and VAS scores at all timepoints before and after treatment， as well as wrist joint function grades assessed by the Dienst score and the G-W score at 12 weeks after treatment （P＞0.05）. Compared to those before treatment， both groups showed increased palmar tilt， radial inclination， and radial height 1 week and 4-6 weeks after treatment， and decreased VAS scores （P＜0.05）. Compared to those 1 week after treatment， both groups showed a decrease in palmar tilt， an increase in radial inclination and radial height， and a reduction in VAS score 4-6 weeks after treatment（P＜0.05）. In type A and B subgroups， the surgical treatment group had a higher radial inclination than the TCM group 4-6 weeks after treatment， while in the type C subgroup， a higher radial height was shown in the surgical treatment group than in the TCM group 4-6 weeks after treatment（P＜0.05）. In type C subgroup， there was significant difference between groups in the wrist joint function by G-W scores 12 weeks after treatment（P＜0.05）. ConclusionManipulative reduction combined with small splint fixation can maintain fracture alignment and alleviate pain in treating distal radius fractures， which achieves therapeutic outcomes comparable to surgical treatment. It is particularly suitable for type A and B fractures and can be considered an effective treatment option for distal radius fractures.

ObjectiveTo construct an automatic measurement model for palmar tilt and radial inclination suitable for traditional Chinese medicine （TCM） clinical scenarios， and to validate its accuracy and efficiency in TCM manipulative reduction settings. MethodsData on anteroposterior （AP） and lateral X-rays of distal radius fractures were collected from patients admitted to 18 TCM/ integrated TCM and western medicine hospitals in Jiangsu province between September 1st， 2023， and September 1st， 2024， via the Jiangsu Diagnosis and Treatment Big Data Platform for TCM Dominant Diseases. A medical image segmentation framework based on multi-scale feature fusion and edge-awareness was employed， combined with anatomical knowledge specific to TCM orthopedics， to optimize the feature extraction strategy of an artificial intelligence （AI） model. This framework enabled automatic segmentation of fracture regions and measurement of distal radius palmar tilt and radial inclination. The accuracy of the AI model in measuring radial inclination and volar tilt was validated， and the measurement time and average time gain rate of the AI model were compared to those of manual measurement. ResultsA total of 15,444 AP and lateral X-ray images of distal radius fractures were collected， and were divided into a training set （11,144 images， 5066 AP and 6078 lateral）， a validation set （3700 images， 1840 AP and 1860 lateral）， and an independent test set （600 images， 300 AP and 300 lateral） after preprocessing. In the measurement of 300 AP X-rays in the independent test set for radial inclination， when the degree error between AI measurement and manual measurement was ＜3° and ＜5°， AI measurement accuracy was 83% and 93%， respectively. In 300 lateral X-rays in the test set for palmar tilt， when AI measurements had an error of ＜3° and ＜5° compared to manual measurements， corresponding accuracy rate was 78% and 90%， respectively. For 50 X-ray images， AI measurement time was （1.37±0.05） min for radial inclination while manual measurement time was （22.57±2.52） min （P＜0.001）； in terms of palmar tilt， the AI measurement time was （1.33±0.14） min， shorter than （23.70±2.80） min for manual measurement time （P＜0.001）. Average time gain rates for manual and AI measurements were 93.93% and 94.39% respectively. ConclusionAn automatic measurement model for palmar tilt and radial inclination in distal radius fractures has been established， enabling more accurate and efficient assessment as well as providing a tool to support the quantitative evaluation of the efficacy of TCM manipulative reduction and large-sample clinical research.

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Objective To investigate the feasibility and efficacy of mindfulness-based stress reduction (MBSR) in the management of chronic pain among military personnel stationed in plateau area of China. Methods Military personnel who had been stationed at an altitude ranging from 3 300 to 3 500 meters for over four months and suffered from chronic pain were selected as the study subjects by the judgment sampling method. A total of 51 individuals were assigned to the control group, and 53 individuals were assigned to the MBSR group using the random number table method. Individuals of the control group received conventional pain management, while the MBSR group received an additional eight-week MBSR training alongside conventional management. Pain, mindfulness levels, mood state, and psychological resilience of individuals were assessed before and 12 weeks after the intervention using the Brief Pain Inventory (BPI), the Five Facet Mindfulness Questionnaire-Short Form, the Profile of Mood States, and the Connor-Davidson Resilience Scale. Results After the intervention, the BPI scores, and the scores of the pain intensity and pain impact dimensions of individuals in the MBSR group were lower than those in the control group (all P<0.01). The reductions in these three scores were greater in the MBSR group than those in the control group (all P<0.01). Meanwhile, individuals in the MBSR group showed superior improvements in the mindfulness level score, the total mood disturbance, and the psychological resilience score compared with the control group (all P<0.05). The multiple linear regression analysis results showed that the pre-intervention BPI score, post-intervention changes in mindfulness levels, headache and lower back pain were influencing factors for the improvement of the BPI score in the MBSR group individuals (all P<0.05). Conclusion Conducting MBSR in military units in plateau areas is an effective approach for alleviating chronic pain. The pain relief effect is more pronounced in individuals with higher initial pain scores, a greater increase in mindfulness scores after training, and those with headache and low back pain.

BACKGROUND:The lower-limb muscle strength shows a significant physiological decline with aging.There may be a certain correlation between sedentary behavior,fear of falling,age and lower-limb muscle strength,but the influence path and effect relationship among them are not yet clear.OBJECTIVE:To examine the relationship between sedentary behavior and lower-limb muscle strength,and to explore the influences of fear of falling and age in such an association among community-dwelling older adults.METHODS:This cross-sectional study recruited 331 community-dwelling older adults(aged≥60 years)in Shanghai.A questionnaire survey was conducted to collect basic information,demographic data,etc.The Short Form of the International Physical Activity Questionnaire was applied to measure sedentary time.Lower-limb muscle strength was assessed by the 30-second chair-stand test.Fear of falling was measured by the Chinese version of Fall Efficacy Scale-International.Descriptive statistics analysis,correlation analysis,regression-based path analysis and mediation analyses were performed on the data.RESULTS AND CONCLUSION:Valid data from 318 community-dwelling older adults[78.9%females,mean age(67.8±5.5)years old]were finally included in the analysis.There were 185 with sedentary time≥3 hours and 133 with sedentary time<3 hours.(1)There was a positive correlation between sedentary behavior and fear of falling(P<0.01),and there were negative correlations between lower-limb muscle strength and sedentary behavior(P<0.01)and between lower-limb muscle strength and fear of falling(P<0.001).(2)Sedentary behavior negatively predicted lower-limb muscle strength(β=-0.125,P<0.05),and positively predicted fear of falling(β=0.182,P<0.01).Fear of falling negatively predicted lower-limb muscle strength(β=-0.293,P<0.001).(3)Fear of falling mediated the relationship between sedentary behavior and lower-limb muscle strength(β=-0.053,95%confidence interval:-0.100 to-0.018).(4)Sedentary behavior had a statistically significant predictive effect on fear of falling(β=0.164,P<0.01),indicating that age moderates the effect of sedentary behavior on fear of falling.

Purpose To investigate the expression of bone sialoprotein(BSP)in the tissues and cells of endome-trial cancer(EC)and its effects on the proliferation and invasion of EC cells.Methods The expression of BSP was assessed by immunohistochemistry in 235 EC tissues and 88 normal endometrial tissues,and its correlation with clinico-pathological features was analyzed.Western blot was used to compare BSP levels between human endometrial carcinoma cell line(HHUA)and normal human endumetial epithelial cells(HEEC).BSP was knocked down in HHUA cells via transient transfection,and the cells were divided into blank control group and BSP-knockdown group.The effects of BSP knockdown on cell cycle,proliferation,migration,invasion,and apoptosis were evaluated using PI staining,CCK-8,scratch,Transwell,and Annexin V-FITC assays,respectively.Protein levels of TGF-β signaling pathway compo-nents were analyzed by Western blot.Results BSP expression was significantly higher in EC tissues than in normal endometrium(P＜0.001)and correlated with lymph node metastasis and advanced FIGO stage(P＜0.05).BSP pro-tein level was also significantly elevated in HHUA cells(2.455 8±0.008 9)compared to HEECs(1.571 2±0.005 4)(P＜0.01).After knockdown,compared with the control group,the proliferation index(74.4±3.33),migration rate(0.48±0.03),and invasion ability(0.36±0.11)of the cells were increased,and the apoptosis rate(25.97％)of the cells was increased(P＜0.05).Furthermore,the expression levels of TGF-β signaling pathway downstream proteins TGF-β1(0.290 4±0.002 3)、TGF-β2(0.292 9±0.001 6)、Smad2(0.469 3±0.001 1)、Smad3(0.247 0±0.001 7)、pAKT(0.382 1±0.001 9)、ATK(0.119 6±0.001 6)and MEK1(0.258 9±0.000 3)in the BSP-knockdown group of EC cells decreased(P＜0.01).Conclusion BSP is highly expressed in endometrial cancer and promotes cancer cell proliferation,invasion,and metastasis by activating the TGF-β signaling pathway.

Grounded in a comprehensive analysis of the connotation and significance of cultivating and practicing core so-cialist values,this study advances the cultural construction of public hospitals through a"tripartite synergy"strategy.An institu-tional safeguard system is established that foregrounds top-level design,institutional guarantees,and positive orientation.A driv-er-oriented framework for staff care and value guidance is implemented to consolidate cognitive understanding,attitudinal endorse-ment,and behavioral internalization of these values.A full-spectrum practice-based cultivation system is further deployed to rein-force social morality,professional ethics,family virtues,and personal integrity.These initiatives have demonstrably enhanced staff identification,medical service quality,and overall hospital performance.The paper concludes with actionable recommenda-tions on institutional codification,cultural continuity,innovation-driven development,social engagement,and community serv-ice,offering replicable experience for cultural advancement in public hospitals.