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.

Objective To analyze the relationship between hypertension combined with obstructive sleep apnea hypopnea syndrome(OSAHS)and intima-media thickness(IMT)and explore the correlation between the risk of IMT and hypertension with OSAHS patients.Methods Select 50 patients with hypertension and OSAHS patients who were treated in Jiaxing Hospital of Traditional Chinese Medicine during January 2020 to February 2024 as observation group,while 50 patients with simple hypertension were used as control groups to collect two groups of patients'sleep respiratory monitoring disorders(AHI),lowest blood oxygen saturation(L-SaO2)at night,average hemodium oxygen saturation(M-SaO2)at night,dynamic blood pressure 24h,daytime and night's average diastolic blood pressure,IMT,conducting relevant statistical analysis,compares correlation between IMT of two groups and the severity of OSAHS.Results Compared with control group,observation group AHI,IMT,average systolic blood pressure voltage and average diastolic blood pressure increased significantly(P＜0.01),L-SaO2,M-SaO2 decreased significantly(P＜0.01).Observation group AHI and average systolic blood voltage and average diastolic pressure of average systolic blood pressure at 24h,daytime,and night were positively correlated(P＜0.01),L-SaO2,24h and daytime average contraction pressure were negatively correlated(P＜0.05).Observation group AHI and IMT were positive,and L-SaO2,M-SaO2 and IMT were negatively related(P＜0.01).Conclusion Severity of the disease of hypertension combined with OSAHS patients is closely related to patient's blood pressure level and change of IMT.Actively controlling blood pressure and IMT may help improve prognosis of patients,reduce the occurrence of cardiovascular events.The prognostic evaluation has certain clinical value.

BACKGROUND:Research has shown that vanillic acid has anti-inflammatory and anti-oxidative stress effects,but it is unclear whether it has a protective effect on endplate chondrocytes.OBJECTIVE:To explore the effect and mechanism of vanillic acid on endplate chondrocytes under inflammatory microenvironment.METHODS:(1)Primary endplate chondrocytes were isolated from the intervertebral disc of SD rats and identified by toluidine blue staining and collagenⅡ immunofluorescence.(2)The CCK-8 assay was employed to detect the effects of interleukin-1β and vanillic acid on the proliferation activity of endplate chondrocytes,in order to determine the concentration of vanillic acid for subsequent cell treatment.(3)An inflammatory microenvironment was simulated by adding 10 ng/mL interleukin-1β to the culture medium,and the endplate chondrocytes were treated with low,medium,and high mass concentrations of vanillic acid.The expression levels of inflammatory markers and extracellular matrix proteins were detected by western blot assay and immunofluorescence.(4)The expression of nuclear factor κB signaling pathway-related proteins was detected by western blot assay.RESULTS AND CONCLUSION:(1)The morphology of endplate chondrocytes in adherent culture was pike or triangular in shape,positive for toluidine blue staining and immunofluorescence for collagen Ⅱ,indicating that the experimentally extracted cells were endplate chondrocytes.(2)The CCK-8 assay results showed that treatment with 2.5,5,10,and 20 μg/mL vanillic acid for 24 hours did not significantly inhibit the proliferation of endplate chondrocytes.Compared with the interleukin-1β group,the viability of endplate chondrocytes treated with 5,10,and 20 μg/mL vanillic acid for 24 hours was significantly increased(P＜0.05).Therefore,5,10,and 20 μg/mL vanillic acid was selected as the low,medium,and high dose groups for subsequent treatment of endplate chondrocytes.(3)Compared with the model group(complete medium containing 10 ng/mL interleukin-1β),the expression of NOD-like receptor thermal domain associated protein 3(NLRP3),matrix metalloproteinase 13,matrix metalloproteinase 3,and tumor necrosis factor alpha protein in the endplate chondrocytes of the low,medium,and high doses of vanillic acid groups were significantly reduced(P＜0.05).(4)Compared with the model group,the protein expression of aggrecan and collagen Ⅱ in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid significantly increased(P＜0.05).(5)Compared with the model group,the protein expression of phospho-nuclear factor κB and phospho-inhibitor of nuclear factor κB in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid was significantly reduced(P＜0.05).(6)The above results indicate that vanillic acid may alleviate the inflammatory response and extracellular matrix degradation induced by interleukin-1β in rat endplate chondrocytes by inhibiting the activation of the nuclear factor κB signaling pathway.

Objective To evaluate the efficacy and safety of Qixian Tongluo Formula in the treatment of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome,and to preliminarily explore the molecular mechanism of Qixian Tongluo Formula in improving impaired motor function from the perspective of cross-kingdom regulation of Chinese medicine microRNA(miRNA).Methods A pragmatic randomized controlled trial was conducted with 102 patients in the recovery period of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome in our hospital.Patients were randomly divided into trial group and control group,with 51 cases in each group.The control group received standard Western medicine standard treatment,while the trial group received Qixian Tongluo Formula in addition to the standard treatment,with one dose per day,boiled in water,and taken warm after breakfast and dinner for a course of 2 months.The disability rate was used as the main efficacy indicator,and the incidence of adverse reactions was used as a safety indicator.miRNA from patient serum and Qixian Tongluo decoction were extracted respectively,and high-throughput sequencing was performed.The two sequences were compared to screen out the cross-kingdom gene transfer of Chinese medicine miRNA.Finally,its target genes of miRNA were predicted,and GO function and KEGG pathway enrichment analysis were carried out.Results A total of 67 patients completed the clinical trial,including 36 cases in the trial group and 31 cases in the control group;The disability rate in the trial group(13.9%)was lower than that in the control group(35.5%)(P<0.05);The incidence of adverse reactions was similar between the trial group(7.69%)and the control group(6.06%)(P>0.05);A total of 9530 Qixian Tongluo decoction miRNA sequences were screened,with 150 potentially involved in cross-kingdom gene transfer,including families such as miR-15 and miR-17;According to the target gene prediction of the top 10 miRNAs in cross-kingdom gene transfer of Chinese medicine,345 overlapping target genes were obtained;GO functional enrichment analysis revealed 16 biological processes,7 cellular components,and 2 molecular functions among the top 25 enriched functions,while KEGG pathway analysis mainly focused on the transforming growth factor-βsignaling pathway,neurotrophin signaling pathway,which are closely related to neural repair and functional recovery processes such as glial scar formation and synaptic plasticity after cerebral ischemia.Conclusion Qixian Tongluo Formula can significantly improve the functional independence level of patients with kidney deficiency and blood stasis syndrome in the recovery period of paralysis after cerebral infarction,offering a safe and effective treatment option for these patients;There were a large number of miRNAs in Qixian Tongluo decoction,some of which could cross-kingdom transferred into the human blood circulation,and promote the recovery of motor function in patients with cerebral infarction through multi-target,multi link and multi pathway gene network regulation.This study provides a new idea for subsequent clinical and basic 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.

Objective:To investigate the role of YTHDF2 in cervical lesions and its potential molecular mechanism.Methods:Gene expression data of cervical tissue were obtained from the GEO database to analyze the expression of YTHDF2 mRNA and perform pathway enrichment analysis. Patients with cervical lesions diagnosed by thinprep cytologic test in Gynecological Outpatient Department of Maternal and Child Health Hospital in Jiexiu, Shanxi Province, were selected as the research subjects. Data of cervical lesions and cervical exfoliated cells were collected. HPV infection status was detected by flow-through hybridization, and the expression of YTHDF2 mRNA was detected by reverse transcription real-time polymerase chain reaction. The expression of YTHDF2 in cervical lesions and the mediating role of HPV infection in the relationship between YTHDF2 and squamous intraepithelial lesion (SIL) were evaluated. YTHDF2-related genes were screened from multiple datasets in the GEO and ENCORI databases, and their expression, immune infiltration, and survival analysis were performed to assess the association between YTHDF2 and prognosis. Results:Compared with normal cervical tissue, YTHDF2 was highly expressed in cervical lesion tissue ( P<0.05). A total of 3 672 differentially expressed genes were screened from the dataset GSE49339. Gene Ontology analysis showed that YTHDF2 was mainly involved in transcription regulation. Kyoto Encyclopedia of Genes and Genomes analysis showed that YTHDF2 might be related to HPV infection and other signaling pathways. In the mediation analysis, χ2 test results showed that the expression level of YTHDF2 was significantly different among groups ( χ2=22.47, P<0.001). Trend χ2 test further showed that the expression level of YTHDF2 was upregulated with the degree of cervical precancerous lesions (trend χ2=10.26, P=0.001). Multivariate logistic regression analysis indicated that high YTHDF2 expression increased the risk of low-grade squamous intraepithelial lesions ( OR=3.15, 95% CI: 1.93-5.15) and high-grade squamous intraepithelial lesions ( OR=1.85, 95% CI: 1.01-3.39). Mediation effect analysis revealed a partial mediating effect of HPV infection between YTHDF2 and SIL, accounting for 32.02% of the total effect. Twelve YTHDF2 related genes were screened by the intersection of multiple datasets. The immune infiltration analysis results showed that YTHDF2 and related genes KLF4, E2F3 and HOXC6 were associated with immune infiltration (all P<0.05). Multivariate Cox proportional hazard regression model analysis showed that low expression of KLF4 ( HR=0.53, 95% CI: 0.30-0.94) and high expression of RHOB ( HR=1.80, 95% CI: 1.04-3.13) were risk factors for the prognosis of cervical cancer. Conclusion:YTHDF2 is highly expressed in cervical lesions and may have been involved in the regulation of HPV infection-related pathways and its downstream related genes are related to immune infiltration and prognosis of cervical cancer, providing a theoretical basis for the study of mechanisms related to cervical lesions.

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.