Objective To explore the policy foundations of early family education and rehabilitation support systems for children with developmental disabilities aged zero to three years,based on the International Classification of Functioning,Disability and Health(ICF),and to construct a comprehensive,whole-person and whole-lifecycle support system integrating early childhood education and rehabilitation services for families;and to propose corresponding sys-tem architecture,construction pathways and governance models.Methods Policy documents were compared,which were related to children's rehabilitation from the World Health Orga-nization,early education guidelines for children with disabilities from the United Nations Educational,Scientific and Cultural Organization,the U.S.Individuals with Disabilities Education Act,European Union children's reha-bilitation policies,and the"14th Five-Year Plan"from China Disabled Persons'Federation.The related policy frameworks and key content of early family education and rehabilitation were reviewed,and the composition,implementation pathways and governance models of the support system were systymatically analyzed.Results The support system consisted of early screening and assessment,family education and parent training,counsel-ing and personalized education and rehabilitation support,community support and resource integration,and re-mote digital support platforms.The study proposed the implementation pathways for five systems,including early screening and assessment,family education and parent training,counseling and personalized rehabilitation support,community support and resource integration,and remote digital support platforms.It emphasized gover-nance mechanisms such as multidisciplinary collaboration,interdepartmental coordination and support from re-mote digital platforms to build a continuous service chain from standardized assessments to interdepartmental collaboration.Conclusion The person-centered approach and whole life span development concept based on the ICF model,as well as the guiding principles of the health services continuum,provide systematic theoretical and policy support for early childhood education and rehabilitation for children with developmental disabilities aged zero to three years.Through multidisciplinary collaboration,interdepartmental coordination and the application of digital platforms,a scientific,continuous and child-centered support system can be built.This not only facilitates early detection and precise intervention but also promotes multi-party collaboration among families,communities and profes-sional institutions.It will further integrate disability prevention,rehabilitation and healthcare services,thereby im-proving children's functional abilities and family quality of life.

Objective To explore the policy foundations of early family education and rehabilitation support systems for children with developmental disabilities aged zero to three years,based on the International Classification of Functioning,Disability and Health(ICF),and to construct a comprehensive,whole-person and whole-lifecycle support system integrating early childhood education and rehabilitation services for families;and to propose corresponding sys-tem architecture,construction pathways and governance models.Methods Policy documents were compared,which were related to children's rehabilitation from the World Health Orga-nization,early education guidelines for children with disabilities from the United Nations Educational,Scientific and Cultural Organization,the U.S.Individuals with Disabilities Education Act,European Union children's reha-bilitation policies,and the"14th Five-Year Plan"from China Disabled Persons'Federation.The related policy frameworks and key content of early family education and rehabilitation were reviewed,and the composition,implementation pathways and governance models of the support system were systymatically analyzed.Results The support system consisted of early screening and assessment,family education and parent training,counsel-ing and personalized education and rehabilitation support,community support and resource integration,and re-mote digital support platforms.The study proposed the implementation pathways for five systems,including early screening and assessment,family education and parent training,counseling and personalized rehabilitation support,community support and resource integration,and remote digital support platforms.It emphasized gover-nance mechanisms such as multidisciplinary collaboration,interdepartmental coordination and support from re-mote digital platforms to build a continuous service chain from standardized assessments to interdepartmental collaboration.Conclusion The person-centered approach and whole life span development concept based on the ICF model,as well as the guiding principles of the health services continuum,provide systematic theoretical and policy support for early childhood education and rehabilitation for children with developmental disabilities aged zero to three years.Through multidisciplinary collaboration,interdepartmental coordination and the application of digital platforms,a scientific,continuous and child-centered support system can be built.This not only facilitates early detection and precise intervention but also promotes multi-party collaboration among families,communities and profes-sional institutions.It will further integrate disability prevention,rehabilitation and healthcare services,thereby im-proving children's functional abilities and family quality of life.

The dried rattan stem of the Fibraurea Recisa Pierre plant contains the active ingredient known as fibrauretine (FN). Although it greatly affects Alzheimer's disease (AD), the mechanism of their effects still remains unclear. Proteomics and transcriptomics analysis methods were used in this study to determine the mechanism of FN in the treatment of AD. AD model is used through bilateral hippocampal injection of Aβ1-40. After successful modeling, FN was given for 30 days. The results showed that FN could improve the cognitive dysfunction of AD model rats, reduce the expression of Aβ and P-Tau, increase the content of acetylcholine and reduce the activity of acetylcholinesterase. The Kyoto Encyclopedia of Genes and Genomes enriched differentially expressed genes and proteins are involved in signaling pathways including metabolic pathway, AD, pathway in cancer, PI3K-AKT signaling pathway, and cAMP signaling pathway. Transcriptomics and proteomics sequencing resulted in 19 differentially expressed genes and proteins. Finally, in contrast to the model group, after FN treatment, the protein expressions and genes associated with the PI3K-AKT pathway were significantly improved in RT-qPCR and Western blot and assays. This is consistent with the findings of transcriptomic and proteomic analyses. Our study found that, FN may improve some symptoms of AD model rats through PI3K-AKT signaling pathway.

Objective To analyze three-dimensional imaging characteristics and advantages for severe portal vein stenosis after liver transplantation, and to evaluate clinical efficacy of portal vein stent implantation. Methods Clinical data of 10 patients who received portal vein stent implantation for severe portal vein stenosis after liver transplantation were retrospectively analyzed. Imaging characteristics of severe portal vein stenosis, and advantages of three-dimensional reconstruction imaging and interventional treatment efficacy for severe portal vein stenosis were analyzed. Results Among 10 patients, 3 cases were diagnosed with centripetal stenosis, tortuosity angulation-induced stenosis in 2 cases, compression-induced stenosis in 2 cases, long-segment stenosis and/or vascular occlusion in 3 cases. Three-dimensional reconstruction images possessed advantages in accurate identification of stenosis, identification of stenosis types and measurement of stenosis length. All patients were successfully implanted with portal vein stents. After stent implantation, the diameter of the minimum diameter of portal vein was increased [(6.2±0.9) mm vs. (2.6±1.7) mm, P<0.05], the flow velocity at anastomotic site was decreased [(57±19) cm/s vs. (128±27) cm/s, P<0.05], and the flow velocity at the portal vein adjacent to the liver was increased [(41±6) cm/s vs. (18±6) cm/s, P<0.05]. One patient suffered from intrahepatic hematoma caused by interventional puncture, which was mitigated after conservative observation and treatment. The remaining patients did not experience relevant complications. Conclusions Three-dimensional visualization technique may visually display the location, characteristics and severity of stenosis, which is beneficial for clinicians to make treatment decisions and assist interventional procedures. Timely implantation of portal vein stent may effectively reverse pathological process and improve portal vein blood flow.

Breast cancer surgery has been changing from radical mastectomy to modified radical mastectomy and breast-conserving surgery with less trauma and fewer complications. Breast conserving surgery has evolved into oncoplastic breast conserving surgery, which combines both breast conserving and plastic surgery. The application of autologous tissue flap is a research hotspot in oncoplastic breast conserving surgery. This article reviews the indications and contraindications of tissue flap technology in breast cancer, surgical methods and categories, application occasions of different types of tissue flaps, early and delayed postoperative complications, and the impact of different postoperative adjuvant treatments on tissue flaps, based on the latest research on oncoplastic breast conserving surgery both domestically and internationally.

Breast cancer surgery has been changing from radical mastectomy to modified radical mastectomy and breast-conserving surgery with less trauma and fewer complications. Breast conserving surgery has evolved into oncoplastic breast conserving surgery, which combines both breast conserving and plastic surgery. The application of autologous tissue flap is a research hotspot in oncoplastic breast conserving surgery. This article reviews the indications and contraindications of tissue flap technology in breast cancer, surgical methods and categories, application occasions of different types of tissue flaps, early and delayed postoperative complications, and the impact of different postoperative adjuvant treatments on tissue flaps, based on the latest research on oncoplastic breast conserving surgery both domestically and internationally.

ObjectiveTo screen the preparation technology of Baoyuan chewable tablets and to preliminarily elucidate its anti-fatigue effect and mechanism. MethodTaking encapsulation rate of volatile oil， extract rate and extraction rate of active ingredients as indexes， single factor test and orthogonal test were used to optimize the volatile oil inclusion， aqueous decoction and formulation molding processes of Baoyuan chewable tablets. ICR rats were randomly divided into the blank group， model group， Gaoshan Hongjingtian oral liquids group（6.01 mL·kg^-1） and and Baoyuan chewable tablets low， medium， and high dose groups（2.1， 4.2， 8.4 g·kg^-1）， 8 mice in each group， and were administered by gastric gavage at the corresponding dose once a day， the blank and model groups were given equal volume of saline for 15 d. After the last administration for 30 min， the mice were loaded with 5% of the body mass of lead at the tail and swam until exhaustion to establish the fatigue model， and the weighted swimming time of the mice in each group was recorded， meanwhile， the muscle tissues of the mice were sliced， stained by hematoxylin-eosin（HE） and subjected to pathological observation， and the levels of blood urea nitrogen（BUN）， lactic acid（LA）， liver glycogen（LG）， activities of lactate dehydrogenase（LDH） and creatine kinase（CK） in the serum were determined. ResultThe optimal inclusion process of cinnamon oil in Baoyuan chewable tablets was 10∶1 for β-cyclodextrin-volatile oil， and inclusion at 50 ℃ for 2 h with saturated aqueous solution method. The optimal water extraction process was to extract twice， adding 10 times of water to extract for 50 min for the first time， and adding 9 times of water to extract for 40 min for the second time. The ratio of the extract of Baoyuan chewable tablets with microcrystalline cellulose， maltodextrin， mannitol， citric acid， magnesium stearate was 63∶13∶8∶17∶17∶1∶1， the tablets were pressed by wet granulation， the each tablet weight was 1.2 g， and the hardness was 60-80 N. Compared with the model group， Baoyuan chewable tablets low， medium， and high dose groups could significantly prolong the exhaustion time of mice in weight bearing swimming（P<0.05， P<0.01）， and improve the exercise endurance of the body， and the results of HE staining showed that all dose groups of Baoyuan chewable tablets could significantly improve the muscle tissue damage caused by exercise， significantly reduce the levels of BUN， LA and the activities of LDH and CK in serum（P<0.01）， and significantly increase the content of LG（P<0.05， P<0.01）. ConclusionThe optimized preparation process of Baoyuan chewable tablets is stable and feasible， and the preparation can improve exercise endurance by increasing the LG level in liver tissue， and relieve muscle soreness by accelerating the removal of LA from the body， and reduce CK and LDH activities to exert anti-fatigue effects.

Purpose: Immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) has become the first-line treatment for advanced renal cell carcinoma, despite the lack of prognostic biomarkers. Cyclin-dependent kinase 5 (CDK5) affects the tumor microenvironment, which may influence the efficacy of TKI+IO. Materials and Methods: Two cohorts from our center (Zhongshan Metastatic Renal Cell Carcinoma [ZS-MRCC] cohort, Zhongshan High-risk Localized Renal Cell Carcinoma [ZS-HRRCC] cohort) and one cohort from a clinical trial (JAVELIN-101) were enrolled. The expression of CDK5 of each sample was determined by RNA sequencing. Immune infiltration and T cell function were evaluated by flow cytometry and immunohistochemistry. Response and progression-free survival (PFS) were set as primary endpoints. Results: Patients of low CDK5 expression showed higher objective response rate (60.0% vs. 23.3%) and longer PFS in both cohorts (ZS-MRCC cohort, p=0.014; JAVELIN-101 cohort, p=0.040). CDK5 expression was enhanced in non-responders (p < 0.05). In the ZS-HRRCC cohort, CDK5 was associated with decreased tumor-infiltrating CD8+ T cells, which was proved by immunohistochemistry (p < 0.05) and flow cytometry (Spearman’s ρ=–0.49, p < 0.001). In the high CDK5 subgroup, CD8+ T cells revealed a dysfunction phenotype with decreased granzyme B, and more regulatory T cells were identified. A predictive score was further constructed by random forest, involving CDK5 and T cell exhaustion features. The RFscore was also validated in both cohorts. By utilizing the model, more patients might be distinguished from the overall cohort. Additionally, only in the low RFscore did TKI+IO outperform TKI monotherapy. Conclusion High-CDK5 expression was associated with immunosuppression and TKI+IO resistance. RFscore based on CDK5 may be utilized as a biomarker to determine the optimal treatment strategy.

Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Anaplastic Lymphoma Kinase/therapeutic use* ; Crizotinib/therapeutic use* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/pharmacology* ; Gene Frequency

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment