OBJECTIVE To investigate the ameliorative effect and mechanism of short-acting exenatide on diabetic cognitive dysfunction. METHODS Spontaneously diabetic db / db mice were randomly divided into model group （normal saline） and exenatide group （50 μg/kg）， with db / m mice as the normal control group （normal saline）， with 8 mice in each group. Mice in each group were subcutaneously injected with corresponding drugs or normal saline twice daily for 8 consecutive weeks. Body weight and fasting blood glucose were measured at a fixed time every week. Cognitive function was evaluated by Morris water maze test. The levels of oxidative st ress indicators [malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH） ] ， cyclic adenosine monophosphate （cAMP） and protein kinase A （PKA） were detected in hippocampus tissue of mice. The hippocampal neuronal HT22 cells of mice were divided into control group （25 mmol/L glucose）， high glucose group （125 mmol/L glucose）， high glucose+exenatide group （125 mmol/L glucose+20 nmol/L exenatide）， high glucose+exenatide+H89 （PKA inhibitor） group （125 mmol/L glucose+20 nmol/L exenatide+10 μmol/L H89）， and high glucose+H89 group （125 mmol/L glucose+10 μmol/L H89）. After 48 h of intervention with corresponding solutions/culture medium， the levels of oxidative stress indicators， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and the phosphorylation level of dynamin-related protein 1 （Drp1） were measured. RESULTS Animal experiments showed that compared with the normal control group， the model group exhibited significantly increased body weight， fasting blood glucose and MDA level in the hippocampus （ P ＜0.05）， as well as significantly prolonged escape latency （ P ＜0.05）； swimming speed significantly slowed down， the time spent in the target quadrant， the number of platform crossings， and the levels of SOD， GSH， cAMP and PKA in the hippocampus were significantly decreased （ P ＜0.05）. Compared with model group， all the above indicators （except for swimming speed） in the exenatide group were significantly reversed （ P ＜0.05）. Cell experiments showed that compared with high glucose group， the high glucose+exenatide group had significantly decreased MDA level （ P ＜0.05）， and significantly increased levels of SOD， GSH， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and phosphorylation level of Drp1 （ P ＜0.05）. Compared with high glucose+exenatide group， the above indicators in the high glucose+exenatide+H89 group were significantly reversed （ P ＜0.05）. CONCLUSIONS Short-acting exenatide can activate the cAMP/PKA pathway， promote Drp1 phosphorylation， and increase the activities of mitochondrial respiratory enzymes， thereby maintaining mitochondrial stability， reducing oxidative stress injury， and ultimately improving diabetic cognitive dysfunction.

Objective: To systematically evaluate the association between random urinary electrolyte levels and hypertension among children and adolescents in Guizhou Province, so as to provide evidence for region specific dietary guidance and interventions. Methods: In 2023, a total of 2 480 children and adolescents aged 6 to 17 years were recruited from a nine-year coherent style school in Guizhou Province in a children health cohort, with follow ups conducted in 2024 and 2025. Random urine samples were collected to measure urinary sodium, potassium, calcium, and chloride, and the urinary sodium to potassium ratio (Na/K) was calculated. The diagnosis of hypertension was based on the criteria established by the Chinese Guidelines for Hypertension Prevention and Treatment (2024 revised edition) and relevant research. Linear mixed models and multinomial Logistic regression were used to assess the associations of urinary electrolytes with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and the risk of hypertension. Results: At baseline, SBP, DBP, and MAP were 102.33 (94.33, 110.33), 61.33 (56.33, 67.00) and 75.22 (69.67, 81.33)mmHg among children and adolescents, respectively. After adjusting for potential confounders and two follow-ups, higher urinary Na/K ratio was positively associated with higher of SBP ( β=0.054, 95%CI =0.028- 0.081 ) and MAP ( β=0.038, 95%CI =0.010-0.066), as well as higher risks of hypertension ( OR=1.248, 95%CI =1.006-1.548) (all P <0.05). Higher of urinary chloride levels were positively associated with higher of SBP ( β=0.088, 95%CI = 0.009- 0.167), whereas higher of urinary potassium (SBP: β=-0.062, 95%CI =-0.096 to -0.028; MAP: β=-0.041, 95%CI = -0.078 to -0.005) and calcium levels (SBP: β=-0.036, 95%CI =-0.065 to -0.007) were negatively associated with blood pressure (all P < 0.05 ). Conclusion The urinary Na/K, as a comprehensive electrolyte marker, more stably reflects sodium load and excretory pressure in children and adolescents, and may serve as an early predictor of hypertension risk.

BACKGROUND:The titanium alloy bone trabecular bone socket cup prosthesis printed by 3D technology has superior biological characteristics,which helps to promote osteogenic differentiation of stem cells.The Kidney Tonifying and Blood Activating Decoction has the functions of tonifying the kidneys,strengthening tendons,promoting blood circulation,and relieving pain.However,the application of the combination of the two in elderly hip arthroplasty is rarely reported.OBJECTIVE:To evaluate the application value and safety of 3D printed titanium alloy bone trabecular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction in elderly hip arthroplasty.METHODS:A total of 200 elderly patients who received hip arthroplasty in Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to January 2024 were selected and randomly divided into control group(n=100)and trial group(n=100).The control group underwent Pinnaele cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction,while the trial group underwent 3D printed titanium alloy bone trabecular cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction.The medication was taken continuously for 1 week before hip arthroplasty and for 4 weeks after arthroplasty.The differences in pain,swelling,hemorheology,inflammatory factors,bone metabolism,intra-articular stress,and hip abduction muscle strength were compared between the two groups to evaluate the clinical efficacy and safety of the two treatment options.RESULTS AND CONCLUSION:(1)Four weeks after surgery,the pain visual analog scale score,limb swelling,whole blood viscosity,and plasma viscosity of the trial group were lower than those of the control group(P＜0.05).The interleukin-6 level of the trial group was lower than that of the control group,and the interleukin-10 level was higher than that of the control group(P＜0.05).The levels of type Ⅰ collagen carboxyl terminal peptide β specific sequence and tartrate-resistant acid phosphatase 5b in the trial group were lower than those in the control group,while the levels of osteocalcin,bone-specific phosphatase and typeⅠ procollagen amino-terminal propeptide were higher than those in the control group(P＜0.05).The intra-articular stress and hip abduction muscle strength in the trial group were higher than that of the control group(P＜0.05).(2)Three months after surgery,the excellent and good treatment rate in the trial group was higher than that in the control group,and the incidence of safety evaluation events such as postoperative incision hematoma and infection was lower than that in the control group(P＜0.05).(3)It suggests that 3D printed titanium alloy trabecular acetabular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction can improve the blood rheology of elderly patients with hip arthroplasty,inhibit inflammatory response,reduce postoperative pain and swelling,and enhance bone metabolism,thereby promoting postoperative hip joint function recovery,and reducing the incidence of adverse events,with high safety.

BACKGROUND:The titanium alloy bone trabecular bone socket cup prosthesis printed by 3D technology has superior biological characteristics,which helps to promote osteogenic differentiation of stem cells.The Kidney Tonifying and Blood Activating Decoction has the functions of tonifying the kidneys,strengthening tendons,promoting blood circulation,and relieving pain.However,the application of the combination of the two in elderly hip arthroplasty is rarely reported.OBJECTIVE:To evaluate the application value and safety of 3D printed titanium alloy bone trabecular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction in elderly hip arthroplasty.METHODS:A total of 200 elderly patients who received hip arthroplasty in Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to January 2024 were selected and randomly divided into control group(n=100)and trial group(n=100).The control group underwent Pinnaele cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction,while the trial group underwent 3D printed titanium alloy bone trabecular cup prosthesis hip arthroplasty combined with modified Kidney Tonifying and Blood Activating Decoction.The medication was taken continuously for 1 week before hip arthroplasty and for 4 weeks after arthroplasty.The differences in pain,swelling,hemorheology,inflammatory factors,bone metabolism,intra-articular stress,and hip abduction muscle strength were compared between the two groups to evaluate the clinical efficacy and safety of the two treatment options.RESULTS AND CONCLUSION:(1)Four weeks after surgery,the pain visual analog scale score,limb swelling,whole blood viscosity,and plasma viscosity of the trial group were lower than those of the control group(P＜0.05).The interleukin-6 level of the trial group was lower than that of the control group,and the interleukin-10 level was higher than that of the control group(P＜0.05).The levels of type Ⅰ collagen carboxyl terminal peptide β specific sequence and tartrate-resistant acid phosphatase 5b in the trial group were lower than those in the control group,while the levels of osteocalcin,bone-specific phosphatase and typeⅠ procollagen amino-terminal propeptide were higher than those in the control group(P＜0.05).The intra-articular stress and hip abduction muscle strength in the trial group were higher than that of the control group(P＜0.05).(2)Three months after surgery,the excellent and good treatment rate in the trial group was higher than that in the control group,and the incidence of safety evaluation events such as postoperative incision hematoma and infection was lower than that in the control group(P＜0.05).(3)It suggests that 3D printed titanium alloy trabecular acetabular cup prosthesis combined with modified Kidney Tonifying and Blood Activating Decoction can improve the blood rheology of elderly patients with hip arthroplasty,inhibit inflammatory response,reduce postoperative pain and swelling,and enhance bone metabolism,thereby promoting postoperative hip joint function recovery,and reducing the incidence of adverse events,with high safety.

Objective: To investigate the associations between childhood obesity and performance of six minute walk test (6MWT), providing evidence for exercise tolerance assessment and exercise intervention strategies for children and adolescents. Methods: From March 2021 to December 2023, a cohort study was conducted among students recruited from a primary and secondary school in Chongqing, a total of 709 valid samples were included. The 6MWT was used to assess exercise tolerance, with vital signs measured before and after the test. Anthropometric indicators, including height, weight, and waist circumference, were measured using standardized procedures. Generalized additive models (GAM) and restricted cubic spline (RCS) regression were employed to analyze the nonlinear relationships between obesity related indicators and six minute walk distance (6MWD). Results: The mean 6MWD of participants was (602.59±70.73)m. GAM showed that after adjusting for confounding factors, body mass index (BMI) and weight had non linear relationships with 6MWD [effective degrees of freedom were 1.55 and 7.13 respectively], and overweight/obesity was associated with a decrease in 6MWD ( β =-18.65) (all P <0.01). Further RCS regression analysis showed that both BMI and weight showed an "inverted U shaped" non linear relationship with 6MWD in the overall population and sex stratified subgroups; the 6MWD of females was lower than that of males, and it showed a significant downward trend with the increase of BMI or weight (all P <0.05). Conclusion Body weight and BMI in children and adolescents have an important impact on 6MWD, and obesity in children and adolescents is markedly associated with decline in exercise tolerance.

Objective To explore the efficacy and safety of a zanubrutinib-based combination regimen as first-line treatment for patients with B-cell chronic lymphoproliferative disorder (B-CLPD). Methods A retrospective analysis was performed on 26 patients with B-CLPD, including indolent B-cell non-Hodgkin lymphoma (B-iNHL), mantle cell lymphoma (MCL), and other unclassifiable B-CLPD, who were newly diagnosed and treated at the Department of Hematology, Zhongshan Hospital (Xiamen), Fudan University between January 2021 and January 2025. Patients were divided into two groups according to the treatment regimen: BR (bendamustine plus rituximab) and ZBR (zanubrutinib combined with BR regimen). Baseline characteristics, treatment responses, and the incidence of treatment-related adverse events (TRAE) were compared between the two groups. Results No statistically significant differences in baseline characteristics were observed between the two groups. All patients completed at least four cycles of treatment. There were no significant differences between the BR and ZBR groups in partial response rate (46.2% vs 53.8%), complete response rate (53.8% vs 15.4%), overall response rate (100.0% vs 84.6%), or TRAE incidence. After the first cycle, the lymphocyte count was higher in the ZBR group than in the BR group (P＝0.002); no other statistically significant differences in other hematologic parameters were observed at any treatment cycle. Conclusions In patients with B-iNHL, MCL, and other unclassifiable B-CLPD, the ZBR regimen demonstrates similar safety and response rates to the BR regimen. These findings support further investigation into the clinical value of ZBR as first-line treatment regimen in a limited course for indolent lymphoid malignancies.

ObjectiveTo review the current application status， practical challenges， and ethical issues of artificial intelligence （AI） in the field of hospice care， and to conduct a critical evaluation， with a view to offering a reference for promoting the deep integration of AI into clinical hospice care practice in China. MethodsRelevant domestic and international literature was retrieved to comprehensively analyze the application scenarios of AI in hospice care， the practical barriers encountered， and the ethical controversies， and to explore clinical optimization pathways. ResultsAI is gradually transforming the traditional service model of hospice care， with its applications primarily focusing on patient monitoring， symptom management， predictive analytics， clinical decision support， and other aspects. However， its development faced significant practical constraints and complex ethical challenges. ConclusionWhile AI holds immense potential to enhance the quality of hospice care， its application must be grounded in a core ethical framework centered on dignity， empathy， and patient autonomy. Relevant international explorations have been relatively extensive， whereas domestic studies remain in their infancy. Future research urgently warrants an in-depth exploration of the ethical and practical challenges to find localized integration pathways suited to China’s national context.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

OBJECTIVES: To explore the mechanism by which Pulsatilla saponin D (PSD) inhibits invasion and metastasis of triple-negative breast cancer (TNBC). METHODS: The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC. The "PSD-target-disease" interaction network was constructed and protein-protein interaction (PPI) analysis was performed to obtain the core targets, which were analyzed for KEGG pathway and GO functional enrichment. Molecular docking study of the core targets and PSD was performed, and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells. RESULTS: Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets. GO analysis yielded 175 entries related to the binding of biomolecules (protein, DNA and RNA), enzyme activities, and regulation of gene transcription. KEGG analysis yielded 46 entries involving pathways in cancer, chemical carcinogenesis-receptor activation, microRNAs in cancer, chemical carcinogenesis-reactive oxygen species, PD-L1 expression and PD-1 checkpoint pathway in cancer. Molecular docking showed high binding affinities of PSD to MTOR, HDAC2, ABL1, CDK1, TLR4, TERT, PIK3R1, NFE2L2 and PTPN1. In cultured TNBC cells, treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2, MMP9, N-cadherin and the core proteins p-mTOR, ABL1, TERT, PTPN1, HDAC2, PIK3R1, CDK1, TLR4 as well as NFE2L2 expressionin the cell nuclei. CONCLUSIONS The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.
Humans ; Triple Negative Breast Neoplasms/metabolism* ; Saponins/pharmacology* ; Pulsatilla/chemistry* ; Female ; Molecular Docking Simulation ; Cell Line, Tumor ; Neoplasm Invasiveness ; Protein Interaction Maps ; Neoplasm Metastasis ; Signal Transduction/drug effects* ; Cell Movement/drug effects*