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 observe the effect of ropivacaine combined with dexmedetomidine in serratus anterior plane block on postoperative analgesia in patients undergoing breast cancer surgery.Methods Ninety patients scheduled for modified radical mastectomy in this hospital from May to October 2023 were divided in-to three groups by using random number table method:the R0.375 group,the DR0.375 group and the R0.500 group,with 30 cases in each group.All the three groups received serratus anterior plane block before surgery.The R0.375 group was injected with 20 mL of 0.375%ropivacaine,the DR0.375 group with 20 mL of a mix-ture of 0.375%ropivacaine and 1.0 μg/kg dexmedetomidine,and the R0.500 group with 20 mL of 0.500%ropivacaine.All patients received opioid-based patient-controlled intravenous analgesia pump after surgery.The numerical rating scale(NRS)was used to assess resting and movement pain at 1,2,6,12 and 24 hours postoperatively,and the pain-time area under the curve(AUC)was calculated.Postoperative opioid consump-tion,time of first analgesic drugs use were recoreded;sedation status at 1 hour postoperatively was evaluated by the American society of anesthesiologists(ASA)grading,quality of life at 24 hours postoperatively was as-sessed by the 15-item quality of recovery(QoR-15)scale,and postoperative adverse reactions were recorded.Results Compared with the R0.375 group,AUC of the resting pain-time and movement pain-time and the opioid consumption at 12 and 24 hours postoperatively of the DR0.375 group and the R0.500 groups were re-duced(P<0.05),while QoR-15 score after surgery was increased(P<0.05).The time of first analgesic drugs use in the R0.500 group was significantly longer than that in the R0.375 group(P<0.05).At one hour after surgery,all the three groups were evaluated as having mild to moderate sedation,with no statistical-ly significant differences among groups(P>0.05).There were also no statistically significant differences in the incidence of postoperative adverse reactions among the three groups(P>0.05).Conclusion Dexmedeto-midine can significantly improve the analgesic effect of low-concentration ropivacaine in serratus anterior plane block and reduce postoperative opioid consumption.

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.

OBJECTIVE To observe the effect of the Chinese herbal compound Weidiao No.3 Formula(WD-3)combined with immunotherapy and chemotherapy on survival outcomes in patients with advanced non-small cell lung cancer(NSCLC)with lung-spleen qi dificiency type.METHODS A total of 216 patients with stage Ⅲb-Ⅳ NSCLC without driver gene mutations and with lung-spleen qi vacuity pattern and admitted to the oncology departments of Wuxi Hospital of Traditional Chinese Medicine and Jiangnan Uni-versity Affiliated Hospital between January 1,2020,and March 1,2025,were enrolled.Based on whether they received WD-3 oral treatment(≥3 months),they were divided into a Chinese medicine exposure group(n=98;WD-3+immunotherapy combined with chemo-therapy)and a non-exposure group(n=118;immunotherapy combined with chemotherapy alone).Propensity score matching(PSM)was used to balance baseline characteristics.Overall survival(OS),progression-free survival(PFS),and baseline characteristics were com-pared between the two groups.Cox proportional hazards regression model was used to analyze the association between exposure and outcome,and sensitivity analysis was performed.RESULTS After PSM,there were no statistically significant differences in baseline characteristics between the two groups(P>0.05).After matching,the median OS(32.92 months)and median PFS(9.07 months)in the Chinese medicine exposure group were longer than those in the non-exposure group(23.24 months and 7.89 months,respectively),with statistically significant differences(P<0.05).Multivariate analysis was conducted,incorporating age,PD-L1 expression,KPS score,pathological type,and other factors as covariates to assess the independent association between WD3 exposure and OS and PFS outcomes.The results indicated that WD3 exposure was statistically significant in reducing the risk of death(OS outcome)and disease progression(PFS outcome).Specifically,for the OS outcome,the HR was 0.626,with a 95%CI of 0.438 to 0.894,and P=0.01;for the PFS outcome,the HR was 0.721,with a 95%CI of 0.535 to 0.972,and P=0.032.Sensitivity analysis showed robust results(E-value>2.1).CONCLUSION WD-3 combined with immunotherapy and chemotherapy may prolong OS and PFS and reduce mortality risk in patients with advanced NSCLC without driver gene mutations and with lung-spleen qi dificiency type,achieves adequate therapeutic effects.

Objective:To evaluate the impact of oral melatonin on clinical pregnancy outcomes in elderly infer-tile patients with diminished ovarian reserve(DOR)after in vitro fertilization and embryo transfer(IVF-ET).Methods:Sixty-two elderly infertile patients with DOR who underwent IVF at the Reproductive Medicine Center of Qinghai Province People's Hospital from January 1,2022 to June 30,2023 were selected.They were divided into intervention group(24 cases)and control group(38 cases)according to whether they received oral melatonin pretreatment before ovulation induction.Follicular fluid without diluent or blood contamination was collected from the first large follicle on the day of oocyte retrieval,and melatonin levels and 8-hydroxy-2'-deoxyglycoside(8-OHdG)levels in the follicular gluid were measured.Ovulation promotion indicators and pregnancy outcomes were compared and analyzed between the two groups.Results:The concentration of melatonin in follicular fluid in the intervention group was significantly higher than that in the control group(31.75 ng/L vs.10.40 ng/L,P＜0.001),the concentration of 8-OHdG was lower than that of the control group(133.61 ng/L vs.145.30 ng/L,P=0.004);the implantation rate in the intervention group was significantly higher than that in the control group(56.10％vs.26.87％,P=0.002),and the biochemical pregnancy rate in the intervention group was significantly higher than that in the control group(12.50％vs.0,P=0.050).There were no significant differences in normal fertilization rate,high-quality embryo rate,clinical pregnancy rate and cumulative live birth rate between the two groups(P＞0.05).Conclusions:Oral melatonin can increase its level in follicular fluid,which is beneficial in improving endom-etrial receptivity,and has a certain positive effect on improving IVF-ET outcomes.

Objective:To evaluate the impact of oral melatonin on clinical pregnancy outcomes in elderly infer-tile patients with diminished ovarian reserve(DOR)after in vitro fertilization and embryo transfer(IVF-ET).Methods:Sixty-two elderly infertile patients with DOR who underwent IVF at the Reproductive Medicine Center of Qinghai Province People's Hospital from January 1,2022 to June 30,2023 were selected.They were divided into intervention group(24 cases)and control group(38 cases)according to whether they received oral melatonin pretreatment before ovulation induction.Follicular fluid without diluent or blood contamination was collected from the first large follicle on the day of oocyte retrieval,and melatonin levels and 8-hydroxy-2'-deoxyglycoside(8-OHdG)levels in the follicular gluid were measured.Ovulation promotion indicators and pregnancy outcomes were compared and analyzed between the two groups.Results:The concentration of melatonin in follicular fluid in the intervention group was significantly higher than that in the control group(31.75 ng/L vs.10.40 ng/L,P＜0.001),the concentration of 8-OHdG was lower than that of the control group(133.61 ng/L vs.145.30 ng/L,P=0.004);the implantation rate in the intervention group was significantly higher than that in the control group(56.10％vs.26.87％,P=0.002),and the biochemical pregnancy rate in the intervention group was significantly higher than that in the control group(12.50％vs.0,P=0.050).There were no significant differences in normal fertilization rate,high-quality embryo rate,clinical pregnancy rate and cumulative live birth rate between the two groups(P＞0.05).Conclusions:Oral melatonin can increase its level in follicular fluid,which is beneficial in improving endom-etrial receptivity,and has a certain positive effect on improving IVF-ET outcomes.

OBJECTIVE To observe the effect of the Chinese herbal compound Weidiao No.3 Formula(WD-3)combined with immunotherapy and chemotherapy on survival outcomes in patients with advanced non-small cell lung cancer(NSCLC)with lung-spleen qi dificiency type.METHODS A total of 216 patients with stage Ⅲb-Ⅳ NSCLC without driver gene mutations and with lung-spleen qi vacuity pattern and admitted to the oncology departments of Wuxi Hospital of Traditional Chinese Medicine and Jiangnan Uni-versity Affiliated Hospital between January 1,2020,and March 1,2025,were enrolled.Based on whether they received WD-3 oral treatment(≥3 months),they were divided into a Chinese medicine exposure group(n=98;WD-3+immunotherapy combined with chemo-therapy)and a non-exposure group(n=118;immunotherapy combined with chemotherapy alone).Propensity score matching(PSM)was used to balance baseline characteristics.Overall survival(OS),progression-free survival(PFS),and baseline characteristics were com-pared between the two groups.Cox proportional hazards regression model was used to analyze the association between exposure and outcome,and sensitivity analysis was performed.RESULTS After PSM,there were no statistically significant differences in baseline characteristics between the two groups(P>0.05).After matching,the median OS(32.92 months)and median PFS(9.07 months)in the Chinese medicine exposure group were longer than those in the non-exposure group(23.24 months and 7.89 months,respectively),with statistically significant differences(P<0.05).Multivariate analysis was conducted,incorporating age,PD-L1 expression,KPS score,pathological type,and other factors as covariates to assess the independent association between WD3 exposure and OS and PFS outcomes.The results indicated that WD3 exposure was statistically significant in reducing the risk of death(OS outcome)and disease progression(PFS outcome).Specifically,for the OS outcome,the HR was 0.626,with a 95%CI of 0.438 to 0.894,and P=0.01;for the PFS outcome,the HR was 0.721,with a 95%CI of 0.535 to 0.972,and P=0.032.Sensitivity analysis showed robust results(E-value>2.1).CONCLUSION WD-3 combined with immunotherapy and chemotherapy may prolong OS and PFS and reduce mortality risk in patients with advanced NSCLC without driver gene mutations and with lung-spleen qi dificiency type,achieves adequate therapeutic effects.

IKBKG is the essential modulator for nuclear factor-κB(NF-κB) signaling pathway, and mutations within this gene can lead to anhidrotic ectodermal dysplasia and immunodeficiency (EDA-ID). Here we report a male patient, who presented with mild frontal bossing, sparse hair, skin pigmentation, conical teeth, and recurrent infections involving bacteria, fungi, and viruses after one month of age, together with hypogammaglobulinemia. These symptoms were consistent with the phenotype of EDA-ID. Genetic analysis revealed a hemizygous mutation c.1249T > G (p.Cys417Gly) in exon 10 of the IKBKG gene in the patient. The mother of the patient was identified as heterozygous carriers of the same mutation. Immunological assessment revealed a significant reduction in memory B cells. The patient showed no skewed TCR diversity. PHA-induced T-cell proliferation was impaired. IFN-γ secretion by Th cells was significantly reduced after PHA stimulation. IκBα degradation rate retained the same in the patient. We summarized the clinical features of the patient and conducted immunological analysis, in order to increase pediatricians′awareness of this rare disease. For boys with early-onset recurrent infections together with ectodermal dysplasia, IKBKG mutation should be considered. In addition, genetic analysis is needed to exclude pseudogene interference and functional evaluations are required.

Objective: To develop an assessment tool for risky road behavior tendencies among middle school students in western China, as well as to determine the relevant indices and their weights, so as to provide the reference for road safety prevention and control for middle school students in western China. Methods: A Delphi study was employed to construct the assessment tool for risky road behavior tendencies among middle school students in western China. In August 2023, eighteen experts in related fields such as traffic safety, education, and healthcare were invited to achieve Delphi consensus. The final indices were initially selected based on the consulting results,followed by the determination of their individual and combined weights using the analytic hierarchy process. Results: The finalized assessment tool comprised 3 primary indicators, 13 secondary indicators, and 100 tertiary indicators. The positivity coefficient of experts was 100%, accompanied by the authority coefficient 0.90. The mean importance scores for the three primary indicators varied from 4.67 to 4.78, while those for the 13 secondary indicators ranged from 4.22 to 4.89. The Kendall coefficient W was statistically significant at 0.32 ( χ 2=96.83, P <0.05). The weights assigned to the three primary indicators were:ability (0.329 4), opportunity (0.337 3), and motivation (0.333 3). The secondary indicators with the top three highest combined weights were social influence (0.027 4), knowledge (0.027 3), and skills (0.026 7). Conclusions The assessment tool for risky road behavior tendencies among middle school students in western China demonstrates high expert consensus, with balanced weighting of primary and secondary indicators. Expanded use of the assessment tool would provide the data support for intervention work.