1.Effects and mechanism of short-acting exenatide on improving diabetic cognitive dysfunction
Xin LING ; Deming WANG ; Qi LU ; Jinyue HUANG ; Xian ZHENG ; Xiaona ZHU
China Pharmacy 2026;37(5):589-594
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.
2.Enhanced radiotheranostic targeting of integrin α5β1 with PEGylation-enabled peptide multidisplay platform (PEGibody): A strategy for prolonged tumor retention with fast blood clearance.
Siqi ZHANG ; Xiaohui MA ; Jiang WU ; Jieting SHEN ; Yuntao SHI ; Xingkai WANG ; Lin XIE ; Xiaona SUN ; Yuxuan WU ; Hao TIAN ; Xin GAO ; Xueyao CHEN ; Hongyi HUANG ; Lu CHEN ; Xuekai SONG ; Qichen HU ; Hailong ZHANG ; Feng WANG ; Zhao-Hui JIN ; Ming-Rong ZHANG ; Rui WANG ; Kuan HU
Acta Pharmaceutica Sinica B 2025;15(2):692-706
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.
3.Fibroblast activation protein targeting radiopharmaceuticals: From drug design to clinical translation.
Yuxuan WU ; Xingkai WANG ; Xiaona SUN ; Xin GAO ; Siqi ZHANG ; Jieting SHEN ; Hao TIAN ; Xueyao CHEN ; Hongyi HUANG ; Shuo JIANG ; Boyang ZHANG ; Yingzi ZHANG ; Minzi LU ; Hailong ZHANG ; Zhicheng SUN ; Ruping LIU ; Hong ZHANG ; Ming-Rong ZHANG ; Kuan HU ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(9):4511-4542
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.
4.Effect of ropivacaine combined with dexmedetomidine in serratus anterior plane block on postoperative analgesia in patients undergoing breast cancer surgery
Lyudan HUANG ; Weijuan ZHU ; Jing HUANG ; Xiaona ZHU
Chongqing Medicine 2025;54(8):1854-1858
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.
5.Effect of Melatonin on IVF-ET Pregnancy Outcome in Elderly Infertile Patients with Diminished Ovarian Reserve
Shengyan JIAN ; Ronghua MA ; Xiaona LI ; Jinchun LV ; Qingli HUANG ; Zhengfang XIONG
Journal of Practical Obstetrics and Gynecology 2025;41(10):847-851
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.
6.The Impact of WeiDiao No.3 Formula on the Survival Outcomes of Patients with Advanced Non-Small Cell Lung Cancer of Lung-Spleen Qi Deficiency Type:A Retrospective Cohort Study
Liming ZHU ; Yuetong XIA ; Xiaona HUANG ; Jiayao XU ; Chunhui JIN
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(12):1647-1656
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.
7.Effect of Melatonin on IVF-ET Pregnancy Outcome in Elderly Infertile Patients with Diminished Ovarian Reserve
Shengyan JIAN ; Ronghua MA ; Xiaona LI ; Jinchun LV ; Qingli HUANG ; Zhengfang XIONG
Journal of Practical Obstetrics and Gynecology 2025;41(10):847-851
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.
8.The Impact of WeiDiao No.3 Formula on the Survival Outcomes of Patients with Advanced Non-Small Cell Lung Cancer of Lung-Spleen Qi Deficiency Type:A Retrospective Cohort Study
Liming ZHU ; Yuetong XIA ; Xiaona HUANG ; Jiayao XU ; Chunhui JIN
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(12):1647-1656
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.
9.Practice of rotation of key position personnels from the perspective of hospital internal control
Haifeng YU ; Xiaona LU ; Ying HOU ; Yan HUANG
Chinese Journal of Hospital Administration 2024;40(5):339-342
Strengthening the management of key positions in medical and health institutions, implementing rotation management of personnels in key positions, is of great significance for regulating the operation of power and preventing corruption risks. A tertiary grade A hospital in Qingdao has implemented a rotation system for personnels in key positions among functional department from an internal control perspective since 2022. On the basis of conducting job risk assessment, the hospital has developed a key position rotation system, determining the scope, rotation cycle, and rotation method for key position personnels, and formulated key position rotation plan. The Party Committee Office and the Human Resources Department were responsible for organizing and implementing it, and evaluating the implementation effect. From 2022 to 2023, 61 key positions were rotated between departments and within departments, accounting for 37.7% of the total number of key positions. Compared with 2021, the number of petitions and reports received by the Discipline Inspection and Supervision Office for key positions in 2022 has decreased by 12.5%, which can provide reference for other medical and health institutions to carry out anti-corruption risk management.
10.The current research status of domestic and international nursing case teaching:a knowledge map analysis based on CiteSpace
Yuenna CHEN ; Lan WU ; Han JIANG ; Xiaona OUYANG ; Xueqin HUANG
Modern Hospital 2024;24(9):1460-1465,1468
Objective To explore the research status and future development trends of nursing case teaching at home and abroad,and to provide reference and guidance for the development of case teaching in nursing profession in China.Methods Data sources include the China National Knowledge Infrastructure(CNKI),Wanfang Data,and Web of Science databases.The CiteSpace software was used to visually analyze the research status and trends of nursing case teaching from January 2013 to Octo-ber 2023,covering nearly 11 years.Results A total of 2 889 valid articles were extracted.The important literature on nursing case teaching in China experienced a period of stable growth followed by rapid growth from 2013 to 2021.However,the number of publications and the number of publications in core journals on nursing case teaching abroad were higher than those in China.After 2021,both domestic and foreign publications on nursing case teaching showed a slow decline.The research on nursing case teaching in both domestic and foreign contexts is mainly conducted by universities,and the collaborative relationships between for-eign institutions and scholars are stronger than those within China.The research topics and hotspots in both domestic and foreign contexts are concentrated on the teaching applications for nursing students.Conclusion Nursing case teaching in China contin-ues to attract attention;however,compared to nursing case teaching abroad,the depth and breadth of research need to be further improved.Additionally,the collaboration between domestic authors and institutions is relatively limited.

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