1.Synthesis, preclinical evaluation and pilot clinical study of a P2Y12 receptor targeting radiotracer 18FQTFT for imaging brain disorders by visualizing anti-inflammatory microglia.
Bolin YAO ; Yanyan KONG ; Jianing LI ; Fulin XU ; Yan DENG ; Yuncan CHEN ; Yixiu CHEN ; Jian CHEN ; Minhua XU ; Xiao ZHU ; Liang CHEN ; Fang XIE ; Xin ZHANG ; Cong WANG ; Cong LI
Acta Pharmaceutica Sinica B 2025;15(2):1056-1069
As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an 18F-labeled PET tracer (QTFT) that targets the P2Y12, a receptor highly expressed on anti-inflammatory microglia. [18F]QTFT exhibited high binding affinity to the P2Y12 (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [18F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y12 antagonist. Furthermore, [18F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y12 in anti-inflammatory microglia. In a pilot clinical study, [18F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [18F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y12 overexpressed in anti-inflammatory microglia.
2.A cohort study of lipid levels and recurrence risk of ischemic stroke in a community-based natural population in Songjiang District, Shanghai
Yangbo GENG ; Huayuan FEI ; Yunlong KAN ; Minhua TANG ; Yunhui WANG ; Jianguo YU ; Jiedong XU ; Yiling WU ; Genming ZHAO ; Yonggen JIANG ; Yan JIN
Shanghai Journal of Preventive Medicine 2025;37(7):562-568
ObjectiveTo investigate the recurrence of ischemic stroke (IS) and to analyze the association between four indices of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and the risk of IS recurrence by analyzing the follow-up data related to IS in the community-based natural population of Songjiang District, Shanghai, so as to provide a scientific basis for improving the prognosis of stroke patients in the community and controlling IS recurrence. MethodsA prospective follow-up study was conducted among the IS patients in the community-based cohort population, collecting data about patient’s age, gender, disease history, biochemical indicators, and etc. Cox regression model and restricted cubic spline model were used to analyze the relationship between different levels of plasma lipids and the recurrence of IS in these patients. ResultsA total of 1 368 patients with IS were included. The total follow-up duration was 7 171.46 person-years, with a median follow-up time of 6.24 years. There were 420 cases of IS recurrence, resulting in a cumulative recurrence rate of 30.70%. The results of multivariate Cox regression analysis showed that the recurrence risk of IS was reduced when the baseline TC and LDL-C levels of IS patients were in the ranges of 4.65‒5.67 mmol·L-1 and 2.52‒3.46 mmol·L-1, respectively. The results of restricted cubic spline analysis showed a U-shaped relationship between baseline TC and LDL-C levels and the recurrence risk in IS patients. ConclusionThe cumulative recurrence rate of patients with IS in the community of Songjiang District in Shanghai is high, and the levels of TC and LDL-C at baseline survey are correlated with the recurrence of IS in these patients. It is suggested to pay more attention to the levels of LDL-C and TC in patients with IS, so as to improve the prognosis.
3.Mediating effects of cardiovascular health status in association between educational level and cardiovascular disease
Yanan WU ; Minhua TANG ; Biying WANG ; Yiling WU ; Liping YI ; Hongjie YU ; Yunlong KAN ; Shuai ZHU ; Xiaohua LIU ; Yonggen JIANG ; Genming ZHAO
Chinese Journal of Epidemiology 2025;46(5):840-849
Objective:To analyze the mediating effect of cardiovascular health status (CVH) on the association between educational level and cardiovascular disease (CVD).Methods:The participants were from Shanghai Suburban Adult Cohort and Biobank, and questionnaire survey, physical examination, blood biochemistry were conducted from 2016 to 2020 for baseline information collection, and follow up was conducted until March 31, 2024 based on the medical data, CVD incidence data and death surveillance data at different levels. The associations of educational level, CVH and time to CVD onset of the study population were analyzed using the accelerated failure time model to analyze the mediating effects of CVH, health behaviors, and health factors in the association of educational level and time to CVD onset. The mediating effects of educational level, gender, and age moderated associations were also analyzed.Results:A total of 57 312 participants were included, with 2 780 new cases of CVD during a median follow-up of 6.71 (6.71-6.72) years, and a mean incidence density of 7.77/1 000 person-years (95% CI: 7.48/1 000 person-years -8.06/1 000 person-years). In total, the less educational level and the lower CVH, the higher CVD incidence density ( P<0.05). The results of accelerated failure time models showed that the time ratio for CVD-free survival was 1.15 (95% CI: 1.06-1.24) and 1.33 (95% CI: 1.10-1.60) for moderate and high educational level, respectively. The results of the mediation effect analysis showed that the association between moderate and high educational level and time to CVD onset was 29.60% (20.50%-50.00%) and 36.10% (23.80%-59.00%), 9.97% (5.07%-20.00%) and 13.84% (6.84%-29.00%), 15.24% (9.64%-27.00%) and 17.55% (11.58%-33.00%) of mediators mediated by CVH, health behaviors, health factors, respectively. Among them, there was an exposure-mediated interaction of educational level and a positive moderating effect of age. Conclusion:CVH, health behaviors and health factors had a proportionate mediating effect in the association between educational level and risk of CVD development.
4.Genetic evolution analysis of chicken-origin H3N8 subtype avian influen-za virus and study on its pathogenicity to hamsters
Ting LI ; Mengyao WANG ; Fangfang QIAO ; Liji ZHANG ; Wenjing YANG ; Yuxin ZHANG ; Jiangwu HUANG ; Wanting ZHOU ; Minhua SUN ; Jun HE ; Ming LIAO
Chinese Journal of Pathophysiology 2025;41(9):1862-1872
AIM:A strain was isolated and identified as the H3N8 subtype of the avian influenza virus from a sick chicken at a farm in Yangjiang,Guangdong Province,named A/chicken/Yangjiang/552/2023(abbreviated as YJ/552).The aim of this research is to determine its genetic evolution,biological properties and pathogenicity in hamsters.This study may provide a theoretical strategy for preventing and treating the H3N8 subtype avian influenza virus-induced epidemic.METHODS:A strain of H3N8 avian influenza virus from chickens was characterised by phylogenetic analy-sis,antigenic diversity,receptor-binding specificity,neuraminidase activity,replication,and transmission in hamsters and a systematic pathological analysis was conducted.RESULTS:This novel avian influenza virus was generated through complex recombination of Eurasian avian H3 genes,North American avian N8 genes and six internal genes of H9N2 sub-type AIV.The cleavage site of the outer protein,HA,was PEKQTR↓GLF,which is characteristic of the low pathogenic avian influenza virus.The HA gene of YJ/552 exhibited the highest nucleotide homology with A/China/ZMD-22-2/2022(H3N8)at 99.09%,while the NA gene showed the highest homology with A/chicken/Dongguan/879/2022(H3N8)at 99.01%.This strain preferentially binds to avian-type receptors and could bind to human-type receptors.This virus could effectively replicate in the trachea and lungs of inoculated and contact hamsters.CONCLUSION:YJ/552 is a recombi-nant H3N8 avian influenza virus replicated in the upper respiratory system and transmitted in hamsters.This study pro-vides data support for the early warning and prevention of H3 subtype avian influenza viruses.
5.Effects of quality control circles combined with the strength concept in health education for pediatric leukemia patients
Chun GU ; Minhua WANG ; Jinling MA ; Rongrong LI
Chinese Journal of Modern Nursing 2025;31(2):253-257
Objective:To explore the effects of quality control circles (QCCs) combined with the strength concept in health education for pediatric leukemia patients.Methods:Totally 185 pediatric leukemia patients admitted to the Children's Hospital of Soochow University from January 2021 to August 2023 were selected as participants by convenience sampling. They were randomly divided into a control group ( n=92) and an observation group ( n=93) based on odd and even numbering. Patients in the control group received standard health education, while those in the observation group underwent QCC-based health education activities incorporating the strength concept. Dietary behavior improvement, treatment adherence, quality of life, and patient satisfaction with nursing care were compared between the two groups before and after the intervention. Results:After the intervention, dietary behavior scores in both groups decreased significantly, with the observation group showing significantly lower scores than the control group ( P<0.05). Treatment adherence and quality of life scores improved significantly in both groups, with the observation group scoring higher than the control group across all dimensions ( P<0.05). Moreover, the observation group demonstrated higher patient satisfaction with nursing care compared to the control group ( P<0.05) . Conclusions:The application of QCC activities combined with health education based on the strength concept effectively improves dietary behavior, treatment adherence, quality of life, and satisfaction with nursing care among pediatric leukemia patients, which is worth promoting in clinical practice.
6.Mediating effects of cardiovascular health status in association between educational level and cardiovascular disease
Yanan WU ; Minhua TANG ; Biying WANG ; Yiling WU ; Liping YI ; Hongjie YU ; Yunlong KAN ; Shuai ZHU ; Xiaohua LIU ; Yonggen JIANG ; Genming ZHAO
Chinese Journal of Epidemiology 2025;46(5):840-849
Objective:To analyze the mediating effect of cardiovascular health status (CVH) on the association between educational level and cardiovascular disease (CVD).Methods:The participants were from Shanghai Suburban Adult Cohort and Biobank, and questionnaire survey, physical examination, blood biochemistry were conducted from 2016 to 2020 for baseline information collection, and follow up was conducted until March 31, 2024 based on the medical data, CVD incidence data and death surveillance data at different levels. The associations of educational level, CVH and time to CVD onset of the study population were analyzed using the accelerated failure time model to analyze the mediating effects of CVH, health behaviors, and health factors in the association of educational level and time to CVD onset. The mediating effects of educational level, gender, and age moderated associations were also analyzed.Results:A total of 57 312 participants were included, with 2 780 new cases of CVD during a median follow-up of 6.71 (6.71-6.72) years, and a mean incidence density of 7.77/1 000 person-years (95% CI: 7.48/1 000 person-years -8.06/1 000 person-years). In total, the less educational level and the lower CVH, the higher CVD incidence density ( P<0.05). The results of accelerated failure time models showed that the time ratio for CVD-free survival was 1.15 (95% CI: 1.06-1.24) and 1.33 (95% CI: 1.10-1.60) for moderate and high educational level, respectively. The results of the mediation effect analysis showed that the association between moderate and high educational level and time to CVD onset was 29.60% (20.50%-50.00%) and 36.10% (23.80%-59.00%), 9.97% (5.07%-20.00%) and 13.84% (6.84%-29.00%), 15.24% (9.64%-27.00%) and 17.55% (11.58%-33.00%) of mediators mediated by CVH, health behaviors, health factors, respectively. Among them, there was an exposure-mediated interaction of educational level and a positive moderating effect of age. Conclusion:CVH, health behaviors and health factors had a proportionate mediating effect in the association between educational level and risk of CVD development.
7.Evaluation of short-term outcomes of surgical intervention for severe pulmonary stenosis in infants and young children
Yong ZHANG ; Pengyu WANG ; Liang WANG ; Yiming TAN ; Fangran XIN ; Xu ZHANG ; Chunzhen ZHANG ; Zijun ZHOU ; Lihua LYV ; Minhua FANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(10):584-588
Objective:To evaluate the short-term efficacy of surgical treatment for severe pulmonary stenosis(PS) in infants and young children, and to clarify the impact of different surgical timings on the efficacy of PS treatment.Methods:A retrospective analysis was conducted on 24 infants and young children who underwent surgical treatment for severe PS at the General Hospital of Northern Theater Command, PLA, from January 1, 2020, to October 1, 2024. Among them, 13 were males and 11 were females. The average weight of the patients was(9.2±3.6) kg, the average gestational age was(39.3±1.7) weeks, and the average age was(15.0±13.5) months. Preoperative clinical symptoms and signs(e.g., cyanosis, shortness of breath), transpulmonary valve pressure gradient(TPVPG), right ventricular systolic pressure(RVSP), and Em/Am were recorded. The patients were divided into two groups based on surgical timing: the infant group(under 1 year old, n=12) and the toddler group(1-3 years old, n=12).Results:There were no deaths among all patients. The postoperative ICU stay was significantly longer in the infant group compared to the toddler group( P<0.05). Compared to preoperative values, surgical treatment significantly improved TPVPG, reduced RVSP, and enhanced right ventricular diastolic function, which stabilized by 3 months postoperatively( P<0.05). Intergroup comparisons revealed that the infant group had significantly lower TPVPG at 6 months postoperatively compared to the toddler group. Additionally, right ventricular diastolic function improved significantly in the infant group postoperatively, while no significant improvement was observed in the toddler group. Younger age and reduced right ventricular diastolic function were identified as major risk factors for prolonged mechanical ventilation(>24 hours). Conclusion:Surgical treatment for PS during infancy and early childhood is safe and effective. Comprehensive preoperative evaluation is crucial, and early surgical intervention is recommended for patients with impaired right ventricular function to improve prognosis.
8.Distribution and drug resistance of pathogens from blood culture of children in intensive care unit based on PIC database
Shuanglin XU ; Xiaohui LIN ; Yujia WANG ; Lingling ZHANG ; Minhua LIN
Chinese Journal of Nosocomiology 2025;35(14):2154-2158
OBJECTIVE To investigate the distribution and drug resistance of pathogens isolated from the children with bloodstream infection in pediatric intensive care unit(PICU)so as to provide guidance for empirical clinical treatment of infections.METHODS Based on the Pediatric Intensive Care Database(PIC,http://pic.nbscn.org),the etiological data were collected from the PICU children of Children's Hospital,Zhejiang University School of Medicine by R software in 2010-2019 and were retrospectively analyzed.The species,distribution and drug resist-ance of the pathogens isolated from the children were observed.RESULTS Totally 991 strains of pathogens were isolated,727(73.36%)of which were gram-positive bacteria,213(21.49%)were gram-negative bacteria,and 51(5.15%)were fungi.Staphylococcus epidermidis(320 strains,32.29%)was the predominant species of the gram-positive bacteria,followed by Staphylococcus hominis(118 strains,11.91%),Staphylococcus capitis(55 strains,5.55%)and Enterococcus faecium(Group D,33 strains,3.33%);Klebsiella pneumoniae(59 strains,5.95%),Escherichia coli(58 strains,5.85%),Acinetobacter baumannii(25 strains,2.52%)and Pseudo-monas aeruginosa(18 strains,1.82%)were the major species of gram-negative bacteria.The analysis of drug re-sistance showed that the gram-positive bacteria were generally resistant to β lactams and maintained sensitive to vancomycin and linezolid;the gram-negative bacteria showed high drug resistance rates,especially,A.baumannii and P.aeruginosa,showed multi-drug resistance.CONCLUSIONS The gram-positive bacteria are dominant among the pathogens isolated from the PICU children with bloodstream infections.The empirical treatment should be performed based on the distribution and drug resistance data of the pathogens,and sensitive drugs should be cho-sen for optimization of the treatment regimen.
9.Evaluation of short-term outcomes of surgical intervention for severe pulmonary stenosis in infants and young children
Yong ZHANG ; Pengyu WANG ; Liang WANG ; Yiming TAN ; Fangran XIN ; Xu ZHANG ; Chunzhen ZHANG ; Zijun ZHOU ; Lihua LYV ; Minhua FANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(10):584-588
Objective:To evaluate the short-term efficacy of surgical treatment for severe pulmonary stenosis(PS) in infants and young children, and to clarify the impact of different surgical timings on the efficacy of PS treatment.Methods:A retrospective analysis was conducted on 24 infants and young children who underwent surgical treatment for severe PS at the General Hospital of Northern Theater Command, PLA, from January 1, 2020, to October 1, 2024. Among them, 13 were males and 11 were females. The average weight of the patients was(9.2±3.6) kg, the average gestational age was(39.3±1.7) weeks, and the average age was(15.0±13.5) months. Preoperative clinical symptoms and signs(e.g., cyanosis, shortness of breath), transpulmonary valve pressure gradient(TPVPG), right ventricular systolic pressure(RVSP), and Em/Am were recorded. The patients were divided into two groups based on surgical timing: the infant group(under 1 year old, n=12) and the toddler group(1-3 years old, n=12).Results:There were no deaths among all patients. The postoperative ICU stay was significantly longer in the infant group compared to the toddler group( P<0.05). Compared to preoperative values, surgical treatment significantly improved TPVPG, reduced RVSP, and enhanced right ventricular diastolic function, which stabilized by 3 months postoperatively( P<0.05). Intergroup comparisons revealed that the infant group had significantly lower TPVPG at 6 months postoperatively compared to the toddler group. Additionally, right ventricular diastolic function improved significantly in the infant group postoperatively, while no significant improvement was observed in the toddler group. Younger age and reduced right ventricular diastolic function were identified as major risk factors for prolonged mechanical ventilation(>24 hours). Conclusion:Surgical treatment for PS during infancy and early childhood is safe and effective. Comprehensive preoperative evaluation is crucial, and early surgical intervention is recommended for patients with impaired right ventricular function to improve prognosis.
10.Distribution and drug resistance of pathogens from blood culture of children in intensive care unit based on PIC database
Shuanglin XU ; Xiaohui LIN ; Yujia WANG ; Lingling ZHANG ; Minhua LIN
Chinese Journal of Nosocomiology 2025;35(14):2154-2158
OBJECTIVE To investigate the distribution and drug resistance of pathogens isolated from the children with bloodstream infection in pediatric intensive care unit(PICU)so as to provide guidance for empirical clinical treatment of infections.METHODS Based on the Pediatric Intensive Care Database(PIC,http://pic.nbscn.org),the etiological data were collected from the PICU children of Children's Hospital,Zhejiang University School of Medicine by R software in 2010-2019 and were retrospectively analyzed.The species,distribution and drug resist-ance of the pathogens isolated from the children were observed.RESULTS Totally 991 strains of pathogens were isolated,727(73.36%)of which were gram-positive bacteria,213(21.49%)were gram-negative bacteria,and 51(5.15%)were fungi.Staphylococcus epidermidis(320 strains,32.29%)was the predominant species of the gram-positive bacteria,followed by Staphylococcus hominis(118 strains,11.91%),Staphylococcus capitis(55 strains,5.55%)and Enterococcus faecium(Group D,33 strains,3.33%);Klebsiella pneumoniae(59 strains,5.95%),Escherichia coli(58 strains,5.85%),Acinetobacter baumannii(25 strains,2.52%)and Pseudo-monas aeruginosa(18 strains,1.82%)were the major species of gram-negative bacteria.The analysis of drug re-sistance showed that the gram-positive bacteria were generally resistant to β lactams and maintained sensitive to vancomycin and linezolid;the gram-negative bacteria showed high drug resistance rates,especially,A.baumannii and P.aeruginosa,showed multi-drug resistance.CONCLUSIONS The gram-positive bacteria are dominant among the pathogens isolated from the PICU children with bloodstream infections.The empirical treatment should be performed based on the distribution and drug resistance data of the pathogens,and sensitive drugs should be cho-sen for optimization of the treatment regimen.

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