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.Mechanism of mitochondrial DNA-ROS-Drp1 axis in regulating phenotypic transformation of vascular smooth muscle cells
Chenqing LI ; Yanyan HE ; Yingkun HE ; Bing ZHANG ; Jia LIANG ; Yao LIU ; Chenming SI ; Yang LIU ; Yu WANG ; Chi MA ; Tianxiao LI
Chinese Journal of Neuromedicine 2025;24(10):997-1012
Objective:To investigate the mechanism of mitochondrial DNA (mtDNA)-reactive oxygen species (ROS)-dynamin-related protein 1 (Drp1) axis in regulating phenotypic transformation of vascular smooth muscle cells (VSMCs).Methods:(1) VSMCs were divided into a control group, a synthetic VSMCs group, and a Drp1 siRNA+synthetic VSMCs group; cells in the Drp1 siRNA+synthetic VSMCs group were transfected with 50 nmol/L Drp1 siRNA for 48 h; cells in the latter two groups were treated with 20 ng/mL platelet-derived growth factor (PDGF)-BB, while cells in the control group were treated with an equal volume of solvent. After another 24 h of culture, Drp1 expression in VSMCs, and mitochondrial Drp1 and mitofusin 2 (Mfn2) expressions were detected by Western blotting, and changes in mitochondrial morphology were detected by mitochondrial fluorescent staining. (2) VSMCs were divided into a control group, a synthetic VSMCs group, and a mitochondrial fission inhibitor 1 (Mdivi-1)+synthetic VSMCs group; cells in the Mdivi-1+synthetic VSMCs group were pretreated with 50 μmol/L Mdivi-1 for 2 h; and cells in the latter two groups were treated with 20 ng/mL PDGF-BB, while cells in the control group were treated with an equal volume of solvent. After 24 hours of continued culture, expressions of α-smooth muscle actin (α-SMA), smooth muscle protein 22-α (SM22-α), proliferating cell nuclear antigen (PCNA), and Cyclin D1 were detected by Western blotting; invasion and migration abilities of VSMCs were detected by Transwell assay and scratch wound healing assay, respectively. (3) VSMCs were divided into a control group, a synthetic VSMCs group, and a N-acetylcysteine (NAC)+synthetic VSMCs group; cells in the NAC+synthetic VSMCs group were pretreated with 5 mmol/L NAC for 1 h; cells in the latter two groups were treated with 20 ng/mL PDGF-BB, while cells in the control group were treated with an equal volume of solvent. After 24 h of continued culture, expressions of Drp1, phosphorylated (p)-Drp1, α-SMA, SM22-α, PCNA, and Cyclin D1 were detected by Western blotting; changes in mitochondrial morphology were detected by mitochondrial fluorescent staining; intracellular ROS level was detected by 2', 7' -dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe; cell invasion and migration abilities were detected by Transwell assay and scratch wound healing assay, respectively. (4) VSMCs were divided into a control group, a synthetic VSMCs group, and a 5-Aza-2'-deoxycytidine (5-Aza-dC)+synthetic VSMCs group; cells in the 5-Aza-dC+synthetic VSMCs group were pretreated with 2 μmol/L 5-Aza-dC for 1 h; and then, cells in the latter two groups were treated with 20 ng/mL PDGF-BB, while cells in the control group were treated with an equal volume of solvent. After 24 h of continued culture, agarose gel electrophoresis was used to analyze the methylation degree in the mitochondrial D-loop region; intracellular ROS level was detected using DCFH-DA fluorescent probe; expressions of mitochondrial DNMT1, α-SMA, SM22-α, PCNA, and Cyclin D1 were detected by Western blotting; invasion and migration abilities were detected by Transwell assay and scratch wound healing assay, respectively.Results:(1) Compared with the control group and synthetic VSMCs group, the Drp1 siRNA+synthetic VSMCs group had significantly decreased Drp1 protein expression ( P<0.05). Compared with the control group, the synthetic VSMCs group had significantly increased Drp1 protein expression and decreased Mfn2 protein expression in the mitochondria ( P<0.05); compared with the synthetic VSMCs group, the Drp1 siRNA+synthetic VSMCs group had statistically decreased Drp1 protein expression and increased Mfn2 protein expression in the mitochondria ( P<0.05). Results of mitochondrial fluorescent staining showed that mitochondria in the control group were with filamentous structure, while mitochondrial fission in the synthetic VSMCs group was enhanced, and morphology of mitochondria in the Drp1 siRNA+synthetic VSMCs group tended to be continuous and complete. (2) Compared with the control group, the synthetic VSMCs group had statistically decreased α-SMA and SM22-α protein expressions and increased PCNA and Cyclin D1 protein expressions ( P<0.05). Compared with the synthetic VSMCs group, the Mdivi-1+synthetic VSMCs group had significantly increased α-SMA and SM22-α protein expressions and decreased PCNA and Cyclin D1 protein expressions ( P<0.05). Results of Transwell and scratch wound healing assays showed that compared with the control group, the synthetic VSMCs group had larger number of migrating cells and faster cell scratch healing; compared with the synthetic VSMCs group, the Mdivi-1+synthetic VSMCs group had smaller number of migrating cells and slower cell scratch healing. (3) Compared with the control group (1.10±0.02), the synthetic VSMCs group (1.53±0.02) had significantly increased p-Drp1 protein expression ( P<0.05). Compared with the synthetic VSMCs group, the NAC+synthetic VSMCs group (0.90±0.02) had statistically decreased p-Drp1 protein expression ( P<0.05). Results of mitochondrial fluorescent staining showed that mitochondria in cells of the control group were in a filamentous structure, while mitochondrial fission in cells of the synthetic VSMCs group was enhanced, and morphology of mitochondria in the NAC+synthetic VSMCs group tended to be continuous and complete. Results of DCFH-DA fluorescent probe showed that ROS level in the synthetic VSMCs group was higher than that in the control group, and ROS level in the NAC+synthetic VSMCs group was lower than that in the synthetic VSMCs group. Compared with the control group, the synthetic VSMCs group had significantly decreased α-SMA and SM22-α protein expressions and increased PCNA and Cyclin D1 protein expressions ( P<0.05). Compared with the synthetic VSMCs group, the NAC+synthetic VSMCs group had significantly increased α-SMA and SM22-α protein expressions and decreased PCNA and Cyclin D1 protein expressions ( P<0.05). Results of Transwell and scratch wound healing assays showed that compared with the control group, the synthetic VSMCs group had larger number of migrating cells and faster cell scratch healing; compared with the synthetic VSMCs group, the NAC+synthetic VSMCs group had smaller number of migrating cells and slower cell scratch healing. (4) Results of agarose gel electrophoresis showed that compared with the control group, the synthetic VSMCs group had significantly increased methylation rate in the mitochondrial D-loop region ( P<0.05); compared with the synthetic VSMCs group, the 5-Aza-dC+synthetic VSMCs group had statistically decreased methylation rate in the mitochondrial D-loop region ( P<0.05). Compared with the control group, the synthetic VSMCs group had statistically increased mitochondrial DNMT1 protein expression (1.03±0.03 vs. 0.55±0.03, P<0.05); and compared with the synthetic VSMCs group, the the 5-Aza-dC+synthetic VSMCs group (0.62±0.03) had significantly decreased mitochondrial DNMT1 protein expression ( P<0.05). Results of DCFH-DA fluorescent probe showed that ROS level in the synthetic VSMCs group was higher than that in the control group; ROS level in the 5-Aza-dC+synthetic VSMCs group was lower than that in the synthetic VSMCs group. Compared with the control group, the synthetic VSMCs group had significantly decreased α-SMA and SM22-α protein expressions and increased PCNA and Cyclin D1 protein expressions ( P<0.05). Compared with the synthetic VSMCs group, the 5-Aza-dC+synthetic VSMCs group had significantly increased α-SMA and SM22-α protein expressions and decreased PCNA and Cyclin D1 protein expressions ( P<0.05). Results of Transwell and scratch wound healing assays showed that compared with the control group, the synthetic VSMCs group had larger number of migrating cells and faster scratch healing. Compared with the synthetic VSMCs group, the 5-Aza-dC+synthetic VSMCs group had smaller number of migrating cells and slower scratch healing. Conclusion:The mtDNA-ROS-Drp1 axis may regulate the phenotypic transformation of VSMCs by modulating mitochondrial epigenetic modifications.
3.Comparision of aripiprazole and risperidone in improving psychiatric symptoms among chronic schizophrenia patients
Jianfeng WANG ; Bangwen LIU ; Yanyan ZHANG ; Yanping XUE ; Liang GUO ; Yanhai WU
Sichuan Mental Health 2025;38(2):108-114
BackgroundAtypical antipsychotics have been widely used in patients with chronic schizophrenia, and aripiprazole and risperidone are the most commonly used drugs. The mechanism of action of the two is different, while previous studies have provided insufficient credible evidence from multiple perspectives to support the comparative efficacy of the two drugs in improving symptoms in patients with chronic schizophrenia. ObjectiveTo compare the efficacy of aripiprazole and risperidone on the improvement of symptoms, prepulse inhibition (PPI), cognitive functioning and neurotrophic factors in patients with chronic schizophrenia, so as to provide effective treatment regimens for these patients. MethodsA total of 86 patients with chronic schizophrenia attending the psychiatry department of the Third People's Hospital of Fuyang from March 2021 to March 2023 and fulfilling the diagnostic criteria of International Classification of Diseases, tenth edition (ICD-10) were enrolled and grouped using random number table method, each with 43 cases. Aripiprazole group was given oral aripiprazole once daily at an initial dose of 5 mg for one week and then gradually increased to a maximum dose of 25 mg. Risperidone group received oral risperidone twice daily at an initial dose of 0.5 mg for one week and then gradually increased to a maximum dose of 3 mg. Treatment in both groups lasted 3 months. Before treatment and 3 months after treatment, Patients were required to complete Positive and Negative Symptom Scale (PANSS), detection of both strong and weak PPIs in a startle modification passive attention paradigm, Wisconsin Card Sorting Test (WCST) and the measurement of neurotrophic factors at baseline and after treatment. The adverse reactions were recorded. Analysis of covariance was used to test the difference between the PANSS score, PPI, WCST and neurotrophic factor levels of the groups, with the pretest used as the covariate. Results3 months after treatment, no statistical difference was found in the scores of PANSS general psychopathology subscale, positive symptom subscale, negative symptom subscale and total score between two groups after treatment (F=0.621, 0.815, 0.743, 0.752, P>0.05). There were no statistically significant differences between the two groups in PPI inhibition rate, single intense stimulus amplitude, single intense stimulus latency, prepulse inhibition amplitude, or prepulse inhibition latency (F=0.174, 0.001, 0.183, 0.171, 0.001, P>0.05). There was no statistically significant difference in the total number of WCST tests between two groups (F=0.512, P>0.05), whereas aripiprazole group reported significantly larger total numbers of categories completed and correct responses as well as smaller total numbers of random errors and perseverative errors compared to risperidone group (F=3.737, 4.621, 4.892, 5.130, P<0.05). A significant increase in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) along with a reduction in glial fibrillary acidic protein (GFAP) were documented in risperidone group when compared to risperidone group (F=4.414, 3.781, 6.319, P<0.05). No significant difference was demonstrated in the incidence of adverse reactions between the two groups (χ2=0.261, P>0.05). ConclusionAripiprazole may be more beneficial than risperidone in improving cognitive functioning and neurotrophic factor levels in patients with chronic schizophrenia. [Funded by Scientific Research Project of Fuyang Municipal Health Commission in 2021 (number, FY2021-147)]
4.Construction of an Active Monitoring Model for Adverse Events of Pediatric Antimicrobial Drugs Based on the China Hospital Pharmacovigilance System
Xiu JIN ; Rui WU ; Yongmei LIANG ; Yanyan ZHOU ; Mandi XU ; Yanping LI
Journal of Kunming Medical University 2025;46(9):98-106
Objective To develop an active monitoring model for adverse drug events(ADEs)related to antimicrobial use in children based on the China hospital pharmacovigilance system(CHPS).Methods Trigger items for the active monitoring model were initially drafted through a review of relevant literature,adverse reaction databases,and drug label warnings,and subsequently refined using the Delphi method.A retrospective analysis was performed on pediatric inpatients who received antibiotics at Anning First People's Hospital between January 1 and December 31,2024.The detection rate and positive predictive value(PPV)of the active monitoring model were calculated and compared with spontaneous ADE reports from the same period.Risk factors for ADEs were further analyzed using logistic regression.Results 25 trigger items were established for the active monitoring model.Among 1,784 cases,233 ADEs were identified,yielding a detection rate of 13.06%(233/1,784).The spontaneous reporting rate of adverse events during the same period was 1.85%(33/1,784).The difference between the two was statistically significant(P<0.001).There were 727 positive trigger events,with 299 cases of ADE detected,resulting in an overall PPV of 41.13%(299/727).Logistic regression revealed that antibiotic use exceeding 3 days(OR=1.454,95%CI:1.012-2.088)was significantly associated with ADE occurrence.Conclusion Compared with conventional spontaneous reporting,the active monitoring model can significantly improve the detection rate of ADEs of pediatric antimicrobial drugs and achieve active and real-time monitoring of drug adverse events.
5.Advance in correlation between ITGA2 gene and disease
Yuan HOU ; Yanyan LIANG ; Wanyu FENG ; Ruhan YI ; Hua ZHU
International Journal of Pediatrics 2025;52(5):334-337
The integrin alpha 2(ITGA2)gene locates on chromosome 5q11.2,encodes the α 2 subunit of the integrin family.The α 2 subunit is found on many cell surfaces.The α 2 subunit plays an important role in the regulation of platelet aggregation,cell migration,cell proliferation and angiogenesis.Through a wide range of studies conducted in recent years,researchers have discovered that this gene is linked to some diseases,such as rheumatoid arthritis,pediatric sickle cell disease,Kawasaki disease,malignant tumor and biliary atresia.These studies have contributed to the early identification of diseases associated with this gene and the exploration of diagnostic and therapeutic solutions for them.This article reviews the advancements in research concerning the association of ITGA2 gene with various diseases.
6.Advances in IP-10 and its genetic polymorphisms in relation to Kawasaki disease
Meng WANG ; Yanyan LIANG ; Wanyu FENG ; Xuewen SU ; Hua ZHU
International Journal of Pediatrics 2025;52(6):405-409
Kawasaki disease(KD)is an acute systemic vasculitis primarily affecting small- and medium-sized arteries in children,with widespread inflammation as the major pathological hallmark. A subset of patients with KD exhibit resistance to high-dose intravenous immunoglobulin(IVIG)therapy,which significantly increases the risk of developing severe cardiovascular complications,particularly coronary artery lesions(CAL). Interferon gamma-inducible protein 10(IP-10),a chemokine,exerts its biological functions by binding to its specific receptor,chemokine receptor 3(CXCR3). In the relevant research on KD,the association between IP-10 and IP-10 gene polymorphism with KD has garnered significant attention from both domestic and international researchers. This article reviews the recent research progress on the relationship between IP-10,its gene polymorphism and KD,with the aim of providing references for the pathogenesis,prevention,treatment and prognosis of KD.
7.Role of G protein-coupled receptor 120 in respiratory diseases
Yanyan ZHAO ; Lijun ZHANG ; Xiaochun ZHANG ; Xiangyan LIANG ; Yufeng ZHAO
Basic & Clinical Medicine 2025;45(2):244-248
G protein-coupled receptor 120(GPR120)is one of the membrane receptors for long chain free fatty acids and is distributed in alveolus macrophages and airway epithelial Club cells.GPR120 activation alleviates the inflammation of respiratory tract,improves airway hyper-responsiveness,stimulates proliferation of Club cells and promotes the repair of respiratory epithelium,which may attenuate asthma and acute lung injury.
8.Analyzing the characteristics of newly diagnosed occupational disease in Guangdong Province, 2019-2023
Hankun YANG ; Shunhua LIANG ; Yuli ZENG ; Yanyan WANG ; Yiyu YU ; Ming HUA ; Yongshun HUANG
China Occupational Medicine 2025;52(4):416-420
Objective To analyze the epidemiological characteristics of newly diagnosed occupational diseases in Guangdong Province from 2019 to 2023. Methods Data on newly diagnosed occupational diseases reported in Guangdong Province from 2019 to 2023 were collected from the national occupational disease network reporting system. The spectrum of occupational diseases and their distribution by region, industry, and population were analyzed. Results A total of 4 136 newly diagnosed occupational disease cases were reported in Guangdong Province from 2019 to 2023, showing an overall downward trend. Newly diagnosed cases were classified into eight categories and 53 types of occupational diseases. In terms of the number of cases, the top five categories were occupational diseases of the ear, nose, throat and oral cavity;occupational pneumoconiosis and other respiratory diseases; occupational diseases caused by physical factors; occupational chemical poisoning; and occupational tumors, accounting for 98.62% of all cases. The top ten specific disease types were occupational noise-induced deafness, occupational silicosis, occupational other pneumoconiosis, occupational chronic benzene poisoning, occupational heatstroke, occupational hand-arm vibration disease, occupational coal workers′ pneumoconiosis, occupational welders′ pneumoconiosis, occupational tumor (leukemia caused by benzene exposure), and occupational chronic n-hexane poisoning, accounting for 94.85% of all cases. Most of the cases were distributed in the Pearl River Delta region, accounting for 89.19%; as well as manufacturing industry, accounting for 84.89%. Male cases accounted for 87.02%. Most diagnoses occurred in individuals aged >40-60 years, accounting for 74.73%. Conclusion Newly diagnosed occupational diseases in Guangdong Province from 2019 to 2023 showed the following characteristics: concentration of categories and disease types, polarization of regional distribution, industry clustering, and population difference. The disease spectrum is evolving from a dual-disease predominance toward a multi-disease predominance.
9.Clinical features of heat illness and related factors for progression to heatstroke:an analysis of 164 cases
Yanyan WANG ; Qin WANG ; Wei XU ; Jingbing LIANG ; Caiping SONG
Journal of Army Medical University 2025;47(10):1043-1048
Objective To explore the clinical characteristics of patients with heat illness and the related factors for progression to heatstroke so as to provide a basis for early clinical intervention.Methods A case-control study design was adopted.A total of 164 patients with heat illness admitted to a hospital in Hainan Province from January 2018 to December 2023 were included,and divided into a heatstroke group(21 cases)and a non-heatstroke group(143 cases).Univariate and multivariate logistic regression analyses were used to evaluate the associations of body temperature,heart rate and mean arterial pressure at admission with the progression to heatstroke.Results The incidence of organ dysfunction in the patients with heat illness was 45.12%(74/164),and 12.80%(21/164)progressed to heatstroke.Multivariate logistic regression analysis showed that at admission,body temperature>40 ℃(OR=10.11,95%CI:2.86~35.78),heart rate>100 beats/min(OR=9.07,95%CI:2.75~29.94),and mean arterial pressure<70 mmHg(OR=9.05,95%CI:2.75~29.75)were the related factors affecting the progression of heat illness patients to heatstroke.Conclusion The incidence of organ dysfunction in heat illness patients is relatively high.Body temperature,heart rate and mean arterial pressure at admission may be the related factors for predicting the progression of heat illness to heatstroke.
10.Construction and operation of the operation system for clinical research achievements transformation in a public hospital
Bingwei WANG ; Wenping ZHOU ; Ruoyan HAN ; Liang MA ; Changpeng LIU ; Ying ZHAO ; Yan ZHENG ; Wengang YI ; Yanyan LIU
Chinese Journal of Hospital Administration 2025;41(5):372-377
A scientific and efficient comprehensive operation system for the transformation of clinical research achievements is an important guarantee to fully release the capability of public hospitals of the achievement transformation. A public hospital, focusing on the bottleneck problems faced in the process of transforming scientific and technological achievements, began to explore the construction of a comprehensive operation system for the transformation of clinical research achievements and implemented it throughout the hospital from October 2023. By improving the organizational structure and setting up full-time management positions; formulating supporting policies and perfecting the incentive mechanism; drawing a systematic portrait and creating a standard pathway; expanding the transformation platform and promoting coordinated development; innovating management services and strengthening digital empowerment; and highlighting publicity and education to enhance the capability of transformation, the hospital has effectively promoted the transformation of clinical research achievements. This practice can provide a reference for other hospitals to improve the management of clinical research achievements transformation and promote high-quality hospital development.

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