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.Anti-ulcerative Colitis Mechanism of Huaihuasan and Active Ingredients of Its Component Drugs: A Review
Xueli XU ; Jiacheng GU ; Zuowu XI ; Yanyan WANG ; Kexin DENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):295-305
Huaihuasan, first recorded in Experiential Prescriptions for Universal Relief (Pu Ji Ben Shi Fang), is a classic prescription for the treatment of ''hematochezia due to intestinal wind''. In 2018, it was included by the National Administration of Traditional Chinese Medicine as one of the first 100 classic prescriptions. This formula consists of four ingredients, i.e., Sophorae Flos, Platycladi Cacumen, Schizonepetae Spica, and Aurantii Fructus. It is known for its ability to clear the intestines, dispel wind, cool the blood, and stop bleeding. In modern clinical practice, Huaihuasan, often with modifications, is widely used to treat various digestive tract diseases, including ulcerative colitis (UC), with significant long-term effects. UC is a chronic, non-specific inflammatory bowel disease. Currently, Western medicine primarily treats UC with glucocorticoids, aminosalicylates, and immunosuppressants, which have good short-term efficacy but numerous adverse reactions, high recurrence rates, and the need for lifelong medication. Modern clinical studies have shown that Huaihuasan can significantly improve symptoms of UC, such as abdominal pain and diarrhea, reduce disease activity scores (Sutherland), promote intestinal mucosal healing, alleviate anxiety and depression, and significantly improve the quality of life of patients. Pharmacological studies have shown that the main active components of Huaihuasan include quercetin, rutin, kaempferol, naringenin, and volatile oils. These compounds exert their effects by inhibiting inflammatory responses and protecting the intestinal mucosal barrier. They also exhibit antioxidant properties and regulate various signaling pathways, including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), nuclear factor-κB (NF-κB), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), and the KRAS-regulated mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway. These multi-target pathways improve UC symptoms, inhibit inflammation-cancer transition, and help maintain intestinal homeostasis. However, the precise mechanism of action has not yet been systematically elucidated. This paper reviews the research progress on Huaihuasan and main ingredients from its component drugs, focusing on their effects against UC. It also discusses current research limitations and suggests strategies for improvement, aiming to provide a reference for further studies on Huaihuasan in the treatment of UC and the development of new drugs.
3.Interpretation of"Standard for infection prevention and control in hemodialysis department(center)"WS/T854-2025
Yanyan WU ; Min DENG ; Huixue JIA ; Anhua WU ; Li ZUO ; Yunxi LIU ; Jiancheng ZHAO ; Jiansheng LIANG ; Yun YANG ; Ling LIN
Chinese Journal of Nosocomiology 2025;35(20):3045-3048
Hemodialysis patients exhibit compromised immune function and require long-term repeated vascular punctures as therapeutic approach,the risk of infection increases.Hospital-associated infection in hemodialysis de-partment(center)happens from time to time,which has already become a concern for the medical community,patients and social media.This paper outlines the task origin of China's"Standard for infection prevention and control in hemodialysis department(center)"(WS/T854-2025),the compilation basis and explanations for its key content,feasibility and implementation recommendations,as well as the clarifications on common issues encoun-tered during its promotion and enforcement.
4.Clinical characteristics and correlation between laboratory indicators and prognosis of children with severe Mycoplasma pneumoniae pneumonia
Yanyan CHAI ; Fang DENG ; Yuanyuan XU ; Yao SHENG ; Yaping LIANG ; Wenjia TONG ; Danqun JIN
Chinese Journal of Nosocomiology 2025;35(20):3124-3127
OBJECTIVE To analyze the clinical characteristics and the correlation between laboratory indicators and prognosis of severe Mycoplasma pneumoniae pneumonia(SMPP)in children.METHODS A total of 85 children with SMPP admitted to Anhui Provincial Children's Hospital from Nov.2021 to May 2024 were selected as the study subjects.Based on clinical typing at admission,they were divided into a high-risk group(n=59)and a low-risk group(n=26).The clinical manifestations,laboratory indicators and outcomes at 28 days of treatment were compared between the two groups.RESULTS The duration of fever and cough before admission in the high-risk group was(7.17±1.09)days and(6.79±1.25)days,respectively,which was longer than that in the low-risk group(P<0.05).There were no statistically significant differences in pulmonary auscultation(wheezing rales,moist rales)and extrapulmonary complications between the two groups.The levels of C-reactive protein(CRP),serum amyloid A(SAA),platelets(PLT),fibrinogen(FIB),D-dimer(DD)and N-terminal pro-brain natriuretic peptide(NT-proBNP)in the high-risk group were(11.62±1.45)mg/L,(226.88±36.83)mg/L,(3 18.57±39.82)×109/L,(4.28±0.74)g/L,(0.81±0.12)μg/ml and(2 295.48±413.75)pg/ml,respectively,all of which were higher than those in the low-risk group(P<0.05).Within 28 days after treatment of children in both groups,one patient in the high-risk group died.CONCLUSIONS Compared with children with SMPP in the low-risk group,those in the high-risk group have a higher risk of prognostic mor-tality,suggesting a correlation between the children's blood CRP,SAA,PLT,FIB,DD and NT-proBNP levels and the prognosis of children with SMPP.
5.Research Progress on the Prevention and Treatment of Ulcerative Colitis by Traditional Chinese Medicine Based on the MAPK Signaling Pathway
Linguo CAO ; Yanyan WANG ; Kexin DENG ; Jiaqing LIU ; Zuowu XI ; Zongyue GAO ; Kai WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(9):2624-2635
Ulcerative colitis(UC)is a common chronic non-specific intestinal inflammatory disease clinically.Its pathogenesis is complex,prolonged the disease course,and it is frequent clinical recurrence.In recent years,the incidence of UC has shown an upward trend and tends to younger onset,which seriously affects the quality of life of patients and increases the social medical burden.Mitogen-activated protein kinase(MAPK)plays an important role in the occurrence and development of UC,participating in inflammatory response,oxidative stress,autophagy,apoptosis,pyroptosis,and intestinal barrier.MAPK may be a new target for the treatment of UC.Traditional Chinese medicine has a long history and remarkable curative effect in treating UC,with the advantages of multiple pathways,multiple targets,and multiple components.In recent years,many studies have shown that single Chinese herbal medicines and compound prescriptions can mediate MAPK signaling pathway to inhibit inflammatory response and oxidative stress,regulate autophagy,inhibit apoptosis and pyroptosis,repair the intestinal barrier,and treat UC in many aspects.This article reviews the MAPK signaling pathway,the mechanism by which the MAPK signaling pathway regulates UC,and the research progress of traditional Chinese medicine in treating UC based on the MAPK signaling pathway,hoping to provide theoretical support for the treatment of UC by traditional Chinese medicine and new ideas and references for the research of related new drugs.
6.Interpretation of"Standard for infection prevention and control in hemodialysis department(center)"WS/T854-2025
Yanyan WU ; Min DENG ; Huixue JIA ; Anhua WU ; Li ZUO ; Yunxi LIU ; Jiancheng ZHAO ; Jiansheng LIANG ; Yun YANG ; Ling LIN
Chinese Journal of Nosocomiology 2025;35(20):3045-3048
Hemodialysis patients exhibit compromised immune function and require long-term repeated vascular punctures as therapeutic approach,the risk of infection increases.Hospital-associated infection in hemodialysis de-partment(center)happens from time to time,which has already become a concern for the medical community,patients and social media.This paper outlines the task origin of China's"Standard for infection prevention and control in hemodialysis department(center)"(WS/T854-2025),the compilation basis and explanations for its key content,feasibility and implementation recommendations,as well as the clarifications on common issues encoun-tered during its promotion and enforcement.
7.Clinical characteristics and correlation between laboratory indicators and prognosis of children with severe Mycoplasma pneumoniae pneumonia
Yanyan CHAI ; Fang DENG ; Yuanyuan XU ; Yao SHENG ; Yaping LIANG ; Wenjia TONG ; Danqun JIN
Chinese Journal of Nosocomiology 2025;35(20):3124-3127
OBJECTIVE To analyze the clinical characteristics and the correlation between laboratory indicators and prognosis of severe Mycoplasma pneumoniae pneumonia(SMPP)in children.METHODS A total of 85 children with SMPP admitted to Anhui Provincial Children's Hospital from Nov.2021 to May 2024 were selected as the study subjects.Based on clinical typing at admission,they were divided into a high-risk group(n=59)and a low-risk group(n=26).The clinical manifestations,laboratory indicators and outcomes at 28 days of treatment were compared between the two groups.RESULTS The duration of fever and cough before admission in the high-risk group was(7.17±1.09)days and(6.79±1.25)days,respectively,which was longer than that in the low-risk group(P<0.05).There were no statistically significant differences in pulmonary auscultation(wheezing rales,moist rales)and extrapulmonary complications between the two groups.The levels of C-reactive protein(CRP),serum amyloid A(SAA),platelets(PLT),fibrinogen(FIB),D-dimer(DD)and N-terminal pro-brain natriuretic peptide(NT-proBNP)in the high-risk group were(11.62±1.45)mg/L,(226.88±36.83)mg/L,(3 18.57±39.82)×109/L,(4.28±0.74)g/L,(0.81±0.12)μg/ml and(2 295.48±413.75)pg/ml,respectively,all of which were higher than those in the low-risk group(P<0.05).Within 28 days after treatment of children in both groups,one patient in the high-risk group died.CONCLUSIONS Compared with children with SMPP in the low-risk group,those in the high-risk group have a higher risk of prognostic mor-tality,suggesting a correlation between the children's blood CRP,SAA,PLT,FIB,DD and NT-proBNP levels and the prognosis of children with SMPP.
8.Research Progress on the Prevention and Treatment of Ulcerative Colitis by Traditional Chinese Medicine Based on the MAPK Signaling Pathway
Linguo CAO ; Yanyan WANG ; Kexin DENG ; Jiaqing LIU ; Zuowu XI ; Zongyue GAO ; Kai WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(9):2624-2635
Ulcerative colitis(UC)is a common chronic non-specific intestinal inflammatory disease clinically.Its pathogenesis is complex,prolonged the disease course,and it is frequent clinical recurrence.In recent years,the incidence of UC has shown an upward trend and tends to younger onset,which seriously affects the quality of life of patients and increases the social medical burden.Mitogen-activated protein kinase(MAPK)plays an important role in the occurrence and development of UC,participating in inflammatory response,oxidative stress,autophagy,apoptosis,pyroptosis,and intestinal barrier.MAPK may be a new target for the treatment of UC.Traditional Chinese medicine has a long history and remarkable curative effect in treating UC,with the advantages of multiple pathways,multiple targets,and multiple components.In recent years,many studies have shown that single Chinese herbal medicines and compound prescriptions can mediate MAPK signaling pathway to inhibit inflammatory response and oxidative stress,regulate autophagy,inhibit apoptosis and pyroptosis,repair the intestinal barrier,and treat UC in many aspects.This article reviews the MAPK signaling pathway,the mechanism by which the MAPK signaling pathway regulates UC,and the research progress of traditional Chinese medicine in treating UC based on the MAPK signaling pathway,hoping to provide theoretical support for the treatment of UC by traditional Chinese medicine and new ideas and references for the research of related new drugs.
9.Improvement of Depression-like Behavior of Depression Model Mice by Sinisan via Regulating GSK-3β/A20/C/EBPβ to Inhibit Activation of Microglia
Hongyun CHEN ; Dongying YANG ; Huiqing LIAO ; Yanyan ZENG ; Linke PAN ; Shasha BAI ; Di DENG ; Yafei SHI ; Rong ZHANG ; Lei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):16-23
ObjectiveTo investigate the antidepressant effect of Sinisan (SNS) by regulating glycogen aynthase kinase-3β (GSK-3β)/tumor necrosis factor alpha-induced protein 3(A20)/CCAAT enhancer binding protein β(C/EBPβ) to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group, model group, fluoxetine group (5.0 mg·kg-1), low-dose Sinisan group (4.9 g·kg-1), medium-dose Sinisan group (9.8 g·kg-1), and high-dose Sinisan group (19.6 g·kg-1), with 12 mice in each group. After one week of adaptive feeding, chronic unpredictable mild stress (CUMS) was performed to establish the depression model. In the fifth week, drug treatment was conducted for four weeks. In the ninth week, behavioral tests were performed, including sucrose preference test (SPT), open field test (OPT), elevated plus maze (EPM) test, and forced swimming test (FST). Western blot was used to detect the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), nitric oxide synthase (iNOS), GSK-3β, A20, and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 (Iba1) and cluster of differentiation 68 (CD68) in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS, compared with the normal group, the mice in the model group had a significantly reduced sucrose preference rate (P<0.01), and the activity in the central area of the OPT was significantly reduced (P<0.01). The activity in the open arm area of the EPM test was significantly reduced (P<0.05), and the immobility time of FST was increased (P<0.01). The expression levels of inflammatory proteins IL-1β, IL-6, and iNOS were increased (P<0.01), and the fluorescence co-localization index of Iba1 and CD68 was increased (P<0.05). The protein expression levels of GSK-3β and C/EBPβ were significantly increased (P<0.05, P<0.01). After four weeks of SNS intervention, compared with the model group, the mice in the SNS group had significantly increased sucrose preference rate (P<0.01), significantly increased activities in the central area and the open arm area in the OPT and the EPM test (P<0.05), and significantly reduced immobility time in the FST (P< 0.01). The protein expression levels of IL-1β, IL-6, and iNOS were significantly decreased (P<0.05), and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group (P<0.05). The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased (P<0.01), and that of A20 was significantly increased (P<0.01). ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.
10.Experimental study to construct the three-dimensional scaffold of rabbit cartilage-shedding cells and evaluate their compatibility with stem cells
Juju XU ; Yanyan XIE ; Zhiyi GUO ; Yukai MA ; Linhong WANG ; Meirong YANG ; Zhaoling DENG ; Baolai HUA ; Zhenyu YAN
Acta Laboratorium Animalis Scientia Sinica 2024;32(8):1012-1022
Objective To prepare decellularized scaffolds from rabbit cartilage at various concentrations and assess their physicochemical properties and compatibility with stem cells to provide an experimental basis for cartilage repair.Methods Bone marrow mesenchymal stem cells(BMSCs)were cultured using the Percoll density gradient separation method,and this was followed by flow cytometric analysis and testing of their osteogenic and chondrogenic differentiation capabilities.Cartilage pieces were excised from rabbit knees and hip joints and subjected to physical crushing,repeated freeze-thaw cycles,and mixed enzymatic digestion for decellularization.To compare and observe the physicochemical properties of the decellularized scaffolds at different concentrations,three groups of scaffolds(labelwd A,B,and C)were designed with concentrations of 100%,50%and 30%,with three replicates each.Third-generation PKH26-labeled BMSCs were seeded onto optimally concentrated scaffolds and cultured for 1 week to observe cell growth.Results Flow cytometry detected BMSC surface antigens with positive expression of CD44 and CD90 and negative expression of CD45.Osteogenic induction stained with alizarin red showed red calcific nodules,and chondrogenic induction stained with alcian blue showed blue cartilaginous nodules.No apparent cell morphology was observed in the three groups of scaffolds stained with hematoxylin-eosin,and toluidine blue.There was a significant difference in DNA concentration between decellularized samples and non-decellularized scaffolds(P<0.05).The content of glycosaminoglycans was slightly lower than the normal values.Significant differences were observed between the three groups of scaffolds in terms of pore size,water absorption,porosity,tensile strength,and Young's modulus(P<0.05).After co-cultivation of stem cells with the scaffolds,cell adhesion was found to be good.Conclusions Percoll density gradient separation can obtain high-purity rabbit BMSCs,and the mixed decellularization method is superior.Group B scaffolds were the most suitable for tissue-engineered cartilage repair.BMSCs cultured in vitro grew well on Group B scaffolds.

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