1.Molecular Mechanisms of Salvia Miltiorrhiza and Its Active Ingredients against Colorectal Cancer: A Review
Jianing GUO ; Xiaochen NI ; Kaiyuan ZHANG ; Wei FAN ; Chuhang WANG ; Chao XU ; Jianbo HUANG ; Tao JIANG ; Guangji ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):307-314
Colorectal cancer (CRC) is one of the most common cancers, with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages, CRC lacks specific symptoms, and most patients are diagnosed at advanced stages, making it a major research focus in the field of gastrointestinal tumors. Currently, clinical CRC treatments face several common challenges, including high surgical risks, frequent metastasis and recurrence, drug resistance, and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine (TCM), it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation, invasion, migration, and angiogenesis, and promote apoptosis and autophagy, thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects, including activating blood circulation to dispel blood stasis, unlocking meridians to relieve pain, clearing heat to calm irritability, and cooling blood to reduce abscesses. It contains a variety of chemical components, including diterpenoids, phenolic acids, flavonoids, polysaccharides, nitrogen-containing compounds, steroids, and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms, including cell cycle arrest, promotion of apoptosis, inhibition of cell invasion and migration, induction of autophagy, suppression of tumor angiogenesis, and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.
2.Effect of Ligustilide on Neutrophil Extracellular Traps in Rats with Cerebral Ischemia-reperfusion Injury
Qian WU ; Yang WANG ; Jianing ZHOU ; Zhihan WAN ; Ke HU ; Qi HUANG ; Ning WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):82-88
ObjectiveTo explore the possible mechanisms by which ligustilide (LIG) exerts neuroprotective effects on ischemic stroke (IS) by inhibiting the release of neutrophil extracellular traps (NETs), promoting blood-brain barrier repair, and alleviating post-ischemic neuroinflammation, thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion (MCAO) model was established in rats. The rats were divided into the sham operation (Sham) group, model (Model) group, low- and high-dose LIG groups (20, 40 mg·kg-1), and the NET inhibitor CI-amidine group (CI-amidine, 10 mg·kg-1). Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurological deficit scoring, and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 (H3Cit). Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors, including interleukin-18 (IL-18) and interleukin-1β (IL-1β). ResultsCompared with the Sham group, the Model group exhibited significant brain tissue injury (P<0.05), significantly increased neutrophil numbers and NET expression (P<0.05), significantly impaired blood-brain barrier permeability (P<0.05), and significantly increased expression of inflammatory factors (P<0.05). Compared with the Model group, both low- and high-dose LIG significantly alleviated brain tissue injury in rats (P<0.01), inhibited neutrophil numbers and NET expression (P<0.01), reduced blood-brain barrier damage (P<0.01), and suppressed the expression of inflammatory factors IL-18 and IL-1β (P<0.01), thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.
3.Effect of Ligustilide on Neutrophil Extracellular Traps in Rats with Cerebral Ischemia-reperfusion Injury
Qian WU ; Yang WANG ; Jianing ZHOU ; Zhihan WAN ; Ke HU ; Qi HUANG ; Ning WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):82-88
ObjectiveTo explore the possible mechanisms by which ligustilide (LIG) exerts neuroprotective effects on ischemic stroke (IS) by inhibiting the release of neutrophil extracellular traps (NETs), promoting blood-brain barrier repair, and alleviating post-ischemic neuroinflammation, thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion (MCAO) model was established in rats. The rats were divided into the sham operation (Sham) group, model (Model) group, low- and high-dose LIG groups (20, 40 mg·kg-1), and the NET inhibitor CI-amidine group (CI-amidine, 10 mg·kg-1). Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurological deficit scoring, and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 (H3Cit). Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors, including interleukin-18 (IL-18) and interleukin-1β (IL-1β). ResultsCompared with the Sham group, the Model group exhibited significant brain tissue injury (P<0.05), significantly increased neutrophil numbers and NET expression (P<0.05), significantly impaired blood-brain barrier permeability (P<0.05), and significantly increased expression of inflammatory factors (P<0.05). Compared with the Model group, both low- and high-dose LIG significantly alleviated brain tissue injury in rats (P<0.01), inhibited neutrophil numbers and NET expression (P<0.01), reduced blood-brain barrier damage (P<0.01), and suppressed the expression of inflammatory factors IL-18 and IL-1β (P<0.01), thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.
4.Morphologic and functional effect of core training combined with respiratory training on multifidus and transversus abdominis in patients with lumbar disc herniation
Jianing SONG ; Xiaole LOU ; Huan LIU ; Xue HAN ; Lei XU ; Min WANG
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):107-116
ObjectiveTo explore the effect of respiratory training based on core stabilization training on lumbar disc herniation. MethodsFrom January, 2023 to October, 2024, 96 patients with lumbar disc herniation admitted to the First Affiliated Hospital of Bengbu Medical University were divided into control group (n = 32), core group (n = 32) and respiratory group (n = 32). All the groups underwent conventional rehabilitation therapy, with core stabilization training in the core group and respiratory training combined with core stabilization training in the respiratory group, additionally, for four weeks. Before and after training, the scores of Visual Analogue Scale, Japanese Orthopaedic Association (JOA) and Oswestry Dysfunction Index (ODI) were compared, the average electromyographic value (AEMG) and root mean square (RMS) value of the multifidus and transversus abdominis were detected by surface electromyography (sEMG); and the thickness of the multifidus and transversus abdominis were measured by musculoskeletal ultrasonography bilaterally. ResultsThe intra-group effect (F > 597.796, P < 0.001), inter-group effect (F > 16.535, P < 0.001) and interaction effect (F > 49.622, P < 0.001) were significant in the scores of VAS, JOA and ODI; which were better in the respiratory group than in the control group and the core group (P < 0.05), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 7971.631, P < 0.001), inter-group effect (F > 177.760, P < 0.001) and interaction effect (F > 478.771, P < 0.001) were significant in the thickness of the transversus abdominis and multifidus; which were better in the respiratory group than in the control group and the core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 144303.007, P < 0.001), inter-group effect (F > 1495.458, P < 0.001) and interaction effect (F > 3121.361, P < 0.001) were significant in the RMS of the multifidus and transversus abdominis; which were better in the respiratory group than in the control group and the core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 1890.532, P < 0.001), inter-group effect (F > 607.132, P < 0.001) and interaction effect (F > 824.923, P < 0.001) were significant in the AEMG of the multifidus and transversus abdominis; which were better in the respiratory group than in the control group and core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). ConclusionCore training combined with respiratory training can more effectively reduce pain and improve dysfunction by enhancing the strength and control of the core muscles, thus improving the quality of life of patients with lumbar disc herniation.
5.Molecular classification of head and neck squamous cell carcinoma based on hypoxia-related genes and clinical significance of STC2
ZHU Jianing ; WANG Tiantian ; ZHANG Rui ; SONG Hongquan
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(5):345-358
Objective :
To construct a molecular classification system for head and neck squamous cell carcinoma (HNSCC) utilizing hypoxia-related gene (HAG) expression profiles, and to comprehensively examine the clinicopathological significance and biological functions of the hypoxia gene stanniocalcin 2 (STC2) in HNSCC.
Methods :
Transcriptomic data and clinical information of 546 HNSCC samples were obtained from The Cancer Genome Atlas (TCGA) database, and based on the expression profiles of 200 HRGs, HNSCC was classified subclasses using non-negative matrix factorization (NMF). HNSCC was classified into three subclasses (C1, C2, and C3), and the molecular characteristics and prognostic differences of the subclasses were assessed by comparing the tumor mutation load, functional enrichment analysis, drug sensitivity, and clinical features among the subclasses. LASSO-Cox regression was used to screen prognosis-related genes and construct prognostic models. Using oral squamous cell carcinoma (OSCC)-related data in the TCGA database, we analyzed the expression differences of STC2 in OSCC and control samples, and detected the mRNA and protein expression of STC2 in oral squamous carcinoma samples using qRT-PCR and immunohistochemistry. We knocked down STC2 in CAL-27 cells and verified the knockdown efficiency by qRT-PCR and Western blot. CCK-8 assay and cell scratch assay were used to assess the effect of STC2 on cell proliferation and migration ability.
Results:
Based on HRGs expression profiles, HNSCC was categorized into three subclasses (C1, C2, and C3). Subclass C1 had moderate hypoxic activity and good prognosis; subclass C2 had the highest hypoxic activity, poor prognosis, and poor sensitivity to CTLA-4 inhibitors (P<0.05); subclass C3 had the lowest hypoxic activity and moderate prognosis, and STC2 belonged to subclass C3. The frequency of cyclin-dependent kinase inhibitor 2A (CDKN2A), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and tumor protein p53 (TP 53) mutations was higher in HNSCC. C1 genomic gain and deletion burden were significantly higher than C3 subclass (P<0.05) and C2 genomic gain than C3 subclass (P<0.05). The C2 subclass was significantly enriched in hypoxia-associated pathways, such as glycine metabolism and base excision repair (P<0.05). The C1, C2, and C3 subclasses were significantly positively correlated in terms of sex (male) (Cramer’s V=0.15), radiation exposure (Cramer’s V=0.12), medication (Cramer’s V=0.18), and pathological grading (G1/G2) (Cramer’s V=0.25) (P<0.05). Nine prognosis-related genes were screened by LASSO-Cox regression, among which high expression of STC2 was positively correlated with poorer overall survival (OS) in HNSCC patients (P<0.01). Bioinformatics analysis showed that STC2 mRNA expression was higher in OSCC than in normal controls (P<0.05). qRT-PCR and immunohistochemistry confirmed that both mRNA and protein expression of STC2 were significantly upregulated in OSCC tissues and cells (P<0.01). In vitro experiments showed that STC2 expression was knocked down to approximately 80% in CAL-27 cells (P<0.001), and the STC2 knockdown group had a reduced value-added rate (P<0.001) and a reduced percentage of scratch closure (P<0.05) compared with the control group.
Conclusion
We successfully constructed a molecular typing system for HNSCC based on the expression profiles of HRGs and categorized HNSCC into three subclasses with significant prognostic differences, among which the C2 subclass had the highest hypoxic activity and the poorest prognosis. STC2 was highly expressed in HNSCC and suggested a poor prognosis, demonstrating that it may be a potential target for HNSCC treatment.
6.Analysis of visual field manifestations of non-arteritic anterior ischemic optic neuropathy
Yue LI ; Ying WANG ; Wenxin JIAO ; Jilu LIN ; Jianing WANG
International Eye Science 2025;25(4):671-675
AIM: To observe the manifestations and distribution patterns of visual field in non-arteritic anterior ischemic optic neuropathy(NAION).METHODS: Retrospective observational study. The investigation encompassed 183 patients(246 eyes)diagnosed with NAION who were evaluated at the Neuro-Ophthalmology/Acupuncture Department within the Eye Hospital, China Academy of Chinese Medical Sciences from June 2018 to December 2023. Recorded clinical data covered demographic details, incidence, disease duration, presence of systemic diseases, and histories of tobacco and alcohol use, along with best-corrected visual acuity(BCVA), visual field index(VFI), type of visual field defect, and thickness of the peripapillary retinal nerve fiber layer(pRNFL).RESULTS: A total of 183 patients(246 eyes)were enrolled. The cohort consisted of 101 males and 82 females; 120 exhibited unilateral symptoms, while 63 showed bilateral symptoms, with a mean age of 56.20±9.78 years(range 29-81 years). The types of visual field defects observed were varied: 90 eyes(36.6%)had diffuse loss, 63 eyes(25.6%)experienced inferior hemifield loss, 32 eyes(13.0%)displayed ring scotomas, 22 eyes(8.9%)had arcuate scotomas, 11 eyes(4.5%)presented with quadrant defects, 15 eyes(6.1%)had sectorial or wedge defects, and 13 eyes(5.3%)showed superior hemifield loss. The BCVA(LogMAR)and VFI of patients with diffuse visual field loss were poorer than patients with other types of visual defects(all P<0.05). There were statistically significant differences in visual field defects among patients of different genders and ages(all P<0.05). However, history of hypertension, diabetes, hyperlipidemia, sleep apnea and other systemic diseases, history of smoking and alcohol, and course of disease did not show specificity in the NAION visual field(all P>0.05).CONCLUSION:NAION manifests with a broad spectrum of visual field impairments across different genders, age, and levels of visual functionality. Extensive future research is necessary to identify additional reasons influencing the types of visual field damage in NAION.
7.Rules on acupoint selection and treatment for epigastric pain based on the data mining of ancient acupuncture-moxibustion prescriptions.
Suyun LI ; Jianing WANG ; Zhongnan LI ; Qingyang CHAI ; Xianghong JING
Chinese Acupuncture & Moxibustion 2025;45(2):253-261
The rules of acupoint selection and treatment were identified and discovered from the collected ancient acupuncture-moxibustion prescriptions recorded the earliest for epigastric pain. The database of ancient acupuncture-moxibustion prescriptions for epigastric pain was set up using Excel2016 software. After the disease term, etiology, pathogenesis, symptoms and acupoints were normalized, the underlying multi-dimensional correlation among the elements of acupuncture-moxibustion was explored, using the frequency statistics and the association rule of Apriori algorithm. In the ancient time, in treatment with acupuncture-moxibustion therapy for epigastric pain, the acupoints of the high use frequency were sequenced as Zhongwan (CV12), Shangwan (CV13), Zusanli (ST36), Neiguan (PC6), Gongsun (SP4), Pishu (BL20) and Weishu (BL21). The common combinations of acupoints included the pairs of back-shu points, the combination of back-shu points and front-mu points, the combination of front-mu points and yuan-source points and the combination of back-shu points and the lower he-sea points. The highly involved acupoints were those from the conception vessel, pericardium meridian, spleen meridian, stomach meridian and bladder meridian; and they were commonly distributed on the abdomen, the yin parts of the foot and the arm, the yang part of the leg and on the back. Regarding the etiologies such as parasites, food retention, masses, qi stagnation and stomach cold, Zhongwan (CV12) and Shangwan (CV13) were coordinated; and Sanyinjiao (SP6) and Daling (PC7) were highly associated with masses. Besides cold injury, parasites and masses, for the epigastric pain caused by other factors of etiology (qi stagnation, stomach cold and food retention), moxibustion therapy was greatly applicable. For epigastric pain combined with qi reversion in the lower abdominal region, Qichong (ST30), Sanyinjiao (SP6), Tianshu (ST25) and Zusanli (ST36) must be selected. Dadu (SP2) and Taibai (SP3) must be used if the distention in the chest and abdomen accompanied; and Zhongzhu (TE3) be used if back pain involved. Zusanli (ST36) was commonly selected for hiccups. For the other accompanied symptoms, Zhongwan (CV12) was used, which is consistent with the acupoint selection of main symptoms. On the trunk, moxibustion was generally used at Weishu (BL21), Pishu (BL20), Geshu (BL17), Zhongwan (CV12), Juque (CV14) and Qihai (CV6), except Shangwan (CV13). Among the acupoints below the elbows and knees, moxibustion was commonly applicable at Zusanli (ST36), and acupuncture was often used at Gongsun (SP4) and Daling (PC7).
Acupuncture Points
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Humans
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Moxibustion/history*
;
History, Ancient
;
Acupuncture Therapy/history*
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Data Mining
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Abdominal Pain/history*
8.Composition principles for chest obstruction and heart pain based on data mining of ancient acupuncture-moxibustion prescriptions.
Jianing WANG ; Xianghong JING ; Suyu LI
Chinese Acupuncture & Moxibustion 2025;45(10):1505-1511
OBJECTIVE:
To retrieve and collate the earliest recorded texts in ancient acupuncture-moxibustion prescriptions for chest obstruction and heart pain, and explore the acupoint composition principles.
METHODS:
The Excel 2016 software was used to build a data set of ancient textual records on acupuncture-moxibustion prescriptions for chest obstruction and heart pain. After the terminology related to etiology, pathogenesis, accompanying symptoms, acupoints, and treatment methods unified, the frequency statistical analysis and association rule algorithms were applied to analyze the implicit association patterns among various elements of syndrome differentiation, treatment selection, and acupoint selection in ancient prescriptions from multiple dimensions.
RESULTS:
The basic acupoints of high frequency in ancient acupuncture-moxibustion treatment for chest obstruction and heart pain were Daling (PC7), Neiguan (PC6), Taixi (KI3), Taichong (LR3), Shangwan (CV13), Yongquan (KI1), and Xinshu (BL15). The prescription was mostly composed of yuan-source points. Besides, the combinations of two of five-shu points, five-shu points with luo-connecting points, and yuan-source points with luo-connecting points were common. The high-frequency points were from the pericardium meridian of hand-jueyin, conception vessel, kidney meridian of foot-shaoyin, liver meridian of foot-jueyin, and bladder meridian of foot-taiyang, generally distributed on the yin part of the arm, abdominal region, the yin part of foot, the back, and the yin part of the leg. Zhigou (TE6), Zusanli (ST36), Baihui (GV20), and Jiuwei (CV15), as well as the specific acupoint combinations, were used for chest obstruction and heart pain due to qi stagnation. Moxibustion was more suitable for chest obstruction and heart pain caused by qi reversion, cold and qi stagnation. Shaohai (HT3) was invariably selected when hand tremor was accompanied; Zhongchong (PC9) combined with Daling (PC7) was selected specially for feverish sensation in the palms. Moxibustion was exclusively applied to Shangwan (CV13), and Taixi (KI3) was often stimulated with moxibustion. At Neiguan (PC6) and Daling (PC7), moxibustion was delivered in combination with acupuncture (high confidence was presented in acupuncture).
CONCLUSION
In ancient acupuncture-moxibustion treatment for chest obstruction and heart pain, the points of the pericardium meridian of hand-jueyin are predominant, coordinated with those of the liver meridian of foot-jueyin, kidney meridian of foot-shaoyin, conception vessel, and bladder meridian of foot-taiyang. It follows the principles of acupoint selection, "the pericardium acting on behalf of the heart", "regulating qi as the priority", "combination of yuan-source points with luo-connecting points", and "selecting nearby points along the affected meridians".
Humans
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Moxibustion/history*
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Acupuncture Therapy/history*
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Acupuncture Points
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History, Ancient
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Data Mining
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Chest Pain/history*
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Prescriptions/history*
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Meridians
9.Clinical efficacy of arthroscopic medial patellofemoral complex reconstruction for recurrent patellar dislocation with high-grade trochlear dysplasia.
Fengyi HU ; Qingyang MENG ; Nayun CHEN ; Jianing WANG ; Zhenlong LIU ; Yong MA ; Yuping YANG ; Xi GONG ; Cheng WANG ; Ping LIU ; Weili SHI
Journal of Peking University(Health Sciences) 2025;57(5):947-955
OBJECTIVE:
To investigate the midterm clinical efficacy of medial patellofemoral complex (MPFC) reconstruction for recurrent patellar dislocation with high-grade trochlear dysplasia.
METHODS:
A retrospective analysis was carried out among adult patients who underwent arthroscopically assisted MPFC reconstruction between January 2014 and December 2020. Dejour classification was evaluated to grade trochlear dysplasia; tibial tubercle-trochlear groove (TT-TG) distance and Insall-Salvati index were measured. Preoperative and postoperative patient-reported outcome measures (PROMs) were compared, including International Knee Documentation Committee (IKDC) score, Kujala score, Lysholm score and Tegner score. Information regarding returning-to-sport rate, re-instability events and complications was collected. Patellar tilt (PT), lateral patellar displacement (LPD) and bisect offset (BSO) ratio were measured based on axial computed tomography before and after surgery to assess the patellofemoral congruence.
RESULTS:
A total of 46 MPFC reconstructions in 43 patients were enrolled, including 16 male and 27 female. Mean age at surgery was (22.2±7.6) years (range: 14-44 years). Mean follow-up was (49.9±22.6) months (range: 18-102 months). The percentages of Dejour B, C and D dysplasia were 37.0% (17/46), 43.5% (20/46), and 19.6% (9/46), respectively. Mean Insall-Salvati index was 1.2±0.2 (range: 0.85-1.44), and mean TT-TG distance was (19.6±3.5) mm (range: 10.6-28.7 mm). At latest follow-up, there were significant improvements in all PROMs (P < 0.001): IKDC score, from 56.3±15.1 to 86.2±8.1; Kujala score, from 58.9±15.6 to 92.6±5.4; Lysholm score, from 63.7±15.0 to 94.0±5.7; Tegner score, from 3.1±1.4 to 4.7±1.4, and there were no significant differences in the improvements of the scores between the patients with Dejour B, C and D dysplasia. Overall, ninety percent of the patients returned to their preoperative sports level. One patient reported a postoperative subluxation, while no cases of infection, limited range of motion or patella fracture were observed. PT, LPD and BSO ratio were all significant altered (P < 0.001) after MPFC reconstruction.
CONCLUSION
Arthroscopically assisted MPFC reconstruction yielded satisfactory midterm clinical results for recurrent patellar dislocation with high-grade trochlear dysplasia. No significant differences of improvements in knee function were observed among the three types of high-grade trochlear dysplasia.
Humans
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Patellar Dislocation/surgery*
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Male
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Female
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Adult
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Arthroscopy/methods*
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Retrospective Studies
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Adolescent
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Young Adult
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Patellofemoral Joint/surgery*
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Recurrence
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Plastic Surgery Procedures/methods*
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Patella/surgery*
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Treatment Outcome
10.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.


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