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.Non-alcoholic fatty liver disease related health outcomes and influencing factors among community inhabitants
Yunlong KAN ; Yongmei LI ; Minhua TANG ; Yangbo GENG ; Genming ZHAO ; Yonggen JIANG
Shanghai Journal of Preventive Medicine 2024;36(6):596-601
ObjectiveTo describe different non-alcoholic fatty liver disease (NAFLD) outcomes among community inhabitants, and further to explore the correlation between bio-indicator level variance and the outcomes. MethodsPhysical indicators (height, weight, waist circumstances, hip circumstances, blood pressure, etc), biochemical indicators [fasting plasma glucose, HbA1c, serum triglycerides(TG), serum total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), liver related transaminase, etc] and clinical imaging (B-scan ultrasonography) were collected during the follow-up from the Songjiang Natural Population Sub-cohort. The identification of NAFLD was supported by the definition criteria from Guidelines for the diagnosis and treatment of non⁃alcoholic fatty liver disease. Paired t-test and multifactorial logistic regression model were used to compare the difference between the indicator level of the subjects from different outcome subgroups and to further analyze the correlation between these indicator variance and different NAFLD outcomes. ResultsDuring a median follow-up time of 2.94 years, 12 076 subjects were involved. The cumulative NAFLD incidence and remission rate were 21.57% and 31.15%, respectively. The proportion of subjects who still had NAFLD was 27.96%. Among subjects with newly-developed NAFLD, indicators including blood pressure, BMI, fasting plasma glucose, and plasma lipid level increased, while in the remission subgroup, blood pressure, BMI(WHR), waist-hip ratio(WHR), and TG level were significantly decreased. Increased level of systolic pressure, WHR, BMI, HbA1c, and LDL-C might be the risk factors to the occurrence of NAFLD. While decreased level of WHR, BMI, TC and LDL-C level and elevated HDL-C level were likely to be the influencing factors of NAFLD remission process. ConclusionThe NAFLD morbidity in the community inhabitants is relatively high. BMI, WHR, fasting plasma sugar and plama lipid level variance may act as the influencing factors towards different NAFLD outcomes.
3.Regularity and mechanism of traditional Chinese medicine compound prescriptions in the treatment of primary osteoporosis
Jingtao ZHANG ; Minhua HU ; Shitao LIU ; Shuyuan LI ; Zexin JIANG ; Wenxing ZENG ; Luyao MA ; Qishi ZHOU
Chinese Journal of Tissue Engineering Research 2024;28(16):2555-2560
BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.
4.Research progress on community health management models for elderly hypertensive patients
Xiaopeng LI ; Xiuqi ZHANG ; Minhua ZHANG ; Weiwen ZHOU
Modern Hospital 2024;24(3):452-456
Objective Summarize domestic and international community health management models and characteristics for elderly hypertensive patients,providing references for the development of community health management in China.Methods Employ literature research to retrieve relevant documents on community health management models for elderly hypertensive pa-tients,and analyze the characteristics and applicability of different models through summarization and comparative analysis.Results In China,community health management models for elderly hypertensive patients include family doctor contracting serv-ices,Hospital-Community-Home health management model,traditional Chinese medicine health management model,"Internet+"health management model,PDCA cycle model,PRECEDE-PROCEED model,and comprehensive community management model.Foreign studies can be categorized into self-management model,Health Rise model,Community Health2(CH2)model,and community pharmacy management model.Conclusion Conducting hypertension health management for elderly patients at the community level is effective,serving as a widely applicable strategy for chronic disease prevention and control.Continued ex-ploration of the scientific and effective aspects of different management models,improving the efficiency and effectiveness of com-munity health management,can contribute more evidence for the formulation of scientific and effective strategies for chronic dis-ease prevention and control.
5.Thirty years' evolution and prospects of minimally invasive gastrointestinal surgery in China
Minhua ZHENG ; Shuchun LI ; Junjun MA ; Zhanwei FU
Chinese Journal of General Surgery 2024;39(1):1-5
After more than thirty years of development, laparoscopic surgery technology has become the main platform for surgery and has been widely applied in various fields of surgery. The safety, feasibility and efficacy of laparoscopic technique have already been confirmed in colorectal surgery. In recent years, with a deeper understanding of concepts such as laparoscopic fascial anatomy, laparoscopic colorectal surgery has made new explorations and advances in surgical approach selection, NOSES, lymph node dissection range, preservation of Denonvillier's fascia, functional protection, lateral lymph node dissection, selection of anal preservation techniques for ultra-low rectal cancer, and totally laparoscopic digestive tract reconstruction. In the field of laparoscopic gastric surgery, evidence-based medical evidence in China has entered a harvest period, moreover, functional preservation surgery, esophageal gastric junction adenocarcinoma, and total laparoscopic anastomosis have also become hot topics in this field with new progress. The medical equipment related to minimally invasive surgery has also been developping in recent years and has played an important role in improving minimally invasive surgery.
6.Clinical study about ictal facial dystonia of medial temporal lobe epilepsy
Sixian LI ; Yuanqing WANG ; Chen YAO ; Minhua ZHANG ; Man ZHANG ; Xiaodong CAI
Chinese Journal of Nervous and Mental Diseases 2024;50(10):580-585
Objective To study the clinical and electrophysiological characteristics about ictal facial dystonia of medial temporal lobe epilepsy.Method Data was collected from patients with mesial temporal lobe epilepsy originating from unilateral temporal lobe structures through preoperative evaluation at the Functional Neurology Department of the Second People's Hospital of Shenzhen between July 1,2019 and September 1,2023.All patients did not have seizures for at least 1 year after operation.The ictal symptoms of each patient were analyzed and the patients with ictal facial dystonia were selected and the clinical and electrophysiological characteristics of ictal facial dystonia were summarized.Results Nineteen of 47 patients diagnosed as mesial temporal lobe epilepsy had ictal facial dystonia,of which the electroencephalogram starting at the right side in 11 cases and at the left side in 8 cases.Fifteen patients had the symptom in the first 1/3 period of seizure.Fifteen patients had bilateral symmetrical muscle contraction.Thirteen patients showed with negative expression,5 with neutral expression,and 1 with negative or positive expression in different seizures.None of the patient had the drop of the corners of the mouth.Five patients underwent stereotactic-electroencephalogram(SEEG),including 3 patients with bilateral implantation and 2 patients with unilateral implantation.SEEG showed that the medial temporal structure,insula and orbital lobes were all involved in the onset of ictal facial dystonia.Conclusion The medial temporal lobe epilepsy often present ictal facial dystonia in the first 1/3 period of seizure,with bilaterally symmetrically facial contraction,often accompanied by negative expression,but without drop of the corners of the mouth.The lateralization value of ictal facial dystonia is limited and this symptom involves a wide brain network structure.
7.Advancements and prospects of minimally invasive surgery in the era of intelligent medicine
Minhua ZHENG ; Junjun MA ; Kefan DAI ; Shuchun LI
Chinese Journal of Digestive Surgery 2024;23(4):543-547
After nearly 40 years of development, minimally invasive techniques have been widely applied in curative surgeries for various types of tumors. The safety and efficacy of minimally invasive surgery has being fully validated. With the continuous iteration and updating of medical equipments, the convenience and precision of surgeries have been significantly enhanced, marking the advancement of minimally invasive surgery into a phase of high-level platform. With the rapid development of information technology, we have gradually entered the era of intelligent medicine, where the integration of technologies such as artificial intelligence will inject new vitality into the development of minimally invasive surgery. Combined with the latest research trends, the authors provide an in-depth analysis of how artificial intelligence plays a unique role in key aspects of minimally invasive surgery, including preoperative assessment and planning, intraoperative moni-toring and alerting, and comprehensive postoperative management. Additionally, the authors discuss how to utilize these innovative technologies to further promote reforms in medical education and prospects for the development of telemedicine service. In the era of intelligent medicine, the develop-ment of minimally invasive surgery should adhere to the principle of "bold innovation, cautious practice", guided by the concept of "patient-centeredness". By promoting interdisciplinary collabora-tion between medicine and engineering, accelerating the translation of scientific and technological achievements into clinical practice, we can ensure that minimally invasive surgical techniques better serve the health and well-being of the people.
8.Epidemiological status and clinical characteristics of 225 cases of non-tuberculous mycobacterial pulmonary disease in Hainan Province
WU Haifeng ; WENG Minhua ; LIU Rui ; ZHOU Guizhong ; LI Wenting
China Tropical Medicine 2024;24(4):463-
Abstract: Objective To explore the epidemiological and clinical characteristics of non-tuberculous mycobacterial(NTM) pulmonary disease in Hainan in recent years, and to provide data support for the prevention and treatment of NTM pulmonary disease. Methods Medical records of patients diagnosed with NTM pulmonary disease who treated at the Second Affiliated Hospital of Hainan Medical University (Hainan Provincial Tuberculosis Hospital) from January 2018 to December 2022 were collected. The demographics, regional distribution, temporal distribution, distribution of mycobacterial species, clinical symptoms, and radiological imaging changes of these patients were analyzed. Results A total of 225 confirmed cases of NMT pulmonary disease were collected in this study, with 133(59.1%) female patients outnumbering 92(40.9%) male patients. The disease predominantly affected people over 50 years old, with 192 cases (85.3%), and the major onset age range was 61-<81 years old, with a median age of 63 and an average age of 62. Farmers comprised the majority of the patients, with 112 cases (49.8%). More patients were from the western region (90 cases, 40.0%) than from the central region (76 cases, 33.8%), followed by the eastern region (59 cases, 26.2%). A total of 10 strains were detected from 225 samples, with the most common strains being Mycobacterium intracellulare (92 cases, 40.9%), Mycobacterium chelonae/abscessus(80 cases, 35.6%), and Mycobacterium avium (15 cases, 6.7%), followed by Mycobacterium kansasii (5 cases, 2.2%), Mycobacterium fortuitum (4 cases, 1.8%), and Mycobacterium parascrofulaceum (3 cases, 1.3%). There were 10 cases (4.5%) of mixed infections, including Mycobacterium avium and Mycobacterium intracellulare (8 cases, 3.6%), Mycobacterium intracellulare and Mycobacterium chelonae/abscessus (1 case, 0.4%), and Mycobacterium fortuitum and Mycobacterium chelonae/abscessus (1 case, 0.4%). The primary clinical manifestations of NTM pulmonary disease included cough and sputum (219 cases, 97.3%), hemoptysis (92 cases, 40.9%), fever (61 cases, 27.1%), dyspnea (57 cases, 25.3%), night sweats (52 cases, 23.1%), weight loss (50 cases, 22.2%), and thoracodynia (35 cases, 15.6%). There was no significant difference in symptoms between male and female patients. Pleural thickening (188 cases, 83.6%) and bronchiectasis (151 cases, 67.1%) were the most common imaging changes in NTM pulmonary disease, followed by cavities (93 cases, 41.3%), emphysema (41 cases, 18.2%), and lung damage (28 cases, 12.4%). Male patients were more likely to have lung damage and emphysema, while female patients were more likely to have bronchiectasis. Conclusions The distribution of NTM species is diverse in Hainan area, with Mycobacterium intracellulare, Mycobacterium chelonae/abscessus, and Mycobacterium avium are dominant species. NTM pulmonary disease and pulmonary tuberculosis have similar clinical features, which requires attention for differentiation in clinical practice.
9.Clinical value of magnetic resonance imaging based integrated deep learning model for predic-ting the times of linear staplers used in middle-low rectal cancer resection
Zhanwei FU ; Zhenghao CAI ; Shuchun LI ; Luyang ZHANG ; Lu ZANG ; Feng DONG ; Minhua ZHENG ; Junjun MA
Chinese Journal of Digestive Surgery 2023;22(9):1129-1138
Objective:To investigate the clinical value of magnetic resonance imaging (MRI) based integrated deep learning model for predicting the times of linear staplers used in double stapling technique for middle-low rectal cancer resection.Methods:The retrospective cohort study was conducted. The clinicopathological data of 263 patients who underwent low anterior resection (LAR) for middle-low rectal cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from January 2018 to December 2022 were collected as training dataset. There were 183 males and 80 females, aged 63(55,68)years. The clinicopathological data of 128 patients with middle-low rectal cancer were collected as validation dataset, including 83 males and 45 females, with age as 65(57,70)years. The training dataset was used to construct the prediction model, and the validation dataset was used to validate the prediction model. Observation indicators: (1) clinicopathological features of patients in the training dataset; (2) influencing factors for ≥3 times using of linear staplers in the operation; (3) prediction model construction; (4) efficiency evaluation of prediction model; (5) validation of prediction model. Measurement data with skewed distribution were represented as M( Q1, Q3), and Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test. Wilcoxon rank sum test was used for non-parametric data analysis. Univariate analysis was conducted using the Logistic regression model, and multivariate analysis was conducted using the Logistic stepwise regression model. The receiver operating characteristic (ROC) curve was draw and the area under the curve (AUC) was calculated. The AUC of the ROC curve >0.75 indicated the prediction model as acceptable. Comparison of AUC was conducted using the Delong test. Results:(1) Clinicopathological features of patients in the training dataset. Of the 263 patients, there were 48 cases with linear staplers used in the operation ≥3 times and 215 cases with linear staplers used in the operation ≤2 times. Cases with preoperative serum carcinoembryonic antigen (CEA) >5 μg/L, cases with anastomotic leakage, cases with tumor diameter ≥5 cm were 20, 12, 13 in the 48 cases with linear staplers used ≥3 times in the operation, versus 56, 26, 21 in the 215 cases with linear staplers used ≤2 times in the operation, showing significant differences in the above indicators between them ( χ2=4.66, 5.29, 10.45, P<0.05). (2) Influencing factors for ≥3 times using of linear staplers in the operation. Results of multivariate analysis showed that preoperative serum CEA >5 μg/L and tumor diameter ≥5 cm were independent risk factors for ≥3 times using of linear staplers in the operation ( odds ratio=2.26, 3.39, 95% confidence interval as 1.15-4.43, 1.50-7.65, P<0.05). (3) Prediction model construction. According to the results of multivariate analysis, the clinical prediction model was established as Logit(P)=-2.018+0.814×preoperative serum CEA (>5 μg/L as 1, ≤5 μg/L as 0)+ 1.222×tumor diameter (≥5 cm as 1, <5 cm as 0). The image data segmented by the Mask region convolutional neural network (MASK R-CNN) was input into the three-dimensional convolutional neural network (C3D), and the image prediction model was constructed by training. The image data segmented by the MASK R-CNN and the clinical independent risk factors were input into the C3D, and the integrated prediction model was constructed by training. (4) Efficiency evaluation of prediction model. The sensitivity, specificity and accuracy of the clinical prediction model was 70.0%, 81.0% and 79.4%, respectively, with the Yoden index as 0.51. The sensitivity, specificity and accuracy of the image prediction model was 50.0%, 98.3% and 91.2%, respectively, with the Yoden index as 0.48. The sensitivity, specificity and accuracy of the integrated prediction model was 70.0%, 98.3% and 94.1%, respectively, with the Yoden index as 0.68. The AUC of clinical prediction model, image prediction model and integrated prediction model was 0.72(95% confidence interval as 0.61-0.83), 0.81(95% confidence interval as 0.71-0.91) and 0.88(95% confidence interval as 0.81-0.95), respectively. There were significant differences in the efficacy between the integrated prediction model and the image prediction model or the clinical prediction model ( Z=2.98, 2.48, P<0.05). (5) Validation of prediction model. The three prediction models were externally validated by validation dataset. The sensitivity, specificity and accuracy of the clinical prediction model was 62.5%, 66.1% and 65.6%, respectively, with the Yoden index as 0.29. The sensitivity, specificity and accuracy of the image prediction model was 58.8%, 95.5% and 92.1%, respectively, with the Yoden index as 0.64. The sensitivity, specificity and accuracy of the integrated prediction model was 68.8%, 97.3% and 93.8%, respectively, with the Yoden index as 0.66. The AUC of clinical prediction model, image prediction model and integrated prediction model was 0.65(95% confidence interval as 0.55-0.75), 0.75(95% confidence interval as 0.66-0.84) and 0.84(95% confidence interval as 0.74-0.93), respec-tively. There was significant differences in the efficacy between the clinical prediction model and the integrated prediction model ( Z=3.24, P<0.05). Conclusion:The MRI-based deep-learning model can help predicting the high-risk population with ≥3 times using of linear staplers in resection of middle-low rectal cancer with double stapling technique.
10.Cux1+ proliferative basal cells promote epidermal hyperplasia in chronic dry skin disease identified by single-cell RNA transcriptomics
Minhua HUANG ; Ning HUA ; Siyi ZHUANG ; Qiuyuan FANG ; Jiangming SHANG ; Zhen WANG ; Xiaohua TAO ; Jianguo NIU ; Xiangyao LI ; Peilin YU ; Wei YANG
Journal of Pharmaceutical Analysis 2023;13(7):745-759
Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hy-perplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+ PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the tran-scriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.

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