1.Expert consensus on the positioning of the "Three-in-One" Registration and Evaluation Evidence System and the value of orientation of the "personal experience"
Qi WANG ; Yongyan WANG ; Wei XIAO ; Jinzhou TIAN ; Shilin CHEN ; Liguo ZHU ; Guangrong SUN ; Daning ZHANG ; Daihan ZHOU ; Guoqiang MEI ; Baofan SHEN ; Qingguo WANG ; Xixing WANG ; Zheng NAN ; Mingxiang HAN ; Yue GAO ; Xiaohe XIAO ; Xiaobo SUN ; Kaiwen HU ; Liqun JIA ; Li FENG ; Chengyu WU ; Xia DING
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):445-450
Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.
2.EGCG Promotes Aβ Clearance of Microglia Through Blockage of the HDAC6-PI3K/AKT/mTOR Signalling Axis Followed by Autophagy Activation
Yu LIN ; Kaiwen HUANG ; Honghai HONG ; Dan ZHU ; Yousheng MO ; Dongli LI ; Shuhuan FANG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):486-497
ObjectiveTo clarify whether epigallocatechin gallate (EGCG) is involved in the clearance of amyloid β-protein (Aβ) and autophagy induction by microglia, so as to explore the potential mechanisms of EGCG in the prevention and treatment of Alzheimer's disease (AD). MethodsSix-month-old APP/PS1 mice were randomly divided into model and EGCG groups, with some additional wild type (WT) mice as the control group, each group consisting of 15 mice. The EGCG group received continuous gavage administration[5 mg/(kg·d)] for 8 weeks, followed by the open field test and Y-maze to assess the learning and memory abilities of the mice. Thioflavin-S staining was used to evaluate the content and distribution of amyloid β-protein (Aβ)in the brain parenchyma of the mice, and immunofluorescence was employed to detect the expression levels of Aβ1-42, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba1) in the hippocampal tissue of the mice. Additionally, N9 mouse microglial cells were induced with 20 µmol/L Aβ1-42, and the cell viability was measured after treatment with different concentrations of EGCG (5 µmol/L, 10 µmol/L, 20 µmol/L). Western blotting was used to detect the levels of Aβ1-42, low density lipoprotein receptor-related protein 1(LRP1), receptor for advanced glycation endproducts (RAGE), amyloid precursor protein (APP), insulin degrading enzyme (IDE), neprilysin (NEP), microtubule associated protein 1 hydrogen chain 3(LC3)-Ⅱ/LC3-Ⅰ, phosphatidylinositol 3-hydroxy kinase(PI3K), p-PI3K, protein kinase B (AKT), p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, and histone deacetylase 6(HDAC6). Finally, through the co-culture of microglial cells and neuronal SH-SY5Y cells, cell viability and Caspase-3 levels were measured to verify the protective effect of EGCG-mediated Aβ clearance on neurons. ResultsEGCG increased the activity time and frequency of APP/PS1 mice in the central area of the open field (P<0.05), and enhanced the percentage of alternation in the Y-maze test (P<0.01); EGCG reduced Aβ deposition in the hippocampal tissue of APP/PS1 mice and increased the number of microglia; in vitro experiments showed that EGCG improved the survival rate of Aβ-induced N9 cells (P<0.01), upregulated RAGE activity (P<0.05), and promoted the internalization and phagocytosis of Aβ (P<0.01). ECGC activated microglial autophagy by downregulating the level of HDAC6 (P<0.05), inhibiting the phosphorylation of PI3K, AKT, mTOR (P<0.001), and increasing the LC3-Ⅱ/LC3-I ratio (P<0.001); EGCG improved the survival rate of SH-SY5Y cells (P<0.05) and reduced the activity of Caspase-3 (P<0.01) by clearing Aβ1-42 through microglia, and had a protective effect on neurons. ConclusionEGCG activates microglial autophagy to clear Aβ by targeting and inhibiting the HDAC6-PI3K/AKT/mTOR axis.
3.Vesicle fusion mechanisms mediated by synaptosomal-associated protein 25 and its role in insulin secretion defects in type 2 diabetes mellitus
Jingbo ZHU ; Kaiwen YU ; Yating LU ; Yan LU
Journal of Clinical Medicine in Practice 2025;29(13):137-144
The occurrence and development of type 2 diabetes mellitus(T2DM)are closely as-sociated with defects in insulin secretion.Synaptosomal-associated protein 25(SNAP25),as a core component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor(SNARE)complex,directly mediates the fusion of insulin secretion granules with the cell membrane and regu-lates the dynamic balance of insulin secretion stimulated by glucose.The expression defect of SNAP25 in patients with T2DM and model animals directly leads to vesicle fusion disorder,constituting the core pathological link of insulin secretion disorder and exacerbating the deterioration of β-cell func-tion.SNAP25 may serve as a key hub for multi-target synergistic intervention,and its genetic poly-morphism and the plasticity of its regulatory network offer novel strategies for precision therapy.This article innovatively integrated multidimensional regulatory mechanisms,including calcium channel ac-tivity,G-protein-coupled signaling and epigenetic modifications,to systematically analyze the spatio-temporal-specific regulatory network of SNAP25 in insulin secretion,providing a theoretical basis for T2DM therapeutic strategies targeting vesicle fusion.
4.Screening and validation of blood composite markers for diagnosing prostate cancer
Kang LIU ; Kaiwen FENG ; Dongrong YANG ; Jin ZHU
Chinese Journal of Urology 2025;46(6):447-454
Objective:To investigate the diagnostic efficacy of differentially expressed proteins in the plasma of prostate cancer patients.Methods:Plasma samples were collected from patients who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from January to March 2023. Among them,there were 30 patients with prostate cancer,aged(75.10 ± 9.33)years,with a median serum PSA value of 24.60(5.38,516.00)ng/ml,and 30 patients with benign prostatic hyperplasia,aged(72.90 ± 7.30)years,with a median serum PSA value of 2.21(0.44,4.38)ng/ml Label-free quantitative proteomic technology was used to detect differentially expressed proteins in the plasma. Combined with TCGA transcriptome changes and relevant literature,the differentially expressed candidate proteins with the most significant up-regulation were selected.In addition,prostate biopsy tissue samples were collected from another 14 patients who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from September to November 2023. Among them,there were 8 patients with prostate cancer,aged(72.25 ± 6.52)years,with a median serum PSA value of 74.65(5.63,151.00)ng/ml,and 6 patients with benign prostatic hyperplasia,aged(70.83 ± 5.04)years,with a median serum PSA value of 5.06(3.34,28.70)ng/ml. Immunohistochemical staining was performed using antibodies corresponding to the candidate proteins to analyze the expression differences of the candidate proteins between the 8 prostate cancer cases and the 6 benign prostatic hyperplasia cases.Plasma samples were collected from 44 patients with prostate diseases who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from March to September 2023. Among them,there were 30 patients with prostate cancer,aged(71.58 ± 7.99)years,with a median serum PSA value of 29.85(1.25,108.00)ng/ml,and 14 patients with benign prostatic hyperplasia,aged(69.00 ± 8.94)years,with a median serum PSA value of 1.78(0.61,12.40)ng/ml. Area under the curve(AUC)was calculated to analyze the diagnostic efficacy of each protein for prostate cancer. Detect the expression levels of candidate proteins in plasma by ELISA,draw the ROC curve,calculate the area under the curve(AUC),and analyze the diagnostic efficacy of each protein for prostate cancer.Results:A total of 34 most significant upregulated proteins and 72 downregulated proteins were detected by proteomics and eight proteins were detected by referring to TCGA data and literatures. Percentage of positive cells of SPON2,FGB,PCSK6,ORM1,ORM2,HP,SND1,and SUSD2 in prostate cancer tissues(51.97 ± 10.81,42.97 ± 6.76,49.83 ± 12.46,53.85 ± 11.52,50.46 ± 11.13,39.69 ± 10.96,52.01 ± 13.03,45.92 ± 9.55)were significantly higher than in BPH(36.31 ± 19.87,21.85 ± 10.99,21.59 ± 5.61,20.36 ± 4.75,24.38 ± 11.55,20.75 ± 3.75,23.60 ± 6.51,19.69 ± 8.45)( P < 0.05). FGB,HP,and ORM1 were significantly increased in plasma of prostate cancer patients compared to BPH patients(ng/ml)[(689.9 ± 659.7)ng/ml vs.(200.0 ± 127.1)ng/ml,(1.819 ± 0.833)ng/ml vs.(1.126 ± 0.362)ng/ml,(733.5 ± 385.0)ng/ml vs.(344.7 ± 214.6)ng/ml, P < 0.05],with AUC values 0.803,0.781,and 0.832,respectively. The combined diagnostic efficacy of the three proteins FGB,HP,and ORM1 for prostate cancer is significantly better than that of any single protein(AUC = 0.953),with higher sensitivity(81.48%)and specificity(100.0%). Conclusions:FGB,HP,ORM1 were significantly increased in plasma of prostate cancer patients compared to BPH patients,indicating higher diagnostic efficacy. The combined diagnostic efficacy FGB,HP,and ORM1 for prostate cancer is significantly better than that of any single protein,and they exhibit higher sensitivity and specificity.
5.Screening and validation of blood composite markers for diagnosing prostate cancer
Kang LIU ; Kaiwen FENG ; Dongrong YANG ; Jin ZHU
Chinese Journal of Urology 2025;46(6):447-454
Objective:To investigate the diagnostic efficacy of differentially expressed proteins in the plasma of prostate cancer patients.Methods:Plasma samples were collected from patients who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from January to March 2023. Among them,there were 30 patients with prostate cancer,aged(75.10 ± 9.33)years,with a median serum PSA value of 24.60(5.38,516.00)ng/ml,and 30 patients with benign prostatic hyperplasia,aged(72.90 ± 7.30)years,with a median serum PSA value of 2.21(0.44,4.38)ng/ml Label-free quantitative proteomic technology was used to detect differentially expressed proteins in the plasma. Combined with TCGA transcriptome changes and relevant literature,the differentially expressed candidate proteins with the most significant up-regulation were selected.In addition,prostate biopsy tissue samples were collected from another 14 patients who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from September to November 2023. Among them,there were 8 patients with prostate cancer,aged(72.25 ± 6.52)years,with a median serum PSA value of 74.65(5.63,151.00)ng/ml,and 6 patients with benign prostatic hyperplasia,aged(70.83 ± 5.04)years,with a median serum PSA value of 5.06(3.34,28.70)ng/ml. Immunohistochemical staining was performed using antibodies corresponding to the candidate proteins to analyze the expression differences of the candidate proteins between the 8 prostate cancer cases and the 6 benign prostatic hyperplasia cases.Plasma samples were collected from 44 patients with prostate diseases who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from March to September 2023. Among them,there were 30 patients with prostate cancer,aged(71.58 ± 7.99)years,with a median serum PSA value of 29.85(1.25,108.00)ng/ml,and 14 patients with benign prostatic hyperplasia,aged(69.00 ± 8.94)years,with a median serum PSA value of 1.78(0.61,12.40)ng/ml. Area under the curve(AUC)was calculated to analyze the diagnostic efficacy of each protein for prostate cancer. Detect the expression levels of candidate proteins in plasma by ELISA,draw the ROC curve,calculate the area under the curve(AUC),and analyze the diagnostic efficacy of each protein for prostate cancer.Results:A total of 34 most significant upregulated proteins and 72 downregulated proteins were detected by proteomics and eight proteins were detected by referring to TCGA data and literatures. Percentage of positive cells of SPON2,FGB,PCSK6,ORM1,ORM2,HP,SND1,and SUSD2 in prostate cancer tissues(51.97 ± 10.81,42.97 ± 6.76,49.83 ± 12.46,53.85 ± 11.52,50.46 ± 11.13,39.69 ± 10.96,52.01 ± 13.03,45.92 ± 9.55)were significantly higher than in BPH(36.31 ± 19.87,21.85 ± 10.99,21.59 ± 5.61,20.36 ± 4.75,24.38 ± 11.55,20.75 ± 3.75,23.60 ± 6.51,19.69 ± 8.45)( P < 0.05). FGB,HP,and ORM1 were significantly increased in plasma of prostate cancer patients compared to BPH patients(ng/ml)[(689.9 ± 659.7)ng/ml vs.(200.0 ± 127.1)ng/ml,(1.819 ± 0.833)ng/ml vs.(1.126 ± 0.362)ng/ml,(733.5 ± 385.0)ng/ml vs.(344.7 ± 214.6)ng/ml, P < 0.05],with AUC values 0.803,0.781,and 0.832,respectively. The combined diagnostic efficacy of the three proteins FGB,HP,and ORM1 for prostate cancer is significantly better than that of any single protein(AUC = 0.953),with higher sensitivity(81.48%)and specificity(100.0%). Conclusions:FGB,HP,ORM1 were significantly increased in plasma of prostate cancer patients compared to BPH patients,indicating higher diagnostic efficacy. The combined diagnostic efficacy FGB,HP,and ORM1 for prostate cancer is significantly better than that of any single protein,and they exhibit higher sensitivity and specificity.
6.Augmented Central Pain Processing Occurs after Osteoporotic Vertebral Compression Fractures and Is Associated with Residual Back Pain after Percutaneous Vertebroplasty
Kaiwen CHEN ; Tian GAO ; Yu ZHU ; Feizhou LYU ; Jianyuan JIANG ; Chaojun ZHENG
Asian Spine Journal 2024;18(3):380-389
Methods:
Preoperatively, all 160 patients with OVCFs underwent pressure-pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM), and imaging assessments. Pain intensity and pain-related disability were evaluated before and after PVP.
Results:
Preoperatively, patients with OVCFs had lower PPTs in both local pain and pain-free areas and lower CPM and higher TS in pain-free areas than healthy participants (p<0.05). Unlike patients with acute fractures, patients with subacute/chronic OVCFs showed higher TS with or without lower CPM in the pain-free area compared with healthy participants (p<0.05). Postoperatively, RBP occurred in 17 of 160 patients (10.6%). All preoperative covariates with significant differences between the RBP and non-RBP groups were subjected to multivariate logistic regression, showing that intravertebral vacuum cleft, posterior fascia edema, numeric rating pain scale scores for low back pain at rest, and TS were independently associated with RBP (p<0.05).
Conclusions
Augmented central pain processing may occur in patients with OVCFs, even in the subacute stage, and this preexisting CS may be associated with RBP. Preoperative assessment of TS in pain-free areas may provide additional information for identifying patients who may be at risk of RBP development, which may be beneficial for preventing this complication.
7.Correlations of serum Apelin-13 and fatty acid binding protein 4 levels with postmenopausal osteoporosis
Manling XU ; Jingbo ZHU ; Kaiwen YU ; Ling CHEN ; Huaying FAN ; Qingtao FAN ; Qiuping WANG ; Yan LU
Journal of Clinical Medicine in Practice 2024;28(11):73-78
Objective To investigate the correlations of serum Apelin-13 and fatty acid binding protein 4 (FABP4) levels with metabolic and bone metabolic indicators in postmenopausal women with different bone mass. Methods A total of 145 postmenopausal women were selected as subjects and divided into three groups based on bone mineral density (BMD) test results: normal bone mass group(49 cases), osteopenia (ON) group(51 cases), and osteoporosis (OP) group(45 cases). Serum Apelin-13, FABP4 levels, bone metabolic indicators, and biochemical indicators were measured and compared among the three groups. Spearman correlation analysis was used to analyze the correlations of Apelin-13, FABP4, and other indicators with BMD. Multivariate Logistic regression analysis was performed to analyze the risk factors for OP, and the receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of serum Apelin-13 for postmenopausal osteoporosis (PMOP). Results The serum Apelin-13 level in the OP group was lower than that in the ON group and the normal bone mass group (
8.The value of urine protein kinase Y-linked gene promoter site methylation in early diagnosis of prostate cancer
Weifeng LIU ; Zheng DAI ; Yibin ZHOU ; Kaiwen FENG ; Kai WEI ; Gule SUN ; Dongrong YANG ; Jin ZHU
The Journal of Practical Medicine 2024;40(5):688-694
Objective To explore the clinical value of methylation at promoter sites of urine protein kinase Y-linked(PRKY)gene in the early diagnosis of prostate cancer(PCa).Methods Urine samples were collected from 50 suspected PCa patients.After extracting DNA,the methylation levels of the PRKY gene promoter sites cg05163709,cg08045599,and cg05618150 were detected using quantitative methylation-specific PCR(qMSP).Simultaneously,the patients were divided into the benign prostatic hyperplasia(BPH)group and the PCa group.The differences in clinical indicators between the two groups were analyzed,as well as the methylation status of the PRKY gene promoter sites in the urine of the two groups of patients.The receiver operating charac-teristic(ROC)curve of PRKY promoter sites methylation was established,and the area under the curve(AUC)was calculated to analyze the diagnostic value of PRKY promoter sites methylation in PCa,and to perform com-bined diagnosis with clinical indicators.Results The methylation rates of cg05163709 and cg05618150 in urine specimens of PCa patients were significantly higher than those of BPH patients.The AUC for cg05163709 methyla-tion in diagnosing PCa was 0.762,with a sensitivity of 86.70%.It showed better performance in early screening for PCa compared to total prostate specific antigen(tPSA),percentage free prostate specific antigen(f/tPSA)and prostate specific antigen density(PSAD)index.We found that the AUC for cg05618150 methylation in conjunc-tion with PSAD in diagnosing PCa was 0.787,with a sensitivity of 86.70%.The AUC of cg05163709 methylation and PSAD in the joint diagnosis of PCa was 0.855,and the specificity could reach 95.00%.Conclusion The methylation of urine PRKY gene promoter sites cg05163709 and cg05618150 shows high sensitivity and specificity in diagnosing PCa,making them promising biomarkers for early detection of PCa.
9.Analgesic and anti-inflammatory effects of galangin: a potential pathway to inhibit transient receptor potential vanilloid 1 receptor activation
Kaiwen LIN ; Datian FU ; Zhongtao WANG ; Xueer ZHANG ; Canyang ZHU
The Korean Journal of Pain 2024;37(2):151-163
Background:
Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear.
Methods:
Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalininduced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX- 2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR.
Results:
Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenantriggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF- κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA.
Conclusions
Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.
10.Study on the influence of reconstruction algorithms of image on the image quality and precision of automatic registration of imaging system with megavolt grade
Xiaoyu LIU ; Gaoxiang CHEN ; Changxin YAN ; Peichao BAN ; Hongtao YU ; Shilong ZHU ; Kaiwen CHEN ; Chuanbin XIE
China Medical Equipment 2024;21(6):6-11
Objective:To compare and study the improvement of different iterative reconstruction(IR)algorithms of the tomotherapy(TOMO)Radixact system on the image quality of megavoltage computed tomography(MVCT)imaging system,and the influence of that on the precision of automatic registration,and to explore the reconstruction algorithm that is suitable for clinical application.Methods:Using the MVCT imaging system to respectively scan the Tomo-Phantom HE phantom and the Catphan 604 phantom,and to analyze three groups of images were generated by three kinds of reconstruction algorithms,which included the Standard(STD)algorithm,IR General(IR-G)algorithm and IR Soft Tissue(IR-ST)algorithm,in MVCT image.The noise index(NI),uniformity index(UI)of image,modulation transfer function(MTF),low contrast visibility(LCV)index and contrast-to-noise ratio(CNR)of three groups of images were calculated respectively.The Lucy phantom was used to test the accuracy of automatic registration algorithm.The registration data of four dimensions,included left-right(X-axis),head-foot(Y-axis),vertical(Z-axis)and free rotation(Roll)around the Y-axis,were used to conduct verification analysis for the influences of them on the precision of automatic registration.Results:The NI values of IR-G and IR-ST reconstruction algorithms were respectively 39.58±0.10 and 14.62±0.26,which were better than 39.58±0.10 of STD algorithm,and the UI values of them were respectively 19.87±0.83 and 15.84±2.51,which were better than 24.51±1.81 of STD algorithm,and LCV values of them were respectively 2.50±0.03 and 1.74±0.11,which were better than 3.67±0.04 of STD algorithm.All of them appeared significant increase,but the resolution with high contrast of MTF were respectively 0.23 and 0.21,which were lower than 0.32 of STD.The overall image quality of the IR algorithms was superior to that of the STD algorithm.In the accuracy test of the automatic registration algorithm,the registration precisions of IR-G and IR-ST algorithms on Y-axis were respectively(0.360±0.142)mm and(0.245±0.050)mm,which were significantly higher than 0.145±0.136 of STD algorithm,and the differences of them were significant(Z=6.0,15.0,P<0.05).The differences of registration precisions of other directions were not significant(P>0.05).Conclusion:The IR algorithm has advantages in terms of noise,uniformity and resolution with low-contrast,however,it shows reduction on resolution with high-contrast.This reduction of resolution with high-contrast do not lead to the decrease of the precision of automatic registration.


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