1.Exploring mechanism of action and validation of key regulatory pathways of selenshenzhi prescription in treatment of esophageal cancer based on network pharmacology
Ke-Yi JI ; Su-Hui WU ; Jia-Yao YUAN ; Han-Bing LI ; Shun-Cai WANG ; Long-Jie WANG ; Lin-Lin WANG ; Qi-Long GAO
Chinese Pharmacological Bulletin 2024;40(11):2174-2184
Aim To study the main active components and potential mechanism of selenshenzhi prescription a-gainst esophageal cancer by network pharmacology and in vivo and in vitro experiments.Methods The com-mon target was extracted from TCMSP,OMIM and GeneCards databases,and the PPI network was con-structed using STRING database.DAVID database was used for GO and KEGG enrichment analysis,and a network was constructed based on STRING and DAVID database for in vivo and in vitro experimental verifica-tion.Results Prediction results showed that a total of 100 active ingredients and 749 related targets were ob-tained,and 168 common targets were obtained between selenoshenzhi recipe and esophageal cancer,which were involved in the PI3K-AKT signaling pathway and proteoglycan signaling pathways in cancer.Selenshenz-hi prescription was used to conduct preliminary verifi-cation of related targets for human esophageal cancer EC9706 based on in vitro experiments.The results showed that selenshenzhi prescription could significantly inhibit the proliferation of esophageal cancer cells and induce the apoptosis of EC9706 through the expression of Bax,Bcl-2,caspase-3 and other key apoptotic pro-teins.Lastly,the core target and pathway of selensh-enzhi prescription were preliminically verified based on in vivo animal experiments on nude mice with esopha-geal cancer.The results showed that selenshenzhi pre-scription could significantly inhibit tumor proliferation,promote tumor cell apoptosis,and induce tumor apop-tosis by regulating the expression of key proteins on PI3K/AKT signaling pathway.Conclusions Selensh-enzhi prescription can control the occurrence and de-velopment of esophageal cancer through the synergistic effect of multi-components,multi-targets and multi-pathways,and provide a theoretical basis for further clinical investigation of the mechanism of selenshenzhi prescription in the treatment of esophageal cancer in the future.
2.Progress in imaging research of neurovascular coupling disorders in Alzheimer's disease
Ting LI ; Rongfeng QI ; Bing ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(11):1007-1012
Alzheimer's disease (AD) is a progressive neurodegenerative disease, and in-depth study of its pathogenesis to enable early diagnosis of the disease, as well as identification of potential therapeutic targets, are the current research priority. Cerebrovascular dysfunction is considered to be an important pathophysiological mechanism in AD. Neurovascular coupling, which serves as a bridge between neural activity and vascular response, has emerged as a new frontier in the study of cerebrovascular dysfunction in AD. It provides a new perspective to reveal the correlation between vascular pathology and AD. This article reviewd and summarized existing research on changes in cerebral blood perfusion and neural electrical activity across the AD continuum, using various imaging techniques to assess neurovascular coupling. The results indicate that compensatory mechanisms in cerebral blood perfusion can be observed in AD using multiple imaging techniques, and reductions in cerebral blood perfusion and neural electrical activity correlate with the deterioration of cognitive function. Neurovascular coupling indicators derived from multimodal imaging demonstrate good sensitivity and specificity in distinguishing healthy individuals from patients with varying degrees of cognitive impairment, holding promise as effective imaging biomarkers for assessing AD.
3.Clinical characteristics and prognosis of patients with myelodysplastic syndrome with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50%
Yanping ZENG ; Bing LI ; Tiejun QIN ; Zefeng XU ; Shiqian QU ; Lijuan PAN ; Qingyan GAO ; Meng JIAO ; Junying WU ; Huijun WANG ; Chengwen LI ; Yujiao JA ; Qi SUN ; Zhijian XIAO
Chinese Journal of Hematology 2024;45(7):651-659
Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.
4.Changes in the microstructure and bone mineral density of vertebral tra-becular bone in the early stages of spinal Mycobacterium tuberculosis in-fection
Jun-Bao CHEN ; Yi LUO ; Nan-Jun XIONG ; Xiao-Jiang HU ; Chao-Feng GUO ; Qi-Le GAO ; Yan-Bing LI
Chinese Journal of Infection Control 2024;23(8):1001-1006
Objective To observe and compare the changes of vertebral bone mineral density(BMD)in the early stages of spinal Mycobacterium tuberculosis infection.Methods Patients who underwent spinal surgery at Xiangya Hospital,Central South University from January 1 to December 31,2023 were continuously enrolled(spinal tuber-culosis group),based on gender matching,non-spinal tuberculosis surgical patients treated for spinal stenosis were selected as the control group.Dual-energy X-ray scans were performed on the enrolled patients,difference in verte-bral BMD between two groups of patients was compared.An animal model of spinal Mycobacterium tuberculosis in-fection(referred to as the animal model)was constructed,differences in microstructure of trabecular bone between spinal tuberculosis group and control group was compared,and the bone volume/tissue volume(BV/TV),the thickness of trabecular bone(Tb.Th),the number of trabecular bone(Tb.N),and sparse density of trabecular(Tb.Sp)were used as evaluation indexes to further analyze the bone quality differences between the diseased verte-brae and the neighboring vertebrae.Results 69 patients were included in the spinal tuberculosis group and the con-trol group,respectively.The BMD of patients in the spinal tuberculosis group(0.793[0.712,0.869]g/cm2)was lower than that of the control group(0.907[0.800,1.020]g/cm2),difference was statistically significant(P<0.05).Microstructure of trabecular bone BV/TV([18.4±5.4]%),Tb.Th([0.124±0.010]mm)in the spinal tuberculosis group of animal model were significantly altered compared with BV/TV([22.6±3.2]%),Tb.Th([0.160±0.017]mm)in the control group(both P<0.05).In the spinal tuberculosis group,microstructure of diseased vetebral trabecular bone BV/TV([25.5±6.7]%)and Tb.N([1.871±0.443]/mm)were significantly lower than BV/TV([26.6±6.8]%)and Tb.N([1.969±0.454]/mm)in the neighboring vertebrae,both with statistically difference(both P<0.05).Conclusion In the early stages of spinal Mycobacterium tuberculosis infec-tion,microstructure of vertebral trabecular bone can be altered,leading to a decrease in BMD.
5.Structure-activity Omics of Traditional Chinese Medicine: A Case Study of Anti-inflammatory and Analgesic Effect of Qizhi Weitong Granules
Xiansheng MENG ; Ying ZHENG ; Ying MENG ; Bing QI ; Sicong LIU ; Xi LUO ; Xinpeng QIN ; Yongrui BAO ; Shuai WANG ; Tianjiao LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):129-135
The complex chemical composition and limited research ideas of traditional Chinese medicine (TCM) have led to the unclear material basis and mechanism of the medicinal effects, which is a common problem hindering the modernization of TCM in China. The introduction of computer virtual technology has provided a new perspective for TCM research. In this study, we established the research method of structure-activity omics to study the relationships between the structures and effects of different compounds in TCM based on the chemical structures of TCM components and to analyze and predict the material basis and multitarget synergistic mechanism of TCM. Furthermore, a structure-activity omics study was carried out with the anti-inflammatory and analgesic effects of Qizhi Weitong granules as an example. This study provides support for screening the pharmacodynamic components and analyzing the active ingredients of TCM and gives insights into the research on the material basis and mechanism of compound efficacy and the development of lead compounds of TCM, thus promoting the modern research and the innovative development of TCM.
6.Structure-activity Omics on Anti-inflammatory and Analgesic Effect of Bupleuri Radix in Qizhi Weitong Granules
Xi LUO ; Bing QI ; Ying MENG ; Xinpeng QIN ; Yongrui BAO ; Tianjiao LI ; Liang WANG ; Shuai WANG ; Xiansheng MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):146-153
ObjectiveTo identify the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Bupleuri Radix by structure-activity omics. MethodA mouse model of pain was established with formaldehyde to examine the anti-inflammatory and analgesic effects of saikosaponins in vivo. The core targets of the active components in Bupleurum Radix for the anti-inflammatory and analgesic effects were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and Search Tool for Recurring Instances of Neighbouring Genes (STRING). The key core targets with high binding affinity were screened based on the comprehensive score in the molecular docking between different types of saikosaponins and core targets. The structure-activity relationship was discussed and analyzed based on the binding of compounds to pharmacodynamic targets. ResultSaikosaponins alleviated the foot swelling induced by formaldehyde and reduced the content of prostaglandin E2 (PGE2) in the mouse model, showcasing a significant inhibitory effect on the inflammatory pain caused by PGE2. Nine components and 39 targets of saikosaponins, as well as 3 074 targets of anti-inflammatory and analgesic effects were screened out, and 22 common targets shared by saikosaponins and the effects were obtained as the direct targets. The protein-protein interaction (PPI) analysis showed that the main active components of Bupleurum Radix were saikosaponins a, b1, b2, b3, c, d, e, f, and v, and the key targets were fms-related receptor tyrosine kinase 1 (FLT1), kinase insert domain receptor (KDR), fibroblast growth factor 2 (FGF2), vascular endothelial growth factor A (VEGFA), and signal transducer and activator of transcription 3 (STAT3). Molecular docking between saikosaponins and the top 5 targets with high degrees in PPI network analysis revealed 25 highly active docks, including 6 docks with scores of 5-6 and 18 docks with scores above 6. ConclusionThis study adopted structural-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Bupleuri Radix in vivo, providing new ideas and methods for identifying the pharmacodynamic substances in traditional Chinese medicine.
7.Structure-activity Omics on Anti-inflammatory and Analgesic Effect of Aurantii Fructus in Qizhi Weitong Granules
Sicong LIU ; Xinpeng QIN ; Bing QI ; Xi LUO ; Tianjiao LI ; Yongrui BAO ; Shuai WANG ; Ling HAN ; Xiansheng MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):154-161
ObjectiveTo explain the pharmacodynamic substances of Aurantii Fructus flavonoids that exert anti-inflammatory and analgesic effects using a structure-activity omics approach. MethodOn the basis of the previous in vitro pharmacological screening conducted by the research team, an in vivo pharmacological study of Aurantii Fructus flavonoids was carried out. Core targets of the anti-inflammatory and analgesic active components of flavonoids of Aurantii Fructus were identified using various network databases, including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the Online Mendelian Inheritance in Man (OMIM), and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Computer-aided virtual screening technology was used to dock different types of Aurantii Fructus flavonoids with core targets. The key core targets with high binding activity were selected based on the comprehensive scores of each target and the active structures. Using these targets as bridges, the structures of one or more types of chemical components in Aurantii Fructus were closely linked to pharmacological effects. The structure-activity relationship between the clear pharmacodynamic compounds and their effects was explored through the binding patterns of various structures with pharmacodynamic targets. ResultAurantii Fructus flavonoids demonstrated significant anti-inflammatory and analgesic effects on dextran sulfate sodium (DSS)-induced colitis in mice, which could improve symptoms and significantly reduce the levels of inflammatory factors interleukin-6 (IL-6) and interleukin-1β (IL-1β)(P<0.05). Twelve active components of Aurantii Fructus flavonoids were identified and categorized into nine dihydroflavonoids and three flavonoids based on their structures of the parent nuclei. Through Venn analysis, 167 anti-inflammatory and analgesic targets for Aurantii Fructus were identified. Based on degree value and molecular docking comprehensive scores, prostaglandin-endoperoxide synthase 2(PTGS2) and mitogen-activated protein kinase 3(MAPK3) were selected for further structural analysis. Structural analysis revealed that components containing glycoside structures exhibited higher binding activity with anti-inflammatory and analgesic targets. ConclusionThis study utilized a structure-activity omics approach based on in vivo pharmacodynamic experiments to analyze the material basis of the anti-inflammatory and analgesic effects of Aurantii Fructus flavonoids. The structure-activity omics approach provides new ideas and methods for elucidating the pharmacodynamic substances of Chinese medicine.
8.Analysis of obesity factors among public primary school students in a town, Minhang District, Shanghai
Danhong MO ; Weizhong ZHAO ; Duojun XU ; Bing LI ; Xiaosa WEN ; Qi ZHAO ; Wenhao XUE
Shanghai Journal of Preventive Medicine 2024;36(1):84-89
ObjectiveTo identify and analyze the possible influencing factors of obesity among public primary school students in Minhang District, Shanghai. MethodsBasic data, collected through questionnaire stars, was imported with merged physical examination data into Excel to form a database. Data were collected by questionnaire and analyzed by SPSS 22.00. Independent sample t-test was used for the data with normal distribution. Nonparametric test was used for the data with non-normal distribution. χ2 test was used for the quantitative data. Logistic regression was used for univariate and multivariate analysis
9.Diagnostic efficacy of optimized T-SPOT.TB in differentiating spinal tu-berculosis from other spinal infection
Ying ZHOU ; Xiao-Jiang HU ; Zhong-Jing JIANG ; Jun-Bao CHEN ; Guang ZHANG ; Hong-Qi ZHANG ; Yan-Bing LI ; Qi-Le GAO
Chinese Journal of Infection Control 2024;23(2):148-154
Objective To explore the efficacy of T-cell spot test of tuberculosis infection(T-SPOT.TB)in the differential diagnosis of spinal tuberculosis(STB),and optimize diagnostic efficacy through the optimal cut-off value of receiver operating characteristic(ROC)curve.Methods Clinical data of patients with spinal infection in a hospi-tal from January 2010 to May 2019 were collected,including preoperative T-SPOT.TB test results,white blood cell count,C-reactive protein,erythrocyte sedimentation rate,procalcitonin,and tuberculosis antibodies,etal.Clinical diagnosis was conducted based on diagnostic criteria.The sensitivity and specificity of T-SPOT.TB in preoperative diagnosis of STB and other spinal infection was analyzed,and the diagnostic efficacy of the optimized T-SPOT.TB indicators was evaluated.Results A total of 132 patients were included in this study,out of whom 78 patients(59.09%)were diagnosed with STB,and 54(40.91%)were diagnosed with non-tuberculosis(non-TB)spinal in-fection.The sensitivity and specificity of T-SPOT.TB in differential diagnosis of STB were 67.68%and 66.67%,respectively.Univariate logistic regression analysis showed that compared with non-TB spinal infection,the OR va-lue of T-SPOT.TB test in diagnosing STB was 4.188(95%CI:1.847-9.974,P<0.001).The optimized T-SPOT.TB evaluation index through ROC curve to determine the optimal cut-off values of ESAT-6,CFP-10,and CFP-10+ESAT-6 for differential diagnosis of STB and non-TB spinal infection were 12.5,19.5,and 36,respec-tively,and area under curve(AUC)values were 0.765 6,0.741 5,and 0.778 6,respectively,all with good diag-nostic efficacy.CFP-10+ESAT-6 had the highest AUC.CFP-10+ESAT-6 specific spot count had higher efficacy in the diagnosis of STB,with a diagnostic accuracy of 75.56%,higher than 67.42%of pre-optimized T-SPOT.TB.Conclusion T-SPOT.TB test has high diagnostic efficacy in differentiating STB from non-TB spinal infection.Posi-tivity in T-SPOT.TB test,especially with spot count of CFP-10+ESAT-6 over 36,indicates a higher likelihood of STB.
10.Study on the effect of different administration regimens of iprrazole enteric-coated tablets on inhibiting gastric acid secretion
Ting-Yuan PANG ; Zhi WANG ; Zi-Shu HU ; Zi-Han SHEN ; Yue-Qi WANG ; Ya-Qian CHEN ; Xue-Bing QIAN ; Jin-Ying LIANG ; Liang-Ying YI ; Jun-Long LI ; Zhi-Hui HAN ; Guo-Ping ZHONG ; Guo-Hua CHENG ; Hai-Tang HU
The Chinese Journal of Clinical Pharmacology 2024;40(1):92-96
Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH>3 after 20 mg qd and 10 mg bid were 82.64%and 61.92%,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Result Analysis
Print
Save
E-mail