1.RNA Interference and its Applications in Cancer Therapy
Fuguo WU ; Yirong CHEN ; Xuechun WANG ; Li CHENG
Journal of International Oncology 2007;34(11):862-866
RNA interference(RNAi), a highly conserved process of post-transcriptional gene silencing, can be induced by small interfering double-stranded RNA that mediate sequence-specific mRNA degradation. In the past several years, RNAi has been widely used as both an experimental tool to study mammalian gene function and a potential therapeutic approach to treat human diseases. In addition, some new proteins which involve in RNAi pathway have been characterized in mammalian cells. Here, we summarize the various molecules in RNAi, mechanism of action, and the current therapeutic applications in cancers.
2.Related Factors of Hyperhomocysteinemia among Non-hypertensive People Aged between 40-70 Years in Tianjin
Huili CHEN ; Yuemin SUN ; Xuechun WANG ; Quan SI ; Wei YAO
Tianjin Medical Journal 2014;(6):613-615
Objective To investigate the concentration of homocysteine (Hcy) and related factors of hyperhomocyste-inemia (hHcy,Hcy≥15μmol/L) among non-hypertensive people aged between 40-70 in Tianjin. Methods Non-hyperten-sive community residents aged 40-70 years were enrolled randomly from May 2011 to December 2012 in six districts in Tian-jin. Plasma Hcy was assessed by enzyme cycling method. Factors related to hHcy were analyzed in multivariate logistic re-gression models. Results Our study included 874 participants (mean age is 57 ± 6 years, 25.5%of all are males) and the con-centration of Hcy was 12.0 μmol/L. The OR (odds ratio)(95%CI; P)for hHcy were 1.048(1.015,1.083; P=0.004), 4.191 (2.359,7.448;P<0.001), 1.280(0.896,1.829;P=0.175), 0.460(0.259,0.816;P=0.008)respectively for age, male, smoking, exercise, and the odd ratio for hHcy were 0.290(0.179, 0.469;P<0.001), 0.168(0.092,0.309;P<0.001)for consumption of vegetable and fruits 250-500 g/d and>500g/d, compared with<250 g/d. Conclusion Male and age were adverse factors for hHcy, consumption of vegetable and fruits, and exercise were positive factors.
3.Innovation of Preventive Medicine Education Model and Cultivating Students' Creativity
Kai ZHANG ; Xuechun WANG ; Ting CHEN ; Chunzhi ZHANG
Chinese Journal of Medical Education Research 2006;0(11):-
The modern preventive medicine education system should be reformed,the author proposed the preventive medicine education should establish multi-disciplinary and multi-level training way: depending on the high-quality curriculum of preventive medicine,constructing the platform of the preventive medicine education;setting up the new idea of preventive medicine education,taking the educational model innovation;breaking up the traditional thought pattern,displaying creative thought;developing the exploration of the non-preventive medicine specialized preventive medicine educational pattern.
4.Exploration and Practices of Tutorial System to Undergraduates in Medical Colleges and Universities
Ting CHEN ; Kai ZHANG ; Wenjun WANG ; Chunzhi ZHANG ; Xitong YUE ; Xuechun WANG
Chinese Journal of Medical Education Research 2005;0(05):-
This text briefly introduces tutorial system's history evolution and development and expounds its necessity and realistic meaning,emphasizing that practising such a guidance program is necessary for developing students' innovative ability and individuality,and for strengthening the construction of the teachign staff,which is the call of students and the responsibility of education,and the inevitable choice under credit system.It focuses on how to set up effective and practical tutorial system of the undergraduate course from the construction of tutors'troops,the feasible measures and system,and tutor stimulative mechanism.
5.Effects of Keningfang decoction on heat shock protein 70 expression in lung of mice with influenza virus pneumonia
Qinhe YANG ; Xuechun TANG ; Xiaoyin CHEN ; Shengquan PENG ; Xuemei CHEN ; Bingde LUO ; Jingbo SUN ; Yunsheng XU ; Min MA
Chinese Journal of Pathophysiology 1989;0(06):-
AIM: To study the preventive effects of Keningfang decoction on the experimental influenza virus pneumonia in mice and its mechanism. METHODS: Fifty NIH mice were divided into five groups randomly (ten mice in each group), normal control group, model group, virazole treatment group, Keningfang I treatment group, Keningfang II treatment group. The FM 1 virus strain that kept in frozen condition were revived and cultured in chick embryo. The mice in every group that were lightly anesthetized by aether, and infected by dropping FM 1 15 LD 50 into the nose, except for the normal control group, by equal volume distilled water. Mice were treated with drugs or distilled water two days before the model was made (0 3 mL, 2 times a day). The mice were treated with drug for six days, then was killed, the lungs were collected, and kept in -70 ℃. HSP70 was measured in the lung tissue by Western blot. Pathologic changes of the mice lungs were observed under microscope. RESULTS: Compared with the normal control group, HSP70 in the other groups were increased significantly (P
6.Deciphering bioactive compounds of complex natural products by tandem mass spectral molecular networking combined with an aggregation-induced emission based probe
Zhenzhong YANG ; Jun LI ; Xuechun CHEN ; Xiaoping ZHAO ; Yi WANG
Journal of Pharmaceutical Analysis 2022;12(1):129-135
Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we proposed a robust and convenient strategy for deciphering the bioactive profile of natural products by mass spectral molecular networking combined with rapid bioassay.As a proof-of-concept,the strategy was applied to identify angiotensin converting enzyme(ACE)inhibitors of Fangjihuangqi decoction(FJHQD),a traditional medicine clinically used for the treatment of heart failure.The chemical profile of FJHQD was comprehensively revealed with the assistance of tandem mass spectral molecular networking,and a total of 165 compounds were identified.With characterized constituents,potential clinical applications of FJHQD were predicted by Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine,and a range of cardiovascular related diseases were significantly enriched.ACE inhibitory activities of FJHQD and its constituents were then investigated with an aggregation-induced emission based fluorescent probe.FJHQD exhibited excellent ACE inhibitory effects,and a bioactive molecular network was established to elucidate the ACE inhibitory profile of constituents in FJHQD.This bioactive molecular network provided a panoramic view of FJHQD's ACE inhibitory ac-tivities,which demonstrated that flavones from Astragali Radix and Glycyrrhizae Radix et Rhizoma,saponins from Astragali Radix,and sesquiterpenoids from Atractylodis Macrocephalae Rhizoma were principal components responsible for this effect of FJHQD.Among them,four novel ACE inhibitors were the first to be reported.Our study indicated that the proposed strategy offers a useful approach to un-cover the bioactive profile of traditional medicines and provides a pragmatic workflow for exploring bioactive components.
7.Omics analysis of angiotensin converting enzyme 2 inhibitory mutation-related inflammatory response and intervention drugs and its significance on corona virus disease 2019
Jundong ZHANG ; Ximeng CHEN ; Haoran CHEN ; Xiaohua CHI ; Bin GUO ; Peng ZHI ; Zhuoyang LI ; Geliang LIU ; Haomin ZHANG ; Bo YANG ; Yixing WANG ; Haiying WANG ; Xuechun LU
Chinese Journal of Infectious Diseases 2020;38(10):609-615
Objective:To analyze the inflammatory mechanism and potential intervention drugs related to angiotensin converting enzyme 2 (ACE2) inhibitory mutations in order to provide reference for the treatment of corona virus disease 2019 (COVID-19).Methods:The data of lung adenocarcinoma with ACE2 mutations were screened from the cancer genome atlas (TCGA) database. The data were analyzed by R program language edgeR package and cluster Profiler package, gene ontology (GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Using String online analysis website for protein-protein interaction (PPI) network analysis, screening out the core genes, and finally using the Epigenomic Precision Medicine Prediction Platform (EpiMed) for multi-group association analysis of key genes, and drug candidates prediction.Results:A total of 1 005 differential genes were obtained, of which 91 were up-regulated and 914 down-regulated. A total of 71 GO were enriched, including 45 items related to biological processes, 16 items related to cell components, and 10 items related to molecular function. A total of 13 KEGG pathways were enriched, mainly in inflammatory pathways, various viral infectious diseases, transcriptional regulation, drug metabolism and protein digestion and absorption pathways. The differentially expressed genes were introduced into String online analysis website for PPI network analysis, a total of 252 proteins were obtained, and 10 core genes were H2A clustered histone 16(HIST1H2AL), H3 clustered histone 2 (HIST1H3B), H3 clustered histone 7 (HIST1H3F), H3 clustered histone 11 (HIST1H3I), H3 clustered histone 3 (HIST1H3C), H2B clustered histone 3 (HIST1H2BB), H2B clustered histone 6 (HIST1H2BI), H4 clustered histone 2 (HIST1H4B), H1-4 linker histone (HIST1H1E), H2A clustered histone 4 (HIST1H2AB). Interferon-α, resveratrol, celecoxib, heartleaf houttuynia herb, weeping forsythia capsule, dexamethasone, Chinese pulsatilla root, tumor necrosis factor-α inhibitors, liquorice root and famciclovir might be drugs for the treatment of ACE2 mutation-related inflammation.Conclusions:Inflammation associated with ACE2 inhibitory mutations is similar to the pathogenesis of COVID-19, which could lead to disease by promoting the activation of inflammatory pathways such as mitogen-activated protein kinase (MAPK), the Janus kinase signal transducer and activator of transcription (JAK/STAT), mammalian target of rapamycin (mTOR). Celecoxib, interferon and resveratrol may have the potential therapeutic effects on COVID-19.
8.Transcriptomic mechanisms and efficacy analysis of D-CAG regimen for treatment of acute myeloid leukemia after failure to initial induction of remission
Zhanqiang ZHANG ; Jundong ZHANG ; Peng ZHI ; Zining WANG ; Haoran CHEN ; Hongyi LI ; Xuechun LU
Journal of Leukemia & Lymphoma 2022;31(5):271-277
Objective:To investigate the transcriptomic mechanisms and clinical efficacy of D-CAG regimen for the treatment of acute myeloid leukemia (AML) after failure to initial induction of remission.Methods:The transcriptome data of AML cells before and after the use of dexitabine before August 28, 2021 was searched in Gene Expression Omnibus (GEO) database with "decitabine" as the search term. The R language package was used for differential expression analysis and Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis of the data. Protein-protein interaction network (PPI) analysis was conducted on the STRING online analysis website. The accurate treatment prediction platform designed based on logistic omics theory (EpiMed) was used to make drug-disease-target correlation analysis. The clinical data of 18 AML patients treated with D-CAG regimen after failure to induction of remission with standard anthracycline and cytarabine regimen ("3+7" regimen) in the 305th Hospital of Chinese PLA from October 8, 2015 to July 9, 2018 were searched and analyzed, and the curative effect was evaluated. The effects of the dose and duration of each drug on the efficacy were analyzed.Results:The transcriptome data of AML cells before and after the use of decitabine in GSE40442 dataset of the GPL5188 platform were finally selected, updated on July 10, 2014. A total of 366 differentially expressed genes were screened, including 201 up-regulated genes and 165 down-regulated genes. The differential genes were mainly related to cell cycle regulation, bone marrow leukocyte migration and differentiation, transcriptional regulation, bone marrow hematopoiesis and other signaling pathways. Ten core genes such as ANXA5, IL-10, THBS1, TLR4, JUN and CXCL12 were screened by PPI analysis. Drug-disease-target analysis showed that dexitabine had a potential therapeutic effect on various blood diseases such as diffuse large B-cell lymphoma, thrombocytopenia, T-cell acute lymphocytic leukemia, aplastic anemia, and AML. Of the 18 patients, after initial induction of remission, 7 (38.8%) patients achieved partial remission (PR), and 11 (61.2%) patients had no response (NR); after one cycle of re-induction remission therapy, 9 patients had complete remission (CR), 5 patients had PR, 4 patients had NR, and the overall response rate (ORR) was 77.8% (14/18). Compared with patients with NR, the CR rate was higher in patients with PR after initial induction therapy, which were 85.7% (6/7) and 27.3% (3/11), and the difference was statistically significant ( χ2=5.84, P = 0.025). The median duration of cytarabine in CR patients was longer than that in NR patients [10 d (7-14 d) vs. 5 d (2-8 d), Z = 3.89, P = 0.002] and the median ratio of the number of bone marrow blast cells to the duration cytarabine was lower in CR patients than that in NR patients [2.29 (0.89-9.10) vs. 8.10 (3.00-38.50), Z = -2.19, P = 0.006]; the median dose of cytarabine in CR patients was lower than NR patients, which were 50 mg·m -2·d -1 (30-150 mg·m -2·d -1) and 100 mg·m -2·d -1 (50-500 mg·m -2·d -1), and the difference was not statistically significant ( Z = -1.80, P = 0.074). Conclusions:AML patients with PR after initial induction and failure to initial induction of remission may be more likely to achieve CR after the treatment of D-CAG regimen, and this change may be related to the epigenetic regulation of decitabine.
9.Effect of sarcopenia on the perioperative clinical outcomes of esophageal squamous cell carcinoma
Wenze TIAN ; Zhenbing YOU ; Mingzhi ZHANG ; Mengzhou CHEN ; Xuechun LENG ; Dafu XU ; Chao JIANG ; Kang XU ; Keping XU
Chinese Journal of Digestive Surgery 2023;22(11):1322-1329
Objective:To investigate the effect of sarcopenia on the perioperative clinical outcomes of esophageal squamous cell carcinoma (ESCC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 1 148 ESCC patients who were admitted to the Affiliated Huaian No.1 People′s Hospital of Nanjing Medical University from January 2020 to December 2021 were collected. There were 789 males and 359 females, aged (67±7)years. All patients under-went thoracoscopic and laparoscopic radical esophagectomy for esophageal cancer. Observation indicators: (1) incidence of sarcopenia in patients with ESCC; (2) comparison of general data between ESCC patients complicated with sarcopenia and those without sarcopenia; (3) comparison of clinical outcomes between ESCC patients complicated with sarcopenia and those without sarcopenia; (4) analysis of influencing factors for sarcopenia in ESCC patients. Measurement data of normal distri-bution were represented by Mean± SD, and comparison between groups was conducted using the t test. Count data were represented as absolute numbers, and comparison between groups was conducted using the chi-square test. Ordinal data was analyzed using the Mann-Whitney U test. Logistic regression analysis was used to conduct univariate analysis. Logistic backward stepwise regression model was used to conduct multivariate analysis. Results:(1) Incidence of sarcopenia in patients with ESCC. Among 1 148 ESCC patients, 469 cases were complicated with sarcopenia, 679 were without sarcopenia. The incidence of sarcopenia was 40.854%(469/1 148). Among the 469 patients with sarcopenia, there were 313 males and 156 females. There were 125 cases <65 years old, 145 cases ≥65 years old but <70 years old, 106 cases ≥70 years old but<75 years old, 93 cases ≥75 years old, respectively. (2) Comparison of general data between patients with ESCC complicated with sarco-penia and those without sarcopenia. The age, tumor diameter, body mass index, cases in stage T1, T2, T3, preoperative albumin, preoperative serum prealbumin, psoas muscle index, psoas muscle density were (68±7)years, (3.3±1.5)cm, (22.4±2.9)kg/m 2, 100, 105, 264, (43±4)g/L, (193±38)mg/dL, (3.9±0.8)cm 2/m 2, (48±8)HU of 469 ESCC patients complicated with sarcopenia, versus (66±7)years, (3.2±1.4)cm, (23.8±3.0)kg/m 2, 173, 170, 336, (44±4)g/L, (206±37)mg/dL, (6.0±2.2)cm 2/m 2, (50±7)HU of 679 ESCC patients without sarcopenia, showing significant differences between the two groups ( t=5.74, 2.11, 7.57, Z=-2.93, t=2.25, 5.52,20.36, 4.18, P<0.05). (3) Comparison of clinical outcomes between patients with ESCC complicated with sarcopenia and those without sarcopenia. The duration of postoperative hospital stay, cases with postoperative hospital stay>30 days, pneumonia, acute respiratory failure, anastomotic fistula, and abnormal heart rhythm were (17±9)days, 32, 158, 39, 33, and 103 of 469 ESCC patients complicated with sarcopenia, respectively, versus (15±6)days, 15, 102, 18, 19, and 85 of 679 ESCC patients without sarcopenia, showing significant differences between the two groups ( t=4.89, χ2=15.04, 55.17, 18.86, 11.52, 18.06, P<0.05). (4) Analysis of influencing factors for sarcopenia in ESCC patients. Results of multivariate analysis showed that age ≥65 years was an independent risk factor for sarcopenia in ESCC patients ( odds ratio=1.64, 95% confidence interval as 1.26-2.14, P<0.05). Preoperative serum prealbumin ≥200 mg/dL, psoas muscle density ≥48 HU and body mass index >24 kg/m 2 were independent protective factors for sarcopenia in ESCC patients ( odds ratio=0.64, 0.72, 0.53, 95% confidence interval as 0.50-0.82, 0.56-0.92, 0.41-0.69, P<0.05). Conclusions:Age ≥65 years is an independent risk factor for sarcopenia in ESCC patients. Preoperative serum prealbumin ≥200 mg/dL, psoas muscle density ≥48 HU and body mass index >24 kg/m 2 are independent protective factors for sarcopenia in ESCC patients. Compared with patients without sarcopenia, ESCC patients with sarcopenia are more prone to postoperative compli-cations such as pneumonia, acute respiratory failure, anastomotic fistula, and arrhythmia, and have a longer postoperative hospital stay.
10.Bioinformatics prediction of molecular mechanism and intervention drugs of SARS-related immune injury and their significance for COVID-19 treatment
Haomin ZHANG ; Haoran CHEN ; Yakun YANG ; Ximeng CHEN ; Jundong ZHANG ; Bin GUO ; Peng ZHI ; Zhuoyang LI ; Geliang LIU ; Bo YANG ; Xiaohua CHI ; Yixing WANG ; Xuechun LU
Chinese Journal of Microbiology and Immunology 2020;40(3):165-173
Objective:To investigate the omics mechanism of SARS-related immune injury and predict targeted therapeutic drugs through clinical bioinformatics analysis of the transcriptome data of SARS virus in order to provide reference for clinical treatment of COVID-19.Methods:The transcriptome data of SARA virus were collected from the Gene Expression Oibus (GEO) and used to screen differential genes. Enrichment analysis and protein interaction analysis were performed to investigate the mechanism of immune damage associated with SARS. A platform of epigenetics in precision medicine (EpiMed) was established to predict potential therapeutic drugs.Results:The mechanism of SARS-related immune injury was complex, involving affecting the function of immune cells through signaling pathways such as Toll-like receptors, increasing cytokines in plasma through Th17 signaling pathway and inducing autoimmune responses after autoantibodies were generated by molecules such as IL-6, NF-κB, and TNF. Drugs such as Chuanqiong and Etanercept might have therapeutic effects on SARS-related immune damage.Conclusions:SARS virus could cause abnormal expression of many immune-related molecules and signaling pathways. Drugs such as Chuanqiong and Etanercept might have therapeutic effects on SARS-related immune damage. This study might provide reference for clinical treatment of COVID-19.