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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.
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Severe upper extremity tendon injuries can have a major impact on the life of their victims. For patients with multiple tendon defects, allogeneic tendon transplantation is one of the fine methods to reconstruct their limb function because of its advantages of limited trauma and significant clinical effects. Before allogeneic tendon transplantation, clinical orthopaedists should fully understand its advantages, disadvantages and indications so that they can choose the most suitable protocols for diagnosis and treatment of the patients. Chinese and foreign scholars have done a lot of work in research of and report on allogeneic tendon transplantation since its first application to repair and reconstruct tendons. This article reviews the preservation, treatment, immune rejection and clinical effects of allogeneic tendon transplantation in upper limb injury.
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Objective@#To investigate the difference of temporary memory system and brain biochemical metabolites between patients with depressive obsessive-compulsive disorder and simple obsessive-compulsive disorder.@*Methods@#From June 2017 to June 2018, 31 patients with simple obsessive-compulsive disorder, 33 patients with depressive obsessive-compulsive disorder and 25 healthy volunteers were selected as subjects. The temporary memory ability of the three groups was tested by n-back, Stoop color association test and digital breadth test. Three brain sublimation metabolites, N-acetylaspartate acid (NAA), choline complex (Cho) and creatine (Cr), were detected by proton magnetic resonance pop (1H-MRS) in bilateral prefrontal white matter, anterior cingulate cortex and anterior cingulate cortex. The ratio of NAA/Cr and Cho/Cr was calculated with Cr as reference material.@*Results@#The scores of Yale-brown obsessive-compulsive severity scale (Y-BOCS) and Hamilton depression rating scale 24 (HAMD24) in the patients with simple obsessive-compulsive disorder and depression obsessive-compulsive disorder group were significantly higher than those in the healthy control group, and the scores of HAMD24 in the patients with depression obsessive-compulsive disorder group were significantly higher than those in the patients with simple obsessive-compulsive disorder group, with statistically significant difference (P<0.05). The number of correct n-back in the simple obsessive-compulsive group and the depressive obsessive-compulsive group was significantly lower than that in the healthy control group (P<0.05). The digital span test (DST) scores of the patients in the simple obsessive-compulsive disorder group and the depressive obsessive-compulsive disorder group were (14.37±2.96) and (12.39±2.14), which were significantly lower than those in the healthy control group (17.46±3.28) (P<0.05). There was no significant difference in NAA/Cr and Cho/Cr between the three groups (P>0.05). Compared with the healthy control group, the NAA/Cr value of bilateral prefrontal white matter in the simple obsessive-compulsive group and the depression obsessive-compulsive group was significantly lower, and the difference was statistically significant (P<0.05).@*Conclusions@#Both patients with simple obsessive-compulsive disorder and depressive obsessive-compulsive disorder had speech memory impairment and bilateral prefrontal white matter nerve function decline, while depressive obsessive-compulsive disorder patients also had central executive memory impairment.
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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.
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Objective To investigate the difference of temporary memory system and brain biochemical metabolites between patients with depressive obsessive-compulsive disorder and simple obsessivecompulsive disorder.Methods From June 2017 to June 2018,31 patients with simple obsessive-compulsive disorder,33 patients with depressive obsessive-compulsive disorder and 25 healthy volunteers were selected as subjects.The temporary memory ability of the three groups was tested by n-back,Stoop color association test and digital breadth test.Three brain sublimation metabolites,N-acetylaspartate acid (NAA),choline complex (Cho) and creatine (Cr),were detected by proton magnetic resonance pop (1 H-MRS) in bilateral prefrontal white matter,anterior cingulate cortex and anterior cingulate cortex.The ratio of NAA/Cr and Cho/Cr was calculated with Cr as reference material.Results The scores of Yale-brown obsessivecompulsive severity scale (Y-BOCS) and Hamilton depression rating scale 24 (HAMD24) in the patients with simple obsessive-compulsive disorder and depression obsessive-compulsive disorder group were significantly higher than those in the healthy control group,and the scores of HAMD24 in the patients with depression obsessive-compulsive disorder group were significantly higher than those in the patients with simple obsessive-compulsive disorder group,with statistically significant difference (P ＜ 0.05).The number of correct n-back in the simple obsessive-compulsive group and the depressive obsessive-compulsive group was significantly lower than that in the healthy control group (P ＜0.05).The digital span test (DST) scores of the patients in the simple obsessive-compulsive disorder group and the depressive obsessive-compulsive disorder group were (14.37 ± 2.96) and (12.39 ± 2.14),which were significantly lower than those in the healthy control group (17.46 ± 3.28) (P ＜ 0.05).There was no significant difference in NAA/Cr and Cho/Cr between the three groups (P ＞ 0.05).Compared with the healthy control group,the NAA/Cr value of bilateral prefrontal white matter in the simple obsessive-compulsive group and the depression obsessivecompulsive group was significantly lower,and the difference was statistically significant (P ＜ 0.05).Conclusions Both patients with simple obsessive-compulsive disorder and depressive obsessive-compulsive disorder had speech memory impairment and bilateral prefrontal white matter nerve function decline,while depressive obsessive-compulsive disorder patients also had central executive memory impairment.
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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.
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Objective To find the target of auranofin with the antibacterial activity against gramnegative bacteria and to investigate the effect of the combination of auranofin and vorinostat on the antibacterial activity against gram-negative bacteria.Methods The strains of E.coli lacking thioredoxin reductase (TrxR)was used to find the target gene.The potential synergies of the combination of auranofin and vorinostat for E.coli strain,A.baumannii strain,P.aeruginosa strain,K.pneumonia strain and muhidrug-resistant (MDR)A.baumannii strain were evaluated using susceptibility tests,micro-dilution checkerboard tests and time-kill studies.The genes related to Trx (trxA,trxB,trxC) and the gene expressed glutathione (gor) of E.coli BW25113 strains (WT) were separately knocked out to observe the effect of auranofin on minimum inhibitory concentration (MIC) and the time-kill kinetics of △trxC and △gor.Furthermore,the complemented strains (C-trxA,C-trxB,C-trxC,C-gor) were used to verify and define the genetic targets.Results According to the results of susceptibility tests,MICs of auranofin were 64 mg/L for E.coli strain BW25113 and K.pneumonia strain ATCC 43816,128 mg/L for P.aeruginosa strain PA14 and 32 mg/L for both A.baumannii strain ATCC 17978 and A.baumannii strain AB5075.However,MICs of vorinostat are 512 mg/L for all isolates.The fractional inhibitory concentration indexes (FICIs) of the combination of auranofin and vorinostat for E.coli strain BW25113,A.baumannii strain ATCC 17978,MDR A.baumannii strain AB5075,K.pneumonia starin ATCC 43816 and P.aeruginosa strain PAl4 were 0.313,0.375,0.375,0.375,and 0.375,respectively,with all values ＜ 0.5,which showed synergy.In susceptibility tests of knockout strains,MICs of auranofin for △trxC increased from 64 mg/L to 256 mg/L,decreased to 16 mg/L for △gor,and no changes for △trxA and △trxB.Auranofin showed the same antibacterial activities against the complemented strains (C-trxC,C-gor) and E.col BW25113,which decreased by about 1.8 lg colong formins units (CFU)/mL of bacterial counts.However,the antibacterial activity of auranofin was significantly reduced for △trxC,and decreased by ＜ 1 lg CFU/mL of bacterial counts.For Agor,bacterial counts decreased 4.6 lg CFU/mL,and the antibacterial activity markedly increased.Conclusions The potential target gene of auranofin against gram-negative bacteria could be trxC,which provides new ideas and methods for the clinical treatment of multidrug-resistant gram-negative bacteria.
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BACKGROUND@#Current research shows that platelet to lymphocyte ratio (PLR) has important prognostic value in renal cell carcinoma, esophageal cancer, gastric cancer, liver cancer and colon cancer. The aim of the study is to evaluate the prognostic value of PLR in non-small cell lung cancer (NSCLC) through meta-analysis.@*METHODS@#Literature search for PubMed, EMBASE, Web of Science, Medline, Cochrane Library, China National Knowledge Internet (CNKI), China Biomedical Medicine disc (CBMdisc), VIP, Wanfang Database using computer electronic system to study the association between PLR and overall survival (OS) and disease-free survival (DFS). Each eligible study data is extracted and a meta-analysis is performed using the hazard risk (HR) and 95% confidence interval (95%CI) to assess the prognostic value of PLR, the time limit for the search is to build the library until November 2018.@*RESULTS@#We include a total of 15 research literatures involving 5,524 patients for meta-analysis. According to the results of the meta-analysis: The OS of the higher PLR group is significantly lower than that of the lower PLR group (HR=1.69, 95%CI: 1.45-1.97, P<0.000,01, I²=46.2%, Pheterogeneity=0.026); the DFS of the higher PLR group is significantly lower than that of the lower PLR group (HR=1.41, 95%CI: 1.14-1.74, P=0.001, I²=46.2%, Pheterogeneity=0.026). Subgroup analysis show that the OS of the higher PLR group is still significantly lower than the lower PLR group (P<0.05) after grouping by ethnicity, sample size, PLR cutoff value and treatment.@*CONCLUSIONS@#Increased PLR is associated with poor prognosis in NSCLC, so PLR may be an important biological predictive marker for NSCLC patients, however, its clinical application still needs to be verified through more research in the future.
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Humans , Blood Platelets , Cell Biology , Carcinoma, Non-Small-Cell Lung , Blood , Diagnosis , Pathology , Lung Neoplasms , Blood , Diagnosis , Pathology , Lymphocytes , Cell Biology , Platelet Count , PrognosisABSTRACT
OBJECTIVE: To extract and isolate Isatidis indigotica polysaccharide A(with uniform molecular weight) and to study its structure.METHODS: Hydrosoluble crude polysaccharides were extracted from Isatidis indigotica before being separated and purified by column chromatography to obtain polysaccharide A.The purity and relative molecular weight of polysaccharide A were determined by high performance gel chromatography(HPGPC) and the chemical structure each polysaccharide constituent was studied by UV detection,IR spectral analysis,NMR detection,periodate oxidation and Smith degradation methods.RESULTS: The average molecular weight of polysaccharide A was 11 700.Arabinose and galactose were the major monosaccharide;? was the major configuration of glycosidic bond was predominantly,and 1→3 was the main linkage while 1→4 and/or 1→2 linkages were also presented in polysaccharides A.CONCLUSION:Isatidis indigotica polysaccharides A is a new compound,and its purity remains as high as above 96%.
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Objective The aim of our study was to examine the utility of a mutielectrode basket catheter (MBC) in the mapping and Ablation of atrial tachycardias (ATs). Methods and Results This study of ATs was conducted in 15 patients. The MBC recording and pacing capabilities, mapping performance and ablation with MBC was evaluated. Stable endocardial electrograms were recorded in 88±4% of electrodes. 64±5% electrode pairs could be used to stimulate the heart. Earliest endocardial activation was recorded from MBC and standard catheters were 41±9 and 45.9±8 m before the onset of P-wave,respectively (P=0.21). Ablation successed in 7 patients (87.5%). Conclusion The MBC allows comprehensive and reliable endocardial mapping during ATs, which facilitates successful ablation in the patients with ATs.