1.Value of Cuproptosis genes and characteristic genes in predicting prognosis,immunity and tumor microenvironment in acute myeloid leukemia
Yinzhen LI ; Weixia NONG ; Mei ZHANG ; Dongsheng RUI ; Wei LEI ; Wenli BAI ; Rui LI ; Yazhou ZHANG ; Kui WANG
Acta Universitatis Medicinalis Anhui 2024;59(6):1013-1022
Objective To screen Cuproptosis genes and characteristic genes for differential prognosis in acute mye-loid leukemia(AML)and explore their prognosis in AML as well as their biological roles and correlations in the immune and tumor microenvironment.Methods AML clinical,transcriptome,genomic,and copy number data were downloaded from three major databases,TCGA,GEO,and UCSC,and Cuproptosis genes were collected from published studies.From the perspective of multiomics,the effects of Cuproptosis gene and characteristic gene on survival,immunity,tumor microenvironment,stem cell correlation and drug sensitivity were studied by various bioinformatics methods,meta-analysis and secondary typing.Results One Cuproptosis gene was identified as a differential prognostic gene in AML and five characteristic genes were identified as influencing the prognosis of AML patients by influencing Cuproptosis,and a prognostic model was established.The differential genes were mainly concentrated in mitochondrial activity,REDOX enzyme and energy metabolism.In terms of immunity,macrophage M0,neutrophils,activated memory CD4 T cells and Tregs were positively correlated with risk score,while macro-phage M2,resting mast cells,immature CD4 T cells,helper follicular T cells and memory B cells were negatively correlated with risk score.In terms of tumor microenvironment,the immune cell score of the low-risk group was lower than that of the high-risk group,and in the total score,the tumor microenvironment score of the low-risk group was also lower than that of the high-risk group,indicating that the tumor purity of the high-risk group was lower than that of the low-risk group.However,there was no significant association between stem cells in the high-risk and low-risk groups,and a total of 14 drugs were found to be sensitive to treat AML.Conclusion Cuproptosis gene and characteristic gene are closely related to immune and tumor microenvironment in AML by constructing a prognostic model of AML.
2.Application of convolutional neural network in flow cytometry diagnosis of acute myeloid leukemia
Wei Lei ; Zhiwei Li ; Dongsheng Rui ; Mei Zhang ; Yujuan Guo ; Wenli Bai ; Kui Wang
Acta Universitatis Medicinalis Anhui 2023;58(7):1189-1193
Objective :
A convolutional neural network (CNN) model was established to automatically analyze flow
cytometry (FCM) data to achieve the preliminary diagnosis of acute myeloid leukemia(AML) , and explore the feasibility of applying CNN model to FCM data analysis.
Methods :
The exploratory study of CNN application was carried out using the bone marrow FCM data obtained by the FlowRepository database and the Clinical Testing Center of Xinjiang Uygur Autonomous Region People ′ s Hospital , and the data had been clinically confirmed whether AML was present. Among them , the public data was divided into training sets , validation sets and test sets according to 6 ∶ 2 ∶ 2 , and local data was used for external test; In order to adapt the FCM data to the CNN model , an
FCM data structure based on the image matrix principle was proposed , and after preprocessing the original data , the variables related to the preliminary diagnosis of AML were extracted , including sidescattered light and the expression levels of CD45 , CD13 , CD33 , HLA⁃DR , CD117 , CD34 , and each variable was written into the matrix. Cell sampling and data augmentation methods were used to increase the sample size of the training set , the keras software package was used to build the LeNet⁃5 CNN model in Python , and the training set and the validation set were used for model training and parameter tuning respectively to evaluate the performance of the model on the test set.
Results :
The accuracy of CNN to identify AML on the two test sets was 0. 931 , 0. 851 , the sensitivity was 0. 667 ,
0. 636 , the specificity was 0. 968 , 0. 940 , and the area under the receiver operating characteristic curve was 0. 940
and 0. 917.
Conclusion
Based on the proposed FCM data structure , the CNN model can realize the preliminary
diagnosis of AML , indicating that CNN has certain application value in FCM data analysis.
3.Effectiveness of a new health education pathway for echinococcosis control among primary school students in hyper-endemic regions
Yan KUI ; Shuai HAN ; Bai-Xue LIU ; Tian TIAN ; Wen-Jie YU ; Ren-Xin YAO ; Xu WANG ; Wei-Ping WU
Chinese Journal of Schistosomiasis Control 2021;33(3):254-261
Objective To investigate the effectiveness of a new health education pathway for echinococcosis control among primary school students in regions highly prevalent for echinococcosis in China. Methods Six primary schools were randomly selected from echinococcosis hyper-endemic regions, with 13 classes assigned to the intervention group and 9 to the control group, and all students in these 21 classes were recruited as the study subjects. Echinococcosis health education was performed through the pathway of assessing the current status-strengthening the building of teaching resources-focusing on practices in the intervention group, while routine health education was given in the control group. A questionnaire survey was performed to assess the score of echinococcosis control knowledge (including theoretical knowledge score and mean daily practical capability score) before and after the health education interventions to evaluate the effectiveness of this new health education pathway for echinococcosis control. Results The mean score of echinococcosis control knowledge was 68.86 ± 18.70 points at baseline, with the mean theoretical knowledge score of 40.97 ± 10.75 points, and the mean daily practical capability score of 27.89 ± 12.50 points. Clustering analysis showed three types of populations, including “unsatisfactory”, “learn and apply creatively”, and “rote learning”, which accounted for 24.62% (240/975), 45.74% (446/975) and 29.64% (289/975), respectively. The mean score of echinococcosis control knowledge was 81.08 ± 18.15 points in the intervention group during the final assessment, with the mean theoretical knowledge score of 43.65 ± 9.40 points, and the mean daily practical capability score of 37.43 ± 12.22 points, and both were significantly higher relative to baseline (t = −4.201 and −15.202, both P values < 0.01). The mean score of echinococcosis control knowledge was comparable between at baseline (70.55 ± 19.46 points) and final assessment (71.74 ± 19.37 points) in the control group (t = −0.87, P > 0.05). Conclusions The awareness of echinococcosis control knowledge is fair among primary school students in echinococcosis hyper-endemic regions; however, the capability of combining theoretical learning and practices requires to be improved. The health education mode based on the pathway of assessing the current status-strengthening the building of teaching resources-focusing on practices seems to remarkably improve the understanding of echinococcosis control knowledge among primary school students in echinococcosis hyper-endemic regions.
4.VSD technique combined with Ointment for the treatment of foot skin defects.
Wen-Bo BAI ; Ruo-Xiao ZHANG ; Jun-Kui XU ; Jun LU ; Xiao-Jun LIANG ; Jun-Hu WANG
China Journal of Orthopaedics and Traumatology 2020;33(9):873-877
OBJECTIVE:
To explore the clinical effect of vacuum sealing drainage (VSD) technique and Ointment in the treatment of foot skin defect.
METHODS:
From November 2017 to April 2019, 21 patients (21 feet) with foot skin defect were treated with VSD technique and Ointment. There were 17 males and 4 females, aged from 24 to 60 years old with an average of (37.8±11.2) years, 9 cases caused by traffic accident injury, 6 cases by heavy injury, 6 cases by falling injury. The time from injury to operation was for 3 to 36 (8.6±7.2) h, and the area of foot skin defect was for 20.35 to 83.43(47.2±19.5) cm. All patients underwent debridement or phaseⅠtemporary fixation in emergency, and three-dimensional imagingof the foot was performed by using Mimics software, and the defect area was rendered. The quality of wound healing and complications were observed, and the clinical effect was evaluated by Maryland foot function score.
RESULTS:
All the 21 patients were followed up for 7 to 17 (10.8±2.7) months. There was no infection or nonunion in all patients. At the final follow-up, the skin margin of the healing site grew tightly, the skin was elastic, the texture was tough, the appearance was no obvious carbuncle. The time of wound healing was for 18 to 63 (41.2±13.3) days. Eight patients underwent stageⅡfixation or/and fusion, and all incisions healed by stageⅠ. According to Maryland's foot scoring, 9 cases got excellent results, 11 good, and 1 middle.
CONCLUSION
VSD can effectively remove the necrotic tissue of the wound, provide a smooth drainage of the wound, combine with Ointment to prevent infection and promote the rapid growth of granulation tissue, whose whole treatment cycle was short, the wound healing site was highquality, the limb function was good, and the clinical effect was satisfactory.
Adult
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Drainage
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Female
;
Humans
;
Male
;
Middle Aged
;
Negative-Pressure Wound Therapy
;
Skin Transplantation
;
Soft Tissue Injuries
;
surgery
;
Treatment Outcome
;
Young Adult
5.Glycyrrhizic acid activates chicken macrophages and enhances their Salmonella-killing capacity in vitro.
Bai-Kui WANG ; Yu-Long MAO ; Li GONG ; Xin XU ; Shou-Qun JIANG ; Yi-Bing WANG ; Wei-Fen LI
Journal of Zhejiang University. Science. B 2018;19(10):785-795
OBJECTIVE:
Salmonella enterica remains a major cause of food-borne disease in humans, and Salmonella Typhimurium (ST) contamination of poultry products is a worldwide problem. Since macrophages play an essential role in controlling Salmonella infection, the aim of this study was to evaluate the effect of glycyrrhizic acid (GA) on immune function of chicken HD11 macrophages.
METHODS:
Chicken HD11 macrophages were treated with GA (0, 12.5, 25, 50, 100, 200, 400, or 800 μg/ml) and lipopolysaccharide (LPS, 500 ng/ml) for 3, 6, 12, 24, or 48 h. Evaluated responses included phagocytosis, bacteria-killing, gene expression of cell surface molecules (cluster of differentiation 40 (CD40), CD80, CD83, and CD197) and antimicrobial effectors (inducible nitric oxide synthase (iNOS), NADPH oxidase-1 (NOX-1), interferon-γ (IFN-γ), LPS-induced tumor necrosis factor (TNF)-α factor (LITAF), interleukin-6 (IL-6), and IL-10), and production of nitric oxide (NO) and hydrogen peroxide (H2O2).
RESULTS:
GA increased the internalization of both fluorescein isothiocyanate (FITC)-dextran and ST by HD11 cells and markedly decreased the intracellular survival of ST. We found that the messenger RNA (mRNA) expression of cell surface molecules (CD40, CD80, CD83, and CD197) and cytokines (IFN-γ, IL-6, and IL-10) of HD11 cells was up-regulated following GA exposure. The expression of iNOS and NOX-1 was induced by GA and thereby the productions of NO and H2O2 in HD11 cells were enhanced. Notably, it was verified that nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways were responsible for GA-induced synthesis of NO and IFN-γ gene expression.
CONCLUSIONS
Taken together, these results suggested that GA exhibits a potent immune regulatory effect to activate chicken macrophages and enhances Salmonella-killing capacity.
Animals
;
Cells, Cultured
;
Chickens
;
Glycyrrhizic Acid/pharmacology*
;
Macrophage Activation/drug effects*
;
NF-kappa B/physiology*
;
Phagocytosis/drug effects*
;
Salmonella/drug effects*
;
Signal Transduction/drug effects*
6.Protective effects of total flavonoids extraction from ficus lacor leaves on A549 cells
Yang WANG ; Kui HU ; Ling CHEN ; Yan SU ; Jiahui MA ; Hong XIAO ; Qunhua BAI
Chongqing Medicine 2017;46(16):2178-2182
Objective To investigate the extraction method of total flavonoids from the leaves of ficus lacor and the protec tive effects of extraction on the cellular damage to provide a basis for the research on the phamaceutical value of ficus lacor leaves.Methods The ethanol extraction method was adopted to extract the total flavonoids in the leaves of ficus lacor and the extraction efficiency was calculated with rutin as the standard.The rotenone induced human lung adenocarcinoma cellular damage served as the model,then the influencesof the extraction on the cellular viability,cellular morphology,production of reactive oxygen species (ROS) and apoptosis were researched.Results The extraction efficiency of total flavonoids in the leaves of ficus lacor by 60% ethanol was 5.02%;the extraction at the concentration of 32 mg/L could significantly inhibit the decrease of cell viability,cellular shape change,ROS production and apoptosis of A549 cells induced by 100μg/L rotenone.Conclusion The ethanol extraction method can be used to extract the total flavonoids in the leaves of ficus lacor and the extraction has the protective effects on the A549 cellular dam age induced by rotenone,the leaves of ficus lacor have the potential for further researching its pharmaceutical value.
7.Study on active ingredient and mechanism in preventing vascular dementia of Tianzhusan coming from Tujia medicine.
Wen-bin ZHOU ; Li LIN ; Zhi-yong LI ; Tian BI ; Tian-yuan YE ; Cui-qiang MA ; Bao HONG-JUAN ; Hong-ping WANG ; Bai-xia ZHANG ; Kuo-kui SONG ; Yan-wen LI ; Yun WANG
China Journal of Chinese Materia Medica 2015;40(13):2668-2673
To make clear of the absorbed components of Tianzhusan (TZS) and its possible mechanism in preventing vascular dementia (VD), the rats' models of VD were prepared by a permanent ligation of the bilateral common carotid arteries. After 60 days, rats were administrated with TZS for 0.1 g x kg(-1), and the volume is 0.02 mL x g(-1). After 3 days, the medicated serum was prepared and detected by UPLC, and then we predicted the possible chemical structure of the absorbed components of TZS. According to the absorbed components, the potential targets of TZS were found by ligand profiling of Discovery Studio 3.5. All of these target genes were submitted to DAVID onine for gene set enrichment analysis (GSEA). The 5 absorbed components of TZS have been predicted, and four of them have been identified as parishin B, parishin C, parishin, pennogenin-3-O-alpha-L-rhamnopyranosy-(1-->2)-beta-D-glucoside. Through reverse finding targets, we got 861 pharmacophore models and 9 pathways from KEGG, BIOCARTA after document verification. These results showed that the efficacy mechanism of TZS on VD perhaps were be related with these absorbed components and pathways. If the traditional herbs could be proved effective by efficacy tests, the serum pharmacochemistry, computer-aided drug design, system biology and other technologies can be used in the next experiments, which will be beneficial to fast discovery of material basis and mechanisms of traditional medicine coming form ethnic minorities.
Animals
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Dementia, Vascular
;
prevention & control
;
Drug Discovery
;
Drugs, Chinese Herbal
;
therapeutic use
;
Gastrodia
;
chemistry
;
Male
;
Medicine, Chinese Traditional
;
Rats
;
Rats, Sprague-Dawley
;
Spectrometry, Mass, Electrospray Ionization
;
Trillium
;
chemistry
8.The toxic and protective effects of Polygonum multiflorum on normal and liver injured rats based on the symptom-based prescription theory.
Jing-yao PANG ; Zhao-fang BAI ; Ming NIU ; Can TU ; Zhi-jie MA ; Yan-ling ZHAO ; Kui-jun ZHAO ; Yun YOU ; Jia-bo WANG ; Xiao-he XIAO
Acta Pharmaceutica Sinica 2015;50(8):973-979
The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.
Alanine Transaminase
;
blood
;
Animals
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Aspartate Aminotransferases
;
blood
;
Bile Acids and Salts
;
metabolism
;
Bilirubin
;
blood
;
Chemical and Drug Induced Liver Injury
;
drug therapy
;
Drugs, Chinese Herbal
;
pharmacology
;
Fallopia multiflora
;
chemistry
;
HMGB1 Protein
;
metabolism
;
Hepatocytes
;
drug effects
;
Interleukin-1beta
;
metabolism
;
Liver
;
drug effects
;
pathology
;
Plant Extracts
;
pharmacology
;
Rats
;
Tumor Necrosis Factor-alpha
;
metabolism
9.Protection and bidirectional effect of rhubarb anthraquinone and tannins for rats' liver.
Lu-shan QIN ; Hai-ping ZHAO ; Yan-ling ZHAO ; Zhi-jiel MA ; Ling-na ZENG ; Ya-ming ZHANG ; Ping ZHANG ; Dan YAN ; Zhao-fang BAI ; Yue LI ; Qing-xiu HAO ; Kui-jun ZHAO ; Jia-bo WANG ; Xiao-he XIAO
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(6):698-703
OBJECTIVETo compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver.
METHODSOne hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis.
RESULTSCompared with the blank control group, all biochemical indices increased in the blank group (P < 0.05, P < 0.01). HA also increased in the blank + high dose TA group; AST, ALT, and HA also increased in the blank +high dose TT group (P < 0.05). Compared with the model group, AST, ALT, ALP, HA, and TGF-beta1 significantly decreased in the model + low dose TA group, the model + high dose TA group, the model + low dose TT group (P < 0.05, P < 0.01). Serum AST, ALT, and ALP also decreased in the model + high dose TT group (P < 0.05, P < 0.01). Pathological results showed that mild swollen liver cells in the model + high dose TA group. Fatty degeneration and fragmental necrosis around the central veins occurred in the blank + high dose TA group. The pathological injury was inproved in the model +low dose TA group. Two common factors, liver fibrosis and liver cell injury, were extracted by using factor analysis. TA showed stronger improvement of the two common factors than TT.
CONCLUSIONSRhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.
Animals ; Anthraquinones ; adverse effects ; pharmacology ; Carbon Tetrachloride ; toxicity ; Chemical and Drug Induced Liver Injury ; drug therapy ; pathology ; Dose-Response Relationship, Drug ; Female ; Liver ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry ; Tannins ; adverse effects ; pharmacology
10.Controlled release by novel lysostaphin-loaded hydroxyapatite/chitosan composites.
Jin-Cheng WANG ; Bai XUE ; Kui-Kui GE ; Yi-Han WANG ; Guo-Dong LI ; Qing-Shan HUANG
Acta Pharmaceutica Sinica 2014;49(9):1331-1339
Lysostaphin is highly effective on eliminating methicillin resistant Staphylococcus aureus (MRSA). In order to achieve controlled release of lysostaphin, a biocompatible drug carrier is needed. Hydroxyapatite/chitosan (HA/CS) composites were chosen to carry lysostaphin and sample composites with different weight ratios of HA to CS, including 80/20, 70/30, 60/40, and 40/60, were prepared. Multiple analyses were performed to determine the structural and physicochemical properties of the composites, including scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. We immersed HA/CS composites loaded with 1 wt% lysostaphin to test in vitro release activity and cultured MC3T3-E1 cells to carry out biocompatibility test. The result of the release behavior of the composites revealed that the controlled release of lysostaphin from 60/40 HA/CS composites was the highest release rate of (87.4 ± 2.8)%, which lasted for 120 hours. In biocompatibility testing, MC3T3-E1 cells were able to proliferate on the surface of these composites, and the extract liquid from the composites could increase the growth of the cells. These results demonstrate the controlled release of lysostaphin from HA/CS composites and their biocompatibility, suggesting the potential application of these composites to bone injury and infection applications.
3T3 Cells
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Animals
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Biocompatible Materials
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Chitosan
;
chemistry
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Delayed-Action Preparations
;
Drug Carriers
;
chemistry
;
Durapatite
;
chemistry
;
Lysostaphin
;
pharmacology
;
Materials Testing
;
Methicillin-Resistant Staphylococcus aureus
;
Mice
;
Microscopy, Electron, Scanning
;
X-Ray Diffraction


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