BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine t...BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.展开更多
BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate ...BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.展开更多
Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactiv...Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.展开更多
Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,h...Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.展开更多
Colorectal cancer(CRC)is a major global health problem with high morbidity and mortality rates.Surgical resection is the main treatment for early-stage CRC,but detecting it early is challenging.Therefore,effective the...Colorectal cancer(CRC)is a major global health problem with high morbidity and mortality rates.Surgical resection is the main treatment for early-stage CRC,but detecting it early is challenging.Therefore,effective therapeutic targets for advanced patients are still lacking.Exosomes,tiny vesicles in body fluids,play a crucial role in tumor metastasis,immune regulation,and drug resistance.Interestingly,they can even serve as a biomarker for cancer diagnosis and prognosis.Studies have shown that exosomes can carry miRNA,mediate the polarization of M1/M2 macrophages,promote the proliferation and metastasis of cancer cells,and affect the prognosis of CRC.Since the gastrointestinal tract has many macrophages,understanding the mechanism behind exosomal miRNA-mediated macrophage polarization in CRC treatment is crucial.This article summarizes recent advancements in the study of exosomal miRNAs in CRC and their potential as diagnostic and prognostic markers.展开更多
Background:Colorectal cancer is a major global health concern,exacerbated by tumor necrosis factor-alpha(TNF-α)and its role in inflammation,with the effects of Mitotic Arrest Deficient 2 Like 2(MAD2L2)in this context...Background:Colorectal cancer is a major global health concern,exacerbated by tumor necrosis factor-alpha(TNF-α)and its role in inflammation,with the effects of Mitotic Arrest Deficient 2 Like 2(MAD2L2)in this context still unclear.Methods:The colorectal carcinoma cell lines HCT116 and SW620 were exposed to TNF-αfor a period of 24 h to instigate an inflammatory response.Subsequent assessments were conducted to measure the expression of inflammatory cytokines,the activity within the p38 mitogen-activated protein kinase(p38 MAPK)and Phosphoinositide 3-Kinase/AKT Serine/Threonine Kinase pathway(PI3K/AKT)signaling cascades.Transcriptome sequencing and subsequent integrative analysis with the Cancer Genome Atlas(TCGA)program database revealed a significant downregulation of the key factor MAD2L2.Enhancement of MAD2L2 expression was facilitated via lentiviral vector-mediated transfection.The influence of this overexpression on TNF-α-prompted inflammation,intracellular signaling pathways,and the migratory and invasive behaviors of the colorectal cancer cells was then scrutinized.Results:TNF-αtreatment significantly increased the expression of Interleukin-1 beta(IL-1β)and Interleukin-6(IL-6),activated the MAPK p38 and PI3K/AKT signaling pathways,and enhanced cell migration and invasion.A decrease in MAD2L2 expression was observed following TNF-αtreatment.However,overexpression of MAD2L2 reversed the effects of TNF-α,reducing IL-1βand IL-6 levels,attenuating PI3K/AKT pathway activation,and inhibiting cell migration and invasion.Conclusions:Overexpression of MAD2L2 attenuates the pro-inflammatory effects of TNF-α,suggesting that MAD2L2 plays a protective role against TNF-α-induced migration and invasion of colorectal carcinoma cells.Therefore,MAD2L2 holds potential as a therapeutic target in the treatment of colorectal cancer.展开更多
BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction.Although the relationship between...BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction.Although the relationship between certain single probiotics and HBC has been explored,the impact of the complex ready-to-eat Lactobacillus paracasei N1115(LP N1115)supplement on patients with HBC has not been determined.AIM To compare the changes in the microbiota,inflammatory factor levels,and liver function before and after probiotic treatment in HBC patients.METHODS This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020.Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only.Fecal samples were collected at the onset and conclusion of the 12-wk intervention period.The structure of the intestinal microbiota and the levels of serological indicators,such as liver function and inflammatory factors,were assessed.RESULTS Following LP N1115 intervention,the intestinal microbial diversity significantly increased in the intervention group(P<0.05),and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria.Additionally,the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors(P<0.05).CONCLUSION LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota,improving liver function,and reducing inflammatory factor levels.展开更多
BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To in...BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.METHODS The GeneCards and OMIM databases were used to derive the GC targets,while the Pharm Mapper database provided the PA targets.Utilizing the STRING database,a protein-protein interaction network was constructed and core targets were screened.The analyses of Gene Ontology,Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis were conducted,and molecular docking and clinical correlation analyses were performed on the core targets.Ultimately,the network pharmacology findings were validated through in vitro cell assays,encompassing assessments of cell viability,apoptosis,cell cycle,cloning,and western blot analysis.RESULTS According to network pharmacology analysis,the core targets were screened,and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC,according to KEGG enrichment analysis.The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation,induce apoptosis,and pause the cell cycle.CONCLUSION Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets.This has also been supported by in vitro cell studies,which serve as benchmarks for further research.展开更多
BACKGROUND The precise role of mitochondrial carrier homolog 2(MTCH2)in promoting malignancy in gastric mucosal cells and its involvement in gastric cancer cell metastasis have not been fully elucidated.AIM To determi...BACKGROUND The precise role of mitochondrial carrier homolog 2(MTCH2)in promoting malignancy in gastric mucosal cells and its involvement in gastric cancer cell metastasis have not been fully elucidated.AIM To determine the role of MTCH2 in gastric cancer.METHODS We collected 65 samples of poorly differentiated gastric cancer tissue and adjacent tissues,constructed MTCH2-overexpressing and MTCH2-knockdown cell models,and evaluated the proliferation,migration,and invasion of human gastric epithelial cells(GES-1)and human gastric cancer cells(AGS)cells.The mito-chondrial membrane potential(MMP),mitochondrial permeability transformation pore(mPTP)and ATP fluorescence probe were used to detect mitochondrial function.Mitochondrial function and ATP synthase protein levels were detected via Western blotting.RESULTS The expression of MTCH2 and ATP2A2 in gastric cancer tissues was significantly greater than that in adjacent tissues.Overexpression of MTCH2 promoted colony formation,invasion,migration,MMP expression and ATP production in GES-1 and AGS cells while upregulating ATP2A2 expression and inhibiting cell apoptosis;knockdown of MTCH2 had the opposite effect,promoting overactivation of the mPTP and promoting apoptosis.CONCLUSION MTCH2 can increase the malignant phenotype of GES-1 cells and promote the proliferation,invasion,and migration of gastric cancer cells by regulating mitochondrial function,providing a basis for targeted therapy for gastric cancer cells.展开更多
Computer-aided diagnosis of pneumonia based on deep learning is a research hotspot.However,there are some problems that the features of different sizes and different directions are not sufficient when extracting the f...Computer-aided diagnosis of pneumonia based on deep learning is a research hotspot.However,there are some problems that the features of different sizes and different directions are not sufficient when extracting the features in lung X-ray images.A pneumonia classification model based on multi-scale directional feature enhancement MSD-Net is proposed in this paper.The main innovations are as follows:Firstly,the Multi-scale Residual Feature Extraction Module(MRFEM)is designed to effectively extract multi-scale features.The MRFEM uses dilated convolutions with different expansion rates to increase the receptive field and extract multi-scale features effectively.Secondly,the Multi-scale Directional Feature Perception Module(MDFPM)is designed,which uses a three-branch structure of different sizes convolution to transmit direction feature layer by layer,and focuses on the target region to enhance the feature information.Thirdly,the Axial Compression Former Module(ACFM)is designed to perform global calculations to enhance the perception ability of global features in different directions.To verify the effectiveness of the MSD-Net,comparative experiments and ablation experiments are carried out.In the COVID-19 RADIOGRAPHY DATABASE,the Accuracy,Recall,Precision,F1 Score,and Specificity of MSD-Net are 97.76%,95.57%,95.52%,95.52%,and 98.51%,respectively.In the chest X-ray dataset,the Accuracy,Recall,Precision,F1 Score and Specificity of MSD-Net are 97.78%,95.22%,96.49%,95.58%,and 98.11%,respectively.This model improves the accuracy of lung image recognition effectively and provides an important clinical reference to pneumonia Computer-Aided Diagnosis.展开更多
Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-t...Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-target and multi-pathway mode of action.Material&Methods:This study investigates the protective mechanisms and benefits of PDMSCs in mitigating the effects of controlled cortical impact(CCI)in rats and glutamate-induced oxidative stress injury in HT22 cells in vitro.Our primary objective is to provide evidence supporting the clinical application of PDMSCs.Results:In the in vivo arm of our investigation,we observed a swift elevation of matrix metalloproteinase-9(MMP-9)in the proximal cortex of injured brain tissues after CCI.PDMSCs,distinguished by their heightened expression of metalloproteinase tissue inhibitors-1 and-2(TIMP-1 and TIMP-2):were intravenously administered via the caudal vein.This intervention yielded significant reductions in the permeability of the blood-brain barrier(BBB):the extent of brain edema,the levels of inflammatory cytokines IL-1βand TNF-αin damaged brain tissue,and the activation status of microglia in CCI-afflicted rats.In the realm of in vitro experiments,PDMSC-conditioned media demonstrated substantial reductions in mortality rates and cleaved caspase-3 levels in glutamate-induced HT22 cells compared with conventional media.Notably,this advantage was negated upon the introduction of neutralizing antibodies targeting TIMP-1 and TIMP-2.Conclusion:Collectively,our findings underscore the potential of PDMSCs in alleviating oxidative stress injury and secondary brain injury in the pathological process of TBI.展开更多
Background:This study aimed to portray the atomic intelligence and prognostic implications of differentially expressed genes and their involvement in biological pathways in endometrial carcinoma,with a specific focus ...Background:This study aimed to portray the atomic intelligence and prognostic implications of differentially expressed genes and their involvement in biological pathways in endometrial carcinoma,with a specific focus on the impacts of exercise on cancer.Methods:We utilized a multi-faceted approach,including volcano plots,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses,Venn diagrams,protein-protein interaction networks,Kaplan-Meier survival analysis,Gene Set Variety Analysis,and single-cell transcriptomic analysis.Furthermore,we profiled tumor mutational scenes,assessed the prognostic value of immune-related features,and conducted a comprehensive examination of genetic variations and their impact on tumor mutational burden across different cancer types.Multidimensional genomic interactions and methylation elements were also investigated.Using real-time quantitative PCR and immunofluorescence staining,the effects of B-cell lymphoma 2(BCL2)silencing on TNF-αand caspase-3 gene expression were evaluated.Results:Our study identified a noteworthy number of differentially expressed genes in endometrial carcinoma with potential links to athletic performance traits.BCL2 expression levels were found to be associated with survival outcomes,and its changeability across cancers was related to immune cell infiltration and immune checkpoint gene expression.Single-cell investigations uncovered cellular complexity within tumor microenvironments and critical biological pathways in BCL2-overexpressing cells.The expression flow and mutational effect of BCL2 in endometrial carcinoma were characterized,and the prognostic implications of immune-related features were assessed.Hereditary variations,including copy number variations and their relationship with gene expression and tumor mutational burden,were investigated.Multidimensional genomic transaction highlighted the essential role of regulatory genes in cancer pathogenesis.Silencing of the BCL2 gene significantly inhibited the proliferation of HEC-108 cells and promoted apoptosis,as evidenced by decreased TNF-αgene expression and increased caspase-3 gene expression.Immunofluorescence staining further confirmed these results.Conclusion:This study gives a point-by-point understanding of the atomic intelligence and prognostic implications in endometrial carcinoma and across various other cancers.BCL2’s role as a modulatory factor within the tumor-resistant environment and its potential impact on disease prognosis and response to immunotherapy were underscored.The multidimensional genomic analysis provides insights into the complex interaction between genetic and epigenetic variables in cancer,which may shed light on future therapeutic strategies.This study indicates that silencing the BCL2 gene can significantly inhibit tumor cell proliferation and promote apoptosis through the regulation of the TNF-αand caspase-3 pathways.展开更多
BACKGROUND Diabetic retinopathy(DR)is a common microvascular complication of diabetes mellitus.Its blindness rate is high;therefore,finding a reasonable and safe treatment plan to prevent and control DR is crucial.Cur...BACKGROUND Diabetic retinopathy(DR)is a common microvascular complication of diabetes mellitus.Its blindness rate is high;therefore,finding a reasonable and safe treatment plan to prevent and control DR is crucial.Currently,there are abundant and diverse research results on the treatment of DR by Chinese medicine Traditional Chinese medicine compounds are potentially advantageous for DR prevention and treatment because of its safe and effective therapeutic effects.AIM To investigate the effects of Buqing granule(BQKL)on DR and its mechanism from a systemic perspective and at the molecular level by combining network pharmacology and in vivo experiments.METHODS This study collected information on the drug targets of BQKL and the therapeutic targets of DR for intersecting target gene analysis and protein-protein interactions(PPI),identified various biological pathways related to DR treatment by BQKL through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses,and preliminarily validated the screened core targets by molecular docking.Furthermore,we constructed a diabetic rat model with a high-fat and high-sugar diet and intraperitoneal streptozotocin injection,and administered the appropriate drugs for 12 weeks after the model was successfully induced.Body mass and fasting blood glucose and lipid levels were measured,and pathological changes in retinal tissue were detected by hematoxylin and eosin staining.ELISA was used to detect the oxidative stress index expression in serum and retinal tissue,and immunohistochemistry,real-time quantitative reverse transcription PCR,and western blotting were used to verify the changes in the expression of core targets.RESULTS Six potential therapeutic targets of BQKL for DR treatment,including Caspase-3,c-Jun,TP53,AKT1,MAPK1,and MAPK3,were screened using PPI.Enrichment analysis indicated that the MAPK signaling pathway might be the core target pathway of BQKL in DR treatment.Molecular docking prediction indicated that BQKL stably bound to these core targets.In vivo experiments have shown that compared with those in the Control group,rats in the Model group had statistically significant(P<0.05)severe retinal histopathological damage;elevated blood glucose,lipid,and malondialdehyde(MDA)levels;increased Caspase-3,c-Jun,and TP53 protein expression;and reduced superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)levels,ganglion cell number,AKT1,MAPK1,and MAPK3 protein expression.Compared with the Model group,BQKL group had reduced histopathological retinal damage and the expression of blood glucose and lipids,MDA level,Caspase-3,c-Jun and TP53 proteins were reduced,while the expression of SOD,GSH-Px level,the number of ganglion cells,AKT1,MAPK1,and MAPK3 proteins were elevated.These differences were statistically significant(P<0.05).CONCLUSION BQKL can delay DR onset and progression by attenuating oxidative stress and inflammatory responses and regulating Caspase-3,c-Jun,TP53,AKT1,MAPK1,and MAPK3 proteins in the MAPK signaling pathway mediates these alterations.展开更多
Multimodal lung tumor medical images can provide anatomical and functional information for the same lesion.Such as Positron Emission Computed Tomography(PET),Computed Tomography(CT),and PET-CT.How to utilize the lesio...Multimodal lung tumor medical images can provide anatomical and functional information for the same lesion.Such as Positron Emission Computed Tomography(PET),Computed Tomography(CT),and PET-CT.How to utilize the lesion anatomical and functional information effectively and improve the network segmentation performance are key questions.To solve the problem,the Saliency Feature-Guided Interactive Feature Enhancement Lung Tumor Segmentation Network(Guide-YNet)is proposed in this paper.Firstly,a double-encoder single-decoder U-Net is used as the backbone in this model,a single-coder single-decoder U-Net is used to generate the saliency guided feature using PET image and transmit it into the skip connection of the backbone,and the high sensitivity of PET images to tumors is used to guide the network to accurately locate lesions.Secondly,a Cross Scale Feature Enhancement Module(CSFEM)is designed to extract multi-scale fusion features after downsampling.Thirdly,a Cross-Layer Interactive Feature Enhancement Module(CIFEM)is designed in the encoder to enhance the spatial position information and semantic information.Finally,a Cross-Dimension Cross-Layer Feature Enhancement Module(CCFEM)is proposed in the decoder,which effectively extractsmultimodal image features through global attention and multi-dimension local attention.The proposed method is verified on the lung multimodal medical image datasets,and the results showthat theMean Intersection overUnion(MIoU),Accuracy(Acc),Dice Similarity Coefficient(Dice),Volumetric overlap error(Voe),Relative volume difference(Rvd)of the proposed method on lung lesion segmentation are 87.27%,93.08%,97.77%,95.92%,89.28%,and 88.68%,respectively.It is of great significance for computer-aided diagnosis.展开更多
The precise detection and segmentation of tumor lesions are very important for lung cancer computer-aided diagnosis.However,in PET/CT(Positron Emission Tomography/Computed Tomography)lung images,the lesion shapes are ...The precise detection and segmentation of tumor lesions are very important for lung cancer computer-aided diagnosis.However,in PET/CT(Positron Emission Tomography/Computed Tomography)lung images,the lesion shapes are complex,the edges are blurred,and the sample numbers are unbalanced.To solve these problems,this paper proposes a Multi-branch Cross-scale Interactive Feature fusion Transformer model(MCIF-Transformer Mask RCNN)for PET/CT lung tumor instance segmentation,The main innovative works of this paper are as follows:Firstly,the ResNet-Transformer backbone network is used to extract global feature and local feature in lung images.The pixel dependence relationship is established in local and non-local fields to improve the model perception ability.Secondly,the Cross-scale Interactive Feature Enhancement auxiliary network is designed to provide the shallow features to the deep features,and the cross-scale interactive feature enhancement module(CIFEM)is used to enhance the attention ability of the fine-grained features.Thirdly,the Cross-scale Interactive Feature fusion FPN network(CIF-FPN)is constructed to realize bidirectional interactive fusion between deep features and shallow features,and the low-level features are enhanced in deep semantic features.Finally,4 ablation experiments,3 comparison experiments of detection,3 comparison experiments of segmentation and 6 comparison experiments with two-stage and single-stage instance segmentation networks are done on PET/CT lung medical image datasets.The results showed that APdet,APseg,ARdet and ARseg indexes are improved by 5.5%,5.15%,3.11%and 6.79%compared with Mask RCNN(resnet50).Based on the above research,the precise detection and segmentation of the lesion region are realized in this paper.This method has positive significance for the detection of lung tumors.展开更多
BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated...BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.展开更多
Background:Recurrent miscarriage(RM)affects an estimated 1-3%of couples attempting to conceive,and its molecular components stay ineffectively caught on.This study aims to explore potential therapeutic targets for RM ...Background:Recurrent miscarriage(RM)affects an estimated 1-3%of couples attempting to conceive,and its molecular components stay ineffectively caught on.This study aims to explore potential therapeutic targets for RM by examining gene expression patterns and biological pathways in both mouse and human RM models.Meanwhile,explore relevant traditional Chinese medicine(TCM)components targeting potential therapeutic targets.Methods:We utilized the GSE211251 mouse and the GSE26787 human datasets,employing gene set enrichment analysis and gene metaphysics analysis to examine differentially expressed genes and enriched pathways.Single-cell RNA analysis uncovered cellular heterogeneity and arranged pharmacology-mapped potential drug-target intelligence.We employed molecular docking strategies to assess the affinity of TCM components for key proteins.Results:In the mouse model,genes such as Ly6f1 and Gpr26 were upregulated,while Stc5a and Galca exhibited downregulation.Gene set enrichment analysis identified key pathways,including the tumor necrosis factor-mediated signaling pathway.In human samples,Gene Ontology analysis highlighted processes such as apoptosis and cell adhesion.Single-cell RNA analysis revealed distinct cellular populations between normal and RM samples.Systems pharmacology identified C-X-C motif chemokine receptor 4(CXCR4)and endothelin 1(EDN1)as potential key targets,and molecular docking confirmed that stearic acid from TCM appears to regulate these proteins.Conclusion:This study presents a comprehensive analysis of the genetic and cellular underpinnings of RM,identifying CXCR4 and EDN1 as promising therapeutic targets.Stearic acid from TCM could provide targeted treatment by modulating these key proteins,paving the way for new RM treatment strategies.展开更多
Background:Glioma-induced refractory epilepsy can be alleviated through conventional exercise,providing a potential therapeutic approach to manage this condition.This study aims to investigate the underlying mechanism...Background:Glioma-induced refractory epilepsy can be alleviated through conventional exercise,providing a potential therapeutic approach to manage this condition.This study aims to investigate the underlying mechanisms.Methods:Bioinformatics methodologies were employed to scrutinize gene expression data from public repositories such as GEO,with a specific focus on mobility-related genes in epilepsy.Through differential and enrichment analyses,differentially expressed genes(DEGs)were identified,while protein-protein interaction networks elucidated pivotal hub genes.Results:Our analysis revealed 32 DEGs,comprising 23 upregulated and 9 downregulated genes.Enrichment analysis underscored significant alterations in immune pathways in epilepsy.Two central hub genes,haptoglobin(HP)and prostaglandin-endoperoxide synthase 2(PTGS2),were found to be modulated by Arginase 1(ARG1)and Chemokine(C-X-C motif)ligand 8(CXCL8).GSVA analysis associated elevated PTGS2 expression with metabolic pathways,while increased HP expression was correlated with angiogenesis and inflammation.Subsequent experiments validated HP’s role in tumor cell proliferation,emphasizing its potential as a therapeutic target.Conclusion:This study highlights the crucial involvement of HP and PTGS2 genes in the etiology of epilepsy,linked to discrepancies in the immune system.These findings offer fresh perspectives on the management of epilepsy,emphasizing the neuroprotective possibilities of targeting specific gene pathway.展开更多
Background:EBV-miR-BARTs exhibit significant relevance in epithelial tumors,particularly in EBVassociated gastric and nasopharyngeal cancers.However,their specific mechanisms in the initiation and progression of gastr...Background:EBV-miR-BARTs exhibit significant relevance in epithelial tumors,particularly in EBVassociated gastric and nasopharyngeal cancers.However,their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored.Material and Methods:Initially,EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines.Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45,and downregulation in EBVpositive cells(SUN-719).The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation,migration,and glycolytic processes,with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-βinhibitor.Results:EBV-miRNA-BART6-5p exhibits pronounced upregulation in EBV-associated gastric cancer tissues and EBV-positive cells,while its target gene SMAD4 demonstrates downregulated expression.Upregulation of it can promote the proliferation and migration of gastric cancer cells.Additionally,We found EBV-miRNA-BART6-5p promotes glycolysis of gastric cancer cells.Inhibition of the TGF-β/SMAD4 signaling pathway resulted in suppressed proliferation and migration of gastric cancer cells,concomitant with a diminished glycolytic capacity.Conclusion:In this study,we found that EBV-miRNA-BART6-5p can target SMAD4,effectively increasing glycolysis in gastric cancer cells by regulating the TGF-β/SMAD4 signaling pathway,thereby enhancing the proliferation and metastasis of gastric cancer cells.Our findings may offer new insights into the metabolic aspects of gastric cancer.展开更多
BACKGROUND Due to frequent and high-risk sports activities,the elbow joint is susceptible to injury,especially to cartilage tissue,which can cause pain,limited movement and even loss of joint function.AIM To evaluate ...BACKGROUND Due to frequent and high-risk sports activities,the elbow joint is susceptible to injury,especially to cartilage tissue,which can cause pain,limited movement and even loss of joint function.AIM To evaluate magnetic resonance imaging(MRI)multisequence imaging for improving the diagnostic accuracy of adult elbow cartilage injury.METHODS A total of 60 patients diagnosed with elbow cartilage injury in our hospital from January 2020 to December 2021 were enrolled in this retrospective study.We analyzed the accuracy of conventional MRI sequences(T1-weighted imaging,T2-weighted imaging,proton density weighted imaging,and T2 star weighted image)and Three-Dimensional Coronary Imaging by Spiral Scanning(3D-CISS)in the diagnosis of elbow cartilage injury.Arthroscopy was used as the gold standard to evaluate the diagnostic effect of single and combination sequences in different injury degrees and the consistency with arthroscopy.RESULTS The diagnostic accuracy of 3D-CISS sequence was 89.34%±4.98%,the sensitivity was 90%,and the specificity was 88.33%,which showed the best performance among all sequences(P<0.05).The combined application of the whole sequence had the highest accuracy in all sequence combinations,the accuracy of mild injury was 91.30%,the accuracy of moderate injury was 96.15%,and the accuracy of severe injury was 93.33%(P<0.05).Compared with arthroscopy,the combination of all MRI sequences had the highest consistency of 91.67%,and the kappa value reached 0.890(P<0.001).CONCLUSION Combination of 3D-CISS and each sequence had significant advantages in improving MRI diagnostic accuracy of elbow cartilage injuries in adults.Multisequence MRI is recommended to ensure the best diagnosis and treatment.展开更多
基金West Light Foundation of the Ningxia Key Research and Development Program,No.2023BEG02015High-level Key Discipline Construction Project of State Administration of Traditional Chinese Medicine,No.2022-226+1 种基金Talent Development Projects of Young Qihuang of National Administration of Traditional Chinese Medicine,No.2020-218National Natural Science Foundation of China,No.82374261.
文摘BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.
基金Supported by Ningxia Key Research and Development Program,No.2023BEG02015Ningxia Science and Technology Benefiting People Program,No.2022CMG03064+1 种基金Ningxia Natural Science Foundation,No.2022AAC02039National Natural Science Foundation of China,No.82260879 and No.82374261.
文摘BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.
基金supported by the National Natural Science Foundation of China,Nos.81941011(to XL),31771053(to HD),31730030(to XL),31971279(to ZY),31900749(to PH),31650001(to XL),31320103903(to XL),31670988(to ZY)the Natural Science Foundation of Beijing,Nos.7222004(to HD)+1 种基金a grant from Ministry of Science and Technology of China,Nos.2017YFC1104002(to ZY),2017YFC1104001(to XL)a grant from Beihang University,No.JKF-YG-22-B001(to FH)。
文摘Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.
文摘Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.
基金Natural Science Foundation of Ningxia(2020AAC03403,2020AAC03178)National Natural Science Foundation of China(82260716,82060663).
文摘Colorectal cancer(CRC)is a major global health problem with high morbidity and mortality rates.Surgical resection is the main treatment for early-stage CRC,but detecting it early is challenging.Therefore,effective therapeutic targets for advanced patients are still lacking.Exosomes,tiny vesicles in body fluids,play a crucial role in tumor metastasis,immune regulation,and drug resistance.Interestingly,they can even serve as a biomarker for cancer diagnosis and prognosis.Studies have shown that exosomes can carry miRNA,mediate the polarization of M1/M2 macrophages,promote the proliferation and metastasis of cancer cells,and affect the prognosis of CRC.Since the gastrointestinal tract has many macrophages,understanding the mechanism behind exosomal miRNA-mediated macrophage polarization in CRC treatment is crucial.This article summarizes recent advancements in the study of exosomal miRNAs in CRC and their potential as diagnostic and prognostic markers.
基金supported by the Ningxia Hui Autonomous Region key research and development programs(Grant No.2021BEG03084)the National Natural Science Foundation of China(Grant No.31660336).
文摘Background:Colorectal cancer is a major global health concern,exacerbated by tumor necrosis factor-alpha(TNF-α)and its role in inflammation,with the effects of Mitotic Arrest Deficient 2 Like 2(MAD2L2)in this context still unclear.Methods:The colorectal carcinoma cell lines HCT116 and SW620 were exposed to TNF-αfor a period of 24 h to instigate an inflammatory response.Subsequent assessments were conducted to measure the expression of inflammatory cytokines,the activity within the p38 mitogen-activated protein kinase(p38 MAPK)and Phosphoinositide 3-Kinase/AKT Serine/Threonine Kinase pathway(PI3K/AKT)signaling cascades.Transcriptome sequencing and subsequent integrative analysis with the Cancer Genome Atlas(TCGA)program database revealed a significant downregulation of the key factor MAD2L2.Enhancement of MAD2L2 expression was facilitated via lentiviral vector-mediated transfection.The influence of this overexpression on TNF-α-prompted inflammation,intracellular signaling pathways,and the migratory and invasive behaviors of the colorectal cancer cells was then scrutinized.Results:TNF-αtreatment significantly increased the expression of Interleukin-1 beta(IL-1β)and Interleukin-6(IL-6),activated the MAPK p38 and PI3K/AKT signaling pathways,and enhanced cell migration and invasion.A decrease in MAD2L2 expression was observed following TNF-αtreatment.However,overexpression of MAD2L2 reversed the effects of TNF-α,reducing IL-1βand IL-6 levels,attenuating PI3K/AKT pathway activation,and inhibiting cell migration and invasion.Conclusions:Overexpression of MAD2L2 attenuates the pro-inflammatory effects of TNF-α,suggesting that MAD2L2 plays a protective role against TNF-α-induced migration and invasion of colorectal carcinoma cells.Therefore,MAD2L2 holds potential as a therapeutic target in the treatment of colorectal cancer.
基金Supported by The Health System Research Project of Ningxia Hui Autonomous Region of China,No.2022-NWKY-061.
文摘BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction.Although the relationship between certain single probiotics and HBC has been explored,the impact of the complex ready-to-eat Lactobacillus paracasei N1115(LP N1115)supplement on patients with HBC has not been determined.AIM To compare the changes in the microbiota,inflammatory factor levels,and liver function before and after probiotic treatment in HBC patients.METHODS This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020.Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only.Fecal samples were collected at the onset and conclusion of the 12-wk intervention period.The structure of the intestinal microbiota and the levels of serological indicators,such as liver function and inflammatory factors,were assessed.RESULTS Following LP N1115 intervention,the intestinal microbial diversity significantly increased in the intervention group(P<0.05),and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria.Additionally,the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors(P<0.05).CONCLUSION LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota,improving liver function,and reducing inflammatory factor levels.
基金Supported by Ningxia Science and Technology Benefiting People Program,No.2022CMG03064National Natural Science Foundation of China,No.82260879Ningxia Natural Science Foundation,No.2022AAC03144 and 2022AAC02039.
文摘BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.METHODS The GeneCards and OMIM databases were used to derive the GC targets,while the Pharm Mapper database provided the PA targets.Utilizing the STRING database,a protein-protein interaction network was constructed and core targets were screened.The analyses of Gene Ontology,Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis were conducted,and molecular docking and clinical correlation analyses were performed on the core targets.Ultimately,the network pharmacology findings were validated through in vitro cell assays,encompassing assessments of cell viability,apoptosis,cell cycle,cloning,and western blot analysis.RESULTS According to network pharmacology analysis,the core targets were screened,and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC,according to KEGG enrichment analysis.The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation,induce apoptosis,and pause the cell cycle.CONCLUSION Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets.This has also been supported by in vitro cell studies,which serve as benchmarks for further research.
基金the Medical Science Research Projects in Hebei Province,No.20221526and Natural Science Foundation,No.2022-271.
文摘BACKGROUND The precise role of mitochondrial carrier homolog 2(MTCH2)in promoting malignancy in gastric mucosal cells and its involvement in gastric cancer cell metastasis have not been fully elucidated.AIM To determine the role of MTCH2 in gastric cancer.METHODS We collected 65 samples of poorly differentiated gastric cancer tissue and adjacent tissues,constructed MTCH2-overexpressing and MTCH2-knockdown cell models,and evaluated the proliferation,migration,and invasion of human gastric epithelial cells(GES-1)and human gastric cancer cells(AGS)cells.The mito-chondrial membrane potential(MMP),mitochondrial permeability transformation pore(mPTP)and ATP fluorescence probe were used to detect mitochondrial function.Mitochondrial function and ATP synthase protein levels were detected via Western blotting.RESULTS The expression of MTCH2 and ATP2A2 in gastric cancer tissues was significantly greater than that in adjacent tissues.Overexpression of MTCH2 promoted colony formation,invasion,migration,MMP expression and ATP production in GES-1 and AGS cells while upregulating ATP2A2 expression and inhibiting cell apoptosis;knockdown of MTCH2 had the opposite effect,promoting overactivation of the mPTP and promoting apoptosis.CONCLUSION MTCH2 can increase the malignant phenotype of GES-1 cells and promote the proliferation,invasion,and migration of gastric cancer cells by regulating mitochondrial function,providing a basis for targeted therapy for gastric cancer cells.
基金supported in part by the National Natural Science Foundation of China(Grant No.62062003)Natural Science Foundation of Ningxia(Grant No.2023AAC03293).
文摘Computer-aided diagnosis of pneumonia based on deep learning is a research hotspot.However,there are some problems that the features of different sizes and different directions are not sufficient when extracting the features in lung X-ray images.A pneumonia classification model based on multi-scale directional feature enhancement MSD-Net is proposed in this paper.The main innovations are as follows:Firstly,the Multi-scale Residual Feature Extraction Module(MRFEM)is designed to effectively extract multi-scale features.The MRFEM uses dilated convolutions with different expansion rates to increase the receptive field and extract multi-scale features effectively.Secondly,the Multi-scale Directional Feature Perception Module(MDFPM)is designed,which uses a three-branch structure of different sizes convolution to transmit direction feature layer by layer,and focuses on the target region to enhance the feature information.Thirdly,the Axial Compression Former Module(ACFM)is designed to perform global calculations to enhance the perception ability of global features in different directions.To verify the effectiveness of the MSD-Net,comparative experiments and ablation experiments are carried out.In the COVID-19 RADIOGRAPHY DATABASE,the Accuracy,Recall,Precision,F1 Score,and Specificity of MSD-Net are 97.76%,95.57%,95.52%,95.52%,and 98.51%,respectively.In the chest X-ray dataset,the Accuracy,Recall,Precision,F1 Score and Specificity of MSD-Net are 97.78%,95.22%,96.49%,95.58%,and 98.11%,respectively.This model improves the accuracy of lung image recognition effectively and provides an important clinical reference to pneumonia Computer-Aided Diagnosis.
基金financially supported by the Key Research Projects of Ningxia Hui Autonomous Region of China under Grant No.2018BCG01002(to HCX).
文摘Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-target and multi-pathway mode of action.Material&Methods:This study investigates the protective mechanisms and benefits of PDMSCs in mitigating the effects of controlled cortical impact(CCI)in rats and glutamate-induced oxidative stress injury in HT22 cells in vitro.Our primary objective is to provide evidence supporting the clinical application of PDMSCs.Results:In the in vivo arm of our investigation,we observed a swift elevation of matrix metalloproteinase-9(MMP-9)in the proximal cortex of injured brain tissues after CCI.PDMSCs,distinguished by their heightened expression of metalloproteinase tissue inhibitors-1 and-2(TIMP-1 and TIMP-2):were intravenously administered via the caudal vein.This intervention yielded significant reductions in the permeability of the blood-brain barrier(BBB):the extent of brain edema,the levels of inflammatory cytokines IL-1βand TNF-αin damaged brain tissue,and the activation status of microglia in CCI-afflicted rats.In the realm of in vitro experiments,PDMSC-conditioned media demonstrated substantial reductions in mortality rates and cleaved caspase-3 levels in glutamate-induced HT22 cells compared with conventional media.Notably,this advantage was negated upon the introduction of neutralizing antibodies targeting TIMP-1 and TIMP-2.Conclusion:Collectively,our findings underscore the potential of PDMSCs in alleviating oxidative stress injury and secondary brain injury in the pathological process of TBI.
基金supported by the Science and Technology Beneficiary Program of Ningxia Hui Autonomous Region(No.2023CMG03027)the Ningxia Key Research and Development Program(No.2022BEG03167)the National Natural Science Foundation of China(No.82060275).
文摘Background:This study aimed to portray the atomic intelligence and prognostic implications of differentially expressed genes and their involvement in biological pathways in endometrial carcinoma,with a specific focus on the impacts of exercise on cancer.Methods:We utilized a multi-faceted approach,including volcano plots,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses,Venn diagrams,protein-protein interaction networks,Kaplan-Meier survival analysis,Gene Set Variety Analysis,and single-cell transcriptomic analysis.Furthermore,we profiled tumor mutational scenes,assessed the prognostic value of immune-related features,and conducted a comprehensive examination of genetic variations and their impact on tumor mutational burden across different cancer types.Multidimensional genomic interactions and methylation elements were also investigated.Using real-time quantitative PCR and immunofluorescence staining,the effects of B-cell lymphoma 2(BCL2)silencing on TNF-αand caspase-3 gene expression were evaluated.Results:Our study identified a noteworthy number of differentially expressed genes in endometrial carcinoma with potential links to athletic performance traits.BCL2 expression levels were found to be associated with survival outcomes,and its changeability across cancers was related to immune cell infiltration and immune checkpoint gene expression.Single-cell investigations uncovered cellular complexity within tumor microenvironments and critical biological pathways in BCL2-overexpressing cells.The expression flow and mutational effect of BCL2 in endometrial carcinoma were characterized,and the prognostic implications of immune-related features were assessed.Hereditary variations,including copy number variations and their relationship with gene expression and tumor mutational burden,were investigated.Multidimensional genomic transaction highlighted the essential role of regulatory genes in cancer pathogenesis.Silencing of the BCL2 gene significantly inhibited the proliferation of HEC-108 cells and promoted apoptosis,as evidenced by decreased TNF-αgene expression and increased caspase-3 gene expression.Immunofluorescence staining further confirmed these results.Conclusion:This study gives a point-by-point understanding of the atomic intelligence and prognostic implications in endometrial carcinoma and across various other cancers.BCL2’s role as a modulatory factor within the tumor-resistant environment and its potential impact on disease prognosis and response to immunotherapy were underscored.The multidimensional genomic analysis provides insights into the complex interaction between genetic and epigenetic variables in cancer,which may shed light on future therapeutic strategies.This study indicates that silencing the BCL2 gene can significantly inhibit tumor cell proliferation and promote apoptosis through the regulation of the TNF-αand caspase-3 pathways.
基金Supported by National Natural Science Foundation of China,No.81960836Ningxia Natural Science Foundation,No.2020AAC03126Ningxia Higher Education Scientific Research Project,No.NGY2020045。
文摘BACKGROUND Diabetic retinopathy(DR)is a common microvascular complication of diabetes mellitus.Its blindness rate is high;therefore,finding a reasonable and safe treatment plan to prevent and control DR is crucial.Currently,there are abundant and diverse research results on the treatment of DR by Chinese medicine Traditional Chinese medicine compounds are potentially advantageous for DR prevention and treatment because of its safe and effective therapeutic effects.AIM To investigate the effects of Buqing granule(BQKL)on DR and its mechanism from a systemic perspective and at the molecular level by combining network pharmacology and in vivo experiments.METHODS This study collected information on the drug targets of BQKL and the therapeutic targets of DR for intersecting target gene analysis and protein-protein interactions(PPI),identified various biological pathways related to DR treatment by BQKL through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses,and preliminarily validated the screened core targets by molecular docking.Furthermore,we constructed a diabetic rat model with a high-fat and high-sugar diet and intraperitoneal streptozotocin injection,and administered the appropriate drugs for 12 weeks after the model was successfully induced.Body mass and fasting blood glucose and lipid levels were measured,and pathological changes in retinal tissue were detected by hematoxylin and eosin staining.ELISA was used to detect the oxidative stress index expression in serum and retinal tissue,and immunohistochemistry,real-time quantitative reverse transcription PCR,and western blotting were used to verify the changes in the expression of core targets.RESULTS Six potential therapeutic targets of BQKL for DR treatment,including Caspase-3,c-Jun,TP53,AKT1,MAPK1,and MAPK3,were screened using PPI.Enrichment analysis indicated that the MAPK signaling pathway might be the core target pathway of BQKL in DR treatment.Molecular docking prediction indicated that BQKL stably bound to these core targets.In vivo experiments have shown that compared with those in the Control group,rats in the Model group had statistically significant(P<0.05)severe retinal histopathological damage;elevated blood glucose,lipid,and malondialdehyde(MDA)levels;increased Caspase-3,c-Jun,and TP53 protein expression;and reduced superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)levels,ganglion cell number,AKT1,MAPK1,and MAPK3 protein expression.Compared with the Model group,BQKL group had reduced histopathological retinal damage and the expression of blood glucose and lipids,MDA level,Caspase-3,c-Jun and TP53 proteins were reduced,while the expression of SOD,GSH-Px level,the number of ganglion cells,AKT1,MAPK1,and MAPK3 proteins were elevated.These differences were statistically significant(P<0.05).CONCLUSION BQKL can delay DR onset and progression by attenuating oxidative stress and inflammatory responses and regulating Caspase-3,c-Jun,TP53,AKT1,MAPK1,and MAPK3 proteins in the MAPK signaling pathway mediates these alterations.
基金supported in part by the National Natural Science Foundation of China(Grant No.62062003)Natural Science Foundation of Ningxia(Grant No.2023AAC03293).
文摘Multimodal lung tumor medical images can provide anatomical and functional information for the same lesion.Such as Positron Emission Computed Tomography(PET),Computed Tomography(CT),and PET-CT.How to utilize the lesion anatomical and functional information effectively and improve the network segmentation performance are key questions.To solve the problem,the Saliency Feature-Guided Interactive Feature Enhancement Lung Tumor Segmentation Network(Guide-YNet)is proposed in this paper.Firstly,a double-encoder single-decoder U-Net is used as the backbone in this model,a single-coder single-decoder U-Net is used to generate the saliency guided feature using PET image and transmit it into the skip connection of the backbone,and the high sensitivity of PET images to tumors is used to guide the network to accurately locate lesions.Secondly,a Cross Scale Feature Enhancement Module(CSFEM)is designed to extract multi-scale fusion features after downsampling.Thirdly,a Cross-Layer Interactive Feature Enhancement Module(CIFEM)is designed in the encoder to enhance the spatial position information and semantic information.Finally,a Cross-Dimension Cross-Layer Feature Enhancement Module(CCFEM)is proposed in the decoder,which effectively extractsmultimodal image features through global attention and multi-dimension local attention.The proposed method is verified on the lung multimodal medical image datasets,and the results showthat theMean Intersection overUnion(MIoU),Accuracy(Acc),Dice Similarity Coefficient(Dice),Volumetric overlap error(Voe),Relative volume difference(Rvd)of the proposed method on lung lesion segmentation are 87.27%,93.08%,97.77%,95.92%,89.28%,and 88.68%,respectively.It is of great significance for computer-aided diagnosis.
基金funded by National Natural Science Foundation of China No.62062003Ningxia Natural Science Foundation Project No.2023AAC03293.
文摘The precise detection and segmentation of tumor lesions are very important for lung cancer computer-aided diagnosis.However,in PET/CT(Positron Emission Tomography/Computed Tomography)lung images,the lesion shapes are complex,the edges are blurred,and the sample numbers are unbalanced.To solve these problems,this paper proposes a Multi-branch Cross-scale Interactive Feature fusion Transformer model(MCIF-Transformer Mask RCNN)for PET/CT lung tumor instance segmentation,The main innovative works of this paper are as follows:Firstly,the ResNet-Transformer backbone network is used to extract global feature and local feature in lung images.The pixel dependence relationship is established in local and non-local fields to improve the model perception ability.Secondly,the Cross-scale Interactive Feature Enhancement auxiliary network is designed to provide the shallow features to the deep features,and the cross-scale interactive feature enhancement module(CIFEM)is used to enhance the attention ability of the fine-grained features.Thirdly,the Cross-scale Interactive Feature fusion FPN network(CIF-FPN)is constructed to realize bidirectional interactive fusion between deep features and shallow features,and the low-level features are enhanced in deep semantic features.Finally,4 ablation experiments,3 comparison experiments of detection,3 comparison experiments of segmentation and 6 comparison experiments with two-stage and single-stage instance segmentation networks are done on PET/CT lung medical image datasets.The results showed that APdet,APseg,ARdet and ARseg indexes are improved by 5.5%,5.15%,3.11%and 6.79%compared with Mask RCNN(resnet50).Based on the above research,the precise detection and segmentation of the lesion region are realized in this paper.This method has positive significance for the detection of lung tumors.
基金Supported by National Natural Science Foundation of China,No.81573695,No.81860894,and No.81674096Ningxia Key Research and Development Plan Project,No.2021BEG03106.
文摘BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.
基金support from the Ningxia Hui Autonomous Region Key Research and Development Program(Project No.2021BEG03041).
文摘Background:Recurrent miscarriage(RM)affects an estimated 1-3%of couples attempting to conceive,and its molecular components stay ineffectively caught on.This study aims to explore potential therapeutic targets for RM by examining gene expression patterns and biological pathways in both mouse and human RM models.Meanwhile,explore relevant traditional Chinese medicine(TCM)components targeting potential therapeutic targets.Methods:We utilized the GSE211251 mouse and the GSE26787 human datasets,employing gene set enrichment analysis and gene metaphysics analysis to examine differentially expressed genes and enriched pathways.Single-cell RNA analysis uncovered cellular heterogeneity and arranged pharmacology-mapped potential drug-target intelligence.We employed molecular docking strategies to assess the affinity of TCM components for key proteins.Results:In the mouse model,genes such as Ly6f1 and Gpr26 were upregulated,while Stc5a and Galca exhibited downregulation.Gene set enrichment analysis identified key pathways,including the tumor necrosis factor-mediated signaling pathway.In human samples,Gene Ontology analysis highlighted processes such as apoptosis and cell adhesion.Single-cell RNA analysis revealed distinct cellular populations between normal and RM samples.Systems pharmacology identified C-X-C motif chemokine receptor 4(CXCR4)and endothelin 1(EDN1)as potential key targets,and molecular docking confirmed that stearic acid from TCM appears to regulate these proteins.Conclusion:This study presents a comprehensive analysis of the genetic and cellular underpinnings of RM,identifying CXCR4 and EDN1 as promising therapeutic targets.Stearic acid from TCM could provide targeted treatment by modulating these key proteins,paving the way for new RM treatment strategies.
基金supported by the Ningxia Natural Science Foundation(Grant No.2022AAC03741)the Ningxia Medical University Scientific Research Fund(Grant No.XZ2021025).
文摘Background:Glioma-induced refractory epilepsy can be alleviated through conventional exercise,providing a potential therapeutic approach to manage this condition.This study aims to investigate the underlying mechanisms.Methods:Bioinformatics methodologies were employed to scrutinize gene expression data from public repositories such as GEO,with a specific focus on mobility-related genes in epilepsy.Through differential and enrichment analyses,differentially expressed genes(DEGs)were identified,while protein-protein interaction networks elucidated pivotal hub genes.Results:Our analysis revealed 32 DEGs,comprising 23 upregulated and 9 downregulated genes.Enrichment analysis underscored significant alterations in immune pathways in epilepsy.Two central hub genes,haptoglobin(HP)and prostaglandin-endoperoxide synthase 2(PTGS2),were found to be modulated by Arginase 1(ARG1)and Chemokine(C-X-C motif)ligand 8(CXCL8).GSVA analysis associated elevated PTGS2 expression with metabolic pathways,while increased HP expression was correlated with angiogenesis and inflammation.Subsequent experiments validated HP’s role in tumor cell proliferation,emphasizing its potential as a therapeutic target.Conclusion:This study highlights the crucial involvement of HP and PTGS2 genes in the etiology of epilepsy,linked to discrepancies in the immune system.These findings offer fresh perspectives on the management of epilepsy,emphasizing the neuroprotective possibilities of targeting specific gene pathway.
基金supported by National Health Commission Key Laboratory of Gastrointestinal Tumour Diagnosis and Treatment 2022 Master/Postdoctoral Fund Project(NHCDP2022005)Gansu Provincial Science and Technology Department Joint Scientific Research Fund Project(23JRRA1545)+1 种基金Gansu Provincial Hospital Intra-Hospital Research Fund Project(22GSYYD-37)International Co-Operation Project of Gansu Provincial Science and Technology Department(No.20YF8WA096).
文摘Background:EBV-miR-BARTs exhibit significant relevance in epithelial tumors,particularly in EBVassociated gastric and nasopharyngeal cancers.However,their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored.Material and Methods:Initially,EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines.Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45,and downregulation in EBVpositive cells(SUN-719).The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation,migration,and glycolytic processes,with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-βinhibitor.Results:EBV-miRNA-BART6-5p exhibits pronounced upregulation in EBV-associated gastric cancer tissues and EBV-positive cells,while its target gene SMAD4 demonstrates downregulated expression.Upregulation of it can promote the proliferation and migration of gastric cancer cells.Additionally,We found EBV-miRNA-BART6-5p promotes glycolysis of gastric cancer cells.Inhibition of the TGF-β/SMAD4 signaling pathway resulted in suppressed proliferation and migration of gastric cancer cells,concomitant with a diminished glycolytic capacity.Conclusion:In this study,we found that EBV-miRNA-BART6-5p can target SMAD4,effectively increasing glycolysis in gastric cancer cells by regulating the TGF-β/SMAD4 signaling pathway,thereby enhancing the proliferation and metastasis of gastric cancer cells.Our findings may offer new insights into the metabolic aspects of gastric cancer.
文摘BACKGROUND Due to frequent and high-risk sports activities,the elbow joint is susceptible to injury,especially to cartilage tissue,which can cause pain,limited movement and even loss of joint function.AIM To evaluate magnetic resonance imaging(MRI)multisequence imaging for improving the diagnostic accuracy of adult elbow cartilage injury.METHODS A total of 60 patients diagnosed with elbow cartilage injury in our hospital from January 2020 to December 2021 were enrolled in this retrospective study.We analyzed the accuracy of conventional MRI sequences(T1-weighted imaging,T2-weighted imaging,proton density weighted imaging,and T2 star weighted image)and Three-Dimensional Coronary Imaging by Spiral Scanning(3D-CISS)in the diagnosis of elbow cartilage injury.Arthroscopy was used as the gold standard to evaluate the diagnostic effect of single and combination sequences in different injury degrees and the consistency with arthroscopy.RESULTS The diagnostic accuracy of 3D-CISS sequence was 89.34%±4.98%,the sensitivity was 90%,and the specificity was 88.33%,which showed the best performance among all sequences(P<0.05).The combined application of the whole sequence had the highest accuracy in all sequence combinations,the accuracy of mild injury was 91.30%,the accuracy of moderate injury was 96.15%,and the accuracy of severe injury was 93.33%(P<0.05).Compared with arthroscopy,the combination of all MRI sequences had the highest consistency of 91.67%,and the kappa value reached 0.890(P<0.001).CONCLUSION Combination of 3D-CISS and each sequence had significant advantages in improving MRI diagnostic accuracy of elbow cartilage injuries in adults.Multisequence MRI is recommended to ensure the best diagnosis and treatment.
