1.Disulfidptosis-related lncRNAs establish new prognostic features and predict immunotherapeutic response in pancreatic cancer
Mingzheng TANG ; Xiaofeng LI ; Yao RONG ; Zhihang WU ; Guorong MA ; Songhua LIU ; Hui CAI
Journal of China Medical University 2024;53(1):20-26
Objective To screen long non-coding RNA(lncRNA)associated with disulfidptosis and investigate the immune landscape between lncRNA and pancreatic cancer,for effective guidance in clinical practice.Methods The normal and pancreatic cancer tissue samples were obtained from The Cancer Genome Atlas database,and the lncRNA associated with disulfidptosis was identified based on the Cox and LASSO regression analyses.A risk prognosis model was constructed,and its predictive performance was verified using comprehensive methods.An accurate nomogram was construted to predict the prognosis of patients with pancreatic cancer.The biological differences were analyzed via Gene Ontology,Gene Set Enrichment Analysis,and an immunoassay.The immunotherapy response was estimated using the tumor mutational burden(TMB)score.Results A total of 251 disulfidptosis-related lncRNAs were successfully identified,and three groups of lncRNAs were selected as the reference for the risk model.Pathway analysis showed that immune-related pathways were associated with disulfidptosis-related lncRNA risk models.The risk score was significantly correlated with immune cell infiltration and the ESTIMATE score.Patients with higher risk scores had elevated TMB,indicating that high-risk patients exhibited a better immune checkpoint blockade response.Conclusion The findings of this study contribute to a deeper understanding of disulfidpto-sis-related lncRNA and provide a potential therapeutic strategy for pancreatic cancer.
2.Construction of competitive endogenous RNA network mediated by lung ischemia-reperfusion core genes
Xiaofeng LI ; Mingzheng TANG ; Xixi LIU ; Ziqing SONG ; Guoxin ZHANG ; Kaiyin YANG ; Lingyun ZHANG
Organ Transplantation 2024;15(1):70-81
Objective To analyze the core genes of lung ischemia-reperfusion injury and construct a competitive endogenous RNA (ceRNA) network. Methods Original data of GSE145989 were downloaded from the Gene Expression Omnibus (GEO) database as the training set, and the GSE172222 and GSE9634 datasets were used as the validation sets, and the differentially-expressed genes (DEG) were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Protein-protein interaction (PPI) network was constructed, and the core genes were screened, and the diagnostic values of these core genes and the immune infiltration levels of immune cells were evaluated. The ceRNA network was constructed and validated. The targeted drugs based on ceRNA network were assessed. Results A total of 179 DEG were identified, including 61 down-regulated and 118 up-regulated genes. GO analysis showed that DEGs were associated with multiple biological processes, such as cell migration, differentiation and regulation, etc. They were correlated with cell components, such as vesicle membrane, serosa and membrane raft, etc. They were also associated with multiple molecular functions, such as chemokine receptor, G protein-coupled receptor, immune receptor activity and antigen binding, etc. KEGG pathway enrichment analysis revealed that DEG were involved in tumor necrosis factor (TNF), Wnt, interleukin (IL)-17 and nuclear factor (NF)-κB signaling pathways, etc. PPI network suggested that CD8A, IL2RG, STAT1, CD3G and SYK were the core genes of lung ischemia-reperfusion injury. The ceRNA network prompted that miR-146a-3p, miR-28-5p and miR-593-3p were related to the expression level of CD3G. The miR-149-3p, miR-342-5p, miR-873-5p and miR-491-5p were correlated with the expression level of IL-2RG. The miR-194-3p, miR-512-3p, miR-377-3p and miR-590-3p were associated with the expression level of SYK. The miR-590-3p and miR-875-3p were related to the expression level of CD8A. The miR-143-5p, miR-1231, miR-590-3p and miR-875-3p were associated with the expression level of STAT1. There were 13 targeted drugs for CD3G, 4 targeted drugs for IL-2RG, 28 targeted drugs for SYK and 3 targeted drugs for lncRNA MUC2. No targeted drugs were identified for CD8A, STAT1 and other ceRNA network genes. Conclusions CD8A, IL2RG, STAT1, CD3G and SYK are the core genes of lung ischemia-reperfusion injury. The research and analysis of these core genes probably contribute to the diagnosis of lung ischemia-reperfusion injury and providing novel research ideas and therapeutic targets.
3.Expression and prognostic value of prohibitin in gastrointestinal cancers based on bioinformatics
Xiaofeng LI ; Xixi LIU ; Ziqing SONG ; Mingzheng TANG ; Hui CAI ; Lingyun ZHANG
Journal of Army Medical University 2024;46(16):1838-1848
Objective To explore the expression of prohibitin(PHB)in tumor tissues and analyze its effect on the prognosis of patients with digestive system malignant tumor(DT)and its mechanism.Methods ①The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)database were used to compare the expression of PHB in tumor tissues and normal tissues.②Five pairs of gastric cancer and adjacent tissues and 5 pairs of colon cancer and adjacent tissues were collected,and RT-qPCR was used to verify the mRNA expression levels.③ RT-qPCR and Western blotting were used to verify the differential expression of PHB in normal gastric mucosa cells(GES-1),gastric cancer cells(AGS,MKN45 and HGC27),normal colon cells NCM-460 and human colon cancer cell line SW480.④R language was used to analyze the effect of PHB on the prognosis,tumor microenvironment,tumor mutation burden and microsatellite instability of DT patients.⑤CIBERSORT algorithm was used to study the correlation between PHB expression in tumor tissues and tumor immune cell infiltration.Gene Set Enrichment Analysis(GSEA)was used to explore the biological function of PHB.⑥R language was used to analyze the relationship between PHB and drug sensitivity.Results ①PHB was highly expressed in colon cancer,cholangiocarcinoma,esophageal cancer,liver cancer,rectal cancer and gastric cancer(P<0.01).②RT-qPCR and Western blotting showed that PHB was highly expressed in the tissues and cell lines of gastric cancer(P<0.01)and colon cancer(P<0.01).③The differential expression of PHB was associated with poor prognosis of hepatocellular carcinoma(P=0.002).In cholangiocarcinoma,gastric cancer,pancreatic cancer,liver cancer and esophageal cancer,PHB was positively correlated with tumor mutation burden and microsatellite instability(P<0.05).④PHB was positively correlated with M2 macrophages in colon cancer(P=0.03).In cholangiocarcinoma,it was positively correlated with activated CD4+memory T cells(P<0.05).In esophageal carcinoma,it was positively correlated with activated hypertrophy(P=0.03).It was positively correlated with M0 and M2 macrophages and monocytes in hepatocellular carcinoma(P<0.05).It was positively correlated with resting dendritic cells,eosinophils and activated CD4+memory T cells in rectal cancer(P<0.05).It was positively correlated with M0 macrophages,activated mast cells,neutrophils,resting natural killer cells,activated CD4+memory T cells and follicular helper T cells in gastric cancer(P<0.05).⑤PHB was mainly enriched in class I receptors,PPAR and calcium signaling pathways(P<0.05).⑥ The expression of PHB was positively correlated with the sensitivity of 13 drugs,including ammonafide,prasinolide and abiraterone(P<0.05).Conclusion The expression of PHB is significantly related to the infiltration of various immune cells in DT and poor prognosis in DT patients,which may become a new biomarker and potential immunomodulatory target of DT.
4.Effect of PEG-PLGA co-loaded resveratrol nanoparticles on colon cancer cells through EMT and PI3K/Akt signaling pathways
Hongliang GAO ; Hao ZHANG ; Mingzheng LI
International Journal of Biomedical Engineering 2024;47(5):457-462
Objective:To investigate the effects of polyethylene glycol-poly (lactic-co-glycolic acid) (PEG-PLGA) co-loaded resveratrol nanoparticles on colon cancer cells through epithelial-mesenchymal transition (EMT) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways.Methods:Human colon cancer HCT116 cells were randomly divided into the control group and the experimental group. The experimental group was supplemented with 50 μl of 10 μmol/L PEG-PLGA co-loaded resveratrol nanoparticle solution, and the control group was supplemented with the same volume of medium without adding any treatment substance. Cell viability was determined using the MTT assay, apoptosis rate was analyzed by flow cytometry, and cell migration ability was detected by a scratch test. Western Blot was used to analyze the expression of proteins of related signaling pathways such as apoptosis, EMT, and PI3K/Akt.Results:Compared with the control group, the survival rate of colon cancer cells in the experimental group was reduced and the apoptosis rate was increased ( P < 0.05). Compared with the control group, the scratch width of HCT116 cells in the experimental group was greater ( P < 0.001). Compared with the control group, the expression of B-cell lymphoma-2 (Bcl-2) protein in the experimental group was down-regulated ( P < 0.01), while the expression of Bcl-2 associated X protein (Bax) was up-regulated ( P < 0.05). Compared with the control group, the expression of N-cadherin protein in the experimental group was down-regulated, while the expression of E-cadherin was up-regulated ( P < 0.01). Compared with the control group, the levels of p-PI3K and p-Akt in the experimental group were down-regulated (both P < 0.01). Conclusions:PEG-PLGA co-loaded resveratrol nanoparticles can reduce the cell viability, proliferation, and migration of colon cancer cells, which may be related to the inhibition of EMT and PI3K/Akt signaling pathways.
5.Advances in the study of CAV1 in digestive tract tumors
Zhihang WU ; Mingzheng TANG ; Xiaofeng LI ; Yao RONG ; Yan CUI ; Haibang PAN
Chinese Journal of Comparative Medicine 2024;34(7):110-120
Digestive tract tumors are currently one of the most common types of cancer,including esophageal cancer,gastric cancer,hepatocellular carcinoma,pancreatic cancer,and colorectal cancer.Their prognoses are poor and the treatments require further improvement.Caveolin-1(CAV1)has a dual regulatory effect on digestive tract tumors as a tumor suppressor and cancer promoter.CAV 1 plays a major role in cell proliferation,invasion,metastasis,angiogenesis,and drug tolerance of digestive tract tumors.The regulation of CAV1 protein and its related signaling pathways may be a strategy for the treatment of digestive tract tumors.This review analyzes the relationship between CAV 1 and digestive tract tumors in terms of structure,function,expression regulation,regulation of epithelial-mesenchymal transition,and drug resistance in digestive tract tumors to provide new ideas for the diagnosis and treatment of digestive tract tumors.
6.FBXO43 expression in pan-cancer and its relationship with immune cell infiltration and prognosis
Songhua LIU ; Yao RONG ; Mingzheng TANG ; Yunyang CHEN ; Pengfei LI ; Xiaojun YANG
Journal of China Medical University 2024;53(9):834-844
Objective To investigate the expression of FBXO43in various cancers and its relationship with immune cell infiltration and prognosis using bioinformatics.Methods Gene expression data for 33 cancers were obtained from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases to analyze FBXO43expression.Clinical and survival data were sourced from the TCGA database.Gene Expression Profiling Interactive Analysis(GEPIA)was used to assess the correlation between FBXO43expression and the clinical stage.Kaplan-Meier survival analysis was used to evaluate the relationship between FBXO43expression and prognosis.R lan-guage was used to analyze the associations between FBXO43expression and clinical stages,immune cell infiltration,immune checkpoint genes,tumor mutation burden(TMB),microsatellite instability(MSI),and mismatch repair(MMR)genes.The potential biological mech-anisms of FBXO43were explored using gene set enrichment analysis(GSEA).Moreover,qRT-PCR was performed to measure FBXO43 expression in normal gastric mucosal cells(GES-1),gastric cancer cells(HGC-27,MGC-803,and MKN-45),normal liver cells(LO-2),and liver cancer cells(SMMC-7721,HEPG2,HuH7,and MHCC97-H).Results Combined TCGA and GTEx database statistics revealed higher FBXO43expression in 26 types of cancer tissues,including adrenocortical carcinoma(ACC),bladder urothelial carcinoma,breast invasive carcinoma,cervical squamous cell carcinoma and endocervical adenocarcinoma,cholangiocarcinoma,colon adenocarcinoma,and diffuse large B-cell lymphoma,than in normal tissues(P<0.05).However,FBXO43expression was lower in three types of cancer tissues:kidney chromophobe(KICH),testicular germ cell tumor(TGCT),and thyroid carcinoma(P<0.05).GEPIA data analysis showed that FBXO43expression positively correlated with the clinical stages of ACC,KICH,kidney renal clear cell carcinoma(KIRC),and kidney renal papillary cell carcinoma(KIRP)and negatively correlated with the clinical stages of ovarian serous cystadenocarcinoma(OV)and TGCT(P<0.05).Kaplan-Meier survival analysis indicated that abnormal FBXO43expression was associated with the prognosis of various cancers(P<0.05).Specifically,high FBXO43expression was a risk factor for ACC,KICH,KIRC,KIRP,low-grade glioma,liver hepato-cellular carcinoma,mesothelioma,and sarcoma,but protective in thymoma(THYM).The XCELL algorithm found that FBXO43expres-sion was negatively correlated with immune scores in nine types of cancer tissues,including glioblastoma multiforme,KIRP,acute myeloid leukemia,lung squamous cell carcinoma,and OV,and closely related to immune cell infiltration levels in 24 types of cancer tissues,espe-cially showing a significant negative correlation with most immune cells in SARC(P<0.01).Correlation analysis revealed a significant association between FBXO43and TMB,MSI,and MMR in all cancers.GSEA analysis indicated that FBXO43is involved in the cell cycle and immune-related functions in various tumors.qRT-PCR results showed that FBXO43expression was upregulated in liver cancer cells and downregulated in gastric cancer cells(all P<0.05).Conclusion Abnormal FBXO43expression is closely associated with the occur-rence and progression of multiple cancers.Thus,FBXO43may serve as a novel marker of immune cell infiltration and prognosis,thereby offering new directions for targeted cancer therapy.
7.Systematic review of the economic evaluation of influenza vaccines in the Guangdong-Hong Kong-Macao Greater Bay Area
Mingzheng HU ; Yanshang WANG ; Ming WANG ; Wentao LI ; Dawei ZHU ; Ping HE
China Pharmacy 2023;34(6):699-703
OBJECTIVE To systematically analyze the status of health economic evaluation studies of influenza vaccination in Guangdong-Hong Kong-Macao Greater Bay Area (GBA) of China, and to provide a methodological reference for future scholars to carry out economic evaluations of influenza vaccine in GBA. METHODS Seven English databases such as PubMed and Embase and three Chinese databases such as CNKI and Wanfang database were searched. The economic evaluation studies of influenza vaccines with the study area of GBA were collected. The search time frame was from the inception to June 30, 2022. After screening the literature and extracting key information, descriptive analysis was conducted on the study design, evaluation methods, model settings, results and conclusions of these collected papers, and the quality of the papers was evaluated using Quality of Health Economic Studies. RESULTS A total of 12 papers were included, of which 7 had a study region of Hong Kong in China, 6 had an older target group, 5 had a society-wide perspective, and the study time frame ranged from 6 months to 9 years. Besides, 8 papers used cost-utility analysis, only 2 used an epidemic model; 8 papers conducted sensitivity analyses, and most of them conducted both one-way sensitivity analysis and probabilistic sensitivity analysis. Moreover, the results of the economic evaluation of 10 papers showed that (combined) vaccination or increased vaccination rates were more economical. In addition, 4 of the 12 papers had a quality score>75, which were considered high-quality studies. CONCLUSIONS Although most of the included studies showed that vaccination was economical, the quality of the existing paper needed to be improved. It is recommended that subsequent studies on the economic evaluation of influenza vaccines in GBA may consider adding economic evaluations for Macau and other cities in Guangdong of China, prioritizing dynamic models and recent data from local residents, and referring to relevant tools and guidelines to improve thestandardization and scientificity of the study design.
8.Arthroscopic minimally invasive reduction for talus posterior process fractures
Mingzheng WU ; Ming XIE ; Li YAN ; Qingsong ZHANG ; Rui HU ; Feng LIU ; Shanqing LI ; Ruokun HUANG
Chinese Journal of Orthopaedic Trauma 2023;25(1):77-82
Objective:To evaluate the efficacy of arthroscopic minimally invasive reduction in the treatment of talus posterior process fractures.Methods:The clinical data were retrospectively studied of the 42 patients with talus posterior process fracture who had been admitted to Department of Orthopedics, The Fourth Hospital of Wuhan from January 2010 to June 2021. There were 25 males and 17 females, aged from 21 to 60 years (average, 40.5 years). They were assigned into 2 groups according to their different treatments. In the arthroscopic group of 15 cases, arthroscopic reduction and internal fixation (ARIF) were conducted via the posteromedial and posterolateral approaches; in the open reduction group of 27 cases, open reduction and internal fixation (ORIF) were conducted via the posteromedial para-Achilles approach. The 2 groups were compared in terms of operation time, blood loss, hospital stay, fracture clinical healing time, postoperative complications, and the American Society for Foot and Ankle Surgery (AOFAS) ankle-hindfoot score at one year postoperation.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P> 0.05). The arthroscopic group incurred significantly less blood loss [(32.0±11.5) mL], hospital stay [(5.3±1.8) d], and fracture clinical healing time [(4.6±1.0) months], and a significantly lower incidence of postoperative complications [20.0% (3/15)] than the open reduction group did [(80.0±15.2) mL, (8.4±2.4) d, (6.3±2.2) months, and 29.6% (8/27)], but significantly longer operation time [(74.0±8.9) min] than the open reduction group [(62.9±5.1) min] ( P<0.05). The AOFAS ankle-hindfoot scores at one year postoperation in both groups were higher than those before operation. The AOFAS ankle-hindfoot scores in the arthroscopic group [(83.0±13.0) points] were significantly higher than those in the open reduction group [(72.3±16.0) points] ( P<0.05). Conclusion:ARIF is a preferred minimally invasive treatment for talus posterior process fractures, because it leads to a smaller incision, less blood loss, shorter hospital stay, quicker clinical healing, a lower incidence of postoperative complications, and better functional improvement of the ankle and hindfoot than ORIF.
9.Correlation of immune inflammatory index with occurrence, development and prognosis of hepatocellular carcinoma
Mingzheng LI ; Yan WANG ; Shiming WANG
Cancer Research and Clinic 2023;35(3):236-240
Hepatocellular carcinoma is a typical chronic inflammatory-associated malignancy. Chronic inflammation continuously damages the reticuloendothelial system of the liver and leads to impairment of immune surveillance, which in turn leads to dysregulation of the immune environment. Immune escape caused by impaired surveillance system can improve the immunogenicity of tumor, which plays an important role in the occurrence and development of tumors. Studies have shown that the indicators including immune inflammatory cells such as neutrophils, platelets and lymphocytes can predict the prognosis of hepatocellular carcinoma, the individualized treatment and early intervention for patients on this basis is expected to improve the prognosis of patients. The article introduces the role of immune cells in the occurrence and development of hepatocellular carcinoma, and summarizes the relationship between peripheral blood immune inflammatory indicators and prognosis of hepatocellular carcinoma.
10.Early predictors for acute kidney injury in acute pancreatitis
Yan WANG ; Mingzheng LI ; Yufeng LIU ; Shiming WANG
Journal of Clinical Hepatology 2022;38(5):1192-1197
Acute pancreatitis (AP) is one of the common acute abdominal diseases of the digestive system, and early treatment to avoid aggravation to severe pancreatitis (SAP) is the key to guaranteeing prognosis. AP with acute kidney injury (AKI) can significantly increase the mortality rate of pancreatitis. Early diagnosis of AP with AKI is a top priority to reduce mortality rate. This article reviews the current studies on the early predictors for AKI in AP and briefly describes commonly used indicators (neutrophil-to-lymphocyte ratio, cystatin C, renal vascular resistance index, and neutrophil gelatinase-associated lipocalin) and other valuable indicators. It is pointed out that a combination of various markers based on their sensitivity and specificity has a promising future in the diagnosis of AKI in AP.

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