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ABSTRACT Background: Adriamycin (ADM) resistance remains an obstacle to gastric cancer chemotherapy treatment. Objective: The objective of this study was to study the role and mechanism of transcription factor E2F7 in sensitivity to ADM chemotherapeutic agents in gastric cancer. Methods: Cell viability and cell sensitivity were assessed by CCK-8 and IC50 values of ADM were calculated. The impact of ADM on cellular proliferative capacity was assessed through colony formation assay. The binding relationship between E2F7 and PKMYT1 was then verified by dual luciferase assay and chromatin immunoprecipitation assay. ERK1/ERK2 and p-ERK1/p-ERK2 protein expression levels were detected by western blot. Results: In both gastric cancer tissue and ADM-resistant cells, a conspicuous upregulation of E2F7 and PKMYT1 was observed. Upregulated PKMYT1 was notably enriched in the MAPK signaling pathway. Enhanced levels of E2F7 were shown to not only drive gastric cancer cell proliferation but also engender a reduction in the sensitivity of these cells to ADM. Furthermore, PKMYT1 emerged as a downstream target of E2F7. Activation of E2F7 culminated in the transcriptional upregulation of PKMYT1, and silencing E2F7 reversed the inhibitory impact of PKMYT1 overexpression on ADM sensitivity in gastric cancer cells. Conclusion: E2F7/PKMYT1 axis might promote the proliferation and partially inhibit ADM sensitivity of gastric cancer cells by activating the MAPK pathway.
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Objective:To investigate the efficacy of Balanophora involucrata Hook.f.in treatment of hyperuricemia(HUA)based on network pharmacology,molecular docking,and hyperuricemia models in vivo and in vitro,and to clarify the main targets of its active components and related signaling pathway mechanism.Methods:The potential targets of Balanophora involucrata Hook.f.in treatment of HUA were identified by Databases such as the Traditional Chinese Medicine Database in Taiwan,the Chinese Herbal Medicine Identification Database,Professional Chemical Database,TargetNet Database,SwissTargetPrediction Database,GeneCards,Therapeutic Target Database(TTD),DrugBank Database,DisGeNET Database,Online Mendelian Inheritance in Man(OMIM)Database,and Venny Database.STRING Database and Cytoscape software were used to construct the active component-predictive target network and protein-protein interaction(PPI)network for Balanophora involucrata Hook.f.;topological analysis was used to select the main active components and core targets;Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by R software;AutoDock Vina software was used for molecular docking validation.The NRK-52E cells were divided into blank control group,blank administration group,model group,and different concentrations(2.0,10.0,and 50.0 μmol·L-1)of erythrodiol(EDT)groups.High-performance liquid chromatography culture(HPLC)was used to detect the uric acid(UA)levels in the cell culture supernatants in various groups.The male ICR mice were divided into blank control group,blank administration group,model group,and EDT group;the mice in the last two groups were used to prepare the HUA models;kits were used to detect the levels of UA,creatinine(Cr),and blood urea nitrogen(BUN)in serum of the mice in various groups;the bilateral kidney tissue of the mice was harvested and weighed;the kidney indexes of the mice in various groups were calculated;TUNEL staining was used to observe the apoptosis in kidney tissue of the mice in various groups;Western blotting method was used to detect the expression levels of protein kinase B(AKT),phosphorylated AKT(p-AKT),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and matrix metalloproteinase-9(MMP-9)proteins in kidney tissue of the mice in various groups.Results:Six active components of Balanophora involucrata Hook.f.were identified,involving 116 intersecting targets and 14 core targets.The enrichment analysis yielded 1 828 GO terms and 145 signaling pathways.The molecular docking results showed that EDT had good binding activity with MMP-9.The high uric acid cell experiment results showed that compared with blank control group,the UA level in the cells in model group was significantly increased(P<0.01);compared with model group,the UA levels in the cells in 2.0,10.0,and 50.0 μmol·L-1 EDT groups were significantly decreased(P<0.01).Compared with blank control group,the levels of UA,Cr,and BUN in serum of the mice in model group were increased(P<0.01),and the kidney indexes were significantly increased(P<0.01);compared with model group,the levels of UA,Cr,and BUN in serum of the mice in EDT group were decreased(P<0.05 or P<0.01),and the kidney index was significantly decreased(P<0.05 or P<0.01).Compared with blank control group,the number of apoptotic cells in kidney tissue of the mice in model group was increased;compared with model group,the number of the apoptotic cells in kidney tissue of the mice in EDT group was significantly decreased.Compared with blank control group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in model group were significantly decreased(P<0.05 or P<0.01),while the expression levels of Bax and MMP-9 proteins were significantly increased(P<0.01);compared with model group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in EDT group were significantly increased(P<0.05 or P<0.01),and the expression levels of Bax and MMP-9 proteins were significantly decreased(P<0.01).Conclusion:The active component of Balanophora involucrata Hook.f.,EDT,has a UA-decreasing effect and may inhibit the apoptosis and alleviate the kidney injury by activating the PI3K/AKT signaling pathway.
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Objective To discuss the feasibility and safety of simultaneous bilateral adrenal vein sampling(AVS)using two 4F-MPA1 catheters via right elbow vein access.Methods A total of 51 consecutive patients with primary aldosteronism,who received simultaneous bilateral AVS using two 4F-MPA1 catheters(one of the two catheters was shaped into pig tail figure)via right elbow vein access at Xiangyang Municipal Central Hospital between October 2021 and October 2022,were enrolled in this study.The used catheter,the success rate of simultaneous bilateral AVS,and the incidence of complications rate were calculated.Results The 4F-MPA1 catheter was used for all of the right AVS,while a specially shaped 4F-MPA1 catheter was used for the main trunk vein AVS of the left adrenal gland and the central vein AVS of the left adrenal gland.The success rate of simultaneous bilateral AVS was 92.2%(47/51).Adrenal hematoma occurred in one patient(1.96%).Conclusion The technique of simultaneous bilateral AVS using two 4F-MPA1 catheters via right elbow vein access is simple to operate,less traumatic,and clinically safe and feasible.However,due to the small sample used in this study,the clinical value of this technique still needs further investigation and verification.
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Objective To explore the changes and clinical significance of D-dimer(D-D),prothrombin fragment 1+2(F1+2)and P-selectin in patients with acute deep venous thrombosis of lower extremities(DVT)before and after catheterization and thrombolysis.Methods A total of 186 patients with acute DVT in the Third People's Hospital of Yunnan Province from March 2020 to March 2022 were selected as the study objects.And all of them underwent catheterization and hemolysis and were followed up in the outpatient form 12 months after the surgery.4 cases were lost to follow-up,and a total of 182 cases completed postoperative follow-up.Postthrombotic syndrome(PTS)was divided into PTS group(n = 27)and non-PTS group(n = 155)according to whether post-thrombotic syndrome(PTS)occurred 12 months after the surgery.The general data of the two groups and the expression of D-D,F1+2,P-selectin in plasma before and after thrombolytic therapy were compared,and the influencing factors of PTS were analyzed by Logistic analysis.Receiver operating characteristic curve(ROC)and area under curve(AUC)were plotted to analyze the value of plasma D-D,F1+2,P-selectin in predicting the occurrence of PTS,and relative risk(RR)was used to analyze the influence of different plasma D-D,F1+2,P-selectin expression on PTS.Results Age,BMI,venous patency score,and plasma D-D,F1+2,P-selectin expression 1 week and 1 month after thrombolysis in PTS group were higher than those in non-PTS group(P<0.05).Logistic showed that BMI and plasma D-D,F1+2 and P-selectin 1 week and 1 month after thrombolysis were the influential factors for PTS in acute DVT patients(P<0.05).ROC curve showed that the combined efficacy of D-D,F1+2 and P-selectin 1 month after thrombolysis was significantly better than that of D-D,F1+2 and P-selectin 1 week after thrombolysis in predicting PTS.One month after thrombolysis,the risk of PTS in patients with high plasma D-D,F1+2,P-selectin expression was 4.211,2.550 and 3.189 times higher than that in patients with low plasma D-D,F1+2,P-selectin expression.Conclusion The expression of D-D,F1+2 and P-selectin in plasma increases after thrombolysis in acute DVT patients,and the combination of D-D,F1+2 and P-selectin can predict the occurrence of PTS.
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Objective·To analyze the expression changes of adhesion G protein-coupled receptor F1(ADGRF1)in the occurrence and development of pancreatic ductal adenocarcinoma(PDAC),and explore the impact of ADGRF1 on the proliferation of PDAC cells and the potential molecular mechanisms that promote PDAC progression.Methods·The expression of ADGRF1 at mRNA level was analyzed based on the Gene Expression Omnibus(GEO)database and The Cancer Genome Atlas(TCGA)database,respectively.The expression of ADGRF1 in normal pancreatic ductal epithelial cells(hTERT-HPNE)and various PDAC tumor cells was detected by using real-time fluorescence quantitative PCR(qPCR)and Western blotting.Immunohistochemical staining(IHC)was used to detect the differential expression of ADGRF1 in cancer tissues and adjacent tissues of PDAC patients.After knocking down ADGRF1 with small interfering RNA(siRNA)transfection,the changes in the proliferation ability of PDAC AsPC-1 and SW1990 cells were detected through CCK8 assay and plate cloning experiment.Stable overexpression of ADGRF1 was constructed in PDAC Patu8988 cell line,and the proliferation changes induced by overexpression of ADGRF1 were evaluated through CCK8 assay.RNA sequencing(RNA-seq),gene set enrichment analysis(GSEA),and immune infiltration analysis were utilized to predict signaling pathways associated with ADGRF1-mediated promotion of PDAC cancer progression.Results·Analysis of the TCGA database and GEO database revealed higher expression of ADGRF1 mRNA in PDAC tissues compared to normal pancreatic tissues(all P=0.000).qPCR and Western blotting results demonstrated up-regulation of ADGRF1 mRNA and protein levels in various PDAC cells compared to hTERT-HPNE cells(all P<0.05).IHC results confirmed higher ADGRF1 expression in PDAC cancer tissues compared to adjacent tissues.Furthermore,downregulation of ADGRF1 inhibited the proliferation of PDAC AsPC-1 and SW1990 cell lines,while overexpression of ADGRF1 promoted the proliferation of Patu8988 cells(all P<0.05).RNA-seq,GSEA enrichment analysis,and immune infiltration analysis revealed that ADGRF1 expression was related to signaling pathways such as interferon-α(IFN-α),tumor necrosis factor-α(TNF-α),and nuclear factor κB(NF-κB).Conclusion·ADGRF1 is highly expressed in PDAC cells and tissues,and promotes the proliferation of PDAC cells via immune-related signaling pathways.
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Objective To investigate the expression and clinical relevance of heterogeneous nuclear ribonucleoproteins F(HNRNPF)in prostate cancer and its effect on the proliferation,migration and invasion of prostate cancer cells.Methods The expression and immune infiltration characteristics of HNRNPF in prostate cancer and its correlation with the clinicopathological characteristics of prostate cancer patients were analyzed using TCGA database and GEO database.The HNRNPF gene was silenced by RNA interference in prostate cancer cell PC-3 and DU145,then the changes in cell proliferation ability was detected by CCK-8,EdU and colony formation assays,and the changes in cell migration and invasion abilities were detected by Transwell and wound-healing assays.Results The expression of HNRNPF was significantly increased in prostate cancer compared with normal prostate tissue and significantly associated with T stage,Gleason score,prostate specific antigen and the infiltration level of multiple immune cells of prostate cancer patients.The prostate cancer patients with high expression of HNRNPF had shorter overall survival and disease-specific survival.HNRNPF silencing decreased the proliferation,migration,and invasion abilities of prostate cancer cells PC-3 and DU145.Conclusion HNRNPF is a gene that is highly expressed in prostate cancer,has significant clinical relevance,and can promote the proliferation,migration,and invasion of prostate cancer cells.
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This article reports the diagnosis and treatment of a patient with primary hyperparathyroidism(PHPT)and vitamin D deficiency.The patient was a young male with a insidious onset.Multiple tests have shown hypercalcemia,hypophosphatemia,hypercalciuria,and hyperparathyroidism.There was no renal dysfunction,and the diagnosis of PHPT was clear.There were kidney stones and vitamin D deficiency at the same time.The patient met the surgical indications,but the difficulty in preoperative localization was that ultrasound examination showed suspicious masses in both parathyroid regions,and the 99mTc-MIBI imaging result was negative.Finally,accurate preoperative localization was achieved through 18F-fluorocholine PET/CT,and the patient was cured after surgery.
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Objective To investigate the expression of centromeric protein F(CENPF)and microribonucleic acid 1-3p(miR-1-3p)in the serum of patients with advanced gastric cancer and their correlation with prognosis.Methods Sixty patients with advanced gastric cancer admitted to our hospital from March 2019 to March 2020 were collected as the study group,while 60 healthy volunteers who underwent physical examinations at our hospital's physical examination center during the same period were collected as the control group.Real-time fluorescence quantitative PCR(qRT-PCR)method was applied to detect the expression levels of serum CENPF and miR-1-3p in each group;Pearson method was applied to analyze the correlation between serum levels of CENPF and miR-1-3p;Kaplan-Meier method was applied to analyze the relationship between the expression of CENPF,miR-1-3p,and prognosis in patients with advanced gastric cancer;and COX regression was applied to analyze risk factors affecting the prognosis of patients with advanced gastric cancer.Results Compared with the control group,the CENPF level in the study group was obviously increased,while the miR-1-3p level was obviously reduced(P＜0.05).The correlation analysis results showed that there was a negative correlation between serum CENPF and miR-1-3p levels in patients with advanced gastric cancer(r =-0.650,P＜0.001).There were obvious differences in CENPF and miR-1-3p levels among different TNM stages and lymph node metastasis status(P＜0.05).The 3-year survival rate of patients in the high expression group of CENPF was 19/30(63.33%),which was obviously lower than that in the low expression group,28/30(93.33%)(χ2 = 7.954,P＜0.001);the 3-year survival rate of patients in high expression group of miR-1-3p was 29/30(96.67%),which was obviously higher than that in the low expression group,18/30(60.00%)(χ2 = 11.882,P = 0.001).Multivariate COX regression analysis showed that TNM staging,lymph node metastasis,CENPF,and miR-1-3p expression were risk factors affecting the prognosis of patients with advanced gastric cancer(P＜0.05).Conclusion The serum CENPF level in patients with advanced gastric cancer obviously increase,while miR-1-3p level obviously decrease,both of which are related to prognosis.
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BACKGROUND:Ginseng extracts have been found to significantly improve osteoarthritis,but the therapeutic effects of ginseng polysaccharide extracts on osteoarthritis have not been reported. OBJECTIVE:To investigate the effect of ginseng polysaccharide on the expression of prostaglandin E2/6-keto-prostaglandin F1α in traumatic osteoarthritis model rats. METHODS:Sixty male Sprague-Dawley rats were selected and randomly divided into healthy group,model group,ginseng polysaccharide low-dose group,ginseng polysaccharide medium-dose group,ginseng polysaccharide high-dose group and dexamethasone group.Except for 10 rats in the healthy group,the other rats were taken to establish traumatic osteoarthritis models.The healthy group and model group were given 0.2 mL of normal saline intraperitoneally.The low-,medium-,and high-dose groups were intraperitoneally injected with 0.1,0.25,0.5 μg/mL ginseng polysaccharide,respectively.In the dexamethasone group,0.2mg/kg dexamethasone(0.2 mL)was injected intraperitoneally.Injections were given once every 3 days,for 4 consecutive weeks.Serum prostaglandin E2 and 6-keto-prostaglandin F1α levels were detected by ELISA.The bone and joint function of rats were assessed by the Mankin's score.Hematoxylin-eosin staining was used to observe the pathologic morphology of the knee joints of rats.Western blot and PCR were used to detect the protein and mRNA expression of tumor necrosis factor α and interleukin-1β,interleukin-10 in articular cartilage tissue,respectively. RESULTS AND CONCLUSION:Compared with the model group,serum prostaglandin E2 levels were decreased in the medium-dose group and dexamethasone group,while serum 6-keto-prostaglandin F1α levels were increased(P<0.05).Compared with the medium-dose group and dexamethasone group,the above-mentioned indicators were significantly improved in the high-dose group,and there was no significant difference between the medium-dose group and dexamethasone group(P>0.05).Compared with the model group,the Mankin's score was reduced in the medium-dose group and dexamethasone group(P<0.05),but there was no significant difference between the medium-dose group and dexamethasone group(P>0.05).Compared with the medium-dose group and dexamethasone group,the Mankin's score was significantly reduced in the high-dose group(P<0.05).The cartilage tissue layer of rats in the model and low-dose groups was significantly thinned,the cracks and chondrocytes deep into the bone layer were largely lost,the tide line was seriously broken and blurred,the collagen fibers in the synovial layer were increased and thickened,and a large number of chondrocytes were destroyed and arranged irregularly.These pathological changes were improved in the medium-dose group and dexamethasone group compared with the model group as well as improved in the high-dose group compared with the medium-dose group.Compared with the model group,the expression of tumor necrosis factor-α and interleukin-1β was reduced,while the expression of interleukin-10 was increased in the medium-dose group and dexamethasone group(P<0.05).These indicators in the joint were significantly improved in the high-dose group compared with the medium-dose group and dexamethasone group(P<0.05),but there was no significant difference between the medium-dose group and dexamethasone group(P>0.05).To conclude,ginseng polysaccharide can improve the inflammatory level and pathological morphology of traumatic osteoarthritis rats and reduce the Mankin's score.Its mechanism may be related to the regulation of prostaglandin E2/6-keto-prostaglandin F1α levels.
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BACKGROUND:Heterotopic ossification is a dynamic growth process.Diverse heterotopic ossification subtypes have diverse etiologies or induction factors,but they exhibit a similar clinical process in the intermediate and later phases of the disease.Acquired heterotopic ossification produced by trauma and other circumstances has a high incidence. OBJECTIVE:To summarize the molecular biological mechanisms linked to the occurrence and progression of acquired heterotopic ossification in recent years. METHODS:The keywords"molecular biology,heterotopic ossification,mechanisms"were searched in CNKI,Wanfang,PubMed,Embase,Web of Science,and Google Scholar databases for articles published from January 2016 to August 2022.Supplementary searches were conducted based on the obtained articles.After the collected literature was screened,131 articles were finally included and summarized. RESULTS AND CONCLUSION:(1)The occurrence and development of acquired heterotopic ossification is a dynamic process with certain concealment,making diagnosis and treatment of the disease difficult.(2)By reviewing relevant literature,it was found that acquired heterotopic ossification involves signaling pathways such as bone morphogenetic protein,transforming growth factor-β,Hedgehog,Wnt,and mTOR,as well as core factors such as Runx-2,vascular endothelial growth factor,hypoxia-inducing factor,fibroblast growth factor,and Sox9.The core mechanism may be the interaction between different signaling pathways,affecting the body's osteoblast precursor cells,osteoblast microenvironment,and related cytokines,thereby affecting the body's bone metabolism and leading to the occurrence of acquired heterotopic ossification.(3)In the future,it is possible to take the heterotopic ossification-related single-cell osteogenic homeostasis as the research direction,take the osteoblast precursor cells-osteogenic microenvironment-signaling pathways and cytokines as the research elements,explore the characteristics of each element under different temporal and spatial conditions,compare the similarities and differences of the osteogenic homeostasis of different types and individuals,observe the regulatory mechanism of the molecular signaling network of heterotopic ossification from a holistic perspective.It is beneficial to the exploration of new methods for the future clinical prevention and treatment of heterotopic ossification.(4)Meanwhile,the treatment methods represented by traditional Chinese medicine and targeted therapy have become research hotspots in recent years.How to link traditional Chinese medicine with the osteogenic homeostasis in the body and combine it with targeted therapy is also one of the future research directions.(5)At present,the research on acquired heterotopic ossification is still limited to basic experimental research and the clinical prevention and treatment methods still have defects such as uncertain efficacy and obvious side effects.The safety and effectiveness of relevant targeted prevention and treatment drugs in clinical application still need to be verified.Future research should focus on clinical prevention and treatment based on basic experimental research combined with the mechanism of occurrence and development.
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Objective:To investigate the value of traditional metabolic parameters, CT features and intratumoral heterogeneity parameters measured by 18F-FDG PET/CT in predicting the mutation status of the epidermal growth factor receptor (EGFR) gene in patients with adenocarcinoma. Methods:A total of 147 patients (73 males, 74 females, age (59.8±10.2) years) with pathological confirmed adenocarcinoma between January 2016 and June 2020 in the Affiliated Hospital of Jining Medical University were retrospectively included. The differences of clinical data (smoking history, tumor location and clinical stage), CT features (maximum diameter, ground-glass opacity content, lobulation, speculation, cavitation, air-bronchogram, pleural retraction and bronchial cut-off sign), 18F-FDG PET/CT traditional metabolic parameters (SUV max, SUV mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)) and intratumoral heterogeneity parameters ( CV, heterogeneity index (HI)) were analyzed between patients with EGFR mutation and patients with EGFR wild-type. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Multivariate logistic regression was used to analyze the predictors of EGFR mutation. ROC curve analysis was used to evaluate the predictive value of clinical and PET/CT information. Results:Among 147 patients, 87 were with EGFR mutation and 60 were with EGFR wild-type. There were significant differences in gender (male/female), smoking history (with/without), location (peripheral lesion/central lesion), pleural retraction (with/without), SUV max, SUV mean, TLG, CV and HI ( χ2 values: 4.72-23.89, z values: from -2.31 to 5.74, all P<0.05). Multivariate logistic regression analysis showed that smoking history (odds ratio ( OR)=0.167, 95% CI: 0.076-0.366; P<0.001), pleural retraction ( OR=1.404, 95% CI: 1.115-3.745; P=0.012), SUV max ( OR=0.922, 95% CI: 0.855-0.995; P=0.003), TLG ( OR=0.991, 95% CI: 0.986-0.996; P=0.001) and HI ( OR=0.796, 95% CI: 0.700-0.859; P<0.001) were predictors of EGFR mutation. ROC curve analysis showed the AUC of HI was 0.779, with the sensitivity of 76.67%(46/60) and the specificity of 79.31%(69/87). The predictive model was constructed by combining smoking history, pleural retraction, TLG, SUV max and HI, and the AUC was 0.908, with the sensitivity of 88.33%(53/60) and the specificity of 68.97%(60/87). The difference of AUCs between HI and the predictive model was statistically significant ( z=3.71, P<0.001). Conclusion:HI can predict EGFR mutations better, and the predictive value for EGFR mutations can be enhanced when combining HI with smoking history, pleural retraction, TLG and SUV max.
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Objective:To investigate whether the image quality of total-body PET/CT (TB PET/CT) with 1 min acquisition can meet the clinical diagnostic requirements.Methods:From May 2019 to September 2021, a total of 90 malignant tumor patients (60 males, 30 females, age 31-86 years) with primary lesions confirmed by pathological diagnosis in Zhongshan Hospital, Fudan University were respectively analyzed. All patients underwent conventional PET/CT (C PET/CT) scan with conventional clinical acquisition and TB PET/CT scan with 1 min acquisition after injecting 18F-FDG in random order. Paired t test or Wilcoxon signed rank test was used to analyze the image quality of these two scans. Results:SUV max of primary lesions in TB PET/CT group was significantly higher than that in C PET/CT group (15.9(7.9, 24.6) vs 12.5(5.8, 16.6); z=8.14, P<0.001), so were signal-to-noise ratio (SNR) of the blood pool, liver, muscles (9.3±3.0, 11.4(9.5, 14.2), 8.3(7.3, 10.1) vs 6.2±1.7, 9.4(7.7, 11.8), 6.0(4.9, 7.1)), tumor-to-blood pool ratio (TBR) (9.3(4.3, 14.8) vs 8.5(4.3, 11.1)), tumor-to-liver ratio (TLR) (6.7(3.0, 10.4) vs 6.1(2.9, 7.7)), tumor-to-muscle ratio (TMR) (23.2(11.5, 38.0) vs 18.3(9.6, 26.6); t=9.36, z values: 4.44-7.40, all P<0.001). Conclusion:The image quality of TB PET/CT scan with 1 min acquisition can meet the diagnostic requirements, and is better than the C PET/CT image quality with conventional clinical acquisition.
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Objective:To evaluate the predictive value of 18F-FDG PET-based radiomics models for lymphovascular invasion (LVI) and visceral pleural invasion (VPI) in lung adenocarcinoma (LAC) prior to surgery. Methods:Eighty-seven patients with LAC (42 males, 45 females, age: (64.6±9.0) years; 90 lesions) pathologically confirmed in the Affiliated Taizhou People′s Hospital of Nanjing Medical University between August 2018 and August 2022 were retrospectively included. Based on the radiomics features extracted from PET images, the machine learning models were constructed by using the support vector machine (SVM), logical regression (LR), decision tree (DT), and K-nearest neighbor (KNN) algorithm. Stratified sampling (Python′s StratifiedkFold function) was employed to divide the data into training set and test set at a ratio of 8∶2. The model stability was assessed using the 50% discount cross-validation. The ROC curve was drawn, and the AUC was calculated to evaluate the value of radiomics models in predicting LVI and VPI in LAC. Delong test was used to compare AUCs of different models.Results:The radiomics models (SVM, LR, DT, KNN) based on PET images showed good predictive value for LVI and VPI in patients with LAC. For LVI, the AUCs were 0.91, 0.90, 0.91, 0.91 in the training set, and were 0.85, 0.87, 0.77, 0.78 in the test set; for VPI, the AUCs were 0.86, 0.86, 0.84, 0.81 in the training set, and were 0.82, 0.80, 0.69, 0.78 in the test set. The F1 scores of the SVM model were the best (0.59 and 0.66 for predicting LVI and VPI respectively). The Delong test showed that there were no significant differences in AUCs among the four models ( z values: from -1.46 to 1.71, all P>0.05). Conclusions:The machine learning models based on 18F-FDG PET radiomics features are effective in predicting LVI and VPI in patients with LAC prior to surgery. These models can assist clinicians in stratifying the risk of LAC and making informed clinical decisions. The SVM model has the best performance in predicting LVI and VPI.
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Objective:To investigate the value of radiomics signatures based on 18F-FDG PET/CT for predicting molecular classification and Ki-67 expression of breast cancer. Methods:A total of 134 female patients ((55.4±13.3) years) who underwent 18F-FDG PET/CT examination and were diagnosed with breast cancer by pathology in the First Affiliated Hospital of Soochow University from April 2016 to May 2023 were retrospectively enrolled. LIFEx software was used to extract radiomics features and the least absolute shrinkage and selection operator (LASSO) algorithm and independent-sample t test were used to screen potentially meaningful features and calculate the radiomics score, which were considered as radiomics models. Clinical characteristics were selected by supervised logistic regression and clinical models were established. Radiomics features and clinical characteristics were incorporated to logistic regression analysis to establish combined models. ROC curves were drawn and the differences among AUCs were analyzed by Delong test. Results:Among 134 patients, 22 were with triple negative breast cancer (TNBC), 47 were human epidermal growth factor receptor 2 (HER2) over-expression type, 37 were Luminal A type and the rest 28 were Luminal B type. The expression of Ki-67 was high in 85 patients, and was low in the rest 49 patients. The AUCs (95% CI) of the combined models for predicting TNBC, HER2 overexpression type, Luminal A type and Ki-67 expression were 0.843(0.770-0.900), 0.808(0.723-0.876), 0.825(0.711-0.908) and 0.836(0.762-0.894), respectively, which were higher than those of clinical models ( z values: 1.97-3.06, all P<0.05). Conclusion:The predictive model combining radiomics signatures based on 18F-FDG PET/CT and clinical characteristics can well predict the molecular classification and Ki-67 expression level of breast cancer.
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Objective:To investigate the diagnostic value of machine learning model based on 18F-FDG PET/CT for polymyalgia rheumatica (PMR). Methods:From November 2014 to December 2022, 177 patients (119 males, 58 females; age: 67.0 ( 61.0, 72.0) years) admitted to the Department of Rheumatology and Immunology, the First People′s Hospital of Changzhou, with suspected PMR and undergoing 18F-FDG PET/CT examination were retrospectively analyzed. Patients were randomly divided into training set and validation set at the ratio of 7∶3. Three machine learning models, including classification and regression tree (CART), the least absolute shrinkage and selection operator (LASSO) algorithm, and logistic regression, were established based on the PET/CT imaging features to aid in the diagnosis of PMR. The diagnostic efficacy of each model was evaluated by ROC curve analysis and differences among AUCs were analyzed by Delong test. Results:There were 78(44.1%, 78/177) PMR patients and 99(55.9%, 99/177) non-PMR patients, and 124 patients in the training set and 53 patients in the validation set. The logistic regression model (training set: AUC=0.961; validation set: AUC=0.930) was superior to the CART (training set: AUC=0.902, z=2.96, P=0.003; validation set: AUC=0.844, z=2.46, P=0.014) in diagnosing PMR, and was similar to LASSO algorithm (training set: AUC=0.957, z=0.95, P=0.340; validation set: AUC=0.930, z=0.00, P=1.000), but with fewer sites evaluated. The simplified PMR-Logit score had the AUC of 0.951 in the overall population, with the sensitivity of 89.74%(70/78) and the specificity of 90.91%(90/99). Conclusion:Machine learning models based on 18F-FDG PET/CT imaging features are expected to be an effective diagnostic tool for PMR.
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Objective:To compare and choose the best method for measuring metabolic tumor volume (MTV) of nasal extranodal natural killer/T-cell lymphoma (ENKTL), evaluate the prognostic value of 18F-FDG PET/CT metabolic parameters and clinical staging/scoring systems for patients with nasal ENKTL, and explore the added value of the two combinations for prognostic prediction. Methods:From January 2016 to September 2022, 44 patients (26 males, 18 females; age (47.5±13.6) years) pathologically diagnosed with nasal ENKTL who underwent 18F-FDG PET/CT imaging before treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively collected. SUV 2.5, SUV 4.0 and 41%SUV max were used as thresholds to measure MTV and total lesion glycolysis (TLG), and the consistency was analyzed by Bland-Altman analysis. The ROC curve analysis was used to compare the prognostic efficiency of different methods and determine the best method. The prognostic values of different clinical factors and clinical staging/scoring systems between groups were evaluated by corrected χ2 test. The independent factors were screened by Cox-regression model, and the combined diagnosis model was constructed by logistic regression. Results:Of 44 patients, 6(13.6%) were dead, with the overall survival (OS) of 32.05(11.77, 64.43) months, and the 2-year and 5-year OS rates of 86.6% and 82.5%, respectively. The mortality of different groups in age (≥60 and <60 years), prognostic index of natural killer cell lymphoma (PINK) score (low- and high-risk), and international prognostic index (IPI) score (low- and high-risk) were significantly different ( χ2 values: 5.02, 4.12, 3.88, all P<0.05). The consistency of MTV measured by different thresholds was good. Among them, the MTV measured by threshold of SUV 2.5 had the highest predictive efficiency with the AUC of 0.737. Multivariate analysis showed that MTV (hazard ratio ( HR)=10.488, 95% CI: 1.864-59.026, P=0.008) was the independent influencing factor of OS. By removing other factors, minimization model was obtained, including MTV and PINK score ( P values: 0.006, 0.048). The prediction model of MTV combined with PINK score improved prognostic efficacy with the AUCs of MTV, PINK score and the combination model of 0.781, 0.741 and 0.912, respectively. Conclusions:MTV measured by threshold of SUV 2.5 has better prognostic predictive value. MTV is the independent prognostic factor for OS in nasal ENKTL patients. MTV combined with PINK score has better prognostic value.
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Objective:To evaluate the value of 18F-FDG PET metabolic parameters in predicting histopathological grade of soft tissue sarcoma (STS). Methods:From December 2012 to December 2021, 51 patients (26 males, 25 females, age range: 32-84 years) who underwent 18F-FDG PET/CT imaging before treatment and confirmed STS pathologically in the First Affiliated Hospital of Dalian Medical University were retrospectively collected. 18F-FDG PET metabolic parameters SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG) and intertumoral FDG uptake heterogeneity (IFH) were measured. Kruskal-Wallis rank sum test was used to analyze the differences in metabolic parameters among different groups and Spearman rank correlation analysis was used to analyze the correlation of each metabolic parameter and histological grade. Logistic regression was used to screen and construct the prediction model for high-grade STS. ROC curve was plotted and Delong test was used to analyze the differences among AUCs. Results:The metabolic parameters SUV max, MTV, TLG and IFH were significantly different among French Federation of Cancer Centers Sarcoma Group (FNCLCC)Ⅰ( n=8), Ⅱ( n=10) and Ⅲ ( n=33) grade groups ( H values: 16.24, 10.52, 19.29 and 16.99, all P<0.05), and each metabolic parameter was positively correlated with histological grade ( rs values: 0.58, 0.45, 0.52, and 0.62, all P<0.05). Multivariate logistic regression analysis showed that SUV max(odds ratio ( OR)=1.27, 95% CI: 1.06-1.51, P=0.009) and IFH ( OR=6.83, 95% CI: 1.44-32.27, P=0.015) were independent risk indicators for high-grade STS. The prediction model constructed by combining SUV max and IFH had better diagnostic efficacy for differentiating high-grade STS with the AUC of 0.93, and the sensitivity of 93.9%(31/33) and the specificity of 16/18, respectively. The AUC of prediction model was significant different from SUV max, MTV, TLG and IFH (AUCs: 0.81, 0.78, 0.86 and 0.85; z values: 2.69, 2.53, 1.94 and 1.97, all P<0.05). Conclusions:The metabolic parameters SUV max, MTV, TLG and IFH are valuable predictors for histological grade of STS. The combination of SUV max and IFH may be a more meaningful method than using each of the above metabolic parameters alone.
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Objective:To explore the prognostic value of baseline 18F-FDG PET/CT metabolic parameters in locally advanced cervical cancer (LACC) after concurrent chemoradiotherapy (CCRT). Methods:From September 2015 to October 2021, the clinical data of 180 LACC patients (age: 22-76 years) who underwent 18F-FDG PET/CT before CCRT at Affiliated Cancer Hospital of Shandong First Medical University were analyzed retrospectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUV max, and SUV mean were computed by using the margin threshold of 42%SUV max. The optimal threshold for predicting progression-free survival (PFS) was obtained by ROC curve analysis. The Kaplan-Meier method was applied for survival analysis, and the log-rank test was applied to compare the survival rate between groups. Multivariate Cox proportional hazard regression was used to analyze progression for PFS. Results:The median follow-up was 19.1 months, and 54 patients (30.0%, 54/180) suffered from disease progression. ROC curve analysis showed that the optimal cut-off value of MTV was 31.145 ml, with the AUC of 0.641. Para-aortic lymph node (PALN) metastasis had the highest AUC value (0.589) among the clinical factors, followed by International Federation of Gynecology and Obstetrics (FIGO) stage (0.581). The 1-year PFS rates of patients with MTV<31.145 ml ( n=88) and MTV≥31.145 ml ( n=92) were 80.68% and 59.78%, respectively ( χ2=13.72, P<0.001). Multivariate Cox analysis demonstrated that pathological type (hazard ratio ( HR)=3.075, 95% CI: 1.370-6.901, P=0.006), FIGO stage ( HR=1.955, 95% CI: 1.031-3.707, P=0.040), PALN metastasis ( HR=2.136, 95% CI: 1.202-3.796, P=0.010) and MTV ( HR=2.449, 95% CI: 1.341-4.471, P=0.004) were the significant predictors for PFS. Conclusions:Pathological type, FIGO stage, PALN metastasis and MTV are independent prognostic risk factors for PFS. MTV as the baseline 18F-FDG PET/CT metabolic parameter, can realize prognostic stratification analysis.
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Objective:To evaluate the value of 18F-FDG PET/CT for preoperative localization of epileptogenic foci in refractory epilepsy patients with negative MRI. Methods:Clinical data (550 lobes) of 55 epilepsy patients (38 males, 17 females, age (20.0±8.1) years) with negative MRI who underwent preoperative 18F-FDG PET/CT-MRI between January 2014 and June 2020 at the First Affiliated Hospital of Jinan University were retrospectively analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT, video electroencephalogram (VEEG), PET/CT+ VEEG and PET/CT-VEEG for localizing epileptogenic foci were calculated using stereoelectroencephalography (SEEG) and the outcomes of at least 1 year of postoperative follow-up as reference standards. χ2 test was used to compare the efficiencies of different examination modalities for unilobar, multilobar and all patients. Results:The correct lateralization rate of epileptogenic foci was 92.6%(25/27) using PET/CT. The sensitivity, specificity, accuracy, PPV and NPV of PET/CT for localization of epileptogenic foci were 65.1%(54/83), 77.9%(364/467), 76.0%(418/550), 34.4%(54/157) and 92.6%(364/393), respectively. The sensitivities of PET/CT-VEEG for localization of epileptogenic foci in all patients and patients with multilobar epilepsy were higher than those of VEEG alone (75.9%(63/83) vs 45.8%(38/83), 68.6%(35/51) vs 31.4%(16/51); χ2 values: 15.80, 14.16, both P<0.001). The specificities of PET/CT+ VEEG for localization of epileptogenic foci in all patients and patients with unilobar epilepsy were higher than those of VEEG alone (97.6%(456/467) vs 94.6%(442/467), 97.9%(282/288) vs 94.1%(271/288); χ2 values: 5.66, 5.48; P values: 0.017, 0.019). The sensitivity of PET/CT-VEEG (PET/CT and VEEG concordance) for localization of epileptogenic foci was higher than that of PET/CT+ VEEG (PET/CT and VEEG discordance) (8/9 vs 28.4%(21/74); χ2=10.40, P=0.001), and its specificity and accuracy were higher than those of PET/CT-VEEG (PET/CT and VEEG discordance) (93.4%(57/61) vs 71.7%(291/406), 92.9%(65/70) vs 72.1%(346/480); χ2 values: 13.23, 13.96; both P<0.001). Conclusions:18F-FDG PET/CT can localize and lateralize epileptogenic foci in patients with negative MRI. The combination of 18F-FDG PET/CT and VEEG improves the sensitivity, specificity, and accuracy for epileptogenic foci detection. 18F-FDG PET/CT is more accurate in detecting epileptogenic foci when it is concordant with VEEG.
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Objective:To analyze the clinical value of 18F-FDG PET/MR for precise localization of epileptogenic foci in patients with refractory epilepsy. Methods:From February 2019 to December 2021, 81 patients (52 males, 29 females; age (30.0±10.9) years) with refractory epilepsy confirmed in Ruijin Hospital Shanghai Jiao Tong University School of Medicine were retrospectively enrolled. All patients underwent preoperative PET/MR exam, and the possible position of the epileptogenic foci were determined by PET/MR imaging and pre-surgical evaluation, then the stereoelectroencephalography (SEEG) electrodes were implanted. Surgery was performed, and outcome was assessed by using a modified Engel classification two years after surgery. χ2 test was used to compare the detection rates of MRI and PET/MR fusion imaging in localizing epileptogenic foci and the detection rates of epileptogenic foci in temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE) by PET/MR. Results:MRI correctly localized seizure foci in 38 patients, with the detection rate of 46.91%(38/81), while PET/MR detected seizure foci in 73 patients, with the detection rate of 90.12%(73/81; χ2=35.05, P<0.001). There were 63 TLE and 18 ETLE patients. The detection rate of PET/MR in localizing seizure foci in TLE patients was 95.24%(60/63), which was significantly higher than that in ETLE patients (13/18; χ2=5.94, P=0.015). After 2 years follow-up, the postoperative efficacy rate of TLE patients with Engel grades Ⅰ-Ⅱ was 76.19%(48/63), which was 13/18 of ETLE patients ( χ2=0.12, P=0.731). Conclusion:Hybrid PET/MR imaging can accurately locate epileptogenic foci, especially for MRI negative lesions, which provides precision imaging information for surgical planning and improves surgical success rate.