Objective To investigate the effects of low background radiation environments in deep underground settings on the biological behavior of NP69 human nasopharyngeal epithelial cells(NP69 cells)and the underlying molecular mechanisms.Methods A parallel control experimental design was adopted and NP69 cells were synchronously cultured in settings of three underground depths at the China in situ Deep-Underground Facility&Life Observatory(DeUFO)—ground level(DeUFO-0 m),1 000 m underground(DeUFO-1 000 m),and 1 500 m underground(DeUFO-1 500 m).Changes in cell proliferation and migration capabilities were assessed using the Cell Counting Kit-8(CCK-8)assay and scratch assay,respectively.High-throughput RNA sequencing(RNA-Seq)was performed to identify differentially expressed genes(DEGs).Functional annotation and pathway enrichment analysis of the DEGs were performed using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.Results CCK-8 assay revealed that,after 72 h of culture,the absorbance value of the DeUFO-0 m group was 1.35 times and 1.27 times those of the those of the DeUFO-1 000 m and DeUFO-1 500 m groups,respectively(both P<0.000 1).After 96 h of culture,the absorbance value of the DeUFO-0 m group was 1.52 times and 1.41 times those of the DeUFO-1 000 m and DeUFO-1 500 m groups,respectively(both P<0.000 1).Colony formation assays revealed that the number of cell colonies in the DeUFO-0 m group was 1.59 times and 1.27 times those in the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.001).The scratch assay revealed that the 36-hour wound healing rate of the DeUFO-0 m group was 2.22 times and 4.00 times those of the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.000 1).Transwell assays revealed that the number of migrating cells in the DeUFO-0 m group was 2.08 times and 2.56 times those in the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.000 1).Transcriptome sequencing analysis revealed consistent upregulation of CELF2,CELF4,CGB8,GRHL2,and DMRTA2 genes in the DeUFO-1 000 m and DeUFO-1 500 m groups.Pathway enrichment analysis indicated significant enrichment of extracellular matrix(ECM)remodeling-associated pathways and gene expression regulation pathways in the experimental groups(false discovery rate[FDR]<0.05).Conclusion The low background radiation environment in deep underground settings suppresses the proliferation and migration activities of NP69 cells by mediating ECM remodeling and post-transcriptional regulatory mechanisms through the regulation of target genes such as the CELF family.This study provides experimental evidence for establishing a dose-response relationship between environmental radiation and cellular effects.

The lung function of patients with occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") combined with chronic obstructive pulmonary disease (COPD) declines rapidly. Inhaled pharmacotherapy is crucial in the treatment of patients with pneumoconiosis combined with COPD. At present, pressurized metered-dose inhalers, dry powder inhalers, and soft mist inhalers are commonly used to deliver bronchodilators (including long-acting β2-adrenergic agonists, long-acting muscarinic antagonists, or their fixed-dose combinations) in inhaled pharmacotherapy. Peak inspiratory flow (PIF) is a commonly used indicator for evaluating the effectiveness of inhalation therapy. Patients with good coordination of hand and mouth, and a high PIF (≥30 L/min) can be treated with pressurized metered-dose inhalers or dry powder inhalers, whereas patients with poor coordination or insufficient PIF (<30 L/min) should be treated with pressurized metered-dose inhalers combined with a spacer or with nebulizers. In addition, the effectiveness of inhalation therapy is affected by individual factors, such as treatment adherence and pulmonary function, as well as drug-related factors, including the use of inhaled corticosteroids and the selection of bronchodilators. Inhaled pharmacotherapy appears to have substantial potential in the treatment of pneumoconiosis complicated with COPD. Future efforts should focus on the development of more effective inhaled drugs with fewer adverse effects and more user-friendly inhalation devices, as well as on optimizing inhalation treatment regimens to enable precision therapy and improve therapeutic efficacy.

Objective:To investigate the effect of growth stimulation expressed gene 2(ST2)on intestinal microflora of mice with ConA-induced autoimmune hepatitis(AIH)by knockout.Methods:ST2 gene knockout mice were constructed by gene knockout technique.On this basis,AIH mouse model was established by ConA induction.The relative expression of cytokines was detected by real-time fluorescence quantitative PCR(RT-PCR).Intestinal microorganisms were sequenced using the 16S rRNA high-through put sequencing method,and the sequencing results were analyzed using Microbial Ecology related software and database.Results:Com-pared with the control group,ALT and AST were decreased,the damage of liver was mild,and the relative expression of IL-6 was also decreased in the liver of mice with ConA-induced AIH after ST2 gene knockout.There was no significant difference in the ACE and CHAO indices of the abundance of reactive flora.There was no significant difference between Shannon index and Simpson index re-flecting bacterial diversity.Psychrobacter,unclassified_Clostridia,Halothiobacillus,Clostridium_XlVa and Haemophilus genus content increased;Romboutsia,Rikenella,Parabacteroides and unclassified_Clostridiales bacterial content reduce.The areas under the receiv-er operator characteristic(ROC)curves were 0.88,0.89,0.88,0.80,0.90,0.90,0.84,0.91 and 0.84,respectively.Conclusion:Knockout of ST2 gene expression in mice with AIH can reduce liver injury and inflammation,and does not affect the distribution abun-dance and diversity of intestinal flora.However,there are differences among bacteria genera,and it has good diagnostic value.

Objective:A nomogram model for predicting double positivity of microvascular invasion (MVI) and vascular endothelial-to-mesenchymal transition (VETC) in patients with hepatocellular carcinoma (HCC) was constructed and its predictive performance was evaluated.Methods:A retrospective analysis was conducted on 326 HCC patients who were treated at the Third People's Hospital of Nantong and the First Affiliated Hospital of Soochow University from January 2013 to June 2023, including 240 males and 86 females, with an average age of (58.7±9.0) years. The 326 patients were randomly divided into a training set ( n=228) and a test set ( n=98) at a ratio of 7: 3 using the random number table method. The training set was divided into a double-positive group ( n=54) and a control group ( n=174) based on whether the HCC patients were double positive for MVI and VETC. Univariate and multivariate logistic regression analyses were performed to identify the influencing factors of double positivity of microvascular invasion in HCC patients, and a nomogram for predicting double positivity of microvascular invasion patterns was constructed based on the multivariate. The predictive performance and clinical net benefit of the nomogram were evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. Results:There were statistically significant differences in alpha-fetoprotein, gamma-glutamyl transferase, and phosphatidylinositol proteoglycan between the two groups (all P<0.05). Multivariate logistic regression analysis showed that LI-RADS category ( OR=8.58, 95% CI: 1.87-39.38), intratumoral hemorrhage ( OR=2.16, 95% CI: 1.14-4.07), and intratumoral arteries ( OR=2.59, 95% CI: 1.19-5.64) were all influencing factors of double positivity of microvascular invasion patterns in HCC patients (all P<0.05). Based on the multivariate results, a nomogram was constructed. In the training set, the area under the ROC curve for predicting double positivity of microvascular invasion patterns in HCC patients was 0.769 (95% CI: 0.720-0.814). In the test set, the area under the ROC curve for predicting double positivity of microvascular invasion patterns in HCC patients was 0.756 (95% CI: 0.622-0.850). The calibration curve showed a good fit between the predicted model and the ideal curve. Decision curve analysis showed that the clinical applicability was good when the threshold was 0.01-0.80 in the training set and 0.01-0.65 in the test set. Conclusion:The nomogram model based on LI-RADS category, intratumoral hemorrhage, and intratumoral arteries can effectively predict double positivity of microvascular invasion patterns in HCC patients and has good clinical applicability.

Objective:To investigate the effect of growth stimulation expressed gene 2(ST2)on intestinal microflora of mice with ConA-induced autoimmune hepatitis(AIH)by knockout.Methods:ST2 gene knockout mice were constructed by gene knockout technique.On this basis,AIH mouse model was established by ConA induction.The relative expression of cytokines was detected by real-time fluorescence quantitative PCR(RT-PCR).Intestinal microorganisms were sequenced using the 16S rRNA high-through put sequencing method,and the sequencing results were analyzed using Microbial Ecology related software and database.Results:Com-pared with the control group,ALT and AST were decreased,the damage of liver was mild,and the relative expression of IL-6 was also decreased in the liver of mice with ConA-induced AIH after ST2 gene knockout.There was no significant difference in the ACE and CHAO indices of the abundance of reactive flora.There was no significant difference between Shannon index and Simpson index re-flecting bacterial diversity.Psychrobacter,unclassified_Clostridia,Halothiobacillus,Clostridium_XlVa and Haemophilus genus content increased;Romboutsia,Rikenella,Parabacteroides and unclassified_Clostridiales bacterial content reduce.The areas under the receiv-er operator characteristic(ROC)curves were 0.88,0.89,0.88,0.80,0.90,0.90,0.84,0.91 and 0.84,respectively.Conclusion:Knockout of ST2 gene expression in mice with AIH can reduce liver injury and inflammation,and does not affect the distribution abun-dance and diversity of intestinal flora.However,there are differences among bacteria genera,and it has good diagnostic value.

Objective:A nomogram model for predicting double positivity of microvascular invasion (MVI) and vascular endothelial-to-mesenchymal transition (VETC) in patients with hepatocellular carcinoma (HCC) was constructed and its predictive performance was evaluated.Methods:A retrospective analysis was conducted on 326 HCC patients who were treated at the Third People's Hospital of Nantong and the First Affiliated Hospital of Soochow University from January 2013 to June 2023, including 240 males and 86 females, with an average age of (58.7±9.0) years. The 326 patients were randomly divided into a training set ( n=228) and a test set ( n=98) at a ratio of 7: 3 using the random number table method. The training set was divided into a double-positive group ( n=54) and a control group ( n=174) based on whether the HCC patients were double positive for MVI and VETC. Univariate and multivariate logistic regression analyses were performed to identify the influencing factors of double positivity of microvascular invasion in HCC patients, and a nomogram for predicting double positivity of microvascular invasion patterns was constructed based on the multivariate. The predictive performance and clinical net benefit of the nomogram were evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. Results:There were statistically significant differences in alpha-fetoprotein, gamma-glutamyl transferase, and phosphatidylinositol proteoglycan between the two groups (all P<0.05). Multivariate logistic regression analysis showed that LI-RADS category ( OR=8.58, 95% CI: 1.87-39.38), intratumoral hemorrhage ( OR=2.16, 95% CI: 1.14-4.07), and intratumoral arteries ( OR=2.59, 95% CI: 1.19-5.64) were all influencing factors of double positivity of microvascular invasion patterns in HCC patients (all P<0.05). Based on the multivariate results, a nomogram was constructed. In the training set, the area under the ROC curve for predicting double positivity of microvascular invasion patterns in HCC patients was 0.769 (95% CI: 0.720-0.814). In the test set, the area under the ROC curve for predicting double positivity of microvascular invasion patterns in HCC patients was 0.756 (95% CI: 0.622-0.850). The calibration curve showed a good fit between the predicted model and the ideal curve. Decision curve analysis showed that the clinical applicability was good when the threshold was 0.01-0.80 in the training set and 0.01-0.65 in the test set. Conclusion:The nomogram model based on LI-RADS category, intratumoral hemorrhage, and intratumoral arteries can effectively predict double positivity of microvascular invasion patterns in HCC patients and has good clinical applicability.

Objective:To develop a nomogram to predict vessels that encapsulate tumor cluster and/or microvascular invasion-positive hepatocellular carcinoma (VM-HCC) based on multiregional radiomics score derived from multisequence MRI.Methods:Clinical data of 209 patients with HCC undergoing radical liver resection at Affiliated Nantong Hospital 3 of Nantong University from January 2016 to December 2021 were retrospectively analyzed, including 149 males and 60 females, aged (58.5±9.2) years. Patients were divided into a training set ( n=146) and a testing set ( n=63). The patients in training set were further classified into two groups based on pathological results: the VM-HCC group ( n=76) and the non-VM-HCC group ( n=70). Radiomics features were extracted from the arterial phase and hepatobiliary phase images within the tumor, peritumor, and combined regions of interest. The arterial phase and hepatobiliary phase features from the same regions were integrated to obtain dual-sequence features. After feature selection, linear support vector machines (SVM) and linear regression machine learning classifiers were employed to construct radiomics models for different sequences and regions. The optimal radiomics model was selected based on the area under the receiver operating characteristic (ROC) curve from the testing set. Logistic regression analysis was performed to identify independent predictors of VM-HCC, and a visual nomogram was constructed using the results of the multivariate logistic regression analysis and the radiomics score of the optimal radiomics model. ROC curves were plotted, and area under curve (AUC) were calculated to evaluate the models’ discriminatory ability. Calibration curves and decision curve analysis (DCA) were utilized to assess the model’s calibration and clinical utility. Results:Among the radiomics models, the dual-sequence-combined region model based on the SVM classifier exhibited the best AUC in the testing set (AUC=0.764, 95% CI: 0.646-0.882). Multivariate logistic regression analysis indicated that HCC patients with protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels >40 mAU/ml ( OR=4.266, 95% CI: 1.921-9.473, P<0.001) had a higher risk of VM-HCC. The nomogram combining PIVKA-II>40 mAU/ml and radiomics score achieved AUC of 0.806 (95% CI: 0.733-0.867) in the training set and 0.817 (95% CI: 0.699-0.903) in the testing set for predicting VM-HCC. The calibration curves of the nomogram showed good fit in both the training and testing sets. DCA indicated that the model possesses good clinical utility. Conclusion:The nomogram based on multiregional radiomics score derived from multisequence MRI demonstrates a good predictive performance for VM-HCC, which could facilitate the risk stratification of recurrence in HCC patients.

Objective To observe the value of the scoring model of MRI features for predicting proliferative hepatocellular carcinoma(HCC).Methods Data of 241 patients with pathologically confirmed HCC,including 90 cases of proliferative HCC and 151 cases of non-proliferative HCC were analyzed retrospectively.Univariate and multivariate logistic regression were used to compare the clinical and MRI findings evaluated according to liver imaging reporting and data system version 2018 between groups.The independent predictive factors of proliferative HCC were screened,and scores were assigned according to the weight,then a scoring model was constructed.Receiver operating characteristic(ROC)curve was drawn,and the area under the curves(AUC)were calculated to assess the predictive efficacy of this model.The patients were divided into high and low proliferation risk subgroups based on the optimal score thresholds.The recurrence free survival(RFS)rates and early RFS rates were compared between groups and subgroups.Results MRI showed tumor corona enhancement,arterial phase annular hyper-enhancement,intratumoral vessels,much focus parenchymal low enhancement and irregular tumor margins were all independent predictive factors for proliferative HCC(OR=3.287,2.362,4.542,2.997,2.379,all P＜0.05),which were then were scored with 7,5,9,7 and 5,respectively,with a total score of 0-33.AUC of the obtained scoring model for predicting proliferative HCC was 0.818.Taken 9 points as the optimal score thresholds,97 cases were assigned into high proliferation subgroup and 144 into low proliferation risk subgroups).Significant differences of RFS rates and early RFS rates were found between groups and subgroups(all P＜0.05).Conclusion MRI features scoring model could effectively predict proliferative HCC.

Purpose To investigate the pathological characteristics of hepatocellular carcinoma(HCC)with irregular rim-like arterial phase enhancement(IRE)using gadoxetic acid-enhanced,and its early recurrence prognostic significance after surgery.Materials and Methods This retrospective study included 131 patients with surgically confirmed HCCs who underwent gadoxetic acid-enhanced MRI from February 2015 to September 2021 in the Third People's Hospital of Nantong.According to the enhancement pattern of gadoxetic acid-enhanced MRI in arterial phase,HCC were divided into IRE-HCC and non-IRE-HCC.Clinical,pathological and imaging characteristics were compared between IRE-HCC and non-IRE-HCC.Logistic regression analyses were performed to identify clinical,pathological and imaging features associated with IRE-HCC.Early recurrence(within 2 years)was evaluated by using Kaplan-Meier analysis.Cox regression analysis was performed to determine independent predictors of early recurrence.Results Cytokeratin 19(CK19)(OR=9.027,95%CI 2.533-32.170,P=0.001),microvascular invasion(OR=3.606,95%CI 1.024-12.701,P=0.046)and diffusion weighted imaging target signs(OR=10.370,95%CI 3.046-35.303,P=0.000)were independent predictors for IRE-HCC.The 2-year cumulative recurrence-free survival rate postoperative of IRE-HCC was 24.1%,which was significantly shorter than that of non-IRE-HCC(55.9%,χ2=19.971,P=0.000).Microvascular invasion(HR=2.206,95%CI 1.152-4.226,P=0.017)and IRE(HR=2.454,95%CI 1.408-4.275,P=0.002)were independent predictors of early postoperative recurrence of HCC.Conclusion IRE-HCC are associated with CK19,microvascular invasion and diffusion weighted imaging target signs,and have a high recurrence rate and poor prognosis in the early postoperative period.

Objective To investigate the value of the liver imaging reporting and data system v2018(LI-RADS v2018)and other imaging features in predicting preoperative risk and postoperative prognosis of isolated macrotrabecular-massive hepatocellular carcinoma(MTM-HCC).Methods Patients with isolated hepatocellular carcinoma(HCC)confirmed by pathology after preoperative MRI examination were selected,and all patients were randomly assigned to a training group(n=146)and a validation group(n=62)in a 7∶3 ratio.Least absolute shrinkage and selection operator(LASSO)regression and multivariate logistic regression were used to screen independent prognostic factors of MTM-HCC and construct a nomogram.Patients were stratified into high-risk and low-risk subgroups based on the nomogram scores.Kaplan-Meier survival curves and Log-rank tests were used to compare the recurrence-free survival(RFS)among different subgroups of patients.Results Multivariate logistic regression analysis revealed that intratumoral vessels[odds ratio(OR)=3.480,95％confidence interval(CI)1.110-10.912,P=0.032],arterial phase hypovascular component ≥20％(OR=4.615,95％CI 1.728-12.321,P=0.002),and corona enhancement(OR=4.814,95％CI 1.816-12.766,P=0.002)were independent predictors of MTM-HCC.The nomogram constructed based on these indicators demonstrated area under the curve(AUC)of the receiver operating characteristic(ROC)curve was 0.834 and 0.764 for predicting MTM-HCC in the training and validation groups,respectively.The RFS predicted by the nomogram was significantly different between the high-risk and low-risk subgroups and both the pathologically confirmed MTM-HCC positive and negative groups(P＜0.05).Conclusion Intratumoral vessels,arterial phase hypovascular component ≥20％,and corona enhancement are independent predictors of MTM-HCC.The constructed nomogram based on these predictors demonstrates good diagnostic efficacy for MTM-HCC and has significant prognostic value for patients'RFS.