ObjectiveTo investigate the effects and potential mechanisms of Babaodan （BBD） against acetaminophen （APAP）-induced acute liver injury （ALI） based on transcriptomics. MethodsA total of 36 male C57BL/6 mice were randomly divided into 6 groups （n=6 per group）： normal group， model group， N-acetylcysteine group （NAC， 120 mg·kg^-1）， and BBD low-， medium-， and high-dose groups （BBD-L， BBD-M， BBD-H groups， 75， 150， 300 mg·kg^-1， respectively）. Except for the normal group， all other groups were subjected to APAP-induced ALI. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） were measured in each group. Hepatic levels or activities of malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） were detected using commercial kits. Hematoxylin-eosin （HE） staining was performed to evaluate the degree of liver histopathological damage. Transcriptomic analysis was employed to screen differentially expressed genes （DEGs）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify differential pathways involved in BBD intervention against ALI. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were applied to validate the expression of differential genes and related pathway proteins. Additionally， glucose （GLU） consumption， as well as lactate （LD） and adenosine triphosphate （ATP） content were assessed across all mouse groups. ResultsPharmacodynamic evaluation showed that， compared with the normal group， the model group exhibited significantly elevated serum levels of ALT， AST， TC， TG， and LDL-C （P<0.01）， significantly increased MDA level （P<0.01）， and significantly decreased GSH-Px level （P<0.05）. Compared with the model group， BBD intervention at different doses significantly reduced the serum levels of ALT， AST， TC， TG， and LDL-C （P<0.05， P<0.01）， increased GSH-Px level （P<0.05， P<0.01）， significantly decreased MDA level （P<0.01）， and ameliorated hepatic histopathological injury. Liver transcriptomic analysis revealed that， following high-dose BBD intervention， the core genes were mainly enriched in pathways related to inflammatory responses and energy metabolic reprogramming， including the interleukin-17 （IL-17） signaling pathway， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， fructose and mannose metabolism， and glycolysis. Real-time PCR validation demonstrated that， compared with the normal group， the mRNA expression levels of glycolysis-related genes ［hexokinase 1 （HK1）， hexokinase 2 （HK2）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 4 （PFKFB4）， pyruvate kinase M （PKM）， and lactate dehydrogenase A （LDHA）］， as well as inflammatory cytokines ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）］ were significantly upregulated in the model group （P<0.05， P<0.01）. Compared with the model group， the BBD-H group showed significantly decreased mRNA expression of HK1， HK2， PFKFB3， PFKFB4， PKM， LDHA， TNF-α， IL-6， and IL-1β （P<0.05， P<0.01）. Western blot results indicated that， compared with the normal group， the model group had significantly increased expression of glycolysis-related proteins ［glucose transporter 1 （GLUT1）， HK1， PFKFB3， and PKM］， inflammatory proteins ［interleukin-18 （IL-18）， TNF-α， and IL-1β］， and phosphorylated （p）-PI3K and p-Akt proteins （P<0.05， P<0.01）. Compared with the model group， the BBD-H group exhibited significantly decreased expression of GLUT1， HK1， PFKFB3， PKM， IL-18， TNF-α， IL-1β， p-PI3K， and p-Akt （P<0.05， P<0.01）. Metabolic indicator measurements showed that， compared with the model group， the BBD-H group showed significantly reduced GLU consumption， LD and ATP content （P<0.05， P<0.01）. ConclusionBBD may alleviate APAP-induced ALI through dual regulation of metabolic reprogramming and inflammatory responses， potentially via inhibition of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the effects and potential mechanisms of Babaodan （BBD） against acetaminophen （APAP）-induced acute liver injury （ALI） based on transcriptomics. MethodsA total of 36 male C57BL/6 mice were randomly divided into 6 groups （n=6 per group）： normal group， model group， N-acetylcysteine group （NAC， 120 mg·kg^-1）， and BBD low-， medium-， and high-dose groups （BBD-L， BBD-M， BBD-H groups， 75， 150， 300 mg·kg^-1， respectively）. Except for the normal group， all other groups were subjected to APAP-induced ALI. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） were measured in each group. Hepatic levels or activities of malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） were detected using commercial kits. Hematoxylin-eosin （HE） staining was performed to evaluate the degree of liver histopathological damage. Transcriptomic analysis was employed to screen differentially expressed genes （DEGs）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify differential pathways involved in BBD intervention against ALI. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were applied to validate the expression of differential genes and related pathway proteins. Additionally， glucose （GLU） consumption， as well as lactate （LD） and adenosine triphosphate （ATP） content were assessed across all mouse groups. ResultsPharmacodynamic evaluation showed that， compared with the normal group， the model group exhibited significantly elevated serum levels of ALT， AST， TC， TG， and LDL-C （P<0.01）， significantly increased MDA level （P<0.01）， and significantly decreased GSH-Px level （P<0.05）. Compared with the model group， BBD intervention at different doses significantly reduced the serum levels of ALT， AST， TC， TG， and LDL-C （P<0.05， P<0.01）， increased GSH-Px level （P<0.05， P<0.01）， significantly decreased MDA level （P<0.01）， and ameliorated hepatic histopathological injury. Liver transcriptomic analysis revealed that， following high-dose BBD intervention， the core genes were mainly enriched in pathways related to inflammatory responses and energy metabolic reprogramming， including the interleukin-17 （IL-17） signaling pathway， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， fructose and mannose metabolism， and glycolysis. Real-time PCR validation demonstrated that， compared with the normal group， the mRNA expression levels of glycolysis-related genes ［hexokinase 1 （HK1）， hexokinase 2 （HK2）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3）， 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 4 （PFKFB4）， pyruvate kinase M （PKM）， and lactate dehydrogenase A （LDHA）］， as well as inflammatory cytokines ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）］ were significantly upregulated in the model group （P<0.05， P<0.01）. Compared with the model group， the BBD-H group showed significantly decreased mRNA expression of HK1， HK2， PFKFB3， PFKFB4， PKM， LDHA， TNF-α， IL-6， and IL-1β （P<0.05， P<0.01）. Western blot results indicated that， compared with the normal group， the model group had significantly increased expression of glycolysis-related proteins ［glucose transporter 1 （GLUT1）， HK1， PFKFB3， and PKM］， inflammatory proteins ［interleukin-18 （IL-18）， TNF-α， and IL-1β］， and phosphorylated （p）-PI3K and p-Akt proteins （P<0.05， P<0.01）. Compared with the model group， the BBD-H group exhibited significantly decreased expression of GLUT1， HK1， PFKFB3， PKM， IL-18， TNF-α， IL-1β， p-PI3K， and p-Akt （P<0.05， P<0.01）. Metabolic indicator measurements showed that， compared with the model group， the BBD-H group showed significantly reduced GLU consumption， LD and ATP content （P<0.05， P<0.01）. ConclusionBBD may alleviate APAP-induced ALI through dual regulation of metabolic reprogramming and inflammatory responses， potentially via inhibition of the PI3K/Akt signaling pathway.

Objective To develop nanobodies with broad-spectrum reactivity,specificity,and high sensitivity that can be used for detecting multiple subtypes of influenza A virus,and to establish a nanobody-based enzyme-linked immunosorbent assay(ELISA)method.Methods Gene sequences of twelve nanobodies against influenza A virus were retrieved from the National Center for Biotechnology Information(NCBI)and nanobody databases.The nanoantibodies were prepared using molecular biological techniques including gene synthesis and recombinant expression.The binding activity,specificity,sensitivity,and affinity of these nanobodies were determined by ELISA screening and Gator affinity analysis.A double-antibody sandwich ELISA assay was established by combining the selected nanobody with a traditional mouse monoclonal antibody.Results Twelve nanobodies were expressed and purified.Two nanobodies capable of binding to multiple subtypes of influenza virus including H1,H3,H5,H7,and H9 were obtained and designated as VHH54 and KV108.Both nanobodies showed no cross-reactivity with other respiratory virus antigens.Furthermore,the KV108 nanobody exhibited the highest binding affinity,with a dissociation constant of 5.94×10-9mol/L for the influenza virus nucleoprotein(NP),and the lowest detection concentration for the NP antigen reached 0.00064 μg/mL.The double-antibody sandwich ELISA,using a combination of KV108 and a mouse monoclonal antibody,could sensitively detect the five common subtypes of influenza A virus(H1N1,H3N2,H5N1,H7N9,and H9N2).The lowest detection limit reached 110-403 PFU/mL,which was higher than that of the commercial colloidal gold kitfor influenza virus detection.Conclusion This study has identified a nanobody KV108,which is capable of binding to multiple subtypes of influenza virus,and established a nanobody-based ELISA method that can detect multiple subtypes of influenza A virus.This study can facilitate the development of nanobody-based influenza detection technologies.

Objective:To construct an in situ pancreatic tumor model in mice and explore the mechanism of neuromedin U (NMU) remodeling the metabolic microenvironment of pancreatic tumors via the Hedgehog signaling pathway.Methods:C57BL/6 NMU -/- heterozygous mice were bred in one cage with a female-to-male ratio of 2:1. The tail tissues of offspring rats were taken, and knockout primers were designed according to the sequence structure of NMU gene. The C57BL/6 NMU -/- mouse genotypes were identified by polymerase chain reaction (PCR) and agarose gel electrophoresis. Five C57BL/6 NMU -/- homozygotes and five wild type mice aged 8 to 9 weeks were selected, and Panc02 cell suspension of pancreatic cancer in logarithmic growth phase was injected into pancreatic tail tissue to construct tumor bearing mice model of pancreatic tumor in situ. After 3 weeks of tumor loading, flow cytometry was used to detect the abundance changes of CD8 + T cells in the spleen tissues of two groups of mice. GSE102238 (data published in August 2017) and GSE62452 (data published in July 2016) datasets were download from the Gene Expression Omnibus (GEO) database, including 119 samples of pancreatic cancer tissue and 111 samples of normal pancreatic tissue adjacent to cancer, and the differential expression factors of the two groups of samples were screened. R language limma package was used to analyze the differential expression of NMU mRNA in pancreatic cancer tissues and adjacent normal tissues; the relative expression level of NMU mRNA in pancreatic cancer patients of different ages and tumor grades was analyzed by ggpubr package. The relative expression level data of NMU mRNA in pancreatic tumor patients were extracted, and the patients were divided into high expression group (>2.48) and low expression group (<2.48) based on the median value (2.48). The CIBERSORT algorithm was used to calculate the difference in the content of infiltrating immune cells in pancreatic tumors between the two groups of patients. The overall survival of patients with different relative expression levels of NMU mRNA in the OncoLnc database (59 cases in the high expression group and 59 cases in the low expression group) was compared. The data of 178 patients with pancreatic cancer in TCGA-PAAD of The Cancer Genome Atlas (TCGA) database (updated in March 2024) were download. According to the median value of relative expression of NMU mRNA (2.740), the patients were divided into the high expression group (>2.740) and the low expression group (<2.740), with 89 cases in each group. GSEA software was used to analyze the biological functions and pathways in which the genes enriched significantly. The molecules and key targets for molecular docking were explored using the large molecule protein interaction tool PDBePISA. Spearman correlation analysis was performed using R language data packets. Results:The results of C57BL/6 NMU -/- mouse genotypes analyzed by using the gel electrophoresis pattern of PCR amplification products of tail tissues showed that the wild type was one 380 bp electrophoretic band, the homozygous type was one 450 bp electrophoretic band, and the heterozygous type was 450 bp and 380 bp electrophoretic bands. After identifying and screening pure strains mouse, reproduction was carried out, and C57BL/6 NMU -/- homozygous mice were successfully obtained. The results of flow cytometry analysis showed that the proportion of CD8 + T cells in the spleen tissues of C57BL/6 NMU -/- wild-type and homozygous pancreatic tumor bearing mice was (30.38±0.37)% and (37.00±0.48)%, with a statistically significant difference between the two groups ( t = 9.79, P < 0.001). The absolute values of CD8 + T cells were (8.36±0.27)×10 4 and (10.20±0.28)×10 4, respectively, and the difference was statistically significant ( t = 3.71, P = 0.013). In the GEO database GSE102238 and GSE62452 datasets, there were differentially expressed genes in pancreatic cancer tissues compared with adjacent tissues, including 219 up-regulated genes and 325 down-regulated genes in pancreatic cancer tissues; among them, NMU was an upregulated differentially expressed gene. The relative expression of NMU mRNA in patients aged > 65 year or grade G3-G4 was higher than that in patients aged ≤ 65 years or grade G1-G2, and the differences were statistically significant (both P < 0.05). The analysis results of CIBERSORT algorithm showed that the expression abundance of CD8 + T cells, initial CD4 + T cells, activated memory CD4 + T cells, and γδ T cells in the high expression group of NMU was lower than that in the low expression group (all P < 0.05). The overall survival of the high expression group of NMU was worse than that of the low expression group in the OncoLnc database ( P = 0.010). GSEA enrichment analysis and Spearman correlation analysis revealed significant changes in the Hedgehog signaling pathway, biosynthesis of unsaturated fatty acids and pyrimidine nucleotide metabolism, which affected tumor metabolic remodeling. Conclusions:NMU may remodel the tumor microenvironment of pancreatic cancer by regulating Hedgehog signaling pathway.

The Healthy China 2030 Plan set the goal of reducing premature deaths from diabetes by 30% by 2030. However, there has been a lack of assessment of premature mortality for diabetes since the action plan was issued. This study used data from the Global Burden of Disease Study 2021, calculated the premature deaths for diabetes by sex, provinces, and subtypes from 1990 to 2021. We explored the temporal trend of premature mortality using the average annual percent change (AAPC) for different sexes, provinces, and subtypes from 1990 to 2021. Furthermore, we predicted premature mortality for diabetes through 2030 for China and its provinces according to the average annual change rate from 2010 to 2021. There was a first slow upward trend in premature mortality for diabetes from 0.5% in 1990 to 0.6% in 2004, and then a decline until 2021 with premature mortality of 0.4%. By 2030, only Fujian (30.3%) will achieve the desired level of reduction, with only seven provinces meeting the target for females and none for males. There is a large range in the degree of decline between inland and coastal regions, showing obvious geographic differences, and there should be a focus on balancing medical resources.
Humans ; China/epidemiology* ; Female ; Male ; Mortality, Premature/trends* ; Diabetes Mellitus/mortality* ; Goals ; Middle Aged ; Adult

OBJECTIVE To explore the expressions of eosinophilic chemotactic factor 11(CCL11),leukotriene B4(LTB4),percentage of neutrophils(NEUT％)and C-reactive protein(CRP)in peripheral blood of the children with Mycoplasma pneumoniae(MP)infection complicated with plastic bronchitis and analyze the clinical signifi-cance.METHODS A total of 80 children with MP pneumonia complicated with plastic bronchitis who were trea-ted in the Second Hospital of Longyan City,Fujian Province from Jan.2020 to Dec.2023 were assigned as the study group,and 115 patients with MP pneumonia were chosen as the control group.The clinical data,manifesta-tions and Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)score were statistically analyzed.The levels of peripheral blood CCL11,LTB4,NEUT％and CRP were observed and compared between the two groups.Pearson analysis was performed for the associations of the levels of CCL11,LTB4,NEUT％and CRP with the PRISM Ⅲscore.The value of the joint detection of CCL11,LTB4,NEUT％and CRP in diagnosis of the MP pneumoni-a-induced plastic bronchitis was analyzed.RESULTS There were significant differences in reduction of bronchial breathing sound,pleural effusion and PRISM Ⅲ score between the two groups(P＜0.05).There were significant differences in the levels of peripheral blood CCL11,LTB4,NEUT％and CRP between the study group and the control group(P＜0.05);the CRP level of the study group was(29.42±8.14)mg/L,higher than that of the control group(t=10.138,P＜0.001).The levels of CCL11,LTB4,NEUT％and CRP were positively correlated with the PRISM Ⅲ score(r=0.723,0.710,0.771,0.754,respectively,all P＜0.001).The area under the curve(AUC)of the single detection of CCL11,LTB4,NEUT％and CRP was remarkably higher in diagnosis of MP pneumonia-induced plastic bronchitis than that of the joint detection of the four markers(P＜0.05).CONCLUSIONS The children with MP pneumonia complicated with plastic bronchitis show increased expressions of CCL11,LTB4,NEUT％and CRP.The four markers are positively correlated with the PRISM Ⅲ score.The four markers have high values in diagnosis of the MP pneumonia complicated with plastic bronchitis.

The gradient field, one of the core magnetic fields in magnetic resonance imaging (MRI) systems, is generated by gradient coils and plays a critical role in spatial encoding and the generation of echo signals. The uniformity or linearity of the gradient field directly impacts the quality and distortion level of MRI images. However, traditional point measurement methods lack accuracy in assessing the linearity of gradient fields, making it difficult to provide effective parameters for image distortion correction. This paper introduced a spherical measurement-based method that involved measuring the magnetic field distribution on a sphere, followed by detailed magnetic field calculations and linearity analysis. This study, applied to assess the nonlinearity of asymmetric head gradient coils, demonstrated more comprehensive and precise results compared to point measurement methods. This advancement not only strengthens the scientific basis for the design of gradient coils but also provides more reliable parameters and methods for the accurate correction of MRI image distortions.
Magnetic Resonance Imaging/instrumentation* ; Humans ; Image Processing, Computer-Assisted/methods* ; Nonlinear Dynamics ; Magnetic Fields ; Algorithms ; Phantoms, Imaging

OBJECTIVE To explore the expressions of eosinophilic chemotactic factor 11(CCL11),leukotriene B4(LTB4),percentage of neutrophils(NEUT％)and C-reactive protein(CRP)in peripheral blood of the children with Mycoplasma pneumoniae(MP)infection complicated with plastic bronchitis and analyze the clinical signifi-cance.METHODS A total of 80 children with MP pneumonia complicated with plastic bronchitis who were trea-ted in the Second Hospital of Longyan City,Fujian Province from Jan.2020 to Dec.2023 were assigned as the study group,and 115 patients with MP pneumonia were chosen as the control group.The clinical data,manifesta-tions and Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)score were statistically analyzed.The levels of peripheral blood CCL11,LTB4,NEUT％and CRP were observed and compared between the two groups.Pearson analysis was performed for the associations of the levels of CCL11,LTB4,NEUT％and CRP with the PRISM Ⅲscore.The value of the joint detection of CCL11,LTB4,NEUT％and CRP in diagnosis of the MP pneumoni-a-induced plastic bronchitis was analyzed.RESULTS There were significant differences in reduction of bronchial breathing sound,pleural effusion and PRISM Ⅲ score between the two groups(P＜0.05).There were significant differences in the levels of peripheral blood CCL11,LTB4,NEUT％and CRP between the study group and the control group(P＜0.05);the CRP level of the study group was(29.42±8.14)mg/L,higher than that of the control group(t=10.138,P＜0.001).The levels of CCL11,LTB4,NEUT％and CRP were positively correlated with the PRISM Ⅲ score(r=0.723,0.710,0.771,0.754,respectively,all P＜0.001).The area under the curve(AUC)of the single detection of CCL11,LTB4,NEUT％and CRP was remarkably higher in diagnosis of MP pneumonia-induced plastic bronchitis than that of the joint detection of the four markers(P＜0.05).CONCLUSIONS The children with MP pneumonia complicated with plastic bronchitis show increased expressions of CCL11,LTB4,NEUT％and CRP.The four markers are positively correlated with the PRISM Ⅲ score.The four markers have high values in diagnosis of the MP pneumonia complicated with plastic bronchitis.

Objective:To construct an in situ pancreatic tumor model in mice and explore the mechanism of neuromedin U (NMU) remodeling the metabolic microenvironment of pancreatic tumors via the Hedgehog signaling pathway.Methods:C57BL/6 NMU -/- heterozygous mice were bred in one cage with a female-to-male ratio of 2:1. The tail tissues of offspring rats were taken, and knockout primers were designed according to the sequence structure of NMU gene. The C57BL/6 NMU -/- mouse genotypes were identified by polymerase chain reaction (PCR) and agarose gel electrophoresis. Five C57BL/6 NMU -/- homozygotes and five wild type mice aged 8 to 9 weeks were selected, and Panc02 cell suspension of pancreatic cancer in logarithmic growth phase was injected into pancreatic tail tissue to construct tumor bearing mice model of pancreatic tumor in situ. After 3 weeks of tumor loading, flow cytometry was used to detect the abundance changes of CD8 + T cells in the spleen tissues of two groups of mice. GSE102238 (data published in August 2017) and GSE62452 (data published in July 2016) datasets were download from the Gene Expression Omnibus (GEO) database, including 119 samples of pancreatic cancer tissue and 111 samples of normal pancreatic tissue adjacent to cancer, and the differential expression factors of the two groups of samples were screened. R language limma package was used to analyze the differential expression of NMU mRNA in pancreatic cancer tissues and adjacent normal tissues; the relative expression level of NMU mRNA in pancreatic cancer patients of different ages and tumor grades was analyzed by ggpubr package. The relative expression level data of NMU mRNA in pancreatic tumor patients were extracted, and the patients were divided into high expression group (>2.48) and low expression group (<2.48) based on the median value (2.48). The CIBERSORT algorithm was used to calculate the difference in the content of infiltrating immune cells in pancreatic tumors between the two groups of patients. The overall survival of patients with different relative expression levels of NMU mRNA in the OncoLnc database (59 cases in the high expression group and 59 cases in the low expression group) was compared. The data of 178 patients with pancreatic cancer in TCGA-PAAD of The Cancer Genome Atlas (TCGA) database (updated in March 2024) were download. According to the median value of relative expression of NMU mRNA (2.740), the patients were divided into the high expression group (>2.740) and the low expression group (<2.740), with 89 cases in each group. GSEA software was used to analyze the biological functions and pathways in which the genes enriched significantly. The molecules and key targets for molecular docking were explored using the large molecule protein interaction tool PDBePISA. Spearman correlation analysis was performed using R language data packets. Results:The results of C57BL/6 NMU -/- mouse genotypes analyzed by using the gel electrophoresis pattern of PCR amplification products of tail tissues showed that the wild type was one 380 bp electrophoretic band, the homozygous type was one 450 bp electrophoretic band, and the heterozygous type was 450 bp and 380 bp electrophoretic bands. After identifying and screening pure strains mouse, reproduction was carried out, and C57BL/6 NMU -/- homozygous mice were successfully obtained. The results of flow cytometry analysis showed that the proportion of CD8 + T cells in the spleen tissues of C57BL/6 NMU -/- wild-type and homozygous pancreatic tumor bearing mice was (30.38±0.37)% and (37.00±0.48)%, with a statistically significant difference between the two groups ( t = 9.79, P < 0.001). The absolute values of CD8 + T cells were (8.36±0.27)×10 4 and (10.20±0.28)×10 4, respectively, and the difference was statistically significant ( t = 3.71, P = 0.013). In the GEO database GSE102238 and GSE62452 datasets, there were differentially expressed genes in pancreatic cancer tissues compared with adjacent tissues, including 219 up-regulated genes and 325 down-regulated genes in pancreatic cancer tissues; among them, NMU was an upregulated differentially expressed gene. The relative expression of NMU mRNA in patients aged > 65 year or grade G3-G4 was higher than that in patients aged ≤ 65 years or grade G1-G2, and the differences were statistically significant (both P < 0.05). The analysis results of CIBERSORT algorithm showed that the expression abundance of CD8 + T cells, initial CD4 + T cells, activated memory CD4 + T cells, and γδ T cells in the high expression group of NMU was lower than that in the low expression group (all P < 0.05). The overall survival of the high expression group of NMU was worse than that of the low expression group in the OncoLnc database ( P = 0.010). GSEA enrichment analysis and Spearman correlation analysis revealed significant changes in the Hedgehog signaling pathway, biosynthesis of unsaturated fatty acids and pyrimidine nucleotide metabolism, which affected tumor metabolic remodeling. Conclusions:NMU may remodel the tumor microenvironment of pancreatic cancer by regulating Hedgehog signaling pathway.

Objective Liver cancer is the second leading cause of tumor-related death.The efficacy of local thermal ablation is comparable to surgical resection for the early hepatocellular carcinoma(HCC),and the ablation technique is minimally invasive,repeatable,and has a low complication rate.However,early recurrence((2 years)is the main cause of death after HCC ablation,but there is still a lack of accurate and reliable prediction models for early recurrence.Therefore,this survey intended to construct prediction models for early recurrence of HCC after ablation by using preoperative gadoxetic acid disodium-enhanced magnetic resonance(MR)images data combined with radiomics methods,evaluate and verify their predictive efficacy.To explore the application value of contrast-enhanced MRI imaging before ablation in the prognosis assessment of HCC patients,and to provide reliable data and theoretical basis for clinical treatment decisions.Methods A retrospective study was performed on 120 patients with HCC who underwent ablation and all the patients were underwent contrast-enhanced MRI examination within 1 month.A total of 1318 radiomic features were extracted from each patient by using preoperative T2-weighted sequence(T2WI)images of contrast-enhanced MRI.After feature selection,six machine learning algorithms would be used for construction of models and comparison.Finally,Logistic regression analysis was used to establish a clinical model,a radiomics model and a combined model which included the above risk factors and radiologic features.The nomogram was constructed based the combined model to evaluate the differentiation,accuracy and clinical benefit.Results Five radiomic features most closely related to early recurrence were identified and selected for model construction.The radiomic model had effective predictive performance,with AUC of 0.80 in the training sets.Two clinical risk factors associated with early recurrence,including tumor number and peritumoral hypodensity on the hepatobiliary phase,were selected to established a clinical-radiological-radiomics(CRRM)model,with AUC as high as 0.92 in the validation sets.The nomogram of CRRM model was constructed and the calibration curves indicated the goodness of fit.Decision curve analysis further confirmed the clinical usefulness of CRRM model.Conclusion The radiomics model of preoperatively contrast-enhanced MRI-T2WI image features was identified be effective to predict HCC early recurrence.In contrast,the CRRM model could be used as a more comprehensive and superior tool to predict individual probability of early recurrence.Patients at high risk of early recurrence could be identified and the appropriate and effective preoperative treatments could also be taken,to improve the prognosis and long-term survival rate of HCC patients the individualized treatment strategies should be formulated.