Purpose To investigate the change of network topology attribute of brain structure in obese adolescents using graph theory analysis.Materials and Methods A total of 86 obese adolescents in Children's Hospital of Nanjing Medical University from January 2023 to April 2024 were prospectively collected,including 60 patients in the simple obesity group(OB group),26 patients in the obese group with metabolic syndrome(MS group).Meanwhile,24 healthy volunteers were recruited as the control group.Diffusion tensor imaging scan of the head,anthropological characteristics examination and blood test were performed.The differences of global and local topology properties among the three groups were compared.Global or node attributes with statistical differences were correlated with clinical indicators.Results There were significant differences in body height,body weight,body mass index,waist circumference,diastolic blood pressure,systolic blood pressure and high density lipoprotein cholesterol among the three groups(χ2/F=3.208-5.085,all P<0.05).Compared with the control group,there were significant differences in total body fat,triglyceride,total cholesterol,alanine amino-transferase,aspartate aminotransferase and fasting insulin between the OB group and the MS group(all P<0.05).No statistically significant differences were observed in the small world attribute,shortest path length and global efficiency among the three groups(all P>0.05).A statistically significant difference was observed in the clustering coefficient and local efficiency among the three groups(F=2.534,3.012,both P<0.05),with the values of clustering coefficient and local efficiency of OB group were significantly lower than those of the control group(P<0.05).The node attribute differences occurred in the left frontal lobe,right insula,right anterior central gyrus,left anterior cingulate gyrus,left anterior cuneus and bilateral occipital lobes.The connection value between module Association and Limbic in control group was significantly lower smaller than those of the OB group(P=0.033).A negative correlation was observed between local efficiency and age(r=-0.239),body weight(r=-0.254),body mass index(r=-0.230)and waist circumference(r=-0.263,all P<0.05).The modularity was negatively correlated with fasting insulin(r=-0.325,P<0.05).Conclusion Adolescent obesity leads to the abnormal topological properties of structural network in some brain regions,which may be associated with the abnormal cognitive function and could provide neuroimaging evidence for clinical intervention.

Objective To observe MRI manifestations of temporomandibular joint(TMJ)involvement of juvenile idiopathic arthritis(JIA).Methods Sixteen children with JIA who underwent MR examination of TMJ were retrospectively enrolled.Clinical data were collected,MRI manifestations of inflammation domain and damage domain of TMJ were observed,and evaluation based on JIA MRI scoring system for TMJ(JAMRIS-TMJ)was performed.Results Among 16 children with JIA,14 exhibited symptoms associated with TMJ involvement.One or multiple abnormal MRI manifestations were noticed in 25(25/32,78.13％)TMJ,including bone marrow edema in 12(12/32,37.50％),effusion in 8(8/32,25.00％)and synovial thickening in 6(6/32,18.75％),condylar flattening in 10(10/32,31.25％),bone erosion in 6(6/32,18.75％)and articular disc abnormalities in 2(2/32,6.25％)TMJ,while no obvious abnormality was observed in 7(7/32,21.88％)TMJ.Among 4 JIA children who underwent enhanced MR scanning,enhanced bone marrow was found in 2(2/8,25.00％),while synovial enhancement was observed in 4(4/8,50.00％)TMJ.According to JAMRIS-TMJ scoring,for inflammation domain,there were 7(7/32,21.88％)normal TMJ,17(17/32,53.13％)mild and 8(8/32,25.00％)moderate/severe inflammation TMJ,while for damage domain,there were 12(12/32,37.50％)normal TMJ,14(14/32,43.75％)mild and 6(6/32,18.75％)moderate/severe damage TMJ.Conclusion MRI manifestations of TMJ involvement of JIA mainly included bone marrow edema,joint effusion,condylar flattening and so on.

Purpose To investigate the change of network topology attribute of brain structure in obese adolescents using graph theory analysis.Materials and Methods A total of 86 obese adolescents in Children's Hospital of Nanjing Medical University from January 2023 to April 2024 were prospectively collected,including 60 patients in the simple obesity group(OB group),26 patients in the obese group with metabolic syndrome(MS group).Meanwhile,24 healthy volunteers were recruited as the control group.Diffusion tensor imaging scan of the head,anthropological characteristics examination and blood test were performed.The differences of global and local topology properties among the three groups were compared.Global or node attributes with statistical differences were correlated with clinical indicators.Results There were significant differences in body height,body weight,body mass index,waist circumference,diastolic blood pressure,systolic blood pressure and high density lipoprotein cholesterol among the three groups(χ2/F=3.208-5.085,all P<0.05).Compared with the control group,there were significant differences in total body fat,triglyceride,total cholesterol,alanine amino-transferase,aspartate aminotransferase and fasting insulin between the OB group and the MS group(all P<0.05).No statistically significant differences were observed in the small world attribute,shortest path length and global efficiency among the three groups(all P>0.05).A statistically significant difference was observed in the clustering coefficient and local efficiency among the three groups(F=2.534,3.012,both P<0.05),with the values of clustering coefficient and local efficiency of OB group were significantly lower than those of the control group(P<0.05).The node attribute differences occurred in the left frontal lobe,right insula,right anterior central gyrus,left anterior cingulate gyrus,left anterior cuneus and bilateral occipital lobes.The connection value between module Association and Limbic in control group was significantly lower smaller than those of the OB group(P=0.033).A negative correlation was observed between local efficiency and age(r=-0.239),body weight(r=-0.254),body mass index(r=-0.230)and waist circumference(r=-0.263,all P<0.05).The modularity was negatively correlated with fasting insulin(r=-0.325,P<0.05).Conclusion Adolescent obesity leads to the abnormal topological properties of structural network in some brain regions,which may be associated with the abnormal cognitive function and could provide neuroimaging evidence for clinical intervention.

Objective To investigate the molecular mechanism of hepatic fibrosis(HF)regulation by liver sinusoidal endothelial cells(LSECs)via endothelial mesenchymal transition(EnMT),and to predict the natural active components using bioinformatics,machine learning,and cellular experiments.Methods HF and EnMT gene matrices were obtained and the intersecting genes were extracted and enriched using Limma difference analysis and weighted gene co-expression network analysis(WGCNA).The diagnostic genes were screened using a combination of random forest method,support vector machine-recursive feature elimination and network topology analysis,and immune infiltration analysis and prediction of natural active ingredients were performed.The expression of diagnostic genes and the pharmacological effects of the predicted ingredients were finally verified by cellular experiments.Results Differential analysis yielded 3034 EnMT-associated and 4133 HF-associated differential genes.WGCNA analysis yielded 4589 EnMT-associated Hub genes and 763 HF-associated Hub genes.Thirty-eight intersecting genes were extracted,which were mainly enriched in the pathways of basement membrane and extracellular matrix receptor interaction.Four diagnostic genes,CFP,COL4A2,ITGA1,and GRPEL1,were screened by multidimensional analysis.Immune infiltration analysis showed that the diagnostic genes were closely associated with mast cell resting state,memory B cells,and memory CD4+T cells.Reverse transcription-polymerase chain reaction analysis showed significantly increased mRNA expression levels of the four diagnostic genes in the Jagged1-induced model group(P＜0.05).The predicted components,sterol,kaempferol,and quercetin,all had good binding activities with the diagnostic genes.Enzyme-linked immunosorbent assay result confirmed that all three active components significantly reduced the expression of collagen type Ⅳ α2 chain protein in Jagged1-induced LSECs,with quercetin having the most significant effect(P＜0.01).Conclusions This study elucidated the molecular mechanism of hepatic sinusoidal endothelial cells involved in the pathological process of HF through mesenchymal transition.We also propose a diagnostic marker system including CFP,COL4A2,ITGA1,and GRPEL1 as core genes.The result also suggest that natural active ingredients,such as quercetin,may exert anti-HF pharmacological effects by targeting these diagnostic genes.

Objective To investigate the molecular mechanism of hepatic fibrosis(HF)regulation by liver sinusoidal endothelial cells(LSECs)via endothelial mesenchymal transition(EnMT),and to predict the natural active components using bioinformatics,machine learning,and cellular experiments.Methods HF and EnMT gene matrices were obtained and the intersecting genes were extracted and enriched using Limma difference analysis and weighted gene co-expression network analysis(WGCNA).The diagnostic genes were screened using a combination of random forest method,support vector machine-recursive feature elimination and network topology analysis,and immune infiltration analysis and prediction of natural active ingredients were performed.The expression of diagnostic genes and the pharmacological effects of the predicted ingredients were finally verified by cellular experiments.Results Differential analysis yielded 3034 EnMT-associated and 4133 HF-associated differential genes.WGCNA analysis yielded 4589 EnMT-associated Hub genes and 763 HF-associated Hub genes.Thirty-eight intersecting genes were extracted,which were mainly enriched in the pathways of basement membrane and extracellular matrix receptor interaction.Four diagnostic genes,CFP,COL4A2,ITGA1,and GRPEL1,were screened by multidimensional analysis.Immune infiltration analysis showed that the diagnostic genes were closely associated with mast cell resting state,memory B cells,and memory CD4+T cells.Reverse transcription-polymerase chain reaction analysis showed significantly increased mRNA expression levels of the four diagnostic genes in the Jagged1-induced model group(P＜0.05).The predicted components,sterol,kaempferol,and quercetin,all had good binding activities with the diagnostic genes.Enzyme-linked immunosorbent assay result confirmed that all three active components significantly reduced the expression of collagen type Ⅳ α2 chain protein in Jagged1-induced LSECs,with quercetin having the most significant effect(P＜0.01).Conclusions This study elucidated the molecular mechanism of hepatic sinusoidal endothelial cells involved in the pathological process of HF through mesenchymal transition.We also propose a diagnostic marker system including CFP,COL4A2,ITGA1,and GRPEL1 as core genes.The result also suggest that natural active ingredients,such as quercetin,may exert anti-HF pharmacological effects by targeting these diagnostic genes.

Investigated the mechanisms by which baicalein regulates nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)to ameliorate lipopolysaccharide(LPS)-induced sepsis-asso-ciated acute kidney injury(AKI)in mice.Sixty male C57BL/6 mice were randomly divided into six groups:control,model,low-dose baicalein(50 mg/kg),medium-dose baicalein(100 mg/kg),high-dose baicalein(200 mg/kg),and high-dose baicalein+brusatol(4 mg/kg).Baicalein was adminis-tered orally for 7 days as a preventative measure.Sepsis was induced via intraperitoneal injection of LPS.Murine sepsis score(MSS)was assessed within 12 hours post-induction.Serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an automatic biochemical analyzer and enzyme-linked immunosorbent assays(ELISA),respectively.Histopathological changes in kidney tissues were ob-served via hematoxylin-eosin(HE)staining.Western blot analysis was employed to determine the protein expression levels of Nrf2,HO-1,caspase-8,TNF-α,IL-1β,and IL-6 in kidney tissues.Additionally,total superoxide dismutase(SOD)activity in kidney tissues was assessed using com-mercially available kits.Compared to the model group,baicalein treatment significantly improved renal histopathological changes,alleviated cellular damage,and reduced the levels of inflammatory cytokines(TNF-α,IL-1βand IL-6)(P＜0.01)and kidney injury markers(Scr and BUN)(P＜0.01).Moreover,baicalein treatment significantly increased the protein expression levels of Nrf2 and HO-1(P＜0.01)and enhanced antioxidant enzyme activity.In conclusion,baicalein may pro-tect against LPS-induced sepsis-associated AK1 in mice by modulating the Nrf2/HO-1 signaling pathway,thereby attenuating oxidative stress,reducing inflammation,and disrupting the vicious cycle between inflammation and oxidative stress.

Investigated the mechanisms by which baicalein regulates nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)to ameliorate lipopolysaccharide(LPS)-induced sepsis-asso-ciated acute kidney injury(AKI)in mice.Sixty male C57BL/6 mice were randomly divided into six groups:control,model,low-dose baicalein(50 mg/kg),medium-dose baicalein(100 mg/kg),high-dose baicalein(200 mg/kg),and high-dose baicalein+brusatol(4 mg/kg).Baicalein was adminis-tered orally for 7 days as a preventative measure.Sepsis was induced via intraperitoneal injection of LPS.Murine sepsis score(MSS)was assessed within 12 hours post-induction.Serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an automatic biochemical analyzer and enzyme-linked immunosorbent assays(ELISA),respectively.Histopathological changes in kidney tissues were ob-served via hematoxylin-eosin(HE)staining.Western blot analysis was employed to determine the protein expression levels of Nrf2,HO-1,caspase-8,TNF-α,IL-1β,and IL-6 in kidney tissues.Additionally,total superoxide dismutase(SOD)activity in kidney tissues was assessed using com-mercially available kits.Compared to the model group,baicalein treatment significantly improved renal histopathological changes,alleviated cellular damage,and reduced the levels of inflammatory cytokines(TNF-α,IL-1βand IL-6)(P＜0.01)and kidney injury markers(Scr and BUN)(P＜0.01).Moreover,baicalein treatment significantly increased the protein expression levels of Nrf2 and HO-1(P＜0.01)and enhanced antioxidant enzyme activity.In conclusion,baicalein may pro-tect against LPS-induced sepsis-associated AK1 in mice by modulating the Nrf2/HO-1 signaling pathway,thereby attenuating oxidative stress,reducing inflammation,and disrupting the vicious cycle between inflammation and oxidative stress.

Objective To observe MRI manifestations of temporomandibular joint(TMJ)involvement of juvenile idiopathic arthritis(JIA).Methods Sixteen children with JIA who underwent MR examination of TMJ were retrospectively enrolled.Clinical data were collected,MRI manifestations of inflammation domain and damage domain of TMJ were observed,and evaluation based on JIA MRI scoring system for TMJ(JAMRIS-TMJ)was performed.Results Among 16 children with JIA,14 exhibited symptoms associated with TMJ involvement.One or multiple abnormal MRI manifestations were noticed in 25(25/32,78.13％)TMJ,including bone marrow edema in 12(12/32,37.50％),effusion in 8(8/32,25.00％)and synovial thickening in 6(6/32,18.75％),condylar flattening in 10(10/32,31.25％),bone erosion in 6(6/32,18.75％)and articular disc abnormalities in 2(2/32,6.25％)TMJ,while no obvious abnormality was observed in 7(7/32,21.88％)TMJ.Among 4 JIA children who underwent enhanced MR scanning,enhanced bone marrow was found in 2(2/8,25.00％),while synovial enhancement was observed in 4(4/8,50.00％)TMJ.According to JAMRIS-TMJ scoring,for inflammation domain,there were 7(7/32,21.88％)normal TMJ,17(17/32,53.13％)mild and 8(8/32,25.00％)moderate/severe inflammation TMJ,while for damage domain,there were 12(12/32,37.50％)normal TMJ,14(14/32,43.75％)mild and 6(6/32,18.75％)moderate/severe damage TMJ.Conclusion MRI manifestations of TMJ involvement of JIA mainly included bone marrow edema,joint effusion,condylar flattening and so on.

ObjectiveTo explore the mechanism of Huanglian Jiedutang in inhibiting the pyroptosis mediated by NOD-like receptor protein 3 （NLRP3） inflammasomes and alleviating the acute liver injury （ALI） induced by lipopolysaccharide （LPS） in the mouse model of sepsis. MethodFifty-four male C57BL/6 mice were randomized into blank， model， low- （3.08 g·kg^-1）， medium- （6.15 g·kg^-1）， and high-dose （12.30 g·kg^-1） Huanglian Jiedutang， and positive control （dexamethasone） groups （n=9）. The mice were administrated with Huanglian Jiedutang at different doses by gavage for 7 days， and then LPS （15 mg·kg^-1） was injected intraperitoneally for the modeling of sepsis. In the positive control group， dexamethasone （0.05 g·kg^-1） was injected intraperitoneally 1.5 h after modeling， and the mouse sepsis score （MSS） was recorded 12 h after modeling. The mice were sacrificed for the collection of blood and liver tissue samples. The levels of alanine transaminase （ALT） and aspartate transaminase （AST） were measured by a biochemical analyzer. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， IL-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the pathological changes in the liver tissue. The content of NLRP3 was observed by the immunofluorescence assay. The expression of apoptosis-associated speck-like protein containing CARD （ASC） was detected by immunohistochemistry. The protein levels of NLRP3， ASC， Caspase-1， and gasdermin D （GSDMD） in the liver tissue were determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to determine the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18. ResultCompared with the blank group， the model group showed elevated levels of ALT and AST （P<0.01） and risen levels of inflammatory cytokines in the serum （P<0.01）. In addition， the modeling resulted in edema and necrosis in the liver， and up-regulated the protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.01） and the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the drug intervention groups showed reduced content of inflammatory cytokines （P<0.01）， alleviated pathological damage in the liver tissue， and down-regulated protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.05，P<0.01） and mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05，P<0.01） in the liver tissue. ConclusionHuanglian Jiedutang can inhibit pyroptosis and reduce inflammation by inhibiting the activation of NLRP3 inflammasomes， thus demonstrating a therapeutic effect on acute liver injury in the mouse model of sepsis induced by LPS.

ObjectiveTo explore the protective mechanism of paeoniflorin on mice with ulcerative colitis （UC） through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） autophagy pathway. MethodUC mouse model was established by allowing mice freely drink 4% DSS， and 56 BALB/c male mice were randomly divided into model group， AMPK inhibitor group （20 mg·kg^-1）， paeoniflorin （50 mg·kg^-1） + inhibitor （20 mg·kg^-1） group， and high dose （50 mg·kg^-1）， medium dose （25 mg·kg^-1）， and low dose （12.5 mg·kg^-1） paeoniflorin groups. After seven days of drug intervention， the protective effect of paeoniflorin on mice with UC was determined by comparing the body weight， disease activity index （DAI） changes， and Hematoxylin-eosin （HE） staining results. Enzyme linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of mice in each group， and immunofluorescence was utilized to detect microtubule-associated protein 1 light chain 3 （LC3） content in the colon， AMPK， mTOR proteins， and their phosphorylated proteins including p-AMPK and p-mTOR in the colon tissue were detected by Western blot， and the mRNA expression levels of AMPK， mTOR， Beclin1， LC3， and p62 were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the model group showed a decrease in body mass， an increase in DAI score， and severe pathological damage to the colon. The levels of inflammatory factors including TNF-α and IL-6 increased in serum （P<0.01）， while the protein levels of LC3 and p-AMPK/AMPK were down-regulated in colon tissue， and those of p-mTOR/mTOR were up-regulated （P<0.01）. The mRNA expression levels of AMPK and LC3 were down-regulated， while the mRNA expression levels of mTOR and p62 were up-regulated （P<0.01）. Compared with the model group and the paeoniflorin + inhibitor group， the mice treated with paeoniflorin showed an increase in body mass， a decrease in DAI score， a reduction in pathological damage to colon tissue， and a reduction in the levels of inflammatory factors of TNF-α and IL-6 in serum （P<0.05）. The protein levels of LC3 and p-AMPK/AMPK in colon tissue were up-regulated， while the protein levels of p-mTOR/mTOR were down-regulated （P<0.01）. The mRNA expression levels of AMPK， Beclin1， and LC3 were up-regulated， while the mRNA expression of mTOR and p62 were down-regulated （P<0.01）. The colon tissue of the inhibitor group was severely damaged， and the trend of various indicators was completely opposite to that of the high dose paeoniflorin group. ConclusionPaeoniflorin can enhance autophagy and reduce inflammatory damage in mice with UC by activating the AMPK/mTOR signaling pathway and thus play a protective role.