ObjectiveTo verify the therapeutic effect of Yinqi Sanhuang Jiedu decoction （YQSH） on carbon tetrachloride （CCl₄）-induced hepatic fibrosis in mice， and to explore whether its effect was related to the inhibition of neutrophil infiltration and the formation of neutrophil extracellular traps （NETs）. MethodsThe 36 C57BL/6J mice were randomly divided into control group， model group， positive drug silybin （SF） group （55 mg·kg^-1·d^-1）， YQSH-L group， YQSH-M group， and YQSH-H group （8.325， 16.65， 33.3 g·kg^-1·d^-1， respectively），n=6 in each group. Except for the control group， mice in all other groups were intraperitoneally injected with CCl₄ to induce hepatic fibrosis. After successful modeling， each drug administration group was given the corresponding drugs by gavage for eight weeks. Hematoxylin-eosin （HE） staining， Sirius red staining and Masson staining were used to observe the pathological changes of liver tissue. Liver elasticity was detected by a color Doppler ultrasound system. Immunohistochemistry and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were performed to detect the protein expression and mRNA levels of C-X-C motif chemokine ligand 1 （CXCL1）， CXCL2 and CXCL5. Neutrophil levels were detected by flow cytometry. The expression of neutrophil elastase （NE） and myeloperoxidase （MPO） positive protein was observed by immunofluorescence. The contents of MPO， NE and CitH3 were detected by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the control group， the liver of the model group showed obvious inflammatory cell infiltration and collagen deposition， and the liver elasticity， CXCL1， CXCL2， CXCL5 expression， neutrophil level， and MPO， NE and CitH3 levels were significantly increased （P<0.05， P<0.01）. Compared with the model group， inflammatory cell infiltration and collagen deposition in the liver tissue of mice were reduced after YQSH treatment. Moreover， the liver elasticity was reduced （P<0.01）. The protein expression （P<0.01） and mRNA level of CXCL1， CXCL2 and CXCL5 were decreased（P<0.05，P<0.01）. The neutrophil level was decreased （P<0.01）， the expression of MPO and NE positive protein was significantly decreased（P<0.05，P<0.01）， and the levels of MPO， NE and CitH3 were decreased （P<0.05， P<0.01）. ConclusionThe anti-hepatic fibrosis effect of YQSH may be related to its inhibition of chemokines （CXCL1， CXCL2， CXCL5）， reduction of neutrophil infiltration， and inhibition of NETs generation.

ObjectiveTo verify the therapeutic effect of Yinqi Sanhuang Jiedu decoction （YQSH） on carbon tetrachloride （CCl₄）-induced hepatic fibrosis in mice， and to explore whether its effect was related to the inhibition of neutrophil infiltration and the formation of neutrophil extracellular traps （NETs）. MethodsThe 36 C57BL/6J mice were randomly divided into control group， model group， positive drug silybin （SF） group （55 mg·kg^-1·d^-1）， YQSH-L group， YQSH-M group， and YQSH-H group （8.325， 16.65， 33.3 g·kg^-1·d^-1， respectively），n=6 in each group. Except for the control group， mice in all other groups were intraperitoneally injected with CCl₄ to induce hepatic fibrosis. After successful modeling， each drug administration group was given the corresponding drugs by gavage for eight weeks. Hematoxylin-eosin （HE） staining， Sirius red staining and Masson staining were used to observe the pathological changes of liver tissue. Liver elasticity was detected by a color Doppler ultrasound system. Immunohistochemistry and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were performed to detect the protein expression and mRNA levels of C-X-C motif chemokine ligand 1 （CXCL1）， CXCL2 and CXCL5. Neutrophil levels were detected by flow cytometry. The expression of neutrophil elastase （NE） and myeloperoxidase （MPO） positive protein was observed by immunofluorescence. The contents of MPO， NE and CitH3 were detected by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the control group， the liver of the model group showed obvious inflammatory cell infiltration and collagen deposition， and the liver elasticity， CXCL1， CXCL2， CXCL5 expression， neutrophil level， and MPO， NE and CitH3 levels were significantly increased （P<0.05， P<0.01）. Compared with the model group， inflammatory cell infiltration and collagen deposition in the liver tissue of mice were reduced after YQSH treatment. Moreover， the liver elasticity was reduced （P<0.01）. The protein expression （P<0.01） and mRNA level of CXCL1， CXCL2 and CXCL5 were decreased（P<0.05，P<0.01）. The neutrophil level was decreased （P<0.01）， the expression of MPO and NE positive protein was significantly decreased（P<0.05，P<0.01）， and the levels of MPO， NE and CitH3 were decreased （P<0.05， P<0.01）. ConclusionThe anti-hepatic fibrosis effect of YQSH may be related to its inhibition of chemokines （CXCL1， CXCL2， CXCL5）， reduction of neutrophil infiltration， and inhibition of NETs generation.

ObjectiveTo validate the therapeutic effect of Yinqi Sanhuang Jiedu decoction （YQSH） on a mouse model of carbon tetrachloride （CCl₄）-induced liver fibrosis and to investigate its correlations with the Piezo-type mechanosensitive ion channel component 1 （Piezo1）-Yes-associated protein （YAP） mechanical signaling axis and macrophage polarization. MethodsFifty-four C57BL/6J mice were randomized into a blank control group， a 4-week model group， a 6-week model group， a 8-week model group， a positive drug （silymarin， 55 mg·kg^-1·d^-1） group， and low-， medium-， and high-dose （8.325， 16.65， 33.3 g·kg^-1·d^-1， respectively） YQSH groups. Except the 6-week model group （n=12）， each of the other groups had 6 mice. Mice in other groups except the blank control group received intraperitoneal injections of 10% CCl₄ twice weekly for the modeling of liver fibrosis. Drug interventions began one week after the initial modeling through gavage， and the blank control and model groups received 0.2 mL of normal saline via gavage. The histopathological changes and collagen deposition in the liver were observed via hematoxylin-eosin （HE）， Masson's trichrome， and Sirius red staining. Serum activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， as well as serum levels of total protein （TP）， albumin （ALB）， total bilirubin （TBIL）， hyaluronic acid （HA）， laminin （LN）， procollagen type Ⅲ （PCⅢ）， and collagen type Ⅳ （Ⅳ-C）， were measured. The levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the liver tissue were determined by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA levels of Piezo1 and YAP1 in the liver tissue were determined by immunohistochemistry （IHC） and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. Co-localization of Piezo1 with YAP1， and YAP1 with inducible nitric oxide synthase （iNOS） was observed by the immunofluorescence （IF） assay. The proportions of M1-type （F4/80⁺CD80⁺） and M2-type （F4/80⁺CD206⁺） macrophages in the liver tissue were examined by flow cytometry. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses and gene set enrichment analysis （GSEA） were performed through transcriptomic sequencing. ResultsCompared with the blank control group， the model group exhibited gradually worsened liver fibrosis at the 4^th， 6^th， and 8^th weeks. The 6- and 8-week model groups showcased inflammatory cell infiltration and collagen deposition in the liver （P<0.01） and upregulated protein levels of both Piezo1 and YAP1 （P<0.01）. Compared with the model groups， treatment with YQSH improved the liver function （P<0.05， P<0.01）， alleviated liver fibrosis （P<0.05， P<0.01）， and reduced intrahepatic inflammatory cell infiltration and collagen deposition （P<0.01）. Furthermore， the treatment downregulated the protein and mRNA levels of Piezo1 and YAP1 （P<0.05， P<0.01）， lowered the levels of inflammatory factors TNF-α and IL-1β （P<0.05， P<0.01）， and decreased the ratio of CD80 （M1-type）/CD206 （M2-type） macrophage proteins （P<0.01）. The IF assay showed co-localization of YAP1 with Piezo1 and iNOS. Compared with the model groups， YQSH treatment downregulated the expression of Piezo1， YAP1， and iNOS （P<0.05， P<0.01）. Transcriptomic analysis suggested that the anti-liver fibrosis effect of YQSH may be related to the Hippo signaling pathway （P<0.05）. ConclusionThe anti-liver fibrosis effect of YQSH may be related to its inhibition of the Piezo1-YAP signaling axis and regulation of macrophage polarization.

ObjectiveTo validate the therapeutic effect of Yinqi Sanhuang Jiedu decoction （YQSH） on a mouse model of carbon tetrachloride （CCl₄）-induced liver fibrosis and to investigate its correlations with the Piezo-type mechanosensitive ion channel component 1 （Piezo1）-Yes-associated protein （YAP） mechanical signaling axis and macrophage polarization. MethodsFifty-four C57BL/6J mice were randomized into a blank control group， a 4-week model group， a 6-week model group， a 8-week model group， a positive drug （silymarin， 55 mg·kg^-1·d^-1） group， and low-， medium-， and high-dose （8.325， 16.65， 33.3 g·kg^-1·d^-1， respectively） YQSH groups. Except the 6-week model group （n=12）， each of the other groups had 6 mice. Mice in other groups except the blank control group received intraperitoneal injections of 10% CCl₄ twice weekly for the modeling of liver fibrosis. Drug interventions began one week after the initial modeling through gavage， and the blank control and model groups received 0.2 mL of normal saline via gavage. The histopathological changes and collagen deposition in the liver were observed via hematoxylin-eosin （HE）， Masson's trichrome， and Sirius red staining. Serum activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， as well as serum levels of total protein （TP）， albumin （ALB）， total bilirubin （TBIL）， hyaluronic acid （HA）， laminin （LN）， procollagen type Ⅲ （PCⅢ）， and collagen type Ⅳ （Ⅳ-C）， were measured. The levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the liver tissue were determined by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA levels of Piezo1 and YAP1 in the liver tissue were determined by immunohistochemistry （IHC） and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. Co-localization of Piezo1 with YAP1， and YAP1 with inducible nitric oxide synthase （iNOS） was observed by the immunofluorescence （IF） assay. The proportions of M1-type （F4/80⁺CD80⁺） and M2-type （F4/80⁺CD206⁺） macrophages in the liver tissue were examined by flow cytometry. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses and gene set enrichment analysis （GSEA） were performed through transcriptomic sequencing. ResultsCompared with the blank control group， the model group exhibited gradually worsened liver fibrosis at the 4^th， 6^th， and 8^th weeks. The 6- and 8-week model groups showcased inflammatory cell infiltration and collagen deposition in the liver （P<0.01） and upregulated protein levels of both Piezo1 and YAP1 （P<0.01）. Compared with the model groups， treatment with YQSH improved the liver function （P<0.05， P<0.01）， alleviated liver fibrosis （P<0.05， P<0.01）， and reduced intrahepatic inflammatory cell infiltration and collagen deposition （P<0.01）. Furthermore， the treatment downregulated the protein and mRNA levels of Piezo1 and YAP1 （P<0.05， P<0.01）， lowered the levels of inflammatory factors TNF-α and IL-1β （P<0.05， P<0.01）， and decreased the ratio of CD80 （M1-type）/CD206 （M2-type） macrophage proteins （P<0.01）. The IF assay showed co-localization of YAP1 with Piezo1 and iNOS. Compared with the model groups， YQSH treatment downregulated the expression of Piezo1， YAP1， and iNOS （P<0.05， P<0.01）. Transcriptomic analysis suggested that the anti-liver fibrosis effect of YQSH may be related to the Hippo signaling pathway （P<0.05）. ConclusionThe anti-liver fibrosis effect of YQSH may be related to its inhibition of the Piezo1-YAP signaling axis and regulation of macrophage polarization.

Objective:To investigate the characteristics of Internet addiction(IA)in adolescents with depression and explore its relationship with impulsivity and aggressive personality traits.Methods:A total of 71 adolescent patients with depressive disorders were recruited from the Child Psychiatry Outpatient Clinic of Peking University Sixth Hospital between April 2021 and November 2022 (15 males, 56 females; median age 14 [13, 15] years) as the depressive disorder group. Additionally, 83 healthy adolescents (27 males, 56 females; median age 14 [13, 17] years) were recruited as the control group during the same period. Internet addiction was assed using the Chinese version of Young′s Internet Addiction Test (YIAT), with a total score≥50 indicating internet addiction. Impulsivity was evaluated using the Barratt Impulsiveness Scale-11(BIS-11), and aggression was measured with the Buss-Perry Aggression Questionnaire(BPAQ). Differences in internet addiction, impulsivity, and aggression between the depression group and the control group were analyzed. Pearson correlation analysis was used to explore the correlation between internet addiction and impulsivity, aggression. Hierarchical linear regression models were used to analyze the factors influencing internet addiction, and a parallel mediation model was used to examine the mediating effect of impulsivity and aggressive personality traits in the relationship between depressive disorders and internet addiction.Results:The prevalence of IA was significantly higher in adolescents with depression than the healthy control group [57.75%(41/71) vs 31.33%(26/83); χ 2=10.87, P<0.001]. Adolescents with depressive disorders also exhibited higher impulsivity (65.5±9.2 vs 57.0±9.2, t=-5.72, P<0.001) and aggression (56.3±16.0 vs 42.4±15.1, t=-5.13, P<0.001) compared to the control group. Internet addiction was positively correlated with aggression ( r=0.47, P<0.01) and impulsivity ( r=0.57, P<0.01). Hierarchical regression analysis with the YIAT total score as the dependent variable revealed that impulsivity ( β=0.48, P<0.001) and aggression ( β=0.24, P<0.001) significantly predicted internet addiction. Mediation analysis indicated that depressive disorders indirectly indirectly influenced internet addiction through parallel paths of impulsivity and aggression, with a total indirect effect of 0.543 (95% CI: 0.362-0.761). Conversely, internect addiction influenced depressive disorders through reverse parallel pathway of impulsivity and aggression with a total indirect effect of 0.038 (95% CI: 0.021-0.067). Direct effects were not significant in either direction. Conclusion:Adolescents with depressive disorders exhibit more internet addiction. Impulsivity and aggressive personality traits play bidirectional mediating roles in the relationship between depressive disorders and internet addiction.

Objective To observe the value of MR T2WI intratumoral and peritumoral CT radiomics for predicting von Hippel-Lindau(VHL)gene mutation in renal carcinoma.Method Totally 150 patients with renal carcinoma were retrospectively enrolled and divided into training set(n=105)and validation set(n=45)at the ratio of 7∶3,and furtherly assigned into mutation subgroup and wild subgroup according to with VHL gene mutation or not.Multivariate logistic regression analysis was performed to screen the independent risk factors of VHL gene mutation in renal carcinoma,then a clinical model was constructed.The optimal radiomics features were extracted and screened based on intratumoral+peritumoral 2 mm regions shown on MR T2WI.Logistic regression algorithm was used to construct radiomics model,and finally a combined model was established based on radiomics model and clinical model.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting VHL gene mutation in renal carcinoma.Result Patients'age,smoking history,hypertension history,other family histories and β2-microglobulin were all independent clinical risk factors for VHL gene mutation in renal carcinoma(all P＜0.05).The efficacy of clinical model,radiomics model and combined model for predicting VHL gene mutation in renal carcinoma increased successively(all P＜0.05),with AUC of 0.758,0.831 and 0.952 in training set,0.729,0.803 and 0.896 in validation set,respectively.Conclusion MR T2WI intratumoral and peritumoral CT radiomics had good efficacy for predicting VHL gene mutation in renal carcinoma.Combining with clinical features could further improve predicting efficacy of model.

Objective To explore the value of ZOOMit intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI)technology in assessing renal function in diabetic kidney disease(DKD)and non-diabetic kidney disease(non-DKD).Methods Based on the estimated glomerular filtration rate(eGFR),50 DKD patients and 50 non-DKD patients were enrolled,with each group contained 21 mild cases(mild group)and 29 moderate to severe cases(moderate to severe group).All subjects underwent ZOOMit IVIM-DWI examination and the parameter values of the renal cortex and medulla were measured.The differences of IVIM-DWI parameters in renal cortex and medulla between DKD and non-DKD patients,and the correlation with eGFR,and diagnostic efficacy were compared.Results In the DKD patients,the f value of the medulla,the D value of the cortex,and the D* value of the medulla showed statistically significant differences between mild group and moderate to severe group(t=7.836,3.337,2.515,P<0.05),and all were positively correlated with eGFR(r=0.750,0.375,0.404,P<0.05).In the non-DKD patients,the f value of the medulla and the D* value of the medulla showed statistically significant differences between mild group and moderate to severe group(t=2.619,2.453,P<0.05),and were positively correlated with eGFR(r=0.425,0.360,P<0.05).In both DKD and non-DKD patients,the f value of the medulla showed the best efficacy in distinguishing between mild and moderate to severe DKD,with the area under the curve(AUC)=0.961(DeLong test P<0.05).Conclusion ZOOMit IVIM-DWI technology can be used for renal function in DKD and non-DKD,with the f value of the medulla being more suitable for the assessment of renal function in DKD.

Objective To explore the value of ZOOMit intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI)technology in assessing renal function in diabetic kidney disease(DKD)and non-diabetic kidney disease(non-DKD).Methods Based on the estimated glomerular filtration rate(eGFR),50 DKD patients and 50 non-DKD patients were enrolled,with each group contained 21 mild cases(mild group)and 29 moderate to severe cases(moderate to severe group).All subjects underwent ZOOMit IVIM-DWI examination and the parameter values of the renal cortex and medulla were measured.The differences of IVIM-DWI parameters in renal cortex and medulla between DKD and non-DKD patients,and the correlation with eGFR,and diagnostic efficacy were compared.Results In the DKD patients,the f value of the medulla,the D value of the cortex,and the D* value of the medulla showed statistically significant differences between mild group and moderate to severe group(t=7.836,3.337,2.515,P<0.05),and all were positively correlated with eGFR(r=0.750,0.375,0.404,P<0.05).In the non-DKD patients,the f value of the medulla and the D* value of the medulla showed statistically significant differences between mild group and moderate to severe group(t=2.619,2.453,P<0.05),and were positively correlated with eGFR(r=0.425,0.360,P<0.05).In both DKD and non-DKD patients,the f value of the medulla showed the best efficacy in distinguishing between mild and moderate to severe DKD,with the area under the curve(AUC)=0.961(DeLong test P<0.05).Conclusion ZOOMit IVIM-DWI technology can be used for renal function in DKD and non-DKD,with the f value of the medulla being more suitable for the assessment of renal function in DKD.

Objective To observe the value of MR T2WI intratumoral and peritumoral CT radiomics for predicting von Hippel-Lindau(VHL)gene mutation in renal carcinoma.Method Totally 150 patients with renal carcinoma were retrospectively enrolled and divided into training set(n=105)and validation set(n=45)at the ratio of 7∶3,and furtherly assigned into mutation subgroup and wild subgroup according to with VHL gene mutation or not.Multivariate logistic regression analysis was performed to screen the independent risk factors of VHL gene mutation in renal carcinoma,then a clinical model was constructed.The optimal radiomics features were extracted and screened based on intratumoral+peritumoral 2 mm regions shown on MR T2WI.Logistic regression algorithm was used to construct radiomics model,and finally a combined model was established based on radiomics model and clinical model.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting VHL gene mutation in renal carcinoma.Result Patients'age,smoking history,hypertension history,other family histories and β2-microglobulin were all independent clinical risk factors for VHL gene mutation in renal carcinoma(all P＜0.05).The efficacy of clinical model,radiomics model and combined model for predicting VHL gene mutation in renal carcinoma increased successively(all P＜0.05),with AUC of 0.758,0.831 and 0.952 in training set,0.729,0.803 and 0.896 in validation set,respectively.Conclusion MR T2WI intratumoral and peritumoral CT radiomics had good efficacy for predicting VHL gene mutation in renal carcinoma.Combining with clinical features could further improve predicting efficacy of model.

Objective:To investigate the characteristics of Internet addiction(IA)in adolescents with depression and explore its relationship with impulsivity and aggressive personality traits.Methods:A total of 71 adolescent patients with depressive disorders were recruited from the Child Psychiatry Outpatient Clinic of Peking University Sixth Hospital between April 2021 and November 2022 (15 males, 56 females; median age 14 [13, 15] years) as the depressive disorder group. Additionally, 83 healthy adolescents (27 males, 56 females; median age 14 [13, 17] years) were recruited as the control group during the same period. Internet addiction was assed using the Chinese version of Young′s Internet Addiction Test (YIAT), with a total score≥50 indicating internet addiction. Impulsivity was evaluated using the Barratt Impulsiveness Scale-11(BIS-11), and aggression was measured with the Buss-Perry Aggression Questionnaire(BPAQ). Differences in internet addiction, impulsivity, and aggression between the depression group and the control group were analyzed. Pearson correlation analysis was used to explore the correlation between internet addiction and impulsivity, aggression. Hierarchical linear regression models were used to analyze the factors influencing internet addiction, and a parallel mediation model was used to examine the mediating effect of impulsivity and aggressive personality traits in the relationship between depressive disorders and internet addiction.Results:The prevalence of IA was significantly higher in adolescents with depression than the healthy control group [57.75%(41/71) vs 31.33%(26/83); χ 2=10.87, P<0.001]. Adolescents with depressive disorders also exhibited higher impulsivity (65.5±9.2 vs 57.0±9.2, t=-5.72, P<0.001) and aggression (56.3±16.0 vs 42.4±15.1, t=-5.13, P<0.001) compared to the control group. Internet addiction was positively correlated with aggression ( r=0.47, P<0.01) and impulsivity ( r=0.57, P<0.01). Hierarchical regression analysis with the YIAT total score as the dependent variable revealed that impulsivity ( β=0.48, P<0.001) and aggression ( β=0.24, P<0.001) significantly predicted internet addiction. Mediation analysis indicated that depressive disorders indirectly indirectly influenced internet addiction through parallel paths of impulsivity and aggression, with a total indirect effect of 0.543 (95% CI: 0.362-0.761). Conversely, internect addiction influenced depressive disorders through reverse parallel pathway of impulsivity and aggression with a total indirect effect of 0.038 (95% CI: 0.021-0.067). Direct effects were not significant in either direction. Conclusion:Adolescents with depressive disorders exhibit more internet addiction. Impulsivity and aggressive personality traits play bidirectional mediating roles in the relationship between depressive disorders and internet addiction.