Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

Objective To explore serum levels of serine/threonine protein kinase 4(MST4)and heat shock protein 70(HSP70)in children with idiopathic immune thrombocytopenia(ITP)and their clinical signifi-cance.Methods Totally 98 children with ITP admitted to Northwest Women and Children's Hospital from April 2019 to April 2023 were retrospectively selected as the ITP group,and 50 healthy children who under-went physical examination during the same period were selected as the control group.Enzyme linked immu-nosorbent assay was used to detect serum levels of MST4 and HSP70,and the serum MST4 and HSP70 levels in children with different ITP levels were compared.The correlation between the indicators were analyzed by Pearson correlation.Logistic regression model was used to screen the prognostic factors of ITP,and the as-sessment value of serum MST4 and HSP70 on ITP prognosis was analyzed by subject working characteristic curve.Results Serum MST4,HSP70,and CD8 in the ITP group were higher than those in the control group,while PLT,CD3+,CD4+,CD4+/CD8+were lower than those in the control group,with statistical significance(P＜0.05).Serum MST4 and HSP70 levels in mild group,moderate group and severe group were increased successively,with statistical significance(P＜0.05).Correlation analysis showed that serum MST4 and HSP70 were positively correlated with CD8+(P＜0.05),and negatively correlated with PLT,CD3+,CD4+,CD4+/CD8+(P＜0.05).The disease course,serum MST4 and HSP70 of ITP children in the poor prognosis group were higher than those in the good prognosis group,and the differences were statistically significant(P＜0.05).Logistic regression analysis showed that the course of disease(OR=1.579,P＜0.001),serum MST4(OR=1.451,P＜0.001)and serum HSP70(OR=1.442,P＜0.001)were independent risk factors af-fecting the prognosis of children with ITP.The area under the curve of serum MST4 and HSP70 combined in the assessment of poor prognosis of ITP children was larger than that of serum MST4 and HSP70,and the difference was statistically significant(Z=4.568,4.672,both P＜0.001).Conclusion The elevated serum MST4 and HSP70 levels in children with ITP are related to the severity of the disease and cellular immune function.The combination of the two has a high evaluation value for the prognosis of children with ITP.

Objective To investigate the prevalence and influencing factors of polypoid lesion of gallbladder(PLG)of soldiers stationed on an island.Methods A total of 687 soldiers stationed on an island who underwent annual physical examination from October to December 2020 were selected.They took transabdominal ultrasound and blood biochemical examination,and filled out the questionnaire.There were 62 cases with PLG(PLG group)and 625 cases without PLG(non-PLG group).Age,body mass index(BMI),blood pressure,smoking,eating habits,blood biochemical indexes,and self-rating depression scale(SDS)scores were compared between the two groups.Logistic regression analysis was performed to obtain the independent risk factors for the prevalence of PLG of the soldiers.Results There were significant differences in age,BMI,blood pressure,smoking,irregular diet,total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C)and SDS scores between the two groups(all P<0.05).Multivariate Logistic regression analysis showed that age,high BMI,smoking,irregular diet,high TC,high TG,high LDL-C,and high SDS scores were independent risk factors for PLG(all P<0.05).Conclusion There is a high overall prevalence of PLG in the soldiers of this island,which is related to age,high BMI,smoking,irregular diet,high TC,high TG,high LDL-C,and high SDS scores.

Objective To investigate the changes of macrophages and hemophagocytes in bone marrow smears of patients with multiple myeloma(MM)before and after chemotherapy and their correlation with clinical prognostic value.Methods A total of 300 MM patients treated in Liaocheng Second People's Hospital Affiliated to Shandong First Medical University from June 2018 to June 2023 were selected as the study objects.All patients received at least 3 courses of chemotherapy and were divided into the remission group(n=214)and the non-remission group(n=86)according to the clinical effect.Immunoglobulin(Ig)A,IgG,CD3+,CD4+,CD8+,interleukin(IL-2),IL-4,IL-6,IL-17,tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β,macrophages and hemophagocytes were detected in the two groups and compared between the two groups.COX regression was used to analyze the relationship between immunological indexes and non-remission of chemotherapy.The relationship between macrophages and hemophagocytes and non-remission of chemotherapy was analyzed by restricted cubic spline.The multiplicative interaction of macrophages and hemophagocytes on non-remission of chemotherapy was analyzed using an unconditioned Logistic regression model,and the additive interaction was analyzed using the interaction calculation table.Receiver operating characteristic(ROC)curve analysis of macrophages and hemophagocytes alone or in combination to determine the value of chemotherapy non-remission.Results The overall response rate(ORR)and non-response rate(NRR)of MM patients were 71.33%and 28.67%respectively.Compared with before treatment,IgA,IgG,CD8+,IL-6,IL-17,TNF-α,TGF-β,macrophages and hemophagocytes were significantly decreased in both groups after treatment(tslow=9.252～61.177,tnot slow=4.057～35.797).CD3+,CD4+,CD4+/CD8+,IL-2 and IL-4 were significantly increased(tslow=9.706～33.940,tnot slow=4.227～16.167),and the differences were statistically significant(all P<0.05).After treatment,compared with the remission group,IgA,IgG,CD8+,IL-6,IL-17,TNF-α,TGF-β,macrophages and hemophagocytes in the non-remission group were significantly higher than those in remission group(t=3.362～30.028),CD3+,CD4+,CD4+/CD8+,IL-2 and IL-4 were significantly lower than those in remission group(t=3.736～13.998).and the differences were statistically significant(all P＜0.05).After adjusting the influence of other factors by COX regression,the trend test of macrophages and hemophagocytes was still statistically significant the trend test of macrophages and hemophagocytes was still statistically significant(P<0.05).Patients with≥5 macrophages/tablet and≥3 hemophagocytes/tablet had a significantly increased risk of non-remission from chemotherapy(P<0.05).There were additive(OR=6.157,95%CI:3.768～12.978)and multiplicative(OR=5.648,95%CI:1.035～17.492)interactions between macrophages and hemophagocytes in the non-remission of chemotherapy.Compared with the single judgment of macrophages and hemophagocytes,the combination of the two has the highest accuracy in determining chemotherapy non-remission(P＜0.05).Conclusion Macrophages and hemophagocytic cells in MM patients after chemotherapy are significantly lower than those before chemotherapy,with≥5 macrophages/tablet and≥3 hemocyte phages/tablet,indicating that the risk of non-remission in patients with chemotherapy increased significantly,and the combination of the two can accurately judge the clinical efficacy.

Objective To investigate the changes of macrophages and hemophagocytes in bone marrow smears of patients with multiple myeloma(MM)before and after chemotherapy and their correlation with clinical prognostic value.Methods A total of 300 MM patients treated in Liaocheng Second People's Hospital Affiliated to Shandong First Medical University from June 2018 to June 2023 were selected as the study objects.All patients received at least 3 courses of chemotherapy and were divided into the remission group(n=214)and the non-remission group(n=86)according to the clinical effect.Immunoglobulin(Ig)A,IgG,CD3+,CD4+,CD8+,interleukin(IL-2),IL-4,IL-6,IL-17,tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β,macrophages and hemophagocytes were detected in the two groups and compared between the two groups.COX regression was used to analyze the relationship between immunological indexes and non-remission of chemotherapy.The relationship between macrophages and hemophagocytes and non-remission of chemotherapy was analyzed by restricted cubic spline.The multiplicative interaction of macrophages and hemophagocytes on non-remission of chemotherapy was analyzed using an unconditioned Logistic regression model,and the additive interaction was analyzed using the interaction calculation table.Receiver operating characteristic(ROC)curve analysis of macrophages and hemophagocytes alone or in combination to determine the value of chemotherapy non-remission.Results The overall response rate(ORR)and non-response rate(NRR)of MM patients were 71.33%and 28.67%respectively.Compared with before treatment,IgA,IgG,CD8+,IL-6,IL-17,TNF-α,TGF-β,macrophages and hemophagocytes were significantly decreased in both groups after treatment(tslow=9.252～61.177,tnot slow=4.057～35.797).CD3+,CD4+,CD4+/CD8+,IL-2 and IL-4 were significantly increased(tslow=9.706～33.940,tnot slow=4.227～16.167),and the differences were statistically significant(all P<0.05).After treatment,compared with the remission group,IgA,IgG,CD8+,IL-6,IL-17,TNF-α,TGF-β,macrophages and hemophagocytes in the non-remission group were significantly higher than those in remission group(t=3.362～30.028),CD3+,CD4+,CD4+/CD8+,IL-2 and IL-4 were significantly lower than those in remission group(t=3.736～13.998).and the differences were statistically significant(all P＜0.05).After adjusting the influence of other factors by COX regression,the trend test of macrophages and hemophagocytes was still statistically significant the trend test of macrophages and hemophagocytes was still statistically significant(P<0.05).Patients with≥5 macrophages/tablet and≥3 hemophagocytes/tablet had a significantly increased risk of non-remission from chemotherapy(P<0.05).There were additive(OR=6.157,95%CI:3.768～12.978)and multiplicative(OR=5.648,95%CI:1.035～17.492)interactions between macrophages and hemophagocytes in the non-remission of chemotherapy.Compared with the single judgment of macrophages and hemophagocytes,the combination of the two has the highest accuracy in determining chemotherapy non-remission(P＜0.05).Conclusion Macrophages and hemophagocytic cells in MM patients after chemotherapy are significantly lower than those before chemotherapy,with≥5 macrophages/tablet and≥3 hemocyte phages/tablet,indicating that the risk of non-remission in patients with chemotherapy increased significantly,and the combination of the two can accurately judge the clinical efficacy.

Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

OBJECTIVE To investigate the effects and potential mechanism of persimmon leaf (PL) extract against ferroptosis induced by H2O2 in IEC-6 cells.METHODS Using IEC-6 cells as object,the effects of ferroptosis inhibitor ferrostatin-1 on IEC-6 cell viability induced by H2O2 were investigated;IEC-6 cells were divided into control group,H2O2 group,H2O2+PL 25 μg/mL group and H2O2+PL 50 μg/mL group.The levels of oxidant stress indexes[content of malondialdehyde (MDA),activity of superoxide dismutase (SOD),and levels of reactive oxygen species (ROS)],mitochondrial membrane potential (MMP) as well as mRNA and protein expressions of nuclear factor-erythroid-2 related factor 2 (Nrf2),heme oxygenase-1 (HO-1),NADPH/quinone oxidoreductase-1 (NQO-1),cystine/glutamate anti-porter (xCT),glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH) were detected.RESULTS Ferroptosis inhibitor ferrostatin-1 could significantly increase the survival rate of H2O2-induced cells (P<0.01).Compared with the control group,MDA content,ROS level,mRNA expressions of Nrf2 and NQO-1 as well as protein expressions of Nrf2 and HO-1 were increased or up-regulated significantly,while SOD activity,MMP,mRNA expressions of xCT,GPX4 and FTH as well as protein expressions of GPX4 and FTH were decreased or down-regulated significantly (P<0.01 or P<0.05).Compared with the H2O2 group,oxidative stress indexes of H2O2+PL 25,50 μg/mL groups were reversed to different extents,MMP level was increased significantly,as well as mRNA and protein expressions of Nrf2,HO-1,NQO-1,xCT,GPX4 and FTH were up-regulated to different extents;there were statistical significances in some indexes between groups (P<0.01 or P<0.05).CONCLUSIONS PL extract can alleviate mitochondrial membrane damage and abnormal accumulation of ROS caused by H2O2,which may be related to the inhibition of ferroptosis by activating the Nrf2/HO-1 signaling pathway.

Cetuximab is a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR) for the treatment of metastat-ic colorectal cancer (mCRC). However,most patients treated with cetuximab experience disease progression due to the development of sec-ondary drug resistance,presenting a significant challenge in managing cetuximab therapy. Existing studies have found that cetuximab resist-ance mechanisms are not only linked to the RAS/RAF/PIK3CA genetic mutations but also closely associated with the abnormal activation of PI3K/AKT/mTOR,Wnt/β-catenin,c-MET/HGF,and RAS-MAPK signaling pathways. Additionally,HER2 and MET amplification,microsatellite instability,changes in tumor metabolism,and alterations in the tumor microenvironment may also contribute to cetuximab resistance in pa-tients. This review focuses on the potential molecular mechanisms of cetuximab resistance in the treatment of mCRC,and provides new ideas for overcoming cetuximab resistance in clinic.

Objective:A nationwide multi-center and large sample survey was conducted to compare the validity of the Mini International Neuropsychiatric Interview (Hypo-) Manic Episode with Mixed Features-DSM-5 Module (MINI-M) questionnaire and the Clinically Useful Depression Outcome Scale Supplemented with Questions for the DSM-5 Mixed Features Specifier (CUDOS-M) depression subscale in identifying mixed features in patients experiencing (hypo-) manic episodes.Methods:Using a convenience sampling method, 366 patients with bipolar disorder experiencing acute (hypo-) manic episodes who met the inclusion and exclusion criteria were recruited. The diagnosis of "with mixed features" was based on the DSM-5 criteria for mixed features. The predictive validity of the MINI-M questionnaire and the CUDOS-M depression subscale to screen mixed features was analyzed using the receiver operating characteristic (ROC) curve. Additionally, the difference in area under the ROC curve (AUC) between the two instruments was compared.Results:The AUC for the MINI-M questionnaire and the CUDOS-M depression subscale in screening mixed features were 0.79 (95 %CI=0.75-0.84) and 0.81 (95 %CI=0.77-0.86), respectively. There was no statistically significant difference in AUC between the two measurements ( Z=-1.19, P>0.05). Among patients with acute (hypo-) manic episodes, 45.9% (168/366) presented with mixed features according to the DSM-5 criteria, while the corresponding figures were 43.7% (160/366) using the MINI-M questionnaire (total score≥3) and 42.1% (154/366) using the CUDOS-M depression subscale (total score≥20). Screening results were comparable among the three measures. Conclusion:Mixed features are common among patients experiencing acute (hypo-) manic episodes. The MINI-M questionnaire and the CUDOS-M depression subscale demonstrate equivalent validity in identifying mixed features.

In the context of the emphasis on the claims of multiple subjects in fourth-generation educational evaluation, the subjective experience of students has gradually become one of the key contents of educational evaluation. However, there is still a vague understanding of the conceptual source, specific definition, and measurement indicators of the student experience theory, and a more systematic theoretical system has not yet been formed. With the UE user experience thinking in the business field as the core meta-theory, this article integrates value-added evaluation and the idea of three-source flow, elaborates on the core concept connotation of compound student experience teaching evaluation, and builds a five-dimensional evaluation model for student experience with "aesthetic experience, interactive experience, emotional experience, behavioral experience, and discursive experience" as the first-level indicators based on literature research, expert interviews, and multi-round group discussions. It is hoped that student evaluation will force teachers to improve the contents and form of teaching and help to achieve breakthrough reform of the teaching system as a whole.