Abstract:Objective To investigate the interaction between human microRNA chromosome 8:96(hsa-miR-Chr8:96)and helper T cell 17(Th17)in dilated cardiomyopathy(DCM)and the value of predicting the occurrence of heart failure(HF).Methods In total,153 patients with DCM admitted from September 2021 to March 2024 were selected as the observation group,and 153 healthy physical examinees in the same period were selected as the control group.The expression levels of hsa-miR-Chr8:96 in peripheral blood and the level of Th17 cells at admission or during physical examination were compared between the two groups.The interaction between hsa-miR-Chr8:96 and Th17 cells was analyzed.After standardized treatment in the observation group.The expression levels of hsa-miR-Chr8:96 and Th17 cells in the peripheral blood of patients with and without HF were observed.Multivariate logistic regression analysis was used to analyze the influencing factors of DCM complicated with HF,and smooth curve fitting was used to analyze the relationship between hsa-miR-Chr8:96,Th17 cells and DCM complicated with HF.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of hsa-miR-Chr8:96 and Th17 cells for DCM complicated with HF.Results The expression levels of hsa-miR-Chr8:96 and Th17 cells in the peripheral blood of the observation group were higher than those of the control group at admission(P<0.01).After adjusting for other factors such as gender and age,the positive additive interaction between high levels of hsa-miR-Chr8:96 and high levels of Th17 cells existed in DCM(P<0.01).After follow-up of the observation group,3 patients were lost to follow-up,and 96 patients did not develop HF,while 54 patients developed HF.The expression levels of B-type natriuretic peptide,left ventricular end-diastolic diameter,hsa-miR-Chr8:96,and Th17 cells in the observation group of patients with HF were higher than those of patients without HF at admission,and the left ventricular ejection fraction was lower than that of patients without HF(P<0.01).Multivariate logistic regression analysis showed that hsa-miR-Chr8:96 and Th17 cells were independent influencing factors for DCM complicated with HF(P<0.01).Smooth curve fitting analysis showed that after correcting for other factors,hsa-miR-Chr8:96 and Th17 cells had a positive linear relationship with DCM complicated with HF.As the levels of hsa-miR-Chr8:96 and Th17 cells increased,the risk of DCM complicated with HF gradually increased(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of hsa-miR-Chr8:96 and Th17 cells for predicting DCM complicated with HF was 0.765 and 0.775,respectively.The AUC of the combined prediction of hsa-miR-Chr8:96 and Th17 cells for DCM complicated with HF was 0.884,and the combined predictive value was better than the individual prediction(Z=2.654,2.357,P=0.008,0.018).Conclusion The high levels of hsa-miR-Chr8:96 and Th17 cells in DCM have a significant synergistic effect and are independent influencing factors for DCM complicated with HF.Combined detection can significantly improve the predictive value for DCM complicated with HF.This biomarker combination is helpful for identifying high-risk patients and providing important theoretical basis and transformation direction for early intervention and individualized prevention strategies.

Abstract:Objective To investigate the changes in the levels of serum NOD-like receptor pyrin domain-containing protein 3(NLRP3),fibroblast growth factor 21(FGF21),and transforming growth factor-β1(TGF-β1)in patients with severe pneumonia and their correlation with the gut microbiota.Methods A total of 133 patients with severe pneumonia(observation group),110 patients with common pneumonia(control group),and 100 healthy physical examinees(healthy group)between February 2023 and June 2024 were selected.According to the Acute Physiology and Chronic Health Evaluation Ⅱ score(APACHE Ⅱ),the patients with severe pneumonia were divided into low-risk subgroup(n=43),medium-risk subgroup(n=56),and high-risk subgroup(n=34).The observation group was further divided into the survival subgroup(n=76)and the death subgroup(n=57)based on the 28-day survival status after admission.The levels of serum NLRP3,FGF21,and TGF-β1 in each group were detected,and the number of gut microbiota in the observation group and the control group was compared.Pearson correlation analysis was used to analyze the correlation between the levels of serum NLRP3,FGF21,and TGF-β1 and the gut microbiota in patients with severe pneumonia.Multivariate logistic regression analysis was used to analyze the influencing factors of the prognosis of patients with severe pneumonia,and the receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum NLRP3,FGF21,and TGF-β1 for the prognosis of patients with severe pneumonia.Results The levels of serum NLRP3,FGF21,and TGF-β1 in the observation group and the control group were higher than those in the healthy group.The levels of serum NLRP3,FGF21,TGF-β1 and the number of Escherichia coli and Enterococcus in the observation group were higher than those in the control group,while the number of Bacteroides,Bifidobacterium,and Lactobacillus was lower than that in the control group(P<0.05,P<0.01).The levels of serum NLRP3,FGF21,and TGF-β1 were higher in the medium-risk and high-risk subgroups than in the low-risk subgroup,and higher in the high-risk subgroup than in the medium-risk subgroup(P<0.05).The levels of serum NLRP3,FGF21,and TGF-β1 in the survival subgroup were lower than those in the death subgroup(P<0.01).The levels of serum NLRP3,FGF21,and TGF-β1 were positively correlated with Escherichia coli and Enterococcus,and negatively correlated with Bacteroides,Bifidobacterium,and Lactobacillus(P<0.01).Serum NLRP3,FGF21,and TGF-β1 were all risk factors for the prognosis of patients with severe pneumonia(P<0.05).The combined detection of serum NLRP3,FGF21,and TGF-β1 had a higher predictive value for the prognosis of patients with severe pneumonia than the prediction by each indicator alone(P<0.05).Conclusion The levels of serum NLRP3,FGF21,and TGF-β1 in patients with severe pneumonia are elevated,and the gut microbiota changes.The levels of serum NLRP3,FGF21,and TGF-β1 are related to the gut microbiota.In the meantime,the combined detection of serum NLRP3,FGF21,and TGF-β1 has certain predictive value for the prognosis of patients with severe pneumonia.

Abstract:Objective To investigate the effect of vestibular function training assisted by conventional rehabilitation training in the treatment of viral encephalitis complicated with chronic consciousness disorders in children.Methods A total of 98 children with viral encephalitis complicated with chronic consciousness disorder who were admitted from January 2020 to December 2024 were selected and divided into the vestibular training group(n=49)and the conventional training group(n=49)by random number table method.They were given vestibular function training combined with conventional rehabilitation training and conventional rehabilitation training respectively for a total of 4 weeks of treatment.The clinical symptoms[Revised Coma Recovery Scale(CRS-R),Full Outline of Unresponsiveness(FOUR)Scale score],the time to regain consciousness,parent satisfaction,and treatment safety of the two groups were compared,and the degree of cerebral function impairment before and after treatment was also compared.Results After treatment,the CRS-R scores and FOUR scale scores of both groups increased,which were higher in the vestibular training group than in the conventional training group(P<0.05,P<0.01).The time to regain consciousness in the vestibular training group was shorter than that in the conventional training group(P<0.01).After treatment,the degree of cerebral function impairment in the vestibular training group was lower than that in the conventional training group(P<0.01).The scores of therapeutic effect,treatment process,professionalism of medical staff,service attitude and total score of parent satisfaction in the vestibular training group were all higher than those in the conventional training group(P<0.01).There was no significant difference in the incidence of adverse reactions between the two groups during the treatment period(P>0.05).Conclusion Vestibular function training assisted by conventional rehabilitation training can improve the clinical symptoms and cerebral function in children with viral encephalitis complicated with chronic consciousness disorders,enhance parent satisfaction,and has high safety profile.

Abstract:Objective To investigate the effect of hyperoside(Hyp)against high glucose-induced injury in rat glomerular endothelial cells(RGECs)based on the thioredoxin-interacting protein(TXNIP)/NOD-like receptor pyrin domain-containing protein 3(NLRP3)pathway.Methods Rat RGECs with a fusion degree of 70%to 80%were selected and divided into the normal group(cultured in a 5.5 mmol/L glucose medium),the high glucose group(cultured in a 30 mmol/L glucose medium),the Hyp-low group(30 mmol/L glucose+100 μg/mL Hyp treatment),the Hyp-high group(30 mmol/L glucose+400 μg/mL Hyp treatment),the pcDNA group(transfected with pcDNA plasmid+30 mmol/L glucose medium culture),the pcDNA-TXNIP group(transfected with pcDNA-TXNIP plasmid+30 mmol/L glucose medium culture),the Hyp-high+pcDNA group(transfected with pcDNA plasmid+30 mmol/L glucose+400 μg/mL Hyp treatment),and the Hyp-high+pcDNA-TXNIP group(transfected with pcDNA-TXNIP plasmid+30 mmol/L glucose+400 μg/mL Hyp treatment).5-Bromo-2'-deoxyuridine(BrdU)and MTT were used to detect the proliferation of rRGECs,and flow cytometry was employed to examine the apoptosis of rat RGECs.The levels of malondialdehyde(MDA),nitric oxide(NO),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in rat RGECs were measured.FITC-polyethylene glycol was used to assess the permeability of rat RGECs,and real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of TXNIP and NLRP3 in rat RGECs.Results The optical density(OD),BrdU positive ratio,and NO in the high glucose group were lower than those in the normal group(P<0.05).The OD,BrdU positive ratio,and NO were higher in the Hyp-low group and Hyp-high group than in the high glucose group(P<0.05),and higher in the Hyp-high group than in the Hyp-low group(P<0.05).The OD,BrdU positive ratio,and NO were lower in the pcDNA-TXNIP group than in the pcDNA group(P<0.05),and lower in the Hyp-high+pcDNA-TXNIP group than in the Hyp-high+pcDNA group(P<0.05).The cell apoptosis rate,permeability,MDA,TNF-α,IL-6 levels,and TXNIP,NLRP3 mRNA,and protein expression in the high glucose group were higher than those in the normal group(P<0.05),which,however,were lower in the Hyp-low group and Hyp-high group than in the high glucose group(P<0.05).The cell apoptosis rate,permeability,MDA,TNF-α,IL-6 levels,and TXNIP,NLRP3 mRNA,and protein expression in the Hyp-high group were lower than those in the Hyp-low group(P<0.05),which were higher in the pcDNA-TXNIP group than in the pcDNA group(P<0.05),and higher in the Hyp-high+pcDNA-TXNIP group than in the Hyp-high+pcDNA group(P<0.05).Conclusion Hyp reduces high glucose-induced rat RGECs by inhibiting the TXNIP/NLRP3 pathway.

Abstract:Objective To explore the diagnostic value of combined detection of serum nuclear transcription factor κB(NF-κB),gastrin-17(G-17),and human leukocyte antigen-G(HLA-G)for early gastric cancer related to Helicobacter pylori(Hp)infection.Methods A total of 135 patients with Hp infection admitted from February 2023 to February 2025 were selected as the research subjects.According to the results of gastric histopathological biopsy,they were divided into the control group(n=51),the precancerous lesion group(n=44),and the early gastric cancer group(n=40).The general data and serum levels of NF-κB,G-17 and HLA-G of the three groups were compared.Pearson correlation analysis was used to assess the correlations among serum levels of NF-κB,G-17,and HLA-G in patients with Hp infection,and multivariate logistic regression was used to analyze the influencing factors of early gastric cancer in patients with Hp infection.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of serum NF-κB,G-17 and HLA-G for early gastric cancer related to Hp infection.Results The proportion of family history of gastric cancer and the number of neutrophils in the control group,precancerous lesion group and early gastric cancer group increased successively,while the number of lymphocytes decreased successively(P<0.05,P<0.01).The levels of serum NF-κB,G-17 and HLA-G in the control group,precancerous lesion group and early gastric cancer group increased successively(P<0.05).Pearson correlation analysis revealed that serum NF-κB was positively correlated with G-17 and HLA-G levels(r=0.522,0.481,P<0.001)in patients with Hp infection,and that serum G-17 was positively correlated with HLA-G levels(r=0.493,P<0.001).Multivariate logistic regression analysis showed that the levels of serum NF-κB,G-17,and HLA-G were risk factors for early gastric cancer in patients with Hp infection(P<0.01).The results of the ROC curve analysis showed that the areas under the ROC curve of serum NF-κB,G-17,and HLA-G detected in combination for the diagnosis of early gastric cancer in patients with Hp infection were all higher than those diagnosed by serum NF-κB,G-17 and HLA-G alone(Z=4.763,4.196,3.389,P<0.05).Conclusion The levels of serum NF-κB,G-17 and HLA-G in patients with Hp infection-related early gastric cancer increase,and the combined detection of the three has a high diagnostic value for Hp infection-related early gastric cancer.

Abstract:Objective To investigate the diagnostic value of serum α-enolase(ENO1)and suppressor of cytokine signaling 3(SOCS3)for disease activity in patients with rheumatoid arthritis(RA).Methods A total of 177 RA patients admitted from February 2020 to May 2025 were selected as the observation group.Then,based on the 28-joint disease activity score C reactive protein(CRP)(DAS28-CRP),the patients were further divided into the moderate-to-high disease activity subgroup(moderate/high subgroup)and the low disease activity/remission subgroup(low/remission subgroup).Another 177 healthy individuals who underwent physical examinations during the same period were selected as the control group.The levels of serum ENO1 and SOCS3 in each group were detected by enzyme-linked immunosorbent assay(ELISA),and the relative risk(RR)analysis was conducted to analyze the impact of the expression levels of serum ENO1 and SOCS3 on the disease activity of RA patients.Multivariate logistic regression was used to analyze the influencing factors of disease activity in RA patients.The receiver operating characteristic(ROC)curve was drawn to evaluate the value of serum ENO1 and SOCS3 levels in diagnosing disease activity in RA patients,and a decision curve was employed to analyze the clinical utility of serum ENO1 and SOCS3 levels in diagnosing disease activity in RA patients.Results Compared with the control group,the serum ENO1 level in the observation group increased,while the serum SOCS3 level decreased(P<0.01).Compared with the low/remission subgroup,the medium/high subgroup had a longer disease duration,increased Visual Analogue Scale(VAS)score,CRP,erythrocyte sedimentation rate(ESR),and serum ENO1 level,and decreased serum SOCS3 level(P<0.01).The risk of moderate/high disease activity in patients with high ENO1 levels was 96.9%,which was higher than that in patients with low levels,and the risk of moderate/high disease activity in patients with high SOCS3 levels was 131.7%,which was lower than that in patients with low levels(P<0.01).In the multivariate logistic regression analysis model that included disease duration,VAS score,CRP and ESR,serum ENO1 remained an independent risk factor for disease activity in RA patients,while serum SOCS3 was an independent protective factor(P<0.05).The area under the ROC curve for the combined diagnosis of disease activity in RA patients by serum ENO1 and SOCS3 levels was significantly higher than that by an indicator alone(P<0.01).When the risk threshold was set between 0.10 and 0.82,the net benefit rate of serum ENO1 and SOCS3 detected in combination for the diagnosis was always higher than that of ENO1 and SOCS3 alone for the diagnosis.Conclusion The expression of serum ENO1 in RA patients is upregulated,while the expression of SOCS3 is downregulated.Both are closely related to disease activity,and combined diagnosis can effectively improve the diagnostic value for disease activity.

Abstract:Objective To investigate the effects of circular RNA partitioning defective 3 homolog(CircPARD3)on the proliferation,apoptosis and invasion of acute myeloid leukemia(AML)cells via regulating the miR-485-5p/homeobox protein B6(HOXB6)axis.Methods Human bone marrow stromal cell line HS-5 and human AML cell lines AML2,U937,and HL-60 were selected.U937 cells were cultured in vitro and randomly divided into the control group,the negative control group,the miR-485-5p mimics group,the CircPARD3 siRNA group,and the CircPARD3 siRNA+miR-485-5p inhibitor group.After grouping and transfection,the mRNA and protein expressions of CircPARD3,miR-485-5p and HOXB6 in each group of cells were determined by RT-qPCR and Western blot.The apoptosis,proliferation,migration and invasion of cells in each group were detected by flow cytometry,Edu staining,cell scratch and Transwell assay,respectively.Cell apoptosis and the expression of proteins related to epithelial-mesenchymal transition were detected by Western blot.The targeted regulatory effects of CircPARD3 on miR-485-5p and miR-485-5p on HOXB6 in U937 cells were analyzed by dual-luciferase reporter assay.Results The mRNA and protein expressions of CircPARD3 and HOXB6 in U937,AML2 and HL-60 cells were all increased compared with those in HS-5 cells(P<0.05),while the expressions of miR-485-5p were lower than in those in HS-5 cells(P<0.05).Compared with the control group,the mRNA and protein expressions of HOXB6,proliferation rate,migration number,invasion number,and Vimentin protein expression in the CircPARD3 siRNA group and the miR-485-5p mimics group were all decreased(P<0.05).The expressions of miR-485-5p,the apoptosis rate,and the protein expressions of Bax,Cleaved Caspase-3,and E-cadherin were all increased(P<0.05).Compared with the CircPARD3 siRNA group,the mRNA and protein expressions of HOXB6,proliferation rate,migration number,invasion number,and Vimentin protein expression in the CircPARD3 siRNA+miR-485-5p inhibitor group were all increased(P<0.05),while the expressions of miR-485-5p,the apoptosis rate,and the protein expressions of Bax,Cleaved Caspase-3,and E-cadherin were all decreased(P<0.05).CircPARD3 could target and down-regulate the expression of miR-485-5p in U937 cells,and miR-485-5p could target and down-regulate the expression of HOXB6.Conclusion Knockdown of CircPARD3 expression can induce apoptosis of AML cells and inhibit their proliferation and invasion by regulating the miR-485-5p/HOXB6 axis.

Abstract:Objective To discuss whether LncRNA KCNQ1OT1 can regulate the miR-7-5p/Yes-associated protein 1(YAP1)axis and affect the high glucose-induced human retinal microvascular endothelial cells(HRMECs)injury.Methods HRMECs were divided into the control group,the high glucose group,the KCNQ1OT1 negative control group,the KCNQ1OT1 interference group,the KCNQ1OT1 interference+miRNA inhibition negative control group,the KCNQ1OT1 interference+miR-7-5p inhibition group,and the KCNQ1OT1 interference+YAP1 empty vector group,and KCNQ1OT1 interference+YAP1 overexpression group.The control group was treated with 5.5 mmol/L glucose for 48 h,while the high glucose group was treated with 25.0 mmol/L glucose for 48 h.For the other cells that needed transfection,the corresponding plasmids were first transfected into each group of cells using Lipofectamine 2000 transfection reagent,and then the cells were treated with 25.0 mmol/L glucose for 48 h.The expression levels of KCNQ1OT1,miR-7-5p,and YAP1 mRNA were detected in each group,as well as the levels of lactate dehydrogenase(LDH),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β),reactive oxygen species(ROS),and malondialdehyde(MDA),the activities of superoxide dismutase(SOD)and catalase(CAT),the status of apoptosis,and the protein expression levels of Bcl-2-associated X protein(Bax),B-cell lymphoma-2(Bcl-2),Cleaved caspase-3,and YAP1 in each group.Additionally,to validate the targeting relationship between miR-7-5p and KCNQ1OT1/YAP1 was verified.Results Compared with the control group,the high-glucose group showed increased mRNA expression levels of KCNQ1OT1 and YAP1;elevated levels of TNF-α,IL-6,IL-1β,LDH,MDA,and ROS,as well as a higher apoptosis rate;increased protein expression levels of Bax,Cleaved caspase-3,and YAP1;decreased expression of miR-7-5p and reduced Bcl-2 protein expression;and decreased activities of CAT and SOD(P<0.05).Interfering with the expression of KCNQ1OT1 could improve the above index levels in HRMECs(P<0.05).Inhibition of miR-7-5p expression or overexpression of YAP1 could both weaken the improvement effect of silencing KCNQ1OT1 expression on HRMECs injury induced by high glucose(P<0.05).Conclusion Silencing the expression of KCNQ1OT1 may alleviate high glucose-induced HRMECs injury by regulating the miR-7-5p/YAP1 axis.

Abstract:Objective To investigate the effect of acupoint application as an adjuvant therapy on chemotherapy-induced adverse reactions and immune status in patients with advanced non-small cell lung cancer(NSCLC).A total of 120 patients undergoing chemotherapy for advanced NSCLC that were admitted from January 2023 to October 2024 were selected and randomly divided into the observation group(n=60)and the control group(n=60)at a ratio of 1∶1.The control group received standard chemotherapy regimens,while the observation group was supplemented with acupoint application at Zusanli,Feishu,and Pishu on this basis.A total of 4 courses of treatment were administered.The clinical efficacy,traditional Chinese medicine(TCM)syndrome scores before and after treatment,as well as CD4+/CD8+,CD3+,CD4+,complement C3,complement C4,interleukin-1 β(IL-1β),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-2(IL-2),interleukin-6(IL-6),and natural killer cells(NK),interleukin-10(IL-10),the proportions of myeloid-derived suppressor cells(MDSC)and regulatory T cells(Treg),the incidence of chemotherapy-induced toxic and side effects and the quality of life during treatment were compared between the two groups.Results After treatment,the objective response rate and disease control rate of the observation group were higher than those of the control group(P<0.05).After treatment,the TCM syndrome scores of both groups were lower than those before treatment,and the scores of the observation group were lower than those of the control group(P<0.05,P<0.01).After treatment,the levels of CD4+/CD8+,CD3+,CD4+,complement C3,complement C4,IFN-γ,IL-2,and NK cells in the observation group were higher than those in the control group,while IL-1β,TNF-α,IL-6,IL-10,and the proportions of MDSC and Treg were lower than those in the control group(P<0.05,P<0.01).The incidence of hematological toxicity and gastrointestinal reactions in the observation group was lower than that in the control group(P<0.05).After treatment,Karnofsky Performance Status Score and the scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module in the control group were lower than those before treatment,and the above scores in the observation group were higher than those in the control group after treatment(P<0.05,P<0.01).Conclusion Acupoint application as an adjunctive therapy helps alleviate the chemotherapy-induced adverse reactions,regulate the immune status,and improve the therapeutic efficacy and quality of life in patients with advanced NSCLC.

Abstract:Objective To investigate the distribution of allergen-specific immunoglobulin E(sIgE)in children with atopic dermatitis(AD)in the Suzhou area.Methods A total of 767 children with AD aged 0-14 years admitted between January 2023 and December 2024 were enrolled as research subjects.Serum levels of sIgE against 26 allergens were detected using fluorescence immunoassay,and the positive rates and distribution characteristics of sIgE were analyzed across different genders,ages,and seasons among the pediatric patients.Results Among the 767 children,647(84.4%)tested positive for sIgE to at least one allergen.The positive rate for food sIgE was 55.7%,with the top three being egg/egg white(44.6%),milk(32.5%),and wheat(11.9%).The positive rate for inhalant sIgE was 38.5%,with the top three being Dermatophagoides farinae(30.1%),Dermatophagoides pteronyssinus(29.2%),and Alternaria alternata(16.4%).The positive rate of sensitization to food sIgE was the highest in children aged<1 year(P<0.01)and gradually decreased with age thereafter.The positive rate of inhalant sIgE was the highest at 58.5%in children aged 7-10 years(P<0.01).There was no significant seasonal difference in the overall positive rate of food sIgE among AD children(P>0.05),whereas the positive rate of inhalant sIgE was higher in summer and autumn(P<0.05).Single-allergen analysis showed that the positive rates for Dermatophagoides farinae and Dermatophagoides pteronyssinus-specific sIgE were both higher in summer and autumn,and the positive rate for Alternaria alternata-specific sIgE was significantly higher in autumn than in other seasons(P<0.05,P<0.01).Among the 767 children,34.4%were positive for sIgE to three or more allergens.Regarding the proportion of sIgE concentration levels≥grade 3,Dermatophagoides farinae ranked the highest(67.1%),followed by Dermatophagoides pteronyssinus(67.0%),and Alternaria alternata(65.1%).Conclusion The distribution of certain allergens among children with AD in the Suzhou area shows certain variations across different age groups and seasons.Therefore,rational planning and timely avoidance of high-risk allergens are necessary for the prevention and treatment of atopic dermatitis.

Abstract:Objective To investigate the role of β-2 microglobulin(B2M)gene in breast cancer progression and its impact on the sensitivity to programmed death-ligand 1(PD-L1)inhibitors.Methods RNA sequencing data of breast cancer were downloaded from The Cancer Genome Atlas(TCGA)database.B2M expression was detected in 1,121 samples,the correlation between B2M and PD-L1 gene expression was systematically analyzed.Mouse breast cancer cells(4T1 cells)were selected to establish B2M knockdown 4T1 cells(B2M KD 4T1 cells),so as to explore the effects of B2M expression on PD-L1 levels and cell functions.A subcutaneous tumor model was established with B2M KD 4T1 cells via in vivo experiments and treated with PD-L1 inhibitors,to evaluate the impact of the B2M gene on immune cell infiltration and therapeutic sensitivity.Results The gene expression levels of B2M and PD-L1 were elevated in breast cancer cells.In vitro functional experiments confirmed that B2M knockdown could significantly inhibit the proliferation of 4T1 cells,accompanied by enhanced apoptosis and decreased PD-L1 expression.PD-L1 had independent biological functions,which could promote the proliferation,invasion and migration of 4T1 cells while inhibiting apoptosis,thus exhibiting similar functional tendencies and regulatory outcomes similar to those of B2M.In vivo tumor-bearing experiments showed that the tumor volume formed by B2M knockdown 4T1 cells in mice was significantly suppressed,and showed no significant response to PD-L1 inhibitor treatment.Conclusion B2M knockdown may inhibit the proliferation of breast cancer cells by reducing immune cell recruitment and PD-L1 expression,and concomitantly impair the sensitivity of these cells to PD-L1 inhibitors.

Abstract:Objective To investigate the early predictive value of whole blood cell-derived inflammatory markers for severe mycoplasma pneumoniae pneumonia(SMPP)in children.Methods In total,84 children with SMPP admitted from February 2023 to February 2025 were selected as the severe group,and 67 children with mild mycoplasma pneumoniae pneumonia(MPP)admitted during the same period were selected as the non-severe group.The monocyte-to-lymphocyte ratio(MLR),systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),systemic inflammatory response index(SIRI),and platelet-to-lymphocyte ratio(PLR)were compared between the two groups.According to the prognosis of children with SMPP,they were further divided into a good prognosis subgroup(n=40)and a poor prognosis subgroup(n=44).The differences in whole blood cell-derived inflammatory markers between the two groups were analyzed.The influencing factors of the occurrence and poor prognosis of SMPP in children were clarified through multivariate logistic regression analysis.Pearson correlation analysis was used to analyze the correlations between MLR,SII,NLR,SIRI,PLR and the poor prognosis of children with SMPP.The predictive value of various whole blood cell-derived inflammatory markers detected alone and in combination for the occurrence and prognosis of SMPP in children was evaluated by the receiver operating characteristic(ROC)curve.Results The proportions of children with lung involvement≥2/3 lobes,the incidence of large lung consolidation shadows,MLR,SII,NLR,SIRI and PLR in the severe group were all higher than those in the non-severe group(P<0.05,P<0.01).The levels of MLR,SII,NLR,SIRI and PLR in the poor prognosis subgroup were all higher than those in the good prognosis subgroup(P<0.05,P<0.01).Pearson correlation analysis showed that MLR was strongly and positively correlated with poor prognosis in children with SMPP,SII,NLR,and SIRI were moderately and positively correlated with poor prognosis in children with SMPP,and PLR was weakly and positively correlated with poor prognosis in children with SMPP(P<0.01).Multivariate logistic regression analysis showed that MLR,SII,NLR,SIRI and PLR were all independent risk factors for SMPP in children(P<0.05,P<0.01).The extent of lung involvement,MLR,SII,NLR,SIRI and PLR were all independent risk factors for poor prognosis in children with SMPP(P<0.05,P<0.01).ROC curve analysis showed that the area under the ROC curve(AUC)for MLR,SII,NLR,SIRI,and PLR detected in combination for the prediction of SMPP occurrence in children was 0.969(95%CI:0.927,0.990),with a sensitivity of 91.67%and a specificity of 89.55%,which was significantly better than the prediction of each index alone(P<0.01).The AUC of MLR,SII,NLR,SIRI and PLR detected in combination for the prognostic prediction of children with SMPP was 0.930(95%CI:0.877,0.965),with a sensitivity of 96.67%and a specificity of 85.55%,which was significantly better than the prediction of each index alone(P<0.01).Conclusion The whole blood cell-derived inflammatory markers MLR,SII,NLR,SIRI,and PLR are closely related to the occurrence,development,and poor prognosis of SMPP in children.They can be used as independent risk factors for the progression and poor prognosis of MPP,and their combined detection can improve the predictive value.

Abstract:Objective To evaluate the inhibitory effect of the natural product peiminine on malignant biological behaviors in human glioma cells and to elucidate its mechanisms based on transcriptomic analysis.Methods The effect of different concentrations of peiminine on the viability of human glioma cell lines U251 and LN229 was assessed by CCK-8 assay to determine half-maximal inhibitory concentration(IC50)values.IC50-adjacent concentrations(80 μmol/L for U251 and 110 μmol/L for LN229)were used as effective intervention concentrations for subsequent experiments.Effects of peiminine on cell proliferation,migration,and invasion were evaluated by colony formation,cell scratch wound healing,and Transwell assays,and apoptosis was analyzed by flow cytometry.Transcriptome sequencing of U251 cells treated with peiminine was conducted to identify differentially expressed genes(DEGs)for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The key gene RHOU expression was validated by Western blot analysis.A stable RHOU knockdown cell line was established and treated in combination with peiminine.The role of RHOU in peiminine-induced apoptosis was investigated using flow cytometry.Gene set enrichment analysis(GSEA)and quantitative real-time PCR(RT-qPCR)were performed to verify the regulatory effects of RHOU on key downstream components of the E2F signaling pathway.Results Peiminine significantly inhibited the viability of U251 and LN229 cells in a dose-dependent manner,effectively suppressed the colony formation,migration,and invasion capabilities of glioma cells,and markedly induced cellular apoptosis.Transcriptomic analysis identified 1,507 DEGs primarily enriched in pathways related to cell cycle,cell proliferation,apoptosis,and cell adhesion.Among these,RHOU was significantly downregulated among the DEGs.Western blot confirmed significantly decreased RHOU protein expression after peiminine treatment.RHOU silencing enhanced peiminine-induced pro-apoptotic effect.GSEA based on RHOU expression showed significant enrichment of the E2F signaling pathway.RHOU knockdown significantly downregulated the mRNA expression levels of key E2F pathway genes,including E2F1,CCND1,and CCNE1.Conclusion Peiminine significantly downregulated the expression of key gene RHOU,thereby inhibiting the activity of the downstream E2F signaling pathway and ultimately blocking the malignant biological progression of glioma cells.

Abstract:Objective To investigate the immunomodulatory effect of albumin-bound Paclitaxel combined with Sintilimab on advanced esophageal cancer,and to analyze the survival benefit.Methods A total of 126 patients with advanced esophageal cancer admitted to Rugao People's Hospital from March 2020 to March 2023 were selected,and divided into the observation group(n=63)and the control group(n=63)using a random number table method.The control group was given albumin-bound Paclitaxel,while the observation group was given albumin-bound Paclitaxel combined with Sintilimab.The clinical efficacy,tumor markers[cytokeratin 19 fragment(CYFRA21-1),squamous cell carcinoma antigen(SCC-Ag),carbohydrate antigen 125(CA125),carcinoembryonic antigen(CEA)],immune function indicators(Th1/Th2,Th17/Treg),PD-1/PD-L1 signaling pathway indicators,Karnofsky performance status(KPS)scores,overall survival,and toxic side effects were compared between the two groups.Results The objective remission rate[38.10%(24/63)]and disease control rate[87.30%(55/63)]of the observation group were higher than those of the control group[20.63%(13/63),71.43%(45/63)](P<0.05).After 2 and 4 cycles of treatment,the serum SCC-Ag,CYFRA21-1,CA125 and CEA in the observation group were lower than those in the control group(P<0.05);after 2 and 4 cycles of treatment,compared with the control group,the observation group showed higher Th1/Th2,and lower Th17/Treg,PD-1 and PD-L1(P<0.05).The improvement rate of quality of life,progression free survival and overall survival in the observation group were higher or longer than those in the control group(P<0.05).There was no significant difference in the incidence of abnormal liver dysfunction,nausea and vomiting,decreased hemoglobin and leucopenia between the two groups(P>0.05),but the incidence of rash in the observation group[57.14%(36/63)]was higher than that in the control group[34.92%(22/63)](P<0.05).Conclusion Combination therapy of Sintilimab and albumin-bound Paclitaxel shows significant efficacy in the treatment of advanced esophageal cancer.It can regulate serum tumor marker levels,improve immune function,reduce the activity of the PD-1/PD-L1 signaling pathway to inhibit disease progression,enhance survival benefits,and improve quality of life.However,attention should be paid to the observation of rash reactions during treatment.

Abstract:Objective To investigate the postoperative changes of tear cytokines in patients with advanced refractory glaucoma and their impact on ocular surface-related indicators.Methods In total,120 patients(240 eyes)with advanced refractory glaucoma admitted from January 2023 to June 2024 were selected as the observation group,all of whom underwent glaucoma drainage device(GDD)implantation.Another 85 healthy individuals(170 eyes)who underwent ophthalmic examinations during the same period were selected as the control group.The changes in tear cytokine levels[interleukin-1α(IL-1α),interleukin-2(IL-2),tumor necrosis factor-α(TNF-α),transforming growth factor-β(TGF-β),interleukin-10(IL-10),vascular endothelial growth factor(VEGF)]and ocular surface-related indicators[tear film break-up time(BUT),Schirmer I test(SIt)values,and corneal fluorescein staining(CFS)scores]were observed and recorded at 1 d before surgery and at 1,7,30,and 60 d after surgery in the observation group,and the levels of the above indicators were compared with those in the control group.Pearson correlation analysis was used to investigate the correlation between changes in IL-1α,IL-2,TNF-α,TGF-β,IL-10,VEGF levels and SIt values,CFS scores,and BUT.Results There were significant differences in the levels of IL-1α,IL-2,TNF-α,TGF-β,IL-10,and VEGF in the observation group when compared at 1 d before surgery and at 1,7,and 30 d after surgery(P<0.05).There was no significant difference in the levels of IL-1α,IL-2,TNF-α,TGF-β,IL-10,and VEGF in the observation group when compared at 1 d before surgery and at 60 d after surgery(P>0.05),nor significant difference compared with the control group(P>0.05).The differences in BUT,SIt values,and CFS scores in the observation group at 1 d before surgery and at 1,30,and 60 d after surgery were statistically significant(P<0.05),and the levels of the above indicators in the observation group were comparable to those in the control group at 60 d after surgery(P>0.05).Pearson correlation analysis showed that IL-1α,IL-2,TNF-α,TGF-β,IL-10,and VEGF in the observation group were positively correlated with SIt value and CFS score,and negatively correlated with BUT(P<0.05).Conclusion In the early postoperative period(1-30 d),the levels of IL-1α,IL-2,TNF-α,TGF-β,IL-10,and VEGF in the tears of patients with advanced refractory glaucoma are significantly increased,and returned to preoperative levels at 60 d after surgery.The above cytokines are positively correlated with SIt values and CFS scores,and negatively correlated with BUT.

Abstract:Objective To investigate the expression changes and clinical significance of serum pepsinogen(PG)and triggering receptor expressed on myeloid cells-1(TREM-1)in patients with reflux esophagitis(RE).Methods A total of 140 patients with RE who were treated from October 2021 to October 2023 were selected as the observation group,and 140 healthy adults who underwent physical examination during the same period were selected as the control group.Serum PG(PGⅠ and PGⅡ)and TREM-1 were detected by ELISA.Multivariate logistic regression was used to analyze the influencing factors of RE.Receiver operating characteristic(ROC)was used to analyze the diagnostic efficacy of serum PGⅠ,PGⅡ and TREM-1 levels for RE.Results The levels of interleukin(IL)-2,IL-6,Il-1β,PGⅡ,TREM-1 and tumor necrosis factor-α(TNF-α)in the observation group were significantly higher than those in the control group,while the level of PGⅠ was significantly lower than that in the control group(P<0.01).Serum IL-2,IL-6,IL-1β,TNF-α,PGⅡ and TREM-1 were risk factors for RE,while serum PGⅠ was a protective factor for RE(P<0.01).ROC curve analysis showed that the area under the ROC curve(AUC)of combined detection of PGⅠ,PGⅡ and TREM-1 in the diagnosis of RE was significantly higher than that of PGⅠ alone(Z=5.940,P<0.001)and PGⅡ alone(Z=6.764,P<0.001)and TREM-1 alone(Z=6.791,P<0.001).Conclusion The expression levels of serum PGⅡ and TREM-1 in patients with RE are increased,while the expression level of PGⅠ is decreased.The combined detection of the three can improve the diagnostic efficacy of RE.

Abstract:Objective To investigate the mechanism of Naringenin(NGN)in the treatment of steroid(glucosteroid)-induced osteonecrosis of the femoral head(SONFH).Methods A SONFH rat model was established using Methylprednisolone(MPS)treatment,followed by intervention with NGN and zinc protoporphyrin(ZnPP).Micro-CT was used to analyze the morphological changes in femoral head tissues,and the levels of osteocalcin(OCN)in rat serum as well as heme oxygenase-1(HO-1)and hypoxia-inducible factor-1α(HIF-1α)in femoral bone tissue were measured.A cellular model was constructed by treating MC3T3-E1 cells with Dexamethasone(DEX),followed by NGN intervention.Bioinformatics analysis combined with molecular docking technology was used to predict the target of NGN,and the Pulldown experiment was performed for validation.The expression of HO-1 was knocked down through cell transfection,to analyze the viability,proliferation,apoptosis,and migration of MC3T3-E1 cells,and angiogenesis assays were conducted to evaluate the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Results Micro-CT analysis revealed that,compared with the control group,the trabecular thickness and trabecular number were significantly reduced in the MPS group,while the bone surface area/bone volume ratio and trabecular separation were significantly increased(P<0.001).In vitro experimental results indicated that DEX inhibited the proliferation of MC3T3-E1 cells,promoted cell apoptosis,and increased reactive oxygen species generation(P<0.01),and that DEX suppressed the formation of mineralized nodules,a key indicator of osteogenic differentiation,and downregulated the expression of osteogenesis-related genes(Runt-related transcription factor 2,osteopontin,osteocalcin)(P<0.01).However,NGN treatment partially reversed these effects.DEX significantly inhibited the migration of HUVECs,angiogenesis,and the expression of angiogenesis-related markers(platelet endothelial cell adhesion molecule-1,vascular endothelial growth factor,and von Willebrand factor)(P<0.01).In contrast,NGN treatment did not significantly affect the aforementioned effects,but the treatment with NGN conditioned medium[CM(NGN)]partially reversed these effects(P<0.01).Bioinformatics analysis combined with Pulldown assay results indicated that HO-1 was the target of NGN.DEX treatment significantly downregulated the expression of HO-1,while NGN intervention partially counteracted the inhibitory effect induced by DEX(P<0.01);knockdown of HO-1 negated the therapeutic effects of NGN(P<0.01).Compared with MPS administration alone,the combined administration of NGN and MPS upregulated the expression of HO-1 and HIF-1α in rat femoral head tissues.However,the HO-1 inhibitor ZnPP further upregulated the expression of HO-1 but downregulated the protein level of hypoxia-inducible factor-α(HIF-1α)(P<0.01).Conclusion NGN exerts its therapeutic effects on SONFH by activating the expression and activity of HO-1,which regulates the HIF-1α/VEGF pathway to promote osteoblast differentiation,bone formation,and angiogenesis.

Abstract:Objective To investigate the effect of Telitacicept combined with Methotrexate on the levels of rheumatoid factor(RF)and anti-cyclic citrullinated peptide(CCP)antibody in patients with moderate-to-severe rheumatoid arthritis(RA).Methods A total of 120 patients with moderate-to-severe RA diagnosed from January 2023 to January 2025 were selected and divided into the Telitacicept group(n=40),the Methotrexate group(n=40)and the combination group(n=40)by random number table method according to different treatment regimens.The Telitacicept group was treated with Telitacicept,the Methotrexate group was treated with Methotrexate,and the combination group was treated with Telitacicept combined with Methotrexate.The therapeutic effects,swollen joint count(SJC),tender joint count(TJC),the duration of morning stiffness,the Visual Analogue Scale(VAS)pain score,the clinical disease activity index(CDAI)score,the disease activity score in 28 joints(DAS28),the Health Assessment Questionnaire(HAQ)score,the erythrocyte sedimentation rate(ESR),as well as the levels of serum RF,anti-CCP antibody,C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α)were compared among the three groups.The adverse reactions during the treatment period of the three groups were statistically compared.Results After treatment,the total effective rate of the combination group was 95.00%(38/40),which was higher than that of the Telitacicept group at 80.00%(32/40)and the Methotrexate group at 75.00%(30/40,P<0.05).After treatment,the SJC and TJC in the combination group were less than those in the Telitacicept group and the Methotrexate group,and the duration of morning stiffness was shorter than that in the Telitacicept group and the Methotrexate group;the VAS score,CDAI score,DAS28 score,HAQ score,ESR,as well as the levels of serum RF,anti-CCP antibody,CRP and TNF-α were lower than those in the Telitacicept group and the Methotrexate group(P<0.05).There was no statistical difference in the incidence of adverse reactions among the three groups(P>0.05).Conclusion Telitacicept combined with Methotrexate can improve the clinical efficacy and quality of life of patients with moderate-to-severe RA,effectively improve the levels of RF and anti-CCP antibodies,and has favorable safety profile.

Abstract:Objective To investigate the causal relationship between circulating white blood cells(WBC)and juvenile idiopathic arthritis(JIA)using a two-sample Mendelian randomization(MR)analysis,and to provide a reference for the treatment strategy of JIA.Methods Relevant data of WBC and JIA were extracted from the public data of genome-wide association studies.Then,bidirectional MR analysis was conducted using the inverse variance weighted method(IVW),MR-Egger regression method,mixed contamination method,and Bayesian weighted Mendelian randomization.A series of sensitivity analyses were used to verify the robustness of the results.Results After MR analysis,false discovery rate(FDR)correction and sensitivity verification,calculations using IVW as the main method showed that neutrophils could reduce the risk of JIA(OR=0.752,95%CI:0.622,0.908,P=0.003,PFDR=0.003),and that JIA could lead to increased monocyte counts(bete=0.015,95%CI:0.007,0.022,P=1.90E-04,PFDR=1.14E-03).Conclusion A bidirectional causal association is identified between WBC and the risk of JIA occurrence.