Objective: To compare the effects of immediate versus delayed post-space preparation on the bond strength of fiber posts and the fracture resistance of roots after root canal obturation using iRoot SP and the single-cone technique, and to provide an experimental basis for the selection of the timing of clinical post-space preparation. Methods: This study was approved by the Medical Ethics Committee of the institution, and written informed consent was obtained from all participants. Seventy-two extracted human single-rooted premolars were randomly divided into two groups (n = 36 each): the immediate post-space preparation group (post-space preparation performed immediately after root canal obturation) and the delayed post-space preparation group (post-space preparation performed 1 week after root canal obturation). Cleanliness of the root canal walls was assessed with a dental microscope after preparation in both groups; the ultrastructural characteristics of the dentinal surface were examined via scanning electron microscopy; the fracture resistance of roots was measured with root fracture resistance tests; the bond strength of the fiber posts was measured with the thin-slice push-out test; and the bond failure modes were observed and analyzed under a stereomicroscope. Results: Under dental microscopy, the dentin surface of the immediate post-space preparation group appeared cleaner than that of the delayed post-space preparation group. Scanning electron microscopy revealed that most dentinal tubules remained open in the immediate post-space preparation group, while the tubules in the delayed post-space preparation group showed incomplete patency. The fracture resistance of the immediate post-space preparation group was (2 872 ± 241.5) N and that of the delayed post-space preparation group was (2 934 ± 353.1) N, with no statistically significant difference (t = -0.328, P = 0.751). The push-out bond strength of the immediate post-space preparation group (10.310 ± 2.907) MPa was significantly higher than that of the delayed post-space preparation group (7.917 ± 2.429) MPa, with a statistically significant difference (t = 4.457, P < 0.001). Analysis of failure modes showed that adhesive-to-dental interface failure was the predominant mode in both groups. Conclusion Following root canal obturation with iRoot SP using the single-cone technique, immediate post-space preparation yields superior fiber post bond strength compared to delayed post-space preparation, without compromising root fracture resistance.

AIM:To investigate the mechanism by which interleukin-13(IL-13)influences vascular smooth muscle cell(VSMC)phenotypic transformation and subsequently contributes to vascular intimal hyperplasia in rats.METHODS:A total of 32 male SD rats,aged 5～7 weeks and weighing 330～360 g,were randomly divided into 4 groups(n=8 per group):normal(Nor)group,normal treatment(Nor+IL-13 neutralizing antibody,Nor+IL-13Nab)group,inju-ry(Inj)group,and injruy treatment(Inj+IL-13Nab)group.A 2F balloon catheter was used to induce mechanical injury in the left common carotid artery of SD rats to establish a vascular intimal hyperplasia model.Hematoxylin-eosin staining was performed to observe vascular structural changes.Enzyme-linked immunosorbent assay(ELISA)kits were used to measure IL-13 and transforming growth factor-β1(TGF-β1)levels.Human aortic smooth muscle cells(HA-SMCs)were cultured in vitro.Flow cytometry was conducted to assess peripheral blood CD4+IL-13+T cell content.Real-time quantita-tive PCR(RT-qPCR)was employed to evaluate gene expression levels of α-smooth muscle actin,osteopontin,calponin,collagen type Ⅰ/Ⅲ,proliferating cell nuclear antigen and Ki-67 antigen.Transwell and scratch wound assays were per-formed to assess cell migration.RESULTS:Compared with the model group,administration of IL-13Nab significantly in-hibited vascular intimal hyperplasia induced by mechanical vascular injury by antagonizing high plasma IL-13 levels(P<0.01).Immunofluorescence and mRNA analysis showed that neutralizing high plasma IL-13 suppressed collagen accumu-lation(P<0.01)and VSMC phenotypic transformation(P<0.01)in the injured vessels but did not inhibit peripheral blood CD4+IL-13+T cell activation.Incubation of HA-SMCs with recombinant human IL-13(rhIL-13)promoted cell pro-liferation and migration(P<0.01)as well as phenotypic transformation(P<0.01).Additional evidence suggested that rhIL-13-induced HA-SMC phenotypic transformation was associated with the regulation of TGF-β1 secretion by HA-SMCs.CONCLUSION:Interleukin-13 promotes vascular intimal hyperplasia by regulating VSMC phenotypic transformation through TGF-β1 secretion in rat models.

Objective To propose a multiple regression-variational auto-encoders(MR-VAE)model to realize precise and non-invasive prediction of intra-abdominal pressure(IAP)in critically ill patients.Methods At first,a dataset was constructed by retrospectively analysing baseline characteristics and clinical indicators of 100 critically ill patients admitted to the Intensive Care Unit of Daping Hospital of Army Medical University between 30 August 2019 and 30 March 2021.Then,a MR-VAE prediction model was developed by integrating a feedforward neural network for supervised regression onto a variational autoencoder(VAE)framework and incorporating multiple regression strategies to mitigate feature interference.Finally,the MR-VAE model had its performance evaluated by its comparison with five classical models including support vector machines(SVM),convolutional neural networks(CNN),Scikit-learn integrated model(SIM),multi-layer perceptron(MLP)and K-nearest neighbors(KNN),and its prediction accuracy verified by testing the data of 10 randomly selected patients.Results The MR-VAE model behaved the best when compared with the five classical models,with a mean squared error(MSE)of 0.207,a root mean square error(RMSE)of 0.454,a mean absolute error(MAE)of 0.361,a median absolute deviation(MAD)of 0.243,an explained variance score(EVS)of 0.814 and a R2of 0.823,which also outperformed the five models in fitting performance,convergence and final loss.In random sample testing,the MR-VAE model exhibited high consistency between predicted and actual values.Conclusion The MR-VAE model proposed can accurately predict IAP,which has great potential in reducing the repeated measurements of IAP in critically ill patients and providing new ideas for the early diagnosis and treatment of IAH.

Objective To investigate the imaging features of Langerhans cell histiocytosis(LCH)in the long bones of the limbs in children.Methods The clinical and imaging data of 23 children with long bones of the limbs were analyzed retrospectively.X-ray examinations were performed in 21 cases,CT scans in 16 cases,and MRI scans in 19 cases.Results The lesions were located in femur in 14 cases,tibia in 3 cases,fibula in 2 cases,humerus in 1 case,ulna in 2 cases,and both tibia and fibula in 1 case.Lesions were found in the diaphysis in 16 cases and the metaphysis in 7 cases(involving the epiphysis in 2 cases).Bone destruction appeared as oval,irregular,or eccentric shapes,with clear boundaries in 17 cases,blurred boundaries in 6 cases,and sclerosis in 6 cases.The average CT value was(48.27±8.20)HU,with"gear-like"changes in the axial view in 10 cases."Sleeve-like"periosteal reaction was observed in 14 cases,localized periosteal reaction in 5 cases,and no periosteal reaction in 4 cases.The lesions showed iso-or slightly hypointense signals on T1 WI,hyperintense signals on T2 WI,and hyperintense signals on diffusion weighted imaging(DWI),with an average apparent diffusion coefficient(ADC)value of(1.26±0.17)×10-3 mm2/s.Soft tissue masses were found in 7 cases.After enhancement,moderate to marked enhancement was observed in 9 cases,with lace-like enhancement in 6 cases.Among the 17 cases followed up,13 cases returned to normal or had only residual bone cortical thickening,3 cases showed a reduction in lesion size,and 1 case died.Conclusion The imaging features of LCH in the long bones in children have certain characteristics,but can still be easily confused with infections or malignant bone tumors.A comprehensive analysis combining clinical and imaging features is necessary to improve diagnostic accuracy.

Aim To study the effect of anti-PD-L1 monoclonal antibody on high-fat diet-induced athero-sclerosis in ApoE-/-mice.Methods Twenty-four ApoE-/-mice were randomly divided into the normal group,high-fat group,and high-fat+anti-PD-L1 mAb group.After 70 days,the blood samples were harves-ted.Blood vessels(aortic root to abdominal aorta)and liver from each groups were stained with Oil Red O.Hematoxylin-eosin staining(HE)was employed to vis-ualize structural changes in liver.Enzyme-linked im-munosorbent assay(ELISA)was applied to detect the serum levels of total cholesterol(CHO),triglyceride(TG),high-density lipoprotein(HDL-c),low-density lipoprotein(LDL-c)and inflammatory factors(IFN-γ,TNF-α,IL-1 β).Flow cytometry was used to detect the proportion of lymphocytes(CD4 and CD8).RT-PCR was utilized to assess the expressions of IFN-γ,TNF-α,IL-1 β,CD4 and CD8 in liver.Results Compared with the high-fat group,the treatment with anti-PD-L1 monoclonal antibody promoted vascular wall and liver lipid accumulation,and also up-regulated serum and liver content of cholesterol(CHO),triglyceride(TG)and high-density lipoprotein(HDL-c).Treatment with anti-PD-L1 monoclonal antibody up-regulated the con-tent of alanine aminotransferase(GPT)and aspartate aminotransferase(GOT)in serum and liver,but not al-kaline phosphatase(AKP).ELISA test indicated that treatment with anti-PD-L1 monoclonal antibody stimu-lated the serum level of IFN-γ,TNF-α and IL-1 β.Fur-thermore,the mRNA level of IFN-γ,TNF-α and IL-1 βin liver was also up-regulated after treatment with anti-PD-L1 monoclonal antibody.With flow cytometry,we observed that treatment with anti-PD-L1 monoclonal antibody promoted hepatic CD8+T and CD8+IFN-γ+T cell activation,but had no effect on CD4+IFN-γ+T cell activation under high-fat feeding conditions.Con-clusions Anti-PD-L1 monoclonal antibody adminis-tered under high-fat feeding conditions can damage liv-er function and aggravate atherosclerosis by activating liver CD8+IFN-γ+T cells.

Family with sequence similarity 3 member A(FAM3A),a novel mitochondrial protein,plays a pivotal role in hepatic glucose and lipid metabolism by enhancing ATP synthesis and secretion and mod-ulating the ATP-P2 receptor-Akt signaling pathway.Dysregulation of FAM3A is closely associated with the pathogenesis of non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM).In this study,targeting FAM3A as a therapeutic candidate,we conducted virtual screening to identify 47 small-molecule compounds with potential binding activity.Surface plasmon resonance(SPR)analysis re-vealed three compounds exhibiting high binding affinity to FAM3 A.Further structural characterization of the FAM3A-compound complexes,combined with intermolecular interaction analysis,elucidated the binding mode of the lead compound Index 2(taxifolin)to FAM3A at atomic resolution.These findings provide critical insights into the molecular mechanisms underlying ligand-FAM3A interactions and deliver valuable chemical scaffolds for the development of therapeutics targeting NAFLD and T2DM.This work establishes a foundation for advancing drug discovery efforts focused on FAM3A-mediated metabolic disor-ders.

Objective:To investigate the effect of preoperative nabuliumab adjuvant chemotherapy on tumor marker levels in patients with early and middle stage non-small cell lung cancer(NSCLC).Methods:Using a prospective study method, 106 patients with early and middle stage NSCLC patients who underwent pulmonary lobectomy at Jiaozhou Central Hospital of Qingdao from January 2019 to January 2021 were selected and divided into two groups according to a random number table method, with 53 patients in each group. The control group received preoperative adjuvant chemotherapy with docetaxel, while the observation group received preoperative adjuvant chemotherapy with nivolumab. The pathological response rate, tumor markers, disease-related indicators, adverse reactions, surgical conditions were compared between the two groups.Results:After treatment, the pathological remission rate in the observation group was higher than that in the control group: 69.81% (37/53) vs. 41.51% (22/53), there was statistical difference ( χ2 = 8.60, P<0.05). After treatment, the levels of serum thymidine kinase 1 (TK1), carbohydrate antigen 125, specific tissue polypeptide antigen and transforming growth factor beta 1, lactate dehydrogenase, vascular endothelial growth factor in the observation group were lower than those in the control group: (1.42 ± 0.37) pmol/L vs. (1.73 ± 0.42) pmol/L, (43.55 ± 4.19) kU/L vs. (47.85 ± 5.36) kU/L, (4.12 ± 1.05) μg/L vs. (6.85 ± 1.39) μg/L, (38.75 ± 5.85) μg/L vs. (43.72 ± 6.19) μg/L, (173.65 ± 15.37) U/L vs. (189.75 ± 20.18) U/L, (367.52 ± 14.35) ng/L vs. (393.47 ± 18.49) ng/L, there were statistical differences ( P<0.05). The incidence rate of diarrhea, nausea and vomiting, and bone marrow suppression in the observation group were lower than those in the control group: 11.32%(6/53) vs. 30.19%(16/53), 15.09%(8/53) vs. 43.40%(23/53), 22.64%(12/53) vs. 56.60%(30/53), there were statistical differences ( χ2 = 5.74, 10.26, 12.78, P<0.05). The R0 resection rate and the incidence of surgery-related adverse reactions between the two groups had no statistical differences ( P>0.05). Conclusions:Preoperative nivolumab based adjuvant chemotherapy can improve the treatment effect of early and middle stage NSCLC patients undergoing pulmonary lobectomy, regulate tumor marker levels, inhibit tumor progression, reduce the risk of gastrointestinal reactions and bone marrow suppression, and does not affect surgical treatment.

Objective:To investigate the relationship between peripheral blood amyloid protein A(SAA),C-reactive protein(CRP)/prealbumin(PA),vascular endothelial growth factor(VEGF)and the severity,pulmonary function,and prognosis of children with Mycoplasma pneumoniae pneumonia(MPP).Methods:106 children with MPP who were admitted to Huichang County Maternal and Child Health Hospital of Ganzhou from February 2023 to August 2024 were selected as the study subjects(MPP group),they were divided into good prognosis group(n=77)and poor prognosis group(n=29)according to the 28 days prognosis,they were divided into mild group(n=61)and severe group(n=45)according to the disease severity.Another 90 healthy children who underwent physical examinations during the same period were selected as the control group.The peripheral blood SAA,CRP/PA,VEGF,and pulmonary function indicators between the control group and MPP group were compared,and the peripheral blood SAA,CRP/PA,and VEGF levels between the mild group and severe group were compared,Pearson and Spearman correlation analysis was used to investigate the correlation between peripheral blood SAA,CRP/PA,VEGF and pulmonary function indicators and disease severity in children with MPP.The levels of peripheral blood SAA,CRP/PA,and VEGF between poor prognosis group and good prognosis group were compared.Receiver operating characteristic(ROC)curve was used to analyze the value of peripheral blood SAA,CRP/PA,VEGF detection alone and in combination for evaluating the 28 days prognosis in children with MPP.Results:The peripheral blood SAA,CRP/PA,and VEGF levels in the MPP group were higher than those in the control group,while the forced expiratory volume in one second(FEV1),peak expiratory flow(PEF),and forced vital capacity(FVC)were lower than those in the control group(P＜0.05).Peripheral blood SAA,CRP/PA,and VEGF levels in the severe group were higher than those in the mild group(P＜0.05).Peripheral blood SAA,CRP/PA,VEGF were negatively correlated with FEV1,PEF,FVC,but positively correlated with the severity of the disease(P＜0.05).Peripheral blood SAA,CRP/PA,and VEGF in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).The area under the curve(AUC)values of peripheral blood SAA,CRP/PA,and VEGF for evaluating the 28 days prognosis of MPP patients were 0.514,0.562,and 0.585,respectively,the AUC of 28 days prognosis evaluation in children with MPP by combined detection of peripheral blood SAA,CRP/PA,and VEGF was 0.725,significantly higher than that of individual detection.Conclusion:Abnormal elevation of peripheral blood SAA,CRP/PA,and VEGF levels is involved in the progression of MPP,the injury of pulmonary function,and poor prognosis.combined detection of peripheral blood SAA,CRP/PA,and VEGF levels can effectively evaluate the short-term prognosis of MPP patients.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective To propose a multiple regression-variational auto-encoders(MR-VAE)model to realize precise and non-invasive prediction of intra-abdominal pressure(IAP)in critically ill patients.Methods At first,a dataset was constructed by retrospectively analysing baseline characteristics and clinical indicators of 100 critically ill patients admitted to the Intensive Care Unit of Daping Hospital of Army Medical University between 30 August 2019 and 30 March 2021.Then,a MR-VAE prediction model was developed by integrating a feedforward neural network for supervised regression onto a variational autoencoder(VAE)framework and incorporating multiple regression strategies to mitigate feature interference.Finally,the MR-VAE model had its performance evaluated by its comparison with five classical models including support vector machines(SVM),convolutional neural networks(CNN),Scikit-learn integrated model(SIM),multi-layer perceptron(MLP)and K-nearest neighbors(KNN),and its prediction accuracy verified by testing the data of 10 randomly selected patients.Results The MR-VAE model behaved the best when compared with the five classical models,with a mean squared error(MSE)of 0.207,a root mean square error(RMSE)of 0.454,a mean absolute error(MAE)of 0.361,a median absolute deviation(MAD)of 0.243,an explained variance score(EVS)of 0.814 and a R2of 0.823,which also outperformed the five models in fitting performance,convergence and final loss.In random sample testing,the MR-VAE model exhibited high consistency between predicted and actual values.Conclusion The MR-VAE model proposed can accurately predict IAP,which has great potential in reducing the repeated measurements of IAP in critically ill patients and providing new ideas for the early diagnosis and treatment of IAH.