Background: Patients with coarctation of the aorta (CoA) and an interrupted aortic arch (IAA) may present with small mitral valves (MVs) and a reduced left ventricular (LV) volume. Biventricular repair (BVR) in these patients is dependent on adequate size of the left cardiac structures.Purpose: This study evaluated the impact of the hemodynamic characteristics of atrial septal defects (ASDs) on MV growth following surgical repair. Methods: We retrospectively reviewed the data of patients diagnosed with CoA or IAA between 2007 and 2024. The z score for MV size measured 6 months postoperatively (Z2) was compared with the preoperative MV size (Z1). The factors associated with MV growth were also studied. Results: A total of 161 patients with CoA or IAA were included. Transthoracic echocardiography was used to assess the MV and LV dimensions preoperatively and 6 months postoperatively. Of the cohort, 155 (96.3%) underwent initial BVR and 6 underwent single-ventricle palliation. MV z scores significantly increased following BVR (mean change: +0.45±1.35; P<0.001) but decreased after single-ventricle repair (-0.56±0.49, P=0.04). Multivariate analysis identified the initial MV z score and ASD pressure gradient as independent predictors of MV growth (R2=0.39). Conclusion Annular growth of the MV was not observed in patients who underwent single-ventricle palliation. In contrast, among patients who achieved BVR, those with a small preoperative MV annulus and low ASD pressure gradient demonstrated subsequent catch-up MV growth, suggesting that adequate left-sided preload is essential for MV development.

The amino-terminal pro-C-type natriuretic peptide(NT-proCNP)is a diagnostic inflam-matory marker clinically used for diagnosing bacterial infections.This study aims to establish a phage display library of single-chain variable fragment(scFv)antibodies against canine NT-proC-NP and to screen for scFvs with high binding affinity to NT-proCNP.Initially,NT-proCNP was prepared using prokaryotic expression system and was used to immunize New Zealand White rab-bits.Upon achieving the desired serum titer,total RNA was extracted from the splenocytes of rab-bits and reverse transcribed into cDNA.Using this cDNA as a template,degenerate primers were employed to amplify the genes of the rabbit antibody light chain variable region(VL)and heavy chain variable region(VH).The VL and VH regions were spliced together to form a complete scFv fragment via overlap extension PCR.The scFv was then ligated into the phagemid pComb3XSS and electroporated into competent E.coli TG1 cells to construct a rabbit-derived anti-NT-proCNP scFv immunological library.This library underwent four rounds of enrichment and screening to isolate specific single-chain antibodies.The selected antibody was subsequently ex-pressed in a soluble form within a prokaryotic system,and its immunological activity was evalua-ted.Using phage display technology,this study successfully identified a single-chain antibody scFv-1-CNP with strong antigen-binding activity and genetic sequence characteristics of scFvs,providing a research direction for further exploration of scFv applications in the detection of NT-proCNP.

Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.

Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.

Aim To explore the biological mechanism of ligustilide in the prevention and treatment of osteo-porosis by regulating H-type blood vessels,combined with animal experiments for verification,based on net-work pharmacology and molecular docking technology Methods The possible mechanism of ligustilide regu-lating H-type blood vessels to prevent osteoporosis was predicted by network pharmacology.Molecular docking technology was used to verify the binding ability of the core target EGFR to ligustilide.The rat model of osteo-porosis was established and divided into the sham group,model group,ligustilide high,medium and low dose(80,40,20 mg·kg-1)groups.The pathological changes of femur were observed by HE staining.The expressions of CD31,EMCN,OSX+and RUNX2+pro-tein in tibial metaphysis were detected by immunofluo-rescence.The expression of p-EGFR,p-PI3K and p-Akt protein was detected by Western blot.Results The results of network pharmacology showed that a total of 20 intersection targets were obtained.EGFR,PTGS2,ESR1 and ICAM1 were core targets,and mo-lecular docking showed that EGFR had a strong bind-ing ability with ligustilide.The signaling pathways of ligustilide in the prevention and treatment of osteoporo-sis by regulating the expression of H-type blood vessels were mainly enriched in PI3K-Akt,TNF,etc.Com-pared with the model group,ligustilide could signifi-cantly increase the number of trabecular bone and im-prove the destruction of bone microstructure.The ex-pression of CD31,EMCN,OSX+and RUNX2+signifi-cantly increased(P＜0.01,P＜0.05),the formation of H-type blood vessels were promoted,and the expres-sion of p-EGFR,p-PI3K and p-Akt significantly in-creased(P＜0.01,P＜0.05).Conclusions Ligusti-lide can increase the expression of H-type blood vessels in bone tissue of osteoporosis model rats,reduce the damage of bone trabecula and improve bone micro-structure effectively.EGFR-mediated PI3K/Akt signa-ling pathway may be the key way to exert its biological effects.

Objective:To observe the early efficacy of intense pulsed light(IPL)combined with non-ablative fractional laser(NAFL)in preventing postoperative pathological scar formation and intervention of inflammatory factors.Methods:93 patients with postoperative pathological scar formation who were admitted to our hospital from March 2022 to September 2024 were selected,they were divided into control group A(silicone gel treatment,n=31),control group B(NAFL on the basis of control group A,n=31)and study group(IPL on the basis of control group B,n=31)using the random number table method.The clinical efficacy,simple quality of life scale(SF-36),vancouver scar scale(VSS),inflammatory factors[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)],and adverse reactions among three groups were compared.Results:The clinical total effective rate in the study group were higher than those in the control group A and control group B(P＜0.05).SF-36 increased sequentially and VSS decreased sequentially in control group A,control group B,and study group after treatment(P＜0.05).CRP,IL-6,and TNF-α decreased sequentially in control group A,control group B,and study group after treatment(P＜0.05).There was no significant difference in the incidence of adverse reactions among the three groups(P＞0.05).Conclusion:IPL combined with NAFL in preventing postoperative pathological scar formation,can effectively reduce scar formation,reduce inflammatory factors levels,improve patients' quality of life,and be safe and reliable.

Objective:To observe the early efficacy of intense pulsed light(IPL)combined with non-ablative fractional laser(NAFL)in preventing postoperative pathological scar formation and intervention of inflammatory factors.Methods:93 patients with postoperative pathological scar formation who were admitted to our hospital from March 2022 to September 2024 were selected,they were divided into control group A(silicone gel treatment,n=31),control group B(NAFL on the basis of control group A,n=31)and study group(IPL on the basis of control group B,n=31)using the random number table method.The clinical efficacy,simple quality of life scale(SF-36),vancouver scar scale(VSS),inflammatory factors[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)],and adverse reactions among three groups were compared.Results:The clinical total effective rate in the study group were higher than those in the control group A and control group B(P＜0.05).SF-36 increased sequentially and VSS decreased sequentially in control group A,control group B,and study group after treatment(P＜0.05).CRP,IL-6,and TNF-α decreased sequentially in control group A,control group B,and study group after treatment(P＜0.05).There was no significant difference in the incidence of adverse reactions among the three groups(P＞0.05).Conclusion:IPL combined with NAFL in preventing postoperative pathological scar formation,can effectively reduce scar formation,reduce inflammatory factors levels,improve patients' quality of life,and be safe and reliable.

Objective:To investigate the prevalence, severity, and influencing factors of chronic periodontitis in patients with type 2 diabetes mellitus (T2DM) in Nanjing.Methods:From June to August 2022, by using a multi-stage stratified cluster random sampling method, a total of 1 477 community-dwelling T2DM patients aged 35 years and older were selected and included from the National Essential Public Health Services Program for T2DM health management. Physical examinations, laboratory tests, and questionnaire surveys were conducted. Study participants were divided into chronic periodontitis group and non-chronic periodontitis group. The chronic periodontitis group was defined as having interproximal clinical attachment loss (CAL) detected at least at two non-adjacent sites, or having buccal/lingual CAL≥3 mm at least at two sites with probing depth (PD)≥3 mm, while excluding CAL caused by non-periodontal reasons. The remaining participants were classified as the non-chronic periodontitis group. In the chronic periodontitis group, patients who had PD≥6 mm at least at two sites with CAL≥5 mm were defined as severe periodontitis, with remaining cases classified as mild-to-moderate periodontitis.Results:The prevalence of chronic periodontitis among T2DM patients was 70.1% (962/1 373), with mild to moderate and severe periodontitis prevalence rates of 62.4% (857/1 373) and 7.6% (105/1 373), respectively. After complex weighted processing, the prevalence of chronic periodontitis in T2DM patients was 67.9%, with mild to moderate and severe periodontitis prevalence rates of 61.2% and 6.7%, respectively. Multivariate logistic regression analysis showed that after adjusting all covariates, compared with mental workers, the risk of chronic periodontitis was significantly higher in retired people ( OR=1.78, 95 %CI: 1.75-1.81, P<0.001), unemployed/others ( OR=2.18, 95 %CI: 2.14-2.22, P<0.001), and physical workers ( OR=3.80, 95 %CI: 3.73-3.87, P<0.001). In terms of blood glucose control status, compared with the group that met both control targets, the risk of chronic periodontitis was significantly higher in the group that met only one target ( OR=1.28, 95 %CI: 1.27-1.30, P<0.001) and the group that met neither target ( OR=3.29, 95 %CI: 3.25-3.34) ( P<0.001). The results of ordered Logistic regression showed that after adjusting for all covariates, compared with male patients, female patients had a significantly lower risk of progression to severe periodontitis ( OR=0.77, 95 %CI: 0.76-0.78, P<0.001). In terms of the score of healthy lifestyle, compared with those with a score of 0-2, the risk of progression to severe periodontitis was significantly lower in those with a score of 3 ( OR=0.85, 95 %CI: 0.84-0.86, P<0.001) and 4 ( OR=0.51, 95 %CI: 0.50-0.52, P<0.001). In terms of blood glucose control, compared with the group that met both control targets, the risk of progression to severe periodontitis was significantly higher in the group that met only one target ( OR=1.27, 95 %CI: 1.26-1.29, P<0.001) and the group that meet neither target ( OR=3.24, 95 %CI: 3.21-3.28, P<0.001). Furthermore, poor blood glucose control was significantly positively associated with increased periodontitis severity, demonstrating that worse glycemic control status corresponded to a higher risk of worsening periodontitis severity ( P<0.001). Conclusions:There is an association between the glycemic control status of T2DM patients and chronic periodontitis.

BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.

Objective To identify the key factors affecting the risk of medical surges and their coupling relation5 ships,providing strategic support for medical institutions to optimize risk management and emergency governance.Methods 17 influencing factors were determined based on WSR theory,and an expert scoring method was employed to assess the impact strength among the factors.The DEMATEL method was applied to calculate the centrality,cau5 sality,influence,and being influenced degrees of the influencing factors.The ISM method was used to construct a hierarchical structure of the influencing factors related to medical surge risks,thereby revealing the connections and interaction mechanisms among these factors.Results Seven critical influencing factors were identified,including the crisis decision-making capacity and leadership effectiveness of emergency managers,the completeness of the emer5 gency system and dynamic execution capabilities,and the cross-departmental coordination mechanism and com5 mand collaboration efficiency.Deep driving factors and coupling pathways were also revealed.Conclusion The risk of medical surges exhibits multi-factorial coupling cascade effects;attention should be directed towards the construc5 tion of mid-to-deep level mechanisms such as information systems,institutional frameworks,and organizational management,to enhance targeted capabilities and systemic resilience in risk governance.