Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Objective To investigate the dynamic mechanical responses and damage characteristics of peri-implant bone structures subjected to impact load.Methods A finite element model of the peri-implant bone microstructure was established,and an initial velocity was applied to the rigid body to simulate the impact load.A stress failure criterion was employed and a user-material subroutine was developed to assess failure.Subsequently,bone damage after the impact load was analyzed according to the material subroutine.Results After the impact load,the stress on the cortical bone increased rapidly,reaching a peak value(16.01 MPa)immediately.In contrast,the stress on the trabecular bone at the bottom of the implant reached its peak value(5.85 MPa)at 0.1 μs.The impact load resulted in stress waves that propagated and diffused within the bone structure,causing changes in the bone structure damage over time.The generated impact energy could be absorbed and dissipated by the trabecular bone through deformation.The deformed trabecular bone experienced damage and failure upon reaching the yield limit,whereas the cortical bone did not experience damage or failure under an impact load.Conclusions Structural changes in the trabecular bone should be considered in patients with impact damage.The numerical model established in this study can effectively predict bone impact damage by combining the structural mechanical properties and geometric characteristics of the bones.These findings can serve as a reference for assessing bone damage and post-damage treatment in patients subjected to impact loads in clinical practice.

Objective:To investigate the antigen-sparing effects of crude polysaccharides from Cistanche deserticola Y. C.Ma (CPCD) for influenza virus vaccine (IVV). Methods:ICR mice were immunized subcutaneously with CPCD combined with different doses of IVV (0.01 μg and 0.1 μg). Hemagglutinin inhibition (HI) assay was used to detect HI titers in serum samples. Indirect ELISA was performed to detect the levels of specific IgG antibodies and their subtypes in serum samples. The proliferation of splenic lymphocytes was detected by MTT assay. The percentages of CD4 + , CD8 + and CD44 + T cells and the levels of IFN-γ in splenic cells isolated from the vaccinated mice were analyzed by flow cytometry. Results:CPCD significantly increased HI titers (234.67±47.70 vs 149.33±47.70, P<0.05), promoted the production of IgG ( A450 value: 1.16±0.63 vs 0.30±0.21, P<0.05) and IgG1 ( A450 value: 1.09±0.60 vs 0.26±0.21, P<0.05) and enhanced splenic lymphocyte proliferation ( P<0.05). CPCD also significantly up-regulated the expression of CD4 + [(41.97±4.58)% vs (25.43±1.48)%, P<0.05], CD8 + [(12.67±0.33)% vs (9.02±1.07)%, P<0.05], CD4 + CD44 + [(11.77±0.69)% vs (8.64±0.71)%, P<0.05] and CD8 + CD44 + [(6.70±0.67)% vs (4.66±0.39)%, P<0.05] T cell subsets as well as the secretion of IFN-γ in CD4 + [(1.36±0.07)% vs (0.87±0.06)%, P<0.05] and CD8 + [(2.09±0.20)% vs (1.42±0.08)%, P<0.05] T cells. In addition, there was no significant difference between CPCD combined with low-dose IVV group and high-dose IVV alone group ( P>0.05), implying a 10-fold antigen sparing. Conclusions:CPCD, as an adjuvant for influenza virus vaccine, could enhance humoral and cellular immune responses and reduce antigen dose, which might be a potential adjuvant for seasonal or pandemic influenza vaccines.

Objective To investigate the efficacy of using Xinjiang wild Artemisia rupestris L. crude polysaccharides ( WARCP) as an immunologic adjuvant for influenza virus vaccine( IVV) .Methods ICR mice were subcutaneously immunized with 0.3 μg of IVV and 1.5 μg of IVV alone or co-administered with 200 μg of WARCP on 0 d and 14 d.Antibody levels in serum samples were detected by using indirect ELISA.MTT method was used to measure the proliferation of splenocytes.The growth conditions of mice were observed as well.Results No significant differences in the body weight were observed between mice from different groups (P>0.05).The levels of influenza virus-specific IgG, IgG1 and IgG2a were signifi-cantly increased in mice injected with WARCP adjuvant (P<0.05).The levels of IgG antibody in mice im-munized with low-dose of IVV and WARCP were significantly higher than those in mice immunized with high-dose of IVV alone (P<0.05), indicating at least 80% reduction in vaccine dosage by adding WARCP as adjuvant.Moreover, WARCP significantly promoted the proliferation of lymphocytes (P<0.05).Conclu-sion Adding WARCP to IVV enhanced the efficacy of IVV by boosting humoral and cellular immunity re-sponses with the advantages of high safety and dose-sparing.This study suggested the possibility of using WARCP as a novel immunologic adjuvant for influenza virus vaccine.

Objective To verify the value of routine laboratory markers for assessment of liver fibrosis status in chronic hepatitis B virus (HBV) carriers.Methods A total of 196 patients who were clinically diagnosed with chronic HBV carriers with liver biopsy and routine laboratory test were included in this study. The data of complete blood count, aspartate aminofransferase/alanine aminotransferase (AST/ALT),aspartate aminotransferase to platelet ratio index (APRI) and ageplatelet index (API) were collected and calculated.Patients were divided into group S0 (n=112) and group S1- S3 (n =84) based on liver fibrosis stages.Measurement data were analyzed by Wilcoxon rank sum test and enumeration data were analyzed by chi square test.Results All 196 enrolled HBV carriers were HBV DNA positive,with 156 (79.6％) HBeAg-positive.Age,ALT,AST,AST/ALT,APRI and API were all significantly higher in group S1- S3 than those in group S0 (statistic value=7.705,6.33,7.095,4.977,11.059,8.936,respectively; all P＜0.05).However,PLT level was lower in the former group compared to that in the latter group (statistic value=10.196,P＜0.05 ).The area under receiver operating characteristic curve (AUROC) of APRI and API were 0.827and 0.829,respectively.The highest sensitivity and negative prediction value (NPV) were 70.46 ％and 71.43 ％ respectively when using API.The best specificity and positive prediction value (PPV)was 92.94％ and 92.86％,respectively when using APRI.When APRI≥0.30 was used as the cut-off of liver fibrosis,97.62 ％ of 119 patients were diagnosed with liver fibrosis; when API≥4.0 was used as the cut-off of liver fibrosis, 96.43％ of 112 patients were diagnosed with liver fibrosis.Conclusion APRI and API are two simple and feasible non-invasive biochemical markers that can be used to determine liver fibrosis status in chronic HBV carriers.