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.

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

Two thousand five hundred and sixty swab samples were collected from December 2022 to December 2023 in China.PCR was used to detect FBoV and amplify its VP2 and NS1 gene cod-ing equences,and bioinformatics was used to analyze the genetic diversity of FBoV.The results showed that the total positive rate of FBoV was 4.6％(119/2 560).Genetic variation analysis showed that FBoV existed in a variety of genotypes,and FBOV-1 was the main epidemic type in China.The 15 FBoV-1 strains,four FBoV-2 strains and one FBoV-3 strains identified in this study were genetically close to the strains identified in China,the United States,Thailand,Australia and Portugal.Sequence analysis showed that the identities of amino acid sequence of NS1 and VP2 genes between the sequenced strains and the reference strains were 59.13％-99.25％and 96.41％-100.00％,respectively.The amino acid identities of NS1 and VP2 among the newly sequenced FBoV strains were 60.00％-100.00％and 96.41％-100.00％,respectively,which indicated that the FBov strains circulating in China had great genetic diversity.This study enriched the data for elucidating the epidemic status of FBoV in China,and provided the basis for the subsequent diag-nosis,prevention and control of FBoV.

Objective To investigate the distribution of plantar pressures and bone stresses of the foot with high,normal and low arch morphologies,and reveal the influence of arch morphology on foot biomechanical properties.Methods A total of 127 young females were recruited.The foot type was classified by collecting the morphological data of the foot with the three-dimensional(3D)foot scanner,and three types of the foot arch morphology were selected for analysis.The geometric model of foot bone was obtained by CT scanning,so as to establish the biomechanical finite element model of the foot.A load of 50％human body weight was applied to the model to simulate the state of bipedal standing.Results The calculated plantar contact area was compared with the measured results,and the relative error values were smaller than 10％,which proved the validity of the finite element model.The peak plantar pressure under three types of arch morphologies was located in the hind foot region,and the heel pressure of high-and low-arched foot was higher than that of normal-arched foot.Compared with normal-arched foot,high-arched foot showed a significant increase in stress in the hind foot area,the peak stress of soft tissues was 299.45％higher,and the peak bone stress was 93.19％higher.For low-arched foot,the plantar contact area increased by 13.28％and calcaneal stress increased by 98.09％.The peak bone stresses of high-,normal-and low-arched foot were located at the talus,which were 9.903,19.921 and 36.308 MPa,respectively.Conclusions This study supports the association between abnormal arch morphology,foot pain and foot diseases,and provides a basis and direction for the design of orthopedic insoles and arch support structures for abnormal feet.

Objective To explore the peak moment characteristics of lower limb joints,as well as the contribution rate and compensation mechanism of lower limb joints when older adults with a history of falls cross obstacles at different paces.Methods Thirty healthy older adults and 30 eldely fallers were recruited.The Qualisys infrared high-speed motion capture system and the Kistler three-dimensional force platform were used to collect the biomechanical data of the older adults when they crossed an obstacle with a height of 15％of their height at three walking speeds(1.05,1.41,1.74 m/s).The data were then modeled and analyzed using Visual 3D software.Results As walking speed increased,the peak knee extension moment,peak ankle plantar flexion moment,and double peak value of hip flexion moment in healthy group all increased significantly(P＜0.05).Compared with healthy group,the double peak values of hip flexion moment in faller group were significantly smaller than those in healthy group(P＜0.05).During walking at moderate speed,the contribution rate of the left hip joint in faller group was significantly higher than that of healthy group(P=0.025),while the contribution rate of the ankle joint was significantly lower(P=0.044).The margin of stability in the anterior-posterior direction at the moment of ground contact of the stance leg and the stride leg increased with walking speed(P=0.007,P=0.002).Conclusions Compared with healthy older adults,the elderly fallers have lower peak torque,peak ground reaction force,and dynamic stability in the anterior-posterior direction.As the walking speed increases,the mechanical parameters and the margin of stability of older adults increase significantly,and walking stability is improved.Compared with healthy older adults,elderly fallers usually rely more on the contribution of hip joint movements and reduce the involvement of ankle joints.It is recommended to incorporate fast walking exercises into the daily fall prevention exercise program for older adults,with combination of coordinated training of the hip,knee,and ankle joints.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Objective:To establish the predictive model for major adverse cardiovascular events(MACE) following endovascular repair in elderly patients with abdominal aortic aneurysm(AAA).Methods:The clinical data and postoperative MACE were retrospectively collected from elderly patients with AAA who underwent their first endovascular aneurysm repair(EVAR)in Beijing Hospital and Tibet Autonomous Region People's Hospital between January 2016 and December 2023.Patients were randomly divided into training and validation cohorts at a ratio of 7∶3.Predictive models were using logistic regression, LASSO regression, random forest, linear discriminant analysis, na?ve Bayes, k-nearest neighbor algorithm, support vector machine, decision tree, and AdaBoost.Models were evaluated using receiver operating characteristic(ROC)curves.Results:A total of 171 elderly AAA patients were enrolled, aged 60 to 94 years(mean 73.0 ± 7.5 years), of whom 145 were male.MACE occurred after EVAR in 30 patients(17.5%). LASSO regression identified monocyte count, history of coronary artery disease, the ratio of maximum AAA diameter to body mass index(DBR), neutrophil-lymphocyte count ratio(NLR), and age as significant predictors, yielding an area under the ROC curve(AUC)of 0.816.Logistic regression achieved an AUC of 0.813 in the training cohort and 0.772 in the validation cohort.Among all models, AdaBoost demonstrated the best performance, with an AUC of 0.92 in the validation cohort.Conclusions:Age, monocyte count, DBR, NLR and creatinine could predict the occurrence of MACE after EVAR in AAA patients.The AdaBoost model provides the most accurate prediction of postoperative MACE.

Objective To explore the correlation between serum chemokine C-C ligand 21(CCL21),NOD like receptor protein 3(NLRP3)and hemorrhagic transformation(HT)after mechanical thrombectomy in patients with acute cerebral infarction(ACI).Methods A total of 210 ACI patients who underwent mechanical thrombectomy were selected and divided into the HT group(19 cases)and the non HT group(191 cases)based on the re-examination of head CT 24-hours after treatment.The differences in clinical data and serum levels of CCL21 and NLRP3 were compared between two groups.Multivariate Logistic regression analysis was used to analyze the influencing factors of HT occurrence.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum CCL21 and NLRP3 for HT.Results The proportion of atrial fibrillation,anterior circulation infarction and preoperative National Institutes of Health Stroke Scale(NIHSS)scores were higher in the HT group than those in the non HT group(P＜0.05).The preoperative serum levels of CCL21 and NLRP3 were higher in the HT group than those in the non HT group(P＜0.05).The Logistic regression model analysis results showed that atrial fibrillation,anterior circulation infarction,preoperative NIHSS score,CCL21 and NLRP3 were risk factors for postoperative HT in ACI patients(P＜0.05).The application of receiver operating characteristic(ROC)curve analysis results showed that the area under the curve(AUC)for predicting HT occurrence by CCL21 was 0.850(95％CI:0.763-0.936).The AUC predicted by NLRP3 was 0.787(95％CI:0.703-0.871),and the combined detection of the two further improved the predictive value(AUC=0.921,95％CI:0.867-0.976).Conclusion CCL21 and NLRP3 are closely related to the occurrence of HT in ACI patients after mechanical thrombectomy,and which are influencing factors for the occurrence of HT after mechanical thrombectomy.

Objective To observe the value of CT radiomics machine learning(ML)model for predicting stone free rate(SFR)of urinary calculi after retrograde intrarenal surgery(RIRS).Methods Totally 216 patients with urinary calculi who underwent RIRS were retrospectively enrolled and divided into residual group(n=73)and non-residual group(n=143).Univariate and multivariate logistic regression(LR)were performed to analyze clinical data and CT manifestations of stones to screen independent predictors of SFR after RIRS.Window width and window level normalization combined with max-min normalization(denoted as method a),max-min normalization(denoted as method b),window width and window level normalization(denoted as method c)and non-normalization(denoted as method d)of pre-RIRS abdominal CT were performed,respectively,and the best radiomics features of stones were extracted and screened to establish ML models,including support vector machine(SVM),LR and stochastic gradient descent(SGD)models,and the best ML model was screened.RUSS and modified S.T.O.N.E scores were evaluated based on pre-RIRS CT for predicting SFR of urinary calculi after RIRS.A combined model was then constructed with the independent predictors and the best ML model.The predictive efficacy of each model and scoring system were assessed.Results The number of stones,CT value and volume of the maximum stone were all independent predictors of SFR after RIRS(all P＜0.05).The area under the curve(AUC)of SVM model constructed with images preprocessed by method b was the highest(0.861),higher than that of the total scores of RUSS and modified S.T.O.N.E(AUC=0.750,0.759,both P＜0.05)but not different from that of combined model(AUC=0.853,P=0.775).Conclusion Radiomics SVM model based on max-min normalization preprocessed CT could effectively predict SFR of urinary calculi after RIRS.