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 investigate the clinical management,complications,and prognostic prediction model of bronchopulmonary dysplasia(BPD)in preterm infants.Methods:A total of 854 very preterm infants(gestational age ≤ 32 weeks)admitted to the Neonatal Intensive Care Unit(NICU)of Shanghai Children's Hospital from January 2018 to December 2022 were retrospectively enrolled.After applying inclusion and exclusion criteria,713 infants were included.Based on the 2018 National Institute of Child Health and Human Development(NICHD)diagnostic criteria for BPD,the cohort was divided into a BPD group(n=164)and a non-BPD group(n=549).Clinical data of infants and maternal characteristics were compared between groups.Univariate and stepwise multivariate logistic regression analyses were performed to identify independent risk factors for BPD and evaluate clinical management.A nomogram model was subsequently developed to predict BPD prognosis.Results:Gestational age,duration of non-invasive ventilation,total oxygen therapy time,total hospital stay,hemodynamically significant patent ductus arteriosus(hsPDA),maximum diameter of patent ductus arteriosus(PDA),fetal growth restriction(FGR),use of vasoactive agents,and proportion of pulmonary surfactant administration were identified as independent risk factors for BPD(all P＜0.05,OR＞0).The nomogram model demonstrated excellent predictive performance,with an area under the receiver operating characteristic curve(AUC)of 0.93 and a calibration curve slope approaching 1.The Hosmer-Lemeshow goodness-of-fit test indicated satisfactory model calibration(x2=8.2865,P=0.406).Conclusion:Gestational age,non-invasive ventilation duration,total oxygen therapy time,total hospital stay,hsPDA,PDA maximum diameter,FGR,vasoactive agents,and pulmonary surfactant use are critical predictors of BPD in preterm infants.The prognostic models for BPD incidence and severity,constructed based on these factors,exhibit strong predictive accuracy and may serve as a valuable clinical tool for risk stratification and early intervention.

Background and Aims:Sleeve gastrectomy(SG)has become the most widely performed bariatric procedure worldwide,but postoperative gastroesophageal reflux disease(GERD)remains a major concern.This multicenter study aimed to identify independent risk factors associated with GERD after SG to guide preoperative assessment and intraoperative management.Methods:Clinical data of 672 patients who underwent SG between January 2020 and December 2022 in six bariatric centers and completed a 12-month follow-up were retrospectively analyzed.Demographic characteristics,esophagogastric junction(EGJ)integrity graded by the AFS system,operative parameters,and postoperative outcomes were compared between patients with and without GERD.Multivariate logistic regression was used to identify predictors of postoperative GERD.Results:The overall incidence of GERD after SG was 24.7%(166/672).Multivariate analysis revealed that a preoperative BMI>35 kg/m2(OR=1.68,P=0.033),EGJ integrity AFS grade>2(OR=2.90,P=0.006),and preoperative reflux symptoms(OR=2.44,P=0.030)were independent risk factors for GERD.A staple line more than 1 cm from the angle of His(OR=0.45,P<0.001)and a bougie size>36 Fr(OR=0.08,P=0.001)were protective factors.Conclusion:High BMI,impaired EGJ integrity,and preoperative reflux symptoms significantly increase the risk of GERD after SG,whereas adequate preservation of the His angle and appropriate bougie calibration may reduce it.Comprehensive preoperative EGJ assessment and standardized surgical techniques are essential for minimizing postoperative reflux.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

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.

Aim To mine the competing ceRNA net-works associated with programmed cell death in the pathophysiological mechanisms of atherosclerosis(AS)based on bioinformatics,in order to identify new targets for the diagnosis and treatment of AS.Methods Firstly,the GSE97210 and GSE28858 datasets were screened from the GEO database.Differentially ex-pressed lncRNA,mRNA and miRNA were identified,following which a IncRNA-miRNA-mRNA regulatory network was constructed in Cytoscape 3.7.2 software based on ceRNA theory.Second,GO and KEGG en-richment analysis of mRNA in the ceRNA network was performed.Finally,the mRNAS within the ceRNA net-work were compared with genes related to autophagy,pyroptosis and ferroptosis to establish a ceRNA network related to programmed cell death.Results A total of 1208 DElncRNAS,4723 DEmRNAS and 139 DEmiR-NAS were identified.A ceRNA network was estab-lished,comprising 64 lncRNAS,8 miRNAS and 167 mRNAS.The mRNAS within the CeRNA network were mainly enriched in biological processes such as positive regulation of transcription and migration,protein bind-ing,and signaling pathways including PI3K-Akt signa-ling pathway,and mTOR signaling pathway.Finally,this study established 7 lncRNA-mediated ceRNA regu-latory pathways associated with pyroptosis and 23 ln-cRNA-mediated regulatory pathways for ferroptosis and autophagy.Conclusion This study has successfully constructed a ceRNA network related to programmed cell death,which helps us understand the mechanism by which programmed cell death leads to AS.

Objective:To investigate the clinical management,complications,and prognostic prediction model of bronchopulmonary dysplasia(BPD)in preterm infants.Methods:A total of 854 very preterm infants(gestational age ≤ 32 weeks)admitted to the Neonatal Intensive Care Unit(NICU)of Shanghai Children's Hospital from January 2018 to December 2022 were retrospectively enrolled.After applying inclusion and exclusion criteria,713 infants were included.Based on the 2018 National Institute of Child Health and Human Development(NICHD)diagnostic criteria for BPD,the cohort was divided into a BPD group(n=164)and a non-BPD group(n=549).Clinical data of infants and maternal characteristics were compared between groups.Univariate and stepwise multivariate logistic regression analyses were performed to identify independent risk factors for BPD and evaluate clinical management.A nomogram model was subsequently developed to predict BPD prognosis.Results:Gestational age,duration of non-invasive ventilation,total oxygen therapy time,total hospital stay,hemodynamically significant patent ductus arteriosus(hsPDA),maximum diameter of patent ductus arteriosus(PDA),fetal growth restriction(FGR),use of vasoactive agents,and proportion of pulmonary surfactant administration were identified as independent risk factors for BPD(all P＜0.05,OR＞0).The nomogram model demonstrated excellent predictive performance,with an area under the receiver operating characteristic curve(AUC)of 0.93 and a calibration curve slope approaching 1.The Hosmer-Lemeshow goodness-of-fit test indicated satisfactory model calibration(x2=8.2865,P=0.406).Conclusion:Gestational age,non-invasive ventilation duration,total oxygen therapy time,total hospital stay,hsPDA,PDA maximum diameter,FGR,vasoactive agents,and pulmonary surfactant use are critical predictors of BPD in preterm infants.The prognostic models for BPD incidence and severity,constructed based on these factors,exhibit strong predictive accuracy and may serve as a valuable clinical tool for risk stratification and early intervention.

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Background and Aims:Sleeve gastrectomy(SG)has become the most widely performed bariatric procedure worldwide,but postoperative gastroesophageal reflux disease(GERD)remains a major concern.This multicenter study aimed to identify independent risk factors associated with GERD after SG to guide preoperative assessment and intraoperative management.Methods:Clinical data of 672 patients who underwent SG between January 2020 and December 2022 in six bariatric centers and completed a 12-month follow-up were retrospectively analyzed.Demographic characteristics,esophagogastric junction(EGJ)integrity graded by the AFS system,operative parameters,and postoperative outcomes were compared between patients with and without GERD.Multivariate logistic regression was used to identify predictors of postoperative GERD.Results:The overall incidence of GERD after SG was 24.7%(166/672).Multivariate analysis revealed that a preoperative BMI>35 kg/m2(OR=1.68,P=0.033),EGJ integrity AFS grade>2(OR=2.90,P=0.006),and preoperative reflux symptoms(OR=2.44,P=0.030)were independent risk factors for GERD.A staple line more than 1 cm from the angle of His(OR=0.45,P<0.001)and a bougie size>36 Fr(OR=0.08,P=0.001)were protective factors.Conclusion:High BMI,impaired EGJ integrity,and preoperative reflux symptoms significantly increase the risk of GERD after SG,whereas adequate preservation of the His angle and appropriate bougie calibration may reduce it.Comprehensive preoperative EGJ assessment and standardized surgical techniques are essential for minimizing postoperative reflux.