ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Objective:To explore the adaptability of health resources allocation and the economic development level in Sichuan Province and its influencing factors,so as to provide reference and suggestions for optimizing health resources allocation.Methods:Based on the panel data of 21 cities(states)in Sichuan Province,it analyzes the adaptability of health resources allocation and economic development in Sichuan Province from 2017 to 2021 and its influencing factors through entropy method,coupling coordination model and grey relational model.Results:From 2017 to 2021,the allocation level of health resources in most areas of Sichuan Province showed a gradual upward trend,but the rising speed was obviously lower than the growth rate of economic development;In 2021,the adaptability between the allocation of health resources and the level of economic development in most parts of Sichuan Province is still in a low coordination stage.Conclusion:Different regions should adopt differentiated development strategies based on their actual geographical conditions,optimize the allocation of health resources according to local conditions,and promote the coordinated development of health resource allocation and economic level.

Anticoagulants are widely used in the prevention and treatment of thromboembolism.Existing anticoagulants share the common feature of antagonizing or blocking critical steps in the coagulation cascade,which also increases the risk of bleeding.Studies have indicated that factor Ⅺ inhibitors represent a potential therapeutic option for balancing thrombosis and bleeding risks.In recent years,various factor Ⅺ inhibitors,including antisense oligonucleotides(ASOs),monoclonal antibodies,synthetic small molecules,natural peptides,and aptamers,have been extensively researched as potentially exploitable anticoagu-lants.Research findings also suggest that factor Ⅺ inhibitors can reduce bleeding risks while ensuring anticoagulant efficacy,ex-hibiting potential for thrombosis prevention and treatment in patient populations such as those with end-stage renal disease,non-cardioembolic ischemic stroke,and acute coronary syndrome.This article reviewed the mechanisms of action,drug classes,pharma-cological characteristics,and clinical research progress of factor Ⅺ inhibitors,aiming to provide insights into the development of new anticoagulants and clinical anticoagulant therapies.

Objective To investigate the value of early maternal serological indicators in predic-ting the delivery of full-term small-for-gestational-age(SGA)infants.Methods The clinical data of pregnant women who delivered at Beijing Tongzhou District Maternal and Child Health Hospital from August 2023 to August 2024 were analyzed.A total of 180 pregnant women who delivered full-term SGA infants were included in case group,and 180 pregnant women who delivered full-term appropri-ate-for-gestational-age(AGA)infants during the same period were included in control group.The levels of serum pregnancy-associated plasma protein A(PAPP-A),placenta growth factor(PLGF),and soluble fms-like tyrosine kinase-1(sFlt-1)in the first trimester(11 to 13 weeks+6 days of ges-tation)of the two groups were compared.Receiver operating characteristic(ROC)curves were used to analyze the predictive value of early maternal serological indicators for the delivery of full-term SGA infants.Results The levels of serum PAPP-A and PLGF in the first trimester of the case group were lower than those in the control group,while the level of sFlt-1 was higher(P＜0.05).The area un-der the ROC curve(AUC)for the combined detection of serum PAPP-A,PLGF,and sFlt-1 levels in the first trimester in predicting the delivery of full-term SGA infants was 0.823,which was higher than the AUCs for detection of each indicator(0.738,0.720,0.724)(P＜0.05).Conclusion The detection of early maternal PAPP-A,PLGF,and sFlt-1 levels can reflect the fetal growth status in utero.The combined detection of these three indicators has a higher predictive value for the delivery of full-term SGA infants by pregnant women,which is helpful for clinicians to take intervention measures in advance.

Objective:To identify the risk factors for ascending aortic dilatation and develop a prediction model using LASSO-Logistic regression in patients with normally functioning bicuspid aortic valves（BAV）.Methods:Eight-four adult patients with BAV diagnosed as having normal valve function by transthoracic echocardiography who attended to the General Hospital of Ningxia Medical University between June 2024 and April 2025 were prospectively selected，there were 42 patients with ascending aortic dilatation and 42 patients without dilatation.The patients were divided into a training set（60 cases）and a test set（24 cases）using stratified random sampling at a ratio of 7 to 3 via the R caret package. All subjects underwent transthoracic echocardiography，lipid and plasma matrix metalloproteinases（MMP）and tissue inhibitors（TIMP）levels detection. The inverse probability of treatment weighting（IPTW）method was employed to control for potential confounding factors. LASSO and multifactorial binary Logistic regression was applied to screen the independent risk factors for ascending aortic dilatation of BAV and development a nomogram prediction model. The accuracy，consistency and clinical applicability of the prediction model were evaluated by applying the ROC curve，calibration curve，and decision curve analysis（DCA），respectively.Results:①After adjustment for IPTW，LASSO-Logistic regression analysis identified left ventricular global longitudinal strain（LVGLS）and plasma MMP-2 levels as independent risk factors for ascending aortic dilatation in BAV patients with normal valve function.②The nomogram prediction model constructed based on the above screening features，and the area under the curve（AUC）of ROC for the training set and test set were 0.917 and 0.903，with specificities of 0.867 and 0.917，and sensitivities of 0.933 and 0.916，respectively. ③Calibration curves demonstrated satisfactory alignment，with C-indices of 0.908（95% CI=0.879～0.937）for the training set and 0.903（95% CI=0.874 - 0.932）for the test set. Hosmer-Lemeshow goodness-of-fit tests indicated strong consistency between predicted and observed outcomes，with P-values of 0.138 and 0.750 for the training and test sets，respectively.The DCA curve demonstrated that within a threshold probability range of 0.04 - 0.90 in the test set，the clinical decision-making model provided a higher net benefit rate for patients with BAV. Conclusions:LVGLS absolute value reduction and elevated plasma MMP-2 levels are independent risk factors for predicting ascending aortic dilatation in BAV patients with normal valve function. The prediction model based on LASSO-Logistic regression has good predictive value，providing a scientific basis for clinical decision-making in patients with BAV and aortic diseases.

Objective:To explore the adaptability of health resources allocation and the economic development level in Sichuan Province and its influencing factors,so as to provide reference and suggestions for optimizing health resources allocation.Methods:Based on the panel data of 21 cities(states)in Sichuan Province,it analyzes the adaptability of health resources allocation and economic development in Sichuan Province from 2017 to 2021 and its influencing factors through entropy method,coupling coordination model and grey relational model.Results:From 2017 to 2021,the allocation level of health resources in most areas of Sichuan Province showed a gradual upward trend,but the rising speed was obviously lower than the growth rate of economic development;In 2021,the adaptability between the allocation of health resources and the level of economic development in most parts of Sichuan Province is still in a low coordination stage.Conclusion:Different regions should adopt differentiated development strategies based on their actual geographical conditions,optimize the allocation of health resources according to local conditions,and promote the coordinated development of health resource allocation and economic level.

Anticoagulants are widely used in the prevention and treatment of thromboembolism.Existing anticoagulants share the common feature of antagonizing or blocking critical steps in the coagulation cascade,which also increases the risk of bleeding.Studies have indicated that factor Ⅺ inhibitors represent a potential therapeutic option for balancing thrombosis and bleeding risks.In recent years,various factor Ⅺ inhibitors,including antisense oligonucleotides(ASOs),monoclonal antibodies,synthetic small molecules,natural peptides,and aptamers,have been extensively researched as potentially exploitable anticoagu-lants.Research findings also suggest that factor Ⅺ inhibitors can reduce bleeding risks while ensuring anticoagulant efficacy,ex-hibiting potential for thrombosis prevention and treatment in patient populations such as those with end-stage renal disease,non-cardioembolic ischemic stroke,and acute coronary syndrome.This article reviewed the mechanisms of action,drug classes,pharma-cological characteristics,and clinical research progress of factor Ⅺ inhibitors,aiming to provide insights into the development of new anticoagulants and clinical anticoagulant therapies.

Objective:To identify the risk factors for ascending aortic dilatation and develop a prediction model using LASSO-Logistic regression in patients with normally functioning bicuspid aortic valves（BAV）.Methods:Eight-four adult patients with BAV diagnosed as having normal valve function by transthoracic echocardiography who attended to the General Hospital of Ningxia Medical University between June 2024 and April 2025 were prospectively selected，there were 42 patients with ascending aortic dilatation and 42 patients without dilatation.The patients were divided into a training set（60 cases）and a test set（24 cases）using stratified random sampling at a ratio of 7 to 3 via the R caret package. All subjects underwent transthoracic echocardiography，lipid and plasma matrix metalloproteinases（MMP）and tissue inhibitors（TIMP）levels detection. The inverse probability of treatment weighting（IPTW）method was employed to control for potential confounding factors. LASSO and multifactorial binary Logistic regression was applied to screen the independent risk factors for ascending aortic dilatation of BAV and development a nomogram prediction model. The accuracy，consistency and clinical applicability of the prediction model were evaluated by applying the ROC curve，calibration curve，and decision curve analysis（DCA），respectively.Results:①After adjustment for IPTW，LASSO-Logistic regression analysis identified left ventricular global longitudinal strain（LVGLS）and plasma MMP-2 levels as independent risk factors for ascending aortic dilatation in BAV patients with normal valve function.②The nomogram prediction model constructed based on the above screening features，and the area under the curve（AUC）of ROC for the training set and test set were 0.917 and 0.903，with specificities of 0.867 and 0.917，and sensitivities of 0.933 and 0.916，respectively. ③Calibration curves demonstrated satisfactory alignment，with C-indices of 0.908（95% CI=0.879～0.937）for the training set and 0.903（95% CI=0.874 - 0.932）for the test set. Hosmer-Lemeshow goodness-of-fit tests indicated strong consistency between predicted and observed outcomes，with P-values of 0.138 and 0.750 for the training and test sets，respectively.The DCA curve demonstrated that within a threshold probability range of 0.04 - 0.90 in the test set，the clinical decision-making model provided a higher net benefit rate for patients with BAV. Conclusions:LVGLS absolute value reduction and elevated plasma MMP-2 levels are independent risk factors for predicting ascending aortic dilatation in BAV patients with normal valve function. The prediction model based on LASSO-Logistic regression has good predictive value，providing a scientific basis for clinical decision-making in patients with BAV and aortic diseases.

Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.

Persistent pulmonary hypertension of the newborn (PPHN) is a common and critical disease in the neonatus characterized by persistent pulmonary hypertension and hypoxemia, with a high mortality.Except for intubation and ventilator support, recognized treatments often require the application of pulmonary vasodilators drugs, such as inhaled nitric oxide, Sildenafil, etc, each with its own advantages.In recent years, L-citrulline, as a potential therapeutic option, has shown huge potential in PPHN treatment.The purpose of this review is to explore the possible potential of L-citrulline in the treatment of PPHN in terms of therapeutic mechanism, pharmacokinetics, current status of research and future perspectives.