ObjectiveTo explore the potential mechanism of Xiaoqinglongtang（XQL） in the prevention and treatment of high altitude pulmonary edema（HAPE） by network pharmacology， molecular docking， and molecular dynamics simulation， and to verify it by in vivo animal model. MethodsIn this study， the active ingredients， drug targets， and HAPE-related targets of XQL were collected from BATMAN-TCM， GeneCards， and Online Mendelian Inheritance in Man（OMIM） databases. The protein-protein interaction（PPI） network was constructed by using intersection targets， and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part， a mouse model of HAPE induced by hypobaric hypoxia（simulated 6 000 m altitude for 48 h） was established. The control effect was evaluated by hematoxylin-eosin（HE） staining， lung tissue water content， lung tissue wet/dry weight ratio， real-time quantitative polymerase chain reaction（Real-time PCR） detection of gene expression levels， and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL， 2 142 targets， 716 HAPE-related targets， and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin （IL）-6， tumor necrosis factor （TNF）， protein kinase B1 （Akt1）， and hypoxia-inducible factor-1α （HIF-1α） were screened. The results of GO analysis of common targets involved 738 biological processes（BP）， 72 cellular components（CC）， and 135 molecular functions（MF）. KEGG analysis effectively enriched two important signaling pathways： Phosphoinositol 3-kinase （PI3K）/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia（6 000 m， 48 h）， the lung tissue water content， lung tissue wet/dry weight ratio， and pathological injury score of the model group were significantly increased（P<0.01）， accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium， a significant increase in inflammatory cells， a significant widening of the alveolar septum， and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes（P<0.01）. The results of inflammatory factor expression showed that compared with the control group， the model group showed significantly up-regulated expression of TNF-α， IL-6， and IL-1β in the lung tissue（P<0.01）. Compared with the model group， the XQL administration group had significantly decreased expression of inflammatory factors（P<0.05， P<0.01）. The mRNA expression of key pathway related genes PI3K， Akt1， mammalian target of rapamycin（mTOR）， and HIF-1α was significantly increased in the model group（P<0.01）， and decreased in a concentration-dependent manner after XQL administration（P<0.05， P<0.01）. The expression levels of key proteins PI3K， phosphorylation（p）-PI3K， Akt1， p-Akt1， mTOR， p-mTOR， and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group， the model group showed increased expression of key proteins（P<0.05， P<0.01）. Compared with the model group， the XQL administration group exhibited decreased expression of key proteins（P<0.05， P<0.01）. ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.

BackgroundAnxiety exhibits a rising prevalence among college students. Investigating the mechanisms through which family function relates to anxiety and examining the moderating role of emotion regulation strategies within this context hold substantial implications for promoting mental health among college students. However， existing research has not sufficiently elucidated the complex interplay among family function， emotion regulation， and anxiety among college students. Further research is warranted to clarify the underlying mechanisms linking family function to anxiety outcomes and to examine the potential moderating role of emotion regulation strategies in this causal pathway. ObjectiveTo explore the relationship between family function and anxiety among lower-grade college students， and to validate the moderating role of emotion regulation strategies in this relationship， thereby offering evidence-based insights for anxiety reduction interventions in this population. MethodsIn March 2023， a total of 1 980 first- and second-year students from a comprehensive university in Shanghai were selected using the cluster sampling method. A self-designed demographic questionnaire， the Emotion Regulation Questionnaire （ERQ）， the Family Adaptability and Cohesion Evaluation Scale Ⅱ-Chinese Version （FACES Ⅱ-CV）， and the Symptom Checklist-90 （SCL-90） were utilized for assessment. Pearson correlation analysis and Spearman correlation analysis were employed to test the correlations of each variable. Hierarchical linear regression analysis was conducted to certify the moderating role of emotion regulation strategies in the relationship between family function and anxiety. ResultsCompared with female students， male students scored significantly lower on ERQ cognitive reappraisal （t=-5.793， P<0.01） but significantly higher on ERQ expressive suppression （t=8.359， P<0.01）. For lower-grade college students， scores on adaptability and cohesion subscales of FACES Ⅱ-CV showed a positive association with cognitive reappraisal in ERQ （r=0.251， 0.302， P<0.01）， while simultaneously displaying negative correlations with both expressive suppression in ERQ （r=-0.113， -0.154， P<0.01） and anxiety in SCL-90 （r=-0.243， -0.202， P<0.01）. Notably， anxiety scores in SCL-90 were inversely related to cognitive reappraisal scores in ERQ （r=-0.159， P<0.01） but directly associated with expressive suppression scores in ERQ （r=0.171， P<0.01）. Hierarchical regression analysis indicated that cognitive reappraisal significantly moderated the relationship between family cohesion and anxiety （β=-0.421， P<0.01）. ConclusionThe cognitive reappraisal strategy serves as a moderator in the relationship between family cohesion and anxiety， potentially mitigating the escalation of anxiety levels associated with family dysfunction. ［Funded by Science and Technology Development Fund of Shanghai Pudong New Area （number， PKJ2023-Y21）］

ObjectiveTo explore the potential mechanism of Xiaoqinglongtang（XQL） in the prevention and treatment of high altitude pulmonary edema（HAPE） by network pharmacology， molecular docking， and molecular dynamics simulation， and to verify it by in vivo animal model. MethodsIn this study， the active ingredients， drug targets， and HAPE-related targets of XQL were collected from BATMAN-TCM， GeneCards， and Online Mendelian Inheritance in Man（OMIM） databases. The protein-protein interaction（PPI） network was constructed by using intersection targets， and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part， a mouse model of HAPE induced by hypobaric hypoxia（simulated 6 000 m altitude for 48 h） was established. The control effect was evaluated by hematoxylin-eosin（HE） staining， lung tissue water content， lung tissue wet/dry weight ratio， real-time quantitative polymerase chain reaction（Real-time PCR） detection of gene expression levels， and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL， 2 142 targets， 716 HAPE-related targets， and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin （IL）-6， tumor necrosis factor （TNF）， protein kinase B1 （Akt1）， and hypoxia-inducible factor-1α （HIF-1α） were screened. The results of GO analysis of common targets involved 738 biological processes（BP）， 72 cellular components（CC）， and 135 molecular functions（MF）. KEGG analysis effectively enriched two important signaling pathways： Phosphoinositol 3-kinase （PI3K）/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia（6 000 m， 48 h）， the lung tissue water content， lung tissue wet/dry weight ratio， and pathological injury score of the model group were significantly increased（P<0.01）， accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium， a significant increase in inflammatory cells， a significant widening of the alveolar septum， and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes（P<0.01）. The results of inflammatory factor expression showed that compared with the control group， the model group showed significantly up-regulated expression of TNF-α， IL-6， and IL-1β in the lung tissue（P<0.01）. Compared with the model group， the XQL administration group had significantly decreased expression of inflammatory factors（P<0.05， P<0.01）. The mRNA expression of key pathway related genes PI3K， Akt1， mammalian target of rapamycin（mTOR）， and HIF-1α was significantly increased in the model group（P<0.01）， and decreased in a concentration-dependent manner after XQL administration（P<0.05， P<0.01）. The expression levels of key proteins PI3K， phosphorylation（p）-PI3K， Akt1， p-Akt1， mTOR， p-mTOR， and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group， the model group showed increased expression of key proteins（P<0.05， P<0.01）. Compared with the model group， the XQL administration group exhibited decreased expression of key proteins（P<0.05， P<0.01）. ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.

Objective: To develop a depression recognition model by integrating the spirit-expression diagnostic framework of traditional Chinese medicine (TCM) with machine learning algorithms. The proposed model seeks to establish a TCM-informed tool for early depression screening, thereby bridging traditional diagnostic principles with modern computational approaches. Methods: The study included patients with depression who visited the Shanghai Pudong New Area Mental Health Center from October 1, 2022 to October 1, 2023, as well as students and teachers from Shanghai University of Traditional Chinese Medicine during the same period as the healthy control group. Videos of 3 – 10 s were captured using a Xiaomi Pad 5, and the TCM spirit and expressions were determined by TCM experts (at least 3 out of 5 experts agreed to determine the category of TCM spirit and expressions). Basic information, facial images, and interview information were collected through a portable TCM intelligent analysis and diagnosis device, and facial diagnosis features were extracted using the Open CV computer vision library technology. Statistical analysis methods such as parametric and non-parametric tests were used to analyze the baseline data, TCM spirit and expression features, and facial diagnosis feature parameters of the two groups, to compare the differences in TCM spirit and expression and facial features. Five machine learning algorithms, including extreme gradient boosting (XGBoost), decision tree (DT), Bernoulli naive Bayes (BernoulliNB), support vector machine (SVM), and k-nearest neighbor (KNN) classification, were used to construct a depression recognition model based on the fusion of TCM spirit and expression features. The performance of the model was evaluated using metrics such as accuracy, precision, and the area under the receiver operating characteristic (ROC) curve (AUC). The model results were explained using the Shapley Additive exPlanations (SHAP). Results: A total of 93 depression patients and 87 healthy individuals were ultimately included in this study. There was no statistically significant difference in the baseline characteristics between the two groups (P > 0.05). The differences in the characteristics of the spirit and expressions in TCM and facial features between the two groups were shown as follows. (i) Quantispirit facial analysis revealed that depression patients exhibited significantly reduced facial spirit and luminance compared with healthy controls (P < 0.05), with characteristic features such as sad expressions, facial erythema, and changes in the lip color ranging from erythematous to cyanotic. (ii) Depressed patients exhibited significantly lower values in facial complexion L, lip L, and a values, and gloss index, but higher values in facial complexion a and b, lip b, low gloss index, and matte index (all P < 0.05). (iii) The results of multiple models show that the XGBoost-based depression recognition model, integrating the TCM “spirit-expression” diagnostic framework, achieved an accuracy of 98.61% and significantly outperformed four benchmark algorithms—DT, BernoulliNB, SVM, and KNN (P < 0.01). (iv) The SHAP visualization results show that in the recognition model constructed by the XGBoost algorithm, the complexion b value, categories of facial spirit, high gloss index, low gloss index, categories of facial expression and texture features have significant contribution to the model. Conclusion This study demonstrates that integrating TCM spirit-expression diagnostic features with machine learning enables the construction of a high-precision depression detection model, offering a novel paradigm for objective depression diagnosis.

Objective: To explore the association between types of obesity and 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among hypertensive patients, so as to provide the basis for formulating ASCVD prevention strategies for hypertensive patients. Methods: From January to December 2021, hypertensive patients who were under follow-up management and completed health examinations at three community health service centers in Linping District, Hangzhou City were selected by a cluster sampling method. Basic information, lifestyle, disease history, height, weight, waist circumference (WC), and blood biochemical indicators were collected through health examination data. Based on assessments of body mass index (BMI) and WC, participants were categorized into four types: non-obese, general obesity only, central obesity only, and combined obesity. The Prediction for ASCVD risk in China (China-PAR) was used to assess 10-year ASCVD risk, which was categorized as low, moderate, and high risk. Multivariable logistic regression models were used to analyze the association between different types of obesity and ASCVD risk among hypertensive patients. Results: A total of 10 408 hypertensive patients were included, with a median age of 68.00 (interquartile range, 10.00) years. There were 4 301 (41.32%) males and 6 107 (58.68%) females. The proportions of non-obese, general obesity only, central obesity only, and combined obesity were 34.93% (3 635 individuals), 22.85% (2 378 individuals), 4.32% (450 individuals), and 37.90% (3 945 individuals), respectively. There were 3 389 (33.52%) cases at high risk of ASCVD. Among them, high ASCVD risk was observed in 1 107 (30.45%), 896 (37.68%), 122 (27.11%), and 1 364 (34.58%) patients with non-obese, general obesity only, central obesity only, and combined obesity, respectively. Multivariable logistic regression analysis showed that after adjusting for gender, age, smoking, drinking, physical activity, and diabetes, the risk of high ASCVD in hypertensive patients with general obesity only and combined obesity was 1.383 times (95%CI: 1.235-1.548) and 1.225 times (95%CI: 1.109-1.354) that of non-obese hypertensive patients, respectively. Conclusions General obesity only and combined obesity can increase the 10-year high risk of ASCVD among hypertensive patients. It is necessary to strengthen comprehensive management of body weight and WC among hypertensive patients to reduce the risk of ASCVD.

ObjectiveTo investigate the effect of Yaoshu Zhuyu Fang on the regulation of the microRNA-17-5P (miR-17-5P)/murine double minute 2 (MDM2)/p53 axis in the proliferation and apoptosis of rat intervertebral disc annulus fibrosus cells, and its potential molecular mechanism. MethodsIntervertebral disc annulus fibrosus tissues were obtained from 8-week-old SPF-grade male SD rats, and annulus fibrosus cells were isolated and obtained by enzyme digestion and mechanical dispersion. Annulus fibrosus cells were divided into 6 groups: Group C was the blank control group, in which annulus fibrosus cells were not treated with interleukin-1β (IL-1β) but were cultured in RPMI 1640 complete medium. Group β was the degeneration model group constructed by treating annulus fibrosus cells with 10 ng/mL IL-1β for 24 h. Group β+B was the IL-1β + blank serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% blank serum for 24 h. Group β+W was the IL-1β + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. Group β+I was the IL-1β + miR-17-5P inhibitor group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor. Group β+I+W was the IL-1β + miR-17-5P inhibitor + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor, and finally treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. CCK-8 assay was used to detect cell survival rate. Flow cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used to detect the expression levels of miR-17-5P, MDM2 mRNA, and p53 mRNA in cells. Western blotting was used to detect the protein expression levels of MDM2 and p53 in cells. Dual-luciferase reporter system was used to analyze the targeting relationship between miR-17-5P and MDM2. ResultsCompared with Group C, Group β showed a significant decrease in cell survival rate (P<0.001), a significant increase in cell apoptosis rate (P<0.001), significantly increased expression of miR-17-5P, p53 mRNA, and p53 protein (P<0.001), and significantly decreased expression of MDM2 mRNA and protein (P<0.001). Compared with Group β, Group β+W, Group β+I, and Group β+I+W showed significantly increased cell survival rate, significantly decreased apoptosis rate, significantly decreased expression of miR-17-5P, p53 mRNA, and p53 protein, and significantly increased expression of MDM2 mRNA and protein (P<0.001). Moreover, changes in the above indicators were greater in Group β+I+W (P<0.001). Circular RNA Interactome predicted that miR-17-5P had specific binding sites with the 3' untranslated region (3'UTR) of MDM2. Transfection of miR-17-5P mimic significantly reduced the luciferase expression level of co-transfected luciferase reporter plasmid containing wild-type MDM2 3'UTR (P<0.05), but had no significant effect on luciferase expression in cells co-transfected with luciferase reporter plasmid containing mutant MDM2 3'UTR (P>0.05). ConclusionYaoshu Zhuyu Fang down-regulates the expression of miR-17-5P, promotes the synthesis of MDM2 protein, thereby down-regulates p53, promotes proliferation, and inhibits the apoptosis of rat intervertebral disc annulus fibrosus cells.

OBJECTIVE To evaluate the clinical efficacy of dapagliflozin in patients with pulmonary hypertension associated with left heart disease （PH-LHD） and its effect on prognosis， and to provide evidence for its clinical application. METHODS A total of 135 hospitalized patients with PH-LHD admitted to Wuxi No. 2 People’s Hospital from January 1， 2023 to June 30， 2025 were retrospectively included. According to the treatment regimen， the patients were divided into a control group （74 cases， receiving conventional treatment） and a dapagliflozin group （61 cases， receiving dapagliflozin in addition to conventional treatment）. Blood pressure [systolic blood pressure， diastolic blood pressure， and pulmonary artery systolic pressure （PASP）]， echocardiographic cardiac function parameters [cardiac output， cardiac index， left ventricular ejection fraction （LVEF）， right ventricular ejection fraction （RVEF）， left atrial diameter， and left ventricular wall thickness]， inflammatory factors [interleukin-6 （IL-6） and high-sensitivity C-reactive protein （hs-CRP）]， brain natriuretic peptide （BNP）， and 6-minute walking distance （6MWD） were compared between the two groups before treatment and after 12 weeks of treatment. All-cause mortality and the frequency of rehospitalization due to worsening heart failure during follow-up were also compared. RESULTS After 12 weeks of treatment， systolic blood pressure， diastolic blood pressure， PASP， left atrial diameter， IL-6， hs-CRP， and BNP levels were significantly decreased or shortened in both groups， while cardiac index and 6MWD were significantly increased or prolonged compared with those before treatment （ P ＜0.05）. Cardiac output in the dapagliflozin group was significantly increased compared with that before treatment （ P ＜0.05）. Systolic blood pressure， PASP， left atrial diameter， IL-6， hs-CRP， and BNP levels in the dapagliflozin group were significantly lower or shorter than those in the control group， while cardiac output， cardiac index， and 6MWD were significantly higher or longer than those in the control group （ P ＜0.05）. There were no statistically significant differences in LVEF， RVEF， or left ventricular wall thickness between the two groups （ P ＞0.05）. The median follow-up times in the control group and dapagliflozin group were 17.9 months and 17.3 months， respectively. During follow-up， all-cause mortality in the dapagliflozin group was lower than that i n the control group， but the difference was not statistically significant （ P ＞0.05）； the frequency of rehospitalization due to worsening heart failure was significantly lower than that in the control group （ P ＜0.05）. CONCLUSIONS On the basis of conventional treatment， the addition of dapagliflozin can further reduce pulmonary artery pressure， inflammatory factor levels， and BNP levels in patients with PH-LHD， improve some cardiac function-related parameters and exercise tolerance， and reduce the frequency of rehospitalization due to worsening heart failure.

[Objective] To analyze the influencing factors of repeat blood donor lapsing using a zero-inflated poisson regression model (ZIP). [Methods] The blood donation behavior of 12 498 whole blood donors from 2020 was tracked until December 31, 2023. The factors influencing the frequency of blood donations in a given year was analyzed using ZIP, and donors with 0 blood donation in that year were considered to have lapsed. The changes in relevant influencing factors associated with each blood donation were measured and modeled for analysis. [Results] The zero-inflated part of ZIP showed that the risk of lapsing of male blood donors was 2.24 times that of female blood donors (OR 95% CI:1.864-2.696, P<0.001); the risk of lapsing of the 35-44 age group and over 45 age group was respectively 40% (OR 95% CI:0.455-0.790, P<0.001) and 61%(OR 95% CI:0.268-0.578, P<0.001) lower than that of the under 25 age group; the risk of lapsing for those who have donated blood twice and ≥3 times was respectively 50% (OR 95% CI:0.405-0.609, P<0.001) and 81% (OR 95% CI:0.154-0.225, P<0.001) lower than that of first-time donors; the risk of lapsing of those with junior high or high school education was 1.2 times that of those with a college degree or higher (OR 95% CI:1.033-1.384, P<0.05); the risk of lapsing for the divorced group was 2.02 times that of the married group (OR 95% CI:1.445-2.820, P<0.001); the risk of lapsing for those with an income (Yuan) of 10 000 to 50 000, 50 000 to 100 000 and more than 100 000 was respectively 0.67 (OR 95% CI:0.552-0.818, P<0.001), 0.72 (OR 95% CI:0.591-0.884, P=0.002) and 0.67 (OR 95% CI:0.535-0.834, P<0.001) times that of those with an income (Yuan) of less than 10 000. The results of the Poisson part are consistent with the results of the zero-inflated part in terms of age and education level. [Conclusion] Blood donor lapsing is overall related to factors such as gender, age, donation frequency, education, marital status and family income. It's essential to care for those blood donors prone to lapse to retain more regular blood donors.

BACKGROUND:Prostaglandin E1(PGE1)has been shown to play a regulatory role in vasodilatation,inflammation,and leukocyte migration and adhesion,but its effects on spinal cord microcirculation after traumatic spinal cord injury(SCI)remain poorly understood. OBJECTIVE:To investigate the mechanism underlying the protective effects of PGE1 administered during the acute phase of traumatic SCI in rats on the regulation of vascular-related factors and microcirculatory function. METHODS:Seventy-two female Sprague-Dawley rats were divided into three groups(n=24 per group):control group,SCI group,and PGE1 group.An in vivo SCI model was established using Allen's blow method.Rats in the PGE1 group were injected with PGE1(10 μg/kg)via the tail vein immediately after SCI.Spinal cord microcirculatory blood flow and oxygen saturation,spinal cord microvessel diameter and area,spinal cord water content,vascular function regulators(von Willebrand factor,thromboxane A2,prostacyclin,endothelin-1),and inflammatory factors(tumor necrosis factor-α,interleukin-1β)were measured at 2 and 24 hours after SCI. RESULTS AND CONCLUSION:At 2 hours after SCI,the diameter and area of spinal cord microvessels,spinal cord microcirculatory blood flow,and oxygen saturation in the PGE1 group were higher than those in the SCI group(P<0.05),the water content of the spinal cord was lower than that in the SCI group(P<0.05),and the level of plasma von Willebrand Factor,the ratio of thromboxane A2/prostacyclin of the spinal cord and the level of endothelin-1 were lower than those in the SCI group(P<0.05).At 24 hours after SCI,the spinal cord microvessel area,blood flow,and oxygen saturation of rats in the PGE1 group were higher than those in the SCI group(P<0.05),the spinal cord water content was lower than that in the SCI group(P<0.05),and the levels of plasma von Willebrand factor,spinal cord tissue thromboxane A2/prostacyclin ratio and the levels of endothelin-1,tumor necrosis factor-α and interleukin-1β were lower than those in the SCI group(P<0.05).The diameter and area of spinal cord microvessels,spinal cord microcirculatory blood flow and blood oxygen saturation of rats in the SCI group were higher than those in the SCI group at 24 hours post-injury(P<0.05),and the levels of plasma von Willebrand factor,spinal tissue thromboxane A2/prostacyclin ratio,tumor necrosis factor-α and interleukin-1β were higher than those at 2 hours post-injury(P<0.05),but the level of endothelin-1 in spinal cord tissue was lower than that at 2 hours(P<0.05).The blood flow and oxygen saturation of spinal cord microcirculation in the PGE1 group rats at 24 hours post-injury were lower than those at 2 hours post-injury(P<0.05),and the diameter and area of spinal cord microvessels and water content of the spinal cord were higher than those at 2 hours post-injury(P<0.05).The above results indicate that intravenous administration of PGE1 in SCI rats immediately after injury can regulate vascular function regulators,inflammatory factors and improve microcirculation of the spinal cord after SCI,which provides a potential basis for the search of drugs for the treatment of acute SCI.

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.