Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

Objectives:To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model.Methods:This is a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method, patients were randomly divided into a model group( n=166) and a validation group( n=41) according to an 4∶1 ratio. There were 118 males and 48 females in the modeling group,with an age ( M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (range: 25.0 to 81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the related factors of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,validated by internal and external validation of the model. Results:Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT, D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set, and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model( P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806, suggesting that the model had a good generalization prediction ability. Conclusions:The levels of ALT, D-dimer, and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

Objectives:To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model.Methods:This is a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method, patients were randomly divided into a model group( n=166) and a validation group( n=41) according to an 4∶1 ratio. There were 118 males and 48 females in the modeling group,with an age ( M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (range: 25.0 to 81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the related factors of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,validated by internal and external validation of the model. Results:Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT, D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set, and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model( P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806, suggesting that the model had a good generalization prediction ability. Conclusions:The levels of ALT, D-dimer, and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.