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.

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 explore the effect of aerobic exercise on sarcopenia in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism.Methods Forty-eight SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group(group NC,n=12),a normal control+aerobic exercise group(group NA,n=12),a CT26 tumor-associated sarco-penia group(group TS,n=12)and a CT26 tumor-associated sarcopenia+aerobic exercise group(group TSA,n=12).After a 2-week adaptive exercise period,CT26 cell suspension(0.2 mL,1×107 cells/mL)was subcutaneously injected into the dorsal region of mice in group TS and group TSA,while group NC and group NA were inoculated with 0.2 mL normal saline.One day later,group NA and group TSA underwent a 4-week aerobic treadmill running intervention(14 m/min,60 min/day,6 days/week).If a mouse failed to complete the target intensity on a given day,its running speed was reduced by 20%the following day.Moreover,group NA and group TSA received no exercise interven-tion.General health status of all groups was monitored throughout the study.The forelimb gripping force,rotarod walking time and the cross-sectional area of gastrocnemius muscle fibers were measured.Moreover,the ultrastructural changes of gastrocnemius were observed by transmission electron micro-scope,while the cecum contents were observed by 16S rRNA sequencing.Meanwhile,the pathological morphological changes of small intestine wall were observed using HE,while the contents of tumor ne-crosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)and lipopoly saccharide(LPS)of serum and gastrocnemius muscle were determined by using ELISA.Moreover,small intestine zonula occludens-1(ZO-1),Occludin and muscle ring finger 1(MuRF1),muscle atrophy F-box(MAF-bx),Toll-like receptor 4(TLR4)/myeloid differentiation factor 8(MyD88)/nuclear transcription factor-κB(NF-κB)signal pathway related proteins expression levels of gastrocnemius muscle,as well as muscle ring finger 1(MuRF1)and muscle atrophy F-box(MAF-bx)were detected using Western blot.Results(1)Subcutaneous tumors were prominent in group TS.The forelimb gripforce,wet weight and cross-sectional area of gastrocnemius,and rotarod walking time in group TS at the 5th and 6th weekends were significantly lower than group NC(P<0.01),while the relative expression levels of MuRF1 and MAF-bx proteins in the gastrocnemius muscle in group TS were significantly higher than the latter group(P<0.05,P<0.01).Moreover,transmission electron microscopy revealed sparse and dis-organized muscle fiber arrangement in group TS,with visible Z-lines but indistinct M-lines,as well as shortened,poorly defined,and thin sarcomeres.(2)The group TSA exhibited significantly higher α-diversity indices(Shannon,Chao1,and Observed species)in gut microbiota compared to group TS(P<0.05,P<0.01,P<0.05),while the β-diversity differed to some extent between the two groups.At phylum level,the F/B ratio was lower in group NA than that group NC,with that of group TSA low-er than group TS.At genus level,the relative abundances of Muribaculaceae,Bacteroides,Roseburia,and Alistipes in group NA were higher than group NC,and those of Alloprevotellaand Helicobacter were significantly lower,while those of Muribaculaceae,Lachnospiraceae_NK4A136_group,Roseburia,Bacteroides,Lachnospiraceae_UCG-001 of group TSA were significantly higher than group TS.Nota-bly,Roseburia and Alistipes were the most significantly enriched genera in group TSA and group TS(LDA score>4 for both).(3)The inflammatory cells of the small intestine wall in group TSA signifi-cantly reduced than those in group TS(P<0.05).Moreover,the expression level of ZO-1 proteins in the small intestine wall were significantly higher in group NA than group NC,and that of ZO-1 and Occludin proteins in the small intestine wall was significantly higher in group TSA than those in group TS(P<0.05).(4)The group NA exhibited significantly lower LPS concentrations in the gastrocne-mius muscle compared to group NC(P<0.05).Similarly,the group TSA showed reduced LPS levels in both serum and gastrocnemius compared to group TS(P<0.05).The relative protein expression of p-IκBα and p-NF-κB p65 significantly decreased in group TSA compared to group TS(P<0.05).The group TS displayed elevated concentrations of pro-inflammatory cytokines(TNF-α,IL-1β)in serum and gastrocnemius compared to group NC(P<0.01,P<0.05).The group TSA demonstrated significantly lower levels of TNF-α and IL-6 in these tissues in comparison with group TS(P<0.05,P<0.01).Conclusion Aerobic exercise can improve gut microbiota α diversity,adjusting its composition,improv-ing intestinal mucosal barrier function,reducing the LPS-induced pro-inflammatory response,and delay-ing skeletal muscle atrophy.The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle,which has a positive effect on Gut-Muscle Axis.

Background and Aims:Tumor deposits(TDs)may influence prognosis beyond the current 8th edition AJCC pTNM nodal classification in gastric cancer(GC).This study investigates the prognostic value of TD number and proposes an improved pN staging(mpN)that classifies patients with TD number>1 as pN3b.We validated the mpN staging against the 8th AJCC pN staging.Methods:A dual-center retrospective cohort study was performed,including 1 327 patients who underwent radical gastrectomy at Sun Yat-sen University Cancer Center(2011-2015;test cohort)and 340 patients from Guangdong Provincial People's Hospital(2015-2022;validation cohort).Patients were dichotomized into low-TD(≤1)and high-TD(>1)groups.Outcomes were overall survival(OS)and disease-free survival(DFS).Survival analyses used Kaplan-Meier curves,IPTW,and Cox regression.Predictive performance of staging systems was assessed by time-dependent ROC(tROC)/tAUC,concordance index(C-index)and Akaike information criterion(AIC).Results:TDs were present in 435/1 327(32.7%)in the test cohort.Presence of TD was associated with worse OS(IPTW-adjusted HR=2.69,95%CI=2.18-3.31,P<0.01)and DFS(HR=2.82,95%CI=2.32-3.42,P<0.01).In multivariable models,TD remained an independent adverse factor for OS(HR=1.65,95%CI=1.34-2.05;P<0.01)and DFS(HR=1.74,95%CI=1.43-2.11,P<0.01).Increasing TD number correlated with progressively poorer survival;X-tile identified>1 as an optimal cutoff,with high-TD patients showing markedly worse outcomes(OS:adjusted HR=3.65,95%CI=2.74-4.88;DFS:adjusted HR=3.74,95%CI=2.85-4.91;both P<0.01).Incorporation of TD number into the mpN staging(assigning TD>1 to pN3b)improved prognostic discrimination:in the test cohort 5-year OS tAUC was 0.746 for mpN vs.0.703 for AJCC pN(C-index 0.738 vs.0.721,AIC 5 805.27 vs.5 849.30);similar improvements were observed in the validation cohort.Conclusion:TD presence and number exert significant negative prognostic impact in GC.Classifying patients with TD number>1 as pN3b enhances prognostic accuracy.Routine reporting of TD counts and further prospective multicenter validation of mpN staging are warranted.

Objective:To explore the diagnostic value of serum soluble semaphorin 4D (sSema4D) and soluble CD40 ligand (sCD40L) in left ventricular hypertrophy (LVH) in patients with primary hypertension (EH).Methods:Eighty-four patients with EH combined with LVH admitted to Qingdao Hospital of Shandong First Medical University from December 2022 to December 2023 were prospectively selected as the study group, and 84 patients with EH and without LVH admitted to Qingdao Hospital of Shandong First Medical University during the same period were regarded as the control group. Enzyme linked immunosorbent assay was applied to detect the levels of sSema4D and sCD40L. Employing Pearson correlation coefficient, the study assessed the association between concentrations of sSema4D and sCD40L in serum and various echocardiographic measurements. A multivariate Logistic regression model was engaged to probe into the contributing factors for the development of LVH. ROC curve was plotted to analyze the diagnostic value of serum sSema4D and sCD40L for EH combined with LVH.Results:Serum sSema4D and sCD40L levels were significantly higher in the study group than in the control group: (8.56 ± 2.19) μg/L vs. (5.12 ± 1.43) μg/L, (4.02 ± 1.03) μg/L vs. (3.22 ± 0.98) μg/L, and the differences were statistically significant ( P<0.05). The duration of hypertension, LVEDD, IVSTD, LVPWT, and LVMI were significantly higher in the study group than in the control group: (7.33 ± 1.53) years vs. (4.26 ± 1.35) years, (50.28 ± 3.33) mm vs. (44.45 ± 3.76) mm, (11.64 ± 3.21) mm vs. (9.53 ± 2.89) mm, (12.45 ± 1.52) mm vs. (9.13 ± 0.98) mm, (126.11 ± 15.28) g/m 2 vs. (81.15 ± 11.31) g/m 2, and the differences were statistically significant ( P<0.05). According to Pearson correlation analysis, it was known that both serum sSema4D and sCD40L were positively correlated with LVEDD, IVSTD, LVPWT and LVMI ( r = 0.425 and 0.533, 0.612 and 0.436, 0.513 and 0.628, 0.589 and 0.618; P<0.05). Multivariate Logistic regression analysis showed that hypertension duration, LVEDD, IVSTD, LVPWT, LVMI, sSema4D, sCD40L were risk factors for LVH in EH patients ( P<0.05). According to the ROC curve, the AUC for diagnosing EH combined with LVH with serum sSema4D was 0.848, the AUC for diagnosing EH combined with LVH with serum sCD40L was 0.725, and the AUC for diagnosing EH combined with LVH with serum sCD40L was 0.888, the combination of sCD40L and sCD40L was superior to their respective individual diagnoses ( Z = 2.651 and 2.526, P<0.05). Conclusions:The serum levels of sSema4D and sCD40L in patients with EH combined with LVH are obviously elevated, which are influencing factors for the occurrence of EH combined with LVH. Combined testing of the two has high diagnostic value for EH combined with LVH.

Objective To explore the effect of aerobic exercise on sarcopenia in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism.Methods Forty-eight SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group(group NC,n=12),a normal control+aerobic exercise group(group NA,n=12),a CT26 tumor-associated sarco-penia group(group TS,n=12)and a CT26 tumor-associated sarcopenia+aerobic exercise group(group TSA,n=12).After a 2-week adaptive exercise period,CT26 cell suspension(0.2 mL,1×107 cells/mL)was subcutaneously injected into the dorsal region of mice in group TS and group TSA,while group NC and group NA were inoculated with 0.2 mL normal saline.One day later,group NA and group TSA underwent a 4-week aerobic treadmill running intervention(14 m/min,60 min/day,6 days/week).If a mouse failed to complete the target intensity on a given day,its running speed was reduced by 20%the following day.Moreover,group NA and group TSA received no exercise interven-tion.General health status of all groups was monitored throughout the study.The forelimb gripping force,rotarod walking time and the cross-sectional area of gastrocnemius muscle fibers were measured.Moreover,the ultrastructural changes of gastrocnemius were observed by transmission electron micro-scope,while the cecum contents were observed by 16S rRNA sequencing.Meanwhile,the pathological morphological changes of small intestine wall were observed using HE,while the contents of tumor ne-crosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)and lipopoly saccharide(LPS)of serum and gastrocnemius muscle were determined by using ELISA.Moreover,small intestine zonula occludens-1(ZO-1),Occludin and muscle ring finger 1(MuRF1),muscle atrophy F-box(MAF-bx),Toll-like receptor 4(TLR4)/myeloid differentiation factor 8(MyD88)/nuclear transcription factor-κB(NF-κB)signal pathway related proteins expression levels of gastrocnemius muscle,as well as muscle ring finger 1(MuRF1)and muscle atrophy F-box(MAF-bx)were detected using Western blot.Results(1)Subcutaneous tumors were prominent in group TS.The forelimb gripforce,wet weight and cross-sectional area of gastrocnemius,and rotarod walking time in group TS at the 5th and 6th weekends were significantly lower than group NC(P<0.01),while the relative expression levels of MuRF1 and MAF-bx proteins in the gastrocnemius muscle in group TS were significantly higher than the latter group(P<0.05,P<0.01).Moreover,transmission electron microscopy revealed sparse and dis-organized muscle fiber arrangement in group TS,with visible Z-lines but indistinct M-lines,as well as shortened,poorly defined,and thin sarcomeres.(2)The group TSA exhibited significantly higher α-diversity indices(Shannon,Chao1,and Observed species)in gut microbiota compared to group TS(P<0.05,P<0.01,P<0.05),while the β-diversity differed to some extent between the two groups.At phylum level,the F/B ratio was lower in group NA than that group NC,with that of group TSA low-er than group TS.At genus level,the relative abundances of Muribaculaceae,Bacteroides,Roseburia,and Alistipes in group NA were higher than group NC,and those of Alloprevotellaand Helicobacter were significantly lower,while those of Muribaculaceae,Lachnospiraceae_NK4A136_group,Roseburia,Bacteroides,Lachnospiraceae_UCG-001 of group TSA were significantly higher than group TS.Nota-bly,Roseburia and Alistipes were the most significantly enriched genera in group TSA and group TS(LDA score>4 for both).(3)The inflammatory cells of the small intestine wall in group TSA signifi-cantly reduced than those in group TS(P<0.05).Moreover,the expression level of ZO-1 proteins in the small intestine wall were significantly higher in group NA than group NC,and that of ZO-1 and Occludin proteins in the small intestine wall was significantly higher in group TSA than those in group TS(P<0.05).(4)The group NA exhibited significantly lower LPS concentrations in the gastrocne-mius muscle compared to group NC(P<0.05).Similarly,the group TSA showed reduced LPS levels in both serum and gastrocnemius compared to group TS(P<0.05).The relative protein expression of p-IκBα and p-NF-κB p65 significantly decreased in group TSA compared to group TS(P<0.05).The group TS displayed elevated concentrations of pro-inflammatory cytokines(TNF-α,IL-1β)in serum and gastrocnemius compared to group NC(P<0.01,P<0.05).The group TSA demonstrated significantly lower levels of TNF-α and IL-6 in these tissues in comparison with group TS(P<0.05,P<0.01).Conclusion Aerobic exercise can improve gut microbiota α diversity,adjusting its composition,improv-ing intestinal mucosal barrier function,reducing the LPS-induced pro-inflammatory response,and delay-ing skeletal muscle atrophy.The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle,which has a positive effect on Gut-Muscle Axis.

Background and Aims:Tumor deposits(TDs)may influence prognosis beyond the current 8th edition AJCC pTNM nodal classification in gastric cancer(GC).This study investigates the prognostic value of TD number and proposes an improved pN staging(mpN)that classifies patients with TD number>1 as pN3b.We validated the mpN staging against the 8th AJCC pN staging.Methods:A dual-center retrospective cohort study was performed,including 1 327 patients who underwent radical gastrectomy at Sun Yat-sen University Cancer Center(2011-2015;test cohort)and 340 patients from Guangdong Provincial People's Hospital(2015-2022;validation cohort).Patients were dichotomized into low-TD(≤1)and high-TD(>1)groups.Outcomes were overall survival(OS)and disease-free survival(DFS).Survival analyses used Kaplan-Meier curves,IPTW,and Cox regression.Predictive performance of staging systems was assessed by time-dependent ROC(tROC)/tAUC,concordance index(C-index)and Akaike information criterion(AIC).Results:TDs were present in 435/1 327(32.7%)in the test cohort.Presence of TD was associated with worse OS(IPTW-adjusted HR=2.69,95%CI=2.18-3.31,P<0.01)and DFS(HR=2.82,95%CI=2.32-3.42,P<0.01).In multivariable models,TD remained an independent adverse factor for OS(HR=1.65,95%CI=1.34-2.05;P<0.01)and DFS(HR=1.74,95%CI=1.43-2.11,P<0.01).Increasing TD number correlated with progressively poorer survival;X-tile identified>1 as an optimal cutoff,with high-TD patients showing markedly worse outcomes(OS:adjusted HR=3.65,95%CI=2.74-4.88;DFS:adjusted HR=3.74,95%CI=2.85-4.91;both P<0.01).Incorporation of TD number into the mpN staging(assigning TD>1 to pN3b)improved prognostic discrimination:in the test cohort 5-year OS tAUC was 0.746 for mpN vs.0.703 for AJCC pN(C-index 0.738 vs.0.721,AIC 5 805.27 vs.5 849.30);similar improvements were observed in the validation cohort.Conclusion:TD presence and number exert significant negative prognostic impact in GC.Classifying patients with TD number>1 as pN3b enhances prognostic accuracy.Routine reporting of TD counts and further prospective multicenter validation of mpN staging are warranted.

Objective:To explore the diagnostic value of serum soluble semaphorin 4D (sSema4D) and soluble CD40 ligand (sCD40L) in left ventricular hypertrophy (LVH) in patients with primary hypertension (EH).Methods:Eighty-four patients with EH combined with LVH admitted to Qingdao Hospital of Shandong First Medical University from December 2022 to December 2023 were prospectively selected as the study group, and 84 patients with EH and without LVH admitted to Qingdao Hospital of Shandong First Medical University during the same period were regarded as the control group. Enzyme linked immunosorbent assay was applied to detect the levels of sSema4D and sCD40L. Employing Pearson correlation coefficient, the study assessed the association between concentrations of sSema4D and sCD40L in serum and various echocardiographic measurements. A multivariate Logistic regression model was engaged to probe into the contributing factors for the development of LVH. ROC curve was plotted to analyze the diagnostic value of serum sSema4D and sCD40L for EH combined with LVH.Results:Serum sSema4D and sCD40L levels were significantly higher in the study group than in the control group: (8.56 ± 2.19) μg/L vs. (5.12 ± 1.43) μg/L, (4.02 ± 1.03) μg/L vs. (3.22 ± 0.98) μg/L, and the differences were statistically significant ( P<0.05). The duration of hypertension, LVEDD, IVSTD, LVPWT, and LVMI were significantly higher in the study group than in the control group: (7.33 ± 1.53) years vs. (4.26 ± 1.35) years, (50.28 ± 3.33) mm vs. (44.45 ± 3.76) mm, (11.64 ± 3.21) mm vs. (9.53 ± 2.89) mm, (12.45 ± 1.52) mm vs. (9.13 ± 0.98) mm, (126.11 ± 15.28) g/m 2 vs. (81.15 ± 11.31) g/m 2, and the differences were statistically significant ( P<0.05). According to Pearson correlation analysis, it was known that both serum sSema4D and sCD40L were positively correlated with LVEDD, IVSTD, LVPWT and LVMI ( r = 0.425 and 0.533, 0.612 and 0.436, 0.513 and 0.628, 0.589 and 0.618; P<0.05). Multivariate Logistic regression analysis showed that hypertension duration, LVEDD, IVSTD, LVPWT, LVMI, sSema4D, sCD40L were risk factors for LVH in EH patients ( P<0.05). According to the ROC curve, the AUC for diagnosing EH combined with LVH with serum sSema4D was 0.848, the AUC for diagnosing EH combined with LVH with serum sCD40L was 0.725, and the AUC for diagnosing EH combined with LVH with serum sCD40L was 0.888, the combination of sCD40L and sCD40L was superior to their respective individual diagnoses ( Z = 2.651 and 2.526, P<0.05). Conclusions:The serum levels of sSema4D and sCD40L in patients with EH combined with LVH are obviously elevated, which are influencing factors for the occurrence of EH combined with LVH. Combined testing of the two has high diagnostic value for EH combined with LVH.

Objective:To investigate the relationship between the expression levels of serum glycogen synthase kinase-3β (GSK-3β) and mothers against decapentaplegic homolog 4 (SMAD4) in patients with acute coronary syndrome (ACS) and the severity and prognosis of coronary artery disease.Methods:A total of 192 ACS patients admitted to Shandong First Medical University Affiliated Qingdao Hospital from June 2020 to May 2022 were selected as the ACS group, while 192 non ACS patients admitted to the same hospital were selected as the non ACS group. Enzyme-linked immunosorbent assay method was applied to determine the expression levels of serum GSK-3β and SMAD4 in two groups. The Gensini score was applied to evaluate the degree of coronary artery disease in patients, Spearman method was applied to analyze the correlation between serum GSK-3β, SMAD4 expression levels and Gensini score in ACS patients. Receiver operating characteristic (ROC) curve was applied to analyze the predictive efficacy of serum GSK-3β and SMAD4 levels on the prognosis of ACS patients.Results:The serum levels of GSK-3β and SMAD4 in the ACS group were significantly higher than those in the non ACS group: (2.70 ± 0.40) μg/L vs. (2.24 ± 0.41) μg/L, (12.19 ± 2.10) μg/L vs. (9.79 ± 2.82) μg/L, and there were statistical differences ( P<0.05). The serum levels of GSK-3β and SMAD4 in ACS patients with mild, moderate and severe coronary artery disease increased sequentially ( P<0.05). Spearman analysis showed that serum GSK-3β and SMAD4 levels in ACS patients were positively correlated with Gensini total score ( r = 0.569 and 0.587, P<0.01). In ACS patients, 48 cases had poor prognosis, and the incidence of poor prognosis was 25.00% (48/192); 144 cases had a good prognosis. The serum levels of GSK-3β and SMAD4 in ACS patients with poor prognosis were significantly higher than those in ACS patients with good prognosis: (3.15 ± 0.53) μg/L vs. (2.55 ± 0.36) μg/L, (14.03 ± 2.08) μg/L vs. (11.58 ± 2.11) μg/L, and there were statistical differences ( P<0.05). The ROC curve result indicated that the area under the curve (AUC) for predicting poor prognosis in ACS patients with serum GSK-3β and SMAD4 levels alone and in combination was 0.799, 0.784 and 0.858, respectively, the AUC predicted by the combination of the two was obviously higher than the AUC predicted separately ( Z = 2.04 and 2.75, P = 0.041 and 0.006). Conclusions:The expression levels of GSK-3β and SMAD4 in the serum of ACS patients are abnormally elevated. They are positively correlated with the degree of coronary artery disease in ACS patients, and both have good predictive power for adverse prognosis in ACS patients, while the combined use of the two has better predictive performance.

The establishment of mother-infant bonding is closely related to maternal mental health and early growth and development of infants. This paper reviews the concept, evaluation tools, influencing factors and intervention measures of maternal-infant bonding, in order to provide a basis for promoting the normal establishment of postpartum maternal infant relationships and maternal infant health.