ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

Objective:To evaluate the effect of intraoperative optimization of regional cerebral oxygen saturation(rSO 2C) intervention on postoperative delirium(POD) in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass(CPB). Methods:Two hundred and seventy-three pediatric patients of both sexes, aged 28 days-6 yr, with American Society of Anesthesiologists Physical Status classification ≤Ⅳ, scheduled for elective cardiac surgery under CPB, were divided into intervention group( n=136) and control group( n=137) based on the computer random coding. In intervention group, optimized intervention measures were given when rSO 2C was below 75% of the baseline value for more than 1 min. In control group, rSO 2C was not monitored during operation, and intraoperative management was performed according to the routine monitoring indicators of pediatric cardiac surgery under CPB. The occurrence of POD within 7 days after operation was evaluated, and the duration and first occurrence time of POD were recorded. Results:Compared with control group, no significant change was found in the incidence of POD( P>0.05), the first occurrence time of POD was significantly prolonged, and the duration of POD was shortened in intervention group( P<0.05). Conclusions:Intraoperative optimization of rSO 2C intervention can delay the time to the first occurrence of POD and shorten the duration in pediatric patients undergoing cardiac surgery under CPB.

Objective:To investigate the clinical application effects of free transplantation of lobulated inguinal flaps.Methods:This study was a retrospective observational study. From July 2019 to April 2024, 34 patients with skin defect wounds whose wounds in one part met the inclusion criteria were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital, including 28 males and 6 females, aged 26 to 59 years. The wound area in the recipient area ranged from 3.0 cm×2.0 cm to 25.0 cm×20.0 cm. The lobulated inguinal flap pedicled with the branch of the superficial circumflex iliac artery were obtained in 19 patients, and the lobulated inguinal flap pedicled with the main artery of the superficial circumflex iliac artery and the superficial inferior epigastric artery were obtained in 15 patients. The total area of the flaps ranged from 6.0 cm×2.2 cm to 27.0 cm×23.0 cm. The flaps were divided into 2 to 4 lobes, and the area of each lobe ranged from 2.0 cm×1.0 cm to 17.0 cm×12.0 cm. Each lobe of the flaps was reassembled, spliced, or directly transplanted onto the wounds, and the donor wounds were sutured in layers. The survival of each lobe of the flaps and wound healing in the recipient and donor areas were observed, and the wound recovery in the recipient and donor areas were followed up. At the last follow-up, the patient's satisfaction with the efficacy was assessed by 5-grade Likert scale.Results:A small amount of necrosis appeared in the tip of one lobe of the flaps in 4 patients after surgery, which healed after trimming. The flaps of the remaining 30 patients survived. The wounds in the recipient areas healed smoothly. There was a small amount of necrosis at the suture edge of the donor areas in 3 patients, which healed after local trimming and dressing change. The donor wounds healed well in the remaining 31 patients. During the follow-up of 6 to 42 months, all the recipient wounds were well repaired, and the shape of the donor areas was good. At the last follow-up, 15 patients were very satisfied with the efficacy, 15 were relatively satisfied, and 4 were generally satisfied.Conclusions:Through preoperative ultrasonic examination and positioning, the inguinal flap is designed according to the course of blood vessels and lobulated with the branch of the superficial circumflex iliac artery or the main artery of the superficial circumflex iliac artery and the superficial inferior epigastric artery as the pedicles. The anatomical process is reliable and the blood flow of the flap after being lobulated is rich, which can meet the repair needs of various skin defect wounds. The repair effect is good, and the damage in the donor area is small, which is worthy of promotion.

Objective To elucidate the molecular mechanism of reserpine-induced depression using network toxicology,molecular docking techniques,behavioral assessments of animal models,and histopathological analyses.Methods Core targets were screened using multi-database network toxicology,followed by the construction of a protein-protein interaction network and validation of core targets through molecular docking.Sprague Dawley rats were divided randomly into control and reserpine(0.5 mg/kg)groups,and administered the corresponding treatments once daily for 4 consecutive days.Behavioral changes were assessed using the forced-swim and open-field tests.Serum neurotransmitters were quantified by enzyme-linked immunosorbent assay and neuropathological damage was observed via tissue staining.Target gene expression regulation was verified by Western blot.Results Network toxicology screening and molecular docking simulation demonstrated that reserpine exhibited significant binding affinity with the dopamine D2 receptor,cyclic-AMP response element binding protein,and serine/threonine-protein kinase 1(AKT1).Animal experiments demonstrated that reserpine-treated rats displayed depression-like behaviors,including motor inhibition(P＜0.01),with decreased serum levels of norepinephrine and 5-hydroxytryptamine(P＜0.01),respectively.Pathological observations revealed microglial proliferation in the cerebral cortex,increased apoptosis,and reduced Nissl bodies in the hippocampal CA1 region.Down-regulation of brain-derived neurotrophic factor(BDNF)in brain tissue and decreased expression of hippocampal AKT1 and phosphorylated AKT1 were also observed.Conclusions Reserpine influences monoamine transmitter metabolism and neuronal structural integrity via the inhibition of BDNF and AKT1 protein expression,resulting in depressive-like behavior and cerebral nerve damage in rats.

Objective To investigate the causal relationship between psychiatric and psychological disorders(depression,bipolar dis-order,and schizophrenia)and non-alcoholic fatty liver disease(NAFLD).Methods The two-sample Mendelian randomization(MR)method was adopted,with depression,bipolar disorder,and schizophrenia as exposure variables and NAFLD as the outcome variable.The single nucleotide polymorphisms(SNPs)independently associated with exposure variables were obtained from the summary data of the genome-wide association study(GWAS)as instrumental variables for MR analysis.The analysis results of the inverse-variance weighted(IVW)were used as the primary outcome indicators,while those of the MR Egger regression method,weighted median,and weighted mode as supplementary results.The Cochran's Q test,MR-Egger intercept,and"leave-one-out"method were used for sensi-tivity analysis.Results The results of IVW analysis showed that depression was positively correlated with the incidence risk of NAFLD(OR=1.21,95％CI:1.01-1.44,P＜0.05),while bipolar disorder was negatively correlated with the incidence risk of NAFLD(OR=0.91,95％CI:0.84-1.00,P＜0.05).No causal relationship was found between schizophrenia and NAFLD.The heterogeneity and sen-sitivity analysis supported the robustness of the results of the study.Conclusion Depression and bipolar disorder are causally associat-ed with the incidence of NAFLD.Depression is associated with an increased risk of NAFLD,while bipolar disorder is associated with a reduced risk of NAFLD.

Objective To evaluate the diagnostic value of dual-layer spectral CT(DLCT)virtual non-contrast(VNC)imaging combined with iodine maps in differentiating early post-endovascular therapy(EVT)intracranial hemorrhage from contrast extravasation.Methods Retrospective analysis of 97 patients who underwent DLCT immediately after EVT was conducted.Taking 24-hour follow-up CT/MRI as the gold standard,patients were divided into hemorrhage and non-hemorrhage groups,and their clinical data were compared.VNC CT values and iodine concentration(IC)were measured.Spearman's rank correlation was used to analyze the relationship between VNC CT and IC values,and ROC curve analysis using R software to evaluate the diagnostic performance of VNC,iodine maps,and their combination.Results Among 97 patients,51(52.6%)showed no intracranial hyperdense lesions,while 46(47.4%)with abnormal densities were analyzed.Using 24-hour postoperative CT/MRI as reference stan-dard,among the 46 patients ultimately included in the analysis,38 cases(82.6%)were non-hemorrhagic and 8 cases(17.4%)hemorrhagic.No significant differences existed in age,sex,or treatment methods(all P>0.05).VNC CT values and IC showed significantly negative correlation(r=-0.537,P<0.01).ROC analysis revealed AUCs of 0.917(95%CI:0.786～0.999)for VNC,0.878(95%CI:0.719～0.999)for IC,and 0.919(95%CI:0.812～0.999)for the combination of the two(P<0.05 for combined vs.individual methods).Optimal thresholds were 53.6 HU for VNC and 0.605 mg/ml for IC.Based on the final analysis of 46 enrolled patients,the sensitivity of VNC,iodine map,and their combination in differentiating early cerebral hemorrhage from contrast extravasation was 88.9%,94.3%,and 91.4%,respectively;the specificity 94.3%,77.8%,and 88.9%,respectively;and the accuracy 90.9%,90.9%,and 93.2%,respectively.Conclusion The DLCT VNC-iodine map combination significantly im-proves differentiation between post-EVT hemorrhage and contrast extravasation,and it is recommended for routine clinical application.

Objective To investigate the causal relationship between psychiatric and psychological disorders(depression,bipolar dis-order,and schizophrenia)and non-alcoholic fatty liver disease(NAFLD).Methods The two-sample Mendelian randomization(MR)method was adopted,with depression,bipolar disorder,and schizophrenia as exposure variables and NAFLD as the outcome variable.The single nucleotide polymorphisms(SNPs)independently associated with exposure variables were obtained from the summary data of the genome-wide association study(GWAS)as instrumental variables for MR analysis.The analysis results of the inverse-variance weighted(IVW)were used as the primary outcome indicators,while those of the MR Egger regression method,weighted median,and weighted mode as supplementary results.The Cochran's Q test,MR-Egger intercept,and"leave-one-out"method were used for sensi-tivity analysis.Results The results of IVW analysis showed that depression was positively correlated with the incidence risk of NAFLD(OR=1.21,95％CI:1.01-1.44,P＜0.05),while bipolar disorder was negatively correlated with the incidence risk of NAFLD(OR=0.91,95％CI:0.84-1.00,P＜0.05).No causal relationship was found between schizophrenia and NAFLD.The heterogeneity and sen-sitivity analysis supported the robustness of the results of the study.Conclusion Depression and bipolar disorder are causally associat-ed with the incidence of NAFLD.Depression is associated with an increased risk of NAFLD,while bipolar disorder is associated with a reduced risk of NAFLD.

Objective:To evaluate the effect of intraoperative optimization of regional cerebral oxygen saturation(rSO 2C) intervention on postoperative delirium(POD) in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass(CPB). Methods:Two hundred and seventy-three pediatric patients of both sexes, aged 28 days-6 yr, with American Society of Anesthesiologists Physical Status classification ≤Ⅳ, scheduled for elective cardiac surgery under CPB, were divided into intervention group( n=136) and control group( n=137) based on the computer random coding. In intervention group, optimized intervention measures were given when rSO 2C was below 75% of the baseline value for more than 1 min. In control group, rSO 2C was not monitored during operation, and intraoperative management was performed according to the routine monitoring indicators of pediatric cardiac surgery under CPB. The occurrence of POD within 7 days after operation was evaluated, and the duration and first occurrence time of POD were recorded. Results:Compared with control group, no significant change was found in the incidence of POD( P>0.05), the first occurrence time of POD was significantly prolonged, and the duration of POD was shortened in intervention group( P<0.05). Conclusions:Intraoperative optimization of rSO 2C intervention can delay the time to the first occurrence of POD and shorten the duration in pediatric patients undergoing cardiac surgery under CPB.

Objective To evaluate the diagnostic value of dual-layer spectral CT(DLCT)virtual non-contrast(VNC)imaging combined with iodine maps in differentiating early post-endovascular therapy(EVT)intracranial hemorrhage from contrast extravasation.Methods Retrospective analysis of 97 patients who underwent DLCT immediately after EVT was conducted.Taking 24-hour follow-up CT/MRI as the gold standard,patients were divided into hemorrhage and non-hemorrhage groups,and their clinical data were compared.VNC CT values and iodine concentration(IC)were measured.Spearman's rank correlation was used to analyze the relationship between VNC CT and IC values,and ROC curve analysis using R software to evaluate the diagnostic performance of VNC,iodine maps,and their combination.Results Among 97 patients,51(52.6%)showed no intracranial hyperdense lesions,while 46(47.4%)with abnormal densities were analyzed.Using 24-hour postoperative CT/MRI as reference stan-dard,among the 46 patients ultimately included in the analysis,38 cases(82.6%)were non-hemorrhagic and 8 cases(17.4%)hemorrhagic.No significant differences existed in age,sex,or treatment methods(all P>0.05).VNC CT values and IC showed significantly negative correlation(r=-0.537,P<0.01).ROC analysis revealed AUCs of 0.917(95%CI:0.786～0.999)for VNC,0.878(95%CI:0.719～0.999)for IC,and 0.919(95%CI:0.812～0.999)for the combination of the two(P<0.05 for combined vs.individual methods).Optimal thresholds were 53.6 HU for VNC and 0.605 mg/ml for IC.Based on the final analysis of 46 enrolled patients,the sensitivity of VNC,iodine map,and their combination in differentiating early cerebral hemorrhage from contrast extravasation was 88.9%,94.3%,and 91.4%,respectively;the specificity 94.3%,77.8%,and 88.9%,respectively;and the accuracy 90.9%,90.9%,and 93.2%,respectively.Conclusion The DLCT VNC-iodine map combination significantly im-proves differentiation between post-EVT hemorrhage and contrast extravasation,and it is recommended for routine clinical application.