ObjectiveTo investigate the anatomical features of three-dimensional （3D） reconstruction of the hepatic pedicle based on the Laennec’s capsule， as well as its application value in the development of extra-sheath dissection/occlusion clamp and precise hepatectomy. MethodsA retrospective analysis was performed for the abdominal contrast-enhanced CT data of 100 patients without anatomical abnormalities of the hepatic pedicle in The General Hospital of Western Theater Command from January 2021 to June 2024. The Hisense CAS system combined with the 3D U-net deep learning algorithm was used for 3D reconstruction of the hepatic pedicle at the level of Laennec’s capsule， and the hepatic pedicle was measured in terms of the length， outer diameter， and angle of the main trunk and branches. An extra-sheath hepatic pedicle dissection/occlusion clamp was developed based on the above measurements， and a total of 30 patients scheduled for right hemihepatectomy were enrolled and randomly divided into device group and control group， with 15 patients in each group. The two groups were compared in terms of hepatic pedicle handling time， time of operation， intraoperative blood loss， and the incidence rate of bile duct injury. The independent-samples t test was used for comparison of continuous data between two groups， and the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsThe results of 3D reconstruction revealed four variants in the main trunk branches of the hepatic pedicle， with type Ⅰ （left-right branching） accounting for 88% （88/100）， type Ⅱ （trifurcation type） accounting for 5% （5/100）， type Ⅲ （right anterior branching） accounting for 5% （5/100）， and type Ⅳ （special type） accounting for 2% （2/100）. The outer diameter of the main hepatic pedicle was 24.10±6.16 mm， the length of the left main branch was 20.59±6.38 mm， and the length of the right main branch was 21.99±7.98 mm. Compared with the control group， the device group had significantly shorter hepatic pedicle handling time （14.10±1.30 minutes vs 17.50±2.00 minutes， t=-5.620， P=0.001） and time of operation （217.00±28.28 minutes vs 241.87±19.49 minutes， t=-2.804， P=0.009）. The device group had a significantly lower incidence rate of bile duct injury than the control group （0 vs 20%， P=0.031）. Conclusion3D reconstruction based on the Laennec’s capsule can accurately display the anatomical variations of the hepatic pedicle. The extra-sheath hepatic pedicle dissection/occlusion clamp developed based on such data can optimize the process of hepatic pedicle management and improve surgical safety， and therefore， it holds promise for clinical application.

Objectives:To investigate the prognostic value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with atrial fibrillation(AF)and heart failure(HF).Methods:Patients with AF and HF from hospitals diagnosed by the Heart Failure Center in Guangdong Province between January 2017 and December 2021 were selected.Major adverse cardiovascular events(MACE)were used as the follow-up endpoint.Statistical methods such as the area under the receiver operating characteristic(ROC)curve(AUC),net reclassification index(NRI),and integrated discrimination improvement(IDI)were applied to evaluate the predictive value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with AF and HF.Results:A total of 1 839 patients were enrolled in this study,comprising 703 patients in the MACE group and 1 136 patients in the non-MACE group.Compared with the non-MACE group,the MACE group exhibited significantly advanced age,higher prevalence of New York Heart Association class Ⅳ and coronary artery disease,lower diastolic blood pressure and estimated glomerular filtration rate levels,and elevated serum N-terminal pro-B-type natriuretic peptide concentrations(all P<0.05).Additionally,significantly lower proportions of patients in the MACE group received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocorticoid receptor antagonists,or anticoagulant therapy(all P<0.05).Multivariable logistic regression analysis revealed that each 1-point increment in both CHA2DS2-VASc and R2CHA2DS2-VASc scores was associated with approximately 10%increased risk of MACE.ROC curve analysis demonstrated that the AUC values for predicting MACE in AF patients with HF were 0.555(95%CI:0.528-0.582,P<0.001)for CHA2DS2-VASc and 0.576(95%CI:0.549-0.608,P<0.001)for R2CHA2DS2-VASc,indicating marginally superior discriminatory capacity of the R2CHA2DS2-VASc score.Delong's test confirmed statistically significant differences between the two scoring systems(P=0.001).The R2CHA2DS2-VASc score demonstrated a NRI of 0.259(95%CI:0.166-0.352,P<0.001)and an IDI of 0.007(95%CI:0.005-0.010,P<0.001)compared with the conventional CHA2DS2-VASc score.Although the R2CHA2DS2-VASc score exhibited slightly better predictive accuracy and outcome discrimination capacity than the original scoring system,both scores demonstrated suboptimal clinical predictive performance.Conclusions:Both the R2CHA2DS2-VASc and CHA2DS2-VASc scores show suboptimal performance for predicting the risk of MACE in patients with AF and HF,and the predicting performance of R2CHA2DS2-VASc score is marginally superior to CHA2DS2-VASc score in this patient cohort.

OBJECTIVE To explore the potential mechanisms of forkhead box protein A1(FOXA1)in benzo[a]pyrene(BaP)-induced carcinogenesis by investigating the effect of FOXA1 by knockout on microRNA(miRNA)expression profiles in BaP malignant transformed cells THBEc1 and establishing regulatory networks between FOXA1,miRNA and their target genes.METHODS FOXA1 knockout THBEc1 cells THBEc1-ΔFOXA1-c34 and control cells THBEc1-ctrl were used as study models.Western blotting was employed to determine FOXA1 protein expression levels.Next-generation sequencing(NGS)tech-nology was used to identify differentially expressed miRNAs between THBEc1-ΔFOXA1-c34 and THBEc1-ctrl cells,with subsequent validation by RT-qPCR.Five databases(ENCORI,miRDB,mirDIP,miRWalk and TargetScan 8.0)were used in conjunction with NGS results of mRNA between THBEc1-ΔFOXA1-c34 and THBEc1-ctrl to predict different expressed genes(DEGs)regulated by the identified differentially expressed miRNAs.GO and KEGG enrichment analyses were conducted on the DEGs using the DAVID database.Interaction network analysis of the proteins encoded by the DEGs was performed using STRING 12.0 and Cytoscape 3.10.2 software.RESULTS No FOXA1 expression was detected in THBEc1-ΔFOXA1-c34 cells.A differential analysis of miRNA expressions revealed 33 miRNAs with a fold change of＞2 or＜0.5 and a false discovery rate of＜0.05 between THBEc1-ΔFOXA1-c34 and THBEc1-ctrl cells,13 of which were down-regulated and 20 were up-regulated in THBEc1-ΔFOXA1-c34 cells.A regulatory network was formed by 11 down-regulated miRNAs and 32 up-regulated mRNAs,while a second network included 16 up-regulated miRNAs and 56 down-regulated mRNAs.The 27 differentially expressed miRNAs participated in various biological processes through the regulation of 88 DEGs,primarily associated with cell growth,proliferation,migration,apoptosis,angiogenesis,epithe-lial-mesenchymal transition,and signal transduction(TGF-β,Hippo,NF-kappa B and MAPK pathways).CONCLUSION The miRNA expression profile in BaP-malignant transformed THBEc1 cells is altered following FOXA1 knockout that may disrupt TGF-β and MAPK signaling pathways by changing miRNA expression levels,thereby inhibiting cell proliferation and migration.

Acute pancreatitis(AP)is a severe digestive system emergency characterized by high morbidity and mortality,with a complex pathogenesis involving multiple signaling pathways.Among them,the RhoA/ROCK signaling pathway plays a crucial role in the onset and progression of AP,influencing pancreatic inflammation,fibrosis,microcirculatory regulation,and interactions with other signaling pathways.Studies have shown that inhibiting the RhoA/ROCK signaling pathway can effectively alleviate AP severity,reduce inflammatory cytokine levels,and improve pancreatic microcirculation,offering new therapeutic insights and potential strategies for AP treatment.Therefore,this review systematically summarizes the structure and function of the RhoA/ROCK signaling pathway,explores its mechanistic role in AP progression,and further discusses its potential clinical applications.By integrating existing research findings,this paper aims to provide new perspectives on the role of this signaling pathway in AP and offer a theoretical foundation for future basic research and clinical applications.

Objective To investigate the protective effect of high-altitude hypoxia acclimatization against hepatic ischemia-reperfusion injury(HIRI)in rats,as well as the mechanism of action of high-altitude hypoxia acclimatization in activating autophagy.Methods A total of 56 male Sprague-Dawley rats were randomly divided into plain sham-operation group(P-S group),plain model group(P-M group),acute high-altitude hypoxia sham-operation group(AHH-S group),acute high-altitude hypoxia model group(AHH-M group),high-altitude hypoxia acclimatization sham-operation group(HHA-S group),high-altitude hypoxia acclimatization model group(HHA-M group),and high-altitude hypoxia acclimatization model group with the adenosine monophosphate-activated protein kinase(AMPK)inhibitor compound C(HHA-M-CC group),with 8 rats in each group.The rats in the acute high-altitude hypoxia groups and the high-altitude hypoxia acclimatization groups were placed in a low-pressure oxygen chamber at an altitude of 5 000 meters for 1 week and 12 weeks,respectively;the rats in the sham-operation groups were given laparotomy to expose the portal vein without vascular clamping;the rats in the HHA-M-CC group were given abdominal injection of 20 mg/kg CC at 1 hour before surgery,while those in the other groups were given injection of an equal volume of normal saline.An automatic biochemical analyzer was used to measure the levels of liver function parameters including alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBil);HE staining was used to observe liver histopathological changes;transmission electron microscopy was used to observe the formation of autophagosomes in liver tissue;RT-qPCR was used to measure the mRNA expression levels of AMPK and Unc-51 like autophagy activating kinase 1(ULK1)in liver tissue;Western Blot was used to measure the protein expression levels of phosphorylated AMPK(p-AMPK),phosphorylated ULK1(p-ULK1),Beclin-1,and microtubule-associated protein 1 light chain 3 Ⅱ(LC3Ⅱ).An analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was sued for comparison between two groups.Results Compared with the AHH-M and HHA-M-CC groups,the HHA-M group had significantly reductions in the levels of ALT,AST,and TBil(all P<0.05),alleviation of liver histopathological injury,a significant reduction in Suzuki score(all P<0.05),a reduction in the degree of abnormal morphological structure of hepatocytes under transmission electron microscopy,and significant increases in the number of autophagosomes,the mRNA expression levels of AMPK and ULK1(all P<0.05),and the protein expression levels of p-AMPK,p-ULK1,Beclin-1,and LC3Ⅱ(all P<0.05).Conclusion High-altitude hypoxia acclimatization can alleviate HIRI in SD rats by activating the AMPK/ULK1 signaling pathway and enhancing autophagy in hepatocytes.

Objective To investigate the protective effect of high-altitude hypoxia acclimatization against hepatic ischemia-reperfusion injury(HIRI)in rats,as well as the mechanism of action of high-altitude hypoxia acclimatization in activating autophagy.Methods A total of 56 male Sprague-Dawley rats were randomly divided into plain sham-operation group(P-S group),plain model group(P-M group),acute high-altitude hypoxia sham-operation group(AHH-S group),acute high-altitude hypoxia model group(AHH-M group),high-altitude hypoxia acclimatization sham-operation group(HHA-S group),high-altitude hypoxia acclimatization model group(HHA-M group),and high-altitude hypoxia acclimatization model group with the adenosine monophosphate-activated protein kinase(AMPK)inhibitor compound C(HHA-M-CC group),with 8 rats in each group.The rats in the acute high-altitude hypoxia groups and the high-altitude hypoxia acclimatization groups were placed in a low-pressure oxygen chamber at an altitude of 5 000 meters for 1 week and 12 weeks,respectively;the rats in the sham-operation groups were given laparotomy to expose the portal vein without vascular clamping;the rats in the HHA-M-CC group were given abdominal injection of 20 mg/kg CC at 1 hour before surgery,while those in the other groups were given injection of an equal volume of normal saline.An automatic biochemical analyzer was used to measure the levels of liver function parameters including alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBil);HE staining was used to observe liver histopathological changes;transmission electron microscopy was used to observe the formation of autophagosomes in liver tissue;RT-qPCR was used to measure the mRNA expression levels of AMPK and Unc-51 like autophagy activating kinase 1(ULK1)in liver tissue;Western Blot was used to measure the protein expression levels of phosphorylated AMPK(p-AMPK),phosphorylated ULK1(p-ULK1),Beclin-1,and microtubule-associated protein 1 light chain 3 Ⅱ(LC3Ⅱ).An analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was sued for comparison between two groups.Results Compared with the AHH-M and HHA-M-CC groups,the HHA-M group had significantly reductions in the levels of ALT,AST,and TBil(all P<0.05),alleviation of liver histopathological injury,a significant reduction in Suzuki score(all P<0.05),a reduction in the degree of abnormal morphological structure of hepatocytes under transmission electron microscopy,and significant increases in the number of autophagosomes,the mRNA expression levels of AMPK and ULK1(all P<0.05),and the protein expression levels of p-AMPK,p-ULK1,Beclin-1,and LC3Ⅱ(all P<0.05).Conclusion High-altitude hypoxia acclimatization can alleviate HIRI in SD rats by activating the AMPK/ULK1 signaling pathway and enhancing autophagy in hepatocytes.

Objectives:To investigate the prognostic value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with atrial fibrillation(AF)and heart failure(HF).Methods:Patients with AF and HF from hospitals diagnosed by the Heart Failure Center in Guangdong Province between January 2017 and December 2021 were selected.Major adverse cardiovascular events(MACE)were used as the follow-up endpoint.Statistical methods such as the area under the receiver operating characteristic(ROC)curve(AUC),net reclassification index(NRI),and integrated discrimination improvement(IDI)were applied to evaluate the predictive value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with AF and HF.Results:A total of 1 839 patients were enrolled in this study,comprising 703 patients in the MACE group and 1 136 patients in the non-MACE group.Compared with the non-MACE group,the MACE group exhibited significantly advanced age,higher prevalence of New York Heart Association class Ⅳ and coronary artery disease,lower diastolic blood pressure and estimated glomerular filtration rate levels,and elevated serum N-terminal pro-B-type natriuretic peptide concentrations(all P<0.05).Additionally,significantly lower proportions of patients in the MACE group received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocorticoid receptor antagonists,or anticoagulant therapy(all P<0.05).Multivariable logistic regression analysis revealed that each 1-point increment in both CHA2DS2-VASc and R2CHA2DS2-VASc scores was associated with approximately 10%increased risk of MACE.ROC curve analysis demonstrated that the AUC values for predicting MACE in AF patients with HF were 0.555(95%CI:0.528-0.582,P<0.001)for CHA2DS2-VASc and 0.576(95%CI:0.549-0.608,P<0.001)for R2CHA2DS2-VASc,indicating marginally superior discriminatory capacity of the R2CHA2DS2-VASc score.Delong's test confirmed statistically significant differences between the two scoring systems(P=0.001).The R2CHA2DS2-VASc score demonstrated a NRI of 0.259(95%CI:0.166-0.352,P<0.001)and an IDI of 0.007(95%CI:0.005-0.010,P<0.001)compared with the conventional CHA2DS2-VASc score.Although the R2CHA2DS2-VASc score exhibited slightly better predictive accuracy and outcome discrimination capacity than the original scoring system,both scores demonstrated suboptimal clinical predictive performance.Conclusions:Both the R2CHA2DS2-VASc and CHA2DS2-VASc scores show suboptimal performance for predicting the risk of MACE in patients with AF and HF,and the predicting performance of R2CHA2DS2-VASc score is marginally superior to CHA2DS2-VASc score in this patient cohort.

Acute pancreatitis(AP)is a severe digestive system emergency characterized by high morbidity and mortality,with a complex pathogenesis involving multiple signaling pathways.Among them,the RhoA/ROCK signaling pathway plays a crucial role in the onset and progression of AP,influencing pancreatic inflammation,fibrosis,microcirculatory regulation,and interactions with other signaling pathways.Studies have shown that inhibiting the RhoA/ROCK signaling pathway can effectively alleviate AP severity,reduce inflammatory cytokine levels,and improve pancreatic microcirculation,offering new therapeutic insights and potential strategies for AP treatment.Therefore,this review systematically summarizes the structure and function of the RhoA/ROCK signaling pathway,explores its mechanistic role in AP progression,and further discusses its potential clinical applications.By integrating existing research findings,this paper aims to provide new perspectives on the role of this signaling pathway in AP and offer a theoretical foundation for future basic research and clinical applications.

OBJECTIVE To explore the potential mechanisms of forkhead box protein A1(FOXA1)in benzo[a]pyrene(BaP)-induced carcinogenesis by investigating the effect of FOXA1 by knockout on microRNA(miRNA)expression profiles in BaP malignant transformed cells THBEc1 and establishing regulatory networks between FOXA1,miRNA and their target genes.METHODS FOXA1 knockout THBEc1 cells THBEc1-ΔFOXA1-c34 and control cells THBEc1-ctrl were used as study models.Western blotting was employed to determine FOXA1 protein expression levels.Next-generation sequencing(NGS)tech-nology was used to identify differentially expressed miRNAs between THBEc1-ΔFOXA1-c34 and THBEc1-ctrl cells,with subsequent validation by RT-qPCR.Five databases(ENCORI,miRDB,mirDIP,miRWalk and TargetScan 8.0)were used in conjunction with NGS results of mRNA between THBEc1-ΔFOXA1-c34 and THBEc1-ctrl to predict different expressed genes(DEGs)regulated by the identified differentially expressed miRNAs.GO and KEGG enrichment analyses were conducted on the DEGs using the DAVID database.Interaction network analysis of the proteins encoded by the DEGs was performed using STRING 12.0 and Cytoscape 3.10.2 software.RESULTS No FOXA1 expression was detected in THBEc1-ΔFOXA1-c34 cells.A differential analysis of miRNA expressions revealed 33 miRNAs with a fold change of＞2 or＜0.5 and a false discovery rate of＜0.05 between THBEc1-ΔFOXA1-c34 and THBEc1-ctrl cells,13 of which were down-regulated and 20 were up-regulated in THBEc1-ΔFOXA1-c34 cells.A regulatory network was formed by 11 down-regulated miRNAs and 32 up-regulated mRNAs,while a second network included 16 up-regulated miRNAs and 56 down-regulated mRNAs.The 27 differentially expressed miRNAs participated in various biological processes through the regulation of 88 DEGs,primarily associated with cell growth,proliferation,migration,apoptosis,angiogenesis,epithe-lial-mesenchymal transition,and signal transduction(TGF-β,Hippo,NF-kappa B and MAPK pathways).CONCLUSION The miRNA expression profile in BaP-malignant transformed THBEc1 cells is altered following FOXA1 knockout that may disrupt TGF-β and MAPK signaling pathways by changing miRNA expression levels,thereby inhibiting cell proliferation and migration.

Objective To investigate the etiology, symptoms, diagnosis, surgical treatment, and outcomes of acute necrotizing mediastinitis (ANM) in order to guide future diagnosis and treatment of ANM. Methods The clinical data of patients with ANM referred to West China Hospital, Sichuan University from March 2012 to April 2021 were retrospectively analyzed. The etiology, clinical manifestations, demographic characteristics, bacterial culture results, surgical approach and prognostic factors of these patients were summarized. Results A total of 176 patients were enrolled in this study. The median age was 60 ( 0-84) years. There were 124 (70.5%) males and 52 (29.5%) females. The most common origin of infection was neck (n=66, 37.5%). The most common symptom was fever (n=85, 48.3%). Streptococcus constellatus represented the most common pathogens in secretion culture. Surgical treatment was administered to 119 (67.6%) patients through different approaches, including 54 (30.7%) patients of cervical approach, 9 (5.1%) patients of thoracotomy, 18 (10.2%) patients of video-assisted thoracoscopic surgery (VATS), 7 (4.0%) patients of cervical combined with thoracotomy, 30 (17.0%) patients of cervical combined with VATS, and 1 (0.6%) patient of subxiphoid approach. Among this cohort, 144 (81.8%) patients were cured, while 32 (18.1%) patients died. Age-adjusted Charlson comorbidity index (OR=2.95, P=0.022), perioperative sepsis (OR=2.84, P=0.024), and non-surgical treatment (OR=2.41, P=0.043) were identified as independent predictors of poor outcomes. Conclusion For patients with corresponding history and manifestations of ANM, it is crucial to go through imaging examination to confirm the presence of an abscess and guide the selection of surgical approach. Once the diagnosis of ANM is made, it is imperative to promptly perform surgical intervention for effective drainage. Our study highlights the significance of age-adjusted Charlson comorbidity index, perioperative sepsis and surgical treatment in predicting patients’ outcomes.