ObjectiveTo investigate the mechanism of action of Jiedu Huayu granules in improving liver injury in mice with acute liver failure （ALF） by observing its effect on a mouse model of ALF after prophylactic administration， and to provide a basis for clinical medication. MethodsA total of 60 specific pathogen-free male C57BL/6J mice were divided into normal group， model group， Jiedu Huayu granules group （JDHY group）， and farnesoid X receptor （FXR） agonist （GW4064） group using a random number table， with 15 mice in each group. The model of ALF was induced by a single intraperitoneal injection of D-galactosamine combined with lipopolysaccharide. The mice in the JDHY group were given prophylactic administration of 0.3 g/mL drug solution of Jiedu Huayu granules by gavage for 3 days before modeling， those in the normal group and the model group were given 0.9% NaCl solution by gavage， and those in the GW4064 group were given intraperitoneal injection of GW4064 for 3 consecutive days before modeling. The mice were sacrificed after modeling， and serum and liver tissue samples were collected. A veterinary automatic biochemical analyzer was used to measure the serum levels of total bilirubin （TBil）， total bile acids （TBA）， gamma-glutamyl transferase （GGT）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in mice from each group； HE staining was used to observe liver pathological changes； RT-PCR was used to measure the mRNA expression levels of FXR， fibroblast growth factor 15 （FGF15）， fibroblast growth factor receptor 4 （FGFR4）， small heterodimer partner （SHP）， and bile salt export pump （BSEP） in mice， and Western blot was used to measure the protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP. A one-way analysis of variance was used for comparison between groups， and the Dunett method was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in the serum levels of TBil， ALT， AST， TBA， and GGT （all P<0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant reductions in the serum levels of TBil， ALT， AST， TBA， and GGT （all P <0.01）. HE staining showed that compared with the model group， the JDHY group and the GW4064 group had milder pathological injury， a reduction in the area of hepatocyte necrosis， and alleviation of cellular swelling and edema. Compared with the normal group， the model group had significant reductions in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant increases in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.05）. ConclusionJiedu Huayu granules may alleviate liver injury in mice with ALF through the FXR/SHP axis.

Hepatic encephalopathy （HE） is a common complication of severe liver disease in the end stage， and it is urgently needed to improve the rate of effective treatment and clarify the pathogenesis of HE. The liver is a crucial hub for immune regulation， and disruption of immune homeostasis is a key factor in the pathological mechanisms of HE. As the main metabolites of intestinal flora， short-chain fatty acids （SCFAs） play a vital role in the biological processes of both innate and adaptive immunity and can regulate the proliferation and differentiation of immune cells maintain the homeostasis of intestinal microenvironment and the integrity of barrier function. Studies have shown that SCFAs participate in bidirectional and dynamic interactions with the liver-gut-brain axis through immunomodulatory pathways， thereby playing an important role in the diagnosis， treatment， and prognostic evaluation of HE. Starting from the immunoregulatory effect of SCFAs， this article summarizes and analyzes the crosstalk relationship between SCFAs and the liver-gut-brain axis and the significance of SCFAs in the diagnosis and treatment of HE， in order to provide new ideas for optimizing clinical prevention and treatment strategies.

Nuclear factor-kappa B （NF-κB） is an important intracellular transcription factor widely involved in the processes such as immune response， inflammatory response， cell proliferation， and apoptosis. The abnormal activation of the NF-κB signaling pathway plays a pivotal role in various liver diseases including chronic hepatitis， liver fibrosis， liver cirrhosis， and hepatocellular carcinoma. Extensive studies have shown that inhibiting NF-κB activity may effectively reduce inflammation and fibrosis and improve metabolic disorders. Several natural compounds， such as matrine and salvianolic acid B， have shown the potential in suppressing NF-κB activity， thereby exerting anti-inflammatory， anti-fibrotic， and anti-tumor effects. This article systematically reviews the critical role of the NF-κB signaling pathway in liver diseases and its potential as a therapeutic target， in order to highlight its potential as a therapeutic target for liver diseases and provide new directions for the treatment of liver diseases.

OBJECTIVE To optimize the extraction process of organic acids from Angelica sinensis using deep eutectic solvents （DESs）， and conduct characterization， antioxidant activity evaluation， and extraction mechanism analysis. METHODS The conductor-like screening model for realistic solvation with segment activity coefficients （COSMO-SAC） was employed to screen the types of DESs. With total organic acid content as the response value， single-factor experiments and Box-Behnken response-surface methodology were used to optimize the extraction conditions. Using A. sinensis decoction pieces and/or A. sinensis methanol extract as references， scanning electron microscope and Fourier transform infrared spectrometer （FTIR） were applied to characterize the products. Additionally， the 1，1-diphenyl-2-picrylhydrazyl （DPPH） and 2，2′-azino-bis（3-ethylbenzothiazoline-6- sulfonic acid） （ABTS） free radical scavenging capacities were determined. Density functional theory （DFT） was used to analyze the extraction mechanism of ferulic acid and chlorogenic acid by the DESs. RESULTS & CONCLUSIONS The optimal DESs was choline chloride-propanediol. The optimal extraction conditions for organic acids from A. sinensis were as follows： choline chloride- propanediol molar ratio of 1∶1， DESs water content of 70%， solid-liquid ratio of 1∶10， heating temperature of 57 ℃， and heating and stirring time of 8 min. In three validation experiments， the total organic acid content was 2.92 mg/g， yielding a relative error of 0.34% compared to the predicted value （2.91 mg/g）. Compared with A. sinensis decoction pieces and methanol extracts， the agglomerated structure of the DESs extract powder almost disappeared， showing the presence of lamellar structures similar to those of the intestinal wall. Compared with the methanol extract， the DES extract exhibited higher FTIR characteristic peak intensity and peak area integration， as well as stronger scavenging capacities against DPPH and ABTS free radicals. The extraction of organic acids from A. sinensis by DESs is the result of the combined effects of polarity matching， hydrogen bonding， and structural adaptation.

Hepatocellular carcinoma （HCC） is a malignant tumor with high incidence and mortality rates worldwide. Recent studies have shown that neutrophil extracellular traps （NETs） play an important role in the development， progression， and immune escape of HCC. NETs are released by neutrophils and mainly consist of DNA， histones， and antimicrobial molecules， and in addition to immune defense， they are also involved in the initiation， metastasis， and thrombosis of HCC. This article elaborates on the formation and regulatory mechanisms of NETs， explores their potential mechanisms in the initiation， metastasis， immune escape， and thrombosis of HCC， and discusses the prospect of NETs as a target for the diagnosis and treatment of HCC， in order to provide new ideas for the precise treatment of HCC in the future and promote the early diagnosis and effective treatment of HCC.

Objective:To investigate the impact of various mutations in the gD protein of PRV-2022 strain on its binding to the Nectin-1 receptor.Methods:We employed PCR, RT-qPCR and gene sequencing techniques for identification of the PRV-2022 strain. Furthermore, bioinformatics method were utilized to analyze the genetic evolution of the gD gene in PRV-2022 strain. Recombinant expression plasmid containing mutations at amino acids positions 69 and 82 within the extracellular domain of gD protein from PRV-2022 strain was constructed and expressed in vitro. The binding ability between different mutant forms of recombinant gD protein and Nectin-1 receptor was compared using His-pull down and biolayer interference techniques. Results:The gD gene of the PRV-2022 strain was obtained, and genetic evolution analysis revealed that the PRV-2022 strain belonged to the same branch as strains isolated prior to 2011, with a close genetic distance. The expression plasmids for gD extracellular domain containing A69V and S82N amino acid mutations were successfully constructed, enabling the expression and purification of recombinant PRV gD extracellular domain protein. Interaction studies demonstrated that gD-69, gD-82, gD-2022, and gD-Bartha proteins interacted with human Nectin-1. Notably, compared to the classical PRV vaccine strain Bartha, double mutation of amino acids 69 and 82 in the gD protein exhibited the highest affinity to human Nectin-1 receptor, whereas individual mutations at either site decreased this affinity.Conclusions:Introduction of A69V and S82N mutations in the gD protein significantly affected its binding ability to human Nectin-1 receptor. Simultaneous occurrence of A69V and S82N mutations resulted in the highest affinity towards human Nectin-1 receptor.

Background and objective Invasive mucinous adenocarcinoma(IMA)was a rare and specific type of lung adenocarcinoma,which was often characterized by fewer lymphatic metastases.Therefore,it was difficult to evaluate the prognosis of these tumors based on the existing tumor-node-metastasis(TNM)staging.So,this study aimed to develop Nomo-grams to predict outcomes of patients with pathologic N0 in resected IMA.Methods According to the inclusion criteria and exclusion criteria,IMA patients with pathologic N0 in The Affiliated Lihuili Hospital of Ningbo University(training cohort,n=78)and Ningbo No.2 Hospital(validation cohort,n=66)were reviewed between July 2012 and May 2017.The prognostic value of the clinicopathological features in the training cohort was analyzed and prognostic prediction models were established,and the performances of models were evaluated.Finally,the validation cohort data was put in for external validation.Results Univariate analysis showed that pneumonic type,larger tumor size,mixed mucinous/non-mucinous component,and higher overall stage were significant influence factors of 5-year progression-free survival(PFS)and overall survival(OS).Multivariate analysis further indicated that type of imaging,tumor size,mucinous component were the independent prognostic factors for poor 5-year PFS and OS.Moreover,the 5-year PFS and OS rates were 62.82％and 75.64％,respectively.In subgroups,the sur-vival analysis also showed that the pneumonic type and mixed mucinous/non-mucinous patients had significantly poorer 5-year PFS and OS compared with solitary type and pure mucinous patients,respectively.The C-index of Nomograms with 5-year PFS and OS were 0.815(95％CI:0.741-0.889)and 0.767(95％CI:0.669-0.865).The calibration curve and decision curve analysis(DCA)of both models showed good predictive performances in both cohorts.Conclusion The Nomograms based on clinicopathological characteristics in a certain extent,can be used as an effective prognostic tool for patients with pathologic N0 after IMA resection.

Objective To investigate associations between three-dimensional(3D)morphology of cervical vertebrae and skeletal mat-uration by cone-beam computed tomography(CBCT)and establish corresponding regression models for quantitatively evaluating cervical vertebral maturation(CVM).Methods The analyzed sample consisted of 358 CBCT images(175 male,183 female),of which 277 images were randomly selected as the model development group and 81 as the performance test group.Twenty-one 3D morphological pa-rameters were defined and measured,incorporating all parts of the cervical vertebrae,including the cervical vertebral bodies,transverse processes,spinous processes,pedicles,lamina,and articular processes.The cervical vertebral maturation index(CVMI)was determined by experienced orthodontists as reference standard.Spearman's rank correlation coefficient and multivariable stepwise regression analysis were used to identify the associations and build regression models.The performance test group was employed to ex-amine each model's reliability.Paired-samples Wilcoxon signed-rank test compared the CVMI of the model prediction with the reference standard.Results Three-dimensional morphological changes in various parts of the cervical vertebrae correlated with CVMI(P＜0.05).Six 3D morphometric parameters were each recognized for male and female models,three of which were identical.The adjusted R2 was 0.899 for males and 0.902 for females,with corresponding accuracies of 85.0%and 85.4%,respectively.These models showed no difference as compared with the reference standard(P＞0.05).Con-clusion New associations were found between 3D morphology of cer-vical vertebrae and skeletal maturation.The 3D-driven morphometric CVM assessment method and corresponding regression models exhibited good credibility and high consistency with experts.

Pseudorabies virus (PRV) is a porcine herpesvirus that exhibits cross-species infectivity, primarily affecting pigs as its natural host. Since its initial discovery, PRV has rapidly disseminated worldwide and inflicted substantial economic losses on the swine industry. In recent years, sporadic cases of human infections with PRV have been reported, highlighting the potential risk of interspecies transmission to humans. With further analysis of the pathogenic characteristics of PRV and a deeper understanding of its pathogenic mechanism, preventing PRV from becoming a human infectious disease has become a focus of current research and prevention and control work. To comprehensively understand the variant characteristics of PRV, this study presents an overview of cutting-edge advancements in terms of its genetic variations and epidemiological characteristics, aiming to establish a foundation for more effective implementation of relevant prevention and control work.

Pseudorabies virus (PRV) is a porcine herpesvirus that exhibits cross-species infectivity, primarily affecting pigs as its natural host. Since its initial discovery, PRV has rapidly disseminated worldwide and inflicted substantial economic losses on the swine industry. In recent years, sporadic cases of human infections with PRV have been reported, highlighting the potential risk of interspecies transmission to humans. With further analysis of the pathogenic characteristics of PRV and a deeper understanding of its pathogenic mechanism, preventing PRV from becoming a human infectious disease has become a focus of current research and prevention and control work. To comprehensively understand the variant characteristics of PRV, this study presents an overview of cutting-edge advancements in terms of its genetic variations and epidemiological characteristics, aiming to establish a foundation for more effective implementation of relevant prevention and control work.