A phytochemical study of the root extract of Hemerocallis fulva var. kwanso Regel resulted in the isolation and structural characterization of four lignans (1‒4), three flavanones (5, 6, and 8), one chalcone (9), and two monoterpenes (7 and 10). Enzyme inhibition assays revealed that two flavanone glucosides (5 and 6) showed significant inhibitory effect against protein tyrosine phosphatase 1B (PTP1B), with IC50 values of 31.38 µM and 51.46 µM, respectively. Further enzyme kinetic studies demonstrated that these two compounds acted as noncompetitive PTP1B inhibitors, with Ki values of 30.88 µM and 50.38 µM, respectively.

ObjectiveTo investigate the mechanism by which Shengjiang Pingchuan Zhike pills （SPZP） alleviate airway injury in the rat model of cough variant asthma （CVA） via regulating autophagy through activating the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/Unc-51-like autophagy activating kinase 1 （ULK1） signaling pathway based on transcriptomics， thus providing experimental evidence for the clinical application of SPZP. MethodsForty SPF-grade SD rats were enrolled in the present study and randomly via the random number table method assigned into four groups： a blank group， a model group， a SPZP （2 160 mg·kg^-1·d^-1） group， and a positive drug （montelukast sodium， MTL， 0.9 mg·kg^-1·d^-1）group， with 10 rats in each group. After one week of adaptive feeding， the rat model of cough variant asthma （CVA） was established by two-week sensitization with ovalbumin （OVA） and aluminium hydroxide， followed by capsaicin atomization challenge. Rats in the blank group received an equal volume of normal saline during modeling. Upon successful modeling， rats in the SPZP group and positive drug group were administrated with SPZP suspension and MTL solution， respectively， while those in the blank and model groups received the same dose of normal saline by gavage. The whole intervention lasted for 21 consecutive days. After the intervention， general behaviors of rats in each group were observed. Pulmonary function indicators were subsequently detected. Hematoxylin-eosin （HE） staining was performed to visualize the pathological morphology of the lung tissue， and periodic acid-Schiff （PAS） staining was adopted to evaluate airway mucus secretion. Transcriptomic sequencing was conducted to screen differentially expressed genes in the lung tissue across groups. The levels of inflammatory cytokines including interleukin （IL）-4， IL-5， immunoglobulin E （IgE）， and interferon-γ （IFN-γ） in the bronchoalveolar lavage fluid （BALF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence staining was used for detecting the co-localization of autophagy-related protein Beclin-1 and phosphorylated mammalian target of rapamycin （p-mTOR）. Transmission electron microscopy was employed to count autophagosomes and observe mitochondrial morphological changes in the lung tissue. Western blot assay was utilized to measure the expression levels of AMPK/mTOR/ULK1 axis-related proteins， including AMPK， phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， mTOR， phosphorylated mammalian target of rapamycin （p-mTOR）， ULK1， and phosphorylated Unc-51-like autophagy activating kinase 1 （p-ULK1） as well as the autophagy biomarkers Beclin-1 and selective autophagy adaptor protein p62 in lung specimens. ResultsCompared with the blank group， the model group exhibited markedly elevated cough frequency accompanied by wheezing and stridor， dull fur， poor mental activity， diminished motor activity， accelerated respiratory rate， and weakened sensory response and mobility to external stimuli， accompanied by a declining tendency of body mass. Meanwhile， the model group exhibited decreased dynamic lung compliance， increased airway resistance （P<0.01）， severe pathological damage and excessive mucus secretion in the lung tissue （P<0.01）， and elevated levels of IL-4， IL-5， and IgE and declined level of IFN-γ in the BALF （P<0.01）. Ultrastructural observation revealed damaged mitochondrial morphology and a sharp reduction in the number of autophagosomes in the lung tissue. In addition， the expression of p-AMPK， p-ULK1， and Beclin-1 were downregulated， whereas p-mTOR and p62 were highly expressed （P<0.05， P<0.01） in the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses demonstrated significant enrichment of AMPK， mTOR， and autophagy-related pathways. Compared with the model group， both the positive drug group and SPZP group obtained visible improvements in general behavioral manifestations and obvious recovery of pulmonary function indicators （P<0.05）， alleviated pulmonary pathological lesions and suppressed excessive airway mucus secretion （P<0.05）， recovered levels of inflammatory cytokines in the BALF （P<0.05）， restored mitochondrial morphology， increased autophagosomes， upregulated expression levels of p-AMPK， p-ULK1， and Beclin-1， and downregulated expression levels of p-mTOR and p62 （P<0.05）. ConclusionSPZP can effectively ameliorate airway inflammation and improve the pulmonary function in the rat model of CVA by activating the AMPK/mTOR/ULK1 signaling pathway， enhancing autophagy in the lung tissue， and inhibiting excessive airway mucus secretion and immune inflammatory imbalance.

The neurophysiological mechanisms by which exercise improves cognitive function have not been fully elucidated. A comprehensive and systematic review of current domestic and international neurophysiological evidence on exercise improving cognitive function was conducted from multiple perspectives. At the molecular level, exercise promotes nerve cell regeneration and synaptogenesis and maintains cellular development and homeostasis through the modulation of a variety of neurotrophic factors, receptor activity, neuropeptides, and monoamine neurotransmitters, and by decreasing the levels of inflammatory factors and other modulators of neuroplasticity. At the cellular level, exercise enhances neural activation and control and improves brain structure through nerve regeneration, synaptogenesis, improved glial cell function and angiogenesis. At the structural level of the brain, exercise promotes cognitive function by affecting white and gray matter volumes, neural activation and brain region connectivity, as well as increasing cerebral blood flow. This review elucidates how exercise improves the internal environment at the molecular level, promotes cell regeneration and functional differentiation, and enhances the brain structure and neural efficiency. It provides a comprehensive, multi-dimensional explanation of the neurophysiological mechanisms through which exercise promotes cognitive function.
Animals ; Humans ; Brain/physiology* ; Cognition/physiology* ; Exercise/physiology* ; Nerve Regeneration/physiology* ; Neuronal Plasticity/physiology*

Purpose To investigate the clinical and imaging features and diagnostic points of hemophilic pseudotumor(HPT).Materials and Methods A total of 50 HPT patients in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2015 to August 2023 were selected.Gender,haemophilia category,site of disease and X-ray,CT and MRI manifestations of HPT were retrospectively analyzed.Results A total of 50 patients with HPT were collected,49 male patients and one female patient.There were 48 cases of haemophilia A,one case of haemophilia B and one case of vascular haemophilia.Imaging manifestations were single bone and adjacent soft tissue involvement in 22 cases;multi-bone and single joint in four cases;multi-bone and multi-joint in ten cases;simple skeletal muscle and soft tissue involvement in six cases;abdominopelvic cavity and retroperitoneal space in six cases;and small intestinal wall in two cases.X-ray and CT mainly showed that the bone was destroyed by expansion,partially combined with osteolysis of the bone destruction,residual coarse bone ridge could be seen in the damaged area,and the sclerotic edge could be seen in the edge of the bone destruction.The main body of the lesion showed mixed density,and the enhancement scanning of the bone destruction area and soft tissue mass did not see the exact enhancement.MRI showed bone destruction area,soft tissue mass formation,which could better reflect its pathological characteristics,i.e.,the haematoma signals in different periods.Conclusion HPT commonly affect the femur and pelvic bones,and can involve multiple bones,joints,the abdominal and pelvic cavities,the retroperitoneum and the intestinal wall.The primary manifestation is the formation of massive hematomas within soft tissues,with varying stages of hemorrhage.When bone is involved,it typically presents as expansive bone destruction accompanied by the formation of large pseudotumors.The edges of the destruction area may show bone sclerosis.The pseudotumors exhibit characteristics of hematomas at different stages.A definitive diagnosis can be made by integrating imaging findings,clinical data and laboratory tests.

Bioassay-guided fractionation of the methanolic extract of Artemisia iwayomogi Kitamura led to the isolation of 12 known compounds (1‒12). Notably, this study marks the first report of 3-epimeridinol (1) being isolated and structurally characterized from a natural source. Additionally, compounds 3, 4, and 7 were isolated from the Asteraceae family for the first time. The structural elucidation of the isolated compound was achieved through analysis of 1D, 2D NMR, and MS data. Upon evaluation of their inhibitory effects against lipopolysaccharideinduced nitric oxide production, compound 12 demonstrated significant inhibitory activity with greater potency than the reference compound quercetin. These results established A. iwayomogi as a promising source of antiinflammatory agents.

Bioassay-guided fractionation of the methanolic extract of Artemisia iwayomogi Kitamura led to the isolation of 12 known compounds (1‒12). Notably, this study marks the first report of 3-epimeridinol (1) being isolated and structurally characterized from a natural source. Additionally, compounds 3, 4, and 7 were isolated from the Asteraceae family for the first time. The structural elucidation of the isolated compound was achieved through analysis of 1D, 2D NMR, and MS data. Upon evaluation of their inhibitory effects against lipopolysaccharideinduced nitric oxide production, compound 12 demonstrated significant inhibitory activity with greater potency than the reference compound quercetin. These results established A. iwayomogi as a promising source of antiinflammatory agents.

AIM To investigate the effects of Liangxue Heying Formula-medicated serum(LXHY-MS)on human umbilical vein endothelial cells(HUVECs)induced by lipopolysaccharide(LPS).METHODS CCK-8,DCFH-DA fluorescence probe and Western blot method were used to screen the LPS concentration in modeling and the serum LXHY concentration for treatment.The HUVECs divided into the normal group,the model group and the LXHY-MS group had their SOD activity detected by automatic biochemical analyzer;their MDA level detected by colorimetry;their protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 detected by Western blot;and their mROS expression and recruitment effect on THP-1 photographed with high connotation.With the use of JAK2/STAT3 pathway inhibitor(AG490),the HUVECs divided into the normal group,the AG490 group,the LPS group,the LPS+AG490 group,the LPS+LXHY-MS group,and LPS+LXHY-MS+AG490 group were subjected to the corresponding treatment,followed by the detection of their protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 by Western blot.RESULTS Compared with the normal group,the model group displayed decreased SOD activity(P＜0.01),increased MDA level(P＜0.05),increased ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2,p-STAT3 protein expressions(P＜0.05,P＜0.01),and increased mROS expression and THP-1 cells recruitment.Compared with the model group,the LXHY-MS group shared increased SOD activity(P＜0.05),decreased MDA level(P＜0.01),decreased ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2,p-STAT3 protein expressions(P＜0.05,P＜0.01),reduced mROS expression and THP-1 cells recruitment.Given the use of AG490,the model group displayed increased protein expressions of ICAM-1,VCAM-1,IL-6,TNF-α,p-JAK2 and p-STAT3 in contrast to the normal group(P＜0.05,P＜0.01);each intervened group showed decreased expressions of related proteins in contrast to the model group(P＜0.05,P＜0.01).CONCLUSION LXHY-MS may protect the injury due to the activation of HUVECs by inhibiting the JAK2/STAT3 signaling pathway.

OBJECTIVE To investigate the protective effect of farrerol against lipopolysaccharide(LPS)induced acute lung injury(ALI)in mice and the mechanisms.METHODS ①ICR rats were randomly divided into the normal control group,model group and model+farrerol group,with 6 rats in each.The normal control group and model group were given an equal amount of normal saline intragaically for 4 d.The model+farrerol group was given 20 and 40 mg·kg-1 intragaically for 4 d,while the normal control group was given an equal amount of normal saline intragaically on the 5th day.The model group and model+farrerol group were injected with 3 mg·kg-1 LPS solution for 24 h to construct an animal model of ALI.② Mouse alveolar macrophages(MH-S)were cultured and randomly divided into the cell control group,model group and model+farrerol group.Cell control group(conventional culture for 24 h),model group(100 μg·L-1 LPS combined with 40 μg·L-1 IFN-γ co-incubation for 24 h),model+farrerol group(5,10 and 20 μmol·L-1 farrerol pretreatment of MH-S cells for 24 h,and then 100 μg·L-1 LPS combined with 40 μg·L-1 IFN-γ co-incubation for 24 h),an inflammatory cell model was established in vitro.HE was used to observe the pathological changes of the lungs.The wet-dry weight ratio(W/D)was used to assess pulmonary edema while Evans blue dye(EBD)was used to detect pulmonary vascular permea-bility.The activity of myeloperoxidase(MPO)was detected by colorimetry.The number of white blood cells in BALF was counted with a blood cell counting plate.Cell proliferation assay(CCK-8)was used to determine the cell viability.The levels of interleukin-1β(IL-1β),tumor necrosis factor α(TNF-α),IL-6 and IL-10 in lung tissue,bronchoalveolar lavage fluid(BALF)and cell supernatants were detected via enzyme-linked immunosorbent assay(ELISA).The protein levels of inducable nitric oxide synthase(iNOS),arginase 1(ARG1),phosphorylated NF-κB p65,NOD-like receptor protein 3(NLRP3),cysteinyl aspartate specific proteinase1(caspase1)and gasdermin family member(GSDMD-N terminal)in lung tissue and MH-S cells were detected with Western blot.RESULTS ① Compared with the normal control group,the histopathological changes,Injury score,W/D ratio,pulmonary vascular permeability,MPO content,leukocyte count,pro-inflammatory factor IL-1β,TNF-α,IL-6 levels,iNOS,phosphorylated NF-κB p65,NLRP3,caspase1 and GSDMD-N-terminal protein expression in lung tissues were signifi-cantly increased in the model group(P<0.05,P<0.01)while the expression levels of anti-inflammatory factors IL-10 and ARG1 were decreased(P<0.05,P<0.01).Compared with the model group,the Injury score,W/D ratio,pulmonary vascular permeability,leukocyte number,MPO content,proinflammatory factor content and iNOS,phosphorylated NF-κB p65,NLRP3,caspase1 and GSDMD-N-terminal protein levels were significantly decreased in the model+farrerol group(P<0.05,P<0.01)while the levels of anti-inflammatory factor IL-10 and ARG1 protein were increased(P<0.05,P<0.01).② The results of in vitro experiments showed that compared with the cell control group,the contents of IL-1β,TNF-α and IL-6 and the expression levels of iNOS,phosphorylated NF-κB p65,NLRP3,caspase1 and GSD-MD-N-terminal protein were increased(P<0.05,P<0.01),and that the content of anti-inflammatory factor IL-10 and expression level of ARG1 protein were decreased(P<0.01).Compared with the model group,the content of proinflammatory factor and the expressions of iNOS,phosphorylated NF-κB p65,NLRP3,caspase1 and GSDMD-N protein in the model+farrerol group were significantly decreased(P<0.05,P<0.01)while the expression levels of IL-10 and ARG1 protein were increased(P<0.05,P<0.01).CONCLUSION Farrerol can alleviate acute lung injury induced by LPS in mice,possibly by inhibiting the phosphorylation of NF-κB p65 and activation of NLRP3 inflammatome,alleviating pyroptosis of cells and regulating macrophage polarization.

OBJECTIVE: To investigate the effect of TBL1XR1 mutation on cell biological characteristics of diffuse large B-cell lymphoma (DLBCL). METHODS: The TBL1XR1 overexpression vector was constructed and DNA sequencing was performed to determine the mutation status. The effect of TBL1XR1 mutation on apoptosis of DLBCL cell line was detected by flow cytometry and TUNEL fluorescence assay; CCK-8 assay was used to detect the effect of TBL1XR1 mutation on cell proliferation; Transwell assay was used to detect the effect of TBL1XR1 mutation on cell migration and invasion; Western blot was used to detect the effect of TBL1XR1 mutation on the expression level of epithelial-mesenchymal transition (EMT) related proteins. RESULTS: The TBL1XR1 overexpression plasmid was successfully constructed. The in vitro experimental results showed that TBL1XR1 mutation had no significant effect on apoptosis of DLBCL cells. Compared with the control group, TBL1XR1 mutation enhanced cell proliferation, migration and invasion of DLBCL cells. TBL1XR1 gene mutation significantly increased the expression of N-cadherin protein, while the expression of E-cadherin protein decreased. CONCLUSION TBL1XR1 mutation plays a role in promoting tumor cell proliferation, migration and invasion in DLBCL. TBL1XR1 could be considered as a potential target for DLBCL therapy in future research.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Proliferation ; Mutation ; Receptors, Cytoplasmic and Nuclear/genetics* ; Apoptosis ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Cell Movement ; Repressor Proteins/genetics* ; Nuclear Proteins/genetics* ; Cadherins/metabolism*

OBJECTIVE: To explore the clinical characteristics and prognosis of children with SIL-TAL1-positive T-cell acute lymphoblastic leukemia ( SIL-TAL1⁺ T-ALL). METHODS: The clinical data of 110 children with newly diagnosed T-ALL admitted to the pediatric department of our hospital from January 2010 to December 2018 were reviewed to compare the clinical characteristics, treatment response and prognosis between SIL-TAL1⁺ group and SIL-TAL1^-group. RESULTS: Among the 110 children with T-ALL, 25 cases (22.7%) were in the SIL-TAL1⁺ group and 85 cases (77.3%) in the SIL-TAL1^- group. The white blood cell (WBC) count in the SIL-TAL1⁺ group was significantly higher than that in the SIL-TAL1^- group (P < 0.05), while the other clinical characteristics and treatment response were not significantly different between the two groups. The 5-year overall survival (OS) rates of SIL-TAL1⁺ group and SIL-TAL1^- group were 80.0% and 75.5%, and 5-year disease-free survival (DFS) rates were 76.0% and 72.9%, respectively. There were no significant differences in OS rate and DFS rate between the two groups ( P >0.05). In children aged < 10 years, the 5-year OS rate of SIL-TAL1⁺ group and SIL-TAL1^- group was 100% and 75.1%, respectively, and the difference between the two groups was statistically significant (P < 0.05). CONCLUSION Although the WBC level is significantly higher in children with SIL-TAL1⁺ T-ALL than that in those with SIL-TAL1^- T-ALL, the treatment efficacy is similar between the two groups. In children aged < 10 years, the longterm survival rate is superior in the SIL-TAL1⁺ group.
Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Prognosis ; Child ; Male ; Female ; Survival Rate ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Child, Preschool ; Oncogene Proteins, Fusion ; Leukocyte Count