OBJECTIVES: To explore the therapeutic mechanism of Arctium lappa extract for treatment of Post-Viral Pneumonia Pulmonary Fibrosis (PPF). METHODS: The chemical constituents of Arctium lappa extracts were identified using UHPLC-Q-TOF-MS/MS. Mouse models of pulmonary fibrosis established by tracheal instillation of bleomycin were treated with Arctium lappa extract, and body weight changes were recorded and lung tissue pathology was examined using HE and Masson staining. Metabolomics analysis was used to identify the differential metabolites and the associated metabolic pathways in the treated mice. The common targets of viral pneumonia and pulmonary fibrosis were acquired from the publicly available databases, and the core targets and active constituents were screened using the protein-protein interaction (PPI) network, GO and KEGG enrichment analyses, and molecular docking, and a "gene-metabolite" regulatory network was constructed. The expressions of the core targets were detected in the lung tissues of the treated mice using Western blotting. RESULTS: Fifty-three chemical constituents were identified from Arctium lappa extract. In the mouse models of pulmonary fibrosis, treatment with Arctium lappa extract significantly improved weight loss and ameliorated lung inflammation and fibrosis. The differential metabolites in the treated mice were enriched in energy metabolism pathways involving citrate cycle, pentose phosphate pathway, glycolysis, tryptophan metabolism, glutamate metabolism and glutathione metabolism, which regulated the production of energy metabolism intermediates. Twenty-three key active compounds (mostly lignans and phenolic acids) and 82 core targets were screened, which were associated with the non-canonical Smad signaling pathways (including PI3K/AKT, HIF-1, MAPK, and Foxo) that participated in the regulation of energy metabolism. Arctium lappa extract also regulated the expressions of epithelial-mesenchymal transition (EMT)‑related proteins (fibronectin, vimentim, and Snail, etc.) and inhibited MAPK signaling pathway activation. CONCLUSIONS Preliminary findings suggest that Arctium lappa treats fibrosis by regulating metabolism to inhibit EMT and involves the modulation of non-canonical Smad signaling pathways, such as MAPK providing theoretical support for its clinical application and further research in treating PPF.
Arctium/chemistry* ; Animals ; Pulmonary Fibrosis/metabolism* ; Mice ; Metabolomics ; Network Pharmacology ; Plant Extracts/pharmacology* ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation

Objective There is a Few studies explored the association between vitamin intake and meta-bolic dysfunction-associated fatty liver disease(MAFLD),while the existing results were still contradictory.This study aimed to investigate the association between dietary vitamins and all-cause mortality as well as fibrosis risk in patients with MAFLD.Methods The data were extracted from the third National Health and Nutrition Examination Surveys 1988-1994.Dietary vitamins was assessed using a 24 h diet recall,including vitamin A,vitamin B6,vitamin B12,vitamin C,vitamin D,thiamin,riboflavin,folic acid and α-tocopherol.The non-alcoholic fatty liver disease fibrosis score(NFS)<-1.455 was considered as non-advanced fibrosis,while NFS≥-1.455 was considered as advanced fibrosis.Results A total of 3844 MAFLD participants were included in this study.The median time of follow-up was 310 months.1739 participants(45.3%)were deceased during the follow-up.The intake of thiamin,riboflavin,α-tocopherol,VB6,and VB12 were significantly higher in patients with NFS-determined non-advanced fibrosis(P<0.05).After adjusting,a significantly lower risk of fibrosis was found in patients with the highest quartile(>11.5 mg/d)of α-tocopherol intake compared to the lowest intake group(P = 0.031).Compared to the lowest quartile group,the risk of mortality was reduced by 0.34 folds in the group consuming the highest quartile amount(>130 mg/d)of VC(HRs:0.66,95%CI:0.51～0.85,P = 0.001).Conclusions More α-tocopherol intake reduced fibrosis grade in MAFLD patients.VC intake may reduce all-cause mortality in patients with MAFLD.

Objective:To evaluate the hemodynamics of patients with moyamoya disease before and 6 months after cerebral revascularization using phase-contrast magnetic resonance imaging (PC-MRI), and to analyze the risk factors for postoperative cerebral hyperperfusion syndrome (CHS).Methods:Patients with moyamoya disease underwent combined revascularization in Huadong Hospital Affiliated to Fudan University from January 2017 to April 2019 were enrolled retrospectively. PC-MRI was performed before and 6 months after surgery. The blood flow velocity, blood flow and the region of interest (ROI) area of the vascular lumen in internal carotid artery, external carotid artery, superficial temporal artery and vertebral artery were recorded. Multivariate logistic regression analysis was used to determine the independent correlated factors of CHS. Results:A total of 80 patients with moyamoya disease were included, including 35 males (43.75%), aged 42.4±10.1 years (range 19-60 years). The blood flow velocity ( P<0.05), blood flow ( P<0.01) and area of ROI ( P<0.01) of the superficial temporal artery were significantly increased at 6 months after surgery compared with the before surgery, and the blood flow of the vertebral artery was slower compared with the before surgery ( P<0.05). Univariate analysis showed that diabetes, predominant hemispheric operation, preoperative increased superficial temporal artery blood flow rate, reduced internal carotid artery flow, and increased external carotid artery flow were the possible risk factors for occurring CHS in patients with moyamoya disease after surgery. Multivariate logistic regression analysis showed that the predominant hemispheric operation (odds ratio [ OR] 4.627, 95% confidence interval [ CI] 1.019-21.009; P=0.047), preoperative superficial temporal artery blood flow ( OR 1.208, 95% CI 1.053-1.387; P=0.007) and external carotid artery blood flow ( OR 0.139, 95% CI 0.027-0.719; P=0.019) were independently associated with postoperative CHS. Conclusions:PC-MRI can evaluate the hemodynamic parameters of intracranial and extracranial major blood vessels, and it can be used as one of the important basis to evaluate the postoperative risk of moyamoya disease.

Objective To study the inhibition effect of non custodial terpenes-3β-alcohol to experimentally in-duced autoimmune encephalomyelitis in guinea pigs. Methods Different doses (25 mg/kg, 50 mg/kg and 100 mg/kg) of non custodial terpenes-3β-alcohol were given to the experimentally induced autoimmune encephalomyelitis model of guinea pigs by gavage for 8 weeks. Plasma levels of CD4+/CD8+, IL-1, IL-2, IL-6, IL-10, neuropeptide Y (NPY), beta endorphin (β-EP) , transforming growth factor-β(TGF-β), matrix metalloproteinase (MMP-2), nitric oxide synthase (NOS) and leuko-cyte differentiation antigen CD3 were assessed. The brain neuron morphology changes was observed under light microscopy while its ultrastructure changes was observed under electron microscope. NOS expression in neurons was observed through immunofluoresce technology. Results Non custodialterpenes-3β-alcohol inhibited the increase of plasma CD4+/CD8+, IL-1, IL-2, IL-6, IL-10, MMP-2, CD3 and NPY while decrease of plasmaβ-EP, brain TGF-β. It also increase NOS expres-sion in neuronal cytoplasm and maintained neuron morphology. Conclusion Non custodial terpenes-3β-alcohol inhibit-ed the experimental autoimmune encephalomyelitis in guinea pig.

Objective To study the impact of active control of the trajectory of the center of gravity on the effectiveness of balance training and balance assessment. Methods Two groups of subjects ( group 1 30-45 years old, group 2 45-60 years old ) were evaluated and trained using both active center of gravity trajectory control and static balance methods. Results The percentages of success in controlling the center of gravity were the same when both groups were trained using static balance. Group 1's success percentage was higher than that of group 2 after active center of gravity trajectory training. Their affected lower limbs performed better in wave trace training than after static balance training, and performance improved with increased wave trace amplitude. Conclusions Wave tracing can stimulate the lower limbs of patients with active control force and improve their balance. The wave assessment is superior to static assessment, as it can objectively reflect ability in active center of gravity control and adjust the lower limbs of subjects whose static balance ability is at the same level.

Objective To observe the meshed capillary pattern(CP)on the surface of colorectal lesions by narrow-band imaging system with magnifying endoscopy(NBI-ME),and to distinguish neoplasm from non-neoplasm by the change of capillary patterns.Methods A total of 144 colorectal lesions in 102 patients detected by conventional colonoscopy were evaluated by NBI-ME to observe the CP on surface,and by staining magnifying colonoscopy to observe the pit pattern.Results All lesions were resected endoscopically (129/144)or by surgery(15/144),and the pathological evaluation diagnosed 30 cases of non-neoplasm (including 20 cases of hyperproliferative polyps and 10 of inflammatory polyps)and 1 14 cases of neoplasm (including 95 cases of adenoma and 19 cases of adenocarcinoma).The diagnostic accuracy rate,sensitivity and specificity of conventional colonoscopy were 75.7%,85.1%and 40.O%,respectively,which were significantly lower than those of NBI-ME and staining magnifying colonoscopy(P＜0.005),while there was no significant difference between NBI-ME and staining magnifying colonoscopy.The CP of type Ⅰ,Ⅱ,Ⅳ and Ⅵa were totally correspondent with pit pattern of type Ⅰ,Ⅱ,Ⅳ and ⅤI. Conclusion NBI-ME findings of colorectal lesions correlated with those of staining magnifying colonoscopy.These two techniques are both helpful in differentiating colorectal neoplasms from non-neoplasms.

Objective To reproduce an animal model of acute hepatic failure at high altitude areas for use in the research of extracorporeal artificial liver support. Methods General condition, survival time, relevant biochemistry indexes and pathological changes of the pigs treated by two peritoneal injections of thioacetamide in the dose of 50mg/kg, 100mg/kg and 150mg/kg respectively. Results All the pigs in the 3 experimental groups displayed clinical symptoms and signs and biochemistry changes similar to that of human patients with acute hepatic failure, and the 100mg/kg group may be the most ideal model. Conclusion The animal model of pig treated with two peritoneal injections of thioacetamide 100mg/kg is suitable for the research of extracorporeal artificial liver support for hepatic failure at high altitude.

Objective To describe the clinical features, operative methods and postoperative management of the intra-axial tumors of medullocervical junction, and to make differential diagnosis for different subtypes.Methods Fifteen patients with intra-axial tumors of medullocervical junction were treated from August 1988 to June 1997. The diagnoses were confirmed by MRI and histological examinations. The tumors were divided into two subtypes according to the clinical features and the main body of the tumor. The distinctive points of the two subtypes and the appropriate surgical methods of different pathological type tumors were expounded.Results Tumors were totally removed in 10 patients and subtotally in 5. There was no death caused by operation. Postoperative complications included respiratory disturbance in six cases, upper digestive tract bleeding in one, depressed cough reflex in two, most of which recovered after proper treatment. On discharge, the nervous system status was improved in 11 cases, stable in 2 and worsened in 2.Conclusions The intra-axial tumors of medullocervical junction can be divided into cervicomedullary and medullocervical subtypes. The MRI examination is decisive in the distinction of the diagnosis, and is important in the determination of the nature of the medullar cystic lesions and the guidance of the resection of tumor extent. The cervicomedullary tumors are more amenable to an aggressive surgical treatment, during which the surgeon should remove the tumors first in the cervical spinal cord area, then in the medullar area with the tumor resection expanding rostrally. It can make the operation safer to remove the tumors using appropriate techniques varied with pathological types of the tumors. Managing postoperative respiratory disturbances without delay is one of the important points in improving the therapeutic effect.