BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may ...BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.展开更多
Melanosomes, isolated by centrifugal separation from culture broth of B16 melanoma cells derived from mouse, were observed by scanning electron microscopy (SEM), and by transmission electron microscopy (TEM). Some int...Melanosomes, isolated by centrifugal separation from culture broth of B16 melanoma cells derived from mouse, were observed by scanning electron microscopy (SEM), and by transmission electron microscopy (TEM). Some interesting structural features were found inside and outside of the melanosomes. By SEM observation, the melanosomes were ellipsoid shape, their surface was not smooth and was covered with rough substructure, 10 to 20 nm particles. By TEM, uneven structure and micro particles were observed in the melanosomes. Furthermore, three-dimensional analysis was tried by using the ultra-high voltage electron microscopy(UHVEM). Micrographs of the melanosomes were taken at various tilted angles by UHVEM, after preparing 500 nm thickness specimens stained with lead citrate. From the micrographs collected, the three-dimensional structures were reconstructed by using i-mode software. Melanin stained by lead and non stained parts was clearly observed in the reconstructed structure. Non stained parts were round, regular size, and distributed widely in the melanosomes.展开更多
Objective:To study the effect of Compound Biejiaruangan Tablets combined with entecavir therapy on liver fibrosis process and immune response state in patients with chronic hepatitis b.Methods: Patients with chronic v...Objective:To study the effect of Compound Biejiaruangan Tablets combined with entecavir therapy on liver fibrosis process and immune response state in patients with chronic hepatitis b.Methods: Patients with chronic viral hepatitis b who were treated in the Affiliated Hospital of Inner Mongolia Medical University between May 2015 and March 2017 were selected as the research subjects and divided into the combined group who accepted Compound Biejiaruangan Tablets combined with entecavir therapy and the control group who accepted entecavir monotherapy. The contents of collagen metabolism indexes and inflammatory response molecules in serum as well as the contents of immune cells in peripheral blood were determined before treatment and 24 weeks after treatment.Results: 24 weeks after treatment, PC-III, C-IV, MMP1, MMP2, TIMP1, IL-1β, IL-18, MIF, RANTES, MIP-1 and MIP-1β contents in serum as well as Th2, Treg and Th17 contents in peripheral blood of both groups of patients were significantly lower than those before treatment whereas Th1 contents in peripheral blood were significantly higher than those before treatment, and PC-III, C-IV, MMP1, MMP2, TIMP1, IL-1β, IL-18, MIF, RANTES, MIP-1 and MIP-1β contents in serum as well as Th2, Treg and Th17 contents in peripheral blood of combined group of patients were significantly lower than those of control group whereas Th1 content in peripheral blood was significantly higher than that of control group.Conclusion: Compound Biejiaruangan Tablets combined with entecavir therapy can delay the liver fibrosis process and improve the immune response state in patients with chronic hepatitis b.展开更多
Defining and visualizing the three-dimensional(3 D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanis...Defining and visualizing the three-dimensional(3 D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3 D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography(SR-μCT). In situ formed 3 D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3 D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral“roadways”. Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed3 D microstructures, a “subterranean river model” for the drug release mechanism has been defined to explain the drug release mechanism.展开更多
基金Supported by National Science and Technology Major Project,No.2014ZX10005001 and No.2018ZX10302204National Natural Science Foundation of China,No.81730109 and No.82274305+2 种基金Shanghai Key Specialty of Traditional Chinese Clinical Medicine,No.shslczdzk01201China Postdoctoral Science Foundation,No.2022M722162Siming Youth Fund of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,No.SGKJ-202104.
文摘BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.
文摘Melanosomes, isolated by centrifugal separation from culture broth of B16 melanoma cells derived from mouse, were observed by scanning electron microscopy (SEM), and by transmission electron microscopy (TEM). Some interesting structural features were found inside and outside of the melanosomes. By SEM observation, the melanosomes were ellipsoid shape, their surface was not smooth and was covered with rough substructure, 10 to 20 nm particles. By TEM, uneven structure and micro particles were observed in the melanosomes. Furthermore, three-dimensional analysis was tried by using the ultra-high voltage electron microscopy(UHVEM). Micrographs of the melanosomes were taken at various tilted angles by UHVEM, after preparing 500 nm thickness specimens stained with lead citrate. From the micrographs collected, the three-dimensional structures were reconstructed by using i-mode software. Melanin stained by lead and non stained parts was clearly observed in the reconstructed structure. Non stained parts were round, regular size, and distributed widely in the melanosomes.
文摘Objective:To study the effect of Compound Biejiaruangan Tablets combined with entecavir therapy on liver fibrosis process and immune response state in patients with chronic hepatitis b.Methods: Patients with chronic viral hepatitis b who were treated in the Affiliated Hospital of Inner Mongolia Medical University between May 2015 and March 2017 were selected as the research subjects and divided into the combined group who accepted Compound Biejiaruangan Tablets combined with entecavir therapy and the control group who accepted entecavir monotherapy. The contents of collagen metabolism indexes and inflammatory response molecules in serum as well as the contents of immune cells in peripheral blood were determined before treatment and 24 weeks after treatment.Results: 24 weeks after treatment, PC-III, C-IV, MMP1, MMP2, TIMP1, IL-1β, IL-18, MIF, RANTES, MIP-1 and MIP-1β contents in serum as well as Th2, Treg and Th17 contents in peripheral blood of both groups of patients were significantly lower than those before treatment whereas Th1 contents in peripheral blood were significantly higher than those before treatment, and PC-III, C-IV, MMP1, MMP2, TIMP1, IL-1β, IL-18, MIF, RANTES, MIP-1 and MIP-1β contents in serum as well as Th2, Treg and Th17 contents in peripheral blood of combined group of patients were significantly lower than those of control group whereas Th1 content in peripheral blood was significantly higher than that of control group.Conclusion: Compound Biejiaruangan Tablets combined with entecavir therapy can delay the liver fibrosis process and improve the immune response state in patients with chronic hepatitis b.
基金the National Nature Science Foundation of China (Nos.81803446,81803441 and 81773645)Key Program for International Science and Technology Cooperation Projects of China (2020YFE0201700)the Youth Innovation Promotion Association of CAS (2018323)。
文摘Defining and visualizing the three-dimensional(3 D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3 D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography(SR-μCT). In situ formed 3 D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3 D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral“roadways”. Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed3 D microstructures, a “subterranean river model” for the drug release mechanism has been defined to explain the drug release mechanism.
