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OBJECTIVE@#To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients.@*METHODS@#A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented.@*RESULTS@#The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns.@*CONCLUSION@#Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).
Subject(s)
Adult , Female , Humans , Male , Young Adult , Adenine , Therapeutic Uses , Antiviral Agents , Therapeutic Uses , Double-Blind Method , Drug Therapy, Combination , Drugs, Chinese Herbal , Therapeutic Uses , Hepatitis B e Antigens , Allergy and Immunology , Hepatitis B, Chronic , Drug Therapy , Allergy and Immunology , Medicine, Chinese Traditional , Organophosphonates , Therapeutic UsesABSTRACT
ObjectiveAnimal model is an important means to study the pathogenesis and drug therapy of diabetic nephropathy. In this paper, the techniques of bioinformatics were used to analyze the common susceptibility genes and pathways in the kidneys of three diabetic nephropathy animal models of BKS db/db, BKS eNOS-/db/db and DBA-STZ3, so as to discover new and important genes and pathways, thus providing new ideas for the study of the pathogenesis of diabetic nephropathy.MethodsThe GSE33744 dataset was downloaded from the GEO database, and the differential genes of three animal models of diabetic nephropathy were analyzed by Limma package in R language. The genes differentially expressed in all models were obtained by intersection, and were then analyzed by GO, KEGG and PPI networks and screened for key genes and pathways.Results144 genes were differentially expressed in three animal models of diabetic nephropathy. GO analysis showed that these genes were enriched in the cell membrane and extracellular regions; in biological processes such as innate immune response, oxidation-reduction process and immune system process; and in molecular functions such as oxidoreductase activity, carbohydrate binding and heme binding. KEGG analysis indicated that the differential genes were enriched in signaling pathways such as PPAR signaling pathway, arachidonic acid metabolism, butyric acid metabolism and circadian rhythm. PPI network analysis suggested that Cd68, Ccl6, Fcer1g, Tyrobp, Clec4n, Lyz2, Ms4a6d, Ly86, Ctss, Cfp and Mpeg1 may be the key genes in the development of diabetic nephropathy.ConclusionSome genes and signaling pathways are altered in multiple kidneys of the diabetic animal models, suggesting that these genes and pathways play an important role in the pathogenesis of diabetic nephropathy.
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<p><b>BACKGROUND</b>The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate.</p><p><b>METHODS</b>The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment.</p><p><b>DISCUSSION</b>The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).</p>
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Objective To investigate filtration efficiency of convertible vena cava filters on treating pulmonary embolism under the condition of different thrombus diameter and content. Methods Three kinds of convertible vena cava filter models with different filtering unit structures (L-style, S-style, W-style) were constructed to numerically simulate hemodynamics based on computational fluid dynamic (CFD) methods, and their filtration efficiency were comparatively analyzed under the condition of different thrombus diameter (5, 10, 15 mm) and content (10%, 15%, 20%). Results With the increasing of thrombus diameter and content, the volume fraction of thrombus distributed on the filter bars increased and filtration efficiency of the filter became better. When the thrombus diameter was 5 mm, the S-style filter’s filtration efficiency was the best as compared with the other two styles of filters. When the thrombus diameter was 10 mm, the W-style filter showed the best filtration efficiency. When the thrombus diameter was 15 mm, the S-style and W-style filter showed the same filtration efficiency, which was better than the L-style filter. Conclusions The implantation of vena cava filters will cause hemodynamic changes, and its filtration efficiency is not only related to filtering unit structures, but also closely related to the diameter and content of thrombus. These results provide a theoretical reference basis for the design and clinical choice of the novel convertible vena cava filter.
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Objective To investigate filtration efficiency of convertible vena cava filters on treating pulmonary embolism under the condition of different thrombus diameters and contents.Methods Three kinds of convertible vena cava filter models with different filtering unit structures (L-style,S-style,W-style) were constructed to numerically simulate hemodynamics based on computational fluid dynamic (CFD) methods,and their filtration efficiency was comparatively analyzed under the condition of different thrombus diameters (5,10,15 mm) and contents (10％,15％,20％).Results With the increasing of thrombus diameter and content,the volume fraction of thrombus distributed on the filter bars increased and the filtration efficiency of the filter became better.When the thrombus diameter was 5 mm,the S-style filter's filtration efficiency was the best as compared with the other two kinds of filters.When the thrombus diameter was 10 mm,the W-style filter showed the best filtration efficiency.When the thrombus diameter was 15 mm,the S-style and W-style filter showed the same filtration efficiency,which was better than the L-style filter.Conclusions The implantation of vena cava filters will cause hemodynamic changes,and its filtration efficiency is not only related to filtering unit structures,but also closely related to the diameter and content of thrombus.These results provide a theoretical reference basis for the design and clinical choice of the novel convertible vena cava filter.
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Objective To investigate filtration efficiency of convertible vena cava filters on treating pulmonary embolism under the condition of different thrombus diameters and contents.Methods Three kinds of convertible vena cava filter models with different filtering unit structures (L-style,S-style,W-style) were constructed to numerically simulate hemodynamics based on computational fluid dynamic (CFD) methods,and their filtration efficiency was comparatively analyzed under the condition of different thrombus diameters (5,10,15 mm) and contents (10％,15％,20％).Results With the increasing of thrombus diameter and content,the volume fraction of thrombus distributed on the filter bars increased and the filtration efficiency of the filter became better.When the thrombus diameter was 5 mm,the S-style filter's filtration efficiency was the best as compared with the other two kinds of filters.When the thrombus diameter was 10 mm,the W-style filter showed the best filtration efficiency.When the thrombus diameter was 15 mm,the S-style and W-style filter showed the same filtration efficiency,which was better than the L-style filter.Conclusions The implantation of vena cava filters will cause hemodynamic changes,and its filtration efficiency is not only related to filtering unit structures,but also closely related to the diameter and content of thrombus.These results provide a theoretical reference basis for the design and clinical choice of the novel convertible vena cava filter.
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<p><b>OBJECTIVE</b>To investigate the regulatory effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on the activation of c-jun N-terminal kinase (JNK) signal transduction pathway and its role in silicotic fibrosis.</p><p><b>METHODS</b>A rat model of silicosis was developed by intratracheal instillation. Sixty rats were randomly divided into 4-week control group (n = 10), 8-week control group (n = 10), 4-week silicosis model group (n = 10), 8-week silicosis model group (n = 10), AcSDKP treatment group (n = 10), and AcSDKP prevention group (n = 10). The content of hydroxyproline in lung tissue was measured using a p-dimethylaminoben-zaldehyde reagent; the expression levels of transforming growth factor (TGF)-beta 1 (TGF-β1), phospho-JNK, JNK, and c-jun in lung tissue were measured by Western blot. The lung fibroblasts from neonatal rats were cultured, and the 4th generation of cells were used in the experiment; these cells were divided into control group, TGF-β1 stimulation group, SP600125 intervention group, and AcSDKP intervention group. The distributions of phospho-JNK and c-jun in lung fibroblasts were observed by immunocytochemistry; the expression levels of type I collagen and type III collagen in lung fibroblasts were measured by Western blot.</p><p><b>RESULTS</b>The expression levels of TGF-β1, phospho-JNK, and c-jun and the content of hydroxyproline in the AcSDKP treatment group were 70.60%, 78.03%, 79.85%, and 71.28%, respectively, of those in the 4-week silicosis model group (P < 0.05) and 77.99%, 66.73%, 69.94%, and 64.82%, respectively, of those in the 8-week silicosis model group (P < 0.05); the expression levels of TGF-β1, phospho-JNK, and c-jun and the content of hydroxyproline in the AcSDKP prevention group were 84.56%, 61.18%, 64.73%, and 74.96%, respectively, of those in the 8-week silicosis model group (P < 0.05). The expression levels of phospho-JNK and c-jun in the AcSDKP intervention group were 54.59% and 55.56%, respectively, of those in the TGF-β1 stimulation group; the expression levels of type I collagen and type III collagen in the AcSDKP intervention group were 79.9% and 84.4%, respectively, of those in the TGF-β1 stimulation group (P < 0.05).</p><p><b>CONCLUSION</b>AcSDKP exerts anti-silicotic fibrosis effect probably by inhibiting the activation of JNK signal transduction pathway mediated by TGF-β1 and the deposition of interstitial collagen.</p>
Subject(s)
Animals , Male , Rats , JNK Mitogen-Activated Protein Kinases , Metabolism , Lung , Metabolism , Pathology , Oligopeptides , Pharmacology , Pulmonary Fibrosis , Metabolism , Pathology , Rats, Wistar , Signal Transduction , Silicosis , Metabolism , PathologyABSTRACT
<p><b>OBJECTIVE</b>To compare macroporous microcarrier Cytopore 2 and Cultispher S for their effects in microgravity culture of CL-1 cells.</p><p><b>METHODS</b>CL-1 cells were cultured on Cytopore 2 and Cultispher S respectively in a rotational cell culture system (RCCS) in a volume of 50 ml. Dynamic morphological observation and cell counting and functional test were carried out during the cell culture.</p><p><b>RESULTS</b>The cells were capable of adhering to and proliferating on both of the microcarriers, reaching the growth peak on day 9 of cell culture with the maximum cell density of 4x10(6)/ml on cultispher S. Albumin was significantly higher in the supernatant of Cytopore 2 than in that of Cultispher S on days 10, 11, and 12 (P<0.05), and the urea level in the supernatant of cytopore 2 was also significantly higher on days 10 and 11 (P<0.05).</p><p><b>CONCLUSION</b>The cells cultured on Cytopore 2, though with a smaller cell number, display better functions than those cultured on Cultispher S under RCCS conditions.</p>
Subject(s)
Humans , Cell Culture Techniques , Methods , Cell Division , Physiology , Cell Line , Cellulose , Gelatin , Hepatocytes , Cell Biology , Liver, Artificial , Porosity , Tissue Engineering , Methods , Tissue Scaffolds , WeightlessnessABSTRACT
<p><b>OBJECTIVE</b>to investigate the effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on the expressions of c-Raf, ERK1/2 and TGF-β1 in the lung of rats with silicosis, thus to investigate the regulating of AcSDKP on the Ras-Raf-ERK1/2 signal transduction pathway.</p><p><b>METHODS</b>rats were instilled with silica through trachea as silicotic models and administered AcSDKP in the experiment. Rats were divided into 6 groups randomly, 10 rats in each group: Control 1 and 2 of silicotic model: each rat was intratracheally instilled with 1.0 ml normal sodium and was killed after 4 or 8 weeks; Silicotic model 1 and Silicotic model 2: each rat was intratracheally instilled with 1ml silica suspension and was killed after 4 or 8 weeks; Anti-fibrosis treatment of AcSDKP: after each rat was intratracheally instilled with 1ml silica suspension for 4 weeks, AcSDKP 800 microg × kg(-1) × d(-1) was administered into every rat and rats were killed at the eighth week; Preventing fibrosis treatment of AcSDKP: after AcSDKP 800 microg × kg(-1) × d(-1) was administered into every rat for 48 hours, each rat was intratracheally instilled with 1.0 ml silica suspension and rats were killed at the eighth week. The expression of c-Raf, phospho-c-Raf, ERK1/2, phospho-ERK1/2 and TGF-β1 was measured by immunohistochemistry and western blot assay.</p><p><b>RESULTS</b>compared with the corresponding control groups, the expressions of phospho-c-Raf, phospho-ERK1/2 and TGF-β1 increased in the lung tissue of the silicotic models. Compared with the corresponding model groups, after administration AcSDKP, the expressions of phospho-c-Raf, phospho-ERK1/2 and TGF-β1 in the lung tissue reduced obviously. In anti-fibrosis treatment of AcSDKP group, expressions of phospho-c-Raf, phospho-ERK1/2 and TGF-β1 decreased to 52.25%, 51.72% and 67.74% compared with those of the silicotic model 1, and expressions of phospho-c-Raf, phospho-ERK1/2 and TGF-β1 decreased to 49.37%, 55.76%, 65.63% compared with those of the silicotic model 2; In preventing fibrosis treatment of AcSDKP group, expressions of phospho-c-Raf, phospho-ERK1/2 and TGF-β1 decreased to 54.64%, 55.76% and 78.91% compared with those of the silicotic model 2 (P < 0.05) while the expressions of c-Raf and ERK1/2 were not different significantly among each groups.</p><p><b>CONCLUSION</b>AcSDKP possibly plays an important role in anti-silicotic fibrosis by blocking the TGF-β-induced Ras-Raf-ERK1/2 signal transduction pathway.</p>
Subject(s)
Animals , Male , Rats , Lung , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , Oligopeptides , Pharmacology , Proto-Oncogene Proteins c-raf , Metabolism , Rats, Wistar , Signal Transduction , Silicosis , Metabolism , Transforming Growth Factor beta , MetabolismABSTRACT
In order to investigate the expression and the relationship of ubiquitin associated protein 1 (ubap1) gene and tumor-suppressor gene p16 in acute leukemia, 68 cases of acute leukemia and 22 control cases were selected in this experiment, FQ-PCR technique was used to detect the mRNA expression level of ubap1 gene and p16 gene in their bone marrow cells. The results showed that as compared with the control group, the ubap1 gene in acute leukemia group highly expressed (p<0.01), while the p16 gene lowly expressed (p<0.01). But grouping of patients according to FAB revealed that as compared with the control group, the ubap1 gene expression displayed statistical difference only in M4 and M5 of adult AML (p<0.05), while the p16 gene expression in all groups of adult AML showed significant difference (p<0.05) except M1 and M2. In addition to this, the ubap1 gene and p16 gene mRNA expression in AL was not relate with chromosome abnormality (p>0.05). A negative correlation (r=-0.827, p<0.01) was found between the ubap1 gene and p16 gene mRNA expressions in the control group. It is concluded that the upregulation of ubap1 gene expression mainly and the downregulation of p16 gene expression mainly may simultaneously participate in the pathogenesis of acute leukemia. High expression of ubap1 gene influences the M4 and M5 subtypes in AML. This discovery provides important theoretical basis for the further investigation of pathogenesis and targeting therapy of AL.
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Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Bone Marrow Cells , Metabolism , Carrier Proteins , Genetics , Case-Control Studies , Cyclin-Dependent Kinase Inhibitor p16 , Genetics , Gene Expression , Leukemia , Genetics , Metabolism , Pathology , RNA, Messenger , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of AcSDKP on collagen synthesis and degradation in cultured rat cardiac fibroblasts.</p><p><b>METHODS</b>Neonatal rat cardiac fibroblasts were isolated and stimulated by PDGF. The cell proliferation was observed by (3)H-TdR incorporation assay. The synthesis of collagen was measured by (3)H-proline incorporation assay. The expression of type I and type III collagen and MMP-1 protein were measured by Western blot. The MMP-2 and MMP-9 activity was evaluated with zymography assay.</p><p><b>RESULTS</b>PDGF stimulated cardiac fibroblasts proliferation with increased collagen synthesis and type I and type III collagen protein expressions as well as MMP-2 and MMP-9 activities and MMP-1 expression. AcSDKP inhibited cardiac fibroblasts proliferation induced by PDGF and reduced collagen synthesis and type I and type III collagen protein expression. AcSDKP also further up-regulated MMP-2 and MMP-9 activities and MMP-1 expression in cardiac fibroblasts induced by PDGF.</p><p><b>CONCLUSION</b>AcSDKP inhibited proliferation and collagen synthesis and up-regulated matrix metalloproteinases activity or expression induced by PDGF, which was possibly related with the effect of AcSDKP anti-fibrosis.</p>
Subject(s)
Animals , Rats , Cell Proliferation , Cells, Cultured , Collagen , Fibroblasts , Metabolism , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Myocytes, Cardiac , Metabolism , Oligopeptides , Physiology , Platelet-Derived Growth Factor , Rats, WistarABSTRACT
The study of mammary gland bioreactor is in the ascendant. In order to generate transgenic goats of well-controlled expression of exogenic genes, we constructed a human lactoferrin (hLF) gene targeting vector containing promoter, exon 1, intron1 and some of exon 2 (about 6.1 kb fragment) and exon 6 approximately 9 (about 3.3 kb fragment) of the goat beta-casein gene as well as hLF minigene, neo gene inserted into them and tk gene ligated to the 3' end of the construct. The 9.4 kb goat genomic sequences as homologous arms were initially amplified by PCR with local goat tissue DNA. The expression vector was named pBC-tk-neo-hlf. Then the recombinant plasmid pBC-tk-neo-hlf containing hLF minigene was transfected into mice mammary tumor cell line C127 by liposome, cell clones were selected with G418. After proliferating, the transfected cells were induced with insulin, luteotropic hormone and hydrocortisone. The result of Western-blotting analysis showed that the transfected cells can secrete hLF protein, and the recombinant protein expressed in cultured cell supernatant has the similar molecular weight as the native protein. The expression level detected by ELISA was 0.21 microg/mL. This result indicated that the targeting vector could efficiently direct the expression of hLF in mammary cells,and it confirmed the validity of the constructed vector. At the same time, C127 cell line proved to be useful for evaluating the regulation of a foreign gene expression in mammary gland specific expression vector.