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This study aims to evaluate the methodological and reporting quality of diagnosis and treatment guidelines for hyperuricemia as well as the expert consensuses and promote the understanding and application of the diagnosis and treatment guidelines for hyperuricemia. With "hyperuricemia" "guidelines" "consensus" "recommendations" as the key words in titles, the authors searched for the published clinical guidelines on hyperuricemia in Chinese against CNKI, Wanfang, VIP, Medlive and the official website of the industry association. The retrieval time limit was until May 31, 2021. The appraisal of guidelines for research and evaluation Ⅱ(AGREEⅡ) and the reporting items for practice guidelines in health care(RIGHT) were employed to evaluate the methodological quality and reporting quality of 14 guidelines/consensuses included. The average scores of the guidelines/consensuses were 80.85%(48.61%-98.61%) for the domain of scope and purpose, 34.52%(0-69.44%) for the domain of stakeholder involvement, 35.53%(6.25%-92.19%) for the domain of rigor of development, 55.85%(23.61%-86.11%) for the domain of clarity of presentation, 26.19%(0-76.04%) for the domain of applicability, and 21.42%(0-50.00%) for the domain of editorial independence. Nine guidelines/consensuses were of medium overall quality with grade B recommendation, and five guidelines/consensuses were of poor quality with grade C recommendation. The RIGHT classified the fourteen guidelines/consensuses into one of high reporting quality, three of medium reporting quality, and ten of low reporting quality. The results of this study indicate that the standardization and rigor of the methodological quality and the reporting quality of the clinical guidelines/consensuses for hyperuricemia in China remain to be strengthened.
Subject(s)
Humans , China , Consensus , Hyperuricemia/drug therapy , Publications , Reference StandardsABSTRACT
The aim of this study was to elucidate the mechanism of nuciferine on alleviating obesity based on modulating gut microbiota, ameliorating chronic inflammation, and improving gut permeability. In this study, the obese model mice were induced by high-fat diet and then randomly divided into model group, and nuciferine group; some other mice of the same week age were fed with normal diet as normal group. In the modeling process, the mice were administered intragastrically(ig) for 12 weeks. In the course of both modeling and treatment, the body weight and food intake of mice in each group were measured weekly. After modeling and treatment, the Lee's index, weight percentage of inguinal subcutaneous fat, and the level of blood lipid in each group were measured. The pathological changes of adipocytes were observed by HE staining to evaluate the efficacy of nuciferine treatment in obese model mice. 16 S rRNA sequencing analysis was conducted to study the changes in diversity and abundance of gut microbiota after nuciferine treatment. Enzyme-linked immunosorbent assay(ELISA) and quantitative Real-time polymerase chain reaction(qPCR) were used to detect the levels of inflammatory factors interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and the expression of related genes in adipose tissue of mice in each group, so as to evaluate the effect of nuciferine on chronic inflammation of mice in obese model group. qPCR was used to detect the expression of occludin and tight junction protein 1(ZO-1)gene in colon tissure, so as to evaluate the effect of nuciferine on intestinal permeability of mice in obese group. Nuciferine decreased the body weight of obese mice, Lee's index, weight percentage of inguinal subcutaneous fat(P<0.05), and reduced the volume of adipocytes, decreased the level of total cholesterol(TC), triglyceride(TG), and low density lipoprotein cholesterol(LDL-C)(P<0.05) in serum, improved dysbacteriosis, increased the relative abundance of Alloprevotella, Turicibacter, and Lactobacillus, lowered the relative abundance of Helicobac-ter, decreased the expression of inflammatory cytokines IL-6, IL-1β, and TNF-α genes in adipose tissue(P<0.01), decreased the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in serum(P<0.05), and increased the expression of occludin and ZO-1 genes related to tight junction in colon tissue(P<0.01). Nuciferine could treat obesity through modulating gut microbiota, decreasing gut permeability and ameliorating inflammation.
Subject(s)
Animals , Mice , Aporphines , Diet, High-Fat/adverse effects , Gastrointestinal Microbiome , Mice, Inbred C57BL , Mice, Obese , Obesity/geneticsABSTRACT
Objective: The aim of this study is to discover the possible working mechanisms of Ardisiae Japonicae Herba (AJH) on hepatoma carcinoma (HCC). Methods: In this study, ethanol extract of AJH was prepared and used to treat HCC cell in vitro. Furthermore, a genomic wide RNA sequencing (RNA-seq) was performed to screen deregulated genes in HCC cells after the treatment of AJH extract. The gene and protein expression related to lipid metabolism in HCC cells were also investigated to validate the results obtained from RNA-seq. Results: AJH extract could inhibit HCC cell proliferation in vitro. RNA-seq analysis has identified 1,601 differentially expressed genes (DEGs, fold change ≥ 2.0 or fold change ≤ 0.5, P < 0.05) in HCC after AJH extract treatment, which included 225 up-regulated genes and 1,376 down-regulated genes. KEGG pathway analysis of DEGs demonstrated that lipid metabolism was a potential pathway related to AJH treatment. In agreement with the RNA-seq data, qPCR and Western-blot analysis indicated that expression of genes and proteins related to lipid metabolism (SREBP1, ACC, ACLY and FASN) were significantly down-regulated in AJH treatment group as compared with the control group. Furthermore, AJH extract could also decrease lipid contents and cellular free fatty acid levels in HCC cells. Conclusion: Ethanol extract of AJH could inhibit HCC cell proliferation in vitro, the possible mechanism may be related to the inhibition of lipid metabolism.
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Objective To investigate the incidence and bacterial etiology of stent associated respiratory tract infec-tion (SARTI) caused by two types of airway stents.Methods Silicone and coated metal airway stent were placed into patients with central airway stenosis caused by varied pathologies. The incidence of stent related respiratory tract infection,bacteria etiology of SARTI and improved dyspnea score were compared between two groups receiving different airway stent.Results 1)Totally 171 patients received airway stents, and among them, 39 patients (22.81%) developed SARTI.2)The incidence of SARTI in metal stent group and silicone stent group was 29.21% (26/89) vs.15.85% (13/82),P<0.05;3)Bacterial spectrum of SARTI was different in metal and silicone stent groups:staphylococcus aureus was 38.46% vs. 69.23%,respectively;candida albicans was 23.08% vs. 0%,re-spectively;Singular proteus was 7.26% vs.0%,respectively;4)The narrowed lumen was improved from 74.27%± 7.13% to 17.64%±6.22%in the metal stent group,while the data was improved from 74.94%±9.18% to 12.68%± 8.32% in the silicone stent group (P<0.01). Accordingly, the dyspnea symptomscore was improvedfrom 2.85 ± 0.89 to 0.85±0.68 in metal stent group,and from 2.88±0.91 to 0±0.61 in the silicone stent group (P<0.05). Conclusions Compared with metal airway stents,silicone stents have a lower incidence of SARTI,which mightbe due to the projections in the silicon stent surface and wider expanded in the bronchial stenosis.
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The mechanisms involved in virus-induced severe hepatitis have not been fully elucidated.In this study,we investigated the role of gamma delta T cell receptors (γδ) T cells in the pathogenesis of fulminant viral hepatitis (FVH) induced by murine hepatitis virus strain 3 (MHV-3).The model of FVH was established by intraperitoneal injection of MHV-3 into Balb/cJ mice.The survival days of mice,and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined.The proportions ofγδ T cells in blood,spleen and liver,and cytokines secreted by hepatic γδ T cells were analyzed by flow cytometry.The function of hepatic γδ T cells was examined by cytotoxicity assay.Balb/cJ mice died in 3 to 6 days post MHV-3 infection,with severe hepatic necrosis and significant augmentation of serum ALT and AST levels.The proportions of γδ T ceils in blood,spleen and liver were significantly increased post MHV-3 infection,while those of the early activating molecule CD69-expressing γδ T cells and productions of cytokines tumor necrosis factor-alpha (TNF-α) and interferon-γ (IFN-γ) increased remarkably in the liver.These highly activated liver γδ T cells were cytotoxic to MHV-3-infected hepatocytes in vitro and this effect of liver γδ T cells against hepatocytes might involve the TNF-α and IFN-γ pathway.These results demonstrated that γδ T cells might contribute to the pathogenesis ofMHV-3-induced FVH through the effector cytokines TNF-α and IFN-γ.
ABSTRACT
The mechanisms involved in virus-induced severe hepatitis have not been fully elucidated.In this study,we investigated the role of gamma delta T cell receptors (γδ) T cells in the pathogenesis of fulminant viral hepatitis (FVH) induced by murine hepatitis virus strain 3 (MHV-3).The model of FVH was established by intraperitoneal injection of MHV-3 into Balb/cJ mice.The survival days of mice,and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined.The proportions ofγδ T cells in blood,spleen and liver,and cytokines secreted by hepatic γδ T cells were analyzed by flow cytometry.The function of hepatic γδ T cells was examined by cytotoxicity assay.Balb/cJ mice died in 3 to 6 days post MHV-3 infection,with severe hepatic necrosis and significant augmentation of serum ALT and AST levels.The proportions of γδ T ceils in blood,spleen and liver were significantly increased post MHV-3 infection,while those of the early activating molecule CD69-expressing γδ T cells and productions of cytokines tumor necrosis factor-alpha (TNF-α) and interferon-γ (IFN-γ) increased remarkably in the liver.These highly activated liver γδ T cells were cytotoxic to MHV-3-infected hepatocytes in vitro and this effect of liver γδ T cells against hepatocytes might involve the TNF-α and IFN-γ pathway.These results demonstrated that γδ T cells might contribute to the pathogenesis ofMHV-3-induced FVH through the effector cytokines TNF-α and IFN-γ.
ABSTRACT
Based on essence, yin yang and five elements in basic TCM philosophy, this article proposed that congenital qi plays an important role in the regeneration of tissues and organs in TCM. Combination of medicine stem cell theory of congenital essence of nutrition is the key to stimulate repair of tissue and organ function regeneration;Yin-yang harmony and generation and restriction among five elements are the theoretical basis for functional regeneration regulation of zangfu organs in TCM. It is considered that TCM has unique advantages in preventing functional damage of zangfu organs, promoting tissue regeneration, and preventing abnormal tissue regeneration. Proceeding from traditional thinking of TCM, it may become an innovation and breakthrough for TCM regenerative medicine theory.
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<p><b>OBJECTIVE</b>To examine the association of genetic variants with characteristic symptoms of type 2 diabetes mellitus (T2DM).</p><p><b>METHODS</b>A matched case-control study was performed to investigate the association between common variants in four genes (CDKAL1, GLIS3, GRK5, and TCF7L2) and symptoms of T2DM. Symptoms were examined with questionnaire for 710 subjects. Genomic DNA was extracted from peripheral blood mononuclear cell by salting-out procedure. Genotyping was carried out by direct sequencing of the unpurified polymerase chain reaction products.</p><p><b>RESULT</b>Most of the T2DM patients pressented characteristic symptoms, such as feeling weak in limbs (P =0.0057), hand tremor (P =0.0208), bradymasesis (P =0.0234), and polyuria (P =0.0051). Some of the T2DM patients shared characteristic symptoms, such as desire for cold drinks (P =0.0304), polyphagia (P =0.0051), and furred tongue (P =0.028). The impaired glucose regulation (IGR) cases took only one characteristic symptom of frequent micturition (P =0.0422). GLIS3 rs7034200 and GRK5 rs10886471 were significantly associated with increased T2DM risk (GLIS3 rs7034200 under dominant model: P=0.0307; GRK5 rs10886471 under recessive model: P=0.0092). However, only the rs10886471 polymorphism in GRK5 showed a significant effect on both differentiated symptoms and T2DM risk. The C-allele was involved in both dampness-heat encumbering Pi (Spleen) syndrome (P =0.047) and qi-yin deficiency syndrome (P =0.002) via increased GRK5 expression.</p><p><b>CONCLUSIONS</b>Both T2DM and IGR exhibited its corresponding characteristic symptoms. The variants of GRK5 were involved with both qi-yin deficiency syndrome and dampness-heat encumbering Pi syndrome.</p>
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Excessive activation of macrophages is implicated in various inflammatory injuries. Salidroside (Sal), one of the main bioactive components of Rhodiola Sachalinensis, has been reported to possess anti-inflammatory activities. This study aimed to examine the effect of Sal on the activation of macrophages and the possible mechanism. The lipopolysaccharide (LPS)-stimulated phrobol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage models were established. The changes in the inflammatory profiles of THP-1-derived macrophages were determined. The results showed that Sal significantly decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), interleukin-1beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) at both mRNA and protein levels in THP-1-derived macrophages, and the effect was dose-depedent. Moreover, NF-κB activation was significantly suppressed and the phosphorylation of ERK, p38 and JNK was substantially down-regulated after Sal treatment. The findings suggested that Sal can suppress the activation of LPS-stimulated PMA-differetiated THP-1 cells, as evidenced by the decreased expression of iNOS, COX2, IL-1β, IL-6 and TNF-α, and the mechanism involves the inhibition of NF-κB activation and the phosphorylation of the MAPK signal pathway.
ABSTRACT
Excessive activation of macrophages is implicated in various inflammatory injuries. Salidroside (Sal), one of the main bioactive components of Rhodiola Sachalinensis, has been reported to possess anti-inflammatory activities. This study aimed to examine the effect of Sal on the activation of macrophages and the possible mechanism. The lipopolysaccharide (LPS)-stimulated phrobol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage models were established. The changes in the inflammatory profiles of THP-1-derived macrophages were determined. The results showed that Sal significantly decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), interleukin-1beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) at both mRNA and protein levels in THP-1-derived macrophages, and the effect was dose-depedent. Moreover, NF-κB activation was significantly suppressed and the phosphorylation of ERK, p38 and JNK was substantially down-regulated after Sal treatment. The findings suggested that Sal can suppress the activation of LPS-stimulated PMA-differetiated THP-1 cells, as evidenced by the decreased expression of iNOS, COX2, IL-1β, IL-6 and TNF-α, and the mechanism involves the inhibition of NF-κB activation and the phosphorylation of the MAPK signal pathway.
Subject(s)
Humans , Cell Line , Down-Regulation , Genetics , Allergy and Immunology , Glucosides , Pharmacology , Lipopolysaccharides , Allergy and Immunology , Macrophages , Allergy and Immunology , Mitogen-Activated Protein Kinases , Genetics , NF-kappa B , Genetics , Phenols , Pharmacology , Signal Transduction , Genetics , Allergy and ImmunologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the protective effects of sodium tanshinone B (STB) on brain damage following focal ischemia-reperfusion (I/R) injury through interfering with N-methyl-D-aspartic acid receptor (NMDAR) and excitatory and inhibitory amino acids, and evaluate the potential mechanisms of the neuroprotective activity of STB.</p><p><b>METHODS</b>Transient forebrain ischemia was induced by middle cerebral artery occlusion (MCAO). The rats were randomized into a sham operated group, a model group (I/R) and three STB different dose groups. Rats were pretreated with STB at the doses of 4, 8, 16 mg/kg (STB(1), STB(2), STB(3)) for 3 days before MCAO. The expression of NMDAR1 was detected by immunohistochemistry and Western blotting. The concentrations of glutamate and γ-aminobutyric acid (GABA) were analyzed using high performance liquid chromatography.</p><p><b>RESULTS</b>STB treatment reduced neurological defect scores, cerebral infarction volume and brain water content. The levels of NMDAR1 were significantly higher in the l/R and STB(1) groups than that of the sham and the STB(3) groups (P<0.01). Optical density of NMDAR1 was significantly increased in cornu ammonis (CA)1 region of the l/R group (P<0.05). STB treatment reduced NMDAR1 optical density in the CA1 region (P<0.01). The levels of glutamate were significantly lower in the hippocampus in the STB(3) group than that of the l/R, STB(1) and STB(2) groups (P<0.01).</p><p><b>CONCLUSION</b>Preconditioning with STB appears to be a simple and promising strategy to reduce or even prevent cerebral l/R injury and has potential for future clinical application.</p>
Subject(s)
Animals , Rats , Brain Ischemia , Pathology , Cytoprotection , Disease Models, Animal , Abietanes , Pharmacology , Drug Evaluation, Preclinical , Drugs, Chinese Herbal , Pharmacology , Hippocampus , Pathology , Models, Biological , Neurons , Pathology , Physiology , Neuroprotective Agents , Pharmacology , Random Allocation , Reperfusion Injury , Pathology , Treatment OutcomeABSTRACT
<p><b>BACKGROUND</b>Islet transplantation is an effective way of reversing type I diabetes. However, islet transplantation is hampered by issues such as immune rejection and shortage of donor islets. Mesenchymal stem cells can differentiate into insulin-producing cells. However, the potential of human umbilical cord mesenchymal stem cells (huMSCs) to become insulin-producing cells remains undetermined.</p><p><b>METHODS</b>We isolated and induced cultured huMSCs under islet cell culture conditions. The response of huMSCs were monitored under an inverted phase contrast microscope. Immunocytochemical and immunofluorescence staining methods were used to measure insulin and glucagon protein levels. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect gene expression of human insulin and PDX-1. Dithizone-staining was employed to determine the zinc contents in huMSCs. Insulin secretion was also evaluated through radioimmunoassay.</p><p><b>RESULTS</b>HuMSCs induced by nicotinamide and β-mercaptoethanol or by neurogenic differentiation 1 gene (NeuroD1) transfection gradually changed morphology from typically elongated fibroblast-shaped cells to round cells. They had a tendency to form clusters. Immunocytochemical studies showed positive expression of human insulin and glucagon in these cells in response to induction. RT-PCR experiments found that huMSCs expressed insulin and PDX-1 genes following induction and dithizone stained the cytoplasm of huMSCs a brownish red color after induction. Insulin secretion in induced huMSCs was significantly elevated compared with the control group (t = 6.183, P < 0.05).</p><p><b>CONCLUSIONS</b>HuMSCs are able to differentiate into insulin-producing cells in vitro. The potential use of huMSCs in β cell replacement therapy of diabetes needs to be studied further.</p>
Subject(s)
Female , Humans , Pregnancy , Cell Differentiation , Genetics , Physiology , Cells, Cultured , Cellular Reprogramming , Genetics , Physiology , Immunohistochemistry , Insulin-Secreting Cells , Cell Biology , Metabolism , Mesenchymal Stem Cells , Cell Biology , Reverse Transcriptase Polymerase Chain Reaction , Umbilical Cord , Cell Biology , Wharton Jelly , Cell BiologyABSTRACT
<p><b>OBJECTIVE</b>Primary airway neoplasms are extremely rare in the pediatric age group. This paper reports 4 children with primary airway neoplasms to explore the clinical manifestations, safety and efficacy of bronchoscopic interventions.</p><p><b>METHOD</b>The data of pathology, photographic documentation and imaging studies were analyzed.</p><p><b>RESULT</b>Of the 4 reported lesions, 2 were characterized by low-grade (2 with mucoepidermoid carcinoma) and 2 by high grade malignant (spindle cell carcinoma and malignant lymphoma). Onset of clinical manifestations occurred at the ages of 7 months to 7 years. All of them were initially misdiagnosed as bronchitis, asthma or atelectasis. The lesions located in trachea in 2 patients, in left bronchus of 1 patient and in right middle bronchus of 1 case. Atelectases occurred in bilateral bronchus where the lesions obstructed almost the entire lumen at the time of diagnosis. The diagnosis of airway masses depends upon maintaining a high index of suspicion, complemented by imaging and timely diagnostic endoscopy. The lesions were completely removed in 3/4 patients except 1 died during bronchoscopic procedures.</p><p><b>CONCLUSION</b>The children with malignant airway neoplasms were presented with cough and wheezing without specific manifestations. Bronchoscopic interventions were effective in the treatment of non-operative cases. General anesthesia is strongly recommended for interventional bronchoscopy.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Male , Bronchoscopy , Retrospective Studies , Tracheal Neoplasms , Diagnosis , TherapeuticsABSTRACT
<p><b>BACKGROUND</b>Inhalational anesthesia with sevoflurane for endotracheal intubation without muscle relaxant is now used widely for pediatric patients. This study assessed the efficacy and safety of induction with high concentration sevoflurane and of nasotracheal intubation without muscle relaxant in infants with increased or decreased pulmonary blood flow (PBF) and undergoing surgery for congenital heart diseases.</p><p><b>METHODS</b>Fifty-five infants aged 2 - 12 months, weighing 4.7 - 10.0 kg, and scheduled for congenital cardiac surgery were enrolled. Subjects were divided into those with increased (IPBF group, n = 29) and decreased (DPBF group, n = 26) pulmonary blood flow. All infants received inhalational induction with 8% sevoflurane in 100.0% oxygen at a gas flow rate of 6 L/min. Nasotracheal intubation was performed 4 minutes after induction. Sevoflurane vaporization was decreased to 4.0% for placement of a peripheral intravenous line and invasive hemodynamic monitors. Five minutes later, sedatives and muscle relaxant were administered and the vaporizer was adjusted to 2% for maintenance of anesthesia. Bispectral index (BIS) scores, circulatory parameters, satisfactory and successful intubation ratios, adverse reactions, and complications of intubation were recorded.</p><p><b>RESULTS</b>Times to loss of lash and pain reflexes were longer for the DPBF group (P < 0.01). Satisfactory intubation ratios were 93.1% and 61.5% for the IPBF and DPBF groups, respectively (P = 0.008). Successful intubation ratios were 96.6% and 76.9% for the IPBF and DPBF groups, respectively (P = 0.044). Following sevoflurane inhalation, blood pressures decreased significantly in the IPBF group but remained stable in the DPBF group. BIS scores declined to similar stable values, and a "nadir BIS" was recorded for both groups. No obvious adverse reactions or complications of intubation were noted perioperatively.</p><p><b>CONCLUSIONS</b>Induction with high concentration sevoflurane, although faster for infants with IPBF, is safe for infants with IPBF or DPBF. However, nasotracheal intubation without muscle relaxant after induction with high concentration sevoflurane is less successful and less satisfactory for infants with DPBF and should be used with caution in this patient group.</p>
Subject(s)
Female , Humans , Infant , Male , Anesthetics, Inhalation , Blood Circulation , Heart Defects, Congenital , General Surgery , Intubation, Intratracheal , Lung , Methyl Ethers , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of Cox7a2 on the LH-induced testosterone production and the involved autophagy regulating signals in TM3 mouse Leydig cells.</p><p><b>METHODS</b>The Cox7a2-pEYFP-N1 fluorescent protein vector was constructed and transfected into TM3 mouse Leydig cells. The level of testosterone was determined by ELISA, and the effects of Cox7a2 on the expression of the steroidogenic acute regulatory protein (StAR) and the phosphorylation of the autophagy regulatory factor P70S6K were detected by Western blot.</p><p><b>RESULTS</b>LH stimulation increased the StAR protein expression and testosterone production, while Cox7a2 decreased P70S6K phosphorylation, reduced StAR expression and consequently inhibited LH-induced testosterone biosynthesis in the TM3 Leydig cells.</p><p><b>CONCLUSION</b>Cox7a2 inhibits testosterone production by decreasing the StAR protein expression, which might be at least in part related with the activation of autophagy in TM3 mouse Leydig cells.</p>
Subject(s)
Animals , Male , Mice , Autophagy , Cells, Cultured , Electron Transport Complex IV , Genetics , Leydig Cells , Metabolism , Luteinizing Hormone , Pharmacology , Phosphoproteins , Metabolism , Phosphorylation , Ribosomal Protein S6 Kinases, 70-kDa , Metabolism , TestosteroneABSTRACT
<p><b>OBJECTIVE</b>To explore the mechanisms of a novel potassium channel gene named KCTD9 (potassium channel tetramerization domain containing 9) in model of fulminant viral hepatitis induced by murine hepatitis virus 3 (MHV-3).</p><p><b>METHODS</b>78 BALB/cJ mice(6 male) were randomly and equally assigned to two groups, model group of fulminant viral hepatitis induced by MHV3 and its control. 75 C3H/HeJ female mice were done into two groups, 39 for model group of chronic hepatitis induced by MHV3, 36 for control. Various samples including spleen, liver and lymphocytes from mice of two model groups and the controls were examined for KCTD9 expression by real time quantitative PCR and Immunohistochemistry. Independent-samples T test or one-way ANOVA were carried out in different groups.</p><p><b>RESULTS</b>Increased expressions of KCTD9 mRNA was observed in livers of both model mice of fulminant viral hepatitis and chronic hepatitis. Compared with the control mice, the expressions of KCTD9 mRNA were up-regulated by 577.1-, 8.8-, 59.4- and 10.8-fold in hepatic NK cells, CD4+ T cells, CD8+ T cells and splenic NK cells respectively in model mice of fulminant viral hepatitis 48 hr post MHV-3 infection, whereas down-regulation by 43% and 69% in splenic CD4 + T cells and CD8+ T cells were found respectively. In contrast, in model mice of chronic viral hepatitis the expressions of KCTD9 mRNA were down-regulated by 71% and 51% in hepatic CD4+ T cells and NK cells, respectively. The expression of KCTD9 protein was mainly evidenced in infiltrative mononuclear cells of liver as shown by immunohistochemistry. Basal expression was also investigated and showed constitutive expression of KCTD9 in brain, thymus and other organs in BALB/cJ mice.</p><p><b>CONCLUSION</b>A novel potassium channel gene KCTD9 was highly expressed in hepatic NK cells and T cells of fulminant hepatitis mice induced by MHV-3.</p>
Subject(s)
Animals , Female , Male , Mice , CD4-Positive T-Lymphocytes , Allergy and Immunology , Metabolism , Hepatitis, Viral, Animal , Allergy and Immunology , Metabolism , Virology , Killer Cells, Natural , Allergy and Immunology , Metabolism , Liver , Metabolism , Virology , Mice, Inbred BALB C , Mice, Inbred C3H , Murine hepatitis virus , Potassium Channels , Genetics , MetabolismABSTRACT
<p><b>BACKGROUND</b>The body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index was shown at predicting the risk of death, exacerbation and disease severity among patients with COPD, but few studies verified relationship between BODE index and health related quality of life (HRQoL) among Chinese COPD patients. The objective of this study was to evaluate the relationship between BODE index and HRQoL in cross-sectional and longitudinal association analyses.</p><p><b>METHODS</b>A multi-center prospective cohort study was initially conducted in 491 stable COPD patients in Beijing, China. Health status (HRQoL) was assessed by St. George's Respiratory Questionnaire (SGRQ); the BODE index was calculated for each patient; dyspnea was assessed using the 5-grade Medical Research Council dyspnea scale. Other measurements included socio-demographic, body mass index (BMI), lung function test and 6-minute-walk test (6MWT). Patients were then followed monthly for 12 months.</p><p><b>RESULTS</b>Only 450 patients completed the 1-year follow up and were enrolled in our present analyses. Mean age was (65.2 +/- 10.6) years, men 309 (68.7%). The BODE index was categorized into 4 subgroups: 0 - 2, 3 - 4, 5 - 6 and 7 - 10. At baseline BODE index was gradually increased with baseline total SGRQ and SGRQ subscales (P trend < 0.001). For individual components of BODE index, with the decrease of airflow limitation, and 6MWD, and with the increase of Medical Research Council (MRC) dyspnea grade, total SGRQ and SGRQ subscales were increased correspondingly, P trend < 0.05, respectively. Similar association patterns were found between baseline BODE index and its individual components and mean SGRQ scores at the end of 1-year follow up. By multiple linear regression analyses, baseline BODE index was not only significantly associated with SGRQ score at baseline but also with SGRQ score at the end of 1-year follow up after adjustment for age, male, current smoking, betas being 0.434 and 0.378, respectively.</p><p><b>CONCLUSIONS</b>BODE index is associated with SGRQ score cross-sectionally and longitudinally among stable COPD patients. BODE index might have potential to be used as a sensitive tool to assess the status of quality of life and to monitor disease progression among stable COPD patients.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Body Mass Index , Cross-Sectional Studies , Dyspnea , Pathology , Exercise Tolerance , Physiology , Linear Models , Longitudinal Studies , Prospective Studies , Pulmonary Disease, Chronic Obstructive , Pathology , Quality of Life , Respiratory Function Tests , Smoking , Surveys and QuestionnairesABSTRACT
<p><b>OBJECTIVE</b>To investigate role of CD4-CD8- T cells in murine hepatitis virus type 3 (MHV-3) induced chronic viral hepatitis in C3H/Hej mice and to identify their surface markers.</p><p><b>METHODS</b>Thirty C3H/Hej mice received 10 Pfu MHV-3 intraperitoneally, the CD4-CD8- T cells were isolated using magnetic bead sorting on 0, 4, 15, 30, 40 days post MHV-3 infection. The cytotoxic effects of CD4-CD8- T cells on normal and infected hepatocytes, CD8+ T cells and unrelated-virus (murine cytomegalovirus, MCMV) infected CD8+ T cells were examined by non-radioactive cytotoxicity assay. The surface markers of CD4-CD8- T cells were determined by flow cytometry.</p><p><b>RESULTS</b>MHV-3 infected CD4-CD8- T cells showed significant cytotoxic effect on CD8+ T cells, but not on infected hepatocytes or MCMV infected CD8+ T cells. The analysis of cell surface markers demonstrated that the CD4-CD8- T cells are a completely new T cell subset.</p><p><b>CONCLUSIONS</b>CD4-CD8- T cells have significant cytotoxic effect on virus specific CD8+ T cells in MHV-3 infected C3H/Hej mice, which suggests that CD4-CD8- T cells have immune modulatory functions in the development of chronic viral hepatitis. The phenotype of these CD4-CD8- T cells detected by flow cytometry is TCR alpha beta +CD3+CD4- CD8- CD25- CD28- CD30- CD44+.</p>
Subject(s)
Animals , Female , Mice , CD4-Positive T-Lymphocytes , Allergy and Immunology , CD8-Positive T-Lymphocytes , Allergy and Immunology , Coronavirus Infections , Allergy and Immunology , Pathology , Virology , Flow Cytometry , Hepatitis, Viral, Animal , Allergy and Immunology , Pathology , Virology , Liver , Allergy and Immunology , Pathology , Mice, Inbred C3H , Murine hepatitis virus , Spleen , Allergy and Immunology , Pathology , T-Lymphocyte Subsets , Allergy and Immunology , Time FactorsABSTRACT
<p><b>BACKGROUND</b>Epidermal growth factor (EGF), a mitogenic polypeptide that binds to cell surface receptors, is an important regulator of cell differentiation and fetal lung surfactant synthesis. We investigated the preventive and therapeutic effects of EGF in respiratory distress syndrome, by administering EGF and dexamethasone (Dex) to mother rat before delivery.</p><p><b>METHODS</b>Six female Sprague-Dawley (SD) rats were assigned to three groups (2 rats each); EGF or Dex was given to pregnant rats (EGF group and Dex group, respectively) from gestational day 16 to day 18 by intraperitoneal injection, while the group with normal saline injection was used as negative controls. Fetal rats were taken out of womb by hysterotomy on day 19 of pregnancy, then 24 fetal rats were randomly chosen from each group. Their body weights were measured, and pulmonary surfactant protein-A and -B (SP-A and SP-B) antigens were determined by immunohistochemical staining in each group. The histologic structure was examined under a light microscope, a light microscopic image system or an electron microscope.</p><p><b>RESULTS</b>The expressions of SP-A and SP-B could be detected in each group. A significant difference was observed for SP-A and SP-B in the EGF and Dex groups compared with the control group (P < 0.01). Image analysis showed that the relative values of air space area and interalveolar septa area in the EGF and Dex groups were significantly greater than those in the control group (P < 0.01), while no significant difference was found between the two groups (P > 0.05). The ultrastructural features of fetal lungs showed that the number of alveolar type II cells containing lamellar bodies in the EGF and Dex groups was apparently increased compared with that in the control group. The mean body weight of fetus from the Dex group was smaller than that from the control group ((1.3192 +/- 0.0533) g, (1.3863 +/- 0.0373) g), but there was no significant difference between the EGF group and the control group ((1.3986 +/- 0.0730) g, (1.3863 +/- 0.0373) g).</p><p><b>CONCLUSIONS</b>Maternal treatment with EGF and Dex on days 16 - 18 of gestation could promote morphogenesis and increase the surfactant levels in premature fetal lung. However, maternal treatment with Dex, not EGF, decreased the body weight.</p>
Subject(s)
Animals , Female , Pregnancy , Rats , Dexamethasone , Pharmacology , Epidermal Growth Factor , Pharmacology , Immunohistochemistry , Lung , Embryology , Microscopy, Electron, Transmission , Pulmonary Surfactant-Associated Protein A , Metabolism , Pulmonary Surfactant-Associated Protein B , Metabolism , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVES</b>To investigate the role of liver natural killer cells (NK cells) in murine hepatitis virus strain 3 (MHV-3) induced murine fulminant hepatitis.</p><p><b>METHOD</b>Balb/cJ mice (6-8 weeks, female) were intraperitoneally injected with 100 PFU MHV-3. The numbers of NK cells in their livers, spleens, blood and bone marrow and the expression of CD69 on liver NK cells at 0, 24, 48 and 70 h after MHV-3 infection were analyzed by flow cytometry. The cytotoxic activity of liver NK cells was detected by a non-radioactive cytotoxicity assay. The levels of IFN gamma produced by hepatic NK cells were detected by intracellular cytokine staining.</p><p><b>RESULT</b>Following MHV-3 infection, the proportion of liver NK cells in the mice increased remarkably and reached the peak (43.9%+/-2.3%) at 48 h, then kept a high proportion until the mice were sacrificed. The proportion of NK cells in the peripheral blood also significantly increased and reached the peak (18.0%+/-5.4%) at 48 h. However, there were few NK cells in the peripheral blood at 70 h after infection; the ratio was only 1.3%+/-0.6%. In the spleens and bone marrow, the proportions of NK cells were both significantly decreased from 0 h to 48 h and then slightly increased. The expression of CD69 on liver NK cells was highly up-regulated after the infection and the cytotoxic activity of hepatic NK cells at 48 h was also significantly enhanced. In addition, an increase in IFN gamma production by hepatic NK cells was observed at 48 h.</p><p><b>CONCLUSION</b>After MHV-3 infection, NK cells were recruited to the liver quickly, probably from the spleen and bone marrow. Recruited NK cells remarkably express CD69, enhance cytotoxic activity and IFN gamma production, which correlate with the disease severity of fulminant viral hepatitis. Our results suggest that liver NK cells may play a pivotal role in the pathogenesis of fulminant viral hepatitis.</p>