OBJECTIVETo investigate the changes of hepcidin and ferropotin 1 expression in murine model of iron overload.

METHODSThe murine model of iron overload was established, C57BL/6 mice were injected with iron dextran intraperitoneally (10 mg) every 3 days for 4 weeks. Blood routine, serum ferritin and pathological sections were tested at the appointed time-point respectively (before iron injection, 2 weeks and 4 weeks after treatment of iron injection). The serum hepcidin was assayed by enzyme-linked immunosorbent method. The expression of ferroportin 1 in bone marrow cells was detected by RT-PCR and Western blot, respectively. The labile iron pool of bone marrow cells was measured by flow cytometry.

RESULTSThe absolute number and percentage of reticulocytes in the iron-overloaded mice were significantly decreased along with the increase of iron injection times (r=-0.938, r=-0.947), while no significant change was found in the number of white blood cells, hemoglobin level and platelet count. The level of serum ferritin was increased along with increase of iron injection time (r=0.894). Iron overload was found in pathological sections of different organs. Furthermore, serum hepcidin was increased along with increase of iron injection time (r=0.957). RT-PCR and Western blot analyses showed that the expressions of ferroportin 1 at mRNA and protein level were increased in the murine model of iron overload (P<0.05). Labile iron pool in bone marrow cells was also found to be increased in the murine model of iron overload(P<0.05).

CONCLUSIONThe expressions of hepcidin and ferroportin 1 are increase in a murine model of iron overload, which may be contributed to the suppression effect on erythropoiesis in bone marrow.

OBJECTIVETo explore the role of the receptor for advanced glycation end products (RAGE) in regulating the expression of MUC5AC and mucus production in a mouse model of toluene diisocyanate (TDI)?induced asthma.

METHODSBALB/c mice were randomly divided into control group, vehicle (AOO) group, TDI?induced asthma group and RAGE inhibitor (FPS?ZM1) group. PAS staining, Western blotting, and immunohistochemistry were used to analyze the changes in mucus production and MUC5AC expression in the airway of the mice, and the expression of p?ERK was detected with Western blotting. In vitro cultured human bronchial epithelial cell line 16HBE was transfected with lentiviral vector carrying short hairpin RNA targeting RAGE (shRNA?RAGE) and subsequently challenged with a TDI?human serum albumin (TDI-HSA) conjugate, and the changes in cellular MUC5AC mRNA expression as detected using RT-PCR; the protein expressions of ERK and p?ERK in the cells were examined with Western blotting. The effect of ERK inhibitor U0126 pretreatment on MUC5AC mRNA expression was also analyzed in the cells.

RESULTSCompared with the control mice, TDI-induced asthmatic mice showed significantly higher rates of PAS positivity and increased MUC5AC and p?ERK expressions in the airway (P<0.05). Treatment with FPS?ZM1 significantly decreased PAS positivity and lowered MUC5AC and p?ERK expressions in the airway of the asthmatic mice (P<0.05). Exposure of 16HBE cells to TDI?HSA caused a significant increase in MUC5AC mRNA expression and p?ERK protein expression (P<0.05), while RAGE knockdown obviously suppressed TDI?HSA-induced upregulation of p-ERK and MUC5AC mRNA (P<0.05). Treatment with the ERK inhibitor U0126 also lowered TDI?HSA?induced up?regulation of MUC5AC mRNA in the cells (P<0.05).

CONCLUSIONRAGE signaling induces MUC5AC expression via extracellular signal-regulated kinase pathway to promote mucus overproduction in mice with TDI-induced asthma.

This paper systematically studies relevant literatures at home and abroad in recent years. China National Knowledge Internet (CNKI) was used to collect the literatures for acute pharyngitis treated with traditional Chinese medicine from January 1, 2006, to December 31, 2016, and the bibliometric method was employed for statistical analysis. A total of 493 papers were preliminarily selected. According to the inclusion criteria and exclusion criteria, 182 eligible articles were selected. According to the evaluation and analysis of the literatures, the Guidelines for Clinical Research of New Drugs is currently used as the common standards for the diagnosis and treatment of acute pharyngitis; Chinese patent medicines are the main traditional Chinese medicine for treating this disease; Decoctions for treatment of this disease include Lonicerae Japonicae Flos, Scutellariae Radix, Platycodonis Radix, Forsythiae Fructus, Glycyrrhizae Radix et Rhizoma, Scrophdlariae Radix, Isatidis Radix, and Ophiopogonis Radix; The bloodletting puncture is the common external therapy. Traditional Chinese medicine and Western medicine have their own characteristics in the treatment of this disease. Western medicine for the treatment of acute pharyngitis are mainly antiviral, antibiotic and glucocorticoid drugs, whose disadvantages are toxicity, side effects, drug resistance and double infections. Traditional Chinese medicine doctors have rich experiences in the treatment of the disease, which is characterized by treatment determination based on syndrome differentiation, safe and reliable medication, significant curative effect, low drug resistance, and wide varieties of traditional Chinese medicine forms, convenient portability and taking, low price, and low toxic and side effects. It is an arduous and significant task to explore traditional Chinese medicine, and study and develop new-type effective drugs.

OBJECTIVETo evaluate fractional exhaled nitric oxide (FENO) level in patients with subacute cough and its value in predicting the patients' response to inhaled corticosteroids (ICS) treatment.

METHODSA total of 100 patients with persistent cough lasting more than 3 weeks were enrolled, including 52 patients with subacute cough and 48 with chronic cough. FENO, spirometry, and responses to ICS therapy of the patients were evaluated.

RESULTSThe recruited patients had a median (inter-quartile ranges) FENO level of 19 ppb (12-30 ppb). Patients with chronic cough had a significantly higher median FENO level than those with subacute cough (20.5 vs 16 ppb; Z=-2.245, P=0.025). A FENO level ≥25 ppb was recorded in 15 (28.8%) patients with subacute cough, as compared with 20 (41.6%) in patients with chronic cough (χ(2)=1.801, P=0.179). With a FENO ≥25 ppb as the critical value to justify ICS treatment, 15 patients with subacute cough received ICS and 14 (93.3%) of them showed obvious relief of cough after 2 weeks of therapy, a response rate similar to that of 85.0% (17/20) in patients with chronic cough receiving the treatment (χ(2)=0.588, P=0.443). In patients with subacute cough, those with cough variant asthma (CVA) or eosinophilic bronchitis (EB) had a significantly higher median FENO level than those with postinfectious cough [(16 (11-31) ppb vs 11 (8-19) ppb, P<0.01]. In the etiological analysis, CVA or EB was identified in 23 (44.2%) of the patients with subacute cough, as compared 21 (43.8%) in patients with chronic cough (χ(2)=0.002, P=0.961).

CONCLUSIONFENO may be an important indicator for etiological diagnosis of subacute cough and for predicting the response to ICS treatment.

Adrenal Cortex Hormones ; therapeutic use ; Breath Tests ; Chronic Disease ; Cough ; diagnosis ; drug therapy ; Exhalation ; Female ; Humans ; Male ; Nitric Oxide ; analysis

The liver injury induced by Polygonum multiflorum Thunb. (PM) was investigated based on idiosyncratic hepatotoxicity model co-treated with lipopolysaccharide (LPS) at a non-hepatotoxic dose. Sprague-Dawley (SD) rats were intragastrically administered with three doses (18.9, 37.8, 75.6 g crude drug per kg body weight) of 50% alcohol extracts of PM alone or co-treated with non-toxic dose of LPS (2.8 mg·kg(-1)) via tail vein injection. The plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were assayed and the isolated livers were evaluated for histopathological changes. The dose-toxicity relationships of single treatment of PM or co-treatment of LPS were investigated comparatively to elucidate the idiosyncratic hepatotoxicity of PM. The results showed that no significant alterations of plasma ALT and AST activities were observed in the groups of solo-administration of LPS (2.8 mg·kg(-1), i.v.) or different dosage (18.9, 37.8 and 75.6 g·kg(-1), i.g.) of PM, compared to normal control group (P > 0.05); while significant elevations were observed in the co-administration groups of PM and LPS. Treatment with LPS alone caused slight infiltration of inflammatory cells in portal area but no evident hepatocytes injury. Co-treatment with LPS and PM (75.6 g·kg(-1), i.g.) caused hepatocyte focal necrosis, loss of central vein intima and a large number of inflammatory cell infiltration in portal areas. When further reduce the dosage of PM, significant increases of plasma ALT and AST activities (P < 0.05) were still observed in co-administration groups of LPS and PM (1.08 or 2.16 g·kg(-1)), but not in LPS or PM solo-administration groups. Nevertheless, the co-treatment of low dosage of PM (0.54 g·kg(-1)) with LPS did not induce any alteration of plasma ALT and AST. In conclusion, intragastric administration with 75.6 g·kg(-1) of PM did not induce liver injury in normal rats model; while the 2 folds of clinical equivalent dose of PM (1.08 g·kg(-1)) could result in liver injury in the LPS-based idiosyncratic hepatotoxicity model, which could be used to evaluate the idiosyncratic hepatotoxicity of PM.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Chemical and Drug Induced Liver Injury ; pathology ; Hepatocytes ; pathology ; Lipopolysaccharides ; Polygonum ; toxicity ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the effect of Huatuo Zaizao extractum (HTZZ) on focal cerebral ischemia/reperfusion (I/R) neurogenesis in rats induced by middle cerebral artery occlusion (MCAO) and its mechanism.

METHODTotally 55 healthy adult male Sprague-Dawley rats were divided into the sham operation group, the MCAO model group and HTZZ high, middle and low dose groups (5, 2.5, 1.25 g x kg(-1)), with 11 rats in each group, and orally administered with drugs. The focal cerebral ischemia model was established by performing a middle cerebral artery occlusion (MCAO, 90 min) followed by a seven-day reperfusion (once a day). The neurogenesis and expressions of extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) were detected by the immunofluorescent staining. The enzyme linked immunosorbent assay (ELISA) was adopted to determine the vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF).

RESULTMCAO (90 min) followed by a seven-day reperfusion resulted in the significant increase in the number of penumbra cortex newborn neurons (BrdU(+) -NeuN(+)), which was accompanied by the growth of ERK and CREB phosphorylation and VEGF and BDNF levels. HTZZ could promote the generation of newborn neurons (BrdU(+)-NeuN(+)) and the ERK and CREB phosphorylation and increase VEGF and BDNF levels at the ischemic side.

CONCLUSIONHTZZ could promote the neurogenesis, which may be the interventional targets of effective traditional Chinese medicine Huatuo Zaizao extractum in promoting the self-repair function of the cerebral ischemic areas.

Animals ; Brain Ischemia ; drug therapy ; genetics ; metabolism ; physiopathology ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Male ; Neurogenesis ; drug effects ; Neurons ; cytology ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

Adult ; Bronchopulmonary Sequestration ; diagnosis ; diagnostic imaging ; Female ; Humans ; Pregnancy ; Ultrasonography, Prenatal

OBJECTIVETo explore the etiopathogenisis, diagnosis and early treatment of postoperative pyogenic infection in patients with lumbar disc diseases.

METHODSFrom March 2009 to March 2012,7 patients with postoperative pyogenic infection were retrospectivly analyzed. There were 6 males and 1 female,ranging in age from 42 to 62 years old,with an average of 46.5 years old. Among 7 cases,outside the spinal canal suppurative infection occurred in 6 cases and inside the spinal canal infection in 1 case and with temporary paralysis. All the patients were treated with continuous saline lavage-drainage of low pressure impulse during operation. Unitive sensitive antibiotics were applied for 4-6 weeks after operation until CRP and ESR completely normal or the biochemistry and routine examination of the cerebrospinal fluid completely normal for the patients with intracranial pyogenic infection.

RESULTSAll the 7 cases obtained recovery and the length of stay was for 2-3 months. No remnant symptoms of nervous system were found at the leave hospital.

CONCLUSIONPostoperative pyogenic infection in patients with lumbar disc diseases is an emergency,and easily results in misdiagnosis in clinic. So the early diagnosis is very important. Early debridement is the only measure to retrieve the life of patient,continuous saline lavage-drainage of low pressure impulse may remove the remnant focus of the deep soft tissue space,and removel of the internal fixation can ensure the postoperative pyogenic infection completely control.

Adult ; Bacterial Infections ; diagnosis ; therapy ; Debridement ; Early Intervention (Education) ; Female ; Humans ; Intervertebral Disc Degeneration ; surgery ; Intervertebral Disc Displacement ; surgery ; Length of Stay ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Postoperative Complications ; diagnosis ; therapy ; Retrospective Studies

OBJECTIVETo observe the effect and mechanism of Huatuo Zaizao extractum (HTZZ) on focal ischemia/reperfusion (I/R) blood-brain barrier injury induced by middle cerebral artery occlusion.

METHODSixty healthy male adult Sprague-Dawley rats was randomly divided into the sham operation group, the MCAO model group, the Tanakan (20 mg x kg(-1)) group, and high, middle and low-dose HTZZ groups (5, 2.5, 1.25 g x kg(-1)), with 10 in each group and single-dose duodenal administration. Middle cerebral artery occlusion was adopted to establish the rat focal I/R model. After ischemia for 90 min and reperfusion for 24 h, the pathological injury at the ischemia side was observed by HE staining. The blood-brain barrier structure was observed under transmission electron microscope. Expressions of G protein-coupled receptor kinases 2 (GRK2), matrix metalloproteinases 2 (MMP-2) and MMP-9 were detected by western blotting technique.

RESULTAfter 90 min MCAO/24 h reperfusion, penumbra cerebral cortical micro-vessels showed edema, mitochondrial injury, vacuolation, membrane injury and reduction. Along with the changes, sub-cells of G protein-coupled receptor kinase 2 (GRK2) in cortical penumbra brain tissues transferred from cytoplasm to membrane, with increase in expressions of MMP-2 and MMP-9. HTZZ could effectively recover cerebral micro-vascular endothelial edemaand blood-brain barrier ultrastructure injury induced by I/R, reduce expression of functional (membrane coupling) GRK2, and inhibit expressions of MMP-2 and MMP-9.

CONCLUSIONCell membrane coupling GRK2 may be the effective target of Huatuo Zaizao extractum.

Animals ; Behavior, Animal ; drug effects ; physiology ; Blood-Brain Barrier ; drug effects ; injuries ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; G-Protein-Coupled Receptor Kinase 2 ; metabolism ; Gene Expression Regulation, Enzymologic ; drug effects ; Infarction, Middle Cerebral Artery ; complications ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Microvessels ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; complications ; metabolism ; physiopathology

BACKGROUNDWhile the incidence of paroxysmal nocturnal hemoglobinuria (PNH) is relatively high in Northern China, the exact mechanism of the disease remains unknown. Immunoregulatory cytokine polymorphisms can directly regulate the expression levels of cytokines, which play a crucial role in many diseases. The purpose of this study was to study cytokine gene single nucleotide polymorphisms (SNPs) and the correlated cytokine expression levels in relationship to the PNH pathogenesis.

METHODSPeripheral blood samples were collected from 30 PNH patients and 40 healthy donors; all of the samples were collected from the Han people of Northern China. Eight SNP loci in five cytokine genes, including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-β), interleukin-6 (IL-6), and IL-10, and aplastic anemia (AA) were assessed. TNF-a, TGF-b, IFN-g, IL-6, and IL-10 were analyzed by sequence-specific primer polymerase chain reaction (PCR-SSP). The plasma protein levels of TNF-a, TGF-b, and IFN-g were assessed by an ELISA.

RESULTSThe PNH patients had a lower frequency of the TC/GG genotype of the TGF-b gene (P < 0.01) and a higher frequency of the C allele in the TGF-b gene (+10) compared to the controls (P < 0.05). The predominant genotype of the +874 locus of the IFN-g gene was TA in the PNH patients, while that in the predominant genotype was AA in the control group and was statistically significant (P < 0.001). The frequency of the T allele in the IFN-g gene was dramatically higher in the PNH patients than in the controls (P < 0.05). The PNH patients had a reduced frequency of the GC and CC genotypes, as well as the C allele at locus -174 of the IL-6 gene compared to the controls (P < 0.01). In addition, the plasma concentrations of TNF-a, TGF-b, and IFN-g were significantly higher in the PNH group compared to the control group (P < 0.01).

CONCLUSIONSExpression levels of the TNF-a, TGF-b, and IFN-g cytokines play an important role in PNH. The GC and CC genotypes, as well as the C allele of the IL-6 gene may protect the Han people of Northern China against PNH. Additionally, the TC/GG genotype of the TGF-b gene may be the protective allele. In contrast, the TA genotype and the T allele for the IFN-g gene, as well as the C allele of TGF-b may be susceptible to PNH. However, SNPs in the TNF-a and IL-10 genes did not correlate with PNH development. Alternatively, the increased plasma concentrations of TNF-a, TGF-b, and IFN-g in PNH patients may also be related to PNH development.

Adult ; Aged ; Alleles ; Anemia, Aplastic ; genetics ; Asian Continental Ancestry Group ; China ; Cytokines ; blood ; genetics ; Enzyme-Linked Immunosorbent Assay ; Female ; Genotype ; Hemoglobinuria, Paroxysmal ; blood ; genetics ; Humans ; Interferon-gamma ; blood ; genetics ; Interleukin-10 ; blood ; genetics ; Interleukin-6 ; blood ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Transforming Growth Factor beta ; genetics ; Tumor Necrosis Factor-alpha ; blood ; genetics ; Young Adult