The clinical characteristics and airway inflammatory phenotypes in 35 patients with severe asthma / 中华内科杂志

Objective@#To analyze the clinical features and airway inflammatory phenotypes in patients with severe asthma.@*Methods@#Patients with severe asthma were recruited in this cross-sectional study in our center. History of asthma, blood and sputum samples, and respiratory function were tested and recorded. The phenotypes of inflammation in airway were evaluated.@*Results@#A total of 35 asthmatic patients with the mean age 41.4 years were involved in this study from January 2013 to December 2013. The disease duration were (14.3±13.6) years with mostly male in China-Japan Friendship Hospital. Thirteen patients reported the history of smoking. Twenty-one patients had the complications such as allergic rhinitis, followed by chronic rhinosinusitis of 11 cases, nasal polyp of 7 cases, gastroesophageal reflux disease of 5. The forced expiratory volume in one second/predicted value ratio (FEV1%pred) in 29 patients was lower than 80%.Twenty-one participants did not react in bronchial reversibility test. Sixteen patients were administrated with oral cortical steroids (OCS). The average annual cost per patient was 22 thousand RMB. Sixteenrefractory asthmatics were diagnosed as eosinophilic asthma.@*Conclusions@#The clinical features associated with severe asthma include male gender, smoking, persistent airway limitation. Systemic use of corticosteroids is common and treatment costs are high. The eosinophilic asthma is the main inflammatory phenotype in patients with severe asthma.

The clinical characteristics and airway inflammatory phenotypes in 35 patients with severe asthma / 中华内科杂志

To analyze the clinical features and airway inflammatory phenotypes in patients with severe asthma. Methods Patients with severe asthma were recruited in this cross?sectional study in our center. History of asthma, blood and sputum samples, and respiratory function were tested and recorded. The phenotypes of inflammation in airway were evaluated. Results A total of 35 asthmatic patients with the mean age 41.4 years were involved in this study from January 2013 to December 2013. The disease duration were (14.3 ± 13.6) years with mostly male in China?Japan Friendship Hospital. Thirteen patients reported the history of smoking. Twenty?one patients had the complications such as allergic rhinitis, followed by chronic rhinosinusitis of 11 cases, nasal polyp of 7 cases, gastroesophageal reflux disease of 5. The forced expiratory volume in one second/predicted value ratio (FEV1%pred) in 29 patients was lower than 80%.Twenty?one participants did not react in bronchial reversibility test. Sixteen patients were administrated with oral cortical steroids (OCS). The average annual cost per patient was 22 thousand RMB. Sixteenrefractory asthmatics were diagnosed as eosinophilic asthma. Conclusions The clinical features associated with severe asthma include male gender, smoking, persistent airway limitation. Systemic use of corticosteroids is common and treatment costs are high. The eosinophilic asthma is the main inflammatory phenotype in patients with severe asthma.

Research progress of dedifferentiation and mechanism of beta cell in type 2 diabetes mellitus / 中国基层医药

Islet βcell dysfunction is one of the important links in the development of type 2 diabetes (T2DM).The latest research shows that the main cause of the continuous β-cell dysfunction under metabolic stress is mainly the dedifferentiation of β-cells,and become endocrine progenitor -like cells with multiple differentiation potentials.Studies have found that the process of dedifferentiation of pancreatic islet βcells is reversible.This finding has provided possibilities and new ideas for preventing and reversing the progressive decline of βcell function and delaying the occurrence of T2DM.

The relationship between smoking status and epidermiology of asthma in people aged over 14 years in China / 中华内科杂志

Objective To study the relationship between bronchial asthma and smoking status in Chinese people.Methods Asthma epidemiological survey and stratified-cluster-random method survey were performed in residents over 14 years in 8 provinces (cities) of China from February 2010 to August 2012.Asthma was diagnosed based upon case history,clinical signs and lung function test.Smoking status was investigated by questionnaire.Results Sampling population was 180 099 and 164 215 were valid.A total of 2 034 subjects were diagnosed as asthma including 79 692 men and 84 523 women.The overall prevalence rate of asthma was 1.24％ (2 034/164 215).Smokers were 23.8％ (39 137/164 215) in the whole population.Smokers were 34.5％ (702/2 034) in asthmatic patients,compared with 23.7％ (38 435/ 162 181) in no-asthmatic population.The incidence of asthma was 1.79％ and 1.06％ in smokers and nonsmokers respectively (P ＜0.001),suggesting that OR of smoking was 1.70 (95％ CI 1.55-1.86,P ＜ 0.001).According to asthma control test (ACT) score,the level of asthma control in non smoking group was higher than that in smoking group(43.2％ vs 35.3％).The times of hospitalization due to acute exacerbations (0.51 vs 0.41 events/person/year),total hospitalization rate (27.35 ％ vs 20.12％),annual emergency room visits (0.80 vs 0.60 events/person/year) and emergency room visit rate (31.77％ vs 24.47％) were all much higher in smoking asthmatic patients than those in non smoking asthmatic patients,indicating that the level of asthma control in smoking patients was significantly worse than in non smoking patients.Conclusions The smoking rate in Chinese people over 14 years is still high.The prevalence rate of asthma in smokers is significantly higher than that of non-smokers.The level of asthma control in smokers is significantly worse than that in non smokers.

Effects of simvastatin on bone loss in vertebrae and intervertebral disc degeneration in ovariectomized rats / 医学研究生学报

Objective Simvastatin, as a widely used lipid-lowering drug, exhibits a potential effect of promoting bone forma-tion. The present study aimed to investigate the effect of oral simvastatin on lumbar vertebral bone mass and intervertebral disc ( IVD) degeneration in ovariectomized ( OVX ) rats. Methods Thirty female Sprague-Dawley rats were subjected to dual OVX ( n=20) or sham surgery ( n=10) and the OVX rats were treated orally with either saline vehicle (OVX+V, n=10) or simvastatin (OVX+SIM, n=10 ) at 5 mg per kg of the body weight per day. After 6 months of intervention, the microstructure of the L3 vertebra was ob-served by micro-CT, the bone mineral density ( BMD) in the L5-6 ver-tebrae determined by dual-energy X-ray absorptiometry, and histo-logical changes of the L5-6 vertebrae analyzed by van Gieson stainingand semi-quantitative evaluation. Results Compared with the sham-operation group, both the OVX+V and OVX+SIM groups showed significantly decreased BMD in L5([0.2933±0.0110] vs [0.2423±0.0081] and [0.2598±0.0249] g/cm2, P<0.05), L6 ([0.2907±0.0150] vs [0.2395±0.0061] and [0.2572±0.0121] g/cm2, P<0.05), and L5-6([0.2860±0.0115] vs [0.2380± 0.0059] and [0.2528±0.0126] g/cm2, P<0.05), but all the 3 parameters were remarkably higher in the OVX+SIM than in the OVX+V group (P<0.05). Micro-CT analysis manifested significantly lower BV/TV and Tb.N but higher Tb.Sp in the OVX+V than in the sham operation group ( P<0.05) . Abundant notochordal cells and extracellular matrix in the nucleus pulposus with well-arranged outer annulus fibrosus were observed in the rats of the sham operation group. The animals of the OVX+V and OVX+SIM groups displayed de-generation of the nucleus pulposus, annulus fibrosus, reduced notochordal cells and their replacement by chondrocyte-like cells in the nucleus pulposus, mucoid degeneration in the matrix, and disruption of the nuclear-annular border in the annulus fibrosus. The disc de-generation scores were significantly higher in the OVX+V and OVX+SIM than in the sham operation group (4.35±0.9 and 3.53±0.42 vs 2.48±0.92, P<0.05). Conclusion OVX induces not only bone loss in vertebrae but also IVD degeneration in rats, while simvasta-tin can partly prevent bone loss in lumbar vertebrae without aggravating IVD degeneration in OVX rats.

Morphology of the intervertebral disc in high fat combined with streptozotocin-induced type Ⅱ diabetic rats / 中国组织工程研究

BACKGROUND:Rat models of diabetes mellitus type 2 (T2DM) are usually induced by the combination of high-fat diet and low-dose streptozotocin, but their effects on the intervertebral disc have not yet been reported. Endplate sclerosis is an important factor contributing to intervertebral disc degeneration. OBJECTIVE:To evaluate whether the rat T2DM model induced by high-fat diet combined with low-dose streptozotocin is suitable for the study of T2DM related intervertebral disc degeneration. METHODS:Thirty-two 3-month-old female Sprague-Dawley rats were divided into four groups (n=8 per group), including sham, bilateral variectomy, DM, and bilateral variectomy plus DM groups, followed by subjected to bilateral ovariectomy and/or high-fat diet combined with low-dose streptozotocin, respectively. The blood glucose level, body mass and glucose tolerance were determined. The bone mineral density of the lumbar spine was measured after 8-week streptozotocin treatment. The L5-6 segments were removed and cut through midst sagittal plane after decalcification, and then underwent Von Gieson staining and histological degeneration scoring, and the disc height and endplate thickness were measured. RESULTS AND CONCLUSION:Fasting blood glucose and random blood glucose levels in the DM and bilateral variectomy plus DM groups were significantly higher than those in the other two groups, and the insulin sensitivity in the DM and bilateral variectomy plus DM groups were significantly lower than that in the other groups (P<0.05). L4-6 vertebral bone mineral density in the bilateral variectomy group was significantly lower than that in the sham group (P<0.05);L5-6 vertebral bone mineral density in the DM and bilateral variectomy plus DM groups was significantly lower than that in the sham group (P<0.05). L5-6 vertebral histological scores in the DM and bilateral variectomy plus DM groups were significantly higher than those in the other groups (P<0.05). Similar with the bilateral variectomy group, there were chondrometaplasia and mucoid degeneration of nucleus pulposus cells in the bilateral variectomy plus DM group, and the histological scores were significantly higher than those in the sham and DM groups (P<0.05). Compared with the sham group, the intervertebral disc height in the bilateral variectomy and bilateral variectomy plus DM groups was significantly decreased (P<0.05). While, there was no significant difference in the endplate thickness among groups. These results indicate the combination of high-fat diet and low-dose streptozotocin-induced rat T2DM models possess diabetic characteristics, but the rat intervertebral disc tissues show no significant differences from the normal ones;therefore, this model may be unsuitable for the study on T2DM-related intervertebral disc degeneration.

The protective action and its mechanism of 5-hydroxy-1 H-indazole in SH-SY5 Y cells / 中国药理学通报

Aim To study the protection and possible mechanism of 5-hydroxy-1 H-indazole against 1-methyl-4-phenylpyridinium iodide ( MPP+)-induced SH-SY5 Y cell apoptosis. Methods An apoptotic model was es-tablished in human neuroblastoma SH-SY5 Y by MPP+in vitro. MTT analysis was used to evaluate the protec-tive effect of 5-hydroxy-1H-indazole. Immunochemistry and Hoechst33258 nuclear staining were used to ob-serve the neuroprotection and anti-apoptosis of 5-hy-droxy-1H-indazole. Western blot was used to detect the levels of P-tau ( Ser396 ) closely related to neuronal apoptosis and its upstream kinases:P-GSK-3β and CDK5 . Results MPP+ induced activation of GSK-3β, increase of activity of CDK5 , tau hyperphosphory-lation and neuronal cell apoptosis. However,5-hydrox-y-1 H-indazole reduced the activities of GSK-3β and CDK5,then decreased the level of tau hyperphosphory-lation and inhibited MPP+-induced SH-SY5 Y cells ap-optosis. Conclusions 5-hydroxy-1H-indazole could attenuate MPP+-induced SH-SY5 Y neuronal cell apop-tosis. Possible mechanism is that 5-hydroxy-1H-in-dazole inhibits GSK-3βand CDK5 two signal transduc-tion pathways to lower the level of tau phosphorylation, then plays a role of neuroprotection.

Inhibition of Tau phosphorylation protects SH-SY5Y cells from MPP +-induced apoptosis by 6-Hydroxy-1H-indazole / 中国药理学通报

Aim To study the protective effect of 6-Hydroxy-1 H-indazole via inhibition of Tau phosphoryla-tion on MPP +-induced SH-SY5Y cells apoptotsis. Methods An apoptotic model induced by 1 -methy-4-phenylpridnium ion (MPP +)was established in cul-tured human neuroblastoma SH-SY5Y in vitro.MTT a-nalysis was used to evaluate the protective effect of pre-treatment of cells with 6-Hydroxy-1 H-indazole for 2 h. Hoechst33258 staining was used to observe apoptotic situation.Immunohistochemistry was used to detect the p-Tau (Ser396)expression.Results The viability of cells exposed to 200 μmol · L -1 MPP + for 48h was (47.80 ±0.84)% (P <0.01 ),MPP + induced phos-phorylation of Tau at Ser396 and neuronal apoptosis, while 6-Hydroxy-1 H-indazole inhibited MPP +-induced cellular apoptosis,increased the number of TH-positive cells via inhibiting Tau phosphorylation.Conclusion These results indicate that Tau may be a new target used to cure neurodegenerative disorders such as PD.

p38 mitogen-activated protein kinase signal transduction pathway is involved in osteoarthritis / 中国组织工程研究

BACKGROUND: p38 mitogen-activated protein kinase signal transduction pathway is a member of the mitogen-activated protein kinase family. It plays an important role in the development of osteoarthritis. OBJECTIVE: To review the progress of p38 mitogen-activated protein kinase signal transduction pathway in the pathological process of osteoarthritis. METHODS: An online search of CNKI and PubMed databases was performed for articles using keywords of “p38 mitogen-activated protein kinase signal transduction pathway, osteoarthritis, articular cartilage, chondrocyte” in Chinese and English, respectively. Relevant articles were summarized from three aspects of introduction of p38 signal transduction pathway, the role of p38 mitogen-activated protein kinase signal transduction pathway in osteoarthritis and the inhibitor of p38 in osteoarthritis. A total of 90 articles were included. According to inclusion criteria, a number of 46 articles were retained at last. RESULES AND CONCLUSION: p38 mitogen-activated protein kinase signal transduction pathway has a close relation with chondrocyte hypertrophy and calcification, chondrocyte apoptosis, synthesis of cartilage matrix metal oproteinase, production of proinflammatory cytokines, and exerts a significant effect on the development of osteoarthritis. p38 mitogen-activated protein kinase is involved in the formation and development of osteoarthritis through a variety of complex mechanisms and plays a very important role. Therefore, blocking p38 mitogen-activated protein kinase signaling pathway may be a new target in the treatment of osteoarthritis.

The protective action of chromomycin on dopaminergic neurons / 中国药理学通报

Aim To study the effect of chromomycin on MPP~+-induced dopaminergic neuronal apoptosis.Methods An apoptosis model induced by 1-methyl-4-phenylpridnium ion(MPP~+)was established in cultured fetal mesencephalic neurons in vitro.Dopaminergic neuronal apoptosis was detected by Hoechst 33258 staining and phospho-Tau levels were detected by immunofluorescence.Results 10 μmol·L~(-1) MPP~+ hyperphosphorylated Tau at Ser396 and induced dopaminergic neuronal apoptosis.Chromomycin increased the number of TH-positive cells via inhibiting Tau phosphorylation.Conclusion These results indicate thatchromomycin inhibits Tau phosphorylation at Ser396 and therefore protects dopaminergic mesencephalic neurons from apoptosis induced by MPP+,which suggests that Chromomycin may be used to cure neurodegenerative disorders such as Parkinson's disease in clinic.

Pathogenesis of osteoarthritis and its relationship with the Wnt/?-catenin pathway / 中国矫形外科杂志

The recently published articles about the pathogenesis of osteoarthritis were reviewed.Osteoarthritis(OA)is characterized by cartilage degradation,osteophyte and involvement of the synovium.Mechanics,inflammatory mediators and aging collide studies in developmental,genetic and joint disease models indicate that Wnt/?-catenin signaling is critically involved in these processes.Many different factors contribute to the onset and progression of OA and Wnt/?-catenin signaling plays a vital role in these processes.

An Inhibitor of p38 MAPK Prevents Apoptosis of Cultured Cerebellar Granule Neurons via Inhibiting the Activity of JNK / 中山大学学报(医学科学版)

【Objective】To study the effect of the specific p38 mitogen-activated protein kinase(p38 MAPK) inhibitor SB203580 on apoptosis of cerebellar granule neurons induced by low potassium.【Methods】Apoptosis was induced by switching the cultured cerebellar granule neurons from a culture medium containing K+ 25 mmol*L-1 to a medium containing K+ 5 mmol*L-1 (cLK).Fragmentation of DNA was analyzed using agarose gel eletrophoresis.SAPK/JNK activity was measured by SAPK/JNK assay kit.【Results】Low potassium resulted in apoptosis as characterized by morphological and biochemical features,but the specific p38 MAPK inhibitor SB203580 improved the survival of cerebellar granule neurons cultured in cLK medium by blocking apoptosis in a concentration-dependent manner.The expression and phosphorylation of c-Jun increased and the activity of c-Jun N-terminal protein kinase (JNK) elevated when cerebellar granule neurons were cultured in cLK medium.But when the cerebellar granule neurons cultured in cLK medium were exposed to 25 μmol*L-1 SB203580,the expression and phosphorylation of c-Jun and the activity of JNK were both decreased evidently.【Conclusions】These results indicate that SB203580 inhibits the activation of JNK and phosphorylation of c-Jun,and therefore protects granule neurons from apoptosis induced by low potassium.

Expression of IL-8 and CXCR2 on Keratinocytes from Psoriatic Lesions / 中华皮肤科杂志

Objective To investigate the expression of IL-8 and CXCR2 on keratinocytes from psoriatic lesions and their roles on clinical and pathologic manifestations. Methods The chemotaxis of psoriatic lesional keratinocytes was detected by micropore loculus test. The concentration of IL-8 was determined in the cultured supernatants of psoriatic keratinocytes by ELISA. The expression of CXCR2 on keratinocytes from affected skin was tested by flow cytometry. Results The chemotaxis for neutrophils by the cultured supernatants of psoriatic lesional keratinocytes was significantly stronger than that by controls. The concentration of IL-8 in the cultured supernatants of psoriatic lesional keratinocytes was also increased. The expression of CXCR2 on psoriatic keratinocytes was significantly increased. Conclusions The psoriatic epidermal hyperproliferation may be correlated with up regulation of IL-8 production and CXCR2 expression on psoriatic keratinocytes. At the same time, the psoriatic inflammation may be partly related to the increase of secretion of IL-8, which has chemotactic capacity, by keratinocytes. IL-8 and CXCR2 may be involved in the pathogenesis of psoriasis.