Erythromycin attenuates oxidative stress-induced cellular senescence via the PI3K-mTOR signaling pathway in chronic obstructive pulmonary disease.

Background and Purpose: Chronic obstructive pulmonary disease (COPD) is proposed to hasten lung aging. Erythromycin protects against oxidative stress and inflammatory responses. However, the potential anti-senescence effect of erythromycin remains disclosed. In the present study, we investigated whether erythromycin influenced oxidative stress-induced cellular senescence and investigated its related mechanisms. Methods: A cigarrete smoke (CS) -induced emphysema mouse model and a H2O2-induced premature senescence model in human bronchial epithelial cell line (BEAS-2B) were established. Senescence-related markers (P53, P21 and SA-ß-Gal activity), and levels of oxidative stress biomarkers (MDA, SOD and ROS) were measured. Additionally, cells were pretreated with rapamycin (mTOR inhibitor) or erythromycin, and the expression levels of components of the PI3K-mTOR signaling pathway were measured in BEAS-2B cells. Results: Exposed to H2O2, increased SA-ß-gal activity was observed in BEAS-2B cells suggesting premature senescence. Erythromycin inhibited the expression of P53 and P21 in the CS-induced emphysema mouse model. MDA levels significantly increased and SOD levels decreased in the CS-exposed mice and H2O2-induced BEAS-2B cells. Rapamycin and erythromycin significantly suppressed the expression of P53 and P21. Additionally, rapamycin and erythromycin inhibited the PI3K-mTOR signaling pathway. Conclusion: Our findings suggest that erythromycin ameliorates oxidative stress-induced cellular senescence via the PI3K-mTOR signaling pathway. Hence, we establish a theoretical foundation for the clinical application of erythromycin for COPD prevention and treatment.

Application of the mandarin Chinese version of the Leicester cough questionnaire in the chronic disease management of adult patients with severe asthma / 中华健康管理学杂志

Objective:To explore the application of the mandarin Chinese version of the Leicester cough questionnaire (LCQ-MC) in the chronic disease management of adult patients with severe asthma.Methods:Thirty patients with severe asthma without a smoking history who received treatment and chronic disease management in the First Affiliated Hospital of Guangxi Medical University from December 2018 to December 2020 and met the inclusion criteria were selected as the research subjects. Their clinical symptoms, LCQ-MC, asthma control test (ACT), mini asthma quality of life questionnaire (MiniAQLQ), visual analogue scale (VAS) and lung function test were recorded. The reliability of LCQ-MC and its correlation with ACT, MiniAQLQ, VAS and lung function were analyzed.Results:Among the 30 patients, there were 14 males and 16 females, with an average age of (50.5±10.5) years old and a medical history of (38.3±15.5) years. The main manifestations were cough which was observed in 29 cases (96.7%), wheezing in 25 cases (83.3%), nasal symptoms in 14 cases (46.7%) and chest tightness in 11 cases (36.7%). All lung functions were consistent with the diagnosis of asthma. The total score of LCQ-MC was (16.1±4.2), in which the physiological, psychological and social dimensions were (5.0±1.2), (5.6±1.6), (5.5±1.7), respectively; and ACT (18.9+5.5), MiniAQLQ (4.9±1.4), VAS (33.5±32.4). The Cronbach′s α for the questionnaire was more than 0.70, and the results were positively correlated with ACT and MiniAQLQ ( r=0.553, 0.593, P=0.002, 0.001), negatively correlated with VAS ( r=-0.762, P<0.001). The correlations between LCQ-MC and these scores were consistent with the results after 6 months. Conclusion:Cough is an important symptom of severe asthma, and LCQ-MC can be effectively used for evaluation and chronic disease management of adult patients with severe asthma.

Tafamidis, a Noninvasive Therapy for Delaying Transthyretin Familial Amyloid Polyneuropathy: Systematic Review and Meta-Analysis

BACKGROUND AND PURPOSE: Tafamidis functions to delay the loss of function in transthyretin familial amyloid polyneuropathy (TTR-FAP), which is a rare inherited amyloidosis with progressive sensorimotor and autonomic polyneuropathy. This systematic literature review and meta-analysis evaluated the efficacy and safety of tafamidis in TTR-FAP patients, with the aim of improving the evidence-based medical evidence of this treatment option for TTP-FAP. METHODS: A systematic search of the English-language literature in five databases was performed through to May 31, 2018 by two reviewers who independently extracted data and assessed the risk of bias. We extracted efficacy and safety outcomes and performed a meta-analysis. Statistical tests were performed to check for heterogeneity and publication bias. RESULTS: The meta-analysis identified six relevant studies. The tafamidis group showed smaller changes from baseline in the Neuropathy Impairment Score–Lower Limbs [mean difference (MD)=−3.01, 95% confidence interval (CI)=−3.26 to −2.75, p < 0.001] and the Norfolk Quality of Life-Diabetic Neuropathy total quality of life score (MD=−6.67, 95% CI=−9.70 to −3.64, p < 0.001), and a higher modified body mass index (MD=72.45, 95% CI=69.41 to 75.49, p < 0.001), with no significant difference in total adverse events [odds ratio (OR)=0.69, 95% CI=0.35 to 1.35, p=0.27]. The incidence of adverse events did not differ between tafamidis and placebo treatment except for fatigue (OR=0.13, 95% CI=0.02 to 0.72, p=0.02) and hypesthesia (OR=0.16, 95% CI=0.03 to 0.92, p=0.04). CONCLUSIONS: This systematic review and meta-analysis has demonstrated that tafamidis delays neurologic progression and preserves a better nutritional status and the quality of life. The rates of adverse events did not differ between the patients in the tafamidis and placebo groups. Tafamidis might be a safer noninvasive option for patients with TTR-FAP.

The Correlation between the ABCB1 rs1045642 Polymorphism and Clopidogrel Resistance among Chinese Han Patients with Ischemic Stroke / 中国医科大学学报

Objective To investigate the relationship between the ABCB1 rs1045642 polymorphism and clopidogrel resistance (CR) among Chinese Han patients with ischemic stroke.Methods In total,110 patients with acute ischemic stroke were included in the study.Venous blood samples (2 mL) were collected after oral administration of 75 mg/d clopidogrel;the platelet aggregation rate was measured before clopidogrel administration and after 7 days of clopidogrel administration.CR is defined as no more than 10％ change in the platelet aggregation rate over two times.Based on the results,patients were divided into the CR group and non-CR (NCR) group.Genomic DNA was extracted,the target gene was amplified by PCR,and the SNP was determined by RFLP.Results The TT genotype frequency of ABCB1 rs1045642 was significantly higher in the CR group than in the NCR group (P =0.003).T allele carriers in CR group show much more (57.1％ vs 34％,P =0.001) compared with those in the NCR group.Conclusion The ABCB1 rs1045642 polymorphism may be an independent risk factor and the T allele may be a gene indicating risk for CR among Chinese Han patients with ischemic stroke.

Factors associated with quality of life in epileptics in northen China and the variations between men and women / 中华神经科杂志

Objective To determine main factors associated with quality of life in epileptics in northen China especially seizure severity and stigma, and the variations between men and women. Methods All patients with epilepsy aged 18-65 years were selected from the First Affiliated Hospital of China Medical University, tested from March 2014 to March 2015. All of them completed the general social science data, the Quality of Life Inventory in Epilepsy-31 (QOLIE-31), Liverpool Adverse Events Profile (LEAP), the National Hospital Seizure Severity Scale (NHS3), Epilepsy Stigma Scale (ESS), Self-rating Anxiety Scale ( SAS) and Hamilton Depression Scale ( HAMD) assessment. Results A total of 123 patients with epilepsy (60 men, 63 women) were interviewed. QOLIE-31 scores were 55. 81 ± 10. 17 in female patients, 65. 35 ± 10. 89 in male patients, the difference being statistically significant (t=2. 90, P<0. 05). ESS (1(0,2)), SAS(31. 85 ± 8. 16), HAMD (4. 38 ± 2. 90) scores of female patients were higher than that of male patients (0(0,0), 26. 93 ± 3. 45, 2. 80 ± 1. 39;U= -2. 710, t=2. 48, 2. 20, all P<0. 05). Multiple factors analysis and multiple stepwise regression analysis on quality of life revealed that depression (β= -0. 516, P<0. 01) and the severity of epilepsy (β= -0. 338, P=0. 01) were two strong predictors of QOLIE-31 overall scores. The linear regression showed that there was a direct link between shame and degree of depression (β = 0. 515, P= 0. 001 ) . Conclusions The main factors affecting the quality of life in epileptics in northen China are depression and seizure severity. Compared with male patients, female patients have a lower quality of life, and poorer psychological status, such as shame, depression and anxiety. There is a direct link between shame and depression in epileptics.

Role of ATP-binding Cassette Transporter G1 in Atherosclerosis / 中国医科大学学报

The adenosine triphosphate (ATP)-binding cassette transporter G1 (ABCG1),a member of the superfamily of ATP-binding cassette transporters,is involved in the efflux of cholesterol and phospholipids from cells,and it maintains the intracellular hpid homeostasis.ABCG1 deficiency results in foam cell formation,endothelial dysfunction,and inflammatory reaction,and it further leads to the development and progression of atherosclerosis.However,the role of ABCG1 in atherosclerosis in animal experiments and human studies is still a debatable matter.In this paper,the recent findings on the role of ABCG1 in atherosclerotic disease are reviewed.

Multiple Microelectrode Guided Precise Positioning of Sensory-motor Area of the Subthalamic Nucleus / 中国医科大学学报

Objective To explore the significance of multiple microelectrode guided technique in determining the sensory?motor area of the sub?thalamic nucleus(STN)in deep brain stimulation(DBS)surgeries. Methods A total of 22 electrophysiological recording data of STNs recorded by multiple microelectrode was retrospectively analyzed ,while another 20 electrophysiological recording data of STNs recorded by a single micro?electrode was recruited as the control group. Results A total of 64 microelectrodes were used in 22 STNs guided by multiple electrophysiological recording electrodes. Sensory or motor activated potentials were recorded in 21 sides(95.5%),while regular discharge was recorded in one side. The average length of typical STN activity on the optimal channel of multiple electrophysiological recording electrodes was 5.58±0.53 mm,and the average length of sensory or motor activated potentials was 3.27±1.54 mm. In contrast,the average length of typical STN activity recorded by single microelectrode was 5.02±1.01 mm. However,sensory or motor activated potentials were recorded in 13 sides(65.0%)with the average length of 1.36±0.98 mm. Among the 22 STNs guided by multiple electrophysiological recording electrodes,the final implanted target was consistent with the initially selected anatomic target in 13 sides(coincidence rate,59.1%). In 9 sides,the electrophysiological target was inconsistent with the initially selected anatomic target. Conclusion STN DBS performed with multiple electrophysiological recording electrodes resulted in better outcomes of recording of the average length of typical STN activity or the average length of sensory or motor activated potentials of STN ,final confirmation of STN sensory motor area and determination of the optimal channel of implantation. Application of multiple electrophysiological recording electrodes provides a premise for the precise electrode placement in STN DBS surgeries.

Thyroid diseases and cerebrovascular diseases / 国际脑血管病杂志

The relationship between thyroid diseases and cerebrovascular diseases is getting increasingly attention. Studies have shown that thyroid diseases are associated with many kinds of cerebrovascular diseases, such as ischemic cerebrovascular disease, moyamoya disease, cerebral venous thrombosis, and artery dissection. This article review the advances in research on the correlation between thyroid diseases and cerebrovascular diseases.

Cigarette smoke extract promotes senescence by reducing expression of HDAC2 in C2C12 myoblasts / 中国病理生理杂志

AIM:To investigate whether the cigarette smoke extract (CSE) causes senescence of C2C12 myo-blasts and the relationship between senescence and histone deacetylase 2(HDAC2).METHODS: Murine C2C12 cells were induced to differentiate into myoblasts.The HDAC2 activator and inhibitor were used to investigate the effects of CSE in the myoblasts on cell senescence and the expression of HDAC2.The expression of HDAC2 at mRNA and protein levels was determined by real-time PCR and Western blot, respectively, and the positive cell rate of β-galactosidase staining for cell senescence was also detected.RESULTS:The optimal concentration of CSE was 60 mL/L and the intervention time was 24 h.After the intervention of CSE, the positive cell rate ofβ-galactosidase staining was increased, accompanied with the reduction of HDAC2 expression at mRNA and protein levels.The expression of HDAC2 at mRNA and protein levels was increased by 4, 5, 6, 7-tetrabromobenzotriazole (TBB), accompanied with the reduction of positive cell rate ofβ-galacto-sidase staining.Furthermore, when HDAC2 expression at mRNA and protein levels was reduced by HDAC2 inhibitor valp-roic acid, the positive cell rate of β-galactosidase staining was increased.CONCLUSION: CSE promotes the senescence by reducing the expression of HDAC2 in C2C12 myoblasts.

Effect of cigarette smoking condensate on HDAC2 and inflammatory me-diators in mouse myoblast C2 C12 cells / 中国病理生理杂志

AIM:To investigate the effect of cigarette smoking condensate on histone deacetylase 2 (HDAC2) and inflammatory mediators in mouse myoblast C 2C12 cells.METHODS:C2C12 cells were treated with cigarette smoke extract (CSE).HDAC2 siRNA was transfected into the cells using Lipofectamine TM 2000.The levels of interleukin-8 (IL-8) and tumor necrosis factor-α( TNF-α) in the culture supernatants were measured by ELISA , and the expression of HDAC2 at mRNA and protein levels was determined by real-time PCR and Western blotting .RESULTS:The expression of HDAC2 at mRNA and protein levels in CSE group was lower than that in control group (P<0.05).The supernatant levels of IL-8 and TNF-αin CSE group were significantly higher than those in control group ( P<0.05 ) .When the cells were transfected with HDAC2 siRNA followed by CSE stimulation , the expression of HDAC2 at mRNA and protein levels was de-creased , and the supernatant levels of IL-8 and TNF-αwere significantly increased as compared with CSE group and control group (P<0.05).CONCLUSION: Under the oxidative stress condition , C2C12 cells generate high levels of IL-8 and TNF-αby down-regulating the expression of HDAC2.

The value of CD8 +T cell expression in rats with chronic bronchitis / 医学研究生学报

Objective CD8 +T cells increased in the airway of patients with chronic obstructive pulmonary disease and exis -ted constantly .The aim was to investigate the role of CD 8 +T-cells in rats with chronic bronchitis ( CB) which was induced by cigarette smoking and intratracheal injection with lipopolysaccharide ( LPS) . Methods 18 health Wistar rats were radomly divided into sham smoking group(group A), CB group(group B) and N-acetylcysteine prevention group (group C).The rats in group B and group C re-ceived intratracheal injection with LPS twice and exposed to cigarette smoking for 4 weeks to induce CB model .The rats in Group C re-ceiving intragastric administration with N-acetylcysteine (NAC)(200mg/kg) before received LPS and smoking.Group A was the sham smoking group.The lung tissue of all rats were stained by HE then evaluated about pathological scores .The expression of nuclear fac-tor-κB (NF-κB), major histocompatibility complex class I (MHCI), CD8 +T cell and Vascular endothelial growth factor (VEGF) in airway were detected by immunohistochemisty which was stained by labeled streptavidin biotin method . Results The pathological scores of airway ( 10 .83 ±3 .31 ) in group B were higher than (1.17 ±2.40) in group A(P <0.05).The pathological scores of airway(4.66 ±2.25) in group C were less than (10.83 ±3.31) in group B(P <0.05).The expression of NF-κB(4.84), MHC I (2.48),CD8 +T cell(5.35)and VEGF(5.02) in airway increased in group B when compared with (1.18, 1.25, 1.33) and (1.18) in group A respectively(P <0.05).The expression of NF-κB (2.18), MHC I(1.46),CD8 +(2.35)and VEGF(2.02) in airway decreased in group C when compared with (4.84), MHC I(2.48),CD8 +T cell(5.35)and VEGF(5.02) in group B respectively (P<0.05 ). There were positive correlations between the expression of NF-κB, MHC I and CD8 +T cells in airways(r=0.670, r=0.701, respec-tively, all P<0.01).There were positive correlations between the expression of CD 8 +T cells and VEGF the pathological scores of air-ways(r=0.689, r=0.782, respectively, all P<0.01). Conclusion NAC can inhibit airway inflammation which is regulated by CD8 +T-cells and VEGF through suppressing the expression of NF -κB and MHC I.

Effect of erythromycin on cigarette smoke-induced histone deacetylase-3 protein expression in human macrophages / 中国免疫学杂志

Objective:To study the effect of erythromycin(EM) on cigarette smoke-induced histone deacetylase-3(HDAC3) protein expression in human macrophages in vitro .Methods:The Aqueous cigarette smoke extract ( CSE) was always prepared fresh on the day of the experiment .The U937 monocytic cells were differentiated into macrophages by using phorbol 12-myristate 13-acetate (PMA) according to standard procedures .The U937 differentiated cells were treated with either CSE (1%) or EM (1 μg/ml) pre-treatment, and HDAC inhibitor trichostatin A (TSA;100 ng/ml) for 24 h.HDAC activity was measured with a colorimetric assay kit and Western blot was used for HDAC3 and factor nuclear-kappaB (NF-κB) protein assays.The levels of tumor necrosis factor-α(TNF-α) release in the supernatant were determined by enzyme linked immunosorbent assay (ELISA).Results:CSE(1%) significantly de-creased HDAC activity and HDAC 3 protein levels at 24 h.Preincubation with EM (1μg/ml ) for 24 h significantly inhibit CSE (1%) induced decrease of HDAC3 protein expression.Furthermore, Preincubation with EM(1 μg/ml) for 24 h significantly inhibit NF-κB activity and TNF-αrelease in human macrophages .Conclusion:EM is able to restore HDAC3 levels decreased by cigarette smoke and inhibit NF-κB activity resulting in decreasing CSE-mediated TNF-αrelease, which has shown an important explanation that EM possess the anti-inflammatory effect induced by cigarette smoke .

Expression of interleukin-17 in a murine model of experimental systemic sclerosis and its correlation with transforming growth factor-beta 1 / 中华风湿病学杂志

ObjectiveThe expression and significance of interleukin(IL)-17 in a murine model of experimental systemic sclerosis(SSc) was studied and its correlation with transforming growth factor-beta 1 (TGF-β1) was explored.Methods Thirty female BALB/c mice were randomly divided into 3 groups,including a control group, bleomycin(BLM) injection for 4 weeks group(model 1 group) and a termination injection of BLM 4 weeks group(model 2 group).The pathological changes of skin and lung were detected.The mRNA expressions of IL-17A,RORγt,TGF-β1 mRNA were evaluated by real-time PCR.Enzyme linked immunosorbent assay was used to measure the levels of IL-17 and TGF-β1 in the serum and bronchoalveolar lavage fluid(BALF).Comparisons among groups were performed by variance analysis.ResultsSkin and lung of the model groups showed evident inflammatory cell infiltration and increased deposition of collagen fibers.The score of dermal inflammation and lung fibrosis was significantly higher in the model 1 and model 2 groups (2.5±0.8,3.0±1.8), (2.4±0.8,3.1±1.2) as compared to that of the control group (0.9±0.7,0.9±1.0),(F=12.19,8.367,25.11,4.641; all P＜0.05).The amount of hydroxyproline was markedly increased in the model groups than in the control group.Compared with those of the control group,the mRNA levels of IL-17A,RORγt,TGF- 31 in the skin and lung of the model 1 group were higher.The levels of IL-17 in serum and BALF of the model 1 group was significantly increased and the levels of TGF- β1 were increased in BALF and decreased in the serum (all P＜0.05).The mRNA levels of IL-17A in skin and lung had a positive correlation with the mRNA levels of TGF- β1,score of dermal inflammation and lung fibrosis.The levels of IL-17 in serum had a positive correlation with hydroxyproline of the skin and lung.ConclusionIL-17 may participate in systemic immune-mediated inflammation and changes of skin and lung in SSc and when combined with TGF-β1 togetter will cause damage to skin and lung in SSc.

The clinical characteristics of intra-acinar pulmonary artery inflammation and its effect on clinical parameters in smokers with normal lung function and patients with chronic obstructive pulmonary disease / 中华内科杂志

ObjectiveTo study the pathological characteristics of intra-acinar pulmonary artery inflammation and its correlation with smoking index and disease progression in smokers with normal lung function and smokers with chronic obstructive pulmonary disease (COPD).MethodsPatients requiting lung resection for peripheral lung cancer were divided into group A (nonsmokers with normal lung function,n = 10), group B (smokers with normal lung function, n = 13), and group C (smokers with stable COPD,n = 10).The lung tissue far away from rumor were resected to compare the pathological changes of intraacinar pulmonary arteries and infiltration level of inflammatory cell in pulmonary non-muscularized arteries (NMA), pulmonary partially muscularized arteries (PMA) and muscularized arteries (MA) among the three groups.The correlation analysis was made among infiltration level, smoking index, percentage of predicted value of forced expiratory volume in one second (FEV,％ Pred), six-minute-walk distance (6MWD) and BODE index.Results (1) Both group B and group C showed the intima and media thickness of MA was significantly higher, the lumen area of MA was narrower and the proportion of MA was higher, and collagenous fiber of MA adventitial proliferated and area increased in group C(P ＜0.05 or P ＜0.01).(2) In group B and group C, the percentage of the intra-acinar pulmonary arteries that contained leukocytes, T lymphocytes, CD8+ T lymphocytes and the number of these positive cells infiltrating the intraacinar pulmonary arteries were increased, especially an increased number of CD8+ T lymphocytes infiltrating in the arterial adventitia as compared with group A, moreover there were significant difference between group C and group B (P ＜ 0.05 or P ＜ 0.01).In group B and group C, the degree of these positive cellsinfiltrating NMA, PMA and MA presented a decreasing sequence (P ＜ 0.05 or P ＜ 0.01).Among the intima, media and adventitia of MA, the infiltration of these positive cells was the highest in the adventitia.Among group A, group B and group C, infiltration degree of CD4+ T lymphocyte, B lymphocyte, macrophage and neutrophil demonstrated no significant difference, also among NMA, PMA and MA (P ＞ 0.05).(3)The number of leukocytes, T lymphocytes, CD8+T lymphocytes infiltrating MA showed a positive correlation with the thickness of MA (r =0.563,0.627,0.589 ,P ＜0.01 ,respectively) and smoking index (r =0.551,0.665, 0.600, P ＜ 0.01, respectively), moreover the degree of these cells infiltrating MA demonstrated negative correlation with FEV1 ％ Pred (r = - 0.763, - 0.703, - 0.767, P ＜ 0.01, respectively).Also infiltrating degree of T lymphocytes and CD8+ T lymphocytes was positively correlated with BODE(r = 0.390,0.476,P ＜ 0.05, respectively). Furthermore the infiltrating degree of CD8+ T lymphocytes had negative correlation with 6MWD (r = - 0.356, P ＜ 0.05).Conclusions(1) Pulmonary arterial inflammation appears in smokers with normal lung function and smokers with COPD patients.It involves in all types of intra-acinar pulmonary arteries especially NMA and infiltrates whole layer of MA with a characteristic of CDs+T lymphocytes infiltrating in the adventitia of intra-acinar pulmonary arteries. (2)Pulmonary inflammation is closely correlated to cigarette smoking and clinical parameters such as BODE index, FEV1％pred and 6MWD.It is one of the key factors affecting the progression of COPD.

The expression and mechanisms of interleukin-17 in CD8+ T cells of mice with cigarette smoke-induced emphysema / 中华内科杂志

Objective To evaluate the expression of Tc17 in a cigarette smoke-induced mice model of emphysema.To explore the probable mechanisms about how Tc17 cells to elevate in lungs of mice.Methods Forty male Balb/c mice were randomly divided into four groups,including control group ( 12 weeks,C12),control group (24 weeks,C24),smoke-exposure group (12 weeks,S12) and smoke-exposure group (24 weeks,S24 ),10 mice each group,Emphysema of mice was observed by HE pigmentation.Morphological changes were evaluated by mean linear intercepts (Lm) and destructive index (DI).The proportion of CD8+ IL-17 + Tc17,CD8+ IL-17 + CC chemokine receptor type 6 ( CCR6 ) + and 6CCR6 + Tc17 cells in lungs of mice was determined by flow cytometry.The mRNA expressions of retinoidrelated orphan nuclear receptor(RORγt) and IL-17 were evaluated by real-time PCR.The levels of IL-1 β,IL-6,IL-23,transforming growth factor β (TGFβ) and CC chemokine ligand 20 (CCL20) were tested by ELISA.Correlations among these indexes were analyzed.Results Lm and DI were significantly higher in S12 and S24 than in C12 and C24,S24 in particular (t value 4.378-15.188,all P ＜ 0.05).The percentages of Tc17 in S12 and S24[(9.28 ± 1.12)%,( 13.13 ±3.56)%]was significantly increased as compared with that in C12 and C24[(2.40 ±0.60 )%,(2.64 ±0.96 )%],S24 in particular.The mRNA levels of RORγt and IL-17 in S12 and S24 were higher than in C12 and C24,S12 and S24 in particular.There was significant difference (all P ＜0.05 ).The frequency of Tc17 cells had a positive correlation with Lm and DI ( r value were 0.734 and 0.884 respectively,P ＜ 0.01 ).The percentages of CD8+ IL-17 + CCR6 +T cells and CCR6 + Tc17 were significantly elevated in S12 and S24 compared to C12 and C24,S24 in particular (all P ＜ 0.05 ).There was positive correlation between Tc17 cell ratio and CCL20 levels( r =0.899,P ＜0.01 ).The levels of IL-1 β,IL-6,IL-23 and TGFβ in S12 and S24 were significantly increased as compared with that in C12 and C24.There was significant difference (all P ＜0.05).Meanwhile,the frequency of Tc17 cells had a positive correlation with IL-1β,IL-6,IL-23,and TGFβ.Conclusions An up-regulation of proportions Tc17 in lungs of cigarette smoke-induced emphysema mice were detected.The CCR6/CCL20 axis and the increased IL-1β,IL-6,IL-23 and TGFβ probably contributed to this up-regulation.

CYP4F2 gene V433M polymorphism is associated with ischemic stroke in the male Northern Chinese Han population.

BACKGROUND: CYP4F2 is a member of the cytochrome P450 enzymes and is responsible for metabolizing arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE); 20-HETE plays a role in the regulation of vascular tone in the cerebral, coronary, and renal circulation. The present study aimed to evaluate whether or not the CYP4F2 gene polymorphism V433M (rs2108622) is involved in ischemic stroke in the Northern Chinese Han population. METHODS: In a case-control study, the participants included 302 (193 males and 109 females) patients with ischemic stroke and 350 (212 males and 138 females) healthy subjects. The V433M polymorphism of the CYP4F2 gene was analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) with the restriction enzyme PvuII. RESULTS: The frequencies of the GG genotype and the G allele were higher in participants with ischemic stroke than in the control group (P=0.018). Multiple logistic regression analysis revealed the significance of the rs2108622 in males after adjustment for confounding factors. No difference was found in all participants and females. CONCLUSION: The GG genotype and G allele were associated with ischemic stroke in the male Northern Chinese Han population.

Clinical-MRI correlation study of medullary infarction / 中华神经科杂志

Objective To investigate the relation between lesions of medullary infarction and clinical symptoms and signs.Methods Eleven patients with medullary infarction confirmed by MRI were identified.Their clinical presentations and the relation between clinical presentation and location of lesion in MRI were assessed and analyzed.Results Among the 11 patients,5 cases suffered from lateral medullary infarction,6 medial medullary infarction(including two cases of bilateral infarction).Regarding clinical symptoms,common symptoms in lateral medullary infarction are blurred speech,dizziness,choking water,swallowing difficulties and facial numbness;in medial medullary infarction are limb weakness and blurred speech.The common signs of lateral medullary infarction are dysarthria,sensory disturbance,Horner sign and facial paralysis;in medial medullary infarction are paralysis of limbs and peripheral paralysis of the tongue.Conclusion Clinical manifestations are vailed depending on the sites of medullary infarction.MRI is helpful in diagnosing of medullary infarction.

Effects of Fragile Mental Retardation Protein on Cerebellar Neuron Development and Migration in Mouse Model / 中国医科大学学报

Objective To investigate the effects of fragile X mental retardation protein（FMRP）on the development and migration of cerebellar neurons in mouse model.Methods Plasmids containing FMRPmutant-EGFP or EGFP were established and transfected into the lateral ventricle of the embryo mouse.Fragile X syndrome（FXS）genotype of the mouse model was identified.Nissl staining and immunofluorescence staining were conducted to assess the changes in neuron development and migration.Results In the experimental group,Nissl staining showed that the deep cerebellar neuclei contracted and divided by white matter,and the non-polarized Purkinje cells retained in internal granular layer;while immunofluorescence staining showed that Tbr2-positive unipolar brush cells changed the migration pathway and accumulated in the ventricular zone.Conclusion Cerebellar neurons showed abnormal formation and migration with the absence of FMRP.

Effect of combination of bone marrow stromal cells and bcl-2 gene therapy on expression of basic fibroblast growth factor in focal cerebra ischemic rat brain / 国际脑血管病杂志

Objective To investigate the efficacy of the combination of bone marrow stromal cells (BMSCs) and bcl-2 gene in the treatment cerebral ischemia taxi its effect on the expression of basic fibroblast growth factor (bFGF) in rats.Methods Forty Wistar rats were used to establish middle cerebral artery occlusion model. They were randomly divided into 4 groups: saline control, bcl-2, BMSCs and BMSCs + bcl-2 groups (n = 10 in each group). Every group was redivided into 3- and 14-day after reperfusion subgroups (n = 5 in each subgroup). Neurological scores of the experimental rats were assessed. BMSCs were labeled with bromodeoxyuridine (BrdU). The distribution and numbers of BMSCs, the expressions of Bcl-2 and bFGF were detected by immunohistochemistry, and apoptotic cells were detected with TUNEL staining in rat brain. Results The neurological score at day 3 after reperfusion in the BMSCs + bcl-2 group was significantly lower than that in the saline control group (P < 0. 05), and at day 14, it was significantly lower than that in the other 3 groups (all P <0. 05). A large number of BrdU-positive BMSCs were observed in the infarcted hemisphere in the BMSCs + bcl-2 and BMSCs groups. The numbers of BrdU-positive BMSCs at day 3 and 14 after reperfusion in the BMSCs + bcl-2 group were significantly higher than those in the BMSCs group (all P <0. 05). The expressions of Bcl-2 in the infarcted hemisphere at day 3 and 14 after reperfusion in BMSCs +hel-2 group wre significantly higher than those in the other 3 groups (all P <0. 05). The expressions of Bcl-2 at all time points were increased more significantly than those in the other 3 groups (all P <0. 05). The numbers of apoptosis in brain at all time points in the BMSCs + bcl-2 group were decreased more significantly than those in the other 3 groups (all P <0. 05). Conclusions Both BMSCs and bcl-2 genes have the therapeutic effect on cerebral ischemia. The efficacy of combination of both ,of them is significantly superior to monotherapy. They may significantly improve the neurological function and increase the expression of bFGF in rats. Its mechanism may be that bcl-2 genes have inhibited BMSCs apoptosis at the same time of anti-apoptosis in brain.

Mesenchymal stromal cells for cerebral infarction / 国际脑血管病杂志

Although there are many drugs for the treatment'of cerebral infarction, no satisfactory efficacy has achieved. Mesenehymal stromal cells (MSCs) have multilineage differentiation potential and self-renewing capability, and can differentiate into neurons. The transplanted MSCs can improve neurological deficit after cerebral infarction, promote the recovery of neurological function, and thereby reduce the disability of cerebral infarction through the mechanisms such as releasing nutritional factors and growth nutritional factors, promoting angiogenesis. The use of MSCs for cell transplantation is likely to be an ideal means in the treatment of cerebral infarction.