The Notch Signaling Pathway Regulates Differentiation of NG2 Cells into Oligodendrocytes in Demyelinating Diseases.

NG2 cells are highly proliferative glial cells that can self-renew or differentiate into oligodendrocytes, promoting remyelination. Following demyelination, the proliferative and differentiation potentials of NG2 cells increase rapidly, enhancing their differentiation into functional myelinating cells. Levels of the transcription factors Olig1 and Olig2 increase during the differentiation of NG2 cells and play important roles in the development and repair of oligodendrocytes. However, the ability to generate new oligodendrocytes is hampered by injury-related factors (e.g., myelin fragments, Wnt and Notch signaling components), leading to failed differentiation and maturation of NG2 cells into oligodendrocytes. Here, we review Notch signaling as a negative regulator of oligodendrocyte differentiation and discuss the extracellular ligands, intracellular pathways, and key transcription factors involved.

Erythromycin Regulates Cigarette Smoke-Induced Proinflammatory Mediator Release Through Sirtuin 1-Nuclear Factor κB Axis in Macrophages and Mice Lungs.

BACKGROUND: Macrolides have anti-inflammatory and antioxidative stress function, but their pharmacological regulation remains unclear. Sirtuin 1 (SIRT1) is redox-sensitive protein belongs to class III histone/protein deacetylases, SIRT1 regulates the acetylation/expression of nuclear factor κB (NF-κB) and is involved in the airway inflammation of chronic obstructive pulmonary disease. OBJECTIVES: The present study was designed to examine the effects of erythromycin (EM) on the SIRT1-NF-κB axis and NF-κB-dependent proinflammatory cytokines. METHODS: Human macrophages were preincubated with EM and then treated with cigarette smoke extract (CSE). The mice were treated by injecting drugs to gastric with EM before cigarette smoke exposure. Reactive oxygen species (ROS) released by treated human macrophages were detected using flow cytometry. The expression of SIRT1 and NF-κB was analyzed by western blotting. SIRT1 and the RelA/p65 subunits of NF-κB interaction were detected by coimmunoprecipitation. We found that EM suppressed CSE-induced ROS released in human macrophages, which coincided with increases in SIRT1 protein expression in the macrophages and lungs of mice, resulting in suppressed -NF-κB acetylation and expression correlated with a reduction of inflammatory mediators. CONCLUSION: These findings suggest that EM increased SIRT1, leading to acetylation/expression of NF-κB, and thereby decreasing cigarette smoke-driven NF-κB-dependent proinflammatory cytokine.

Enhanced activation of circulating plasmacytoid dendritic cells in patients with Chronic Obstructive Pulmonary Disease and experimental smoking-induced emphysema.

Plasmacytoid dendritic cells (pDCs) are key cells bridging the innate with adaptive immunity. However, the phenotypic characteristics of circulating pDCs and its role in smoking related-Chronic Obstructive Pulmonary Disease (COPD) remain largely unknown. The aim of this study was analyzed the phenotype of circulating pDCs and the expression of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells in patients with COPD by using multi-colour flow cytometry. The cytokine profiles in peripheral blood from all subjects were measured by ELISA. The influence of cigarette smoke on pDCs was evaluated in an experimental mouse model of emphysema. Circulating pDCs in patients with COPD and in mice exposed to cigarette smoke expressed high levels of co-stimulatory molecules CD40 or CD86 accompanied by exaggerated IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells. In vitro, cigarette smoke directly promoted pDCs maturation and release of IFN-α, IL-6 and IL-12, subsequently inducing differentiation of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells from mouse naïve CD8+T cells. These data suggested that circulating pDCs display an enhanced activation phenotype in patients with COPD and in experimental smoking mouse model of emphysema, which might contribute to exaggerated IFN-γ producing CD8+T and IL-17-producing CD8+T cell-mediated immune responses.

Zinc alpha2 glycoprotein protects against obesity-induced hepatic steatosis.

BACKGROUND/AIM: Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, impaired insulin sensitivity, and chronic low-grade inflammation. Our previous studies indicated that zinc alpha2 glycoprotein (ZAG) alleviates palmitate (PA)-induced intracellular lipid accumulation in hepatocytes. This study is to further characterize the roles of ZAG on the development of hepatic steatosis, insulin resistance (IR), and inflammation. METHODS: ZAG protein levels in the livers of NAFLD patients, high-fat diet (HFD)-induced or genetically (ob/ob) induced obese mice, and in PA-treated hepatocytes were determined by western blotting. C57BL/6J mice injected with an adenovirus expressing ZAG were fed HFD for indicated time to induce hepatic steatosis, IR, and inflammation, and then biomedical, histological, and metabolic analyses were conducted to identify pathologic alterations in these mice. The molecular mechanisms underlying ZAG-regulated hepatic steatosis were further explored and verified in mice and hepatocytes. RESULTS: ZAG expression was decreased in NAFLD patient liver biopsy samples, obese mice livers, and PA-treated hepatocytes. Simultaneously, ZAG overexpression alleviated intracellular lipid accumulation via upregulating adiponectin and lipolytic genes (FXR, PPARα, etc.) while downregulating lipogenic genes (SREBP-1c, LXR, etc.) in obese mice as well as in cultured hepatocytes. ZAG improved insulin sensitivity and glucose tolerance via activation of IRS/AKT signaling. Moreover, ZAG significantly inhibited NF-ĸB/JNK signaling and thus resulting in suppression of obesity-associated inflammatory response in hepatocytes. CONCLUSIONS: Our results revealed that ZAG could protect against NAFLD by ameliorating hepatic steatosis, IR, and inflammation.

Different Doses of Clazosentan for Aneurismal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials.

Clazosentan therapy has been found to be effective in reducing the incidence of vasospasm after aneurismal subarachnoid hemorrhage (aSAH). The objective of this meta-analysis was to determine whether different doses of clazosentan treatment significantly reduced the incidence of delayed ischemic neurological deficits (DINDs) and new cerebral infarction (NCI). We systematically searched PubMed, Embase, Cochrane library and Medline from inception until October, 2015. All randomized controlled trials related to the functions of clazosentan in aSAH were included. Analyses were performed following the method guideline of Cochrane Back Review Group. Four randomized placebo-controlled trials met eligibility criteria and enrolled a total of 2159 patients. The meta-analysis demonstrated a significant decrease in the incidence of DINDs (relative risk, 0.49 and 95% CI, 0.33-0.73) and NCI (relative risk, 0.42 and 95% CI, 0.25-0.71) in patients treated with a high dose of clazosentan (15 mg/h) after aSAH. In addition, a high dose of clazosentan (15 mg/h) had no more effect on the incidence of adverse events than that of a low dose (1-5 mg/h). The results of the present meta-analysis show that a high dose of clazosentan significantly reduced the incidence of the vasospasm-related DINDs and NCI. Further study is required to fully understand the potential usefulness of clazosentan in patients with aSAH.

Neutrophil extracellular traps induced by cigarette smoke activate plasmacytoid dendritic cells.

BACKGROUND: Neutrophil extracellular traps (NETs) represent a distinct strategy by which neutrophils trap, confine and eliminate invading microorganisms. Emerging evidence suggests that NETs exert a deleterious effect to the host in the absence of microbial stimuli. However, the role of NETs in smoking-related lung diseases remains to be elucidated. OBJECTIVES: To evaluate the formation of NETs in the context of chronic inflammation induced by cigarette smoking and explore its potential role in an experimental mouse model of emphysema. METHODS: The formation and degradation of NETs in cigarette smoke exposed mice was assessed with a fluorescence microscope. The potential influences of NETs on plasmacytoiddendritic cells were also investigated. RESULTS: NETs were more prone to formation by polymorphonuclearneutrophils but defective in degradation in cigarette smoke exposed mice. Cigarette smoke extract (CSE) served as an important facilitator that triggered neutrophils to undergo NETosis in vitro. Furthermore, CSE-induced NETs were capable of driving plasmacytoiddendritic cell maturation and activation, thereby initiating a T-cell-mediated immune response. CONCLUSIONS: NETs may represent a critical connection between innate and adaptive immune responses under conditions of chronic inflammation induced by cigarette smoke exposure.

Dendritic cells induce Tc1 cell differentiation via the CD40/CD40L pathway in mice after exposure to cigarette smoke.

Dendritic cells and CD8(+) T cells participate in the pathology of chronic obstructive pulmonary disease, including emphysema, but little is known of the involvement of the CD40/CD40L pathway. We investigated the role of the CD40/CD40L pathway in Tc1 cell differentiation induced by dendritic cells in a mouse model of emphysema, and in vitro. C57BL/6J wild-type and CD40(-/-) mice were exposed to cigarette smoke (CS) or not (control), for 24 wk. In vitro experiments involved wild-type and CD40(-/-) dendritic cells treated with CS extract (CSE) or not. Compared with the control groups, the CS mice (both wild type and CD40(-/-)) had a greater percentage of lung dendritic cells and higher levels of major histocompatability complex (MHC) class I molecules and costimulatory molecules CD40 and CD80. Relative to the CS CD40(-/-) mice, the CS wild type showed greater signs of lung damage and Tc1 cell differentiation. In vitro, the CSE-treated wild-type cells evidenced more cytokine release (IL-12/p70) and Tc1 cell differentiation than did the CSE-treated CD40(-/-) cells. Exposure to cigarette smoke increases the percentage of lung dendritic cells and promotes Tc1 cell differentiation via the CD40/CD40L pathway. Blocking the CD40/CD40L pathway may suppress development of emphysema in mice exposed to cigarette smoke.

Combination of erythromycin and dexamethasone improves corticosteroid sensitivity induced by CSE through inhibiting PI3K-δ/Akt pathway and increasing GR expression.

Corticosteroid insensitivity, which is induced by cigarette smoke extract (CSE), is a significant barrier when treating chronic obstructive pulmonary disease (COPD). Erythromycin (EM) has been shown to have an anti-inflammatory role in some chronic airway inflammatory diseases, particularly diffuse panbronchiolitis and cystic fibrosis. Here, we explored whether the combination therapy of EM and dexamethasone (Dex) reverses corticosteroid insensitivity and investigated the molecular mechanism by which this occurs. We demonstrated that the combination of EM and Dex restored corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from COPD patients and U937 cells after CSE exposure. Moreover, pretreatment with 10, 50, or 100 µg/ml EM reversed the HDAC2 protein reduction induced by CSE exposure in a dose-dependent manner. U937 cells exposed to CSE show a reduction in histone deacetylase (HDAC) activity, which was potently reversed by EM or combination treatment. Although 10 and 17.5% CSE increased phosphorylated Akt (PAkt) expression in a concentration-dependent manner, preapplication of EM and the combination treatment in particular blocked this PAkt increase. Total Akt levels were unaffected by CSE or EM treatments. Furthermore, the combination treatment enhanced glucocorticoid receptor (GR)α expression. Our results demonstrate that the combination therapy of EM and Dex can restore corticosteroid sensitivity through inhibition of the PI3K-δ/Akt pathway and enhancing GRα expression.

Prediction of cervical lymph node metastasis in solitary papillary thyroid carcinoma based on ultrasound radiomics analysis.

Objective: To assess the utility of predictive models using ultrasound radiomic features to predict cervical lymph node metastasis (CLNM) in solitary papillary thyroid carcinoma (PTC) patients. Methods: A total of 570 PTC patients were included (456 patients in the training set and 114 in the testing set). Pyradiomics was employed to extract radiomic features from preoperative ultrasound images. After dimensionality reduction and meticulous selection, we developed radiomics models using various machine learning algorithms. Univariate and multivariate logistic regressions were conducted to identify independent risk factors for CLNM. We established clinical models using these risk factors. Finally, we integrated radiomic and clinical models to create a combined nomogram. We plotted ROC curves to assess diagnostic performance and used calibration curves to evaluate alignment between predicted and observed probabilities. Results: A total of 1561 radiomics features were extracted from preoperative ultrasound images. After dimensionality reduction and feature selection, 16 radiomics features were identified. Among radiomics models, the logistic regression (LR) model exhibited higher predictive efficiency. Univariate and multivariate logistic regression results revealed that patient age, tumor size, gender, suspicious cervical lymph node metastasis, and capsule contact were independent predictors of CLNM (all P < 0.05). By constructing a clinical model, the LR model demonstrated favorable diagnostic performance. The combined model showed superior diagnostic efficacy, with an AUC of 0.758 (95% CI: 0.712-0.803) in the training set and 0.759 (95% CI: 0.669-0.849) in the testing set. In the training dataset, the AUC value of the nomogram was higher than that of the clinical and radiomics models (P = 0.027 and 0.002, respectively). In the testing dataset, the AUC value of the nomogram model was also greater than that of the radiomics models (P = 0.012). However, there was no significant statistical difference between the nomogram and the clinical model (P = 0.928). The calibration curve indicated a good fit of the combined model. Conclusion: Ultrasound radiomics technology offers a quantitative and objective method for predicting CLNM in PTC patients. Nonetheless, the clinical indicators persists as irreplaceable.

[Effects of kidney stem cells on injure-recovery of human renal tubular epithelial cells].

OBJECTIVE: To investigate the protective effects and the mechanism of kidney stem cells (KSC) on the injured tubular epithelial cells. METHODS: KSC were isolated from rat renal papilla. The human kidney epithelial cells (HKC) injury model was induced with 0.1 µmol/L antimycin A for 30 minutes. The injured HKC were co-cultured with KSC or supernatant of cultured KSC. The apoptosis of HKC were detected by flow cytometry. The changes of ATP in the HKC and the level of malondialdehyde (MDA), superoxide dismutase (SOD) and lactate dehydrogenase (LDH) in the supernatant of cultured HKC were detected after being co-cultured with KSC. RESULTS: The study of the co-culture showed that KSC was less capable to migrate through the micropores of Transwell compared with bone marrow stem cells. However, after being co-cultured with the KSC conditional supernatant, ATP content of injured HKC, total SOD value in the supernatant of injured HKC were increased, and the MDA and LDH in the supernatant of injured HKC decreased. CONCLUSION: KSC have protected effects and participate in the repair of injured HKC.

Impact of Pulmonary Arterial Elastance on Right Ventricular Mechanics and Exercise Capacity in Repaired Tetralogy of Fallot.

BACKGROUND AND OBJECTIVES: Pathophysiological changes of right ventricle (RV) after repair of tetralogy of Fallot (TOF) are coupled with a highly compliant low-pressure pulmonary artery (PA) system. This study aimed to determine whether pulmonary vascular function was associated with RV parameters and exercise capacity, and its impact on RV remodeling after pulmonary valve replacement. METHODS: In a total of 48 patients over 18 years of age with repaired TOF, pulmonary arterial elastance (Ea), RV volume data, and RV-PA coupling ratio were calculated and analyzed in relation to exercise capacity. RESULTS: Patients with a low Ea showed a more severe pulmonary regurgitation volume index, greater RV end-diastolic volume index, and greater effective RV stroke volume (p=0.039, p=0.013, and p=0.011, respectively). Patients with a high Ea had lower exercise capacity than those with a low Ea (peak oxygen consumption [peak VO2] rate: 25.8±7.7 vs. 34.3±5.5 mL/kg/min, respectively, p=0.003), while peak VO2 was inversely correlated with Ea and mean PA pressure (p=0.004 and p=0.004, respectively). In the univariate analysis, a higher preoperative RV end-diastolic volume index and RV end-systolic volume index, left ventricular end-systolic volume index, and higher RV-PA coupling ratio were risk factors for suboptimal outcomes. Preoperative RV volume and RV-PA coupling ratio reflecting the adaptive PA system response are important factors in optimal postoperative results. CONCLUSIONS: We found that PA vascular dysfunction, presenting as elevated Ea in TOF, may contribute to exercise intolerance. However, Ea was inversely correlated with pulmonary regurgitation (PR) severity, which may prevent PR, RV dilatation, and left ventricular dilatation in the absence of significant pulmonary stenosis.

[Effects of Different Types of Plastic Film Mulching on Soil Quality, Root Growth, and Yield].

Aiming to address the problem of soil environmental pollution caused by the large-scale use of plastic film in agricultural production in China, field experiments were carried out by applying degradable plastic film. Pumpkin was used as the research material to explore the effects of black common plastic film (CK), white degradation plastic film (WDF), black degradation plastic film (BDF), and black CO2-based degradable plastic film (C-DF) on soil physicochemical properties, root growth and yield, and soil quality. The results showed that the soil water content and temperature of the three degradable plastic films were lower than those of ordinary plastic films to different degrees; there was no significant difference in soil organic matter content among the treatments. The soil available potassium content of the C-DF treatment was lower than that of CK, and WDF and BDF had no significant effect. Compared with those in CK and WDF, soil total nitrogen and available nitrogen contents in the BDF and C-DF treatments were lower, and the difference between treatments reached a significant level. Compared with that of CK, the catalase activities of the three types of degradation membranes were significantly increased by 2.9%-6.8%, and the sucrase was significantly decreased by 33.3%-38.4%. Compared with that in CK, the soil cellulase activity in the BDF treatment was significantly increased by 63.8%, whereas WDF and C-DF had no significant effects. The three types of degradable film treatments could promote the growth of underground roots, and the growth vigor was obviously enhanced. The yield of pumpkin treated with BDF and C-DF was close to that of CK, and the yield of pumpkin treated with BDF was significantly lower than that of CK by 11.4%. The experimental results showed that the effects of the BDF and C-DF treatments on soil quality and yield were comparable to those of CK. According to the results, two types of black degradable plastic film can effectively replace ordinary plastic film in the high-temperature production season.

Erythromycin enhances CD4+Foxp3+ regulatory T-cell responses in a rat model of smoke-induced lung inflammation.

Heavy smoking can induce airway inflammation and emphysema. Macrolides can modulate inflammation and effector T-cell response in the lungs. However, there is no information on whether erythromycin can modulate regulatory T-cell (Treg) response. This study is aimed at examining the impact of erythromycin on Treg response in the lungs in a rat model of smoking-induced emphysema. Male Wistar rats were exposed to normal air or cigarette smoking daily for 12 weeks and treated by gavage with 100 mg/kg of erythromycin or saline daily beginning at the forth week for nine weeks. The lung inflammation and the numbers of inflammatory infiltrates in bronchoalveolar lavage fluid (BALF) were characterized. The frequency, the number of Tregs, and the levels of Foxp3 expression in the lungs and IL-8, IL-35, and TNF-α in BALF were determined by flow cytometry, RT-PCR and ELISA, respectively. Treatment with erythromycin reduced smoking-induced inflammatory infiltrates, the levels of IL-8 and TNF-α in the BALF and lung damages but increased the numbers of CD4+Foxp3+ Tregs and the levels of Foxp3 transcription in the lungs, accompanied by increased levels of IL-35 in the BALF of rats. Our novel data indicated that erythromycin enhanced Treg responses, associated with the inhibition of smoking-induced inflammation in the lungs of rats.

[Serological Characteristics and Molecular Biological Mechanism of AEL.02 Subtype].

OBJECTIVE: To explore the serological characteristics and molecular biological mechanism of an ael subtype specimen. METHODS: The ABO blood typing was identified by routine blood group serological and absorption/elution methods; PCR-SBT method for ABO genotyping: 7 exons of ABO gene were amplified by PCR, the amplified products were purified, and then sequencing primers were designed and the amplified products were sequenced directly for analysis; 3D molecular model was constructed and the difference of free energy (ΔΔG) was used to predict the GTA mutant stability. RESULTS: A antigen was not detected on erythrocytes through absorption and elution tests, which was not consistent with the serological characteristics of ael, and the serological typing results were ambiguous. The ABO genotype was ABO*AEL.02/O.01.01, and there were two mutations in exon 7 of the gene, c.467C>T and c.646T>A, which could lead to the replacement of proline with leucine at position 156 (p.Pro156Leu) and phenylalanine with isoleucine at position 216 on the GTA, respectively. The 3D model predicts that the mutations do not introduce new hydrogen bonds to the GTA mutant and do not form a new secondary structure, but can lead to an increase in the ΔΔG value of the GTA mutant, suggesting a decrease in protein stability. CONCLUSION: The serological characteristics alone is not reliable to determine the ael subype; the ael phenotype may be due to the GTA mutant that reduces enzyme stability.

Acupuncture for chronic sciatica: protocol for a multicenter randomised controlled trial.

BACKGROUND: Chronic Sciatica is a disabling condition causing considerable medical, social and financial implications. Currently, there is no recognised long-term effective treatment to alleviate sciatica. Acupuncture has been widely used for treating chronic pains with persistent analgesic effects. We aim to evaluate the efficacy and safety of acupuncture for chronic sciatica with follow-up in 52 weeks. METHODS AND ANALYSIS: This is a multicenter randomised sham-controlled trial. A total of 216 patients with chronic sciatica will be enrolled and randomly assigned to the acupuncture or sham acupuncture group. There will be 10 treatment sessions applied in 4 weeks with frequency decreased over time. Patients will complete follow-ups during 52 weeks. The primary outcomes are changes in leg pain intensity and disability from baseline to week 4. Secondary outcomes include back pain intensity, frequency and bothersomeness, quality of life, and global perceived effect. Adverse events will be recorded in detail. ETHICS AND DISSEMINATION: Ethical approval of this trial was granted from the ethics committee of Beijing University of Chinese Medicine and all study centres (No. 2020BZYLL0803). Written informed consent will be obtained from enrolled patients. Trial results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2100044585 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 24 March 2021); preresults.

Animal Models of Cerebral Changes Secondary to Spinal Cord Injury.

Spinal cord injuries (SCIs) are difficult to treat. The first animal SCI model (featuring the dropping of a weight) was established by Allen in 1911, and other animal models have been developed since then. Most animal studies have focused only on the molecular features of SCIs, which remain disputed. Recently, it has become clear that SCI may trigger mental and cognitive disorders, however, and brain changes secondary to SCI are under investigation. No consensus on an optimal animal model for cerebral research has emerged. We discuss the appropriate SCI models for studying secondary brain changes.

Erythromycin inhibits cigarette smoke-induced inflammation through regulating the PPARγ/NF-κB signaling pathway in macrophages.

Chronic obstructive pulmonary disease is characterized by chronic inflammation of the airway and lungs. Accumulating evidence has suggested that erythromycin (EM) plays a protective role against cigarette smoke-induced oxidative stress and the inflammatory response. However, the underlying mechanisms remain relatively unclear. The present study aimed to investigate the role of EM in inhibiting cigarette smoke-induced inflammation in human macrophages and its potential mechanism. A Cell Counting Kit-8 assay was used to determine the optimum concentration of EM and cigarette smoke extract (CSE) and it was found that 0.1 and 1% CSE and 0.1, 1.0 and 10 µg/ml EM exerted no significant effect on the cell proliferation activity, whereas 2 and 3% CSE exerted a significant inhibitory effect over the cell proliferation activity. We observed that 10 µmol/ml GW9662 (A PPARγ antagonist) and the presence of 1% CSE could promote the expression and activation of NF-κB p65. And this increased the expression of IL-6, IL-8 and reactive oxygen species (ROS). At the same time, 10 µmol/ml GW9662 and 1% CSE was found to inhibit the expression and activation of peroxisome proliferator activated receptors γ (PPARγ); However, 1 µg/ml EM was discovered to reverse these effects. Co-immunoprecipitation subsequently discovered an interaction between PPARγ and NF-κB p65. In conclusion, the present study suggested that EM may reduce the damage of PPARγ by inhibiting oxidative stress and reducing the expression of ROS and finally relieving cigarette smoke-induced inflammation through the PPARγ/NF-κB signaling pathway in macrophages.

Effect of 6 months of erythromycin treatment on inflammatory cells in induced sputum and exacerbations in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation and is associated with acute exacerbations. Macrolide antibiotics have been shown to exhibit anti-inflammatory effects in some chronic airway inflammatory diseases. OBJECTIVE: The aim of this study was to assess the effect of treatment with erythromycin on airway inflammation and health outcome in COPD patients. METHODS: We conducted a randomized, placebo-controlled, double-blind trial of erythromycin for a period of 6 months. Thirty-six COPD patients were randomized to treatment with oral erythromycin (125 mg, three times/day) or placebo. The primary outcomes were neutrophil number in sputum and exacerbations. RESULTS: Thirty-one patients completed the study. At the end of treatment, neutrophil counts in the sputum were significantly decreased in the group treated with erythromycin compared with placebo-treated patients (p = 0.005). Total cells in the sputum and neutrophil elastase in sputum supernatant were also significantly decreased in those treated with erythromycin compared with the placebo group (p = 0.021 and p = 0.024, respectively). The mean exacerbation rate was lower in the erythromycin group than in the placebo group (relative risk = 0.554, p = 0.042). Kaplan-Meier survival analysis showed that erythromycin significantly delayed the time to the first COPD exacerbation compared with placebo (p = 0.032). CONCLUSIONS: Erythromycin treatment in COPD patients can reduce airway inflammation and decrease exacerbations and may therefore be useful in the management of COPD.

[Surgical management of petroclival meningiomas invading into cavernous sinus].

OBJECTIVE: To analyze the clinical features, surgical strategy and management outcomes of petroclival meningioma invading into cavernous sinus. METHODS: Fifteen cases with petroclival meningioma invading into cavernous sinus were retrospectively analyzed. The presigmoidal approach was selected to remove tumors. The surgical strategy for tumor in cavernous sinus was partial resection combined with radiosurgery. Postoperative cranial nerve function and patient survival status were analyzed. RESULTS: The main symptoms of subtype of petroclival meningiomas were headache, abducens nerve palsy and trigeminal neuropathy. Gross total tumor removal was achieved in 13 cases and more than 90% resection in 2 cases. There was no operative death. Nine cases suffered from new postoperative cranial nerve deficits. After a follow-up of 6 - 59 months, complete improvement was achieved in oculomotor nerve deficits, much improvement in VII nerve deficit, but V and VI nerve function deficits improved slightly. The tumor progression-free survival rate was 86.7%. CONCLUSION: Rational surgical strategy to petroclival meningiomas invading into cavernous sinus should be suggested to reduce the operative morbidity and improve the survival quality of these patients.

Fluid Shear Stress Induces Endothelial Cell Injury via Protein Kinase C Alpha-Mediated Repression of p120-Catenin and Vascular Endothelial Cadherin In Vitro.

OBJECTIVE: The present study aimed to characterize the mechanism of fluid shear stress (FSS)-induced endothelial cell (EC) injury via protein kinase C alpha (PKCα)-mediated vascular endothelial cadherin (VE-cadherin) and p120-catenin (p120ctn) expression. METHODS: We designed a T chamber system that produced stable FSS on ECs in vitro. Human umbilical vein endothelial cells (HUVECs) in which PKCα was knocked down and normal HUVECs were cultured on the coverslips. FSS was impinged on these 2 types of ECs for 0 hours and 6 hours. The morphology and density of HUVECs were evaluated, and expression levels of phosphorylated PKCα, p120-catenin (p120ctn), VE-cadherin, phosphorylated p120ctn at S879 (p-S879p120ctn), and nuclear factor kappa B (NF-κB) were analyzed by Western blot. RESULTS: HUVECs exposed to FSS were characterized by a polygonal shape and decreased cell density. The phosphorylated PKCα level was increased under FSS at 6 hours (P < 0.05). In normal HUVECs during FSS, p120ctn and VE-cadherin were decreased, whereas p-S879p120ctn and NF-κB were increased, at 6 hours (P < 0.05). In HUVECs after PKCα knockdown, p120ctn and VE-cadherin were not significantly changed (P > 0.05), p-S879p120ctn was undetectable, but NF-κB was decreased (P < 0.05) at 6 hours. CONCLUSIONS: The possible mechanism of FSS-induced EC injury may be as follows: 1) PKCα induces low expression of p120ctn, which leads to activation of NF-κB and degradation of VE-cadherin; 2) PKCα-mediated phosphorylation of p120ctn at S879 disrupts p120ctn binding to VE-cadherin.