Coculture with interleukin-10 overexpressed chondrocytes: a cell therapy model to ameliorate the post-traumatic osteoarthritis development.

Autologous chondrocyte (CH) transplantation is a novel strategy to treat post-traumatic osteoarthritis (PTOA). In this study, an in vitro coculture model was used to explore the effects of interleukin (IL)-10 overexpressed CHs on degenerated CHs. The original CHs were isolated from the patients' knee joint cartilage and pretreated with IL-1ß to get degenerated CHs. Moreoer, CHs were transfected with a lentivirus vector to overexpress IL-10. After coculture with the degenerated CHs, the apoptosis, collagen X, IL-6, and TNF-α of original CHs were increased, and the collagen II and IL-10 were decreased compared to the separated culture condition. Coculture with original CHs did not alleviate the degeneration of the IL-1ß-pretreated CHs. However, coculture with the IL-10-overexpressed CHs rescued the proliferation, collagen II, aggrecan, SOX9, and IL-10 expression, and suppressed the apoptosis, collagen X, RUnx2, IL-6, and TNF-α levels in the IL-1ß pretreated CHs. Additionally, the IL-10-overexpressed CHs also maintained a healthy state when cocultured with the degenerated CHs. Therefore, transplanting the IL-10-overexpressed CHs in the treatment of PTOA would obtain a more durable and visible effect in alleviating the CH degeneration.

Prognostic value of the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification in stage IB lung adenocarcinoma.

BACKGROUND: Patients with pathological stage IB lung adenocarcinoma have a variable prognosis, even if received the same treatment. This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage IB lung adenocarcinoma. METHODS: We identified 276 patients with pathological stage IB adenocarcinoma who had undergone surgical resection at the Nanjing Chest Hospital between 2005 and 2010. The histological subtypes of all patients were classified according to the 2011 IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification. Kaplan-Meier and Cox regression analyses were used to analyze the correlation between the IASLC/ATS/ERS classification and patients' prognosis. RESULTS: Two hundred and seventy-six patients with pathological stage IB adenocarcinoma had an 86.2% 5-year overall survival (OS) and 80.4% 5-year disease-free survival (DFS). Patients with micropapillary and solid predominant tumors had a significantly worse OS and DFS as compared to those with other subtypes predominant tumors (p = 0.003 and 0.001). Multivariate analysis revealed that the new classification was an independent prognostic factor for both OS and DFS of pathological stage IB adenocarcinoma (p = 0.009 and 0.003). CONCLUSION: Our study revealed that the new IASLC/ATS/ERS classification was an independent prognostic factor of pathological stage IB adenocarcinoma. This new classification is valuable of screening out high risk patients to receive postoperative adjuvant therapy.

Vascular endothelial growth factor and soluble intercellular adhesion molecule-1 in lung adenocarcinoma with malignant pleural effusion: correlations with patient survival and pleural effusion control.

The mechanisms by which vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) contribute to lung cancer growth have not been fully elucidated. This study aimed to assess the role of VEGF and sICAM-1 in control of pleural effusions (PE) and survival in patients with primary human lung adenocarcinoma. Using enzyme-linked immunoadsorbent assay, the concentrations of VEGF and sICAM-1 were measured in pleural effusions and serum from a total of 79 lung adenocarcinoma patients with malignant pleural effusions (MPE) and 24 patients with tuberculosis. Data were correlated with the efficacy of MPE control and survival. Compared to patients with tuberculosis, the levels of VEGF and sICAM-1 in both PE and serum were significantly higher in patients with lung adenocarcinoma. Statistically significant correlation was observed between PE VEGF levels and MPE control. PE VEGF≥2760 pg/ml was used as a cut-off point for failure to MPE control (odds ratio=7.06; 95% confidence interval (CI), 2.40-20.78; P<0.001). The median progression-free survival (PFS) from response assessment was 3 months. In a multivariate analysis, PE VEGF (hazard ratio [HR], 1.16; 95% CI, 1.02-1.32), serum sICAM-1 (HR, 1.90; 95% CI, 1.17-3.07) were confirmed as independent prognostic factors for PFS. The levels of VEGF in PE can be used to predict the therapeutic efficacy in the control of MPE and this, together with serum level of sICAM-1 is potential survival factors in lung adenocarcinoma patients with MPE.

Association of the CD226 single nucleotide polymorphism with systemic lupus erythematosus in the Chinese Han population.

A novel non-synonymous (Gly307Ser) variant, rs763361, of the CD226 gene on chromosome 18q22 was recently shown to be associated with multiple autoimmune diseases. Taking into consideration that different autoimmune diseases may share some common pathogenic pathways, in this study we performed case-control studies to assess any genetic linkage with systemic lupus erythemtosus (SLE). An association between the Gly307Ser single nucleotide polymorphism (SNP) and susceptibility to SLE was identified. The TT genotype [odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.07-3.01, P = 0.025] and the T allele (OR = 1.34, 95% CI = 1.05-1.74, P = 0.018) of the rs763361 SNP were associated with the risk of SLE. This finding indicates that polymorphism of Gly307Ser (rs763361) in exon 7 of the CD226 gene may be associated with the development of SLE.

Evaluation of ventilatory responses in severe acidemia in diabetic ketoacidosis.

Ventilatory response in patients with severe acidemia in diabetic ketoacidosis (DKA) was unresolved. Thus, 83 patients with uncomplicated DKA were studied for the relation between arterial blood pH, calculated bicarbonate concentration (HCO3) and carbon dioxide tension (PCO2). The equation for the PCO2/HCO3 pair was: PCO2 = 1.58 x HCO3 + 7.6 (SE 2.55, r = 0.95, p < 0.01); for the PCO2/pH pair was: PCO2 = 43.8 x pH-293 (SE 6.23, r = 0.66, p < 0.01). The correlation coefficient for the PCO2/HCO3 pair was significantly greater compared to the PCO2/pH pair (p < 0.001). Multiple regression analysis showed that severe acidemia (pH < or = 7.10) per se was independently associated with PCO2 for the PCO2/HCO3 pair, but not for the PCO2/pH pair. Thus, our patients were divided into 2 groups for the PCO2/HCO3 pair: group 1 with pH < or = 7.10 (n = 25) and group 2 with pH > 7.10 (n = 58). The equations were: group 1:PCO2 = 3.18 x HCO3 + 2.88 (SE 1.72, r = 0.87, p < 0.01); group 2:PCO2 = 1.65 x HCO3 + 6.6 (SE 2.6, r = 0.95, p < 0.01). There was a significant difference between these 2 equations (p < 0.01). Mathematical simulations with 10 sets of 25 or 58 random pH/PCO2 pairs (and calculated HCO3) for "group 1' and "group 2' also showed similar results, albeit with less precision. Hence, ventilatory response in DKA varies between patients with severe acidemia and those with moderate acidemia by the PCO2/HCO3 pair, but not by the PCO2/pH pair.

Effects of bronchoconstriction on breathing during normoxia and hypoxia in anesthetized cats.

The effect of an increase in bronchomotor tone on control of breathing during both normoxia and hypoxia, and the role of vagal afferents in regulating these responses were studied in 15 anesthetized cats. Minute ventilation (VE) was measured with a pneumotachograph connected in series with a tracheal cannula. Total diaphragmatic EMG activity per minute (means p X f, peak EMG moving average X respiratory frequency) was measured to assess the central inspiratory drive. Bronchoconstriction was generated by inhalation of methacholine aerosol (10-30 breaths, 0.5% solution) which increased total lung resistance to approximately 400% of the control value. Transient hypoxia was induced by allowing the cats to rebreathe a hypoxic gas mixture (4.5% O2 balanced N2) for approximately 1 min. During normoxia, bronchoconstriction increased VE from a baseline of 100 to 129 +/- 7% (mean +/- SEM; P less than 0.05) and increased (means p X f) from 100 to 174 +/- 16% (P less than 0.01). During hypoxia, the response of (means p X f) to bronchoconstriction (404 +/- 40%) was still greater than without bronchoconstriction (306 +/- 35%; P less than 0.01), but the responses of VE were not significantly different between these two conditions (P greater than 0.05). After sectioning both vagus nerves the bronchoconstriction-induced increase in central inspiratory drive was either reduced (during normoxia) or abolished (during hypoxia). These results suggest that stimulation of vagal bronchopulmonary afferents are involved in regulating the ventilatory responses to bronchoconstriction. Other non-vagal factors, such as intrinsic properties and reflex responses of the respiratory muscles, may also contribute, in part, to the observed responses.

Effect of bronchoconstriction on the firing behavior of pulmonary stretch receptors.

To study the effect of bronchoconstriction on the activity of pulmonary stretch receptors (PSRs), acetylcholine aerosols (0.05% solution) were delivered continuously into the lungs while the afferent activity of a single PSR was recorded from a filament of the vagus nerve. The relationship between the PSR frequency (fPSR) and the transpulmonary pressure (Ptp) was examined during both constant volume ventilation and hyperinflation. During bronchoconstriction, the peak fPSR for the same tidal volume increased significantly (P less than 0.05) compared to the control response obtained with saline aerosols. However, the fPSR at functional residual capacity decreased in the receptors above the carina but increased in those below. Bronchoconstriction induced a hysteresis in the dynamic Ptp-fPSR relationship during hyperinflation in 11 out of the 21 receptors studied: a clockwise hysteresis was found in those receptors above the carina whereas a counterclockwise one in those below. Results of these studies suggest that the response of PSRs to bronchoconstriction depends on their locations in the tracheobronchial tree.