Cardioprotective activity of placental growth factor in a rat model of acute myocardial infarction: nanoparticle-based delivery versus direct myocardial injection.

BACKGROUND: To comparatively evaluate the cardioprotective activity of placental growth factor (PGF) delivered through direct injection and a nanoparticle-based system respectively and to study the underlying mechanisms in a rat model of acute myocardial infarction (AMI). METHODS: Poly lactic-co-glycolic acid (PLGA)-based PGF-carrying nanoparticles (PGF-PLGANPs) were created. The mean size and morphology of particles were analyzed with particle size analyzer and transmission electronic microscopy (TEM). Encapsulation efficiency and sustained-release dose curve were analyzed by ELISA. Sprague-Dawley rats were randomized into four groups (n = 10). While animals in the first group were left untreated as controls, those in the other 3 groups underwent surgical induction of AMI, followed by treatment with physiological saline, PGF, and PGF-PLGANPs, respectively. Cardiac function was evaluated by transthoracic echocardiography at 4 weeks after treatment. At 6 weeks, rats were sacrificed, infarction size was analyzed with Masson trichrome staining, and protein contents of TIMP-2, MT1-MMP and MMP-2 at the infarction border were determined by immunohistochemistry and western blotting analysis. RESULTS: PGF was released for at least 15 days, showing successful preparation of PGF-PLGANPs. Coronary artery ligation successfully induced AMI. Compared to physiological saline control, PGF, injected to the myocardium either as a nude molecule or in a form of nanoparticles, significantly reduced infarction size, improved cardiac function, and elevated myocardial expression of TIMP-2, MT1-MMP, and MMP-2 (P < 0.05). The effect of PGF-PLGANPs was more pronounced than that of non-encapsulated PGF (P < 0.05). CONCLUSION: Target PGF delivery to myocardium may improve cardiac function after AMI in rats. PLGA-based nanoparticles appear to be a better approach to delivery PGF. PGF exerts its cardioprotective effect at least partially through regulating metalloproteinase-mediated myocardial tissue remodeling.

Interactions of thymic stromal lymphopoietin with interleukin-4 in adaptive immunity during Aspergillus fumigatus keratitis.

AIM: To investigate the potential interactions of thymic stromal lymphopoietin (TSLP) with interleukin-4 (IL-4) in adaptive immunity during fungal keratitis (FK). METHODS: An FK mouse model was induced with Aspergillus fumigatus (AF) hyphal infection. Mice were divided into several groups: untreated, phosphate buffer saline (PBS), infected with AF, and pretreated with a scrambled siRNA, a TSLP-specific siRNA (TSLP siRNA), murine recombinant TSLP (rTSLP), immunoglobulin G (IgG), murine recombinant IFN (rIFN-γ), murine recombinant IL-4 (rIL-4), rIL-13, murine recombinant IL-17A (rIL-17A), and murine recombinant IL-17F (rIL-17F) groups. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) or Western blot were performed to determine mRNA and protein levels in the inflamed cornea. Cytokine locations were observed by immunofluoresence staining after AF hyphal infection. RESULTS: Compared to those in the untreated group, TSLP and T helper type 1 (Th1) cytokine levels in the AF group were upregulated at 24h post infection (hpi), and those of T helper type 2 (Th2) and T helper type 17 (Th17) cytokines were increased at 5d post infection (dpi). Th2 cytokine levels were decreased in the TSLP siRNA-pretreated group and increased in the rTSLP-pretreated group compared with the AF group. The TSLP level was increased in the rIL-4-pretreated group, but there were no significant changes among the other groups. Immunofluorescence staining showed cytokine locations after AF hyphal infection. CONCLUSION: TSLP induces a Th2 immune response and promots Th2 T cell differentiation in vivo. IL-4 promotes TSLP secretion. Therefore, TSLP with IL-4 regulates adaptive immunity in FK.

Primary tumour resection showed survival benefits for non-small-cell lung cancers with unexpected malignant pleural dissemination.

OBJECTIVES: Although non-small-cell lung cancer (NSCLC) with malignant pleural nodules is generally contraindicated for surgery, there is no consensus concerning on-site operative decisions for unexpected, intraoperatively encountered malignant pleural disseminations. The rationale underlying the primary tumour removal and other aggressive interventions remains controversial. METHODS: All surgical NSCLC cases (9576) of Shanghai Pulmonary Hospital between January 2005 and December 2013 were reviewed. Among them, 83 cases (0.9%) met the definition of 'unexpected' macroscopic malignant pleural nodules, despite routine preoperative evaluations for tumour metastasis. No pleural effusion was visualized in 52 cases during operations, and 31 had pleural effusion in minimal volume (<300 ml). Survivals were calculated with the Kaplan-Meier method and risk factors were evaluated by the log-rank test. RESULTS: The overall 3- and 5-year survival rates were 36.1 and 16.8%, respectively. The median survival time (MST) after surgery was significantly longer in the group without pleural effusion (37 months) compared with the group with pleural effusion (22 months, P = 0.005). Twenty-one cases had only biopsy, whereas 62 cases had primary tumour resection. Primary tumour resection had significantly better outcome compared with biopsy (MST: respectively, 35 vs 17 months, 3-year survival rate 45.8 vs 11.8%, P = 0.001). No baseline differences emerged in characteristics between biopsy and primary tumour resection groups including targeted therapy. Multivariate analysis showed that primary tumour resection (HR: 3.678, P = 0.014), no pleural effusion (HR: 3.409, P = 0.001) and adenocarcinoma (HR: 5.481, P = 0.002) were favourable prognostic factors in patients with malignant pleural nodules. CONCLUSIONS: Patients with malignant pleural nodules but without pleural effusion had better survival compared with those with effusions. Primary tumour resection had survival benefits for patients with unexpected intraoperatively proven malignant pleural nodules.

Conservative management of empyema-complicated post-lobectomy bronchopleural fistulas: experience of consecutive 13 cases in 9 years.

BACKGROUND: Bronchopleural fistula (BPF) is an infrequent but life-threatening complication after lung surgery. Tentative closure of the fistula and irrigation have been the conventional treatments, but are also surgically challenging and associated with a considerable failure rate. This study reports on a conservative practice of this difficult issue, in aim to examine its outcomes. METHOD: All enrolled cases were handled consecutively from September 2006 to June 2015. The empyema was first properly drained till disseminated pneumonia controlled. After conducting lavage, tube drainage was gradually transited to postural drainage. During the follow-up, information on tube removal, fistula healing, and survival were recorded. RESULTS: Thirteen cases were enrolled, including 9 rights and 4 lefts. The primary diseases were lung cancer [10], lung abscess [1], organizing pneumonia [1], and aspergillosis [1]. Early fistula (≤30 days postoperatively) occurred in 8 cases and late fistula (>30 days postoperatively) in 5 cases. Two patients underwent debridement to ascertain complete drainage. Chest tubes retained from 7 to 114 days (mean 40.54±30.49 days) before removal. At follow-up, we observed gradually narrowing-down of all residual cavities, and symptoms of fistula and empyema eventually disappeared in all patients. No complication or death occurred during the follow-up. CONCLUSIONS: Conservative management by a combination of tube and postural drainage provides an effective and safe treatment for empyema-complicated post-lobectomy BPFs.

Marital status is an independent prognostic factor for tracheal cancer patients: an analysis of the SEER database.

BACKGROUND: Although marital status is an independent prognostic factor in many cancers, its prognostic impact on tracheal cancer has not yet been determined. The goal of this study was to examine the relationship between marital status and survival in patients with tracheal cancer. RESULTS: Compared with unmarried patients (42.67%), married patients (57.33%) had better 5-year OS (25.64% vs. 35.89%, p = 0.009) and 5-year TCSS (44.58% vs. 58.75%, p = 0.004). Results of multivariate analysis indicated that marital status is an independent prognostic factor, with married patients showing better OS (hazard ratio [HR] = 0.78, 95% confidence interval [CI] 0.64-0.95, p = 0.015) and TCSS (HR = 0.70, 95% CI 0.54-0.91, p = 0.008). In addition, subgroup analysis suggested that marital status plays a more important role in the TCSS of patients with non-low-grade malignant tumors (HR = 0.71, 95% CI 0.53-0.93, p = 0.015). METHODS: We extracted 600 cases from the Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by Pearson chi-squared test, t-test, log-rank test, and multivariate Cox regression analysis. Overall survival (OS) and tracheal cancer-specific survival (TCSS) were compared between subgroups with different pathologic features and tumor stages. CONCLUSIONS: Marital status is an independent prognostic factor for survival in patients with tracheal cancer. For that reason, additional social support may be needed for unmarried patients, especially those with non-low-grade malignant tumors.

[Relationship between the quantities of peripheral dendritic cells and of serum HBV DNA and the inflammatory reaction levels in the liver].

OBJECTIVES: To investigate the relationship between the quantity of peripheral dendritic cell (DC) and of serum HBV DNA and the inflammatory level in chronic hepatitis B (CHB). METHODS: The myeloid DC (DC1) and plasmacytoid DC (DC2) in fresh peripheral blood were enumerated by using three-color flow cytometry in chronic hepatitis B patients and healthy donors. The hepatic inflammatory levels were evaluated by percutaneous liver biopsy. The serum HBV DNA levels were determined by real-time PCR. RESULTS: CHB patients with serum HBV DNA < or = 10(6) copies/ml exhibited a significant increase in the percentage of circulating DC2 in comparison with those of CHB patients with serum HBV DNA > or = 10(6) and with healthy donors (P < 0.05). The two latter groups showed no significant differences between each other. There was also no significant difference in the relative quantity of peripheral blood DC1 among the three groups mentioned above (P = 0.162). No evidence was found to support that the relative quantity of peripheral blood DC2 was associated with the clinical severity of the disease or the inflammatory level in the liver (P > 0.05). CONCLUSION: The relative quantity of peripheral blood DC2 is associated with HBV DNA level. It is suggested that DC2 may play a pivotal role in inhibiting HBV replication in CHB patients. There was no relationship found between relative quantities of DCs and the inflammatory level in the liver.

Prognostic analysis of the bronchoplastic and broncho-arterioplastic lobectomy of non-small cell lung cancers-10-year experiences of 161 patients.

BACKGROUND: Bronchoplastic and broncho-arterioplastic lobectomy is technically demanding. Present study performed a prognostic analysis of lobectomy patient based on 10-year data in a high-volume center. METHODS: Overall, 161 non-small cell lung cancer (NSCLC) cases underwent bronchoplastic and broncho-arterioplastic lobectomy between January 2004 and November 2013. Follow-up information was obtained for 88.8% patients. Prognostic analysis was performed with the Cox proportional hazards model. RESULTS: There were 133 bronchoplastic and 28 broncho-arterioplastic procedures. In detail, 97 sleeve and 64 wedge broncho-resection and reconstructions were conducted; pulmonary artery sleeve reconstructions were performed in 26 cases and tangential resection in 135 cases. 90-day post-operative mortality was 3.1% (5/161), and 24.8% (40/161) patients had post-operative complications. 5-year overall survival was 53.4% and 5-year disease-free survival (DFS) was 48.2% for the entire case series; these survival rates were 67.7% and 55.7% for stage I (n=31), 64.4% and 58.9% for stage II (n=62), and 36.9% and 31.9% for stage III disease, respectively. Univariate analysis revealed that age >65 and higher grade of pN were associated with worse overall survival while right side tumor, non-squamous histology type, and higher grade of pT and pN were associated with worse DFS. Multivariate analysis revealed that pN is the only independent factor of worse outcome. CONCLUSIONS: Bronchoplastic and broncho-arterioplastic lobectomy are safe procedures for indicated NSCLC patients associated with a low rate of post-operative complications but favorable long-term survival. Recognition of prognostic factors helps improve outcomes for these patients.

Loss of p120 catenin aggravates alveolar edema of ventilation induced lung injury.

BACKGROUND: p120 catenin (p120ctn) is an adheren junction protein that regulates barrier function, but its role has not been explored in alveolar edema induced by ventilation. We measured stretch-induced cell gap formation in MLE 12 cells due to the loss of p120. We hypothesized that alveolar permeability was increased by high lung inflation associated with alveolar epithelia cell tight junctions being destroyed, which resulted from the loss of p120. METHODS: Cultured MLE12 cells were subjected to being stretched or un-stretched (control) and some cells were pretreated with pp2 (c-src inhibitor). After the end of stretching for 0, 1, 2, and 4 hours, the cells were lysed, and p120 expression and c-src activation was determined by Western blotting analysis. In vivo, SD rats were taken to different tidal volumes (Vt 7 ml/kg or 40 ml/kg, PEEP = 0, respiratory rate 30-40 betas/min) for 0, 1, 2, and 4 hour and some were pretreated with pp2, and alveolar edema was calculated. RESULTS: It was found that p120 expression was reduced and c-src activation increased in a time-dependent and strain-dependent manner due to cyclic-stretch of the alveolar epithelial cells. These changes could be reversed by inhibition of c-src. We obtained similar changes in rats when they were subjected to large tidal volumes and the alveolar edema increased more than in rats in the low Vt group. Pretreated the rats with inhibition of c-src had less pulmonary edema induced by the high tidal volume ventilation. CONCLUSIONS: Cyclic stretch MLE 12 cells induced the loss of p120 and may be the same reason by high tidal volume ventilation in rats can aggravate alveolar edema. Maintenance of p120 expression may be a novel therapeutic strategy for the prevention and treatment of ventilation induced lung injury (VILI).

Correlation between interleukin-6 and ammonia in patients with overt hepatic encephalopathy due to cirrhosis.

OBJECTIVE: Previous studies have shown that elevated serum levels of interleukin-6 (IL-6) correlate with the severity of overt hepatic encephalopathy (OHE) in cirrhotic patients. However, the correlation between serum IL-6 levels and plasma ammonia levels in these patients remains unclear. Therefore, the present study investigated this correlation between both variables in cirrhotic patients with OHE. METHODS: Fifty-five cirrhotic patients with various grades of OHE, 29 cirrhotic patients without OHE, and 30 healthy controls were recruited. Concentrations of plasma ammonia and serum IL-6 were simultaneously measured. RESULTS: In cirrhotic patients with OHE, the severity of OHE, represented by the West Haven criteria, correlated with serum IL-6 levels (r=0.43, P<0.05) and plasma ammonia levels (r=0.59, P<0.05). IL-6 and ammonia were found to be significant independent predictors of OHE severity (P<0.05 for both variables). Furthermore, the severity of liver cirrhosis, determined by Child-Pugh scores, correlated with serum IL-6 levels (r=0.45, P<0.05) and plasma ammonia levels (r=0.68, P<0.05) in these patients. Moreover, there was a significant positive correlation between serum IL-6 levels and plasma ammonia levels (r=0.58, P<0.05) in cirrhotic patients with OHE, but not in patients without OHE (r=0.42, P>0.05) or healthy controls (r=0.27, P>0.05). The correlation between IL-6 and ammonia was independent of infectious precipitating factors. CONCLUSIONS: The results of the present study suggest that IL-6 might be involved in the mechanism by which ammonia contributes to the pathogenesis of OHE. There is also evidence of a potential synergistic interaction between proinflammatory cytokines and ammonia in the pathogenesis of OHE.