Reducing the toxicity of silver-based antibacterial agents used in gels and improving their biocompatibility are of great significance in the development of wound dressings. Thus, a highly crosslinked organic–inorganic hybrid porous polyphosphazene nanospheres (PRV-HMSs) were prepared via precipitation polymerization. The structures and properties were investigated. The results indicated that PRV-HMSs have uniform particle size about 500 nm, excellent thermal stability, high silver loading (26.5 wt.%) and remarkable sustained-release properties after loading AgNO 3 (up to 2 weeks). The antibacterial effects were investigated with zone of inhibition testing, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), Live/Dead bacterial staining assay and bacterial growth curve assays. The silver-loaded nanospheres have excellent bactericidal effects for E. coli or S. aureus and an average bactericidal rate of 94.02% and 94.67% in the 120 hour long-acting antibacterial test. The cytotoxicity and laser confocal immunofluorescence staining experiments indicate that the simple combination of nanospheres and agar not only give low cytotoxicity, but also significantly promote the activation of macrophages, which showing potential application in the wound dressings based on hydrogel.
Malignant mesothelioma(MM) is a rare but highly invasive carcinoma associated with asbestos exposure. Its incidence is in rising trend and most cases occur in pleura and peritoneum. The majority of patients diagnosed at late stage with poor prognosis that the median overall survival is only 12 months. Accurate diagnosis depends on the histopathology combined with immunohistochemistry. At present, the treatment of MM is mainly based on the tumor reduction or resection surgery combined with chemotherapy and radiotherapy. The potential molecular target needs to be further investigated. In this paper, we summary the incidence, diagnosis and treatment of MM, which will benefit the diagnosis and treatment of MM in China.
Abstract Background Malignant pleural mesothelioma (MPM) is a rare and aggressive carcinoma located in pleural cavity. Due to lack of effective diagnostic biomarkers and therapeutic targets in MPM, the prognosis is extremely poor. Because of difficulties in sample extraction, and the high rate of misdiagnosis, MPM is rarely studied. Therefore, novel modeling methodology is crucially needed to facilitate MPM research. Methods A novel patient-derived xenograft (PDX) modeling strategy was designed, which included preliminary screening of patients with pleural thickening using computerized tomography (CT) scan, further reviewing history of disease and imaging by a senior sonographer as well as histopathological analysis by a senior pathologist, and PDX model construction using ultrasound-guided pleural biopsy from MPM patients. Gas chromatography-mass spectrometry-based metabolomics was further utilized for investigating circulating metabolic features of the PDX models. Univariate and multivariate analysis, and pathway analysis were performed to explore the differential metabolites, enriched metabolism pathways and potential metabolic targets. Results After screening using our strategy, 5 out of 116 patients were confirmed to be MPM, and their specimens were used for modeling. Two PDX models were established successfully. Metabolomics analysis revealed significant metabolic shifts in PDX models, such as dysregulations in amino acid metabolism, TCA cycle and glycolysis, and nucleotide metabolism. Conclusions To sum up, we suggested a novel modeling strategy that may facilitate specimen availability for MM research, and by applying metabolomics in this model, several metabolic features were identified, whereas future studies with large sample size are needed.
Neuroendocrine neoplasms (NENs) are heterogeneous neoplasms, which are sometimes malignant, although predicting metastasis is difficult. INSM1 is a transcription factor expressed transiently in embryonic neuroendocrine (NE) tissue, thought to coordinate termination of cell division with differentiation of NE and neuroepithelial cells. In adult tissues, INSM1 has been identified in multiple tumors of NE or neuroepithelial origin but has not been thoroughly investigated as a potential neoplastic marker.We evaluated INSM1 as a semiquantitative immunohistochemical (IHC) marker for NE and neuroepithelial neoplasms and as a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) marker for gastrointestinal NENs (GI-NENs).Using IHC, we found in normal adult tissue that INSM1 expression was highly restricted to nuclei of NE cells and tissues. INSM1 was not detected in any adult nonneoplastic, non-NE tissue. In neoplastic tissue, INSM1 was detectable by IHC in 88.3% of 129 NEN specimens. In contrast, INSM1 was detected by IHC in only one of 27 neoplasms without a neuroepithelial or NE component. Using qRT-PCR, we evaluated INSM1 gene expression in 113 GI-NEN specimens.INSM1 expression was significantly increased in neoplastic vs nonneoplastic tissue. Furthermore, among midgut GI-NENs, neoplasms with known metastases showed significantly higher expression than those that had not yet metastasized.
Abstract Background Nodular goiters (NG) and follicular adenoma (FA) are common thyroid benign nodules and thyroid nodules with intermediate features between nodular goiter and follicular (ING) is used to describe the disease with borderline features. The genetic landscape of these three diseases is poorly investigated comparatively. Methods Clinical information of NG, ING and FA was retrieved and reviewed. Cytology and histology of the pathologic archives were reviewed to confirm the diagnosis. DNA and RNA were extracted to be submitted to qPCR assay to detect BRAF, TERT, RET, RAS, PAX8 and NTRK genetic aberration. Results The demographic, clinical, image and cytologic features in NG and ING are similar. Most disease presents a benign clinical and cytologic behavior, causing no diagnostic difficulty. Low frequency (< 10%) RAS gene was found in NG and ING. Patients with FA are older than whom with NG or ING. FA lesion size is smaller than ones in NG or ING. Although sonography demonstrated most FA nodules as benign category, the cytologic evaluation demonstrated a considerable percentage (45%) of atypia disease. Additionally, much higher frequency of RAS gene abnormality has been found in FA. And PAX8-PPARG gene is found in 17.9% FA and in no NG/ING cases. Conclusion NG/ING and FA is in the same spectrum and represents two ends of the spectrum of thyroid benign nodular condition. Differentiation of ING from NG has little clinical significance and would not be recommended. FA is devoid from NG/ING clinically and genetically. Interpretation of genetic abnormality should be cautious.
Objectives . Many patients with papillary thyroid cancer (PTC) have a high recurrence risk and poor prognosis, and the main obstacle to the clinical diagnosis and treatment of PTC is lack of effective predictive molecular markers. The purpose of this study was to investigate the clinicopathological and prognostic implications of WW domain binding protein 5 (WBP5) expression in PTC. Materials and Methods . Immunohistochemistry of WBP5 was performed using tissue microarrays of 131 patients with PTC who underwent surgery during January 2006 and January 2010 in the Zhejiang Cancer Hospital. Statistical analyses were conducted to evaluate the association between WBP5 expression and the clinicopathological features and to analyze the disease-free survival (DFS) and prognostic factors. Results and Conclusion . The positive expression rate of WBP5 in PTC and the adjacent normal tissues was 42.75% (56/131) and 45.45% (10/22), respectively. WBP5 expression was significantly correlated with bilaterality, capsule invasion, and N-stage, and it was a favorable factor of DFS. Moreover, patients with a high WBP5 expression exhibited reduced risk of disease recurrence compared with that in patients with low WBP5 expression in the univariate analysis, whereas the multivariate analysis suggested that WBP5 was not an independent prognostic factor. Our results indicate that WBP5 might be a favorable prognosis indicator of PTC.
Conducting total thyroidectomy (TT) or subtotal thyroidectomy (ST) in patients with Graves' disease remains controversial. We performed a meta-analysis based on the published randomized controlled trials to evaluate the complications of TT vs ST.We searched multiple electronic databases for prospective, randomized, controlled trials related to safety and effectiveness of TT vs ST. Relative risk (RR) was estimated with 95% confidence interval (CI) based on an intention-to-treat analysis. We considered the following outcomes: recurrent hyperthyroidism, ophthalmopathy progression, temporary and permanent hypoparathyroidism, temporary and permanent recurrent laryngeal nerve palsy (RLNP) and post-operative bleeding.Four trials with 674 patients (342 with TT, 332 with ST) were analysed. Although the overall rates of ophthalmopathy progression were similar between TT and ST (RR 0·92, 95% CI = 0·50-1·71; P = 0·80), TT was associated with a significant reduction in recurrent hyperthyroidism (RR 0·14, 95% CI = 0·05-0·41; P < 0·01). The pooled RR of post-operative bleeding for TT was similar to that for ST (RR 0·32, 95% CI = 0·05-1·96; P = 0·22). However, comparing with ST, the RR of temporary hypoparathyroidism was significantly higher for TT (RR 2·66, 95% CI = 1·89-3·73; P < 0·01). There was no significant difference in permanent hypoparathyroidism (RR 2·30, 95% CI = 0·78-6·76; P = 0·13), temporary (RR 1·08, 95% CI = 0·47-2·48; P = 0·85) and permanent RLNP (RR 1·54, 95% CI = 0·41-5·73; P = 0·52) between the two groups.With regard to ophthalmopathy progression, post-operative bleeding, permanent hypoparathyroidism, temporary and permanent RLNP, TT is consistent with ST in patients with Graves' disease. However, TT is associated with a reduced incidence of recurrent hyperthyroidism and results in an increase in temporary hypoparathyroidism. Therefore, TT should be proposed for the treatment of Graves' disease.
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