KGRT peptide incorporated hydrogel with antibacterial activity for wound healing by optimizing cellular functions via ERK/eNOS signaling.

Bacterial infected wounds, which is characterized by easy infection, multiple inflammation and slow healing, is a complex symptom, resulting from metabolic disorder of the wound microenvironment. In this study, a series of self-healing double-network hydrogels based on KGRT peptide (Lys-Gly-Arg-Thr) with antibacterial, anti-inflammatory and optimizing cellular functions were designed to promote the healing of infected wounds with full-thickness skin defects. Moreover, the dextran hydrogelintroduces a large number of side chains, which are entangled with each other in the Schiff base network to form an interpenetrating structure. The hydrogel might regulate cell metabolism, differentiation and vascular endothelial growth factor (VEGF) function. Importantly, both in vitro and in vivo data showed that hydrogel not only has good antibacterial properties (99.8 %), but also can eradicate bacterial biofilm, effectively reduce inflammation (down-regulated IL-1ß, TNF-α and ROS) and accelerate chronic wound healing process by speeding-up wound closure, increasing granulation tissue thickness, collagen deposition, angiogenesis (up-regulated CD31). The hydrogel could up-regulate mRNA expression of PI3K, AKT, ERK, eNOS, HIF-1α and VEGF, which were correlated with wound healing. Consistently, the hydrogel could promote infected wounds healing and inhibit inflammation through ERK/eNOS signaling pathway. Collectively, hydrogel has excellent clinical application potential for promoting infected wound healing.

Antioxidant-Engineered Milk-Derived Extracellular Vesicles for Accelerating Wound Healing via Regulation of the PI3K-AKT Signaling Pathway.

Inspired by the experience of relieving inflammation in infants with milk, antioxidant-engineered milk-derived extracellular vesicles (MEVs) are developed to evaluate their potential for accelerating wound healing. In this work, MEVs with polydopamines (PDA) are engineered using the co-extrusion method. Subsequently, the authors incorporated them into a Schiff-based crosslink hydrogel, forming a skin dosage form that could facilitate the wound healing process. The antioxidant properties of PDA assist in the anti-inflammatory function of engineered MEVs, while the gel provides better skin residency. The PDA@MEVs+GEL formulation exhibits excellent biocompatibility, pro-angiogenic capacity, and antioxidant ability in vitro. Furthermore, in vivo experiments demonstrate its efficacy in wound repair and inflammation inhibition. Mechanistically, PDA@MEVs+GEL simultaneously promotes the growth, migration, and anti-inflammation of 3T3 cells by activating PI3K-AKT pathway. Moreover, PDA@MEVs+GEL exhibits enhanced functionality in promoting wound healing in vivo, attributed to its ability to inhibit inflammation, stimulate angiogenesis, and promote collagen synthesis. In conclusion, this study delves into the mechanism of MEVs and underscores the improved efficacy of engineered extracellular vesicles. Additionally, the feasibility and prospect of engineered MEVs in treating skin wounds are verified, suggesting that antioxidant-engineered MEVs could be a promising therapeutic agent for wound healing applications.

Prognostic prediction of thrombolytic therapy with rt-PA in acute ischemic stroke patients using an artificial intelligence model.

OBJECTIVE: Through the comparison of different prediction models, we hope to find a promising statistical method to evaluate the prognosis of patients with acute ischemic stroke (AIS) after thrombolytic therapy. METHODS: Data of 518 patients who received thrombolytic therapy were retrospectively collected in this study. Among them, 362 patients met the eligibility criteria, so their data such as age, sex, smoking history, previous medical history, clinical and laboratory indicators were analyzed. According to the 3 month follow-up results, 266 patients were included in a good prognosis group (modified Rankin Scale (mRS) score ≤2) and 96 in a poor prognosis group (3≤mRS≤6). All variables with P<0.05 in univariant and multivariant analyses were assigned in logistic regression model and artificial neural network (ANN) model to predict neurological prognosis, and the performance of the two models were compared. RESULTS: Age, NIHSS scores, the serum concentration of immediate glucose, APTT and MBP at admission were found to be the predictive factors through ANN and logistic regression analysis. The binary logistic regression model revealed that the percentage correction, the precision, recall and F1 score of the regression model were 79%, 69.23%, 37.50% and 48.65%, respectively. While those of ANN were 79.98%, 69.70%, 37.25%, and 49.66%, correspondingly. CONCLUSIONS: ANN model is as effective as a logistic regression model in predicting the prognosis of AIS after thrombolytic therapy with rt-PA. Moreover, ANN is slightly superior to logistic regression in accuracy, precision and F1 score.

Histone methyltransferase enzyme enhancer of zeste homolog 2 counteracts ischemic brain injury via H3K27me3-mediated regulation of PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Epigenetic histone methylation plays a crucial role in cerebral ischemic injury, particularly in the context of ischemic stroke. However, the complete understanding of regulators involved in histone methylation, such as Enhancer of Zeste Homolog 2 (EZH2), along with their functional effects and underlying mechanisms, remains incomplete. METHODS: Here, we employed a rat model of MCAO (Middle cerebral artery occlusion) and an OGD (Oxygen-Glucose Deprivation) model of primary cortical neurons to study the role of EZH2 and H3K27me3 in cerebral ischemia-reperfusion injury. The infarct volume was measured through TTC staining, while cell apoptosis was detected using TUNEL staining. The mRNA expression levels were quantified through quantitative real-time polymerase chain reaction (qPCR), whereas protein expressions were evaluated via western blotting and immunofluorescence experiments. RESULTS: The expression levels of EZH2 and H3K27me3 were upregulated in OGD; these expression levels were further enhanced by GSK-J4 but reduced by EPZ-6438 and AKT inhibitor (LY294002) under OGD conditions. Similar trends were observed for mTOR, AKT, and PI3K while contrasting results were noted for UTX and JMJD3. The phosphorylation levels of mTOR, AKT, and PI3K were activated by OGD, further stimulated by GSK-J4, but inhibited by EPZ-6438 and AKT inhibitor. Inhibition of EZH2 or AKT effectively counteracted OGD-/MCAO-induced cell apoptosis. Additionally, inhibition of EZH2 or AKT mitigated MCAO-induced infarct size and neurological deficit in vivo. CONCLUSIONS: Collectively, our results demonstrate that EZH2 inhibition exerts a protective effect against ischemic brain injury by modulating the H3K27me3/PI3K/AKT/mTOR signaling pathway. The results provide novel insights into potential therapeutic mechanisms for stroke treatment.

Neferine mediated TGF-ß/ERK signaling to inhibit fibrosis in endometriosis.

OBJECTIVE: To investigate the mechanism of Neferine in treating endometriosis fibrosis by TGF-ß/ERK signaling pathway through a combination of network pharmacological analysis of Lotus embryos, in vivo animal experiments, and in vitro cell experiments. METHODS: The active ingredients of the drug lotus embryos, the drug targets and the targets of endometriosis were determined from the TCMSP database, the Swiss Target Prediction database and GeneCard and Online Mendelian Inheritance in Man. The String database and Cytoscape 3.6.3 software were used to construct the network of common target protein interactions between drug and disease, as well as the target network. GO and KEGG enrichment analysis of the common targets was performed. We designed endometriosis mouse models with Neferine to investigate the therapeutic effect of Neferine on the fibrosis model of endometriosis and its mechanism of action. Different methods were used to evaluate the treated endometriotic lesion tissue and the untreated ectopic lesion tissue. The 12Z cells (human endometriosis immortalized cells) were cultured in vitro and treated with Neferine to detect cell viability and the effects of invasion and metastasis. RESULTS: The results of GO function and KEGG enrichment analysis showed that the role pathways of lotus germ were TGF-ß signaling pathway, ERK1/2 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway, and PI3K-Akt signaling pathway. Neferine which is one of the effective active ingredients of lotus germ, significantly inhibited the expression of fibronectin, collagen I, connective tissue growth factor, and smooth muscle actin by activating the TGF-ß/ERK pathway in vivo, which is required for the fibrosis process of endometriosis. Neferine also significantly inhibited the proliferation, invasion and metastasis ability of 12Z cells. CONCLUSION: Neferine inhibits the progression of endometriosis both in vitro and in vivo. Its mechanism of action may involve the regulation of the TGF-ß/ERK signaling pathway, leading to the inhibition of fibrosis in endometriosis.

The Non-uniform Distribution of Horizontal and Vertical Crystalline Lens Rise Using Optical Coherence Tomography.

PURPOSE: To observe the crystalline lens rise (CLR) in horizontal and vertical orientations using anterior segment optical coherence tomography (AS-OCT). METHODS: Non-invasive swept-source AS-OCT was used to measure the lens thickness, CLR, and angle-to-angle distance (ATA) in both the horizontal and vertical orientations. Anterior chamber depth (ACD) and horizontal white-to-white corneal diameter were obtained using the Pentacam HR (Oculus Optikgeräte GmbH). Axial length was obtained using the IOLMaster 700 (Carl Zeiss Meditec AG). The paired t test was used to analyze the difference in CLR between the two orientations. Pearson correlation analysis was performed to investigate the correlations between CLR and other ocular variables. RESULTS: This prospective observational study comprised 99 eyes (99 patients) that underwent Visian Implantable Collamer Lens (STAAR Surgical) implantation for myopic correction. The mean CLR was 64.29 ± 168.04 and 208.09 ± 173.12 µm in the horizontal and vertical orientations, respectively. The vertical CLR (VCLR) was significantly greater than the horizontal CLR (HCLR) (P < .05). Both the HCLR and VCLR were positively correlated with lens thickness and negatively correlated with ACD (all P < .05). The difference in CLR (VCLR-HCLR) was positively correlated with the axial length and the difference in ATA between the two orientations (P < .05). CONCLUSIONS: VCLR was greater than HCLR in most patients with myopia, especially in the longer eyes. This nonuniform distribution in CLR implied different placements of the iridocorneal angles in the horizontal and vertical orientations and should be considered for the selection of ICL size and placement position. [J Refract Surg. 2023;39(5):354-359.].

Long Noncoding RNA TUG1 Aggravates Cerebral Ischemia/Reperfusion Injury by Acting as a ceRNA for miR-3072-3p to Target St8sia2.

Long noncoding RNA taurine-upregulated gene 1 (TUG1) is considered to be involved in postischemic cerebral inflammation, whereas polysialic acid (polySia, PSA), the product of St8sia2, constitutes polysialylated neural adhesion cell molecule (PSA-NCAM) in both mice and humans and that cerebral PSA-NCAM level is elevated in neuronal progenitor cells in response to transient focal ischemia. Herein, we aim to identify novel miRNAs that bridge the functions of St8sia2 and TUG1 in ischemia-associated injuries. In both in vivo (C57BL/6J mouse ischemia/reperfusion, I/R model) and in vitro (mouse neuroblastoma N2A cell oxygen glucose deprivation/reoxygenation, OGD model) settings, we observed upregulated TUG1 and St8sia2 after the induction of ischemic injury, accompanied by reduced miR-3072-3p expression. We performed siRNA-induced TUG1 knockdown combined with the induction of ischemic injury; the results showed that inhibiting TUG1 expression led to the reduced infarct area and improved neurological deficit. Through bioinformatics analysis, miR-3072-3p was found to target both St8sia2 and TUG1, which was subsequently verified by the luciferase reporter system and RNA binding protein immunoprecipitation assay. Also, the addition of miR-3072-3p mimic/inhibitor resulted in reduced/elevated St8sia2 expression at the protein level. Further studies revealed that in both in vivo and in vitro settings, TUG1 bound competitively to miR-3072-3p to regulate St8sia2 expression and promote apoptosis. In summary, targeting the TUG1/miR-3072-3p/St8sia2 regulatory cascade, a novel cascade we identified in cerebral ischemia injury, may render feasible therapeutic possibilities for overcoming cerebral ischemic insults.

Cryptotanshinone Protects against PCOS-Induced Damage of Ovarian Tissue via Regulating Oxidative Stress, Mitochondrial Membrane Potential, Inflammation, and Apoptosis via Regulating Ferroptosis.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. Cryptotanshinone (CRY) has been shown to be effective in reversing reproductive disorders, but whether it can be used in the treatment of polycystic ovary syndrome remains unclear. We aimed to explore whether the mechanism of cryptotanshinone (CRY) in the treatment of polycystic ovary syndrome (PCOS) can be driven via regulating ferroptosis. A rat model of PCOS was established by daily injection of human chorionic gonadotropin and insulin for 22 days. An in vitro model of ischemia-reperfusion (IR) of granulosa cells was established. The in vitro and rat models of PCOS were subjected to different treatments including ferroptosis activators and inhibitors, CRY, and MAPK inhibitor. Oxidative stress was evaluated by measuring the activities of SOD, MDA, and GSH-PX. Total body weight and ovarian weight, as well as the levels of LH and the LH to FSH ratio, significantly increased in rats with PCOS, compared with controls. The expression of Bax was increased in PCOS tissues while PGC1α, NFR1, GPX4, catalase p-ERK, and Bcl-2 were all downregulated. Ferroptosis activator, erastin, had effects similar to those of PCOS while the contrary was found with CRY and ferroptosis inhibitor treatment groups. In vitro, CRY inhibited oxidative stress, MMP, and NF-κB and activated MAPK/ERK signaling by regulating ferroptosis. Overall, this study indicated that CRY protects against PCOS-induced damage of the ovarian tissue, via regulating oxidative stress, MMP, inflammation, and apoptosis via regulating ferroptosis.

[Characteristics of Cd, As, and Pb in Soil and Wheat Grains and Health Risk Assessment of Grain-Cd/As/Pb on the Field Scale].

In recent years, heavy metal pollution in farmlands has become increasingly serious because of human activities such as metal smelting, sewage irrigation, and road traffic in China. A field survey was conducted to investigate characteristics of Cd, As, and Pb in soil and wheat grains and assess the health risk of grain-Cd/As/Pb to humans on the fields scale. The farmland was influenced by smelter and sewage irrigation in the attitude and by road traffic in the horizon. The results showed that in farmland soil with moderate pollution levels, Cd, As, and Pb concentrations in soil samples all exceeded the risk screening values of farmland soil (GB 15618-2018), and the exceeding rates were 100%, 100%, and 36.7% respectively; the exceeding rates of Cd and Pb concentrations in wheat grains were 76.7% and 13.3%, respectively (GB 2762-2017). Distance from smelter, river of sewage irrigation, and road had no significant effect on Cd, As, and Pb concentrations in soil but had a significant effect on Cd and As concentrations in wheat grains, with the median Cd and As concentrations of the closest group being 14.9% and 41.8%, respectively, higher than the highest group (P<0.05). The Pb concentrations in soil and wheat grains were influenced by road traffic; the median Pb concentrations of the closest group were 78.9% and 471%, respectively, higher than the highest group (P<0.05). Cd and As in wheat grains have carcinogenic risks (Ri>1×10-4), RCd > RAs, Rchildren > Radult, while Pb poses no health risks in this farmland.

Surgery performed at night by continuously working surgeons contributes to a higher incidence of intraoperative complications in video-assisted thoracoscopic pulmonary resection: a large monocentric retrospective study.

OBJECTIVES: Our goal was to assess the influence of working hours and working at night on intraoperative complications on surgeons conducting video-assisted pulmonary resections. METHODS: We identified all patients who underwent video-assisted thoracoscopic surgery (VATS) in Shanghai Chest Hospital from January 2015 to April 2017. Univariable and multivariable logistic analyses were used to analyse independent risk factors for intraoperative complications. A 1:4 propensity score matching analysis was conducted to verify those results. RESULTS: A total of 15 767 patients who underwent VATS pulmonary resection were included in this study. Among them, 15 280 patients (96.1%) were operated on during daytime working hours and 487 (3.1%) at night. A total of 203 (1.3%) intraoperative complications occurred. Vascular injury was the main cause of intraoperative complications, accounting for 92.1% (187/203). Multivariable logistic regression indicated that age [odds ratio (OR) = 1.68, 95% confidence interval (CI) 1.43-1.98; P < 0.001], gender (OR = 1.71, 95% CI 1.26-2.32; P = 0.001), surgical experience (OR = 2.07, 95% CI 1.56-2.75; P < 0.001), type of surgery (OR = 0.31, 95% CI 0.20-0.49; P < 0.001) and operative periods (OR = 2.69, 95% CI 1.61-4.86; P < 0.001) were independent predictors for intraoperative complications. The incidence of intraoperative complications during night-time surgery was significantly higher than that during daytime working hours. A 1:4 propensity score matching-based results verification showed that night-time surgery was still an independent risk factor after propensity score matching (OR = 2.76, 95% CI 1.47-5.15; P = 0.002). CONCLUSIONS: The incidence of intraoperative complications from VATS pulmonary resection performed during night hours was significantly higher than that performed during working hours. In the present labour environment, thoracic surgeons should avoid night-time surgery whenever possible.

Low Expression of ASK1-Interacting Protein-1 Is Significantly Correlated with Tumor Angiogenesis and Poor Survival in Patients with Early Stage Non-Small Cell Lung Cancer.

OBJECTIVE: To investigate the expression of tumor suppressor protein ASK1-interacting protein-1 (AIP1) in cancer tissues of patients with early-stage non-small cell lung cancer (NSCLC) and its correlation with tumor progression, tumor angiogenesis and prognosis. METHODS: A total of 136 patients with stage I NSCLC who underwent radical resection of lung cancer in Qianfoshan Hospital of Shandong Province from January 2011 to December 2011 were enrolled. Immunohistochemistry was used to detect AIP1 protein in tumor tissues. Vascular endothelial CD34 immunohistochemical staining was used to count intratumoral microvessel density (MVD). SPSS 19.0 software was used to analyze the relationship between AIP1 protein expression and clinicopathological features, tumor angiogenesis and prognosis. RESULTS: Low expression of AIP1 was more common in tumor tissues with high MVD, and patients with low expression of AIP1 were more likely to have tumor recurrence. Multivariate analysis showed that low expression of AIP1 had predictive value for overall survival, disease-free survival, and disease-specific survival. CONCLUSION: Downregulation of AIP1 protein expression is associated with lung cancer progression, tumor angiogenesis and poor prognosis. Consequently, AIP1 may prove to be an important predictor of recovery from lung cancer and could become a new therapeutic target for lung cancer treatment.

SREBP2 is upregulated in esophageal squamous cell carcinoma and co­operates with c­Myc to regulate HMGCR expression.

Dysregulations of the mevalonate pathway (MVA) have been previously identified. Our previous study demonstrated that 3­hydroxy­3­methylglutaryl­coenzyme A reductase (HMGCR), the rate­limiting enzyme of the MVA pathway, was upregulated in esophageal squamous cell carcinoma (ESCC) and statin­inhibited ESCC tumorigenesis. However, the underlying mechanism of HMGCR regulation in ESCC remains unknown. In the present study, western blotting and immunohistochemistry analysis demonstrated that sterol regulatory element­binding protein 2 (SREBP2), the master regulator for HMGCR, was upregulated in ESCC clinical samples. Overexpression of SREBP2 expression in ESCC cell lines promoted the growth, migration and colony formation of cancer cells in the MTT, Boyden chamber and soft agar assays, respectively, which was inhibited by lovastatin. Downregulation of SREBP2 expression in ESCC cell lines inhibited the viability, and migration and colony formation abilities of cancer cells. Assessment of the molecular mechanism demonstrated that SREBP2 interacted with c­Myc and cooperated with c­Myc to activate HMGCR expression. Collectively, the present study identified SREBP2 as an oncogene associated with the tumorigenesis of ESCC and further demonstrated the therapeutic effects of statins in ESCC.

Longitudinal and Regional Non-uniform Remodeling of Corneal Epithelium After Topography-Guided FS-LASIK.

PURPOSE: To observe the epithelial remodeling over a 9-mm diameter cornea induced by topography-guided femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for myopia correction using spectral-domain optical coherence tomography (SD-OCT). METHODS: Forty-three eyes of 22 patients who underwent topography-guided FS-LASIK for myopic correction were included. The "Pachymetrywide" scan pattern was used to generate the epithelial thickness map using SD-OCT preoperatively and 1, 3, and 6 months postoperatively. Epithelial thickness was compared and analyzed by section and zone. RESULTS: Compared to the preoperative values, the change in the average epithelial thickness in the central, paracentral, and mid-peripheral zones was 2.09, 4.53, and -0.87 µm at 1 month; 3.00, 4.61, and -0.97 µm at 3 months; and 3.28, 4.55, and -0.81 µm at 6 months postoperatively, respectively. From 1 to 3 months postoperatively, the central epithelial thickness changed significantly (P = .021), whereas the epithelial thickness in the paracentral (P = .973) and mid-peripheral (P = .996) zones stabilized. No significant epithelial thickness change was observed in the zones between 3 and 6 months postoperatively (all P > .05). The epithelial thickness in the paracentral inferotemporal section increased by 12.7% at 6 months after surgery. The central epithelial hyperplasia showed no correlation with the change in postoperative manifest refraction spherical equivalent (P = .313). CONCLUSIONS: After topography-guided FS-LASIK, the 9-mm diameter epithelial thickness showed a longitudinal and regional non-uniform redistribution. Central epithelial remodeling stabilized more slowly. The greatest increase in epithelial thickness was observed in the paracentral inferotemporal section. This epithelial remodeling did not cause refractive regression. [J Refract Surg. 2019;35(2):88-95.].

Low expression level of ASK1-interacting protein-1 correlated with tumor angiogenesis and poor survival in patients with esophageal squamous cell cancer.

OBJECTIVE: To investigate the expression of tumor suppressor protein ASK1-interacting protein-1 (AIP1) in human esophageal squamous cell carcinoma (ESCC) and its role in tumor progression, angiogenesis, and prognosis. METHODS: A total of 117 biopsy samples were obtained from ESCC patients. None of the patients had distant metastasis before surgery, and did not receive preoperative chemotherapy or radiotherapy. Immunohistochemistry was used to detect the expression of AIP1 protein and vascular endothelial growth factor receptor 2 (VEGFR2) in ESCC specimens collected from 117 patients who underwent esophageal cancer radical surgery. Microvessel density (MVD) was evaluated by immunohistochemical staining of vascular endothelial CD34. The correlation between AIP1 protein and clinicopathological characteristics, tumor angiogenesis, and prognosis was analyzed. RESULTS: The downregulation of AIP1 protein in esophageal carcinoma tissues was detected in 63 cases. This downregulation significantly correlated with lymph node metastasis, clinicopathological staging, and tumor MVD (P<0.05). Survival analysis showed that ESCC patients with a low expression of AIP1, a high expression of VEGFR2, and a high level of MVD had a lower 5-year survival rate (P<0.05). Multivariate analysis confirmed that the downregulation of AIP1 significantly affected patient survival. CONCLUSION: The downregulation of AIP1 correlated with ESCC progression, tumor angiogenesis, and poor prognosis. AIP1 could be a promising biomarker for predicting ESCC prognosis and a potential target for anti-angiogenic therapy.

Comparison of clinical features and survival between thymic carcinoma and thymic carcinoid patients.

OBJECTIVES: Thymic carcinoma (TC) and thymic carcinoid (TCD) are aggressive thymic epithelial neoplasms with a poor prognosis. Due to rarity, little is known about their comparative clinical characteristics, treatment outcomes and patterns of relapse. METHODS: A retrospective cohort study was performed on 287 patients with TC and 56 patients with TCD who were treated at the Shanghai Chest Hospital between February 2003 and April 2014. Patient demographics, tumour stage, treatment, pathologic findings and postoperative outcomes were compared between the two tumour types using both multivariable Cox regression analysis and propensity-matched analysis. RESULTS: Compared to patients with TC, significantly more patients with TCD were male, had larger tumours, and displayed a greater proportion of lymph node metastases. However, overall survival was similar (60.7% 5-year survival for TC, 80.7% for TCD, P = 0.159), as was disease-free survival (41.1% 5-year survival for TC, 37.6% for TCD, P = 0.696) and patterns of relapse. Multiple Cox regression analysis identified younger patients [hazard ratio (HR) 1.018; 95% confidence interval (CI) 1.000-1.035; P = 0.047], more completeness of resection (HR 1.424; 95% CI 1.105-1.836; P = 0.006), adjuvant radiotherapy (HR 0.455; 95% CI 0.276-0.751; P = 0.002), and no adjuvant chemotherapy (HR 1.799; 95% CI 1.017-3.183; P = 0.044) as independent factors predicting better overall survival. Completeness of resection (HR 1.258; 95% CI 1.022-1.548; P = 0.031) and TNM stage (HR 1.479; 95% CI 1.107-1.977; P = 0.008) were independent predictors of disease-free survival. Propensity matching produced 46 patients in each group and no significant difference on overall survival or disease-free survival was found. CONCLUSIONS: Patients with TCD have discrete features but share a similar clinical course to those with TC. The importance of complete resection in both of these thymic malignancies is emphasized. Further investigation at multiple centers with the longer follow-up data is required to substantiate our conclusion.

Surgical treatment of thymoma: an 11-year experience with 761 patients.

OBJECTIVES: Thymomas are rare, and information regarding their surgical outcomes and possible prognostic factors is limited. In this study, we aimed to determine the clinicopathological characteristics of thymoma and estimate independent predictors of both overall and disease-free survival in thymoma patients. METHODS: We carried out a retrospective review of the clinicopathological characteristics and prognostic factors in 761 consecutive patients with pathologically confirmed thymoma treated in Shanghai Chest Hospital between January 2001 and December 2011. Survival was calculated using the Kaplan-Meier method and evaluated with log-rank tests. Multivariable analysis was performed using the Cox regression model. RESULTS: Complete follow-up information was available for 544 patients. The overall survival rate was 92.8% at 5 years and 90.5% at 10 years. The 5- and 10-year disease-free survival was 87.9 and 82.1%, respectively. On multiple Cox regression analysis, the Masaoka-Koga clinical stage [odds ratio (OR), 2.057; 95% confidence interval (CI), 1.454-2.911; P < 0.01] and sex (OR, 2.244; 95% CI, 1.115-4.519; P = 0.02) were found to be independent predictors of overall survival. The Masaoka-Koga clinical stage (OR, 2.127; 95% CI, 1.487-3.042; P < 0.01) and completeness of resection (OR, 2.935; 95% CI, 1.410-6.109; P < 0.01) predicted disease-free survival. CONCLUSIONS: The four-tiered Masaoka-Koga clinical stage is the most important prognostic factor, predicting not only overall survival but also disease-free survival after thymoma resection. Completeness of resection predicts disease-free survival, and the World Health Organization histological classification may not have significant prognostic implications.

Evaluation of the proposed International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancies Interest Group (ITMIG) staging revisions in thymic well-differentiated neuroendocrine carcinoma patients.

OBJECTIVES: In 2014, the International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancies Interest Group (ITMIG) launched a worldwide Tumor Node Metastasis (TNM) staging proposal for the next edition of thymic tumours. The objective of the current study was to evaluate the proposed new staging system specific to the thymic well-differentiated neuroendocrine carcinoma (TWDNC). METHODS: From November 2003 to July 2014, 61 consecutive patients were enrolled in this study with pathologically confirmed TWDNC in Shanghai Chest Hospital. Clinical and pathological data were retrospectively reviewed. Survival analysis was performed using the Kaplan-Meier and log-rank tests. Validity evaluation was addressed by Cox proportional hazards regression model, after adjusting for potential confounders and visually assessing the distinction of curves generated based on the staging system of Masaoka-Koga and the proposed TNM ones. RESULTS: Thymic carcinoids made up 4% of total thymic tumours in our institution. The 5-year overall survival (OS) rate and the disease-free survival (DFS) rate were 72 and 41%, respectively. Neither Masaoka-Koga staging system nor the proposed TNM system showed ordered appropriateness visually in survival curves and the prognostic demarcation between stages was poor on both OS and DFS. CONCLUSIONS: The IASLC/ITMIG suggested that the TNM and Masaoka-Koga staging systems fail to predict the clinical course of TWDNC patients. Collaborative effort is needed in the future staging validation as ITMIG recommended.

Integrin αv promotes proliferation by activating ERK 1/2 in the human lung cancer cell line A549.

Lung cancer is a leading cause of cancer-related death worldwide, and non-small cell lung cancer (NSCLC) constitutes ~85% of lung cancers. However, the mechanisms underlying the progression of NSCLC remain unclear. In this study, we found the mRNA and protein expression levels of integrin αv are both increased in NSCLC tissues compared to healthy ones, which indicates that integrin αv may play an important role in NSCLC progression. To further investigate the roles of integrin αv in NSCLC, we overexpressed the integrin αv gene in the NSCLC cell line A549, and found that the cell proliferative ability increased. The apoptosis of A549 cells was inhibited with overexpression of integrin αv. To elucidate the molecular mechanism underlying the role of integrin αv in promoting NSCLC progression, we studied the expression of proteins from a number of important pathways associated with tumorigenesis, and found that the extracellular signal regulated protein kinase (ERK)1/2 signaling pathway may be involved in the mediation of the observed integrin αv effects. component of an important pathway for tumorigenesis, the ERK 1/2. Following inhibition of ERK 1/2 signaling, the proliferation of A549 cells induced by integrin αv was reduced, while the inhibition of apoptosis was attenuated. Our findings demonstrate that integrin αv promotes the proliferation of the human lung cancer cell line A549 by activating the ERK 1/2 signaling pathway, which suggests that this pathway may be a promising target for the treatment of human lung cancer.

The correlation of morphological features of chest computed tomographic scans with clinical characteristics of thymoma.

OBJECTIVES: Chest computed tomography (CT) scanning has been widely utilized in thymoma identification and staging as well as in follow-up monitoring for recurrence. However, the relationship between some CT imaging features and pathological types, clinical stage, completeness of resection, or prognosis in thymoma has not been well explored. METHODS: We retrospectively reviewed preoperative CT imaging for 238 thymoma patients, who had undergone thymectomy from October 2007 to December 2011. All CT parameters were assessed in each case based on clinical and pathological data. Survival analysis was performed by using the Kaplan-Meier and log-rank tests. RESULTS: Tumour contours (P = 0.008), homogeneity (P = 0.009), degree of enhancement (P = 0.013), fat plane obliteration with adjacent structures (P < 0.001), the presence of mediastinal lymphadenopathy (P = 0.010), irregular infiltration into the lung (P = 0.012) and tumour shape (P = 0.007) were associated with the World Health Organization (WHO) histological classification. Lobulated or irregular tumour contours (P < 0.001), presence of calcifications (P = 0.002), infiltration of surrounding fat (P < 0.001), irregular infiltration into the lung (P < 0.001), irregular infiltration into vascular (P < 0.001), more abutment of vessels (P < 0.001) and pulmonary changes adjacent to the tumour (P < 0.001) were associated with the more advanced Masaoka-Koga clinical stage. Tumour contours (P < 0.001), infiltration of surrounding fat (P = 0.008), irregular infiltration into the lung (P < 0.001) and degree of abutment of vessel circumference (P = 0.001) were associated with completeness of resection. With multivariate analysis, no CT image features could reliably predict on the overall or disease-free survival rate. CONCLUSIONS: CT imaging does have some features, which are significantly correlated with the WHO classification, the Masaoka-Koga clinical staging and the completeness of resection, although it has no definite role to evaluate preoperatively the survival rate of thymoma patients.

Responses of glutathione-related antioxidant defense system in serum of Nile tilapia (Oreochromis niloticus) exposed to sublethal concentration of methomyl and recovery pattern.

Tilapia were exposed to sublethal concentrations of 0, 0.2, 2, 20, or 200 µg/L for 30 days, and then transferred to methomyl-free water for 18 days. GST, GPx, GR, GSH, and GSSG in tilapia serum were examined at 0, 6, 12, 18, 24, and 30 days after methomyl exposure and at 18 days after transferring to methomyl-free water. There were no significant changes in antioxidants activities and contents in serum of tilapia exposed to 0.2 µg/L. Significant increases in GST, GR, GPx, and GSSG accompanied by a decrease in GSH were observed following methomyl exposure to 2, 20, or 200 µg/L, suggesting the presence of oxidative stress. Thus, it would appear the 0.2 µg/L methomyl might be considered the no observed adverse effect level. Recovery data showed that the effects produced by lower concentration of 20 µg/L were reversible but not at the higher 200 µg/L concentration.