Comparison of bleb morphologies between phacoemulsification combined with Ex-PRESS mini shunt implantation, phacotrabeculectomy and trabeculectomy alone: a two-year retrospective in vivo confocal microscopy study.

BACKGROUND: To compare the bleb morphologies of phacoemulsification combined with Ex-PRESS implantation (Phaco-ExPRESS), phaco trabeculectomy (Phaco-Trab), and trabeculectomy (Trab) in postoperative two years. METHODS: Patients with primary open-angle glaucoma (POAG) with or without cataracts were included in this study. All patients underwent surgeries of either Phaco-ExPRESS, Phaco-Trab, or Trab. The morphologic structures of the filtering bleb, including microcysts area, hyperreflective dot density, and stromal connective tissue under in vivo confocal microscope (IVCM), were compared between the three groups. The data were collected preoperatively and postoperatively at 2 weeks, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months. RESULTS: Eighty-nine eyes from 89 patients were enrolled, including 32 in the Phaco-ExPRESS group, 25 in the Phaco-Trab group, and 32 in the Trab group. In a 24-month follow-up, bleb morphologies in Phaco-ExPRESS were similar to the Trab group. The area of epithelial microcysts was significantly increased in Phaco-ExPRESS and Trab groups while significantly decreased in Phaco-Trab. At postoperative 24 months, the complete success rate was 65.1% in Phaco-ExPRESS, 32.0% in Phaco-Trab, and 59.4% in the Trab group (P = 0.03). The phaco-Trab group had more postoperative anti-glaucoma medications than the other two groups (P < 0.05). CONCLUSIONS: Phaco-ExPRESS group and Trab group had similar blebs morphologies in IVCM, with larger microcyst area, looser connective tissue, and less inflammation than Phaco-Trab, indicating that the function of blebs in the Phaco-ExPRESS and Trab group, was more potent than that of Phaco-Trab. All these surgical methods provided adequate IOP control, but Phaco-Trab required more anti-glaucoma medications.

Recycling Waste Glyceroborate to Aqueous Lubricant for Tribological Applications.

The present study attempts to explore the direct recyclability of glyceroborate from medicine pharmaceutical production wastewater into an aqueous lubricant instead of conventional waste processing methods from the tribological view. In order to determine the tribological feasibility, the physicochemical properties of crude pharmaceutical wastewater are investigated and compared with those of pure glycerol to access their potential lubrication properties. The results demonstrated that the crude pharmaceutical wastewater has better friction-reducing and antiwear properties under the same working conditions. Besides outstanding lubricating properties, the friction-induced formation of borate tribo-film and intermediate FeOOH compound favors lowering of the shear stress between the rubbing surfaces. This finding better provides an alternative to transform glyceroborate from medicine pharmaceutical production wastewater after simple distillation processing to a potential aqueous lubricant.

Activated CX3CL1/Smad2 Signals Prevent Neuronal Loss and Alzheimer's Tau Pathology-Mediated Cognitive Dysfunction.

Neurofibrillary tangles likely cause neurodegeneration in Alzheimer's disease (AD). We demonstrate that the CX3CL1 C-terminal domain can upregulate neurogenesis, which may ameliorate neurodegeneration. Here we generated transgenic (Tg-CX3CL1) mice by overexpressing CX3CL1 in neurons. Tg-CX3CL1 mice exhibit enhanced neurogenesis in both subgranular and subventricular zones. This enhanced neurogenesis correlates well with elevated expression of TGF-ß2 and TGF-ß3, and activation of their downstream signaling molecule Smad2. Intriguingly, the enhanced adult neurogenesis was mitigated when Smad2 expression was deleted in neurons, supporting a role for the CX3CL1-TGF-ß2/3-Smad2 pathway in the control of adult neurogenesis. When Tg-CX3CL1 mice were crossed with Alzheimer's PS19 mice, which overexpress a tau P301S mutation and exhibit age-dependent neurofibrillary tangles and neurodegeneration, overexpressed CX3CL1 in both male and female mice was sufficient to rescue the neurodegeneration, increase survival time, and improve cognitive function. Hence, we provide in vivo evidence that CX3CL1 is a strong activator of adult neurogenesis, and that it reduces neuronal loss and improves cognitive function in AD.SIGNIFICANCE STATEMENT This study will be the first to demonstrate that enhanced neurogenesis by overexpressed CX3CL1 is mitigated by disruption of Smad2 signaling and is independent of its interaction with CX3CR1. Overexpression of CX3CL1 lengthens the life span of PS19 tau mice by enhancing adult neurogenesis while having minimal effect on tau pathology. Enhancing neuronal CX3CL1, mainly the C-terminal fragment, is a therapeutic strategy for blocking or reversing neuronal loss in Alzheimer's disease or related neurodegenerative disease patients.

DDX56 modulates post-transcriptional Wnt signaling through miRNAs and is associated with early recurrence in squamous cell lung carcinoma.

BACKGROUND: Early recurrence is a major obstacle to prolonged postoperative survival in squamous cell lung carcinoma (SqCLC). The molecular mechanisms underlying early SqCLC recurrence remain unclear, and effective prognostic biomarkers for predicting early recurrence are needed. METHODS: We analyzed primary tumor samples of 20 SqCLC patients using quantitative proteomics to identify differentially-expressed proteins in patients who experienced early versus late disease recurrence. The expression and prognostic significance of DDX56 was evaluated using a SqCLC tumor tissue microarray and further verified using different online databases. We performed in vitro and in vivo experiments to obtain detailed molecular insight into the functional role of DDX56 in SqCLC. RESULTS: We found that DDX56 exhibited increased expression in tumors of patients who experienced early versus late disease recurrence. Increased DDX56 expression in SqCLC tumors was subsequently confirmed as an independent prognostic factor of poor recurrence-free survival in independent SqCLC cohorts. Functionally, DDX56 promotes SqCLC cell growth and migration in vitro, and xenograft tumor progression in vivo. Mechanistically, DDX56 post-transcriptionally promotes expression of multiple Wnt signaling pathway-related genes, including CTNNB1, WNT2B, and represses a subset of miRNAs, including miR-378a-3p, a known suppressor of Wnt signaling. Detailed analysis revealed that DDX56 facilitated degradation of primary miR-378a, leading to down-regulation of mature miR-378a-3p and thus derepression of the target gene WNT2B. CONCLUSION: We identified DDX56 as a novel independent prognostic biomarker that exerts its oncogenic effects through miRNA-mediated post-transcriptional regulation of Wnt signaling genes to promote early SqCLC recurrence. DDX56 may assist in identifying SqCLC patients at increased risk of early recurrence and who could benefit from Wnt signaling-targeted therapies.

Associations of COVID-19 lockdown with gestational length and preterm birth in China.

BACKGROUND: The effects of COVID-19 lockdown measures on maternal and fetal health remain unclear. We examined the associations of COVID-19 lockdown with gestational length and preterm birth (PTB) in a Chinese population. METHODS: We obtained medical records of 595,396 singleton live infants born between 2015 and 2020 in 5 cities in Guangdong Province, South China. The exposed group (N = 101,900) included women who experienced the COVID-19 Level I lockdown (1/23-2/24/2020) during pregnancy, while the unexposed group (N = 493,496) included women who were pregnant during the same calendar months in 2015-2019. Cumulative exposure was calculated based on days exposed to different levels of emergency responses with different weighting. Generalized linear regression models were applied to estimate the associations of lockdown exposure with gestational length and risk of PTB (< 37 weeks). RESULTS: The exposed group had a shorter mean gestational length than the unexposed group (38.66 vs 38.74 weeks: adjusted ß = - 0.06 week [95%CI, - 0.07, - 0.05 week]). The exposed group also had a higher risk of PTB (5.7% vs 5.3%; adjusted OR = 1.08 [95%CI, 1.05, 1.11]). These associations seemed to be stronger when exposure occurred before or during the 23rd gestational week (GW) than during or after the 24th GW. Similarly, higher cumulative lockdown exposure was associated with a shorter gestational length and a higher risk of PTB. CONCLUSIONS: The COVID-19 lockdown measures were associated with a slightly shorter gestational length and a moderately higher risk of PTB. Early and middle pregnancy periods may be a more susceptible exposure window.

A B7-CD28 family based signature demonstrates significantly different prognoses and tumor immune landscapes in lung adenocarcinoma.

B7 family ligands and CD28 family receptors have complicated interaction for modulating immune functions. They play a central role in response to immunotherapy and outcome of patients with lung adenocarcinoma (LUAD). Thus, we analyzed B7-CD28 family gene expression profiles in LUAD and generated a signature to predict prognosis and immune host status. B7-CD28 family gene expression profiles and clinical data of LUAD from The Cancer Genome Atlas (TCGA) were analyzed. In the training cohort, prognostic association was assessed and then a prognostic signature was built with stepwise multivariable Cox analysis. The signature was validated by Kaplan-Meier and multivariable Cox analysis in several published gene expression datasets and a Fudan University cohort. Expression of immune cell populations and other immunotherapy predictors was further investigated. In TCGA LUAD cohort, eight B7-CD28 family genes had prognostic association with p values <0.05. Stepwise regression generated a gene signature including two genes, CD28 and CD276. Signature high-risk cases had worse overall survival (OS) and disease-free survival (DFS) in three published gene expression datasets and a Fudan University validation cohort. The B7-CD28 family based signature also significantly stratified OS and DFS in important clinical subsets, including stage I-II and EGFR mutant subsets. Signature high- and low-risk tumor had significantly different expressions of PD-L1 and tumor infiltrating leukocytes. The B7-CD28 family based signature demonstrates significantly different prognoses and tumor immune landscapes in LUAD. Whether it could serve as potential biomarkers for immunotherapy needs further investigation.

Extended Right Thoracic Approach Compared With Limited Left Thoracic Approach for Patients With Middle and Lower Esophageal Squamous Cell Carcinoma: Three-year Survival of a Prospective, Randomized, Open-label Trial.

OBJECTIVE: To investigate whether survival is improved by using the right thoracic approach (extended lymphadenectomy) compared with the left thoracic approach (limited lymphadenectomy) for esophageal cancer. BACKGROUND: The optimal surgical technique for esophageal cancer remains unclear. METHODS: Between May 2010 and July 2012, 300 patients with middle and lower thoracic esophageal carcinoma were randomized to receive esophagectomy through either the right or left thoracic approach. Of these, 286 patients with squamous cell carcinoma determined by postoperative pathology were included in this analysis. Disease-free survival (DFS) and overall survival (OS) were compared between the right (n = 146) and left thoracic groups (n = 140). RESULTS: The median follow-up was 55.9 months [95% confidence interval (CI): 53.1-58.6]. The 3-year DFS rates were 62% and 52% in the right and left thoracic arms, respectively [hazard ratio (HR) 0.709; 95% CI, 0.506-0.995; P = 0.047, log-rank test]. The 3-year OS rates were 74% and 60%, respectively (HR, 0.663; 95% CI, 0.457-0.961; P = 0.029). Subgroup analyses revealed longer DFS in the right thoracic arm (vs left thoracic arm) in patients with lymph node involvement (HR, 0.632; 95% CI, 0.412-0.969, P = 0.034), but not in patients without lymph node involvement (HR, 0.757; 95% CI, 0.434-1.320, P = 0.325), and in patients with R1-2 resection margins (HR, 0.495; 95% CI, 0.290-0.848, P = 0.009), but not R0 margins (HR, 0.944; 95% CI, 0.603-1.477, P = 0.801). CONCLUSIONS: Compared with the left thoracic approach, the right thoracic approach associated with increased DFS and OS in esophageal squamous cell carcinoma patients, particularly in those with lymph node involvement and/or R1-2 resection margins.

Prevalence, clinicopathologic characteristics, and molecular associations of EGFR exon 20 insertion mutations in East Asian patients with lung adenocarcinoma.

PURPOSE: To define the prevalence, clinicopathologic characteristics and molecular associations of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in East Asian lung adenocarcinoma patients. METHODS: A total of 1,086 lung adenocarcinomas were sequenced for EGFR mutations. EGFR and HER2 copy number variations; total and phosphorylated (p) protein expression of ErbB family members including EGFR, HER2, and HER3; phosphorylated protein expression of downstream signaling molecules including Akt and Erk; and clinicopathologic features in lung adenocarcinomas with EGFR exon 20 insertion mutations were all investigated. RESULTS: EGFR exon 20 insertion mutations were present in 2.9 % of lung adenocarcinomas and 4.7 % of all the EGFR mutations. Compared to those with classic activating EGFR mutations, lung adenocarcinomas with exon 20 insertion mutations were characterized by significantly younger age at diagnosis (P = 0.032 for exon 20 insertions vs. L858R) and shorter relapse-free survival [P = 0.045 for exon 20 insertions versus (vs) exon 19 deletions]. Molecularly, samples harboring exon 20 insertion mutations had lower expression of phosphorylated (p)-EGFR (P < 0.001) and HER3 (P = 0.016). In addition, higher expression of p-Akt (P = 0.007) and lower expression of p-Erk (P = 0.009) were observed in tumors with exon 20 insertion mutations. CONCLUSIONS: Lung adenocarcinomas with EGFR exon 20 insertion mutations were present in a substantial proportion. This subset showed distinct clinicopathologic features, less dependence on EGFR molecularly, and different pathway activation patterns compared to those with classic EGFR activating mutations.

A mapping-knowledge-domain analysis of ERP research on language processing.

The event-related potentials (ERPs) technique represents a newly developed methodology in cognitive neuroscience and has significantly extended the scope of linguistic studies, offering valuable insights into cognitive processes related to language. While extant literature reviews have addressed specific facets of ERP research on language processing, a comprehensive overview of this domain remains notably absent. This study aims to fill this gap by pioneering a mapping-knowledge-domain analysis of ERP research on language processing using Citespace, a visualized bibliometric software. The current study conducted a meticulous survey and evaluation of relevant literature extracted from the Web of Science core collection. Initially, this study outlines the spatial-temporal distribution within this domain. Subsequently, employing document co-citation analysis, keyword co-occurrence analysis, cluster analysis, and burst detection analysis, this study delved deeper into the research landscape. Findings reveal that key areas in ERP research on language processing predominantly focus on sentence comprehension, reading comprehension, and mismatch negativity, with notable emphasis on topics such as speech perception, temporal dynamics, and working memory. The current study advocates for future investigations to concentrate on larger linguistic units, explore the integration of ERP components and their functional significance, and scrutinize individual differences among participants. These directions are imperative for advancing the understanding of language processing mechanisms.

Global, regional and national burden of retinopathy of prematurity among childhood and adolescent: a spatiotemporal analysis based on the Global Burden of Disease Study 2019.

BACKGROUND: This study aimed to provide a comprehensive assessment of burden estimates and the secular trend of vision loss due to retinopathy of prematurity (ROP) among people younger than 20 years, at the global, regional and national levels. METHODS: Data were obtained from the Global Burden of Disease Study 2019 database. The average annual percentage change (AAPC) was calculated to quantify the temporal trends in the measures of vision loss. RESULTS: In 2019, the global age-standardised rates (ASRs) of prevalence per 100 000 population was 86.4 for vision loss, specifically, 35 for moderate vision loss, 19.9 for severe vision loss, 31.6 for blindness due to ROP among people younger than 20 years. Moreover, the ASR of years lived with disability per 100 000 was 10.6 for vision loss, specifically, 1.1 for moderate vision loss, 3.6 for severe vision loss, 5.9 for blindness, respectively. From 1990 to 2019, the ASR of prevalence of blindness and vision loss due to ROP significantly increased, while its burden slightly decreased. Males showed higher ASR of prevalence than females in 2019, whereas females have larger increasing trend than males from 1990 to 2019. The global highest ASR of disease burden was observed in South Asia and Southern sub-Saharan Africa, as well as low sociodemographic index (SDI) regions in 2019. CONCLUSIONS: Globally, although the burden decreased, the prevalence of childhood and adulthood vision loss due to ROP continues to increase. Reasonable resource allocation and advanced intervention are recommended to prevent and control the vision loss due to ROP.

Identification of diabetic retinopathy classification using machine learning algorithms on clinical data and optical coherence tomography angiography.

BACKGROUND: To apply machine learning (ML) algorithms to perform multiclass diabetic retinopathy (DR) classification using both clinical data and optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional observational study, clinical data and OCTA parameters from 203 diabetic patients (203 eye) were used to establish the ML models, and those from 169 diabetic patients (169 eye) were used for independent external validation. The random forest, gradient boosting machine (GBM), deep learning and logistic regression algorithms were used to identify the presence of DR, referable DR (RDR) and vision-threatening DR (VTDR). Four different variable patterns based on clinical data and OCTA variables were examined. The algorithms' performance were evaluated using receiver operating characteristic curves and the area under the curve (AUC) was used to assess predictive accuracy. RESULTS: The random forest algorithm on OCTA+clinical data-based variables and OCTA+non-laboratory factor-based variables provided the higher AUC values for DR, RDR and VTDR. The GBM algorithm produced similar results, albeit with slightly lower AUC values. Leading predictors of DR status included vessel density, retinal thickness and GCC thickness, as well as the body mass index, waist-to-hip ratio and glucose-lowering treatment. CONCLUSIONS: ML-based multiclass DR classification using OCTA and clinical data can provide reliable assistance for screening, referral, and management DR populations.

Extent of surgical resection for radiologically subsolid T1N0 invasive lung adenocarcinoma: When is a wedge resection acceptable?

OBJECTIVE: To evaluate whether wedge resection (WR) was appropriate for the patients with peripheral T1 N0 solitary subsolid invasive lung adenocarcinoma. METHODS: Patients with peripheral T1N0 solitary subsolid invasive lung adenocarcinoma who received sublobar resection were retrospectively reviewed. Clinicopathologic characteristics, 5-year recurrence-free survival, and 5-year lung cancer-specific overall survival were analyzed. Cox regression model was used to elucidate risk factors for recurrence. RESULTS: Two hundred fifty-eight patients receiving WR and 1245 patients receiving segmentectomy were included. The mean follow-up time was 36.87 ± 16.21 months. Five-year recurrence-free survival following WR was 96.89% for patients with ground-glass nodule (GGN) ≤2 cm and 0.25< consolidation-to-tumor ratio (CTR) ≤0.5, not statistically different from 100% for those with GGN≤2 cm and CTR ≤0.25 (P = .231). The 5-year recurrence-free survival was 90.12% for patients with GGN between 2 and 3 cm and CTR ≤0.5, significantly lower than that of patients with GGN ≤2 cm and CTR ≤0.25 (P = .046). For patients with GGN≤2 cm and 0.25

ANCCA protein expression is a novel independent poor prognostic marker in surgically resected lung adenocarcinoma.

BACKGROUND: AAA+ nuclear coregulator cancer associated (ANCCA) is found to be overexpressed in various cancer types and could play a role in common and fundamental cellular processes. A recent study suggested that ANCCA was a likely driver whose expression explained the behavior of differentially expressed proliferation-related genes in lung adenocarcinoma. However, protein expression of ANCCA in lung adenocarcinoma and its association with clinicopathologic parameters and commonly reported driver mutations remains unexplored. METHODS: ANCCA expression was evaluated by immunohistochemistry in 143 surgically resected lung adenocarcinomas and was correlated with clinicopathologic and molecular variables including adenocarcinoma histologic subtypes, tumor, node, metastasis status, relapse-free survival, overall survival, EGFR mutations, KRAS mutations, HER2 mutations and ALK fusions. RESULTS: Positive ANCCA expression was significantly associated with male sex, smokers, poorly differentiated tumors, nonlepidic predominant subtype, more advanced T stage, lymph nodal metastasis and late disease stage. Cox multivariate analysis revealed that ANCCA-positive expression was an independent predictor of worse relapse-free survival [hazard ratio (HR) 1.736, 95 % confidence interval (CI) 1.075-2.804; P = .024) and overall survival (HR 7.758, 95 % CI 2.955-20.370; P < .001). The addition of ANCCA protein expression to the prognostic model using pathologic stage markedly improved the prognostic accuracy; the concordance index increased from .692 to .788, and the Akaike information criterion decreased from 354.20 to 336.11. CONCLUSIONS: We have identified ANCCA protein expression as a novel independent poor prognostic indicator in lung adenocarcinoma. Prospective studies are warranted to validate its potential prognostic value in combination with the current staging system.

Bleeding-related re-exploration following pulmonary resection: a report of a single-center experience.

PURPOSE: Postoperative bleeding is a potentially fatal complication after lung surgery and usually requires re-operation. The aim of this study was to analyze the characteristics of bleeding-related re-exploration following pulmonary resection and reduce the incidence of this complication. METHODS: From January 2016 to December 2020, 14,104 patients underwent pulmonary resection for lung cancer or pulmonary nodule at Fudan University Shanghai Cancer Center, China. We evaluated cases with bleeding-related re-exploration, and analyzed the relationship between postoperative bleeding and clinical characteristics. We further developed a protocol to reduce the proportion of bleeding-related re-exploration in our center. RESULTS: Bleeding-related re-exploration occurred in 85 (0.60%) out of 14,104 patients. The sources of postoperative bleeding included surgical incision (20, 23.53%), parietal pleura (20, 23.53%), bronchial artery (14, 16.47%), lung parenchyma (13, 15.29%), pulmonary vessel (5, 5.88%) and rare source of bleeding. There were various patterns of postoperative bleeding. Open thoracotomy had a significantly higher bleeding rate than video-assisted thoracoscopic surgery (VATS) (1.27% vs 0.34%, p < 0.0001). The bleeding rate of pneumonectomy, lobectomy, segmentectomy and wedge resection was significantly different (1.78%, 0.88%, 0.46% vs 0.28%, p < 0.0001). All patients were discharged successfully except for one patient died of respiratory failure. A protocol based on these findings was developed to reduce the proportion of bleeding-related re-exploration in our center. CONCLUSION: Our findings revealed that the source of bleeding, surgical approach and procedure affected the pattern of postoperative bleeding. Postoperative bleeding could be managed properly on the timely decision of re-exploration considering its origin, severity, onset and risk factors.

Associations of concomitant retinopathy and depression with mortality in a nationally representative population.

OBJECTIVE: To evaluate the interaction effects between retinopathy and depression on mortality risks in genral population and subpopulation with diabetes. METHODS: Prospective analyses were conducted on data from the National Health and Nutrition Examination Surveys study. Associations of retinopathy, depression and their interaction with all-cause, cardiovascular disease (CVD)-specific, cancer-specific and other-specific mortality risk were estimated using Kaplan-Meier curves and multivariate Cox proportional hazards models. RESULTS: Among 5367 participants, the weighted prevalence of retinopathy and depression was 9.6 % and 7.1 %, respectively. After a follow-up period of 12.1 years, 1295 deaths (17.3 %) occurred. Retinopathy was associated with an increased risk of all-cause (hazard ratio [HR]; 95 % confidence interval [CI]) (1.47; 1.27-1.71), CVD-specific (1.87; 1.45-2.41), and other-specific (1.43; 1.14-1.79) mortality. Similar relationship was observed between depression and all-cause mortality (1.24; 1.02-1.52). Retinopathy and depression had a positive multiplicative and additive interaction effect on all-cause (Pinteraction = 0.015; relative excess risk of interaction [RERI] 1.30; 95 % CI 0.15-2.45) and CVD-specific mortality (Pinteraction = 0.042; RERI 2.65; 95 % CI -0.12-5.42). Concomitant retinopathy and depression was more markedly associated with all-cause (2.86; 1.91-4.28), CVD-specific (4.70; 2.57-8.62), and other-specific mortality risks (2.18; 1.14-4.15) compared to those without retinopathy and depression. These associations were more pronounced in the diabetic participants. CONCLUSIONS: The co-occurrence of retinopathy and depression increases the risk of all-cause and CVD-specific mortality among middle-aged and older adults in the United States, especially in population with diabetes. Focus on diabetic patients and active evaluation and intervention of retinopathy with depression may improve their quality of life and mortality outcomes.

Cleavage of neuregulin-1 by BACE1 or ADAM10 protein produces differential effects on myelination.

Neuregulin-1 (Nrg1) is encoded by a single gene and exists in naturally secreted and transmembrane isoforms. Nrg1 exerts its signaling activity through interaction with its cognate ErbB receptors. Multiple membrane-anchored Nrg1 isoforms, present in six different membrane topologies, must be processed by a protease to initiate a signaling cascade. Here, we demonstrate that BACE1 and ADAM10 can process type I and III Nrg1 at two adjacent sites. Our cleavage site mapping experiments showed that the BACE1 cleavage site is located eight amino acids downstream of the ADAM10 cleavage site, and this order of cleavage is the opposite of amyloid precursor protein cleavage by these two enzymes. Cleavages were further confirmed via optimized electrophoresis. Cleavage of type I or III Nrg1 by ADAM10 and BACE1 released a signaling-capable N-terminal fragment (ntf), either Nrg1-ntfα or Nrg1-ntfß, which could similarly activate an ErbB receptor as evidenced by increased phosphorylation of Akt and ERK, two downstream signaling molecules. Although both Nrg1-ntfα and Nrg1-ntfß could initiate a common signaling cascade, inhibition or down-regulation of ADAM10 alone in a co-culture system did not affect normal myelination, whereas specific inhibition of BACE1 impaired normal myelination. Thus, processing of Nrg1 by BACE1 appears to be more critical for regulating myelination. Our results imply that a significant inhibition of BACE1 could potentially impair Nrg1 signaling activity in vivo.

The role of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) for qualitative diagnosis of mediastinal and hilar lymphadenopathy: a prospective analysis.

BACKGROUND: Recently EBUS-TBNA, which has a sensitivity of 94.6%, specificity of 100% and diagnostic accuracy rate of 96.3% as previously reported, has been widely used for patients with mediastinal and hilar lymphadenopathy or suspected lung cancer to get accurate diagnosis. The purpose of the current study was to evaluate the usefulness of EBUS-TBNA in obtaining cytological and histological diagnosis of mediastinal and hilar lymph nodes compared to the results obtained with conventional mediastinoscopy as previously reported, and to assess the relationship of diagnostic accuracy and number of passes and size of lymph nodes. METHODS: 101 patients with mediastinal and hilar lymphadenopathy or suspected lung cancer in our institution were included in this prospective study. EBUS-TBNA was performed in all cases. The final diagnosis was confirmed by cytology, surgical results, and/or clinical follow-up for at least 6 months. Sensitivity, specificity, accuracy, and positive and negative predictive values were calculated using standard formulas. RESULTS: In 101 patients, EBUS-TBNA was successfully performed to obtain samples from 225 lymph nodes, 7 lung masses, 1 mediastinal mass and 2 esophageal masses. 63 malignant tumors and 38 benign diseases were confirmed. Epidermal growth factor receptor mutation was detected in 10 biopsy samples, and epidermal growth factor receptor mutation was detected in 4 cases. With respect to the correct diagnosis of mediastinal and hilar lymphadenopathy, EBUS-TBNA had a sensitivity of 95.08%, specificity of 100%, positive predictive value of 100%, negative predictive value of 93.02%, and overall accuracy of 97.02%. The relationship of diagnostic accuracy and number of lymph node passes or size of lymph nodes was both insignificant (p = 0.27; p = 0.23). The procedure was uneventful without complications. CONCLUSIONS: EBUS-TBNA is an accurate and safe tool in diagnosis of mediastinal and hilar lymphadenopathy. It cannot completely replace mediastinoscopy, it may indeed reduce the number of mediastinoscopy procedures. In some cases, it can necessarily be the first-line procedure before mediastinoscopy.

The expression of prolyl hydroxylase domain enzymes are up-regulated and negatively correlated with Bcl-2 in non-small cell lung cancer.

The prolyl hydroxylase domain enzymes (PHDs) play the most notable role in cellular oxygen sensing and oxygen homeostasis, the transcription of PHD genes are involved in the protection against hypoxia and oxidative stress. Intratumoral hypoxia exists in malignant solid tumors primarily due to rapid cancer cell proliferation with high metabolic demands and defective structural and functional vasculature. Previous studies have demonstrated that all the three PHDs have the ability to hydroxylate hypoxia inducible factor (HIF) polypeptides, which are the key molecules in maintaining the oxygen homeostasis. However, PHDs play multiple physiological and pathological roles. There is scant data regarding expression of PHDs genes in non-small cell lung cancer (NSCLC) tissues. In Addition, the relationship between PHDs and apoptosis has never been explored in NSCLC. In this article, we examined the expression of PHD genes and their relationship with the tumor behavior and apoptosis-associated factors in NSCLC. Our results indicated that the expression of PHDs was much higher in lung cancer tissue than that of adjacent normal tissue, and the high expression of PHD3 was associated with early tumor stage and well differentiation in NSCLC. Moreover, increased PHD3 expression was significantly correlated with the low expression of Bcl-2, suggesting its potential role in inducing apoptosis.

Video-assisted thoracoscopic solitary pulmonary nodule resection after CT-guided hookwire localization: 43 cases report and literature review.

BACKGROUND: Peripheral subpleural solitary pulmonary nodules can be visualized and resected easily at thoracoscopy, but it is very difficult to localize deep nonpalpable pulmonary nodules that lie in lung parenchyma. The purpose of this article was to study the effectiveness of video-assisted thoracoscopic solitary pulmonary nodules resection after computed tomography (CT)-guided hookwire localization and to review the literature related to solitary pulmonary nodule diagnosis and treatment. METHODS: From April 2008 to June 2009, 43 patients with a solitary pulmonary nodule who had undergone CT-guided hookwire localization and video-assisted thoracoscopic surgery (VATS) were studied. RESULTS: Two cases were considered unsuccessful, other patients underwent CT-guided hookwire localization successfully, and ten patients had an asymptomatic minimal pneumothorax that did not require any intervention. The diameter of nodules ranged from 5 to 30 mm as measured by CT (mean 17.2±7.5 mm). The distance between the center of nodule and visceral pleural ranged from 2 to 40 mm (mean 18.5±9.3 mm). Of the 41 scheduled VATS procedures, 38 patients underwent thoracoscopic wedge resection. Twenty-two of 41 patients who revealed primary lung cancer after frozen-section examination underwent VATS lobectomy and lymphadenectomy. Three patients were converted to thoracotomy, and a major postoperative hemothorax occurred in one patient. No intra- or postoperative mortality or morbidity was recorded. CONCLUSIONS: Video-assisted thoracoscopic solitary pulmonary nodule resection after CT-guided hookwire localization is a safe and effective procedure for accurate diagnosis and resection of indeterminate solitary pulmonary nodules.

[Evaluation of the value of EBUS-TBNA in diagnosis of mediastinal lesions].

OBJECTIVE: To evaluate the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in diagnosis of mediastinal lesions and to discuss its optimal indication. METHODS: One hundred and twenty three patients with mediastinal lesions who underwent EBUS-TBNA were included in this study. The accuracy, sensitivity, specificity, positive and negative predictive value of EBUS-TBNA in diagnosis of mediastinal lesions were analyzed according to the final diagnosis and evaluate its value and the optimal indication. RESULTS: In the 123 patients, EBUS-TBNA was successfully performed to obtain samples from 286 stations of lymph nodes (2.33 stations/per patient). The puncture success rate was 100%. The procedure was uneventful without complications. Final diagnosis indicated that there were 83 positive and 40 negative patients. EBUS-TBNA had a sensitivity of 95.2%, specificity of 100%, positive predictive value of 100%, negative predictive value of 90.0%, and overall accuracy of 96.8%. For diagnosis of the epithelial cancer, EBUS-TBNA had an accuracy of 98.8%, sensitivity of 98.8%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 100%. EBUS-TBNA failed to reveal three lymphomas. For diagnosis of benign mediastinal diseases, EBUS-TBNA had a diagnosis rate of 47.2% which had a confirmed clinical application value. CONCLUSIONS: EBUS-TBNA may be expected to replace the mediastinoscopy as a superior choice for diagnosis of mediastinal epithelial cancers. EBUS-TBNA can not replace mediastinoscopy but being a promising tool for diagnosis of benign mediastinal lesions including granulomas. For certain special diseases such as lymphoma, mediastinoscopy cannot be replaced. However, EBUS-TBNA can be a potentially favorite choice for early stage screening.