HMCDA: a novel method based on the heterogeneous graph neural network and metapath for circRNA-disease associations prediction.

Circular RNA (CircRNA) is a type of non-coding RNAs in which both ends are covalently linked. Researchers have demonstrated that many circRNAs can act as biomarkers of diseases. However, traditional experimental methods for circRNA-disease associations identification are labor-intensive. In this work, we propose a novel method based on the heterogeneous graph neural network and metapaths for circRNA-disease associations prediction termed as HMCDA. First, a heterogeneous graph consisting of circRNA-disease associations, circRNA-miRNA associations, miRNA-disease associations and disease-disease associations are constructed. Then, six metapaths are defined and generated according to the biomedical pathways. Afterwards, the entity content transformation, intra-metapath and inter-metapath aggregation are implemented to learn the embeddings of circRNA and disease entities. Finally, the learned embeddings are used to predict novel circRNA-disase associations. In particular, the result of extensive experiments demonstrates that HMCDA outperforms four state-of-the-art models in fivefold cross validation. In addition, our case study indicates that HMCDA has the ability to identify novel circRNA-disease associations.

The impact of psychological capital on turnover intention among Chinese nurses: A moderated mediation model.

AIMS: This study examined how the mediating effect of psychological distress and the moderating role of social support influence the connection between psychological capital and turnover intention among Chinese nurses. BACKGROUND: Nurses play a crucial role in medical and health services, but turnover intentions are common among them. METHODS: A cross-sectional survey was conducted involving 4865 nurses in China. The Chinese Psychological Capital Questionnaire, Depression, Anxiety and Stress Scale, Social Support Rating Scale, and Turnover Intention Scale were used to gather data. Bootstrap and simple slope methods were used to test the mediating effect of psychological distress and the moderating effect of social support. RESULTS: Psychological capital had a significant direct impact on turnover intention among nurses (B = -0.040, t = -10.032, p < .001). Psychological distress had a mediation effect of 46.89% between psychological capital and turnover intention. Moreover, social support had a moderating role in the relationship between psychological distress and psychological capital and between psychological distress and turnover intention. CONCLUSIONS: Psychological capital correlated negatively with psychological distress and turnover intention and indirectly influenced turnover intention through psychological distress. Social support moderated the first and second half of the path in the mediating model of psychological distress. These findings have implications for early intervention for and the prevention of turnover intention in nurses. IMPLICATIONS FOR NURSING MANAGEMENT: This study's findings can inform the design of effective nurse support programmes to reduce the impact of psychological distress on turnover intention among nurses.

Impact of occupational exposure on job satisfaction and overall happiness among Chinese physicians and nurses: A cross-sectional study.

AIMS: This study aims to investigate the impact of occupational exposure on job satisfaction and overall happiness and to identify related factors of job satisfaction and overall happiness among physicians and nurses. BACKGROUND: Occupational exposure against physicians and nurses has become one of the most serious public health issues worldwide. METHODS: A cross-sectional study was conducted among physicians and nurses from 14 public tertiary hospitals using purposive sampling. Propensity score matching was used to compare job satisfaction and overall happiness among physicians and nurses with and without occupational exposure. Furthermore, binary logistic regression analysis was used to identify and analyse the influencing factors of job satisfaction and overall happiness. RESULTS: A total of 2139 physicians and nurses (55.59%) from 3791 participants had experienced occupational exposure hazards. Before matching, the job satisfaction and overall happiness among the physicians and nurses were 38.54% and 42.14%, respectively. Participants who experienced occupational exposure were more likely to develop job dissatisfaction (OR = 1.08, 95% confidence interval [CI]: 0.90-1.28) and overall unhappiness (OR = 1.24, 95% CI: 1.05-1.46) than those who did not. Participants' work experience, self-evaluated health status, satisfaction with the work environment, evaluation of doctor-patient relationship and stress were common factors affecting job satisfaction and overall happiness. CONCLUSIONS: Our findings suggest that physicians and nurses who experience occupational exposure are more likely to develop job dissatisfaction and overall unhappiness, especially if they have shorter work experience and a tense or neutral relationship with patients. IMPLICATIONS FOR NURSING MANAGEMENT: It is necessary to pay attention to the occupational exposure. When physicians and nurses experience occupational exposure, managers could provide support to prevent job dissatisfaction and unhappiness.

Immunogenomic analysis reveals LGALS1 contributes to the immune heterogeneity and immunosuppression in glioma.

Mutualistic and dynamic communication between tumour cells and the surrounding microenvironment accelerates the initiation, progression, chemoresistance and immune evasion of glioblastoma (GBM). However, the immunosuppressive mechanisms of GBM has not been thoroughly elucidated to date. We enrolled six microenvironmental signatures to identify glioma microenvironmental genes. The functional enrichment analysis such as ssGSEA, ESTIMATE algorithm, Gene Ontology, Pathway analysis is conducted to discover the potential function of microenvironmental genes. In vivo and in vitro experiments are used to verify the immunologic function of LGALS1 in GBM. We screen eight glioma microenvironmental genes from glioma databases, and discover a key immunosuppressive gene (LGALS1 encoding Galectin-1) exhibiting obviously prognostic significance among glioma microenvironmental genes. Gliomas with different LGALS1 expression have specific genomic variation spectrums. Immunosuppression is a predominate characteristic in GBMs with high expression of LGALS1. Knockdown of LGALS1 remodels the GBM immunosuppressive microenvironment by down regulating M2 macrophages and myeloid-derived suppressor cells (MDSCs), and inhibiting immunosuppressive cytokines. Our results thus implied an important role of microenvironmental regulation in glioma malignancy and provided evidences of LGALS1 contributing to immunosuppressive environment in glioma and that targeting LGALS1 could remodel immunosuppressive microenvironment of glioma.

Overexpression of Annexin A2 Receptor Inhibits Neovascularization via the Promotion of Krüppel-Like Transcription Factor 2.

BACKGROUND/AIMS: Annexin A2 receptor (AX2R) can mediate annexin A2 signalling and induce apoptosis in a variety of cells, but its role in neovascularization (NV) remains unclear. Krüppel-like transcription factor 2 (KLF2) is known to be expressed in a range of cell types and to participate in a number of processes during development and disease, such as endothelial homeostasis, vasoregulation and vascular growth/remodelling. The aim of our study was to investigate the role of AX2R in NV and the plausible molecular mechanism. METHODS: We constructed a eukaryotic overexpression plasmid for AX2R (Lenti-AX2R) by using polymerase chain reaction (PCR). The full-length human AX2R gene was transfected into human retinal endothelial cells (HRECs) and human umbilical vein endothelial cells (HUVECs) using lentivirus vectors to overexpress AX2R. All experiments were divided into three groups: control, negative control (Lenti-EGFP), and Lenti-AX2R.Cell proliferation, cell migration, tube formation, mouse aortic ring assays and mouse matrigel plug assay were applied to analyse the effect of AX2R in NV. Furthermore, we conducted flow cytometry to evaluate whether AX2R could influence the cell cycle. A series of cell cycle-related proteins including cyclin A1, cyclin B1, cyclin D1, cyclin E1, CDK1, and p-CDC2 were detected by WB. The mRNA and protein levels of KLF2, vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) were further quantified by RT-PCR and WB to reveal the possible mechanism. RESULTS: Overexpression of AX2R significantly inhibited cell proliferation, migration and tube formation in both types of endothelial cells (ECs), HRECs and HUVECs. It also suppressed vessel sprouting in the mouse aortic ring assay and NV in mouse matrigel plug assay. Furthermore, infection with Lenti-AX2R lentivirus arrested the cell cycle in S/G2 and influenced the expression of a series of cell cycle-related proteins. We also found that the overexpression of AX2R increased the expression of KLF2, mediating VEGF and VEGFR2. CONCLUSIONS: Overexpression of AX2R contributes to the inhibition of NV via suppressing KLF2 ubiquitin-dependent protein degradation, which might therefore be a therapeutic option for NV. It could be considered more broadly as an anti-angiogenic agent in the treatment of neovascular-related diseases in the future.

Impact of workplace violence against nurses' thriving at work, job satisfaction and turnover intention: A cross-sectional study.

AIMS AND OBJECTIVES: To investigate the interrelationships between workplace violence, thriving at work and turnover intention among Chinese nurses and to explore the action mechanism among these variables. BACKGROUND: Workplace violence is a dangerous occupational hazard globally, and it is pervasive in the health service industry. As a corollary, workplace violence may produce many negative outcomes among nursing staff. Consequently, it hinders nurses' professional performance and reduces nursing quality. DESIGN: A cross-sectional online survey was conducted. METHODS: A total of 1,024 nurses from 26 cities in China were recruited from February-May 2016. An anonymous questionnaire was used in this survey. Participants' completed data were collected using a demographics form and a 26-item questionnaire consisting of scales addressing workplace violence, thriving at work, job satisfaction, subjective well-being and turnover intention. To evaluate multivariate relationships, some multiple linear hierarchical regression analyses were performed. RESULTS: Workplace violence significantly negatively influenced nurses' job satisfaction and thriving at work, and significantly positively influenced nurses' turnover intention. Job satisfaction significantly predicted thriving at work and turnover intention. Job satisfaction not only fully mediated the relationship between workplace violence and thriving at work, but also partially mediated the relationship between workplace violence and turnover intention. Subjective well-being moderated the relationship between workplace violence and job satisfaction and the relationship between workplace violence and nurses' turnover intention. CONCLUSIONS: Adverse effects of workplace violence were demonstrated in this study. Decreases in job satisfaction were a vital mediating factor. The moderating effect of subjective well-being was helpful in reducing the harm of workplace violence to nurses and in decreasing their turnover intention. RELEVANCE TO CLINICAL PRACTICE: Workplace violence and its negative impact on nursing work should not go unnoticed by nursing managers. Nurses' subjective well-being is critical in controlling and mitigating the adverse effects of workplace violence.

Prevalence of Workplace Violence Against Chinese Nurses and Its Association with Mental Health: A Cross-sectional Survey.

OBJECTIVES: The aim of this study to investigate the prevalence of workplace violence (WPV) in nurses in hospitals in China, and its influence on nurses' mental health. METHODS: A cross-sectional, anonymous survey was conducted with 886 nurses (effective response rate: 87.46%) from Heilongjiang Province of China. RESULTS: Findings revealed that 595 of the 886 participating nurses (67.2%) were exposed to different levels of WPV. Further, WPV was correlated positively with nurses' anxiety (r=0.256, P<0.01) and depression (r=0.131, P<0.01) levels. In addition, this survey demonstrated that service years (r=0.263, P<0.01) played a moderating role in the relationship between WPV and anxiety, and gender (r=0.135, P<0.01) played a moderating role in the association between WPV and depression. CONCLUSIONS: WPV is an extensive problem in the work setting of nurses and it poses a major threat to Chinese nurses. Chinese nurses encounter hospital workplace violence frequently, and WPV has a considerably negative impact on the mental health and well-being of the nurses. It is critical to establish a more secure working environment for Chinese nursing staff to minimize the health threats caused by the negative outcomes associated with WPV, such as symptoms caused by anxiety and depression. This study also confirmed that new nurses and female nurses were more likely to be affected by WPV. Thus, addressing WPV should be one of the top concerns for both the government and the society.

Overexpression of Transforming Acidic Coiled Coil­Containing Protein 3 Reflects Malignant Characteristics and Poor Prognosis of Glioma.

Gliomas are malignant primary brain tumors with poor prognosis. Recently, research was indicative of a tight connection between tumor malignancy and genetic alterations. Here, we propose an oncogenic implication of transforming acidic coiled-coil-containing protein 3 (TACC3) in gliomas. By comprehensively analyzing the Chinese glioma genome atlas (CGGA) and publicly available data, we demonstrated that TACC3 were overexpressed along with glioma grade and served as an independent negative prognostic biomarker for glioma patients. Functions' annotations and gene sets' enrichment analysis suggested that TACC3 may participate in cell cycle, DNA repair, epithelium-mesenchymal transition and other tumor-related biological processes and molecular pathways. Patients with high TACC3 expression showed CD133⁺ stem cell properties, glioma plasticity and shorter overall survival time under chemo-/radio-therapy. Additionally, a TACC3 associated the miRNA-mRNA network was constructed based on in silico prediction and expression pattern, which provide a foundation for further detection of TACC3-miRNA-mRNA axis function. Collectively, our observations identify TACC3 as an oncogene of tumor malignancy, as well as a prognostic and motoring biomarker for glioma patients.

SiRNA directed against annexin II receptor inhibits angiogenesis via suppressing MMP2 and MMP9 expression.

BACKGROUND/AIMS: Annexin II receptor (AXIIR) is able to mediate Annexin II signal and induce apoptosis, but its role in angiogenesis remains unclear. This study tries to investigate the role of AXIIR in angiogenesis and the plausible molecular mechanism. METHODS/RESULTS: RNA interference technology was used to silence AXIIR, and the subsequent effects in vitro and in vivo were evaluated thereafter. Our data indicated that human umbilical vein endothelial cells (HUVECs) expressed AXIIR and knockdown of AXIIR significantly inhibited HUVECs proliferation, adhesion, migration, and tube formation in vitro and suppressed angiogenesis in vivo. Furthermore, AXIIR siRNA induced cell arrest in the S/G2 phase while had no effect on cell apoptosis. We found that these subsequent effects might be via suppressing the expression of matrix metalloproteinase 2and matrix metalloproteinase 9. CONCLUSION: AXIIR participates in angiogenesis, and may be a potential therapeutic target for angiogenesis related diseases.

Prevalence and factors associated with job burnout among nurses in China: A cross-sectional study.

AIM: Many people see nursing as a high-pressure, high-risk profession. Therefore, job burnout among nursing staff has become an important topic of study and has received widespread attention worldwide. This research intended to evaluate the frequency of and variables related with work burnout among nurses in public hospitals in China. DESIGN: Using a multistage random sample procedure, a cross-sectional survey was carried out in the eastern, central and western areas of China. METHODS: The Maslach Inventory-Human Service Survey and demographic information made up the two sections of the questionnaire. Of the 5250 questionnaires sent, 4865 were deemed legitimate, yielding an effective response rate of 92.67%. A linear regression analysis was performed to investigate the variables linked to nursing work burnout. RESULTS: Among the 4865 nurses, women accounted for 97.4% of the survey respondents, most of whom were aged 26-35 years. Results showed that the total scores of emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (PA) were 20.02 ± 12.04, 4.78 ± 5.54 and 34.42 ± 10.32 respectively. 50.7% of subjects obtained high or moderated scores on EE, 32.8% of subjects obtained high or moderated scores on DP and 80.4% of subjects obtained low or moderated scores on PA. Age, department, position, post-establishment, work shift type in recent months, overtime times in recent months and night shift frequency in recent months were negatively correlated with EE, and child status, monthly income, working days per week and sleep quality in recent 1 month were positively correlated with it (F = 141.827, P < 0.01, R2 = 0.243). Age, gender, department, post-establishment, overtime hours in recent months and night shift frequency in recent months were negatively correlated with DP, and child status and sleep quality in the last 1 month were positively correlated with it (F = 78.794, p < 0.01, R2 = 0.115). Child status, years of nursing work and sleep quality in the last 1 month were negatively correlated with PA, whereas age, position, work shift type in recent months and night shift frequency in recent months were positively correlated with it (F = 67.981, p < 0.01, R2 = 0.089).

Histone lactylation driven by mROS-mediated glycolytic shift promotes hypoxic pulmonary hypertension.

Increased mitochondrial reactive oxygen species (mROS) and glycolysis have been established in pulmonary hypertension (PH). However, the effect of elevated mROS on glycolytic shift and how increased glycolysis promotes hypoxic pulmonary artery smooth muscle cell (PASMC) proliferation and vascular remodeling remain elusive. Here, we reported that hypoxia-induced mROS inhibit HIF-1α hydroxylation and further trigger PASMC glycolytic switch through the upregulated HIF-1α/PDK1&PDK2/p-PDH-E1α axis, which facilitates lactate accumulation and histone lactylation. Through H3K18la and HIF-1α ChIP-seq analysis, we found that the enhanced histone lactylation of HIF-1α targets, such as Bmp5, Trpc5, and Kit, promotes PASMC proliferation. Knockdown of Pdk1&2 blunts lactate production, histone lactylation marks, and PASMC proliferation. Moreover, pharmacological intervention with lactate dehydrogenase inhibitor diminishes histone lactylation and ameliorates PASMC proliferation and vascular remodeling in hypoxic PH rats. Taken together, this study provides proof of concept for anti-remodeling therapy through lactate manipulation.

Plasma exosomal miR-1290 and miR-29c-3p as diagnostic biomarkers for lung cancer.

Background: Enhancing the diagnostic efficacy of early-stage lung cancer is crucial for improving prognosis. The objective of this study was to ascertain dependable exosomal miRNAs as biomarkers for the diagnosis of lung cancer. Methods: Exosomal miRNA candidates were identified through miRNA sequencing and subsequently validated in various case-control sets using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The correlation between the expression of exosomal miRNAs and the clinicopathological features of lung cancer was investigated. To assess the diagnostic efficacy of exosomal miRNAs for lung cancer, the receiver operating characteristic (ROC) curve analysis was conducted. The optimal cutoff value of exosomal miRNAs was determined in the testing cohort and subsequently confirmed in the validation cohort. Results: The results showed that the expression of exosomal miR-1290 was significantly elevated, while that of miR-29c-3p was significantly decreased in the plasma of lung cancer patients, especially in those with early-stage lung cancer, compared to individuals with benign lung conditions (P < 0.01). Exosomal miR-1290 and miR-29c-3p demonstrated superior diagnostic efficacy compared to conventional tumor biomarkers in distinguishing between lung cancer and benign lung diseases, as evidenced by their respective area under the curve (AUC) values of 0.934 and 0.868. Furthermore, exosomal miR-1290 and miR-29c-3p exhibited higher diagnostic efficiency in early-stage lung cancer than traditional tumor markers, with AUC values of 0.947 and 0.895, respectively. Notably, both exosomal miR-1290 and miR-29c-3p displayed substantial discriminatory capacity in distinguishing between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), as indicated by their respective AUC values of 0.810 and 0.842. Conclusions: The findings of this study provided evidence that exosomal miR-1290 and miR-29c-3p hold significant potential as biomarkers for the early detection of lung cancer, as well as for differentiating between NSCLC and SCLC.

Hydrogen saline treatment attenuates hyperoxia-induced retinopathy by inhibition of oxidative stress and reduction of VEGF expression.

OBJECTIVE: Retinal neovascularization or retinopathy is a proliferative disorder of the retinal capillaries and is the primary cause of blindness. Some studies have shown that oxidative stress plays an important role in hyperoxia-induced retinal neovascularization. Previous reports have indicated that hydrogen has a therapeutic, antioxidant activity by selectively reducing hydroxyl radicals. This study examined the therapeutic effect of hydrogen saline on retinopathy in an established mouse model of hyperoxia-induced retinopathy. METHODS: Mouse pups were exposed to 75% O(2) from postnatal day 7 (P7) to P12. Hydrogen saline was administered by intraperitoneal injection (5 ml/kg) daily for 5 days. On P17, the pups were decapitated, and retinal neovascularization was assessed using fluorescence imaging and histopathological examination. Vascular endothelial growth factor (VEGF) expression was evaluated using real-time polymerase chain reaction and fluorescence immunohistochemistry. Oxidative stress was quantified based on the malondialdehyde (MDA) level. RESULTS: Hydrogen saline decreased retinal neovascularization, reduced the mRNA and protein expression of VEGF, and suppressed the MDA levels. CONCLUSIONS: Hydrogen saline may be a potential treatment for hyperoxia-induced retinopathy that acts via the inhibition of oxidative stress and the reduction of VEGF expression.

Altered microRNA expression profiles in retinas with diabetic retinopathy.

Rats with streptozotocin (STZ)-induced diabetes were studied in order to identify abnormal microRNA (miRNA) expression profiles in diabetic retinopathy (DR) and to ascertain miRNAs associated with DR. Histopathologically, we observed characteristic features of DR in rats at 10 weeks after STZ injection. Investigation of miRNA expression profiles in the retinas of control and diabetic rats using miRNA microarrays revealed that many miRNAs were abnormally expressed in DR. On the basis of their fold changes and probability values, a total of 37 miRNAs were selected for further validation by real-time PCR analysis. The results showed that 11 miRNAs were significantly upregulated and 6 miRNAs were notably downregulated in DR. Furthermore, these changes in retinal miRNA expression levels paralleled the course of DR. Levels of miR-182, miR-96, miR-183, miR-211, miR-204, and miR-124 were significantly increased during the progress of DR, whereas miR-10b, miR-10a, miR-219-2-3p, miR-144, miR-338, and miR-199a-3p were significantly decreased. Our data indicate that the aberrant miRNA expression profiles in DR are associated with the development of DR. Modulation of retinal miRNA expression levels may provide a potential therapeutic strategy for DRs.

Annexin A2 promotes development of retinal neovascularization through PI3K/ AKT signaling pathway.

PURPOSE: Retinal Neovascularization (RNV) is a pathological characteristic of ocular diseases. Annexin A2 (ANXA2) plays important roles in RNV while the mechanism remains unclear. The study aimed to explore relationship between ANXA2 and PI3K/AKT signaling pathway in RNV. METHODS: We used human retinal vascular endothelial cells (HRECs) and oxygen-induced retinopathy (OIR) mice model to show ANXA2 can promote the development of RNV through PI3K/AKT signaling pathway. We divided HRECs into six groups by infecting lentivirus containing appropriate plasmid and adding corresponding solution. Assays showing ability of HRECs were performed in vitro. Mice were randomly divided into three groups and treated accordingly. RESULTS: Expression of ANXA2 and activity of PI3K/AKT signaling pathway in HRECs were detected. RNV and expression of ANXA2 in mice retinas were detected. Results showed that ANXA2 expression is positively related with RNV-forming ability of HRECs in vitro and development of RNV in vivo while low activity of PI3K/AKT signaling pathway could attenuate the role of ANXA2. CONCLUSIONS: We can make ANXA2 and PI3K/ AKT signaling pathway as a promising target for the regulation of pathological neovascularization of the retina, which also provides a novel idea for effective prevention and treatment of diseases related to RNV in future.

Nomogram model for predicting oculomotor nerve palsy in patients with intracranial aneurysm.

AIM: To explore the risk factors of oculomotor nerve palsy (ONP) in patients with intracranial aneurysm (IA) and develop a nomogram model for predicting ONP of IA patients. METHODS: A total of 329 IA patients were included. Logistic regression analysis was applied to identify independent factors, which were then integrated into the nomogram model. The performance of the nomogram model was evaluated by calibration curve, receiver operating curve (ROC), and decision curve analysis. RESULTS: Univariate and multivariate logistic regression analysis indicated posterior communicating artery (PCoA) aneurysm [hazard ratio (HR)=17.13, P<0.001] and aneurysm diameter (HR=1.31, P<0.001) were independent risk factors of ONP in IA patients. Based on the results of logistic regression analysis, a nomogram model for predicting the ONP in IA patients was constructed. The calibration curve indicated the nomogram had a good agreement between the predictions and observations. The nomogram showed a high predictive accuracy and discriminative ability with an area under the curve (AUC) of 0.863. The decision curve analysis showed that the nomogram was powerful in the clinical decision. PCoA aneurysm (HR=3.38, P=0.015) was identified to be the only independent risk factor for ONP severity. CONCLUSION: PCoA aneurysm and aneurysm diameter are independent risk factors of ONP in IA patients. The nomogram established is performed reliably and accurately for predicting ONP. PCoA aneurysm is the only independent risk factor for ONP severity.

Photodynamic therapy for primary tracheobronchial malignancy in Northwestern China.

BACKGROUND: Photodynamic therapy (PDT) has been routinely performed to treat tracheobronchial malignancy. However, the experience in tracheobronchial adenoid cystic carcinoma (ACC) and peripheral lung cancer is still insufficient. This study aimed to share the experience of PDT for patients with primary tracheobronchial malignancy, especially the adenoid cystic carcinoma and peripheral lung cancer, and evaluated the efficacy and safety of PDT in Northwestern Chinese patients. METHODS: This study retrospectively analyzed the clinical data of 23 patients with primary tracheobronchial malignancy receiving PDT in our center. The short-term effect was evaluated by the objective tumor response and the clinical response. The long-term effect was estimated by recurrence-free survival (RFS). RESULTS: Of 23 patients, SR was achieved in 18 patients and MR in 3 patients. The clinical symptoms and the quality of life were significantly improved after PDT (P<0.05). And the mean RFS was 8.9 ± 1.9 months. SR for 6 cases of ACC were achieved with significant improvement of clinical symptoms and quality of life. No procedure-related complications appeared. And PDT was successfully performed for the peripheral lung cancer with the guidance of electromagnetic navigation bronchoscopy (ENB). CONCLUSIONS: This study demonstrated that PDT achieved satisfactory efficacy and safety for Northwestern Chinese patients with primary tracheobronchial malignancy. Patients with ACC can benefit from PDT. And ENB-guided PDT is a novel and available option for the peripheral lung cancer. In short, this study accumulated valuable experience for the application of PDT in Chinese patients with primary tracheobronchial malignancy.

DNA Damage Repair in Brain Tumor Immunotherapy.

With the gradual understanding of tumor development, many tumor therapies have been invented and applied in clinical work, and immunotherapy has been widely concerned as an emerging hot topic in the last decade. It is worth noting that immunotherapy is nowadays applied under too harsh conditions, and many tumors are defined as "cold tumors" that are not sensitive to immunotherapy, and brain tumors are typical of them. However, there is much evidence that suggests a link between DNA damage repair mechanisms and immunotherapy. This may be a breakthrough for the application of immunotherapy in brain tumors. Therefore, in this review, first, we will describe the common pathways of DNA damage repair. Second, we will focus on immunotherapy and analyze the mechanisms of DNA damage repair involved in the immune process. Third, we will review biomarkers that have been or may be used to evaluate immunotherapy for brain tumors, such as TAMs, RPA, and other molecules that may provide a precursor assessment for the rational implementation of immunotherapy for brain tumors. Finally, we will discuss the rational combination of immunotherapy with other therapeutic approaches that have an impact on the DNA damage repair process in order to open new pathways for the application of immunotherapy in brain tumors, to maximize the effect of immunotherapy on DNA damage repair mechanisms, and to provide ideas and guidance for immunotherapy in brain tumors.

Neutrophil extracellular traps mediate the crosstalk between glioma progression and the tumor microenvironment via the HMGB1/RAGE/IL-8 axis.

Objective: Neutrophil extracellular traps (NETs) produced by tumor-infiltrating neutrophils (TINs) are associated with poor prognosis in patients with several types of cancer. However, the mechanisms underlying the involvement of NETs in glioma progression remain largely unknown. This study aimed to elucidate the roles of NETs in biological processes that drive the crosstalk between glioma progression and the tumor microenvironment. Methods: Neutrophil infiltration and NETs formation were investigated in glioma tissue through immunohistochemistry, and their relationships with clinicopathological features and outcomes were statistically evaluated. The effects of NETs on glioma cell progression were studied in a co-culture system. In vivo and in vitro experiments validated the reactive oxygen species activity and cytokine production of TINs, as well as the ERK signaling pathway activation and the metastasis of gliomas. Results: Neutrophil infiltration and NETs formation were induced in high-grade glioma compared with low-grade glioma. NETs induced by TINs were determined to be an oncogenic marker of high-grade gliomas and to be involved in cell proliferation and invasion. NETs overproduction promoted glioma cell proliferation, migration, and invasion. Furthermore, HMGB1 was found to bind to RAGE and activate the NF-κB signaling pathway in vitro. In addition, NETs stimulated the NF-κB signaling pathway, thus promoting IL-8 secretion in glioblastoma. Subsequently, IL-8 recruited neutrophils which in turn mediated NETs formation via the PI3K/AKT/ROS axis in TINs. Conclusions: Our results suggest that NETs produced by TINs mediate the crosstalk between glioma progression and the tumor microenvironment by regulating the HMGB1/RAGE/IL-8 axis. Targeting NETs formation or IL-8 secretion may be an effective approach to inhibit glioma progression.

Vascular endothelial growth factor upregulates expression of annexin A2 in vitro and in a mouse model of ischemic retinopathy.

PURPOSE: Annexin A2 has been shown to play a role in many neovascularization diseases. We investigated the effect of vascular endothelial growth factor (VEGF) on annexin A2 expression and related intracellular signaling mechanisms in a mouse model of ischemia-induced retinal neovascularization. METHODS: Annexin A2 expression and the effect of vascular endothelial growth factor (VEGF) on annexin A2 ex pression in retinal neovascularization were assayed by real-time PCR, western blot analysis. The effect of Annexin A2 on retinal neovascularization were assayed by siRNA interference and overexpression of Annexin A2, fluorescence imaging, and immunofluorescence histochemistry in a mouse model of ischemia-induced retinal neovascularization. RESULTS: Expression of annexin A2 mRNA and protein were increased in the mouse model of ischemia-induced retinal neovascularization and in RF/6A cells treated with VEGF. In RF/6A cells, increased expression of annexin A2 was inhibited by the VEGF receptor 2 (VEGFR2) inhibitor SU10944, and by anti-VEGFR2 neutralizing antibody, and was increased by VEGF. Mice with ischemic retinopathy showed increased expression of annexin A2 in vascular endothelial cells, and enhanced retinal neovascularization after intraocular injection of an adenoviral vector containing an annexin A2 expression cassette. Conversely, annexin A2 knockdown suppressed retinal neovascularization in these mice. CONCLUSIONS: These findings suggest that annexin A2 might induce retinal neovascularization through a VEGF-VEGFR2 pathway in ischemia-induced retina neovascularization. Therefore, annexin A2 is an angiogenesis activator and may be a potential target for the development of effective therapeutic strategies for the treatment of retinal neovascularization.