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Objectives: This study intends to appraise the feasibility of double sleeve lobectomy after neoadjuvant chemotherapy in central non-small-cell lung cancer with bronchovascular aggression., Methods: This retrospective study included non-small-cell lung cancer patients who received double sleeve lobectomy from January 2014 to June 2020. Patients were divided into 2 groups: the neoadjuvant chemotherapy group and the non-neoadjuvant chemotherapy group. Demographic data and perioperative outcomes were compared between these 2 groups., Results: Of the 110 patients who received double sleeve lobectomy during this period, 35 patients (31.8%) received neoadjuvant chemotherapy. Compared with the non-neoadjuvant chemotherapy group, patients who received neoadjuvant chemotherapy were associated with younger age (P = 0.026), smaller pathologic tumour size (P = 0.005), higher forced expiratory volume in 1 s (P = 0.007), higher forced expiratory volume in 1 s of predicted value (P = 0.005) and higher clinical stage (P < 0.001). In the neoadjuvant chemotherapy group, 18 patients (51.4%) attained a partial response and 17 patients (48.6%) achieved stable disease. The postoperative hospital stays (P = 0.042) and chest tube drainage duration (P = 0.030) were longer in the neoadjuvant chemotherapy group and other perioperative performances were similar between these 2 groups. No statistically significant difference was reported in postoperative complications and mortality between these 2 groups., Conclusions: The intraoperative performance and postoperative outcomes of double sleeve lobectomy following neoadjuvant chemotherapy were similar to direct surgery, indicating that double sleeve lobectomy after neoadjuvant chemotherapy is feasible and safe in central lung cancer involving both the pulmonary artery and bronchus., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Aberrant activation of stimulator of interferon genes (STING) is tightly associated with multiple types of disease, including cancer, infection, and autoimmune diseases. However, the development of STING modulators for the therapy of STING-related diseases is still an unmet clinical need. We employed a high-throughput screening approach based on the interaction of small-molecule chemical compounds with recombinant STING protein to identify functional STING modulators. Intriguingly, the cyclin-dependent protein kinase (CDK) inhibitor Palbociclib was found to directly bind STING and inhibit its activation in both mouse and human cells. Mechanistically, Palbociclib targets Y167 of STING to block its dimerization, its binding with cyclic dinucleotides, and its trafficking. Importantly, Palbociclib alleviates autoimmune disease features induced by dextran sulphate sodium or genetic ablation of three prime repair exonuclease 1 (Trex1) in mice in a STING-dependent manner. Our work identifies Palbociclib as a novel pharmacological inhibitor of STING that abrogates its homodimerization and provides a basis for the fast repurposing of this Food and Drug Administration-approved drug for the therapy of autoinflammatory diseases., (© 2022 The Authors.)

Background: Occupational exposure seriously threatens the physical and mental health of professionals and has become an important public health problem. In clinical medical and nursing work, medical staff, especially nursing staff, are faced with the status quo of occupational exposure with high risk, serious harm, and severe situation. Therefore, a sound management system must be established to control the occupational exposure of nurses., Aims: According to the PRECEDE management model, evaluate the operating room nurses' knowledge, belief, and behavior scores on the protection of surgical smoke, understand their awareness of surgical smoke and the current status of protection, improve the mastery rate and protection compliance of surgical smoke-related knowledge in the operating room, reduce the harm of surgical smoke to the human body, and provide a basis for smoke protection. Materials and methods . 125 doctors working in the operating room of our hospital were selected as the control group of this study, and 112 nonsmoke-exposed nurses working in the operating room of our hospital were selected as the observation group. The nurses' knowledge-belief behavior scores and self-evaluation scores of smoke influence were counted before and after the intervention in the operating room. SPSS25.0 was used to process the data. Tests and repeated measures analysis of variance were used to compare the effects before and after intervention., Results: After one month of intervention, the knowledge scores of nurses in the operating room on the protection of surgical smoke increased significantly, and the difference was significant ( P < 0.05); the scores of related concepts, physical properties, chemical properties, and authoritative protection standards increased significantly ( P < 0.05). There was no significant increase in the scores of smoke hazards ( P > 0.05); the attitude of smoke protection increased significantly, which was statistically significant ( P < 0.05); and the behavior compliance of smoke protection was significantly increased, which was statistically significant ( P < 0.05). After one month of intervention, the self-evaluation score of smoke effect of operating room nurses decreased significantly, and the difference was statistically significant ( P < 0.05). The data was analyzed by repeated measure analysis of variance. The knowledge of surgical smoke ( F = 65.570, P < 0.001), attitude ( F = 78.307, P < 0.001), and behavior ( F = 403.015, P < 0.001) scores gradually increased. The observation group's total cholesterol, low-density lipoprotein cholesterol, and the proportion of low-density lipoprotein cholesterol were higher than that of the control group, and the proportion of high-density lipoprotein cholesterol was lower than that of the control group. The difference was statistically significant P < 0.05., Conclusion: After the intervention of operating room nurses under the guidance of PRECEDE management mode, the theoretical knowledge of operating room nurses is effectively improved, the operations are standardized, the self-evaluation scores of smoke influence are reduced, and the safety level of operating room is improved. More importantly, the health of nursing staff is fully guaranteed., Competing Interests: There are no conflicts of interest., (Copyright © 2022 Hong Ye et al.)

Stem cell spheroids are advanced building blocks to produce chondroid. However, the multi-step operations including spheroids preparation, collection and transfer, the following 3D printing and shaping limit their application in 3D printing. The present study fabricates an 'ALL-IN-ONE' bioink based on granular hydrogel to not only produce adipose derived stem cell (ASC) spheroids, but also realize the further combination of chondrocytes and the subsequent 3D printing. Microgels (6-10 μ m) grafted with β-cyclodextrin (β-CD) (MG β-CD ) were assembled and crosslinked by in-situ polymerized poly (N-isopropylacrylamide) (PNIPAm) to form bulk granular hydrogel. The host-guest action between β-CD of microgels and PNIPAm endows the hydrogel with stable, shear-thinning and self-healing properties. After creating caves, ASCs aggregate spontaneously to form numerous spheroids with diameter of 100-200 μ m inside the hydrogel. The thermosensitive porous granular hydrogel exhibits volume change under different temperature, realizing further adsorbing chondrocytes. Then, the granular hydrogel carrying ASC spheroids and chondrocytes is extruded by 3D printer at room temperature to form a tube, which can shrink at cell culture temperature to enhance the resolution. The subsequent ASC spheroids/chondrocytes co-culture forms cartilage-like tissue at 21 d in vitro , which further matures subcutaneously in vivo , indicating the application potential of the fully synthetic granular hydrogel ink toward organoid culture., (© 2022 IOP Publishing Ltd.)

Background: This study evaluated the efficacy of bronchial sleeve lobectomy with pulmonary arterioplasty compared with pneumonectomy in centrally located non-small cell lung cancer with bronchovascular invasion., Methods: The cohort consisted of 212 patients receiving pneumonectomy and 156 patients undergoing bronchial sleeve lobectomy with pulmonary arterioplasty. Propensity score matching was used to create a fully balanced cohort, after which, baseline characteristics, perioperative performance, and oncologic results were compared between the 2 groups., Results: A total of 139 pneumonectomy patients were matched with 139 sleeve lobectomy patients. In the matched cohort, bronchial sleeve lobectomy with pulmonary arterioplasty was associated with longer operative time (P < .001), decreased perioperative transfusion rate (P = .002), shorter postoperative hospital stays (P < .001), shorter intensive care unit stays (P = .040), and lower Clavien-Dindo Classification (P = .016). In respect to survival outcomes, a log-rank test revealed no significant difference in overall survival (P = .381) and recurrence-free survival (P = .619) between the 2 surgical procedures., Conclusions: Bronchial sleeve lobectomy with pulmonary arterioplasty could achieve superior perioperative outcomes and equivalent oncologic efficacy compared with pneumonectomy, indicating that this complex procedure is safe and reliable for centrally located non-small cell lung cancer concurrently involving the pulmonary artery and bronchus., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The shelterin protein complex is required for telomere protection in various eukaryotic organisms. In mammals, the shelterin subunit TRF2 is specialized in preventing ATM activation at telomeres and chromosome end fusion in somatic cells. Here, we demonstrate that the zebrafish ortholog of TRF2 (encoded by the terfa gene) is protecting against unwanted ATM activation genome-wide. The terfa-compromised fish develop a prominent and specific embryonic neurodevelopmental failure. The heterozygous fish survive to adulthood but exhibit a premature aging phenotype. The recovery from embryonic neurodevelopmental failure requires both ATM inhibition and transcriptional complementation of neural genes. Furthermore, restoring the expression of TRF2 in glial cells rescues the embryonic neurodevelopment phenotype. These results indicate that the shelterin subunit TRF2 evolved in zebrafish as a general factor of genome maintenance and transcriptional regulation that is required for proper neurodevelopment and normal aging. These findings uncover how TRF2 links development to aging by separate functions in gene expression regulation and genome stability control., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Group 2 innate lymphoid cells (ILC2s) are highly heterogeneous tissue-resident lymphocytes that regulate inflammation and tissue homeostasis in health and disease. However, how these cells integrate into the tissue microenvironment to perform tissue-specific functions is unclear. Here, we show neuropilin-1 (Nrp1), which is induced postnatally and sustained by lung-derived transforming growth factor beta-1 (TGFβ1), is a tissue-specific marker of lung ILC2s. Genetic ablation or pharmacological inhibition of Nrp1 suppresses IL-5 and IL-13 production by ILC2s and protects mice from the development of pulmonary fibrosis. Mechanistically, TGFβ1-Nrp1 signaling enhances ILC2 function and type 2 immunity by upregulating IL-33 receptor ST2 expression. These findings identify Nrp1 as a tissue-specific regulator of lung-resident ILC2s and highlight Nrp1 as a potential therapeutic target for pulmonary fibrosis., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: To investigate the potential factors affecting methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in patients with human immunodeficiency virus (HIV) infection., Methods: A systematic search of publications listed in electronic from inception up to August 2020 was conducted. A random-effects model was used to calculate odds ratio (OR) with 95% confidence interval (CI)., Results: A total of 31 studies reporting 1410 MRSA events in 17 427 patients with HIV infection were included. Previous hospitalization (OR 1.80; 95% CI 1.37, 2.36), previous antibiotic therapy (OR 2.69; 95% CI 2.09, 3.45), CD4+ count (OR 1.79; 95% CI 1.41, 2.28), Centers for Disease Control and Prevention classification of stage C (OR 2.66; 95% CI 1.80, 3.93), skin lesions (OR 2.02; 95% CI 1.15, 3.55), intravenous device use (OR 2.61; 95% CI 1.59, 4.29) and an MRSA colonization history (OR 6.30; 95% CI 2.50, 15.90) were significantly associated with an increased risk of MRSA colonization and infection. Antiretroviral therapy (OR 0.71; 95% CI 0.50, 0.99) and current antibiotic use (OR 0.13; 95% CI 0.05, 0.32) were significantly associated with a reduced risk of MRSA colonization and infection., Conclusion: MRSA colonization and infection in HIV-infected patients is associated with a number of risk factors.

Objective: In this study, we investigated that the effects and possible mechanisms of the α7 nAChR subunit duplicate form (CHRFAM7A) affected inflammation in the model of intracranial infection., Methods: Mice of the model group were injected (intracranial injection) with Staphylococcus aureus. Mouse microglial BV2 cell was exposed with 200 ng of LPS for 4 h., Results: CHRFAM7A mRNA expressions were reduced in patients with intracranial infection. CHRFAM7A mRNA and protein expressions were suppressed in mice with intracranial infection in a time-dependent manner. CHRFAM7A reduced inflammation in mice with intracranial infection. The inhibition of CHRFAM7A reduced inflammation in mice with intracranial infection. CHRFAM7A suppressed p38 MAPK in mice with intracranial infection. The inhibition of p38 MAPK shows the effects of CHRFAM7A in intracranial infection., Conclusion: Our data demonstrate that the expression of the CHRFAM7A was down-regulated in patients with intracranial infection and reduced inflammation in in vitro model by p38 MAPK, which suggests the potential role of CHRFAM7A as a diagnostic biomarker for intracranial infection., (© 2022 S. Karger AG, Basel.)

Background: The P2Y12 receptor is a kind of purinoceptor that is engaged in platelet aggregation, and P2Y12 inhibitors have been used in clinical antithrombotic therapy. The P2Y12 receptor in microglia induces interleukin-1β (IL-1β) expression, which is a key mediator of depression in the brain. Although peripheral P2Y12 is involved in neuropathic pain, whether P2Y12 expression in the medial prefrontal cortex (mPFC) is associated with comorbidities of visceral pain and depression remains unclear. Accumulating evidence suggests that electroacupuncture (EA) is effective in treating inflammatory bowel disease (IBD), but its mechanism is unknown. This study aimed to determine whether P2Y12 expression in the mPFC is associated with comorbidities of visceral pain and depression in IBD and whether EA treats IBD by targeting the P2Y12 receptor., Methods: We used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced IBD mice. P2Y12 short hairpin RNA (shRNA) was stereotaxically injected into the bilateral mPFC. EA was performed on bilateral "Dachangshu" (BL25) acupoints once a day for 7 days. Von Frey filaments and colorectal distension were used to detect the mechanical pain threshold and visceral pain sensitivity. The sucrose preference test, tail suspension test and forced swimming test were used to evaluate depression in mice. Western blotting was used to test the expression of P2Y12 and IL-1β. Immunofluorescence staining was used to assess microglial activity., Results: We found that IBD mice presented visceral pain and depression associated with increased P2Y12 expression in the mPFC. P2Y12 shRNA significantly attenuated visceral pain and depression in IBD mice. P2Y12 shRNA significantly downregulated IL-1β expression and inhibited the activation of microglia in the mPFC of IBD mice. Meanwhile, EA played a similar role of P2Y12 shRNA. EA significantly downregulated P2Y12 expression, weakened the activation of microglia, and then inhibited IL-1β expression in the mPFC, thus relieving visceral pain and depression in IBD mice., Conclusion: The present study provided new ideas that the P2Y12 receptor in the mPFC could be a new target for the treatment of comorbid visceral pain and depression by EA. This may not only deepen our understanding of the analgesic and antidepressant mechanisms of EA but also promote the application of EA to treat IBD., (© 2021. The Author(s).)

Acquired resistance to growth factor receptor tyrosine kinase inhibitors limits the therapeutic benefits gained by EGFR-mutant lung adenocarcinoma (LUAD) patients treated with gefitinib. Circular RNAs (circRNAs) are novel noncoding RNAs implicated in the regulation of chemoresistance in malignancies. However, whether circRNAs participate in the development of EGFR-TKI resistance in LUAD remains to be clarified. Here, we report that circASK1 (hsa&#95;circ&#95;0007798) is significantly downregulated in gefitinib-resistant cells and enhances the gefitinib sensitivity of LUAD cells. Mechanistically, we identified a novel protein encoded by circASK1, ASK1-272a.a, which is essential for ASK1/JNK/p38 signaling activation and mediates the chemosensitivity-inducing effect of circASK1 in LUAD. Importantly, this novel isoform competes with ASK1 for binding to Akt1, therefore antagonizing Akt1-induced ASK1 phosphorylation and inactivation, leading to the activation of ASK1-induced apoptosis and alleviating gefitinib resistance. Moreover, increased YTHDF2-mediated endoribonucleolytic cleavage of m 6 A-modified circASK1 accounts for its downregulation in gefitinib-resistant cells. The clinical data and in vivo model further corroborated the suppressive effect of circASK1 and its encoded protein on gefitinib resistance. Our study provides a novel therapeutic target to overcome gefitinib resistance in LUAD patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Zebrafish is broadly used as a model organism in gene loss-of-function studies in vivo, but its employment in vitro is greatly limited by the lack of efficient gene knockdown approaches in zebrafish cell lines such as ZF4. In this article, we attempted to induce silencing of telomere associated genes in ZF4 by applying the frequently-used siRNA transfection technology and a novel moiety-linked morpholino (vivo-MO). By proceeding with integrated optimization of siRNAs transfection and vivo-MOs treatment, we compared five transfection reagents and vivo-MOs simultaneously to evaluate the efficiency of terfa silencing in ZF4. 48 h after siRNAs transfection, Lipofectamine™ 3000 and X-tremeGENE™ HP leaded to knockdown in 35% and 43% of terfa transcription, respectively, while vivo-MO-terfa modulated 58% down-expression of zfTRF2 in contrast to vivo-MO-ctrl 72 h after treatment. Further siRNAs transfection targeting telomere associated genes by X-tremeGENE™ HP showed silencing in 40-68% of these genes without significant cytotoxicity and off-target effect. Our results confirmed the feasibility of gene loss-of-function studies in a zebrafish cell line, offered a systematic optimizing strategy to employ gene silencing experiments, and presented Lipofectamine™ 3000, X-tremeGENE™ HP and vivo-morpholinos as candidate gene silencing approaches for zebrafish in vitro gene loss-of-function studies. Successfully knockdown of shelterin genes further opened a new field for telomeric study in zebrafish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: To evaluate the prognosis between patients with non-small cell lung cancer (NSCLC) invading difference depth of chest wall and estimate the impact of rib invasion on the pathological T classifications (pT)., Methods: We retrospectively evaluated 521 patients with resected pT3-4 NSCLC. Propensity-score matching (PSM) balanced the known confounders of the prognosis, resulting in two sets (rib invasion vs the pT3 and pT4 group). Recurrence-free survival (RFS) and Overall survival (OS) was assessed by Cox regression and Kaplan-Meier methods. Time-dependent receiver operating characteristic (ROC) curves were used to assess the additional benefit for survival prediction after reclassifying rib invasion cases., Results: Chest wall invasion occurred in 171 patients (62 rib invasion, 51 parietal pleural invasion [PL3] and 58 soft tissue invasion). Rib invasion was found to be an independent prognostic factor for both RFS (p = 0.006) and OS (p < 0.001) of pT3-4 NSCLC. The survival of rib invasion group was the worst (RFS: 13.1%; OS: 19.8%), followed by PL3 (RFS: 34.2%, P = 0.001; OS: 48.8%; p < 0.001) and the soft tissue invasion group (RFS: 40.6%, p = 0.001; OS: 57.7%, p < 0.001). Besides, the prognosis of rib invasion group was also found to be worse than those of pT3 (RFS: p < 0.001; OS: p < 0.001) and pT4 group (RFS: p = 0.002; OS: p < 0.001). After PSM, the 5-year RFS rate of rib invasion group were still lower than that of pT3 and pT4 group (p < 0.001); the 5-year OS rate of rib invasion was similar with that of pT4 group (p = 0.066) but lower than that of pT3 group (p = 0.014). The time-dependent ROC curves demonstrated that reclassifying rib invasion as pT4 disease provided an additional benefit for survival prediction (p < 0.001)., Conclusion: The rib invasion group had a worse prognosis than the PL3 and pT3 groups. The prognostic impact of rib invasion should be further validated as a pT4 disease in the TNM classification., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Surgical resection plays an essential role in the treatment of Pulmonary Tuberculosis (PTB). There are few reports comparing lobectomy and sublobectomy for pulmonary TB with cavity. To compare the advantages between lobectomy and sublobectomy for localized cavitory PTB, we performed a single-institution cross sectional cohort study of the surgical patients., Methods: We consecutively included 203 patients undergoing lobectomy or sublobectomy surgery for localized cavitary PTB. All patients were followed up, recorded and compared their surgical complication, outcome and associated characteristics., Results: Both groups had similar outcomes after follow up for 13.1 ± 12.1 months, however, sublobectomy group suffered fewer intraoperative blood losses, shorter length of stay, and fewer operative complications than lobectomy group (P <  0.05). Both groups obtained satisfactory outcome with postoperatively medicated for similar period of time and few relapse (P > 0.05)., Conclusion: Both sublobectomy and lobectomy resection were effective ways for cavitary PTB with surgical indications. If adequate anti-TB chemotherapy had been guaranteed, sublobectomy is able to be recommended due to more lung parenchyma retain, faster recover, and fewer postoperative complications.

Electroacupuncture (EA) has been accepted to effectively relieve neuropathic pain. Current knowledge of its neural modulation mainly covers the spinal cord and subcortical nuclei, with little evidence from the cortical regions. Using in vivo two-photon imaging in mice with chronic constriction injury, we found that EA treatment systemically modulated the Ca 2+ activity of neural circuits in the primary somatosensory cortex, including the suppression of excitatory pyramidal neurons, potentiation of GABAergic somatostatin-positive interneurons, and suppression of vasoactive intestinal peptide-positive interneurons. Furthermore, EA-mediated alleviation of pain hypersensitivity and cortical modulation were dependent on the activation of endocannabinoid receptor 1. These findings collectively reveal a cortical circuit involved in relieving mechanical or thermal hypersensitivity under neuropathic pain and identify one molecular pathway directing analgesic effects of EA., Competing Interests: The authors declare no conflict of interests., (© 2021 The Authors.)

Non-small cell lung cancer (NSCLC) represents for approximately 85% of all lung cancers, which is the most common cancer worldwide. Tumor-associated macrophages (TAM) are crucial for tumor progression, which was widely believed to be mediated by long non-coding RNAs (LncRNAs). We aimed to explore the effect of one LncRNA, GNAS-AS1, in TAM-associated NSCLC progression. Relative mRNA levels were determined by qRT-PCR. Western blot and ELISA were used to detect protein levels. Proliferation in vitro was assessed by MTT and clone formation assays. Migration and invasion of cell lines were evaluated by transwell-based assays. Interaction between molecules was detected by luciferase report assay. GNAS-AS1 expression was dramatically enhanced in TAM, NSCLC cell lines, and clinical tumor tissues, and negatively correlated with overall survival of NSCLC patients. GNAS-AS1 promoted macrophage M2 polarization and NSCLC cell progression via directly inhibiting miR-4319, which could target N-terminal EF-hand calcium binding protein 3 (NECAB3) to inhibit its expression. GNAS-AS1/miR-4319/NECAB3 axis promotes tumor progression of NSCLC by altering macrophage polarization. This novel mechanism may provide potential strategy for NSCLC treatment.

Objective: Nutritional factors such as extensively hydrolyzed casein (eHC) have been proposed to exert anti-inflammatory activity and affect clinical outcomes such as tolerance development in cow's milk allergy. Granzyme B (GrB) induces apoptosis in target cells and also controls the inflammatory response. Whether eHC could affect the activity of granzyme B and play a role in GrB-mediated inflammatory responses in vitro was unknown., Methods: The activity of GrB was measured using the substrate Ac-IEPD-pNA. Inflammatory responses were induced with GrB in HCT-8 and THP-1 cells, and pro-inflammatory cytokines were determined at the transcriptional and protein level., Results: GrB could induce the expression of IL-1β in HCT-8 cells, and IL-8 and MCP-1 in THP-1 cells, respectively. Interestingly, GrB acted synergistically on LPS-induced inflammation in HCT-8 cells and eHC reduced pro-inflammatory responses in both GrB and LPS-mediated inflammation. Further analyses revealed that eHC could inhibit the biological activities and cytotoxic activities of GrB and then could reduce GrB-mediated inflammatory response., Conclusion: The results from the current study suggest that anti-inflammatory activity of extensively hydrolyzed casein is, to a certain extent, mediated through modulation of granzyme B activity and responses.

To investigate the involvement of peripheral adenosine receptors in the effect of electroacupuncture (EA) on visceral pain in mice with inflammatory bowel disease (IBD). 2,4,6-Trinitrobenzene sulfonic acid (TNBS) was used to induce the visceral pain model. EA (1 mA, 2 Hz, 30 min) treatment was applied to bilateral acupoints "Dachangshu" (BL25) 1 day after TNBS injection once daily for 7 consecutive days. Von Frey filaments were used to measure the mechanical pain threshold. Western blot was used to detect the protein expression levels of adenosine 1 receptor (A1R), adenosine 2a receptor (A2aR), adenosine 2b receptor (A2bR), adenosine 3 receptor (A3R), substance P (SP), and interleukin 1 beta (IL-1β) in colon tissue. EA significantly ameliorated the disease-related indices and reduced the expression of SP and IL-1β in the colon tissues of mice with IBD. EA increased the expression of A1R, A2aR, and A3R and decreased the expression of A2bR in the colon tissue. Furthermore, the administration of adenosine receptor antagonists influenced the effect of EA. EA can inhibit the expression of the inflammatory factors SP and IL-1β by regulating peripheral A1, A2a, A2b, and A3 receptors, thus inhibiting visceral pain in IBD mice.

Long noncoding RNAs (lncRNAs) played in authentic biological cell roles such as cell apoptosis, cycle, differentiation, development, migration and invasion. However, the expression pattern and function of a new lncRNA LINC01296 in non-small cell lung cancer (NSCLC) are unknown and need to be studied. In our study, we indicate that the expression of LINC01296 was overexpressed in NSCLC samples compared to adjacent non-tumor tissues. Ectopic expression of LINC01296 promoted NSCLC cell proliferation and migration. Moreover, we demonstrated that LINC01296 has a potential binding site for miR-5095 by using online program tool StarBase. Overexpression of LINC01296 inhibited the expression of miR-5095 in the A549 cell. Furthermore, the miR-5095 expression was downregulated in the NSCLC tissues than in the adjacent non-tumor tissues. In addition, we found that there is a negative correlation between miR-5095 expression and LINC01296 level in the NSCLC tissues. Overexpression of miR-5095 suppressed NSCLC cell proliferation and migration. Finally, we demonstrate that ectopic expression of LINC01296 promoted cell proliferation and migration via inhibiting miR-5095 expression. These results suggested that LINC01296 might act a role as an oncogene in the tumorigenesis and development of NSCLC., Competing Interests: None.

There has been growing interest in extending the coverage of ground particulate matter with aerodynamic diameter ≤ 2.5 μm (PM 2.5 ) monitoring networks based on satellite remote sensing data. With broad spatial and temporal coverage, a satellite-based monitoring network has a strong potential to complement the ground monitor system in terms of the spatiotemporal availability of the air quality data. However, most existing calibration models focus on a relatively small spatial domain and cannot be generalized to a national study. In this paper, we proposed a statistically reliable and interpretable national modeling framework based on Bayesian downscaling methods to be applied to the calibration of the daily ground PM 2.5 concentrations across the conterminous United States using satellite-retrieved aerosol optical depth (AOD) and other ancillary predictors in 2011. Our approach flexibly models the PM 2.5 versus AOD and the potential related geographical factors varying across the climate regions and yields spatial- and temporal-specific parameters to enhance model interpretability. Moreover, our model accurately predicted the national PM 2.5 with an R ² at 70% and generated reliable annual and seasonal PM 2.5 concentration maps with its SD. Overall, this modeling framework can be applied to national-scale PM 2.5 exposure assessments and can also quantify the prediction errors.

Our aim is to estimate associations between acute increases in particulate matter with diameter of 2.5 µm or less (PM 2.5 ) concentrations and risk of infant bronchiolitis and otitis media among Massachusetts births born 2001 through 2008.Our case-crossover study included 20,017 infant bronchiolitis and 42,336 otitis media clinical encounter visits. PM 2.5 was modeled using satellite, remote sensing, meteorological and land use data. We applied conditional logistic regression to estimate odds ratios (ORs) and confidence intervals (CIs) per 10-µg/m 3 increase in PM 2.5. We assessed effect modification to determine the most susceptible subgroups. Infant bronchiolitis risk was elevated for PM 2.5 exposure 1 day (OR = 1.07, 95% CI = 1.03-1.11) and 4 days (OR = 1.04, 95% CI = 0.99-1.08) prior to clinical encounter, but not 7 days. Non-significant associations with otitis media varied depending on lag. Preterm infants were at substantially increased risk of bronchiolitis 1 day prior to clinical encounter (OR = 1.17, 95% CI = 1.08-1.28) and otitis media 4 and 7 days prior to clinical encounter (OR = 1.09, 95% CI = 1.02-1.16 and OR = 1.08, 95% CI = 1.02-1.15, respectively). In conclusion, preterm infants are most susceptible to infant bronchiolitis and otitis media associated with acute PM 2.5 exposures.

After publication of the article [1], it was brought to our attention that a number in Table 1 is incorrect.

Background: Associations between ambient particulate matter < 2.5 μm (PM 2.5 ) and asthma morbidity have been suggested in previous epidemiologic studies but results are inconsistent for areas with lower PM 2.5 levels. We estimated the associations between early-life short-term PM 2.5 exposure and the risk of asthma or wheeze clinical encounters among Massachusetts children in the innovative Pregnancy to Early Life Longitudinal (PELL) cohort data linkage system., Methods: We used a semi-bidirectional case-crossover study design with short-term exposure lags for asthma exacerbation using data from the PELL system. Cases included children up to 9 years of age who had a hospitalization, observational stay, or emergency department visit for asthma or wheeze between January 2001 and September 2009 (n = 33,387). Daily PM 2.5 concentrations were estimated at a 4-km resolution using satellite remote sensing, land use, and meteorological data. We applied conditional logistic regression models to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI). We also stratified by potential effect modifiers., Results: The median PM 2.5 concentration among participants was 7.8 μg/m 3 with an interquartile range of 5.9 μg/m 3 . Overall, associations between PM 2.5 exposure and asthma clinical encounters among children at lags 0, 1 and 2 were close to the null value of OR = 1.0. Evidence of effect modification was observed by birthweight for lags 0, 1 and 2 (p < 0.05), and season of clinical encounter for lags 0 and 1 (p < 0.05). Children with low birthweight (LBW) (< 2500 g) had increased odds of having an asthma clinical encounter due to higher PM 2.5 exposure for lag 1 (OR: 1.08 per interquartile range (IQR) increase in PM 2.5 ; 95% CI: 1.01, 1.15)., Conclusion: Asthma or wheeze exacerbations among LBW children were associated with short-term increases in PM 2.5 concentrations at low levels in Massachusetts.

Satellite-retrieved aerosol optical properties have been extensively used to estimate ground-level fine particulate matter (PM 2.5 ) concentrations in support of air pollution health effects research and air quality assessment at the urban to global scales. However, a large proportion, ~70%, of satellite observations of aerosols are missing as a result of cloud-cover, surface brightness, and snow-cover. The resulting PM 2.5 estimates could therefore be biased due to this non-random data missingness. Cloud-cover in particular has the potential to impact ground-level PM 2.5 concentrations through complex chemical and physical processes. We developed a series of statistical models using the Multi-Angle Implementation of Atmospheric Correction (MAIAC) aerosol product at 1 km resolution with information from the MODIS cloud product and meteorological information to investigate the extent to which cloud parameters and associated meteorological conditions impact ground-level aerosols at two urban sites in the US: Atlanta and San Francisco. We find that changes in temperature, wind speed, relative humidity, planetary boundary layer height, convective available potential energy, precipitation, cloud effective radius, cloud optical depth, and cloud emissivity are associated with changes in PM 2.5 concentration and composition, and the changes differ by overpass time and cloud phase as well as between the San Francisco and Atlanta sites. A case-study at the San Francisco site confirmed that accounting for cloud-cover and associated meteorological conditions could substantially alter the spatial distribution of monthly ground-level PM 2.5 concentrations., Competing Interests: The authors declare no conflict of interest.

Objectives  Whether pneumonectomy is needed for the treatment of destroyed lungs is still controversial and unresolved in the clinic. Pneumonectomy is destructive and is associated with a significant incidence of postoperative complications. The purpose of this study is to analyze the operative techniques, postoperative morbidity, mortality, and long-term outcomes of patients with destroyed lungs who underwent pneumonectomy. Patients and Methods  We retrospectively analyzed 137 patients with destroyed lungs who underwent pneumonectomy. The data were queried for the details of operative technique, development of perioperative complications, mortality, and long-term survival. Univariate and multivariate analyses were performed to investigate the risk factors of pneumonectomy among the patients. Results  A total of 77 male and 60 female patients were reviewed. The youngest patient was 18 years, and the oldest was 75 years, with a mean age of 40.1 years. Postoperative complications were observed in 25 patients (18.2%). The rate of bronchopleural fistula (BPF) was 5.1% (7/137). Two perioperative deaths (1.5%) were noted. Univariate and multivariate analyses indicated the blood loss (hazard ratio [HR], 5.32; 95% confidence interval [CI], 1.27-18.50; p  = 0.021) was the independent risk factor of postoperative complications, and the type of the disease (HR, 4.50; 95% CI, 1.19-9.69; p  = 0.034) was the independent risk factor of the BPF, for the patients with destroyed lung after pneumonectomy. Conclusion  Pneumonectomy for destroyed lung is a high risk for postoperative complications. Our findings suggested that pneumonectomy in destroyed lung was satisfactory with strict surgical indications, adequate preoperative preparation, and careful operative technique, and the long-term outcomes can be especially satisfactory. Pneumonectomy for destroyed lung is still a treatment option., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated demyelination and degeneration of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is the preferential experimental rodent model for MS. Previous study demonstrated histamine H3 receptor (H3R) was an important factor in pathophysiology of EAE and immethridine was the most selective agonist of H3R. However, whether immethridine has therapeutic effect on EAE and its mechanism remained to be defined. Here we constructed EAE mouse model by immunization of MOG 35-55 peptides with complete Freund's adjuvant, immethridine was used to treat EAE and its therapeutic effect was evaluated. The results showed that the treatment of immethridine could alleviate EAE. The percentage of Th1 and Th17 in the spleen from the treated EAE mice decreased and the surface molecules such as CD40, CD86 or MHCII on dendritic cells (DCs) were also down-regulated. To understand the effect of immethridine on DCs, bone marrow-derived DCs were prepared and the immunological functions were analyzed. The data demonstrated that immethridine could change the expression profiles of cytokines in DCs and inhibit the expression of the co-stimulatory molecules such as CD40 and CD86. Furthermore, immethridine also inhibited the antigen-presenting function of DCs and T cell differentiation induced by DCs. Signaling pathway analysis demonstrated that the phosphorylation of NF-κB p65 but not ERK1/2 in DCs was inhibited after the treatment of immethridine. These data strongly suggested that immethridine could inhibit the function of DCs and indicated the therapeutic potential on EAE., Competing Interests: CONFLICTS OF INTEREST The authors have no financial conflicts of interest.

Chronic particulate matter less than 2.5μm in diameter (PM 2.5 ) exposure can leave infants more susceptible to illness. Our objective is to estimate associations of the chronic PM 2.5 exposure with infant bronchiolitis and otitis media (OM) clinical encounters. We obtained all first time bronchiolitis (n=18,029) and OM (n=40,042) clinical encounters among children less than 12 and 36 months of age, respectively, diagnosed from 2001 to 2009 and two controls per case matched on birthdate and gestational age from the Pregnancy to Early Life Longitudinal data linkage system in Massachusetts. We applied conditional logistic regression to estimate odds ratios (OR) and confidence intervals (CI) per 2-μg/m 3 increase in lifetime average satellite based PM 2.5 exposure . Effect modification was assessed by age, gestational age, frequency of clinical encounter, and income. We examined associations between residential distance to roadways, traffic density, and infant bronchiolitis and OM risk. PM 2.5 was not associated with infant bronchiolitis (OR=1.02, 95% CI=1.00, 1.04) and inversely associated with OM (OR=0.97, 95% CI=0.95, 0.99). There was no evidence of effect modification. Compared to infants living near low traffic density, infants residing in high traffic density had elevated risk of bronchiolitis (OR=1.23, 95% CI=1.14, 1.31) but not OM (OR=0.98, 95% CI=0.93, 1.02) clinical encounter. We did not find strong evidence to support an association between early-life long-term PM 2.5 exposure and infant bronchiolitis or OM. Bronchiolitis risk was increased among infants living near high traffic density., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Tissue-engineered trachea provides a promising approach for reconstruction of long segmental tracheal defects. However, a lack of ideal biodegradable scaffolds greatly restricts its clinical translation. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration owing to natural tubular structure, cartilage matrix components, and biodegradability. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. To address these problems, a laser micropore technique (LMT) was applied in the current study to modify trachea sample porosity to facilitate decellular treatment and cell ingrowth. Decellularization processing demonstrated that cells in LMT treated samples were more easily removed compared with untreated native trachea. Furthermore, after optimizing the protocols of LMT and decellular treatments, the LMT-treated DTM (LDTM) could retain their original tubular shape with only mild extracellular matrix damage. After seeding with chondrocytes and culture in vitro for 8 weeks, the cell-LDTM constructs formed tubular cartilage with relatively homogenous cell distribution in both micropores and bilateral surfaces. In vivo results further confirmed that the constructs could form mature tubular cartilage with increased DNA and cartilage matrix contents, as well as enhanced mechanical strength, compared with native trachea. Collectively, these results indicate that LDTM is an ideal scaffold for tubular cartilage regeneration and, thus, provides a promising strategy for functional reconstruction of trachea cartilage., Statement of Significance: Lacking ideal biodegradable scaffolds greatly restricts development of tissue-engineered trachea. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. By laser micropore technique (LMT), the current study efficiently enhanced the porosity and decellularized efficacy of DTM. The LMT-treated DTM basically retained the original tubular shape with mild matrix damage. After chondrocyte seeding followed by in vitro culture and in vivo implantation, the constructs formed mature tubular cartilage with matrix content and mechanical strength similar to native trachea. The current study provides an ideal scaffold and a promising strategy for cartilage regeneration and functional reconstruction of trachea., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

To estimate PM 2.5 concentrations, many parametric regression models have been developed, while nonparametric machine learning algorithms are used less often and national-scale models are rare. In this paper, we develop a random forest model incorporating aerosol optical depth (AOD) data, meteorological fields, and land use variables to estimate daily 24 h averaged ground-level PM 2.5 concentrations over the conterminous United States in 2011. Random forests are an ensemble learning method that provides predictions with high accuracy and interpretability. Our results achieve an overall cross-validation (CV) R 2 value of 0.80. Mean prediction error (MPE) and root mean squared prediction error (RMSPE) for daily predictions are 1.78 and 2.83 μg/m 3 , respectively, indicating a good agreement between CV predictions and observations. The prediction accuracy of our model is similar to those reported in previous studies using neural networks or regression models on both national and regional scales. In addition, the incorporation of convolutional layers for land use terms and nearby PM 2.5 measurements increase CV R 2 by ∼0.02 and ∼0.06, respectively, indicating their significant contributions to prediction accuracy. A pair of different variable importance measures both indicate that the convolutional layer for nearby PM 2.5 measurements and AOD values are among the most-important predictor variables for the training process.

Dys-regulation of serine-arginine protein kinase 1 (SRPK1) has been reported in non-small cell lung cancer (NSCLC). However, its functions in the progression of NSCLC remain poorly understood. In this study, the expression of SRPK1 in NSCLC tissues was determined using real-time PCR, and the roles of SRPK1 in the progression of NSCLC were investigated. It was found that both the mRNA level and the protein level of SRPK1 were up-regulated in NSCLC tissues. Forced expression of SRPK1 promoted the growth and migration of NSCLC cells, while knocking down the expression of SRPK1 inhibited the growth, migration, and tumorigenicity of NSCLC cells. Mechanism studies showed that SRPK1 activated the transcriptional activity of beta-catenin/T-cell factor (TCF) complex, and knocking down the expression of SRPK1 attenuated the expression of target genes of beta-catenin/T-cell factor (TCF) complex. In addition, silencing the expression of SRPK1 down-regulated the phosphorylation of GSK3beta. Taken together, SRPK1 might play an oncogenic role in NSCLC, and SRPK1 might be a therapeutic target for NSCLC.

Exposures to particulate matter with diameter of 2.5µm or less (PM2.5) may influence risk of birth defects. We estimated associations between maternal exposure to prenatal traffic-related air pollution and risk of cardiac, orofacial, and neural tube defects among Massachusetts births conceived 2001 through 2008. Our analyses included 2729 cardiac, 255 neural tube, and 729 orofacial defects. We used satellite remote sensing, meteorological and land use data to assess PM2.5 and traffic-related exposures (distance to roads and traffic density) at geocoded birth addresses. We calculated adjusted odds ratios (OR) and confidence intervals (CI) using logistic regression models. Generalized additive models were used to assess spatial patterns of birth defect risk. There were positive but non-significant associations for a 10µg/m(3) increase in PM2.5 and perimembranous ventricular septal defects (OR=1.34, 95% CI: 0.98, 1.83), patent foramen ovale (OR=1.19, 95% CI: 0.92, 1.54) and patent ductus arteriosus (OR=1.20, 95% CI: 0.95, 1.62). There was a non-significant inverse association between PM2.5 and cleft lip with or without palate (OR=0.76, 95% CI: 0.50, 1.10), cleft palate only (OR=0.89, 95% CI: 0.54, 1.46) and neural tube defects (OR=0.77, 95% CI: 0.46, 1.05). Results for traffic related exposure were similar. Only ostium secundum atrial septal defects displayed significant spatial variation after accounting for known risk factors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Three decades of rapid economic development is causing severe and widespread PM2.5 (particulate matter ≤ 2.5 μm) pollution in China. However, research on the health impacts of PM2.5 exposure has been hindered by limited historical PM2.5 concentration data., Objectives: We estimated ambient PM2.5 concentrations from 2004 to 2013 in China at 0.1° resolution using the most recent satellite data and evaluated model performance with available ground observations., Methods: We developed a two-stage spatial statistical model using the Moderate Resolution Imaging Spectroradiometer (MODIS) Collection 6 aerosol optical depth (AOD) and assimilated meteorology, land use data, and PM2.5 concentrations from China's recently established ground monitoring network. An inverse variance weighting (IVW) approach was developed to combine MODIS Dark Target and Deep Blue AOD to optimize data coverage. We evaluated model-predicted PM2.5 concentrations from 2004 to early 2014 using ground observations., Results: The overall model cross-validation R(2) and relative prediction error were 0.79 and 35.6%, respectively. Validation beyond the model year (2013) indicated that it accurately predicted PM2.5 concentrations with little bias at the monthly (R(2) = 0.73, regression slope = 0.91) and seasonal (R(2) = 0.79, regression slope = 0.92) levels. Seasonal variations revealed that winter was the most polluted season and that summer was the cleanest season. Analysis of predicted PM2.5 levels showed a mean annual increase of 1.97 μg/m(3) between 2004 and 2007 and a decrease of 0.46 μg/m(3) between 2008 and 2013., Conclusions: Our satellite-driven model can provide reliable historical PM2.5 estimates in China at a resolution comparable to those used in epidemiologic studies on the health effects of long-term PM2.5 exposure in North America. This data source can potentially advance research on PM2.5 health effects in China.

Multiple studies have developed surface PM 2.5 (particle size less than 2.5 µm in aerodynamic diameter) prediction models using satellite-derived aerosol optical depth as the primary predictor and meteorological and land use variables as secondary variables. To our knowledge, satellite-retrieved fire information has not been used for PM 2.5 concentration prediction in statistical models. Fire data could be a useful predictor since fires are significant contributors of PM 2.5 . In this paper, we examined whether remotely sensed fire count data could improve PM 2.5 prediction accuracy in the southeastern U.S. in a spatial statistical model setting. A sensitivity analysis showed that when the radius of the buffer zone centered at each PM 2.5 monitoring site reached 75 km, fire count data generally have the greatest predictive power of PM 2.5 across the models considered. Cross validation (CV) generated an R 2 of 0.69, a mean prediction error of 2.75 µg/m 3 , and root-mean-square prediction errors (RMSPEs) of 4.29 µg/m 3 , indicating a good fit between the dependent and predictor variables. A comparison showed that the prediction accuracy was improved more substantially from the nonfire model to the fire model at sites with higher fire counts. With increasing fire counts, CV RMSPE decreased by values up to 1.5 µg/m 3 , exhibiting a maximum improvement of 13.4% in prediction accuracy. Fire count data were shown to have better performance in southern Georgia and in the spring season due to higher fire occurrence. Our findings indicate that fire count data provide a measurable improvement in PM 2.5 concentration estimation, especially in areas and seasons prone to fire events.

Objective: Tracheal stenosis can be life-threatening and has been seen with an increasing frequency., Methods: Metallic stent-associated stenosis remains a therapeutic challenge because of difficulty in tracheostomy., Results: Here, we report a case with repeated episodes of restenosis after insertion of metallic stents for benign tracheal stenosis which was successfully managed by Montgomery silicone T-tube placement., Conclusion: We further reviewed the literature of reported cases of inappropriate use of metallic stent for benign diseases., (Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

There has been a growing interest in the use of satellite-retrieved aerosol optical depth (AOD) to estimate ambient concentrations of PM2.5 (particulate matter <2.5 μm in aerodynamic diameter). With their broad spatial coverage, satellite data can increase the spatial-temporal availability of air quality data beyond ground monitoring measurements and potentially improve exposure assessment for population-based health studies. This paper describes a statistical downscaling approach that brings together (1) recent advances in PM2.5 land use regression models utilizing AOD and (2) statistical data fusion techniques for combining air quality data sets that have different spatial resolutions. Statistical downscaling assumes the associations between AOD and PM2.5 concentrations to be spatially and temporally dependent and offers two key advantages. First, it enables us to use gridded AOD data to predict PM2.5 concentrations at spatial point locations. Second, the unified hierarchical framework provides straightforward uncertainty quantification in the predicted PM2.5 concentrations. The proposed methodology is applied to a data set of daily AOD values in southeastern United States during the period 2003-2005. Via cross-validation experiments, our model had an out-of-sample prediction R(2) of 0.78 and a root mean-squared error (RMSE) of 3.61 μg/m(3) between observed and predicted daily PM2.5 concentrations. This corresponds to a 10% decrease in RMSE compared with the same land use regression model without AOD as a predictor. Prediction performances of spatial-temporal interpolations to locations and on days without monitoring PM2.5 measurements were also examined.