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Zhifeng Chen,1– 4,* Yulin Shang,5,* Binaya Wasti,6 Yanru Ou,1– 4 Subo Gong,7 Xudong Xiang,8 Ruoyun Ouyang1– 4 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, 410011, People’s Republic of China; 4Diagnosis and Treatment Center of Respiratory Disease in Hunan Province, Changsha, Hunan, 410011, People’s Republic of China; 5Ophthalmology and Otorhinolaryngology, Zigui Country Hospital of Traditional Chinese Medicine, Yichang, Hubei, 443600, People’s Republic of China; 6B & C Medical College, Teaching Hospital and Research Center, Birtamode, 57204, Nepal; 7Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 8Department of Emergency, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruoyun Ouyang, Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan, 410011, People’s Republic of China, Email ouyangruoyun@csu.edu.cnObjective: In the real clinical world, both surgery and medication are used to treat pulmonary aspergillosis (PA), but the prognosis of different treatments is unclear. The purpose of this study was to investigate the diagnosis and treatment, follow-up results and prognostic factors of PA patients in the real world, so as to deepen our understanding of PA and improve the prognosis of PA patients.Materials and Methods: Eligible patients with pathologically diagnosed PA (n = 125) were retrospectively enrolled and followed up. Further comparisons and subgroup analyses were performed between patients receiving surgical and nonsurgical treatments. Univariate and multivariate logistic regression analyses were used to investigate the factors associated with treatment failure.Results: A total of 125 patients with PA were included in the study. Of these, 49 (39.2%) received surgical treatment (25 of whom also received postoperative antifungal therapy), while 76 (60.8%) received antifungal therapy alone. The median age was 59 years (46.5– 67 years). Compared with the nonsurgical group, the surgical group had lower inflammatory cell counts and less inflammatory response, and higher hemoglobin and albumin levels. Multivariate logistic regression analysis showed that white blood cell (WBC) levels > 9.5× 109/L and C-reactive protein (CRP) levels > 8 mg/L were independent predictors linked to treatment failure.Conclusion: PA patients with severe inflammation and poor general health are usually treated with antifungal drugs only. Risk factors including elevated WBC levels and high CRP levels can help identify PA patients who may have a less favorable response to treatment at an early stage. It should be noted that increasing the dose and duration of antifungal therapy may improve patient prognosis.Keywords: pulmonary aspergillosis, antifungal treatment, surgery, treatment failure, prognosis

Zhifeng Chen,1– 4 Yulin Shang,5 Yanru Ou,1– 4 Li Zhou,1– 4 Ting Liu,1– 4 Subo Gong,6 Xudong Xiang,7 Yating Peng,1– 4 Ruoyun Ouyang1– 4 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan, 410011, People’s Republic of China; 4Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 5Ophthalmology and Otorhinolaryngology, Zigui Country Hospital of Traditional Chinese Medicine, Yichang, Hubei, 443600, People’s Republic of China; 6Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 7Department of Emergency, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaCorrespondence: Yating Peng; Ruoyun Ouyang, Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University 139 Middle Renmin Road, Changsha, Hunan, 410011, People’s Republic of China, Email pengyating2011@csu.edu.cn; ouyangruoyun@csu.edu.cnBackground: OSA can cause cognitive impairment (CI). The aim of this study was to investigate whether miR-20a-5p in exosomes derived from bEnd3 cells with IH mediates intercellular crosstalk and induces CI through hippocampal neuronal cell pyroptosis.Materials and Methods: BEnd3-derived exosomes were isolated from the normal oxygen control group (NC-EXOS) and IH group (IH-EXOS). In vitro, exosomes were cocultured with HT22 cells. Meanwhile, in vivo, exosomes were injected into mice via the caudal vein. The spatial memory ability of mice was tested by MWM method to evaluate the effect of exosomes on the cognitive function of mice. Adults diagnosed with OSA underwent the MoCA and ESS tests to assess cognitive function and daytime sleepiness. Spearman’s rank correlation analysis was used to evaluate the correlation between miR-20a-5p and candidate proteins and clinical parameters. Transfection using small interfering RNAs, miRNA mimics, and plasmids to evaluate the role of miR-20a-5p and its target genes. Dual luciferase reporter gene assay was used to confirm the binding of miR-20a-5p to its target gene.Results: IH could cause pyroptosis and inflammation in bEnd3 cells, and promote the expression of miR-20a-5p. Isolated IH-EXOS induced increased pyroptosis and activation of inflammatory response in vitro and in vivo, accompanied by increased expression of miR-20a-5p. In addition, IH-EXOS led to decreased learning and memory ability in mice. Interestingly, AHI was higher and MoCA scores were lower in severe OSA compared to healthy comparisons. In addition, miR-20a-5p and GSDMD were positively correlated with AHI but negatively correlated with MoCA in severe OSA. IH-induced exosomes were rich in miR-20a-5p, and these exosomes were found to deliver miR-20a-5p to HT22 cells, playing a key role in the induction of OSA-CI by directly targeting MFN2.Conclusion: Exosome miR-20a-5p from IH-stimulated bEnd3 cells can promote OSA-CI by increasing HT22 cells pyroptosis through its target MFN2.Keywords: exosome, OSA, cognitive impairment, miR-20a-5p, MFN2, GSDMD

Yating Peng,1– 3 Wei Cheng,1– 3 Jiaxi Duan,1– 3 Yiyang Zhao,1– 3 Zijing Zhou,1– 3 Aiyuan Zhou,1– 3 Minhua Deng,1– 4 Hong Peng,1– 3 Ruoyun Ouyang,1– 3 Yan Chen,1– 3 Ping Chen1– 3 1Department of Pulmonary and Critical Care Medicine, Second Xiang Ya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Institute of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Hunan Centre for Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, 410011, People’s Republic of China; 4Department of Respiratory, PLA Rocket Force Characteristic Medical Center, Beijing, 100088, People’s Republic of ChinaCorrespondence: Ping Chen, Email pingchen0731@csu.edu.cnBackground: Prohibitin has been identified to play roles in cell survival and apoptosis. Here, this study aimed to clarify the role of prohibitin in cigarette smoke extract (CSE)-induced endothelial cell apoptosis.Methods: The protein level of prohibitin was assessed by Western blot in lung tissues from emphysema and control mice. CSE-induced human pulmonary microvascular endothelial cells (hPMECs) were applied to mimic smoke-related cell apoptosis in vitro. Prohibitin was overexpressed in hPMECs with or without CSE. Mitochondrial function was analyzed by JC-1 staining and ATP assay kits. Oxidative stress was assessed by flow cytometry, fluorescence staining and immunocytochemistry. Apoptosis was analyzed by flow cytometry, Western blot and caspase-3 activity assays. In addition, the expression of inflammatory markers was assessed by Western blot and real-time polymerase chain reaction (PCR). The secretion of inflammatory cytokines was measured by ELISA.Results: Prohibitin was downregulated in emphysema mouse tissues compared with control experiments. Consistently, CSE inhibited both the protein and RNA levels of prohibitin in hPMECs in a dose-dependent manner. Gain-of-function experiments indicated that CSE induced collapse of mitochondrial membrane potential (MMP) and loss of ATP, while prohibitin improved mitochondrial function. CSE induced robust ROS production and oxidative DNA damage, while prohibitin decreased this damage. Upregulation of prohibitin protected the apoptosis of hPMECs from CSE. Overexpression of prohibitin significantly reduced the levels of the main proinflammatory cytokines. Finally, prohibitin inhibited nuclear factor-kappa B (NF-κB) p65 accumulation and IκBα degradation induced by CSE.Conclusion: The current findings suggest that CSE-mediated mitochondrial dysfunction, oxidative stress, cell apoptosis and inflammation in hPMECs were reduced by overexpression of prohibitin. We identified prohibitin as a novel regulator of endothelial cell apoptosis and survival in the context of CSE exposure.Keywords: prohibitin, hPMECs, CSE, apoptosis, mitochondrial, inflammation

Yating Peng,1– 3 Jiaxi Duan,1– 3 Xin Li,4 Yuqin Zeng,1– 3 Zijing Zhou,1– 3 Minghua Deng,1– 3,5 Ruoyun Ouyang,1– 3 Yan Chen,1– 3 Shan Cai,1– 3 Ping Chen1– 3 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Centre for Evidence-Based Medicine, Changsha, Hunan, People’s Republic of China; 4Division of Occupational Lung Disease, Hunan Prevention and Treatment Institute for Occupational Diseases, Changsha, Hunan, People’s Republic of China; 5Department of Respiratory, PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of ChinaCorrespondence: Ping Chen Email pingchen0731@csu.edu.cnBackground: Pneumoconiosis has high prevalence of chronic obstructive pulmonary disease (COPD), respiratory morbidity, and mortality.Objective: The aim of the present study was to examine patient characteristics and adherence to inhaled therapy among pneumoconiosis with COPD in a real-world clinical setting.Methods: A cohort of pneumoconiosis patients with COPD prescript with at least one type of long-acting inhaled drug was followed for adherence for 2 years. Demographic and COPD-related characteristics were collected in baseline.Results: In baseline, after adjusting for age, dust exposure duration positively correlated with number of acute exacerbation (AE) frequency in the last year. There were close associations among COPD Assessment Tool (CAT) score, modified Medical Research Council Dyspnea Scale (mMRC) grade, number of AE, and pre-FEV1 value. Of 296 participants originally recruited, 213 participants finished the 2-year follow-up for adherence. 122 (57.28%) were non-adherent to inhaled therapy. The most common reason for non-adherence was “relief of symptoms after short-term controller medication use” (53.28%). Patients who were non-adherent reported higher body mass index (BMI), less AE events in the last year, higher pre-FEV1 value, higher post-FEV1 value and low CAT, mMRC scores compared to adherent in baseline. High pre-FEV1 value (OR = 1.04, CI = 1.018– 1.064) and low mMRC scores (OR = 0.406, CI = 0.214– 0.771) were risk factors found associated with non-adherence.Conclusion: A majority of pneumoconiosis patients complicated with COPD have suboptimal inhaled therapy adherence. Evidence-based, adherence-enhancing interventions should be targeted on less severe subjects.Keywords: adherence, inhaled therapy, pneumoconiosis, COPD

We detected the expressions of hsa_circRNA_000121 and hsa_circRNA_ 004183 in papillary thyroid microcarcinoma (PTMC) and explored their relationship with the invasiveness of PTMC. PTMC patients with (n = 30; metastasis group) and without lymph node metastasis (n = 30; nonmetastasis group) were included. The levels of hsa_circRNA_000121, hsa_circRNA_004183, hsa-miR-4763, hsa-miR-6775, sarcoma gene (SRC), and MMP-14 were detected with real-time polymerase chain reaction. Receiver-operating characteristic (ROC) analyzed the diagnostic value of hsa_circRNA_000121 and hsa_circRNA_004183. Binary logistic regression analysis evaluated the relationship of gene expression with PTMC invasiveness. In PTMC tissue samples, compared with the metastasis group, the expression of hsa_circRNA_000121, hsa_circRNA_004183, SRC, and MMP-14 in the nonmetastasis group decreased, while the expression of hsa-miR-4763 and hsa-miR-6775 increased. In peripheral blood, compared with the metastasis group, the expression of hsa_circ_000121 and hsa_circRNA_004183 in the nonmetastasis group decreased. Both hsa_circRNA_000121 and hsa_circRNA_004183 had good sensitivity and specificity for diagnosing PTMC lymph node metastasis, with a cut-off value of 0.796 and 0.938, respectively. However, the gene expressions were not significantly associated with PTMC lymph node metastasis. Hsa_circRNA_000121 may upregulate SRC expression through hsa-miR-4763, while hsa_circRNA 000121 may upregulate MMP-14 expression through hsa-miR-6775, thereby promoting the aggressiveness of PTMC and ultimately leading to cervical lymph node metastasis. hsa_circRNA_000121 and hsa_circRNA_004183 may become potential biomarkers of PTMC aggressiveness.

The study of urban building combinations is necessary to achieve sustainable urban development, as through such a study we can better grasp the process of urban development and evolution, guide the direction of future urban development, optimize the urban ecological environment, and improve urban livability. With the acceleration of China's urbanization process, the development and evolution of building combinations in China's urban areas are also gaining momentum. Therefore, it is of tremendous practical use to explore the laws related to mixed developments in urban areas to guide rational urban planning and the study of urban microclimates. The analysis is an important foundation for the development of urban landscapes and provides important scientific support for the optimization of the urban ecological environment and the improvement of livability levels. From the data on individual buildings in Guangzhou in 2017, this paper determined basic building combinations in the main urban area using two indexes for building height and building spacing, identified building combinations on a wider scale using a hot-spot analysis, and analyzed the spatial distribution of building combinations and the influence of macro and micro factors. Nine building combinations were identified on the basis of average height and spacing of building convergence surface. As the basic units, the nine basic types were further divided into different combinations to form complex and diverse three-dimensional representations of buildings in the main urban area. Building convergence surface with a scale of hundreds of meters constitute the basic unit of building combination in the main urban area, and are dominated by mixed land use types. The basic types, mainly composed of high-rise buildings, played an obvious role in indicating land use with differences in combinations of each functional area. The basic types of main urban areas have prominent circle differentiation, but the laws for the different types differ. Land price was the core constraining factor for the decrease in urban building height and population density from the urban center to the periphery, as well as the background factor related to differences in urban building combinations. The influence of green spaces, the Pearl River, and the main road on the type, height, and density of the building combination at a micro level complicated building combinations.

As e-commerce has revolutionized the habits and methods of mass consumption, the reliance of the real economy on the Internet for advertising and marketing has become more and more pronounced, and this phenomenon has been exacerbated by the COVID-19 pandemic. Many municipal governments in China have introduced policies to encourage the development of nighttime economy as an important means to revive urban vitality, stimulate mass consumption and promote economic development. This essay takes four established nighttime economy gathering places in Guangzhou as examples, and studies the symbolic consumption process in them from the theoretical perspectives of cultural economy, leisure economy, symbolic economy and cultural capital, thus pointing out the problems of cultural change and cultural vulgarization in the nighttime economy neighborhoods and giving constructive solutions and suggestions for improvement.

Epigenetic modification may affect the expression of multiple inflammatory genes in lungs of patients with chronic obstructive pulmonary disease (COPD). Major epigenetic events include DNA methylation and various post-translational modifications of histones, such as histone methylation, acetylation, phosphorylation, ubiquitination, and sumoylation. Enzymes which regulate these epigenetic modifications can be activated by smoking. Both environmental and genetic factors play significant effect in development of COPD which have been reported by most references; however, little is known about the epigenetic pathways involved in the disease. Understanding the epigenetic mechanisms can help us clarify the pathogenesis of COPD and identify novel targets for developing new therapies for patients with COPD. [ABSTRACT FROM AUTHOR]

Objective To construct a three-dimensional finite element model of human maxillofacial structures to dynamically simulate blast injuries in different maxillofacial regions and analyze the biomechanical characteristics of skull base injuries caused by maxillofacial blast injuries. Methods The head CT data were acquired from a normal male adult and a three-dimensional finite element model of the maxillofacial bones was constructed using finite element modeling software. Using the same parameters of blast yield and distance, we dynamically simulated blast injuries in different maxillofacial regions on this model and analyzed the biomechanical data at 15 selected landmarks in the skull base. Results We successfully simulated the dynamic process of maxillofacial fractures and stress distribution and conduction in the skull base using the constructed model. In the events of an explosion at precisely 5 cm from the front of the nasal bone tip and one at 5 cm from the front of the edge of the right orbit, the stress values of Von Mises at the medial foramen ovale, hypophyseal fossa, clivus and posterior wall of the foramen magnum were greater than those at the other landmarks; when the explosion occurred at 5 cm from the front of the right zygomatic arch, the right greater wing of the sphenoid bone, right medial foramen ovale, hypophyseal fossa, clivus and posterior wall of the foramen magnum sustained greater stress values of Von Mises. Conclusion Finite element modeling is capable of simulating the process of maxillofacial blast injuries. Blast wave impact in different maxillofacial regions results in stress concentration in different areas in relation not only to the structure of skull base but also to the stress conduction pathway.

B TYPE: b Abstract Publication B TOPIC: b Obstructive Lung Diseases B PURPOSE: b Our previous studies have validated Notch1 as an anti-apoptotic signaling in cigarette smoke (CS)-induced endothelial apoptosis. 3-MA treatment inhibited autophagy and aggravated CSE induced apoptosis, while rapamycin promoted autophagy, led to a decrease in cell apoptosis. [Extracted from the article]

This study simulated and predicted the runoff of the Aksu River Basin, a typical river basin supplied by snowmelt in an arid mountain region, with a limited data set and few hydrological and meteorological stations. Two hydrological models, the snowmelt-runoff model (SRM) and the Danish NedbØr-AfstrØmnings rainfall-runoff model (NAM), were used to simulate daily discharge processes in the Aksu River Basin. This study used the snow-covered area from MODIS remote sensing data as the SRM input. With the help of ArcGIS software, this study successfully derived the digital drainage network and elevation zones of the basin from digital elevation data. The simulation results showed that the SRM based on MODIS data was more accurate than NAM. This demonstrates that the application of remote sensing data to hydrological snowmelt models is a feasible and effective approach to runoff simulation and prediction in arid unguaged basins where snowmelt is a major runoff factor.