Search

Xinkai Luo,1,* Ying Wang,2,* Yufei Mao,3,* Xiaowei Xu,1,4 Weifeng Gu,1 Wen Li,1 Chaoming Mao,1 Tingting Zheng,1 Liyang Dong1 1Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 2Department of Respiratory Diseases, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China; 3Department of Ultrasound Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 4Department of Laboratory Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liyang Dong; Tingting Zheng, Email liyangdong@ujs.edu.cn; tingtingzheng@ujs.edu.cnBackground: Nebulization of hypoxic human umbilical cord mesenchymal stem cell-derived extracellular vesicles (Hypo-EVs) can suppress airway inflammation and remodeling in a chronic asthmatic mouse; however, the exact mechanism remains unclear. Recently, airway epithelial barrier defects have been regarded as crucial therapeutic targets in asthma. The aim of this study was to investigate whether and how Hypo-EVs protect against the disruption of the airway epithelial barrier under asthmatic conditions.Methods: The therapeutic effects of Hypo-EVs on airway epithelial barrier defects were evaluated in ovalbumin (OVA)-induced asthmatic mice and in IL-4 and IL-13-induced HBE135-E6E7 cell models by detecting cell monolayer leakage and junctional protein expression. The protein levels in Hypo-EVs were determined by Western blotting, and a gene knockdown approach was used to investigate the biofactors in Hypo-EVs.Results: Nebulization of Hypo-EVs directly alleviated airway epithelial barrier defects in asthmatic mice, as evidenced by colocalization with bronchial epithelial cells, decreased albumin concentration, and increased ZO-1 and E-cadherin expression. In vitro, Hypo-EV treatment dramatically rescued the increase in airway cell permeability, and upregulated the ZO-1 and E-cadherin protein expressions. Based on WB analysis, we found that caveolin-1 (CAV-1) was strongly enriched in Hypo-EVs. The knockdown of CAV-1 protein levels in Hypo-EVs significantly impaired Hypo-EV-mediated barrier protection in vitro and in vivo. Moreover, CAV-1 knockdown significantly abolished the beneficial effects of Hypo-EVs on airway inflammation and remodeling in asthmatic mice. In addition, we showed that IL-4/IL-13-induced airway epithelial barrier defects were mainly related to activation of STAT6 phosphorylation (p-STAT6), and overexpression of CAV-1 or Hypo-EV treatment inhibited the levels of p-STAT6 in IL-4/IL-13-induced HBE135-E6E7 cells.Conclusion: Nebulization of Hypo-EVs can attenuate airway epithelial barrier defects in asthma by delivering CAV-1 to inhibit p-STAT6 expression and may be used to treat other barrier defect diseases.Keywords: nebulization, Hypo-EVs, asthma, airway epithelial barrier, caveolin-1

Jia-wei Xu,1,2,* Fang-fang Chen,1,* Ying-hui Qv,1,* Cong-cong Sun,1 Dong Zhang,1,2 Zhi Guo,1 Yu-jiao Wang,3 Jun-fei Wang,4 Tian Liu,4 Liang Dong,1,2 Qian Qi1,2 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Characteristic Laboratory of Clinical Transformation of Respiratory Biological Immunity and Regenerative Medicine, Jinan, Shandong Province, 250014, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, 250014, People’s Republic of China; 3Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Laboratory Medicine, Jinan, Shandong Province, 250014, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, Shandong Province, 250012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Qi, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, #16766, Jingshi Road, Jinan City, Shandong Province, 250014, People’s Republic of China, Tel +86 13706380314, Email qiqianqlh@163.comPurpose: Bronchiectasis patients are prone to Pseudomonas aeruginosa infection due to decreased level of sphingosine in airway. Adiponectin receptor agonist AdipoRon activates the intrinsic ceramidase activity of adiponectin receptor 1 (AdipoR1) and positively regulates sphingosine metabolism. This study aimed to investigate the potential therapeutic benefit of AdipoRon against Pseudomonas aeruginosa infection.Methods: A mouse model of Pseudomonas aeruginosa lung infection and a co-culture model of human bronchial epithelial cells with Pseudomonas aeruginosa were established to explore the protective effect of AdipoRon. Liquid chromatography-mass spectrometry was used to detect the effect of AdipoRon on sphingosine level in lung of Pseudomonas aeruginosa-infected mouse models.Results: The down-regulation of adiponectin and AdipoR1 in airway of bronchiectasis patients was linked to Pseudomonas aeruginosa infection. By activating AdipoR1, AdipoRon reduced Pseudomonas aeruginosa adherence on bronchial epithelial cells and protected cilia from damage in vitro. With the treatment of AdipoRon, the load of Pseudomonas aeruginosa in lung significantly decreased, and peribronchial inflammatory cell infiltration was lessened in vivo. The reduced level of sphingosine in the airway of Pseudomonas aeruginosa infected mice was replenished by AdipoRon, thus playing a protective role in the airway. Moreover, AdipoRon activated P-AMPKα/PGC1α, inhibited TLR4/P-NF-κB p65, and reduced expression of pro-apoptotic bax. However, the protective effect of AdipoRon on resisting Pseudomonas aeruginosa infection was weakened when AdipoR1 was knocked down.Conclusion: AdipoRon protects bronchial epithelial cells and lung by enhancing their resistance to Pseudomonas aeruginosa infection. The mechanism might be modulating sphingosine metabolism and activating P-AMPKα/PGC1α while inhibiting TLR4/P-NF-κB p65.Keywords: AdipoRon, Pseudomonas aeruginosa, bronchiectasis, AdipoR1, sphingosine metabolism

Yuntao Lu,1,2,* Minyan Yin,3,4,* Ye Yang,1,2,* Wenshuo Wang,1,2 Lili Dong,5 Xue Yang,3,4 Chunsheng Wang,1,2 Xiaolin Wang,3,4 Jinmiao Chen,1,2 Lai Wei1,2 1Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Heart Valve, Shanghai, People’s Republic of China; 3Shanghai Institute of Medical Imaging, Shanghai, People’s Republic of China; 4Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lai Wei; Jinmiao Chen, Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 021 64041990, Email wei.lai@zs-hospital.sh.cn; chen.jinmiao@zs-hospital.sh.cnPurpose: Transcatheter aortic valve replacement (TAVR) induced coronary artery obstruction (CAO) is a rare but devastating complication. Current preventive strategies need additional procedures and may be associated with adverse events. This study aimed to evaluate the early safety and efficacy of stand-alone TAVR using the J-Valve (Jianshi JieCheng Medical Technology Co. Ltd, Shanghai, China) in patients at potential high risk for CAO.Patients and Methods: CAO was defined as coronary ostia obstruction requiring intervention. Patients at potential high risk for CAO were identified retrospectively from 673 consecutive patients who underwent TAVR from January 2015 to July 2021 at Zhongshan Hospital, Fudan University. Procedural results and early outcomes were evaluated according to Valve Academic Research Consortium-3 definitions.Results: A total of 20 consecutive patients (age 72 ± 9 years; 85% female;) were included. The Society of Thoracic Surgeons-Predicted Risk of Mortality was 5% (interquartile range, 4 to 10%). All patients (100%) had at least 2 classical risk factors for CAO by pre-procedural computed tomography analysis, and 90% patients had native aortic valve diseases. TAVR was successful in 95% of cases, with only 1 patient requiring second device implantation. Early safety at 30 days was achieved in all cases without death. All patients were free from CAO, stroke or emergency reintervention. Post-procedural mean aortic valve gradient was 7 (interquartile range, 4, 12) mmHg, and none/trace or mild aortic regurgitation was present in all patients.Conclusion: Stand-alone TAVR using the J-Valve may mitigate the risk of TAVR-induced CAO. Keywords: TAVR, coronary artery obstruction, aortic regurgitation, aortic stenosis, structural heart disease

Abstract The quasi-2-day wave (Q2DW) is a large temperature disturbance in the austral summer-time mesosphere. Its decay-phase movement and phase-speed are poorly understood. Q2DW events observed by the microwave limb sounder (MLS) onboard the NASA Aura satellite reveal that during the temperature Q2DW’s decay-phase, the Q2DW temperature disturbance is still substantial, but its phase-speed reduces exponentially, on average, from around −70 to −20 m/s in around 30-days. Observations also reveal significant interannual variability in these phase-speed values. Q2DW events simulated by the extended Canadian middle atmosphere model (eCMAM) reveal that during the Q2DW decay-phase, the temperature Q2DW phase-speed is strongly correlated with the summer mesosphere easterly jet (SMEJ) wind values. eCMAM also shows that the phase-speed interannual variabilities partially reflect the interannual variabilities of the SMEJ. Planetary-wave diagnostics indicate that during the Q2DW’s decay phase, there is still an active transfer of momentum from the SMEJ into Q2DW. The model simulations therefore indicate that the SMEJ plays a substantial role in the decaying temperature Q2DW phase-speed variabilities observed by MLS. This adds to our knowledge of how the SMEJ affects the Q2DW.

Sitong Feng,1,2,* Ziyao Wu,1,2,* Sisi Zheng,1,2 Linrui Dong,1,2 Hongxiao Jia,1,2 Yanzhe Ning1,2 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanzhe Ning; Hongxiao Jia, Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China, Email ningzy0923@mail.ccmu.edu.cn; jhxlj@ccmu.edu.cnObjective: The thalamus plays a critical role in attentional maintenance. Previous studies have revealed the dysfunction of the thalamus in attention decline after acute sleep deprivation (SD). However, the functional connectivity (FC) between the thalamus subregions and cortical regions underlying attentional impairment after acute SD remains unclear. Here, we aimed to probe the relationship between attentional function and the altered thalamocortical FC after acute SD.Methods: In this study, 25 healthy participants with regular sleep conducted an attentional network test and received a resting-state fMRI scan before and after 24 hours of SD. Then, we analyzed the FC between the thalamus and cerebrum and relationships with attentional function in the enrolled subjects.Results: Our results showed that the participants showed a significantly lower alerting effect, a higher executive effect, and lower accuracy after acute SD. Compared to the rested wakefulness state, we observed decreased FCs between the “somatosensory” thalamic seed and left frontal pole, right frontal pole, left middle temporal gyrus (posterior division), and right middle temporal gyrus (posterior division). Furthermore, the reduced FC between the right middle temporal gyrus and “somatosensory” thalamic seed was negatively associated with the change in orienting effect of the participants.Conclusion: Our findings reveal that the disrupted FC between thalamus subregions and cortical regions may contribute to impaired attention after SD.Keywords: sleep deprivation, fMRI, attention, thalamus, functional connectivity

Wen-Feng Liu,1,2,* Qiu-Yu Jiang,1,2,* Zhuo-Ran Qi,1,2,* Feng Zhang,1,2 Wen-Qing Tang,1,2 Hao-Qi Wang,1,2 Ling Dong1,2 1Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Dong; Hao-Qi Wang, Email dong.ling@zs-hospital.sh.cn; wang.haoqi@zs-hospital.sh.cnBackground: CD276 is an emerging immune checkpoint molecule that has been implicated in various cancers. However, its specific role in hepatocellular carcinoma (HCC) remains unclear. This study examined the impact of CD276 on patient prognosis and the tumor microenvironment (TME).Methods: The Cancer Genome Atlas (TCGA) database was utilized to evaluate CD276 expression in HCC and the association between CD276 and immune indicators was also analyzed. The signaling pathways correlated with CD276 expression were identified by gene set enrichment analysis (GSEA). Different algorithms were used to assess immune cell infiltration. The effect of CD276 knockdown on HCC cell phenotypes and its relationship with macrophage polarization was examined using the cell counting kit 8 (CCK-8) assay and co-culture system.Results: CD276 was upregulated in HCC and associated with unfavorable clinical outcomes. Hgh CD276 expression was associated with enrichment of the G2/M checkpoint, E2F targets, and mitotic spindles. CD276 expression was correlated with the infiltration of immune cells, including high level of tumor-associated macrophages and low levels of CD8+ T cells. Knockdown of CD276 decreased HCC cell proliferation and increased apoptosis. CD276 silencing in HCC cells and co-culture with THP-1–derived macrophages had a regulatory effect on macrophage polarization and macrophage-mediated cell proliferation and migration.Conclusion: CD276 expression in HCC is associated with unfavorable clinical outcomes and may contribute to the development of an immunosuppressive microenvironment. Specifically, CD276 was associated with alterations in immune cell infiltration, immune marker expression, and macrophage polarization during HCC progression, suggesting its potential as a prognostic indicator and promising target for immunotherapeutic intervention in HCC.Keywords: CD276, hepatocellular carcinoma, tumor microenvironment, immune checkpoint molecule, macrophage

Qianwen Zhang,1,* Shengcen Zhang,1,* Binbin Xu,1 Luyan Dong,1 Zhichang Zhao,2 Bin Li1 1Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fujian, 350001, People’s Republic of China; 2Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Li, Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fujian, 350001, People’s Republic of China, Email leonlee307@hotmail.com Zhichang Zhao, Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China, Email slip2046@126.comBackground: Hospital wastewater (HWW) promotes the spread of carbapenem resistance genes (CRGs). Aeromonas carry a large number of CRGs in HWW, they may play a role as a suitable reservoir for CRGs, while resistomes in HWW are still poorly characterized regarding carbapenem resistant Aeromonas. Thus, the aim of the study was to evaluate the molecular epidemiological characteristics of carbapenem resistant Aeromonas in HWW.Methods: A total of 33 carbapenem resistant Aeromonas were isolated from HWW. Antimicrobial susceptibility testing and polymerase chain reaction (PCR) were used to assess the antimicrobial resistance profiles. Molecular typing was performed using enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) and multilocus sequence typing (MLST). The horizontal transmission mode of blaKPC was explored through conjugation and transformation experiments. The stability of blaKPC-IncP-6 plasmids was assessed through plasmid stability and in vitro competition test. The PCR mapping method was used to investigate the structural diversity of blaKPC.Results: The detection rates of blaKPC and cphA in Aeromonas were 97.0% and 39.4% respectively. Aeromonas caviae were grouped into 13 clusters by ERIC-PCR and 12 STs by MLST. Aeromonas veronii were grouped into 11 clusters by ERIC-PCR and 4 STs by MLST. 56.3% blaKPC were located on mobilizable IncP-6 plasmids. blaKPC-IncP-6 plasmid showed high stability and low cost fitness.Conclusion: Carbapenem resistant Aeromonas from HWW mainly carried blaKPC, which exhibited great structural diversity. Aeromonas might serve as reservoirs for blaKPC and blaKPC might spread mainly through transformation in HWW.Keywords: hospital wastewater, carbapenem resistance, Aeromonas, IncP-6, blaKPC

Huaqiao Tang,1,* Liying Dong,1,* Xue Xia,1,* Xinling Chen,1 Meichen Ren,1 Gang Shu,1 Hualin Fu,1 Juchun Lin,1 Ling Zhao,1 Li Zhang,2 Guoqiang Cheng,2 Xianxiang Wang,3 Wei Zhang1 1College of Veterinary, Sichuan Agricultural University, Chengdu, 611130, People’s Republic of China; 2Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610041, People’s Republic of China; 3College of Science, Sichuan Agricultural University, Chengdu, 611130, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zhang, Email Zhangwei26510c@126.comIntroduction: Chrysin has a wide range of biological activities, but its poor bioavailability greatly limits its use. Here, we attempted to prepare casein (cas)-based nanoparticles to promote the biotransfer of chrysin, which demonstrated better bioavailability and anti-infection activity compared to free chrysin.Methods: Cas-based chrysin nanoparticles were prepared and characterized, and most of the preparation process was optimized. Then, the in vitro and in vivo release characteristics were studied, and anti-pulmonary infection activity was evaluated.Results: The constructed chrysin-cas nanoparticles exhibited nearly spherical morphology with particle size and ζ potential of 225.3 nm and − 33 mV, respectively. These nanoparticles showed high encapsulation efficiency and drug-loading capacity of 79.84% ± 1.81% and 11.56% ± 0.28%, respectively. In vitro release studies highlighted a significant improvement in the release profile of the chrysin-cas nanoparticles (CCPs). In vivo experiments revealed that the relative oral bioavailability of CCPs was approximately 2.01 times higher than that of the free chrysin suspension. Further investigations indicated that CCPs effectively attenuated pulmonary infections caused by Acinetobacter baumannii by mitigating oxidative stress and reducing pro-inflammatory cytokines levels, and the efficacy was better than that of the free chrysin suspension.Conclusion: The findings underscore the advantageous bioavailability of CCPs and their protective effects against pulmonary infections. Such advancements position CCPs as a promising pharmaceutical agent and candidate for future therapeutic drug innovations.Keywords: chrysin, nanoparticles, Acinetobacter baumannii, casein

Lin Sun,1,2,* Xu Zhao,1 Yunting Guo,1,* Xiaomin Hou,3– 5 Jieru Li,6 Xiaoxia Ren,7 Lin Dong,1 Ruifeng Liang,1 Jisheng Nie,1 Yiwei Shi,2 Xiaojiang Qin1,2,4,5,8 1School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 4China Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, Shanxi, China; 5Environmental Exposures Vascular Disease Institute, Taiyuan, Shanxi, People’s Republic of China; 6Department of Foreign Languages, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 8Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaojiang Qin, School of Public Health, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel +86-18735379826, Email sph@sxmu.edu.cn Yiwei Shi, Department of Respiratory and Critical Care Medicine, The First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel +86-13835193132, Email chinasyw225@163.comPurpose: Smoking is a major risk factor for the group 3 PH. NT-proBNP is a biomarker for risk stratification in PH. This study aims to investigate the effects of smoking status and smoking index (SI) on group 3 PH and to evaluate the value of SI and SI combined with NT-proBNP in early diagnosis and prediction of disease severity.Patients and Methods: Four hundred patients with group 3 PH at the First Hospital of Shanxi Medical University between January 2020 and December 2021 were enrolled and divided into two groups: mild (30 mmHg ≤ pulmonary artery systolic pressure (PASP)≤ 50 mmHg) and non-mild (PASP > 50 mmHg). The effect of smoking on group 3 PH was analyzed using univariate analysis, and logistic analysis was conducted to evaluate the risk of group 3 PH according to smoking status and SI. Spearman correlation coefficient was used to test the correlation between SI and the index of group 3 PH severity. The predictive value of SI was evaluated using a receiver operating characteristic (ROC) curve.Results: Correlation and logistic analyses showed that SI was associated with PH severity. Smoking status (P=0.009) and SI (P=0.039) were independent risk factors for non-mild group 3 PH, and ROC showed that the predictive value of SI (AUC:0.596) for non-mild PH was better than that of the recognized pro-brain natriuretic peptide (NT-proBNP) (AUC:0.586). SI can be used as a single predictive marker. SI and NT-proBNP can be formulated as prediction models for screening non-mild clinical cases (AUC:0.628).Conclusion: SI is a potentially ideal non-invasive predictive marker for group 3 PH. SI and NT-proBNP could be used to develop a prediction model for screening non-mild PH cases. This can greatly improve the predictive specificity of the established PH marker, NT-proBNP.Keywords: smoking index, NT-proBNP, pulmonary hypertension, chronic lung disease, predictive value

Intense ionization enhancements in the Earth’s ionosphere, known as sporadic-E (Es), can degrade and severely disrupt the propagation of radio signals. Although many previous studies have analyzed the characteristics and morphologies of sporadic-E, few efforts have attempted to model global Es occurrence rates (ORs) at high time resolutions. This study develops a global empirical model of blanketing sporadic-E occurrence rates using a Karhunen–Loéve Expansion (KLE) of a global OR climatology built with Global Navigation Satellite System radio occultation (GNSS-RO) and ionosonde observations. Using an fbE ≥ threshold of 3 MHz, the model outputs a blanketing sporadic-E OR for a given geomagnetic latitude, longitude, day of year, and local solar time. The model outputs are compared to digisonde observations at four sites with varying geomagnetic latitudes, resulting in correlation coefficients ranging from 0.5 to 0.9 for monthly averaged observations and an uncertainty of 11%. Furthermore, the average uncertainty is estimated to be 12%. This Global Empirical Model of Sporadic-E Occurrence Rates (GEMSOR) is capable of providing blanketing sporadic-E OR estimates for global radio frequency (RF) operations.

Tingting Wang,1 Yang Wang,2 Qingyue Liu,1 Wenbin Guo,1 Hongliang Zhang,1 Liangliang Dong,3 Jiajun Sun1 1Department of Intensive Care Unit, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of China; 2Department of Laboratory Medicine, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of China; 3Department of Respiratory Medicine, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of ChinaCorrespondence: Jiajun Sun, Department of Intensive Care Unit, The Second People’s Hospital of Liaocheng, No. 306 Jiankang Road, Linqing, Shandong, People’s Republic of China, Tel +86-13793092818, Email 13793092818@126.comBackground: Malnutrition adversely affects prognosis in various medical conditions, but its implications in older adults with Chronic Obstructive Pulmonary Disease (COPD) in the ICU are underexplored. The geriatric nutritional risk index (GNRI) is a novel tool for assessing malnutrition risk. This study investigates the association between GNRI and 90-day mortality in this population.Methods: We selected older adults with COPD admitted to the ICU from Medical Information Mart for Intensive Care (MIMIC)-IV 2.2 database. A total of 666 patients were categorized into four groups based on their GNRI score: normal nutrition (> 98), mild malnutrition (92– 98), moderate malnutrition (82– 91), and severe malnutrition (≤ 81) groups. We employed a restricted cubic spline (RCS) analysis to assess the presence of a curved relationship between them and to investigate any potential threshold saturation effect.Results: In multivariate Cox regression analyses, compared with individuals had normal nutrition (GNRI in Q4 > 98), the adjusted HR values for GNRI in Q3 (92– 98), Q2 (82– 91), and Q1 (≤ 81) were 1.81 (95% CI: 1.27– 2.58, p=0.001), 1.23 (95% CI: 0.84– 1.79, p=0.296), 2.27 (95% CI: 1.57– 3.29, p< 0.001), respectively. The relationship between GNRI and 90-day mortality demonstrates an L-shaped curve (p=0.016), with an approximate inflection point at 101.5.Conclusion: These findings imply that GNRI is a useful prognostic tool in older adults with COPD in the ICU. An L-shaped relationship was observed between GNRI and 90-day mortality in these patients.Keywords: geriatric nutritional risk index, 90-day mortality, older adults, chronic obstructive pulmonary disease, MIMIC-IV

Shulin Wei,1,2,&ast; Mingxing Li,1,2,&ast; Qin Wang,1,2,&ast; Yueshui Zhao,1,2 Fukuan Du,1,2 Yu Chen,1,2 Shuai Deng,1,2 Jing Shen,1,2 Ke Wu,1,2 Jiayue Yang,1,2 Yuhong Sun,1 Li Gu,1 Xiaobing Li,1 Wanping Li,1 Meijuan Chen,1 Xiao Ling,3 Lei Yu,3 Zhangang Xiao,1,2 Lishu Dong,3 Xu Wu1,2 1Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China; 2South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, 646100, People’s Republic of China; 3Department of Obstetrics, Luzhou Maternal & Child Health Hospital (Luzhou Second People’s Hospital), Luzhou, Sichuan, 646100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lishu Dong, Department of Obstetrics, Luzhou Maternal & Child Health Hospital (Luzhou Second People’s Hospital), Luzhou, Sichuan, 646100, People’s Republic of China, Email 1275607519@qq.com Xu Wu, Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China, Email wuxulz@126.comAbstract: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation. It also plays a therapeutic role in restoring the intestinal mucosal barrier through the homing effect, regulation of the intestinal microbiome, and repair of intestinal epithelial cells. In the latest clinical trials, the safety and efficacy of MSCs in the treatment of IBD have been confirmed by transfusion of autologous or allogeneic bone marrow, umbilical cord, and adipose MSCs, as well as their derived extracellular vesicles. However, regarding the stable and effective clinical use of MSCs, several concerns emerge, including the cell sources, clinical management (dose, route and frequency of administration, and pretreatment of MSCs) and adverse reactions. This article comprehensively summarizes the effects and mechanisms of MSCs in the treatment of IBD and its advantages over conventional drugs, as well as the latest clinical trial progress of MSCs in the treatment of IBD. The current challenges and future directions are also discussed. This review would add knowledge into the understanding of IBD treatment by applying MSCs.Keywords: mesenchymal stem cells, immunomodulation, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, cell therapy

Yan He,1,&ast; Yulei Tang,1,&ast; Silu Wen,1 Lin Dong,1 Fen Li,1,2 Yuqing Deng,1 Zezhang Tao1 1Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zezhang Tao; Yuqing Deng, Email taozezhang111@163.com; qingerdeng0713@163.comBackground: Allergic rhinitis (AR) is globally recognized as a considerable threat to human health with a rising prevalence and a substantial medical and socioeconomic burden. Numerous studies have emphasized the significance of long noncoding RNAs (lncRNAs) in allergic responses. Hence, this research dealt with exploring the involvement of the lncRNA LINC00998 in the mechanism of AR.Methods: LINC00998 expression was assessed by qRT-PCR in peripheral blood mononuclear cells acquired from individuals with AR. Additionally, the potential relationship between LINC00998 and macrophage polarization was observed in vitro. Then we constructed AR mice model and macrophage polarization models using THP-1 cells as well as primary human macrophages to verify the M2 shift in AR and the low expression level of LINC00998 in M2 macrophages. We used gain- and loss-of-function experiments to explore the modification of LINC00998 in macrophage polarization. Furthermore, we explored the underlying mechanism of LINC00998 mediates through qRT-PCR, flow cytometry, and Western blot.Results: The analysis revealed a significant decrease in LINC00998 expression in the samples obtained from patients with AR. LINC00998 is markedly increased in M1 macrophages whereas decreased in M2 macrophages in vitro. Furthermore, suppression of LINC00998 caused a remarkable enhancement in M2 polarization, whereas its overexpression led to its attenuation. Knockdown of LINC00998 led to a remarkable downregulation of BOB.1 mRNA and protein, while overexpression of LINC00998 upregulated their expression. Moreover, it was found that BOB.1 modulated macrophage polarization through the PU.1/IL-1β axis. Meanwhile, the modulation of LINC00098 overexpression on macrophage polarization and PU.1/ IL-1β can be reversed by BOB.1 siRNA.Conclusion: This research revealed the lncRNA LINC00998 altered M2 macrophage polarization by regulating the BOB.1/PU.1/IL-1β axis, which open up new avenues for studying the pathogenesis of AR. Keywords: allergic rhinitis, allergy, macrophage polarization, LncRNA, LINC00998

Liyang Dong,1,&ast; Yafang Zhao,1,&ast; Juan Luo,1,2 Xiaopeng Li,1 Shuxian Wang,1 Menghan Li,1 Peng Zou,1 Hui Kong,1 Qingguo Wang,1 Yan Zhao,1 Huihua Qu1 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingguo Wang; Yan Zhao, Email wangqg8558@sina.com; zhaoyandr@163.comBackground: Acute myocardial infarction (AMI) is a common cardiovascular disease in clinic. Currently, there is no specific treatment for AMI. Carbon dots (CDs) have been reported to show excellent biological activities, which hold promise for the development of novel nanomedicines for the treatment of cardiovascular diseases.Methods: In this study, we firstly prepared CDs from the natural herb Curcumae Radix Carbonisata (CRC-CDs) by a green, simple calcination method. The aim of this study is to investigate the cardioprotective effect and mechanism of CRC-CDs on isoproterenol (ISO) -induced myocardial infarction (MI) in rats.Results: The results showed that pretreatment with CRC-CDs significantly reduced serum levels of cardiac enzymes (CK-MB, LDH, AST) and lipids (TC, TG, LDL) and reduced st-segment elevation and myocardial infarct size on the ECG in AMI rats. Importantly, cardiac ejection fraction (EF) and shortening fraction (FS) were markedly elevated, as was ATPase activity. In addition, CRC-CDs could significantly increase the levels of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and reduce the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in myocardial tissue, thereby exerting cardioprotective effect by enhancing the antioxidant capacity of myocardial tissue. Moreover, the TUNEL staining image showed that positive apoptotic cells were markedly declined after CRC-CDs treatment, which indicate that CRC-CDs could inhibit cardiomyocyte apoptosis. Importantly, The protective effect of CRC-CDs on H2O2 -pretreated H9c2 cells was also verified in vitro.Conclusion: Taken together, CRC-CDs has the potential for clinical application as an anti-myocardial ischemia drug candidate, which not only provides evidence for further broadening the biological application of cardiovascular diseases, but also offers potential hope for the application of nanomedicine to treat intractable diseases. Keywords: acute myocardial infarction, Curcumae Radix Carbonisata, carbon dots, oxidative stress

Qiang Zhou, Yanlin Wan, Le Ma, Liang Dong, Weijian Yuan Department of Orthopaedics, Tianjin First Central Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Qiang Zhou, Department of Orthopaedics, Tianjin First Central Hospital, Fukang Road 24&num;, Tianjin, People’s Republic of China, Email osdoctorzq@126.comPurpose: The purpose of this study is to compare the refracture rate of the cemented vertebral body of percutaneous curved vertebroplasty (PCVP) and bilateral percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (OVCF).Methods: Ninety-four patients with single segment thoracolumbar OVCF were randomly divided into two groups (47 patients in each) and underwent PCVP or bilateral PKP surgery, respectively. Refracture of cemented vertebral body, bone cement injection volume and cement pattern, cement leakage rate, total surgical time, intraoperative fluoroscopy time, preoperative and postoperative Cobb angles and anterior vertebral height, Oswestry disability index questionnaire (ODI) and visual analog scales (VAS) were recorded.Results: The PCVP group had significantly lower refracture incidence of the cemented vertebral than the bilateral PKP group (p< 0.05). There was a significant postoperative improvement in the VAS score and ODI in both group (p< 0.01), and no significant difference was found between two groups. The operation time and intraoperative fluoroscopy times were significantly less in the PCVP group than in the bilateral PKP group (p< 0.01). The mean kyphosis angle correction and vertebral height restoration in the PCVP group was significantly less than that in the bilateral PKP group (p< 0.01).Conclusion: Both PCVP and PKP were safe and effective treatments for OVCF. The PCVP had lower refracture rate of the cemented vertebral than the bilateral PKP group, and PCVP entailed less exposure to fluoroscopy and shorter operation time than bilateral PKP.Keywords: osteoporosis, osteoporotic vertebral compression fractures, percutaneous curved vertebroplasty, percutaneous kyphoplasty

Xun Qiu,1,2,&ast; Libin Dong,1,2,&ast; Kai Wang,1,2 Xinyang Zhong,1,2 Hanzhi Xu,1,2 Shengjun Xu,2 Haijun Guo,2 Xuyong Wei,1,2 Wei Chen,2,3 Xiao Xu1,2 1Department of Surgery, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China; 2Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, People’s Republic of China; 3Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Chen; Xiao Xu, Email jackweichen@zju.edu.cn; zjxu@zju.edu.cnBackground: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Accumulating evidence indicates that hypoxia and lactate metabolism play critical roles in tumor progression and therapeutic efficacy. This study aimed to construct a hypoxia- and lactate metabolism-related prognostic model (HLPM) to evaluate survival and treatment responses for HCC patients and develop a nomogram integrated with HLPM and clinical characteristics for prognosis prediction in HCC.Methods: Expression profile and clinical data of HCC were obtained from TCGA and ICGC databases. The univariate, LASSO and stepwise multivariate Cox analyses were used to identify the hypoxia- and lactate metabolism-related biomarkers, whose expression levels were then validated in 14 pairs tissue samples and single-cell RNA sequencing dataset. Kaplan–Meier survival curves were utilized to assess the prognostic values of biomarkers or models. Analyses of ImmuCellAI, TIDE and drug sensitivity were conducted to evaluate the therapeutic responses of patients. Furthermore, the nomogram integrated with hypoxic and lactate metabolic characteristics was established through univariate and multivariate Cox analyses. ROC curves, C-index, and calibration curves were depicted to evaluate the performance of the nomogram.Results: Five hypoxia- and lactate metabolism-related biomarkers (KIF20A, IRAK1, ADM, PPARGC1A and EPO) were used to construct HLPM. The expression of five prognostic biomarkers was validated in 14 pairs tissue samples and single-cell RNA sequencing dataset. Analyses of ImmuCellAI, TIDE and drug sensitivity implied that patients with low-risk score were more sensitive to immunotherapy and major chemotherapeutic agents. The nomogram that contained age, histological grade and risk score of HLPM was developed and exhibited a better capacity in prognosis prediction than HLPM only.Conclusion: A novel nomogram integrated with hypoxic and lactate metabolic characteristics was developed and validated for prognosis prediction in HCC, providing insight into personalized decision-making in clinical management.Keywords: hepatocellular carcinoma, nomogram, prognosis, lactate metabolism, hypoxia, immunotherapy

Jingcheng Ding,1,&ast; Qian Shi,1,&ast; Ling Dong,2 Hong Su,3 Yijun Du,1 Tianrong Pan,1 Xing Zhong1 1Department of Endocrinology, The Second Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China; 3Department of Epidemiology and Health Statistics, Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xing Zhong, Department of Endocrinology, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei City, Anhui province, People’s Republic of China, Tel +86 18905692292, Email zhongxing761@163.comPurpose: To investigate the relationship between HbA1c variability and vibrating perception threshold (VPT) in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM).Patients and Methods: A total of 367 middle-aged and elderly patients with T2DM were enrolled. All patients were categorized into the control and vibration sensation deficiency group (VSD) based on VPT. Clinical data were collected. The coefficient of variation of glycated hemoglobin A1c (HbA1c-CV) and the mean glycated hemoglobin A1c(HbA1c-Mean) are considered as indexes of HbA1c variability. Multivariate logistic regression analysis, the generalized linear model and ROC curve correlation analysis were used to analyze the correlation of various factors and VPT.Results: The multivariate logistic regression analysis revealed that age, systolic blood pressure (SBP), and HbA1c-CV were identified as risk factors for vibration sensation deficiency in middle-aged and elderly patients with T2DM, while estimated glomerular filtration rate (eGFR), triiodothyronine (T3), and alanine aminotransferase (ALT) were considered as protective factors. In the unadjusted generalized linear model, a significant association was observed between HbA1c-CV and VPT values. After adjusting for age, diabetic duration, SBP, homeostatic model assessment for beta-cell function (HOMA-β), ALT, eGFR, T3, 24-hour urinary protein excretion levels, and HbA1c-Mean, HbA1c-CV remained significantly correlated with VPT values on both sides. (left side, B=2.560, 95% CI 1.298~3.823; P< 0.001; right side, B=2.608, 95% CI 1.498~3.718, P< 0.001). The area under the curve (AUC) for HbA1c-CV and VSD prevalence was 0.723, with a sensitivity of 79.85%, specificity of 56.22%.Conclusion: The risk of developing VSD increases proportionally with higher HbA1c-CV levels in middle-aged and elderly patients with T2DM. Reaching and maintaining blood glucose stability is essential to the mitigation of diabetes peripheral neuropathy occurrence.Keywords: type 2 diabetes mellitus, HbA1c variability, vibrating perception threshold, diabetic peripheral neuropathy

The jamming is found to increase significantly in recent years, and its impact is evident in Global Navigation Satellite System (GNSS) radio occultation (RO) measurements, such as those from COSMIC-2. This article presents an algorithm that applies the RO radiometry to detect and monitor long-term variations of GNSS jamming power from a deeply occulted height (HSL = −140 km). At these heights, the RO signal amplitude is at its noise level because the GNSS transmitter is far behind the Earth shadow. Thus, any enhanced RO amplitudes from these heights are considered as a jamming signal. The algorithm was successfully applied to two conflict zones: Mediterranean Sea and Middle East and Central Africa, where the Global Position System (GPS) jamming was frequently used by state-sponsored electronic warfare. The time series of normalized RO amplitude in these regions show a steady increase of the GPS jamming power since 2017, but a sharp decrease since the start of Russo–Ukrainian War.

Lingling Dong,1,&ast; Yong Wang,1,&ast; Haipin Chen,1 Zhouyang Li,1 Xuchen Xu,1 Jiesen Zhou,1 Huahao Shen,1,2 Zhihua Chen1 1Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihua Chen, Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, People’s Republic of China, Tel +86-571-8898-1913, Fax +86-571-8778-3729, Email zhihuachen@zju.edu.cnBackground: Macrophage-derived matrix metalloproteinase 12 (MMP12) can cause destruction of lung tissue structure and plays a significant role in the development and progression of chronic obstructive pulmonary disease (COPD). MTOR is a serine/threonine kinase that plays a crucial role in cell growth and metabolism. The activity of MTOR in the lung tissues of COPD patients also shows significant changes. However, it is unclear whether MTOR can regulate the development and progression of COPD by controlling MMP12. This study primarily investigates whether MTOR in macrophages can affect the expression of MMP12 and participate in the progression of COPD.Methods: We tested the changes in MTOR activity in macrophages exposed to cigarette smoke (CS) both in vivo and in vitro. Additionally, we observed the effect of MTOR on the expression of MMP12 in macrophages and on lung tissue inflammation and structural damage in mice, both in vivo and in vitro, using MTOR inhibitors or gene knockout mice. Finally, we combined inhibitor treatment with gene knockout to demonstrate that MTOR primarily mediates the expression of MMP12 through the NF-κB signaling pathway.Results: Exposure to CS can enhance MTOR activity in mouse alveolar macrophages. Inhibiting the activity of MTOR or suppressing its expression leads to increased expression of MMP12. Myeloid-specific knockout of MTOR expression can promote the occurrence of CS-induced pulmonary inflammation and emphysema in mice. Inhibiting the activity of NF-κB can eliminate the effect of MTOR on MMP12.Conclusion: Macrophage MTOR can reduce the expression of MMP12 by inhibiting NF-κB, thereby inhibiting the occurrence of COPD inflammation and destruction of lung tissue structure. Activating the activity of macrophage MTOR may be beneficial for the treatment of COPD.Keywords: matrix metalloproteinase 12, MMP12, pulmonary emphysema, cigarette smoke, CS, mechanistic target of rapamycin, MTOR

Linfei Su,1,2 Zehui Lin,1 Youyuan Li,1 Xiaoyan Wang,3 Zengping Lin,3 Lanjuan Dong,3 Ling Wei1 1Department of Psychology, School of Health, Fujian Medical University, Fuzhou, People’s Republic of China; 2Institute of Psychology, School of Education Science, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Fuzhou Xingyu School, Fuzhou, People’s Republic of ChinaCorrespondence: Ling Wei, Tel +86-15960096260, Email ysyang-78@163.comBackground: The own-age effect is the phenomenon in which individuals perceive and recognize faces of their own age better than others in terms of cognitive processing. Previous eye movement studies on children with autism spectrum disorders (ASD) have reported that children with ASD have an attentional bias toward own-age faces and own-age scenes.Methods: The present study used own-age faces as the intervention material and examined the application of the own-age effect in the emotional recognition of faces in ASD. The length of the intervention was 12 weeks, and 2 sessions were conducted each week.Results: The results revealed that the own-age face intervention group gazed at children’s faces significantly more often than before the intervention, gazed at children’s angry faces significantly longer than before the intervention, and gazed at adults’ happy faces significantly longer and more often than before the intervention; the other-age faces intervention group did not differ significantly from the preintervention in gazing at children’s and adults’ faces after the intervention.Conclusion: The results suggest that own-age faces as teaching materials can better promote the emotion recognition ability of children with ASD than other-age faces.Plain language summary: ASD have difficulties with facial emotion recognition and previous study found that children with ASD correctly identified emotions in own-age faces more often than in other-age faces. Therefore, using pictures of children’s faces to intervene in children with ASD is beneficial to improve their facial emotion recognition ability. Previous studies have mostly used questionnaires to assess the effects of peer-matched interventions, and few have used an eye-movement technique that can effectively monitor changes in eye gaze patterns across different emotions.We found that the own-age face intervention group gazed at children’s faces significantly more often than before the intervention, gazed at children’s angry faces significantly longer than before the intervention, and gazed at adults’ happy faces significantly longer and more often than before the intervention. It indicates that own-age faces as teaching materials can better promote the emotion recognition ability of children with ASD than other-age faces.The own-age effect can be applied to experimental materials, the attribute settings of intervention materials, and the selection of accompanying objects to further expand the own-age effect in the educational intervention and training of social and cognitive abilities in ASD. It is expected to help autism improve its social skills and better integrate into the society.Keywords: children with autism spectrum disorders, own-age faces, intervention, eye tracking

Sitong Feng,1,2 Linrui Dong,1,2 Bin Yan,3 Sisi Zheng,1,2 Zhengtian Feng,1,2 Xue Li,1,2 Jiajia Li,1,2 Ning Sun,3 Yanzhe Ning,1,2 Hongxiao Jia1,2 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 3Department of Andrology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Hongxiao Jia; Yanzhe Ning, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Hutong, Xicheng District, Beijing, 100088, People’s Republic of China, Tel +86 010-58303065, Email jhxlj@ccmu.edu.cn; ningzy0923@mail.ccmu.edu.cnPurpose: Several studies have demonstrated that psychogenic erectile dysfunction (pED) patients potentially suffer from cognitive dysfunction. Despite that previous neuroimaging studies have reported abnormal functional connections of brain areas associated with cognitive function in pED, the underlying mechanisms of cognitive dysfunction in pED remain elusive. This study aims to investigate the underlying mechanisms of cognitive dysfunction by analyzing large-scale brain networks.Patients and Methods: A total of 30 patients with pED and 30 matched healthy controls (HCs) were recruited in this study and scanned by resting-state functional magnetic resonance imaging. The Dosenbach Atlas was used to define large-scale networks across the brain. The resting-state functional connectivity (FC) within and between large-scale brain networks was calculated to compare pED patients with HCs. The relationship among cognitive performances and altered FC of large-scale brain networks was further explored in pED patients.Results: Our results showed that the decreased FC within visual network, and between visual network and default mode network, visual network and frontoparietal network, and ventral attention and default mode network were found in pED patients. Furthermore, there was a positive correlation between immediate memory score and FC within visual network. The visuospatial score was negatively correlated with decreased FC between ventral attention network and default mode network.Conclusion: Taken together, our findings revealed the relationship between cognitive impairments and altered FC between large-scale brain networks in pED patients, providing the new evidence about the neural mechanisms of cognitive dysfunction in pED patients.Keywords: large-scale brain network, functional connectivity, cognitive impairment, psychogenic erectile dysfunction

Duanduan Cong,1 Wenyuan Qi,1 Xiaohui Liu,1 Xiaoyu Xu,1 Lingyun Dong,2 Wei Xue,1,&ast; Kexin Li1,&ast; 1Clinical Trial Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Beijing, People’s Republic of China; 2Beijing Yeedozencom Healthcare Science & Technology Co., Ltd, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Xue; Kexin Li, Clinical Trial Centre (The North Building B4), Beijing Hospital, No. 1 Dahua Road, Dongdan, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +861085133632, Email roserebel@126.com; Kexinli6202@163.comPurpose: To study and compare the pharmacokinetic characteristics of enteric-coated sustained-release (EcSr) aspirin tablets with enteric-coated (Ec) aspirin tablets (Bayer S.p.A) in healthy Chinese participants.Patients and Methods: In this open, randomized, single-dose, three-way, crossover study, 18 healthy participants randomly received 100 mg EcSr tablets pre-prandially (a.c.), EcSr tablets post-prandially (p.c.), or Ec tablets a.c. in each period. The concentrations of acetylsalicylic acid (ASA) and salicylic acid (SA) in plasma were determined by the LC-MS/MS method, and the pharmacokinetic parameters were calculated using WinNonlin (version 8.1).Results: The essential PK parameters under the three treatment conditions (ie Ec a.c., EcSr a.c. and EcSr p.c.) were as follows: Cmax, ASA: 758.38± 455.34, 222.77± 98.04 and 194.54± 61.19 ng, Tmax, ASA: 6.75(2,16), 4.5(2,11) and 8.25(5,11) h, T1/2, ASA: 0.43± 0.08, 1.44± 0.59 and 4.32± 10.04 h, AUC0-t, ASA: 1008.88± 452.27, 918.04± 238.40 and 845.55± 183.25 h·ng/mL; Cmax, SA: 6409.38± 2098.52, 2863.53± 679.73 and 2913.75± 853.27ng/mL, Tmax, SA: 7.25(2,24), 10(3.5– 14) and 10(7,14) h, T1/2, SA: 2.21± 0.46, 2.69± 0.72 and 3.51± 2.06h, AUC0–t, SA: 29,131.41± 9376.23, 27,243.97± 7465.16, 27,240.25± 7444.67 h·ng/mL. When taking EcSr aspirin tablets, the 90% confidence intervals of the geometric mean ratios (pre-prandial/post-prandial) of AUC0-t, ASA and AUC0–∞, ASA, Cmax, SA, AUC0-t, SA and AUC0–∞, SA were within the range of 80.00%– 125.00%.Conclusion: EcSr aspirin tablets showed less inter-individual variation in release and absorption than Ec aspirin tablets, which was well reflected by comparing essential PK parameters. Furthermore, meals had no significant effect on the pharmacokinetics of EcSr aspirin tablets.Keywords: acetylsalicylic acid, salicylic acid, enteric-coated sustained-release, pharmacokinetics

Several models for estimating sporadic-E intensity from Global Navigation Satellite System (GNSS) radio occultation (RO) observation have previously been developed using a single perturbation or intensity parameter, such as phase-based total electron content (TEC) or the amplitude-based S4 index. Here, we outline two new models that use a combination of phase and amplitude parameters for the L1 and L2 signals. These models show a significant improvement over the baseline models used for comparison. Furthermore, the GNSS-RO parameters are compared with several different ionosonde intensity parameters including the direct foEs and fbEs measurements along with the metallic-ion based foμEs and fbμEs parameters which account for the background E-region density. Interestingly, the phase-based σϕ scintillation index shows the strongest correlation to foEs and fbEs while amplitude-based S4 shows the strongest correlation to foμEs and fbμEs. While the metallic-ion based foμEs and fbμEs parameters are physically ideal for GNSS-RO observations, we show difficulties in practical implementation due to the reliance on a background E-region density estimate using a model such as the International Reference Ionosphere (IRI). Ultimately, we provide two improved sporadic-E intensity models that can be used for future GNSS-RO based studies along with a recommendation to compare against the ionosonde-based foEs parameter.

Qian Qi,1,2,&ast; Jiawei Xu,1,2,&ast; Yujiao Wang,3,&ast; Jian Zhang,1 Mingxia Gao,1 Yu Li,4 Liang Dong1,2 1Department of Respiratory, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Jinan, Shandong Province, People’s Republic of China; 2Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, People’s Republic of China; 3Department of Clinical Laboratory Medicine, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, People’s Republic of China; 4Department of Respiratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Dong, Department of Respiratory, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, &num;16766, Jingshi Road, Jinan, Shandong Province, 250014, People’s Republic of China, Tel +86 13505401207, Email dl5506@126.comPurpose: To assess the metabolites associated with Pseudomonas aeruginosa infection by analyzing the microbial diversity and metabolomics in lower respiratory tract of bronchiectasis patients and to explore the therapeutic approaches for Pseudomonas aeruginosa infection.Methods: Bronchoalveolar lavage fluid samples from bronchiectasis patients and controls were analyzed by 16S rRNA and ITS sequencing, and metabolomic analysis was performed by liquid chromatography/mass spectrometry. A co-culture model of air-liquid interface cultured human bronchial epithelial cell with Pseudomonas aeruginosa was constructed to verify the correlation between sphingosine metabolism, acid ceramidase expression, and Pseudomonas aeruginosa infection.Results: After screening, 54 bronchiectasis patients and 12 healthy controls were included. Sphingosine levels in bronchoalveolar lavage fluid were positively correlated with lower respiratory tract microbial diversity and negatively correlated with the abundance of Pseudomonas spp. Moreover, sphingosine levels in bronchoalveolar lavage fluid and acid ceramidase expression levels in lung tissue specimens were significantly lower in bronchiectasis patients than in healthy controls. Sphingosine levels and acid ceramidase expression levels were also significantly lower in bronchiectasis patients with positive Pseudomonas aeruginosa cultures than in bronchiectasis patients without Pseudomonas aeruginosa infection. Acid ceramidase expression in air-liquid interface cultured human bronchial epithelial cell had significantly increased after 6 h of Pseudomonas aeruginosa infection, while it had decreased significantly after 24 h of infection. In vitro experiments showed that sphingosine had a bactericidal effect on Pseudomonas aeruginosa by directly disrupting its cell wall and cell membrane. Furthermore, adherence of Pseudomonas aeruginosa on bronchial epithelial cells was significantly reduced after sphingosine supplementation.Conclusion: Down-regulation of acid ceramidase expression in airway epithelial cells of bronchiectasis patients leads to insufficient metabolism of sphingosine, which has a bactericidal effect, and consequently weakens the clearance of Pseudomonas aeruginosa; thus, a vicious circle is formed. Exogenous supplementation with sphingosine aids bronchial epithelial cells in resisting Pseudomonas aeruginosa infection.Keywords: metabolomics, bronchiectasis, sphingosine, Pseudomonas aeruginosa, acid ceramidase

Polar mesospheric cloud (PMC) data obtained from the Aeronomy of Ice in the Mesosphere (AIM)/Cloud Imaging and Particle Size (CIPS) experiment and Himawari-8/Advanced Himawari Imager (AHI) observations are analyzed for multi-year climatology and interannual variations. Linkages between PMCs, mesospheric temperature, and water vapor (H2O) are further investigated with data from the Microwave Limb Sounder (MLS). Our analysis shows that PMC onset date and occurrence rate are strongly dependent on the atmospheric environment, i.e., the underlying seasonal behavior of temperature and water vapor. Upper-mesospheric dehydration by PMCs is evident in the MLS water vapor observations. The spatial patterns of the depleted water vapor correspond to the PMC occurrence region over the Arctic and Antarctic during the days after the summer solstice. The year-to-year variabilities in PMC occurrence rates and onset dates are highly correlated with mesospheric temperature and H2O. They show quasi-quadrennial oscillation (QQO) with 4–5-year periods, particularly in the southern hemisphere (SH). The combined influence of mesospheric cooling and the mesospheric H2O increase provides favorable conditions for PMC formation. The global increase in mesospheric H2O during the last decade may explain the increased PMC occurrence in the northern hemisphere (NH). Although mesospheric temperature and H2O exhibit a strong 11-year variation, little solar cycle signatures are found in the PMC occurrence during 2007–2021.

Fast atmospheric processes such as deep convection and severe storms are challenging to observe and understand without adequate spatiotemporal sampling. Geostationary (GEO) imaging has the advantage of tracking these fast processes continuously at a cadence of the 10 min global and 1 min mesoscale from thermal infrared (TIR) channels. More importantly, the newly-available GEO-GEO stereo observations from our 3D-Wind algorithm provide more accurate height assignment for atmospheric motion vectors (AMVs) than those from conventional TIR methods. Unlike the radiometric methods, the stereo height is insensitive to radiometric TIR calibration of satellite sensors and can assign the feature height correctly under complex situation (e.g., multi-layer clouds and atmospheric inversion). This paper shows a case study from continuous GEO-GEO stereo observations over the Eastern Pacific during 1–5 February 2023, to highlight diurnal variations of clouds and dynamics in the planetary boundary layer (PBL), altocumulus/congestus, convective outflow and tropical tropopause layer (TTL). Because of their good vertical resolution, the stereo observations often show a wind shear in these cloud layers. As an example, the stereo winds reveal the classic Ekman spiral in marine PBL dynamics with a clockwise (counterclockwise) wind direction change with height in the Northern (Southern) Hemisphere subtropics. Over the Southeastern Pacific, the stereo cloud observations show a clear diurnal variation in the closed-to-open cell transition in the PBL and evidence of precipitation at a lower level from broken stratocumulus clouds.

Zhishu Li,1 Jiayue Chen,1 Jia Zeng,2 Ping Shi,2 Xiaomin Xiong,2 Meng Wang,1 Dong Zheng,1 Rui Zhao,1 Lixia Dong1 1Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Guangyuan Central Hospital, Guangyuan, People’s Republic of ChinaCorrespondence: Lixia Dong, Email luckydonglixia@163.comBackground: In patients with tuberculous pleural effusion (TPE) of various ages, the diagnostic accuracy of pleural biomarkers varies, and there are insufficient studies specifically in different age groups. Therefore, we investigated the adenosine deaminase cut-off value and its combination with the gamma interferon release assay for the diagnosis of TPE among patients aged ≥ 40 years.Methods: A retrospective analysis of 198 patients who underwent medical thoracoscopy and were admitted to the hospital between 2015 and 2020 with exudative pleural effusion and either fever, night sweats, fatigue, cough, or other clinical manifestations was performed. The medical thoracoscopy, ADA, and T-SPOT results were analysed in the pleural fluid. The patients were divided into groups based on age: 18– 39, 40– 59, and 60– 87.Results: The best cut-off values of ADA were 29.5, 31.5 and 19.5 U/L, respectively, for the aged 18– 39, aged 40– 87 and aged 60– 87 groups. The accuracy of 31.5 U/L was higher than 40 U/L for aged ≥ 40 years (86 vs 83%). The ADA diagnostic accuracy was higher than that of people under 40 years (83 vs 77%) when cut-off value of ADA was 40 U/L, but the IGRA accuracy was lower than that of people under 40 (87 vs 91%). The sensitivity of ADA or IGRA detection in patients over 40 years was 99%, and the specificity was 78%. The ADA specificity combined with IGRA for TPE was the highest (100%) in the ≥ 40 age group, and the sensitivity was 69%.Conclusion: Our study revealed the best cut-off values of ADA for TBE in different age groups. Combining ADA and IGRA in pleural fluid improves the detection rate of TPE in patients over 40 years of age with exudative pleural effusion. ADA combined with IGRA increases specificity, and ADA or IGRA increases sensitivity substantially.Keywords: adenosine deaminase, interferon gamma releasing assays, aged, diagnosis, pleural effusion, tuberculosis

Jun Cao,1,&ast; Lin Hua,2,&ast; Liang Dong,3 Zhouhuan Wu,4 Guohui Xue2 1Department of Biochemistry and Molecular Biology, School of Medicine, Jiujiang University, Jiujiang, People’s Republic of China; 2Department of Clinical Laboratory, Jiujiang NO.1 People’s Hospital, Jiujiang, People’s Republic of China; 3Department of Rheumatology, Jiujiang NO.1 People’s Hospital, Jiujiang, People’s Republic of China; 4Department of Pharmacology, School of Medicine, Jiujiang University, Jiujiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guohui Xue, Email xueguohui0816@126.comBackground: Inflammatory responses and metabolic abnormalities play essential roles in the pathophysiology of osteoarthritis (OA). Our study aimed to evaluate the association between monocyte-to-high density lipoprotein-cholesterol ratio (MHR) and OA and compared it with other systemic inflammatory markers.Methods: This study recruited 323 OA cases and age- and sex-matched 283 control participants during the same period. Demographic, clinical, and imaging data and laboratory indicators were obtained from participants’ records. Systemic inflammatory markers were calculated for both cohorts. The diagnostic effectiveness of each index for distinguishing patients with OA was analyzed using receiver operating characteristic (ROC) curves. Spearman’s method and ordered logistic regression were used to analyze the association between each indicator and Kellgren and Lawrence (KL) grade.Results: MHR was significantly higher (0.38± 0.18 vs 0.25± 0.07, p < 0.0001) in OA patients than healthy controls. MHR had the largest area under the ROC curve for predicting OA. Analysis of ordered logistic regression indicated that MHR was a risk factor for OA radiological severity. Spearman correlation analysis indicated that MHR significantly correlates with the KL grade. Moreover, MHR was significantly higher in early stage patients than in healthy controls.Conclusion: These results suggest that an elevated MHR could reflect knee OA severity and might be a useful marker for diagnosis and monitoring of OA.Keywords: osteoarthritis, disease severity, monocyte to high-density lipoprotein cholesterol ratio, inflammation, biomarker

Liping Dong,1,2 Ting Sun,2 Ping Tong,2 Jia Guo,3 Xiaoyan Ke1 1Affifiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Clinical Psychology, Yangzhou University Affiliated Northern Jiangsu People’s Hospital, Yangzhou, People’s Republic of China; 3Department of Proctology of Traditional Chinese Medicine, Yangzhou University Affiliated Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Xiaoyan Ke, Child Mental Health Research Center, the Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +8613305176562, Fax +8602982296194, Email kexiaoyan@njmu.edu.cnPurpose: Patients with functional anorectal pain (FAP) often experience psychological distress, impaired quality of life, increased healthcare utilisation, and even suicidal tendencies. However, limited data exists on the psychological correlates of FAP in Chinese patients. Therefore, this study aimed to examine the prevalence of depression, anxiety, and related psychosocial factors in Chinese patients with FAP.Methods: We used a cross-sectional research design and recruited 100 patients with FAP from SuBei Hospital’s multidisciplinary clinic for pelvic floor disorders between January and December 2021. Information on patients’ demographic and disease characteristics was also collected. Depressive and anxiety symptoms were assessed using the Patient Health Questionnaire Depression (PHQ-9) and the Generalised Anxiety Disorder Questionnaire (GAD-7). Multiple logistic regression analysis was used to examine factors associated with depression and anxiety.Results: The prevalence of depressive and anxiety symptoms among patients with FAP was 55% and 46%, respectively. Being a woman, specific marital status (single, divorced, separated, or widowed), longer FAP duration, and sleep disturbance were significantly associated with an increased risk of depressive symptoms. Additionally, specific marital status (single, divorced, separated, or widowed), sleep disturbance, and high Visual Analogue Scale scores were associated with anxiety symptoms.Conclusion: Depressive and anxiety symptoms are prevalent in patients with FAP. Several socio-demographic and clinical predictors have been identified. There is a need for psychologists to be involved in the treatment of patients with FAP. Thus, multidisciplinary treatment may be the optimal treatment strategy.Keywords: functional anorectal pain, depression, anxiety, multidisciplinary treatment

Hua Xiao,&ast; Xia Yu,&ast; Yuanyuan Shang, Ruyan Ren, Yi Xue, Lingling Dong, Liping Zhao, Guanglu Jiang, Hairong Huang National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hairong Huang, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, No. 97 Ma Chang, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86-10-89509159, Fax +86-10-89509160, Email huanghairong@tb123.orgBackground: Sudapyridine (WX-081) has exhibited equivalent efficacy than its counterpart parent drug bedaquiline (BDQ) but better safety profile against Mycobacterium tuberculosis (Mtb). Our study was aimed to evaluate in vitro activity of WX-081 against the clinical isolates of Mtb with different drug-resistance profiles and the intracellular bactericidal activity against the reference strain.Methods: The minimum inhibitory concentrations (MICs) of WX-081 and BDQ were tested against 114 Mtb clinical isolates. The intracellular activity of WX-081 and BDQ against the Mtb reference strain H37Rv in THP-1 cells was also evaluated in parallel.Results: The MICs for WX-081 of the enrolled isolates ranged from 0.0156 μg/mL to 1 μg/mL. The MIC50 and MIC90 of WX-081 were, respectively, 0.25 μg/mL and 0.5 μg/mL, with 95.6% of the enrolled strains having MICs ≤ 0.25 μg/mL. For a given strain, the MIC value of WX-081 was generally equivalent to or 2-fold than MIC of BDQ. The intracellular bacterial killing was acquired with the tested drug concentrations that were presumed attainable during clinical usage.Conclusion: WX-081 exhibited potent efficacy against the clinical isolates in vitro. The intracellular killing effect of sudapyridine against the reference strain supports its potential efficacy in treating TB patients.Keywords: tuberculosis, sudapyridine, bedaquiline, antibacterial activity

Mengzhu Hou,1,&ast; Nan Chen,2,&ast; Lili Dong,3,&ast; Yulian Fang,1 Rui Pan,2 Wei Wang,1 Lu Wang,1 Jing Ning,3 Hanquan Dong3 1Tianjin Pediatric Research Institute, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, People’s Republic of China; 2Department of Clinical Lab, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, People’s Republic of China; 3Department of Respiratory, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Ning; Hanquan Dong, Department of Respiratory, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), No. 238 Longyan Road, Beichen District, Tianjin, 300134, People’s Republic of China, Tel +86 13752230008 ; +86 13820476506, Email jingning2022@126.com; mifits@sina.comPurpose: The data on pediatrics with Multidrug-Resistant (MDR) Klebsiella pneumoniae infections are scarce. This study aims to investigate the molecular epidemiology of MDR Klebsiella pneumoniae, detect the mechanism of drug resistance, and determine the clinical risk factors for carbapenem-resistant Klebsiella pneumonia (CRKP) bloodstream infections (BSIs) in a children’s hospital.Methods: A total of 62 strains were collected from Tianjin Children’s Hospital. Carba NP and polymerase chain reactions (PCR) were performed to detect MDR mechanisms. Multilocus sequence typing (MLST) was used for analyzing strain homology. Clinical data were collected and logistic regression was used for BSI risk factors.Results: ST11 was the principal ST among the CRKP isolates clinically, accounting for 56.45% (35/62); there were also 57.14% (20/35) ST11 CRKP strains co-carrying blaNDM-5 and blaKPC-2, which were resistant to most of the tested antibiotics, being susceptible only to cotrimoxazole and tigecycline. The clinical data showed that 72.73% (40/55) of children with CRKP infection had serious underlying diseases; 20.00% (11/55) patients developed BSIs with the potential to cause multiple organ failure, shock and death. The logistic regression showed that the risk of BSIs caused by CRKP strain infections in children with hematological malignancies after chemotherapy was 7 times that of other children (95%Cl: 1.298– 45.415, P=0.025).Conclusion: ST11 was the prevalent clone in our hospital. The emergence of ST11 CRKP co-carrying blaNDM-5 and blaKPC-2 should be a cause for alarm as they were resistant to most of the tested antibiotics. CRKP strain infections are mainly occurring in young immunocompromised patients and the chemotherapy for hematological malignancies is an independent risk factor for BSIs.Keywords: carbapenem-resistantKlebsiella pneumonia, blaKPC-2, blaNDM-5, ST11, children, bloodstream infection

Zhang S, Wang Q, Li D, et al. Cancer Manag Res. 2020;12:10389–10396. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors did not respond to our queries, nor did they provide original data for their study. As verifying the validity of the published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Zheng S, Zhang M, Bai H, et al. Int J Nanomedicine. 2019;14:9513–9524. The authors have advised due to an error at the time of figure assembly, the image of Spleen at 1 day in Figure 8B on page 9522 is incorrect. The correct Figure 8 is shown below. Figure 8 In vivo toxicity test of Mn-MoS2 QDs: (A(a–l)) Mouse serum biochemistry analysis and blood routine analysis before (0d, control) and after injection of Mn-MoS2 QDs for 1, 7, 21d. (B) Histological images of the heart, lungs, liver, spleen and kidneys of mice 1, 7 and 21 days post-intravenous injection of Mn-MoS2 QDs and in control mice. The organs were sectioned and stained with hematoxylin and eosin (H&E) and observed under a light microscope, scale bar = 100 μm. The authors apologize for this error and advise it does not affect the results of the paper.

Yaoqian Cao,&ast; Jiayue Chen,&ast; Lixia Dong Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixia Dong, Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China, Tel +86 13001385918, Email luckydonglixia@163.comBackground: Pneumocystis pneumonia (PCP) has a high mortality in HIV-negative immunocompromised patients. The occurrence and development of PCP are believed to be correlated with the level of lymphocytes and their subsets. The aim of this study was to determine if the levels of lymphocyte subpopulations and immunoglobulin are associated with PCP.Methods: A total of 74 immunocompromised patients were enrolled in this single-center cohort study. Diagnosis of PCP was based on the relevant pulmonary symptoms and radiological imaging, and the detection of Pneumocystis jirovecii in BAL fluid or biopsy tissue by metagenomic next-generation sequencing (mNGS). All patients were divided into two groups (PCP group and non-PCP group) and the patients in PCP group were then divided into two groupsbased on the outcome of the disease during the hospitalization.Results: We observed a significant lower level of IgG (p=0.000) and B lymphocyte counts (p=0.017) in the PCP group comparing to that in the non-PCP group. CD4+ T cell counts, as well as the ratio of CD4+/CD8+ T cells in circulation and BAL fluid were also lower in the PCP group comparing to those in the non-PCP group. Lactate dehydrogenase (LDH) in the PCP group was significantly higher than that in the non-PCP group (p=0.029). In the PCP group, a lower level of total lymphocytes (p=0.004), T cells (p=0.001), CD4+ cells (p=0.001), and CD8+ cells (p=0.007), as well as the proportion of lymphocytes in BAL fluid (p=0.000) were found in deceased patients comparing to those in the survived group.Conclusion: Our study revealed an important role of humoral immunity in the infection of Pneumocystis jirovecii. The level of B cells and IgG could be used as a supplement to predict the occurrence of PCP. The level of CD4+ and CD8+ lymphocytes was significantly correlated with the outcome of PCP.Keywords: Pneumocystis jirovecii pneumonia, immunosuppression, HIV-negative, lymphocytes, immunoglobulin

Yunzhi Liu,1,2,&ast; Na Zhao,3,&ast; Qishan Xu,1,2 Fan Deng,1 Ping Wang,1,2 Lijun Dong,1,2 Xiao Lu,2 Lihua Xia,3 Mingyong Wang,4 Zhengliang Chen,2 Jia Zhou,2 Daming Zuo1,5 1Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Guangdong Province Key Laboratory of Proteomics, Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 3Department of Medical Laboratory, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, Guangdong, 510399, People’s Republic of China; 4Xinxiang Key Laboratory of Immunoregulation and Molecular Diagnostics, Xinxiang, 453003, People’s Republic of China; 5Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia Zhou, Guangdong Province Key Laboratory of Proteomics, Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Tel +86-20-61648220, Fax +86-20-61648221, Email yuguomm@smu.edu.cn Daming Zuo, Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Tel +86-20-61648552, Fax + 86-20-61648221, Email zdaming@smu.edu.cnObjective: Mannan-binding lectin (MBL), a soluble pattern recognition molecule of the innate immune system, is primarily synthesized in the liver and secreted into the circulation. Low serum level of MBL has been reported to be related to an increased risk of lung diseases. Herein, we aimed to investigate the function of MBL in silicosis-associated pulmonary inflammation.Methods: Serum collected from silicosis patients was tested for correlation between serum MBL levels and Th17 immunity. In vitro studies were performed to further demonstrated the effect of MBL on Th17 polarization. Silica was intratracheally injected in wild type (WT) or MBL-deficient (MBL–/–) mice to induce silicosis-associated lung inflammation and fibrosis. Th17 response was evaluated to explore the effect of MBL on silicosis in vivo.Results: Silicosis patients with high serum MBL levels displayed ameliorative lung function. We demonstrated that serum MBL levels negatively correlated to Th17 cell frequency in silicosis patients. MBL protein markedly reduced expression of IL-17 but enhanced expression of Foxp3 in CD4+ T cells in vitro when subjected to Th17 or Treg polarizing conditions, respectively. The presence of MBL during Th17 cell polarization significantly limited aryl hydrocarbon receptor (AhR) expression and suppressed the signal transducer and activator of transcription 3 (STAT3) phosphorylation. Treatment with the AhR antagonist abolished the effect of MBL on Th17 response. Strikingly, MBL directly bound to AhR and affected its nuclear translocation. Furthermore, MBL–/– mice displayed elevated Th17 cell levels compared with WT mice in response to the silica challenge. The CD4+ T lymphocytes from silica-administrated MBL–/– mice exhibited more AhR expression than the wild-type counterparts.Conclusion: Our study suggested that MBL limited the Th17 immunity via controlling the AhR/STAT3 pathway, thus providing new insight into silicosis and other inflammatory diseases in patients with MBL deficiency.Keywords: silicosis, mannan-binding lectin, aryl hydrocarbon receptor, signal transducer and activator of transcription 3, Th17 cell

Suting Chen,&ast; Fen Wang,&ast; Yi Xue, Fengmin Huo, Junnan Jia, Lingling Dong, Liping Zhao, Guanglu Jiang, Hairong Huang National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China&ast;These authors contributed equally to this workCorrespondence: Hairong Huang, Email huanghairong@tb123.org; Guanglu Jiang, guanglu0725@126.comBackground: Nontuberculous mycobacteria (NTM) and their associated diseases remain neglected. Through minor modifications in our diagnostic algorithm, we observed an unexpected higher number of cultivable NTM isolates. Therefore, a retrospective study was performed thoroughly to investigate the effect of changed laboratory procedures on NTM isolation in a specialized tuberculosis hospital.Methods: NTM isolation rates and composition of NTM species were compared for the two diagnostic algorithms: (1) by using traditional p-nitrobenzoic acid (PNB) selective medium as a preliminary test to identify NTM isolates among the positive cultures (procedure I) and (2) by using the MPT64 antigen detection method to distinguish between Mycobacterium tuberculosis complex (MTBC) isolates and possible NTM isolates after a positive MGIT960 liquid culture (procedure II).Results: The NTM isolation rate in procedure II was significantly higher than the procedure I (18.08% vs 9.71%; P< 0.001). A noticeable increase in the ratio of NTM isolates among the identified mycobacteria was observed over the studied years (ie, from 58.18% in 2019 to 72.93% in 2021), which indicated a more precise prescription of species identification test after prompt information was provided in procedure II. In addition, the consistency of the identified species using multiple specimens from the same patient did not present a significant difference between the procedures.Conclusion: According to our study, NTM infection might be far more underestimated than it is. A diagnostic procedure combining MGIT960 culture and MPT64 antigen detection could timely and easily identify clues of NTM isolates and improve the diagnosis of NTM infections.Keywords: tuberculosis, nontuberculous mycobacteria, p-nitrobenzoic acid, MPT64 antigen, species

Siyuan Huang,1,&ast; Tao Feng,2,&ast; Jing Wang,1 Liang Dong3 1Department of Respiratory, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Respiratory Medicine, Shengli Oilfield Central Hospital, Dongying, People’s Republic of China; 3Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Dong, Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, 250014, People’s Republic of China, Tel +86-13505401207, Email dl5506@126.comBackground: Interleukin (IL)-36α, IL-36β, and IL-36γ belong to the IL-36 family and play an important role in the pathogenesis of many diseases. Chronic obstructive pulmonary disease (COPD) may be correlated with IL-36; however, the specific role of IL-36 in COPD is unclear. In this study, we aimed to clarify whether IL-36 could be an indicator for determining COPD severity and the specific nature of the pro-inflammatory effects of IL-36 in COPD.Methods: A total of 70 patients with COPD and 20 control subjects were included in this study. We collected peripheral blood samples from both the groups, analyzed the blood cell fractions by routine blood examination, and measured the serum levels of IL-36α, IL-36β, and IL-36γ by performing polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, the correlation between the number of neutrophils and eosinophils and the level of IL-36 was also analyzed.Results: We found that level of IL-36 in patients with COPD was positively correlated with the number of neutrophils but not with eosinophils, whereas the correlation was not found in the control group. Moreover, the level of IL-36 was negatively correlated with the level of lung function of patients with COPD, and the levels of IL-36α, IL-36β, and IL-36γ increased with advancing disease severity.Conclusion: In COPD, the pro-inflammatory effect of IL-36 is closely related to neutrophils, and hence, IL-36 might be considered a novel biomarker for determining COPD severity.Keywords: chronic obstructive pulmonary disease, IL-36, neutrophils, inflammation

Lei Dong,1,&ast; Nana Li,1,&ast; Xixi Wei,2 Yongling Wang,2 Liansheng Chang,3 Hongwei Wu,4 Liujiang Song,5 Kang Guo,6 Yuqiao Chang,1 Yaling Yin,2 Min Pan,7 Yuanyuan Shen,8 Feng Wang1 1Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 2Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 3Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 4Department of Chemistry, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 5Department of Ophthalmology, Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27517, USA; 6Department of Oncology, The Third affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China; 7Department of Ultrasound, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, 518034, People’s Republic of China; 8National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Wang, Henan Key Laboratory of Medical Tissue Regeneration, School of Basic Medical Sciences, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453002, People’s Republic of China, Email wfeng100@126.com Min Pan, Department of Ultrasound, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, No. 6001 Beihuan Avenue, Shenzhen, 518034, People’s Republic of China, Email min.pan@siat.ac.cnBackground: The blood–brain barrier (BBB) inhibits the delivery of macromolecular chemotherapeutic drugs to brain tumors, leading to low utilization rates and toxic side effects to surrounding tissues and organs. Ultrasonic targeted microbubble destruction (UTMD) technology can open the BBB, leading to a new type of drug delivery system with particular utility in glioma.Purpose: We have developed a new type of drug-loaded microbubble complex based on poly(lactic-co-glycolic acid) (PLGA) that targets gambogic acid (GA) to the area of brain tumors through UTMD.Methods: GA/PLGA nanoparticles were prepared by the double emulsification method, and cationic microbubbles (CMBs) were prepared by a thin film hydration method. The GA/PLGA-CMB microbubble complex was assembled through electrostatic attractions and was characterized chemically. The anti-glioblastoma effect of GA/PLGA-CMB combined with focused ultrasound (FUS) was evaluated by biochemical and imaging assays in cultured cells and model mice.Results: GA/PLGA-CMB combined with FUS demonstrated a significant inhibitory effect on glioblastoma cell lines U87 and U251 as compared with controls (P< 0.05). Tumor access and imaging analyses demonstrated that administration of GA/PLGA-CMBs combined with FUS can open the BBB and target the treatment of glioblastoma in a mouse model, as compared with control groups (P< 0.05).Conclusion: The combination of PLGA-CMB with FUS provides an effective and biocompatible drug delivery system, and its application to the delivery of GA in a mouse glioblastoma model was successful.Keywords: microbubbles, cavitation effect, glioblastoma, focused ultrasound

Yu H, Dong L, Wang H, et al. Cancer Manag Res. 2021;13:1803–1815. We, the Editor and Publisher of Cancer Management and Research are retracting the published article. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The authors listed in this publication have been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Sea ice fraction (SIF) over the Ross/Amundsen/Bellingshausen Sea (RAB) are investigated using the Modern-Era Retrospective Analysis for Research and Application, Version 2 (MERRA-2), focusing on the differences in time-lagged response to ENSO between the late 20th (1980–2000, L20) and the early 21st century (2001–2021, E21). The findings suggest that the typical Antarctic response to ENSO is influenced by changes in ENSO type/intensity, highlighting the need for caution when investigating the Antarctic teleconnection. Time-lagged regressions onto the mature phase of El Niño reveal that the SIF decrease and SST increase over the RAB is relatively weaker in E21 and most pronounced at 0–4 months lag. Conversely, the SIF in L20 continues to decline and reaches its peak at two-season lag (5–7 months). Tropospheric wind, pressure, and wave activity in response to El Niño in L20 show a zonally oriented high/low-pressure areas with two-season lag, enhancing the poleward flow that plays a key role in sea ice melt in the RAB, while this pattern in E21 is insignificant at the same lag. This study suggests that stronger (weaker) and more eastern (central) Pacific ENSOs on average in L20 (E21) are associated with this decadal change in the SIF response to ENSO.

High-frequency skywave propagation can be heavily impacted by D- and E-region dynamics requiring accurate global measurements to optimize performance. A standard measurement technique is to use ionosondes, but they are unable to measure below 1 MHz and are only available at a limited number of land-locked sites around the globe. In contrast, the Global Navigation Satellite System radio occultation (GNSS-RO) bottom-up method is a new approach specifically designed to generate electron density profiles in the D- and E- region ionosphere. It takes advantage of satellite constellations that currently provide over 20,000 daily measurements and global coverage. In this paper, GNSS-RO profiles were compared against ionosonde profiles at four sites covering a wide latitudinal range, and FIRI modeled profiles corresponding to the same latitude and local solar time. This comparison was completed using daytime profiles when sporadic-E (Es) was not present. The average GNSS-RO profile is found to be a few kilometers higher in altitude than the ionosonde profiles at the minimum frequency, fmin. When the ionosonde profiles are shifted so that the altitudes match at fmin, they are in good agreement up to the E-region peak altitude, hmE. Below fmin, the GNSS-RO profile is in good agreement with the FIRI profile, indicating that the profiles can measure the D- to E- transition region. The frequency of the E-region peak, foE, showed general agreement between the GNSS-RO and ionosonde measurements; however, the hmE agreement was weaker and the GNSS-RO profiles tend to have an hmE in a narrow altitude range for all profiles. Virtual heights were simulated for the GNSS-RO profiles using a numerical ray tracer for direct comparison with ionosonde observations, which showed agreement for many of the virtual heights near fmin, but also indicated a positive bias in the GNSS-RO virtual heights that may be due to low foE or elevated hmE estimates. For a quiet ionosphere, the shifted GNSS-RO electron density profiles were a good match for both measured ionosonde profiles and modeled FIRI profiles and the method is capable of providing global coverage of the D- and E-regions. Future work will require more data for seasonal and morning–afternoon comparisons as well as comparisons for the disturbed ionosphere when the sporadic-E layer is present.

Honglin Li,1,&ast; Chunzheng Ma,1,&ast; Sisi Chang,2 Yutan Xi,2 Shuai Shao,2 Mengli Chen,2 Juan Ren,2 Mingyue Sun,1 Liang Dong1 1Oncology Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 2Oncology Department, Henan Provincial University of Traditional Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Honglin Li, Oncology Department, Henan Provincial Hospital of Traditional Chinese Medicine, No. 6 Dongfeng Road, Zhengzhou, 450002, People’s Republic of China, Email 46991701@qq.com Chunzheng Ma, Oncology Department, Henan Provincial Hospital of Traditional Chinese Medicine, No. 6 Dongfeng Road, Zhengzhou, 450002, People’s Republic of China, Email mchzh666@126.comObjective: Traditional Chinese medicine (TCM) is an ancient form of personalized medicine and may improve morbidity and mortality in patients with esophageal cancer. This retrospective study aimed to evaluate the utility of TCM in the treatment of stage IV esophageal squamous cell carcinoma (SCC).Methods: We collected the medical records of patients with stage IV SCC admitted to Henan Provincial Hospital of Traditional Chinese Medicine and Linzhou Hospital of Traditional Chinese Medicine between July 2017 and June 2020. We used univariate and multivariate analyses to determine if the use of TCM improved patient prognosis. Moreover, cluster analysis was used to classify the patients according to TCM syndrome type and identify the most frequently used combinations of remedies.Results: After that 402 patients were included in PSM, of which 196 (48.8%) were treated with traditional Chinese medicine. TCM prolonged the survival time of patients with stage IV esophageal SCC (P=0.084), and was an independently associated with prognosis as demonstrated by Cox multivariate regression analysis [risk ratio (RR) =0.543, 95% confidence interval (CI): 0.390– 0.755, P< 0.001]. Association analysis revealed 75 cases (38.26%) had obstruction of phlegm and qi syndrome, 53 cases (27.04%) had phlegm and blood stasis syndrome, 38 cases (19.39%) had yang-qi deficiency syndrome, and 30 cases (15.31%) had heat retention and fluid consumption syndrome.Conclusion: Treatment with TCM derived therapies may increase the survival time of patients with stage IV esophageal SCC. Since these patients were diagnosed with different TCM syndromes, individualized TCM therapy is essential for improving symptoms and survival.Keywords: esophageal cancer, survival time, traditional Chinese medicine syndrome type, syndrome differentiation, syndrome treatment

Lujia Dong,1,&ast; Di Liu,2,&ast; Dongshuai Jing,1 Huihui Xu,1 Chenxiao Zhang,1 Donglei Qi,1 Dechun Liu1 1Department of Gastrointestinal Surgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang City, Henan Province, 471003, People’s Republic of China; 2Department of Thyroid Surgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang City, Henan Province, 471003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dechun LiuDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, No. 24 Jinghua Road, Jianxi District, Luoyang City, Henan Province, 471003, People’s Republic of ChinaEmail liudechunluoyang@163.comBackground: ALDOA-related specific transcript (ARST) is a recently identified long non-coding RNA (lncRNA) that suppresses glioma progression, while its role in other cancers is unclear. This study explored the role of ARST in colorectal cancer (CRC).Methods: The present study included 60 CRC patients, 60 patients with colon polyps (CP), 60 colitis patients, 60 hemorrhoid patients and 60 healthy controls. All participants were subjected to the collection of plasma, and paired CRC and non-tumor tissues were collected from CRC patients. All samples were subjected to RNA isolation and RT-qPCR to detect the expression of ARST. ROC curve and survival curve analysis were performed to evaluate the diagnostic and prognostic values of plasma ARST for CRC.Results: The expression levels of ARST were lower in CRC plasma samples compared to that in the patient groups and controls (p < 0.01), while other patient groups and controls showed no significant difference. The expression levels of ARST were also lower in CRC tissues compared to that in non-tumor tissues (p < 0.01). Plasma expression levels of ARST effectively distinguished CRC patients from other patients and controls. The expression levels of ARST were closely correlated with patients’ survival. Chi-squared test analysis showed that ARST was closely associated with patients’ distant metastasis but not tumor size.Conclusion: ARST is downregulated in CRC, and it might be applied in the diagnosis and prognosis of CRC.Keywords: ALDOA-related specific transcript, colorectal cancer, diagnosis, prognosis

Na Lv,1 Ying Wang,2 Min Zhao,2 Lina Dong,3 Hongen Wei2 1Department of Physiology, Basic Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Neurology, Shanxi Provincial People’s Hospital, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Central Laboratory, Shanxi Provincial People’s Hospital, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Hongen WeiDepartment of Neurology, Shanxi Provincial People’s Hospital, The Fifth Clinical Medical College of Shanxi Medical University, 29 Shuangta Road, Taiyuan, 030012, People’s Republic of ChinaTel +86 351 4960173Fax +86 351 4961994Email hongen.wei@sxmu.edu.cnAbstract: In developmental biology, transcription factors are involved in regulating the process of neural development, controlling the differentiation of nerve cells, and affecting the normal functioning of neural circuits. Transcription factors regulate the expression of multiple genes at the same time and have become a key gene category that is recognized to be disrupted in neurodevelopmental disorders such as autism spectrum disorders. This paper briefly introduces the expression and role of PAX2 in neurodevelopment and discusses the neurodevelopmental disorders associated with Pax2 mutations and its possible mechanism. Firstly, mutations in the human Pax2 gene are associated with abnormalities in multiple systems which can result in neurodevelopmental disorders such as intellectual disability, epilepsy and autism spectrum disorders. Secondly, the structure of Pax2 gene and PAX2 protein, as well as the function of Pax2 gene in neural development, was discussed. Finally, a diagram of the PAX2 protein regulatory network was made and a possible molecular mechanism of Pax2 mutations leading to neurodevelopmental disorders from the perspectives of developmental process and protein function was proposed.Keywords: PAX2, neural development, disorders, mechanism

Tao Wang,1,&ast; Lei Dong,2,&ast; Juanjuan Sun,3,&ast; Jialiang Shao,1 Jian Zhang,1 Siteng Chen,1 Chaofu Wang,2 Gangfeng Wu,4 Xiang Wang1 1Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Urology, Shaoxing People’s Hospital, Shaoxing, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gangfeng WuDepartment of Urology, Shaoxing People’s Hospital, No. 568 Zhongxing North Road, Shaoxing, Zhejiang, 312000, People’s Republic of ChinaEmail gaffwu@sina.comXiang WangDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of ChinaEmail xiang.wang1@shgh.cnBackground: The Gleason grading system is a major tool used for prediction of prostate cancer (PCa) behavior. Because of heterogeneity and sampling errors, prognosis is variable even among patients with the same Gleason score (GS). Therefore, more accurate biomarkers that complement the Gleason system are needed to improve the clinical management of PCa.Methods: Formalin-fixed, paraffin embedded tissue samples were obtained from radical prostatectomy (RP) (patient set 1, n=53) and needle biopsy (patient set 2, n=107; patient set 3, n=119). Cancer tissues from pure regions of each Gleason pattern (GP) were separately collected using laser-captured microdissection, followed by Real-time-PCR to determine the relative expression of miRNAs, including miR-1-5p, miR-21-5p, miR-30d-5p, miR-100-5p, miR-145-5p, miR-224-5p, and miR-708-5p. miRNA’s association with Gleason upgrading (GU) was evaluated using receiver operator characteristics (ROC) curve and multivariate logistic regression analysis. The integrated miRNA targets prediction and enrichment analyses were performed to determine the potential functions of miRNA.Results: It was found that miR-145-5p in GP3 from radical prostatectomy (RP) were overexpressed in patients with GS6 PCa compared with GS7 patients, which was further confirmed in a larger biopsy cohort. ROC curve analysis revealed that miR-145-5p in biopsy was significantly associated with GU upon RP. In multivariate analyses, miR-145-5p was an independent predictor of GU.Conclusion: Our study indicated that differential expression of miRNAs existed in GP3 from pure GS6 and GS7 PCa, highlighting a path toward the clinical use of miRNAs in predicting GU and assisting in treatment modality selection.Keywords: prostate cancer, microRNA, biopsy, active surveillance, Gleason upgrading

Xia Yu,&ast; Fengmin Huo,&ast; Fen Wang,&ast; Shu’an Wen, Guanglu Jiang, Yi Xue, Lingling Dong, Liping Zhao, Rui Zhu, Hairong Huang National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hairong HuangBeijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beiguan St, No. 9, Tongzhou Qu, Beijing, 101149, People’s Republic of ChinaEmail huanghairong@tb123.orgBackground: The antimicrobial activities of some new oxazolidinones against slowly growing mycobacteria (SGM) have never been well evaluated.Methods: We evaluate the in vitro susceptibility of 20 reference strains and 157 clinical isolates, pertaining different SGM species, against four oxazolidinones, ie, delpazolid, sutezolid, tedizolid and linezolid. In addition, the association of linezolid resistance and mutations in 23srRNA, rplC, rplD were also tested.Results: Sutezolid presented the strongest antimicrobial activity against the clinical isolates of M. intracellulare than the other oxazolidinones, with MIC50 at 2 μg/mL and MIC90 at 4 μg/mL. MICs of sutezolid were usually 4- to 8-fold lower than these of linezolid against M. intracellulare and M. avium. The tested isolates of M. kansasii were susceptible to all of the four oxazolidinones. According to the multiple sequence alignment, novel 23srRNA mutations (A2267C and A2266G) in M. intracellulare and rplD mutations (Thr147Ala) in M. avium were identified in this study which have plausible involvement in rendering resistance against linezolid.Conclusion: This study showed that sutezolid harbors the strongest inhibitory activity against M. intracellulare, M. avium and M. kansasii in vitro, which provided important insights on the potential clinical application of oxazolidinones for treating SGM infections.Keywords: slowly growing mycobacteria, delpazolid, sutezolid, tedizolid, linezolid, antimicrobial activity

Maoti Wei,1,&ast; Li Dong,2,&ast; Fenghua Wang,1 Kai Cui,3 Delong Ma,2 Ning Yang,4 Yuming Li4 1Center of Clinical Epidemiology, TEDA International Cardiovascular Hospital, Tianjin, People’s Republic of China; 2Department of Pediatrics, Center Hospital of Beikuo Town, Rizhao City, Shandong Province, People’s Republic of China; 3Department of Disease Prevention and Control, Hospital of Gaoxing Town, Rizhao City, Shandong Province, People’s Republic of China; 4Department of Hypertension, TEDA International Cardiovascular Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yang; Yuming Li Email yangningzxdl@sina.com; cardiolab@live.comObjective: To understand the prevalence and control of type 2 diabetes mellitus (T2DM) in a rural area, a cross-sectional study was carried out.Methods: Blood glucose was determined in residents over 60 years during the National Basic Public Health Service project carrying on in a rural town of Shandong province. Combined with detail information of diabetic history, the prevalence rate of this disease was calculated with a cutoff of more than 7.0 mmol/L of fasting plasma glucose (FPG). Furthermore, according to FPG levels, the control rate of diabetes was evaluated. Basic information and clinical laboratory tests were analyzed with proper methods for univariate analysis. Multivariable logistic analysis was used to explore multiple variables associated with the control effect of T2DM.Results: The prevalence rate of T2DM was 13.5% (95% CI 12.4%∼ 14.7%) without age difference in residents over 60-year old (X2= 1.078, P = 0.898). And the rate was higher in the female (16.1%, 95% CI 14.4%∼ 17.8%) than that in the male (11.3%, 95% CI 9.7%∼ 12.9%). The control rate of diabetes was 44.5% (95% CI 39.4– 49.6%, cutoff < 6.1 mmol/L for FPG) and 59.6% (95% CI 54.5– 64.6%, cutoff < 7.0 mmol/L for FPG), respectively. Most T2DM residents had balance foods, and a high proportion of drugs or insulin were used; however, the proportion of keeping exercise and modifying behaviors was low. Nearly 80% of the diabetic individuals used at least one drug or insulin. However, the more drugs or insulin used, the higher the FPG level was.Conclusion: A relative high level of T2DM prevailed in the rural area under fast economy-transforming. T2DM was controlled poor and measures should be further optimized to achieve ideal effect, especially for the use of anti-diabetic drugs.Keywords: rural area, type 2 diabetes mellitus, the control of diabetes

Dong Zhang,1 Jin-tao Zhang,1 Yun Pan,1 Xiao-fei Liu,1 Jia-wei Xu,2 Wen-jing Cui,1 Xin-rui Qiao,1 Liang Dong1,2 1Department of Respiratory, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, People’s Republic of ChinaCorrespondence: Liang DongDepartment of Respiratory, Shandong Provincial Qianfoshan Hospital Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, People’s Republic of ChinaEmail dl5506@126.comIntroduction: Alveolar epithelial tight junction damage and glycocalyx syndecan-1 (SDC-1) degrading are key factors to pulmonary edema of acute lung injury (ALI). Matrix metalloproteinase-9 (MMP-9) was involved in glycocalyx shedding, which was vital in SDC-1 degrading. This study aimed to investigate the effects of MMP-9-mediated SDC-1 shedding on tight junction in LPS-induced ALI.Methods: Mice were intratracheally atomized with 5 mg/kg LPS to stimulate different periods and LPS stimulation for 6 hours for further studies. A549 cells was stimulated for 6 hours by active MMP-9 protein to assess the effects of active MMP-9 protein on SDC-1 and tight junction. Afterward, the mice treated with MMP-9 shRNA or A549 cells were treated with MMP-9 siRNA before LPS stimulation for 6 hours to explore the effects on glycocalyx SDC-1 and tight junction. Moreover, the mice were treated with recombinant SDC-1 protein or A549 cells were over-expressed by pc-SDC-1 before LPS stimulation for 6 hours to explore the effects of SDC-1 on tight junction.Results: The mice persistent exposure to LPS showed that MMP-9 expression, glycocalyx SDC-1 shedding (SDC-1 decreased in alveolar epithelium and increased in the BALF), tight junction impairment, FITC-albumin infiltration, and other phenomena began to appear after 6 hours of LPS treatment in this study. The levels of SDC-1 and tight junction significantly decreased by active MMP-9 protein stimulation for 6 hours in the A549 cells. Therefore, LPS stimulation for six hours was selected for investigating the underlying effects of MMP-9-mediated SDC-1 shedding on the alveolar epithelial tight junction and pulmonary edema. Further vivo analysis showed that down regulation MMP-9 expression by MMP-9 shRNA significantly alleviated glycocalyx SDC-1 shedding (SDC-1 increased in alveolar epithelium and decreased in the BALF), tight junction (occludin and ZO-1) damage, and FITC-albumin infiltration in LPS-induced early ALI mice. The vitro results also showed that MMP-9 siRNA alleviated glycocalyx SDC-1 shedding (SDC-1 increased in cell culture medium and decreased in cell surface) and tight junction damage by downregulating MMP-9 expression in LPS-stimulated A549 cells. In addition, pretreatment with recombinant mouse SDC-1 protein significantly alleviated glycocalyx (SDC-1 increased in alveolar epithelium) and tight junction damage, and FITC-albumin infiltration in LPS-induced early ALI mice. Overexpression SDC-1 by pc-SDC-1 also significantly decreased tight junction damage in LPS-stimulated A549 cells.Conclusion: Glycocalyx SDC-1 shedding mediated by MMP-9 significantly aggravated tight junction damage, which further increased the pulmonary edema.Keywords: glycocalyx, SDC-1, MMP-9, tight junction, early ALI

Sisi Chang,1 Yahui Zhu,2 Yutan Xi,2 Fuyan Gao,2 Juanjuan Lu,2 Liang Dong,1 Chunzheng Ma,1 Honglin Li1 1Department of Oncology, Henan Provincial Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou, Henan Province, People’s Republic of China; 2Department of Oncology, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Chunzheng Ma; Honglin LiHenan Provincial Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine), Zhengzhou, Henan Province, People’s Republic of ChinaTel +86-18801611544Email mchzh666@126.com; 46991701@qq.comPurpose: To evaluate the role of DSCC1 in LUAD.Patients and Methods: Based on TCGA and GTEx, the Wilcoxon rank-sum test was used to compare the expression differences of DSCC1 between the normal samples of GTEx combined TCGA and the unpaired tumor samples of TCGA, and to compare DSCC1 expression values between tumor tissues and paired normal LUAD tissues in the TCGA cohort. Kruskal–Wallis rank-sum test, Wilcoxon rank-sum test, and logistics regression were used to compare the relationship between the expression of DSCC1 and the clinicopathological parameters. The biological function of DSCC1 was annotated by GSEA and ssGSEA, while Kaplan–Meier and Cox regression analysis were used to evaluate the prognostic value of DSCC1. Furthermore, the time-dependent ROC curve was used to analyze the diagnostic efficacy of DSCC1 in LUAD.Results: We downloaded the RNA-Seq data of 513 LUAD cases. The expression of DSCC1 was significantly correlated with T stage (OR = 1.04(1.02– 1.07), P = 0.002), pathological stage (OR=1.03 (1.01– 1.05), P = 0.008) and TP53 status (OR=1.10 (1.07– 1.14), P < 0.001). The high expression of DSCC1 was significantly correlated with DSS (HR=1.56 (1.07– 2.26), P = 0.021) and OS (HR=1.53 (1.14– 2.05), P = 0.004). Moreover, ROC curve analysis (AUC=0.845, CI (0.820-0.870)) indicated DSCC1 as a potential diagnostic molecule for LUAD. In the group with high DSCC1 expression phenotype, down-regulation of EGFR signal, reduction of IL-6 deprivation, cell cycle, and p53 signal pathway were significantly abundant. Spearman correlation analysis showed that the expression of DSCC1 was positively correlated with the infiltration of Th2 cells, T Helper cells.Conclusion: Our results suggest that DSCC1 may be an important biomarker for the treatment of LUAD.Keywords: DSCC1, LUAD, GSEA, prognosis, biomarker

Lei Shao, Chuan Zhang, Li Dong, Wen Da Zhou, Rui Heng Zhang, Wen Bin Wei Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wen Bin WeiBeijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, 1 Dong Jiao Min Xiang, Dong Cheng District, Beijing, 100730, People’s Republic of ChinaTel +86-10-58269516Fax +86-10-6512 5617Email weiwenbintr@163.comPurpose: To explore the prevalence and associations of vitreous macular traction (VMT) in Chinese population.Methods: A population-based cross-sectional study with 3468 individuals (mean age of 64.6 ± 9.8 years) based on Beijing Eye Study 2011. Participants underwent detailed ophthalmic examinations, including spectral domain optical coherence tomography (SD-OCT). VMT was defined as abnormal posterior vitreous detachment with anatomical deformation of the fovea, which may include pseudocyst, macular schisis, cystoid macular edema, and subretinal fluid.Main Outcome Measure: Prevalence of VMT.Results: A VMT was detected in 151 (2.3%) eyes (prevalence rate (mean ± SE): 2.3± 0.2%; 95% CI: 1.9%, 2.7%) of 80 (2.4%) subjects (prevalence rate: 2.4± 0.3%; 95% CI: 1.9%, 2.9%). Mean age of all subjects with VMT was 70.1± 8.7 years (median, 70.0 years; range, 50– 90 years), mean refractive error was − 0.22 ± 2.38D (median, 0.25 D; range, − 15.00 to 5.25D). In multivariate analysis, prevalence of VMT was associated with elder age (P=0.001, OR 1.06), female gender (P = 0.036, OR 1.77), subfoveal retinal thickness (P = 0.005, OR 1.01), and subfoveal choroidal thickness (P = 0.026, OR 0.10).Conclusion: In adult Chinese in Greater Beijing, the prevalence of VMT was 2.3% for eyes or 2.4% for subjects. While it was associated with elder age, female gender, thicker subfoveal retinal thickness and thinner subfoveal choroidal thickness.Keywords: vitreous macular traction, optical coherence tomography, the Beijing Eye Study