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Mei-Lan Wang,1,* Lu Hui Png,2,* Jing Ma,1 Ken Lin,1 Mei-hua Sun,1 Yi-Jun Chen,3 Xian-Chao Tang,4 Xian-Yun Bi,1 Ying-Qin Gao,1 Tie-Song Zhang1 1Department of Otolaryngology, Head and Neck Surgery, Kunming Children’s Hospital, Kunming, People’s Republic of China; 2Department of Otorhinolaryngology – Head and Neck Surgery, Singapore General Hospital, Singapore, Singapore; 3Department of Otolaryngology, Head and Neck Surgery, Kunming Children’s Hospital, Kunming Medical University, Kunming, People’s Republic of China; 4Department of Radiology, Kunming Children’s Hospital, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lu Hui Png; Tie-Song Zhang, Email Luhpng@gmail.com; zhangtiesong@etyy.cnObjective: We aim to determine the utility of CT scan as a method to accurately confirm pediatric airway foreign bodies (AFBs), the current gold standard of which is chest X-ray as the primary imaging modality in the investigation screening of AFBs with progression to microlaryngobronchoscopy.Methods: A retrospective cohort study of children diagnosed with suspected AFBs between July 2019 and June 2020 was conducted. The primary outcome of missed AFBs from radiologic investigations was recorded.Results: A total of 226 children with an average age of 1.94 years were included in this study. One hundred and two children were eventually admitted to the hospital for microlaryngobronchoscopy. A total of 89 cases were initially examined by chest X-ray with the diagnosis confirmed in 26 cases. The initial examination was chest CT scan in 105 cases, of which the diagnosis was confirmed in 46 cases. The initial examination was chest CT scan with airway reconstruction in 32 cases, and the diagnosis was confirmed in 17 cases. Patients with negative chest CT scan with airway reconstruction were observed to have resolution of symptoms with no further need for bronchoscopy.Conclusion: Chest CT scan with airway reconstruction had the highest rate of confirmed diagnosis of pediatric AFBs on initial scanning, followed by chest CT scan, and finally chest X-ray with fluoroscopy; there was no missed diagnosis in chest CT scan with airway reconstruction. Chest CT scan with airway reconstruction can accurately and quickly detect AFBs and reduce unnecessary bronchoscopy.Keywords: airway foreign body, chest X-ray, chest CT scan, airway reconstruction, microlaryngobronchoscopy

Xin-Yuan Chen,1,&ast; Xin-Jie Zhu,1,&ast; Min Chen,1 Mei-Ping Lu,1 Mei-Lin Wang,2,3 Min Yin,1,4 Ruo-Xi Chen,1 Zhong-Fei Wu,1 Dong-Yun Bu,1 Zheng-Dong Zhang,2,3 Lei Cheng1,4 1Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 4International Centre for Allergy Research, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Cheng, Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email chenglei@jsph.org.cn Zheng-Dong Zhang, Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People’s Republic of China, Email drzdzhang@njmu.edu.cnBackground: Genetic variants in GARP (also known as LRRC32) have been reported to have significant associations with asthma and eczema in special populations, but little is known about allergic rhinitis. This study purposes to evaluate the association of single nucleotide polymorphisms (SNPs) in GARP with house dust mite (HDM)-sensitized persistent allergic rhinitis (PER) in a population of Han Chinese.Methods: In this hospital-based case–control study, 534 HDM-sensitized PER patients and 451 healthy controls were recruited from East China. In this population, six SNPs in GARP were identified. Serum total and specific IgE levels were measured with ImmunoCAP. Secondary structure and minimum free energy were predicted by RNAfold.Results: rs79525962 was associated with the risk of HDM-sensitized PER (P < 0.05). The individuals with CT+TT genotype demonstrated a higher risk of HDM-sensitized PER than those with CC genotype (adjusted OR = 1.393, 95% CI = 1.019– 1.904). The homozygous genotype CC of rs3781699 rendered a lower risk of HDM-sensitized PER than the wild-type genotype AA (adjusted OR = 0.646, 95% CI = 0.427– 0.976); however, the genotype and allele frequencies of rs3781699 demonstrated no associations with HDM-sensitized PER (P > 0.05). rs79525962 increased the risk of HDM-sensitized PER in the subgroup aged ≥ 16 years (adjusted OR = 1.745, 95% CI = 1.103– 2.760), and this high risk was also found in the females (adjusted OR = 1.708, 95% CI = 1.021– 2.856). The G-C haplotype of rs1320646-rs3781699 rendered a lower risk of HDM-sensitized PER than the common haplotype G-A (adjusted OR = 0.819, 95% CI = 0.676– 0.993). The secondary structure of GARP altered in response to different genotypes of rs79525962 and rs3781699.Conclusion: SNP rs79525962 in the GARP gene marks a risk locus of HDM-sensitized PER in Chinese Hans.Keywords: allergic rhinitis, mites, GARP, LRRC32, single nucleotide polymorphism, genetic association studies

Ruo-Xi Chen,1,&ast; Meng-Di Dai,1,&ast; Qing-Zhao Zhang,1 Mei-Ping Lu,1 Mei-Lin Wang,2,3 Min Yin,1,4 Xin-Jie Zhu,1 Zhong-Fei Wu,1 Zheng-Dong Zhang,2,3 Lei Cheng1,4 1Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 4International Centre for Allergy Research, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Cheng, Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email chenglei@jsph.org.cn Zheng-Dong Zhang, Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People’s Republic of China, Email drzdzhang@njmu.edu.cnABSTRACT: Background: Allergic rhinitis (AR) is a nasal inflammatory disease resulting from a complex interplay between genetic and environmental factors. The association between Toll-like receptor (TLR) signaling pathway and environmental factors in AR pathogenesis remains to be explored. This study aims to assess the genetic association of AR with single nucleotide polymorphisms (SNPs) in TLR signaling pathway, and investigate the roles of gene–gene and gene–environment interactions in AR.Methods: A total of 452 AR patients and 495 healthy controls from eastern China were enrolled in this hospital-based case–control study. We evaluated putatively functional genetic polymorphisms in TLR2, TLR4 and CD14 genes for their association with susceptibility to AR and related clinical phenotypes. Interactions between environmental factors (such as traffic pollution, residence, pet keeping) and polymorphisms with AR were examined using logistic regression. Models were stratified by genotype and interaction terms, and tested for the significance of gene–gene and gene–environment interactions.Results: In the single-locus analysis, two SNPs in CD14, rs2563298 (A/C) and rs2569191 (C/T) were associated with a significantly decreased risk of AR. Compared with the GG genotype, the GT and GT/TT genotypes of TLR2 rs7656411 (G/T) were associated with a significantly increased risk of AR. Gene–gene interactions (eg, TLR2 rs7656411, TLR4 rs1927914, and CD14 rs2563298) was associated with AR. Gene–environment interactions (eg, TLR4 or CD14 polymorphisms and certain environmental exposures) were found in AR cases, but they were not significant after Bonferroni correction.Conclusion: The genetic polymorphisms of TLR2 and CD14 and gene–gene interactions in TLR signaling pathway were associated with susceptibility to AR in this Han Chinese population. However, the present results were limited to support the association between gene–environment interactions and AR.Keywords: allergic rhinitis, toll-like receptors, CD14, single nucleotide polymorphism, gene–gene interaction, gene–environment interaction

Yu Li,1,&ast; Mei-Ling Wang,1,&ast; Bo Zhang,1 Xiao-Xu Fan,1 Qin Tang,1 Xue Yu,2 Li-Na Li,2 Ang-Ran Fan,2 Hong-Sheng Chang,1 Lan-Zhen Zhang1 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China; 2School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan-Zhen Zhang; Hong-Sheng Chang, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Northeast Corner of the Intersection of Sunshine South Street and Baiyang East Road, Fangshan District, Beijing, 102488, People’s Republic of China, Tel +86 10 5391 2122, Email zhanglanzhen01@126.com; chs1971@sina.comBackground: There is growing evidence to suggest that ginsenoside Rd (GRd) has a therapeutic effect on depression, but the specific mechanisms behind its activity require further study.Objective: This study is designed to investigate the antidepressant-like effect and underlying mechanisms of GRd.Methods: In this study, the behavioral despair mouse model of depression and chronic unpredictable mild stress (CUMS) rat model of depression were established to explore the effects of GRd on depression-like behavior and its underlying mechanisms. Behavioral tests were used to evaluate the replication of animal models and depression-like behaviors. The hypoxia-inducible factor-1α (HIF-1α) blocker 2-methoxyestradiol (2-ME) was injected to determine the role of HIF-1α in the antidepressant-like effect of GRd. In addition, molecular biology techniques were used to determine the mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators, that is synapsin 1 (SYN 1) and postsynaptic density protein 95 (PSD 95). In silico binding interaction studies of GRd with focused target proteins were performed using molecular docking to predict the affinity and optimal binding mode between ligands and receptors.Results: Our data show that GRd significantly reversed depression-like behavior and promoted mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators. However, the antidepressant-like effect of GRd disappeared upon inhibition of HIF-1α expression following administration of 2-ME. Furthermore, molecular docking results showed that GRd possessed significant binding affinity for HIF-1α, VEGF, and VEGFR-2.Conclusion: Our results show that GRd exhibits significant antidepressant-like effect and that HIF-1α signaling pathway is a promising target for the treatment of depression.Keywords: ginsenoside Rd, antidepressant effect, HIF-1α-VEGF signaling pathway, VEGFR-2, synaptic plasticity-related regulators, molecular docking

Zi-Hong Liang,1 Yan-Bo Jia,2 Mei-Ling Wang,1 Zi-Ru Li,1 Min Li,1 Yong-Li Yun,1 Run-Xiu Zhu1 1Department of Neurology, Inner Mongolia Autonomous Region People’s Hospital, Huhhot, Inner Mongolia, People’s Republic of China; 2Department of Orthopaedics, The Second Affiliated Hospital of Inner Mongolia Medical University, Huhhot, Inner Mongolia, People’s Republic of ChinaCorrespondence: Run-Xiu ZhuDepartment of Neurology, Inner Mongolia Autonomous Region People’s Hospital, No. 20 Zhaowuda Road, Huhhot, Inner Mongolia010017, People’s Republic of ChinaTel +86 0 471 328 3999Fax +86 0 471 328 3999Email xcinhah-21@foxmail.comBackground: Post-stroke depression (PSD) is one of the most common psychiatric diseases afflicting stroke survivors. This study was conducted to assess the efficacy of ginkgo biloba extract as augmentation of venlafaxine in treating PSD.Methods: The included PSD patients were randomly assigned into the experiment group (receiving ginkgo biloba extract plus venlafaxine) and control group (receiving venlafaxine alone). The treatment was continued for eight weeks. The Hamilton Depression Rating Scale (HDRS) and the Self-rating Depression Scale (SDS) were used to assess the depressive symptoms. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the neurological defect, and the Activities of Daily Living (ADL) was used to assess recovery of abilities of patients after stroke. Meanwhile, the levels of serum 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) were measured before and after treatment. The dose of venlafaxine used and adverse events were also recorded.Results: Each group had 40 PSD patients. After treatment, the depressive symptoms, neurological defect and living function were significantly improved in both groups. But the patients receiving ginkgo biloba extract plus venlafaxine had the significantly lower average HDRS score (p=0.0008), SDS score (p

Zi-Hong Liang,1 Yan-Bo Jia,2 Zi-Ru Li,1 Min Li,1 Mei-Ling Wang,1 Yong-Li Yun,1 Li-Jun Yu,1 Lei Shi,1 Run-Xiu Zhu11Department of Neurology, Inner Mongolia Autonomous Region People’s Hospital, Huhhot, Inner Mongolia, People’s Republic of China; 2Department of Orthopaedics, The Second Affiliated Hospital of Inner Mongolia Medical University, Huhhot, Inner Mongolia, People’s Republic of ChinaBackground: Depression can seriously affect the quality of life of type 2 diabetes mellitus (T2DM) patients after stroke. However, there were still no objective methods to diagnose T2DM patients with poststroke depression (PSD). Therefore, we conducted this study to deal with this problem.Methods: Gas chromatography-mass spectroscopy (GC-MS)-based metabolomics profiling method was used to profile the urinary metabolites from 83 nondepressed T2DM patients after stroke and 101 T2DM patients with PSD. The orthogonal partial least-squares discriminant analysis was conducted to explore the metabolic differences in T2DM patients with PSD. The logistic regression analysis was performed to identify the optimal and simplified biomarker panel for diagnosing T2DM patients with PSD. The receiver operating characteristic curve analysis was used to assess the diagnostic performance of this biomarker panel.Results: In total, 23 differential metabolites (7 decreased and 16 increased in T2DM patients with PSD) were found. A panel consisting of pseudouridine, malic acid, hypoxanthine, 3,4-dihydroxybutyric acid, fructose and inositol was identified. This panel could effectively separate T2DM patients with PSD from nondepressed T2DM patients after stroke. The area under the curve was 0.965 in the training set and 0.909 in the validation set. Meanwhile, we found that the galactose metabolism was significantly affected in T2DM patients with PSD.Conclusion: Our results could be helpful for future development of an objective method to diagnose T2DM patients with PSD and provide novel ideas to study the pathogenesis of depression.Keywords: type 2 diabetes mellitus, post-stroke depression, metabolite, metabolomics

Yi-Yen Lee,1,2,* Aliaksandr A Yarmishyn,3,4,* Mong-Lien Wang,3,4 Hsiao-Yun Chen,4,5 Shih-Hwa Chiou,3–5 Yi-Ping Yang,4,5 Chun-Fu Lin,1,2 Pin-I Huang,2,6 Yi-Wei Chen,2,6 Hsin-I Ma,7 Ming-Teh Chen1,2 1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, 2Faculty of Medicine, National Yang-Ming University, 3Institute of Pharmacology, National Yang-Ming University, 4Department of Medical Research, Taipei Veterans General Hospital, 5Institute of Clinical Medicine, National Yang Ming University, 6Cancer Center, Radiation Oncology Division, Taipei Veterans General Hospital, 7Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan *These authors contributed equally to this work Background: Glioblastoma multiforme (GBM) is the most malignant brain tumor, and there is no effective treatment strategy. Patients with GBM have a median overall survival of only 14.6 months. Current treatment consists of safe and maximal surgical excision, followed by concurrent chemoradiotherapy and maintenance chemotherapy. There are several obstacles that hinder the effectiveness of this aggressive treatment. Temozolomide (TMZ) is an oral alkylating drug that acts through alkylating the O6 position of guanine in DNA that leads to cell death. However, the expression and enzymatic activity of the DNA repair protein MGMT limits the therapeutic benefit from treatment with TMZ. MGMT reduces the efficacy of alkylating drugs by removing the methyl or alkyl group from damaged O6-methylguanine. Expression levels of MGMT play an important role in the outcome of GBM patients. miRNAs are a group of small regulatory RNAs that control target gene expression by binding to mRNAs. miR-142-3p has been found to be an important factor in the development and maintenance of the oncogenic state. Results: In this study, we sought to investigate whether miR-142-3p can regulate MGMT gene expression in GBM cells. Here, we show that miR-142-3p downregulates MGMT expression through binding to the 3′-UTR of MGMT mRNA, thus affecting protein translation. Responsiveness to TMZ was significantly enhanced after transfection with miR-142-3p. Overexpression of miR-142-3p also sensitized GBM cells to alkylating drugs. Conclusion: Above all, our findings demonstrate that miR-142-3p plays a critical role in regulating MGMT expression, has great potential for future clinical applications, and acts as a new diagnostic marker for this intractable disease. Keywords: glioblastoma, O6-methylguanine-DNA methyltransferase, miR-142-3p, carmustine, temozolomide

A recombinant porcine interferon alpha (rPoIFN-α) has been developed and patented previously (Chinese patent number ZL200810020180.4). In the current study, we investigated the inhibitory effects of the rPoIFN-α on the propagation of porcine transmissible gastroenteritis virus (TGEV) at different doses in porcine kidney cell line (PK-15). To quantitatively determine the inhibition of viral growth by rPoIFN-α, TCID50 assay, plaque formation assay, real-time qRT-PCR, western blot and immunofluorescence assay were adopted to evaluate the changes of viral infectious particles, viral genome copy numbers and viral protein expression levels respectively. The results demonstrated that all the three batches of the rPoIFN-α tested inhibited TGEVinduced cytopathic effect in PK-15 cells with very similar potency. rPoIFN-α inhibited TGEV proliferation more strongly than human IFN-α product. The inhibitory activity of rPoIFN-α on TGEV growth in culture was dose dependent, and the activity was gradually reduced with the decreasing of the concentration of rPoIFN-α.

Meiling Wang,1,2,* Xiaoyu Cao,2,* Qingxin Liu,2 Wenbin Ma,1,2 Xiaoqian Guo,1,3 Xuewu Liu1 1Department of Neurology, Qilu Hospital of Shandong University, Jinan, 2Department of Neurology, Binzhou Medical University Hospital, Binzhou, 3Department of Neurology, Jining First People’s Hospital, Jining, Shandong, People’s Republic of China *These authors contributed equally to this work Objective: The objective of this study was to analyze the clinical manifestation, course, evolution, image manifestation, and treatments of LGI1 limbic encephalitis (LE). Patients and methods: Studies confirmed that LE with the complex antibody of voltage-gated potassium channels is LGI1 LE. Since then, LE cases have been reported. In this study, 10 typical LE cases were searched in PubMed. These cases and one additional case, which we reported herein, were retrospectively analyzed. Results: All the patients suffered from recent memory deterioration. The following cases were observed: eight with faciobrachial dystonic seizures (FBDS), six with different kinds of epileptic seizures (four complex partial seizures, one myoclonus seizure, and one generalized tonic–clonic seizure), four with FBDS and different kinds of epileptic seizures at the same time, five with mental disorders (one visual hallucination, one paranoia, one depression, one anxiety, and one dysphoria), five with hyponatremia, and two with sleep disorder. The brain MRI of nine patients revealed abnormalities in the mediotemporal lobe and the hippocampus. The LGI1 antibodies in the blood and/or cerebrospinal fluid (CSF) were positive. The content of the CSF protein of two patients increased slightly. The tumor marker of all the patients was normal, but capitate myxoma was detected in the combined pancreas duct of one patient. Gamma globulin and hormone treatments were administered to nine patients. Of these patients, six received a combination of antiepileptic drugs. The clinical symptoms of all the patients improved. Conclusion: LGI1 LE is an autoimmune encephalitis whose clinical manifestations are memory deterioration, FBDS, epileptic seizure, mental disorders, and hyponatremia. Brain MRI shows that this autoimmune disease mainly involves the mediotemporal lobe and the hippocampus. This condition can also be manifested with other autoimmune encephalitis cases but can be rarely associated with tumors. After patients with LGI1 LE receive gamma globulin and hormone treatments, their clinical prognosis is good. Keywords: positive LGI1, limbic encephalitis, epilepsy, FBDS, immunotherapy

Yu Zhu,1,* Huiliang Cao,2,* Shichong Qiao,1,* Manle Wang,2,3 Yingxin Gu,1 Huiwen Luo,1 Fanhao Meng,2 Xuanyong Liu,2 Hongchang Lai1 1Department of Oral and Maxillofacial Implantology, Shanghai Key Laboratory of Stomatology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 2State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 3School of Materials Engineering, Shanghai University of Engineering Science, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: A versatile strategy to endow dental implants with long-term antibacterial ability without compromising the cytocompatibility is highly desirable to combat implant-related infection. Silver nanoparticles (Ag NPs) have been utilized as a highly effective and broad-spectrum antibacterial agent for surface modification of biomedical devices. However, the high mobility and subsequent hazardous effects of the particles on mammalian cells may limit its practical applications. Thus, Ag NPs were immobilized on the surface of sand-blasted, large grit, and acid-etched (SLA) titanium by manipulating the atomic-scale heating effect of silver plasma immersion ion implantation. The silver plasma immersion ion implantation-treated SLA surface gave rise to both good antibacterial activity and excellent compatibility with mammalian cells. The antibacterial activity rendered by the immobilized Ag NPs was assessed using Fusobacterium nucleatum and Staphylococcus aureus, commonly suspected pathogens for peri-implant disease. The immobilized Ag NPs offered a good defense against multiple cycles of bacteria attack in both F. nucleatum and S. aureus, and the mechanism was independent of silver release. F. nucleatum showed a higher susceptibility to Ag NPs than S. aureus, which might be explained by the presence of different wall structures. Moreover, the immobilized Ag NPs had no apparent toxic influence on the viability, proliferation, and differentiation of rat bone marrow mesenchymal stem cells. These results demonstrated that good bactericidal activity could be obtained with very small quantities of immobilized Ag NPs, which were not detrimental to the mammalian cells involved in the osseointegration process, and promising for titanium-based dental implants with commercial SLA surfaces. Keywords: silver nanoparticles, surface modification, antibacterial effects, cytotoxicity, plasma immersion ion implantation

Contents Protein disulphide isomerase family A3 (PDIA3) has an activity of thioredoxin, widely expressed in multiple tissues and involved in multiple cellular processes. It was recently found in human and mouse sperm cells and could affect sperm-egg fusion. Therefore, the present investigation aims to identify PDIA3 mRNA and protein in rat testis and sperm cells. Rat PDIA3 cDNA was cloned by RT-PCR. The cRNA riboprobe was transcribed from PDIA3 cDNA and was used to display PDIA3 mRNA location in rat testes by in situ hybridization. PDIA3 protein distribution was also observed in testis and sperm cells by immunohistochemistry and immunocytochemistry, respectively. The rat PDIA3 transcript and protein were localized in the cells from spermatocytes to the spermatozoa phases of rat testes, mostly in the pachytene spermatocytes. PDIA3 protein was also observed on the intact sperm membrane including the tail. The rat PDIA3 gene is transcribed and translated through the whole spermatogenesis process, and the PDIA3 protein is spread all over the sperm cell membrane. The results provide some primary information about PDIA3 in testis and sperm for further study on PDIA3 function in rat spermatogenesis and sperm-egg fusion. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Digital chest imaging has replaced film chest radiographs in many centers, but the International Labour Organization classification system, which is the most widely used system for recognition and classification of dust-related abnormalities, is predicated on film chest radiographs. The purpose of this study was to evaluate the equivalency of digital chest radiographs (including both hard copy and soft copy) with film radiographs for the recognition and quantification of abnormalities consistent with pneumoconiosis using the International Labour Organization classification system. Materials and Methods: Digital chest images and film images, obtained from 107 subjects with a range of parenchymal and pleural abnormalities, were classified in random order by six B readers. Results: Readings of film and soft copy images were equivalent for small opacity profusion; readings of hard copy images had significantly greater prevalence of small opacities compared to film and soft copy. The prevalence of large opacities differed significantly among all three image formats: hard copy greater than film greater than soft copy. However, film and soft copy readings for large opacities did not differ significantly when images demonstrating the coalescence of small opacities that had not yet become a large opacity were grouped with large opacities. The prevalence of pleural abnormalities differed significantly among all three image formats: film greater than hard copy greater than soft copy. Conclusions: Film and soft copy images can be recommended for the recognition and classification of dust-related parenchymal abnormalities using International Labour Organization classifications. The role of digital radiography in reading for pleural abnormalities requires additional investigation. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVE: Spirometry is performed to monitor lung health, but variability between tests can hinder recognition of excessive FEV(1) declines. We sought to describe the relationship between FEV(1) changes over 1 to 5 years and FEV(1) declines over longer terms, using 21,821 test results from 1,884 workers who participated in an annual health monitoring program at a chemical plant between 1973 and 2003. METHODS: Test results from workers with five or more valid results over >/= 10 years were included in our analysis (mean initial worker age, 35 years; range, 18 to 62 years; 91% male; 35% current smokers and 41% nonsmokers). For each worker, long-term FEV(1) slopes (milliliters per year) were calculated by simple linear regression using all available results and compared to changes in FEV(1) between two tests over 1 to 5 years, expressed in both milliliters and percentage of initial value. RESULTS: Long-term (mean, 18 years; range, 10 to 30 years) slopes averaged - 29.1 mL/yr (- 27, - 29, and - 37 mL/yr for male never-smokers, former smokers, and current smokers, and - 20, - 26, and - 27 mL/yr for female never-smokers, former smokers, and current smokers, respectively). Excessive short-term and long-term declines were defined by lower fifth percentile values. Individuals with abnormal short-term declines were found to be 3 to 18 times more likely to ultimately show excessive long-term declines; with the strength of the association increasing with the length of the short-term testing interval. Better test operating characteristics resulted if abnormal short-term FEV(1) change was based on percentage change (ie, percentage per year) rather than absolute change (ie, milliliters per year). CONCLUSIONS: Our findings provide guidance for interpreting periodic spirometry results from individuals exposed to respiratory hazards. [ABSTRACT FROM AUTHOR]

Post-artesunate delayed hemolysis (PADH) occurred in 6 of 24 children treated with artesunate for severe malaria in the United States; however, severe hemolysis requiring hospitalization or transfusion was rare. In children in the United States treated with artesunate, counseling, and symptom monitoring may be preferred to weekly laboratory surveillance for PADH., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Reports of burnout and poor mental health are at all-time highs among working U.S. adults.  Simultaneously, failure to promote diversity, equity, and inclusion (DEI) is among the top characteristics of an unhealthy work culture and has contributed to high rates of employee attrition. Though many organizations across multiple sectors have made pledges to prioritize employee health and invest in DEI in recent years, few have explicitly addressed these two issues as interconnected. The link between the workplace as a determinant of mental and physical health is well-established. Several studies demonstrate that experiencing discrimination in the workplace is associated with detrimental physical and mental health outcomes. Additionally, the way work is structured directly and indirectly contributes to employee health inequities. In this commentary, we make the connection between employee health and organizational DEI and propose guiding principles to synchronize DEI and employee health initiatives in the workplace. These include: investing in DEI as a cornerstone for developing a healthy workforce for all; recognizing differences in employee experiences, needs, and their connection to health; prioritizing systemic approaches to promote employee health and organizational DEI. Embedding employee health and DEI efforts into broader organizational strategy is a crucial step towards fostering equitable practices that promote inclusive work environments and positive employee well-being., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Delirium is a common complication in intensive care unit (ICU) patients. It can lead to various adverse events. In this study, we investigated the effectiveness of combining the use of the PREdiction of DELIRium (PRE-DELIRIC) model for delirium risk assessment and the use of a multicomponent care bundle for delirium assessment, prevention, and care in terms of reductions in the incidence of delirium among surgical ICU patients., Methods: This retrospective study included surgical ICU patients who had received PRE-DELIRIC-guided SMART/SmART care (SMART care: SmART bundle plus multidisciplinary team; SmART care: Sleep/sweet sense of home (creating a comforting and restful environment for patients), Assessment (regular and thorough evaluation of patient needs and conditions), Release (revised endotracheal tube care/removal, restraint device care, and immobility reduction for patient comfort), and Time (reorientation of time to optimize patient care schedules) in our hospital between May 2022 and March 2023 (intervention group) and individuals who had received usual care between January 2021 and April 2022 (historical control group). The SmART intervention involves providing care in the following domains: sleep/sweet sense of home, assessment, release, and time. Patients with a PRE-DELIRIC score of >30% received SMART care, which includes multidisciplinary (physicians, pharmacists, respiratory therapists, and physiotherapists) care in addition to SmART care. For the control group, usual care was provided following the guidelines for the prevention and management of pain, agitation, delirium, immobility, and sleep disruption. The primary outcome was delirium incidence during ICU stay, which was assessed using the Intensive Care Delirium Screening Checklist. The secondary outcomes were the duration of ICU stay, rate of unplanned self-extubation, and status of ICU discharge., Results: The intervention and control groups comprised 184 and 197 patients, respectively; their mean ages were 63.7 ± 18.4 years and 62.4 ± 19.5 years, respectively. The incidence of delirium was significantly lower (p = 0.001) in the intervention group (22.3%) than in the control group (47.7%)., Conclusion: Our findings suggest that the PRE-DELIRIC-guided SMART/SmART care intervention is effective in preventing and managing delirium among surgical ICU patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Antibiotic-induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cell therapies. In this study, we observed that prior exposure to broad-spectrum ABX with extended anaerobic coverage like piperacillin-tazobactam and meropenem was associated with worsened anti-CD19 CAR-T therapy survival outcomes in large B-cell lymphoma patients (n=422), compared to other ABX classes. In a discovery subset of these patients (n=67), we found that the use of these ABX was in turn associated with substantial dysbiosis of gut microbiome function, resulting in significant alterations of the gut and blood metabolome, including microbial effectors such as short-chain fatty acids (SCFAs) and other anionic metabolites, findings that were largely reproduced in an external validation cohort (n=58). Broader evaluation of circulating microbial metabolites revealed reductions in indole and cresol derivatives, as well as trimethylamine N-oxide, in patients who received ABX treatment (discovery n=40, validation n=28). These findings were recapitulated in an immune-competent CAR-T mouse model, where meropenem-induced dysbiosis led to a systemic dysmetabolome and decreased murine anti-CD19 CAR-T efficacy. Furthermore, we demonstrate that SCFAs can enhance the metabolic fitness of CAR-T cells, leading to improved tumor killing capacity. Together, these results suggest that broad-spectrum ABX deplete metabolically active commensals whose metabolites are essential for enhancing CAR-T efficacy, shedding light on the intricate relationship between ABX exposure, microbiome function and their impact on CAR-T cell efficacy. This highlights the potential for modulating the microbiome to augment CAR-T immunotherapy., (Copyright © 2024 American Society of Hematology.)

Constructing nanoscale spin devices has been a crucial pursuit in the field of nano spintronics. Here, by using the density functional theory (DFT) and nonequilibrium Green's function (NEGF) method, high-performance nanoscale spin-MOSFET devices using half-metallic 2D Cr 2 Se 3 as electrodes are theoretically designed. Specifically, seven typical two-dimensional (2D) semiconductors, Sb, Bi, BP, BAs, MoTe 2 , WTe 2 , and WSeTe (with two different contacting surfaces), are considered here as the channel materials. The properties of contact interfaces between these 2D semiconductors and half-metallic 2D Cr 2 Se 3 are first investigated. It is found that except BP and BAs (having Schottky contacts with Cr 2 Se 3 ), the other 2D semiconductors have vertical Ohmic contacts with Cr 2 Se 3 among which Cr 2 Se 3 /Sb, Cr 2 Se 3 /MoTe 2 , Cr 2 Se 3 /WTe 2 , Cr 2 Se 3 /WSeTe-Se, and Cr 2 Se 3 /WSeTe-Te retain the half-metallic characteristic. Then, these 2D semiconductors with Ohmic vertical contacts are further used to construct spin-MOSFET devices. The results show that devices constructed by half-metallic vertical contacting systems have nearly 100% SIE and therefore giant MR (>10 7 %) when the gate voltage varies. Furthermore, four designed spin-MOSFET devices, namely, Cr 2 Se 3 /MoTe 2 , Cr 2 Se 3 /WTe 2 , Cr 2 Se 3 /WSeTe-Se, and Cr 2 Se 3 /WSeTe-Te spin-MOSFET have high efficient gate modulations on the magnitude of completely spin-polarized source-drain current with Cr 2 Se 3 /WTe 2 having the smallest SS value of 134.1 mV/dec. The calculations suggest that Cr 2 Se 3 is a good candidate for constructing spin-MOSFET devices. Our study sheds light on the design of high-performance nanoscale spin-MOSFET devices by using two-dimensional half-metallic electrodes.

The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. The ventral hippocampus (vHPC) is critical for the expression of anxiety. However, current studies primarily focus on vHPC neurons, leaving the role for vHPC astrocytes in anxiety largely unexplored. Here, genetically encoded Ca 2+ indicator GCaMP6m and in vivo fiber photometry calcium imaging are used to label vHPC astrocytes and monitor their activity, respectively, genetic and chemogenetic approaches to inhibit and activate vHPC astrocytes, respectively, patch-clamp recordings to measure glutamate currents, and behavioral assays to assess anxiety-like behaviors. It is found that vHPC astrocytic activity is increased in anxiogenic environments and by 3-d subacute restraint stress (SRS), a well-validated mouse model of anxiety disorders. Genetic inhibition of vHPC astrocytes exerts anxiolytic effects on both innate and SRS-induced anxiety-related behaviors, whereas hM3Dq-mediated chemogenetic or SRS-induced activation of vHPC astrocytes enhances anxiety-like behaviors, which are reversed by intra-vHPC application of the ionotropic glutamate N-methyl-d-aspartate receptor antagonists. Furthermore, intra-vHPC or systemic application of the N-methyl-d-aspartate receptor antagonist memantine, a U.S. FDA-approved drug for Alzheimer's disease, fully rescues SRS-induced anxiety-like behaviors. The findings highlight vHPC astrocytes as critical regulators of stress and anxiety and as potential therapeutic targets for anxiety and anxiety-related disorders., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

NK2 Homeobox 1 (NKX2-1) is a well-characterized pathological marker that delineates lung adenocarcinoma (LUAD) progression. The advancement of LUAD is influenced by the immune tumor microenvironment through paracrine signaling. However, the involvement of NKX2-1 in modeling the tumor immune microenvironment is still unclear. Here, the downregulation of NKX2-1 is observed in high-grade LUAD. Meanwhile, single-cell RNA sequencing and Visium in situ capturing profiling revealed the recruitment and infiltration of neutrophils in orthotopic syngeneic tumors exhibiting strong cell-cell communication through the activation of CXCLs/CXCR2 signaling. The depletion of NKX2-1 triggered the expression and secretion of CXCL1, CXCL2, CXCL3, and CXCL5 in LUAD cells. Chemokine secretion is analyzed by chemokine array and validated by qRT-PCR. ATAC-seq revealed the restrictive regulation of NKX2-1 on the promoters of CXCL1, CXCL2, and CXCL5 genes. This phenomenon led to increased tumor growth, and conversely, tumor growth decreased when inhibited by the CXCR2 antagonist SB225002. This study unveils how NKX2-1 modulates the infiltration of tumor-promoting neutrophils by inhibiting CXCLs/CXCR2-dependent mechanisms. Hence, targeting CXCR2 in NKX2-1-low tumors is a potential antitumor therapy that may improve LUAD patient outcomes., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objectives: Vocal fold leukoplakia (VFL) is a precancerous lesion of laryngeal cancer, and its endoscopic diagnosis poses challenges. We aim to develop an artificial intelligence (AI) model using white light imaging (WLI) and narrow-band imaging (NBI) to distinguish benign from malignant VFL., Methods: A total of 7057 images from 426 patients were used for model development and internal validation. Additionally, 1617 images from two other hospitals were used for model external validation. Modeling learning based on WLI and NBI modalities was conducted using deep learning combined with a multi-instance learning approach (MIL). Furthermore, 50 prospectively collected videos were used to evaluate real-time model performance. A human-machine comparison involving 100 patients and 12 laryngologists assessed the real-world effectiveness of the model., Results: The model achieved the highest area under the receiver operating characteristic curve (AUC) values of 0.868 and 0.884 in the internal and external validation sets, respectively. AUC in the video validation set was 0.825 (95% CI: 0.704-0.946). In the human-machine comparison, AI significantly improved AUC and accuracy for all laryngologists (p < 0.05). With the assistance of AI, the diagnostic abilities and consistency of all laryngologists improved., Conclusions: Our multicenter study developed an effective AI model using MIL and fusion of WLI and NBI images for VFL diagnosis, particularly aiding junior laryngologists. However, further optimization and validation are necessary to fully assess its potential impact in clinical settings., Level of Evidence: 3 Laryngoscope, 134:4321-4328, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: To describe the gadoxetic acid-enhanced magnetic resonance imaging (MRI) features and follow-up changes of hepatic focal nodular hyperplasia (FNH)-like lesions induced by chemotherapy in patients with colorectal cancer (CRC) and the differential diagnosis of FNH-like lesions and liver metastases., Methods: We retrospectively analyzed the data of patients with CRC who received chemotherapy and gadoxetic-enhanced MRI at our hospital. Based on imaging features and pathological findings, the patients were classified into two groups: FNH-like lesions and liver metastases. Two abdominal radiologists reviewed and compared the signal intensities of all images in each phase for both groups. The characteristics of the FNH-like lesions in the hepatobiliary phase were evaluated, and changes in size of lesions were monitored., Results: Thirty patients with 82 FNH-like lesions and 30 with 49 liver metastases following chemotherapy were included in the study. All MRI findings were statistically significantly different between the two groups (p < 0.05). In FNH-like lesions, three enhancement patterns were observed in the hepatobiliary phase: hyperintense/isointense (18.3%), heterogeneous hyperintense (8.5%), and ring-like enhancement (73.2%). The median time from completion of chemotherapy to development of FNH-like lesions was 31 months. During 4-87 months of follow-up, 27 patients with 73 lesions showed the following outcomes: 41 lesions (56.16%) showed stability, 21 lesions (28.77%) growth, and 11 lesions (15.07%) reduction or disappearance., Conclusion: Gadoxetic acid-enhanced MRI can distinguish between chemotherapy-induced FNH-like lesions and liver metastases in patients with CRC. The FNH-like lesions exhibited three enhancement patterns in the hepatobiliary phase, and the changes varied during follow-up., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study aimed to quantify the global cardiovascular disease (CVD) burden attributable to diet low in fiber among adults aged 60 years and older using data from the Global Burden of Disease (GBD) Study 2019., Methods: We extracted data on CVD mortality, disability-adjusted life-years (DALYs), and risk-factor exposures from the GBD 2019 study for people aged 60 and older. Age-period-cohort models were used to estimate the overall annual percentage change in mortality and DALY rate (net drift, % per year), mortality and DALY rate for each age group from 1990 to 2019 (local drift, % per year), longitudinal age-specific rate corrected for period bias (age effect), and mortality and Daly rate for each age group from 1990 to 2019 (local drift, % per year). And period/cohort relative risk (period/cohort effect)., Results: From 1990 to 2019, global age-standardized cardiovascular disease (CVD) mortality rates attributable to low dietary fiber intake decreased by 2.37% per year, while disability-adjusted life years (DALYs) fell by 2.48% annually. Decreases were observed across all sociodemographic index regions, with fastest declines in high and high-middle SDI areas. CVD mortality and DALY rates attributable to low fiber increased exponentially with age, peaking at 85-89 years, and were higher in men than women. Regarding period effects, mortality and DALY rates declined since 2000, reaching nadirs in 2015-2019. For birth cohort patterns, risks attributable to low fiber intake peaked among early 1900s births and subsequently fell, with more pronounced reductions over time in women., Conclusions: Low dietary fiber intake is a leading contributor to the global cardiovascular disease burden, accounting for substantial mortality and disability specifically among older adults over recent decades., (© 2024. The Author(s).)