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Dongdong Li,1 Lijun Bian,1 Lili Cui,2 Jingying Zhou,1 Gaotian Li,1 Xiaoyan Zhao,1 Liao Xing,1 Jiaxing Cui,1 Bo Sun,1 Chunlai Jiang,1,3,4 Wei Kong,1,3,4 Yong Zhang,1,3,4 Yan Chen1,3,4 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2Beijing Institute of Drug Metabolism, Beijing, People’s Republic of China; 3Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 4NMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yan Chen; Yong Zhang, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China, Tel +86-431-85167751, Fax +86-431-85167674, Email chen_yan0417@126.com; zhypharm@jlu.edu.cnPurpose: Heterologous immunization using different vaccine platforms has been demonstrated as an efficient strategy to enhance antigen-specific immune responses. In this study, we performed a head-to-head comparison of both humoral and cellular immune response induced by different prime-boost immunization regimens of mRNA vaccine and adjuvanted protein subunit vaccine against varicella-zoster virus (VZV) in middle-aged mice, aiming to get a better understanding of the influence of vaccination schedule on immune response.Methods: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared.Results: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation.Conclusion: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.Keywords: varicella-zoster Virus, mRNA vaccine, glycoprotein E, lipid nanoparticles, heterologous prime-boost, cell-mediated immunity

Meiju Deng, Na Chen, Xiaojie Lao, Xiaolei Wang, Jiantao Fu, Lulu Xing, Hongxin Zhao Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaCorrespondence: Hongxin Zhao, Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshun Dongjie, Chaoyang District, Beijing, 100015, People’s Republic of China, Email drzhao66@ccmu.edu.cnPurpose: The study aimed to explore the reasons, efficacy, and safety of switching to dolutegravir (DTG) based regimens in virologically suppressed people living with HIV (PLWH) in tertiary hospitals in China. Therefore, the study could provide a valuable reference for the rational clinical use of DTG.Methods: PLWH’s basic information, treatment details, and reasons for switching were collected, through the electrical clinical medical record system and telephone follow-up. Data included the proportion of PLWH with HIV RNA < 50 copies/mL, changes in immunological indicators, and metabolic metrics at week 48 and week 96.Results: 319 PLWH were included in the analysis. The three major reasons for switching were neurological toxicity (16.30%), simplification (13.79%), and renal toxicity (11.29%). Our study showed high rates of virologic suppression in the per-protocol analysis (week 48: 99.69%; week 96: 99.29%) after switching to DTG-based regimens. The median CD4+ T cell count increased from 579 cells/μL (IQR 420.5– 758) to 642 cells/μL (IQR 466.5– 854) at week 96 (p< 0.0001). An improvement was observed in liver function (ALT: p< 0.0001; AST: p< 0.0001) and fasting glucose (p< 0.0001). However, there was an elevation in creatinine (Cr) (p< 0.0001) and a slight decrease in the estimated glomerular filtration rate (eGFR) (p< 0.0001). Regarding lipid profile, triglyceride (TG) levels declined, while total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels increased. Further analysis revealed that the increase in TC and LDL-C was associated with the withdrawal of tenofovir disoproxil fumarate (TDF). This observed increase in lipid parameters only concerned the PLWH who switched from a TDF-containing regimen to a non-TDF regimen.Conclusion: This study confirmed the virologic efficacy of switching to DTG-based regimens in virologically suppressed PLWH over a 96-week period. The findings also expanded the evidence of immune reconstitution and metabolic safety associated with this switch.Keywords: HIV, dolutegravir, switching, virologically suppressed, lipids profile

Longfei Xing,1,&ast; Xilin Chen,2,3,&ast; Changqing Guo,1 Wenting Zhu,4 Tingyao Hu,1 Weiwei Ma,1 Mei Du,1 Yue Xu,1 Changqing Guo5 1School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s of Republic of China; 2Department of Acupuncture and Rehabilitation, The Fifth College of Clinical Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Acupuncture and Rehabilitation, Guangdong Second Hospital of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 4The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 5Department of Medical Technology, Shijiazhuang Medical College, Shijiazhuang, Hebei Province, People’s of Republic of China&ast;These authors contributed equally to this workCorrespondence: Changqing Guo, Shijiazhuang Medical College, Shijiazhuang, Hebei Province, 050599, People’s of Republic of China, Tel +86-13081033381, Fax +86-82517626, Email 925499172@qq.comPurpose: Mitochondrial dysfunction of chondrocytes has become an area of focus in Knee Osteoarthritis (KOA) in recent years. Activation of mitophagy could promote the survival of chondrocytes and alleviate cartilage degeneration. The aim of this study was to explore whether mitophagy was involved in the cartilage protection of KOA rabbits after electroacupuncture (EA) intervention.Methods: The rabbits were divided into 3 groups, Control group, KOA group, EA group, with 6 rabbits in each group. KOA model rabbits were established by modified Videman’s extended immobilization method for 6 weeks and randomly divided into KOA group and EA group. The rabbits in EA group were treated every other day for 3 weeks. The degree of cartilage degeneration was detected by Safranine O-Fast Green staining and immunofluorescence. The morphological changes of chondrocytes mitochondria were detected by transmission electron microscope. ATP concentration in cartilage was measured by ATP Assay Kit. The changes of Pink1-Parkin signal pathway were detected by immunofluorescence, Western blot, and Real-time PCR.Results: The morphology showed that EA could reduce the degeneration of KOA cartilage and increase the distribution of collagen II. We also found that EA could activate mitophagy in KOA rabbit chondrocytes to remove damaged mitochondria and restore mitochondrial homeostasis, which was manifested as increasing the expression of LC3 II/I, promoting the colocalization of TOM20 and LC3B, reducing the accumulation of mitochondrial markers outer mitochondrial membrane 20 (TOM20) and inner mitochondrial membrane 23 (TIM23), and increasing ATP production in chondrocytes. This regulation might be achieved by upregulating the Pink1-Parkin signal pathway.Conclusion: EA may play a role in protecting KOA cartilage by activating mitophagy mediated through Pink1-Parkin pathway.Keywords: osteoarthritis, electroacupuncture, mitophagy, mitochondria, Pink1-Parkin

Yuandi Wang,1,2,&ast; Lijuan Xing,2,&ast; Lexiu Deng,1,2 Xinsheng Wang,2 Dandan Xu,2 Bu Wang,2 Zhihua Zhang2,&ast; 1Graduate School, Hebei North University, Zhangjiakou City, Hebei Province, People’s Republic of China; 2Department of Respiratory and Critical Care Clinical Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihua Zhang, Department of Respiratory and Critical Care Clinical Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei Province, People’s Republic of China, Tel +86 0313 8033598, Email zzh19641229@163.comPurpose: The efficacy of immunotherapy for non-small cell lung cancer (NSCLC) is limited owing to cold tumors and drug resistance. Therefore, it is important to identify the molecular mechanisms underlying immune evasion in NSCLC. Spontaneous ferroptosis of neutrophils has been suggested as a key mechanism of immunosuppression in cancer. Insulin-like growth factor binding protein 1 (IGFBP1) plays an important role in immune infiltration in several cancers. However, the role of IGFBP1 in NSCLC is unknown. Therefore, in this study, we aimed to investigate the association of IGFBP1 mRNA expression with infiltration of myeloid-derived suppressor cells and prognosis in NSCLC.Patients and Methods: Retrospective RNA-seq data from 990 patients in the Cancer Genome Atlas (TCGA) database were analyzed in relation to patient clinical characteristics. The Timer2 database was used to assess immune infiltration, and the FerrDb V2 database was used to obtain ferroptosis-related genes. Finally, the results were validated by the proteomic analysis of serum samples collected from six patients with NSCLC and six healthy individuals.Results: IGFBP1 expression was enriched in lung adenocarcinoma samples and positively correlated with the pathological grade of NSCLC. IGFBP1 expression was an independent prognostic factor for the overall survival of patients with NSCLC. In addition, IGFBP1 expression correlated with myeloid-derived suppressor cell infiltration. Notably, Gene Ontology analysis of IGFBP1-related genes revealed that the major molecular functions of their protein products were related to NADP+ 1-oxidoreductase activity. Furthermore, expression levels of multiple ferroptosis suppressor genes positively correlated with IGFBP1 expression.Conclusion: High IGFBP1 expression indicates a poor prognosis in patients with NSCLC, which may be related to tumor immunosuppression caused by neutrophil ferroptosis.Keywords: immune infiltration, immunotherapy, lung adenocarcinoma, lung squamous cell carcinoma, myeloid-derived suppressor cells

Yan Guo,1,&ast; Yue Xu,2,&ast; Meng He,2 Xilin Chen,2 Longfei Xing,2 Tingyao Hu,2 Yi Zhang,2 Mei Du,2 Dian Zhang,2 Qian Zhang,2 Bin Li1 1Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, People’s Republic of China; 2School of Acupuncture, Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Li, Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, 23 Meishuguan Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Tel +86-18910781852, Fax +86-87906055, Email libin@bjzhongyi.comPurpose: Knee osteoarthritis (KOA) is a chronic inflammatory disease highly associated with intra-articular hypertension, hypoxia and angiogenesis of synovial tissue. Our previous studies showed that acupotomy could treat KOA in a variety of ways, including reducing cartilage deterioration and enhancing biomechanical qualities. However, the mechanism of hypoxia and angiogenesis induced by acupotomy in KOA synovium remains unclear. This study looked for the benign intervention of acupotomy in synovial pathology.Methods: The rabbits were divided into 3 groups, Normal group, KOA group, and KOA + Acupotomy (Apo) group, with 11 rabbits in each group. The KOA rabbit model was established by the modified Videman method with six weeks. The KOA + Apo group performed the intervention. The tendon insertion of vastus medialis, vastus lateralis, rectus femoris, biceps femoris, and anserine bursa were selected as treatment points in rabbits. Rabbits were treated once every 7 days for 3 weeks. We observed the intra-articular pressure and oxygen partial pressure (BOLD MRI). The synovial morphology was monitored by Hematoxylin-Eosin Staining (HE Staining). The expression of hypoxia-inducible transcription factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) was detected using Immunohistochemical (IHC), Western Blot and Enzyme-Linked Immunosorbent Assay (ELISA).Results: Acupotomy reduced intra-articular hypertension and improved the synovial oxygen situation, synovial inflammatory and angiogenesis. HIF-1α, VEGF, IL-1β and TNF-α expression were downregulated by acupotomy.Conclusion: Acupotomy may reduce inflammation and angiogenesis in KOA rabbit by reducing abnormally elevated intra-articular pressure and improving synovial oxygen environment. The above may provide a new theoretical foundation for acupotomy treatment of KOA.Keywords: acupotomy, KOA, synovium, intra-articular pressure, hypoxia, angiogenesis

Linli Xing,1,&ast; Yiyi Chen,2– 4,&ast; Xia Ling,2– 5 Dandan Wu,6 Lu Sun,2– 4 Jingrong Lin,7 Yan Chen2– 4 1Office of Nutrition and Diet, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 4Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Laboratory Medicine, Blood Center of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Infectious Diseases, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 7Department of Respiratory Medicine, the Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Chen, Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, People’s Republic of China, Tel +86-571-8600-6142, Email chenyan@zju.edu.cn Jingrong Lin, Department of Respiratory Medicine, The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China, Email 44964808@qq.comAbstract: The detection of novel livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) is important in both clinics and livestock. In this study, we report a MRSA-infected patient who was associated with livestock as a butcher, from whom we collected two MRSA strains FJ0318 and FJ0322. To further understand the correlation between these MRSA isolates and livestock, whole-genome sequencing and comparative genomic analyses were performed for these two isolates. Phylogenetic analysis revealed that these two strains were homologous. Multilocus sequence typing showed that these two strains belong to ST7, which is a common lineage in retail meat and meat products in China. The genetic islands in FJ0318 and FJ0322 were different from those in other common clones, such as ST59, ST8, and ST5. A mosaic plasmid with a sequence identical to that of the plasmid pE2 from livestock was found in strain FJ0318. Additionally, a novel prophage island was identified on the chromosome. Furthermore, the sequence of the island was similar to that of phage SP6 identified in livestock. ST7 may originate from livestock and be transmitted to communities, causing invasive infections.Keywords: MRSA, ST7, whole genome analysis, livestock

Wei Bu,1,&ast; Liping Xing,2,&ast; Meixia Xiao,1,&ast; Pan Chang,1 Yaqian Du,1 Hongying Xie3 1Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 2Department of Critical Care Medicine, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 3Nursing Department, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongying Xie, Nursing Department, The First Affiliated Hospital of Gannan Medical University, 23 Youth Road, Zhanggong District, Ganzhou, Jiangxi, 341000, People’s Republic of China, Tel +86-797-8266016, Fax +86-797-8269500, Email xiehongying_20216@163.comObjective: To investigate the willingness of Ganzhou residents to participate in “Internet + Nursing services” and analyse the relevant influencing factors.Methods: From May to June 2021, 426 Ganzhou residents were surveyed using an Internet + Nursing services questionnaire and the relevant influencing factors were analysed. The questionnaire comprised two parts: demographic characteristic section and a questionnaire on residents’ willingness to participate in Internet + Nursing services including for dimensions (awareness, participation, trust and need), a 5-point Likert scale was used.Results: A total of 397 valid questionnaires were recovered, and the total willingness of Ganzhou residents to participate in the service was derived as 11.59 ± 2.14. The results of multiple linear regression analyses showed that the presence of family members with a chronic disease or mobility difficulties, and an awareness and trust of Internet + Nursing services were influencing factors of residents’ participation willingness (P < 0.05).Conclusion: The participation willingness of Ganzhou residents in Internet + Nursing services is modestly low, and the reasons for participation varied. It is suggested that the government and pilot hospitals strengthen the publicity surrounding these services, improve safety measures, strengthen team training, and develop products suitable for the elderly to increase residents’ participation willingness.Keywords: internet + nursing services, willingness to participate, residents, trust, awareness

Mengfei Sun,1,&ast; Qianqian Yang,2,&ast; Chunling Hu,1 Hengchao Zhang,2 Lihua Xing1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Department of Erythrocyte Biology Laboratory, School of Life Sciences, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihua Xing, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshedong Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel/Fax +8613838095088, Email xinglihua95088@163.comPurpose: Autophagy-related genes (ARGs) play an important role in the pathophysiology processes of sepsis-induced acute respiratory distress syndrome (ARDS). However, expression profiles of ARGs have rarely been used to explore the relationship between autophagy and sepsis-induced ARDS. Therefore, we aim to identify and validate the potential ARGs of sepsis-induced ARDS through bioinformatics analysis and experiment validation.Methods: We downloaded GSE32707 data from the Gene Expression Omnibus (GEO) database. The potential differentially expressed genes (DEGs) and differentially expressed ARGs (DEARGs) of sepsis-induced ARDS were screened by R software. Then, we performed functional enrichment analyses to explore the potential biological functions of DEARGs and constructed protein–protein interaction (PPI) networks. Subsequently, correlation analysis and receiver operating characteristic (ROC) curve were used for the DEARGs. In addition, we estimated the proportions of 22 immune cell subsets by using CIBERSORT algorithm. Finally, RNA expression of seven DEARGs were validated by qRT-PCR in blood samples from sepsis-induced ARDS and healthy controls.Results: We identified 28 DEARGs, including 11 up-regulated genes and 17 down-regulated genes, which were primarily involved in autophagy and apoptosis. Seven genes (BAG3, CTSD, ERBB2, MYC, PEA15, RAB24 and SIRT1) with AUC > 0.70 were considered possible to be sepsis-induced ARDS hub genes for ROC curve analysis. CIBERSORT results shown that sepsis-induced ARDS contained a higher proportion of naive CD4+ T cells, gamma delta T cells, monocytes, and neutrophils, and lower levels of CD8+ T cells, memory resting CD4+ T cells, follicular helper T cells were relatively lower. The results of qRT-PCR also demonstrated that the expression levels of BAG3, CTSD, ERBB2, MYC and SIRT1 in sepsis-induced ARDS patients and healthy controls had differences.Conclusion: We identified an association between DEGs and immune infiltration in sepsis-induced ARDS and validated BAG3, CTSD, ERBB2, MYC and SIRT1 that may be have excellent diagnostic performance.Keywords: autophagy, sepsis-induced ARDS, immune infiltration, bioinformatics analysis, Gene Expression Omnibus dataset

Ran Zhang,1,2 Ranran Zhang,3 Ting Luan,4,5 Biwei Liu,6 Yimei Zhang,6 Yaping Xu,1 Xiaorong Sun,5 Ligang Xing6 1Department of Radiation Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Tongji University, Shanghai, People’s Republic of China; 3Department of Medical Imaging, Linyi Cancer Hospital, Linyi, Shandong, People’s Republic of China; 4Department of Graduate, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 5Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 6Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Xiaorong SunDepartment of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, 250000, People’s Republic of ChinaTel/Fax +86 53167626767Email 251400067@qq.comYaping XuDepartment of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Zhengmin Road 507, Shanghai, 200443, People’s Republic of ChinaTel/Fax +86 2165115006Email xuyaping1207@163.comBackground: Clinical occult lymph node metastasis (cOLNM) means that the lymph node is negatively diagnosed by preoperative computed tomography (CT), but has been proven to be positive by postoperative pathology. The aim of this study was to establish and validate a nomogram based on radiomics features for the preoperative prediction of cOLNM in early-stage solid lung adenocarcinoma patients.Methods: A total of 244 patients with clinical T1-2N0M0 solid lung adenocarcinoma who underwent preoperative contrast-enhanced chest CT were divided into a primary group (n = 160) and an independent validation group from another hospital (n = 84). The records of 851 radiomics features of each primary tumor were extracted. LASSO analysis was used to reduce the data dimensionality and select features. Multivariable logistic regression was utilized to identify independent predictors of cOLNM and develop a predictive nomogram. The performance of the predictive model was assessed by its calibration and discrimination. Decision curve analysis (DCA) was performed to estimate the clinical usefulness of the nomogram.Results: The predictive model consisted of a clinical factor (CT-reported tumor size) and a radiomics feature (Rad-score). The nomogram presented good discrimination, with a C-index of 0.782 (95% CI, 0.768– 0.796) in the primary cohort and 0.813 (95% CI, 0.787– 0.839) in the validation cohort, and good calibration. DCA showed that the radiomics nomogram was clinically useful.Conclusion: This study develops and validates a nomogram that incorporates clinical and radiomics factors. It can be tailored for the individualized preoperative prediction of cOLNM in early-stage solid lung adenocarcinoma patients.Keywords: solid lung adenocarcinoma, prediction, clinical occult lymph node, computed tomography, radiomics

Shuyuan Liu,1,2,&ast; Ling Xing,1,3,&ast; Qian Wang,4 Tianyu Xin,2 Handing Mao,1 Ye Tao,5 Jinbao Zhao,2 Xin Li,4 Cong Li,1 Qinghua Li,6 Yan Dou,7 Yixin Li,8 Wei Zhang,9 Bo Ning,10 Qing Song1 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Emergency Department, Sixth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Emergency, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Emergency Department, Third Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Health Care Department, Beijing Huangsi Aesthetic Surgery Hospital, Beijing, People’s Republic of China; 6Department of Intensive Care Unit, The 990th Hospital of Chinese PLA, Zhumadian, People’s Republic of China; 7Department of Intensive Care Unit, The 909th Hospital of Chinese PLA, Zhangzhou, People’s Republic of China; 8Department of Intensive Care Unit, The 910th Hospital of Chinese PLA, Quanzhou, People’s Republic of China; 9Emergency Department, The 900th Hospital of Chinese PLA, Fuzhou, People’s Republic of China; 10Department of Intensive Care Unit, Air Force Medical Center of China, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo NingDepartment of Intensive Care Unit, Air Force Medical Center of China, Beijing, 100142, People’s Republic of ChinaTel +86 15611161110Fax +86 1068410099Email boningbn@163.comQing SongMedical School of Chinese PLA, Beijing, 100853, People’s Republic of ChinaTel +86 13911374534Fax +86 1068182255Email songqing_sq87@163.comObjective: The purpose of this study is to evaluate the factors involved in the early stage of exertional heat stroke (EHS) that are associated with mortality.Methods: In this retrospective, case-control study, patients from 11 tertiary medical centers in China were enrolled from January 1, 2012, to December 31, 2019. Demographic information, underlying diseases, ambient temperature, and relative humidity, clinical manifestations, initial body temperature, time from onset to diagnosis of EHS (including suspected), and the duration of body temperature > 38°C of all enrolled patients were recorded. The occurrence of organ dysfunction within 72 h was evaluated, and in-hospital deaths were recorded. The patients were subsequently divided into a survival group and a non-survival group. The “case” refers to patients in the non-survival group, while the “control” refers to patients without death.Results: Of the 214 hospitalized patients with EHS, 183 survived and 31 died, and the overall mortality was 14.49% (31/214). A binary logistic regression showed that only the duration of body temperature > 38°C (OR 1.80, 95% CI 1.34– 2.42) and the number of organs damaged within 72 h of onset (OR 6.54, 95% CI 2.31– 18.56) were statistically significant in terms of risk of death in hospital (p < 0.05). A goodness of fit test produced a p-value of 0.76. According to receiver operating characteristic curve (ROC) analysis, the areas under the curve (AUC) were 0.989 (95% CI 0.978– 1.000; p < 0.05) and 0.936 (95% CI 0.896– 0.976; p < 0.05).Conclusion: Of the various factors involved in the early stage of the disease, the duration of high body temperature and the number of organs damaged within 72 h of onset were independent risk factors and predictors associated with death.Keywords: heat stroke, exertional, cooling, mortality

Ning Liu,1 Li Xing,1 Weipu Mao,1– 3 Shuqiu Chen,1 Jianping Wu,1 Bin Xu,1 Ming Chen1– 3 1Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, 210009, People’s Republic of China; 2Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, 210009, People’s Republic of China; 3Department of Urology, Nanjing Lishui District People’s Hospital, Zhongda Hospital Lishui Branches, Southeast University, Nanjing, 211200, People’s Republic of ChinaCorrespondence: Ming Chen; Weipu MaoDepartment of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, People’s Republic of ChinaTel/Fax +86-13913009977; +86-18621571327Email mingchenseu@126.com; maoweipu88@163.comObjective: The purpose of this study was to evaluate the associations between blood glucose and hemoglobin A1c (HbA1c) levels with the degree of stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) in women.Methods: We conducted a cross-sectional study of female participants in the National Health and Nutrition Examination Survey (NHANES) database between 2007 and 2012. Univariate and multivariate logistic regressions were used to assess the relationship between blood glucose and HbA1c levels and the degree of SUI and UUI.Results: A total of 3821 participants were enrolled in the study, of whom 2421 (63.4%) had no SUI, 1133 (29.7%) had monthly SUI, 267 (7.0%) had weekly SUI; 2883 (75.5%) had no UUI, 735 (19.2%) had monthly UUI, 203 (5.3%) had weekly UUI. The levels of blood glucose and HbA1c were positively correlated with SUI and UUI, and increased with increasing degree of UUI. Multivariate logistic regression showed that there was a positive association between blood HbA1c level and degree of SUI.Conclusion: Our study found that blood glucose and HbA1c levels can be used as indicators of SUI and UUI severity in women.Keywords: blood glucose, hemoglobin A1c, national health and nutrition examination survey, stress urinary incontinence, urgency urinary incontinence

Weizhu Zhao,1,2 Haiying Yang,3 Jie Chai,4 Ligang Xing1 1Department of Radiology, Cancer Hospital Affiliated to Shandong First Medical University, Shandong Cancer Hospital and Institute, Jinan, 250117, People’s Republic of China; 2Department of Oncology, Binzhou People’s Hospital, Binzhou, 256610, People’s Republic of China; 3Department of Nursing, Binzhou People’s Hospital, Binzhou, 256610, People’s Republic of China; 4Department of Gastrointestinal Surgery, Cancer Hospital Affiliated to Shandong First Medical University, Shandong Cancer Hospital and Institute, Jinan, 250117, People’s Republic of ChinaCorrespondence: Jie ChaiDepartment of Gastrointestinal Surgery, Cancer Hospital Affiliated to Shandong First Medical University, Shandong Cancer Hospital and Institute, No. 440, Jiyan Road, Jinan, 250117, People’s Republic of ChinaTel +86 18678867800Email gu421720jing@163.comLigang XingDepartment of Radiology, Cancer Hospital Affiliated to Shandong First Medical University, Shandong Cancer Hospital and Institute, No. 440 Jiyan Road, Jinan, 250117, People’s Republic of ChinaTel +86 15553181309Email xinglg@medmail.com.cnAbstract: The transcription factor runt-related protein 2 (RUNX2) has an important impact on the transformation of bone marrow mesenchymal stem cells to osteoblasts. Further studies have shown that RUNX2 plays a key role in the invasion and metastasis of cancers. RUNX2 is a “key” molecule in the regulatory network comprised of multiple signaling pathways upstream and its target downstream molecules. Due to the complex regulatory mechanisms of RUNX2, the specific mechanism underlying the occurrence, development and prognosis of malignant tumors has not been fully understood. Currently, RUNX2 as a promising therapeutic target for cancers has become a research hotspot. Herein, we reviewed the current literature on the modulatory functions and mechanisms of RUNX2 in the development of malignant tumors, aiming to explore its potential clinical application in the diagnosis, prognosis and treatment of tumors.Keywords: RUNX2, malignant tumor;, research progress

Yanlei Ji,1,2 Qingtao Qiu,3 Jing Fu,4 Kai Cui,5 Xia Chen,6 Ligang Xing,3 Xiaorong Sun6 1Department of Ultrasound Medicine, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 2Department of Ultrasound Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, People’s Republic of China; 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, People’s Republic of China; 4Department of Ultrasound Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, People’s Republic of China; 5Department of PET/CT, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, People’s Republic of China; 6Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, People’s Republic of ChinaCorrespondence: Xiaorong SunDepartment of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, Shandong 250117, People’s Republic of ChinaTel/Fax + 86-531-67626287Email 251400067@qq.comPurpose: To investigate the impact of staging on differences in glucose metabolic heterogeneity between lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) textural analysis and to develop a stage-specific PET radiomic prediction model to distinguish lung ADC from SCC.Patients and Methods: Patients who were histologically diagnosed with lung ADC or SCC and underwent pretreatment 18F-FDG PET/CT scans were retrospectively identified. Radiomic features were extracted from a semiautomatically outlined tumor region in the Chang-Gung Image Texture Analysis (CGITA) software package. The differences in radiomic parameters between lung ADC and SCC were compared stage-by-stage in 253 consecutive NSCLC patients with stages I to III disease. The least absolute shrinkage and selection operator (LASSO) algorithm was used for feature selection. A radiomic signature for each stage was subsequently constructed and evaluated. Then, an individual nomogram incorporating the radiomic signature and clinical risk factors was established and evaluated. The performance of the constructed models was assessed by receiver operating characteristic (ROC) curve analysis, and the nomogram was further validated by calibration curve analysis.Results: The performance of the radiomic signature for distinguishing lung ADC and SCC in both the training and validation cohorts was good, with AUCs of 0.883, 0.854, and 0.895 in the training cohort and 0.932, 0.944, and 0.886 in the validation cohort for stages I, II, and III NSCLC, respectively. The radiomic-clinical nomogram integrating radiomic features with independent clinical predictors exhibited more favorable discriminative performance, with AUCs of 0.982, 0.963, and 0.979 in the training cohort and 0.989, 0.984, and 0.978 in the validation cohort for stages I, II, and III, respectively.Conclusion: Differences in PET radiomic features between lung ADC and SCC varied in different stages. Stage-specific PET radiomic prediction models provided more favorable performance for discriminating the histological subtype of NSCLC.Keywords: non-small-cell lung cancer, positron emission tomography, PET, textural analysis, heterogeneity, staging

Hui Li,1– 3 Yanlong Liu,4– 6 Lifei Xing,7 Xiaoyu Yang,8 Jinzhong Xu,9 Qiushi Ren,1 Kuan-Pin Su,4,10,11 Yanye Lu,1 Fan Wang2,3,12 1Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, People’s Republic of China; 2Xinjiang Key Laboratory of Neurological Disorder Research, The Second Affiliated Hospital, Xinjiang Medical University, Urumqi 830063, People’s Republic of China; 3Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot 010110, People’s Republic of China; 4Zhuji Institute of Biomedicine, School of Pharmaceutical Sciences, Wenzhou Medical University, Shaoxing 311800, People’s Republic of China; 5School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 6The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou 325035, People’s Republic of China; 7Department of Neurology, Inner Mongolia North Heavy Industries Group Corp. Ltd Hospital, Baotou 014030, People’s Republic of China; 8Beijing Jishuitan Hospital, Beijing 100035, People’s Republic of China; 9The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling 317500, People’s Republic of China; 10An-Nan Hospital, China Medical University, Tainan, Taiwan; 11College of Medicine, China Medical University, Taichung, Taiwan; 12Beijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, People’s Republic of ChinaCorrespondence: Fan WangBeijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, People’s Republic of ChinaTel +86 10 62715511 ext. 6429Fax +86 10 62716285Email fanwang@bjmu.edu.cnBackground: Cigarette smoking has shown to be associated with sleep disturbance, especially prolonged sleep onset latency (SOL). Cigarette smoking stimulates the release of dopamine (DA) and serotonin (5-HT), which might promote awakening and inhibit rapid eye movement sleep. Dopamine transporter (DAT) and serotonin transporter play a key role in the reuptake of DA and 5-HT from the synaptic cleft into presynaptic neurons. However, the relationship among cigarette smoking, sleep disturbance and neurotransmitters has never been investigated in human cerebrospinal fluid (CSF).Methods: A total of 159 Chinese male subjects (81 active smokers and 78 non-smokers) who would undergo lumbar puncture before the surgery of anterior cruciate ligament reconstruction were recruited and 5mL-CSF samples were collected incidentally. CSF levels of DA, DAT, 5-HT, and serotonin transporter were measured using radioimmunoassay and ELISA. Sociodemographic data and the Pittsburgh Sleep Quality Index (PSQI) scale were collected before surgery.Results: PSQI global scores, SOL, and CSF DA levels were significantly higher in active smokers compared to non-smokers (2.00 [1.00– 4.75] scores vs 4.00 [3.00– 6.00] scores, p = 0.001; 10.00 [5.00– 15.00] minutes vs 15.00 [10.00– 30.00] minutes, p = 0.002; 87.20 [82.31– 96.06]ng/mL vs 107.45 [92.78– 114.38] ng/mL, p < 0.001), while CSF DAT levels were significantly lower in active smokers (0.35 [0.31– 0.39] ng/mL vs 0.29 [0.26– 0.34] ng/mL, p < 0.001).Conclusion: Cigarette smoking was indeed associated with sleep disturbance, shown by prolonged SOL, higher DA levels and lower DAT levels in CSF of active smokers.Keywords: sleep, cigarette smoking, dopamine, cerebrospinal fluid

Xiaoning Zhang1 ,* Xia Zhao1 ,* Yanqing Wang,1 Liqun Xing2 1Department of Chest Surgery, Weifang Yidu Central Hospital, Weifang, Shandong 262500, People’s Republic of China; 2Department of Surgical, Jinan Infectious Disease Hospital, Jinan, Shandong 250021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liqun XingDepartment of Surgery, Jinan Infectious Disease Hospital, 22029 Jingshi Road, Jinan, Shandong 250021, People’s Republic of ChinaEmail jidh_xingliqun@126.comBackground: A long non-coding RNA termed as long intergenic non-protein coding RNA 491 (LINC00491) has been validated as an oncogene to promote cancer progression in colon adenocarcinoma. The goal of this study was to determine the expression and carcinogenic functions of LINC00491 in non-small-cell lung cancer (NSCLC). Besides, it was aimed to understand how LINC00491 affects the malignant processes of NSCLC cells.Methods: The expression of LINC00491 in NSCLC was investigated by bioinformatic analysis and reverse transcription-quantitative PCR. After LINC00491 knockdown, cell counting kit-8 assay, flow cytometry, migration and invasion detection assays as well as nude mice xenograft assay were conducted to test the roles of LINC00491 in NSCLC cells. Two online databases, StarBase 3.0 and miRDB, were utilized to determine the putative target miRNA of LINC00491, and the prediction was subsequently confirmed by luciferase reporter assay, RNA immunoprecipitation assay, reverse transcription-quantitative PCR, Western blotting, and rescue assays.Results: LINC00491 was overexpressed in both NSCLC tissues and cell lines. Functional investigation revealed that depleted LINC00491 facilitated cell apoptosis and decreased cell proliferation, migration, and invasion in vitro. Additionally, the downregulation of LINC00491 impaired NSCLC cell tumor growth in vivo. Mechanistically, LINC00491 functioned as a competing endogenous RNA by sponging microRNA-324-5p (miR-324-5p) in NSCLC cells. miR-324-5p was weakly expressed in NSCLC and exerted tumor-suppressing actions during cancer progression. Furthermore, specificity protein 1 (SP1) was validated as the direct target of miR-324-5p in NSCLC and was under the regulation of LINC00491 via sponging miR-324-5p. Rescue experiments reconfirmed that miR-324-5p inhibition and SP1 overexpression both abrogated the suppressive roles of LINC00491 deficiency in NSCLC cells.Conclusion: LINC00491 promoted the oncogenicity of NSCLC via serving as a miR-324-5p sponge, which further upregulated the expression of SP1. The LINC00491/miR-324-5p/SP1 pathway disclosed a new mechanism of NSCLC pathogenesis and may provide effective targets for better NSCLC treatment.Keywords: non-small-cell lung cancer management, long non-coding RNA, ceRNA hypothesis

Ran Zhang,1,2 Changbin Wang,2,3 Kai Cui,3,4 Yicong Chen,1,2 Fenghao Sun,2,5 Xiaorong Sun,4 Ligang Xing2 1Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Clinical Medicine, Jinan University, Jinan, Shandong, People’s Republic of China; 4Department of Nuclear Medicine, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 5Department of Clinical Medicine, Weifang Medical University, Weifang, Shandong, People’s Republic of ChinaCorrespondence: Xiaorong SunDepartment of Nuclear Medicine, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, Jinan, People’s Republic of ChinaTel/Fax +86 531 6762 6419Email 251400067@qq.comPurpose: The imaging features of patients with early-stage non-small cell lung cancer (NSCLC) receiving stereotactic body radiotherapy (SBRT) are crucial for the decision-making process to establish a treatment plan. The purpose of this study was to predict the clinical outcomes of SBRT from the textural features of pretreatment computed tomography (CT) images.Patients and methods: Forty-one early-stage NSCLC patients who received SBRT were included in this retrospective study. In total, 72 textural features were extracted from the pretreatment contrast-enhanced CT images. Survival analysis was used to identify high-risk groups for progression-free survival (PFS) and disease-specific survival (DSS). Receiver operating characteristic (ROC) curve analysis was utilized to estimate the diagnostic abilities of the textural parameters. Univariable and multivariable Cox regression analyses were performed to evaluate the predictors of PFS and DSS.Results: Four parameters, including entropy (P=0.003), second angular moment (SAM) (P=0.04), high-intensity long-run emphasis (HILRE) (P=0.046) and long-run emphasis (LRE) (P=0.042), were significant prognostic features for PFS. In addition, contrast (P=0.008), coarseness (P=0.017), low-intensity zone emphasis (LIZE) (P=0.01) and large number emphasis (LNE) (P=0.046) were significant prognostic factors for DSS. In the ROC analysis, the area under the curve (AUC) of coarseness for local recurrence (LR) was 0.722 (0.528–0.916), and the AUC of entropy for lymph node metastasis (LNM) was 0.771 (0.556–0.987). The four highest AUCs for distant metastasis (DM) were 0.885 (0.784–0.985) for LNE, 0.846 (0.733–0.959) for SAM, 0.731 (0.500–0.961) for LRE and 0.731 (0.585–0.876) for contrast. In the multivariable analysis, smoking and entropy were independent prognostic factors for PFS.Conclusion: This exploratory study reveals that textual features derived from pretreatment CT scans have prognostic value in early-stage NSCLC patients treated with SBRT.Keywords: computed tomography imaging, clinical outcomes, non-small cell lung cancer, NSCLC, stereotactic body radiation therapy, textural analysis

Yipeng Ding,1,* Quanni Li,1,* Qiong Feng,2 Dongchuan Xu,1 Cibing Wu,2 Jie Zhao,2 Xiaoli Zhou,1 Yixiu Yang,1 Huan Niu,1 Ping He,1 Lihua Xing3 1Department of General Practice, Hainan General Hospital, Haikou, Hainan 570311, People’s Republic of China; 2Hainan General Hospital, University of South China, Haikou, Hainan 570311, People’s Republic of China; 3Department of Respiratory Intensive Care Unit (RICU), The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 45000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yipeng DingDepartment of General Practice, Hainan General Hospital, #19 Xiuhua Road, Haikou, Hainan 570311, People’s Republic of ChinaTel/Fax +86 08 986 622 2502Email DingYP66@163.comLihua XingDepartment of Respiratory Intensive Care Unit (RICU), The First Affiliated Hospital of Zhengzhou University, #1 Jianshe East Road, Zhengzhou, Henan 45000, People’s Republic of ChinaTel/Fax +86 3 716 696 4992Email xinglihua95088@163.comIntroduction: Chronic obstructive pulmonary disease (COPD) is a lung disease closely related to exposure to exogenous substances. CYP2B6 can activate many exogenous substances, which in turn affect lung cells. The aim of this study was to assess the association of single-nucleotide polymorphisms (SNPs) in CYP2B6 with COPD risk in a Chinese Han population.Materials and methods: Genotypes of the five candidate SNPs in CYP2B6 were identified among 318 cases and 508 healthy controls with an Agena MassARRAY method. The association between CYP2B6 polymorphisms and COPD risk was evaluated using genetic models and haplotype analyses.Results: In allele model, we observed that rs4803420 G and rs1038376 A were related to COPD risk. And rs4803420 G/T and G/T-T/T were related to a decreased COPD risk compared to GG genotype in the co-dominant and dominant models, respectively. When comparing with the AA genotype, rs1038376 A/T and A/T-T/T were associated with an increased COPD risk in the co-dominant and dominant models, respectively. Further gender stratification co-dominant and dominant models analysis showed that genotype G/T and G/T-T/T of rs4803420, and genotype A/T and A/T-T/T of rs1038376 were significantly associated with COPD risk compared to the wide type in males and females, while allele C of rs12979270 was only associated with COPD risk in females. Smoking status stratification analysis showed that rs12979270 C was significantly associated with an increased COPD risk under the allele model compared with allele A in the smoking subgroup. Haplotype analysis showed that haplotype GTA and TAA were related to COPD risk.Conclusion: Our data is the first to demonstrate that CYP2B6 polymorphisms may exert effects on COPD susceptibility in the Chinese Han population.Keywords: CYP2B6, chronic obstructive pulmonary disease, COPD, gene polymorphisms, case–control study

Liying Xing,1,2 Li Jing,2 Yuanmeng Tian,2 Min Lin,3 Zhi Du,1 Han Yan,2 Guocheng Ren,4 Yingna Dong,4 Qun Sun,5 Shuang Liu6 1Department of Cardiology, The First Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 2Department of Chronic Disease, Liaoning Provincial Center for Disease Control and Prevention, Shenyang 110005, People’s Republic of China; 3Department of Cardiology, Central Hospital of Ben Xi City, Ben Xi, Liaoning, People’s Republic of China; 4Department of Disease Control and Preventive, Central Hospital of Chao Yang City, Chaoyang, Liaoning, People’s Republic of China; 5Department of Chronic Disease, Disease Control and Prevention of Chao Yang City, Chaoyang, Liaoning, People’s Republic of China; 6Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Shuang LiuDepartment of Cardiovascular Ultrasound, First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning, People’s Republic of ChinaTel +86 1 394 034 0992Fax +86 242 338 8556Email liushuang_cmu1h@163.comBackground: To investigate the status of hypertension and related risk factor disparities between urban and rural areas of northeast China.Methods: A multi-stage, stratified, and cluster random sampling method was used to conduct the cross-sectional survey in Liaoning Province in 2017–2019. Finally, included 18,796 participants (28.9% urban, 71.1% rural) aged ≥40 years. The prevalence and control rate of hypertension were estimated based on Chinese hypertension guidelines and the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines.Results: The mean age of the population was 60.4±9.9 years, and 61.0% were women. The overall prevalence of hypertension was 56.8%. Compared to urban areas, hypertension was more prevalent, but the awareness, treatment, and control rates were lower in rural areas (59.2 vs 50.2, 52.5% vs 47.0%, 46.9% vs 34.9%, and 11.4% vs 3.7%, P

Liang Xing,1,2,* Feng Sun,1,2,* Zhendong Wang,1,2 Yan Li,1,2 Zhifang Yang,1,2 Fengshan Wang,1,3 Guangxi Zhai,3 Haining Tan1,2 1National Glycoengineering Research Center, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, People’s Republic of China; 2Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan 250012, Shandong, People’s Republic of China; 3School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, People’s Republic of China *These authors contributed equally to this work Background: In the past few years, significant progress has been made in inhibiting neovascularization at the tumor site, cutting off the nutrient supply of the tumor, and inhibiting tumor growth and metastasis. However, many proteins/peptides have the disadvantage of poor stability, short half-life, and uncertain targeting ability. Chemical modification can be used to overcome these disadvantages; many polyethylene glycol-modified proteins/peptides have been approved by US FDA. The purpose of this study was to obtain a novel anti-angiogenic chondroitin sulfate (CS)-peptide nanoparticle conjugate with efficient anti-neovascularization and tumor targeting ability and an acceptable half-life. Materials and methods: The CS-ES2-AF nanoparticle conjugate was synthesized and characterized using 1H-nuclear magnetic resonance spectroscopy, transmission electron microscopy, and particle size and zeta potential analyzer. The anti-angiogenic ability was studied using MTT, migration, tube formation, and chick chorioallantoic membrane assays. The targeting ability of CS-ES2-AF was studied by ELISA, surface plasmon resonance, and bioimaging. The pharmacokinetics was also studied.Results: The CS-ES2-AF could self-assemble into stable nanoparticles in aqueous solution, which significantly enhances its anti-neovascularization activity, tumor targeting more explicit, and prolongs its half-life.Conclusion: CS is an effective protein/peptide modifier, and CS-ES2-AF displayed good potential in tumor targeting therapy. Keywords: chondroitin sulfate, ES2-AF, nanoparticles, anti-angiogenesis, targeting

Zhang X, Zhao X, Wang Y, Xing L. Cancer Manag Res. 2020;12:6779–6793. The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised over alleged image duplication in Figures 3C and 6C with similar images from unrelated articles, specifically: Figure 3C, panel SK-MES-1 miR-324-5p mimic appears to have been duplicated with a similar image in Figure 4C from Han et al, 2020 (https://doi.org/10.18632/aging.102628). Figure 6C, panel H522 si-LINC00491+pcDNA3.1 appears to have been duplicated with similar images in Figure 4C and 6C from Han et al, 2020 (https://doi.org/10.18632/aging.102628). The authors responded to our initial queries but were unable to provide a satisfactory explanation for the alleged duplication and could not provide satisfactory original data for their study. The Editor advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

JAEA has been progressing to design HTGR fuels for not only small-type practical HTGRs but also VHTR proposed in GIF which can be utilized for various purposes with high-temperature heat at 750 to 950 °C. To increase economy of these HTGRs, JAEA has been upgrading the design method for the HTGR fuel, which can maintain their integrities at the burnup of three to four times higher than that of the conventional HTTR fuel. Design principles and specifications of various concepts of the high burnup HTGR fuels designed by JAEA are reported. As the latest results on post-irradiation examinations of the high burnup HTGR fuel progressing in a framework of international collaboration with Kazakhstan, irradiation shrinkage rate of the fuel compact as a function of fast neutron fluence was obtained at around 100 GWd/thm. Furthermore, the future R&Ds needed for the high burnup HTGR fuel are described based on these experimental results.

Summary: Reproductive aging in female mammals is an irreversible process associated with declining oocyte quality, which is the rate-limiting factor to fertility. Here, we show that this loss of oocyte quality with age accompanies declining levels of the prominent metabolic cofactor nicotinamide adenine dinucleotide (NAD+). Treatment with the NAD+ metabolic precursor nicotinamide mononucleotide (NMN) rejuvenates oocyte quality in aged animals, leading to restoration in fertility, and this can be recapitulated by transgenic overexpression of the NAD+-dependent deacylase SIRT2, though deletion of this enzyme does not impair oocyte quality. These benefits of NMN extend to the developing embryo, where supplementation reverses the adverse effect of maternal age on developmental milestones. These findings suggest that late-life restoration of NAD+ levels represents an opportunity to rescue female reproductive function in mammals. : Declining oocyte quality is considered an irreversible feature of aging and is rate limiting for human fertility. Bertoldo et al. show that reversing an age-dependent decline in NAD(P)H restores oocyte quality, embryo development, and functional fertility in aged mice. These findings may be relevant to reproductive medicine. Keywords: oocyte, nicotinamide adenine dinucleotide (NAD+), nicotinamide mononucleotide (NMN), SIRT2, female fertility, infertility, reproductive aging, aging, embryo development, in vitro fertilization

Li Zhang,1–3 Junli Chang,1–3 Yongjian Zhao,1–3 Hao Xu,1–3 Tengteng Wang,1–3 Qiang Li,1–3 Lianping Xing,4 Jing Huang,5 Yongjun Wang,1–3,6 Qianqian Liang1–3 1Department of Orthopaedics, Longhua Hospital, 2Institute of Spine, 3Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA; 5School of Life Science, East China Normal University, 6School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China Abstract: Triptolide (TP) exhibits immunosuppressive, cartilage-protective and anti-inflammatory effects in rheumatoid arthritis. However, the toxicity of TP limits its widespread use. To decrease the toxic effects, we developed a novel nano-drug carrier system containing TP using poly-γ-glutamic acid-grafted di-tert-butyl L-aspartate hydrochloride (PAT). PAT had an average diameter of 79±18 nm, a narrow polydispersity index (0.18), a strong zeta potential (-32 mV) and a high drug encapsulation efficiency (EE1=48.6%) and loading capacity (EE2=19.2%), and exhibited controlled release (t1/2=29 h). The MTT assay and flow cytometry results indicated that PAT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells. PAT decreased lipopolysaccharides/interferon γ-induced cytokines expression of macrophage (P

Hydrogen produced without carbon emissions could be a useful fuel as nations look to decarbonize their electricity, transport, and industry sectors. Using the iodine–sulfur (IS) cycle coupled with a nuclear heat source is one method for producing hydrogen without the use of fossil fuels. An economic dispatch model was developed for a nuclear-driven IS system to determine hydrogen sale prices that would make such a system profitable. The system studied is the HTTR-GT/H2, a design for power and hydrogen cogeneration at the Japan Atomic Energy Agency’s High Temperature Engineering Test Reactor. This study focuses on the development of the economic model and the role that input data plays in the final calculated values. Using a historical price duration curve shows that the levelized cost of hydrogen (LCOH) or breakeven sale price of hydrogen would need to be 98.1 JPY/m3 or greater. Synthetic time histories were also used and found the LCOH to be 67.5 JPY/m3. The price duration input was found to have a significant effect on the LCOH. As such, great care should be used in these economic dispatch analyses to select reasonable input assumptions.

Cheng-Qiong Luo,1–3,* Lei Xing,1–3,* Peng-Fei Cui,1 Jian-Bin Qiao,1 Yu-Jing He,1 Bao-An Chen,4 Liang Jin,1,2,5 Hu-Lin Jiang1–3 1State Key Laboratory of Natural Medicines, Department of Pharmaceutics, 2Jiangsu Key Laboratory of Drug Screening, 3Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, 4Department of Hematology, The Affiliated Zhongda Hospital of Southeast University, 5School of Life Science and Technology, China Pharmaceutical University, Nanjing, China *These authors contributed equally to this work Background: The natural compound curcumin (Cur) can regulate growth inhibition and apoptosis in various cancer cell lines, although its clinical applications are restricted by extreme water insolubility and instability. To overcome these hurdles, we fabricated a Cur-coordinated reactive oxygen species (ROS)-responsive nanoparticle using the interaction between boronic acid and Cur. Materials and methods: We synthesized a highly biocompatible 4-(hydroxymethyl) phenylboronic acid (HPBA)-modified poly(ethylene glycol) (PEG)-grafted poly(acrylic acid) polymer (PPH) and fabricated a Cur-coordinated ROS-responsive nanoparticle (denoted by PPHC) based on the interaction between boronic acid and Cur. The mean diameter of the Cur-coordinated PPHC nanoparticle was 163.8 nm and its zeta potential was –0.31 mV. The Cur-coordinated PPHC nanoparticle improved Cur stability in physiological environment and could timely release Cur in response to hydrogen peroxide (H2O2). PPHC nanoparticles demonstrated potent antiproliferative effect in vitro in A549 cancer cells. Furthermore, the viability of cells treated with PPHC nanoparticles was significantly increased in the presence of N-acetyl-cysteine (NAC), which blocks Cur release through ROS inhibition. Simultaneously, the ROS level measured in A549 cells after incubation with PPHC nanoparticles exhibited an obvious downregulation, which further proved that ROS depression indeed influenced the therapeutic effect of Cur in PPHC nanoparticles. Moreover, pretreatment with phosphate-buffered saline (PBS) significantly impaired the cytotoxic effect of Cur in A549 cells in vitro while causing less damage to the activity of Cur in PPHC nanoparticle. Conclusion: The Cur-coordinated nanoparticles developed in this study improved Cur stability, which could further release Cur in a ROS-dependent manner in cancer cells. Keywords: coordination, curcumin, phenylboronic acid, stimuli-responsive, hydrogen peroxide

Auranofin, an FDA-approved drug for rheumatoid arthritis, has emerged as a promising antiparasitic medication in recent years. The gold(I) ion in auranofin is postulated to be responsible for its antiparasitic activity. Notably, aurothiomalate and aurothioglucose also contain gold(I), and, like auranofin, they were previously used to treat rheumatoid arthritis. Whether they have antiparasitic activity remains to be elucidated. Herein, we demonstrated that auranofin and similar derivatives, but not aurothiomalate and aurothioglucose, inhibited the growth of Toxoplasma gondii in vitro. We found that auranofin affected the T. gondii biological cycle (lytic cycle) by inhibiting T. gondiis invasion and triggering its egress from the host cell. However, auranofin could not prevent parasite replication once T. gondii resided within the host. Auranofin treatment induced apoptosis in T. gondii parasites, as demonstrated by its reduced size and elevated phosphatidylserine externalization (PS). Notably, the gold from auranofin enters the cytoplasm of T. gondii, as demonstrated by scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDS) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).IMPORTANCEToxoplasmosis, caused by Toxoplasma gondii, is a devastating disease affecting the brain and the eyes, frequently affecting immunocompromised individuals. Approximately 60 million people in the United States are already infected with T. gondii, representing a population at-risk of developing toxoplasmosis. Recent advances in treating cancer, autoimmune diseases, and organ transplants have contributed to this at-risk populations exponential growth. Paradoxically, treatments for toxoplasmosis have remained the same for more than 60 years, relying on medications well-known for their bone marrow toxicity and allergic reactions. Discovering new therapies is a priority, and repurposing FDA-approved drugs is an alternative approach to speed up drug discovery. Herein, we report the effect of auranofin, an FDA-approved drug, on the biological cycle of T. gondii and how both the phosphine ligand and the gold molecule determine the anti-parasitic activity of auranofin and other gold compounds. Our studies would contribute to the pipeline of candidate anti-T. gondii agents.

Liyong Xing, Zhifei Liu, Gang Deng, Huan Wang, Yanfeng Zhu, Peng Shi, Bingyue Huo, Yindong Li Department of Urology, Tangshan People’s Hospital, Tangshan, People’s Republic of China Purpose: Xanthogranulomatous prostatitis (XP) is a rare form of nonspecific granulomatous prostatitis that can clinically mimic high-grade prostatic carcinoma. It is difficult to diagnose it definitely in clinical settings. Methods: We report a case of XP with prostate-rectal fistula and review the relevant literatures. Result: A 75-year-old man presented with rectal bleeding when he urinated. A locally advanced carcinoma of prostate was suspected initially following the physical, imaging, and hematologic examinations. Subsequently on histopathological and immunohistochemical staining after needle biopsy of the prostate, a diagnosis of XP was made definitely. The patient was catheterized temporarily and treated with tamsulosin and estrogen. The patient underwent uneventful recovery after this conservative therapy. Conclusion: Histologic and immunohistochemical analyses are valuable in differentially diagnosing XP from high-grade prostate carcinoma. Treatment strategy of XP in principle is recommended to be the conservative method. Long-term follow-up earns are highly regarded considering the possibility of coexisting prostate cancer. Keywords: xanthogranulomatous prostatitis, prostate-rectal fistula

Zhang L, Chang J, Zhao Y, et al. Int J Nanomedicine. 2018;13:2051–2064. Following a review of their data post-publication, the authors found errors in Figure 1B on page 2055 and the Liver WTand PAT images used for Figure 4 on page 2059. For accuracy and experimental integrity these images have been corrected, with no impact to the conclusions of the study. The authors apologize for this error. Read the original article

The displacement of a suspension of particles by an immiscible fluid in a capillary tube or in porous media is a canonical configuration that finds application in a large number of natural and industrial applications, including water purification, dispersion of colloids and microplastics, coating and functionalization of tubings. The influence of particles dispersed in the fluid on the interfacial dynamics and on the properties of the liquid film left behind remain poorly understood. Here, we study the deposition of a coating film on the walls of a capillary tube induced by the translation of a suspension plug pushed by air. We identify the different deposition regimes as a function of the translation speed of the plug, the particle size, and the volume fraction of the suspension. The thickness of the coating film is characterized, and we show that similarly to dip coating, three coating regimes are observed, liquid only, heterogeneous, and thick films. We also show that, at first order, the thickness of films thicker than the particle diameter can be predicted using the effective viscosity of the suspension. Nevertheless, we also report that for large particles and concentrated suspensions, a shear-induced migration mechanism leads to local variations in volume fraction and modifies the deposited film thickness and composition.