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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.

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

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.

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

Qiang Wen,1 Zhe Yang,1 Jian Zhu,2 Qingtao Qiu,2 Honghai Dai,1 Alei Feng,1 Ligang Xing3 1Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan 250021, People’s Republic of China; 2Department of Radiation Physics, Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan 250117, People’s Republic of China; 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan 250117, People’s Republic of ChinaCorrespondence: Zhe YangDepartment of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, People’s Republic of ChinaTel +86-18560222576Email sdslyyyz@126.comBackground: The present study constructed and validated models to predict PD-L1 and CD8+TILs expression levels in esophageal squamous cell carcinoma (ESCC) patients using radiomics features and clinical factors.Patients and Methods: This retrospective study randomly assigned 220 ESCC patients to a discovery dataset (n= 160) and validation dataset (n= 60). A total of 462 radiomics features were extracted from the segmentation of regions of interest (ROIs) based on pretreatment CT images of each patient. The LASSO algorithm was applied to reduce the dimensionality of the data and select features. A multivariable logistic regression analysis was adopted to build radiomics signatures. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive accuracy of these models.Results: There was no significant difference between the training and validation datasets for any clinical factors in patients with ESCC. The PD-L1 expression level correlated with the differentiation degree (p= 0.011) and tumor stage (p= 0.032). Smoking status (p= 0.043) and differentiation degree (p= 0.025) were associated with CD8+TILs expression levels. The radiomics signatures achieved good performance in predicting PD-L1 and CD8+TILs with AUCs= 0.784 and 0.764, respectively. The combined model showed a favorable predictive ability compared to radiomics signatures or clinical factors alone and improved the AUCs from 0.669 to 0.871 for PD-L1 and from 0.672 to 0.832 for CD8+TILs. These results were verified in the validation dataset with the AUCs of 0.817 and 0.795, respectively.Conclusion: CT-based radiomics features have a potential value for classifying patients according to PD-L1 and CD8+TILs expression levels. The combination of clinical factors and radiomics signatures significantly improved the predictive performance in ESCC.Keywords: radiomics features, PD-L1, CD8+TILs, esophageal squamous cell carcinoma, computed tomography

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