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Chaoping Ma,1,* Weisong Jiang,2,* Juan Li,1,* Wenwu Sun,2,* Jiyuan Zhang,1 Peixian Xu,1 Yiran Guo,1 Ning Ning,2 Jiaoyan Li,2 Bing Zhao,2 Enqiang Mao,2 Chengjin Gao1 1Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China; 2Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chengjin Gao; Enqiang Mao, Email gaochengjin@xinhuamed.com.cn; maoeq@yeah.netIntroduction: In critically ill patients, the stress hyperglycemia ratio (SHR) was significantly associated with mortality. However, the relationship between SHR and mortality in septic patients is still unclear.In this study, patients with sepsis from two Chinese academic centers were identified and divided into quartiles based on SHR levels.Methods: Multivariable regression analysis will be used to determine associations between SHR and clinical outcomes in sepsis patients.The Kaplan-Meier curve was used to predict mortality in various groups of septic patients.Results: A total of 1835 septic patients were included in the study.The in-hospital, 30-day, and 60-day mortality rates for all septic patients were 22.8%, 18.7%, and 21.7%, respectively. Increased SHR was significantly associated with hospital mortality in multivariate regression analysis.These results were further confirmed in the adjusted analysis, where the hospital mortality and the 60-day mortality of the highest SHR quartile were significantly increased compared to the lowest SHR quartile. However, the highest SHR quartile was not associated with 30-day mortality.In addition, the risk of in-hospital mortality, 30-day mortality and 60-day mortality showed a consistent upward trend with increasing SHR quartile. The survival curve showed that the worst prognosis was in the fourth SHR quartile.Discussion: In conclusion, SHR was significantly associated with hospital mortality in patients with sepsis. This finding indicates that the SHR may be useful in identifying septic patients at higher risk of hospital mortality.Keywords: sepsis, stress hyperglycemia ratio, mortality, Hyperglycemia

Jing Ye,1,2,* Ping Li,1,2,* Pengcheng Liu,1,2 Wenjing Pei,1,2 Ruowen Wang,1,2 Hui Liu,1,2 Changxiu Ma,1,2 Dahai Zhao1,2 1Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China; 2Institute of Respiratory Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dahai Zhao, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, People’s Republic of China, Email zhaodahai@ahmu.edu.cnBackground: Anxiety and depression are two of the most common comorbidities of COPD, which can directly lead to the number of acute exacerbations and hospitalizations of COPD patients and reduce their quality of life. At present, there are many studies on anxiety and depression in stable COPD, but few studies on anxiety and depression in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients.Objective: We aim to explore the changes of serum metabolomics in AECOPD complicated with anxiety and depression and to provide some clues for further understanding its pathogenesis.Methods: This is an observational high-throughput experimental study based on retrospective data extraction. Twenty-one AECOPD with anxiety and depressive patients and 17 healthy controls (HCs) were retrospectively enrolled in the Second Affiliated Hospital of Anhui Medical University. Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) for anxiety and depression were used to assess the patients with AECOPD. Untargeted metabolomics analysis was carried out to investigate different molecules in the serum of all participants. General information of all participants, baseline data and clinical measurement data of AECOPD patients were collected. Statistical analysis and bioinformatics analysis were performed to reveal different metabolites and perturbed metabolic pathways.Results: A total of 724 metabolites in positive ionization mode and 555 metabolites in negative ionization mode were different in AECOPD patients with anxiety and depression. The 1,279 serum metabolites could be divided into 77 categories. Based on multivariate and univariate analysis, 74 metabolites were detected in positive ionization mode, and 60 metabolites were detected in negative ionization as differential metabolites. The 134 metabolites were enriched in 18 pathways, including biosynthesis of unsaturated fatty acids, aldosterone synthesis and secretion, protein digestion and absorption, ovarian steroidogenesis, long−term depression, retrograde endocannabinoid signaling, and so on.Conclusion: This work highlights the key metabolites and metabolic pathways disturbed in AECOPD patients with anxiety and depression. These findings support the use of metabolomics to understand the pathogenic mechanisms involved in AECOPD patients with anxiety and depression.Keywords: metabolomics, AECOPD, anxiety, depression, exacerbation

Yong Zhu,1,* Yongzhe Zhang,2,* Xiuli Yu,3 Huaqiang Zhao,1 Chuan Ma1 1Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, People’s Republic of China; 2Department of Prosthodontics, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 3Department of Stomatology, Chengyang People’s Hospital, Qingdao, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuan Ma, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Fax +86 53188382923, Email machuan@sdu.edu.cnObjective: Tumor cells, inflammatory cells, and chemical factors collaboratively orchestrate a sophisticated signaling network, culminating in the formation of the inflammatory tumor microenvironment (TME). The present study sought to explore the nature of the inflammatory response in HNSCC and to decipher its influence on immunotherapeutic.Materials and Methods: A thorough analysis was performed utilizing the TCGA cohort along with two GEO cohorts. Unsupervised clustering of 200 inflammatory response-related genes (IRGs) was applied using the k-means algorithm to explore the heterogeneity of HNSCC. Additionally, a prognostic signature based on IRGs genes was constructed using Lasso regression. Meanwhiles, the expression of IRGs were identified in tumors and paracancerous tissues at the single-cell level. The crosstalk between IRGs was explored using CellChat and the patterns of incoming and outgoing signals were identified. Finally, qPCR was used to verify the expression of hub genes.Results: There were significant differences in immune-cell function and immune-cell infiltration among three inflammatory response clusters. Additionally, we also constructed a prognostic model which could predicted the responses of common chemotherapeutic drugs and immunotherapy. Furthermore, qPCR and sc-RNA seq corroborated that the expression profiles of the prognostic genes were largely in alignment with the findings from the bioinformatics analysis. Ultimately, the molecular docking demonstrated favorable binding affinities between the pivotal gene-SCC7 and four chemotherapeutic drugs.Conclusion: This research has uniquely shed light on the intricate connection between the inflammatory response profiles and the immune infiltration patterns in HNSCC.Keywords: HNSCC, TME, inflammatory response, immunotherapy, sc-RNA seq

Mina Wang,1,2,&ast; Yashuo Ren,1,&ast; Hongli Xiao,1 Anming Liu,1,2 Chunying Ma,2 Zhuohao Li,2 Zixi Wang,2 Qiuyu Xia,2 Pu Dou,1 Bin Li,2 Peng Chen2 1Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Chen; Bin Li, Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, No. 23 Meishuguanhou Street, Beijing, Dongcheng District, 100010, People’s Republic of China, Email chenpenger@126.com; libin@bjzhongyi.comIntroduction: Parkinson’s disease (PD)-related chronic pain is a prevalent non-motor symptom, this study aimed to detect the effect and safety of fire needling therapy (FNT) for PD-related chronic pain relief.Methods: Patients with PD-related chronic pain were randomly allocated to FNT group and control group with a treatment phase of 8 weeks and a follow-up phase of 4 weeks. Primary outcome was the King’s Parkinson’s Pain Scale (KPPS), Secondary outcomes included Visual Analogue Scale (VAS), Unified Parkinson’s Disease Rating Scale-III (UPDRS-III), and the Parkinson’s Disease Questionnaire-39 (PDQ-39). Study was registered on Chinese Clinical Trial Registry (Registered number: ChiCTR2400084951).Results: 60 participants were randomized, with 30 in the FNT group and 30 in the control group. KPPS was significantly influenced by the interaction of treatment and time, with a significant reduction in pain observed in the FNT group compared to the control group at Week 4 (difference [95% CI]: − 20.693[− 27.619,-13.767], P< 0.001), Week 8 (difference [95% CI]: 44.680[− 52.359,-37.000], P< 0.001), and Week 12 (difference [95% CI]: − 44.982[− 52.771,-37.193], P< 0.001). For VAS, UPDRS-III, and PDQ-39, there were significant differences between groups at Week 4, Week 8, and Week 12.Conclusion: FNT could be an effective and safe method for managing PD-related chronic pain. However, large-sample studies conducted in multiple centers are necessary to further verify the findings in the future.Keywords: parkinson’s disease, pain, fire needling therapy, acupuncture, pilot randomized controlled trial

Meixin Yu,1,&ast; Ling Pei,1,&ast; Han Liu,1 Jiaxin Wang,1 Yun Wen,1 Xian Yang,1 Caixia Ma,1 Xiaofang Zhang,2,3 Liangyan Wu,1 Lihong Wang1,2 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2The Academician Cooperative Laboratory of Basic and Translational Research on Chronic Diseases, Jinan University, Guangzhou, Guangdong, People’s Republic of China; 3The Guangzhou Key Laboratory of Basic and Translational Research on Chronic Diseases, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihong Wang, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Jinan University, No. 613, Huang Pu Avenue West, Guangzhou, Guangdong, People’s Republic of China, Email nd6688@163.comPurpose: To explore the relationship between Red cell distribution width/albumin ratio (RAR) and vascular complications, including atherosclerosis of the lower limbs, diabetic nephropathy(DN), and diabetic retinopathy(DR), in patients with type 2 diabetes mellitus(T2DM).Patients and Methods: The study included 427 patients with type 2 diabetes mellitus who were hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Jinan University (Guangzhou, China) between April 1, 2022 and May 31, 2023. Baseline characteristics were displayed according to the quartiles of the RAR. Logistic regression analysis and receiver operating characteristic curves (ROC) were used to analyze the data.Results: After adjusting for confounders, a higher RAR quartile(the fourth quartile) was associated with an increased risk of atherosclerosis of the lower limbs(OR: 2.973, 95% CI 1.281– 6.906, p = 0.011), and diabetic nephropathy(OR: 2.876, 95% CI 1.315– 6.287, p = 0.008) compared to the lowest RAR quartile. The patients were further divided into two groups according to urinary albumin to creatinine ratio (UACR≥ 30mg/g and UACR < 30mg/g) and Glomerular Filtration Rate (eGFR< 60 mL·min⁻¹ (1.73 m²) ⁻¹ and eGFR≥ 60 mL·min⁻¹ (1.73 m²) ⁻¹). Similar results were observed. However, We found that RAR quartile did not significantly increase the likelihood of developing diabetic retinopathy(OR: 1.183, 95% CI 0.633– 2.211, p = 0.598).Conclusion: The RAR ratio is associated with an increased risk of atherosclerosis of the lower limbs and diabetic nephropathy in patients with T2DM. The RAR ratio may be an important clinical marker of vascular complications in T2DM.Keywords: Type 2 diabetes mellitus, red blood cell distribution width, albumin, complications, inflammation

Juan Li,1,&ast; Shu Wang,2,&ast; Chaoping Ma,1,&ast; Ning Ning,3,&ast; Yingying Huang,1,4,&ast; Min Jiao,1 Jiyuan Zhang,1 Wenwu Sun,3 Jiaoyan Li,3 Bing Zhao,3 Enqiang Mao,3 Zaiqian Che,3 Chengjin Gao1 1Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Intensive Care Medicine, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, 400016, People’s Republic of China; 3Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 4Dementia Research Center, Macquarie University, Sydney, Australia&ast;These authors contributed equally to this workCorrespondence: Chengjin Gao, Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, People’s Republic of China, Email gaochengjin@xinhuamed.com.cn Zaiqian Che, Departments of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Email chezaiqian@163.comPurpose: New-onset atrial fibrillation (NOAF) and sepsis-induced coagulopathy (SIC) are severe complications in septic patients. However, the relationship between NOAF and SIC score has not been clearly defined. This study aims to investigate the association between SIC score and NOAF, as well as their effect on mortality in sepsis.Patients and Methods: This study was a two-center retrospective analysis. Medical data were collected from patients diagnosed with sepsis. The patients were divided into NOAF and non-NOAF groups, and the SIC score was calculated for each group. Univariable and multivariable logistic regression analyses were performed to explore the relationship between the SIC score and NOAF, as well as their effects on mortality. The Kaplan-Meier curve was used to assess the survival rate.Results: A total of 2,280 septic patients were included, with 132 (5.7%) suffering from NOAF. Multivariable logistic regression analyses indicated that age, gender, the Acute Physiology and Chronic Health Evaluation II score (APACHE II), heart rate, renal failure, stroke, chronic obstructive pulmonary disease (COPD), and the SIC score were independent risk factors for NOAF in sepsis. Moreover, NOAF was associated with an increased risk of in-hospital mortality, 28-day mortality, and 90-day mortality. These results were consistent across subgroup analyses.Conclusion: The SIC score was an independent risk factor for NOAF in septic patients, and NOAF was an independent risk factor for predicting mortality.Keywords: sepsis, sepsis-induced coagulopathy, new-onset atrial fibrillation, association, mortality

Rui Shen,1,2,&ast; Kebin Cheng,3,&ast; Guanyi Li,1 Zhendong Pan,4 Xijier Qiaolongbatu,1 Yuting Wang,1 Cui Ma,1 Xucong Huang,1 Li Wang,1 Wenjing Li,1 Yuanyuan Wang,2 Lili Jing,1 Guorong Fan,2 Zhenghua Wu2 1School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, People’s Republic of China; 4Department of Clinical Pharmacy, Eye and ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenghua Wu, Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 85 Wujin Road, Shanghai, 200080, People’s Republic of China, Tel +86-159-0161-7923, Email wuzhenghua@sjtu.edu.cnPurpose: Alisma orientale (AO, Alisma orientale (Sam). Juzep) has been widely employed for the treatment of macular edema (ME) in traditional Chinese medicine due to its renowned water-relief properties. Nonetheless, the comprehensive investigation of AO in alleviating ME remained unexplored. This study aims to identify the active components of AO that target the eye and investigate its pharmacological effects and mechanisms on ME.Methods: The study commenced with UPLC-Triple-TOF/MS analysis to identify the primary constituents of AO. Zebrafish eye tissues were then analyzed after a five-day administration of AO to detect absorbed components and metabolites. Subsequently, network pharmacology, molecular docking, and molecular dynamics simulations were employed to predict the mechanisms of ME treatment via biological target pathways. In vivo experiments were conducted to corroborate the pharmacological actions and mechanisms.Results: A total of 7 compounds, consisting of 2 prototype ingredients and 5 metabolites (including isomers), were found to traverse the blood-eye barrier and localized within eye tissues. Network pharmacology results showed that AO played a role in the treatment of ME mainly by regulating the pathway network of PI3K-AKT and MAPK with TNF-α centered. Computational analyses suggested that 11-dehydro-16-oxo-24-deoxy-alisol A, a metabolite of alisol A, mitigates edema through TNF-α inhibition. Furthermore, zebrafish fundus confocal experiments and HE staining of eyes confirmed the attenuating effects of alisol A on fundus angiogenesis and ocular edema, representing the first report of AO’s ME-inhibitory effects.Conclusion: In this study, computational analyses with experimental validation were used to understand the biological activity and mechanism of alisol A in the treatment of ME. The findings shed light on the bioactive constituents and pharmacological actions of AO, offering valuable insights and a theoretical foundation for its clinical application in managing ME. Keywords: Alisma orientale, macular edema, network pharmacology, zebrafish, TNF-&#x03B1

Simin Liu,1,&ast; Zhiyuan Tian,2 Taiming Zhang,3 Jirong Zhang,3 Yanlei Huo,1,&ast; Chao Ma1 1Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Nuclear Medicine, Zibo Ninth People’s Hospital, Zibo, Shandong, People’s Republic of China; 3Department of Medical Imaging, People’s Hospital of Shuangjiang Autonomous Country, Lincang, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Ma, Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University, Yanchangzhong Road 301, Shanghai, 200072, People’s Republic of China, Tel +86 21-66302075, Email mc_7419@hotmail.comObjective: To explore analgesic effect and bone repair mechanism of non-radioactive technetium-99 conjugated with methylene diphosphonate (99Tc-MDP, brand name, Yunke) on bone metastases (BM).Procedures: In vivo experiment, mouse BM models of prostate cancer RM-1 cell were constructed and divided into Control, Yunke, 99Tc+SnCl2 and MDP groups based on medicine composition. Tumor specimens were inspected for size, X-ray, microCT and histopathology. In vitro experiment, with Cell Counting Kit-8 (CCK8), scratch, clone, apoptosis, Polymerase Chain Reaction (PCR) and Western Blot experiments, effects of Yunke on RM-1 cells and osteoclast-related cells were observed.Results: In vivo experiment, there was no difference in tumor size between Yunke and control group. Contrasted with control group, in Yunke group, trabecular spacing (Tb.Sp) of tumor bone was lower, bone volume/total volume (BV/TV) on marrow cavity and bone cortex were higher. Tunnel staining showed that positive rate of apoptosis in Yunke group was higher than that in control group. Ki67 staining showed that Yunke could not inhibit proliferation of tumor cells. In vitro experiment, CCK8 and scratch experiments showed that Yunke neither can inhibit proliferation nor can inhibit migration of RM-1 cells. High concentration of Yunke promoted late apoptosis of RM-1 cells. Yunke could inhibit BMM cell proliferation, differentiation of osteoclasts, and osteoclast-related transcription factors. Yunke displayed different degrees of inhibitory effects on MAPKs signaling pathway during osteoclast differentiation. It had obvious inhibitory effects on osteoclast-related transcription factors, such as cFOS, NFATC1, ACP-5, CTSK, D2 and MMP-9, the strongest inhibitory effects were observed with ACP-5, CTSK and D2. Yunke also displayed different degrees of inhibitory effects on protein activities of JNK, pERK, ERK and pP38.Conclusion: Yunke cannot inhibit the proliferation and migration of RM-1 cells, so we think it is not recommended for the treatment of primary tumors and prevention of occurrence of tumors metastatic to bones. The mechanism of therapeutic effect of Yunke on BM by inhibiting proliferation of BMM, inhibiting MAPKs signal transduction and activation of transcription factors during differentiation process of BMM-derived osteoclasts, inhibiting number and size of osteoclasts, inhibiting bone resorption and protecting bone destruction through enhancing bone hardness and bone mass. Thereby, we believe that Yunke is more suitable for promoting the repair induced by BMs, delaying its progression and reducing the occurrence of SREs.Keywords: 99Tc-MDP, bone metastases, molecular mechanisms, RM-1, prostate cancer

Ming Cheng,1,2 Cong Ma,1– 3 Hong-Duo Chen,1,2 Yan Wu,1,2 Xue-Gang Xu1,2 1Department of Dermatology, The First Hospital of China Medical University, Shenyang, 110000, People’s Republic of China; 2Key Laboratory of Immunodermatology, Ministry of Education and NHC; National Joint Engineering Research Center for Theranostics of Immunological Skin Diseases, Shenyang, 110000, People’s Republic of China; 3Department of Dermatology and Sexually Transmitted Diseases, The First Hospital of Inner Mongolia University for Nationalities, Tongliao, 028000, People’s Republic of ChinaCorrespondence: Xue-Gang Xu; Yan Wu, Department of Dermatology, The First Hospital of China Medical University, Shenyang, 110000, People’s Republic of China, Email xuxuegang2749290@163.com; jlwuyan@126.comAbstract: Alopecia is considered a widespread yet troubling health issue, with limited treatment options. As membranous structures derived from cells carrying proteins, nucleic acids and lipids, exosomes functionally medicate intercellular communication and alter the responses of recipient cells, resulting in disease restraint or promotion. Exosomes have broad prospects in diagnosis and treatment of diseases. Studies using animal models and at the cellular level have clearly shown that exosomes from several types of cells, including dermal papilla cells and mesenchymal stem cells, have a notable capacity to promote hair growth, suggesting that exosomes may provide a new option to treat alopecia. Here, we present a thorough review of the most recent progress in the application of exosomes to hair growth.Keywords: exosome, hair follicle, alopecia

Changxiu Ma,1 Ying Zhang,1 Tingchao Tian,2 Ling Zheng,1 Jing Ye,1 Hui Liu,1 Dahai Zhao1 1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Huoqiu First People’s Hospital, Huoqiu, 237400, People’s Republic of ChinaCorrespondence: Dahai Zhao, Second Affiliated Hospital, Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, People’s Republic of China, Tel +86-13721027959, Email zhaodahai@ahmu.edu.cnPurpose: To explore the role of the mean apnea–hypopnea duration (MAD) and apnea–hypopnea duration per hour (HAD) in hypoxemia and evaluate whether they can effectively predict the occurrence of hypoxemia among adults with OSA.Patients and Methods: A total of 144 participants underwent basic information gathering and polysomnography (PSG). Logistic regression models were conducted to evaluate the best index in terms of hypoxemia. To construct the prediction model for hypoxemia, we randomly divided the participants into the training set (70%) and the validation set (30%).Results: The participants with hypoxemia tend to have higher levels of obesity, diabetes, AHI, MAD, and HAD compared with non-hypoxemia. The most relevant indicator of blood oxygen concentration is HAD (r = 0.73) among HAD, MAD, and apnea–hypopnea index (AHI). The fitness of HAD on hypoxemia showed the best. In the stage of establishing the prediction model, the area under the curve (AUC) values of both the training set and the validation set are 0.95. The increased HAD would elevate the risk of hypoxemia [odds ratio (OR): 1.30, 95% confidence interval (CI): 1.13– 1.49].Conclusion: The potential role of HAD in predicting hypoxemia underscores the significance of leveraging comprehensive measures of respiratory disturbances during sleep to enhance the clinical management and prognostication of individuals with sleep-related breathing disorders.Keywords: mean apnea–hypopnea duration, obstructive sleep apnea, apnea–hypopnea duration per hour, polysomnography, apnea–hypopnea index

Chao Ma,1,&ast; Haoyu Li,2,3,&ast; Shuwen Lu,4 Xian Li5,6 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Clinical Research Centre of Ophthalmic Disease, Changsha, Hunan, People’s Republic of China; 4Department of Ophthalmology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 5Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK; 6Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK&ast;These authors contributed equally to this workCorrespondence: Chao Ma, Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86-371-66278091, Email gmchao219@163.comAbstract: Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major contributors to visual impairment and blindness worldwide. The development and implementation of effective strategies for managing and preventing the onset and progression of these diseases are crucial for preserving patients’ visual acuity. Melatonin, a neurohormone primarily produced by the pineal gland, exhibits properties such as circadian rhythm modulation, antioxidant activity, anti-inflammatory effects, and neuroprotection within the ocular environment. Furthermore, melatonin has been shown to suppress neovascularization and reduce vascular leakage, both of which are critical in the pathogenesis of degenerative fundus lesions. Consequently, melatonin emerges as a promising therapeutic candidate for degenerative ocular diseases. This review provides a comprehensive overview of melatonin synthesis, its localization within ocular tissues, and its mechanisms of action, particularly in regulating melatonin production, thereby underscoring its potential as a therapeutic agent for degenerative fundus diseases.Keywords: melatonin, fundus degeneration, oxidative stress, inflammation, anti-apoptotic

Chenlu Ma,1 Wen Zhang,1 Shu Da,2 Huan Zhang,3 Xichao Zhang1 1Faculty of Psychology, Beijing Normal University, Beijing, 100875, People’s Republic of China; 2School of Psychology, Nanjing Normal University, Nanjing, 210024, People’s Republic of China; 3Academy of Global Innovation & Governance, University of International Business and Economics, Beijing, 100029, People’s Republic of ChinaCorrespondence: Xichao Zhang, Faculty of Psychology, Beijing Normal University, No. 19 XinJieKouWai Street, HaiDian District, Beijing, 100875, People’s Republic of China, Email xchzhang@bnu.edu.cnPurpose: Environmental uncertainty has reached unprecedented levels in recent years. While there is substantial knowledge about the connection between environmental uncertainty and organizational outcomes, limited attention has been devoted to investigating its impact on employees’ depression and anxiety symptoms. Grounded in job demands-resources theory, this study aims to explore the relationship between environmental uncertainty and employees’ depression and anxiety symptoms, and it further investigates the mediating role of work pressure and the moderating role of union practices.Methods: In September 2022, we undertook a cross-sectional survey study, gathering data from 1081 employees across various enterprises situated in Liaoning, China. Throughout this timeframe, notable global occurrences heightened the awareness of environmental uncertainty. Following the exclusion of participants who did not provide information on the main variables, the final valid sample comprised 940 employees. To test all hypotheses, a series of confirmatory factor analyses and path-analytic procedures were conducted using Mplus 7.0.Results: Our results confirm that environmental uncertainty, as a high job demand, increases employees’ work pressure, thereby elevating rates of anxiety and depression; the indirect relationship between environmental uncertainty and employees’ anxiety and depression through work pressure is stronger when union practices are lower.Conclusion: Our findings indicate the detrimental impact of environmental uncertainty on employees’ mental health, and highlight the roles of work pressure and union practices. In light of this, organizations should take steps to mitigate employees’ perceptions of environmental uncertainty and establish mental health programs, in cooperation with union practices, to protect employees’ mental well-being.Keywords: environmental uncertainty, anxiety, depression, union practices, work pressure

Cheng Ma,1 Minnan Yue,2 Xiaoling Zhu1 1Department of Physical Education, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China; 2School of Energy and Power Engineering, University of Shanghai for science and technology, Shanghai, 200093, People’s Republic of ChinaCorrespondence: Cheng Ma, Department of Physical education, University of Shanghai for science and technology, Shanghai, 200093, People’s Republic of China, Tel +86-13795365789, Email macheng@usst.edu.cnPurpose: To investigate the knowledge, attitudes and practices (KAP) among college students toward physical literacy during COVID-19 school closure.Patients and Methods: This web-based cross-sectional study was conducted between December 9th, 2022 and December 24th, 2022 among college students during COVID-19 school closure. A self-designed questionnaire was developed to collect demographic information of the college students, and assess their KAP toward physical literacy.Results: A total of 969 students were recruited, with mean age of 18.73± 0.97 years. The majority were male (54.70%), urban residents (78.02%), majoring in engineering (58.00%), and having exercise habits (61.09%). The mean KAP scores were 6.57± 0.95, 32.63± 4.07, and 27.06± 7.23, respectively. Positive associations were identified between knowledge and attitude (OR = 2.01, 95% CI: 1.52– 2.66, P < 0.001), and between attitude and practice (OR = 1.17, 95% CI: 1.12– 1.22, P < 0.001). A bachelor’s degree and being in the sophomore year were positively associated with knowledge (OR = 1.51– 4.05, all P < 0.05). Urban residence and being in the sophomore year were negatively associated with attitude (OR = 0.43– 0.59, all P < 0.05), while having daily exercise habits showed the opposite trend (OR = 1.85, 95% CI: 1.33– 2.57, P < 0.001). Father’s education level of high school and technical secondary school (OR = 0.58, 95% CI: 0.37– 0.93, P = 0.023) and having daily exercise habits (OR = 3.88, 95% CI: 2.72– 5.55, P < 0.001) were associated with practice.Conclusion: College students had sufficient knowledge, moderate attitudes and negative practices towards physical literacy during COVID-19 school closure. The findings hold significant potential for developing educational programs, fostering healthier lifestyles and promoting mental well-being among college students during public health outbreaks.Keywords: knowledge, attitude, practice, cross-sectional study, physical literacy

Renzhe Tang,1,&ast; Chong Li,2,&ast; Dongmei Di,1 Lin Zhou,2 Yongxiang Qian,1 Chaohua Qiang,3 Chao Ma,1 Rui Zhou,1 Bin Wang,1 Min Wang1 1Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China; 2Department of Respiratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China; 3Department of Echocardiography, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Wang; Bin Wang, Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, No. 185 of Juqian Street, Changzhou, Jiangsu Province, 213003, People’s Republic of China, Email wangmin80808@163.com; wangbin1987@suda.edu.cnObjective: Obstructive sleep apnea (OSA) is a disorder characterized by disruption in breathing and hypoventilation. In parallel, metabolic syndrome (MetS) mainly co-occur with OSA, however, their association has not been fully elucidated. Therefore, this study aimed to reveal the relationship between OSA and MetS using data from the National Health And Nutrition Examination Survey (NHANES) database and pooled data from Genome-Wide Association Studies (GWAS).Material and Methods: Data from the National Health and Nutrition Examination Survey and pooled data from genome-wide association analysis (GWAS) were used univariate and multivariate logistic regression analyses were carried out to evaluate the correlation between OSA and MetS, and multivariate logistic regression models were utilized for adjusting for potential confounders. Two-sample Mendelian randomization (MR) was used to assess the causal relationship between OSA and MetS. The variance-weighted inverse method was employed as the main method of analysis.Results: A positive relationship of OSA with Mets was evidenced by multivariate logistic regression analysis, and OSA was associated with higher incidence rates of all-cause and cardiovascular mortality. OSA is strongly associated with abdominal obesity, hypertension, hyperglycemia, high triglycerides, and low HDL. Furthermore, except for hypertriglyceridemia, MR analysis indicated that genetically driven OSA was causally associated with a higher risk of MetS.Conclusion: The positive relationship of OSA with Mets was revealed, and higher incidence rates of all-cause mortality and cardiovascular mortality were noted to be correlated with OSA. MR analysis further confirmed the causal relationship of OSA with MetS and cardiovascular disease.Keywords: obstructive sleep apnea, metabolic syndrome, cardiovascular disease, NHANES, Mendelian randomization

Yanjuan Song,1 Jing Hu,2 Chunlian Ma,3– 5 Hua Liu,3– 5 Zhanghua Li,6 Yi Yang3– 5 1Graduate School, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 2Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, People’s Republic of China; 3Fitness Monitoring and Chronic Disease Intervention Research Center, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 4College of Sports Medicine, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 5Hubei Key Laboratory of Exercise Training and Monitoring, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 6Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of ChinaCorrespondence: Yi Yang, Fitness Monitoring and Chronic Disease Intervention research center, Wuhan Sports University, Wuhan, Hubei Province, 430079, People’s Republic of China, Tel +86 139 7129 3990, Email yangyi999999@foxmail.com Zhanghua Li, Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei Province, 430074, People’s Republic of China, Tel +86 189 7161 0121, Email lizhanghua_123@163.comAbstract: The development of numerous diseases is significantly influenced by inflammation. Macrophage-derived exosomes (M-Exos) play a role in controlling inflammatory reactions in various conditions, including chronic inflammatory pain, hypertension, and diabetes. However, the specific targets and roles of M-Exos in regulating inflammation in diseases remain largely unknown. This review summarizes current knowledge on M-Exos biogenesis and provides updated information on M-Exos’ biological function in inflammation modulation. Furthermore, this review highlights the functionalization and engineering strategies of M-Exos, while providing an overview of cutting-edge approaches to engineering M-Exos and advancements in their application as therapeutics for inflammation modulation. Finally, multiple engineering strategies and mechanisms are presented in this review along with their perspectives and challenges, and the potential contribution that M-Exos may have in diseases through the modulation of inflammation is discussed.Keywords: inflammation, macrophage-derived exosomes, biological functions, inflammation modulation, engineering strategies

Jinhui Bu,1,2,&ast; Zhenfei Wang,2,&ast; Chao Ma,1,2 Juan Gao,2 Guangpu Liu,2 Libo Pang,2 Bo He,1 Minghui Dong,1 Quan Zhang,1 Yan Lei,1 Long Xu,2 Sen Huang,1 Yuming Li,3 Guangwang Liu1,2 1Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Orthopedic Surgery, Xuzhou Central Hospital, Xuzhou, People’s Republic of China; 3Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA&ast;These authors contributed equally to this workCorrespondence: Yuming Li, Tel +1-8573524988, Fax +1-8572188459, Email yuming.li@childrens.harvard.edu; Guangwang Liu, Tel +86-18012018238, Fax +86-51683956400, Email guangwangliu@163.comObjective: To validate whether a residual mass demonstrated on early postoperative MR after percutaneous endoscopic lumbar discectomy (PELD) is indeed an intraoperatively retained annulus fibrosus, and explore the correlation between imaging changes in the residual mass and clinical prognosis of patients.Methods: A prospective study of 118 patients were included. During surgery, a contrast medium, Gadopentetate Dimeglumine, was injected around the ruptured annulus fibrosus. The intensity of the T2 signal, the size of the remaining mass (SR), and the cross-sectional area of the spinal canal (SCSA), VAS, and ODI were assessed at preoperative, 1-h (7-day), 6-month, and 12-month postoperative intervals. Based on VAS at 7 days post-surgery, patients were classified into either a non-remission group (Group A, VAS > 3) or a remission group (Group B, VAS ≤ 3).Results: Six patients who developed recurrent LDH were excluded. A residual mass was detected on MRI 1 h after surgery in 94.6% (106/112). During one year of follow-up, 90.1% (101/112) of the patients displayed fibrous annulus remodeling, although 68.7% (77/112) still exhibited herniation. Significant differences were found in the ODI between Groups A and B one week after surgery (p < 0.001). However, no significant differences were observed in T2 signal intensity, SR, and SCSA at 1-h, 6-month and 12-month post-surgery (p > 0.05) between the two groups. In a multiple linear regression analysis, early postoperative ODI changes were associated with T2 signal (B = − 10.22, sig < 0.05), long-term changes were associated with alterations in SR (B = 5.63, sig < 0.05) and SCSA (B = − 0.13, sig < 0.05).Conclusion: The residual mass observed in early postoperative MR images after PELD was the retained annulus fibrosus intraoperatively. Short-term changes in clinical symptoms after PELD were linked to T2 signal intensity, while long-term changes were associated with changes in SR and SCSA.Keywords: spinal endoscopy, residual mass, remodeling of fibrous annulus, contrast medium

Yi Yao,1,&ast; Juan Li,2,&ast; Wenwu Sun,1,&ast; Chaoping Ma,2,&ast; Ning Ning,1 Jiaoyan Li,1 Tongtian Ni,1 Menglu Gui,1 Ying Chen,1 Bing Zhao,1 Jiyuan Zhang,2 Jiyue Zhu,3 Chengjin Gao,2 Huiqiu Sheng,1 Enqiang Mao1 1Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 2Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiqiu Sheng, Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China, Tel +86-15801971839, Email shenghq803@163.com Chengjin Gao, Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Tel +86-18221088783, Email gaochengjin@xinhuamed.com.cnPurpose: Both nonthyroidal illness syndrome (NTIS) and disseminated intravascular coagulation (DIC) are commonly occurred in sepsis. The objective of this study is to evaluate the association between NTIS and DIC, as well as their impacts on the mortality in adults with sepsis.Patients and methods: A total of 1219 septic patients in two Chinese academic centers from October 2012 and October 2022 were enrolled in analysis. We conduct logistic regression models to analyze the independent risk factors for DIC. Modified Poisson regression models are used to estimate the relative risk (RR) of NTIS on the 28 days mortality in septic patients with DIC. Correlation analysis between thyroid function parameters and coagulation parameters is performed with Pearson coefficient be reported.Results: DIC is diagnosed on 388 (31.8%) of all the 1219 enrolled septic patients within 72 hours after admission. In multivariate logistic regression models, NTIS (OR 3.19; CI 2.31– 4.46; p< 0.001) is a statistically significant independent risk factor for DIC after adjustment for potential confounders. Twenty-eight days mortality is significantly higher in DIC patients complicated with NTIS compared with the other DIC patients (23.2% vs 14.0%, p=0.024). This result is also robust in different modified Poisson regression models (Model 1: RR 1.46; CI 1.25– 1.70; p< 0.001; Model 2: RR 1.35; CI 1.14– 1.60; p< 0.001; Model 3: RR 1.18; CI 1.02– 1.37; p=0.026). Correlation analysis reveals that the thyroid function parameters of FT3, FT4 and TSH only have weak correlations with coagulation parameters of platelet count, fibrinogen, FDP, D-dimers, PT, APTT and INR in sepsis.Conclusion: NTIS is an independent risk factor for DIC in adults with sepsis. DIC patients complicated with NTIS have significantly higher severity and higher rate of mortality.Keywords: sepsis, low T3 syndrome, nonthyroidal illness syndrome, thyroid function, disseminated intravascular coagulation

Yongsheng Sun,1 ChengJiang Liu,2 Nianping Zhang,3 Debing Yang,4 Cungen Ma,5 Xi Zhang61Department of Neurology and Psychiatry, Medical College of Shanxi Datong University, Datong, 037009, People’s Republic of China; 2Department of General Medicine, Affiliated Anqing First People’s Hospital of Anhui Medical University, Anhui, 246000, People’s Republic of China; 3Department of Internal Medicine, Medical College of Shanxi Datong University, Datong, 037009, People’s Republic of China; 4Department of Anatomy, Medical College of Shanxi Datong University, Datong, 037009, People’s Republic of China; 5Neurobiology Research Center, Shanxi University of Traditional Chinese Medicine, Jinzhong, 030619, People’s Republic of China; 6Department of Neurology, Second Medical Center, General Hospital of the Chinese People’s Liberation Army, Beijing, 100000, People’s Republic of ChinaCorrespondence: Cungen Ma; Xi Zhang, Email macungen2001@163.com; zhangxiplagh@sina.comObjective: The common chronic non-communicable diseases and epidemiological characteristics of the forsaken elders over 60 in Guangling and Tianzhen were investigated and analyzed to provide reference for health resource allocation, hospital capacity establishing and health management of the forsaken elders in county-level regions.Materials and Methods: The data of 10,331 resident elderly over 60 in Guangling and Tianzhen of Datong Civil Affairs Bureau in the management system for disabled and semi-disabled elderly was collected. The gender, age, main diagnosis and coding of diseases, common chronic non-communicable diseases, and system diseases of the respondents were retrospectively analyzed.Results: The prevalence of the forsaken elders aged over 60 in Guangling and Tianzhen were different. Hypertension, arthritis, type 2 diabetes, hyperlipidemia and cerebral infarction are the top five common chronic non infectious diseases in Guangling, Tianzhen and the two counties. Among the top five common diseases in Guangling, Tianzhen and the two counties, arthritis or rheumatism, hypertension, diabetes or elevated blood sugar were found, which were different in the 60– 65, 66– 70, 71– 75 and 76– 80 groups, with the prevalence increasing with age. The top five diseases in Guangling, Tianzhen and the two counties were consistent, while the ranking changed slightly. The proportion of circulatory diseases, musculoskeletal diseases, connective tissue diseases and endocrine/nutritional and metabolic diseases in 60– 65, 66– 70 and 71– 75 groups increased with age, and was much higher than that in other groups.Conclusion: The prevalence and disease spectrum order of common chronic non-communicable diseases and systemic diseases in Guangling and Tianzhen are diverse, also in gender and age groups. As China’s county-level local administrative divisions have relatively independent administrative autonomy, medical and health resources can be better configured according to the information mined, accurately maintaining and promoting residents’ health. It is suggested to explore the disease management mechanism with county-level administrative divisions as database management units under the background of big data, so as to implement the interconnection and sharing of information among health-related departments in county-level regions.Keywords: chronic non-communicable diseases, system diseases, administrative division, disease spectrum, the forsaken elders

Yepeng Wang,1,&ast; Chao Ma,2,&ast; Xuekun Yang,3 Jun Gao,1 Zhigang Sun2 1Department of Neurosurgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, People’s Republic of China; 2Department of Thoracic Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, People’s Republic of China; 3Department of Neurology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigang Sun, Department of Thoracic Surgery, Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, Shandong Province, People’s Republic of China, Tel +0086 133 7058 2825, Email sunszg@126.comAbstract: Zinc finger protein 217 (ZNF217) is one of the well-researched members of the Krüppel-like factor transcription factor family. ZNF217 possesses a characteristic structure of zinc finger motifs and plays a crucial role in regulating the biological activities of cells. Recent findings have revealed that ZNF217 is strongly associated with multiple aspects of cancer progression, impacting patient prognosis. Notably, ZNF217 is subject to regulation by non-coding RNAs, suggesting the potential for targeted manipulation of such RNAs as a robust therapeutic avenue for managing cancer in the future. The main purpose of this article is to provide a detailed examination of the role of ZNF217 in human malignant tumors and the regulation of its expression, and to offer new perspectives for cancer treatment.Keywords: oncogene, regulation, non-coding RNA, targeted therapy

Miaomiao Sun,1,2 Fahad Alam,3 Cunxiao Ma4 1School of Ethnology and Historiography, Ningxia University, Yinchuan, People’s Republic of China; 2The Party School of the CPC, Ningxia Hui Autonomous Region Party Committee, Ningxia Administration Institute, Yinchuan, People’s Republic of China; 3School of Economics and Management, University of Science and Technology Beijing, Beijing, People’s Republic of China; 4School of Marxism, Shandong Yingcai University, Jinan, People’s Republic of ChinaCorrespondence: Fahad Alam, School of Economics and Management, University of Science and Technology Beijing, Beijing, Email fahadalam@xs.ustb.edu.cnBackground: High turnover rates among nurses are a global concern due to the shortage of skilled professionals and increasing demand for high-quality healthcare. This study aims to enhance understanding of organizational fit by examining the impact of Person-organization fit (P-O fit) on organizational loyalty through the mediating role of organizational support and service quality, and the moderating impact of role ambiguity.Methods: Using a convenience sampling technique, we employed a survey methodology by developing a questionnaire. Data were collected from a sample of 614 nurses in five different healthcare sectors in China. Employing SmartPLS 3.3, we conducted a Structural Equation Modeling (SEM) analysis to examine the relationships among the specified variables.Results: The findings of the structural analysis suggest that the P-O fit influences organizational loyalty in the healthcare sector. Organizational support and service quality were identified as partial mediators of the P-O fit-organizational loyalty link. Additionally, the role of ambiguity represented a negative moderating impact between service quality and organizational loyalty.Discussion: Overall, the study’s findings extend the understanding of person-organization fit, organizational support, service quality, role ambiguity, and organizational loyalty in the context of healthcare sectors and offer implications for medical authorities. Discussions, limitations, practical implications, and suggestions for further research are also provided.Keywords: person-organization fit, organizational support, service quality, role ambiguity, organizational loyalty

Qirong Li,1,2,&ast; Xinyi Zhang,2,&ast; Qiang Feng,2,&ast; Hengzong Zhou,2,&ast; Chaoyang Ma,3 Chao Lin,4 Dongxu Wang,2 Jianmei Yin1 1Department of Otolaryngology-Head and Neck Surgery, the First Hospital of Jilin University, Changchun, People’s Republic of China; 2Laboratory Animal Center, College of Animal Science, Jilin University, Changchun, People’s Republic of China; 3Hepatology Hospital of Jilin Province, Changchun, People’s Republic of China; 4School of Grain Science and Technology, Jilin Business and Technology College, Changchun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongxu Wang; Jianmei Yin, Email wang_dong_xu@jlu.edu.cn; yinjianmei1985@jlu.edu.cnAbstract: Allergic rhinitis (AR) is a chronic allergic disease of the upper respiratory system that affects approximately 10– 40% of the global population. Due to the large number of plant pollen allergens with obvious seasonal variations, AR is common in China. AR is primarily caused by the abnormal regulation of the immune system. Its pathophysiological mechanism involves a series of immune cells and immune mediators, including cytokines. The present review summarizes the common allergens in China and the complex pathophysiological mechanism of AR. Additionally, host allergen contact, signal transduction, immune cell activation, cytokine release, and a series of inflammatory reactions are described according to their sequence of occurrence.Keywords: allergic rhinitis, host immune response, immunoglobulin E, histamine, inflammation

Yuan Wang,1– 3 Chengfeng Ma,1,2 Zhanbing Ma,1,2 Mengyi Yang,1,2 Jing Pu,1,2 Xiuhui Ma,1,2 Xi Wu,1,2 Liang Peng,1,2 Zhenghao Huo,1,2,&ast; Jie Dang1,2,&ast; 1School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Key Laboratory of Fertility Preservation and Maintenance of the Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 3Department of Dermatology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Dang; Zhenghao Huo, Department of Medical Genetics and Cell Biology, School of Basic Medicine, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750001, People’s Republic of China, Tel/Fax +86-951-6980049, Email djjune1978@163.comPurpose: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause systemic damage to multiple organs. This study aims to analyze the value and function of IFI44 in the diagnosis and pathology of SLE by bioinformatics and immune infiltration analysis.Patients and Methods: GSE49454 and GSE65391 of SLE were obtained from the GEO dataset, and R software was employed to identify DEGs and investigate their functions. The PPI network was utilized to identify hub genes associated with SLE. CIBERSORT was used to assess differences in immune cell infiltration in SLE patients and controls. ROC curve analysis was performed to evaluate the diagnostic value of IFI44 in SLE. The expression of IFI44 in PBMCs was detected by RT-qPCR, and the correlation between IFI44 expression and SLE-related clinical indicators was analyzed.Results: A total of 65 DEGs were identified from the GSE49454 and GSE65391 databases. Through PPI analysis, IFI44 and RSAD2 were identified as significantly aberrantly expressed in SLE patients. SLE patients and controls showed a significant difference in the proportion of immune cell infiltration. IFI44 expression was positively correlated with activated DCs, monocytes, PCs, neutrophils, and activated memory CD4+T cells, while negatively correlated with M0 and CD8+T cells. The expression of IFI44 was significantly higher in SLE patients (P< 0.01), especially in male patients (P=0.0376). ROC curve analysis demonstrated that IFI44 had a high diagnostic value for SLE. Correlation analysis indicated that IFI44 expression was correlated with levels of RBC, HGB, HCT, IgA, ESR, UPRO, C3, C4, and ENA in SLE patients.Conclusion: IFI44 may play a role in the pathogenesis of SLE by influencing the immune microenvironment of SLE patients, and thus has the potential to serve as a diagnostic marker and therapeutic target for SLE.Keywords: systemic lupus erythematosus, IFI44, bioinformatics, immune cell infiltration, sexual dimorphism

Ting Lan,1,&ast; Yang Zhao,1,2,&ast; Yu Du,1,3,&ast; Chunyi Ma,1 Rui Wang,1 Qianlei Zhang,1 Shanshan Wang,1 Wenxian Wei,4 Honghua Yuan,2 Qingli Huang1,2 1Medical Technology School of Xuzhou Medical University, Xuzhou City, Jiangsu, 221000, People’s Republic of China; 2Public Experimental Research Center of Xuzhou Medical University, Xuzhou City, Jiangsu, 221004, People’s Republic of China; 3Xuzhou Center for Disease Control and Prevention, Xuzhou City, Jiangsu, 221006, People’s Republic of China; 4Testing Center, Yangzhou University, Yangzhou City, Jiangsu, 225009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Honghua Yuan, Public Experimental Research Center of Xuzhou Medical University, Tong Shan No. 209, Xuzhou, 221004, People’s Republic of China, Tel/Fax +86-516-83262091, Email XUYIyhh@xzhmu.edu.cn Qingli Huang, Medical Technology School, Public Experimental Research Center of Xuzhou Medical University, Tong Shan No. 209, Xuzhou, 221004, People’s Republic of China, Tel/Fax +86-516-83262091, Email qlhuang@xzhmu.edu.cnPurpose: A novel CYPA-targeted, SiO2 encapsulated Au star@AgAu yolk-shell nanostructure (YSNS) was synthesized and used for ovarian cancer early diagnosis and therapy.Methods: Diverse spectroscopic and microscopic methods were utilized to investigate the pattern of the yolk-shell nanostructure. In addition, in vitro and in vivo experiments were carried out.Results: It can be found that the ratio of HAuCl4 and AgNO3 played a critical role in the constitution of the yolk-shell nanostructure. The as-prepared yolk-shell nanostructure showed excellent SERS performance, which could be utilized as SERS substrate for specific sensitivity analysis of ovarian cancer markers cyclophilin A (CYPA) with detectable limit of 7.76&ast;10− 10 μg/mL. In addition, the as-prepared yolk-shell nanostructure possessed outstanding photothermal performance, which could be used as photothermal agent for ovarian cancer therapy. Experiments in vitro and in vivo proved that the as-prepared yolk-shell nanostructures are ideal candidate for early diagnosis and therapy for ovarian cancer in one platform.Conclusion: This work holds promise to offer a new method for the detection and therapy of ovarian cancer in the early stage.Graphical Abstract: Keywords: yolk-shell nanostructure, surface-enhanced Raman scattering, early diagnosis, cancer targeted therapy

Jiao Ma,1,&ast; Zhuoxiao Han,1,&ast; Rui Jiao,1 Guanli Yuan,1 Cuiqing Ma,2 Xixin Yan,1 Aihong Meng1 1Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, 050000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aihong Meng, Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email mengaihong_med@126.comBackground: PM2.5 exposure is one of the major inducements of various respiratory diseases and related mortality. Meanwhile, irisin, a metabolism and thermogenesis-related hormone, is found to be protective against acute lung injury induced by LPS, which indicates its therapeutic function in lung injury. However, the function and underlying mechanism of irisin in PM2.5-induced acute lung injury (ALI) are still unclear. This study is aimed to discover the potential mechanisms of irisin in PM2.5-induced acute lung injury.Methods: Atg5 deficient mice and cells were established to clarify the relationship between irisin and autophagy in PM2.5-induced ALI. We also used Ad-mCherry-GFP-LC3B as a monitor of autophagy flux to claim the effects of irisin on autophagy. Western blotting and qPCR were used to reveal the molecular mechanism.Results: As a result, PM2.5 exposure induced lung injury whereas mitigated by irisin. Moreover, PM2.5 hampered autophagy flux, characterized by accumulation of p62, and autophagosomes, as well as blocked autolysosomes. Irisin improved the disturbed autophagy flux, which was abrogated by deficiency of Atg5. Additionally, we demonstrated that irisin activated AMPK and inhibited mTOR, which indicated the enhanced autophagy. Moreover, blockage of AMPK by compound C terminated irisin’s induction of autophagy in cultured MH-S cells.Conclusion: Our findings reveal that irisin performs protective effects against PM2.5-induced ALI by activating autophagy through AMPK/mTOR signaling pathway.Keywords: irisin, PM2.5, acute lung injury, autophagy

Ge Ban,1 Yingze Hou,2 Zhean Shen,3 Jingjing Jia,1 Lei Chai,1 Chongyang Ma1 1School of Intelligent Medical Engineering, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China; 2Clinical Medical College, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China; 3Department of Biomedical Research, Research and Innovation Center, Xinjiang Institute of Technology, Xinjiang, 843100, People’s Republic of ChinaCorrespondence: Ge Ban, Email bange119@qq.comAbstract: Graphene-family nanomaterials (GFNs) possess mechanical stiffness, optical properties, and biocompatibility making them promising materials for biomedical applications. However, to realize the potential of graphene in biomedicine, it must overcome several challenges that arise when it enters the body’s circulatory system. Current research focuses on the development of tumor-targeting devices using graphene, but GFNs accumulated in different tissues and cells through different pathways, which can cause toxic reactions leading to cell apoptosis and body dysfunction when the accumulated amount exceeds a certain limit. In addition, as a foreign substance, graphene can induce complex inflammatory reactions with immune cells and inflammatory factors, potentially enhancing or impairing the body’s immune function. This review discusses the biomedical applications of graphene, the effects of graphene materials on human immune function, and the biotoxicity of graphene materials.Keywords: graphene family nanomaterials, biomedical, biocompatibility, biomedical limitation, immune system

Chao Ma,1,&ast; Haoyu Li,2,3,&ast; Shuwen Lu,4 Xian Li,5,6 Shuai Wang,1 Wenzhan Wang1 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Ophthalmology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Clinical Research Centre of Ophthalmic Disease, Changsha, Hunan, People’s Republic of China; 4Department of Ophthalmology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 5Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK; 6Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, the University of Manchester, Manchester, UK&ast;These authors contributed equally to this workCorrespondence: Wenzhan Wang, Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +0371-66278091, Email 18003857188@189.cnAbstract: Ocular injuries caused by inflammation, surgery or accidents are subject to a physiological healing process that ultimately restores the structure and function of the damaged tissue. Tryptase and trypsin are essential component of this process and they play a role in promoting and reducing the inflammatory response of tissues, respectively. Following injury, tryptase is endogenously produced by mast cells and can exacerbate the inflammatory response both by stimulating neutrophil secretion, and through its agonist action on proteinase-activated receptor 2 (PAR2). In contrast, exogenously introduced trypsin promotes wound healing by attenuating inflammatory responses, reducing oedema and protecting against infection. Thus, trypsin may help resolve ocular inflammatory symptoms and promote faster recovery from acute tissue injury associated with ophthalmic diseases. This article describes the roles of tryptase and exogenous trypsin in affected tissues after onset of ocular injury, and the clinical applications of trypsin injection.Keywords: trypsin, tryptase, inflammation, proteinase-activated receptor 2, ophthalmology, therapeutic

Xijier Qiaolongbatu,1,&ast; Wenjuan Zhao,1,&ast; Xucong Huang,2,3,&ast; Feng Qian,1 Xinyi Yang,1 Jiaqi Wu,2 Cui Ma,2 Han Qu,1,2 Li Wang,3 Guorong Fan,2 Zhenghua Wu2 1Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3School of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenghua Wu; Guorong Fan, Department of Clinical Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, No. 85 Wujin Road, Shanghai, 200080, People’s Republic of China, Tel +86-133-0177-7863 ; +86-21-36123711, Email zhenghua.wu@shgh.cn; fanguorong@sjtu.edu.cnBackground: Schisandrol A (Sch A) is the main active ingredient of Schisandra chinensis (Turcz.) Baill. Our previous study showed that Sch A has anti-pulmonary fibrosis (PF) activity, but its metabolic-related mechanisms of action are not clear.Methods: Here, we explored the therapeutic mechanisms of Sch A on PF by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) metabolomics approach and network analysis. The metabolites of Sch A in mice (bleomycin + Sch A high-dose group) plasma were identified based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS).Results: 32 metabolites were detected reversed to normal level after treating bleomycin (BLM)-induced PF mice with Sch A. The 32 biomarkers were enriched in energy metabolism and several amino acid metabolisms, which was the first report on the therapeutic effects of Sch A on PF through rescuing the disordered energy metabolism. The UPLC-Q-TOF/MS analysis identified 17 possible metabolites (including isomers) of Sch A in mice plasma. Network analysis revealed that Sch A and 17 metabolites were related to 269 genes, and 1109 disease genes were related to PF. The construction of the Sch A/metabolites-target-PF network identified a total of 79 intersection genes and the TGF-β signaling pathway was determined to be the main signaling pathway related to the treatment of PF by Sch A. The integrated approach involving metabolomics and network analysis revealed that the TGF-β 1-ID3-creatine pathway, TGF-β 1-VIM-carnosine pathway were two of the possible pathways Sch A regulated to modulate metabolic disorders, especially energy metabolism, and the metabolite of Sch A M5 was identified as a most likely active metabolite.Conclusion: The results suggested the feasibility of combining metabolomics and network analysis to reflect the effects of Sch A on the biological network and the metabolic state of PF and to evaluate the drug efficacy of Sch A and its related mechanisms.Graphical Abstract: Keywords: schisandrol A, pulmonary fibrosis, mechanism of action, network analysis, metabonomics

Cheng Ma,1– 4,&ast; Yin Cao,1,&ast; Guang Zhang,1– 3,&ast; Jiannan Qiu,2 Yan Zhou,1 Peng Wang,2 Shuo Wang,2 Dongliang Yan,1 Ding Ma,2 Chunping Jiang,1– 3 Zhongxia Wang1– 3 1Department of Hepatobiliary Surgery, Drum Tower Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 3Department of Tissue Engineering, Jinan Microecological Biomedicine Shandong Laboratory, Jinan, People’s Republic of China; 4Department of Gastrointestinal Surgery, Xuzhou Central Hospital, Xuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongxia Wang; Chunping Jiang, Email freud_t@126.com; chunpingjiang@163.comBackground: The prediction of prognosis of hepatocellular carcinoma (HCC) is of great significance in improving disease outcome and optimizing clinical management, while reliable prognostic indicators are lacking. This study was conducted to develop readily-to-use nomograms for prognosis prediction of HCC after hepatectomy.Materials and Methods: Data of eligible patients were collected and analyzed retrospectively. Independent prognostic factors were identified by Cox regression, and nomograms for the prediction of disease-free survival (DFS) and overall survival (OS) were developed. The performance of the nomograms was evaluated by receiver operating characteristics (ROC) curves, C-indexes and calibration curves and was verified by the validation cohort. The predictive value of the nomograms was also compared with the 8th edition of American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) and the Barcelona Clinic Liver Cancer (BCLC) staging systems.Results: In total, 599 patients were enrolled in the analysis: 420 in the training cohort and 179 in the validation cohort. The optimal cut-off value of Gamma-Glutamyl Transpeptidase-to-Lymphocyte Ratio (GLR) was 19.5. GLR contributed significantly to the nomograms with good predictive power. In ROC analyses, the areas under curve (AUCs) of the nomograms for 1-, 3- and 5-year DFS and OS prediction were 0.758, 0.756, 0.734 and 0.810, 0.799, 0.758, respectively. The C-indexes of the DFS nomogram were 0.697 (95% CI 0.665– 0.729) in the training cohort and 0.710 (95% CI 0.664– 0.756) in the validation cohort. For OS prediction, the C-indexes were 0.741 (95% CI 0.704– 0.778) and 0.758 (95% CI 0.705– 0.811) in the training and validation cohorts, respectively. The calibration curves demonstrated satisfactory agreement between nomogram predictions and actual observations. The nomograms demonstrated superior predictive performance to the TNM and the BCLC staging systems.Conclusion: Our novel nomograms showed adequate performance in the prediction of HCC prognosis after hepatectomy, which may facilitate the risk stratification and individualized management of HCC patients.Keywords: hepatocellular carcinoma, nomogram, gamma-glutamyl transferase, lymphocyte, hepatectomy

Chao Ma,1,&ast; Haoyu Li,2,3,&ast; Shuwen Lu,4 Xian Li,5,6 Shuai Wang,1 Wenzhan Wang1 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Ophthalmology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Clinical Research Centre of Ophthalmic Disease, Changsha, Hunan, People’s Republic of China; 4Department of Ophthalmology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 5Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, England; 6School of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, the University of Manchester, Manchester, England&ast;These authors contributed equally to this workCorrespondence: Wenzhan Wang, Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 371-66278091, Email 18003857188@189.cnAbstract: Ocular lesions due to Brucella infection are uncommon and easily overlooked in clinical management, but must be differentiated from non-infectious eye diseases and treated promptly to protect the patient’s vision. We reviewed the relevant literature and identified 47 patients with ocular complications of Brucella infection. Among them, 28 showed ocular neuropathy, 15 presented with uveitis, and four patients displayed other ocular symptoms. Ocular symptoms accompanying Brucella infection require prompt diagnosis and treatment. The main methods of diagnosis are intraocular fluid tests and blood tests. Early diagnosis and treatment with suitable antibiotics are central to protecting the patient’s vision. Notably, in terms of mechanism of injury, Brucella infection is chronic and cannot be eliminated by phagocytes, and can cause damage to the eye by inducing autoimmune reactions, antigen-antibody complex production, release of endogenous and exogenous toxins, and bacterial production of septic thrombi in the tissues. In this review, we summarize the ocular symptoms, diagnosis, treatment and prognosis of Brucella infection, and discuss the mechanisms of Brucella in ocular lesions, providing a reference for the diagnosis and treatment of Brucella ocular lesions.Keywords: Brucella, infection mechanism, ocular, ocular neuropathy, uveitis

Alexandre Uwimana,&ast; Cong Ma,&ast; Xiang Ma Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Ma, Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Xigang District, Dalian, 116044, People’s Republic of China, Tel +8618098876399, Fax +8641183622844, Email xma9467@vip.sina.comPurpose: Students spend extended hours using electronic devices due to online teaching. Digital eye strain (DES) and dry eye disease (DED) symptoms are both associated with prolonged screen exposure time and may co-occur. This study aimed to evaluate the correlation between DES and DED symptoms and determine the prevalence of DED according to the severity of DES.Patients and Methods: This cross-sectional study was conducted among international students in Chinese universities. The survey was built using Wenjuan Mini Program and distributed using the WeChat platform. The questionnaire assessed participants’ screen exposure, the 20-20-20 rule, ED practices, and DED awareness. Computer Vision Syndrome Questionnaire (CVS-Q) and Dry Eye Questionnaire (DEQ-5) were used to diagnose DES and DED symptoms, respectively.Results: 498 students completed the survey, but 452 were considered for the study. Predictors of DES and DED symptoms were conjunctivitis, eye allergy, glares, tired eye, neck pain, back pain, PhD students, and daily spending > 9h on screen (P < 0.05 for all). We observed that an increase in DES scores also exponentially increases DED scores. Among students diagnosed with DES symptoms, 26.5% had mild to moderate DED symptoms, and 8.2% had severe DED symptoms. In contrast, only 8.4% and 0.9% of those with asymptomatic DES had mild to moderate and severe DED symptoms, respectively (P < 0.000). A strong and significant positive correlation (r = 0.695, P < 0.000) between DES and DED scores was found.Conclusion: We found an extremely high prevalence of DES and DED symptoms compared to the previous studies with a similar population group. We believe that the prevalence of DED may be underestimated in the young population. Training about proper ED practices is mandatory to prevent these deleterious ocular surface conditions.Keywords: COVID-19 pandemic, digital eye strain, dry eye disease, electronic device, online study, university students

Xiaoguang Wu,1,&ast; Siyu Di,1,&ast; Chao Ma1,2 1Normal College, Shihezi University, Shihezi, People’s Republic of China; 2Center of Application of Psychological Research, Shihezi University, Shihezi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Ma, Normal College, Shihezi University, Shihezi, 832000, People’s Republic of China, Tel +86 13935269606, Fax +86 0993-2057553, Email machao131517@126.comPurpose: The current research of the effect of acute stress on individual behavioral inhibition remains divergent. The present study aims to explore the effects of acute stress on behavioral inhibition in college students and to understand the neural oscillatory characteristics of their behavioral inhibition process.Patients and Methods: We invited 27 college students (12 males and 15 females) to participate in the study. The experiment was conducted using the Trier Social Stress paradigm to evoke an acute stress state and an out-of-speech reading to set a neutral state. Participants completed a two-choice Oddball task in the acute stress state and the neutral state, respectively. We used a 64-channel EEG cap to record EEG data from university students during the experimental task. In combination with the ERO technique, we compared the reaction time, the number of errors, and the power of the alpha (8– 13 Hz) and theta (4– 8 Hz) frequency bands at the midline of the frontal lobe for subjects in both states. The correlation between the area under the stress area line and the alpha as well as theta frequency bands was also analyzed.Results: We found that in the two-choice Oddball task, the response inhibition time was shorter, the number of response errors decreased, and the alpha-band power values decreased in the acute stress state compared to the neutral state. For the standard stimulus, the theta-band power increase in the acute stress state.Conclusion: Our results suggest that evoked acute stress promotes behavioral inhibition in college students by affecting their frontal midline neural oscillations.Keywords: stop single task, two-choice oddball, time-frequency analysis, inhibitory control

Hanrui Liu,1 Chengyong Ma,2 Huayan Xu,1 Huan Zhang,3 Rong Xu,1 Kun Zhang,1 Ran Sun,1 Kuan Li,1 Qihong Wu,1 Lingyi Wen,1 Lizhi Zhang,2 Yingkun Guo1 1West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3College of Chemistry and Materials Science, Northwest University, Xi’an, People’s Republic of ChinaCorrespondence: Yingkun Guo, Development and Related Diseases of Women and Children Key Laboratory, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86+18180609256, Email gykpanda@163.com Lizhi Zhang, Department of Radiology, West China Hospital of Sichuan University, No. 37, Guoxue Road, Chengdu, Sichuan, 610041, People’s Republic of China, Email littche_2000@163.comIntroduction: Free radicals in oxidative stress are known to play a pathogenic role in sepsis. A major clinical challenge associated with sepsis is sepsis-associated encephalopathy (SAE). The rapid increase of free radicals in the brain promotes SAE progression. Here, macromolecule free radicals in the mouse brain were uniquely detected by immunospin trapping (IST) and magnetic resonance imaging (MRI).Methods: The new strategy uses spin trapping agent DEPMPO-biotin to capture macromolecule free radicals in lesions and form biotin-DEPMPO-radical adducts. Then, a targeting MRI probe, avidin-BSA@Gd-ESIO, was used to detect the radical adducts through the highly specific binding of avidin and biotin. The avidin-BSA@Gd-ESIO probe was synthesized and systematically characterized. The detection capability of the new strategy was evaluated in vitro and in vivo using a confocal microscope and a 7T MRI, respectively.Results: In reactive oxygen species (ROS)–induced microglial cells, the accumulation of the avidin-BSA@Gd-ESIO probe in the DEPMPO-biotin-treated group was significantly higher than that of control groups. In vivo MRI T1 signal intensities were significantly higher within the hippocampus, striatum, and medial cortex of the brain in mice with a mild or severe degree of sepsis compared with the sham control group. Histological analysis validated that the distribution of the avidin-BSA@Gd-ESIO probe in brain tissue slices was consistent with the MRI images. The fluorescence signals of ROS and avidin-BSA@Gd-ESIO probe were overlapped and visualized using immunofluorescent staining. By evaluating the T1 signal changes over time in different areas of the brain, we estimated the optimal MRI detection time to be 30 minutes after the probe administration.Discussion: This method can be applied specifically to assess the level of macromolecular free radicals in vivo in a simple and stable manner, providing a pathway for a more comprehensive understanding of the role of free radicals in SAE.Graphical-Abstract: Keywords: macromolecule radical, ESIO, spin trapping, sepsis-associated encephalopathy

Jun Fang Chen,1 Xue Mei Zhang,1,2 Kiran Sanjel,1,2 Juan Zhang,2 Cong Ma1 1The Dermatology and Venereology Department, The Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, People’s Republic of China; 2Clinical Medical School, Inner Mongolia Minzu University, Tongliao, People’s Republic of ChinaCorrespondence: Xue Mei Zhang, The Dermatology and Venereology Department, The Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, 028000, People’s Republic of China, Tel +8618504757225, Email tongliaozhangxuemei@126.comPurpose: The purpose of this study was to explore the expression of TNF-α and NF-κB/p65 in Lichen planus skin lesions and their correlation with the pathogenesis of Lichen planus.Patients and Methods: The case group consisted of 30 individuals diagnosed with LP based on clinical and histopathologic examination. The control group consisted of 10 individuals from an Orthopedic Department with normal skin. TNF-α and NF-κB/p65 expression in skin tissue samples was detected by immunohistochemistry.Results: The immunohistochemical results showed that TNF-α and NF-κB/p65 expression levels were significantly higher in LP skin lesions than normal skin tissues (P ≤ 0.05). Positive TNF-α staining mainly occurred in the cytoplasm of keratinocytes of the stratum granulosum, stratum spinosum, and stratum basale in the epidermis and lymphocytes in the superficial dermis. Positive NF-κB/p65 staining mainly occurred in the nucleus and cytoplasm of keratinocytes of the stratum spinosum and stratum basale in the epidermis and lymphocytes in the superficial dermis.Conclusion: TNF-α and NF-κB/p65 are overexpressed in cutaneous LP. The two are positively correlated in LP, suggesting that they both play essential roles in the pathogenesis of LP.Keywords: lichen planus, TNF-α, NF-κB/p65, staining, immunohistochemistry

Zike Sheng,1,&ast; Junjie Li,2,&ast; Tingting Chen,3 Yan Zhu,4 Xueping Yu,5 Xiuhua He,5 Yijuan Zheng,5 Cuiping Ma,6 Minghui Zheng,5 Peiyun Wang,1 Ziqiang Li,1 Yumin Xu,7 Qing Xie,1 Zhijun Su,5 Sumei Chen5 1Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Pharmacy, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 4Clinical Laboratory, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 5Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 6Department of Infection Control, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 7Department of Infection Control, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijun Su; Sumei Chen, Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Licheng District, Quanzhou, People’s Republic of China, Tel +86-595-22277011 ; +86-595-22277173, Fax +86-595-222781, Email su2366@sina.com; chensm561119190@sina.comPurpose: Hypervirulent Klebsiella pneumoniae (hvKP) is emerging globally and can cause various infections. This study aimed to investigate the clinical and microbiological characteristics of bloodstream infection (BSI) caused by hvKP.Patients and Methods: The clinical data of hospitalized patients with K. pneumoniae BSI were retrospectively analyzed. The K. pneumoniae strains were collected and re-identified, and antimicrobial susceptibility testing was performed using the broth microdilution method. Capsular serotypes and virulence genes were detected using polymerase chain reaction, and hvKP was defined as aerobactin positive. Molecular typing was done by multilocus sequence typing. The hvKP and classic K. pneumoniae (cKP) subgroups were compared.Results: Of the 66 nonrepetitive BSI K. pneumoniae strains included, 29 (43.9%) were hvKP. In these BSI hvKP strains, salmochelin and yersiniabactin accounted for 86.2% and 72.4%, respectively. The prevalence of rmpA, iroBCD cluster, ybtS, clbA, and allS was 89.7%, 86.2%, 72.4%, 51.7%, and 41.4%, respectively, which were all significantly different between the hvKP and cKP subgroups. Serotypes K1 and K2 were strongly associated with hypervirulence (P < 0.05). Nineteen sequence types were scattered in the 29 hvKP strains, and the most common was ST23 (24.1%). None of the hvKP strains were carbapenem resistant. Compared with cKP, hvKP was more capable of developing a liver abscess. However, the 30-day mortality rate was lower (13.8% vs 21.6%) in the hvKP subgroup than in the cKP subgroup.Conclusion: This study demonstrated a high proportion of hvKP in BSI K. pneumoniae, most of which were RmpA and siderophore producing, and of multiclonal origin.Keywords: capsular serotypes, hypervirulence, infection, mortality, sequence type

Xin Wang,1,2,&ast; Jie Zhao,1,2,&ast; Rui Zhang,1,&ast; Xinlu Liu,1 Chuanjiang Ma,2 Guangshang Cao,1,2 Yongli Wei,2 Peimin Yang2 1School of Pharmacy, Shandong University of Traditional Chinese Medicine (TCM), Jinan, 250355, People’s Republic of China; 2Grade Three Laboratory of TCM Preparation of National Administration of TCM, Affiliated Hospital of Shandong University of TCM, Jinan, 250014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peimin Yang, Tel +86-0531-68616607, Email jnypm@hotmail.comObjective: This study aims to investigate the hepatoprotective effect and molecular mechanism of Hedyotis diffusa Willd. ethanol extract (HDWE) against isoniazid (INH)-induced liver injury in the zebrafish model.Methods: INH-induced liver injury model was established by adding an immersion bath of INH in 3 days post-fertilisation (dpf) healthy transgenic zebrafish with liver-specific fluorescence (L-FABP: EGFP). HDWE and INH were given to the zebrafish to observe liver morphology and pathology, fluorescence intensity, and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and superoxide dismutase (SOD), as well as the content of glutathione (GSH). The chemical composition of HDWE was analysed using high-performance liquid chromatography coupled with a quadrupole-time-of flight hybrid mass spectrometer (HPLC-Q-TOF-MS). The bioactive compounds, molecular targets and signalling pathways of HDWE were predicted using network pharmacology. Subsequently, molecular docking was adopted to analyze the affinities between the bioactive components and targets by Autodock. Finally, in vitro experiments were conducted to further verify the findings.Results: Our findings showed that HDWE had a remarkable protective effect on INH-induced liver injury in zebrafish. Twenty compounds in HDWE were identified. Nineteen hub targets were identified as possible targets of HDWE, and a compound-target-pathway network was constructed. Nine bioactive compounds, ten molecular targets, and seven key signalling pathways were found to play a pivotal role in the hepatoprotective effect of HDWE against INH-induced liver injury. In vitro studies revealed that the important bioactive compound quercetin-3-O-sambubioside (QSA) could significantly reverse INH-induced cell viability decreases and had a significant effect on the associated targets predicted by network pharmacology and molecular docking.Conclusion: In this study, through the research of hepatoprotective effect of HDWE and bioinformatics analysis, the bioactive compounds, important pathways and key molecular targets were discovered. These findings could provide scientific evidence for the use of HDW in liver injury and prove to help explore its efficacy and the mechanism of action.Keywords: Hedyotis diffusa Willd., hepatoprotective activity, isoniazid-induced liver injury, zebrafish, network pharmacology, molecular docking

Cheng Ma,1,&ast; He Li,1,&ast; Teng Zhang,1 Yifan Wei,1 Helong Zhang,1 Fenglei Yu,1 You Lv,2 Yongxin Ren1 1Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China; 2Department of Orthopaedics, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang, Lianyungang, 222061, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongxin Ren, Tel +86 13585162283, Email renyongxinjsph@163.comPurpose: Both percutaneous endoscopic lumbar discectomy (PELD) and open fenestration discectomy (OFD) are effective and safe surgical procedures for the treatment of LDH. The purpose of this retrospective study was to compare the surgical outcomes of percutaneous endoscopic interlaminar discectomy (PEID) and OFD for single-segment huge lumbar disc herniation (HLDH).Patients and Methods: We retrospectively analyzed 91 patients diagnosed with single-segment HLDH and treated with OFD or PEID. Visual analog scale (VAS), modified Japanese orthopedic association (mJOA) and Oswestry disability index (ODI) were used to assess clinical outcomes at preoperation and postoperatively at 3, 6, 12, and 24months. Modified Macnab criteria were applied to evaluate clinically satisfaction at the final follow-up.Results: In both groups, the VAS and ODI scores at 3, 6, 12, and 24months postoperatively showed a significant decrease and the mJOA score at 3, 6, 12, and 24months postoperatively was significantly increased compared to preoperative results (P< 0.001). According to Macnab criteria at the final follow-up, the overall clinically satisfactory rate was 86.67% in the OFD group and 86.96% in the PEID group. There were no significant differences in VAS, ODI, and mJOA scores between the two groups at preoperation and postoperative 3, 6, 12, and 24months, respectively. In the PEID group, the length of hospitalization and the length of incision were significantly shorter than that in the OFD group (P< 0.0001). However, there was no significant difference in operative time between groups (P=0.81).Conclusion: Collectively, postoperative clinical results were equally favorable for both procedures, with no statistically significant difference between PEID and OFD at the two-year of follow-up. No serious complication was observed in two groups. Compared with the traditional surgery, PEID has the following benefits: less trauma, less bleeding, speedy recovery, and shorter hospitalization. Therefore, PEID may be a promising alternative to traditional surgery.Keywords: percutaneous endoscopic lumbar discectomy, percutaneous endoscopic interlaminar discectomy, open fenestration discectomy, single-segment, huge lumbar disc herniation

Jianhao Xie,1,2,&ast; XueYu Yuan,1,&ast; Weiqing Mao,1,&ast; Haidong Cai,1 Kejia Gao,3 Zhongwei Lv,1 Hui Wang,4 Chao Ma1 1Department of Nuclear Medicine, Tenth People’s Hospital of Tongji University, Shanghai, People’s Republic of China; 2Department of Orthopaedic, Beijing Jishuitan Hospital, Beijing, People’s Republic of China; 3Department of Nuclear Medicine, Shanghai No. 4 People’s Hospital, Shanghai, People’s Republic of China; 4Department of Nuclear Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongwei Lv; Chao Ma, Tel/Fax +86-21-66302075, Email shtjnmd@163.com; mc_7419@hotmail.comObjective: To investigate the effects of 99Tc-methylene diphosphonate (99Tc-MDP) on osteoporosis (OS) in postmenopausal patients with differentiated thyroid cancer (DTC) under thyroid stimulating hormone (TSH) suppression.Patients and Methods: Patients (n = 142) were divided into two groups: (1) 99Tc-MDP (n = 70) and (2) alendronate (n = 72) treatments (NCT 02304757). Bone mineral density (BMD) in the lumbar spine and hip was evaluated by DXA, along with bone turnover markers, safety, and quality of life (QOL) using SF-36 at three time points: before treatment and at 6 and/or 12 months after treatment.Results: The percentage change of BMD in total lumbar spine or hip showed no significant difference throughout the study (P > 0.025). 99Tc-MDP and alendronate treatment alone significantly increased BMD in the lumbar spine, but alendronate treatment also significantly increased BMD in total hip at 6 and 12 months, as compared with the baseline. There were no significant differences in the results of the SF-36 scores between the two treatment groups at any time during the whole study period. 99Tc-MDP significantly increased bone formation markers of osteocalcin at 6 and 12 months (P all < 0.05), PINP at 12 months (P = 0.001), and bone resorption markers of β-CTX at 6 and 12 months (p < 0.05) as compared with the alendronate treated group. No adverse event was observed in the 99Tc-MDP treatment group compared with alendronate (P = 0.014).Conclusion: 99Tc-MDP was as efficacious as alendronate in the improvement of lumbar BMD for DTC patients with OS under TSH stimulation. 99Tc-MDP was shown to be safe and improved patients’ QOL.Keywords: osteoporosis, 99Tc-MDP, thyroid stimulating hormone suppression, differentiated thyroid cancer

Peng Wang, Haotian Liu, Xiao Wang, Xiqing Yuan, Yu Sun, Li Xiao, Wenxuan Li, Chong Ma Faculty of Education, Department of Psychology, Shandong Normal University, Jinan, People’s Republic of ChinaCorrespondence: Li Xiao, Faculty of Education, Shandong Normal University, Jinan, People’s Republic of China, Tel +86-17806815755, Email li_sdnu@163.comBackground: Information technology has become an irreplaceable part of people’s lives, and the interaction between information technology and self-identity has produced a new type of information technology (IT) identity. However, there is no measurement tool for this concept in China. The main aim of the study was to revise Carter’s IT Identity Scale in the context of Chinese cultural background and to determine whether the Chinese version is congruent with the English version.Methods: In this study, we revised the scale on the basis of the information technology identity scale developed by Carter, translated the scale according to the Chinese cultural environment. Our sample size was 408, and all of them were junior middle school students. After testing this sample, we carried out item analysis, validity analysis, and reliability analysis.Results: (1) The correlation coefficients between each item and the total score were significant (0.775– 0.885). (2) The three-factor structure (relatedness, dependence, emotional energy) of the Chinese version of the IT identity scale was consistent with the original scale. The values of the factor loadings of each item in the three factors of confirmatory factor analysis (CFA) were all greater than 0.700, and the model fit indexes (CFI, NFI, NNFI, TLI and IFI) were all greater than 0.900, indicating a good model fit. (3) Average variance extraction (AVE), composite reliability (CR), Pearson correlation, and the square root of AVE indicated good convergence and discriminant validity. (4) The ɑ coefficients and CR of the three dimensions (ie, relatedness, dependence, emotional energy) were all greater than 0.800, and the split coefficients were all greater than 0.800, indicating high reliability.Conclusion: The Chinese version of the information technology identity scale presented satisfactory psychometric properties and shared many similarities with the original version. Ultimately, we revised an information technology identity scale suitable for Chinese culture.Keywords: information technology identity, self-identity, information technology, scale revision

Ma C, Ma N, Qin L, Miao C, Luo M, Liu S. Cancer Manag Res. 2020;12:10035–10046. We, the Editors and Publisher of Cancer Management and Research, have retracted the published article. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors did not respond to our queries, nor did they provide original data for their study. As verifying the validity of the published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Shuo Luan,&ast; Shaoling Wang,&ast; Caina Lin, Shengnuo Fan, Cuicui Liu, Chao Ma, Shaoling Wu Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, SunYat-sen University, Guangzhou, 510120, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoling Wu; Chao Ma, Email wushl@mail.sysu.edu.cn; machao@mail.sysu.edu.cnBackground and Objective: Osteonecrosis of the femoral head (ONFH) is a devastating disease, and there is some evidence that extracorporeal shock wave therapy (ESWT) and intra-articular platelet-rich plasma (PRP) injection might alleviate pain and improve joint function in individuals with ONFH. The objective of this study was to compare the effectiveness and safety of PRP and ESWT in symptomatic ONFH patients.Methods: A total of 60 patients aged 40– 79 with unilateral ONFH at Association Research Circulation Osseous (ARCO) stages I, II, and III were randomly assigned to the PRP (N=30) or the ESWT group (N=30). Four treatment sessions were provided in both groups. Assessments were performed at baseline, and 1-, 3-, 6-, and 12-month. Primary outcomes were measured by the visual analogue scale (VAS), and pressure pain thresholds (PPTs). Secondary outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and magnetic resonance imaging (MRI). The linear mixed-model analysis was used to evaluate the differences between groups and within groups and the “group by time” interaction effects.Results: There were significant differences between groups in terms of changes over time for VAS, PPTs, WOMAC, and HHS since 3-month and maintained up to 12-month (P< 0.05, except for PPTs at 12-month). The simple main effects showed that the patients in PRP group had greater improvements in VAS (mean difference = − 0.82, 95% CI [− 1.39, − 0.25], P=0.005), WOMAC (mean difference = − 4.19, 95% CI [− 7.00, − 1.37], P=0.004), and HHS (mean difference = 5.28, 95% CI [1.94, 8.62], P=0.002). No related adverse events were reported.Conclusion: This study supported the effectiveness and safety of both the PRP injection and ESWT in treating ONFH patients. For symptomatic patients with ONFH, intra-articular PRP injection appeared superior to ESWT in pain relief and functional improvement.Keywords: necrosis of the femoral head, platelet-rich plasma, ultrasound-guided intra-articular injection, extracorporeal shock wave therapy

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

Yongli Zhang,1,2 Mengyao Xie,1,2 Ruoyan Xue,1,2 Qi Tang,1,2 Xiaohui Zhu,1,2 Jian Wang,1,2 Hua Yang,1,2 Chao Ma3– 5 1Department of Otolaryngology, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 2Translational Medicine Center, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 3Institute of Basic Medical Sciences, Department of Human Anatomy, Histology and Embryology, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, People’s Republic of China; 4Joint Laboratory of Anesthesia and Pain, Peking Union Medical College, Beijing, 100730, People’s Republic of China; 5Chinese Institute for Brain Research, Beijing, 102206, People’s Republic of ChinaCorrespondence: Jian Wang; Hua YangDepartment of Otolaryngology, Peking Union Medical College Hospital, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel +86 13673164261; +86 13701127757Fax +86-10-69156311Email wangjianent@163.com; dr_yanghua2021@163.comPurpose: Rapid and accurate diagnosis of the pathological characteristics of head and neck cancer and tumor resection margins is important. The DiveScope cell morphology analyzer (DiveScope) is a new endomicroscope that can rapidly image living tissues and cells. In this study, we preliminarily examined the accuracy of the DiveScope for determining the malignancy of head and neck cancers and the positivity/negativity of tumor resection margins and determined the consistency between diagnostic results with the DiveScope and those of frozen section pathology to provide a foundation for further clinical trials in pathological diagnosis of head and neck cancers and tumor resection margins.Methods: Head and neck cancer samples and resection margin samples were rapidly stained ex vivo before observation under the DiveScope cell morphology analyzer. Experienced pathologists distinguished the benignity and malignancy of the tumors based on images obtained by the DiveScope in a double-blind manner to validate the diagnostic performance of the analyzer.Results: We found that the cell morphology, cell nucleus morphology, karyoplasmic ratio, and even the nucleolus could be clearly distinguished. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of benign and malignant head and neck cancer according to DiveScope results were 10.55 and 0.04, respectively. The PLR and NLR of the head and neck cancer resection margins according to the DiveScope were 19.01 and 0, respectively.Conclusion: The DiveScope showed high accuracy in determining the benignity and malignancy of head and neck cancer and the positivity/negativity of resection margins, and its results were highly consistent with those of intraoperative frozen section pathology tests.Keywords: the DiveScope cell morphology analyzer, head and neck cancer, resection margins, pathological diagnosis

Han She,1,2,&ast; Yi Hu,1,&ast; Yuanqun Zhou,2 Lei Tan,1 Yu Zhu,2 Chunhua Ma,2 Yue Wu,2 Wei Chen,1 Li Wang,2 Zisen Zhang,2 Li Wang,1 Liangming Liu,2 Tao Li2 1Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangming Liu; Tao Li Email liangmingliu@yahoo.com; Lt200132@163.comIntroduction: Vascular leakage plays a vital role in sepsis-induced multi-organ dysfunction. Currently, no specific measures are available for vascular leakage. Ferroptosis, as a recently recognized form of cell death, plays a crucial role in cell dysfunction. It is still unknown whether ferroptosis participates in the occurrence of organ dysfunction following sepsis. Our previous study showed that dexmedetomidine (Dex) could alleviate sepsis-induced organ dysfunction. However, whether the mechanism is related to ferroptosis is not clear.Methods: The publicly available datasets of septic patients were reanalyzed, and septic models in vivo and vitro by cecal ligation and puncture and lipopolysaccharide-stimulated vascular endothelial cells (VECs) were applied. The occurrence of ferroptosis in septic patients and rats was observed, and the protective effects of Dex on ferroptosis, and related mechanisms on regulating metabolic reprogramming and mitochondrial fission were further studied.Results: The transcriptomics data of patients from the GEO database showed that ferroptosis was closely related to sepsis. Sepsis induced significant ferroptosis in VECs by metabolomics analysis. The level of lipid peroxidation was increased in VECs, and the mitochondrial cristae was decreased after sepsis. Metabolomics analysis showed that Dex activated the pentose phosphate pathway and increased glutathione in VECs via up-regulation of G6PD expression. Dex could antagonize sepsis-induced the decrease in the level of Nrf2. The Nrf2 inhibitor reversed the protective effect of Dex on ferroptosis. Further study showed that Dex significantly alleviated sepsis-induced mitochondrial over-division, improved mitochondrial function, and decreased ROS, further inhibiting the ferroptosis of VECs. Dex alleviated the permeability of vessels by reducing ferroptosis and enhanced the intercellular junction of VECs.Conclusion: Dex protects vascular leakage following sepsis by inhibiting ferroptosis. The mechanism is mainly related to metabolic reprogramming via Nrf2 up-regulation and inhibition of mitochondrial fission.Keywords: dexmedetomidine, sepsis, ferroptosis, metabolic reprogramming, mitochondrial fission

Yunxia Tang,1,2,&ast; Chenjie Ma,1,2,&ast; Huali Sun,3 Siyuan Yang,1,2 Fengting Yu,1,2 Xingwang Li,1,2 Linghang Wang1,2 1Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Clinical Center for HIV/AIDS, Capital Medical University, Beijing, People’s Republic of China; 3Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linghang WangBeijing Di Tan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaTel/Fax +86-10- 84323103Email linghang.wang@ccmu.edu.cnPurpose: Human brucellosis is the most common bacterial zoonosis globally that poses a severe health threat. Despite the availability of antibiotic therapy for human brucellosis, its tendencies of chronicity and persistence may lead to severe debilitating and disabling conditions in patients. Comprehensive understanding of the immune response in brucellosis will be helpful in improving the treatment strategies. In this study, we measured serum levels of T helper cell type 1 (Th1), Th2, and Th17 cytokines in patients with acute brucellosis before and after treatment.Patients and Methods: Overall, 30 patients with acute brucellosis from the Beijing Di Tan Hospital and 26 healthy controls were enrolled in this study. All the patients received a 6-week therapy regimen comprising ceftriaxone, doxycycline, and rifampicin. Serum samples were collected from patients with acute Brucella infection and healthy controls before and after treatment. Serum seven cytokine levels of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-6, IL-10), and Th17 (IL-17A) were measured using cytometric bead array.Results: In patients with acute infection, the IL-2, IFN-γ, and IL-10 levels were significantly increased compared with those in healthy controls (P < 0.001). After treatment, IL-2, IFN-γ, and IL-10 levels significantly decreased (P < 0.05) and the TNF-α level significantly increased compared with the corresponding baseline levels and those in healthy controls (P < 0.05). Furthermore, the IFN-γ, IL-4, and IL-10 levels were higher in patients after treatment than in healthy controls (P < 0.05). IL-2 and IL-6 levels exhibited a positive correlation with the C-reactive protein (CRP) level in acute brucellosis (P < 0.05).Conclusion: Levels of most serum Th1 and Th2 cytokines were simultaneously increased in acute infection, followed by reduction in the corresponding cytokine levels and residual cytokine response during treatment. This residual immune response could represent a therapeutic opportunity that may improve the long-term clinical outcomes in patients with acute brucellosis after treatment.Keywords: brucellosis, acute infection, Th1, Th2, cytometric bead array, cytokines

Weixin Hou,1– 4 Xiaoyi Wei,1,2 Jiajun Liang,1– 4 Peng Fang,5 Chongyang Ma,1,2 Qiuyun Zhang,1,2,&ast; Yanbin Gao3,4,&ast; 1Department of Hepatology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Department of Hepatology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People’s Republic of China; 3Department of Endocrinology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4Department of Endocrinology, Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Beijing, People’s Republic of China; 5Department of Infectious Diseases, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuyun Zhang; Yanbin GaoSchool of Traditional Chinese Medicine, Capital Medical University, No. 10 You An Men Wai, Xi Tou Tiao, Feng Tai District, Beijing, 100069, People’s Republic of ChinaTel +86 10 8391 1638; +86 10 8391 1720Email 19970059@ccmu.edu.cn; gyb@ccmu.edu.cnBackground: Acute-on-chronic liver failure (ACLF) is a critical disease with a high fatality rate. Immune dysfunction and inflammatory responses are key risk factors in ACLF. Pyroptosis is a form of programmed cell death characterized by the release of inflammatory cytokines, which causes the strong inflammatory responses. High mobility group box-1 (HMGB1) could induce pyroptosis and is closely related to ACLF. However, the role of HMGB1-induced hepatocyte pyroptosis in ACLF has never been proposed; whether HMGB1-induced hepatocyte pyroptosis participates in the development of ACLF and the mechanisms involved are barely understood.Purpose: This study aimed to clarify the roles of HMGB1-induced hepatocyte pyroptosis in ACLF and the molecular mechanisms involved.Methods: Wistar rats were randomly divided into five groups, viz.: Normal, ACLF model, HMGB1 inhibitor, Caspase-1 inhibitor, and HMGB1 inhibitor+Caspase-1 inhibitor groups. The ACLF rat model was established using 40% carbon tetrachloride-induced liver fibrosis, followed by D-galactosamine and lipopolysaccharide joint acute attacks. The liver function, coagulation function and pathological damage of rats in each group were evaluated. The biological mechanisms of HMGB1-induced pyroptosis and the release of inflammatory cytokines were investigated using Western blot, quantitative real-time PCR (RT-qPCR), immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.Results: The liver function and coagulation function of ACLF rats were seriously impaired; liver tissue showed massive or submassive necrosis, accompanied by inflammatory cell infiltration; the percentage of pyroptotic hepatocytes significantly increased, and a large number of inflammatory cytokines were released. The expression levels of pyroptosis-related genes and proteins in liver tissues and serum significantly increased. But these phenomenons were improved by the inhibition of HMGB1, and the dual inhibition of HMGB1 and Caspase-1 showed a stronger effect.Conclusion: The findings indicate, for the first time, that pyroptosis is a crucial pathophysiological event of ACLF involved in its pathogenesis, and HMGB1-induced hepatocyte pyroptosis expands inflammatory responses to aggravate ACLF, suggesting that it may be a potential therapeutic target for ACLF treatment.Keywords: HMGB1, pyroptosis, inflammatory response, molecular mechanism of ACLF, ACLF treatment

Cheng Ma,1,&ast; He Li,1,&ast; Yifan Wei,1 Lijia Liu,1 Yin Shi,2 Yongxin Ren1 1Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongxin Ren; Yin Shi Tel +86 13585162283Email renyongxinjsph@163.com; shiyin_njmu@foxmail.comPurpose: Percutaneous endoscopic lumbar discectomy (PELD) is a minimally invasive spinal surgery for huge lumbar disc herniation (HLDH). The aim of this study was to investigate the short-term clinical effectiveness of PELD for HLDH with complete dural sac stenosis via an interlaminar approach.Methods: We retrospectively analyzed 56 patients diagnosed with HLDH with complete dural sac stenosis and treated with PELD via an interlaminar approach. Numerical rating scale (NRS), Oswestry disability index (ODI), and modified Japanese orthopedic association (mJOA) were used to evaluate preoperative conditions as well as outcomes at 1, 3, 6 and 12 months postoperatively. At the final follow-up, the clinical effects were evaluated using modified MacNab criteria.Results: All patients were followed for at least 12 months. At 1, 3, 6, and 12 months postoperatively, the NRS and ODI scores were significantly decreased, and the mJOA score significantly increased compared with preoperative results (P< 0.001). According to the Macnab criteria at the final follow-up, it was excellent in 42 patients (75%), good in 9 (16.1%), and fair in 5 (8.9%). The overall clinical satisfactory rate was 91.1%.Conclusion: Our study results suggest that percutaneous endoscopic interlaminar discectomy (PEID) is available for the treatment of HLDH with complete dural sac stenosis, whose benefits are rapid recovery, complete removal of the herniated disc, effective spinal canal decompression, fewer complications, and significant relief of clinical symptoms.Keywords: percutaneous endoscopic lumbar discectomy, percutaneous endoscopic interlaminar discectomy, huge lumbar disc herniation, complete dural sac stenosis, diffusion tensor imaging

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

Fengcui Sun,1 Xiufen Yang,1 Chaoqun Ma,1 Shizhao Zhang,1 Lu Yu,2 Haifei Lu,3 Guoliang Yin,1 Pengpeng Liang,1 Yanan Feng,1 Fengxia Zhang4 1Shandong University of Traditional Chinese Medicine, Jinan, 250000, People’s Republic of China; 2Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China; 3Hubei University of Traditional Chinese Medicine, Wuhan, 430065, People’s Republic of China; 4Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of ChinaCorrespondence: Fengxia ZhangDepartment of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of ChinaTel +8653168616011Email fxzhang0987@163.comAbstract: Hyperlipidemia is a disorder of lipid metabolism, which is a major cause of coronary heart disease. Although there has been considerable progress in hyperlipidemia treatment, morbidity and risk associated with the condition continue to rise. The first-line treatment for hyperlipidemia, statins, has multiple side effects; therefore, development of safe and effective drugs from natural products to prevent and treat hyperlipidemia is necessary. Diosgenin is primarily derived from fenugreek (Trigonella foenum graecum) seeds, and is also abundant in medicinal herbs such as Dioscorea rhizome, Dioscorea septemloba, and Rhizoma polygonati, is a well-known steroidal sapogenin and the active ingredient in many drugs to treat cardiovascular conditions. There is abundant evidence that diosgenin has potential for application in correcting lipid metabolism disorders. In this review, we evaluated the latest evidence related to diosgenin and hyperlipidemia from clinical and animal studies. Additionally, we elaborate the pharmacological mechanism underlying the activity of diosgenin in treating hyperlipidemia in detail, including its role in inhibition of intestinal absorption of lipids, regulation of cholesterol transport, promotion of cholesterol conversion into bile acid and its excretion, inhibition of endogenous lipid biosynthesis, antioxidation and lipoprotein lipase activity, and regulation of transcription factors related to lipid metabolism. This review provides a deep exploration of the pharmacological mechanisms involved in diosgenin-hyperlipidemia interactions and suggests potential routes for the development of novel drug therapies for hyperlipidemia.Keywords: diosgenin, hyperlipidemia, serum cholesterol, lipoprotein cholesterol, mechanism

Rong Ma,1,&ast; Nuernisha Alifu,2,&ast; Zhong Du,1 Shuang Chen,1 Youqiang Heng,1 Jing Wang,1 Lijun Zhu,2 Cailing Ma,1 Xueliang Zhang2 1State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia/Department of Gynecology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia School of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cailing MaState Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia/Department of Gynecology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of ChinaTel +86-13009661999Email hymcl13009661999@126.comXueliang ZhangState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, School of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, 830011, People’s Republic of ChinaTel +86-18999978069Email shuxue2456@126.comPurpose: Indocyanine green (ICG) is a favorable fluorescence nanoprobe for its strong NIR-I fluorescence emission and good photothermal capabilities. However, the stability and tumor targeting ability of ICG is poor, which limits its further applications. To further improve the photothermal and therapeutic efficiency of ICG, bovine serum albumin (BSA) was utilized to encapsulate the ICG and the chemotherapeutic drug doxorubicin (DOX) was loaded to form the BSA@ICG-DOX theranostic nanoplatform.Methods: In this study, ICG-loaded BSA nanoparticles (NPs) and the BSA@ICG-DOX NPs were fabricated using reprecipitation methods. Next, the tumour inhibition ability and biocompatibility of the NPs were evaluated. A subcutaneous xenografted nude mice model was established and imaging guided synergetic therapy was performed with the assistance of BSA@ICG-DOX NPs under 808 nm laser irradiation.Results: The BSA@ICG NPs exhibited strong NIR-I fluorescence emission, excellent photothermal properties, biocompatibility, and tumor targeting ability. To further improve the therapeutic efficiency, the chemotherapeutic drug doxorubicin (DOX) was loaded into the BSA@ICG NPs to form the BSA@ICG-DOX theranostic nanoplatform. The BSA@ICG-DOX NPs were spherical with an average size of ∼ 194.7 nm. The NPs had high encapsulation efficiency (DOX: 19.96% and ICG: 60.57%), and drug loading content (DOX: 0.95% and ICG: 3.03%). Next, excellent NIR-I fluorescence and low toxicity of the BSA@ICG-DOX NPs were verified. Targeted NIR-I fluorescence images were obtained after intravenous injection of the NPs into the subcutaneous cervical tumors of the mice.Conclusion: To improve the anti-tumor efficiency of the ICG@BSA NPs, the chemotherapeutic drug DOX was loaded into the BSA@ICG NPs. The NIR excitation/emission and targeted BSA@ICG-DOX NPs enables high-performance diagnosis and chemo/photothermal therapy of subcutaneous cervical tumors, providing a promising approach for further biomedical applications.Keywords: cervical cancer, indocyanine green, chemo/photothermal therapy, nanoparticles, near-infrared fluorescence imaging