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Man Huang,1,2,* Yudi Jin,3,* Mengyuan Wang,2 Qiang Song,4 Yanjia Fan,1 Yu Zhang,1 Cheng Tian,1 Chi Zhang,1 Shengchun Liu1 1Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Breast Center, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Central Laboratory, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengchun Liu, Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email liushengchun1968@163.comBackground: HER2-low breast cancer represents a distinct subgroup with unique clinical characteristics and treatment challenges. Nevertheless, it remains uncertain whether there exists a distinction in δKi67 between patients with HER2-low and HER2-zero statuses, and whether the prognosis varies among patients with differing HER2 statuses and δKi67.Methods: We conducted a multi-center retrospective study to investigate the correlation between alterations in Ki67 index following NAC and the prognosis among patients with HER2-low or HER2-zero breast cancer. 3 distinct cohorts comprising patients with HER2-negative breast cancer who underwent NAC were included. Comprehensive clinicopathological data were documented, with particular emphasis on evaluating changes in Ki67 index from baseline to post-NAC. These changes were then correlated with disease-free survival (DFS) through rigorous analysis.Results: Three cohorts, comprising 403, 315, and 72 patients respectively, were finally included. The study found that δKi67 did not show significant associations with other variables and were not identified as independent risk factors for survival. Nevertheless, across the three cohorts, following NAC, HER2-low breast cancer patients with δKi67 below the cut-off value demonstrated a better prognosis compared to those with δKi67 above the cut-off value. Additionally, their prognosis was also superior to that of HER2-zero breast cancer patients with δKi67 below the cut-off value.Conclusion: Our study demonstrates that HER2-low breast cancer patients with δKi67 values below the cut-off point after NAC are associated with improved prognosis. Monitoring δKi67 index and HER2 status may help identify patients who are likely to benefit from NAC and guide personalized treatment strategies.Keywords: HER2-low breast cancer, neoadjuvant chemotherapy, Ki67 index, prognosis, survival

Qian Song,1,2,* Kaili Zheng,1,2,* Zixia Ding,1,2 Zhengmiao Miao,1,2 Zhaoxia Liu,1,2 Ming Cheng,3 Jinyao Yi1,2,4 1Medical Psychological Center, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Medical Psychological Institute, Central South University, Changsha, People’s Republic of China; 3Department of Clinical Psychology, Hunan Brain Hospital, Changsha, People’s Republic of China; 4National Clinical Research Center for Mental Disorders, Changsha, 410011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinyao Yi, Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email jinyaoyi@csu.edu.cnBackground: There exist four short forms of the Social Interaction Anxiety Scale (SIAS): 10-item version (SIAS-10), 6-item version by Peters et al (SIAS-6P), 6-item version by Fergus et al (SIAS-6F), and 5-item version (SIAS-5). This study aims to comprehensively examine the psychometric properties of the SIAS-10, SIAS-6P, SIAS-6F, and SIAS-5 and to determine which one performs relatively better in Chinese population.Methods: This study enrolled 733 Chinese college students. The unidimensionality of the SIAS-10, SIAS-6P, SIAS-6F, SIAS-5 was examined using Confirmatory Factor Analysis (CFA). Multi-Group CFA was further adopted to assess measurement equivalence across gender. Internal consistency reliability and criteria-related validity were also evaluated. Additionally, the measurement performance of the SIAS-10, SIAS-6P, SIAS-6F, and SIAS-5 was assessed with Item Response Theory (IRT), which estimated the discrimination parameter and the Item Characteristic Curve (ICC) for each item.Results: Except for the SIAS-5, the SIAS-10, SIAS-6P, and SIAS-6F displayed a good-fit to the one-factor model. Furthermore, the SIAS-10 achieved strict equivalence across gender while other versions did not. The SIAS-10, SIAS-6P, SIAS-6F and SIAS-5 all had acceptable internal consistency and significant correlations with criteria scales. The IRT results showed that the SIAS-10 included more items with higher discrimination and peaked ICCs (indicating more informative), whereas the SIAS-6P included more items with lower discrimination and flat ICCs (indicating less informative).Conclusion: For assessing social anxiety in Chinese under constrained conditions, the SIAS-10 is recommended to clinicians for it measuring equivalently across gender, reflecting the relevant criteria variables well, and discriminating various levels of social anxiety sensitively.Keywords: social anxiety, psychometric properties, measurement equivalence, item response theory, Chinese

Baoliang Liu,1,* Haotian Zheng,1,* Guoyuan Ma,1,2 Hongchang Shen,3 Zhaofei Pang,3 Gemu Huang,4 Qingtao Song,4 Guanghui Wang,1,2 Jiajun Du1,2 1Department of Thoracic Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 4Research and Development Department, Amoy Diagnostics Co., LTD., Xiamen, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guanghui Wang; Jiajun Du, Email wangguanghui66@email.sdu.edu.cn; dujiajun@sdu.edu.cnBackground: Lung cancer is the most common type of cancer in the world. In lung adenocarcinoma (LUAD), studies on receptor tyrosine kinase ROS proto-oncogene 1 (ROS1) have mainly focused on the oncogenic effects of its fusion mutations, whereas ROS1 has been reported to be aberrantly expressed in a variety of cancers and can extensively regulate the growth, survival, and proliferation of tumor cells through multiple signaling pathways. The comprehensive analysis of ROS1 expression has not been fully investigated regarding its predictive value for LUAD patients.Methods: Gene expression profiles collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were used to build and validate prognostic risk models. The association of ROS1 with overall survival and the immune landscape was obtained from the Tumor Immune Estimation Resource (TIMER) database. The following analyses were performed using the R package to determine the model’s validity: pathway dysregulation analysis, gene set enrichment analysis, Gene Oncology analysis, immune invasion analysis, chemotherapy, radiotherapy, and immunotherapy sensitivity analysis. Finally, we conducted a pan-cancer analysis and performed in vitro experiments to explore the regulatory role of intercellular adhesion molecule 5 (ICAM5) in the progression of LUAD.Results: We constructed a 17-gene model that categorized patients into two risk groups. The model had predictive accuracy for tumor prognosis and was specific for patients with high ROS1 expression. Comprehensive analysis showed that patients in the high-risk group were characterized by marked dysregulation of multiple pathways (eg, unfolded protein response), immune suppression of the tumor microenvironment, and poor benefit from immunotherapy and radiotherapy compared with patients in the low-risk group. PLX4720 may be a suitable treatment for the high-risk patient population. The ICAM5 gene has been demonstrated to inhibit the proliferation, cell cycle, invasion, and migration of LUAD cells.Conclusion: We constructed a 17-gene prognostic risk model and found differences in immune-related cells, biological processes, and prognosis among patients in different risk groups based on the correlation between ROS1 and immunity. Personalized therapy may play an essential role in treatment. We further investigated the role of ICAM5 in inhibiting the malignant bioactivity of LUAD cells.Keywords: ROS1, ICAM5, LUAD, immune, prognostic model

Junju Zou,1– 3,* Qianbo Song,2,* Pang Chui Shaw,4 Yongjun Wu,1,5 Zhong Zuo,2 Rong Yu1,3 1School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 3Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 4School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 5School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong Yu, School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China, Email yurong8072@qq.com Zhong Zuo, School of Pharmacy, the Chinese University of Hong Kong, Hong Kong, SAR, 999077, People’s Republic of China, Email joanzuo@cuhk.edu.hkPurpose: Non-alcoholic fatty liver disease (NAFLD) represents a significant global health burden, exhibiting a strong correlation with insulin resistance, obesity, and type 2 diabetes (T2DM). Despite the severity of hepatic steatosis in T2DM patients, no specific drugs have been approved for clinical treatment of the disease. Tangerine peel is one kind of popular functional food and reported to possess hypoglycemic and lipid-lowering potential. In this study, we investigated the effects of Tangerine-peel-derived exosome-like nanovesicles (TNVs) on hepatic lipotoxicity associated with T2DM.Methods: The TNVs was prepared by differential centrifugation of the aqueous extract of Tangerine and chemical properties were characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and LC-MS/MS. The hypoglycemic and lipid-lowering potential of TNVs were possessed by biochemical measurement, RT-PCR, 16S rRNA sequencing, GC/MS, UHPLC-MS/MS, in vivo small animal imaging assay and HE staining. Subsequently, effects of TNVs on lipid accumulation and glycolysis were investigated on 3T3-L1 and AML-12 cells.Results: TNVs significantly inhibited insulin resistance, reduced hepatic lipid accumulation, facilitate intestinal mucosal repair, rescued gut microbiota dysbiosis, regulated colonic SCFA and liver bile acid metabolism in db/db mice. Furthermore, TNVs restored the expression of key genes in glucose and lipid metabolism (ACC, AMPK, CD36, LXRα, PPAR-γ, SREBP-1) while activating the expression of genes related to glycolysis (G6Pase, GLUT2, PCK1, PEPCK) in db/db mice. Further cell-based mechanistic studies revealed that TNVs reduced lipid accumulation in 3T3-L1 and AML-12 cells via regulation of glucose and lipid metabolism-related genes (UCP1, FGFR4, PRDM16, PGC-1α, Tmem26, Cpt1, Cpt2 and PPAR-α).Conclusion: We for the first time demonstrated that TNVs could significantly improve glucose and lipid metabolism via activating the expression of genes related to fatty acid β-oxidation and glycolysis. Keywords: tangerine peel, plant-derived exosome-like nanoparticles, diabetes mellitus, metabolomics, gut microbiota, fat accumulation

Yufeng Yao,1,2 Qiyuan Song,3 Jingnan Zhang,2,4 Yingying Wen,2,4 Xiaoyan Dou2 1Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 2Department of Ophthalmology, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Ophthalmology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 4Shenzhen University Medical College, No.1066 Xueyuan Road, Shenzhen University, Shenzhen, Guangdong Province, People’s Republic of ChinaCorrespondence: Xiaoyan Dou, Email douxy08@163.comAbstract: The retina’s similar structure and function to the brain make it a unique visual “window” for studying cerebral disorders. Ophthalmic artery occlusion (OAO) or retinal artery occlusion (RAO) is a severe ophthalmic emergency that significantly affects visual acuity. Studies have demonstrated that patients with OAO or RAO face a notably higher risk of future acute ischemic stroke (AIS). However, ophthalmologists often overlook multidisciplinary approach involving the neurologist, to evaluate the risk of AIS and devise clinical treatment strategies for patients with OAO or RAO. Unlike the successful use of thrombolysis in AIS, the application of thrombolysis for OAO or RAO remains limited and controversial due to insufficient reliable evidence. In this review, we aim to summarize the anatomical and functional connections between the retina and the brain, and the clinical connection between OAO or RAO and AIS, compare and review recent advances in the effectiveness and safety of intravenous and intra-arterial thrombolysis therapy in patients with OAO or RAO, and discuss future research directions for OAO or RAO. Our goal is to advance the development of multidisciplinary diagnosis and treatment strategies for the disease, as well as to establish expedited pathways or thrombolysis guidelines for vascular intervention.Keywords: retina, brain, ophthalmic artery occlusion, retinal artery occlusion, stroke, thrombolysis

Wenjin Zhang,1 Qiang Song,1 Xiaofei Bi,1 Wei Cui,1 Chengmei Fang,1 Jianya Gao,1 Jinan Li,1 Xiang Wang,1 Kai Qu,1 Xian Qin,1 Xuan An,2,3 Cheng Zhang,1,3 Xianxiang Zhang,1,3 Fang Yan,4 Guicheng Wu1– 3 1Chongqing Municipality Clinical Research Center for Endocrinology and Metabolic Diseases, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 2Department of Hepatology, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 3School of Medicine, Chongqing University, Chongqing, People’s Republic of China; 4Geriatric Diseases Institute of Chengdu, Department of Geriatrics, Chengdu Fifth People’s Hospital, Chengdu, People’s Republic of ChinaCorrespondence: Guicheng Wu, Chongqing University Three Gorges Hospital, Xincheng Road 165#, Wanzhou District, Chongqing, 404000, People’s Republic of China, Tel +(86) 58103079, Fax +86 23 581045783, Email wuguicheng@cqu.edu.cn Fang Yan, Geriatric Diseases Institute of Chengdu, Department of Geriatrics, Chengdu Fifth People’s Hospital, Mashi Street 33#, Wenjiang District, Chengdu, 611130, People’s Republic of China, Tel/Fax +86 28 82661127, Email fangyan@cdutcm.edu.cnPurpose: Pueraria lobata (P. lobata), a dual-purpose food and medicine, displays limited efficacy in alcohol detoxification and liver protection, with previous research primarily focused on puerarin in its dried roots. In this study, we investigated the potential effects and mechanisms of fresh P. lobata root-derived exosome-like nanovesicles (P-ELNs) for mitigating alcoholic intoxication, promoting alcohol metabolism effects and protecting the liver in C57BL/6J mice.Methods: We isolated P-ELNs from fresh P. lobata root using differential centrifugation and characterized them via transmission electron microscopy, nanoscale particle sizing, ζ potential analysis, and biochemical assays. In Acute Alcoholism (AAI) mice pre-treated with P-ELNs, we evaluated their effects on the timing and duration of the loss of the righting reflex (LORR), liver alcohol metabolism enzymes activity, liver and serum alcohol content, and ferroptosis-related markers.Results: P-ELNs, enriched in proteins, lipids, and small RNAs, exhibited an ideal size (150.7 ± 82.8 nm) and negative surface charge (− 31 mV). Pre-treatment with 10 mg/(kg.bw) P-ELNs in both male and female mice significantly prolonged ebriety time, shortened sobriety time, enhanced acetaldehyde dehydrogenase (ALDH) activity while concurrently inhibited alcohol dehydrogenase (ADH) activity, and reduced alcohol content in the liver and serum. Notably, P-ELNs demonstrated more efficacy compared to P-ELNs supernatant fluid (abundant puerarin content), suggesting alternative active components beyond puerarin. Additionally, P-ELNs prevented ferroptosis by inhibiting the reduction of glutathione peroxidase 4 (GPX4) and reduced glutathione (GSH), and suppressing acyl-CoA synthetase long-chain family member 4 (ACSL4) elevation, thereby mitigating pathological liver lipid accumulation.Conclusion: P-ELNs exhibit distinct exosomal characteristics and effectively alleviate alcoholic intoxication, improve alcohol metabolism, suppress ferroptosis, and protect the liver from alcoholic injury. Consequently, P-ELNs hold promise as a therapeutic agent for detoxification, sobriety promotion, and prevention of alcoholic liver injury.Keywords: Pueraria lobata root-derived exosome-like nanovesicles, acute alcoholism, loss of the righting reflex, ethanol metabolism, ferroptosis

Shuqin Chen,1,* Xuepeng Wang,2,* Yong Jin,3 Xueqin Chen,4 Qifa Song,5 Gang Wei,6 Li Li1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of China; 2Department of Infectious Disease, The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of China; 3Department of Internal Medicine, Ningbo Yinzhou No.2 Hospital, Ningbo, People’s Republic of China; 4Department of Traditional Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of China; 5Medical Data Center, The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of China; 6Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Li, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Ningbo University, Ningbo, 31500, People’s Republic of China, Email lilyningbo@163.com Gang Wei, Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100000, People’s Republic of China, Email gangwei_2013@163.comBackground: Changes in body composition accompanied by glucagon-like peptide 1 receptor agonist (GLP-1RA) induced weight loss have drawn much attention. However, fewer studies have reported body composition changes in patients receiving dulaglutide therapy in Chinese population.Methods: A total of 70 overweight/obese type 2 diabetes mellitus (T2DM) patients who received dulaglutide therapy were included. Clinical data were collected. Visceral fat area (VFA) and body composition were also measured. Changes in clinical indicators and body composition of patients before and after intervention were also analyzed. Correlation analysis and multiple linear regression model were used to evaluate the association between hemoglobin A1C (HbA1c) and body composition.Results: The results showed that body weight (BW), VFA, body fat (BF), lean body mass (LBM), skeletal muscle mass (SMM) and water content were reduced after 3 months dulaglutide intervention. The lean body mass percentage (LBMP) and skeletal muscle mass percentage (SMMP) significantly increased. Moreover, there was no significant difference in bone mineral quality (BMQ) after the intervention. The multiple linear regression model revealed that the % change in BF was independently associated with % change in HbA1c (β = 0.449, t = 3.148, p=0.002).Conclusion: These results indicate that dulaglutide intervention does not cause muscle and bone mass loss while inducing weight loss, and % change in BF was independently associated with improved glucose control during dulaglutide therapy. This study offers some positive results to support the clinical application of dulaglutide.Keywords: dulaglutide, obesity, diabetes, body fat mass, visceral fat

Qing Song, Xi Wang,* Zhenhuan Cao,* Chun Xin,* Jingyuan Zhang,* Suwei Li Intensive Care Unit, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Suwei Li, Tel +86 180 9887 5867, Email lisuweicn@163.comAbstract: Apelin is the native ligand for the G protein-coupled receptor APJ. Numerous studies have demonstrated that the Apelin/APJ system has positive inotropic, anti-inflammatory, and anti-apoptotic effects and regulates fluid homeostasis. The Apelin/APJ system has been demonstrated to play a protective role in sepsis and may serve as a promising therapeutic target for the treatment of sepsis. Better understanding of the mechanisms of the effects of the Apelin/APJ system will aid in the development of novel drugs for the treatment of sepsis. In this review, we provide a brief overview of the physiological role of the Apelin/APJ system and its role in sepsis.Keywords: apelin, sepsis, organ dysfunction, hemodynamics, fluid homeostasis

Yiran Zhang,1– 4,* Qingcheng Song,2,3,* Yueyao Zhang,2,3,* Jiheng Xiao,5 Xiangtian Deng,6 Xin Xing,2,3 Hongzhi Hu,5 Yingze Zhang1– 3 1School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China; 2Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 3NHC Key Laboratory of Intelligent Orthopaedic Equipment, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4HeBei Ex&Invivo Biotechnology Co. Ltd, Shijiazhuang, Hebei, 050051, People’s Republic of China; 5Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 6Orthopaedics Research Institute, Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingze Zhang; Hongzhi Hu, Email yzling_liu@163.com; 13720105746@163.comBackground: Although systemic chemotherapy is a standard approach for osteosarcoma (OS) treatment, its efficacy is limited by the inherent or acquired resistance to apoptosis of tumor cells. Ferroptosis is considered as an effective strategy capable of stimulating alternative pathways of cancer cell demise. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy.Methods and Results: A novel nanovehicle composed of arginine-glycine-aspartate (RGD) modified mesoporous silica-coated iron oxide loading Fin56 was rationally prepared (FSR-Fin56). With the RGD-mediated targeting affinity, FSR-Fin56 could achieve selective accumulation and accurate delivery of cargos into cancer cells. Upon exposure to NIR light, the nanovehicle could generate localized hyperthermia and disintegrate to liberate the therapeutic payload. The released Fin56 triggered the degradation of GPX4, while Fe3+ depleted the intracellular GSH pool, producing Fe2+ as a Fenton agent. The local rise in temperature, in conjunction with Fe2+-mediated Fenton reaction, led to a rapid and significant accumulation of ROS, culminating in LPOs and ferroptotic death. The outstanding therapeutic efficacy and safety of the nanovehicle were validated both in vitro and in vivo.Conclusion: The Fin56-loaded FSR nanovehicle could effectively disturb the redox balance in cancer cells. Coupled with NIR laser irradiation, the cooperative CDT and PTT achieved a boosted ferroptosis-inducing therapy. Taken together, this study offers a compelling strategy for cancer treatment, particularly for ferroptosis-sensitive tumors like osteosarcoma. Keywords: chemodynamic therapy, photothermal therapy, Fenton reaction, Fin56, ferroptosis

Qian Song,1,* Ying Chen,2,3,* JianQing Ma,1 Wei Zhou,4 JunYan Song,1 ChunFu Wu,5 Jie Liu2 1Department of Medical Laboratory, North China Medical & Health Group Xingtai General Hospital, Orthopedic Hospital of Xingtai, Xingtai, People’s Republic of China; 2BGI Genomics, BGI-Shenzhen, Shenzhen, People’s Republic of China; 3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 4China National Genebank, BGI-Shenzhen, Shenzhen, People’s Republic of China; 5Yantai Harbor Hospital, Yantai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Liu, BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, People’s Republic of China, Email liujie8@genomics.cn ChunFu Wu, Yantai Harbor Hospital, Yantai, 264000, People’s Republic of China, Email tjnk2009@126.comPurpose: Psoriasis is a chronic, multi-system skin disease that can be influenced by immunological, environmental, and genetic factors. Plasma metabolomic analysis can provide a great deal of information on potential diagnostic biomarkers, pathogenesis and personalized treatment. However, the role of metabolites in psoriasis is unknown.Patients and Methods: We performed an untargeted metabolomic analysis of plasma based on high-resolution liquid chromatography mass spectrometry from 10 plaque psoriasis patients and 10 healthy controls.Results: A total of 301 differential metabolites were detected, of which 10 metabolites were possible potential biomarkers, including vitamins, amino acids, and lipids. At the same time, KEGG pathway enrichment analysis was performed for all detected differential metabolites, and it was found that protein digestion and absorption, amino acid metabolism and lipid metabolism may be jointly involved in regulating the pathogenesis of psoriasis. In addition, the proteins ESR1, OPRM1 and HSD11B1 were identified as possible potential topical therapeutic targets for psoriasis through analysis of the metabolite-protein interaction network.Conclusion: In this study, we identified 10 differential metabolites as possible potential combinatorial biomarkers for the diagnosis of psoriasis. 12 metabolic pathways were significantly enriched that may be closely related to the occurrence and development of psoriasis. Three proteins, ESR1, OPRM1, and HSD11B1, were identified as possible potential therapeutic targets for psoriasis.Keywords: psoriasis, metabolomics, biomarker, KEGG pathway, therapeutic target

Yu Cao,1 Ying Han,2 Jiangping Wu,1 Jianping Sun,3 Yanchao Dai,3 Guifang Qiao,3 Kang Li,3 Ang Li,3 Yonghong Zhang,4 Yingmin Ma,5,* Qingkun Song1,3,* 1Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Center of Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Center of Biobank, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Hepatic Intervention, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Respiratory and Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingmin Ma, Department of Respiratory and Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Youanmen Wai 8, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86-10-83997022, Email ma.yingmin@163.com Qingkun Song, Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Youanmen Wai 8, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86-10-83997022, Email songqingkun@ccmu.edu.cnBackground: For the distinct immune/inflammatory responses from Omicron variant infection, this study aimed to investigate the diagnostic efficacy of systemic inflammatory indicators and the clinical efficacy of corticosteroids on the in-hospital mortality among COVID-19 patients.Methods: Under a retrospective cohort study, 1081 COVID-19 patients were recruited from Beijing Youan Hospital, Capital Medical University between November 16, 2022 and January 30, 2023. We chose neutrophil-to-lymphocyte ratio (NLR), CRP-to-lymphocyte ratio (CLR), and CRP-to-albumin ratio (CAR) as the systemic inflammatory indicators. Receiver operating curve (ROC) and multivariate logistic regression analysis were used to determine the diagnostic efficacy of systemic inflammatory indicators and the association between systemic inflammatory indicators and in-hospital mortality.Results: Among 684 patients included in analysis, 96 died during hospitalization. NLR, CLR and CAR performed well (with an area under the curve (AUC) greater than 0.75) in discriminating in-hospital mortality among COVID-19 patients. The severe status of systemic inflammation, with optimal cut-off value derived from ROC analysis, significantly associated higher risk of in-hospital mortality (OR = 3.81 for NLR ≥ 6.131; OR = 3.76 for CLR ≥ 45.455; OR = 5.10 for CAR ≥ 1.436). Corticosteroids use within 72 hours of admission increased the in-hospital mortality 2.88-fold for COVID-19 patients. In the subgroup of patients with severe systemic inflammation, corticosteroids increased the risk of in-hospital mortality (OR = 2.11 for NLR, p = 0.055; OR = 2.94 for CLR, p = 0.005; OR = 2.31 for CAR, p = 0.036).Conclusion: Systemic inflammatory indicators had good diagnostic performance for in-hospital mortality. Patients with severe systemic inflammatory status should not receive corticosteroid treatment and further studies are warranted for confirmation.Keywords: COVID-19, systemic inflammatory indicators, in-hospital mortality, anti-inflammatory treatment

Wei Cheng,1 Aiyuan Zhou,2 Yuqin Zeng,1 Ling Lin,1 Qing Song,1 Cong Liu,1 Zijing Zhou,1 Yating Peng,1 Min Yang,1 Lizhen Yang,1 Yan Chen,1 Shan Cai,1 Ping Chen1 1Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital; Research Unit of Respiratory Disease; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaCorrespondence: Ping Chen, Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital; Research Unit of Respiratory Disease; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Tel +86-13873115563, Fax +86 731-85295848, Email pingchen0731@csu.edu.cnBackground: The revised Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 group ABE classification has undergone major modifications, which can simplify clinical assessment and optimize treatment recommendations for Chronic Obstructive Pulmonary Disease (COPD). However, the predictive value of the new grouping classification for prognosis is worth further exploration. We aimed to compare the prediction of hospitalization and mortality between this new GOLD group 2023 ABE classification and the earlier 2017 ABCD classification in a Chinese COPD cohort.Methods: Data from 2,499 outpatients with COPD, who first registered in the RealDTC study of Second Xiangya Hospital from December 2016 to December 2019, were collected prospectively and assessed retrospectively. Patients were followed up on all-cause mortality until October 2022 or death.Results: : Of the 2,499 patients with COPD, the risk of hospitalization during the first-year follow-up was higher in group E than in groups A and B. The mortality was higher in group E than in groups A and B, and group B was higher than group A. No differences were seen in the area under the curve (AUC) of 2017 vs 2023 GOLD grouping to predict hospitalization. The time-dependent AUC and concordance index for predicting mortality is slightly higher in the GOLD 2017 ABCD than in the 2023 ABE groups. The new GOLD 12-subgroup (1A– 4E) classification combining the GOLD 1– 4 staging and grouping performed similarly discriminate predictive power for mortality to the GOLD 2017 16-subgroup (A1– 4D) classification.Conclusion: The risk of hospitalization during the first-year follow-up was higher in group E than in groups A and B. The all-cause mortality increased gradually from GOLD group A to E. The GOLD 2023 classification based on ABE groups did not predict mortality better than the earlier 2017 ABCD classifications.Keywords: COPD, mortality, hospitalization, GOLD 2023

Dan Liu,1,&ast; Qing Song,2– 4,&ast; Yuqin Zeng,2– 4 Rong Yi,5 Yi Liu,5 Xin Li,6 Yan Chen,2– 4 Shan Cai,2– 4 Ping Chen2– 4 1Department of Respiratory and Critical Care Medicine, Changsha Hospital of Traditional Chinese Medicine (Changsha Eighth Hospital), Changsha, Hunan, 410000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 4Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, Hunan, 412000, People’s Republic of China; 6Division 4 of Occupational Diseases, Hunan Prevention and Treatment Institute for Occupational Diseases, Changsha, Hunan, 412000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Chen, Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan, 410011, People’s Republic of China, Tel +86 731 8529 5248, Email pingchen0731@csu.edu.cnBackground: We analyzed the clinical characteristics and outcomes in non-frequent exacerbation patients with chronic obstructive pulmonary disease (COPD).Methods: In this retrospective cohort study, we enrolled patients with stable COPD from 12 hospitals. Non-frequent exacerbation was defined as less than two times of exacerbations in the past year. The non-frequent exacerbation patients were classified into less and more symptomatic groups based on the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC). Finally, the non-frequent exacerbation patients with less and more symptomatic were classified into the long-acting muscarinic antagonist (LAMA), long-acting β 2-agonist (LABA)+inhaled corticosteroids (ICS), LABA+LAMA, and LABA+LAMA+ICS groups. Minimum clinically important difference (MCID) was defined as a CAT score decrease of ≥ 2 during six months of follow-up. We recorded the number of exacerbations and mortality during one year of follow-up.Results: A total of 834 (67.5%) non-frequent exacerbation patients with COPD were included in this study. The non-frequent exacerbation patients had a higher education level and body mass index (BMI), and lower CAT and mMRC scores (P< 0.05). In addition, the non-frequent exacerbation patients had lower mortality and risk of future exacerbation, and were more likely to attain MCID (P< 0.05). Furthermore, the non-frequent exacerbation patients with more symptomatic COPD treated with LABA+LAMA or LABA+LAMA+ICS were more likely to attain MCID and had a lower risk of future exacerbation (P< 0.05). However, there were no significant differences among the different inhalation therapies in non-frequent exacerbation patients with less symptomatic COPD.Conclusion: The non-frequent exacerbation patients with COPD had a higher education level and BMI, a lower symptom burden, and better outcomes. In addition, LABA+LAMA should be recommended to non-frequent exacerbation patients with more symptomatic COPD, while mono-LAMA should be recommended to non-frequent exacerbation patients with less symptomatic COPD as the initial inhalation therapy.Keywords: chronic obstructive pulmonary disease, non-frequent exacerbation, minimum clinically important difference, mortality, inhalation therapy

Wei Liu,1,&ast; Qingkun Song,2,&ast; Fang Li,1 Yu Cao,2 Ying Han,3 Jiangping Wu,2 Zhongjie Hu,4 Yonghong Zhang,5 Yingmin Ma6 1Department of Pharmacy, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Center of Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Gastroenterology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Hepatic Intervention, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Respiratory and Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingmin Ma, Beijing Youan Hospital, Capital Medical University, Youanmen Wai 8, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86-10-83997022, Email ma.yingmin@163.comPurpose: Anti-viral and anti-inflammatory therapies were effective in altering virus repletion and immune dysregulation in Coronavirus Disease 2019 (COVID-19) patients. This study aimed to explore the effect of combination therapy on disease progression in a real-world setting.Patients and Methods: A total of 836 patients confirmed with SARS-CoV-2 infection participated in the study from 15 November to 25 December 2022 at Beijing Youan Hospital, Capital Medical University. A prospective cohort study was implemented to investigate the prognostic effect of the combination therapy on virus shedding and clinical recovery.Results: About 78% of patients used nirmatrelvir/ritonavir (N/R, Paxlovid®, Pfizer) negatively, 16% of patients were prescribed nirmatrelvir/ritonavir beyond five days of symptom onset, 4% of patients received N/R monotherapy within five days of symptom onset and 2% of patients received N/R combined with dexamethasone. Compared with untreated patients, N/R monotherapy reduced the median time to 10.0 days from 12.0 days according to the negative conversion of nucleic acid amplification test (NAAT), and combination therapy reduced the time to 7.0 days, and increased to a 1.99 (95% CI 0.92, 4.32) and 14.23-fold (95% CI 4.50, 44.95) probability of negative NAAT, respectively. N/R monotherapy reduced the clinical recovery time to 10.0 days from 13.0 days. Single-use and combined-use non-significantly increased the recovery probability by 61% and 69%, respectively. In mild and moderate patients, the HRs for clinical recovery increased to 1.69 (95% CI 0.73, 3.94) and 2.18 (95% CI 0.29, 16.62), respectively.Conclusion: Combination therapy of N/R and dexamethasone increased negative conversion of NAAT and was associated with a non-significant improvement in clinical recovery. Further studies are warranted to confirm this efficacy.Keywords: N/R, dexamethasone, negative conversion of NAAT, clinical recovery

Zixia Ding,1,2,&ast; Qian Song,1,2,&ast; Jun Chu,1,2 Tao Zou,3 Kaili Zheng,1,2 Zhaoxia Liu,1,2 Wanrong Peng,1,2 Jinyao Yi1,2,4 1Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Medical Psychology Institution, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Department of Psychiatry, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 4National Clinical Research Center for Mental Disorders, Changsha, Hunan, 410011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinyao Yi, Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email jinyaoyi@csu.edu.cnBackground: The present study investigated the applicability of the Cognitive Emotion Regulation Questionnaire (CERQ) in the Chinese community elderly and explored the influence of cognitive emotion regulation strategies on late-life depression.Methods: A total of 367 community elderly aged 60– 94 were deemed eligible and completed CERQ, the Perceived Stress Scale-10, the Geriatric Depression Questionnaire-15, and the State Anxiety Inventory. Confirmatory factor analysis was adopted to verify the 9-factor structure of CERQ. Cronbach’s α coefficient, Ω coefficient and split-half reliability were used to test the internal consistency of CERQ. Pearson correlations among scores of CERQ and other scales were calculated to examine its convergent validity. In addition, a structural equation model was used to further examine the effect of cognitive emotion regulation strategies on the association between perceived stress and late-life depression.Results: All the fitting indexes of CERQ’s 9-factor model met the criterion (χ2/df= 2.26, CFI= 0.916, TLI= 0.904, RMSEA= 0.052). For the total score of CERQ, the Cronbach’s α coefficient and Ω coefficient were both 0.90, and the split-half reliability was 0.74. For the nine subscales, the α coefficients ranged from 0.66 to 0.88, and the Ω coefficients ranged from 0.69 to 0.88. Significant positive correlations were found between the maladaptive dimension of CERQ and other scales (all p < 0.001). The maladaptive emotion regulation strategies indirectly affected the effect of perceived stress on late-life depression (effect size was 21.57%).Conclusion: With good reliability and factor validity, the CERQ showed good applicability in the Chinese elderly population. The influence of perceived stress on depression in the elderly was mediated by maladaptive emotion regulation strategies.Keywords: cognitive emotion regulation, late-life depression, perceived stress, psychometric properties, mediating effect

Ruibin Wang,1 Yuchen Li,2 Yanjie Zhao,3 Feng Shi,4 Quan Zhou,5 Jiangping Wu,6 Shuzhen Lyu,7 Qingkun Song8,9 1Department of Emergency, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Cell and Molecular Biology, Sid Faithfull Brain Cancer Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; 3Department of Medical Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Cancer Research, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 7Department of Breast Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 8Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 9Department of Clinical Epidemiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Qingkun Song, Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Xitoutiao 8, Fengtai Dist, Beijing, People’s Republic of China, Email songqingkun@aliyun.comBackground: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Metformin has been shown to have the potential to inhibit the proliferation of malignant cells. This study aimed to investigate the regulatory effect of metformin on phenotypic tumor-infiltrated lymphocytes (TILs) and mechanisms in TNBC.Methods: Microarray analysis was performed on 4T1 cells post metformin treatment. BALB/c mice were inoculated with 4T1 cells with knockdown/overexpression of C-Jun N-terminal kinase (JNK), and administered with metformin. Phenotypic TILs in the tumor microenvironment (TME) were visualized by immunofluorescence staining.Results: Metformin inhibited 4T1 cell proliferation and increased expression of JNK by 21% in vitro. In vivo, Metformin increased cell counts of CD4+ and CD8+TILs by 100% and 85%, respectively, and the increase of TILs was associated with JNK pathway. Cell counts of CD4+/PD-1+ and CD8+/PD-1+TILs were reduced by 64% and 58%, respectively, post metformin treatment, but the reduction of exhausted TILs was not associated with JNK pathway. Metformin induced a 11% and 20% reduction of IL-6 and TNF-α level in the TNBC model.Conclusion: Our study demonstrated that metformin increased the functional phenotype of TILs and associated with JNK pathway, and suppressed the exhausted phenotype of TILs independently to JNK pathway in TNBC microenvironment. Further studies are needed to explore the basic mechanism of action of the drug. Metformin has potentially enhanced efficacy when used in combination with immunotherapy against TNBC.Keywords: triple-negative breast cancer, metformin, phenotypic tumor-infiltrated lymphocytes, C-Jun N-terminal kinase

Yiran Zhang,1– 4,&ast; Hongzhi Hu,5,&ast; Xiangtian Deng,6,&ast; Qingcheng Song,2 Xin Xing,2,3 Weijian Liu,5 Yingze Zhang1– 3 1School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China; 2Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 3NHC Key Laboratory of Intelligent Orthopaedic Equipment, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4HeBei Ex&Invivo Biotechnology Co. Ltd, Shijiazhuang, Hebei, 050051, People’s Republic of China; 5Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 6Orthopaedics Research Institute, Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingze Zhang; Weijian Liu, Email yzling_liu@163.com; xh_liuweijian@hust.edu.cnBackground: Although chemodynamic therapy (CDT) has attracted enormous attention in anti-tumor studies for converting endogenous hydrogen peroxide (H2O2) into toxic hydroxyl radicals (•OH) by Fenton-type reaction, the treating effects of using CDT alone is still unsatisfying. Recently, glucose oxidase (GOx) was reported to be co-delivered with Fenton agent for synergistic starvation therapy (ST) and CDT. However, the overexpressed glutathione (GSH) and hypoxia in tumor microenvironment (TME) restrict the therapeutic efficacy of ST/CDT.Methods and Results: In this work, a novel nanoplatform composed of GOx plus Fenton agent (Cu2+) encapsulated core and metformin (MET)-loaded manganese dioxide nanosheets (MNSs) shell was prepared and further functionalized by arginine-glycine-aspartate (RGD). With the RGD-mediated affinity with cancer cells, the nanocomposite (GOx-CuCaP@MNSs-MET@PEG-RGD, GCMMR) could accomplish targeting delivery and TME-activated release of cargos. The intracellular GSH was depleted by MnO2/Cu2+ and abundant H2O2 was generated along with the GOx-induced glucose deprivation, which process was further enhanced by MET-mediated hypoxia relief via inhibiting mitochondria-associated respiration. Subsequently generated •OH from Cu+-mediated Fenton-like reaction exerts severe intracellular oxidative stress and cause apoptosis. Moreover, significant inhibition of tumor growth was detected in a subcutaneous xenograft model of osteosarcoma (OS) after GCMMR treatment.Conclusion: The excellent therapeutic efficacy and biosafety of the nanoplatform were confirmed both in vitro and in vivo. Collectively, this study provides an appealing strategy with catalytic cascade enhancement on targeted ST/CDT for cancer treatment, especially for hypoxic solid tumors.Graphical Abstract: Keywords: chemodynamic therapy, starvation therapy, glucose oxidase, Fenton reaction, biomineralization, metformin

Jian Liu, Ying Jiang, Zhe Liu, Qun Song, Zhuo Li Department of Urology, The First Affiliated Hospital of Hunan Normal University Hunan Provincial People’s Hospital, Changsha, People’s Republic of ChinaCorrespondence: Zhuo Li, Tel +8615197591937, Email 376941577@qq.comAbstract: Upper urinary tract obstruction caused by fungal balls is a rare urinary system disease. We admitted an elderly man with symptoms of urinary tract infection and diabetes mellitus. When the patient was transported into the hospital, a CT scan revealed right renal pelvis dilatation and gas buildup, routine urinalysis showing full field of view of white blood cells and middle urinary bacteria and fungi cultures came back negative, leading to the incorrect diagnosis of emphysematous pyelonephritis with Aerogenes infection. When the diagnosis is confirmed, surgery and antifungal therapy are used to deal with both the obstruction and the fungal ball.Keywords: fungal ball, urinary tract obstruction, misdiagnosed, emphysematous pyelonephritis, infection

Qingxiang Liu,1 Ming Xue,1 Qianwen Song,1 Jianfeng Xie,1 Yi Yang,1 Songqiao Liu1,2 1Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2Department of Critical Care Medicine, Nanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch, Nanjing, People’s Republic of ChinaCorrespondence: Yi Yang; Songqiao Liu, Email yiyiyang2004@163.com; liusongqiao@ymail.comBackground: PD-1 is an important immune checkpoint expressed on T lymphocytes and is associated with T-cell function in sepsis. However, the role of PD-1 in naive and memory T-cell responses in sepsis is not well understood. We aimed to determine the expression of PD-1 induced on naive and memory T lymphocytes in patients with sepsis and its association with clinical outcome.Methods: A prospective observational study was conducted at a general intensive care unit (ICU). Whole blood samples were collected from patients within 48 h after sepsis diagnosis. PD-1 expression on naive and memory T cells was measured by flow cytometry. The levels of IFN-γ, IL-2 and TNF-α released by memory T cells were also determined. All patients were followed up to 28 days, and 28-day mortality was recorded.Results: PD-1 expression showed no difference in naive CD4+ T cells (P=0.617) or naive CD8+ T cells (P=0.079) between survivors (n = 21) and nonsurvivors (n = 9). Increased PD-1 expression on memory CD4+ T cells was found in nonsurvivors (P=0.030) and memory CD8+ T cells (P=0.006) in comparison with survivors. According to the cutoff value of the percentage of PD-1 on memory CD8+ T cells in predicting 28-day mortality of patients with sepsis, patients were divided into two groups. The 28-day mortality rates between the two groups were significantly different (P=0.009). A Kaplan Meier curve was constructed to derive a hazard ratio of 9.33 (95% CI: 2.52– 34.60) for the percentage of PD-1 on memory CD8+ T cells regarding 28-day mortality. In addition, the IFN-γ secretion of memory CD4+ T cells (P=0.046) and IL-2 secretion of memory CD8+ T cells (P=0.014) were significantly greater in survivors than nonsurvivors.Conclusion: Flow cytometric assessment of PD-1 expression on memory CD8+ T cells identifies patients with poor outcomes during sepsis.Keywords: PD-1, memory T cells, sepsis, outcome

Chunyan Shao,1– 5,&ast; Ziwei Yu,1– 5,&ast; Tongwang Luo,1– 5,&ast; Bin Zhou,1– 5 Quanjiang Song,1– 5 Zhuoyue Li,1– 5 Xiaoqiang Yu,1– 5 Sheng Jiang,1– 5 Yingshan Zhou,1– 5 Wanyu Dong,1– 5 Xingdong Zhou,1– 5 Xiaodu Wang,1– 5 Houhui Song1– 5 1Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Hangzhou, Zhejiang, 311300, People’s Republic of China; 2Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics & Advanced Technology, Hangzhou, Zhejiang, 311300, People’s Republic of China; 3Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, Hangzhou, Zhejiang, 311300, People’s Republic of China; 4China-Australia Joint Laboratory for Animal Health Big Data Analytics, Hangzhou, Zhejiang, 311300, People’s Republic of China; 5College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houhui Song; Xiaodu Wang, College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China, Tel +86 15064890670 ; +86 18806537583, Email songhh@zafu.edu.cn; xdwang@zafu.edu.cnIntroduction: Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that causes significant economic losses to the global swine industry. Selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. This study aimed to investigate the inhibitory effect of chitosan-coated SeNPs (CS-SeNPs) on PRRSV replication.Methods: In this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 μM). Subsequently, the concentrations of hydrogen peroxide (H2O2) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, and nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID50, and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot.Results: The results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H2O2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The increase in apoptosis rates induced by r-PRRSV-EGFP infection was significantly decreased by CS-SeNPs inoculation through inhibiting ROS generation, JNK phosphorylation levels, and cleavage of caspase-3 and PARP mainly at 48 hpi.Conclusion: These results demonstrated that CS-SeNPs suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication, which suggested the potential antiviral activity of CS-SeNPs that deserves further investigation for clinical applications.Keywords: chitosan-coated selenium nanoparticles, PRRSV, apoptosis, ROS, JNK signaling pathways

Shuqin Chen,1,&ast; Yong Jin,2,&ast; Miao Xu,1 Pingping Zhang,3 Ye Zhou,1 Xingjun Qian,4 Qifa Song,5 Shizhong Bu,6 Jing Sun,7 Li Li1 1Department of Endocrinology and Metabolism, Ningbo First Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 2Department of Internal Medicine, Ningbo Yinzhou Second Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 3School of Public Health, Peking University, Beijing, People’s Republic of China; 4Health Management Center, Ningbo First Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 5Medical Research Center, Ningbo First Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 6Diabetes Research Center, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China; 7School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland, Australia&ast;These authors contributed equally to this workCorrespondence: Li Li, Department of Endocrinology and Metabolism, Ningbo First Hospital, Ningbo, Zhejiang Province, People’s Republic of China, Tel +8613757426626, Email lilyningbo@163.com Jing Sun, School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland, Australia, Tel +61756780924, Email j.sun@griffith.edu.auObjective: The thyroid hormone has been demonstrated to be associated with nonalcoholic fatty liver disease (NAFLD) in different populations. However, the relationship between thyroid hormone and the degree of liver steatosis in overweight/obese subjects is still unclear. Liver ultra-sound attenuation (LiSA) is a newly developed ultrasound attenuation parameter for the analysis of hepatic steatosis. The study aimed to characterize the relationship between thyroid hormone and LiSA in overweight/obese participants.Methods: This case-control study was performed in Ningbo First Hospital, China. A total of 24 lean, 66 overweight and 49 obese participants were consecutively recruited from January 2021 to May 2021. Thyroid hormone and other clinical features were measured. LiSA was acquired by using a Hepatus ultrasound machine. Multiple linear regression analyses were performed to examine associations of LiSA and clinic indices.Results: Obese subjects had higher LiSA, fT3 and TSH levels than lean participants of similar age and sex (P < 0.05). LiSA was positively associated with the fT3 level. The multiple linear regression analyses showed that fT3 (ß = 0.353, P < 0.001) was independently associated with LiSA in overweight/obese participants.Conclusion: The fT3 level was independently associated with the degree of liver steatosis among the overweight/obese participants.Keywords: LiSA, obesity, NAFLD, thyroid hormone

The phase equilibria of Bi-Te-RE (Yb, Nd, Sm, Er, Tb) at 673 K were established through equilibrated alloys. The isothermal sections of Bi-Te-RE (Yb, Nd, Sm, Er, Tb) at 673 K were established according to the result of Scanning Electron Microscopy (SEM), Electron probe micro-analysis (EPMA), and Powder X-ray diffractometry (XRD). In the Bi-Te-Yb system at 673 K, the existence of 4 three-phase equilibria (YbTe+Bi2Te3+Te, YbTe+Bi2Te3+β, YbTe+Bi+β, YbTe+Yb5Bi3+Yb4Bi3) was established, while 3 three-phase regions (NdTe2+β+Bi2Te3, NdTe2+β+Bi, Nd2Te3+Bi+BiTeNd) in Bi-Te-Nd system, 3 threephase regions (SmTe3+Te+Bi2Te3, SmTe1.8+Bi2Te3+β, SmTe1.8+β+Bi) in Bi-Te-Nd system, 3 three-phase regions (TbTe3+Te+Bi2Te3, Tb4Te7+Bi2Te3+β, TbTe+Bi+β) in Bi-Te-Nd system, and 4 three-phase regions (ErTe3+Te+Bi2Te3, ErTe3+Bi2Te3+Er2Te3, Bi2Te3+Er2Te3+β, Er2Te3+β+ErTe, β+ErTe+Bi) in Bi-Te-Nd system were also identified, respectively. Among the Bi-Te-RE (Nd, Sm, Er, Tb, Yb) systems, the solubilities of RE in Bi2Te3 were 0.19 at % Nd, 0.22 at % Sm, 0.28 at % Tb, 0.35 at %Er, and 0.37 at % Yb. In general, the maximum solubility of elements in Bi2Te3 phase alloy became larger with the increase in RE atomic number. A ternary compound BiTeNd in the Bi-Te-Nd ternary system was confirmed in this work.

Na Li, Yuxin Chu, Qibin Song Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of ChinaCorrespondence: Qibin Song Email qibinsong@whu.edu.cnPurpose: To characterize the risk factors for brain metastasis (BM) at presentation and analyze the prognostic factors for patients with small cell lung cancer (SCLC).Patients and Methods: Patients were recruited from the SEER database between 2010 and 2016. They were divided into two groups according to BM status. The incidence trends of SCLC and its BM were analyzed by joinpoint software. The risk factors for BM in SCLC were identified by binary logistic regression models. The prognostic factors for SCLC patients with BM were identified by Cox proportional hazard models.Results: The incidence of SCLC and its BM significantly decreased after 2010. Totally 11,093 patients were collected, including 1717 (15.5%) patients with BM and 9376 (84.5%) patients without BM. In multivariate logistic regression analysis, age, male and higher T stage were independent risk factors for BM in SCLC patients at presentation. SCLC patients with BM showed inferior survival to those without BM. In multivariate Cox regression analysis, increasing age, large tumor size, and higher N stage were risk factors for poor prognosis, while other race, surgery, adjuvant radiotherapy, and chemotherapy were protective factors for SCLC patients with BM. A nomogram was developed for prognosis evaluation of such patients.Conclusion: Age, male and higher T stage were risk factors for BM in SCLC patients at presentation. Increasing age, large tumor size, and advanced N stage may predict poor survival for SCLC patients with BM. Multidisciplinary therapies may provide clinical benefits. This study will help identify patients with higher BM risk and hopefully improve their clinical outcome.Keywords: small cell lung cancer, SCLC, brain metastasis, BM, survival, risk factor

Qingqing Qi,1 Qingxu Song,2 Yufeng Cheng,2 Nana Wang2 1Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Department of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Nana WangDepartment of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaEmail wangna03@163.comBackground: Prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are the most common factors to estimate nutritional and inflammatory status. The aim of this study is to systematically evaluate the prognostic significance of above nutritional and inflammatory indexes for overall survival (OS) and surgical complications in esophageal cancer patients.Methods: Esophageal cancer patients who underwent esophagectomy were retrospectively collected. PNI, NLR, PLR, and SII were introduced to evaluate the baseline nutritional and inflammatory status.Results: A total of 407 patients were included in the present study. Kaplan–Meier survival analysis revealed that PNI-low group, NLR-high group and PLR-high group, all showed a significantly shorter OS (34.38% vs 49.46%, P < 0.001; 36.13% vs 48.26%, P = 0.026 and 33.33% vs 48.52%, P = 0.001 respectively), while no significant difference was found in SII groups (42.33% vs 46.31%, P = 0.067). Multivariable analyses identified PNI (P = 0.002) was an independent prognostic factor for OS, but NLR (P = 0.672) and PLR (P = 0.186) were not. Postoperative complications occurred significantly more frequently in the low-PNI group (29.69% vs 13.26%, P < 0.001). However, no significant differences were found in the postoperative complication rates between different NLR (16.67% vs 22.69%, P = 0.124), PLR (18.03% vs 19.61%, P = 0.867) and SII (15.34% vs 20.49%, P = 0.326) groups. Multivariate logistic regression analysis showed only PNI (P = 0.008) was an independent prognostic factor for postoperative complications.Conclusion: Preoperative low PNI was not only an independent prognostic factor for worse survival in esophageal cancer patients but also associated with high incidence of postoperative complications.Keywords: esophageal cancer, prognostic nutritional index, prognosis, postoperative complications

In considering whether to retain the GRE in graduate school admissions, admissions committees often pursue two objectives: (a) performance in graduate school (e.g., admitting individuals who will perform better in classes and research), and (b) diversity/fairness (e.g., equal selection rates between demographic groups). Drawing upon HR research (adverse impact research), we address four issues in using the GRE. First, we review the tension created between two robust findings: (a) validity of the GRE for predicting graduate school performance (rooted in the principle of standardization and a half-century of educational and psychometric research), and (b) the achievement gap in test scores between demographic groups (rooted in several centuries of systemic racism). This empirical tension can often produce a local diversity-performance tradeoff for admissions committees. Second, we use Pareto-optimal tradeoff curves to formalize potential diversity-performance tradeoffs, guiding how much weight to assign the GRE in admissions. Whether dropping the GRE produces suboptimal admissions depends upon one's relative valuation of diversity versus performance. Third, we review three distinct notions of test fairness--equality, test equity, and performance equity--which have differing implications for dropping the GRE. Finally, we consider test fairness under GRE-optional admissions, noting the missing data problem when GRE is an incomplete variable.Supplemental data for this article is available online at

Sourcing algorithms are technologies used in online platforms to identify, screen, and inform potential applicants about job openings. The popularity of such technologies is rapidly increasing due to their pervasiveness in online advertising and beliefs that sourcing algorithms can decrease time to hire while improving the quality of new hires. What is little known, however, are their potential risks: sourcing algorithms could (intentionally or unintentionally) encode or exacerbate occupational demographic disparities, thereby hindering organizational diversity and/or decreasing the effectiveness of online hiring practices. Because sourcing algorithms identify and screen potential job applicants before they are made aware of employment opportunities, methods for evaluating discrimination in hiring which focus solely on job applicants (e.g., adverse impact ratio), may fail to detect the effects of discriminatory sourcing algorithms. Thus, we propose an expanded model of the employee hiring process to take into account the role of sourcing algorithms. Based on empirical approximations, we conducted a Monte Carlo simulation study to examine the magnitude and nature of sourcing algorithms' influence on hiring outcomes. Our findings suggest that sourcing algorithms could hinder the diversity of new hires while misleadingly suggesting positive diversity outcomes in personnel selection. We provide practical guidance for the use of sourcing algorithms and call for a systematic re‐examination of how to evaluate selection system fairness in the era of algorithmic recruitment. [ABSTRACT FROM AUTHOR]