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Hao Peng,1,2,* Jixue Li,1,* Xiaoru Zhou,1 Zhewen Nong,1 Ruiying Zhang,1 Pei Lu,1 Shasha Ye,1 Liping Lei,3 Chuang Qin,2 Jiangfa Li1,4,5 1Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, Liuzhou People’s Hospital, Liuzhou, 545001, People’s Republic of China; 3Department of Geriatric Medicine, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China; 4Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, People’s Republic of China; 5Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuang Qin, Department of Hepatobiliary and Pancreatic Surgery, Liuzhou People’s Hospital, No. 8, Wenchang Road, Central District, Liuzhou, 545001, People’s Republic of China, Email 382944957@qq.com Jiangfa Li, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, No. 15, Lequn Road, Xiufen District, Guilin, Guangxi, 541001, People’s Republic of China, Email 247546160@qq.comObjective: To explore a more effective and practical comprehensive index for differentiating benign from malignant obstructive jaundice by analyzing the clinical data of patients with benign obstructive jaundice (BJ) group and malignant obstructive jaundice (MJ) group.Methods: A retrospective analysis was conducted on the clinical data of 339 patients with obstructive jaundice. The cases were divided into two data sets: training cohort and validation cohort. The cases were divided into two groups: malignant and benign obstructive jaundice group. Logistic regression analysis was used to build a prediction model for judging the nature of obstructive jaundice, and the prediction model was verified using the validation cohort.Results: Multivariate analysis revealed that CEA, TBIL, and NLR were independent factors in malignant obstructive jaundice. A comprehensive index for differentiating benign from malignant obstructive jaundice was established based on these indicators. The sensitivity, specificity, and receiver operating characteristic curve of this model for differentiating benign from malignant obstructive jaundice were 79.57%, 93.26%, and 0.920, respectively.Conclusion: The prediction model based on the comprehensive index of CEA, TBIL, and NLR has a higher accuracy in differentiating malignant obstructive jaundice.Keywords: obstructive jaundice, comprehensive index, differentiation diagnosis

Abstract Recent reports suggest that plasma riboflavin may serve as a biomarker for BCRP inhibition in humans. However, the clinical data supporting this claim have been limited, with only two studies showing modest increases in riboflavin levels after administration of a BCRP inhibitor. We have recently demonstrated that co‐administration of 375 mg once daily (q.d.) cedirogant, an in vitro BCRP inhibitor, significantly increased rosuvastatin (an OATP1B1/1B3 and BCRP substrate) exposures but did not change the levels of the OATP1B endogenous biomarker coproporphyrin‐I, demonstrating that cedirogant is a clinical BCRP inhibitor. Samples from this same cedirogant clinical drug–drug interaction study were utilized to test the hypothesis that endogenous plasma riboflavin is a biomarker of BCRP inhibition. Plasma riboflavin levels in the absence of cedirogant ranged from 1 to 10 ng/mL across the 11 participants analyzed with minimal (

Lei Gao,1,2,* Yidi Xu,1,2,* Xixue Zhang,1,2 Zhaoshun Jiang,1,2 Jiajun Wu,1,2 Yanjun Dong,1,2 Ming Li,3 Liang Jin,3 Jianjian Qiu,4 Lijue You,5 Chunhui Qin,6 Weidong Gu1,2 1Department of Anaesthesiology, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Radiology, Huadong Hospital affiliated to Fudan University, Shanghai, People’s Republic of China; 4Department of Radiation Oncology, Huadong Hospital affiliated to Fudan University, Shanghai, People’s Republic of China; 5Department of Computer Center, Huadong Hospital affiliated to Fudan University, Shanghai, People’s Republic of China; 6Department of Pain Management, Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weidong Gu, Email hdmz0800@163.comBackground: Performing spinal anaesthesia in elderly patients with ligament calcification or hyperostosis is challenging for novice practitioners. This pilot study aimed to compare the effectiveness of mixed reality-assisted spinal puncture (MRasp) with that of landmark-guided spinal puncture (LGsp) by novice practitioners in elderly patients.Methods: In this pilot study, 36 patients (aged ≥ 65 years) scheduled for elective surgery under spinal anaesthesia by anaesthesiology residents were included. Patients were randomly assigned to the MRasp group (n = 18) or the LGsp group (n = 18). The outcomes included the number of needle insertion attempts, redirection attempts, passes, the rate of successful first-attempt needle insertion, the rate of successful first needle pass, the spinal puncture time, the total procedure time, and the incidence of perioperative complications.Results: The median number of needle insertion attempts was significantly fewer in the MRasp group than in the LGsp group (1.0 vs 2.0, P = 0.023). The proportion of patients with successful first-attempt needle insertion was 72.2% in the MRasp group and 44.4% in the LGsp group (P = 0.176). The incidence of perioperative complications did not significantly differ between the two groups.Conclusion: This pilot study found that novice practitioners made significantly fewer needle insertion attempts in the MRasp group compared to the LGsp group when performing spinal anaesthesia on elderly patients. A future randomized controlled trial (RCT) is warranted to validate its effectiveness.Trial Registration: This trial was registered at https://www.chictr.org.cn/showproj.html?proj=178960 (ChiCTR-IPR-2300068520). Public title: Mixed reality-assisted versus landmark-guided spinal puncture in elderly patients: a randomized controlled pilot study. Principal investigator: Lei Gao. The registration date was February 22, 2023. The date of the first participant enrolment was February 27, 2023.Plain Language Summary: We developed virtual spine-presenting technology and patented optimal trajectory design technology to assist in spinal puncture and reported that the median number of needle insertion attempts was significantly fewer in the mixed reality-assisted spinal puncture group than in the landmark-guided spinal puncture group.Keywords: augmented reality, computer simulation, mixed reality, spinal puncture

Chuang Qin,1 Xiaofei Ye,1 Hongliang Luo,1 Hu Jin,1 Qiang Liu,1 Jiangfa Li2 1Hepatobiliary Surgery, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou City, Guangxi, People’s Republic of China; 2Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical University, Guilin City, Guangxi, People’s Republic of ChinaCorrespondence: Jiangfa Li, Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical University, No. 15, Lequn Road,Xiufeng District, Guilin City, Guangxi, 541001, People’s Republic of China, Email ljf.126@qq.comPurpose: This study contributes to the evolving understanding of the pivotal involvement of Sirtuins (SIRTs) in various human cancers, with a particular focus on elucidating their expression patterns and clinical relevance within the context of hepatocellular carcinoma (HCC). The investigation involves a comprehensive analysis of mRNA expression and prognostic implications associated with distinct SIRTs in HCC.Patients and Methods: Initial data pertaining to SIRT expression in HCC patients were collated from publicly accessible databases. Subsequently, the expression levels of select members of the SIRT family were validated using clinicopathological specimens from HCC patients. Additionally, HCC tissue microarray was employed to scrutinize the correlation between SIRT7 expression and HCC prognosis.Results: The findings indicated a substantial upregulation of SIRT2, SIRT3, SIRT4, SIRT6, and SIRT7 in HCC tissues. Survival analysis underscored a pronounced association between elevated mRNA levels of SIRT3, SIRT6, and SIRT7 and an adverse prognosis for HCC patients. Particularly, SIRT7 emerged as a potential independent risk factor for poor prognosis in HCC patients. Examination of the HCC tissue microarray revealed heightened expression of SIRT7 in 68 cases (54.8%) of HCC tissues. Multivariate analysis established high SIRT7 expression as an independent risk factor for diminished Disease-Free Survival (DFS) and Overall Survival (OS) in HCC patients.Conclusion: The aberrant expression of SIRT7 presents itself may be as a novel biomarker for predicting the prognosis of HCC patients.Keywords: HCC, microarray, prognosis, SIRT7, survivor

Zhiping Qi,1 Su Pan,1 Xiaoyu Yang,1 Renfeng Zhang,1 Cheng Qin,1 Hongye Yan,1 Longchuan Zhu,1 Weijian Kong2 1Department of Orthopedic Surgery, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Weijian Kong; Longchuan Zhu, Email kongweijian0613@sina.com; zhulongchuan0504@163.comPurpose: Spinal cord injury (SCI) is an incurable and disabling event that is accompanied by complex inflammation-related pathological processes, such as the production of excessive reactive oxygen species (ROS) by infiltrating inflammatory immune cells and their release into the extracellular microenvironment, resulting in extensive apoptosis of endogenous neural stem cells. In this study, we noticed the neuroregeneration-promoting effect as well as the ability of the innovative treatment method of FTY720-CDs@GelMA paired with NSCs to increase motor function recovery in a rat spinal cord injury model.Methods: Carbon dots (CDs) and fingolimod (FTY720) were added to a hydrogel created by chemical cross-linking GelMA (FTY720-CDs@GelMA). The basic properties of FTY720-CDs@GelMA hydrogels were investigated using TEM, SEM, XPS, and FTIR. The swelling and degradation rates of FTY720-CDs@GelMA hydrogels were measured, and each group’s ability to scavenge reactive oxygen species was investigated. The in vitro biocompatibility of FTY720-CDs@GelMA hydrogels was assessed using neural stem cells. The regeneration of the spinal cord and recovery of motor function in rats were studied following co-treatment of spinal cord injury using FTY720-CDs@GelMA hydrogel in combination with NSCs, utilising rats with spinal cord injuries as a model. Histological and immunofluorescence labelling were used to determine the regeneration of axons and neurons. The recovery of motor function in rats was assessed using the BBB score.Results: The hydrogel boosted neurogenesis and axonal regeneration by eliminating excess ROS and restoring the regenerative environment. The hydrogel efficiently contained brain stem cells and demonstrated strong neuroprotective effects in vivo by lowering endogenous ROS generation and mitigating ROS-mediated oxidative stress. In a follow-up investigation, we discovered that FTY720-CDs@GelMA hydrogel could dramatically boost NSC proliferation while also promoting neuronal regeneration and synaptic formation, hence lowering cavity area.Conclusion: Our findings suggest that the innovative treatment of FTY720-CDs@GelMA paired with NSCs can effectively improve functional recovery in SCI patients, making it a promising therapeutic alternative for SCI.Keywords: spinal cord injury, carbon dots, FTY720, neural stem cells, hydrogel, GelMA, nerve damage repair

Xiaoyan Sai,* Chu Qin,* Zixiao Zhang,* Haoda Yu, Tao Bian Department of Respiratory Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haoda Yu, Department of Respiratory Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China, Email yhd9988@sina.com Tao Bian, Department of Respiratory Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China, Email biantaophd@126.comBackground: This study sought to explore the underlying mechanism of miR-21 mediated apoptosis and inflammation in chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS).Methods: We detected levels and PTEN/Akt/NF-κB axis protein levels in peripheral lung tissues of COPD patients and CS-exposed mice and HBE cells. Western blotting assay was used to determine the expression of cleaved caspase-3. IL-6 and IL-8 protein was detected in cell supernatant from cells by ELISA. HBE cells were transfected with a miR-21 inhibitor, and co-culture with A549.Results: Increased miR-21 expression, reduced PTEN expression and following activation of Akt in in peripheral lung tissues of COPD patients and CS-exposed mice and HBE cells. Inhibition of miR-21 showed enhanced PTEN levels and reduced the expression of phosphorylated form of Akt and NF-κB. Decreased expression of cleaved caspase-3, IL-6 and IL-8 in A549 cells co cultured with HBE cells transfected with miR-21 inhibitor compared with transfected with miR-21 control inhibitor.Conclusion: MiR-21 contributes to COPD pathogenesis by modulating apoptosis and inflammation through the PTEN/Akt/NF-κB pathway. Targeting miR-21 may increase PTEN expression and inhibit Akt/NF-κB pathway, offering potential diagnostic and therapeutic value in COPD management.Keywords: COPD, miR-21, PTEN/Akt/NF-κB axis, apoptosis, inflammation

Kai Chen,1 Yaohui Yu,1 Yishu Wang,1 Yi Zhu,1 Chaoren Qin,1 Jintao Xu,1 Xiangjie Zou,2 Tianqi Tao,1 Yang Li,1 Yiqiu Jiang1 1Department of Sports Medicine and Joint Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yiqiu Jiang, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, People’s Republic of China, Email jyq_3000@163.comBackground: Astragalus membranaceus (AM) shows promise as a therapeutic agent for osteoarthritis (OA), a debilitating condition with high disability rates. OA exacerbation is linked to chondrocyte ferroptosis, yet the precise pharmacological mechanisms of AM remain unclear.Methods: We validated AM’s protective efficacy in an anterior cruciate ligament transection (ACLT) mouse model of OA. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database was utilized to identify AM’s active components and their targets. FerrDb (a database for regulators and markers of ferroptosis and ferroptosis-disease associations) pinpointed ferroptosis-related targets, while GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), Therapeutic Target Database (TTD), and DrugBank sourced OA-related genes. Molecular docking analysis further validated these targets. Ultimately, the validation of the results was accomplished through in vitro experiments.Results: AM exhibited anabolic effects and suppressed catabolism in OA chondrocytes. Network pharmacology identified 19 common genes, and molecular docking suggested quercetin, an AM constituent, interacts with key proteins like HO-1 and NRF2 to inhibit chondrocyte ferroptosis. In vitro experiments confirmed AM’s ability to modulate the NRF2/HO-1 pathway via quercetin, mitigating chondrocyte ferroptosis.Conclusion: This study elucidates how AM regulates chondrocyte ferroptosis, impacting OA progression, providing a theoretical basis and experimental support for AM’s scientific application.Keywords: systematic pharmacology, osteoarthritis, ferroptosis, Astragalus membranaceus, quercetin

Cheng Qin, Zhiping Qi, Su Pan, Peng Xia, Weijian Kong, Bin Sun, Haorui Du, Renfeng Zhang, Longchuan Zhu, Dinghai Zhou, Xiaoyu Yang Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Xiaoyu Yang, Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, TX, 130041, People’s Republic of China, Email yangxiaoy@jlu.edu.cnAbstract: Spinal cord injury (SCI) treatment represents a major challenge in clinical practice. In recent years, the rapid development of neural tissue engineering technology has provided a new therapeutic approach for spinal cord injury repair. Implanting functionalized electroconductive hydrogels (ECH) in the injury area has been shown to promote axonal regeneration and facilitate the generation of neuronal circuits by reshaping the microenvironment of SCI. ECH not only facilitate intercellular electrical signaling but, when combined with electrical stimulation, enable the transmission of electrical signals to electroactive tissue and activate bioelectric signaling pathways, thereby promoting neural tissue repair. Therefore, the implantation of ECH into damaged tissues can effectively restore physiological functions related to electrical conduction. This article focuses on the dynamic pathophysiological changes in the SCI microenvironment and discusses the mechanisms of electrical stimulation/signal in the process of SCI repair. By examining electrical activity during nerve repair, we provide insights into the mechanisms behind electrical stimulation and signaling during SCI repair. We classify conductive biomaterials, and offer an overview of the current applications and research progress of conductive hydrogels in spinal cord repair and regeneration, aiming to provide a reference for future explorations and developments in spinal cord regeneration strategies. Keywords: neural tissue engineering, electrical stimulation, electrical signal, conductive biomaterials, spinal cord injury microenvironment

Bangzhen Ma,1,2 Yisheng Zhao,3 Xiaoli Liu,4 Mengping Huo,2 Jinghong Wang,2 Jiwei Ma,2 Yang Zhang,2 Chengkun Qin1,2 1Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 2Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 3School of Pharmaceutical Sciences, Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong, 250353, People’s Republic of China; 4Department of Hernia and Abdominal Wall Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of ChinaCorrespondence: Chengkun Qin; Yang Zhang, Shandong Provincial Hospital, 324 Jingwu Road, Huaiyin District, Jinan City, Shandong Province, People’s Republic of China, Email qinchengkun_slyy@163.com; zhangyang@sdfmu.edu.cnBackground: Though nanomedicine-based photothermal therapy (PTT) has demonstrated promising prospect in tumor treatment due to its high therapeutic efficiency and controllable range, the overexpression of heat shock proteins (HSPs) during PTT can lead to intracellular thermal resistance and reduce its effectiveness. Reactive oxygen species (ROS), followed by the application of chemodynamic therapy (CDT) and photodynamic therapy (PDT), can eliminate HSPs and overcome thermal resistance. However, the tumor microenvironment, including hypoxia and glutathione (GSH) overexpression, impedes the production of ROS and therapeutic efficacy of CDT and PDT. Therefore, we proposed a multifunctional nanoplatform (HMPB@TCPP-Cu) driving PTT/ PDT/ CDT synergistic therapy for tumor treatment via modulating ROS and HSPs.Methods and Results: In this work, a novel nanoplatform (HMPB@TCPP-Cu) composed of O2/PTT supplier HMPB (hollow mesoporous Prussian blue) and the loaded PDT/CDT agent (TCPP-Cu2+) was prepared. HMPB acts as an photothermal converter, effectively raising the tumor temperature and inducing apoptosis. HMPB is also a potent catalase-like nanozyme, which can catalyze hydrogen peroxide into oxygen and reduce tumor hypoxia, thus elevating the efficiency of ROS production and the effectiveness of PDT with the wing of sonosensitizer-TCPP. The intracellular glutathione(GSH) was depleted by Cu2+ and •OH was generated along with the Cu2+/Cu+ converting and Cu+-mediated Fenton-like reaction. Subsequently, the increased levels of ROS effectively eliminate intratumoral thermal resistance. The HMPB@TCPP-Cu has achieved synergistic PTT/PDT/CDT for hepatoblastoma treatment and significant inhibition of tumor growth was detected both in vitro and in vivo.Conclusion: This study presents a multifunctional nanoplatform that combines photothermal/ chemodynamic/ photodynamic therapy for efficient hepatoblastoma treatment via modulating ROS and HSPs. Collectively, this study provides an appealing strategy in the cleavage of thermal resistance and a novel assistance and enhancement on thermal-related therapies.Keywords: photothermal therapy, heat shock protein, reactive oxygen species, photodynamic therapy, chemodynamic therapy

Jiajun Wu,1,2,* Lei Gao,1,2,* Qiao Shi,3 Chunhui Qin,4 Kai Xu,1,2 Zhaoshun Jiang,1,2 Xixue Zhang,1,2 Ming Li,5 Jianjian Qiu,6,* Weidong Gu1,2,* 1Department of Anesthesiology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, 200040, People’s Republic of China; 3Department of Anesthesiology, International Peace Maternity and Child Health Hospital of China, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China; 4Department of Pain Management, Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 5Department of Radiology, Huadong Hospital affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 6Department of Radiation Oncology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weidong Gu; Jianjian Qiu, Email hdmz0800@163.com; qiujianjian@fudan.edu.cnPurpose: To evaluate the accuracy of mixed reality (MR)-guided visualization technology for spinal puncture (MRsp).Methods: MRsp involved the following three steps: 1. Lumbar spine computed tomography (CT) data were obtained to reconstruct virtual 3D images, which were imported into a HoloLens (2nd gen). 2. The patented MR system quickly recognized the spatial orientation and superimposed the virtual image over the real spine in the HoloLens. 3. The operator performed the spinal puncture with structural information provided by the virtual image. A posture fixation cushion was used to keep the subjects’ lateral decubitus position consistent. 12 subjects were recruited to verify the setup error and the registration error. The setup error was calculated using the first two CT scans and measuring the displacement of two location markers. The projection points of the upper edge of the L3 spinous process (L3↑), the lower edge of the L3 spinous process (L3↓), and the lower edge of the L4 spinous process (L4↓) in the virtual image were positioned and marked on the skin as the registration markers. A third CT scan was performed to determine the registration error by measuring the displacement between the three registration markers and the corresponding real spinous process edges.Results: The setup errors in the position of the cranial location marker between CT scans along the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) axes of the CT bed measured 0.09 ± 0.06 cm, 0.30 ± 0.28 cm, and 0.22 ± 0.12 cm, respectively, while those of the position of the caudal location marker measured 0.08 ± 0.06 cm, 0.29 ± 0.18 cm, and 0.18 ± 0.10 cm, respectively. The registration errors between the three registration markers and the subject’s real L3↑, L3↓, and L4↓ were 0.11 ± 0.09 cm, 0.15 ± 0.13 cm, and 0.13 ± 0.10 cm, respectively, in the SI direction.Conclusion: This MR-guided visualization technology for spinal puncture can accurately and quickly superimpose the reconstructed 3D CT images over a real human spine.Keywords: mixed reality, spinal puncture, immobilization, superimposition, setup error, registration error

Jianzhuang Guo,1 Chengwei Qin,2 Xiangdong Li,1 Xiaoxuan Zhuang3 1Department of Clinical Laboratory, The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital), Jinan, Shandong, People’s Republic of China; 2Department of Anesthesiology, Shandong Second Provincial General Hospital, Jinan, Shandong, People’s Republic of China; 3International Medical College of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Xiangdong Li; Chengwei Qin, Email lixd03@21cn.com; qinchengweiqcw8k@126.comObjective: To investigate the changes in the proportion of peripheral blood lymphocytes and the expression of HLA II molecules in lymphocytes during acute rejection after renal transplantation.Methods: Thirty-five patients who had undergone renal transplantation were selected. Eighteen patients with clinical and pathological confirmed acute rejection were selected as the test group, and twelve patients without clinical acute rejection symptoms were selected as the control group. Flow cytometry analysis was used to determine the proportion of peripheral blood lymphocytes. The mRNA and protein expression of HLA II molecules on peripheral blood lymphocytes were detected using real-time fluorescence quantification and immunoblotting, respectively.Results: The proportion of T lymphocytes, B lymphocytes, and CD4CD8 double positive T cells in the Control Group were 67.48% ± 5.35%, 10.82% ± 1.26%, and 0.88% ± 0.06%, respectively, and in the Test Group were 87.52% ± 6.28%, 3.36% ± 0.26%, and 0.34% ± 0.03%, with a significant difference respectively. The mRNA and protein expressions of HLA II molecules of peripheral blood B lymphocytes in the control group were significantly higher that these in the test group.Conclusion: The proportion of peripheral blood T lymphocytes, B lymphocytes, CD4CD8 double positive T cells, and the expression of HLA II molecules of peripheral blood lymphocytes can all indicate the occurrence of acute renal transplantation rejection, which were exceedingly useful to clinicians in judging the acute rejection of renal transplantation in the early stages.Keywords: acute rejection, HLA II molecules, kidney transplantation, peripheral blood lymphocytes, flow cytometric analysis

Chao Xiao,1,2,* Xiuen Chen,1,* Lizhi Lu,3 Ziming Ye,2 Xiangren Chen,2 Meiyu Dong,4 Chao Qin2 1Department of Neurology, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Neurology, Forsea Life Insurance Nanning Hospital, Nanning, People’s Republic of China; 4The First Clinical Medical College of Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao Qin, Department of Neurology, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email mdqc2019@126.comObjective: This study aimed to investigate the feasibility and clinical efficacy of endovascular recanalization in patients with chronic internal carotid artery occlusion (CICAO) and explore the application value of computed tomography perfusion (CTP) in endovascular recanalization.Methods: This non-randomized controlled study included 41 patients with CICAO. All patients received active medical treatment. In this study, patients with successful endovascular recanalization and those who refused endovascular recanalization were included in the recanalization and medication groups, respectively. Before and 90 days after treatment, cognitive function was evaluated using the Montreal Cognitive Function Assessment, and neurological function was evaluated using the National Institutes of Health Stroke Scale and modified Rankin scale. For patients with successful endovascular recanalization, brain CTP imaging was performed to evaluate hemodynamic changes in patients with CICAO before and three days after treatment.Results: Overall, 41 symptomatic patients with CICAO were included, and 20 patients received endovascular recanalization therapy, with a success rate of 60% (12/20). The perioperative complication rate was 15% (3/20); there were no events such as hyperperfusion, distal embolism, vascular rupture, or cerebral hemorrhage, and no stroke-related or death-related events. Patients were divided into a medication group (n=21) and recanalization group (n=12). After 90 days of follow-up, patients in the recanalization group showed greater improvement in overall cognitive and neurological function. In addition, successful endovascular recanalization significantly improved cerebral blood perfusion on the occluded side of patients with CICAO.Conclusion: Successful recanalization can effectively improve the overall cognitive and neurological functions of patients in the short term. CTP can be used to quantitatively evaluate not only the cerebral hemodynamic changes after internal carotid artery occlusion but also the improvement of cerebral blood perfusion after successful endovascular recanalization, which provides a reliable method for postoperative follow-up.Keywords: hemodynamics, chronic internal carotid artery occlusion, endovascular recanalization, clinical effect

Shuaiyu Chen,1,&ast; Yan E,1,&ast; Xiaohao Zhang,1,&ast; Bin Wei,1 Siyu Wang,1 Zhaohan Xu,1 Pengyu Gong,2 Yi Xie,3 Chunhua Qin,1 Yingdong Zhang1 1Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China; 3Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhua Qin; Yingdong Zhang, Department of Neurology, Nanjing First Hospital, Nanjing Medical University, No. 68 Changle Road, Nanjing, People’s Republic of China, Tel/Fax +86 2552271000, Email 15366136164@163.com; zhangyingdong@njmu.edu.cnBackground and Purpose: Insulin resistance plays a pivotal role in the pathophysiology of ischemic stroke. This study aimed to determine the relationship between the novel metabolic score for insulin resistance (METS-IR) and symptomatic intracranial hemorrhage (sICH) after endovascular thrombectomy (EVT) in stroke patients.Methods: We retrospectively included patients with large artery occlusion in the anterior circulation and treated by EVT from 2 stroke centers (Nanjing First Hospital from September 2019 to April 2022, and Jinling Hospital from September 2019 to July 2021). The METS-IR was used as an alternative marker of insulin resistance and calculated using laboratory data after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification.Results: Of the 410 enrolled patients (mean age, 69.8 ± 11.7 years; 60.7% men), 50 (12.2%) were diagnosed as sICH. After adjusting for demographic characteristics, poor collateral status, and other potential confounders, higher METS-IR was revealed to be independently associated with sICH (odds ratio, 1.076; 95% confidence interval, 1.034− 1.120; P = 0.001). Similar significant results were obtained when defining METS-IR as a categorical variable. The restricted cubic spline uncovered a linear relationship between METS-IR and sICH (P < 0.001 for linearity). Furthermore, adding METS-IR to the conventional model significantly improved the risk prediction for sICH (net reclassification improvement = 15.8%, P = 0.035; integrated discrimination index = 2.6%; P = 0.017).Conclusion: This study demonstrated a significant association between METS-IR score and sICH in ischemic stroke patients treated with EVT. It could help monitor and manage sICH in patients after EVT.Keywords: METS-IR, insulin resistance, ischemic stroke, symptomatic intracranial hemorrhage, endovascular thrombectomy

Fuda Li,1 Bangzhe Tan,1 Caifeng Qin,2 Yanfei Ke1 1Business School, Hunan Normal University, Changsha, People’s Republic of China; 2Krirk University, Bangkok, ThailandCorrespondence: Caifeng Qin, International College, Krirk University, No. 963, Guangzhou Avenue North, Tianhe District, Guangzhou, Guangdong, 510510, People’s Republic of China, Tel +86 18022127963, Email 705886843@qq.comPurpose and Discussion: Individual knowledge and skills are important factors in promoting employee innovation. Research shows that a large number of employees perceive that their qualification level exceeds the formal requirements of the position. These people may spontaneously seek to change their current situation and dare to develop innovative ideas in an unconventional way. The purpose of this study is to explore the relationship between overqualification and bootlegging through the mediating effect of proactive career behavior on the basis of the human environment matching theory. This study also explored the moderating effect of a proactive personality between overqualification and bootlegging. This study shows that leaders should prioritize the potential of overqualified employees, encourage them to engage in challenging tasks, broaden the innovation channels of individuals and organizations, and monitor bootlegging activities. Highly motivated employees with overqualifications are more likely to actively plan and manage their careers, they will actively seek innovation to solve problems when encountering obstacles in their career development.Participants and Methods: In this study, 457 questionnaires were collected from employees of many enterprises in Hunan Province and Guangdong Province of China. Partial least squares structural equation model based on variance (PLS-SEM) was used for data analysis.Results: The results of the study reveal that there is a significant relationship between overqualification and bootlegging. In addition, proactive career behavior plays an intermediary role in the relationship between overqualification and bootlegging. Moreover, a proactive personality moderates the relationship between overqualification and bootlegging. Finally, the relationship between overqualification and bootlegging is stronger when a proactive personality is strong.Keywords: overqualification, bootlegging, proactive career behavior, proactive personality, person-environment fit theory

Kaifang Wang,1,2 Xin Ning,1 Chuanyue Qin,1 Jianlin Wang,1 Wenjie Yan,1 Xin Zhou,1 Deping Wang,1 Jimin Cao,1 Yanlin Feng1 1Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Cardiology, First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Jimin Cao; Yanlin Feng, Email caojimin@sxmu.edu.cn; feng@sxmu.edu.cnIntroduction: The wide application of copper oxide nanoparticles (CuO NPs) in industry, agriculture, environmental remediation, and biomedicine has increased the risk of human exposure to CuO NPs. Recent studies suggested that CuO NPs have genotoxic and cytotoxic effects on various cells. However, little is known about the toxicity of CuO NPs on major peripheral organs after respiratory exposure.Materials and Methods: We investigated the toxicities of CuO NPs on human bronchial epithelial (BEAS-2B) and human cardiomyocytes (AC16) cells in vitro, and on the lungs, liver, kidneys, and heart of spontaneously hypertensive rats (SHRs) at 24 and 72 h after intrabronchial instillation in vivo.Results: CuO NPs induced concentration-dependent toxicities in both BEAS-2B and AC16 cells mainly through hierarchical oxidative stress mechanisms, involving generation of reactive oxygen species (ROS), upregulation of heme oxygenase-1 (HO-1), mitochondrial dysfunction, and secretion of proinflammatory and profibrogenic cytokines. Respiratory exposure to CuO NPs induced acute multiple organ injuries in SHRs manifesting through inflammation and fibrosis. However, cardiac injury was relatively less severe than injuries in the lungs, liver, and kidneys. Upregulation of serum C-reaction protein (CRP), tumor necrosis factor α (TNF-α), intercellular adhesion molecule 1 (ICAM-1), endothelin-1 (ET-1), angiotensin converting enzyme (ACE), and von Willebrand factor (vWF) after exposure to CuO NPs indicated systematic inflammation, endothelial injury, and potential prothrombosis.Conclusion: Respiratory exposure to CuO NPs induced acute injuries in main peripheral organs, including the lungs, liver, kidneys, and heart. Individuals with existing cardiovascular diseases were susceptible to exposure to CuO NPs. This study provides a warning about the extensive toxic effects of CuO NPs, especially in the susceptible population.Keywords: CuO nanoparticle, nanotoxicology, hierarchical oxidative stress response, intratracheal instillation, spontaneously hypertensive rat

Chunmei Qin,1– 3 Yiting Wang,1,2 Lijun Zhao,1,2 Junlin Zhang,1,2 Honghong Ren,1,2 Yutong Zou,1,2 Yucheng Wu,1,2 Tingli Wang,1,2 Yuancheng Zhao,1,2 Rui Zhang,1,2 Huan Xu,4 Jie Zhang,5 Mark E Cooper,6 Fang Liu1,2 1Division of Nephrology, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Diabetic Kidney Disease, Centre of Diabetes and Metabolism Research, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 3Department of Nephrology, Luzhou People’s Hospital, Luzhou, People’s Republic of China; 4Division of Pathology, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 5Key Laboratory of Transplant Engineering and Immunology, Chengdu, People’s Republic of China; 6Department of Diabetes, Central Clinical School, Monash University, Melbourne, AustraliaCorrespondence: Fang Liu, Division of Nephrology, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-18980601214, Fax +86-28-85422335, Email liufangfh@163.comObjective: The rate of kidney function decline in patients with diabetic kidney disease (DKD) is known to differ. This study analyzed the clinicopathologic features and related risk factors affecting long-term renal survival in Chinese type 2 diabetic patients with rapid estimated glomerular filtration rate (eGFR) decline.Methods: In this retrospective descriptive study, 191 DKD patients were first classified as rapid eGFR decliners and slow eGFR decliners on the basis of the median eGFR slope value (− 8.0 mL/min/1.73 m2/year). In total, 96 patients with rapid eGFR decline were included in the analyses and subsequently allocated to end-stage renal disease (ESRD) and non-ESRD groups. Baseline clinicopathological data of rapid eGFR decliners were collected. Cox proportional hazard analysis was performed to calculate the hazard ratios (HRs) for progression to ESRD.Results: During a median follow-up of 25 months, 52 (54.2%) rapid eGFR decliners progressed to ESRD. These 52 rapid eGFR decliners had poorer renal function, lower hemoglobin and albumin concentrations, higher total cholesterol and baseline proteinuria levels, and more severe interstitial inflammation than those who did not progress to ESRD. After adjustment for age, gender, baseline eGFR, proteinuria, hemoglobin level, serum albumin concentration, and histopathologic parameters, multivariate Cox proportional hazard analysis revealed that eGFR (HR 0.973, 95% CI 0.956– 0.989) and proteinuria (HR 1.125, 95% CI 1.030– 1.228) were associated with the increased risk of progression to ESRD.Conclusion: Higher proteinuria and lower eGFR were independent risk factors for renal progression in Chinese patients with type 2 diabetes and rapid eGFR decline.Keywords: diabetic kidney disease, rapid eGFR decline, clinical, pathological, type 2 diabetes

Recent reports suggest that plasma riboflavin may serve as a biomarker for BCRP inhibition in humans. However, the clinical data supporting this claim have been limited, with only two studies showing modest increases in riboflavin levels after administration of a BCRP inhibitor. We have recently demonstrated that co‐administration of 375 mg once daily (q.d.) cedirogant, an in vitro BCRP inhibitor, significantly increased rosuvastatin (an OATP1B1/1B3 and BCRP substrate) exposures but did not change the levels of the OATP1B endogenous biomarker coproporphyrin‐I, demonstrating that cedirogant is a clinical BCRP inhibitor. Samples from this same cedirogant clinical drug–drug interaction study were utilized to test the hypothesis that endogenous plasma riboflavin is a biomarker of BCRP inhibition. Plasma riboflavin levels in the absence of cedirogant ranged from 1 to 10 ng/mL across the 11 participants analyzed with minimal (<20%) intrasubject variability over a 24‐hour interval. Contrary to expectations, 375 mg q.d. oral administration of cedirogant did not increase riboflavin levels. These data strongly suggest that endogenous plasma riboflavin is not a viable biomarker for BCRP inhibition in humans. [ABSTRACT FROM AUTHOR]

Alterations to post-translational crosslinking modifications in the extracellular matrix (ECM) are known to drive the pathogenesis of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Thus, the methodology for measuring crosslinking dynamics is valuable for understanding disease progression. The existing crosslinking analysis sample preparation and liquid chromatography tandem mass spectrometry (LC-MS/MS) methods are typically labor-intensive and time-consuming which limits throughput. We, therefore, developed a rapid approach minimizing specialized equipment and hands-on time. The LC-MS/MS sample analysis time was reduced to two minutes per sample. We then improved the analytical integrity of the method by developing a novel surrogate matrix approach for the dihydroxylysinonorleucine (DHLNL) crosslink. By modifying sample preparation, we prepared a tissue-based surrogate matrix with undetectable levels of endogenous DHLNL, providing a strategy for quantifying this crosslink with a more relevant standard matrix. We then applied this rapid methodology to evaluating crosslinking in lung fibrosis. We showed an increase in DHLNL in human IPF lung relative to healthy donors, as well as in a fibrotic mouse model. Finally, we demonstrated that this increase in DHLNL could be mitigated with an anti-fibrotic compound, suggesting that this assay has potential for evaluating pharmaceutical compound efficacy. [ABSTRACT FROM AUTHOR]

Cheng Lin,1,2 Xuemei Wang,1 Chaosheng Qin,2 Jingchen Liu1 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Anesthesiology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541001, People’s Republic of ChinaCorrespondence: Jingchen Liu, Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86 18107830301, Fax +86 7715356250, Email jingchenliudoc@sina.comObjective: The quadratus lumborum block provides postoperative analgesia for patients undergoing abdominal surgery, although there are three common approaches to perform this block. The present meta-analysis investigated the effectiveness of posterior quadratus lumborum block (QLB2) after surgery.Methods: PubMed, Embase, and the Cochrane Central Register were searched from inception to 26 August 2021 for randomized controlled trials that evaluated the analgesic efficacy of QLB2 vs control (placebo or no block). The primary outcomes were pain scores at 6 h, 12 h, and 24 h after surgery. The secondary outcomes were morphine consumption at 24 h after surgery and the postoperative complications.Results: The present meta-analysis included 14 studies conducted with a total of 1001 patients. In comparison to control group, the QLB2 group presented significantly lower rest pain scores at 6 h (SMD − 0.59; 95% CI: − 1.05, − 0.12; p = 0.01, I2 = 84%; GRADE = moderate), 12 h (SMD: – 0.83; 95% CI: – 1.47, – 0.19; p = 0.01; I2 = 88%; GRADE = low), and 24 h (SMD: – 0.37; 95% CI: – 0.71, – 0.03; p = 0.03; I2 = 80%; GRADE = moderate) after surgery. The dynamic pain scores were significantly reduced, compared to control, in the QLB2 group at 12 h (SMD: – 0.93; 95% CI: – 1.52, – 0.33; p = 0.002; I2 = 83%; GRADE = low) and 24 h (SMD: – 0.52; 95% CI: – 0.93, – 0.11; p = 0.01; I2 = 83%; GRADE = moderate) after surgery. In addition, the QLB2 group presented reduced postoperative opioid consumption at 24 h (SMD: – 0.45; 95% CI: – 0.86, – 0.03; p = 0.03; I2 = 78%; GRADE = moderate). The subgroup analyses revealed that the analgesic benefit of QLB2 did not persist beyond 24 h when the patients were under spinal anesthesia.Conclusion: Ultrasound-guided QLB2 could provide effective analgesia for patients under general anesthesia by decreasing the intensity of pain and opioid requirement when used within 24 h after abdominal surgery.Keywords: quadratus lumborum block, postoperative pain, opioid, analgesia

Chuying Qin,1 Yinhuai Wang,1 Sai Li,2 Yuanyuan Tang,3 Yunliang Gao1 1Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China; 2Acupuncture and Tuina School, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 3Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of ChinaCorrespondence: Yunliang Gao, Department of Urology, The Second Xiangya Hospital, Central South University, No. 139. Renmin Road, Changsha, 410011, People’s Republic of China, Email yunliang.gao@csu.edu.cnIntroductions: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a poorly understood chronic disorder characterized by bladder-related pain. Chronic psychological stress plays a key role in the exacerbation and development of IC/BPS via unclear mechanisms. This study aimed to investigate the role of endothelin 1 (ET-1) and its receptors in the development of chronic stress-induced bladder dysfunction.Methods: Wistar‐Kyoto rats were exposed to chronic (10 days) water avoidance stress (WAS) or sham stress, with subgroups receiving capsaicin pretreatment to desensitize C-fiber afferents. Thereafter, cystometrograms (CMG) were obtained with visceromotor response (VMR) simultaneously during intravesical saline or ET-1 infusion. CMG recordings were analyzed for the first and the continuous voiding cycles, respectively. Endothelin receptor type A (ETAR) expression was examined in the bladder tissues and L6-S1 dorsal root ganglions (DRGs). Toluidine blue staining was to check the bladder inflammation and double-labeling immunofluorescence (IF) staining was to identify the locations of ETAR, respectively.Results: During saline infusion, WAS rats elicited significant decreases in pressure threshold (PT) and in the ratio of VMR threshold/maximum intravesical pressure (IVPmax), and a significant increase in VMR duration and area under the curve (AUC). ET-1 infusion induced similar alternations in WAS rats, but further significantly diminished the pressure to trigger PT and VMR, together with a more forceful and longer VMR. The sole effect of WAS exposure or ET-1 administration on the micturition reflex could be suppressed by capsaicin pretreatment. WAS exposure significantly induced an increased number of total mast cells in the bladder, while capsaicin pretreatment possibly antagonized them. No significant difference in ETAR expression was found between all groups. IF staining indicated the co-localization of ETAR and calcitonin gene-related peptides in both bladder and DRGs.Conclusion: The activation of ET-1 receptors could enhance chronic stress-induced bladder hypersensitization and hyperalgesia through capsaicin-sensitive C-fiber afferents. Targeting the endothelin pathway may have therapeutic value for IC/BPS.Keywords: endothelin, endothelin receptor type A, interstitial cystitis, pain, psychological stress, voiding dysfunction

Zixiao Zhang,1,&ast; Congli Fu,1,2,&ast; Jiaxin Liu,1 Xiaoyan Sai,1 Chu Qin,1 Tingting Di,1 Yue Yang,1 Yan Wu,1 Tao Bian1 1Department of Respiratory Medicine, Wuxi People’s Hospital Affiliated to Nanjing, Medical University, Wuxi, Jiangsu, 214023, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Bian; Yan WuDepartment of Respiratory Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of ChinaEmail btaophd@sina.com; wuyanyangting@163.comBackground: Nuclear factor E2-related factor 2 (Nrf2) is involved in oxidative stress and lung inflammation and regulates the etiology of chronic obstructive pulmonary disease (COPD). Ferroptosis is characterized by the accumulation of lipid reactive oxygen species (ROS) via ferrous ion-dependent Fenton reactions and is involved in COPD. However, the role of Nrf2 in ferroptosis and its epigenetic regulation in the pathogenesis of COPD remain unclear.Methods: Ferroptosis was detected by 4-HNE, MDA, C11BODIPY, DCFH-DA, Peals’ staining and CCK-8 assays. qPCR and Western blotting were performed to examine the Nrf2 levels in peripheral lung tissues, primary epithelial cells collected from patients with COPD and subjects with normal pulmonary function (never-smoker [control-NS]; smoker [control-S]), and cigarette smoke extract (CSE)-treated human bronchial epithelial (HBE) cells. ELISA was used to quantify IL-8 and IL-1β levels. Methylation of the Nrf2 promoter was analyzed by bisulfite sequencing and pyrosequencing.Results: Ferroptosis was involved in COPD and glutathione peroxidase 4 (GPX4) expression was downregulated in the COPD group. Reactive oxygen species (ROS), lipid peroxides and MDA were increased, but GPX4 and SOD were exhausted in CSE-treated HBE cells. The production of IL-1β and IL-8 was promoted in HBE cells in response to CSE but could be reversed by the ferroptosis inhibitor fer-1. The Nrf2 level was significantly decreased in the COPD group compared with the control-S and control-NS groups. Increased Nrf2 expression enhanced GPX4 and SOD levels and inhibited ferroptosis and proinflammatory cytokines in the supernatant. Inhibition of GPX4 reversed the effect of Nrf2 overexpression and promoted ferroptosis. Two specific CpG sites within the Nrf2 promoter were hypermethylated in the COPD group. Similarly, CSE-treated HBE cells exhibited hypermethylation of the Nrf2 gene.Conclusion: Nrf2 expression was downregulated in the lungs of COPD patients due to hypermethylation of the Nrf2 promoter, inhibiting Nrf2/GPX4 and ferroptosis, which is related to the initiation and progression of COPD. Targeting Nrf2/GPX4 may inhibit ferroptosis, which could provide strategies to delay or treat COPD.Keywords: COPD, Nrf2, ferroptosis, GPX4, DNA methylation, oxidative stress, inflammation