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Yinxue Zhou,1,* Tingyu Wu,2,* Jiaxing Sun,1 Huanhuan Bi,1 Yuting Xiao,1 Yanmei Shao,1 Weizhong Han,1 Hongmei Wang1 1Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiaxing Sun; Hongmei Wang, Email jiaxing20022001@163.com; dor.whm@163.comBackground: EGFR-TKI resistance poses a significant challenge in the treatment landscape of non-small cell lung cancer (NSCLC), prompting extensive research into mechanisms and therapeutic strategies. In this study, we conduct a bibliometric analysis to elucidate evolving research hotspots and trends in EGFR-TKI resistance, offering insights for clinical interventions and scientific inquiries.Methods: Publications spanning from 1996 to 2024, focusing on EGFR-TKI resistance in NSCLC, were sourced from the Web of Science Core Collection. Utilizing VOSviewer 1.6.19, CiteSpace 6.2. R2, and Scimago Graphica 1.0.35, we analyzed these articles to identify countries/regions and institutions, Journals, publications, key contributors, collaborations, and emerging topics.Results: An analysis of 8051 articles by 38,215 researchers from 86 countries shows growing interest in EGFR-TKI resistance mechanisms. Since 1996, publications have steadily increased, surpassing 500 per year after 2016, with a sharp rise in citations. Research articles make up 84% of publications, emphasizing scholarly focus. Global collaboration, especially among researchers in China, the US, and Japan, is strong. Leading institutions like Dana-Farber and Harvard, along with journals such as “Lung Cancer”, are key in sharing findings. Professors Yi-Long Wu and William Pao are prominent contributors. Keyword analysis reveals core themes, including first-generation EGFR-TKIs, emerging agents like osimertinib, and research on the T790M mutation.Conclusion: EGFR-TKI resistance remains a critical issue in NSCLC treatment, driving ongoing research efforts worldwide. Focusing future research on clear identification of resistance mechanisms will guide post-resistance treatment strategies, necessitating further exploration, alongside the validation of emerging drugs through clinical trials. Moreover, “chemo+” treatments following EGFR-TKI resistance require more clinical data and real-world evidence for assessing safety and patient outcomes. As research advances, a multidisciplinary approach will be key to overcoming these challenges. Continued innovation in treatment could greatly enhance patient survival and quality of life.Keywords: EGFR-TKI, resistance, lung cancer, bibliometric, citespace, VOSviewer

Ying Shao,1,&ast; Qianfei Li,2,&ast; Meirong Bian,3 Yue Wang,1 Xiaohong Zhang4 1Department of Ophthalmology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2College of Nursing, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4Nursing Department, Third hospital of Shanxi medical university, Shanxi Bethune hospital, Shanxi academy of medical sciences, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Zhang, Nursing Department, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, NO. 99, Longcheng Street, Xiaodian District, Taiyuan, 030032, People’s Republic of China, Tel +86-13453443366, Email zxhxb2013@126.comBackground: The “Key Points of the Core System of Medical Quality and Safety” (hereinafter referred to as the “Key Points”) was promulgated by the National Health Commission of China in 2018, requiring that nursing ward rounds should be carried out with reference to the three-level ward round system; In 2020 and 2022 editions of the “Evaluation Standards for Tertiary Hospitals”, which were implemented in China, required that nursing ward rounds should be carried out with reference to the “Key Points”. Additionally, the Action Plan for Comprehensively Improving Medical Quality (2023– 2025) also mentions the need to improve the quality of three-level ward rounds. However, there are no detailed guidelines regarding implementing “Nursing Three-level Ward Rounds”.Purpose: This study aimed to investigate the current situation of nursing three-level ward rounds in tertiary hospitals after the promulgation of the “Key Points of the Core System of Medical Quality and Safety” to provide insights and guidelines regarding relevant standards, so as to better implement of the requirements of “nursing ward rounds” in the “Evaluation Standards for Tertiary Hospitals” and “improving the quality of three-level ward rounds” in the “Action Plan”.Methods: A multi-center study was conducted in February 2024, including all tertiary public hospitals in the Shanxi Province, China. A questionnaire survey using the self-designed “Questionnaire on the Implementation of Nursing Three-level Ward Rounds” was carried out. The questionnaire included the basic information of the hospital and the implementation of the three-level (namely I, II, and III) rounds (including “five aspects”: ward round personnel, object, content, frequency, and record), which is expressed by quantity and composition ratio. Next is the text analysis method. First, the “five aspects” of the hospital that filled in the questionnaire survey with “nursing three-level ward rounds have been carried out” were assessed. Second, the five aspects of each hospital were assessed for consistency with the “Nursing Three-level Ward Rounds System” (hereinafter referred to as the “System”) of their respective hospitals.Third, the consistency of the “System” of the hospital with the “Key Points” was assessed. The results of the analysis of the former are expressed in terms of quantity and composition ratio; the results of the latter two were analyzed using Fisher’s exact test method to compare any differences.Results: Notably, 14 of the 67 tertiary public hospitals (20.9%) carried out nursing three-level ward rounds. There were 4– 10 situations in the five aspects of I, II, and III ward rounds filled in by the hospitals. The five aspects of the I, II, III ward rounds in 14 hospitals were significantly comparable with the “System”, which, in turn, was comparable with the “Key Points” (P < 0.05).Conclusion: Not all tertiary public hospitals in the Shanxi Province have not all carried out nursing three-level ward rounds. Furthermore, the five aspects of the hospitals that carried out nursing three-level ward rounds were not entirely consistent in terms of ward round personnel, object, content, frequency, and record. The filling in of the nursing three-level ward rounds carried out by the hospitals is inconsistent with the respective “System”; the “System” of the hospital is not in line with the “Key Points”.Impact on Nursing Work: Nursing administrators should be aware of the newly issued norms and requirements in their workplace, and revise the relevant systems in accordance with the norms and requirements in a timely manner. Additionally, the revision of the system should cover the core requirements of the norms and be practicable. The system should be supervised to ensure that 100% of the implementation is in accordance with the system.Keywords: nursing three-level ward rounds, tertiary hospitals, core system, current status of ward round, multi-center

Yi Shao,&ast; Yunfu Chen,&ast; Xin Lan, Jun Lu, Guangling Tang, Sijie Tang, Ruixue Zhai, Chao Chen, Xinglong Xiong, Jing Shi Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Shi, Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, No. 28 Beijing Road, Guiyi Street, Yunyan District, Guiyang, Guizhou, 550001, People’s Republic of China, Tel +86-18685034016, Email shijing81@gmc.edu.cnBackground: Morin can alleviate vincristine-induced neuropathic pain via inhibiting neuroinflammation. Microglial cells play an important role in initiating and maintenance of pain and neuroinflammation. It remains unclear whether morin exerts antinociceptive properties through the regulation of microglial cells. This study aimed to elucidate the mechanisms of morin against neuropathic pain focusing on microglial cells.Methods: The thermal withdrawal latency and mechanical withdrawal threshold were used as measures of pain behaviours. Histological abnormalities of the sciatic nerve were observed with transmission electron microscopy. The sciatic functional index and the sciatic nerve conduction velocity were used as measures of the functional deficits of the sciatic nerve. Inflammatory factors were detected using ELISA. The expression of M1/M2 polarization markers of microglia and nuclear factor κB (NF-κB) p65 were measured by immunofluorescence, real-time quantitative PCR and Western blotting.Results: Morin alleviated vincristine-induced abnormal pain, sciatic nerve injury, and neuroinflammatory response in rats. Furthermore, morin decreased the expression of NF-κB P65 and M1 activation markers, increased the expression of M2 activation markers. Additionally, phorbol 12-myristate 13-acetate reversed the effects of morin on microglial polarization, the production of inflammatory factors and neuropathic pain, while ammonium pyrrolidine dithiocarbamate showed the opposite effects.Conclusion: Our results demonstrate that morin inhibits neuroinflammation to alleviate vincristine-induced neuropathic pain via inhibiting the NF-κB signalling pathway to regulate M1/M2 microglial polarization.Keywords: neuropathic pain, morin, microglia, NF-κB, neuroinflammation

Fengxing Huang,1,2,&ast; Youwei Wang,1,2,&ast; Yu Shao,1,2,&ast; Runan Zhang,1,2 Mengting Li,1,2 Lan Liu,1,2,&ast; Qiu Zhao1,2,&ast; 1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China; 2Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan Liu; Qiu Zhao, Email lliugi@whu.edu.cn; qiuzhao@whu.edu.cnIntroduction: Immune cell interactions and metabolic changes are crucial in determining the tumor microenvironment and affecting various clinical outcomes. However, the clinical significance of metabolism evolution of immune cell evolution in colorectal cancer (CRC) remains unexplored.Methods: Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data were acquired from TCGA and GEO datasets. For the analysis of macrophage differentiation trajectories, we employed the R packages Seurat and Monocle. Consensus clustering was further applied to identify the molecular classification. Immunohistochemical results from AOM and AOM/DSS models were used to validate macrophage expression. Subsequently, GSEA, ESTIMATE scores, prognosis, clinical characteristics, mutational burden, immune cell infiltration, and the variance in gene expression among different clusters were compared. We constructed a prognostic model and nomograms based on metabolic gene signatures identified through the MEGENA framework.Results: We found two heterogeneous groups of M2 macrophages with various clinical outcomes through the evolutionary process. The prognosis of Cluster 2 was poorer. Further investigation showed that Cluster 2 constituted a metabolically active group while Cluster 1 was comparatively metabolically inert. Metabolic variations in M2 macrophages during tumor development are related to tumor prognosis. Additionally, Cluster 2 showed the most pronounced genomic instability and had highly elevated metabolic pathways, notably those associated with the ECM. We identified eight metabolic genes (PRELP, NOTCH3, CNOT6, ASRGL1, SRSF1, PSMD4, RPL31, and CNOT7) to build a predictive model validated in CRC datasets. Then, a nomogram based on the M2 risk score improved predictive performance. Furthermore, our study demonstrated that immune checkpoint inhibitor therapy may benefit patients with low-risk.Discussion: Our research reveals underlying relationships between metabolic phenotypes and immunological profiles and suggests a unique M2 classification technique for CRC. The identified gene signatures may be key factors linking immunity and tumor metabolism, warranting further investigations. Keywords: CRC, macrophages, metabolic classification, tumor immunity, prognosis model

Yang Zhao,1,&ast; Yi-Han Wang,2,&ast; Wei-Chao Tu,1 Da-Wei Wang,1 Mu-Jun Lu,3,4 Yuan Shao1 1Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai, 201800, People’s Republic of China; 2Department of Urology, Sixth People’s Hospital South Campus Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Urology and Andrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Shanghai Institute of Andrology, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mu-Jun Lu; Yuan Shao, Email lumujun@163.com; shaoyuan10772@163.comBackground: Chronic kidney disease (CKD) is a significant worldwide health concern that leads to high mortality rates. The bioactive substance costunolide (CTD) has demonstrated several pharmacological effects and holds promise as a CKD treatment. This study aims to investigate the impact of CTD on CKD and delve into its mechanisms of action.Methods: Unilateral ureteral obstruction (UUO) methods and renal fibrosis mice models were created. Various concentrations of CTD were injected into UUO mice models to investigate the therapeutic effects of CTD on renal fibrosis of mice. Then, renal morphology, pathological changes, and the expression of genes related to fibrosis, inflammation and ferroptosis were analysed. RNA sequencing was utilized to identify the main biological processes and pathways involved in renal injury. Finally, both overexpression and inhibition of IKKβ were studied to examine their respective effects on fibrosis and inflammation in both in vitro and in vivo models.Results: CTD treatment was found to significantly alleviate fibrosis, inflammation and ferroptosis in UUO-induced renal fibrosis mice models. The results of RNA sequencing suggested that the IKKβ acted as key regulatory factor in renal injury and the expression of IKKβ was increased in vitro and in vivo renal fibrosis model. Functionally, down-regulated IKKβ expression inhibits ferroptosis, inflammatory cytokine production and collagen deposition. Conversely, IKKβ overexpression exacerbates progressive renal fibrosis. Mechanistically, CTD alleviated renal fibrosis and inflammation by inhibiting the expression of IKKβ and attenuating IKKβ/NF-κB pathway.Conclusion: This study demonstrates that CTD could mitigate renal fibrosis, ferroptosis and inflammation in CKD by modulating the IKKβ/NF-κB pathway, which indicates targeting IKKβ has an enormous potential for treating CKD. Keywords: chronic kidney disease, costunolide, renal fibrosis, IKKβ/NF-κB pathway

Huiying Yan,1,&ast; Wei Wang,2,&ast; Tingting Cui,1 Yanxin Shao,3 Mingquan Li,1 Limei Fang,1 Lina Feng1 1Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Department of Intensive Care Unit, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Limei Fang; Lina Feng, Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, People’s Republic of China, Email fanglm008@163.com; Fenglina0001@126.comAbstract: Alzheimer’s disease (AD) is a fatal neurodegenerative disease with a subtle and progressive onset and is the most common type of dementia. However, its etiology and pathogenesis have not yet been fully elucidated. The common pathological manifestations of AD include extraneuronal β-amyloid deposition (Aβ), intraneuronal tau protein phosphorylation leading to the formation of ‘neurofibrillary tangles’ (NFTs), neuroinflammation, progressive loss of brain neurons/synapses, and glucose metabolism disorders. Current treatment approaches for AD primarily focus on the ‘Aβ cascade hypothesis and abnormal aggregation of hyperphosphorylation of tau proteins’, but have shown limited efficacy. Therefore, there is an ongoing need to identify more effective treatment targets for AD. The central nervous system (CNS) inflammatory response plays a key role in the occurrence and development of AD. Neuroinflammation is an immune response activated by glial cells in the CNS that usually occurs in response to stimuli such as nerve injury, infection and toxins or in response to autoimmunity. Neuroinflammation ranks as the third most prominent pathological feature in AD, following Aβ and NFTs. In recent years, the focus on the role of neuroinflammation and microglia in AD has increased due to the advancements in genome-wide association studies (GWAS) and sequencing technology. Furthermore, research has validated the pivotal role of microglia-mediated neuroinflammation in the progression of AD. Therefore, this article reviews the latest research progress on the role of neuroinflammation triggered by microglia in AD in recent years, aiming to provide a new theoretical basis for further exploring the role of neuroinflammation in the process of AD occurrence and development.Keywords: neuroinflammation, microglia, Alzheimer’s disease, review, Trem2

Yue Shao, Rong Li, Guangmei Chen, Lichuan Zhang Department of Respiratory Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, People’s Republic of ChinaCorrespondence: Lichuan Zhang, Department of Respiratory Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, People’s Republic of China, Email zlcdl2015@126.comPurpose: We explored the expression and prognostic value of GALNT6 and the tumor microenvironment of pan-cancer in humans.Methods: In this study, we explored the expression pattern of GALNT6 pan-cancer across multiple databases. The prognostic value of GALNT6 was evaluated using the Kaplan–Meier method. The types and numbers of GALNT6 gene alterations were exhibited using the cBio Cancer Genomics Portal. The correlations between GALNT6 expression and immune infiltration in cancers were analyzed using the database Tumor Immune Estimation Resource 2. We also used the Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analysis to investigate the molecular mechanisms of the GALNT6 gene in tumorigenesis. The expression of GALNT6 was also further verified by qPCR in lung adenocarcinoma tissues.Results: In general, compared with normal tissue, tumor tissue had a higher expression level of GALNT6. GALNT6 showed a protective effect in colon carcinoma and other cancers; however, a high expression level of GALNT6 was detrimental to survival in bladder cancer and in pheochromocytoma and paraganglioma. Mutation, amplification, and deep deletion were the three main types of GALNT6 mutations in tumors. There was a significant positive correlation between GALNT6 expression and immune infiltration of CD8+ T-cells in skin cutaneous melanoma metastasis, based on most of the algorithms used. Moreover, protein processing- and glycoprotein metabolic-associated functions were involved in the functional mechanisms of GALNT6.Conclusion: This first pan-cancer study offers a relatively comprehensive understanding of the oncogenic roles of GALNT6 across different cancer types.Keywords: GALNT6, pan-cancer, survival analysis, mutation, immune infiltration, functional mechanisms

Zhanyi Zhang,1 Mengyuan Li,2 Yujia Geng,1 Wangshu Wang,1 Weihao Wang,1 Ying Shao1 1Department of Plastic and Reconstructive Surgery, the First Hospital of Jilin University, Changchun, Jilin Province, 130000, People’s Republic of China; 2College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, Jilin Province, 130118, People’s Republic of ChinaCorrespondence: Ying Shao, Department of Plastic and Reconstructive Surgery, the First Hospital of Jilin University, Changchun, Jilin Province, 130000, People’s Republic of China, Email shao_ying@jlu.edu.cnPurpose: Previous studies have suggested a relationship between autoimmune diseases and the risk of facial skin aging. However, evidence from population-based studies on this topic is limited, leaving the causal association between these factors unknown. This study aimed to systematically evaluate the causal effects of 18 autoimmune diseases on the risk of facial skin aging, aim of providing strategies to mitigate early facial aging in patients with autoimmune diseases.Patients and Methods: We conducted univariate Mendelian randomization (UVMR) analyses to examine the causal relationship between 18 autoimmune diseases and facial aging using publicly available summary data from genome-wide association studies (GWASs). We also conducted multivariate Mendelian randomization (MVMR) analyses to adjust for confounding factors, including smoking, alcohol consumption, and body mass index (BMI).Results: The main inverse variance weighted (IVW) method revealed that genetically proxied ankylosing spondylitis (AS) (OR 1.017; 95% CI: 1.003– 1.031; P=0.018), sicca syndrome (SS) (OR 1.008; 95% CI: 1.005– 1.011; P= 2.66× 10− 6), systemic lupus erythematosus (SLE) (OR 1.006; 95% 1.001– 1.011; P=0.014), multiple sclerosis (MS) (OR 1.004; 95% CI: 1.001– 1.007; P=0.021), primary sclerosing cholangitis (PSC) (OR 1.002; 95% CI: 1.000– 1.004; P=0.023), and celiac disease (CeD) (OR 1.002; 95% CI: 1.001– 1.004; P=0.009) were significantly associated with higher risk of facial aging. After adjusting for potential confounding factors, the association persisted between AS, SLE, and CeD.Conclusion: These findings indicated that autoimmune diseases play a causal role in facial skin aging. Therefore, patients with autoimmune diseases should take appropriate measures to prevent early facial aging.Keywords: autoimmune disease, facial aging, Mendelian randomization, ankylosing spondylitis, systemic lupus erythematosus, celiac disease

Zhihua Zhang,1 Yuhong Wang,2 Yankun Zhang,3 Shujun Geng,2 Haifeng Wu,4 Yanxin Shao,5 Guannan Kang6 1Department of Science & Education, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 2Department of Tuberculosis, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 3Department of Ophthalmology, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 4Clinical Laboratory, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 5Office of Clinical Pharmacological Center, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 6Department of Tuberculosis, Hebei Chest Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yanxin Shao, Office of Clinical Pharmacological Center, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, No. 372, Sheng Li North Street, Shijiazhuang, Hebei, 050041, People’s Republic of China, Email shaoyanxin163@163.comBackground: Tuberculosis (TB) is one of the most infectious diseases caused by Mycobacterium tuberculosis (M. tb), and the diagnosis of active tuberculosis (TB) and latent TB infection (LTBI) remains challenging.Methods: Gene expression files were downloaded from the GEO database to identify the differentially expressed genes (DEGs). The ssGSEA algorithm was applied to assess the immunological characteristics of patients with LTBI and TB. Weighted gene co-expression network analysis, protein-protein interaction network, and the cytoHubba plug-in of Cytoscape were used to identify the real hub genes. Finally, a diagnostic model was constructed using real hub genes and validated using a validation set.Results: Macrophages and natural killer cells were identified as important immune cells strongly associated with TB. In total, 726 mRNAs were identified as DEGs. MX1, STAT1, IFIH1, DDX58, and IRF7 were identified as real hub immune-related genes. The diagnostic model generated by the five real hub genes could distinguish active TB from healthy controls or patients with LTBI.Conclusion: Our study may provide implications for the diagnosis and drug development of M. tb infections.Keywords: tuberculosis, latent tuberculosis infection, mycobacterium tuberculosis, immune, diagnostic model

Yujian Shao,1,2 Yonglu Chen,2 Mingyue Zhu,3 Yuanyuan Liu,2 Chen Fang,3 Minjun Wang,2 Peng Sun,3 Weiling Fu,2 Jing Huang,3 Shimei Sheng,2 Yanshan Huang2 1Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd, Hangzhou, Zhejiang, People’s Republic of China; 3First Research Institute, Zhejiang Heze Pharmaceutical Technology Co., Ltd, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Yanshan Huang, Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd, Hangzhou, Zhejiang, People’s Republic of China, Email yanshanhuang@doerbio.comIntroduction: Diabetes and obesity are momentous risk factors threatening people’s lives and health. Currently available incretin analogue glucagon-like peptide 1 (GLP-1) possesses huge hypoglycemic effect with the unsatisfactory effect of weight loss. Co-agonists targeting GLP-1R plus glucagon receptor (GCGR) or gastric inhibitory polypeptide receptor (GIPR) show synergistic benefits in glycaemic control and weight loss. Here, we describe a novel dual GIP and GLP-1 receptor agonist, DR10627, and performed a preclinical assessment of it.Methods: The agonistic ability of DR10627 was indirectly assessed by inducing cAMP accumulation in Chinese hamster ovary (CHO) cells transfected with GLP-1R or GIPR in vitro. The plasma pharmacokinetics of DR10627 were analysed in cynomolgus monkeys. The OGTTs were performed in Sprague‑Dawley (SD) rats. The glucose lowering effects were evaluated by repeated administration of DR10627 in diabetic (db/db) mice for 4 weeks. The effects of anti-obesity and improving metabolism of DR10627 were evaluated by repeated administration of DR10627 in diet-induced obesity (DIO) mice for 57 days.Results: DR10627 had the capacity to activate both GLP-1R and GIPR in vitro. The terminal half-life of DR10627 was found to be approximately 4.19– 5.8 h in cynomolgus monkeys. DR10627 had a great improvement in oral glucose tolerance in SD rats. Moreover, DR10627 had a potent glucose-lowering effect in db/db mice, and the hypoglycemic effect of 18 nmol/kg DR10627 was better than that of 50 nmol/kg liraglutide. In addition, 10 and 30 nmol/kg DR10627 possessed the ability of potentiating the weight-loss, lipid-lowing efficacy and improving metabolism to a greater extent than 80 nmol/kg liraglutide.Conclusion: Preclinical assessment demonstrated that administration of DR10627 resulted in glucose lowering in SD rats and db/db mice, and substantial body weight reduction and metabolism improvement in DIO mice. DR10627 is a promising agent deserving further investigation for the treatment of type 2 diabetes and obesity.Keywords: glucagon-like peptide-1, gastric inhibitory polypeptide receptor, obesity, type 2 diabetes, inflammation

Zixia Wu,1,&ast; Weibo Xia,1,&ast; Liling Ou,1 Ling Zheng,1 Bingying Hou,1 Tonghe Pan,2 Wenjie Sun,1 Leo H Koole,1 Yongqing Shao,2 Lei Qi1 1National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, the People’s Republic of China; 2Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, 310000, the People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongqing Shao, Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, 310000, the People’s Republic of China, Tel +86-574 87862193, Email sunniesyq@163.com Lei Qi, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, the People’s Republic of China, 325027, Tel +86-577-88067973, Email imdoll@163.comPurpose: Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED.Methods: NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo, both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice.Results: These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H2O2-exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 μg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels.Conclusion: Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.Keywords: dry eye disease, antioxidant, nitrogen doped graphene quantum dots, Nrf2 antioxidant pathway

Manqiao Wang,&ast; Rong Luan,&ast; Boshi Liu, Yi Gong, Jinzhi Zhao, Xiteng Chen, Qianhui Yang, Jingjie Liu, Juping Liu, Yan Shao, Xiaorong Li Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Shao; Xiaorong Li, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China, Tel +86 17622651170; +86 18622818042, Email sytmueh@163.com; xiaorli@163.comPurpose: To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR).Methods: This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion.Results: The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05).Conclusion: Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement.Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).Keywords: proliferative diabetic retinopathy, ozurdex, pars plana vitrectomy, optical coherence tomography angiography, microperimetry

Chuanlin Ning,1 Huacheng Pei,2 Youjia Huang,1 Sichen Li,1 Yiling Shao1 1School of Media and Communication, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2School of Finance, Shanghai University of Finance and Economics, Shanghai, People’s Republic of ChinaCorrespondence: Yiling Shao, School of Media and Communication, Shanghai Jiao Tong University, No. 800, Dongchuan Road, Minhang District, Shanghai, 200240, People’s Republic of China, Email sylh1996@sjtu.edu.cnBackground: The Healthy China 2030 (HC2030) policy is currently recognized as China’s most significant and influential national health policy. However, despite its implementation in 2016, the policy’s impact has yet to be comprehensively evaluated, particularly in relation to its effectiveness in enhancing population health and promoting public health equity.Methods: We utilized the Difference-in-Differences (DiD) method to evaluate the impact of the HC2030. Our analysis utilized a panel dataset derived from five longitudinal surveys conducted by the China Family Panel Studies (CFPS).Results: The implementation of HC2030 has improved the overall health status of residents, particularly in urban areas and the western and eastern regions. Mechanistic analysis has further unveiled that the policy’s beneficial impact on health outcomes is attributed to a rise in physical activity frequency and the betterment of mental health. Additionally, female, married, and medically insured individuals have demonstrated a significant positive impact of the policy on their health outcomes.Conclusion: Although the HC2030 appears to have effectively improved overall population health, it needs to promote equity in public health adequately. The study suggests adjustments are needed to address the unequal distribution of health outcomes between urban and rural areas and among different regions.Keywords: health China 2030, health policy, policy evaluation, health equity, health communication, public health

Yuming Shao,1 Wenxiang Wu,2 Fangzhou Fan,2 Haifeng Liu,3 Yongliang Ming,2 Wangwei Liao,2 Chunyu Bai,2 Yuhua Gao2 1Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Forensic Science Center of Jining Medical University, Jining, Shandong, 272067, People’s Republic of China; 2Precision Medicine Laboratory for Chronic Non-Communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical University, Jining, Shandong, 272067, People’s Republic of China; 3Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272067, People’s Republic of ChinaCorrespondence: Chunyu Bai; Yuhua Gao, No. 133 Hehua Road, Jining, Shandong, 272067, People’s Republic of China, Tel +86-573-3616565, Email chunyu_bai@hotmail.com; anngyh@126.comAim: Acute pancreatitis is an inflammatory disorder of the pancreas, which causes abnormal activation of immune cells. The macrophages were accumulated in pancreas and infiltrated into islets during the AP process to induce abnormal glucose metabolism. However, the role of macrophages in abnormal glucose metabolism remains understood. Extracellular vesicles act in the regulation of intercellular function, but whether EVs secreted by macrophages contribute to β cell failure and apoptosis in AP is unclear. Based on this, the aim of this study was to reveal the role of macrophages-EVs in AP and develop a treatment for symptoms of hyperglycemia in AP.Methods: The AP model was established and treated by various doses of melatonin to analyze the therapeutic effect. The accumulation and polarization of macrophages in the AP pancreas were observed, and the β cells were incubated with pancreatic derived EVs to analyze the role in β cell failure and apoptosis.Results: The results showed that macrophages were recruited and polarized to M1 phenotype macrophages in the pancreas of AP mice, which obtained inflammatory EVs that contained specific miRNAs to induce β cell failure and apoptosis. Then, the EVs derived from M1 macrophages triggered β cell failure and apoptosis. Melatonin prevented polarization of macrophages to the M1 phenotype in vivo, which reduced the secretion of inflammatory EVs, changed the abundance of miRNAs in EVs, and therefore decreased inflammatory EV-mediated β cell failure and apoptosis.Conclusion: Our results demonstrate that similar to 20S proteasome inhibitor MG132, analyses indicated that melatonin prevented degradation of IκBα through the ubiquitylation pathway to restrict p50 subunits to the cytoplasm of macrophages, inhibited activation of the NF-κB pathway to downregulate the transcription of specific miRNAs, and reduced miRNA transport into EVs.Keywords: acute pancreatitis, diabetes mellitus, macrophages, EVs, melatonin

Huan He,1 Qichun Cui,1 Hengheng Chen,2,&ast; Xiao Huang,3,&ast; Shuai Wang,3,&ast; Tian Yu,2,&ast; Jinqiu Feng,3 Yun Shao1 1Department of Anesthesiology, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200002, People’s Republic of China; 2Department of Preventive Dentistry, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200002, People’s Republic of China; 3Department of Pediatric Dentistry, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Shao, Department of Anesthesiology, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, No. 356 East Beijing Road, Shanghai, 200002, People’s Republic of China, Tel/Fax +86 2163295852, Email shaoyun07078@sina.com Jinqiu Feng, Department of Pediatric Dentistry, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, No 356 East Beijing Road, Shanghai, 200002, People’s Republic of China, Tel/Fax +86 2163601149, Email feng_jinqiu356@fudan.edu.cnPurpose: Sevoflurane is the preferred anesthetic agent for induction and maintenance of ambulatory surgery due to its property of fast onset and recovery. However, it has been recognized as one of the major contributors of emergence delirium. The aim of this study was to evaluate the preventive effect of intranasal dexmedetomidine on the occurrence of emergence delirium in pediatric patients under general anesthesia with sevoflurane.Patients and Methods: Ninety pediatric patients undergoing dental rehabilitation under sevoflurane anesthesia were enrolled in this study. The patients were divided into three groups (n=30 each in the 2 μg/kg dexmedetomidine, 1 μg/kg dexmedetomidine, and control with saline groups). The same volume (0.02mL/kg) of the mixed solution was dropped into the nasal cavity of the children 30 minutes before surgery. We used the Pediatric Anesthesia Emergence Delirium Scale (PAED) to assess the level and incidence of delirium in the post-anesthesia care unit.Results: Compared with the control group, prophylactic use of different dosages of intranasal dexmedetomidine significantly reduces the incidence of ED and severe ED in PACU (P< 0.001). Intranasal administration of 2 μg/kg dexmedetomidine was associated with a better acceptance of mask induction and a better tolerance of separation with parents.Conclusion: Both 2 μg/kg and 1 μg/kg intranasal dexmedetomidine can achieve ED preventive effects in PACU in dental rehabilitation under general anesthesia. A dosage of 2 μg/kg is more effective in preventing severe ED and providing better mask acceptance.Keywords: intranasal dexmedetomidine, emergence delirium, sevoflurane anesthesia, pediatric patients, dental rehabilitation

Dawei Wang,1 Lingchao Sun,1 Yunru Shao,1 Xiaoyan Zhang,1 Phil Maguire,2 Yixin Hu1 1School of Psychology, Shandong Normal University, Ji’nan, Shandong, People’s Republic of China; 2Department of Computer Science, National University of Ireland, Galway, IrelandCorrespondence: Yixin Hu, School of Psychology, Shandong Normal University, Jinan, Shandong Province, 250358, People’s Republic of China, Email huyixin2005@163.comPurpose: Cyberchondria is a problematic or unhelpful behavior pattern that describes excessive or repetitive online health-related information searching related to an enhanced level of health anxiety. Such internet-derived medical anxiety can manifest itself in different ways across cultures. This study explores the unique nature of cyberchondria in the context of Chinese culture, identifying the risk factors for the condition and the possible negative outcomes.Methods: An exploratory factor analysis (EFA) was used to explore whether the structure of the Chinese version of the Cyberchondria Severity Scale (C-CSS) is different from that in western context. Subsequently, a confirmatory factor analysis (CFA) was used to verify the model fit of the C-CSS. Finally, a series of regression analysis were used to test the relationship between cyberchondria and its antecedent variables and consequence variables in Chinese context.Results: Retained 18 items and revised to 3 dimensions (Negative Effects, Excessiveness and Reassurance Seeking), the Chinese version of the Cyberchondria Severity Scale (C-CSS) was developed. In the context of China, the three antecedents were also effective predictors of cyberchondria, and C-CSS is also related to theoretically relevant outcomes.Conclusion: This study initially demonstrated the validity, reliability and applicability of C-CSS to assess the severity of cyberchondria among Chinese undergraduates.Keywords: cyberchondria severity scale, medical anxiety, Chinese health system, validity, reliability

Xiao-Yu Wang,1– 3,&ast; San-Hua Xu,3,&ast; Hong Wei,3,&ast; Min Kang,3 Jie Zou,3 Qian Ling,3 Hui Huang,3 Xu Chen,4 Yi-Xin Wang,5 Yi Shao,3 Yao Yu1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang University, Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, Jiangxi, 330006, People’s Republic of China; 2The First Clinical Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Branch of National Clinical Research Center for Ocular Disease, Nanchang, Jiangxi, 330006, People’s Republic of China; 4Department of Ophthalmology and Visual Sciences, Maastricht University, Maastricht, Limburg Province, 6200MA, Netherlands; 5School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF244HQ, UK&ast;These authors contributed equally to this workCorrespondence: Yi Shao, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email freebee99@163.com Yao Yu, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email yuyao1234562023@163.comPurpose: This study aimed to explore the spontaneous brain activity in patients with diabetic optic neuropathy (DON) by using the amplitude of low-frequency fluctuation (ALFF) technique.Methods: Sixteen DON patients and 16 age- and sex-matched healthy controls (HCs) were recruited. ALFF along with functional MRI method was used to detect the intrinsic brain activity alterations. The mean values of ALFF in DON patients and HCs were analyzed by receiver operating characteristic (ROC) curves. Pearson’s correlation analysis was used to determine the correlation between Hospital Anxiety and Depression Scale (HADS) and ALFF values of DONs.Results: The DON group showed significantly increased ALFF values in the fusiform gyrus, and decreased ALFF values in the medial frontal gyrus/left frontal superior orbit/right frontal medial orbit, and left frontal inferior triangle. ROC curve analysis indicated that the accuracy of AUC was good. The anxiety scale and depression scale of the DON group were negatively correlated with the ALFF values of the medial frontal gyrus.Conclusion: DON is a neurodegenerative disease involving multiple brain regions. The abnormal activity of neurons in these brain regions helps to reveal the underlying neural mechanisms of brain activity related to DON.Keywords: ALFF, fMRI, diabetic optic neuropathy, spontaneous brain activity

Qingyan Liu,1,2,&ast; Shuo Sun,1,&ast; Zhengwei Yang,1,&ast; Yan Shao,1 Xiaorong Li1 1Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, People’s Republic of China; 2Department of Ophthalmology, Anhui NO.2 Provincial People’s hospital, Hefei, 230041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Shao; Xiaorong Li, Email 13820179302@163.com; xiaorli@163.comBackground: Neovascular age-related macular degeneration (nAMD) and its subtype, polypoidal choroidal vasculopathy (PCV), are common choroidal vasculopathies. Although they share many common clinical manifestations and treatment strategies, a lack of comprehensive analysis of these conditions means that it is difficult for researchers to further explore the common pathomechanisms of nAMD and PCV. The aim of this study was to characterize aqueous humor (AH) proteome alterations and identify a novel biomarker related to both nAMD and PCV.Methods: Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) was adopted to analyze the AH proteomes of nAMD, PCV and controls. The target protein was validated using the enzyme-linked immunosorbent assay (ELISA) and subjected to receiver operating characteristic (ROC) curve analysis.Results: A total of 737 different proteins were identified in all the groups, of which 544 were quantifiable. The bioinformatics analysis suggested that immune response activation is the essential event in both nAMD and PCV. Serum amyloid A (SAA) 4 is closely associated with a number of chronic inflammatory diseases, and it was enriched as the hub protein. ROC analysis showed that SAA4 could distinguish both nAMD and PCV from the controls.Conclusion: This comprehensive study provides insights into, and furthers our understanding of, the pathological mechanism of nAMD and PCV. Additionally, the SAA4 level alteration may serve as a common biomarker of nAMD and PCV.Keywords: serum amyloid A 4, inflammation, neovascular age-related macular degeneration, polypoidal choroidal vasculopathy

Xulin Liao,1,2 Chu Qi Li,1 Qian Min Ge,1 Li Ying Tang,3 Ting Su,4 Qiu Yu Li,1 Yi Cong Pan,1 Hui Ye Shu,1 Li Juan Zhang,1 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong SAR, People’s Republic of China; 3Department of Ophthalmology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, People’s Republic of China; 4Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, 02114, USACorrespondence: Yi Shao, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, Yong Wai Zheng Street, Dong Hu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86 791-88692520, Email freebee99@163.comPurpose: The purpose of this study was to use the percent amplitude of fluctuation (PerAF) to study the changes in brain activity and nerve function of herpes zoster keratitis (HZK) patients.Methods: We recruited 20 HZK patients and 20 healthy controls (HCs). Each of these groups included ten males and ten females and were matched in weight and age. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). The percent amplitude of fluctuation (PerAF) method was used for analysis and detected differences between the two groups in the neurological function of brain areas. We also applied the receiver operating characteristic (ROC) curve to analyze the two groups and did a correlation analysis between the PerAF value, anxiety and depression score, and visual acuity.Results: The PerAF signal at the right putamen and right precentral gyrus was significantly higher in patients than in HCs. However, the PerAF value of the left inferior temporal was lower in patients than in HCs. In addition, the HZK patients’ anxiety and depression score (HADS) and visual acuity (V.A.) Log MAR negatively correlated with the PerAF value at the left inferior temporal gyrus.Conclusion: HZK patients had some changes in brain regions, and the changes were also related to their mood and visual acuity. These findings might contribute to other studies on the potential pathological mechanism, disease development, prognosis, and brain function in HZK patients.Keywords: herpes zoster keratitis, resting-state functional magnetic resonance imaging, brain activity patterns, brain region, the percent amplitude of fluctuation

We perform a comprehensive analysis of both the chemical and correlated electronic structure reconstruction of rhombohedral CrX3 (X=Br, Cl, I) van der Waals bulk crystals. Using the generalized gradient approximation (GGA) plus dynamical mean-field theory we explicitly demonstrate the importance of local dynamical correlations for a consistent understanding of emergent Kondo quasiparticles and Mott localized electronic states, showing the interplay between material-dependent one-electron GGA line-shape and multiorbital electronic interactions. To probe the correlated paramagnetic electronic state we performed x-ray absorption spectroscopy measurements for CrCl3 and CrBr3 bulk crystals. Our correlated many-body study is relevant to understanding the electronic structure reconstruction of paramagnetic Cr-trihalide crystals and should be widely applicable to other van der Waals magnetic materials.

Yiyang Shu,1 Yuting Shao,1 Qi Zhou,2 Lixia Lu,3 Zhiyue Wang,1 Li Zhang,1 Yanlong Bi1,4 1Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Exam Center of Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Tongji Eye Institute, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Yanlong Bi, Email biyanlong@tongji.edu.cnAim: To explore the trends in the prevalence and disease burden of cataract from 1990 to 2019, evaluate attributable risk factors, and predict trends over the next decade in China and globally.Methods: Data was obtained from Global Burden of Disease Study 2019. We calculated the age-standardized prevalence rate (ASR) and annual percentage change (EAPC) to show the trends of cataract in China and different regions. We calculated and reported the proportion of disability adjusted life years (DALYs) attributable to risk factors by sex in China and different regions. Then, the Bayesian age-period-cohort (BAPC) analysis model was also used to predict the prevalence trends from 2020 to 2030 in China and globally.Results: The ASR increased from 867.09 in 1990 to 991.56 in 2019 per 100,000 with an EAPC of 0.88 in China. The age-standardized DALY rate of females was higher than males. DALY rates were correlated to household air pollution from solid fuels, tobacco, high fasting plasma glucose and high body-mass index. The projective model indicates that the ASR for cataracts will rise to 1101.35× 106 for male and 1616.63× 106 for female by 2030.Conclusion: The trends from 1990 to 2030 suggested that the burden of cataract remains high in China. Maintaining good lifestyle habits such as switching to clean energy, reducing cigar intake, controlling blood glucose and weight can reduce the risk of cataracts. As aging increases, China should pay more attention to cataract-induced low vision and blindness and develop public policies to reduce the disease burden.Keywords: China, cataract, disease burden, risk factors

Using the generalized gradient approximation plus dynamical mean-field theory (GGA+DMFT) we confirm the importance of multi-orbital dynamical correlations in determining the paramagnetic insulating state of CrI3. While the ferromagnetic phase reveals weak electronic correlation effects due to strong spin-orbital polarization, the Mott insulating state of paramagnetic CrI3 crystal is shown to be driven by the interplay between orbital-dependent one-electron lineshape and multi-orbital electronic interactions. To probe the paramagnetic Mott insulating state we performed x-ray absorption spectroscopy (XAS) measurements for the two structural phases of CrI3. Our study is relevant to understanding the orbital-selective electronic structure reconstruction of Mott insulators and should be applicable to other van der Waals bonded materials from bulk to the ultrathin limit.

Lithium-sulfur (Li–S) battery is one of the most promising candidates for the next generation energy storage systems. However, several barriers, including polysulfide shuttle effect, the slow solid-solid surface reaction pathway in the lower discharge plateau, and corrosion of Li anode still limit its practical applications, especially under the lean electrolyte condition required for high energy density. Here, we propose a solution-mediated sulfur reduction pathway to improve the capacity and reversibility of the sulfur cathode. With this method, a high coulombic efficiency (99%) and stable cycle life over 100 cycles were achieved under application-relevant conditions (S loading: 6.2 mg cm−2; electrolyte to sulfur ratio: 3 mLE gs−1; sulfur weight ratio: 72 wt%). This result is enabled by a specially designed Li2S4-rich electrolyte, in which Li2S is formed through a chemical disproportionation reaction instead of electrochemical routes. A single diglyme solvent was used to obtain electrolytes with the optimum range of Li2S4 concentration. Operando X-ray absorption spectroscopy confirms the solution pathway in a practical Li–S cell. This solution pathway not only introduces a new electrolyte regime for practical Li–S batteries, but also provides a new perspective for bypassing the inefficient surface pathway for other electrochemical processes.

Conventional electrolytes made by mixing simple Mg2+ salts and aprotic solvents, analogous to those in Li-ion batteries, are incompatible with Mg anodes because Mg metal readily reacts with such electrolytes, producing a passivation layer that blocks Mg2+ transport. Here, we report that, through tuning a conventional electrolyte - Mg(TFSI)2 (TFSI- is N(SO2CF3)2-) - with an Mg(BH4)2 cosalt, highly reversible Mg plating/stripping with a high Coulombic efficiency is achieved by neutralizing the first solvation shell of Mg cationic clusters between Mg2+ and TFSI- and enhanced reductive stability of free TFSI-. A critical adsorption step between Mg0 atoms and active Mg cation clusters involving BH4- anions is identified to be the key enabler for reversible Mg plating/stripping through analysis of the distribution of relaxation times (DRT) from operando electrochemical impedance spectroscopy (EIS), operando electrochemical X-ray absorption spectroscopy (XAS), nuclear magnetic resonance (NMR), and density functional theory (DFT) calculations.

Yuanyuan Pan,1,&ast; Yifan Shao,2,&ast; Zhanghuan Chi,3,&ast; Shenhui Jin,1 Junlu Wang1 1Department of Anesthesia, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Anesthesia, Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Anesthesia, Wenzhou People’s Hospital, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junlu Wang, Departments of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel +86 13806689854, Fax +86 0577-55578999-689854, Email wangjunlu973@163.comPurpose: To evaluate transcutaneous electrical acupoint stimulation (TEAS) on the perioperative rehabilitation of patients undergoing laparoscopic myomectomy.Patients and Methods: One hundred and five women undergoing laparoscopic hysteromyomectomy were randomly divided into TEAS group (Group T) and control group (Group C). Propofol and remifentanil were used to stabilize patient blood pressure and keep BIS between 40 and 60. Group T patients received TEAS at LI4/PC6 30 minutes before the operation and lasting until the end of anesthesia, followed by TEAS at ST36/SP6 for 30 minutes in PACU. All required indicators were recorded.Results: Group T patients required lower dosages of remifentanil and vasoactive drugs, and had a reduced incidence of propofol injection pain and intraoperative hypotension compared to Group C. Group T also had a lower maximum NRS score in PACU, lower NRS scores at 1 hour and 24 hours, and a lower incidence of vomiting within 24 hours. In addition, the QoR-40 score for Group T at 24 hours after operation was higher in terms of physical comfort, emotional state, pain and total score.Conclusion: TEAS can reduce the amount of anesthetic, maintain hemodynamic stability, reduce postoperative pain, reduce postoperative vomiting, enhance the recovery of gastrointestinal function, increase the quality of postoperative recovery and thus accelerate overall patient recovery.Keywords: TEAS, laparoscopic myomectomy, QoR-40

Gaoyuan Wang,1 Xiaoyu Chen,2 Yubao Shao,2 Bin Xu1 1Department of Orthopaedics, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Histology and Embryology, Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Bin Xu, Email youchen100@126.comIntroduction: To explore the role of PINK1/Parkin-mediated mitochondrial autophagy in H2O2-induced abnormal proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS).Methods: Firstly, we isolated fibroblast like synoviocytes (RA-FLS) from RA patients. H2O2-induced oxidative stress, and NAC (a ROS inhibitor) or FCCP (a mitochondrial autophagy activator) treatment inhibited ROS level or activate mitochondrial autophagy in RA-FLS. MitoSOX Red, JC-1 kit, DCFH-DA kit and CCK8 kit were used to evaluate mitochondrial redox status, mitochondrial membrane potential, intracellular ROS level and cell activity, respectively. Western blot was used to detect the protein expression. The rat model of Freund’s complete adjuvant arthritis (AA) was established and treated with NAC and FCCP, respectively. The pathological changes of synovium and the percentage of apoptotic cells in synovium were detected by H&E and TUNEL staining, respectively.Results: We have successfully isolated synovial cells from RA patients. Using 5μM H2O2 to stimulate RA-FLS could induce mitochondrial abnormalities of RA-FLS and inhibit RA-FLS autophagy. FCCP could reverse the effect of H2O2 on RA-FLS cell proliferation and apoptosis. NAC could reverse the effect of H2O2 on PINK1/Parkin. Overexpression of PINK1 or Parkin reversed the effect of H2O2 on RA-FLS mitochondrial autophagy, proliferation and apoptosis. The in vivo experiment results showed that both NAC and FCCP could prevent the pathogenesis of RA, reduce RA-FLS cell viability and increase RA-FLS cell apoptosis.Conclusion: The PINK1/Parkin-mediated mitochondrial autophagy participates in H2O2-induced abnormal proliferation of RA-FLS, and targeting of PINK1/Parkin-mediated mitochondrial autophagy may be the key mechanism in the treatment of RA.Keywords: mitochondrial autophagy, rheumatoid arthritis, PINK1, Parkin

Xin Xiong,1,&ast; Rong Rong,2,&ast; Li-Ying Tang,3,&ast; Tie Sun,1 Yi-Cong Pan,1 Hui-Ye Shu,1 Li-Juan Zhang,1 Qian-Min Ge,1 Rong-Bin Liang,1 Yi Shao1 1Department of Pathology and Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Centre of Natural Ocular Disease Clinical Research Center, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 3Department of Ophthalmology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian Province, 361004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Shao, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, Yong Wai Zheng Street, Dong Hu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86 791-88692520, Email freebee99@163.comObjective: To explore the risk factors of ocular metastasis (OM) in patients with hepatocellular carcinoma (HCC) by analyzing the demographic characteristics and serum markers.Methods: From July 2002 to December 2012, 1064 HCC patients were included in our study. The chi-squared test and Student’s t-test were used to assess the difference between OM and any other metastasis (NOM). Receiver operating curve (ROC) was used to analyze the diagnostic value of serum biomarkers in HCC patients with OM.Results: The incidence of OM in HCC patients was 1.88% in our research. There are no significant differences in age, gender, or histopathology in the OM group and the group without any metastasis. Binary logistic regression analysis presented that compared with the patients without cancer metastasis, carbohydrate antigen 125 (CA-125) and hemoglobin (Hb) were risk factors in hepatocellular carcinoma patients with OM (P < 0.05). The ROC curve analysis showed that the areas under the CA-125, Hb, and CA125+Hb curves were 0.877, 0.554, and 0.431, and the cutoff values of CA-125 and Hb each were 115.78 u/mL and 120.50 g/L.Conclusion: Our data suggest that CA-125 and Hb are risk indicators in hepatocellular carcinoma patients with OM, and that CA-125+Hb has potentially greater utility in diagnosing hepatocellular carcinoma.Keywords: hepatocellular carcinoma, ocular metastases, CA-125, Hb, risk factors