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Xinlin Li,1 Kai Chen,1 Xu Feng,1 Xinhua Wu,1 Shiguai Qi,1 Qingmiao Wang,2 Zhengrong Shi1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, Chongqing, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Fifth People’s Hospital of Chongqing, Chongqing, Chongqing, People’s Republic of ChinaCorrespondence: Zhengrong Shi, Email shizr@hospital.cqmu.edu.cnPurpose: The purpose of This study is exploring the intraoperative and perioperative differences between patients undergoing conversion surgery and those undergoing direct surgery, so as to improve preoperative preparation.Methods: The retrospective study was approved by an ethics review committee. A total of 232 patients with hepatocellular carcinoma who underwent surgical resection at the First Affiliated Hospital of Chongqing Medical University from September 2022 to December 2023 were included, comprising 210 operating patients and 53 conversion patients. Propensity score matching was employed for comparison in order to minimize bias.Results: The conversion group had more intraoperative bleeding (each P=0.001), longer operation time (P=0.033; PSM p=0.025), and higher intraoperative blood transfusion rate (p=0.001; PSM p=0.044). The incidence of perioperative complications, including perioperative ascites formation (p=0.011; PSM p=0.005), moderate to severe anemia (p=0.001; PSM p=0.002), postoperative blood transfusion (p=0.004; PSM p=0.036), and postoperative ICU transfer (p=0.041; PSM p=0.025), was higher in the conversion group compared to the operation group. The postoperative hospital stay (p=0.001; PSM p=0.003) was prolonged in the conversion group.Conclusion: Post-conversion operations carry a higher risk of bleeding and are more likely to result in moderate to severe anemia and ascites formation in the perioperative period. However, the risk is reversible with adequate preoperative blood preparation and prompt postoperative symptomatic treatment. Conversion patients should be encouraged to undergo operating therapy when they can withstand surgical resection.Keywords: conversion therapy, hepatocellular carcinoma, perioperative complications, hepatectomy, perioperative complications

Runing Fu,1,* Wenping Lian,1,* Bohao Zhang,2,* Gang Liu,3 Xinyu Feng,1 Yingjie Zhu,1 Jiuan Zhou,1 Xinyu Zhang,4 Shukai Wang,1 Huijuan Huo,1 Daxin Wang,1 Cui Liu,1 Saisai Gao,1 Yajie Ma,4 Mengle Peng1,* 1Department of Clinical Laboratory, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China; 3The Center of Meige Syndrome, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 4Department of Medical Affair, the Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mengle Peng; Yajie Ma, Email pengmengle1990@126.com; szsyywk@sina.comPurpose: Inflammatory markers are known to be associated with many diseases, but their role in Meige syndrome (MS) remains unclear. This study aimed to develop and validate a nomogram for the risk prediction of MS based on inflammatory markers.Patient Data and Methods: Data from 448 consecutive patients with MS at the Third People’s Hospital of Henan Province between January 2022 and December 2023 were retrospectively reviewed. The MS cohort was randomly divided into separate training and validation sets. A nomogram was constructed using a multivariate logistic regression model based on data from the training set. The model’s performance was validated through cross-validation, receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA).Results: A total of five predictors, including red blood cell distribution width (RDW), hemoglobin (HGB), high-density lipoprotein cholesterol (HDL-C), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune‐inflammation index (SII), were identified using multivariate logistic regression from a total of 11 variables. The cross-validation results indicated the stability of the model constructed with the above five predictors. The model showed moderate predictive ability, with an area under the ROC curve of 0.767 in the training set and 0.735 in the validation set. The calibration curve and DCA results indicate that the model has strong consistency and significant potential for clinical application.Conclusion: We constructed a nomogram based on five risk predictors, RDW, HGB, HDL-C, the LMR and the SII, to predict MS and enhance the predictive accuracy for identifying MS risk.Keywords: Meige syndrome, inflammatory marker, nomogram, LMR, SII

Yuan Shi,* Kai Chen,* Xinlin Li,* Xiaodong Li, Xu Feng, Xinhua Wu, Shiguai Qi, Zhengrong Shi Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengrong Shi, Email shizr@hospital.cqmu.edu.cnPurpose: This research aims to compare the efficacy of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) combined with Lenvatinib (Len) to direct liver resection (LR) in patients with resectable or borderline resectable hepatocellular carcinoma (HCC).Methods: This retrospective study included 154 patients with hepatocellular carcinoma (HCC) treated at the a large-scale hepatocellular carcinoma Research Center between March 2019 and June 2023. Patients were assigned to one of two groups: 63 received neoadjuvant hepatic arterial infusion chemotherapy (HAIC) combined with Lenvatinib followed by liver resection (HAIC+Len→LR), while 91 received direct liver resection (LR). The primary outcomes assessed were median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and adverse events (AEs).Results: Patients in the HAIC+Len→LR group demonstrated significantly longer median overall survival (mOS) (40.1 months vs 35.9 months, P=0.001) and median progression-free survival (mPFS) (32.8 months vs 23.8 months, P=0.0023) compared to the LR group. Preoperative complete response (CR) to HAIC was associated with better median duration of response (mDOR) and mOS compared to partial response (PR) (not reached vs 28.9 months, P=0.006; 40.0 vs 29.1 months, P=0.037). Subgroup analysis revealed no significant difference in OS or PFS between the HAIC+Len→LR and LR groups in early Barcelona Clinic Liver Cancer (BCLC) stages. However, in late BCLC stages, the HAIC+Len→LR group exhibited significantly improved OS and PFS (HR 0.471, P=0.016; HR 0.551, P=0.022). Treatment-related grade ≥ 3 adverse events were comparable between the two groups.Conclusion: For patients with resectable or marginally resectable HCC in the intermediate to advanced stages of BCLC, surgery after neoadjuvant HAIC+Len may offer improved long-term prognosis.Keywords: hepatic arterial infusion chemotherapy, lenvatinib, progression-free survival, overall survival, resectable or borderline resectable hepatocellular carcinoma

Xiaoyue Feng,1,* Jianli Shang,1,* Zhengping Gu,1 Junhua Gong,1 Yong Chen,1,2 Youting Liu1,2 1R&D Department, Beijing UPROVEN Medical Technology Co., Ltd., Beijing, Daxing, People’s Republic of China; 2Beijing UPROVEN Institute of Dermatology, Beijing, Daxing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Youting Liu, R&D Department, Beijing UPROVEN Medical Technology Co., Ltd., Yard 5, Tianhua Avenue, Beijing, Daxing, 102699, People’s Republic of China, Tel +86 18510256963, Email YtLiu.adpt@outlook.comAbstract: AZA is a non-phenolic, saturated dicarboxylic acid with nine carbon atoms, naturally produced by the yeast Malassezia. It has diverse physiological activities, including antibacterial, anti-keratinizing, antimelanogenic, antioxidant and anti-inflammatory effects. AZA is widely used in dermatology and is FDA-approved for treating papulopustular rosacea. It also shows significant efficacy in acne vulgaris and melasma. This review summarizes the mechanisms of action and clinical applications of AZA, aiming to provide theoretical support for its clinical and cosmetic use and to facilitate further research.Keywords: azelaic acid, mechanism, rosacea, acne, melasma, safety

Bin Liu,* Bingtian Zhao,* Yan Yin, Yan Jiang, Xue Feng, Lei Wang, Liang Zhai, Guangxin Liu, Dongsheng Shi, Jianwen Qin Department of Respiratory and Critical Medicine, Tianjin Chest Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongsheng Shi; Jianwen Qin, Tianjin Chest Hospital, No. 261, Taierzhuang South Road, Jinnan District, Tianjin, 300051, People’s Republic of China, Email shi_ds@126.com; qinjianwen2005@aliyun.com; 5020200603@nankai.edu.cnPurpose: DNA methylation plays a regulatory role in the oncogenesis and tumor progression and is valuable in the diagnosis and prognosis of cancer. While circulating tumor DNA (ctDNA) is widely used in the detection of oncogenic mutations and the guidance of treatment in advanced non-small cell lung cancer (NSCLC), studies of ctDNA methylation remains insufficient. We aim to investigate the methylation profiles of ctDNA in patients with advanced NSCLC undergoing EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy and to discover novel biomarkers with predictive or prognostic value.Patients and Methods: We recruited 49 patients with EGFR-mutated advanced NSCLC undergoing EGFR-TKI as first-line treatment. Utilizing next-generation sequencing, we examined the somatic mutations and methylation signatures within the tumor-associated genomic regions of ctDNA from pre-treatment blood. Subsequently, we explored the association of these molecular features with the patients’ response to therapy and their progression-free survival (PFS).Results: Genomic mutation profiling revealed no significant association of PFS or best overall response (BOR) and ctDNA status. Evaluation of ctDNA methylation showed a negative correlation between the methylation of small nucleolar RNA (snoRNA) genes and PFS (R=− 0.31, P=0.043). Furthermore, high-level methylation of SNORD3F was associated with poorer PFS (mPFS 346d vs 243d, HR 0.49, 95% CI 0.24– 0.93, P=0.029).Conclusion: Our study explored the prognostic value of ctDNA methylation in patients with advanced NSCLC undergoing targeted therapies and first revealed the predictive role of SNORD3F.Keywords: ctDNA, EGFR, DNA methylation, lung cancer, snoRNA, SNORD3F

Yuqi Zhang,1,2 Keqian Du,1,2 Xiaoxue Feng,1,2 Jia Xu,1,2 Peijun Xu,1,2 Jianlin Huang1,2 1Department of Rheumatology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Jianlin Huang; Peijun Xu, Department of Rheumatology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, People’s Republic of China, Email hjianl@mail.sysu.edu.cn; xupj@mail.sysu.edu.cnPurpose: This study aimed to compare the rates of disease remission evaluated using various remission criteria, including Boolean2.0, Boolean1.0, clinical disease activity index (CDAI), simplified disease activity index (SDAI), and disease activity score using 28 joints based on C-reactive protein (DAS28-CRP) in patients with rheumatoid arthritis (RA).Patients and Methods: A cross-sectional observational analysis was performed using data from patients with RA enrolled in a smart system of disease management group (SSDM). The clinical remission rates of RA patients estimated using the DAS28-CRP, CDAI, SDAI, Boolean1.0 and Boolean2.0 criteria were investigated. Variables were compared using the t-test, Mann–Whitney U-test, or chi-squared test. The agreement between Boolean remission and the DAS28-CRP, CDAI, or SDAI definitions of remission was assessed using McNemar’s test with k coefficient of agreement.Results: A total of 5619 patients were included in the analysis. The mean age of the patients was 56.33 (± 13.01) years, with the majority being female (4491, 79.9%). The rates of remission, as assessed by Boolean2.0, Boolean1.0, DAS28-CRP, CDAI, and SDAI, were 16.6%, 9.7%, 35.2%, 9.1%, and 9.4%, respectively. Comparison with Boolean1.0 criteria revealed higher concordance between Boolean2.0 and DAS28-CRP remission and lower concordance with CDAI and SDAI, regardless of whether the analysis was conducted on the entire population or subgroups based on gender, age or disease duration. Additionally, the administration of different medications may have influenced the rate of Boolean2.0 remission.Conclusion: This study demonstrated a higher concordance between Boolean2.0 criteria and DAS28-CRP remission and a lower concordance with CDAI and SDAI when compared with Boolean1.0 remission criteria.Keywords: Boolean, clinical disease activity index, concordance, disease activity score using 28 joints, remission, simplified disease activity index

Xianling Feng,1,* Fucheng Tao,2,* Min Ren,3,* Mao Niu4 1School of Medical, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 2Department of Stomatology, Shenzhen University General Hospital, Shenzhen, 518055, People’s Republic of China; 3Department of Stomatology, Rizhao Traditional Chinese Medicine Hospital, Rizhao, 276800, People’s Republic of China; 4School of Medical Technology and Nursing, Shenzhen Polytechnic University, Shenzhen, 518055, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao Niu, School of Medical Technology and Nursing, Shenzhen Polytechnic University, 7098 Liuxian Avenue, Nanshan District, Shenzhen, 518055, People’s Republic of China, Tel +86 755 26011160, Fax +86 755 26018477, Email niu1037@szpu.edu.cnObject: The present study intended to evaluate the effect of simvastatin-loaded nanomicelles (SVNs) on promoting new bone formation and reducing alveolar ridge resorption at the tooth extraction sites at the early healing of the extraction sockets.Methods: SVNs were synthesized using a dialysis method. The rabbit tooth extraction model was established, SVNs and simvastatin (SV) were loaded on gelatin sponge and inserted into the extraction socket. CBCT scans were performed at 0, 2, and 4 weeks postoperatively to evaluate bone formation and alveolar ridge absorption in the extraction sockets. And all the animals were sacrificed and the mandibles were harvested. And HE staining and Masson staining were used for histological evaluation of the bone formation in the extraction sockets.Results: Radiographic evaluation showed that compared with the blank control group, at 2 and 4 weeks after extraction, SVNs increased the new bone density in the extraction sockets by 75.7% and 96.5%, and reduced the absorption rate of alveolar ridge length at the extraction sites by 60.8% and 49.1%, respectively. Histological evaluation showed that SVNs significantly improved the maturation of new bone tissue in the extraction sockets.Conclusion: SVNs can significantly accelerate healing and effectively reduce the absorption of alveolar ridge at the extraction sites in the early stage of tooth extraction socket healing.Keywords: alveolar ridge preservation, simvastatin-loaded nanomicelles, tooth extraction sites, bone formation

Yihua Jin,1,* Zhimin Geng,1,2,* Kun Lin,1 Xinyu Gu,1 Xiwei Feng,1 Songling Fu,1 Wei Wang,1 Chunhong Xie,1 Yujia Wang,1 Fangqi Gong1 1Department of Cardiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 2Pediatric Cardiovascular Diseases Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fangqi Gong; Yujia Wang, Email gongfangqi@zju.edu.cn; wangyujia@zju.edu.cnPurpose: Kawasaki disease (KD) is an acute systemic vasculitis that is associated with dysregulated immune responses. Monocytes play a central role in innate immunity. Our previous single-cell RNA sequencing of peripheral blood mononuclear cells (PBMC) revealed a new subset of monocytes in children with KD called L-Selectin+ classical monocytes (SELL+ CM). Therefore, we aimed to investigate the correlation between KD and SELL+ CM.Patients and Methods: Peripheral blood samples were collected from 81 KD patients, 18 febrile patients and 36 healthy children before treatment. Among them, ten KD patients were followed up, and samples were obtained before and after intravenous immunoglobulin (IVIG) treatment. Analysis of SELL+ CM was performed using flow cytometry. Additionally, ROC curve analysis was conducted to assess the diagnostic value of SELL+ CM for KD.Results: Classical monocytes (CM) expressed the highest levels of L-selectin in children with KD. The ratio of SELL+ CM in CM was significantly higher in KD patients than in febrile and healthy children. Following IVIG treatment, the ratio of SELL+ CM in CM showed a downward trend. The receiver operating characteristic (ROC) curve analysis (the area under the curve, AUC = 0.71) indicated the potential diagnostic value of SELL+ CM in KD. The correlation analysis suggested that SELL+ CM may serve as a new clinical index for patients with KD.Conclusion: In KD, the ratio of SELL+ CM in CM significantly increases during the acute phase, which may become a potential biomarker and help facilitate KD diagnosis based on clinical features.Keywords: Kawasaki disease, monocyte subsets, L-Selectin, coronary artery lesions

Guimin Hou,1,* Feng Zhang,1,* Xielin Feng,1 Yan Chen,2 Jinliang Zhang,1 Haiqing Wang1 1Department of Hepatopancreatobiliary Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Pharmacy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiqing Wang, Department of Hepatopancreatobiliary Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China, Tel +86-028-85420945, Email wanghaiqing241286@163.comPurpose: Hepatectomy could provide better survival benefit for hepatocellular carcinoma (HCC) with type I/II portal vein tumor thrombosis (PVTT). However, the postoperative recurrence remains high. We discussed whether neoadjuvant therapy could reduce HCC recurrence for these patients.Patients and Methods: One hundred and thirty-eight resectable HCC with type I–II PVTT were retrospectively included. The neoadjuvant therapy regimens included tyrosine kinase inhibitor (TKI), programmed death 1(PD-1) antibodies and transarterial chemoembolization (TACE). Short-term and long-term outcomes were compared. Propensity score matching (PSM) was performed to minimize the influence of potential confounders.Results: Thirty-three patients underwent neoadjuvant therapy and 105 patients underwent surgery alone. In the neoadjuvant group, 7 (21.2%) patients achieved stable disease, 13 (39.4%) achieved partial response and 13 (39.4%) achieved complete response based on the modified Response Evaluation Criteria in Solid Tumors criterion. By PSM, the neoadjuvant therapy resulted in less microvascular invasion (24.1% vs 50.0%, P=0.021), satellite nodule (6.9% vs 24.1%, P=0.036) and less patients with alpha-fetoprotein> 20(ng/mL) (37.9% vs 69.0%, P=0.006). The neoadjuvant therapy reduced tumor recurrence and prolonged survival. Multivariate analysis found that neoadjuvant therapy was an independent protective factor for overall survival and recurrence free survival.Conclusion: Neoadjuvant treatment presents a promising treatment option for HCC patients with type I/II PVTT.Keywords: hepatocellular carcinoma, neoadjuvant treatment, portal vein tumor thrombosis, TACE, immunotherapy, TKIs

Xinyu Han,1 Tian Qiang Wu,1 Ruiting Yao,1 Chang Liu,1 Lu Chen,2 Xiaoling Feng2 1Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of ChinaCorrespondence: Xiaoling Feng, Department of Gynecology, The First Affiliated Hospital of Heilongjiang University, No. 26, Heping Road, Xiang-Fang District, Harbin City, Heilongjiang Province, People’s Republic of China, Email Doctorfxl@163.comBackground: Observational studies have established a connection between Gastroesophageal reflux disease (GERD) and preterm birth (PTB). Nevertheless, these correlations can be affected by residual confounding or reverse causality, resulting in ambiguity regarding the connection. The objective of this study was to assess the relationship between genetically predicted GERD and PTB.Methods: Initially, we performed bidirectional univariate Mendelian randomization (UVMR) analysis utilizing publicly accessible genome-wide association studies (GWAS) data. The primary analytical approach employed to determine the causal impact between GERD and PTB is the inverse variance weighted technique (IVW). Subsequently, we utilized multivariate Mendelian randomization (MVMR) to adjust for potential factors that could influence the results, such as body mass index (BMI), maternal smoking around birth, educational attainment, household income, and Townsend deprivation index (TDI). Furthermore, we performed a sequence of comprehensive sensitivity analyses to assess the reliability of our MR findings.Results: The UVMR analysis results showed a significant correlation between GERD and PTB (odds ratio [OR]: 1.810; 95% confidence interval [CI]: 1.344– 2.439; P=9.60E-05) in the IVW model, and the Weighted median method (OR=1.591, 95% CI=1.094– 2.315, P=0.015) revealed consistent results. The inverse MR findings suggest no causal link between PTB and the incidence of GERD. In addition, the sensitivity analysis did not detect heterogeneity or horizontal pleiotropy, and the “leave-one-out” examination confirmed that the causal estimation is unlikely to be influenced by the single nucleotide polymorphisms (SNPs) effect. The MVMR analysis demonstrated that the causal association between GERD and PTB still existed after considering BMI, maternal smoking around birth, educational attainment, household income, and TDI (OR=1.921, 95% CI=1.401– 2.634, P=5.08E-05).Conclusion: This study presents evidence indicating that genetically predicted GERD can heighten the risk of PTB. Therefore, it is advisable to perform focused screening for pregnant women with GERD in order to find the initial signs of PTB and promptly apply intervention strategies to extend the duration of pregnancy.Keywords: Mendelian randomization, gastroesophageal reflux disease, preterm birth, causality

Na Wang,1,2 Guofeng Wang,2 Xiuli Feng,2 Teng Yang2 1Department of Endocrinology, Lianyungang Clinical College of Nanjing Medical University, Lianyungang City, Jiangsu Province, 222000, People’s Republic of China; 2Department of Endocrinology, Jinzhou Medical University(The First People’s Hospital of Lianyungang), Lianyungang City, Jiangsu Province, 222000, People’s Republic of ChinaCorrespondence: Guofeng Wang, Department of Endocrinology, Lianyungang Clinical College of Nanjing Medical University (The First People’s hospital of Lianyungang), No. 6 Zhenhua East Road, Haizhou District, Lianyungang City, Jiangsu Province, 222000, People’s Republic of China, Email wangguofengo@21cn.comPurpose: This study aimed to investigate the abnormal infiltration of immune cells in type 1 diabetes mellitus (T1D) and elucidate their regulatory mechanisms.Methods: Public T1D-related gene expression data were obtained from the Gene Expression Omnibus database.The GSE123658 dataset analyzed whole blood RNA-seq data from type 1 diabetic patients and healthy volunteers. The GSE110914 dataset analyzed neutrophils purified from peripheral blood of patients with symptomatic and pre-symptomatic type 1 diabetes (T1D), at risk of T1D, and healthy controls. Immune cell infiltration analysis was performed to identify abnormally infiltrating immune cells. Differentially expressed immune genes (DEIGs) in T1D samples were identified, followed by the construction of an immune gene signature (IGS) using a protein-protein interaction (PPI) network and Least absolute shrinkage and selection operator Cox regression analyses (LASSO Cox regression analyses). The regulatory mechanisms underlying IGS were explored using gene set enrichment analysis. Furthermore, expression validation, diagnostic efficacy evaluation, and upstream miRNA prediction of hub signature genes were performed. We verified the miRNA expression of the key gene colony stimulating factor 1 (CSF1) and microRNA-326 (miR-326) by reverse transcription-quantitative PCR (RT‒qPCR).Results: The proportion of infiltrating T and natural killer (NK) cells differed between the T1D and control samples, and 207 immune genes (IGs) related to these immune cells were extracted. After differential expression, PPI, and LASSO Cox regression analyses, four signature DEIGs were identified for IGS construction: notch receptor 1 (NOTCH1), Janus kinase 3 (JAK3), tumor necrosis factor receptor superfamily member 4(TNFRSF4), and CSF1. Key pathways such as the Toll-like receptor signaling pathway were significantly activated in the high-risk group. Moreover, the upregulation of CSF1 in T1D samples was confirmed using a validation dataset, and CSF1 showed high diagnostic efficacy for T1D. Furthermore, CSF1 was targeted by miR-326.We used validated key genes in T1D patients, several of which were confirmed by RT‒qPCR.Conclusion: In conclusion, the identified key IGs may play an important role in T1D. CSF1 can be developed as a novel diagnostic biomarker for T1D.Keywords: Type 1 diabetes, immune cell infiltration, immune gene signature, diagnosis, CSF1

Cunchuan Chen,1,2,&ast; Huifang Zhang,1,2,&ast; Xia Feng,1,2 Haipeng Wang1,2 1Center for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China; 2NHC Key Laboratory of Health Economics and Policy Research, Shandong University, Jinan, 250012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haipeng Wang, Email wanghaipeng@sdu.edu.cnBackground: This alteration in the policy of COVID-19 resulted in widespread infections throughout China. Most people only need some antiviral drugs such as lopinavir/ritonavir or Chinese herbal preparations for treatment. In this context, the lack of drug knowledge and inadequate drug availability are evident. This study aims to explore the factors influencing drug use and demand during the COVID-19 epidemic.Methods: This study used quota sampling based on gender, age, and place of residence to perform a cross-sectional survey on a sample of 771 adults. The researchers used chi-square tests to understand differences in drug use and demand across characteristics, and binary logistic regression to analyse the influencing factors.Results: The study revealed that 85.9% of the participants used drugs following the COVID-19 infection. Participants with college and above, (OR=2.49, 95% CI=1.27– 4.88) annual personal income between 30,000 and 80,000CNY (OR=2.19, 95% CI=1.35– 3.55) and over 80,000CNY (OR=1.96, 95% CI=1.05– 3.66) were more knowledgeable about using drugs. Gender, (OR=0.69, 95% CI=0.50– 0.95) age, (OR=2.11, 95% CI=1.15– 3.88) residence, (OR=1.58, 95% CI=1.06– 2.37) chronic disease conditions (OR=0.46, 95% CI=0.27– 0.78) and infection symptoms (OR=0.60, 95% CI=0.38– 0.93) as factors influencing the need for drug delivery services. (P< 0.05).Conclusion: Research has revealed that a significant proportion of infected people in China chose drug treatment during COVID-19. Individuals with severe symptoms use more medication and require more drug delivery and storage. Low-education and low-income populations are lacking in drug knowledge, and older adults with underlying medical conditions are more likely to need drug delivery services. Therefore, governments should prioritize vulnerable groups when formulating drug policies and target drug literacy and guidance. In addition, it is recommended that a drug distribution system be set up within the community so that those in need can have quick and easy access to drugs.Keywords: COVID-19, drug use, drug demand, drug delivery, drug stockpiling

Kaiyue Zhang, Chunnan Li, Peitong Wu, Xiaochen Gao, Xueqin Feng, Jiaming Shen, Nanxi Zhang, Xuesheng Hu, Shuo Wang, Hui Zhang, Jingwei Lv, Jiaming Sun Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Jiaming Sun; Jingwei Lv, Changchun University of Chinese Medicine, No. 1035, Boshuo Road, Nanguan District, Changchun, 130117, People’s Republic of China, Tel +0431-86763809, Fax + 8676 3968, Email Sun_jiaming2000@163.com; jingwei-lv@hotmail.comPurpose: Zhixiao Tang (ZXT), a traditional Chinese compound prescription, has been used clinically to treat pneumonia in China. However, the underlying mechanism of ZXT treatment in pneumonia is still unclear. The present study aimed to reveal the potential mechanism of ZXT in pneumonia using a strategy combining metabolomics and network pharmacology.Methods: Initially, the chemical compositions were identified by UPLC-QE-Orbitrap-MS, while the prediction of potential signal pathways was performed through network pharmacology. To assess the anti-inflammatory properties of ZXT in the context of pneumonia, models of 16HBE cells induced by LPS and zebrafish induced by CuSO4 were established to measure levels of inflammatory markers and apoptosis. Subsequently, the differential changes of endogenous metabolites in cells caused by ZXT were examined using metabolomics technology, and the molecular docking analysis of key targets was carried out using Autodock Vina software. Ultimately, the validation of the primary pathways and targets was conducted through quantitative RT-PCR and Western blot techniques.Results: A total of 75 compounds were identified through UPLC-QE-Orbitrap-MS analyses. Network pharmacological analysis shows that it plays an anti-inflammatory role in C-type lectin receptor signaling pathway. After ZXT intervention, the inflammatory factors and apoptosis in cells were significantly reduced. Metabonomics analysis showed that 18 metabolites changed significantly. Four key genes were identified, which exhibited partial compatibility with the findings of network pharmacology. Molecular docking analysis confirmed the substantial affinity of the primary targets for ZXT. Furthermore, ZXT exerted a suppressive effect on neutrophil migration, down-regulated the expression of pro-inflammatory cytokine genes, and inhibited the up-regulation of the Dectin-1/SYK/NF-κB signaling pathway. In vivo cell experiments also yielded consistent experimental outcomes.Conclusion: This study enhances comprehension of the pharmacological mechanism underlying ZXT’s efficacy in pneumonia treatment, thereby establishing a scholarly basis for future research and clinical utilization of ZXT in pneumonia management. Keywords: Zhixiao Tang, pneumonia, network pharmacology, integrated metabolomics, 16HBE, Zebrafish

Xiaona Lang,1 Liyan Xu,2 Lu Li,1 Xin Feng1 1Pharmacy Department, Tianjin Hospital, Tianjin, People’s Republic of China; 2Orthopedic Department, Tianjin Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Xin Feng, Pharmacy Department, Tianjin Hospital, Tianjin, People’s Republic of China, Tel +86-13652001152, Email fx_yutong@126.comObjective: Catalpol, as a natural medicine small-molecule drug, has been proven to have anti-inflammatory and antioxidant pharmacological effects.Methods: The effect of catalpol on oxidative damage of mouse epidermal fibroblast L929 model and its mechanism were investigated by using hydrogen peroxide model, CCK8 method, flow cytometry, and Western blot.Results: The effect of catalpol on Nrf2/HO-1 signaling pathway was further studied to improve oxidative stress in cell models. The results showed that catalpol had no cytotoxicity to L929 cells, and inhibited the apoptosis of L929 cells after oxidative damage in a concentration-dependent manner, thus playing a role in cell protection. The oxidative damage of cells was inhibited by up-regulating the expression of the signature protein of Nrf2/HO-1 signaling pathway and inhibiting the interstitial formation of cells.Conclusion: This study is a preliminary study on the protective function of catalpol against oxidation and apoptosis in dermal fibroblasts, which can provide a theoretical basis and drug guidance for promoting skin wound healing in the later stage.Keywords: catalpol, oxidative damage, Nrf2/HO-1, dermal fibroblasts, oxidative stress

Haiqing Wang,1,&ast; Wentao Bo,1,&ast; Xielin Feng,1 Jinliang Zhang,1 Ge Li,2 Yan Chen3 1Department of Hepatopancreatobiliary Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Emergency, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Department of Pharmacy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Chen; Ge Li, Email cyfy1112@163.com; chenyanyaoxuebu@scszlyy.org.cn; 13982129787@qq.comAbstract: Lenvatinib (LVN) is a potentially effective multiple-targeted receptor tyrosine kinase inhibitor approved for treating hepatocellular carcinoma, metastatic renal cell carcinoma and thyroid cancer. Nonetheless, poor pharmacokinetic properties including poor water solubility and rapid metabolic, complex tumor microenvironment, and drug resistance have impeded its satisfactory therapeutic efficacy. This article comprehensively reviews the uses of nanotechnology in LVN to improve antitumor effects. With the characteristic of high modifiability and loading capacity of the nano-drug delivery system, an active targeting approach, controllable drug release, and biomimetic strategies have been devised to deliver LVN to target tumors in sequence, compensating for the lack of passive targeting. The existing applications and advances of LVN in improving therapeutic efficacy include improving longer-term efficiency, achieving higher efficiency, combination therapy, tracking and diagnosing application and reducing toxicity. Therefore, using multiple strategies combined with photothermal, photodynamic, and immunoregulatory therapies potentially overcomes multi-drug resistance, regulates unfavorable tumor microenvironment, and yields higher synergistic antitumor effects. In brief, the nano-LVN delivery system has brought light to the war against cancer while at the same time improving the antitumor effect. More intelligent and multifunctional nanoparticles should be investigated and further converted into clinical applications in the future. Keywords: lenvatinib, nano-drug delivery system, antitumor, side effects, diagnosis

Xiuwen Chen,1,&ast; Meiyan Zou,1,&ast; Siquan Liu,1 Weilin Cheng,1 Weihong Guo,2 Xiaoli Feng1 1Stomatology Hospital, School of Stomatology, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weihong Guo; Xiaoli Feng, Email drguowh@163.com; dentistfxl226@163.comAbstract: Graphene family nanomaterials (GFNs) have attracted considerable attention in diverse fields from engineering and electronics to biomedical applications because of their distinctive physicochemical properties such as large specific surface area, high mechanical strength, and favorable hydrophilic nature. Moreover, GFNs have demonstrated the ability to create an anti-inflammatory environment and exhibit antibacterial effects. Consequently, these materials hold immense potential in facilitating cell adhesion, proliferation, and differentiation, further promoting the repair and regeneration of various tissues, including bone, nerve, oral, myocardial, and vascular tissues. Note that challenges still persist in current applications, including concerns regarding biosecurity risks, inadequate adhesion performance, and unsuitable degradability as matrix materials. This review provides a comprehensive overview of current advancements in the utilization of GFNs in regenerative medicine, as well as their molecular mechanism and signaling targets in facilitating tissue repair and regeneration. Future research prospects for GFNs, such as potential in promoting ocular tissue regeneration, are also discussed in details. We hope to offer a valuable reference for the clinical application of GFNs in the treatment of bone defects, nerve damage, periodontitis, and atherosclerosis. Keywords: graphene, graphene oxide, regenerative medicine, scaffold, anti-inflammatory, bone regeneration, nerve, angiogenesis, dental pulp stem cells

Shanshan Cui,1 Xiaobo Feng,2 Zhongyuan Xia1 1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 2Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei Province, People’s Republic of ChinaCorrespondence: Zhongyuan Xia, Department of Anesthesiology, Renmin Hospital of Wuhan University, Ziyang Road, Wuchang District, Wuhan, Hubei Province, People’s Republic of China, Email xiazhongyuan2005@aliyun.comBackground: In traditional Chinese medicine, Ligusticum chuanxiong Hort. (LCH) is used to treat neuropathic pain (NP). This study was performed to investigate the underlying pharmacological mechanisms.Methods: The main components of the LCH were obtained from the TCMSP database. The targets of the active components were obtained using the Swiss Target Prediction database and HERB database. The NP-related genes were obtained from the CTD database and GeneCard database. Protein-protein interaction (PPI) network was constructed using the STRING platform and Cytoscape 3.9.0 software. GO and KEGG enrichment analyses were performed using the DAVID database. Interactions between the key components and hub target proteins were verified using molecular docking and molecular dynamics simulation. In addition, microglial cell line HMC3 was induced to polarize to the M1 phenotype using 100 ng/mL lipopolysaccharide (LPS). Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and enzyme-linked immunosorbent assays were used to detect the expression levels of M1 markers and inflammatory factors, respectively.Results: Seven LCH active components of LCH were identified, corresponding to 387 target genes. 2019 NP-related genes were obtained, and a total of 174 NP-related genes were identified as target genes that could be modulated by LCH. Beta-sitosterol, senkyunone, wallichilide, myricanone, and mandenol were considered as the key components of LCH in the treatment of NP. SRC, BCL2, AKT1, HIF1A and HSP90AA1 were identified as the hub target proteins. GO analysis showed that 328 biological processes, 61 cell components, and 85 molecular functions were likely modulated by the components of LCH, and KEGG enrichment analysis showed that 132 signaling pathways were likely modulated by the components of LCH. Beta-sitosterol, senkyunone, wallichilide, myricanone, and mandenol showed good binding activity with hub target proteins including SRC, BCL2, AKT1, and HSP90AA1. In addition, beta-sitosterol inhibited LPS-induced M1 polarization in HMC3 in vitro.Conclusion: This study provides a theoretical basis for the application of LCH in the treatment of NP through multicomponent, multitarget, and multiple pathways.Keywords: neuropathic pain, Ligusticum chuanxiong Hort., network pharmacology, molecular docking, microglia, inflammation

Jia Li,1,2 Wenjing Guo,1,2 Jieru Wang,1,2 Xiaomeng Feng,1,2 Qingsong Lin,1,2,&ast; Yizhou Zheng,1,2 Fengkui Zhang,1,2 Yingchang Mi,1,2 Xiaofan Zhu,1,2 Erlie Jiang,1,2 Zhijian Xiao,1,2 Jianxiang Wang,1,2 Sizhou Feng1,2,&ast; 1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, People’s Republic of China; 2Tianjin Institutes of Health Science, Tianjin, 301600, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sizhou Feng, Hematopoietic Stem Cell Transplantation Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 288 Nanjing Road, Tianjin, 300020, People’s Republic of China, Tel +86-022-23909162, Fax +022-23909047, Email doctor_szhfeng@163.com; szfeng@ihcams.ac.cnObjective: This study aimed to assess the impact of colonization status on the outcomes of Acinetobacter spp. bloodstream infection (BSI) and investigate the homology and within-host evolution between colonizing and bloodstream carbapenem-resistant Acinetobacter spp. (CRA) to inform antibiotic therapeutic decisions.Methods: We analyzed clinical outcomes of 46 hematological patients with Acinetobacter spp. BSI and performed whole-genome sequencing on the remaining CRA isolates.Results: Among the patients, 39.1% (n=18) had prior Acinetobacter spp. colonization. Colonized patients had higher rates of polymicrobial BSI (50.0% vs 21.4%, P=0.044) and CRA BSI (72.2% vs 17.9%, P< 0.001), resulting in elevated inflammatory markers and increased 30-day mortality. Each of the eight pairs of the remaining respiratory colonizing and bloodstream CRA strains belonged to the same genomospecies. Each pair exhibited definitive agreement in at least 21 of the 22 most representative antibiotic susceptibility tests. The minimum spanning tree based on multilocus sequence typing (MLST) and phylogenetic trees based on MLST and single nucleotide polymorphism (SNP) all indicated that each pair shared the same minimum branch. Very few non-synonymous SNPs in genic regions were identified during the transition from respiratory colonization to bloodstream infection, with minimal changes in virulence genes. Homology analysis suggested that CRA BSI originated from colonizing isolates in the respiratory tract.Conclusion: Strict infection control measures are needed to manage Acinetobacter spp. colonisation in hematological patients. Appropriate empirical therapy can be administered for suspected CRA BSI based on the antimicrobial minimum inhibitory concentration of CRA colonising the respiratory tract.Keywords: Acinetobacter, colonization, bloodstream infections, homology, therapy, carbapenem-resistant

Xiaoyue Feng,&ast; Jianli Shang,&ast; Zhengping Gu, Xingyi Luo, Yong Chen, Youting Liu Product Research & Development Center, Beijing Underproved Medical Technology Co., LTD, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youting Liu, Product Research & Development Center, Beijing Underproved Medical Technology Co., LTD, Beijing, 102699, People’s Republic of China, Tel +86 1 851 025 6963, Email YtLiu.adpt@outlook.comAbstract: Lactic acid is the most widely occurring natural organic acid in nature. It not only exhibits mild and safe properties but also possesses multiple physiological activities, such as antibacterial effects, immune regulation, and promotion of wound healing, making it one of the most popular chemical peeling agents. Chemical peels are commonly used in the field of aesthetic dermatology as a non-invasive therapeutic approach. This research aims to provide valuable references for clinical dermatologists by summarizing the characteristics of lactic acid, elucidating its mechanism of action in peeling, and investigating the clinical applications of this compound. Furthermore, it anticipates the potential for lactic acid to be the most suitable chemical peeling agent for Chinese skin.Keywords: lactic acid, physiological activities, clinical applications, Chinese skin

Xiaona Lang,1 Lu Li,1 Yuntao Li,2 Xin Feng1 1Pharmacy Department, Tianjin Hospital, Tianjin, People’s Republic of China; 2Integrative Chinese and Western Medicine Department, Tianjin Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Xin Feng, Pharmacy Department, Tianjin Hospital, Tianjin, People’s Republic of China, Tel +86-13652001152, Email fx_yutong@126.comObjective: The quality of life of diabetic patients is seriously affected by wound healing difficulty, which can lead to increased infection, skin deep tissue injury and continuous pain. By analyzing the research trends and hot spots in this field, the visualization analysis map is constructed.Methods: The contents of the selected articles were sorted out and analyzed by bibliometrics. We use CiteSpace, Vosviewer and HistCite to visualize literature information, including national publication statistics, institutions, authors, journal partnerships, and citations of published articles.Results: Among the 2942 articles, the United States and China ranked first in both article circulation and TGCS, and many countries also cooperated. The collaboration between schools and research institutions is a core part of dissertation research institution collaboration, with most authors coming from the same institution. Most of the literature studies on the mechanisms and methods of promoting diabetic wound healing. Improving cell function or making innovative attempts in local treatment are the fruits of researchers’ efforts to promote diabetic wound healing in recent years.Conclusion: Through the metrology method, the time distribution, author institution, cooperation network, research status, research hotspot and development trend of the literature on the influence of diabetes on wound healing were intuitively displayed, which provided a reference for further research and development direction.Keywords: diabetes, wound healing, bibliometrics, visualized analysis, Citespace

Xian Li,1,&ast; Hong Lai,2,&ast; Peng Wang,3 Shuai Feng,4 Xuexin Feng,4 Chao Kong,3 Dewei Wu,5 Chunlin Yin,5 Jianghua Shen,6 Suying Yan,6 Rui Han,7 Jia Liu,7 Xiaoyi Ren,8 Ying Li,8 Lu Tang,9 Dong Xue,9 Ying Zhao,9 Hao Huang,10 Xiaoying Li,10 Yanhong Zhang,10 Xue Wang,11 Chunxiu Wang,12 Ping Jin,13 Shibao Lu,3 Tianlong Wang,4 Guoguang Zhao,14 Chaodong Wang1 On behalf of the APPLE-MDT Research Team, Xuanwu Hospital, Capital Medical University and National Clinical Research Center for Geriatric Diseases1Department of Neurology & Neurobiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 3Department of Orthopedic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 4Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 5Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 6Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 7Department of Gerontology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 8Department of Nutrition, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 9Department of Oral Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 10Department of Medical Administration, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 11Department of Medical Library, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 12Center for Evidence-Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 13Center for Medical Information, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 14Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaodong Wang, Department of Neurology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, No. 45 Changchun Street, Beijing, 100053, People’s Republic of China, Tel/Fax +86-10-8319-8677, Email cdongwang@xwhosp.orgPurpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions.Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation–Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥ 1 point between the preoperative and postoperative scale was defined as POCD.Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥ 4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028– 5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057– 0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively.Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.Keywords: cognitive dysfunction, postoperative cognitive complications, orthopedic surgery, comprehensive geriatric assessment, risk factors

Tian Liu, Zhenkun Qin, Zhiyue Yang, Xiaoling Feng Division of General Practice, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of ChinaCorrespondence: Xiaoling Feng, Division of General Practice, The Fifth Affiliated Hospital of Xinjiang Medical University, No. 118, Henan West Road, Urumqi, Xinjiang Uygur Autonomous Region, 830011, People’s Republic of China, Email 1874519696@qq.comBackground: Numerous non-invasive serologic tests are available to diagnose and monitor ulcerative colitis (UC), but their accuracy levels are limited. Thus, there is a pressing need for a serologic biomarker with higher precision for clinical practice. This study aims to evaluate the predictive capacity of monocyte/HDL ratio (MHR) and neutrophil/lymphocyte ratio (NLR) for UC disease activity.Patients and Methods: We conducted a retrospective analysis of 81 UC patients and 77 age- and sex-matched healthy controls. UC patients were categorized into active and inactive groups based on the Mayo score. The Mayo endoscopic subscore classified them into mild-to-moderate and severe UC groups.Results: The optimal cut-off values for diagnosing UC were 0.34 for MHR (85.7% sensitivity, 76.0% specificity, 88.9% positive predictive value, 70.4% negative predictive value) and 2.49 for NLR (66.1% sensitivity, 88.0% specificity, 92.5% positive predictive value, 53.7% negative predictive value). The optimal MHR and NLR cut-off values to differentiate between mild-to-moderate UC and severe UC were 0.38 (92.9% sensitivity, 56.6% specificity, 53.1% positive predictive value, 93.7% negative predictive value) and 3.46 (71.4% sensitivity, 88.7% specificity, 76.9% positive predictive value, 85.5% negative predictive value), respectively.Conclusion: NLR and MHR are simple yet effective biological predictors of disease activity in UC patients.Keywords: ulcerative colitis, monocyte/HDL ratio, neutrophil/lymphocyte ratio, disease activity

Kuihan Tang,1 Li Sun,2 Long Chen,2 Xiaobo Feng,1 Jiarui Wu,2 Hao Guo,2 Yong Zheng1 1Department of Orthopedics, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, 550014, People’s Republic of China; 2Department of Orthopedics, Guizhou Provincial People’s Hospital, Guiyang, 550000, People’s Republic of ChinaCorrespondence: Yong Zheng, Email 1210244258@qq.comBackground: Mitochondrial autophagy is closely related to the pathogenesis of osteoarthritis, In order to explore the role of mitochondrial autophagy related genes in knee osteoarthritis (KOA) and its molecular mechanism.Methods: KOA-related transcriptome data were extracted from the Gene Expression Omnibus (GEO) database. Differentially expressed mitochondrial autophagy gene (DEMGs) were screened in patients with KOA by differential expression analysis. The STRING website was used to construct a protein-protein interaction (PPI) network among DEMGs. Molecular complex detection (MCODE) method in Cytoscape software was performed to identify hub DEMGs. Support vector machine recursive feature elimination (SVM-RFE) method was used to construct the hub DEMG diagnosis model. Genes with diagnostic value were identified as biomarkers by plotting receiver operating characteristic (ROC) curves and Expression validation. CIBERSORT algorithm was used to calculate the proportion of 22 immune cells in each sample in the GSE114007 dataset. Finally, biomarker expression was verified by qPCR.Results: A total of 15 DEMGs were obtained and enrichment analyses showed that these DEMG strains were mainly enriched in the mitophagy-animal, shigellosis, autophagy-animal and FoxO signal pathways. The PPI network unveiled 13 DEMGs with interactions. In addition, 8 hub DEMGs (ULK1, CALCOCO2, MAP1LC3B, BNIP3L, GABARAPL1, BNIP3, FKBP8 and FOXO3) were obtained for KOA. And 5 model DEMGs (BNIP3L, BNIP3, MAP1LC3B, ULK1 and FOXO3) were screened. The ROC curves revealed that BNIP3 and FOXO3 has strong diagnostic value in these models of DEMG. Immune-infiltration and correlation analysis showed that BNIP3 and FOXO3 were significantly correlated with three different immune cells, including primary B cells, M0 macrophage and M2 macrophage. The cartilage tissue samples qPCR verification results show that FOXO3 and BNIP3 were all down-regulated in KOA (p < 0.01), and the validation results are consistent with the above analysis.Conclusion: BNIP3 and FOXO3 have been identified as biomarkers for the diagnosis of KOA, which might supply a new insight for the pathogenesis and treatment of KOA.Keywords: Gene Expression Omnibus, diagnostic, bioinformatics analysis, immune infiltration, biomarkers

Xujun Feng, Yuan Shi, Ye Zhang, Fei Lei, Rong Ren, Xiangdong Tang Department of Respiratory and Critical Care Medicine, Sleep Medicine Center, Mental Health Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Rong Ren; Xiangdong Tang, Department of Respiratory and Critical Care Medicine, Sleep Medicine Center, Mental Health Center, West China Hospital, Sichuan University, Dian Xin Nan Jie 28&num;, Chengdu, 610041, People’s Republic of China, Tel +86-28-85422733, Email 498880651@qq.com; 2372564613@qq.comAbstract: Lungs experience frequent interactions with the external environment and have an abundant supply of blood; therefore, they are susceptible to invasion by pathogenic microorganisms and tumor cells. However, the limited pharmacokinetics of conventional drugs in the lungs poses a clinical challenge. The emergence of different nano-formulations has been facilitated by advancements in nanotechnology. Inhaled nanomedicines exhibit better targeting and prolonged therapeutic effects. Although nano-formulations have great potential, they still present several unknown risks. Herein, we review the (1) physiological anatomy of the lungs and their biological barriers, (2) pharmacokinetics and toxicology of nanomaterial formulations in the lungs; (3) current nanomaterials that can be applied to the respiratory system and related design strategies, and (4) current applications of inhaled nanomaterials in treating respiratory disorders, vaccine design, and imaging detection based on the characteristics of different nanomaterials. Finally, (5) we analyze and summarize the challenges and prospects of nanomaterials for respiratory disease applications. We believe that nanomaterials, particularly inhaled nano-formulations, have excellent prospects for application in respiratory diseases. However, we emphasize that the simultaneous toxic side effects of biological nanomaterials must be considered during the application of these emerging medicines. This study aims to offer comprehensive guidelines and valuable insights for conducting research on nanomaterials in the domain of the respiratory system. Keywords: nanoparticles, respiratory system, lungs, nanomaterials, nanotechnology

Xiaoling Feng,1 Xun Mao,1 Jianlin Zhao2,3 1Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, People’s Republic of China; 2The Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jianlin Zhao; Xun Mao, Email zjlchongqing@gmail.com; maoxun@hospital.cqmu.edu.cnObjective: To explore the prenatal diagnosis, clinical characteristics, and perinatal outcomes of placenta accreta spectrum in different placental locations.Methods: This was a retrospective cohort study. Pregnant women who delivered at two tertiary referral hospitals from January 2013 to December 2022 and were ultimately pathologically diagnosed with placenta accreta spectrum were included. They were divided into three groups based on different placental locations (anterior, posterior, and lateral wall/fundus). The differences in prenatal diagnosis, clinical characteristics, and perinatal outcomes among the three groups were compared.Results: There were 115,470 deliveries in a ten-year period at the two hospitals, and 118 case patients were confirmed to have a pathologically diagnosed placenta accreta spectrum. The posterior placenta group had a lower rate of placenta previa (76.9% vs 94.9% vs 100%, p< 0.05) and a higher gestational age at delivery (36.4± 2.45 vs 34.91± 1.76 vs 34.31± 3.41, p< 0.05) compared to the other two groups. The anterior placenta group had a significantly higher rate of invasive (increta/percreta) form placenta accreta spectrum (81.4% vs 36.5% vs 28.6%, p< 0.05) and planned cesarean section (96.6% vs 80.8% vs 71.4%, p< 0.05) compared to the other two groups. In terms of prenatal diagnosis, the anterior placenta group had a significantly higher rate of placenta accreta spectrum prenatal suspicion rate compared to the other two groups (86.4% vs 36.5% vs 57.1%, p< 0.05). The posterior placenta group had a lower rate of preoperative abdominal aortic balloon placement compared to the other two groups (5.8% vs 28.8% vs 28.6%, p< 0.05). There were no statistically significant differences among the three groups in primary perinatal outcomes, though the anterior placenta group had a longer postoperative hospital stay.Conclusion: The prenatal diagnosis rate and proportion of invasive form of placenta accreta spectrum occurring in non-anterior placenta are relatively lower than anterior placenta. There were no significant differences in major perinatal outcomes among the three groups.Keywords: placenta accreta spectrum, placenta location, clinical characteristics, perinatal outcomes

Xiaojie Feng, Lige Ding, Shangzhu Zhang, Huan Zhang Department of Emergency, Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Lige Ding, Department of Emergency, Shijiazhuang Obstetrics and Gynecology Hospital, Zhongshan Road, Shijiazhuang, 050000, Hebei, People’s Republic of China, Tel +86-13673113998, Email 13673113998@163.comIntroduction: We aimed to evaluate the risk factors for the development of deep vein thrombosis (DVT) within one month after delivery in pregnant women of advanced maternal age undergoing cesarean section and explore the predictive value of fasting coagulation indicators in relation to the development of DVT.Methods: A total of 176 eligible postpartum women were included in this study. Sixty-seven cases developed DVT within one month after delivery (DVT group), while 109 cases did not experience DVT (NDVT group). Within 24 hours after cesarean section, fasting coagulation indicators are measured. Coagulation system analysis was performed using the STA-R Evolution fully automated coagulation analyzer.Results: The women who developed DVT were found to be older, had a higher proportion of women with previous childbirth experiences, and had a higher proportion of women with comorbidities. Our results revealed significant differences in the levels of activated partial thromboplastin time and prothrombin time between the NDVT group and the DVT group. In contrast, the DVT group displayed significantly higher levels of D-dimer, plasma fibrinogen and platelet count when compared to the NDVT group. The AUC for the combined test model was substantially higher compared to individual parameters.Discussion: Multiple parameters of the postoperative coagulation state in the combined test model provided a more accurate prediction of DVT occurrence in elderly pregnant women after cesarean section.Keywords: deep vein thrombosis, cesarean section, coagulation, postpartum women

Chen Duan,1 Xuemin Yu,2 Xin Feng,1 Li Shi,3 Deyun Wang4 1Department of Otorhinolaryngology, Qilu Hospital of Shandong University, National Health Commission (NHC) Key Laboratory of Otorhinolaryngology, Shandong University, Jinan, Shandong, 250000, People’s Republic of China; 2Department of Otorhinolaryngology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, NHC Key Laboratory of Otorhinolaryngology (Shandong University), Qingdao, Shandong, 250000, People’s Republic of China; 3Department of Otolaryngology, The Second Hospital of Shandong University, Jinan, Shandong, 250000, People’s Republic of China; 4Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeCorrespondence: Li Shi, Department of Otolaryngology, The Second Hospital of Shandong University, Jinan, Shandong, 250000, People’s Republic of China, Email shili126@sina.com Xin Feng, Department of Otorhinolaryngology, Qilu Hospital of Shandong University, National Health Commission (NHC) Key Laboratory of Otorhinolaryngology, Shandong University, Jinan, Shandong, 250000, People’s Republic of China, Email drfengxin@sdu.edu.cnPurpose: Nasal polyp (NP) is characterized by inflammation of the sinonasal mucosa with predominant inflammatory cell infiltration. Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) are recognized to play an important role in leukocyte migration in airway inflammation. Herein, efforts were made to confirm the expression levels of MMPs/TIMPs and study the relationship between the infiltration of inflammatory cells and local expression levels of MMPs/TIMPs in NPs.Patients and Methods: NP tissues were obtained from 42 Chinese patients with bilateral nasal polyps during the endoscopic sinus surgery. Inferior turbinate (IT) tissues from 19 patients with septal deviation were taken during the rhinoplasty surgery as controls. mRNA and protein levels of MMP1, MMP9, MMP10, MMP12, TIMP1 and TIMP3 were assessed by quantitative PCR and immunohistochemistry.Results: Eosinophilia (72%, 23/32 samples), neutrophilia (41%, 13/32 samples), and increase in macrophages (38%, 12/32 samples) were found in NP tissues. mRNA expression of MMP1 (10.9-fold), MMP9 (4.1-fold), MMP10 (6.7-fold) and MMP12 (3.5-fold) were significantly up-regulated, while TIMP1 (1.5-fold) and TIMP3 (6.0-fold) were significantly down-regulated in NPs (n=42) as compared to the controls (n=19). The immunostaining levels of all 4 MMPs and two TIMPs were higher in NPs than those in controls. The co-localization of MMP1/MMP10/MMP12 and macrophages were identified in NPs. MMP9 was mainly expressed in neutrophils, while TIMP1 or TIMP3 were mostly found in eosinophils in NPs.Conclusion: The results of our study indicate that tissue remodeling is significant in NPs, where MMPs/TIMPs play important roles in both tissue remodeling and inflammatory cells infiltration.Keywords: remodeling, inflammatory cells, extracellular matrix, matrix metalloproteinases

Shan Niu,1,&ast; Xiaoxiao Yin,1,&ast; Bing Pan,2 Haotian Chen,1 Chunxiao Dai,3 Chunnan Tong,4 Fang Chen,2 Xiuqin Feng1 1Nursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Psychiatry, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Psychology, Affiliated Hangzhou First People’s Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Psychiatry, The Second Hospital of Jinhua, Jinhua, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuqin FengNursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, Zhejiang, People’s Republic of China, Email fengxiuqin@zju.edu.cnBackground: Non-suicidal self-injury (NSSI) and depression often co-occur among adolescents with more severe clinical symptoms. This study examined the network structures of NSSI and depressive symptoms in adolescents.Methods: Participants were recruited in the psychiatric outpatient clinics of three tertiary hospitals between April 10 and July 10, 2023. All participants been already found with self-injury behaviors in outpatient when enrolled. NSSI diagnostic criteria and Patient Health Questionnaire-9 (PHQ-9) were utilized to collect NSSI and depressive symptoms separately. We performed a network analysis to visualize the correlation between each symptom and to identify core and bridging symptoms in comorbidities.Results: A total of 248 patients were enrolled in the study, with a mean age of 15.48 (SD = 1.62). Based on the PHQ-9 scores and grades, our results showed that the incidence of depression in adolescents with non-suicidal self-injury behavior was relatively high (N=235, 94.76%), with the majority having severe depression. The network analysis revealed that nodes D-6 “feeling bad, failing or letting yourself or your family down”, D-1 “little interest or pleasure” and D-4 “feeling tired” were the most vital and most central symptoms. The most crucial bridging symptom is the node NSSI-8 “frequent thinking about self-injury”, which connects the NSSI to the depression comorbid network.Conclusion: This study offers a significant symptom-level conceptualization of the association between NSSI and depressive symptoms in a clinical sample of adolescents, which not only enhances our understanding of the comorbid but also identifies potential treatment targets to prevent and treat comorbidity between adolescent NSSI and depression.Keywords: non-suicidal self-injury, depression, comorbidity network, bridge symptoms, network analysis

Boyi Yu,1– 4 Xuanyi Lu,5 Xianglong Feng,1– 4 Ting Zhao,1– 4 Jiaxin Li,1– 4 Yudie Lu,5 Fei Ye,1– 4 Xiongxiong Liu,1– 4 Xiaogang Zheng,1– 4 Zheyu Shen,5 Xiaodong Jin,1– 4 Weiqiang Chen,1– 4 Qiang Li1– 4 1Biomedical Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, People’s Republic of China; 2Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, People’s Republic of China; 3Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, Gansu Province, People’s Republic of China; 4College of Life Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 5School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Xiaodong Jin; Weiqiang Chen, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou, Gansu Province, 730000, People’s Republic of China, Tel +86-931-4969316, Fax +86-931-8272100, Email jinxd@impcas.ac.cn; chenwq7315@impcas.ac.cnIntroduction: Radiotherapy is a widely recognized first-line clinical treatment for cancer, but its efficacy may be impeded by the radioresistance of advanced tumors. It is urgent to improve the sensitivity of radioresistant tumors to radiotherapy. In this work, gadolinium oxide nanocrystals (GONs) were utilized as radiosensitizers to enhance the killing effect and reinforce the immune activation of X-ray irradiation on 4T1 breast cancer cells in vitro and in vivo.Methods: 1.0 T small animal MR imaging (MRI) system was employed to trace GONs in vivo, while 225 kVp X-ray irradiation equipment was utilized for investigating the radiosensitization of GONs in 4T1 breast cancer cells in vitro and in vivo. Western blot, quantitative real-time PCR (RT-qPCR), immunohistochemistry, immunofluorescence, clonal survival assay, flow cytometry and reactive oxygen species assay were used to explore the biological mechanism of GON sensitization.Results: GONs exhibited exceptional utility as contrast agents for both in vivo and in vitro MRI imaging. Interestingly, a single dose of 8.0 Gy X-rays together with GONs failed to confer superior therapeutic effects in tumor-bearing mice, while only 3.0 Gy × 3 fractions X-rays combined with GONs exhibited effective tumor growth inhibition. Moreover, fractionated X-ray irradiation with GONs demonstrated a superior capacity to activate the cGAS-STING pathway.Discussion: Fractionated X-ray irradiation in the presence of GONs has demonstrated the most significant activation of the anti-tumor immune response by boosting the cGAS-STING pathway. Keywords: gadolinium oxide nanoparticles, magnetic resonance imaging, radiosensitization, cGAS-STING pathway, 4T1 breast cancer cells

Zhimin Ding,1,&ast; Jing Gao,2,&ast; Yixuan Feng,1,&ast; Mengyu Wang,1 Huandong Zhao,1 Ruonan Wu,1 Xinyue Zheng,1 Xiaodong Feng,1,2 Mingyin Lai3 1School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Department of Rehabilitation Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3School of Traditional Chinese Medicine, Hainan Medical University, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodong Feng; Mingyin Lai, Email fxd0502@163.com; dearl_0524@163.comBackground: Post-stroke depression (PSD) is one of the most common complications of stroke. Electroacupuncture (EA) is an effective traditional Chinese medicine treatment for PSD, which is widely used in clinical settings. EA has a significant therapeutic effect against PSD, but the mechanism is still unclear. This study aimed to determine whether EA ameliorates depression-like behaviors in PSD rats by regulating the adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK)-mediated mitochondrial function.Methods: Middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS) were used to develop a PSD rat model. To elucidate the role of AMPK in EA treatment, compound C, a selective inhibitor of AMPK, was injected into the lateral ventricle of rats before EA treatment. EA treatment was performed for 14 consecutive days for 30 min per day after PSD modeling. A modified Zea-Longa five-point scale scoring system was used to determine neurologic function in MCAO rats. Behavioral tests were conducted to evaluate depression-like phenotypes in rats. Depression-like behaviors were tested by sucrose preference test (SPT), novelty suppressed feeding test (NSFT), and open-field test (OFT). The structure and morphology of the prefrontal cortex were observed by histopathological hematoxylin-eosin (HE) and Nissl staining. The mitochondrial morphology and function were analyzed by colorimetry, chemiluminescence, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR).Results: EA treatment successfully ameliorated depression-like behaviors, upregulated AMPK expression, and improved mitochondrial function. However, AMPK inhibition by Compound C exacerbated depression-like behaviors and aggravated neuronal and mitochondrial injury in PSD rats.Conclusion: EA treatment improved depression-like behaviors in PSD rats and promoted mitochondrial function by activating AMPK.Keywords: electroacupuncture, post-stroke depression, mitochondria, AMPK

Tingting Ma,1,2,&ast; Hui Zhang,3,&ast; Yuqing Weng,2,&ast; Shudan Tang,3 Jinshan Mao,2 Xin Feng,3 Yuxin Zhang,4 Jianquan Zhang1 1Department of Respiratory and Critical Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518000, People’s Republic of China; 2Department of Respiratory and Critical Medicine, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China; 3Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 4The First Clinical Medical College, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianquan Zhang, Department of Respiratory and Critical Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518000, People’s Republic of China, Tel +8613978123845, Fax +86755-23482484, Email zhangjq76@mail.sysu.edu.cnPurpose: To investigate the role of the CD40-CD40 ligand (CD40L) pathway in the regulation of Th1, Th17, and regulatory T (Treg)-cell responses in an elastin peptide (EP)-induced autoimmune emphysema mouse model.Methods: BALB/c mice were transnasally treated with EP on day 0, injected intravenously with anti-CD40 antibody via the tail vein on day 33, and sacrificed on day 40. The severity of emphysema was evaluated by determining the mean linear intercept (MLI) and destructive index (DI) from lung sections. The proportions of myeloid dendritic cells (mDCs) and Th1, Th17, and Treg cells in the blood, spleen, and lungs were determined via flow cytometry. The levels of the cytokines interleukin (IL)-6, IL-17, interferon (IFN)-γ, and transforming growth factor (TGF)-β were detected via enzyme-linked immunosorbent assay. Ifnγ, IL17a, Rorγt and Foxp3 transcription levels were detected via polymerase chain reaction.Results: CD40+ mDCs accumulated in the lungs of EP-stimulated mice. Blocking the CD40-CD40L pathway with an anti-CD40 antibody alleviated Th1 and Th17 responses; increased the proportion of Treg cells; decreased MLI and DI; reduced the levels of cytokines IL-6, IL-17, and IFN-γ as well as the transcription levels of Ifnγ, IL17a, and Rorγt; and upregulated the expression of TGF-β and Foxp3.Conclusion: The CD40-CD40L pathway could play a critical role in Th1, Th17 and Treg cell dysregulation in EP-mediated emphysema and could be a potential therapeutic target.Keywords: elastin peptide, dendritic cell, Cluster of Differentiation 40, CD40, Th cell, emphysema

We have used angle-dependent soft x-ray absorption spectroscopy (XAS) at the O K edge and first-principles calculations to investigate the electronic structures of iridate-based superlattices (SrIrO3)m/(SrTiO3) (m=1, 2, 3, and ∞). We focus on the pre-edge Ir 5d t2g-O 2p orbital hybridization feature in the XAS spectra. By varying the measurement geometry relative to the incident photon polarization, we are able to extract the dichroic contrast and observe the systematic increase in the anisotropy of Ir 5d orbitals as m decreases. First-principles calculations elucidate the orbital anisotropy coming mainly from the enhanced out-of-plane compression of IrO6 octahedra in the SrIrO3 layers that are adjacent to the inserted SrTiO3 layers. As m decreases, the increased volume fraction of these interfacial SrIrO3 layers and their contact with the SrTiO3 layers within the (SrIrO3)m/(SrTiO3) supercell lead to enhanced orbital anisotropy. Furthermore, the tilt and rotation of IrO6 octahedra are shown to be essential to understand the subtle orbital anisotropy in these superlattices, and constraining these degrees of freedom will give an incorrect trend. Our results demonstrate that the structural constraint from the inserted SrTiO3 layers, in addition to other electronic means such as polar interface and charge transfer, can serve as a knob to control the orbital degree of freedom in these iridate-based superlattices.