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Guoqiang Xu,1,2,* Xiaona Song,2,* Xiaotang Wang,1,2,* Rui Xue,1,2 Xiaoru Yan,1,2 Litao Qin,1,2 Xiaoqi Chang,1,2 Jiping Gao,1 Zhaoyang Chen,1 Guohua Song1 1Laboratory Animal Center Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model, Shanxi Medical University, Taiyuan, People’s Republic of China; 2School of Basic Medical Science, Shanxi Medical University, Taiyuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guohua Song, Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model, Shanxi Medical University, Road Xinjian 56, Taiyuan, 030001, People’s Republic of China, Tel +86-351-4135919, Email ykdsgh@sxmu.edu.cnPurpose: Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy.Methods: We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved.Results: The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the β-catenin signaling pathway and other downstream genes without inducing acute toxicity.Conclusion: Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the β-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future. Keywords: silver nanoparticles, nanocomposite, combination therapy, β-catenin signaling pathway

Qin Xiao,1,* Jing Guo,1,* Yongzhou Lu,1 Jin Gao,1 Chuanlong Jia,1 Minghuan Huang,1 Weifang Chu,1 Wei Yao,1 Peng Ning,2 Qiannan Xu,1 Nan Xu1 1Department of Dermatology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Institute for Regenerative Medicine, Institute for Translational Nanomedicine, Shanghai East Hospital, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiannan Xu; Nan Xu, Department of Dermatology, Shanghai East Hospital, School of Medicine, Tongji University, No. 150 Jimo Road, Shanghai, People’s Republic of China, Tel +86 38804518, Email greatfuturedoctor@hotmail.com; xnhrb1320@sohu.comPurpose: Atopic dermatitis (AD) is a chronic inflammatory skin condition that can affect individuals of all ages. Recent research has shown that oxidative stress plays a crucial role in the development of AD. Therefore, inhibiting oxidative stress may be an effective therapeutic approach for AD. Nano-molybdenum is a promising material for use as an antioxidant. We aimed to evaluate the therapeutic effects and preliminary mechanisms of molybdenum nanoparticles (Mo NPs) by using a murine model of chemically induced AD-like disease.Methods: HaCaT cells, a spontaneously immortalized human keratinocyte cell line, were stimulated by tumor necrosis factor-alpha /interferon-gamma after pre-treatment with Mo NPs. Reactive oxygen species levels, production of inflammatory factors, and activation of the nuclear factor kappa-B and the nuclear factor erythroid 2-related factor pathways were then evaluated. Mo NPs was topically applied to treat a murine model of AD-like disease induced by MC903, a vitamin D3 analog. Dermatitis scores, pruritus scores, transepidermal water loss and body weight were evaluated. AD-related inflammatory factors and chemokines were evaluated. Activation of the nuclear factor kappa-B and nuclear factor erythroid 2-related factor / heme oxygenase-1 pathways was assessed.Results: Our data showed that the topical application of Mo NPs dispersion could significantly alleviate AD skin lesions and itching and promote skin barrier repair. Further mechanistic experiments revealed that Mo NPs could inhibit the excessive activation of the nuclear factor kappa-B pathway, promote the expression of nuclear factor erythroid 2-related factor and heme oxygenase-1 proteins, and suppress oxidative stress reactions. Additionally, they inhibited the expression of thymic stromal lymphopoietin, inflammatory factors, and chemokines, thereby alleviating skin inflammation.Conclusion: Mo NPs present a promising alternative treatment option for patients with AD as they could address three pivotal mechanisms in the pathogenesis of AD concurrently.Keywords: oxidative stress, skin barrier function, chemokines, antioxidants, pro-inflammatory factors

Bowen Wei,1,2,&ast; Qingyun Yue,1,2,&ast; Yuxiu Ka,1,2,&ast; Chenyang Sun,1,2 Yuxing Zhao,1,2 Xiaomei Ning,1,2 Yue Jin,1,2 Jingyue Gao,1,2 Yuanhao Wu,1,2 Wei Liu1,2 1Department of Rheumatism and Immunity, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Liu, Email fengshiliuwei@163.comBackground: Primary Sjögren’s syndrome (pSS) is an autoimmune condition marked by lymphocyte infiltration in the exocrine glands. Our study aimed to identify a novel biomarker for pSS to improve its diagnosis and treatment.Methods: The gene expression profiles of pSS were obtained from the Gene Expression Omnibus (GEO) database. The specific differentially expressed genes (DEGs) were screened by the Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), and Recursive Feature Elimination with Support Vector Machines (SVM-RFE). A biomarker was picked out based on correlation and diagnostic performance, the connection between the biomarker and clinical traits and immune infiltrating cells was explored, and the biomarker’s protein expression level in the serum of pSS patients was detected by enzyme-linked immunosorbent assay (ELISA). The competitive endogenous RNA (ceRNA) network regulated by the biomarker was predicted to verify the reliability of the biomarker in diagnosing pSS.Results: IFI44, XAF1, GBP1, EIF2AK2, IFI27, and IFI6 showed prominent diagnostic ability, with the high accuracy (AUC = 0.859) and significance (R ≥ 0.8) of IFI44 within the training dataset. IFI44 strongly exhibited a negative correlation with resting NK cells, macrophages M0, and eosinophils, and a positive correlation with activated dendritic cells, naive B cells, and activated CD4 memory T cells. Furthermore, IFI44 was significantly positively correlated with clinical traits such as IgG, SSA, SSB, ANA, and ESSDAI, with its protein expression level in the serum of pSS patients being notably elevated compared to controls (p < 0.001). Finally, the ceRNA regulatory network showed that hsa-miR-944, hsa-miR-9-5p, hsa-miR-126-5p, and hsa-miR-335-3p were significantly targeted IFI44, suggesting that IFI44 may serve as a dependable biomarker for pSS.Conclusion: In this study, we dug out IFI44 as a biomarker for pSS, systematically studied the potential regulatory mechanism of IFI44, and verified its reliability as a biomarker for pSS.Keywords: primary Sjögren’s syndrome, machine learning, immune cell infiltration, biomarker, IFI44

Wei Tang,1,2,&ast; Ying Liu,3,&ast; Xin Li,2 Guiyun Leng,2 Ju Gao,2 Yawu Wang,2 Jie Yao,2 Zhou Liu,2 Qiang Zhou,2 Yuanhong Xu1 1Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China; 3High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Xu, Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, Anhui, 230022, People’s Republic of China, Tel +86 135 0569 4447, Fax +86 551 6292 2125, Email xyhong1964@ahmu.edu.cnPurpose: This study aimed to investigate the microbiological characteristics of clinically isolated Staphylococcus aureus with different hemolytic phenotypes in China.Materials and Methods: Using the three-point inoculation method, the hemolytic phenotypes of 1295 clinically isolated S. aureus strains were detected and categorized. Antimicrobial susceptibility testing of all strains was performed using a VITEK 2 Compact System. After sample size matching, plasma coagulase activity, catalase activity, mRNA expression of hemolysin genes (hla, hlb, hlc, and hld), biofilm formation, growth kinetics, inflammatory response of macrophages and cytotoxicity of S. aureus with different hemolytic phenotypes using the rabbit plasma kit, the catalase test on slides, qRT-PCR, crystal violet staining, the microcultivation assay, the ELISA kits, and the CCK-8 assay, respectively.Results: Seven categories of hemolytic phenotypes were identified. Accordingly, strains were categorized into seven different groups, including S. aureus with complete hemolytic phenotype (SCHP), S. aureus with weak hemolytic phenotype (SWHP), S. aureus with incomplete hemolytic phenotype 1 (SIHP-1), SIHP-2, SIHP-3, SIHP-4 and SIHP-5, the last three of which were reported for the first time. Except for the hemolytic phenotype, all seven groups differed in clinical isolation rates, antibiotic resistance profile, plasma coagulase activity, mRNA expression of hemolysin genes, biofilm formation, growth kinetics, inflammatory response of macrophages, and cytotoxicity.Conclusion: S. aureus with different hemolytic phenotypes have distinctive microbiological characteristics. Clinical microbiologists need to be vigilant about the hemolytic phenotypes when culturing S. aureus strains, and actively enhance communication with clinicians to optimize the treatment of infection.Keywords: Staphylococcus aureus, hemolytic phenotype, hemolysin, microbiological characteristics, antibiotic resistance

Jian Gao,1 Jiannan Li,2 Zengyou Luo,1 Hongyong Wang,3 Zhiming Ma1 1Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Colorectal and Anal Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Zhiming Ma, Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China, Email mazhiming@jlu.edu.cnAbstract: Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory condition characterized by recurring inflammation of the intestinal mucosa. However, the existing IBD treatments are ineffective and have serious side effects. The etiology of IBD is multifactorial and encompasses immune, genetic, environmental, dietary, and microbial factors. The nanoparticles (NPs) developed based on specific targeting methodologies exhibit great potential as nanotechnology advances. Nanoparticles are defined as particles between 1 and 100 nm in size. Depending on their size and surface functionality, NPs exhibit different properties. A variety of nanoparticle types have been employed as drug carriers for the treatment of inflammatory bowel disease (IBD), with encouraging outcomes observed in experimental models. They increase the bioavailability of drugs and enable targeted drug delivery, promoting localized treatment and thus enhancing efficacy. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines.Keywords: nanoparticles, inflammatory bowel diseases, targeted delivery, passive targeting, active targeting, drug delivery system

Chenguang Jia,1,&ast; Xiaowei Yao,1,&ast; Zhaoliang Dong,1 Lianbo Wang,1 Fangchao Zhao,2,&ast; Jianguo Gao,1,&ast; Tao Cai3,&ast; 1Department of Orthopedics, Hebei Chest Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Hebei Chest Hospital, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Cai, Hebei Chest Hospital, No. 372, Shengli North Street, Shijiazhuang, Hebei, People’s Republic of China, Tel/Fax +86-311-86911080, Email caitaoxiongke@163.comBackground: Post-translational modifications (PTM) significantly influence the pathogenesis and progression of diverse neoplastic conditions. Nevertheless, there has been limited research focusing on the potential of PTM-related genes (PTMRGs) as tumor biomarkers for predicting the survival of specific patients.Methods: The datasets utilized in this research were obtained from the TARGET and GEO repositories, respectively. The gene signature was constructed through the utilization of LASSO Cox regression method. GSEA and GO was used to identify hub pathways associated with risk genes. The functionality of risk genes in osteosarcoma (OS) cell lines was verified through the implementation of the CCK-8 assay, cell cycle analysis, and immunofluorescence assay.Results: Two distinct PTM patterns and gene clusters were finally determined. Significant differences in the prognosis of patients were found among two different PTM patterns and gene clusters, so were in the function enrichment and the landscape of TME immune cell infiltration. Moreover, we examined two external immunotherapy cohorts and determining that patients in the low-risk group was more likely to profit from immunotherapy. In addition, we mapped the expression of the genes in the signature in distinct cells using single-cell analysis. Finally, CCK-8 assay, cell cycle analysis, and immunofluorescence assay were utilized to confirm that RAD21 was expressed and functioned in OS.Conclusion: In conclusion, this study elucidated the potential link between PTM and immune infiltration landscape of OS for the first time and provided a new assessment protocol for the precise selection of treatment strategies for patients with advanced OS.Keywords: post-translational modifications, osteosarcoma, immune microenvironment, immune therapy, RAD21

Yuan Xu,1 Jie Song,1 Jie Gao,1 Hongjing Zhang2 1Department of Gastroenterology, Dongying People’s Hospital(Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, People’s Republic of China; 2Community Health Service Center in Hekou District, Dongying, Shandong, People’s Republic of ChinaCorrespondence: Yuan Xu, Department of Gastroenterology, Dongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group), No. 317 Nanyi Road, Dongying, Shandong, 257091, People’s Republic of China, Email jry0919@sina.comPurpose: Oxidative stress promotes disease progression by stimulating the humoral and cellular immune responses. However, the molecular mechanisms underlying oxidative stress and immune responses in acute pancreatitis (AP) have not been extensively studied.Patients and Methods: We analyzed the GSE194331 dataset and oxidative stress-related genes (OSRGs). We identified differentially expressed immune cell-associated OSRGs (DE-ICA-OSRGs) by overlapping key module genes from weighted gene co-expression network analysis, OSRGs, and DEGs between AP and normal samples. Functional enrichment analysis was performed to investigate the functions of DE-ICA-OSRGs. We then filtered diagnostic genes using receiver operating characteristic curves and investigated their molecular mechanisms using single-gene set enrichment analysis (GSEA). We also explored the correlation between diagnostic genes and differential immune cells. Finally, we constructed a transcription factor-microRNA-messenger RNA (TF-miRNA-mRNA) network of biomarkers.Results: In this study, three DE-ICA-OSRGs (ARG1, NME8 and VNN1) were filtered by overlapping key module genes, OSRGs and DEGs. Functional enrichment results revealed that DE-ICA-OSRGs were involved in the cellular response to reactive oxygen species and arginine biosynthesis. Latterly, a total of two diagnostic genes (ARG1 and VNN1) were derived and their expression was higher in the AP group than in the normal group. The single-gene GSEA enrichment results revealed that diagnostic genes were mainly enriched in macroautophagy and Toll-like receptor signaling pathways. Correlation analysis revealed that CD8 T cells, resting memory T CD4 cells, and resting NK cells were negatively correlated with ARG1, and neutrophils were positively correlated with ARG1, which was consistent with that of VNN1. The TF-miRNA-mRNA regulatory network included 11 miRNAs, 2 mRNAs, 10 transcription factors (TFs), and 26 pairs of regulatory relationships, like NFKB1-has-miR-2909-VNN1.Conclusion: In this study, two immune cell oxidative stress-related AP diagnostic genes (ARG1 and VNN1) were screened to offer a new reference for the diagnosis of patients with AP. Keywords: acute pancreatitis, oxidative stress, diagnosis, immunity

Yumei Wu,1– 3,&ast; Chunhua Zeng,1– 3,&ast; Jiajia Lv,1– 3 Hongyu Li,1– 3 Jie Gao,1– 3 Zhidong Liu,4 Zeli Yuan1– 3 1Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 2Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 3Guizhou International Scientific and Technological Cooperation Base for Medical Photo-Theranostics Technology and Innovative Drug Development, Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 4Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhidong Liu, Tianjin University of Traditional Chinese Medicine, No. 10 Poyanghu Road, Tianjin, Jinghai District, 301617, People’s Republic of China, Email lonerliuzd@163.com Zeli Yuan, Zunyi Medical University, Zunyi, 563000, People’s Republic of China, Email zlyuan@zmu.edu.cnBackground: Combination therapy offers superior therapeutic results compared to monotherapy. However, the outcomes of combination therapy often fall short of expectations, mainly because of increased toxicity from drug interactions and challenges in achieving the desired spatial and temporal distribution of drug delivery. Optimizing synergistic drug combination ratios to ensure uniform targeting and distribution across space and time, particularly in vivo, is a significant challenge. In this study, cRGD-coated liposomes encapsulating optimized synergistic cepharanthine (CEP; a chemotherapy drug) and IR783 (a phototherapy agent) were developed for combined chemotherapy and photothermal therapy in vitro and in vivo.Methods: An MTT assay was used to evaluate the combination index of CEP and IR783 in five cell lines. The cRGD-encapsulated liposomes were prepared via thin-film hydration, and unencapsulated liposomes served as controls for the loading of CEP and IR783. Fluorescence and photothermal imaging were used to assess the efficacy of CEP and IR783 encapsulated in liposomes at an optimal synergistic ratio, both in vitro and in vivo.Results: The combination indices of CEP and IR783 were determined in five cell lines. As a proof-of-concept, the optimal synergistic ratio (1:2) of CEP to IR783 in 4T1 cells was evaluated in vitro and in vivo. The average diameter of the liposomes was approximately 100 nm. The liposomes effectively retained the encapsulated CEP and IR783 in vitro at the optimal synergistic molar ratio for over 7 d. In vivo fluorescence imaging revealed that the fluorescence signal from cRGD-CEP-IR783-Lip was detectable at the tumor site at 4 h post-injection and peaked at 8 h. In vivo photothermal imaging of tumor-bearing mice indicated an increase in tumor temperature by 32°C within 200 s. Concurrently, cRGD-CEP-IR783-Lip demonstrated a significant therapeutic effect and robust biosafety in the in vivo antitumor experiments.Conclusion: The combination indices of CEP and IR783 were successfully determined in vitro in five cell lines. The cRGD-coated liposomes encapsulated CEP and IR783 at an optimal synergistic ratio, exhibiting enhanced antitumor effects and targeting upon application in vitro and in vivo. This study presents a novel concept and establishes a research framework for synergistic chemotherapy and phototherapy treatment. Keywords: drug delivery, liposomes, synergistic effects, phototherapy

Yamei Bai,&ast; Yuqing Chen,&ast; Meng Tian, Jiaojiao Gao, Yulei Song, Xueqing Zhang, Haiyan Yin, Guihua Xu School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guihua Xu, School of Nursing, Nanjing University of Chinese Medicine, No. 138, Xianlin Avenue, Qixia District, Nanjing, Jiangsu Province, 210023, People’s Republic of China, Tel +86-153-6513-2927, Email 7115@njucm.edu.cnPurpose: Social isolation and depression have an impact on cognitive frailty. However, the underlying mechanisms between these variables have not been well defined. This study aims to investigate the mediating role of depressive symptoms in the association between social isolation and cognitive frailty among older adults in China.Methods: From Mar 2023 to Aug 2023, a cross-sectional study was conducted with 496 community-dwelling older adults aged ≥ 60 years in Nanjing, Jiangsu Province, China. Demographic information was collected using the General Information Questionnaire. The Lubben Social Network Scale-6 (LSNS-6), Geriatric Depression Scale 15-item (GDS-15), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating (CDR), and FRAIL scale were used for the questionnaire survey. Multiple linear regression and binary logistic regression were utilized to explore the associations among social isolation, depressive symptoms, and cognitive frailty, and Bootstrap analysis was used to explore the mediating role of depressive symptoms in social isolation and cognitive frailty.Results: Linear regression results revealed that social isolation was positively associated with depressive symptoms (β = 0.873, p < 0.001). Logistic regression analysis showed that social isolation (OR = 1.769, 95% CI = 1.018~3.075) and depressive symptoms (OR = 1.227, 95% CI = 1.108~1.357) were significantly associated with cognitive frailty. Mediation analysis demonstrated that depressive symptoms significantly mediated the relationship between social isolation and cognitive frailty, with an indirect effect of 0.027 (95% CI = 0.003~0.051), and the mediating effect accounted for 23.6% of the total effect.Conclusion: Social isolation is associated with cognitive frailty in community-dwelling older adults, and depressive symptoms partially mediate the effect between social isolation and cognitive frailty. Active promotion of social integration among older individuals is recommended to enhance their mental health, reduce the incidence of cognitive frailty, and foster active aging.Keywords: cognitive frailty, social isolation, depressive symptoms, older adults

Qiang Zhong,&ast; Xin Pan,&ast; Yuhang Chen, Qiang Lian, Jian Gao, Yixin Xu, Jian Wang, Zhanjun Shi, Hao Cheng Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanjun Shi; Hao Cheng, Nanfang Hospital, Southern Medical University, 1838&num; Guangzhou North Avenue, Guangzhou, People’s Republic of China, Tel +86 2062787924, Email shizhanjun111@gmail.com; haocool317@gmail.comAbstract: The development of metallic joint prostheses has been ongoing for more than a century alongside advancements in hip and knee arthroplasty. Among the materials utilized, the Cobalt-Chromium-Molybdenum (Co-Cr-Mo) and Titanium-Aluminum-Vanadium (Ti-Al-V) alloys are predominant in joint prosthesis construction, predominantly due to their commendable biocompatibility, mechanical strength, and corrosion resistance. Nonetheless, over time, the physical wear, electrochemical corrosion, and inflammation induced by these alloys that occur post-implantation can cause the release of various metallic components. The released metals can then flow and metabolize in vivo, subsequently causing potential local or systemic harm. This review first details joint prosthesis development and acknowledges the release of prosthetic metals. Second, we outline the metallic concentration, biodistribution, and elimination pathways of the released prosthetic metals. Lastly, we discuss the possible organ, cellular, critical biomolecules, and significant signaling pathway toxicities and adverse effects that arise from exposure to these metals. Keywords: metallic joint prostheses, prosthetic metal release, potential toxicity and adverse effects

Yongchao Li,1,&ast; Jinfeng Gao,2,&ast; Shuhua Liu,1 Shijian Chen,3 Xiaoyue Wei,3 Yalun Guan,1 Xuejiao Li,1 Yunfeng Li,1 Zhongqiang Huang,1 Ge Li,1 Yuhong Zhao,3 Pinghua Liu,4 Yu Zhang1 1Guangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, 510663, People’s Republic of China; 2Guangdong Quality Supervision and Testing Station for Medical and Health Care Appliances, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou, 510632, People’s Republic of China; 3School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China; 4Department of Chemistry, Boston University, Boston, MA, 02215, USA&ast;These authors contributed equally to this workCorrespondence: Yu Zhang; Pinghua Liu, Email zhangyugzh@hotmail.com; pinghua@bu.eduBackground: Ergothioneine (EGT) is an antioxidant, which could be detected in human tissues, and human skin cells could utilize EGT and play an anti-oxidative role in keratinocytes. And in this study we are going to elucidate whether EGT could protect the skin from photoaging by Ultraviolet (UV) exposure in mice and its molecule pathway.Methods: Histological analysis was performed for evaluating the skin structure change. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured with biological assay for evaluating oxidative and antioxidative ability of skin exposed to UV light. And the level of marker molecules in mouse skin were detected by hydroxyproline (Hyp) assay, immunohistochemical analysis, Western blot, and quantitative real-time PCR (qRT-PCR). The markers of skin aging and cell death were tested by cell culture and treatment, Western blot and qRT-PCR.Results: EGT decreased the levels of inflammatory factors induced by UV exposure in mouse skin. MDA and SOD activity detection showed that EGT decreased MDA levels, increased SOD activity, and upregulated PI3K/Akt/Nrf2 signals in mouse skin exposed to UV, which further activated Nrf2 in the nucleus and enhanced the expression of Nrf2 target genes. In the cell model, we revealed that EGT could inhibit the increase in senescence-associated β-galactosidase-positive cells and p16 and γ-H2A.X positive cells induced by etoposide and activate PI3K/Akt/Nrf2 signaling. Moreover, a PI3K inhibitor blocked EGT protection against etoposide-induced cell death.Conclusion: The study showed EGT may play an important protective role against cell damage or death through the PI3K/Akt/Nrf2 signaling pathway in skin.Keywords: ergothioneine, skin aging, PI3K/Akt, Nrf2

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

Jinjie Gao,1 Jiajia Zheng,2 Hua Zhang,3 Jijun Wang,1 Hongmei Jing1 1Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Department of Laboratory Medicine, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Hongmei Jing, Tel +86-010-82266785, Email hongmeijing@bjmu.edu.cnObjective: We performed a retrospective analysis to investigate the clinical predictors of bacteremia outcome involving Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) after initial empirical antimicrobial therapy among hematological malignancy cases.Methods: This retrospective study was conducted between April 2018 and April 2023. All bloodstream infections (BSIs) caused by E. coli and K. pneumoniae in hospitalized hematological malignancy (HM) patients were identified. Data on patient demographics, clinical characteristics, empirical antimicrobial treatment, outcomes and the antimicrobial susceptibility were collected from medical records. Multivariate analyses were utilized to assess the risk factors for all-cause mortality within 28 days and carbapenem resistance. Optimal cutoffs for continuous predictive variables were evaluated by receiver operating characteristic (ROC) curve analysis.Results: Among 61 individuals diagnosed with bacteremia, 39 cases were caused by E. coli bacteremia, while the remaining 22 were identified as K. pneumoniae bacteremia. Out of these, there were 10 cases of carbapenem-resistant Enterobacteriaceae (CRE) and 12 cases resulted in all-cause mortality within 28 days. Analysis indicated that Pitt score was an independent risk factor for mortality and a cut-off of 2.5 was a reliable predictor with 83.3% sensitivity and 85.7% specificity, respectively. Impaired mental status and elevated body temperature exceeding 38.6°C as well as a procalcitonin (PCT) level over 8.24 ng/mL on the third day (d3) after antimicrobial treatment were identified as independent risk factors for predicting carbapenem resistance.Conclusion: We found that Pitt score with a cut-off of 2.5 was a reliable predictor for mortality within 28 days in HM bacteremia cases. Impaired mental status and elevated temperature exceeding 38.6°C as well as a procalcitonin (PCT) level over 8.24 ng/mL on d3 after antimicrobial treatment were identified as predictive risk factors to carbapenem resistance.Keywords: antimicrobial resistance, mortality, risk factors, initial clinical response

Jingjing He,1– 3 Jing Gao,1– 3 Yan Zhao,4 Shuai Chen1,3 1Department of Otolaryngology-Head and Neck Surgery, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, People’s Republic of China; 2Teaching Hospital of Fujian Medical University, Xiamen, 361003, People’s Republic of China; 3Xiamen Key Laboratory of Otolaryngology Head and Neck Surgery, Xiamen, 361003, People’s Republic of China; 4Army 73rd Group Military Hospital, Chenggong Hospital Affiliated to Xiamen University, Xiamen, 361000, People’s Republic of ChinaCorrespondence: Shuai Chen, Department of Otolaryngology-Head and Neck Surgery, the First Affiliated Hospital of Xiamen University, School of Medicine, No. 55, Zhenhai Road, Siming District, Xiamen, 361005, People’s Republic of China, Email chenshuai@xmu.edu.cn Yan Zhao, Army 73rd group military hospital, Chenggong Hospital Affiliated to Xiamen University, No. 92-96, Wenyuan Road, Siming District, Xiamen, 361000, People’s Republic of China, Email 46330926@qq.comBackground: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa. However, few studies focus on the distributional characteristics of allergens in AR patients in Southern Fujian Province, China.Methods: A skin prick test (SPT) was performed and eight common allergens including Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dpt), weeds, animal dander, molds, cockroaches, and mangoes were chosen.Results: The positive reactions rate to the allergens was 65.79% in 6689 patients in Southern Fujian Province. Positive reactions to Df and Dpt had a negative association with age, whereas positive reactions to cockroach and weed had a positive association with age. A linear trend analysis demonstrated a significant positive relationship between positive reactions to various allergens from 2016 to 2019. Positive reactions to Df and Dpt were both correlated with the season. Positive reactions to Df, Dpt, cockroach and weed were related to disease duration and positive reactions to cockroach were correlated with city residence. Multivariate analysis revealed that male positive reactions gradually decreased with age (≤ 60), in contrast to female (≤ 60) positive reactions. Statistical difference was observed between the genders with regard to AR incidence from 2016 to 2019. The positive rate of skin tests was highest in summer in men, whereas in women it was lowest in summer. The gender composition ratios of positive cases in Xiamen, Zhangzhou, and Quanzhou cities differed significantly. The proportion of patients with positive reactions to the allergens in the three cities decreased with age. The highest proportions of patients with positive reactions all occurred during summer in the three cities. Furthermore, there were statistically significant differences in the age composition ratios across the seasons.Conclusion: This study analyzed the distributional characteristics of AR allergens in Southern Fujian Province, China. These findings will inform specific immunotherapy for AR patients.Keywords: allergic rhinitis, allergen, skin prick test, Southern Fujian Province in China

Shaohua Tan,1,&ast; Xiangchen Li,2,&ast; Bing Lu,1,3 Yibin Lin,3 Yunxiang Cai,1 Jie He,4 Sisi Chen,2 Junli Gao,2 Junshun Gao,2 Xinhua Qiang1 1Department of Clinical Laboratory, The First People’s Hospital of Huzhou, Huzhou, Zhejiang, 313000, People’s Republic of China; 2Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, 310020, People’s Republic of China; 3School of Medicine, Huzhou University, Huzhou, Zhejiang, 313000, People’s Republic of China; 4Department of Infectious Diseases, The First People’s Hospital of Huzhou, Huzhou, Zhejiang, 313000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinhua Qiang, Department of Clinical Laboratory, The First People’s Hospital of Huzhou, No. 158 Back Square Road, Wuxing District, Huzhou, Zhejiang, 313000, People’s Republic of China, Email qiangxinhua@zjhu.edu.cnAbstract: Carbapenem-resistant Salmonella enterica (S. enterica) pose a significant threat to public health, causing gastroenteritis and invasive infections. We report the first emergence of a carbapenem-resistant S. enterica serovar London strain, A132, carrying the blaNDM-5 gene in China. Whole-genome sequencing and bioinformatics analysis assigned A132 to be ST155, a multidrug-resistant clone frequently reported in China. The strain A132 exhibited resistance to multiple antibiotics, with 20 acquired antibiotic resistance genes (ARGs) identified, predominantly located on the IncFIB plasmid (pA132-1-NDM). Notably, the blaNDM-5 gene was located within an IS 26 flanked-class 1 integron-ISCR1 complex, comprising two genetic cassettes. One cassette is the class 1 integron, which may facilitate the transmission of the entire complex, while the other is the blaNDM-5-containing ISCR1-IS 26-flanked cassette, carrying multiple other ARGs. Genbank database search based on the blaNDM-5-carrying cassette identified a similar genetic context found in transmissible IncFIA plasmids from Escherichia coli (p91) and Enterobacter hormaechei (p388) with a shared host range, suggesting the potential for cross-species transmission of blaNDM-5. To our knowledge, this is the first reported case of Salmonella serovar London ST155 harboring blaNDM-5 gene. Phylogenetic analysis indicated a close relationship between A132 and eight S. London ST155 strains isolated from the same province. However, A132 differed by carrying the blaNDM-5 gene and four unique ARGs. Given the high transmissibility of the F-type plasmid harboring blaNDM-5 and 18 other ARGs, it is imperative to implement vigilant surveillance and adopt appropriate infection control measures to mitigate the threat to public health.Keywords: blaNDM-5, Salmonella London, ST155, carbapenem resistance, IncFIB, integron

Qiong Wu,1,&ast; Shiying An,1,&ast; RueyJyh Lee,1 Dongwen Gao,2 Yinyifan Zhou,1 Longping Peng,1 Chunrui Hu,1 Lei Yao,3 Chang Zhou,4 Li Zhou,5 Junjie Gao,6 Min Cao,1 Meijiao Mao,1 Guanghao Li,1 Bing Deng,1 Yingjia Xu,4 Youhua Wang1 1Department of Cardiology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Ultrasound, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Cardiology, Shanghai Fifth People’s Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 5Department of Cardiology, Shanghai Jiading Nanxiang Hospital, Shanghai, People’s Republic of China; 6Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingjia Xu, Shanghai Fifth People’s Hospital, Fudan University, Minhang District, 128 Ruili Road, Shanghai, 200240, People’s Republic of China, Tel +862164308151, Email xuyingjia@5thhospital.com Youhua Wang, Department of cardiology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Xunhui, 725 South Wan-Ping Road, Shanghai, 200032, People’s Republic of China, Tel +862164385700, Email doctorwyh@163.comBackground: Dilated cardiomyopathy (DCM) is a severe heterogeneous cardiomyopathy characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes, particularly prevalent in China. The challenge lies in the scarcity of targeted therapies with substantial efficacy for DCM. Additionally, traditional anti-heart failure drugs are constrained due to hypotension propensity or limited symptom improvement. Kuoxin Formula (KXF), internally endorsed at Longhua Hospital, demonstrates clear biological evidence for enhancing cardiac function and myocardial remodeling. Previous clinical studies suggest its potential to enhance patients’ quality of life. This trial aims to further evaluate KXF’s safety and efficacy in managing DCM-related heart failure.Methods: This prospective, randomized, double-blind, placebo-controlled, multicenter trial aims to recruit 230 DCM patients from five centers. Participants will be randomly assigned to either KXF or placebo for 12 weeks, with careful monitoring of key indicators and adverse events. The primary outcome measures the proportion of patients with NT-proBNP reduction exceeding 30%. Secondary outcomes include New York Heart Association functional classification, Traditional Chinese Medicine syndrome scores, 6-minute walk test, Lee’s heart failure score, and Minnesota Heart Failure Quality of Life Scale score. Ventricular remodeling will be assessed using cardiac ultrasound and ELISA. Safety metrics and adverse events will be meticulously recorded.Discussion: This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of DCM. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients.Trial Registration: China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023. https://www.chictr.org.cn/bin/project/edit?pid=190926.Keywords: dilated cardiomyopathy, heart failure, Kuoxin Formula, traditional Chinese medicine, clinical trials

Li Ren, Zhaoling Li, Ji Wu, Lian Duan, Jialiang Gao Cardiovascular Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of ChinaCorrespondence: Li Ren, Cardiovascular Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Address: No. 5, Beixiange, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86 18600697916, Email renlirl7961@hotmail.comObjective: This study aimed to assess the knowledge, attitudes and practices (KAP) among elderly coronary heart disease (CHD) patients toward self-perceived health abilities.Methods: This web-based study was carried out between April 2023 and September 2023 at Guang’anmen Hospital, China Academy of Chinese Medical Sciences. A self-developed questionnaire was utilized to collect demographic information from elderly CHD patients, and evaluate their KAP towards self-perceived health abilities.Results: A total of 568 valid questionnaires were collected. Among the participants, the average age was 65.97± 5.50 years, and 298 (52.46%) were female, and the mean scores for knowledge, attitudes, and practices were 6.34± 2.29 (possible range: 0– 9), 35.24± 4.99 (possible range: 9– 45), and 27.79± 10.09 (possible range: 9– 45), respectively. The structural equation model demonstrated that elderly CHD patients’ knowledge directly affects attitudes and practices, with path coefficient of 0.93 (P< 0.001) and 0.39 (P=0.033), respectively. Moreover, attitudes play an intermediary role between knowledge and practice with path coefficient of 0.75 (P< 0.001). Furthermore, residence directly affects knowledge with path coefficient of 0.67 (P< 0.001), cardiac function directly affects knowledge with path coefficient of − 0.97 (P< 0.001) and history of interventional therapy directly affects practice with path coefficient of 4.23 (P< 0.001).Conclusion: Elderly CHD patients demonstrated sufficient knowledge, positive attitudes, and proactive practices towards self-perceived health abilities. However, educational programs and behavior modification are recommended, particularly for elderly with lower age and education, living in rural areas, lacking interventional therapy, obese, or taking multiple CHD medications.Keywords: knowledge, attitudes, practices, cross-dimensional study, coronary heart disease, self-perceived health abilities

Jie Gao,1,&ast; Jie Dou,1,&ast; Hui-Hui Yang,1 Ruo-Ling Guo,1 Chao Jiang,1 Gary Tse,2– 4 Tong Liu,2 Jian-Wei Liu,5 Dong-Lei Luo6 1Chengde Medical University, Chengde, 067000, People’s Republic of China; 2Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China; 3School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, 999077, People’s Republic of China; 4Epidemiology Research Unit, Cardiovascular Analytics Group, PowerHealth Limited, Hong Kong, 999077, People’s Republic of China; 5Department of Cardiothoracic Interventional Vascular Surgery, Chengde Central Hospital/Second Clinical College of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China; 6Department of Cardiology, Chengde Central Hospital / Second Clinical College of Chengde Medical University, Chengde, 067000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong-Lei Luo, Department of Cardiology, Chengde Central Hospital / Second Clinical College of Chengde Medical University, Chengde, 067000, People’s Republic of China, Email dongleiluocn@aliyun.com Jian-Wei Liu, Department of Cardiothoracic Interventional Vascular Surgery, Chengde Central Hospital/Second Clinical College of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China, Email Ljw2112@126.comPurpose: To investigate the clinical application value of diagonal earlobe crease (DELC) in patients with chest pain for the diagnosis of coronary heart disease (CHD) and to construct a risk model by multivariate logistic regression.Patients and Methods: Our trial enrolled prospectively and consecutively 706 chest pain patients with suspected CHD between January 2021 to June 2023 from Chengde Central Hospital. According to coronary angiography results, they were categorized into the CHD (n=457) and non-CHD groups (n=249).Results: The trial demonstrated a significant positive relationship between DELC and CHD. Independent risk factors were sex, age, hypertension, diabetes mellitus, LP (a), Cys C, and DELC, whilst HDL-C was a protective factor, for CHD. Patients with-DELC were older than those in the without-DELC arm (P< 0.001) and had a higher proportion of males than females (61.6% vs 50.0%, P=0.026). After multifactorial correction, independent risk factors for CHD included DELC (OR=1.660, 95% CI:1.153 to 2.388, P=0.006), age (OR=1.024, 95% CI:1.002 to 1.045, P=0.030), gender (OR=1.702, 95% CI:1.141 to 2.539, P=0.009), hypertension (OR=1.744, 95% CI:1.226 to 2.482, P=0.002), diabetes mellitus (OR=2.113, 95% CI:1.404 to 3.179, P< 0.001), LP(a) (OR=1.010, 95% CI:1.003 to 1.017, P=0.005), Cys C (OR=3.549, 95% CI:1.605 to 7.846, P=0.002). The Hosmer and Lemeshow (H-L) test (P=0.818) suggests a high goodness of fit, and the area under the ROC curve was calculated to be 0.721 (95% CI:0.682 to 0.760, P< 0.001), which demonstrates that the model has a superior diagnostic value for CHD.Conclusion: DELC is an independent risk factor for CHD after adjusting for sex, age, hypertension, diabetes mellitus, smoking index, LP (a), Cys C, and HDL-C. Our model can be used clinically for assessing the risk of CHD.Keywords: coronary heart disease, diagonal earlobe crease, coronary angiography, model

Li Xie,1,&ast; Xiangyi Kong,1,2,&ast; Jidong Gao1,2 1Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, People’s Republic of China; 2Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jidong Gao, Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, People’s Republic of China, Email ab168@cicams.ac.cnAbstract: In the vast expanse of restorative surgical procedures, the Deep Inferior Epigastric Perforator (DIEP) flap, originating from the inferior epigastric artery, has emerged as the preferred method of breast reconstruction, attributable to its myriad advantages. The technique provides reliable vascular supply, robust tissue volume for excision, minimal invasiveness to the donor site, with direct closure and concealment of the said site. This paper embarks on an elaborate elucidation of the DIEP surgical procedure, pivoting on the analytical exploration of a particular instance where necrosis of the skin flap occurred following immediate DIEP breast reconstruction in a patient diagnosed with early-stage breast cancer. This patient had previously undergone Nipple Areola Complex Sparing Mastectomy (NSM). We endeavor to extrapolate insights from this singular case of post-NSM DIEP breast reconstruction failure and correlate our findings with current literature dedicated to similar instances of surgical failure in DIEP breast reconstruction.Keywords: breast cancer, NSM, DIEP, breast reconstruction

Wenyu Bao,&ast; Junkang Gao,&ast; Siyu Fang, Shiwei Zhang, Yufeng Wan Department of Otolaryngology, Head and Neck Surgery, Chaohu Hospital Affiliated to Anhui Medical University, Hefei, 238000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufeng Wan, Department of Otolaryngology, Head and Neck Surgery, Chaohu Hospital Affiliated to Anhui Medical University, Hefei, 238000, People’s Republic of China, Email Wanyufeng135@126.comObjective: This study aims to explore the correlation between serum monocyte-to-lymphocyte ratio (MLR) and other inflammatory parameters with the occurrence of obstructive sleep apnea-hypopnea syndrome (OSAHS) in patients.Methods: This study included 310 patients who underwent polysomnography monitoring at our hospital between January 2021 and January 2023. Routine blood inflammatory parameters and polysomnography (PSG) results were also evaluated. The differences in inflammatory markers between the OSAHS and normal groups were compared, and OSAHS independent related factors were screened.Results: The MLR of OSAHS group was significantly higher than that of control group, and the difference was statistically significant. Multivariate logistic regression analysis suggested that MLR is an independent risk factor for OSAHS.Conclusion: High MLR was correlated with OSAHS. The diagnostic value of MLR was better than that of the other inflammatory parameters.Keywords: obstructive sleep apnea hypopnea syndrome, inflammation, monocyte to lymphocyte ratio, polysomnography

Mingzheng Yao,1 Dan Liang,2 Xiuli Zeng,1 Xiaomei Xie,1 Jiali Gao,1 Li’an Huang1 1Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of China; 2Department of Neurology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, People’s Republic of ChinaCorrespondence: Li’an Huang, Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of China, Email huanglian1306@126.comPurpose: Galectin-3 is a key regulator of microglial proliferation and activation and may have dual and time-dependent effects on ischemic stroke. This study aimed to prospectively investigate the dynamic changes in Galectin-3 levels in patients with acute ischemic stroke receiving endovascular therapy and its clinical significance.Patients and Methods: A total of 105 patients with acute ischemic stroke who underwent endovascular therapy were prospectively enrolled. Plasma Galectin-3 was quantitatively detected by an enzyme-linked immunosorbent assay before the operation and at 1 day, 3 days and 7 days after the operation. A linear mixed-effect model, Pearson correlation analysis and receiver operating characteristic (ROC) curve analysis were used to evaluate the dynamic changes in the plasma Galectin-3 concentration and its relationship with clinical outcomes.Results: Increases in plasma Galectin-3 levels at 1 day and 3 days after surgery were associated with early neurological deterioration and death (both P < 0.05). Increased Galectin-3 levels before surgery and at 1 day and 3 days after surgery were associated with poor prognosis (P < 0.05). Pearson correlation analysis revealed that Galectin-3 levels before surgery (r =0.318, P =0.002), at 1 day (r =0.318, P =0.001), 3 days (r =0.429, P < 0.001) and 7 days after surgery (r =0.340, P =0.001) were positively correlated with NIHSS scores. The ROC curve results showed that Galectin-3 concentration had a certain predictive value for death at 1 day (AUC=0.707, P=0.013), 3 days (AUC=0.708, P=0.016) and 7 days after the operation (AUC=0.708, P=0.016), but this predictive value was lower than that of the NIHSS score.Conclusion: In acute ischemic stroke patients receiving endovascular therapy, an increase in the plasma Galectin-3 levels were associated with death, poor prognosis, and early neurological deterioration. Galectin-3 levels were significantly correlated with the NIHSS score and had a certain predictive value for death.Plain Language Summary: Galectin-3 is a key regulator of microglial proliferation and activation and may have dual and time-dependent effects on ischemic stroke. However, relevant clinical studies are less at present. In this study, we found that an increase in the plasma Galectin-3 levels had significant values in death, poor prognosis, and early neurological deterioration in acute ischemic stroke patients receiving endovascular therapy at various times.Keywords: ischemic stroke, Galectin-3, endovascular therapy, inflammation, dynamic change, outcome

Qiong Ge,1,&ast; Zhewen Zhang,2,&ast; Zhiming Cao,2 Dan Wu,3 Changping Xu,1 Jianbiao Yao,3 Jian Gao,1 Yan Feng1 1Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People’s Republic of China; 2College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine Pharmaceutical Technology, Zhejiang Conba Pharmaceutical Co., Ltd, Hangzhou, Zhejiang, 310057, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Feng, Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People’s Republic of China, Tel/Fax +86-571-87115204, Email yfeng@cdc.zj.cnPurpose: This study aims to investigate the in vitro antiviral effects of the aqueous solution of Changyanning (CYN) tablets on Enterovirus 71 (EV71), and to analyze its active components.Methods: The in vitro anti-EV71 effects of CYN solution and its herbal ingredients were assessed by testing the relative viral RNA (vRNA) expression level and the cell viability rates. Material basis analysis was performed using HPLC-Q-TOF-MS/MS detection. Potential targets and active components were identified by network pharmacology and molecular docking. The screened components were verified by in vitro antiviral experiments.Results: CYN solution exerted anti-EV71 activities as the vRNA is markedly reduced after treatment, with a half maximal inhibitory concentration (IC50) of 996.85 μg/mL. Of its five herbal ingredients, aqueous extract of Mosla chinensis (AEMC) and leaves of Liquidambar formosana Hance (AELLF) significantly inhibited the intracellular replication of EV71, and the IC50 was tested as 202.57 μg/mL and 174.77 μg/mL, respectively. Based on HPLC-Q-TOF-MS/MS results, as well as the comparison with the material basis of CYN solution, a total of 44 components were identified from AEMC and AELLF. Through network pharmacology, AKT1, ALB, and SRC were identified as core targets. Molecular docking performed between core targets and the components indicated that 21 components may have anti-EV71 effects. Of these, nine were selected for in vitro pharmacodynamic verification, and only rosmarinic acid manifested in vitro anti-EV71 activity, with an IC50 of 11.90 μg/mL. Moreover, rosmarinic acid can stably bind with three core targets by forming hydrogen bonds.Conclusion: CYN solution has inhibitory effects on EV71 replication in vitro, and its active component was identified as rosmarinic acid. Our study provides a new approach for screening and confirmation of the effective components in Chinese herbal preparation.Keywords: antiviral effects, material basis analysis, component-target-pathway-disease network, protein–protein interaction network, core targets, rosmarinic acid

Mengdi Wang,1,&ast; Shan Wang,1,&ast; Changhao Zhang,2,&ast; Ming Ma,1 Bohua Yan,1 Xinming Hu,2 Tianjiao Shao,2 Yan Piao,2 Lili Jin,2 Jing Gao1 1State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People’s Republic of China; 2College of Pharmacy, Key Laboratory of Natural Medicines of the Changbai Mountain of Ministry of Education, Yanbian University, Yanji, Jilin, 133002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Gao; Lili Jin, Email gjsmmu@126.com; jinlili@ybu.edu.cnAbstract: Long-acting injectable microspheres have been on the market for more than three decades, but if calculated on the brand name, only 12 products have been approved by the FDA due to numerous challenges in achieving a fully controllable drug release pattern. Recently, more and more researches on the critical factors that determine the release kinetics of microspheres shifted from evaluating the typical physicochemical properties to exploring the microstructure. The microstructure of microspheres mainly includes the spatial distribution and the dispersed state of drug, PLGA and pores, which has been considered as one of the most important characteristics of microspheres, especially when comparative characterization of the microstructure (Q3) has been recommended by the FDA for the bioequivalence assessment. This review extracted the main variables affecting the microstructure formation from microsphere formulation compositions and preparation processes and highlighted the latest advances in microstructure characterization techniques. The further understanding of the microsphere microstructure has significant reference value for the development of long-acting injectable microspheres, particularly for the development of the generic microspheres. Keywords: long-acting injectable microsphere, microstructure, PLGA, controlled drug release

Jiameng Gao,1,2,&ast; Zhiyuan Zhang,1,2,&ast; Jing Yu,1,2,&ast; Nan Zhang,1,2 Yu Fu,1,2 Xuemei Jiang,1,2 Zheyu Xia,3 Qingqing Zhang,1,2 Zongmei Wen1,2 1Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Lung Transplantation, Shanghai, People’s Republic of China; 3School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongmei Wen; Qingqing Zhang, Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Tel +86 13761635280 ; +86 13764542055, Email wzm1103@126.com; elfe666@163.comPurpose: Ischemia reperfusion injury (IRI) unavoidably occurs during lung transplantation, further contributing to primary graft dysfunction (PGD). Neutrophils are the end effectors of IRI and activated neutrophils release neutrophil extracellular traps (NETs) to further amplify damage. Nevertheless, potential contributions of NETs in IRI remain incompletely understood. This study aimed to explore NET-related gene biomarkers in IRI during lung transplantation.Methods: Differential expression analysis was applied to identify differentially expressed genes (DEGs) for IRI during lung transplantation based on matrix data (GSE145989, 127003) downloaded from GEO database. The CIBERSORT and weighted gene co-expression network analysis (WGCNA) algorithms were utilized to identify key modules associated with neutrophil infiltration. Moreover, the least absolute shrinkage and selection operator regression and random forest were applied to identify potential NET-associated hub genes. Subsequently, the screened hub genes underwent further validation of an external dataset (GSE18995) and nomogram model. Based on clinical peripheral blood samples, immunofluorescence staining and dsDNA quantification were used to assess NET formation, and ELISA was applied to validate the expression of hub genes.Results: Thirty-eight genes resulted from the intersection between 586 DEGs and 75 brown module genes, primarily enriched in leukocyte migration and NETs formation. Subsequently, four candidate hub genes (FCAR, MMP9, PADI4, and S100A12) were screened out via machine learning algorithms. Validation using an external dataset and nomogram model achieved better predictive value. Substantial NETs formation was demonstrated in IRI, with more pronounced NETs observed in patients with PGD ≥ 2. PADI4, S100A12, and MMP9 were all confirmed to be up-regulated after reperfusion through ELISA, with higher levels of S100A12 in PGD ≥ 2 patients compared with non-PGD patients.Conclusion: We identified three potential NET-related biomarkers for IRI that provide new insights into early detection and potential therapeutic targets of IRI and PGD after lung transplantation.Keywords: ischemia reperfusion injury, neutrophil extracellular traps, lung transplantation, primary graft dysfunction, WGCNA, machine learning

Yang Chen, Xiaoen Bian, Junnan Wang, Fang Yan, Jing Gao, Tao Sun Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Tao Sun, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong, 250021, People’s Republic of China, Email suntaosdph@163.comPurpose: Chronic inflammatory pain is usually treated with oral non-steroidal anti-inflammatory drugs (NSAIDs). However, oral NSAIDs can cause some adverse events, and local preparation is an important alternative drug. Currently, small sample clinical studies show that loxoprofen sodium hydrogel patch (LX-P) has good analgesic and anti-inflammatory effects; however, there is a lack of real-world clinical research data.Patients and Methods: This study included 60 patients with chronic inflammatory pain. They were treated with LX-P without affecting their real-world treatment for two weeks.Results: After 2 weeks of continuous medication, 93.33% of the patients stated that the treatment was effective. Only 3.33% of the patients had a relapse after 4 weeks. Moreover, the swelling range and degree of swelling decreased markedly and the dysfunction of the pain site was markedly alleviated. The total satisfaction of patients after treatment reached 90.00%.Conclusion: In this real-world observational study, LX-P showed good efficacy and safety in patients with chronic inflammatory pain.Keywords: loxoprofen sodium hydrogel patch, real-world study, chronic inflammatory pain, non-steroidal anti-inflammatory drugs

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

Qinzhou Zheng,1,&ast; Cuimin Chen,2,&ast; Yong Liu,3 Jie Gao,2,&ast; Luxin Li,1 Chuan Yin,4 Xiaohuan Yuan1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 2Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Center for Comparative Medicine, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 4Department of Gastroenterology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuan Yin, Department of Gastroenterology, Shanghai Changzheng Hospital, Naval Medical, University, Shanghai, 200003, People’s Republic of China, Email ilse1225@163.com Xiaohuan Yuan, College of Life Science, Mudanjiang Medical University, Mudanjiang, 157001, Heilongjiang, People’s Republic of China, Tel/Fax +86-453-6984647, Email yuanxiaohuan@mdjmu.edu.cnAbstract: Diabetic wounds pose a significant challenge to public health, primarily due to insufficient blood vessel supply, bacterial infection, excessive oxidative stress, and impaired antioxidant defenses. The aforementioned condition not only places a significant physical burden on patients’ prognosis, but also amplifies the economic strain on the medical system in treating diabetic wounds. Currently, the effectiveness of available treatments for diabetic wounds is limited. However, there is hope in the potential of metal nanoparticles (MNPs) to address these issues. MNPs exhibit excellent anti-inflammatory, antioxidant, antibacterial and pro-angiogenic properties, making them a promising solution for diabetic wounds. In addition, MNPs stimulate the expression of proteins that promote wound healing and serve as drug delivery systems for small-molecule drugs. By combining MNPs with other biomaterials such as hydrogels and chitosan, novel dressings can be developed and revolutionize the treatment of diabetic wounds. The present article provides a comprehensive overview of the research progress on the utilization of MNPs for treating diabetic wounds. Building upon this foundation, we summarize the underlying mechanisms involved in diabetic wound healing and discuss the potential application of MNPs as biomaterials for drug delivery. Furthermore, we provide an extensive analysis and discussion on the clinical implementation of dressings, while also highlighting future prospects for utilizing MNPs in diabetic wound management. In conclusion, MNPs represent a promising strategy for the treatment of diabetic wound healing. Future directions include combining other biological nanomaterials to synthesize new biological dressings or utilizing the other physicochemical properties of MNPs to promote wound healing. Synthetic biomaterials that contain MNPs not only play a role in all stages of diabetic wound healing, but also provide a stable physiological environment for the wound-healing process.Keywords: metal nanoparticles, wound healing, diabetic wound, drug delivery, antibacterial activity

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

Changyu Yao,&ast; Jian Kong,&ast; Fei Xu, Shaohong Wang, Shilun Wu, Wenbing Sun, Jun Gao Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenbing Sun; Jun Gao, Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, No. 5 Jingyuan Road, Shijingshan District, Beijing, 100043, People’s Republic of China, Tel +86-010-51718382, Fax +86-010-51718372, Email sunwenbing@bjcyh.com; gaojun8430@163.comPurpose: Systemic inflammatory response syndrome (SIRS) is a common complication of radiofrequency ablation (RFA) for hepatic hemangiomas. RFA can cause hemolytic reactions during hepatic hemangioma ablation. However, the mechanisms underlying RFA-induced SIRS remain unclear.Methods: We established an orthotopic liver hemangioma model and performed radiofrequency ablation. The levels of interleukin (IL)-1β and IL-18 and the production of ROS were measured. The wet-to-dry lung ratio, inflammation score, and in vivo endothelial cell permeability were examined. GSDMD−/− mice were used to investigate the effect of heme-inducing SIRS. RNA sequencing (RNA-seq) was performed to identify the main pathways underlying heme-induced SIRS. Western blotting and immunoprecipitation were used to determine the changes and interactions of associated proteins.Results: The levels of heme, IL-1β, and IL-18 were significantly increased after RFA. The wet-to-dry lung ratio increased in hepatic hemangiomas after RFA, indicating that SIRS occurred. Heme induced increased levels of IL-1β and IL-18, cell death, wet-to-dry lung radio, and inflammation score in vitro and in vivo, indicating that heme induced SIRS and pyroptosis. Furthermore, GSDMD participates in heme-induced SIRS in mice, and GSDMD deletion in mice reverses the effect of heme. Heme regulates NLRP3 activation through the NOX4/ROS/TXNIP-TRX pathway, and an N-acetyl-L-cysteine (NAC) or NOX4 inhibitor (GLX351322) reverses heme-induced SIRS.Conclusion: Our findings suggest that heme induces endothelial cell pyroptosis and SIRS in mice and decreasing heme levels and ROS scavengers may prevent SIRS in hepatic hemangioma after RFA. Keywords: hemangioma, radiofrequency ablation, systemic inflammatory response syndrome, pyroptosis, endothelial cells

Yuan Gao,1,2,&ast; Ting-Lin Zhang,3,&ast; Hong-Jian Zhang,1,2,&ast; Jie Gao,3 Peng-Fei Yang1,2,4 1Oriental Pan-Vascular Devices Innovation College, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 2School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 3Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 4Neurovascular Center, Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng-Fei Yang, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China, Tel +86-15921196312, Fax +86-2131161784, Email 15921196312@163.com Jie Gao, Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China, Tel/Fax +86-21-31162092, Email gaojiehighclea@smmu.edu.cnAbstract: Ischemic stroke, a condition that often leads to severe nerve damage, induces complex pathological and physiological changes in nerve tissue. The mature central nervous system (CNS) lacks intrinsic regenerative capacity, resulting in a poor prognosis and long-term neurological impairments. There is no available therapy that can fully restore CNS functionality. However, the utilization of injectable hydrogels has emerged as a promising strategy for nerve repair and regeneration. Injectable hydrogels possess exceptional properties, such as biocompatibility, tunable mechanical properties, and the ability to provide a supportive environment for cell growth and tissue regeneration. Recently, various hydrogel-based tissue engineering approaches, including cell encapsulation, controlled release of therapeutic factors, and incorporation of bioactive molecules, have demonstrated great potential in the treatment of CNS injuries caused by ischemic stroke. This article aims to provide a comprehensive review of the application and development of injectable hydrogels for the treatment of ischemic stroke-induced CNS injuries, shedding light on their therapeutic prospects, challenges, recent advancements, and future directions. Additionally, it will discuss the underlying mechanisms involved in hydrogel-mediated nerve repair and regeneration, as well as the need for further preclinical and clinical studies to validate their efficacy and safety.Keywords: ischemic stroke, central nervous system, hydrogels, neural restoration, nerve regeneration

Yong Li,1 Ju Gao,1 Lin Jiang,2 Canlin Sun,2 Hua Hong,2 Dapeng Yu2 1Department of Anesthesiology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu Province, People’s Republic of China; 2Department of Anesthesiology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, Jiangsu Province, People’s Republic of ChinaCorrespondence: Dapeng Yu, Department of Anesthesiology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China, Email xiaosiyu1@163.comAbstract: Dexmedetomidine is a selective and potent α2-adrenoceptor agonist used for sedation, analgesia, and anxiolysis, with minimal respiratory depression; therefore, it is widely used in clinical practice. Transient hypertension has been reported to be an indication for the use of dexmedetomidine. The authors report three female patients who experienced hypertensive crisis when used atropine to treat bradycardia caused by dexmedetomidine. The transient hypertension is a relatively common side effect of dexmedetomidine, hypertensive crisis seen with coadministration of atropine is much less frequently reported. This is the first report to describe the use of atropine to treat bradycardia induced by dexmedetomidine, which may cause severe hypertension in female patients. They discuss the reason for and treatment of hypertension caused by administration of atropine and dexmedetomidine together and review the relevant literature.Keywords: dexmedetomidine, atropine, bradycardia, hypertension

Yu Ma, Jinbo Gao, Hongning Guo Department of Stomatology, Tianjin Third Central Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Yu Ma, Department of Stomatology, Tianjin Third Central Hospital, No. 83 Jintang Road, Hedong District, Tianjin, 300170, People’s Republic of China, Tel +86-13102229881, Email mayu881@tom.comBackground: While there is prior evidence for the ability of circular RNAs (circRNAs) to shape the cisplatin (DDP) resistance of cancers in human patients, there has been relatively little research to date focused on the interplay between circRNAs and DDP resistance in the context of OSCC progression to date. In the present analysis, the functional role that circ_0000140 plays as a mediator of chemoresistance to DDP was thus explored in greater detail.Methods: Both qPCR and Western immunoblotting were employed as appropriate to detect circ_0000140, miR-527, and SLC7A11 levels, while interactions among these factors were detected through RNA immunoprecipitation, RNA pull-down, and dual luciferase report assays. MTT assays were used to assess cellular viability as a means of gauging DDP sensitivity.Results: Both tissue samples from DDP-resistant OSCC patient tumors and OSCC cell lines resistant to DDP exhibited pronounced circ_0000140 upregulation. Knocking down this circRNA significantly increased the DDP sensitivity of both tested DDP-resistant OSCC cell lines and promoted ferroptosis, whereas knocking down miR-527 was sufficient to reverse these effects, which were recapitulated by miR-527 overexpression. Conversely, the effects of overexpressing miR-527 were reversed by the restoration of SLC7A11 expression. Consistently, this circRNA was able to increase DDP IC50 values and to suppress ferroptosis in both tested cell lines through this miR-527/SLC7A11 signaling axis.Conclusion: These results revealed that circ_0000140/miR-527/SLC7A11-mediated ferroptosis may provide novel insights into the development of this cancer type and the emergence of chemoresistance in the future.Keywords: Circ_0000140, DDP resistance, oral squamous cell carcinoma, miR-527, SLC7A11, ferroptosis

Chao Gao,1,&ast; Yan Liu,2,&ast; Ting-Lin Zhang,3,&ast; Yi Luo,2,4,&ast; Jie Gao,3,&ast; Jian-Jian Chu,1 Bao-Feng Gong,1 Xiao-Han Chen,1 Tong Yin,1 Jian Zhang,2 You Yin1 1Department of Neurology, Second Affiliated Hospital (Shanghai Changzheng Hospital) of Naval Medical University, Shanghai, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai Jiao Tong University of Medicine, Shanghai, People’s Republic of China; 3Changhai Clinical Research Unit, Shanghai Changhai Hospital of Naval Medical University, Shanghai, People’s Republic of China; 4New Drug Discovery and Development, Biotheus Inc., Zhuhai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: You Yin; Jian Zhang, Tel +86-21-81885463 ; +86- 21-25077150, Email yinyou179@163.com; zhangjian@xinhuamed.com.cnAbstract: Current therapies for Alzheimer’s disease used in the clinic predominantly focus on reducing symptoms with limited capability to control disease progression; thus, novel drugs are urgently needed. While nanoparticles (liposomes, high-density lipoprotein-based nanoparticles) constructed with synthetic biomembranes have shown great potential in AD therapy due to their excellent biocompatibility, multifunctionality and ability to penetrate the BBB, nanoparticles derived from natural biomembranes (extracellular vesicles, cell membrane-based nanoparticles) display inherent biocompatibility, stability, homing ability and ability to penetrate the BBB, which may present a safer and more effective treatment for AD. In this paper, we reviewed the synthetic and natural biomembrane-derived nanoparticles that are used in AD therapy. The challenges associated with the clinical translation of biomembrane-derived nanoparticles and future perspectives are also discussed. Keywords: Alzheimer’s disease, nanoparticles, blood‒brain barrier, liposomes, bionanotechnology, neurodegenerative diseases

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

Yuxiang Xu, Xiaonan Gao, Yunfang Zhu, Qi Zhang, Hongxin Qie, Haopeng Zhao, Jinglin Gao, Mingxia Wang Department of Clinical Pharmacology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, People’s Republic of ChinaCorrespondence: Mingxia Wang, Department of Clinical Pharmacology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People’s Republic of China, Tel +86-311-66696233, Email mxia_wang@163.comPurpose: To develop an UPLC-MS/MS method for the quantitative analysis of pentoxifylline in beagle dog plasma and apply it to a pharmacokinetic study of food effect.Methods: Sample separation was achieved using a Kinetex Phenyl-Hexyl column (50 × 2.1 mm, 1.7 μm) with a gradient elution program in 5.5 min after a simple protein precipitation with methanol. Using the mobile phase that made up by 0.2% formic acid and 5mM ammonium formate water (A) and methanol (B). Quantitation was carried out using the positive ionization mode with multiple reaction monitoring (MRM). A randomized, single-dose, two-period crossover study was conducted in six fasted or fed beagles that received 400 mg pentoxifylline sustained-release tablets (Brand name: Shuanling™, CSPC Pharmaceutical Group). WinNonlin® software was used to calculate pharmacokinetic parameters.Results: The linear calibration range was 2– 1000 ng/mL (r2> 0.99). Both intra- and inter-batch precision were less than 6.27%, and the accuracy ranged from 88.65% to 97.18%. Pentoxifylline was readily absorbed in fasted and fed dogs administered a dose of 400 mg (tmax:1.54h vs 1.83h). Compared to the fasted group, the AUC0→t and Cmax in the fed group increased by 1.71-fold and 1.30-fold, respectively. In the fasted group, the AUC0→t and Cmax values were 4684.08 h•ng/mL and 2402.33 ng/mL, respectively. In the fed group, these values were 8027.75 h•ng/mL and 3119.67 ng/mL. The difference in AUC0-t between the fed and fasted group was statistically significant.Conclusion: The novel optimized UPLC-MS/MS assay is an effective tool for the determination of pentoxifylline and has been successfully applied in pharmacokinetic studies of pentoxifylline in beagle dogs. The administration of pentoxifylline sustained-release tablets with food significantly increased the area under the time curve, and it is recommended that they should be administered during or shortly after feeding.Keywords: pentoxifylline, sustained-release tablets, food effect, UPLC-MS/MS, pharmacokinetics

Hong-Liang Jia,1 Jian Gao,2 Feng Ren,2 Yaping Ma1 1Department of Pediatrics, Affiliated Hospital of Jiangnan University, Wuxi, 214122, People’s Republic of China; 2Department of Clinical Laboratory, Affiliated Hospital of Jiangnan University, Wuxi, 214122, People’s Republic of ChinaCorrespondence: Yaping Ma, Department of Pediatrics, Affiliated Hospital of Jiangnan University, No. 1000 of Hefeng Road, Binhu District, Wuxi, 214122, People’s Republic of China, Tel +86 510-68089896, Email mayp987@163.comObjective: We retrospectively analysed related clinical data to determine the influencing factors to better prevent and treat children’s respiratory tract infection.Methods: The study participants were children with respiratory tract infection who had sputum cultured in our hospital between 2014 and 2021. Sputum samples were extracted using negative suction pressure and sent to the hospital microbiological laboratory for testing. The testing results were analysed.Results: A total of 4610 sputum samples were collected, and 508 positive samples were detected. The positive rate of pathogenic bacteria was 11.02%. Escherichia coli infection was more common in male patients (11.11%), whereas Haemophilus influenzae infection was more common in female patients (17.54%); the infection rates of these 2 bacteria are increasing annually. There were 304 (59.84%) strains of gram-negative bacteria, 172 (33.86%) strains of gram-positive bacteria and 32 (6.3%) strains of fungi. In children between 0 and 3 years old, the proportions of gram-negative bacteria were significantly higher than those of gram-positive bacteria in 2016– 2017, 2018– 2019 and 2020– 2021 (p

Qiang Yang,1,&ast; Jing Gao,2,&ast; Tian-Yu Wang,1 Jun-Can Ding,1 Peng-Fei Hu3 1Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 2Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, Zhejiang Province, 310018, People’s Republic of China; 3Department of Cardiology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng-Fei Hu, Department of Cardiology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China, Tel +86 15267037741, Email 20064012@zcmu.edu.cnPurpose: This study aimed to analyze the hub genes of heart failure with reduced ejection fraction (HFrEF) treated with Empagliflozin using RNA sequencing (RNA-seq) and bioinformatics methods, including machine learning.Methods: From February 2021 to February 2023, nine patients with HFrEF were enrolled from our hospital’s cardiovascular department. In addition to routine drug treatment, these patients received 10 mg of Empagliflozin once daily for two months. Efficacy was assessed and RNA-seq was performed on peripheral blood before and after treatment with empagliflozin. HFrEF-related hub genes were identified through bioinformatics analyses including differential gene expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, immune infiltration analysis, machine learning, immune cell correlation analysis and clinical indicator correlation analysis.Results: The nine patients included in this study completed a two-month treatment regimen, with an average age of 62.11 ± 6.36 years. By performing bioinformatics analysis on the transcriptome from the treatment groups, 42 differentially expressed genes were identified, with six being up-regulated and 36 being down-regulated (|log2FC|> 1 and adj.pvalue< 0.05). Immune infiltration analysis of these genes demonstrated a significant difference in the proportion of plasma between the pre-treatment and post-treatment groups (p< 0.05). Two hub genes, GTF2IP14 and MTLN, were finally identified through machine learning. Further analysis of the correlation between the hub genes and immune cells suggested a negative correlation between GTF2IP14 and naive B cells, and a positive correlation between MTLN and regulatory T cells and resting memory CD4+ T cells (p< 0.05).Conclusion: Through RNA-seq and bioinformatics analysis, this study identified GTF2IP14 and MTLN as the hub genes of HFrEF, and their mechanisms may be related to immune inflammatory responses and various immune cells.Keywords: HFrEF, empagliflozin, RNA-seq, machine learning, bioinformatics

Zhongyuan Xin,1,2,&ast; Mengya Zhang,2,&ast; Hengqing Cui,3,&ast; Xiuwen Ding,2,&ast; Tinglin Zhang,2 Lili Wu,2 Haipo Cui,1 Qian Xue,2 Cuimin Chen,2 Jie Gao2 1School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 2Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 3Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, ‎People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Gao; Cuimin Chen, Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China, Tel +86 21 31162092, Fax +86 21 31161111, Email gaojiehighclea@smmu.edu.cn; 535428425@qq.comAbstract: Cancer is the second leading cause of death worldwide. Its incidence has been increasing in recent years, and it is becoming a major threat to human health. Conventional cancer treatment strategies, including surgery, chemotherapy, and radiotherapy, have faced problems such as drug resistance, toxic side effects and unsatisfactory therapeutic efficacy. Therefore, better development and utilization of biomaterials can improve the specificity and efficacy of tumor therapy. Algae, as a novel living material, possesses good biocompatibility. Although some reviews have elucidated several algae-based biomaterials for cancer treatment, the majority of the literature has focused on a limited number of algae. As a result, there is currently a lack of comprehensive reviews on the subject of anticancer algae. This review aims to address this gap by conducting a thorough examination of algal species that show potential for anticancer activity. Furthermore, our review will also elucidate the engineering strategies of algae and discuss the challenges and prospects associated with their implementation.Keywords: algae, neoplasms, engineering strategies, biomaterials, anticancer mechanism

Rong Zhao,1,&ast; Jianyong Zhang,2,&ast; Qingxiang Gou,3 Jinnan Gao1,2 1General Surgery Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China; 3School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinnan Gao, General Surgery Department, Shanxi Bethune Hospital, Longcheng Street 99, Taiyuan, Shanxi, 030032, People’s Republic of China, Tel +86 15135086600, Email 15135086600@163.comBackground: The role of traditional Chinese medicine (TCM) in breast cancer treatment is controversial. The aim of this study is to explore the popularity of TCM among the breast cancer patients who have been treated with Western medicine (WM) in north China.Methods: An observational, cross-sectional study was conducted. We consecutively recruited 691 breast cancer patients who were diagnosed in Shanxi Bethune Hospital between 1 January 2017 and 31 December 2020 and completed follow-up between June and August 2022. A self-designed questionnaire was used for data collection. Participants were asked about TCM use by phone. Univariate and multivariate analyses were performed as appropriate.Results: At median follow-up of 41 months (range, 17– 61 months), 326 (47.2%) participants used TCM. The results of multivariate logistic regression showed that residential area, education, annual income per capita, experienced TCM treatment before, stage of diagnosis, and trust in TCM were independent predictors of TCM use. The detail of TCM use and the reason for non-TCM use were presented comprehensively.Conclusion: The use of TCM was prevalent among breast cancer patients treated with WM in north China. If WM physician encourage the patients with higher intention to use TCM and provide them with appropriate advices, the quality of life of patients will be further improved through integrating TCM into standard adjuvant therapy.Keywords: traditional Chinese medicine, breast cancer, cross-sectional study, China

Chen Li,1,&ast; Jun Hao,2,&ast; Chuangshi Wang,2 Jie Yang,1 Yitian Zheng,1 Kuo Zhang,3 Wen Hui,4 Xiangbin Meng,1 Jun Gao,1 Wei Li,2 Yi-Da Tang1,5 1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, People’s Republic of China; 2Medical Research and Biometrics Center, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Science and Technology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Yi-Da Tang, Email liwei@mrbc-nccd.com; tangyida@bjmu.edu.cnObjective: The incidence rate of thyroid diseases increased worldwide. This study aims to overview the changing landscape of drug clinical trials on thyroid disease during 2009– 2022.Methods: The detailed information of thyroid disease drug trials registered on the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform for Drug Clinical Studies was searched and collected. The thyroid drug clinical trials were analyzed by the characteristics, time trends, indications, and geographical distribution.Results: Sixty-five thyroid disease drug clinical trials were launched from 2009 to 2022 in China, which included 21 trials in nontumorous thyroid disease and 44 trials in thyroid carcinoma. The number of registered trials of thyroid diseases including thyroid carcinoma and nontumorous thyroid disease increased steadily from 2009 to 2020. Bioequivalence studies accounted for the largest proportion (32[49.2%]), while phase I and Phase II studies both only accounted for 18.5% (12/65). A significant difference was observed in the trials phase, and randomization between thyroid carcinoma and nontumorous thyroid disease. In terms of clinical indications and drug mechanisms, the number of trials in multi-target tyrosine kinase inhibitors for thyroid carcinoma (n=35) ranked first, followed by thyroid hormone for hypothyroidism (n=7), thyrotropin for thyroid carcinoma (n=6). Sixty-five trials were led by 36 principal investigator (PI) units, and more than 30% of PI-leading units were located in Shanghai (n=7) and Beijing (n=4).Conclusion: During the past 13 years, the development of thyroid diseases drugs trials has achieved certain progress in thyroid carcinoma, especially the molecular targeted therapy, yet the development of drug trials on nontumorous thyroid disease was very slow.Keywords: thyroid disease, thyroid carcinoma, nontumorous thyroid disease, China, drug clinical trial

Mingfei Guo,1,2 Jiarong Gao,3 Lei Jiang,4 Yaji Dai4 1Department of Scientific Research, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Anhui Public Health Clinical Center, Hefei, Anhui, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 4Department of Pharmacy, Anhui No.2 Provincial People’s Hospital, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Yaji Dai, Department of Pharmacy, Anhui No.2 Provincial People’s Hospital, Hefei, Anhui, People’s Republic of China, Email dyj920914@163.comBackground: Diabetic nephropathy (DN), as a chronic inflammatory complication of diabetes, is characterized by hyperglycemia, albuminuria and edema, which ultimately becomes the leading cause of end-stage renal disease (ESRD). Astragalus polysaccharide (APS), extracted from the Astragalus membranaceus, was widely used in the treatment of diabetes mellitus. However, the functional roles of APS ameliorate inflammatory responses in DN, which remain poorly understood. Therefore, the purpose of this study was to explore the molecular mechanism of APS on DN in vivo and vitro models.Methods: We explored the beneficial effects of APS in streptozotocin (STZ)-induced DN rat model and high glucose (HG)-treated glomerular podocyte model. The fasting blood glucose (FBG) and ratio of kidney weight to body weight were measured after 4 weeks of APS treatment. The renal injury parameters containing serum creatinine (Scr), blood urea nitrogen (BUN) and 24 h urinary protein were evaluated. The renal pathological examination was observed by hematoxylin-eosin (HE) staining. The levels of IL-1β, IL-6 and MCP-1 were evaluated by ELISA assay. The proliferation of podocytes was determined using CCK-8 assay and flow cytometry. qRT-PCR and Western blot analysis were performed to determine the amounts of TLR4/NF-κB-related gene expression.Results: Our results indicated that APS effectively decreased the levels of FBG, BUN, Scr and renal pathological damage when compared with STZ-induced DN model group. Additionally, APS significantly ameliorated renal injury by reducing inflammatory cytokines IL-1β, IL-6, MCP-1 expression and inhibiting the TLR4/NF-κB pathway activity in DN rats. Consistent with the results in vitro, the HG-induced inflammatory response and proliferation of glomerular podocytes were also alleviated through APS administration.Conclusion: We found that APS ameliorated DN renal injury, and the mechanisms perhaps related to relieving inflammatory responses and attenuating the TLR4/NF-κB signaling pathway.Keywords: diabetic nephropathy, Astragalus polysaccharide, podocytes, TLR4/NF-κB, inflammatory response

Yuyu Jiang,1 Jianlan Guo,2 Mengjie Chen,1 Xueqiong Zou,1 Pingping Sun,1 Jing Gao,1 Baiyila Nuerdawulieti,1 Shanshan Wang1 1Research Office of Chronic Disease Management and Rehabilitation, Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Nursing, Wuxi Higher Health Vocational Technology School, Wuxi, People’s Republic of ChinaCorrespondence: Yuyu Jiang, Research office of chronic disease management and rehabilitation, Wuxi School of Medicine, Jiangnan University, No. 1800 Lihu Avenue, Wuxi, Jiangsu Province, People’s Republic of China, Tel +86-0510-85328363, Email doctoryuyu@jiangnan.edu.cnBackground: Pulmonary rehabilitation is an important part of the management of chronic obstructive pulmonary disease (COPD), but the participation rate of pulmonary rehabilitation in COPD patients is low. Patient decision aids can facilitate patient participation in pulmonary rehabilitation decisions by providing information and incorporating patient values. The aim of this study was to develop a pulmonary rehabilitation decision aid for patients with COPD.Objective: The aim of this study was to develop a WeChat-based pulmonary rehabilitation patient decision aid to help older patients with COPD participate in pulmonary rehabilitation decision-making.Methods: We developed the decision aid in 3 stages: (1) a literature review was performed to determine the evidence for pulmonary rehabilitation options and outcomes for patients with COPD. (2) a semi-structured interview study was conducted to develop and iterate patient decision aids. (3) usability, acceptability and language expression testing in patients and healthcare professionals.Results: A total of 16 randomized controlled studies were included in the literature review. Thirty-six participants received semi-structured interviews. The results of interview include four themes: key points of age-friendly design, content of the tool, presentation requirements of contents and study evidence of the tool and other views and suggestions. The resultant goals-of-care decision aid achieved good usability and acceptability. The frequency of language expression increased in both patients and healthcare professionals.Conclusion: This study uses a systematic development process to develop the first pulmonary rehabilitation decision aid for patients with COPD. It has good usability, acceptability and increased communication between patients and healthcare professionals in the pulmonary rehabilitation decision-making process.Trial Registration: Chinese Clinical Trial Registry (ChiCTR): ChiCTR1900028563; http://apps.who.int/trialsearch/default.aspx.Keywords: chronic obstructive pulmonary disease, shared decision making, pulmonary rehabilitation, patient decision aid

Ren H, Qi Y, Yin X, Gao J. Onco Targets Ther. 2018:11;67-74. We, the Editors and Publisher of OncoTargets and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 1 and 3 with images from other unrelated articles. Specifically, Western blot bands and the background from images in Figure 1B have been duplicated with the bands and background for images from Figure 2D from Liu Y, Zhang B, Shi T, Qin H. miR-182 promotes tumor growth and increases chemoresistance of human anaplastic thyroid cancer by targeting tripartite motif 8. Onco Targets Ther. 2017;10:1115-1122. https://doi.org/10.2147/OTT.S110468. Images for Figure 3C have been duplicated with images for Figure 3 from Qiu, P., Xu, T., Lu, X., Yang, W., Zhang, Y., & Xu, G. (2018). MicroRNA‑378 regulates cell proliferation and migration by repressing RNF31 in pituitary adenoma Retraction in /10.3892/ol.2023.14196. Oncology Letters, 15, 789-794. https://doi.org/10.3892/ol.2017.7431. Images for Figure 3D have been duplicated with images for Figure 2 from Wang, S., Cao, K., He, Q., Yin, Z., & Zhou, J. (2016). miR-199a-5p induces cell invasion by suppressing E-cadherin expression in cutaneous squamous cell carcinoma. Oncology Letters, 12, 97-101. https://doi.org/10.3892/ol.2016.4602 and Figure 2C from Zhao, J., Li, B., Shu, C., Ma, Y., & Gong, Y. (2017). Downregulation of miR‑30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer Retraction in /10.3892/ol.2023.14168. Oncology Letters, 14, 7437-7442. https://doi.org/10.3892/ol.2017.7114. The authors did not respond to our queries and were unable to provide an explanation for the duplicated images or provide data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Meili Cai,1,&ast; Yuqin Zhang,1,&ast; Jingyang Gao,1,&ast; Diliqingna Dilimulati,1 Le Bu,1,2 Xiaoyun Cheng,1,2 Lei Du,2,3 Donglei Zhou,2,3 Jiangfang Zhu,2,3 Shen Qu,1,2 Manna Zhang1,2 1Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 2National Metabolic Management Center, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 3Department of Gastrointestinal Surgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shen Qu; Manna Zhang, Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, 301 Middle Yanchang Road, Shanghai, 200072, People’s Republic of China, Tel +86-021-66301004, Email qushencn@hotmail.com; mannazhang@126.comObjective: To explore the predictors of menstrual recovery in polycystic ovary syndrome (PCOS) women with obesity following laparoscopic sleeve gastrectomy (LSG).Methods: A total of 88 PCOS patients with obesity and 76 control patients with obesity aged 18– 45 years were enrolled between May 2013 and December 2020. PCOS was diagnosed using the Rotterdam diagnostic criteria (2003). Anthropometric measurements, biochemical parameters, sex hormones, and circulating fibrinogen-like protein 1 (FGL-1) levels were collected before and six-month after LSG. The data on postoperative menstrual status, body weight, and fertility were obtained through telephone follow-ups for all individuals with PCOS.Results: Patients with PCOS were followed up for at least six months after surgery, and the mean follow-up time was 3.23 years. At 6 months after LSG, circulating total testosterone (TT), calculated free testosterone (cFT), and FGL-1 levels declined significantly. The mean percent excess weight loss (%EWL) and percent total weight loss (%TWL) in PCOS patients at the final follow-up was 97.52% ± 33.90% and 31.65% ± 10.31%, respectively. The proportion of regular menstruation in PCOS patients significantly increased within six months (75.86% vs 0.03% at baseline). In the logistic regression analysis, time from PCOS diagnosis (P=0.007), body mass index (BMI) (P=0.007), TT (P=0.038) at baseline were demonstrated to be independent predictive factors for the regular menstruation in women with PCOS and obesity within 6 months after LSG.Conclusion: In PCOS patients with obesity, time from PCOS diagnosis, BMI, and TT levels at baseline were independently and negatively associated with menstrual recovery within 6 months after LSG, which could be applied in preoperative evaluation.Keywords: polycystic ovary syndrome, obesity, laparoscopic sleeve gastrectomy, menstruation, fibrinogen-like protein 1

Shuping Cai,1,2,&ast; Jingyuan Gao,3,&ast; Xiaomin Liu,3,&ast; Junhao Yang,3,&ast; Dingyun Feng,1 Guijun Li,2 Sijia Li,1 Hailing Yang,1 Zhang Wang,3 Xinzhu Yi,3 Yuqi Zhou1 1Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guang Dong, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, the Seventh Affiliated Hospital of SUN YAT-SEN University, Shenzhen, Guang Dong, People’s Republic of China; 3Institute of Ecological Sciences, School of Life Sciences, South China Normal University, Guangzhou, Guang Dong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinzhu Yi; Yuqi Zhou, Email labxz@hotmail.com; zhouyuqi@mail.sysu.edu.cnIntroduction: Increasing evidence suggests that seasonal changes can trigger the alternation of airway microbiome. However, the dynamics of the upper airway bacterial ecology of chronic obstructive pulmonary disease (COPD) patients across different seasons remains unclear.Methods: In this study, we present a 16S ribosomal RNA survey of the airway microbiome on 72 swab samples collected in different months (March, May, July, September, and November) in 2019 from 18 COPD patients and from six resampled patients in November in 2020.Results: Our study uncovered a dynamic airway microbiota where changes appeared to be associated with seasonal alternation in COPD patients. Twelve clusters of temporal patterns were displayed by differential and clustering analysis along the time course, systematically revealing distinct microbial taxa that prefer to grow in cool and warm seasons, respectively. Moreover, the upper airway microbiome composition was relatively stable in the same season in different years.Discussion: Given the tight association between airway microbiome and COPD disease progression, this study can provide useful information for clinically understanding the seasonal trend of disease phenotypes in COPD patients.Graphical Abstract: Keywords: chronic obstructive pulmonary disease, upper airway microbiome, seasonal variation

Xiaojing Yin,1,&ast; Yongkang Lai,1,2,&ast; Yiqi Du,1,&ast; Tinglin Zhang,3,&ast; Jie Gao,3 Zhaoshen Li1 1Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China; 2Department of Gastroenterology, Ganzhou People’s Hospital Affiliated to Nanchang University, Ganzhou, Jiangxi, 341000, People’s Republic of China; 3Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaoshen Li; Jie Gao, Email zhsl@vip.163.com; gaojiehighclea@smmu.edu.cnAbstract: Helicobacter pylori (H. pylori) is an infectious pathogen and the leading cause of gastrointestinal diseases, including gastric adenocarcinoma. Currently, bismuth quadruple therapy is the recommended first-line treatment, and it is reported to be highly effective, with > 90% eradication rates on a consistent basis. However, the overuse of antibiotics causes H. pylori to become increasingly resistant to antibiotics, making its eradication unlikely in the foreseeable future. Besides, the effect of antibiotic treatments on the gut microbiota also needs to be considered. Therefore, effective, selective, antibiotic-free antibacterial strategies are urgently required. Due to their unique physiochemical properties, such as the release of metal ions, the generation of reactive oxygen species, and photothermal/photodynamic effects, metal-based nanoparticles have attracted a great deal of interest. In this article, we review recent advances in the design, antimicrobial mechanisms and applications of metal-based nanoparticles for the eradication of H. pylori. Additionally, we discuss current challenges in this field and future perspectives that may be used in anti-H. pylori strategies.Keywords: H. pylori, antimicrobial applications, metal based nanoparticles, antibiotic-free, antimicrobial mechanisms

Xiaohui Wang,1,&ast; Bo Wu,2,&ast; Guogen Sun,3 Wenxi He,4 Jia Gao,1 Teng Huang,1 Jing Liu,1 Qing Zhou,1 Xiaoyu He,5 Shu Zhang,1 Zixiong Zhang,2 He Zhu1 1The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, People’s Republic of China; 2The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Selenium and Human Health Institute, Enshi, Hubei, People’s Republic of China; 3Hubei Selenium and Human Health Institute, Enshi, Hubei, People’s Republic of China; 4Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 5Branch of National Clinical Research Center for Metabolic Diseases, Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zixiong Zhang, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Selenium and Human Health Institute, No. 158, Muyang Avenue, Enshi, Hubei, People’s Republic of China, Email 596099670@qq.com He Zhu, The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei, People’s Republic of China, Email Zhuh@tjh.tjmu.edu.cnPurpose: Pancreatic adenocarcinoma (PAAD) presents an extremely high morbidity and mortality rate. Broccoli has excellent anti-cancer properties. However, the dosage and serious side effects still limit the application of broccoli and its derivatives for cancer therapy. Recently, extracellular vesicles (EVs) derived from plants are emerging as novel therapeutic agents. Thus, we conducted this study to determine the effectiveness of EVs isolated from Se-riched broccoli (Se-BDEVs) and conventional broccoli (cBDEVs) for the treatment of PAAD.Methods: In this study, we first isolated Se-BDEVs and cBDEVs by a differential centrifugation method, and characterized them by using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Then, miRNA-seq was combined with target genes prediction, and functional enrichment analysis to reveal the potential function of Se-BDEVs and cBDEVs. Finally, the functional verification was conducted in PANC-1 cells.Results: Se-BDEVs and cBDEVs exhibited similar characteristics in size and morphology. Subsequent miRNA-seq revealed the expression of miRNAs in Se-BDEVs and cBDEVs. Using a combination of miRNA target prediction and KEGG functional analysis, we found miRNAs in Se-BDEVs and cBDEVs may play an important role in treating pancreatic cancer. Indeed, our in vitro study showed that Se-BDEVs had greater anti-PAAD potency than cBDEVs due to increased bna-miR167a_R-2 (miR167a) expression. Transfection with miR167a mimics significantly induced apoptosis of PANC-1 cells. Mechanistically, further bioinformatics analysis showed that IRS1, which is involved in the PI3K-AKT pathway, is the key target gene of miR167a.Conclusion: This study highlights the role of miR167a transported by Se-BDEVs which could be a new tool for counteracting tumorigenesis.Graphical Abstract: Keywords: selenium, broccoli, extracellular vesicles, apoptosis, pancreatic cancer

Shenglan Ma,1– 3,&ast; Peijun Ju,4,&ast; Qingrong Xia,1– 3 Zhongde Pan,5 Jianliang Gao,1– 3 Loufeng Zhang,1– 3 Hua Gao,1– 3 Junwei Yan,1– 3 Jie Zhang,1– 3 Keming Wang,1– 3 Chao Li,1– 3 Wen Xie,1– 3,&ast; Cuizhen Zhu1– 3,&ast; 1Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Clinical Center for Psychiatry and Mental Health, Hefei Fourth People’s Hospital, Hefei, 230022, People’s Republic of China; 3Anhui Mental Health Center, Hefei, People’s Republic of China; 4Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Traditional Chinese Medicine for Mental Health, Shanghai, People’s Republic of China; 5Shanghai Key Laboratory of Forensic Medicine, Academy of Forensic Science, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Xie; Cuizhen Zhu, Affiliated Psychological Hospital of Anhui Medical University, No. 316 Huangshan Road, Shushan District, Hefei, Anhui, People’s Republic of China, Tel +86 13339102285 ; +86 13705535258, Fax +86 055163616000, Email xiewen0808@sina.com; zhucuizhen88@126.comPurpose: The study aims to clarify the negative psychological state and resilience impairments of schizophrenia (SCZ) with metabolic syndrome (MetS) while evaluating their potential as risk factors.Patients and Methods: We recruited 143 individuals and divided them into three groups. Participants were evaluated using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD)-24, Hamilton Anxiety Rating Scale (HAMA)-14, Automatic Thoughts Questionnaire (ATQ), Stigma of Mental Illness scale and Connor–Davidson Resilience Scale (CD-RISC). Serum biochemical parameters were measured by automatic biochemistry analyzer.Results: The score of ATQ was highest in the MetS group (F = 14.5, p < 0.001), and the total score of CD-RISC, subscale tenacity score and subscale strength score of CD-RISC were lowest in the MetS group (F = 8.54, p < 0.001; F = 5.79, p = 0.004; F = 10.9, p < 0.001). A stepwise regression analysis demonstrated that a negative correlation was observed among the ATQ with employment status, high-density lipoprotein (HDL-C), and CD-RISC (β=− 0.190, t=− 2.297, p = 0.023; β=− 0.278, t=− 3.437, p = 0.001; β=− 0.238, t=− 2.904, p = 0.004). A positive correlation was observed among the ATQ with waist, TG, WBC, and stigma (β=0.271, t = 3.340, p = 0.001; β=0.283, t = 3.509, p = 0.001; β=0.231, t = 2.815, p = 0.006; β=0.251, t=− 2.504, p = 0.014). The area under the receiver-operating characteristic curve analysis showed that among all independent predictors of ATQ, the TG, waist, HDL-C, CD-RISC, and stigma presented excellent specificity at 0.918, 0.852, 0.759, 0.633, and 0.605, respectively.Conclusion: Results suggested that the non-MetS and MetS groups had grievous sense of stigma, particularly, high degree of ATQ and resilience impairment was shown by the MetS group. The TG, waist, HDL-C of metabolic parameters, CD-RISC, and stigma presented excellent specificity to predict ATQ, and the waist showed excellent specificity to predict low resilience level.Keywords: years of education, negative symptoms, waist circumstance

Yefu Yu,1,&ast; Guier Yang,2,&ast; Yanan Wang,1 Faxiang Jin,1 Huiyu Wang,1 Zhongqiang Yu,3 Lanqing Li,4 Xiangcheng Li,4 Junshun Gao,4 Wenfang Xu1 1Department of Clinical Laboratory, Affiliated Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China; 2Emergency Ward of Affiliated Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China; 3Department of Imaging, Affiliated Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China; 4Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, 310016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenfang Xu, Department of Clinical Laboratory, Affiliated Hospital of Shaoxing University, 999 Zhongxing South Road, Yuecheng District, Shaoxing, People’s Republic of China, Tel +8613857589470, Email 0052019050@usx.edu.cn Junshun Gao, Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, 3 Qingchun East Road, Shangcheng District, Hangzhou, People’s Republic of China, Email gjs_919@zuaa.zju.edu.cnBackground: Actinomadura geliboluensis was first isolated in 2012 in Gelibolu, Canakkale, Turkey, and has not been reported to be isolated from humans until now. We have isolated it from the bronchoalveolar lavage fluid (BLF) of a patient with pneumonia and found its drug resistance. It is the first time that Actinomadura geliboluensis has been isolated from humans since its discovery and naming. This case may provide new ideas and methods for the clinical diagnosis and treatment of pulmonary actinomycosis.Case Description: The patient was a 75-year-old male who was hospitalized in a township hospital and failed to improve after penicillin treatment. After admission to our hospital, the patient was treated with piperacillin/tazobactam according to clinical guidelines for 14 days. Actinomadura geliboluensis was isolated from the patient’s BLF and was identified by 16S rRNA sequencing. This report shows the biological characteristics and in vitro drug susceptibility testing, as well as the genomics analysis based on next-generation sequencing (NGS). The results demonstrated that Actinomadura geliboluensis was easy to be mistakenly identified as Actinomyces dental caries by using the Merieux ANC identification card. Based on the MIC test, Actinomadura geliboluensis was susceptible to tetracyclines, quinolones and sulfonamides, but resistant to carbapenems, penicillins and cephalosporins. The K-B test results showed Actinomadura geliboluensis was highly sensitive to piperacillin/tazobactam. Genomic analysis based on NGS showed that the Actinomadura geliboluensis belongs to Planobispora rosea EF-Tu mutants conferring resistance to inhibitor GE2270A, AAC(3)-VIIa, vanRO, chrB, and mexY.Conclusion: Actinomycetes is generally sensitive to Penicillin but Actinomadura geliboluensis is not. In vitro drug susceptibility test is needed to support individualized drug use to avoid delay in the disease.Keywords: Actinomadura geliboluensis, pulmonary actinomycosis, antibiotic resistance, next generation sequencing, genomics

Lisha Zhang,1,&ast; Yuxiu Wang,2,&ast; Yaokun Ye,2 JunYin Gao,2 Fabei Zhu,1 Lingfeng Min2 1Department of Respiratory and Critical Care Medicine, The Yangzhou School of Clinical Medicine, Dalian Medical University, Yangzhou City, Jiangsu Province, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Clinical Medical College, Yangzhou University, Yangzhou City, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingfeng Min, Department of Respiratory and Critical Care Medicine, Clinical Medical College, Yangzhou University, Yangzhou City, Jiangsu Province, People’s Republic of China, Tel +86 19962595724, Email minlingfeng@126.comPurpose: This study aimed to evaluate the clinical outcomes of high-flow nasal cannula (HFNC) compared with conventional oxygen therapy (COT) in patients with hypercapnic chronic obstructive pulmonary disease (COPD), including arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of oxygen (PaO2), respiratory rate (RR), treatment failure, exacerbation rates, adverse events and comfort evaluation.Patients and Methods: PubMed, EMBASE and the Cochrane Library were retrieved from inception to September 30, 2022. Eligible trials were randomized controlled trials and crossover studies comparing HFNC and COT in hypercapnic COPD patients. Continuous variables were reported as mean and standard derivation and calculated by weighted mean differences (MD), while dichotomous variables were shown as frequency and proportion and calculated by odds ratio (OR), with the 95% confidence intervals (Cl). Statistical analysis was performed using RevMan 5.4 software.Results: Eight studies were included, five with acute hypercapnia and three with chronic hypercapnia. In acute hypercapnic COPD, short-term HFNC reduced PaCO2 (MD − 1.55, 95% CI: − 2.85 to − 0.25, I² = 0%, p < 0.05) and treatment failure (OR 0.54, 95% CI: 0.33 to 0.88, I² = 0%, p< 0.05), but there were no significant differences in PaO2 (MD − 0.36, 95% CI: − 2.23 to 1.52, I² = 45%, p=0.71) and RR (MD − 1.07, 95% CI: − 2.44 to 0.29, I² = 72%, p=0.12). In chronic hypercapnic COPD, HFNC may reduce COPD exacerbation rates, but there was no advantage in improving PaCO2 (MD − 1.21, 95% CI: − 3.81 to 1.39, I² = 0%, p=0.36) and PaO2 (MD 2.81, 95% CI: − 1.39 to 7.02, I² = 0%, p=0.19).Conclusion: Compared with COT, short-term HFNC reduced PaCO2 and the need for escalating respiratory support in acute hypercapnic COPD, whereas long-term HFNC reduced COPD exacerbations rates in chronic hypercapnia. HFNC has great potential for treating hypercapnic COPD.Keywords: nasal high-flow oxygen therapy, conventional oxygen therapy, hypercapnia, chronic obstructive pulmonary disease, meta-analysis