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Lingyu Lin,1,&ast; Zhuling Gao,2,&ast; Yanchun Peng,2 Sailan Li,1 Liangwan Chen,1,3 Yanjuan Lin1,2 1Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 2Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 3Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian Province, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanjuan Lin, Department of Nursing, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, People’s Republic of China, Tel +86059186218581, Fax +8683344034, Email fjxhyjl@163.com Liangwan Chen, Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, People’s Republic of China, Fax +86059183301393, Email fjxhlwc@163.comPurpose: Many shift nurses experience poor sleep quality, and the effect on nurses’ cognitive function remains unclear. The study aims to investigate sleep status and explore its association with cognitive function.Methods: This descriptive cross-sectional study was conducted in a tertiary care hospital in Fujian, China between March and September 2022. By convenience sampling method, 588 shift nurses participated in this study. The Pittsburgh Sleep Quality Index (PSQI) and Bergen Shift Work Sleep Questionnaire (BSWSQ) were used to assess sleep quality, while the Chinese version of Ascertain Dementia-8 (AD-8) was used to evaluate cognitive function. A PSQI score ≤ 7 is classified as good sleep quality, and a score > 7 indicates poor sleep quality. An AD-8 score≥ 2 is considered indicative of memory impairment. Multivariate logistic regression analysis was conducted to explore the association between sleep status and memory impairment.Results: A total of 310 (52.6%) participants presented poor sleep quality. Among them, 52.2% of participants had day shift-related sleep problems, 45.9% had evening shift-related sleep problems, 61.9% had night shift-related sleep problems, and 15.0% reported rest-day/vacation-related sleep problems. The prevalence of poor sleep quality and each shift-related sleep problem in the memory impairment group were higher than in the normal memory group (P< 0.05). Multivariate logistic regression analysis indicated that poor sleep quality (OR=2.073, 95% CI: 1.398~3.072), evening shift-related sleep problems (OR=1.707, 95% CI: 1.028~2.835), night shift-related sleep problems (OR=1.859, 95% CI:1.104~3.129), and rest-day/vacation-related sleep problems (OR=2.069, 95% CI:1.170~3.659) was significantly associated with memory impairment.Conclusion: This study highlights the prevalence of poor sleep quality among clinical nurses and identifies poor sleep quality and shift-related sleep problems (excluding day shift) as risk factors for memory impairment. Nurse managers should prioritize sleep quality and focus on cognitive function to enhance nurses’ occupational health.Keywords: nurse, sleep disturbance, memory, cognitive function

Shenghao Zhang,1,&ast; Zhejianyi Gao,2,&ast; Lina Feng,1,3 Mingquan Li1 1Department of Neurology, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin Province, 130021, People’s Republic of China; 2Department of Orthopaedics, Fushun Hospital of Chinese Medicine, Fushun, Liaoning Province, 113008, People’s Republic of China; 3Shandong Key Laboratory of TCM Multi-Targets Intervention and Disease Control, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong Province, 271000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lina Feng; Mingquan Li, Department of Neurology, the Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, 130117, People’s Republic of China, Tel +86-15543120222 ; +86-15948000577, Email Fenglina0001@163.com; Limingquan0001@126.comAbstract: Alzheimer’s disease (AD) is a fatal neurodegenerative disease characterized by its insidious onset and progressive development, making it the most common form of dementia. Despite its prevalence, the exact causes and mechanisms responsible for AD remain unclear. Recent studies have highlighted that inflammation in the central nervous system (CNS) plays a crucial role in both the initiation and progression of AD. Neuroinflammation, an immune response within the CNS triggered by glial cells in response to various stimuli, such as nerve injury, infection, toxins, or autoimmune reactions, has emerged as a significant factor alongside amyloid deposition and neurofibrillary tangles (NFTs) commonly associated with AD. This article aims to provide an overview of the most recent research regarding the involvement of neuroinflammation in AD, with a particular focus on elucidating the specific mechanisms involving microglia and astrocytes. By exploring these intricate processes, a new theoretical framework can be established to further probe the impact of neuroinflammation on the development and progression of AD. Through a deeper understanding of these underlying mechanisms, potential targets for therapeutic interventions and novel treatment strategies can be identified in the ongoing battle against AD.Keywords: alzheimer’s disease, neuroinflammation, microglia, astrocyte, review

Fanlingzi Shen,1,2,&ast; Yu Song,3,&ast; Yan Qiang,1,&ast; Xiangjin Gao,1 Siyuan Li,2 Rui Zhang,1 Zhongzhi Gao,1 Bin Li,1 Wencheng Jiang,4 Ruiping Wang1,2 1Clinical Research Center, Shanghai Skin Diseases Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Dermatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Traditional Chinese Medicine, Shanghai Skin Diseases Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wencheng Jiang, Department of Traditional Chinese Medicine, Shanghai Skin Diseases Hospital, Medical School, Tongji University, 1278 Baode Road, Shanghai, 200443, People’s Republic of China, Email drjiangwencheng@163.com Ruiping Wang, Clinical Research & Innovation Transformation Center, Shanghai Skin Diseases Hospital, Medical School, Tongji University, 1278 Baode Road, Shanghai, 200443, People’s Republic of China, Email w19830901@126.comPurpose: Tobacco smoking and alcohol drinking are positively associated with psoriasis prevalence and disease severity. Researches focusing on the influence of smoking and drinking on the treatment efficacy of psoriasis are still limited, especially their interaction effect. This study aims to explore the interactive effects of smoking and drinking on the treatment efficacy in psoriasis patients.Patients and Methods: From 2021 to 2022, we recruited 560 patients with psoriasis from Shanghai Skin Diseases Hospital. Demographic and clinical features as well as treatment efficacy were collected through questionnaire interview and physical examination during patient’s hospital visit at week 0, week 4 and week 8. Logistic regression model was used to explore the influence of smoking and drinking on the treatment efficacy in psoriasis patients, and multiplicative and additive interaction models were used to verify the interaction effect of smoking and drinking on the treatment efficacy.Results: The prevalence of smoking and drinking among psoriasis patients was respectively 43.8% and 25.4%, and 19.6% of them with both smoking and drinking. Logistic regression analysis showed that patients with smoking (OR=7.78, 95% CI: 5.26~11.49) and drinking (OR=5.21, 95% CI: 3.29~8.27) had higher risk of experiencing the failure to achieve PASI75 at week 8, even with the adjustment of confounders. Moreover, multiplicative as well as additive model showed that tobacco smoking interacted with alcohol drinking which influenced the treatment efficacy more severely (OR=12.74, 95% CI: 7.16~22.67). The proportion of PASI75 achievement in female patients (OR=19.54) and patients with methotrexate (OR=28.31) and biologics (OR=21.61) were more likely being affected by smoking and drinking.Conclusion: Tobacco smoking and alcohol drinking could increase the failure of PASI75 achievement in patients with psoriasis, individually and interactively. We recommend that dermatologists should educate patients to pay attention to the negative effects of smoking and drinking, encourage them to quit, and thus improve the treatment efficacy.Keywords: psoriasis, tobacco smoking, alcohol drinking, interaction, additive model, multiplicative model

Zhaorong Gao,1– 3 Zhen Guo,1– 3 Yongbo Song,1– 3 Xiujing Shi,1– 3 Yingzuo Zhao,1– 3 Conghui Liu1– 3 1Qingdao Eye Hospital of Shandong First Medical University, Eye Institute of Shandong First Medical University, Qingdao, People’s Republic of China; 2State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, People’s Republic of China; 3School of Ophthalmology, Shandong First Medical University, Qingdao, People’s Republic of ChinaCorrespondence: Zhen Guo, Qingdao Eye Hospital of Shandong First Medical University, Eye Institute of Shandong First Medical University, 5 Yanerdao Road, Qingdao, Shandong, 266071, People’s Republic of China, Fax +86532 8761 0087, Email guoz@sdfmu.edu.cnPurpose: With girls typically exhibiting higher rates of myopia than boys, however, the mechanisms behind this gender difference remain unclear. This study aims to investigate the gender disparities in the relationship between myopia, sleep duration, physical activity, and BMI.Patients and Methods: A total of 3138 primary and secondary school students were included. Mplus 8.3 was used to perform the multiple mediation analysis.Results: Sleep duration was indicated to directly affect myopia (β=0.273, 95% CI=0.184− 0.356) and through physical activity, BMI, physical activity and BMI three significantly mediation pathways, respectively. In terms of gender, the mediating direct effect of sleep duration on myopia of boys was 66.96%, which is much higher than that of girls’ 50.91%. And the mediating indirect effect of sleep duration on myopia through physical activity and BMI are 32.65% and 12.10% respectively among girls, both of which are significantly higher than that of boys.Conclusion: The study found that there are significant differences in the impact of sleep duration on myopia in children and adolescents of different genders. In this regard, while paying attention to the sleep duration of children and adolescents, special attention should also be paid to the indirect impact of girls’ physical activity and BMI on myopia, and targeted measures should be formulated according to children of different genders to effectively protect the eye health of children and adolescents.Keywords: myopia, children and adolescents, sleep duration, physical activity, BMI, gender difference

Jian Li,1,&ast; Li Liu,2,&ast; Zhiyun Gao,1 Xia Chuai,3 Xiaokun Liu,4 Xiaobo Zhang,2 Xinyu Zhang,2 Xiaoqing Su,2 Qian Xu,2 Zhuojun Deng2 1Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega Science, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of China; 4Department of Ophthalmology, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuojun Deng, Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email dengzhuojun@126.com; 37700469@hebmu.edu.cnPurpose: The incidence of visceral leishmaniasis (VL), a global infectious disease, has been on the rise in China’s Hebei province. When patients achieve clinical cure, they often do not reach an etiological cure, which may lead to recurrence of the disease. Here, we report a case of visceral leishmaniasis with a negative blood smear and bone marrow cytology.Patients and Methods: A 65-year-old man and bronchoalveolar lavage fluid mNGS.Results: A 65-year-old man developed a chronic fever, anorexia, splenomegaly, and pancytopenia. The blood metagenomic second-generation sequencing (mNGS) revealed Leishmania sequence readings, which led to the diagnosis of VL. After sodium antimony gluconate treatment, the blood smear and bone marrow cytology revealed no Leishmania bodies. However, pancytopenia and respiratory failure did not fully subside, and cardiotoxic damage emerged. The bronchoalveolar lavage fluid (BALF) mNGS was performed to detect the pathogen. Through BALF mNGS, Leishmania sequence was still detectable. Therefore, after the ECG returned to normal, antimony sodium gluconate was administered as a next course of treatment.Conclusion: BALF mNGS may assist in evaluating the therapeutic efficacy of VL with respiratory failure, especially in patients with negative blood and bone marrow cytology.Plain Language Summary: Accurate detection of visceral leishmaniasis is essential for clinical diagnosis.It is uncommon to use alveolar lavage fluid mNGS in etiological diagnosis.Patient with negative bone marrow cytology may refer to alveolar lavage fluid mNGS. Keywords: visceral leishmaniasis, metagenomic second-generation sequencing, bronchoalveolar lavage fluid, parasite diseases, case report

Wenguang Lai,1,&ast; Xiaoli Zhao,2,&ast; Zhiyong Gao,1 Haozhang Huang,3,4 Donghui Huang,1 Yang Zhou,3,4 Guoxiao Liang,3,4 Shiqun Chen,3,4 Jin Liu,3 Yong Liu3 1Department of Pharmacy, Heyuan People’s Hospital; Guangdong Provincial People’s Hospital, Heyuan Hospital, Heyuan, 517001, People’s Republic of China; 2Department of Cardiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 3Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Liu; Jin Liu, Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China, Tel +86 02083827812-10528, Fax +86 02083851483, Email liuyong@gdph.org.cn; ljaw397017568@163.comPurpose: Heart failure with preserved ejection fraction (HFpEF) is inherently a complex inflammatory syndrome, and heightened inflammation is strongly associated with an increased risk of death. However, the association of systemic inflammation levels with total and cardiovascular death among patients with HFpEF remains unknown. We aimed to investigate the prognostic impact of systemic inflammation on all-cause and cardiovascular death among patients with HFpEF.Patients and Methods: Patients with HFpEF were included in this study. Systemic inflammation response index (SIRI) is defined as the multiplication of neutrophil and monocyte divided by lymphocyte count, and patients were divided into four groups based on SIRI quartiles. Cox regression models and competing risk models were used to examine the relationships between SIRI and total and cardiovascular‑specific mortality, respectively.Results: 9,986 patients with HFpEF were included in five tertiary hospitals. During a median follow-up period of 4.4 years, a total of 2004 patients died, of which 965 were cardiovascular deaths. After fully adjusting for confounders, elevated SIRI level was significantly related to the increased risk of all-cause death (Q2, Q3, Q4: adjusted hazard ratio (aHR) [95 confidence interval (CI)%] =1.17[1.01– 1.35], 1.31[1.13– 1.52], 1.51[1.30– 1.76], respectively; P for trend < 0.001). The elevated quartile of SIRI showed higher risks of cardiovascular death, but there was no statistically significant increased risk of cardiovascular death across the lower SIRI quartile (model 3: Q2, Q3, Q4: aHR [95CI%] =1.22[0.99– 1.51], 1.50[1.20– 1.86], 1.73[1.37– 2.18], respectively; P for trend < 0.001).Conclusion: Elevated systemic inflammation level on admission was correlated with an increased risk of all-cause and cardiovascular death among patients with HFpEF. The SIRI may serve as a promising marker of risk stratification for patients with HFpEF.Keywords: heart failure with preserved ejection fraction, systemic inflammatory response index, all-cause death, cardiovascular death

Juan Li,1,&ast; Ziqing Gao,1,&ast; Ning Li,1 Ling Yao,1 Chao Liu,1 Che Xu,1 Xiaohui Ren,1 Aiqin Wang,1 Siqi Gao,2 Miao Wang,2 Xiang Gao,2 Kun Li,3 Jianfeng Wang1 1Department of Ophthalmology, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233004, People’s Republic of China; 2School of Clinical Medicine, Bengbu Medical University, Bengbu, Anhui, 233004, People’s Republic of China; 3School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, 233100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kun Li; Jianfeng Wang, Email liangliang2419@126.com; wangjianfeng1969@163.comBackground: Drug therapy for eye diseases has been limited by multiple protective mechanisms of the eye, which can be improved using well-designed drug delivery systems. Mesoporous silica nanoparticles (MSNs) had been used in many studies as carriers of therapeutic agents for ocular diseases treatment. However, no studies have focused on ocular biosafety. Considering that MSNs containing tetrasulfur bonds have unique advantages and have drawn increasing attention in drug delivery systems, it is necessary to explore the ocular biosafety of tetrasulfur bonds before their widespread application as ophthalmic drug carriers.Methods: In this study, hollow mesoporous silica nanoparticles (HMSNs) with different tetrasulfur bond contents were prepared and characterized. The ocular biosafety of HMSN-E was evaluated in vitro on the three selected ocular cell lines, including corneal epithelial cells, lens epithelial cells and retinal endothelial cells (HREC), and in vivo by using topical eye drops and intravitreal injections.Results: In cellular experiments, HMSNs caused obvious S content-dependent cytotoxic effect. HMSNs with the highest tetrasulfur bond content (HMSN-E), showed the highest cytotoxicity among all the HMSNs, and HREC was the most vulnerable cell to HMSN-E. It was shown that HMSN-E could react with intracellular GSH to generate H2S and decrease intracellular GSH concentration. Treatment of HREC with HMSN-E increased intracellular ROS, decreased mitochondrial membrane potential, and induced cell cycle arrest at the G1/S checkpoint, finally caused apoptosis and necrosis of HREC. Topical eye drops of HMSN-E could cause corneal damage. The intravitreal injection of HMSN-E could induce inflammation in the vitreum and ganglion cell layers, resulting in vitreous opacities and retinal abnormalities.Conclusion: The incorporation of tetrasulfur bonds into HMSN can have toxic effects on ocular tissues. Therefore, when mesoporous silica nanocarriers are designed for ophthalmic pharmaceuticals, the ocular toxicity of the tetrasulfur bonds should be considered.Keywords: ophthalmic safety, hollow mesoporous silica nanoparticles, ophthalmic drug delivery, tetrasulfur bond

Jingliang Wu,1,&ast; Qiao Lu,1,2,&ast; Jialin Zhao,3,&ast; Wendi Wu,3 Zhihua Wang,1 Guohua Yu,4 Guixiang Tian,2 Zhiqin Gao,2 Qing Wang5 1School of Medicine, Weifang University of Science and Technology, Weifang, 262700, People’s Republic of China; 2School of Life Science and Technology, Shandong Second Medical University, Weifang, 261053, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, 261053, People’s Republic of China; 4Department of Oncology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China; 5Department of Stomatology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Wang, Department of Stomatology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China, Tel +86 158 6362 6389, Email wfwq8899@163.comPurpose: Breast cancer is a prevalent malignancy among women worldwide, and malignancy is closely linked to the tumor microenvironment (TME). Here, we prepared mixed nano-sized formulations composed of pH-sensitive liposomes (Ber/Ru486@CLPs) and small-sized nano-micelles (Dox@CLGs). These liposomes and nano-micelles were modified by chondroitin sulfate (CS) to selectively target breast cancer cells.Methods: Ber/Ru486@CLPs and Dox@CLGs were prepared by thin-film dispersion and ethanol injection, respectively. To mimic actual TME, the in vitro “condition medium of fibroblasts + MCF-7” cell model and in vivo “ 4T1/NIH-3T3” co-implantation mice model were established to evaluate the anti-tumor effect of drugs.Results: The physicochemical properties showed that Dox@CLGs and Ber/Ru486@CLPs were 28 nm and 100 nm in particle size, respectively. In vitro experiments showed that the mixed formulations significantly improved drug uptake and inhibited cell proliferation and migration. The in vivo anti-tumor studies further confirmed the enhanced anti-tumor capabilities of Dox@CLGs + Ber/Ru486@CLPs, including smaller tumor volumes, weak collagen deposition, and low expression levels of α-SMA and CD31 proteins, leading to a superior anti-tumor effect.Conclusion: In brief, this combination therapy based on Dox@CLGs and Ber/Ru486@CLPs could effectively inhibit tumor development, which provides a promising approach for the treatment of breast cancer.Keywords: drug delivery, cancer-associated fibroblasts, glucocorticoids, combination therapy

Yiyu Chen,1 Chuxuan Fang,1 Jun Luo,1 Xueling Pan,2 Zongyan Gao,3 Shuangyi Tang,1 Meng Li4– 6 1Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Newborn ICU, Guigang Maternal and Child Health Care Hospital, Guigang City, Guangxi, People’s Republic of China; 3Newborn ICU, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 5Key Laboratory of Clinical Laboratory Medicine, Guangxi Department of Education, Nanning, Guangxi, People’s Republic of China; 6Key Laboratory of Fungi and Mycosis Research and Prevention, Guangxi Health Commission, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Meng Li, Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Tel/Fax +8613367809642, Email gxmulimeng@foxmail.comAbstract: The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasing in recent years. Chinese Infectious Disease Surveillance of Pediatrics (ISPED) showed that in 2022, its resistance rate to meropenem was 18.5%. However, there is limited data available on the treatment of CRKP infection in neonates. In this study, we present a case involving a premature infant infected with OXA-48-producing Klebsiella pneumoniae. The combined susceptibility test revealed a significant synergistic effect between ceftazidime–avibactam(CAZ-AVI), and aztreonam(ATM). The infection was successfully treated with a combination of CAZ-AVI, ATM, and fosfomycin. This case represents the first reported instance of sepsis in a premature infant caused by OXA-48-producing Klebsiella pneumoniae in China. The objective of our study is to evaluate the effectiveness and safety of combination therapy in treating CRKP infections in premature infants. We hope that the findings of this study will provide valuable insights for clinicians in their treatment approach.Keywords: OXA-48, Klebsiella pneumoniae, premature infant, ceftazidime–avibactam, aztreonam

Yang Li,1,&ast; Yuling Sun,1,&ast; Ji Wu,1,&ast; Zhongya Gao,1 Youcai Qiu,1 Lin Han,2 Xuhua Lu1 1Department of Orthopaedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Orthopaedics, Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuhua Lu, Department of Orthopaedics, Shanghai Changzheng Hospital, Naval Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86-21-81885793, Email xuhualu415@163.com Lin Han, Department of Orthopaedics, Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China, Email hanlin1018@163.comBackground and Aim: Cervical hyperextension injury is very frequent with anterior longitudinal ligament (ALL) injury, and the ligament damage has a remarkable effect on whether and what type of operation should be performed. This study aims to establish a new scoring system for the accurate diagnosis of ALL damage.Methods: The imaging data of the consecutive patients was measured and scored by four radiologists. Intraoperative exploration was performed by three surgeons. The crude and adjusted odds ratios (cOR and aOR) and receiver operating characteristic curve (ROC) were constructed to assess the diagnostic accuracy of the scoring system.Results: A total of 255 patients with cervical spine trauma were included in this study. There was no statistical difference in the relationship between demographics and ALL injuries (P > 0.05). Thickness of prevertebral soft tissue (aOR = 11.922, P = 0.004), intervertebral disk angle (aOR = 13.21, P = 0.002), avulsion fracture of the anterior edge of the vertebral body (aOR = 13.844, P = 0.029), ALL disrupted in T1-weighted sequence (aOR = 18.349, P < 0.001), and high signal area in T2-weighted sequence (aOR = 20.898, P = 0.002) had significantly higher diagnostic accuracy. The scoring system’s sensitivity and specificity were 94.0% and 88.1%, respectively, and the accuracy was 90.8%.Conclusion: The study established a new scoring system for ALL injuries based on the analysis of a series of clinical data and statistics. A total of five scoring items, a total score of 7 points, and an ALL injury may be diagnosed when the score is not less than 3 points. This scoring system enables an efficient and accurate diagnosis of all injuries.Keywords: cervical hyperextension injury, anterior longitudinal ligament injury, cervical spine trauma, scoring system

Chenjun Huang,1,&ast; Xiao Xiao,1,&ast; Lin Tong,2,&ast; Zhiyuan Gao,1 Jun Ji,2 Lin Zhou,3 Ya Li,4 Lijuan Liu,5 Huijuan Feng,5 Meng Fang,2 Chunfang Gao1,2 1Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 2Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China; 3Department of Laboratory Medicine, Shanghai Changzheng Hospital, Shanghai, 200003, People’s Republic of China; 4Department of Laboratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 5Department of Laboratory Medicine, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunfang Gao, Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China, Tel +86-21-65161782-1210, Email gaocf1115@163.com; gaocf1115@shutcm.edu.cnPurpose: Early detection of hepatocellular carcinoma (HCC) through surveillance could reduce this cancer-associated mortality. We aimed to develop and validate algorithms using panel serum biomarkers to identify HCC in a real-world multi-center study in China.Patients and Methods: A total of 10,359 eligible subjects, including HCCs and benign liver diseases (BLDs), were recruited from six Chinese medical centers. The three nomograms were built using logistic regression and their sensitivities and specificities were carefully assessed in training and validation cohorts. HCC patients after surgical resection were followed to determine the prognostic values of these algorithms. Prospective surveillance performance was assessed in a cohort of chronic hepatitis B patients during 144 weeks follow-up.Results: Independent risk factors such as alpha-fetoprotein (AFP), lens cuinaris agglutinin-reactive fraction of AFP (AFP-L3), des-gamma-carboxy prothrombin (DCP), albumin (ALB), and total bilirubin (TBIL) obtained from train cohort were used to construct three nomograms (LAD, C-GALAD, and TAGALAD) using logistic regression. In the training and two validation cohorts, their AUCs were all over 0.900, and the higher AUCs appeared in TAGALAD and C-GALAD. Furthermore, the three nomograms could effectively stratify HCC into two groups with different survival and recurrence outcomes in follow-up validation. Notably, TAGALAD could predict HCC up to 48 weeks (AUC: 0.984) and 24 weeks (AUC: 0.900) before clinical diagnosis.Conclusion: The proposed nomograms generated from real-world Chinese populations are effective and easy-to use for HCC surveillance, diagnosis, as well as prognostic evaluation in various clinical scenarios based on data feasibility.Keywords: hepatocellular carcinoma, real-world data, diagnostic, prognosis, algorithm

Yilan Hu,1,2 Jiaqi Bao,1,2 Zhicheng Gao,1,2 Lifang Ye,2 Lihong Wang1,2 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, People’s Republic of ChinaCorrespondence: Lihong Wang, Heart Center, Department of Cardiovascular Medicine, Zhejiang, Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, People’s Republic of China, Email wanglhnew@126.comAbstract: Obesity is becoming increasingly prevalent in China and worldwide and is closely related to the development of hypertension. The pathophysiology of obesity-associated hypertension is complex, including an overactive sympathetic nervous system (SNS), activation of the renin–angiotensin–aldosterone system (RAAS), insulin resistance, hyperleptinemia, renal dysfunction, inflammatory responses, and endothelial function, which complicates treatment. Sodium–glucose cotransporter protein 2 (SGLT-2) inhibitors, novel hypoglycemic agents, have been shown to reduce body weight and blood pressure and may serve as potential novel agents for the treatment of obesity-associated hypertension. This review discusses the beneficial mechanisms of SGLT-2 inhibitors for the treatment of obesity-associated hypertension. SGLT-2 inhibitors can inhibit SNS activity, reduce RAAS activation, ameliorate insulin resistance, reduce leptin secretion, improve renal function, and inhibit inflammatory responses. SGLT-2 inhibitors can, therefore, simultaneously target multiple mechanisms of obesity-associated hypertension and may serve as an effective treatment for obesity-associated hypertension.Keywords: sodium-glucose cotransporter protein 2 inhibitors, obesity-associated hypertension, metabolism, neuro-humoral regulation, inflammation

Zhicheng Gao,1,2,&ast; Jiaqi Bao,1,2,&ast; Liuyang Wu,2 Kaiyu Shen,1 Qiqi Yan,2 Lifang Ye,2 Lihong Wang2 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihong Wang, Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 85894275, Email wanglhnew@126.comPurpose: Lymphocyte to C-reactive protein ratio (LCR) is a recognized systemic inflammatory marker and novel prognostic indicator for several cancers. This study investigated the relationship between preoperative LCR and new-onset atrial fibrillation (NOAF) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).Patients and Methods: Patients with AMI (n=662) with no history of atrial fibrillation (AF) were enrolled and classified into NOAF and non-NOAF groups based on the occurrence of postoperative NOAF during hospitalization. Logistic regression models were used to analyze NOAF risk factors and to assess the association between preoperative LCR and NOAF incidence. We constructed a new nomogram from the selected NOAF risk factors, and tested its predictive performance, degree of calibration, and clinical utility using receiver operating characteristic and calibration curves, decision curve analysis, and clinical impact curves.Results: Overall, 84 (12.7%) patients developed NOAF during hospitalization. The LCR was significantly lower in the NOAF group. Preoperative LCR accurately predicted NOAF after AMI and was correlated with increased NOAF risk. Age, body mass index, diabetes, serum albumin levels, uric acid levels, left atrium (LA) diameter, left ventricular ejection fraction, left circumflex artery stenosis > 50%, and Killip class II status were independent predictors of NOAF after AMI. In addition, a new nomogram combined with LCR was constructed to stratify the risk of NOAF in patients with AMI. The performance of the new nomogram was satisfactory, as shown by the receiver operating characteristic curve, calibration curve, decision curve analysis and clinical impact curve.Conclusion: Preoperative LCR was an independent predictor of NOAF in patients with AMI after PCI. The novel nomogram combined with LCR could rapidly and individually identify and treat patients at a high risk of NOAF.Keywords: C-reactive protein, acute myocardial infarction, atrial fibrillation, nomogram, left ventricular ejection fraction

Xi Wang,1,&ast; Jiyu Xu,2,&ast; Guodong Feng,1 Zhiqiang Gao,1 Wei Sun2 1Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Institute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqiang Gao; Wei Sun, Email gzqent@163.com; sunwei@ibms.pumc.edu.cnBackground: Proteins found in middle ear effusion play crucial roles in the physiological and pathological processes of otitis media with effusion (OME), influencing the etiology and clinical characteristics of this disease. The qualitative and quantitative composition of these proteins depending on the underlying pathogenesis of middle ear effusion. Understanding their physiological and pathological functions is of great importance.Methods: We collected samples from 19 volunteers diagnosed with OME. After offline separation using high-pH reversed-phase liquid chromatography (RPLC), the pooled sample was subjected to LC-MS/MS analysis to obtain a comprehensive profile of the OME proteome. Functional analysis was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Ingenuity Pathway Analysis (IPA) annotations. Data-independent acquisition (DIA) technology was utilized to analyze samples and fix whether the OME proteome could replicate the pathophysiological features associated with this disease. We conducted a differential proteomic analysis between patients with simple OME and patients who had received radiotherapy. The radiotherapy-reduced group was further divided into two subgroups: nasopharyngeal carcinoma (NPC) and other types of carcinoma. Parallel reaction monitoring (PRM) technology was used for validation of 36 differentially expressed proteins (DEPs).Results: A number of 732 proteins were identified in the OME proteome database. Among them, 527 proteins were quantified using peak intensity-based semi-quantification (iBAQ), covering a wide dynamic range of approximately 8 orders of magnitude. Based on the functional analysis, we proposed a hypothetical mechanism of OME.Conclusion: This study managed to put up an inclusive analysis of the OME proteome, establishing the first human OME proteome database. We focused on differential proteomic analysis among different groups to gain a more comprehensive concept of the OME proteome and search for meaningful biomarkers.Keywords: otitis media with effusion, proteome, function annotation, radiotherapy-reduced OME, nasopharyngeal carcinoma

Xufeng Yu,1,&ast; Zhan Gao,1,&ast; Mingzhou Gao,2 Mingqi Qiao1 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 2Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingzhou Gao; Mingqi Qiao, Email gmingzhou@163.com; qmingqi@163.comBackground: GABA-A receptors are the primary mediators of brain inhibitory neurotransmission. In the past years, many studies focused on this channel to decipher the pathogenesis of related diseases but lacked bibliometric analysis research. This study aims to explore the research status and identify the research trends of GABA-A receptor channels.Methods: Publications related to GABA-A receptor channels were retrieved from the Web of Science Core Collection from 2012 to 2022. After screening, the VOSviewer 1.6.18 and Citespace 5.8 R3 were used for bibliometric analysis from journals, countries, institutions, authors, co-cited references and keywords.Results: We included 12,124 publications in the field of GABA-A receptor channels for analysis. The data shows that although there was a slight decrease in annual publications from 2012 to 2021, it remained at a relatively high level. Most publications were in the domain of neuroscience. Additionally, the United States was the most prolific country, followed by China. Univ Toronto was the most productive institution, and James M Cook led essential findings in this field. Furthermore, brain activation, GABAAR subunits expression, modulation mechanism in pain and anxiety behaviors and GABA and dopamine were paid attention to by researchers. And top research frontiers were molecular docking, autoimmune encephalitic series, obesity, sex difference, diagnosis and management, EEG and KCC2.Conclusion: Taken together, academic attention on GABA-A receptor channels was never neglected since 2012. Our analysis identified key information, such as core countries, institutions and authors in this field. Molecular docking, autoimmune encephalitic series, obesity, sex difference, diagnosis and management, EEG and KCC2 will be the future research direction.Keywords: GABA-A receptor, GABA, visual analysis, trends, CiteSpace, VOSviewer

Zheng Gao,1,&ast; Yanyu Yue,2,&ast; Youjia Zhang,1 Wentao Jiang,1 Yepeng Zhang,1 Feng Ran,1 Xiaoqiang Li1 1Department of Vascular Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 2100082, People’s Republic of China; 2Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Ran; Xiaoqiang Li, Email ranfeng_nju@126.com; lixiaoqiang@mju-edu.cnPurpose: To study and compare the clinical outcomes of endovascular therapy with those of hybrid surgery in the treatment of Trans-Atlantic Inter-Society Consensus II (TASC II) D aortoiliac occlusive disease (AIOD).Patients and Methods: Patients with TASC II D-type AIOD who underwent their first surgical treatment at our hospital between March 2018 and March 2021 were enrolled and followed up to evaluate the improvement in symptoms, complications, and primary patency. The Kaplan–Meier method was used to compare the differences in primary patency between the treatment groups.Results: In total, 132 of 139 enrolled patients (94.96%) achieved technical success following treatment. The perioperative mortality rate was 1.44% (2/139), and postoperative complications occurred in two patients. Among the patients who successfully underwent surgery, 120 underwent endovascular treatment (110 patients with stenting and 10 patients with thrombolysis before stenting), 10 underwent hybrid surgery, and 2 underwent open surgery. The follow-up data were compared between the endovascular and hybrid groups. At the end of the follow-up period, the patency rates in the hybrid and endovascular groups were 100% and 89.17% (107/120), respectively. The endovascular group achieved primary patency rates of 94.12%, 92.44%, and 89.08% at 6, 12, and 24 months postoperatively, respectively, whereas the primary patency rate remained at 100% in the hybrid group, with no significant variation between the endovascular and hybrid groups (P = 0.289). The endovascular group was further divided into a stent subgroup (110 patients) and a thrombolysis/stent subgroup (10 patients), and no prominent variation was noted in the primary patency between the two subgroups (P = 0.276).Conclusion: Although open surgery is the gold standard treatment for TASC II D-type AIOD, endovascular and hybrid treatments are feasible and effective. Both methods showed good technical success and early to midterm primary patency rates.Keywords: aortoiliac occlusive disease, endovascular stenting, angioplasty, thrombolysis, hybrid surgery

Peigen Wu,1– 3 Churui Chang,3 Guanglin Zhu,4 Lixiang Zhai,5 Xu Zhang,3 Qiuchan Huan,1,3 Zhengxian Gao,1,3 Huan Deng,2 Yue Liang,1 Haitao Xiao2,3 1Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China; 3School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guizhou, People’s Republic of China; 4Traditional Chinese Medicine Hospital of Qijiang, Chongqing, People’s Republic of China; 5School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong Special Administrative Region, People’s Republic of ChinaCorrespondence: Haitao Xiao, School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China, Email xhaitao@szu.edu.cn Yue Liang, Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China, Email bmqueen@163.comPurpose: To explore the potential mechanism of glycosidic fraction of Picrorhiza scrophulariiflora Pennell (GPS) extract for the treatment of colitis using UPLC-QTOF-MS analysis, network pharmacology and experimental research.Methods: The active components of GPS extract were identified by UPLC-QTOF-MS analysis and extracted their targets from the databases, which was used for network pharmacology analysis. Kyoto Encyclopedia of genes and genomes (KEGG) pathway analysis was performed to discover potential therapeutic mechanisms, and the network pharmacology results were then validated by in vivo and in vitro experiments.Results: The results showed that GPS extract significantly alleviated the clinical signs of colitis, including body weight, disease activity index, colon shortening, and colon tissue damage, and inhibited the transcription and production of colonic IL-1β and IL-6 in DSS-induced colitis mice. In vitro, GPS extract also significantly suppressed nitric oxide (NO) production, iNOS expression, IL-1β and IL-6 transcription of LPS-activated RAW 264.7 cells. Network pharmacology integrated with experimental validation identified that GPS extract significantly suppressed Akt, p38, ERK, and JNK phosphorylation in vivo and in vitro, and luteolin, apocynin, caffeic acid, caffeic acid methyl ester, luteoloside, picroside II, aucubin, cinnamic acid, vanillic acid, and sweroside were the main components responsible for the anti-inflammatory effect of GPS. These findings demonstrate that the potential anti-inflammatory effect of GPS extract against colitis is achieved through suppressing PI3K/Akt and MAPK pathways, and that the abovementioned active components mainly exerted its anti-inflammatory effect.Conclusion: The therapeutic effect of GPS extract on colitis is related to PI3K/Akt and MAPK pathways, which is a promising remedy for colitis therapy.Graphical Abstract: Keywords: Picrorhiza scrophulariiflora, colitis, bioactive compounds, molecular mechanism, network pharmacology

Ugochukwu Odimba,1 Ambikaipakan Senthilselvan,2 Jamie Farrell,1,3 Zhiwei Gao1 1Clinical Epidemiology Unit, Division of Community Health and Humanities, Faculty of Medicine, Memorial University, St. John’s, Newfoundland and Labrador, Canada; 2School of Public Health, University of Alberta, Edmonton, Alberta, Canada; 3Faculty of Medicine, Health Science Centre (Respirology Department), Memorial University, St John’s, Newfoundland and Labrador, CanadaCorrespondence: Zhiwei Gao, Clinical Epidemiology Unit, Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, A1B 3V6, Canada, Tel +17098646523, Email zhiwei.gao@med.mun.caPurpose: Asthma is a chronic heterogeneous respiratory disease resulting from a complex interplay between genetic variations and environmental exposures. There are sex disparities in the prevalence and severity of asthma in males and females. Asthma prevalence is higher in males during childhood but increases in females in adulthood. The mechanisms underlying these sex differences are not well understood; nevertheless, genetic variations, hormonal changes, and environmental influences are thought to play important roles. This study aimed to identify sex-specific genetic variants associated with asthma using CLSA genomic and questionnaire data.Methods: First, we conducted a genome-wide SNP-by-sex interaction analysis on 23,323 individuals, examining 416,562 single nucleotide polymorphisms (SNPs) after quality control, followed by sex-stratified survey logistic regression of SNPs with interaction p-value less than 10® 5.Results: Out of the 49 SNPs with interaction p-value less than 10− 5, a sex-stratified survey logistic regression showed that five male-specific SNPs (rs6701638, rs17071077, rs254804, rs6013213, and rs2968822) in/near KIF26B, NMBR, PEPD, RTN4, and NFATC2 loci, and three female-specific SNPs (rs2968801, rs2864052, and rs9525931) in/near RTN4, and SERP2 loci were significantly associated with asthma after Bonferroni correction. An SNP (rs36213) in the EPHB1 gene was significantly associated with an increased risk of asthma in males [OR=1.35, 95% CI (1.14, 1.60)] but with a reduced risk of asthma in females [OR=0.84, 95% CI (0.76, 0.92)] after Bonferroni correction.Conclusion: We discovered novel sex-specific genetic markers in/near the KIF26B, RTN4, EPHB1, NMBR, SERP2, PEPD, and NFATC2 genes that could potentially shed light on the sex differences in asthma susceptibility in males and females. Future mechanistic studies are required to understand better the underlying sex-related pathways of the identified loci in asthma development.Keywords: asthma, single nucleotide polymorphism, sex-specific, CLSA

Yu Jiang,1,&ast; Xisheng Lin,2,&ast; Yilin Wang,1 Jia Li,1,3 Guoqi Wang,4 Yutong Meng,5 Ming Li,1,3 Yi Li,1,3 Yan Luo,1,3 Zefu Gao,1 Pengbin Yin,1,3 Licheng Zhang,1,3 Houchen Lyu,1,3 Peifu Tang1,3 1Department of Orthopedics, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Rehabilitation, the Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Beijing, People’s Republic of China; 4Department of Pediatrics, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 5Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houchen Lyu; Peifu Tang, Department of Orthopedics, Chinese PLA General Hospital, No. 28, Fuxing Road, Beijing, 100853, People’s Republic of China, Tel +86-13501149301, Email houchenlyu@301hospital.com.cn; pftang301@126.comPurpose: To evaluate the impact of preoperative anemia on postoperative complications after hip fracture surgery.Patients and Methods: We conducted a retrospective study including hip fracture patients at a teaching hospital between 2005 and 2022. We defined preoperative anemia as the last hemoglobin measurement level before surgery < 130 g/L for men and < 120 g/L for women. The primary outcome was a composite of in-hospital major complications, including pneumonia, respiratory failure, gastrointestinal bleeding, urinary tract infection, incision infection, deep venous thrombosis, pulmonary embolism, angina pectoris, arrhythmia, myocardial infarction, heart failure, stroke, and death. Secondary outcomes were cardiovascular events, infection, pneumonia, and death. We used multivariate negative binomial or logistic regression to evaluate the impact of anemia and its severity, categorized as mild (90– 130 g/L for men, 90– 120 g/L for women) or moderate-to-severe (< 90 g/L for both) anemia on outcomes.Results: Of the 3540 included patients, 1960 had preoperative anemia. 188 anemic patients experienced 324 major complications, while 63 non-anemic patients had 94 major complications. The risk of major complications was 165.3 (95% CI, 149.5– 182.4) and 59.5 (95% CI, 48.9– 72.3) per 1000 persons in anemic and non-anemic patients, respectively. Anemic patients were more likely to have major complications than non-anemic patients (adjusted incidence rate ratio (aIRR), 1.87; 95% CI, 1.30– 2.72), which was consistent in mild (aIRR, 1.77; 95% CI, 1.22– 2.59) and moderate-to-severe (aIRR, 2.97; 95% CI, 1.65– 5.38) anemia. Preoperative anemia also increased the risk of cardiovascular events (aIRR, 1.96; 95% CI, 1.29– 3.01), infection (aIRR, 1.68; 95% CI, 1.01– 2.86), pneumonia (adjusted odds ratio (aOR), 1.91; 95% CI, 1.06– 3.57), and death (aOR, 3.17; 95% CI, 1.06– 11.89).Conclusion: Our findings suggest that even mild preoperative anemia is associated with major postoperative complications in hip fracture patients. This finding highlights considering preoperative anemia as a risk factor in surgical decision-making for high-risk patients.Keywords: anemia, hip fracture, postoperative complications, risk factor

Xiang Li, Zhaoyang Gao, Hong Liao School of Foreign Languages and Cultures, Panzhihua University, Panzhihua, 617000, People’s Republic of ChinaCorrespondence: Zhaoyang Gao, School of Foreign Languages and Cultures, Panzhihua University, Panzhihua, 617000, People’s Republic of China, Email gavinstudy@126.comBackground: It is increasingly essential for translators to possess a high level of technological proficiency to succeed in their work, as technology is becoming an integral part and common practice of the translation industry. Several previous studies found that critical thinking, academic self-efficacy, and cultural intelligence independently influenced the translation competence of college students. However, the underlying psychological mechanism through which these salient factors affect student translators’ technology competence has not been fully explored. Therefore, this research sought to examine the systematic interactions between critical thinking, academic self-efficacy, cultural intelligence, and translation technology competence among college students.Methods: This study adopted an empirical approach to collect data from 663 seniors from 7 colleges in China. The questionnaires of the Critical Thinking Disposition Scale (CTDS), General Academic Self-Efficacy Scale (GASE), Short Form measure of Cultural Intelligence (SFCQ), and Translation Technology Competence Scale (TTCS) were used for the online survey. The quantitative data were investigated by employing descriptive statistics with SPSS 27, covariance-based structural equation modelling with AMOS 24 to test the proposed hypotheses by assessing relationships between observed and latent variables, and bootstrap method with PROCESS 3.5 to examine the mediating effects.Results: Critical thinking, academic self-efficacy, and cultural intelligence were significant predictors of students’ translation technology competence. Additionally, academic self-efficacy and cultural intelligence acted as independent and chain mediators in the relationship between critical thinking and student translators’ technology competence.Conclusion: The findings provide valuable insight into how psychological factors, including critical thinking, academic self-efficacy, and cultural intelligence, can impact students’ competence in translation technology. This study contributes to future research and practices that seek to understand how these psychological factors can be leveraged to promote students’ success in translation technologies.Keywords: academic self-efficacy, critical thinking, cultural intelligence, student translator, translation technology competence

Liang Zheng,1,&ast; Zhoujun Kang,1,&ast; Ru Wang,2 Meng Lv,2 Zhirui Gao,1 Haizhou Xu,1 Meitang Wang1 1Emergency Department, Changhai Hospital Affiliated to Navy Medical University, Shanghai, People’s Republic of China; 2Genoxor Medical Science and Technology Inc., Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haizhou Xu; Meitang Wang, Emergency Department, Changhai Hospital Affiliated to Navy Medical University, Changhai Road No. 168, Yangpu District, Shanghai, 200433, People’s Republic of China, Tel +86-21-81873891, Email sealand_xu@126.com; wmt88@sina.comPurpose: Intra-abdominal infections (IAI) are gradually becoming common in the emergency department, though the incidence is low and the prognosis is fair, as the symptoms are similar to other intra-abdominal diseases, rapid and accurate diagnosis of the causative agents is essential for clinical management. This study aimed to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS) in detecting IAI in the emergency department.Patients and Methods: This was a retrospective, single-centered study including patients admitted to the emergency department from January 1st, 2021 to August 31st, 2022 with diagnosis of IAI. The comparison between mNGS and microbial culture using paracentesis fluid samples was performed to evaluate the diagnostic performance of mNGS for IAI. Meanwhile, paracentesis fluid and peripheral blood mNGS were compared to explore the sample specificity. Further, the microbial community structure of the patients with pyogenic liver abscesses (PLA) was analyzed.Results: Thirty-four IAI patients including 23 with pyogenic liver abscesses (PLA), 3 with parapancreatic abscesses, and 8 with other IAI were included in this study. Compared with the conventional microbial culture of paracentesis fluid, mNGS using paracentesis fluid detected more positive cases of IAI (93.75% vs 81.25%), and identified more species of pathogens, especially in obligate anaerobes and viral pathogens. Peripheral blood mNGS presented a relatively high consistency with the paracentesis fluid mNGS (91% mutual positive). The microbial community structure of PLA patients with diabetes is less diverse than that of those without diabetes. Patients with diabetes are at high risk of PLA caused by Klebsiella pneumonia.Conclusion: mNGS has advantages in detecting IAI in the emergency department, and peripheral blood mNGS can be a non-invasive choice for early diagnosis.Keywords: metagenomic next-generation sequencing, mNGS, abdominal infection, pyogenic liver abscesses, PLA, emergency department

Linlin Wu,&ast; Qian Lei,&ast; Zirong Gao,&ast; Wei Zhang&ast; Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Zhang, Email zhangwei_hxicu@163.comAbstract: Acute respiratory distress syndrome (ARDS) is a clinical syndrome that is characterized by an acute onset and refractory hypoxemia. It remains an important contributor to high mortality in critically ill patients, and the majority of clinical randomized controlled trials on ARDS provide underwhelming findings, which is attributed in large part to its pathophysiological and clinical heterogeneity, among other aspects. It is now widely accepted that ARDS is highly heterogeneous, growing evidences support this. ARDS phenotypic and subphenotypic studies aim to further differentiate and identify ARDS heterogeneity in the hope that clinicians can benefit from it, then can diagnose ARDS faster and more accurately and provide targeted treatments. This review collates and evaluates the major phenotype-related research advances of recent years, with a specific focus on ARDS biomarkers and clinical factors.Keywords: acute respiratory distress syndrome, ARDS, phenotypic classification, biomarker, clinical variable

Ping’an Zhang, Yanliang Ma, Xi Chen, Yifan Ma, Luyang Yang, Moqin Zhang, Zhancheng Gao Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Yanliang Ma, Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xi Cheng District, Beijing, 100044, People’s Republic of China, Tel +86-10-88324641, Email helloyl1979@126.comBackground: Allergic bronchopulmonary aspergillosis (ABPA) primarily complicates the course of asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). Mortality data of ABPA and the difference in all-cause mortality between ABPA with and without COPD are not available.Objective: We investigated the difference in all-cause mortality between ABPA with and without COPD.Methods: A retrospective review was performed among patients with the diagnosis of ABPA at Peking University People’s Hospital between January 2010 and March 2022. Logrank test was performed to investigate the difference between all-cause mortality for ABPA with and without COPD and Cox regression analysis was performed to investigate the independent risk factors for all-cause mortality in patients with ABPA.Results: Sixty-one patients with ABPA were enrolled in this study. The follow-up duration was 50.38 months (3– 143 months). In the COPD group, 7 patients died (7/10), while in the non-COPD group, 4 patients died (4/51). The 1-year survival rates of ABPA with and without COPD were 60% and 97.8%, respectively. The 5-year survival rates of ABPA with and without COPD were 40% and 94%, respectively. The Cox regression analysis showed that higher C-reactive protein (CRP) (HR = 1.017, 95% CI 1.004– 1.031, P = 0.013) and complicating COPD (HR = 8.525, 95% CI 1.827– 39.773, P = 0.006) were independent risk factors associated with mortality in patients with ABPA.Conclusion: The all-cause mortality for ABPA with COPD is higher than that for ABPA without COPD. Higher CRP and complicating COPD are independent risk factor for mortality in patients with ABPA.Keywords: allergic bronchopulmonary aspergillosis, pulmonary disease, mortality, risk factor, chronic obstructive pulmonary disease

Jianan Hao,1,2,&ast; Yichao Wang,1,&ast; Lijing Huo,3 Tiantian Sun,1 Yunfeng Zhen,1 Zhe Gao,1 Shuchun Chen,1 Luping Ren1 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Graduate School of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Laboratory Department, Hebei General Hospital, Shijiazhuang, Hebei, 050000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Luping Ren, Endocrinology Department, Hebei General Hospital, 348, Heping West Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email renluping1122@163.comObjective: We aimed to examine the association between bone morphogenetic protein-9 (BMP-9) and type 2 diabetes mellitus (T2DM) in conjunction with non-alcoholic fatty liver disease (NAFLD) and insulin resistance (IR) and to identify evidence supporting the potential role of BMP-9 in the clinical prevention and treatment of T2DM in conjunction with NAFLD.Methods: One hundred and twenty subjects were included in this study. We sorted all of the subjects into four groups of equal size (n=30 each). A trained expert assessed the height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) of the subjects and computed the body mass index (BMI). All subjects had their fasting blood glucose (FBG), fasting insulin (FINS), serum BMP-9, and biochemical indices assessed.Results: Significant variations were observed in BMI, SBP, DBP, ALT, TC, TG, HDL-C, LDL-C, ApoB, FBG, FINS, HOMA-IR, and serum BMP-9 among the four groups (P< 0.05). The level of serum BMP-9 was positively correlated with HDL-C, while the level of serum BMP-9 was negatively correlated with BMI, SBP, DBP, ALT, TC, TG, LDL-C, FBG, FINS, and HOMA-IR. Multiple stepwise regression analyses revealed that FINS, LDL-C, HDL-C, and BMI were independent factors impacting serum BMP-9 levels (P< 0.05). Logistic regression analyses revealed that BMP-9 was a protective factor for T2DM paired with NAFLD, while HOMA-IR was a risk factor.Conclusion: Serum BMP-9 levels are significantly lower in the T2DM+NAFLD group when compared to other groups, and BMP-9 is an independent risk factor for T2DM paired with NAFLD.Keywords: bone morphogenetic protein-9, type 2 diabetes mellitus, non-alcoholic fatty liver disease, insulin resistance, glucose and lipid metabolism

Hao Wu,1,2 Yanhong Liu,2 Liqing Chen,2 Shuangqing Wang,1,2 Chao Liu,2 Heming Zhao,2 Mingji Jin,1,2 Shuangyan Chang,2 Xiuquan Quan,3 Minhu Cui,3 Hongshuang Wan,2,3 Zhonggao Gao,1,2 Wei Huang2 1Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province, 133002, People’s Republic of China; 2State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of China; 3Department of Gastroenterology, Yanbian University Hospital, Yanji, Jilin Province, 133000, People’s Republic of ChinaCorrespondence: Zhonggao Gao; Wei Huang, Tel +86 10 63028096 ; +86 10 63026505, Email zggao@imm.ac.cn; huangwei@imm.ac.cnIntroduction: The blood–brain barrier (BBB) is a key obstacle to the delivery of drugs into the brain. Therefore, it is essential to develop an advanced drug delivery nanoplatform to solve this problem. We previously screened a small rabies virus glycoprotein 15 (RVG15) peptide with 15 amino acids and observed that most of the RVG15-modified nanoparticles entered the brain within 1 h of administration. The high BBB penetrability gives RVG15 great potential for brain-targeted drug delivery systems. Moreover, a multifunctional integrated nanoplatform with a high drug-loading capacity, tunable functionality, and controlled drug release is crucial for tumor treatment. Zeolitic imidazolate framework (ZIF-8) is a promising nanodrug delivery system.Methods: Inspired by the biomimetic concept, we designed RVG15-coated biomimetic ZIF-8 nanoparticles (RVG15-PEG@DTX@ZIF-8) for docetaxel (DTX) delivery to achieve efficient glioblastoma elimination in mice. This bionic nanotherapeutic system was prepared by one-pot encapsulation, followed by coating with RVG15-PEG conjugates. The size, morphology, stability, drug-loading capacity, and release of RVG15-PEG@DTX@ZIF-8 were thoroughly investigated. Additionally, we performed in vitro evaluation, cell uptake capacity, BBB penetration, and anti-migratory ability. We also conducted an in vivo evaluation of the biodistribution and anti-glioma efficacy of this bionic nanotherapeutic system in a mouse mode.Results: In vitro studies showed that, this bionic nanotherapeutic system exhibited excellent targeting efficiency and safety in HBMECs and C6 cells and high efficiency in crossing the BBB. Furthermore, the nanoparticles cause rapid DTX accumulation in the brain, allowing deeper penetration into glioma tumors. In vivo antitumor assay results indicated that RVG15-PEG@DTX@ZIF-8 significantly inhibited glioma growth and metastasis, thereby improving the survival of tumor-bearing mice.Conclusion: Our study demonstrates that our bionic nanotherapeutic system using RVG15 peptides is a promising and powerful tool for crossing the BBB and treating glioblastoma.Keywords: glioblastoma, blood–brain barrier, RVG15, biomimetic nanoparticle, zeolitic imidazolate frameworks-8, ZIF-8

Yukun He,1,&ast; Yifan Wang,1,&ast; Xinqian Ma,1 Lili Zhao,1 Jie Guan,2 Jin Zhao,3 Wenyi Yu,1 Yanjun Li,4 Wentao Ni,1 Zhancheng Gao1 1Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Clinical Laboratory, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Respiratory Diseases, Air Force Medical Center, Chinese People’s Liberation Army, Beijing, People’s Republic of China; 4Clinical Laboratory, The Sixth Medical Center of PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wentao Ni; Zhancheng Gao, Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China, Email wentao.qingdao@163.com; zcgao@bjmu.edu.cnBackground: Cefiderocol (CFDC) is a promising antimicrobial agent against multidrug resistant Gram-negative bacteria. However, CFDC resistance has emerged in carbapenem-resistant Acinetobacter baumannii (CR-AB) but the underlying mechanisms remain unclear.Methods: Whole-genome sequencing and transcriptome sequencing were performed on CFDC-non-susceptible and CFDC-susceptible isolates. Two different recombinant plasmids was electro-transformed into the E. coli BL21 strain to determine the impact of blaPER and the combined impact of blaPER-1 and blaOXA-23 on CFDC resistance.Results: Fifty-five CR-AB isolates with minimum inhibitory concentrations (MICs) ranged from 0.06 mg/L to > 256 mg/L were sequenced, including 47 CFDC-non-susceptible and eight CFDC-susceptible isolates. Two CFDC-non-susceptible isolates belonged to ST104 whereas the remaining isolates belonged to ST2, and blaPER-1 was present only in CFDC-non-susceptible isolates. Amino acid substitutions were noted in penicillin-binding proteins (PBPs) in four CFDC-susceptible isolates, with slightly elevated MICs. The MICs of recombinant E. coli BL21 carrying the blaPER-1 gene increased 64-fold and recombinant E. coli BL21 carrying both the blaPER-1 and blaOXA-23 genes increased 8-fold but both remained within the susceptibility range. Transcriptome sequencing of 17 CFDC-non-susceptible isolates and eight CFDC-susceptible isolates revealed that transcriptional levels of various iron transport proteins, such as fiu, feoA, and feoB, and the energy transduction system, TonB-ExbB-ExbD, were relatively downregulated in CFDC-non-susceptible isolates. GO enrichment analysis revealed that the upregulated genes in CFDC-non-susceptible isolates were mainly associated with redox homeostasis and stress response. Besides, the expression levels of the blaOXA-23 and exbD genes were negatively correlated with the MICs.Conclusion: PER-1 production, iron transport system downregulation, and mutations in PBPs may synergistically impart high-level resistance to CFDC in CR-AB.Keywords: carbapenem-resistant Acinetobacter baumannii, cefiderocol resistance, blaPER-1, iron transporter systems

Alicia Blackmore,1 Holly Etchegary,1,2 Leigh Anne Allwood-Newhook,3 Zhiwei Gao,1 Hai Van Nguyen,4 Kaylah Parsons-Mercer,5 Laurie Twells1 1Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; 2Scientific Patient Engagement Lead of NL SUPPORT Unit, St. John’s, Newfoundland and Labrador, Canada; 3Department of Pediatrics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; 4School of Pharmacy, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; 5Patient Partner, St. John’s, Newfoundland and Labrador, CanadaCorrespondence: Alicia Blackmore, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada, Email Akt104@mun.caPurpose: Patient-oriented research (POR) and patient engagement (PE) has highlighted the value of incorporating patients’ ideas and priorities in health research. Using the guiding principles of POR and PE, the current study conducted PE sessions to gain insight on the perceptions of mothers regarding the costs of infant feeding.Methods: Four patient engagement sessions were held with mothers residing in Newfoundland and Labrador between November 2019 and January 2020. Mothers were targeted through the Brighter Futures Coalition of St. John’s, a not-for-profit community organization. PE sessions were designed in a two-hour format, allowing the research team to engage mothers and identify costs of infant feeding from a mothers’ perspective.Results: Through the guiding principles of patient-oriented research and patient engagement, our research team successful engaged with mothers in discussions surrounding the costs of infant feeding. The sessions allowed for an in-depth discussion surrounding monetary costs (eg, incidentals of breast or formula feeding), the associated costs of infant feeding and the workplace (eg, perceived productivity) and environment impacts (eg, single use plastics). During each session, evaluations were provided to solicit feedback on whether the goals and expectations of mothers had been met, and whether they felt their opinions were heard and understood.Conclusion: By conducting patient engagement sessions, informed by patient-oriented research guiding principles, we were able to successfully recruit and engage mothers in discussions that led to a better understanding of their perspectives on the costs of infant feeding.Keywords: patient engagement, infant feeding, patient-oriented research

Dong Li,1 Zhanwei Gao,2 Jiaming Sun,3 Qin Li,4 Ping Jiang,5 Lijuan Zhang,6 Smita Chawla7 1Peking University Third Hospital, Beijing, People’s Republic of China; 2Japan Friendship Hospital, Beijing, People’s Republic of China; 3Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4General Hospital of Guangzhou Military Command of PLA, Guangzhou, People’s Republic of China; 5Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 6Allergan Aesthetics, an AbbVie Company, Beijing, People’s Republic of China; 7Clinical Development, Allergan Aesthetics, an AbbVie Company, Irvine, CA, USACorrespondence: Smita Chawla, Clinical Development, Allergan Aesthetics, an AbbVie Company, 2525 Dupont Drive, Irvine, CA, 92612, USA, Tel +1 714 246-2213, Email smita.chawla@allergan.comBackground: Hyaluronic acid (HA) soft tissue fillers are used to restore volume loss to the lips and perioral area.Objective: Evaluate the safety and effectiveness of the HA filler Juvéderm® Volbella® (VYC-15L) for lip enhancement in Chinese adults.Methods & Materials: In this multicenter, evaluator-blind study, subjects seeking lip enhancement were randomized 3:1 to VYC-15L or no-treatment control group (with optional treatment delayed by 3 months). Effectiveness endpoints included 1-point improvement on the 5-point Lip Fullness Scale (LFS) assessed by evaluating investigators (EIs) and subjects, and overall volume of lips and change in lip surface area measured from 3-dimensional images. Safety assessments included procedural pain, injection site reactions (ISRs), and adverse events (AEs).Results: The modified intention-to-treat population included 163 subjects (median age, 34 years; 96.9% female). More VYC-15L-treated subjects had a 1-point reduction in EI-reported LFS score at month 3 versus untreated controls (84.7% vs 0%; p < 0.0001), and 65% of the treated subjects self-reported a 1-point LFS improvement at month 3. Procedural pain during injection was mild. The most common ISRs were swelling, tenderness to touch, and firmness. One treatment-related serious AE (injection site compression arterial ischemia) resolved in 16 days.Conclusion: VYC-15L treatment was superior to no treatment at 3 months and was well tolerated by subjects.Clinical Trial Registration Number: NCT03519204.Keywords: dermal fillers, hyaluronic acid, China

Zhan Gao,1,2 Yun Ti,1 Bin Lu,1 Fang-qiang Song,1,3 Lei Zhang,1 Bo-ang Hu,1 Jia-ying Xie,1 Wei Zhang,1 Lu Han,1,4 Ming Zhong1 1The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Qilu College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Critical Care Medicine, Tengzhou Central People’s Hospital, Tengzhou, People’s Republic of China; 4Department of General Practice, Qilu Hospital, Qilu College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Lu Han; Ming Zhong, Email luhan_sdu@163.com; zhongming2sdu@163.comBackground: Previous studies have reported that six transmembrane protein of prostate 2 (STAMP2) attenuates metabolic inflammation and insulin resistance in diabetes mellitus. However, the role of STAMP2 in the diabetic heart is still unclear.Methods: A diabetic rat cardiomyopathy model was established via intraperitoneal STZ injection. STAMP2 was overexpressed in the treatment group using adeno-associated virus. Rat heart diastolic function was measured using echocardiography and a left ventricular catheter, and cardiac interstitial fibrosis was detected by immunohistochemistry and histological staining. Insulin sensitivity and NF-κB expression were shown by Western blotting. NMRAL1 distribution was illustrated by immunofluorescence.Results: STAMP2 expression in the diabetic rat heart was reduced, and exogenous overexpression of STAMP2 improved glucose tolerance and insulin sensitivity and alleviated diastolic dysfunction and myocardial fibrosis. Furthermore, we found that NF-κB signaling is activated in the diabetic heart and that exogenous overexpression of STAMP2 promotes NMRAL1 translocation from the cytoplasm to the nucleus and inhibits p65 phosphorylation.Conclusion: STAMP2 attenuates cardiac dysfunction and insulin resistance in diabetic cardiomyopathy, likely by promoting NMRAL1 retranslocation and NF-κB signaling inhibition.Keywords: STAMP2, diabetic cardiomyopathy, NADPH, NMRAL1, NF-κB

ZhenZhen Gao,1,&ast; Xuan Qi,1,&ast; XingTing Zhang,2 XinZhen Gao,2 XinHua He,1 ShuBin Guo,1 Peng Li1 1Department of Emergency, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100008, People’s Republic of China; 2LIANREN Digital Health Co., Ltd, Beijing, 102208, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Li, Department of Emergency, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100008, People’s Republic of China, Tel +86 010 85231280, Email lipeng9926@126.comObjective: To establish an emergency triage model through the statistical analysis of big data during a particular time period from a hospital information system to improve the accuracy of triage in emergency department (ED).Methods: A total of 276,164 patients who visited the Emergency Medicine Department of Beijing Chao-Yang Hospital from 2017 to 2020 were included in this study, including 123,392 men and 152,772 women aged from 14 to 112 years. The baseline characteristics (age and gender) and medical records (patient’s condition, body temperature, heart rate, breathing, blood pressure, consciousness, and oxygen saturation) of the patients was collected. The data samples were randomly allocated, with 80% as the training set and 20% as the testing set. The patients were divided into levels I, II, III, and IV in accordance with a four-level triage standard. We selected the effective Extreme Gradient Boosting (XGBoost) algorithm as our emergency classification prediction model. The XGBoost model was applied to simulate the thinking process of triage nurses, and the De Long’s test was used to compare the receiver operating characteristic (ROC) curve of different models. The P value was obtained by calculating the variance and covariance of area under the curve (AUC) values of different ROC curves.Results: Level I had 4960 (1.8%) patients, level II had 25,646 (9.29%), level III had 130,664 (47.31%), and level IV had 114,894 (41.6%). The XGBoost model was built following a logic exercise based on the traditional manual pre-inspection and triage results. After verification, the prediction accuracy was 82.57%. The AUC of each disease severity level (levels I, II, III, and IV) was 0.9629, 0.9554, 0.9120, and 0.9296, respectively.Conclusion: The emergency triage prediction model, which achieved a relatively strong accuracy rate, can reduce the work intensity of medical workers and improve their working efficiency.Keywords: emergency, triage, XGBoost model, triage model

Rui Zhao,1 Jianbo Xue,1 Xueli Zhang,1 Maohuan Peng,1 Jing Li,1 Bing Zhou,1 Long Zhao,1 Thomas Penzel,2 Meir Kryger,3 Xiao Song Dong,1 Zhancheng Gao,1 Fang Han1 1Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Sleep Medicine Center, Charité-Universitätsmedizin, Berlin, Germany; 3Division of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USACorrespondence: Xiao Song Dong; Zhancheng Gao, Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, No. 11 Xizhimen Nandajie, Xicheng District, Beijing, 100044, People’s Republic of China, Email dongxiaosong@pkuph.edu.cn; zcgao@bjmu.edu.cnObjective: A novel ring-worn oximeter (Circul) uses reflective photoplethysmography and automated signal processing to calculate oxygen desaturations. We evaluated the ability of Circul to detect obstructive sleep apnea in Chinese adults.Methods: We recruited 207 Chinese Han subjects: 70% males, mean age 48.2± 14.7 years, mean BMI 27.6± 4.8 kg/m2 and mean AHI 28.6± 25.2 events/h. All participants underwent simultaneous polysomnography (PSG) and Circul testing in a sleep laboratory. Oxygen desaturation index (ODI), mean oxygen saturation (MSpO2), cumulative time at SpO2< 90% (CT90), cumulative percentage of sleep time spent with SpO2< 90% (CT90/TST) were derived and compared for the Circul and the PSG.Results: The ODI was 25.3± 24.5 events/h using PSG and 22.2± 24.5 events/h using Circul (P< 0.0001), with an intraclass correlation coefficient (ICC) of 0.884. CT90 and CT90/TST between the two methods were not different; the MSpO2 level calculated by PSG was slightly lower than Circul, 95.0% (93.0– 96.0%) vs 95.3% (93.9– 96.6%), P< 0.0001. Circul-ODI had a good correlation (r=0.91, p< 0.0001) and close agreement with PSG-AHI (Bland-Altman analysis: Mean Difference 6.4, 95% CI − 14.8 to 27.5 events/h). Using a threshold of AHI ≥ 5 events/h, the Circul had 87% sensitivity, 83% specificity, 5.09 positive likelihood ratio (LR+), 86% accuracy, and 0.929 area under the curve (AUC).Conclusion: Circul ring pulse oximetry can detect OSA with reasonable reliability. The Circul system is a reliable and comfortable choice for OSA assessment.Keywords: obstructive sleep apnea, reflective photoplethysmography, pulse oximetry, polysomnography

Hong-Xia Zhang,1 Lu Zhai,1 Zhixiang Gao,2 Jie Yuan3 1Department of Endocrinology, Shanxi Provincial People’s Hospital, Taiyuan, People’ s Republic of China; 2Department of Ultrasonography, Shanxi Provincial People’s Hospital, Taiyuan, People’ s Republic of China; 3Department of Radiology, Shanxi Provincial People’s Hospital, Taiyuan, People’ s Republic of ChinaCorrespondence: Jie Yuan, Tel +86 13834164698, Email doctoryuang@163.comBackground: Visceral obesity is independently associated with hypovitaminosis D. Perirenal fat is a visceral fat type active in performing endocrine functions. However, the relationship between perirenal fat thickness (PrFT) and serum 25-hydroxy vitamin D [25(OH)D] is unclear. The aim of this study is to investigate the relationship between serum 25(OH)D and PrFT in patients with metabolic syndrome (MS) in the community.Methods: From May to September 2020, 332 MS subjects in Qinfengyuan and Dongfang communities in Taiyuan City, China were enrolled in an MS survey. All the participants completed the questionnaire survey and physical examination, and their fasting blood samples were collected for biochemical examination. Abdominal ultrasonography was performed to measure the perirenal fat thickness.Results: The mean serum 25(OH)D level for the 332 MS subjects was 13.5 ng/mL, the proportions of vitamin D deficiency [serum 25(OH)D < 20 ng/mL] and insufficiency [serum 25(OH)D = 20– 29.9 ng/mL] were 60.8% (202) and 24.4% (81), respectively. Among the hypovitaminosis D [serum 25(OH)D < 30 ng/mL] subjects, the prevalence of abdominal obesity (waist circumference ≥ 90cm for men and ≥ 80cm for women) is 61.1%. Pearson correlation analysis showed that lg25(OH)D was significantly and negatively associated with body mass index (BMI), waist circumference (W), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), insulin resistance index (HOMA-IR), uric acid (UA)) and PrFT (all P< 0.05), and positively correlated with high-density lipoprotein cholesterol (HDL-C) (P< 0.05). Multivariate analysis showed that PrFT and HOMA-IR were independently correlated with 25(OH)D.Conclusion: In screening MS patients, approximately 85% of the community MS patients in Taiyuan had hypovitaminosis D; in which 3/5 is abdominal obesity. PrFT is an independent risk factor for hypovitaminosis D in MS subjects.Keywords: metabolic syndrome, 25(OH)D, hypovitaminosis D, perirenal fat thickness

Zhengdong Gao,1,2,&ast; Yaxiao Liu,1,2,&ast; Lekai Zhang,1,2 Zizhuo Yang,1,2 Linchen Lv,1,2 Shuai Wang,1,2 Lipeng Chen,1,2 Nan Zhou,1,2 Yaofeng Zhu,1 Xuewen Jiang,1 Benkang Shi,1,2 Yan Li1,2 1Department of Urology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Key Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Benkang Shi; Yan Li, Department of Urology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, People’s Republic of China, Email bkang68@sdu.edu.cn; yanli@sdu.edu.cnPurpose: Urinary tract infections (UTIs) can evoke a rapid host immune response leading to bladder inflammation and epithelial damage. Neuroimmune interactions are critical for regulating immune function in mucosal tissues. Yet the role of nociceptor neurons in bladder host defense has not been well defined. This study aimed to explore the interaction between nociceptor neurons and bladder immune system during UTIs.Methods: In this study, whether uropathogenic Escherichia coli (UPEC) and lipopolysaccharide (LPS) can directly stimulate nociceptor neurons was detected. Female C57BL/6J mice were treated with high dose of capsaicin, a high-affinity TRPV1 agonist, to ablate nociceptor neurons. Bladder inflammation, barrier epithelial function and bladder immune cell infiltration were assessed after UPEC infection. The level of neuropeptide calcitonin gene-related peptide (CGRP) in infected bladder was detected. Furthermore, the effects of CGRP on neutrophils and macrophages were evaluated both in vitro and in vivo.Results: We found that UPEC and its pathogenic factor LPS could directly excite nociceptor neurons, releasing CGRP into infected bladder, which suppressed the recruitment of neutrophils, the polarization of macrophages and the killing function of UPEC. Both Botulinum neurotoxin A (BoNT/A) and BIBN4096 (CGRP antagonism) blocked neuronal inhibition and prevented against UPEC infection.Conclusion: The present study showed a novel mechanism by which UPEC stimulated the secretion of CGRP from nociceptor neurons to suppress innate immunity.Keywords: UTIs, CGRP, nociceptor neurons, UPEC, innate immune cells

Zhengzheng Gao,1 Jianmin Zhang,1 Xiaolu Nie,2 Xiaohuan Cui1 1Department of Anesthesiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2Center for Clinical Epidemiology and Evidence-based Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of ChinaCorrespondence: Jianmin Zhang, Department of Anesthesiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56 South Lishi Road, Xicheng District, Beijing, 100045, People’s Republic of China, Tel +86 10-59616415, Email sunbrighangel@sina.comBackground: Emergence agitation (EA) has a negative effect on the recovery from general anesthesia in children. This study aimed to evaluate the effectiveness of intravenous ibuprofen in reducing the incidence of EA in children.Methods: This randomized, double-blind, placebo-controlled, single-center study analyzed data from patients aged 3– 9 years undergoing tonsillectomy under general anesthesia with propofol and remifentanil. These patients were randomly assigned to receive either the ibuprofen or the placebo intraoperatively. The primary endpoint was a between-group difference in the incidence of EA at 15 min following extubation. EA was defined as Pediatric Anesthesia Emergence Delirium score ≥ 10. The secondary endpoint included the associated factors of EA.Results: Eighty-nine patients were included in the study. Ibuprofen decreased the incidence of EA at 15 min following extubation (8.9% in the treatment group vs 34.1% in the control group; odds ratio [OR], 0.261; 95% confidence interval [CI], 0.094– 0.724; P=0.004). Compared with the control group, there was a significant reduction in the number of rescue fentanyl doses (P=0.045), and fewer patients experienced moderate to severe pain at 15 min following extubation in the treatment group (P=0.048). Upon logistic regression analysis, high modified Pediatric Anesthesia Behavior and pain scores following surgery were considered the risk factors related to EA (OR, 8.07; 95% CI, 1.12– 58.07, P=0.038 and OR, 2.78; 95% CI, 1.60– 4.82, P< 0.001, respectively). Ibuprofen administration was the protective factor related to EA (OR, 0.05; 95% CI, 0.01– 0.67, P=0.023).Conclusion: Intraoperative ibuprofen infusion can significantly reduce the incidence of EA following general anesthesia with propofol and remifentanil in children.Trial Registration: The study was registered with the Chinese Clinical Trial Registry on 7 April 2021 (number: ChiCTR2100045128; https://www.chictr.org.cn/edit.aspx?pid=124595&htm=4).Keywords: emergence agitation, children, ibuprofen, general anesthesia, protective factor

Joseph Emil Amegadzie,1 John-Michael Gamble,2 Jamie Farrell,1 Zhiwei Gao1 1Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada; 2Faculty of Science, School of Pharmacy, University of Waterloo, Waterloo, Ontario, CanadaCorrespondence: Zhiwei Gao, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St. John’s, NL, A1B 3V6, Canada, Tel +17098646523, Email zhiwei.gao@med.mun.caPurpose: Despite ample evidence underpinning the efficacy of β2-agonists in asthma and chronic obstructive pulmonary disease (COPD), the occurrence of β1- and β2-adrenoceptors in the heart suggests that β2-agonists may have deleterious cardiac effects. We investigated the association between new users of long-or short-acting β2-agonists (LABA or SABA) or ICS (inhaled corticosteroids)/LABA and major adverse cardiovascular events (MACE).Methods: A nested case–control analysis was conducted using the UK Clinical Practice Research Datalink of patients with asthma, COPD or asthma–COPD overlap with initial treatment of LABA, SABA, ICS/LABA, ICS, long-or short-acting muscarinic antagonist (LAMA or SAMA) between 01 January 1998 and 31 July 2018. The primary outcome was MACE, defined as the first occurrence of stroke, heart failure, myocardial infarction, arrhythmia, or cardiovascular death. Each case was matched with up to 10 controls on age, sex, date of cohort-entry, and duration of follow-up. The risk of MACE associated with β2-agonists was estimated using conditional logistic regression after controlling for potential confounders.Results: The cohort included 180,567 new users of β2-agonists, ICS, SAMA, or LAMA. Among asthmatics, β2-agonists were not associated with the risk of MACE (SABA vs ICS: HR 1.29 [0.96– 1.73]; ICS/LABA vs ICS, HR 0.75 [0.33– 1.73]). In contrast, among COPD patients, LABA (HR, 2.38 [1.04– 5.47]), SABA (HR, 2.02 [1.13– 3.59]) and ICS/LABA (HR, 2.08 [1.04– 4.16]) users had an increased risk of MACE compared with SAMA users. Among patients with asthma–COPD overlap, SABA (HR, 2.57 [1.26– 5.24]) was associated with an increased risk of MACE compared with ICS.Conclusion: In conclusion, initiation of LABA, SABA, or ICS/LABA in COPD or SABA in asthma–COPD overlap is associated with increased risk of MACE. No associations were observed among patients with asthma.Keywords: asthma, chronic obstructive pulmonary disease, nested case–control

Zirui Gao, Qianxi Xu, Xue Chen, Dandan Mao, Jianzhong Zhang, Jiang Jin Department of Dermatology, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jiang Jin, Department of Dermatology, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Email PUPH_JiangJin@163.comAbstract: Rhupus syndrome, as an overlap syndrome of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), is relatively rare because of their substantially different immunopathological mechanisms. Herein, we report the first case of primary cutaneous anaplastic large cell lymphoma (PC-ALCL) in a patient with rhupus syndrome and Sjogren’s syndrome and review the relevant literature. A 52-year-old Chinese woman with a history of rhupus syndrome and Sjogren’s syndrome was treated with methotrexate, who developed gradually increasing nodules on the waist. Histopathological studies showed that the dermis and subcutaneous tissue were infiltrated with medium-to-large, atypical lymphocytes with the oval nucleus. The tumor cells showed CD3-, CD4-, CD8-, CD30+, LCA+, and EBV-encoded RNA (EBER) in situ hybridization (ISH) was positive. Therefore, the patient was diagnosed with PC-ALCL. Both immune disorders and EBV infection may be related to the onset of PL-ALCL, and further studies are needed to clarify the pathogenesis.Keywords: lymphoproliferative disease, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, methotrexate

Shirui Li,1 Zhihui Gao,1 Meihan Zhong,1 Zhujun Yu,1 Jianan Li,2 Haoran Bi1,3,4 1Department of Biostatistics, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Key Laboratory of Environment and Health, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Center for Medical Statistics and Data Analysis, Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Haoran Bi, Department of Biostatistics, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People’s Republic of China, Tel/Fax +86-0516-83262660, Email bihaoran1989@sina.com Jianan Li, Key Laboratory of Environment and Health, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People’s Republic of China, Tel/Fax +86-0516-83262659, Email lijianan512133@163.comPurpose: The emergence of the mutant virus has exacerbated the COVID-19 epidemic, and vaccines remain an effective and viable means of resistance. As a socially influential young group, university students’ awareness and acceptance of the COVID-19 vaccine are crucial to achieving herd immunity. This study aimed to assess the awareness and acceptance of the COVID-19 vaccine among Chinese university students and identify possible factors associated with their awareness level and vaccine hesitancy.Patients and Methods: An anonymous cross-sectional survey was conducted among Chinese university students between 10 and 28 June 2021. We collected information on the demographic characteristics, awareness and acceptance of the COVID-19 vaccine, and influencing factors. Sleep disturbances and anxiety disorders were also evaluated. Multinomial logistic regression analyses were performed.Results: Among the 721 participants (aged 18 to 23 years) with a female predominance (68.9%), 40.4% of cases exhibited moderate awareness the COVID-19 vaccine, and 87.4% of cases expressed high acceptance of the vaccine. Participants’ awareness of the COVID-19 vaccine was associated with gender, ethnicity, region of residence, grade level, satisfaction with current state of pandemic control, the perceived likelihood of a COVID-19 pandemic rebound, the source number of COVID-19 information, concerns about differences in vaccine manufacturers, acceptance of current state-approved vaccines and insomnia level. Furthermore, age, preferred channels for vaccination and the acceptance of current state-approved vaccines were significantly associated with their acceptance of the vaccine.Conclusion: This study reflected Chinese university students’ high acceptance, but insufficient awareness of the COVID-19 vaccine, some students have insomnia and anxiety problems. These require the government to take measures such as individualized publicity and education, adding professional psychological counseling courses to improve the university students’ awareness of vaccines and public health events, and comprehensively promote vaccination to cope with the ever-changing situation of the COVID-19 epidemic.Keywords: university students, COVID-19 vaccine, mental health, vaccine hesitancy

Yun Xie,1 Qin Li,2 Zhanwei Gao,3 Jiaming Sun,4 Dong Li,5 Candice Harvey,6 Jiazhi Qu,7 Sean Snow,8 Qingfeng Li1 1Plastic Surgery Department of Shanghai 9th People’s Hospital, Shanghai, People’s Republic of China; 2Plastic Surgery Department of General Hospital of Guangzhou Military Command of PLA, Guangzhou, Guangdong, People’s Republic of China; 3Plastic Surgery Department of Japan Friendship Hospital, Chaoyang, Beijing, People’s Republic of China; 4Plastic Surgery Department of Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5Plastic Surgery Department of Peking University Third Hospital, Haidian, Beijing, People’s Republic of China; 6Allergan Aesthetics, an AbbVie Company, Marlow, UK; 7Allergan Aesthetics, an AbbVie Company, Beijing, People’s Republic of China; 8Allergan Aesthetics, an AbbVie Company, Irvine, CA, USACorrespondence: Qingfeng Li, Shanghai 9th People’s Hospital, No. 639, Zizaoju Road, Shanghai, 200011, People’s Republic of China, Tel + 86-21-53315615, Fax + 86-21-63089567, Email dr.liqingfeng@yahoo.comPurpose: Hyaluronic acid injectable gels are commonly used to treat nasolabial folds (NLFs). We evaluated the safety and effectiveness of VYC-17.5L for correcting NLFs in Chinese subjects.Patients and Methods: This prospective, multicenter, double-blind, within-subject‒controlled study randomized adults with moderate-to-severe NLFs to VYC-17.5L treatment (initial and touch-up) in 1 NLF and control (without lidocaine) in the contralateral NLF. Effectiveness endpoints at 6 months included noninferiority of VYC-17.5L to control in NLF Severity Scale response rate (primary endpoint), subject-reported procedural pain (11-point scale), and investigator and subject assessments using the Global Aesthetic Improvement Scale (GAIS).Results: A total of 175 subjects were included. The primary endpoint was met, with response rates of 84.2% for VYC-17.5L and 82.5% for control. Mean pain scores after initial and touch-up treatments were 2.4 for VYC-17.5L versus 5.2 for control (P < 0.001) and 2.0 versus 3.3 (P < 0.001), respectively. Investigator-rated GAIS scores were 86.5% for VYC-17.5L versus 86.0% for control. There were no between-group differences in subject-rated GAIS scores. Safety profiles were comparable for VYC-17.5L and control.Conclusion: VYC-17.5L was noninferior to control without lidocaine for correcting moderate-to-severe NLFs in Chinese subjects and was superior to control in reducing procedural pain.Keywords: hyaluronic acid, dermal fillers, lidocaine

Yugang Yan,1,2 Ronghua Gao,3 Shaohui Zhang,3 Zhencai Gao,3 Anyong Chen,3 Jianjun Wang,3 Shufang Zhang,3 Wen Dai,3 Fen Li,4 Xiangting Li,3 Guoliang Yang,3 Lixin Liu,3 Xueying Chen2,3 1School of Medical Engineering, Jining Medical University, Jining, Shandong, People’s Republic of China; 2The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, and The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 3Department of Cardiology, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 4Electrocardiogram Room, Jining First People’s Hospital, Jining, Shandong, People’s Republic of ChinaCorrespondence: Xueying Chen, Department of Cardiology, Affiliated Hospital of Jining Medical University, No. 89 Guhuai Road, Jining, 272029, Shandong, People’s Republic of China, Tel +86- 537- 2903508, Fax +86 537-2213030, Email chxy221@163.comBackground: Many studies have shown that glycated hemoglobin (HbA1c) is associated with coronary artery disease (CAD). HbA1c was independently related to angiographic severity in Chinese patients with CAD after adjusting for other covariates. Some traditional cardiovascular drugs may have an impact on this relationship.Methods: This retrospective study enrolled a total of 572 CAD patients who underwent their coronary angiography and had their HbA1c levels measured at the Chinese Hospital. The complexity of the coronary artery lesions was evaluated using the Syntax score, and the subjects were divided into 4 inter quartiles according to HbA1c levels. Covariates included history of traditional cardiovascular drugs.Results: The average age of selected participants was 61.00 ± 9.15 years old, and about 54.72% of them were male. Result of fully adjusted linear regression showed that HbA1c was positively associated with Syntax score after adjusting confounders (β = 1.09, 95% CI: 0.27, 1.91, P = 0.0096). By interaction and stratified analyses, the interactions were observed based on our specification including with the medication history of statins and angiotensin receptor blockers (ARBs) (P values for interaction < 0.05).Conclusion: In this study, we found a positive correlation between the HbA1c levels and the SYNTAX score among CAD individuals, and oral statins and ARBs medication could affect the correlation. Thus, HbA1c measurement could be used for the evaluation of the severity and complexity of coronary lesions among CAD patients.Keywords: HbA1c, SYNTAX score, coronary artery disease, statins, ARBs

Jiao Peng,1– 3,&ast; Xi Li,4,&ast; Lin Zheng,3,5 Lifang Duan,1 Zhengxian Gao,2,5 Die Hu,1 Jie Li,6 Xiaofeng Li,6 Xiangchun Shen,5 Haitao Xiao2 1Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China; 3Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, People’s Republic of China; 4Department of Gastroenterology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 5School of Pharmacy, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, People’s Republic of China; 6Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haitao Xiao, School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China, Email xhaitao@szu.edu.cn Xiangchun Shen, School of Pharmacy, Guizhou Medical University, Guizhou, 550004, People’s Republic of China, Email shenxiangchun@126.comPurpose: GLP-1 based therapy represents a new treatment option for inflammatory bowel disease. Ban-Lan-Gen (BLG) granule, a known anti-viral TCM formulation, exhibits potential anti-inflammatory activities in treating various kinds of inflammation. However, its anti-inflammatory effect on colitis and the underlying mechanisms remain unknown.Methods: Dextran sulfate sodium (DSS)-induced chronic relapsing colitis in mice was established. The disease activity index, histological sign of damage, and levels of proinflammatory cytokines were performed to assess the protective effects of BLG. Serum GLP-1 level and colonic Gcg, GPR41 and GRP43 expression, the community compositions of gut microbiota, the levels of SCFAs in the feces and GLP-1 release from primary murine colon epithelial cells were performed to characterize the effects of BLG on gut microbiota and gut SCFA derived-GLP-1 production.Results: BLG treatment significantly alleviated body weight loss, DAI, colon shortening, colon tissue damage, and pro-inflammatory cytokine levels of TNF-α, IL-1β and IL-6 in the colon tissues. Moreover, BLG treatment could observably restore colonic Gcg, GPR41 and GRP43 expression and serum GLP-1 level of colitic mice, as well as correct the alteration of gut microbiota in colitic mice by increasing the abundances of SCFA-producing bacteria, eg, Akkermansia and Prevotellaceae_UCG-001, and decreasing the abundances of bacteria, eg, Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas, and Oscillibacter. Furthermore, BLG treatment could markedly increase the levels of SCFAs in feces of colitic mice. In parallel, ex vivo assay also showed that and the extract of feces from BLG-treatment mice could greatly stimulate the secretion of GLP-1 from primary murine colon epithelial cells.Conclusion: These findings suggest that the anti-colitis effects of BLG are achieved at least partly by regulating gut microbiota and restoring gut SCFA derived-GLP-1 production, and BLG has the potential to be developed as a promising agent for the treatment of chronic relapsing colitis.Keywords: colitis, Ban-Lan-Gen granule, gut microbiota, short-chain fatty acids, GLP-1

Yukun He,1 Wenyi Yu,1 Pu Ning,1,2 Qiongzhen Luo,1,3 Lili Zhao,1 Yu Xie,1 Yan Yu,1 Xinqian Ma,1 Li Chen,1 Yali Zheng,1,4 Zhancheng Gao1,4 1Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Respiratory & Critical Care Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 4Department of Respiratory, Critical Care, and Sleep Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of ChinaCorrespondence: Yali ZhengDepartment of Respiratory, Critical Care, and Sleep Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of ChinaEmail yali_zheng@126.comZhancheng GaoDepartment of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaEmail zcgao@bjmu.edu.cnBackground: Infiltration of the lower respiratory tract (LRT) microenvironment could be significantly associated with respiratory diseases. However, alterations in the LRT microbiome and metabolome in infectious and inflammatory respiratory diseases and their correlation with inflammation still need to be explored.Methods: Bronchoalveolar lavage samples from 44 community-acquired pneumonia (CAP) patients, 29 connective tissue disease-associated interstitial disease (CTD-ILD) patients, and 30 healthy volunteers were used to detect microbiota and metabolites through 16S rRNA gene sequencing and untargeted high-performance liquid chromatography with mass spectrometry.Results: The composition of the LRT microbial communities and metabolites differed in disease states. CAP patients showed a significantly low abundance and both diseases presented a depletion of some genera of the phylum Bacteroidetes, including Prevotella, Porphyromonas, and health-associated metabolites, such as sphingosine (d16:1), which were negatively correlated with infectious indicators. In contrast, Bacillus and Mycoplasma were both enriched in the disease groups. Streptococcus was specifically increased in CTD-ILD. In addition, co-elevated metabolites such as FA (22:4) and pyruvic acid represented hypoxia and inflammation in the diseases. Significantly increased levels of amino acids and succinate, as well as decreased itaconic acid levels, were observed in CAP patients, whereas CTD-ILD patients showed only a handful of specific metabolic alterations. Functions related to microbial lipid and amino acid metabolism were significantly altered, indicating the possible contributions of microbial metabolism. Dual omics analysis showed a moderate positive correlation between the microbiome and metabolome. The levels of L-isoleucine and L-arginine were negatively correlated with Streptococcus, and itaconic acid positively correlated with Streptococcus.Conclusion: In the LRT microenvironment, shared and specific alterations occurred in CAP and CTD-ILD patients, which were associated with inflammatory and immune reactions, which may provide a new direction for future studies aiming to elucidate the mechanism, improve the diagnosis, and develop therapies for different respiratory diseases.Keywords: community-acquired pneumonia, connective tissue disease-associated interstitial disease, microbiome, metabolome, shared and specific alterations

Jing Lv,1 Zhifei Zhang,2 Zhigang Gao3 1Shandong University of Finance and Economics, Jinan, 250014, People’s Republic of China; 2Tongji University, Shanghai, 201804, People’s Republic of China; 3Shanghai University of Political Science and Law, Shanghai, 201804, People’s Republic of ChinaCorrespondence: Zhigang GaoShanghai University of Political Science and Law, No. 7989, Wai Qingsong Highway, Qingpu District, Shanghai, 201701, People’s Republic of ChinaTel +86 21-39225126Email gaozhigang@shupl.edu.cnPurpose: Employee voice has been considered as an important means to understand the cutting-edge information, gain social status and performance advantage for leaders, employees and the organization, respectively. However, our knowledge about how and when employees’ emotions influence voice remains limited.Design/Methodology/Approach: In order to better illustrate the role of emotion on voice, based on emotion as social information theory and similarity attraction theory, we proposed a research model through which emotion recognition ability affects voice via perceived ambidextrous leadership. A sample of 182 comprised of full-time employees and their 43 immediate supervisors was collected through questionnaires in China, and analyzed via hierarchical regression method.Findings: We found that subordinate’s emotional recognition ability has a significant positive effect on promotive and prohibitive voice, and that perceived ambidextrous leadership plays a significant mediating role between subordinate’s emotional recognition ability and promotive voice, while no mediating role is found between subordinate’s emotional recognition ability and prohibitive voice. In addition, in contrast to leader-subordinate gender dissimilarity, leader-subordinate gender similarity is more effective in strengthening the impact of emotion recognition ability on perceived ambidextrous leadership, and thus promotes employee voice.Originality/Value: This research not only advances our understanding of employee voice, but also provides specific reference for management practices from the perspective of gender.Keywords: emotion recognition ability, perceived ambidextrous leadership, leader-subordinate gender similarity, promotive voice, prohibitive voice

Yubin Tian,1,2,&ast; Yong Zhou,2,&ast; Junhui Liu,1,2 Lei Yi,2 Zhaojia Gao,2,3 Kai Yuan,1,3 Jichun Tong2,3 1School of Medical, Dalian Medical University, Dalian, People’s Republic of China; 2The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 3Heart and Lung Disease Laboratory, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Yuan; Jichun Tong, Email yuankai202001@163.com; tongjichun2012@163.comPurpose: To investigate the expression profile of systemic RNA interference deficient-1 transmembrane family member 1 (SIDT1) in patients with non-small cell lung cancer (NSCLC) and assess its prognostic value and immune infiltration.Materials and Methods: A tissue microarray (TMA) was purchased containing 60 paired NSCLC tissues and matched para-tumor tissues, and another TMA was constructed comprising 140 NSCLC tissues. Then, immunohistochemical staining and scoring were performed. Finally, we evaluated the expression profiles and prognostic values of SIDT1 in NSCLC. Correlation between SIDT1 gene expression and the immune microenvironment of NSCLC was investigated using the ESTIMATE and CIBERSORT algorithms.Results: SIDT1 was mainly detected in the cytoplasm and the cell membrane. SIDT1 expression was significantly higher in tumor tissues than in para-tumor tissues. High expression of SIDT1 was correlated with the NSCLC stage. High SIDT1 expression signals worsening overall survival (OS) in NSCLC patients, especially in stage I. In LUSC, high SIDT1 expression is an independent prognostic factor for worsening OS.Conclusion: High SIDT1 expression predicted a low survival rate in LUSC patients, suggesting it may be a potential target for prognostic assessment of NSCLC patients.Keywords: NSCLC, prognosis, TMA, immune infiltration, SIDT1

Wu Y, Gao Z, Zhang J. Neuropsychiatr Dis Treat. 2020;16:2633–2647. At the authors request, the Editor and Publisher of Neuropsychiatric Disease and Treatment are retracting the published article. The authors informed the journal that they were unable to verify the reported findings and requested to retract the article. Given that additional concerns had also been raised about the reliability of the findings, the Editor agreed with the authors decision. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Sun P, Huang W, Kang L, Jin M, Fan B, Jin H, Wang Q, Gao Z. Int J Nanomedicine. 2017;12:3221–3234 At the authors request, the Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. An investigation by the Publisher found overlap in images from Figure 5. Specifically, The image from Figure 5, 0 h, Blank, has been duplicated with the same image for Figure 5, 0 h, H6R6-NP. The image from Figure 5, 0h, Naked siRNA, has been duplicated with the same image for Figure 5, 0 h, H6R6-NP. The image from Figure 5, 24 h, Naked siRNA, has been duplicated with the same image for Figure 5, 24 h, H6R6-NP. The image from Figure 5, 48 h, Naked siRNA, has been duplicated with the image for Figure 5, 48 h, CS-NP. The authors cooperated with the investigation and provided data associated with the study. However, despite the authors’ assistance, they were unable to provide a satisfactory explanation for how the images came to be duplicated, and the validity of the published work could not be verified. The decision was made to retract the article and the authors agreed with this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Tiejian Li,1,2 Jingyang Sun,1,2 Yinqiao Du,2,3 Zhisen Gao,2,3 Haiyang Ma,2,3 Yonggang Zhou1– 3 1Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 2Department of Orthopedics, The First Medical Center of PLA General Hospital, Beijing, 100048, People’s Republic of China; 3Senior Department of Orthopedics, The Fourth Medical Center of PLA General Hospital, National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Beijing, 100853, People’s Republic of ChinaCorrespondence: Yonggang ZhouDepartment of Orthopedics, PLA General Hospital, Fuxing Road, Haidian District, Beijing, People’s Republic of ChinaTel +8613801287599Email ygzhou301@163.comPurpose: Total knee arthroplasty (TKA) is widely used as a treatment for knee osteoarthritis. Few studies have analysed the factors affecting the squatting ability of patients after TKA. The purpose of this study was to comprehensively analyse the factors affecting squatting ability after TKA and to determine which ones are important.Patients and Methods: Three hundred primary TKA cases with a minimum 3-year follow-up were retrospectively analysed. All patients received a conventional posterior-stabilized TKA implant and underwent a standard perioperative care pathway. The patients were divided into two groups according to the squatting position and knee flexion angle while weight-bearing (Group I – inability to squat group, Group II – ability to squat group). Demographic, operative, and clinical data were collected. Radiographic assessment included joint line elevation, patellar position, posterior condylar offset (PCO), etc. Statistical analysis of the effect of all the above factors on squatting ability was performed.Results: The preoperative range of motion and joint line of Group I were 82.9± 12.6 and 3.24± 1.07, respectively, and those of Group II were 107± 9.6 and 1.83± 0.89 respectively. The univariate analysis showed that age, prosthesis size, preoperative ROM and joint line position were correlated with squatting ability. But in the final multivariate analysis, joint line position and preoperative ROM were independent influencing factors that affected squatting ability after TKA (p value < 0.01).Conclusion: Preoperative ROM and joint line position were independent influencing factors affecting squatting ability after TKA. Patients should be counseled accordingly and be made to understand these factors. To ensure that patients can squat postoperatively, we should improve surgical techniques to control joint line elevation.Keywords: squatting ability, joint line elevation, preoperative ROM, total knee arthroplasty

ZongAn Chen,1,&ast; Zhen Gao,1,&ast; LingLing Xia,1 XiaoQing Wang,2,&ast; LiMing Lu,3,&ast; XiaoLi Wu1,&ast; 1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Orthopedics, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: XiaoLi WuDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of ChinaTel +86-2163089567Email wuxiaoli528@126.comPurpose: Recent studies have confirmed the important role of chronic inflammation in keloid; however, mechanism of chronic inflammation in keloid tissue remains largely unclear, especially the dynamic of infiltrated inflammatory cells.Patients and Methods: Tissue and blood samples collected from keloid patients and healthy subjects were studied by immunohistochemistry and flow cytometry. Fibroblasts from keloid scars and normal skin were isolated by enzymic digestion.Results: We found that CXCL12 expression was elevated which was correlated with decreased dipeptidyl peptidase-4 (DPP4) expression in keloid scars relative to mature scars. In vitro studies suggested that autocrine transforming growth factor β 1 (TGF-β 1) in keloid-derived fibroblasts negatively regulated DPP4 expression which inhibited the reduction of extracellular CXCL12 levels by DPP4. Furthermore, immunofluorescence showed that most fibroblasts in keloid scars were DPP4lowTGFβ 1high compared with DPP4highTGFβ 1low fibroblasts in normal skin tissue, which facilitated extracellular CXCL12 accumulation in fibroblasts in keloid scars. Furthermore, we found that most circulating leukocytes in peripheral blood and tissue-infiltrated inflammatory cells in keloid scars expressed the C-X-C motif chemokine receptor 4 (CXCR4) instead of CXCR7, indicating that the chemotaxis driven by CXCL12 is likely to be mediated mainly by CXCR4.Conclusion: Our study indicated that the TGF-β/DPP4/CXCL12 axis may contribute to chronic inflammation in keloid scars by recruiting inflammatory cells through the CXCR4 receptor.Keywords: keloid, chemokines, inflammation, DPP4, CXCL12, TGF-β 1

Mingji Jin,1,2,&ast; Yan Hou,1– 3,&ast; Xiuquan Quan,1,2,4,&ast; Liqing Chen,1,2 Zhonggao Gao,1,2 Wei Huang1,2 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of China; 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of China; 3Department of Pharmacy, Yanbian University, Yanji, Jilin, 133000, People’s Republic of China; 4Department of Emergency Medicine, Affiliated Hospital of Yanbian University, Yanji, Jilin, 133000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhonggao Gao; Wei Huang Tel +86 010 63028096; +86 010 63026505Email zggao@imm.ac.cn; huangwei@imm.ac.cnBackground: The dual-loaded nano-delivery system can realize chemotherapeutic drug and small interfering RNA (siRNA) co-loading as well as enhance the therapeutic effect of drugs on tumors through a synergistic effect, while reducing their toxic and side effects on normal tissues.Methods: Previously, we developed layered smart nanoparticles (NPs) to co-deliver survivin siRNA as well as small molecule drugs for lung cancer. In this study, we used such smart NPs to co-deliver paclitaxel (PTX) and siRNA against vascular endothelial growth factor (VEGF) gene for breast cancer therapy in mice models. For the prepared NPs, characterizations such as particle size, zeta potential, gel electrophoresis imaging and in vitro stability were investigated. Then, 4T1 cells were used to evaluate the in vitro VEGF silencing capacity, tumor cell inhibitory and anti-apoptotic abilities. Finally, an orthotopic model of mouse breast cancer was established to evaluate the in vivo antitumor effects and safety properties of PTX-siRNAVEGF-NPs.Results: We prepared PTX-siRNAVEGF-NPs with particle size of 85.25 nm, PDI of 0.261, and zeta potential of 5.25 mV. The NPs with VEGF siRNA effectively knocked down the expression of VEGF mRNA. Cell counting kit-8 (CCK-8) and apoptosis assays revealed that the PTX-siRNAVEGF-NPs exhibited antiproliferation effect of PTX on 4T1 cells. The in vivo anti-tumor study indicated that PTX-siRNAVEGF-NPs could exert an antitumor effect by inhibiting the formation and development of new blood vessels in tumor tissues, thereby cutting off nutrient and blood supplies required for tumor tissue growth. Both the anti-tumor efficacy and in vivo safety of the PTX-siRNAVEGF-NPs group were better than that of the PTX-NPs and siRNAVEGF-NPs groups.Conclusion: The combination of PTX and VEGF siRNA exerts good antitumor effect on 4T1 tumor cells. This study provides a theoretical and practical basis for breast cancer therapy.Keywords: paclitaxel, VEGF siRNA, breast cancer, co-delivery

Di Mei,1,&ast; Xiaolong Guo,2,&ast; Yirong Wang,1 Xiaofei Huang,1 Li Guo,1 Pengfei Zou,3 Delong Ge,1 Xinxin Wang,1 Wenhui Lee,4 Tongyi Sun,1 Zhiqin Gao,1 Yuanyuan Gao3 1School of Life Science and Technology, Shandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biopharmaceuticals, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 2School of Basic Medicine, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 3School of Pharmacy, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 4Key Laboratory of Animal Models and Human Disease Mechanism, Institute of Zoology, Kunming, Yunnan, 650233, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqin GaoSchool of Life Science and Technology, Shandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biopharmaceuticals, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of ChinaTel +86 5368462066Email zhiqingao2013@163.comYuanyuan GaoSchool of Pharmacy, Weifang Medical University, Baotong Road, Weifang, Shandong Province, 261053, People’s Republic of ChinaTel +86 536 846 2067Email yyg20062006@126.comBackground: The treatment of Staphylococcus aureus (S. aureus)-infected wounds is difficult. It causes extreme pain to tens of thousands of patients and increases the cost of medical care. The antimicrobial peptide OH-CATH30 (OH30) has a good killing activity against S. aureus and can play a role in accelerating wound healing and immune regulation. Therefore, it shows great potential for wound healing.Purpose: The aim of this study was to overcome the short half-life and easy enzymolysis of OH30 by using graphene oxide conjugated with polyethylene glycol to load OH30 (denoted as PGO-OH30), as well as to evaluate its effect on wounds infected by S. aureus.Methods: PGO-OH30 nanoparticles were prepared by π–π conjugation and characterized. Their cell cytotoxicity, cell migration, infectious full-thickness dermotomy models, and histopathology were evaluated.Results: Characterization and cytotoxicity experiments revealed that the PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability. Cell-migration experiments showed that PGO-OH30 could promote the migration of human immortalized keratinocytes (HaCaT) cells compared with the control group (P< 0.05). In a mouse model of skin wound infection, PGO-OH30 accelerated skin-wound healing and reduced the amount of S. aureus in wounds compared with the control group (P< 0.05). In particular, on day 7, the number of S. aureus was 100 times lower in the PGO-OH30 group than in the control group.Conclusion: The PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability, indicating its good therapeutic effect on a skin wound-infection model.Keywords: OH-CATH30, bacterial infection, graphene oxide, skin wound

Yating Jian,1 Lili Zhao,1 Baixue Jia,2 Xu Tong,2 Tao Li,1 Yulun Wu,1 Xiaoya Wang,1 Zhen Gao,1 Yu Gong,1 Xuelei Zhang,2 Huqing Wang,1 Ru Zhang,1 Lei Zhang,1 Zhongrong Miao,2 Guilian Zhang1 On behalf of ANGEL-ACT Study Group1Department of Neurology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, Shaanxi, People’s Republic of China; 2Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Guilian ZhangDepartment of Neurology, the Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwulu, Xi’an, 710004, Shaanxi, People’s Republic of ChinaTel +86 29 87679346Fax +86 29 87678599Email zhgl_2006@126.comZhongrong MiaoDepartment of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South West Road, Fengtai District, Beijing, People’s Republic of ChinaTel +8613601243293Email zhongrongm@163.comPurpose: Elderly people represent a growing stroke population with different pathophysiological states than younger. Whether intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is beneficial for elderly patients remains unclear. This study compared the efficacy and safety between elderly patients treated with MT alone and those treated with both IVT and MT.Patients and Methods: Patients aged ≥ 65 years who were eligible for IVT within 4.5 h from symptom onset were selected from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) registry, a prospective registry program for patients with endovascular treatment from 111 Chinese stroke centers. The primary efficacy outcome was the 90-day modified Rankin Scale score. We compared efficacy and safety outcomes using ordinal or binary logistic regression or a generalized linear model.Results: In total, 482 elderly patients were included: 187 (38.8%) received IVT and MT (bridging MT) and 295 (61.2%) received MT alone (direct MT). There was no significant difference in the 90-day modified Rankin Scale score between the two groups (median: 4 vs 4 points, respectively; adjusted β=− 0.048, P=0.822). The direct MT group had a shorter onset-to-puncture time (225 vs 255 min, respectively; adjusted β=− 55.074, P=0.002) and a lower rate of parenchymal hemorrhage type 2 within 24 h (2.80% vs 6.63%, respectively; adjusted odds ratio [OR]=0.287, 95% confidence interval [CI]=0.096– 0.856, P=0.025). In addition, the direct MT group showed a trend toward a lower incidence of sICH (5.67% vs 10.06%, adjusted OR=0.453, P=0.061), procedure-related complications (7.12% vs 12.30%, adjusted OR=0.499, P=0.052) and distal or new territorial embolization (4.07% vs 6.95%, adjusted OR=0.450, P=0.093).Conclusion: Direct MT had similar efficacy to bridging MT in terms of the 90-day functional outcome in elderly patients, whereas bridging MT had a longer onset-to-puncture time and increased risk of hemorrhagic transformation and procedure-related complications.Keywords: acute ischemic stroke, endovascular treatment, intravenous thrombolysis, elderly patients