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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,* Li Liu,2,* 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*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