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Yuping Zhu,1 Xunfu Lai,1 Mengting Wang,2 Xin Tang,1 Tianyi Wan,3 Bin Li,1 Xiaoming Liu,1 Jialin Wu,1 Lei He,1 Yulin He1 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Radiology, Yichang Central People’s Hospital, Yichang, People’s Republic of China; 3Department of Radiology, Jiangxi Provincial People’s Hospital, Nanchang, People’s Republic of ChinaCorrespondence: Yulin He, Department of Radiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 0791 8869 3802, Email ndyfy02171@ncu.edu.cnObjective: To separate the resting-state network of patients with dental pain using independent component analysis (ICA) and analyze abnormal changes in functional connectivity within as well as between the networks.Patients and Methods: Twenty-three patients with dental pain and 30 healthy controls participated in this study. We extracted the resting-state functional network components of both using ICA. Functional connectivity differences within 14 resting-state brain networks were analyzed at the voxel level. Directional interactions between networks were analyzed using Granger causality analysis. Subsequently, functional connectivity values and causal coefficients were assessed for correlations with clinical parameters.Results: Compared to healthy controls, we found enhanced functional connectivity in the left superior temporal gyrus of anterior protrusion network and the right Rolandic operculum of auditory network in patients with dental pain (p< 0.01 and cluster-level p< 0.05, Gaussian random field corrected). In contrast, functional connectivity of the right precuneus in the precuneus network was reduced, and were significantly as well as negatively correlated to those of the Visual Analogue Scale (r=− 4.93, p=0.017), Hamilton Anxiety Scale (r=− 0.46, p=0.027), and Hamilton Depression Scale (r=− 0.563, p< 0.01), using the Spearman correlation analysis. Regarding the causal relationship between resting-state brain networks, we found increased connectivity from the language network to the precuneus in patients with dental pain (p< 0.05, false discovery rate corrected). However, the increase in causal coefficients from the verbal network to the precuneus network was independent of clinical parameters.Conclusion: Patients with toothache exhibited abnormal functional changes in cognitive-emotion-related brain networks, such as the salience, auditory, and precuneus networks, thereby offering a new imaging basis for understanding central neural mechanisms in dental pain patients.Keywords: toothache, independent component analysis, resting-state networks, Granger causality

Shunsen Huang,1 Xiaoxiong Lai,1,2 Li Ke,1 Yajun Li,3 Huanlei Wang,1 Xinmei Zhao,1 Xinran Dai,1 Yun Wang1 1State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, 100875, People’s Republic of China; 2Institute of Digital Education, China National Academy of Educational Sciences, Beijing, 100088, People’s Republic of China; 3Shenzhen Institute of Education Sciences, Shenzhen, 518001, People’s Republic of ChinaCorrespondence: Yun Wang, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, No. 19, XinJieKouWai St., HaiDian District, Beijing, 100875, People’s Republic of China, Email wangyun@bnu.edu.cnBackground: The emergence of new technologies, such as artificial intelligence (AI), may manifest as technology panic in some people, including adolescents who may be particularly vulnerable to new technologies (the use of AI can lead to AI dependence, which can threaten mental health). While the relationship between AI dependence and mental health is a growing topic, the few existing studies are mainly cross-sectional and use qualitative approaches, failing to find a longitudinal relationship between them. Based on the framework of technology dependence, this study aimed to determine the prevalence of experiencing AI dependence, to examine the cross-lagged effects between mental health problems (anxiety/depression) and AI dependence and to explore the mediating role of AI use motivations.Methods: A two-wave cohort program with 3843 adolescents (Male = 1848, Mage = 13.21 ± 2.55) was used with a cross-lagged panel model and a half-longitudinal mediation model.Results: 17.14% of the adolescents experienced AI dependence at T1, and 24.19% experienced dependence at T2. Only mental health problems positively predicted subsequent AI dependence, not vice versa. For AI use motivation, escape motivation and social motivation mediated the relationship between mental health problems and AI dependence whereas entertainment motivation and instrumental motivation did not.Discussion: Excessive panic about AI dependence is currently unnecessary, and AI has promising applications in alleviating emotional problems in adolescents. Innovation in AI is rapid, and more research is needed to confirm and evaluate the impact of AI use on adolescents’ mental health and the implications and future directions are discussed.Keywords: artificial intelligence dependence, mental health, anxiety, depression, artificial intelligence use motivation, adolescents

Wen Wei,1,2,&ast; Chengwen Xie,3,&ast; Ronghua Cao,4,&ast; Yanwen Que,3 Xuejing Zhong,5 Zheyuan Chen,6 Fenyan Lv,6 Qianqian Kang,6 Ruiyu Lin,6 Baozhen Cao,7 Xiaomin Lai,7 Mei Tu1 1Department of Endocrinology, Fujian Longyan First Hospital, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 2Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 3Department of Ultrasonography, Fujian Longyan First Hospital, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 4Department of Nuclear Medicine, Fujian Longyan First Hospital, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 5Department of Science and Education, Fujian Longyan First Hospital, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 6Department of Endocrinology, Fujian Longyan First Hospital, Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, Fujian Longyan First Hospital, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei Tu, Department of Endocrinology, Fujian Longyan First Hospital, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China, Tel +86 5972958989, Fax +86 5972292374, Email tm13859596628@163.comObjective: This study aims to examine the clinical significance of ultrasound evaluation of the gastrocnemius muscle (GM) in identifying sarcopenia in patients with type 2 diabetes (T2D).Methods: One hundred and fifty-three patients with T2D were included in this study. We measured the appendicular skeletal muscle mass index (ASMI), handgrip strength, and 6-meter walking speed. The US-derived muscle thickness (MT), cross-sectional area (CSA), and shear wave ultrasound elastography (SWE) of GM were also measured. We assessed the correlations between clinical indicators and US features. The model for screening sarcopenia was established using stepwise logistic regression. Stepwise linear regression was used to identify a set of variables that jointly estimated ASMI. The model’s ability to identify sarcopenia and low muscle mass was assessed by receiver operating characteristic (ROC) curve analysis.Results: The prevalence of sarcopenia in this study was 24.2%. The CSA, MT and SWE values of the patients with sarcopenia were lower than those of patients without sarcopenia (all p < 0.05). ASMI was positively correlated with CSA (r = 0.56, p < 0.001) and MT (r = 0.39, p < 0.001). Handgrip strength was positively correlated with CSA (r = 0.45, p < 0.001), MT (r = 0.25, p < 0.001), and SWE (r = 0.26, p = 0.002). A diagnostic model for sarcopenia was established with a sensitivity of 81.1%, specificity of 75.0%, and an area under the curve (AUC) of 0.800. The estimated ASMI equation was developed and found to have a positive correlation with actual ASMI (r = 0.70, p < 0.001). It was also effective in diagnosing low muscle mass, with an AUC of 0.787 for males and 0.783 for females.Conclusion: Ultrasonographic assessment of the gastrocnemius muscle was found to be a useful and convenient method for detecting sarcopenia in patients with T2D.Keywords: sarcopenia, ultrasound, shear wave elastography, gastrocnemius muscle, T2D

Yanjuan Jiang,1 Jianting Zhu,2 Xiaoyang Lai1 1Department of Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Intensive Care Unit, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Xiaoyang Lai, Department of Endocrinology, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Donghu District, Nanchang, 330006, People’s Republic of China, Tel +8613607916298, Email 1640852510@qq.comBackground: We established a nomogram for ketosis-prone type 2 diabetes mellitus (KP-T2DM) in the Chinese adult population in order to identify high-risk groups early and intervene in the disease progression in a timely manner.Methods: We reviewed the medical records of 924 adults with newly diagnosed T2DM from January 2018 to June 2021. All patients were randomly divided into the training and validation sets at a ratio of 7:3. The least absolute shrinkage and selection operator regression analysis method was used to screen the predictors of the training set, and the multivariable logistic regression analysis was used to establish the nomogram prediction model. We verified the prediction model using the receiver operating characteristic (ROC) curve, judged the model’s goodness-of-fit using the Hosmer-Lemeshow goodness-of-fit test, and predicted the risk of ketosis using the decision curve analysis.Results: A total of 21 variables were analyzed, and four predictors—hemoglobin A1C, 2-hour postprandial blood glucose, 2-hour postprandial C-peptide, and age—were established. The area under the ROC curve for the training and validation sets were 0.8172 and 0.8084, respectively. The Hosmer-Lemeshow test showed that the prediction model and validation set have a high degree of fit. The decision curve analysis curve showed that the nomogram had better clinical applicability when the threshold probability of the patients was 0.03– 0.79.Conclusion: The nomogram based on hemoglobin A1C, 2-hour postprandial blood glucose, 2-hour postprandial C-peptide, and age has good performance and can serve as a favorable tool for clinicians to predict KP-T2DM.Keywords: diabetic ketoacidosis, nomogram, prediction model, ketosis-prone type 2 diabetes mellitus

Yingying Lin,1,&ast; Xiaofan Lai,1,&ast; Tianxiang Lei,2,&ast; Yuan Qiu,3 Qiwen Deng,1 Qi Liu,1 Zhongxing Wang,1 Wenqi Huang1 1Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenqi Huang; Zhongxing Wang, Email huangwq@mail.sysu.edu.cn; wzhxing@mail.sysu.edu.cnBackground: Idiopathic pulmonary fibrosis (IPF) is a disease with unclear etiology and a poor prognosis. Although the involvement of neutrophils in IPF pathogenesis has been suggested, the exact nature of this relationship remains unclear.Methods: We analyzed data from the Gene Expression Omnibus (GEO) using immune infiltration analysis, weighted gene co-expression network analysis (WGCNA), and consensus cluster analysis. Neutrophil-related genes and hub genes related to neutrophils were identified and differentially expressed between IPF patients and healthy controls. We also validated the expression differences of hub genes in a bleomycin-induced mice model.Results: Immune infiltration analysis revealed a significantly decreased percentage of neutrophils in the lung tissue of IPF patients compared with healthy controls (P< 0.001) in both the train and validation sets. Neutrophil-related genes in IPF were identified by WGCNA, and functional enrichment analysis showed that these genes were mainly involved in the cytokine-cytokine receptor interaction pathway and correlated with lung disease, consistent with DEGs between IPF and healthy controls. Eight hub genes related to neutrophils were identified, including MMP16, ARG1, IL1R2, PROK2, MS4A2, PIR, and ZNF436. Consensus cluster analysis revealed a low neutrophil-infiltrating cluster that was correlated with IPF (P< 0.001), and a principal component analysis-generated score could distinguish IPF patients from healthy controls, with an area under the curve of 0.930 in the train set and 0.768 in the validation set. We also constructed a diagnostic model using hub genes related to neutrophils, which showed a reliable diagnostic value with an area under the curve of 0.955 in the train set and 0.995 in the validation set.Conclusion: Our findings provide evidence of a low neutrophil-infiltrating characteristic in the IPF microenvironment and identify hub genes related to neutrophils that may serve as diagnostic biomarkers for the disease.Keywords: neutrophils, idiopathic pulmonary fibrosis, immune infiltration analysis, weighted gene co-expression network analysis, consensus cluster analysis, diagnostic model, biomarkers

Nan Liu,&ast; Ziyu Zheng,&ast; Jinli Liao,&ast; Jiaxin Li, Zhen Yang, Xiaojuan Lai Department of Emergency Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojuan Lai; Zhen Yang, Email laixj3@mail.sysu.edu.cn; yangzh8@mail.sysu.edu.cnIntroduction: Nursing knowledge, critical thinking ability, and self-perceived confidence are imperative to nursing skills in professional nursing practice. Therefore, nurse educators are required to use teaching strategies that will help promote their knowledge, critical thinking, and self-confidence in complex contents such as the nursing of acute upper gastrointestinal bleeding (AUGIB).Purpose: This study compares the effect of student-led and instructor-led ward-round training methods on knowledge acquisition, critical thinking ability, and self-perceived confidence during AUGIB sessions.Methods: Forty nursing students in the first year of the Emergency Nursing Residency Program were randomly divided into a student-led ward round training group (SG) and an instructor-led ward round training group (IG) with a ratio of 1:1. A knowledge quiz, critical thinking ability test, and self-perceived confidence questionnaire were performed before and after the ward round training to assess both groups of students for their knowledge acquisition, critical thinking ability, and self-perceived confidence improvement. Feedback questionnaires were conducted after the training to evaluate students’ perspectives and interests concerning the teaching module.Results: The scores of the post-training quiz were significantly higher than that of the pre-training quiz in both the SG (44.10± 2.92 vs 31.10± 4.27, p< 0.001) and IG (32.35± 2.21 vs 30.55± 2.24, p=0.01). In the post-training quiz, scores achieved by the students from the SG (44.10± 2.92) were significantly higher than those achieved by the students from the IG (32.35± 2.21, p< 0.001). The level of self-perceived confidence improved significantly after ward round training in the SG (p< 0.001). However, there was no statistically significant difference in the IG with respect to the change from pre- to post-training (p=0.43).The students’ critical thinking ability improved significantly in the SG (14.95± 2.58 vs 7.10± 1.79, p< 0.001), while no significant improvement was found in the IG (7.91± 2.28 vs 6.52± 2.21, p=0.07) after ward round training.Conclusion: The teaching method of SWRT improves nursing students’ knowledge acquisition, critical thinking ability, and self-perceived confidence in AUGIB.Keywords: student-led ward round training, knowledge acquisition, critical thinking ability, self-perceived confidence, nursing education

Weihao Chen,1– 4 Yanmin Zhao,1– 4 Yi Luo,1– 4 Jian Yu,1– 4 Huarui Fu,1– 4 Xiaoyu Lai,1– 4 Lizhen Liu,1– 4 Yishan Ye,1– 4 Jingsong He,1– 4 Jie Sun,1– 4 Weiyan Zheng,1– 4 Yi Zhao,1– 4 Guoqing Wei,1– 4 Zhen Cai,1– 4 He Huang,1– 4 Jimin Shi1– 4 1Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, People’s Republic of China; 3Institute of Hematology, Zhejiang University, Hangzhou, People’s Republic of China; 4Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, People’s Republic of ChinaCorrespondence: Jimin Shi; He Huang, Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, People’s Republic of China, Tel/Fax +86-0571-87236706, Email shijimin@zju.edu.cn; huanghe@zju.edu.cnBackground: Bloodstream infection (BSI) is a common and serious complication that may lead to high mortality during the different phases after hematopoietic stem cell transplant (HSCT). We investigated BSI in patients undergoing HSCT to provide an appropriate clinical anti-infection experience and improve the prognosis of recipients with BSI after HSCT.Methods: A total of 105 patients with BSI after HSCT at our center from January 2015 to June 2020 were included in this retrospective study. We analyzed the clinical and microbiological data, and the risk factors for mortality at 3 months after BSI.Results: Of the 1141 HSCT recipients, 105 (9.2%) patients presented with 122 episodes of BSI, of which we isolated 85 (65.9%) gram-negative bacteria, 32 (24.8%) gram-positive bacteria and 12 (9.3%) fungi. Multidrug-resistant bacteria (MDR) were more than 70% of all pathogens and carbapenem-resistant organisms (CRO) were 25.6%. There were 55 episodes of BSI in the pre-engraftment phase and 67 episodes in the post-engraftment phase. The mortality of post-engraftment BSI was significantly higher than that of pre-engraftment (56.7% vs 32.7%, p = 0.005). Through multivariate analysis, the independent risk factors for all-cause mortality at 3 months after BSI were higher levels of procalcitonin (PCT), failure to cover appropriate antibiotics timely, and CRO BSI in pre-engraftment period or multidrug-resistant gram-negative bacteria (MDRGNB) BSI in post-engraftment period.Conclusion: Although the incidence of BSI was lower after HSCT, MDR-dominated BSI had a high mortality rate. Rapid identification of infection or pathogens’ classification with various testing methods and the more sensible and timely antibiotic cover are critical to the outcome of BSI after HSCT.Keywords: bloodstream infection, hematopoietic stem cell transplantation, multidrug-resistant bacteria, all-cause mortality

Jianpeng Yu,1,&ast; Qi Zhou,1,&ast; Ying Xu,1,&ast; Tieyun Wang,1 Jun Du,1 Lifang Zhao,1 Juan Li,1 Haiyan Wang,1 Qianqian Xu,2 Xueli Lai,1 Zhiyong Guo1 1Department of Nephrology, Shanghai Changhai Hospital, Shanghai, People’s Republic of China; 2Department of Rheumatology and Immunology, Shanghai Changhai Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueli Lai; Zhiyong Guo, Email laixueli_changhai@163.com; drguozhiyong@163.comObjective: To investigate the relationship between serum folate (FA) levels and residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD) patients.Methods: Clinical data were collected from 180 hospitalized patients who received CAPD regularly. Patients were divided into the FA deficiency group and the FA non-deficiency group according to serum FA level. Data on age, sex, PD vintage, hemoglobin, mean corpuscular volume, serum FA, total Kt/V, residual kidney Kt/V, peritoneum Kt/V, creatinine clearance (Ccr), ultrafiltration volume, cystatin C (cytC), serum creatinine (Scr), urea nitrogen, retinol-binding protein and the primary disease were gathered from 2 groups. Statistical methods were used to analyze the relationship between serum FA level and RRF.Results: Peritoneal Kt/V, cytC, Scr were higher, and residual kidney Kt/V was lower in FA deficiency group than in non-deficiency group. Univariate correlation showed the peritoneal Kt/V, cytC, Scr negatively correlated with serum FA while residual kidney Kt/V positively correlated with serum FA, and there was a simple linear regression relationship between serum FA and residual kidney Kt/V. Differences were statistically significant (P< 0.05).Conclusion: There is a relationship between serum FA and RRF in CAPD patients. Prospective studies or trials should be performed to clarify the importance of FA supplementation on RRF during peritoneal dialysis.Keywords: folate, continuous ambulatory peritoneal dialysis, residual renal function

Han Li,1 Dongmei Han,1 Haiyan Wang,2 Dan Shu,1 Lei Xu,1 Liufang Hou,1 Ying Xu,2 Xueli Lai2 1The Rehabilitation Department of Nephrology, The First Rehabilitation Hospital of Shanghai, Shanghai, People’s Republic of China; 2Department of Nephrology, Shanghai Changhai Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ying Xu; Xueli Lai, Department of Nephrology, Shanghai Changhai Hospital, Shanghai, 200433, People’s Republic of China, Email ying.looy@hotmail.com; laixueli_changhai@163.comObjective: To analyze the association between vitamin D and the performance of activity of daily living in the elderly.Methods: A total of 94 patients over the age of 65 were eligible to participate if they had undergone a bone mineral density test and if they were in a stable health condition. Subjects were further divided into two groups according to activity of daily living (ADL): the score over 40 of the patients as the high ADL group and the below as the low ADL group.Results: According to univariate analysis, the mean of total hip T score, serum creatinine/cystatin C ratio (CCR), and vitamin D were significantly different between the two groups (P=0.024, 0.008, 0.010). Multivariate ORs showed that the CCR (OR: 0.948; 95%CI: 0.910– 0.989; P=0.013) and vitamin D (OR: 865; 95%CI: 0.752– 0.994; P=0.047) were inversely associated with having low ADL. Furthermore, on multiple linear regression analysis, the Barthel ADL index was related to geriatric nutritional risk index (GNRI), CCR and vitamin D but independent of patients’ age with the slope of 0.732, 0.539, and 0.689 separately, reflected the stronger relative within the variables.Conclusion: We demonstrated that there is a negative correlation of CCR and vitamin D with having low ADL in elderly population. Monitoring the trend of serum vitamin D and CCR, may have a role in the early detection of low ADL with loss of muscle mass and strength in the population of the elderly.Keywords: vitamin D, CCR, elderly, ADL, muscle mass

Zhi Yang,1– 3 Peng Duan,2 Weihong Li,2 Ronghui Nie,2,3 Xiaoyang Lou,2,4 Lina Wang,2 Kexia Wu,2 Jiang Liu,2 Ping Tu,2 Xiaoyang Lai1 1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330008, Jiangxi, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Third Hospital of Nanchang, Nanchang, 330000, Jiangxi, People’s Republic of China; 3Jiangxi Medical College of Nanchang University, Nanchang, 330036, Jiangxi, People’s Republic of China; 4Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi, People’s Republic of ChinaCorrespondence: Xiaoyang Lai Tel +86 13607916298Email 1640852510@qq.comObjective: We investigated the relationship between thyroid hormones and the risk of diabetic kidney disease (DKD) progression.Methods: A total of 452 patients with type 2 diabetes were included, and a cross-sectional analysis was performed. Urine albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used to diagnose persistent albuminuria and stage chronic kidney disease, respectively. The Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline was used to describe the risk of DKD progression (low, moderate, and high or very high risks).Results: The DKD group had higher levels of thyroid-stimulating hormone (TSH) and lower levels of free triiodothyronine (FT3) and free thyroxine (FT4) than the non-DKD group. The prevalence of thyroid dysfunction in the DKD group was significantly higher than in the non-DKD group, especially the prevalence of subclinical hypothyroidism. FT3 levels decreased gradually with the deterioration of DKD. TSH levels increased with an increasing KDIGO category. FT3 and FT4 levels were negatively correlated with serum creatinine levels and ACR, and positively correlated with eGFR. Contrastingly, TSH was positively correlated with ACR, and negatively correlated with eGFR. After adjustment, an increase in FT3 levels significantly reduced the risk of DKD [odds ratio, OR (95% confidence interval, CI)=0.58 (0.42– 0.79)] and DKD progression [ORs (95% CIs)=0.65 (0.45– 0.93) for the moderate risk group and 0.50 (0.33– 0.74) for the high or very high-risk group, using the low-risk group as a reference]. FT3 levels below 4.30 pmol/L in men and 3.99 pmol/L in women were the cut-off points for an increased risk of DKD progression.Conclusion: Low FT3 level is an independent risk factor for DKD and DKD progression. FT3 ≤ 4.30 pmol/L in men and ≤ 3.99 pmol/L in women will greatly increase the risk of kidney disease progression in patients with type 2 diabetes.Keywords: thyroid hormone, prognosis of chronic kidney disease, type 2 diabetes mellitus

Ying Wang,1 Xinping Zhang,1 Xuemei Wang,1 Xiaoquan Lai2 1School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, People’s Republic of China; 2Department of Nosocomial Infection Management, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, People’s Republic of ChinaCorrespondence: Xinping ZhangSchool of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaTel +86 133 4995 0095Email xpzhang602@hust.edu.cnPurpose: Empirical antibiotic therapy should follow the local bacterial susceptibility, and the breakpoints revisions of the antimicrobial susceptibility testing can reflect the changes in the antimicrobial susceptibility of bacteria. This study aimed to analyze whether the changes in the antimicrobial susceptibility to antibiotics caused by the breakpoint revision will affect the empirical antibiotic therapy and its appropriateness.Patients and Methods: A retrospective study was conducted among 831 hospitalized patients infected by Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa from April 10, 2018, to April 11, 2020. We evaluated the appropriateness of empirical therapy based on the antimicrobial susceptibility testing results. The rate of empirical use and appropriateness of fluoroquinolones was calculated, and logistic regression was used to analyze influencing factors of empirical use of fluoroquinolones.Results: The susceptibility rate of the three bacteria to levofloxacin (50.78% vs 32.06%) and ciprofloxacin (48.45% vs 21.90%) was decreased (P< 0.001), while the resistance rate to levofloxacin (45.74% vs 58.73%) and ciprofloxacin (46.90% vs 66.67%) was increased (P< 0.001) after the breakpoints revision. The empirical usage rate of fluoroquinolones in patients infected with Escherichia coli, Klebsiella pneumoniae, or Pseudomonas aeruginosa was 20.94%, which was influenced by the breakpoint revision (P=0.022), age (P=0.007), and the department (P=0.006); the appropriateness rate was 28.74%, affected by the pathogenic bacteria (P=0.001) and multidrug-resistant microorganism (P=0.001), department (P=0.024), and the length of stay before the empirical therapy (P=0.016).Conclusion: The susceptibility of bacteria to antibiotics has changed significantly after the breakpoint revision while the clinicians’ empirical therapy failure to change accordingly, which results in the decrease of the appropriateness of empirical use. It is enlightened that we should conduct more research to evaluate the rational use of antibiotics from the laboratory perspective and carry out interventions such as education and supervision to strengthen the collaboration between the microbiology laboratories and clinicians to improve the empirical antibiotic therapy and slow down the antimicrobial resistance.Keywords: empirical antibiotic therapy, appropriateness, fluoroquinolones, antimicrobial resistance, breakpoint revision, antimicrobial susceptibility testing

Chengjia Zhao,1 Huihui Xu,1 Xinyi Lai,1 Xue Yang,2 Xiaolian Tu,3 Nani Ding,3 Yijun Lv,4 Guohua Zhang1,5 1Department of Psychology, School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 2Center for Health Behaviours Research, JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 3School of Public Health and Management, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 4Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 5The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325007, People’s Republic of ChinaCorrespondence: Yijun Lv; Guohua Zhang Tel +86 577- 86699111; +86 577- 8668 9925Email lyj@wmu.edu.cn; zghcnu@wmu.edu.cnPurpose: Recent research has identified a relationship between perceived stress and problematic smartphone usage. However, little is known about the underlying mediating and moderating mechanisms. The present study aimed to test the relationship between perceived stress and problematic smartphone usage as well as the mediating role of online social support and the moderating role of perceived social support among Chinese undergraduates.Patients and Methods: A sample of 1123 college students participated in the study. The Perceived Stress Scale, Mobile Phone Addiction Index Scale, Online Social Support Questionnaire, and Perceived Social Support Scale were used.Results: Perceived stress was significantly and positively associated with problematic smartphone usage, and online social support partially mediated the relationship between perceived stress and problematic smartphone usage. Moderated mediation analysis suggested that perceived social support moderated the association between perceived stress and online social support. This relationship became stronger for college students with lower levels of perceived social support.Conclusion: The results of this study can contribute to a better understanding of how perceived stress increases the risk of problematic smartphone usage. The importance of reducing online social support and enhancing perceived social support in preventing undergraduates’ problematic smartphone usage is highlighted. The findings should be taken with caution given the convenience sampling and cross-sectional study design.Keywords: problematic smartphone usage, perceived stress, online social support, perceived social support, Chinese undergraduates

Rize Jing,1,2 Tingting Xu,1,3 Hongguo Rong,2 Xiaozhen Lai,1 Hai Fang2,4,5 1School of Public Health, Peking University, Beijing 100083, People’s Republic of China; 2China Center for Health Development Studies, Peking University, Beijing 100083, People’s Republic of China; 3Department of Social and Behavioral Science, Harvard TH Chan School of Public Health, Harvard University, Boston, Massachusetts 02115, USA; 4Peking University Health Science Center- Chinese Center for Disease Control and Prevention Joint Center for Vaccine Economics, Peking University, Beijing 100083, People’s Republic of China; 5Key Laboratory of Reproductive Health, National Health Commission of the People’s Republic of China, Peking University, Beijing 10083, People’s Republic of ChinaCorrespondence: Hai FangChina Center for Health Development Studies, Peking University, Xueyuan Road 38, Mailbox 505, Haidian District, Beijing 100083, People’s Republic of ChinaTel +86-108-280-5702Fax +86-108-280-5695Email hfang@hsc.pku.edu.cnAim: This study aimed to evaluate the longitudinal association between sleep duration and depressive symptoms among the elderly in China.Methods: A data set from China Health and Retirement Longitudinal Study (CHARLS) in 2011, 2013 and 2015 was adopted with a total of 22,847 respondents aged ≥ 60-years-old. A linear regression analysis with generalized estimating equations was employed to examine the longitudinal associations between duration of total sleep, nighttime sleep and daytime nap, and depressive symptoms.Results: An extra hour of total sleep including nighttime sleep and daytime nap was associated with lower incidence of depressive symptoms among the elderly after adjusting all confounders (OR=0.83, 95% CI: 0.82– 0.84). In addition, an extra hour of nighttime sleep (OR=0.82, 95% CI: 0.80– 0.83) or daytime nap (OR=0.93, 95% CI: 0.89– 0.97) was also negatively associated with depressive symptoms among the elderly. After controlling the total sleep time, an extra hour of nighttime sleep was negatively associated with depressive symptoms (OR=0.88, 95% CI: 0.84 to 0.92), while an extra hour of daytime nap displayed a positive association with depressive symptoms (OR=0.88, 95% CI: 0.84 to 0.92). Compared with the moderate nappers, only extended nappers had significantly higher incidence of depressive symptoms (OR=1.32, 95% CI: 1.19 to 1.45).Conclusion: For the elderly in China, increasing their total sleep, nighttime sleep, and/or daytime nap duration would reduce the incidence of depressive symptoms. Moreover, after fixing the total sleep time, increasing nighttime sleep was more beneficial to the decrease of the incidence of depressive symptoms than daytime nap.Keywords: sleep duration, daytime nap, depressive symptoms, China, the elderly

Linli Liu,1 Zhou Lin,1 Beihong Zheng,2 Lanlan Wang,1 Jianqin Zou,1 Sanshan Wu,1 Zhongqing Jiang,1 Qiong Jin,1 Xuedan Lai,1 Peihong Lin1 1Department of Gynecology and Obstetrics, Fuzhou First Hospital Affiliated to Fujian Medical University, Fuzhou 350004, People’s Republic of China; 2Center for Assisted Reproductive Technology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350004, People’s Republic of ChinaCorrespondence: Linli LiuDepartment of Gynecology and Obstetrics, Fuzhou First Hospital Affiliated to Fujian Medical University, Fuzhou City, Fujian Province 350004, People’s Republic of ChinaTel/Fax +86-591-88301693Email applewang814@163.comBackground: Severe preeclampsia may affect placental development, and high homocysteine (Hcy) levels are linked to intellectual disability. However, the correlation between perinatal Hcy levels and intellectual ability remains unknown in severe preeclampsia-affected offspring.Objective: We aimed to investigate the intellectual ability in offspring born from preeclamptic mothers and examine the role of prenatal Hcy in the prediction of intellectual disability in preschool-aged offspring.Methods: The IQ scores were compared between 101 children born to mothers with severe preeclampsia and 202 offsprings born to normotensive mothers. Maternal Hcy levels within 7 days prior to delivery and postnatal cord blood Hcy were measured. The associations of Hcy with IQ scores were evaluated, and the optimal cut-off values for predicting intellectual disability in the offspring were estimated.Results: The children born to mothers with severe preeclampsia had a greater postnatal cord blood Hcy than those born from normotensive mothers (P < 0.001), and the mothers with severe preeclampsia presented a higher prenatal Hcy (P < 0.001). The children born to mothers with severe preeclampsia had significantly lower IQ scores than those born from normotensive mothers, and a higher Hcy was associated with a lower IQ in preeclampsia-affected offspring. The prevalence of intellectual disability was 2.86 times higher in severe preeclampsia-affected offspring than in children born from normotensive mothers, and the prevalence of low IQ was greater in children born to mothers with severe preeclampsia than in those from normotensive mothers. ROC curve analysis showed that both maternal and cord blood Hcy were predictors of intellectual disability, and the optimal cut-off for predicting intellectual disability was 17.7 and 9.75 μmol/L for maternal and cord blood Hcy.Conclusion: Perinatal exposure to severe preeclampsia has an adverse effect on postnatal intellectual development, and high maternal and cord blood Hcy may contribute to this association.Keywords: preeclampsia, homocysteine, intellectual ability, ROC curve analysis

Xuandi Lai,1 Xinran Geng,2 Lishan Tan,1 Jianqiang Hu,2 Shubin Wang1 1Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, People’s Republic of China; 2Nanobiological Medicine Center, Key Laboratory of Fuel Cell Technology of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, People’s Republic of ChinaCorrespondence: Jianqiang HuNanobiological Medicine Center, Key Laboratory of Fuel Cell Technology of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, No. 381, Wushan Road, Tianhe District, Guangzhou 510640, People’s Republic of ChinaTel +86-186 6571 1833Email jqhusc@scut.edu.cnShubin WangDepartment of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology Medical Center, No. 1120, Lianhua Road, Futian District, Shenzhen 518036, People’s Republic of ChinaTel +86-755-83923333Fax +86-755-83061340Email wangshubin2013@163.comBackground: Stimuli-responsive gold nano-assemblies have attracted attention as drug delivery systems in the biomedical field. However, there are challenges achieving targeted delivery and controllable drug release for specific diseases.Materials and Methods: In this study, a glutathione (GSH)-modified fluorescent gold nanoparticle termed AuLA-GSH was prepared and a Co2+-induced self-assembly drug delivery platform termed AuLA-GSH-Co was constructed. Both the pH-responsive character and drug loading behavior of AuLA-GSH-Co were studied in vitro. Kidney-targeting capability was investigated in vitro and in vivo. Finally, the anti-fibrosis efficiency of AuLA-GSH-Co in a mouse model of unilateral ureteral obstruction (UUO) was explored.Results: AuLA-GSH-Co was sensitive to pH changes and released Co2+ in acidic conditions, allowing it to have controllable drug release abilities. AuLA-GSH-Co was found to improve cellular uptake of Co2+ ions compared to CoCl2 in vitro. AuLA-GSH exhibited specific renal targeting and prolonged renal retention time with low non-specific accumulation in vivo. Moreover, the anti-fibrosis efficiency of AuLA-GSH-Co was higher compared to CoCl2 in a mouse model of unilateral ureteral obstruction (UUO).Conclusion: AuLA-GSH-Co could greatly enhance drug delivery efficiency with renal targeting capability and obviously relieve renal fibrosis, providing a promising strategy for renal fibrosis therapy.Keywords: gold nanoparticles, self-assembly, pH sensitivity, drug delivery, renal fibrosis

Yanxia Sun,*,1,2 Xiaolan Lai,*,3 Yue Yu,1,2 Jieyu Li,2,4 Lei Cao,3 Wansong Lin,2,4 Chuanzhong Huang,2,4 Jinrong Liao,2,4 Wei Chen,1,2 Chao Li,5 Chunkang Yang,6 Mingan Ying,6 Qiang Chen,3 Yunbin Ye2,41School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, Fujian Province, People’s Republic of China; 2Laboratory of Immuno-Oncology, Fujian Provincial Cancer Hospital, Fuzhou 350014, Fujian Province, People’s Republic of China; 3Department of Medical Oncology, Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, People’s Republic of China; 4Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, Fujian Province, People’s Republic of China; 5Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou 350014, Fujian Province, People’s Republic of China; 6Department of Abdominal Surgery, Fujian Provincial Cancer Hospital, Fuzhou 350014, Fujian Province, People’s Republic of China*These authors contributed equally to this workBackground: Inhibitor of DNA binding 1 (Id1) is upregulated in multiple cancers, and Id1overexpression correlates with cancer aggressiveness and poor clinical outcomes in cancer patients. However, its roles in cancer stem-like cells (CSCs) and epithelial-mesenchymal transition (EMT) are still elusive.Purpose: This study aimed to examine the role of Id1 on the mediation of CRC stemness and explore the underlying mechanisms.Methods: Id1 and CD133 expression was detected by qPCR assay and immunohistochemistry (IHC) in normal mucosal and primary colorectal cancer (CRC) specimens. Id1 was stably knocked down (KD) in human CRC cell lines. Spheres forming assay and tumorigenic assay were performed to evaluate self-renewal capacity and tumor initiation. Expression of CSC- and EMT-related markers and TCF/LEF activity were assessed in HCT116 cells after Id1 KD.Results: qPCR assay showed higher Id1 and CD133 expression in CRC specimens than in normal mucosal specimens (P

Menglei Wang,1 Xuan Lai,2 Longquan Shao,2 Li Li1 1Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China; 2Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China Abstract: Nanotechnology is an interdisciplinary science that has developed rapidly in recent years. Metallic nanoparticles (NPs) are increasingly utilized in dermatology and cosmetology, because of their unique properties. However, skin exposure to NPs raises concerns regarding their transdermal toxicity. The tight junctions of epithelial cells form the skin barrier, which protects the host against external substances. Recent studies have found that NPs can pass through the skin barrier into deeper layers, indicating that skin exposure is a means for NPs to enter the body. The distribution and interaction of NPs with skin cells may cause toxic side effects. In this review, possible penetration pathways and related toxicity mechanisms are discussed. The limitations of current experimental methods on the penetration and toxic effects of metallic NPs are also described. This review contributes to a better understanding of the risks of topically applied metallic NPs and provides a foundation for future studies. Keywords: metallic nanoparticles, transdermal penetration, toxicity

Jicai Zhang, Xiang Xiao, Jianming Zhu, Ziyun Gao, Xianliang Lai, Xingen Zhu, Guohua Mao Department of Neurosurgery, Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China Purpose: Glioblastoma multiforme (GBM) is the most common malignant brain tumor originating in the central nervous system in adults. Based on nanotechnology such as liposomes, polymeric nanoparticles, and lipid nanoparticles, recent research efforts have been aimed to target drugs to the brain. Methods: In this study, lactoferrin- and arginine–glycine–aspartic acid (RGD) dual-ligand-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers (L/R-T/V-NLCs) were introduced for GBM combination therapy. The physicochemical properties of L/R-T/V-NLCs such as particle size, zeta potential, and encapsulated efficiency are measured. The drug release profile, cellular uptake, cytotoxicity, tissue distribution, and antitumor activity of L/R-T/V-NLCs are further investigated in vitro and in vivo. Results: L/R-T/V-NLCs were stable with nanosize and high drug encapsulation efficiency. L/R-T/V-NLCs exhibited sustained-release behavior, high cellular uptake, high cytotoxicity and synergy effects, increased drug accumulation in the tumor tissue, and obvious tumor inhibition efficiency with low systemic toxicity. Conclusion: L/R-T/V-NLCs could be a promising drug delivery system for glioblastoma chemotherapy. Keywords: gliomatosis cerebri, combination therapy, nanostructured lipid carriers, lactoferrin, arginine–glycine–aspartic acid peptide, vincristine, temozolomide

Qiong Bai, Xuan Lai, Ai-Hua Zhang, Xin-Hong Lu, Shun-Li Tian, Min-Hua Fan, Yue Wang, Tao WangDivision of Nephrology, Peking University Third Hospital, Beijing, People's Republic of ChinaBackground: Cardiovascular disease is more common in patients with chronic kidney disease (CKD) than in the general population. Endothelial dysfunction is an early predictor of cardiovascular events.Objective: We conducted a cross-sectional study in CKD patients to explore the association of metabolic syndrome (MetS) components with endothelial cell function.Methods: We evaluated clinical and laboratory data in 161 CKD patients from stage 1 to stage 5. Endothelial function was estimated by flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter. MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III criteria.Results: Patients were grouped into two groups according to whether or not they had MetS. FMD was significantly lower in the MetS group than in the group without MetS (P = 0.012). In a Pearson's correlation analysis, FMD was significantly negatively correlated with waist circumference in women (r = –0.223, P = 0.03) and fasting blood glucose (r = –0.186, P = 0.001). Multiple linear regression analysis showed that fasting blood glucose was an independently associated factor for FMD.Conclusion: MetS and some components of MetS (waist circumference in women and fasting blood glucose) are closely associated with a decreased FMD in CKD patients.Keywords: metabolic syndrome, endothelial dysfunction, flow-mediated dilatation, chronic kidney disease

Variations in phytoplankton chlorophyll a were studied in Lake Poyang, and these variations were compared with those observed in its tributaries. Samples were collected from January 2009 to January 2013 during the dry, mid-dry and wet seasons. The study showed that chlorophyll a concentrations were significantly higher in the wet season than in the dry and mid-dry seasons (p

Iron-based superconductor family FeX (X = S, Se, Te) has been one of the research foci in physics and material science due to their record-breaking superconducting temperature (FeSe film) and rich physical phenomena. Recently, FeS, the least studied FeX compound (due to the difficulty in synthesizing high quality macroscopic crystals) attracted much attention because of its puzzling superconducting pairing symmetry. In this work, combining scanning tunneling microscopy and angle resolved photoemission spectroscopy (ARPES) with sub-micron spatial resolution, we investigate the intrinsic electronic structures of superconducting FeS from individual single crystalline domains. Unlike FeTe or FeSe, FeS remains identical tetragonal structure from room temperature down to 5 K, and the band structures observed can be well reproduced by our ab-initio calculations. Remarkably, mixed with the 1 × 1 tetragonal metallic phase, we also observe the coexistence of reconstructed insulating phase in the crystal, which not only helps explain the unusual properties of FeS, but also demonstrates the importance of using spatially resolved experimental tools in the study of this compound.

"Invulnerability" of complex network was firstly introduced to virtual water (VW) research, aiming to broaden the scope of studies on water use and management. Beginning with the construction of China's virtual water trade networks (VWTNs) of major grain crops, Node Degree (K) and Betweenness Centrality (B) are employed to evaluate and rank the importance of China's 31 regions. Regions with high values for both indicators are identified as playing pivotal roles in the VWTNs: Jiangsu (ranking 1st for both K and B), Hubei (2nd for K, 3rd for B), Henan (3rd for K, 6th for B), Hebei (4th for K, 4th for B), Hunan (4th for K, 5th for B). Using this ranking to simulate the invulnerability of VWTNs under random and intentional attacks. The results reveal a rapid decrease in both Network Efficiency (E) and Maximum Connectivity (C) under intentional attack. In comparison to seven random attacks, E falls below 0.1 and C drops below 0.5 after only three intentional attacks, and the network completely collapsed after 10 intentional attacks. This highlights the VWTN's vulnerability in maintaining food supply and agricultural water security when key regions are subjected to man‐made destruction, such as military blockades or occupations. Future work should include integrating climate change models, crops yield models, and water resource allocation models to protect the key areas. Furthermore, interdisciplinary approaches are crucial for overcoming the limitations of VW research and these findings will provide valuable insights to enhance the optimal regulation of VWTNs. Key Points: "Invulnerability" was novelly introduced to the virtual water trade networks (VWTNs) to simulate its destruction resistanceNetwork efficiency and maximum connectivity of VWTNs decreased rapidly under intentional attacksWhen key regions subjected to man‐made attacks, China's VWTNs is unable to maintain food supply and agricultural water security [ABSTRACT FROM AUTHOR]