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Wenxian Lin,1– 4 Lizhu Tang,1,2,5 Chenyi Zhuo,1 Xiuli Mao,1– 4 Jiajia Shen,6 Shaoang Huang,3 Shangyang Li,3,7 Yujuan Qin,3,4 Ju Liao,2,3 Yuhong Chen,8 Xiamin Zhang,3,4 Yuting Li,9 Jian Song,4 Lingzhang Meng,4 Xiaofeng Dong,10 Yueyong Li2 1Key Laboratory of Molecular Pathology for Hepatobiliary Diseases of Guangxi, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, The People’s Republic of China; 2Department of Interventional Oncology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, The People’s Republic of China; 3Graduate School, Youjiang Medical University for Nationalities, Baise, 533000, The People’s Republic of China; 4Institute of Cardiovascular Sciences, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530016, The People’s Republic of China; 5Department of Radiation Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, The People’s Republic of China; 6Department of Laboratory Medicine, Nanning Maternity and Child Health Hospital & Nanning Women and Children’s Hospital, Nanning, 530011, The People’s Republic of China; 7Department of Laboratory Medicine, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530016, The People’s Republic of China; 8Department of Nephrology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, The People’s Republic of China; 9Graduate School, Guangxi University of Chinese Medicine, Nanning, 530200, The People’s Republic of China; 10Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530016, The People’s Republic of ChinaCorrespondence: Yueyong Li; Xiaofeng Dong, Email 305017674@qq.com; gandanyingcai@163.comBackground: Cancer-associated fibroblasts (CAFs) play a pivotal role in shaping the microenvironment of hepatocellular carcinoma (HCC). However, the mechanisms through which CAFs influence the progression of HCC remain incompletely understood.Methods: Single-cell RNA sequencing datasets (GSE158723 and GSE112271) were retrieved from the Gene Expression Omnibus (GEO) database at the National Center for Biotechnology Information (NCBI) and analyzed using R software. Our analysis suggested that CAFs may promote liver cancer cell development, possibly through the interaction of pleiotrophin (PTN) and syndecan-2 (SDC2). Clinical samples from HCC patients were collected and processed into frozen sections and single-cell suspensions for Masson staining, immunofluorescence staining, and flow cytometry. Additionally, Huh7 liver cancer cells and LO2 normal liver cells were cultured and subjected to immunofluorescence assays using cell slides.Results: The proportion of CAFs in cancerous tissues was higher than in adjacent non-cancerous tissues, and pleiotrophin (PTN) expression was elevated in cancer tissues compared to adjacent tissues. These findings aligned with the results of the single-cell RNA sequencing (scRNA-seq) analysis. Furthermore, SDC2 expression was significantly upregulated in Huh7 liver cancer cells compared to LO2 normal liver cells.Discussion: This study suggests that CAFs may contribute to HCC progression via the PTN/SDC2 signaling pathway. Our findings provide deeper insights into the interactions between CAFs and HCC cells within the tumor microenvironment (TME).Keywords: CAFs, HCC, PTN, scRNA-seq, TME

Lijuan Zhang,1,2,&ast; Liyan Liu,3,&ast; Guosheng Yan,2 Xu Ma,2 Guizhen Zhu,2 Xinxin Dong,2 Yang Lu,2 Hongtao Zhang1,2,4 1Department of Nephrology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Blood Purification Center, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of Nephrology, The Fifth People’s Hospital of Jinan, Jinan, Shandong, People’s Republic of China; 4Department of Nephrology, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongtao Zhang, Blood Purification Center, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China, Tel +86-13526614646, Email zhtzzu@zzu.edu.cnPurpose: The predictive value of the Systemic Immune-Inflammation Index (SII) on mortality in patients with sepsis-associated acute kidney injury (S-AKI) remains unclear. This study aims to investigate the predictive value of SII levels at the Intensive Care Unit (ICU) on the 28-day mortality of S-AKI patients.Patients and Methods: S-AKI patients admitted to the ICU of Henan Provincial People’s Hospital from January 1, 2023, to December 31, 2023. Patients who were diagnosed with S-AKI were divided into survival and death groups based on their 28-day outcome after ICU admission. Using receiver operating characteristic (ROC) curves to determine the best cut-off values and prognostic abilities of various parameters. Kaplan-Meier survival curves describe the 28-day survival of patients after ICU admission. Cox regression analysis identified the main risk factors associated with mortality in S-AKI patients, constructing a predictive nomogram. The concordance index (C-index) and decision curve analysis were used to validate the predictive ability of this model.Results: A total of 216 patients with S-AKI were included. ROC analysis showed that SII had the highest predictive value for mortality risk in S-AKI patients after ICU admission. Compared with the low-SII group, the high-SII group had higher 28-day (86.7% vs 32.4%, respectively, P < 0.001) mortality rate. Based on Cox regression analysis, a nomogram predictive model was constructed, including age, respiratory failure, SII levels, number of organ dysfunctions at ICU admission, sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHEII). The C-index for predicting the 28-day survival rate was 0.682. Decision curve analysis indicated a high level of clinical predictive efficacy.Conclusion: SII serves as a potential biomarker for predicting the prognosis of S-AKI patients. The constructed nomogram prognostic model can aid in assessing the prognosis of S-AKI patients.Keywords: systemic immune-inflammation index, sepsis-associated acute kidney injury, prognosis, mortality, prediction model

Mingwan Zhou,1 Xueti Dong,2 Weige Wu,3,4 Yun Li4,5 1Psychological Assessment Center, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, People’s Republic of China; 2Psychological Counseling and Treatment Center, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, People’s Republic of China; 3Child Psychology Department, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, People’s Republic of China; 4Department of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Child and Adolescent Psychology Outpatient Clinic, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, People’s Republic of ChinaCorrespondence: Yun Li, Department of Clinical Medicine, Fujian Medical University, No. 1, Xueyuan North Road, Fuzhou, Fujian Province, 350100, People’s Republic of China, Email xiaojiujiuo123@sina.comObjective: Numerous studies have shown that the mental health of middle school students is closely related to problematic mobile phone use. The purpose of this study is to investigate the network structure between the dimensions of the Middle School Students Mental Health Scale and the items of the Self-Rating Questionnaire for Adolescent Problematic Mobile Phone Use by using the network analysis, to clarify the core symptoms and bridge symptoms of the network structure, and to provide ideas and methods for intervening in the mental health and problematic mobile phone use of middle school students.Methods: A stratified cluster sampling method was used to select 1637 students from four general middle schools in Xiamen in June 2020 for the survey, and the Middle School Students Mental Health Scale (MSSMHS-60) and the Self-Rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) were used. SPSS28.0 was used for descriptive statistical analysis and R (version 4.2.1) for network analysis.Results: 1. The core symptoms of the network of middle school students’ mental health and problematic mobile phone use were “spending more time playing with the phone in order to be satisfied”, anxiety, and depression; 2. The bridge symptoms of the network of middle school students’ mental health and problematic mobile phone use were academic stress, psychological disequilibrium, and “depression without phone”.Conclusion: Reducing the time of smartphone use and relieving anxiety and depression can improve the mental health of middle school students and reduce the incidence of problematic mobile phone use; helping middle school students adjust their study pressure and improving their social support level can reduce the severity of problematic mobile phone use.Keywords: problematic mobile phone use, network analysis, middle school students, mental health

Qian Gui,1,&ast; Jingcai Meng,2,&ast; Mingqiang Shen,1 Hongxuan Feng,1 Xiaofeng Dong,1 Daqiang Xu,3 Wenxin Zhu,2 Qingzhang Cheng,1 Linhui Wang,2 Guanhui Wu,1 Yanli Lu3 1Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, 215002, People’s Republic of China; 2Department of Physiology and Neurobiology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 3Department of Radiology, the Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, 215002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanli Lu, Department of Radiology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), 26 Daoqian Street, Suzhou City, Jiangsu Province, People’s Republic of China, Tel +8618251135654, Email luyanli.2009@163.com Guanhui Wu, Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), 26 Daoqian Street, Suzhou City, Jiangsu Province, People’s Republic of China, Email ghwusz26@njmu.edu.cnIntroduction: Previous studies have predominantly explored the relationship of the glymphatic system with motor symptoms in Parkinson’s disease (PD); however, research on non-motor symptoms remains limited. Therefore, this study investigated the association between glymphatic function and non-motor symptoms, including cognitive impairment and sleep disorders, in PD patients.Methods: This study recruited 49 PD patients and 38 healthy controls (HC). Glymphatic function was evaluated using enlarged perivascular spaces (EPVS) in the basal ganglia (BG) region and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Cognition, sleep, anxiety, and depression scales were assessed in all participants. According to the scale scores, PD patients were further divided into several groups to identify the presence of non-motor symptoms. Differences in EPVS numbers and ALPS index between PD subgroups and HC group were compared. Spearman correlation analysis was performed to investigate the association between the PD non-motor symptoms and ALPS index. Additionally, receiver operating characteristic (ROC) curves analysis was conducted for ALPS index to predict cognitive impairment and insomnia in PD patients.Results: PD patients with and without non-motor symptoms all showed more EPVS numbers than the controls, and the EPVS numbers in PD patients with cognitive impairment were also greater than those without. Notably, except for the depression subgroup, PD patients with non-motor symptoms showed significantly lower ALPS index than the controls. The Montreal Cognitive Assessment (MoCA) scores were positively correlated, whereas the Parkinson’s Disease Sleep Scale (PDSS)-2 and REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores were negatively correlated with the ALPS index in PD patients (r=0.3618, P=0.0053; r=− 0.4146, P=0.0015; r=− 0.2655, P=0.0326, respectively). The ALPS index proved to be predictive of cognitive impairment and insomnia in PD patients (AUC=0.7733, P=0.001; AUC=0.7993, P=0.0004, respectively).Conclusion: Glymphatic function is closely associated with cognition and sleep of PD patients.Keywords: glymphatic system, parkinson’s disease, non-motor symptoms, cognition, sleep

Jiaxin Zan,1,2 Xiaojing Dong,1,2 Hong Yang,1,2 Jingjing Yan,1,2 Zixuan He,3 Jing Tian,3 Yanbo Zhang1,2,4 1Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan, People’s Republic of China; 3Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4School of Health Services and Management, Shanxi University of Chinese Medicine, Taiyuan, People’s Republic of ChinaCorrespondence: Jing Tian; Yanbo Zhang, School of Public health, Shanxi Medical University, 56 Xinjian Road, Taiyuan, Shanxi Province, People’s Republic of China, Tel/Fax +86 15535406059, Email 1105551933@qq.com; sxmuzyb@126.comPurpose: This study sought to develop an unbalanced-ensemble model that could accurately predict death outcomes of patients with comorbid coronary heart disease (CHD) and hypertension and evaluate the factors contributing to death.Patients and Methods: Medical records of 1058 patients with coronary heart disease combined with hypertension and excluding those acute coronary syndrome were collected. Patients were followed-up at the first, third, sixth, and twelfth months after discharge to record death events. Follow-up ended two years after discharge. Patients were divided into survival and nonsurvival groups. According to medical records, gender, smoking, drinking, COPD, cerebral stroke, diabetes, hyperhomocysteinemia, heart failure and renal insufficiency of the two groups were sorted and compared and other influencing factors of the two groups, feature selection was carried out to construct models. Owing to data unbalance, we developed four unbalanced-ensemble prediction models based on Balanced Random Forest (BRF), EasyEnsemble, RUSBoost, SMOTEBoost and the two base classification algorithms based on AdaBoost and Logistic. Each model was optimised using hyperparameters based on GridSearchCV and evaluated using area under the curve (AUC), sensitivity, recall, Brier score, and geometric mean (G-mean). Additionally, to understand the influence of variables on model performance, we constructed a SHapley Additive explanation (SHAP) model based on the optimal model.Results: There were significant differences in age, heart rate, COPD, cerebral stroke, heart failure and renal insufficiency in the nonsurvival group compared with the survival group. Among all models, BRF yielded the highest AUC (0.810; 95% CI, 0.778– 0.839), sensitivity (0.990; 95% CI, 0.981– 1.000), recall (0.990; 95% CI, 0.981– 1.000), and G-mean (0.806; 95% CI, 0.778– 0.827), and the lowest Brier score (0.181; 95% CI, 0.178– 0.185). Therefore, we identified BRF as the optimal model. Furthermore, red blood cell count (RBC), body mass index (BMI), and lactate dehydrogenase were found to be important mortality-associated risk factors.Conclusion: BRF combined with advanced machine learning methods and SHAP is highly effective and accurately predicts mortality in patients with CHD comorbid with hypertension. This model has the potential to assist clinicians in modifying treatment strategies to improve patient outcomes. Keywords: coronary heart disease comorbid with hypertension, ensemble learning, balanced random forest, SHAP, Prognosis

Demeng Xia,1,2,&ast; Qingqing Qian,1,&ast; Sheng Wang,3,&ast; Xiao Dong,4 Ying Liu5 1Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 200240, People’s Republic of China; 2Department of Pharmacy, Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200120, People’s Republic of China; 3Department of Traumatic Orthopedics, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 4School of Medicine, Shanghai University, Shanghai, 200444, People’s Republic of China; 5Institute of Translational Medicine, Shanghai University, Shanghai, 200444, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Liu; Xiao Dong, Email liuchanger1984@163.com; dong-xiao@shu.edu.cnIntroduction: Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem.Methods: Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis. However, its poor solubility and lack of targeting severely limits its further application. A novel bone-targeting nanomedicine (PA@TLipo) has been developed to reconstruct the osteoporotic microenvironment by encapsulating pomolic acid in alendronate-functionalized liposomes. Through a series of operations such as synthesis, purification, encapsulation, and labeling, the PA@TLipo have been prepared. Moreover, the cytotoxicity, bone targeting and anti-osteoporosis effect was verified by cell and animal experiments.Results: In the aspect of targeting, the PA@TLipo can effectively aggregate on the bone tissue to reduce bone loss, and in terms of toxicity, PA@TLipo could increase the bone target ability in comparison to nontargeted liposome, thereby mitigating systemic cytotoxicity. Moreover, PA@TLipo inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice.Conclusion: In this study, a novel therapeutic agent was designed and constructed to treat osteoporosis, consisting of a liposome material as the drug pocket, PA as the anti-osteoporosis drug, and ALN as the bone-targeting molecule. And our study is the first to employ a bone-targeted delivery system to deliver PA for OVX-induced bone loss, providing an innovative solution for treating osteoporosis.Keywords: bone targeting, alendronate functionalized liposome, pomolic acid, osteoporosis therapy

Ruijie Zhang,1,&ast; Xinran Dong,2,&ast; Lu Zhang,1,&ast; Xinao Lin,1 Xuefeng Wang,1 Yan Xu,3 Chuyan Wu,4 Feng Jiang,1 Jimei Wang1 1Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China; 2Center for Molecular Medicine, Children’s Hospital of Fudan University, Shanghai, People’s Republic of China; 3Department of Neurology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, People’s Republic of China; 4Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jimei Wang; Feng Jiang, Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China, Email wjm821920@163.com; dxyjiang@163.comBackground: Neonatal sleep is pivotal for their growth and development, yet manual interpretation of raw images is time-consuming and labor-intensive. Quantitative Electroencephalography (QEEG) presents significant advantages in terms of objectivity and convenience for investigating neonatal sleep patterns. However, research on the sleep patterns of healthy neonates remains scarce. This study aims to identify QEEG markers that distinguish between different neonatal sleep cycles and analyze QEEG alterations across various sleep stages in relation to postmenstrual age.Methods: From September 2023 to February 2024, full-term neonates admitted to the neonatology department at the Obstetrics and Gynecology Hospital of Fudan University were enrolled in this study. Electroencephalographic (EEG) recordings were obtained from neonates aged 37– 42 weeks, within 1– 7 days post-birth. The ROC curve was employed to evaluate QEEG features related to amplitude, range EEG (rEEG), spectral density, and connectivity across different sleep stages. Furthermore, regression analyses were performed to investigate the association between these QEEG characteristics and postmenstrual age.Results: The alpha frequency band’s spectral_diff_F3 emerged as the most potent discriminator between active sleep (AS) and quiet sleep (QS). In distinguishing AS from wakefulness (W), the theta frequency’s spectral_diff_C4 was the most effective, whereas the delta frequency’s spectral_diff_P4 excelled in differentiating QS from W. During AS and QS phases, there was a notable increase in entropy within the delta frequency band across all monitored brain regions and in the spectral relative power within the theta frequency band, correlating with postmenstrual age (PMA).Conclusion: Spectral difference showcases the highest discriminative capability across awake and various sleep states. The observed patterns of neonatal QEEG alterations in relation to PMA are consistent with the maturation of neonatal sleep, offering insights into the prediction and evaluation of brain development outcomes.Keywords: quantitative EEG, neonates, sleep, postmenstrual age

Kuocheng Yan,1,&ast; Xiaohui Wang,2,&ast; Yao Han,1,&ast; Yuan Tian,1 Mengwei Niu,1 Xue Dong,1 Xiaowei Li,2 Hao Li,1 Yansong Sun1 1State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China; 2Department of Gastroenterology, the Sixth Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, 100080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Li, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China, Email lihao88663239@126.com Xiaowei Li, Department of Gastroenterology, the Sixth Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, 100080, People’s Republic of China, Email lixwei12@126.comBackground: Infection caused by Helicobacter pylori (H. pylori) affects approximately 50% of the global population. It is a major pathogenic factor for chronic gastritis and gastric cancer. Besides, the resistance to antibiotics such as clarithromycin could reduce the eradication rate. Currently, there is an urgent need for a swift, easy to perform, and highly sensitive detection method for H. pylori and clarithromycin resistance.Methods: We used FAM/Digoxin labeled primers to amplify specific H. pylori 23S rRNA fragments by Recombinase Aided Amplification (RAA), and resistance mutations were distinguished using CRISPR/Cas13a system combined with lateral flow strip. Twenty-eight saliva samples were analyzed using qPCR, gene sequencing and this method to evaluate the detection efficiency.Results: We developed a simultaneous detection method for H. pylori and clarithromycin resistance mutations named sensitive H. pylori easy-read dual detection (SHIELD). The results showed both A2142G and A2143G mutant DNAs causing clarithromycin resistance could be distinguished from the wild type with a concentration of 50 copies/μL, and no cross-reaction with other 5 common gastrointestinal bacteria was observed. For the detection of H. pylori in 28 saliva samples, the positive predictive value of this method was 100% (19/19) in comparison with qPCR. For detecting clarithromycin resistance, the positive predictive value of this method was 84.6% (11/13) compared with gene sequencing.Conclusion: SHIELD assay showed high sensitivity and specificity in detecting H. pylori and clarithromycin resistance mutations. It could be a potential measure in the rapid detection of H. pylori, large-scale screening and guiding clinical medication.Keywords: Helicobacter pylori, clarithromycin resistance mutation, recombinase aided amplification, CRISPR/Cas13a, nucleic acid detection

Yuzhu Qu,1– 3,&ast; Ying Peng,4,&ast; Yan Xiong,5 Xiaohui Dong,3 Peihong Ma,6 Shirui Cheng2,3 1Post-Doctoral Scientific Research Workstation of Affiliated Sport Hospital, Chengdu Sport University, Chengdu, Sichuan, People’s Republic of China; 2Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 3Acupuncture and Brain Science Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 4Medical Aesthetics Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 5Department of Osteoporosis, West China Fourth Hospital Sichuan University, Chengdu, Sichuan, People’s Republic of China; 6Medical Technology School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shirui Cheng, Chengdu University of Traditional Chinese Medicine, 1166 &num; Liutai Avenue, Chengdu, Sichuan, 611137, People’s Republic of China, Email csr1190@163.com Peihong Ma, Tianjin University of Traditional Chinese Medicine, 10 &num; Poyanghu Road, Tuanpo Xincheng West District, Jinghai District, Tianjin, 301617, People’s Republic of China, Email acu_madai@163.comAbstract: Acupuncture has been widely applied for treating knee osteoarthritis (KOA). Numerous studies have found that acupuncture can effectively alleviate KOA symptoms. With the advancement of neuroimaging techniques, integrating neuroimaging with in-depth investigations of acupuncture mechanisms has emerged as a hot topic in traditional Chinese medical neuroscience research. This review aimed to analyze the study design and main findings from neuroimaging studies of acupuncture-related therapy for KOA to provide a reference for future research. Original studies were sourced from English databases (PubMed, Embase, and Cochrane Library) and Chinese databases (Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, the Chongqing VIP database, and Wanfang database). As a result, thirteen articles were ultimately included in this review. Functional magnetic resonance imaging was the most frequently used neuroimaging technique to explore cerebral responses to acupuncture-related therapy for KOA. Findings suggested that acupuncture-related therapy could regulate some brain regions in patients with KOA. Specifically, for acupuncture, it showed that the medial pain pathway and the limbic system were involved in the regulation of KOA. Meanwhile, moxibustion induced a wide range of functional activity throughout the entire brain.Keywords: acupuncture-related therapy, knee osteoarthritis, cerebral response, neuroimaging study

Yingliang Wang,1,2,&ast; Shuguang Ju,1,2,&ast; Huimin Zhou,3,&ast; Yaowei Bai,1,2 Chen Zhou,1,2 Jiacheng Liu,1,2 Xiangjun Dong,1,2 Chuansheng Zheng1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China; 3Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangjun Dong; Chuansheng Zheng, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email dongxiangjun3100@163.com; hqzcsxh@sina.comPurpose: To explore the effect of calcium peroxide nanoparticles (CaO2 NPs) combined with programmed cell death protein 1 (PD-1) inhibitors in the treatment of liver cancer and its related mechanism.Methods: Hepa1-6 cells were cultured to construct the Hepa1-6 mouse liver cancer model. In vivo mechanism study, a unilateral tumor model was established. Eighteen tumor-bearing mice were randomly divided into the control group (intra-tumoral injection of PBS solution) and the experimental group (intra-tumoral injection of CaO2 NPs). A hypoxic probe, pH probe, and micro-CT were used to evaluate the effect of CaO2 NPs on improving hypoxia, neutralizing acidity, and inducing calcium overload within the tumor. To study the effect of CaO2 NPs combined with PD-1 inhibitors on proximal and distal tumors, the bilateral tumor model was established. Forty tumor-bearing mice were randomly divided into the control group (intra-tumoral/intra-peritoneal injection of PBS solution), CaO2 NPs group (intra-tumoral injection of CaO2 NPs), PD-1 group (intra-peritoneal injection of PD-1 inhibitor), and the combination group (intra-tumoral injection of CaO2 NPs and intra-peritoneal injection of PD-1 inhibitors). The administered side was recorded as the proximal tumor. Tumor volume and body weight were measured every 2 days after treatment. On day 8, serum and tumor samples were collected. The immune factors in serum (Interferon-γ (IFN-γ), Tumour necrosis factor-α (TNF-α), Interleukin-2 (IL-2), and Interleukin-10 (IL-10)) and tumor tissue (IFN-γ and TNF-α) were detected by ELISA. H&E staining was used to detect tumor necrosis. Immunohistochemical staining was used to detect the amount of CD4+ and CD8+ T cells within the tumor. By analyzing the tumor volume, pathological indexes, and immune-related indexes, the effects of CaO2 NPs combined with PD-1 inhibitors on proximal and distal tumors were evaluated, and they mediated immunomodulatory effects (including local and systemic immunity), and their effects on tumor burden were studied. In addition, a unilateral tumor model was established to study the effect of CaO2 NPs combined with PD-1 inhibitors on survival time.Results: The results of in vivo mechanism study showed that CaO2 NPs can improve hypoxia, neutralize acidity, and induce calcium overload within tumors. The results of the study on the effect of CaO2 NPs combined with PD-1 inhibitor on proximal and distal tumors showed that, compared with the other three groups, the bilateral tumor burden of the combination group was significantly reduced, the intra-tumoral infiltration of CD8+ and CD4+ T cells were significantly increased, the secretion of anti-tumor immune factors in tumor and serum was increased, and the secretion of pro-tumor immune factors was decreased. Mice in the combination group showed the longest survival compared with the other groups.Conclusion: CaO2 NPs can improve hypoxia, neutralize acidity, and induce calcium overload within tumors, so as to reduce tumor burden and realize an immunosuppressive tumor transformation to a hot tumor, and play a synergistic role with PD-1 inhibitors in anti-liver cancer.Keywords: calcium peroxide nanoparticles, programmed cell death protein 1 inhibitor, Hepa1-6 model, tumor microenvironment, liver cancer

Xingling He,1– 4,&ast; Yanhui Jiang,1,&ast; Sijing Li,1– 4,&ast; Donghua Liu,1– 4 Ziru Li,1– 4 Xiaowei Han,1– 4 Xiaojiao Zhang,1– 4 Xiaoming Dong,1 Haohui Liu,1 Jie Huang,1 Xiaojing Wang,5 Wenjie Long,1 Shihao Ni,1– 4 Zhongqi Yang,1 Taochun Ye1 1Department of Geriatrics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3University Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Chronic Heart Failure, Guangzhou, Guangdong Province, People’s Republic of China; 4Guangzhou Key Laboratory for Chinese Medicine Prevention and Treatment of Chronic Heart Failure, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5Clinical Medical Center, Tasly Pharmaceutical Group Co. Ltd., Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taochun Ye; Zhongqi Yang, Email yetaochun@163.com; yang_zhongqi@163.comBackground: Heart failure (HF) is a serious and terminal stage of various cardiac diseases and the most common complication of coronary heart disease (CHD). Previous clinical studies have shown that Qishen Yiqi dropping pills (QSYQ) have the effect of treating chronic heart failure. This study aims to evaluate the clinical efficacy, safety and optimal effective dose of QSYQ in treating CHD complicating chronic HF with reduced ejection fraction (HFrEF).Methods: We will conduct a randomized, double-blind, placebo controlled, multicenter clinical trial. A total of 228 individuals from 16 hospitals in China will be randomly assigned to the low-dose, high-dose, and placebo groups in a ratio of 1:1:1. The trial consists of a screening period (standard medical treatment for at least 2 weeks) and a 12-week treatment period. After randomization, follow-up will be conducted at the 4th, 8th and 12th week. The primary outcomes will be the 6-Minute Walk Test (6MWT) at Week 12. Secondary outcomes will include 6MWT distance at Week 4 and 8, New York Heart Association (NYHA) functional classification, Traditional Chinese Medicine (TCM) Syndrome score, echocardiography indices, N-terminal pro-B-type natriuretic peptide (NT-proBNP), oxyhemoglobin saturation, Minnesota living with heart failure questionnaire (MLHFQ) score, grasp strength body mass index test and cardiovascular adverse events (AE).Ethics and Dissemination: This trial has been approved by the Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (approval number: ZYYEC [2021]005). Written informed consent will be obtained from all participants. The results of this trial will be publicly shared through academic conferences and peer-reviewed journals.Study Registration: Clinical Trials Registry (NCT04983043, Date: 07/08/2021, https://clinicaltrials.gov/ct2/show/NCT04983043).Keywords: heart failure, coronary heart disease, Chinese medicine, QiShen YiQi Dripping Pill, syndrome of Qi deficiency with blood stasis

Xiaofen Li,1 Jimin Wu,2 Haiyan Lan,2 Weifeng Shan,2 Qiaomin Xu,2 Xiaoli Dong,2 Gongchen Duan2 1Nursing Department, Lishui People’s Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, People’s Republic of China; 2Department of Anesthesiology, Lishui People’s Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, People’s Republic of ChinaCorrespondence: Gongchen Duan, Department of Anesthesiology, Lishui People’s Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, No. 1188, Liyang Street, Lishui, Zhejiang, 323000, People’s Republic of China, Tel/Fax +8618957093030, Email 981225178@qq.comPurpose: This study was performed to evaluate the effects of intraoperative intravenous lidocaine on postoperative delirium in elderly patients with hip fracture.Patients and methods: In total, 100 elderly patients undergoing hip fracture surgery were randomized to the lidocaine group (Group L) or saline (control) group (Group C). Before anesthetic induction, Group L received lidocaine at 1 mg/kg for more than 10 minutes followed by continuous infusion at 1.5 mg/kg/h until the end of surgery. Group C received normal saline, and the injection methods were consistent with those in Group L. General anesthesia was induced with propofol, sufentanil, and cis-atracurium. Anesthesia was maintained by propofol and remifentanil. The primary outcome was the incidence of postoperative delirium in the first 7 postoperative days. The secondary outcomes included the severity of delirium, onset and duration of delirium, emergence agitation, adverse events, total propofol dose, intraoperative opioid dosage, length of post-anesthesia care unit stay, extubation time, and patient satisfaction with postoperative pain management.Results: All 100 patients completed the study. The incidence of postoperative delirium was lower in Group L than in Group C (14% vs 36%, P = 0.011). The delirium severity scores were lower in Group L (3 [3– 4]) than in Group C (4 [4– 5]) (P = 0.017). In addition, the incidences of hypertension, tachycardia, and emergence agitation were significantly lower in Group L than in Group C. No cases of local anesthetic toxicity occurred in either group.Conclusion: Patients received lidocaine at 1 mg/kg for more than 10 minutes followed by continuous infusion at 1.5 mg/kg/h until the end of surgery, which can reduce the incidence of postoperative delirium in elderly patients undergoing hip fracture. In addition, the used regimen of lidocaine would not increase the risk of local anesthetic toxicity.Keywords: lidocaine, postoperative delirium, hip fracture, elderly patients

Dongchu Zhou,1 Xinrui Dong,1 Zhen Zhou,2 Qiao Liu1 1Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, AustraliaCorrespondence: Qiao Liu, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410000, People’s Republic of China, Email liuqiao6767@csu.edu.cnPurpose: The market price of adebrelimab, the first Chinese-developed anti-PD-L1 antibody used as a first-line treatment for extensive stage-small-cell lung cancer (ES-SCLC), has garnered significant public attention. This study sought to investigate the affordable price of adebrelimab for Chinese patients with untreated ES-SCLC through a cost-effectiveness analysis.Patients and Methods: We conducted a cost-effectiveness analysis using a Markov model, incorporating a what-if scenario of adding adebrelimab to first-line etoposide/platinum (EP) chemotherapy is cost-effective for ES-SCLC patients from the perspective of the Chinese healthcare system. The model included three mutually exclusive health states, with transition probabilities derived from the CAPSTONE-1 trial. Health state utilities and costs were acquired from a myriad of authoritative sources. We compared the incremental cost-effectiveness ratios (ICERs) for adebrelimab plus EP chemotherapy (AEP) versus EP with a willingness-to-pay threshold of &dollar;37,654 per quality-adjusted life-years (QALYs) to estimate the affordable price ceiling of the upcoming adebrelimab.Results: For the entire ES-SCLC population, the estimated price ceiling of adebrelimab/mg was &dollar;0.542 (95% CI, &dollar;0.542-&dollar;0.552). Subgroup analyses found that the highest price ceiling of adebrelimab/mg was observed in ES-SCLC patients with lactate dehydrogenase concentration ≤ upper normal limit [&dollar;0.824 (95% CI, &dollar;0.815-&dollar;0.830)]; and the lowest was found in ES-SCLC patients with liver metastasis [&dollar;0.252 (95% CI, &dollar;0.250- &dollar;0.256)]. Sensitivity analysis revealed a heightened probability of cost-effectiveness for the first-line AEP as the price of adebrelimab decreased, encompassing both the entire ES-SCLC population and its subgroups.Conclusion: The affordable price range for adebrelimab/mg Chinese patients with untreated ES-SCLC was estimated to be between &dollar;0.252 and &dollar;0.824, with variations observed across different subgroups. In the context of universal healthcare coverage, our study provides valuable evidence to inform the implementation of a value-based pricing strategy for cancer treatment.Keywords: cost-effectiveness, extensive stage-small-cell lung cancer (ES-SCLC), adebrelimab, drug pricing, China

Xiaomei Chen,1,2 Xunhu Dong,3 Jia Liu,1 Xiao Liu,1 Menghui Deng,1 Yanni Yang1 1School of Nursing, Army Medical University, Chongqing, People’s Republic of China; 2Nursing Department, Qionglai Medical Center Hospital, Qionglai, Chengdu, People’s Republic of China; 3School of Military Preventive Medicine, Army Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Yanni Yang, School of Nursing, Army Medical University, Chongqing, People’s Republic of China, Email yangyanni@tmmu.edu.cnPurpose: The rural–urban gap in sociodemographic, lifestyle, and disease-related characteristics among COPD patients is prevalent. These differences may influence the prevalence of mild cognitive impairment (MCI). This study aimed to compare the prevalence and determinants of MCI between rural and urban areas among COPD patients.Patients and Methods: The cross-sectional study sample comprised 372 COPD patients from China. We evaluated the cognitive function and lung function, collected sociodemographic, lifestyle, and disease-related information, to compare the prevalence of MCI in rural and urban areas. Using multivariate regression analysis to examine the effects of variables to MCI.Results: The prevalence of MCI in rural areas was higher than that in urban areas (65.4% vs 47.9%, P=0.001). The prevalence in farm laborers was almost twice as high as that of non-farm laborers in urban areas (82.6% vs 43.1%), but no significant difference in rural areas (P=0.066). However, the data were lower in subjects who insisted on long-term home oxygen therapy (39.7%, CI:27.8– 51.6, P< 0.001), and who with higher monthly household income (49.6%, CI:40.2– 58.9) in rural areas, but no significant difference in urban areas (P=0.985 and 0.502). Multivariate logistic regression analysis indicated that participants aged 71 years and above, former smokers were at a high risk of MCI in both urban and rural areas. However, participants who slept for 6– 8 hours a day, shopping frequently, or exercised for more than 2 hours a day had a lower risk of MCI in urban areas. But rural participants who insisted on long-term home oxygen therapy had a lower probability of developing MCI.Conclusion: This study revealed that there were significant differences in MCI among COPD patients in rural and urban areas, especially in exercise, sleeping, shopping, and long-term home oxygen therapy. Medical staff should give health guidance according to the actual situation of patients with COPD.Keywords: chronic obstructive pulmonary disease, mild cognitive impairment, urban, rural

Xinyu Nie,1,2 Xinru Dong,1,2 Yuge Hu,1,2 Fangjun Xu,1 Cong Hu,2 Chang Shu1 1Obstetrics and Gynecology Center, First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Reproductive Medicine Center, Prenatal Diagnosis Center, First Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Chang Shu, Email shu_chang@jlu.edu.cnAbstract: Female infertility and pregnancy maintenance are associate with various factors, including quantity and quality of oocytes, genital inflammation, endometriosis, and other diseases. Women are even diagnosed as unexplained infertility or unexplained recurrent spontaneous abortion when failed to achieve pregnancy with current treatment, which are urgent clinical issues need to be addressed. Coenzyme Q10 (CoQ10) is a lipid-soluble electron carrier in the mitochondrial electron transport chain. It is not only essential for the mitochondria to produce energy, but also function as an antioxidant to maintain redox homeostasis in the body. Recently, the capacity of CoQ10 to reduce oxidative stress (OS), enhance mitochondrial activity, regulate gene expression and inhibit inflammatory responses, has been discovered as a novel adjuvant in male reproductive performance enhancing in both animal and human studies. Furthermore, CoQ10 is also proved to regulate immune balance, antioxidant, promote glucose and lipid metabolism. These properties will bring highlight for ovarian dysfunction reversing, ovulation ameliorating, oocyte maturation/fertilization promoting, and embryonic development optimizing. In this review, we systematically discuss the pleiotropic effects of CoQ10 in female reproductive disorders to investigate the mechanism and therapeutic potential to provide a reference in subsequent studies.Keywords: coenzyme Q10, oxidative stress, reactive oxygen species, reproductive, oocyte, endometriosis

Yonghua Ye,1 Yuping Yang,1 Li Yan,1 Li Zhou,2 Shihui Yu,1 Quan Du,3 Xiaoqiao Dong,3 Qiang Yuan,1 Letian Shan,2,4 Le Guo1 1College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Neurosurgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd), Hangzhou, People’s Republic of ChinaCorrespondence: Letian Shan, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Tel +15355015568, Email letian.shan@zcmu.edu.cn Le Guo, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Tel +18986648306, Email le.guo@zcmu.edu.cnPurpose: To explore the pharmacological effects and mechanisms of Qinghao Biejia decoction (QBD) against non-small-cell lung cancer (NSCLC) based on network pharmacology and to verify the anticancer effect of artemisinin B (ART B), the active ingredient of QBD, on H1299 cells.Methods: Ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was applied to explore the chemoprofile of QBD. A zebrafish xenograft model was used to determine the anti-cancer efficacy of QBD. Cell counting kit-8 assay, terminal deoxyribonucleotide transferase-mediated-dUTP nick-end labeling assay; immunofluorescence, and flow cytometry were used to evaluate the in vitro anti-proliferative and pro-apoptotic effects of QBD and ART B on H1299 cells. Subsequently, the related targets and action mechanisms of both QBD and ART B predicted by network pharmacological analyses were experimentally validated by real-time PCR and Western blot assays on H1299 cells.Results: UPLC-QTOF-MS/MS identified a total of 69 compounds (such as ART B, mangiferin, and artemisinic acid) in QBD. The in vivo data showed that QBD significantly inhibited the growth of H1299 cells in xenograft larval zebrafish from 125 to 500 μg/mL. The in vitro data showed that QBD induced apoptosis of H1299 cells, accompanied by down-regulating the expression of BCL-2 and up-regulating the expression of BIM, PUMA, BAX, c-PARP, γ-H2A.X, c-CASP3, and c-CASP8. Alike QBD, ART B exerted similar anti-proliferative and pro-apoptotic effects on H1299 cells. Moreover, ART B inhibited expressions of BCL2L1, AKT1, AKT2, MMP-2, and EGFR, and up-regulated ALB expression. Mechanistically, ART B promoted apoptosis of H1299 cells by inhibiting PI3K/Akt signaling pathway.Conclusion: This study revealed the anti-NSCLC efficacy of QBD. ART B, the effective component of QBD, plays an anti-NSCLC role by down-regulating the PI3K-Akt signaling pathway. It suggests that QBD and ART B are promising drug candidates for NSCLC treatment.Graphical Abstract: Keywords: Qinghao Biejia decoction, non-small-cell lung cancer, larval zebrafish, network pharmacology, artemisinin B

Lu Huang,&ast; Xiuli Dong, Hang Yuan, Lihua Wang&ast; Business School of Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihua Wang, Business School of Sichuan University, Chengdu, Sichuan, People’s Republic of China, Tel +86 +28-85415451, Fax +86 +28-85418379, Email 2470610738@qq.comPurpose: The short video APP has entered the stage of competition for stock, making it crucial to keep users engaged in their APP to promote continuous usage. Previous studies on the continuous use intention of mobile short video APP were relatively limited, with most studies focusing only on promoting factors. Therefore, based on the dual-factor theory of “enabling-inhibiting”, and drawing on the Information System Continuance Model (ECM-ISC) and Cognitive Load Theory, this study extracted two variables, satisfaction and fatigue, to construct an integrated model to explore their enabling and inhibiting effects on continuous use intention.Methods: This study selected TikTok APP users as the respondents, obtained 681 valid questionnaires and analyzed with structural equation modeling (SEM) using SPSS24.0 and Amos23.0 software.Findings: The study investigated the factors that influence users’ continuous use intention of short video APP. It shows that in enabling mechanism, perceived usefulness and social influence will increase user satisfaction and thus promote their continuous use intention, and perceived playfulness has a direct effect on the continuous use intention. In inhibiting mechanism, information overload and communication overload are positively correlated with emotional fatigue, which further reduces the continuous use intention.Contribution/Conclusion: Based on the dual-factor theory of “enabling-inhibiting”, the study established an integration model to more comprehensively reveal the impact mechanism of short video APP users’ continuous use intention. The study found that the fatigue caused by information and communication overload can inhibit users’ continuous use intention of short video APP. Therefore, to improve users’ continuous use intention, short video APP should not only increase users’ satisfaction but also reduce the fatigue caused by overload.Keywords: short video APP, continuous use intention, satisfaction and fatigue, enablers, inhibitors, ECM-ISC model

Xiaoxia Tang,1 Yizhuo Zhang,2 Xinyu Dong,2 Guixing Jiang,2 Defei Hong,2,&ast; Xiaolong Liu2,&ast; 1Operating Room, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2General Surgery, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaolong Liu; Defei Hong, Email hahapoint1234@sina.com; hongdefi@163.comAbstract: At present, the average five-year survival rate of liver cancer in China is only 12.1%. The reason for this association lies in the diagnosis at its middle or/and advanced stage of liver cancer for lacking special clinical symptoms in almost 70% of patients without the chance of effective surgical resection. Epidemiological studies have shown that there are only 30% of patients with an initial diagnosis of liver cancer have the opportunity to undergo radical surgery. Therefore, systematic and comprehensive treatment would play an important role in liver cancer treatment at its middle or/and advanced stage, and the related therapeutic schedule still needs further improvement and optimization. We applied a gene-targeted drug of Icaritin soft capsule in the treatment of a liver cancer patient at its advanced stage. And the level of AFP was found to decrease to 6.4ng/mL from 10.86ng/mL; meanwhile, MRI showed that the primary tumor significantly reduced in size, with shrinking of the hepatogastric space, hepatic aortic side, and renal artery side lymph nodes. After treatment with TACE and Icaritin, the patient had no discomfort and no longer experienced abdominal pain and bloating and gained three kilograms of weight. The therapeutic effect of Icaritin-targeted drugs was completely demonstrated during the later treatment follow-up. That is to say, the multiple anti-tumor characteristics of Icaritin with good safety were fully displayed in this case, and it can be used in combination with other drugs to treat hepatocellular carcinoma in the clinical setting. The results show that Icaritin can put some effects on the combined treatment of patients with liver cancer.Keywords: HCC, patient, systematic and comprehensive treatment, Icaritin, gene-targeted

Shubin Li, Xingna Dong, Limeng Xu, Zhenli Wu Department of Geriatric Medical Center, Inner Mongolia People’s Hospital, Hohhot, 010021, People’s Republic of ChinaCorrespondence: Zhenli Wu, Email zhenliwu@126.comIntroduction: The potential effects of selenium nanoparticles (SeNPs) administration on arsenic exposure-mediated nephrotoxicity by alleviating fibrosis, inflammation, oxidative stress-related damage, and apoptosis remains more detailed investigations.Methods: After the synthesis of selenium nanoparticles (SeNPs) by sodium selenite (Na2SeO3) through a versatile and green procedure, the biosafety of SeNPs was assessed by assaying renal functions and inflammation in mice. Subsequently, nephroprotective effects of SeNPs against sodium arsenite (NaAsO2)-induced damages were confirmed by biochemical, molecular, and histopathological assays, including renal function, histological lesion, fibrosis, inflammation, oxidative stress-related damage, and apoptosis in mice renal tissues and renal tubular duct epithelial cells (HK2 cells).Results: The excellent biocompatibility and safety of SeNPs prepared in this study were confirmed by the non-significant differences in the renal functions and inflammation levels in mice between the negative control (NC) and 1 mg/kg SeNPs groups (p> 0.05). The results of biochemical, molecular, and histopathological assays confirmed that daily administration of 1 mg/kg SeNPs for 4 weeks not only ameliorated renal dysfunctions and injuries caused by NaAsO2 exposure but also inhibited the fibrosis, inflammation, oxidative stress-related damage, and apoptosis in the renal tissues of NaAsO2-exposed mice. In addition, altered viability, inflammation, oxidative stress-related damage, and apoptosis in the NaAsO2-exposed HK2 cells were effectively reversed after 100 μg/mL SeNPs supplementation.Conclusion: Our findings authentically confirmed the biosafety and nephroprotective effects of SeNPs against NaAsO2 exposure-induced damages by alleviating inflammation, oxidative stress-related damage, and apoptosis.Keywords: selenium nanoparticles, arsenite, nephroprotective, inflammation, oxidative stress, apoptosis

Bing Zhang,1,&ast; Xue Dong,2,&ast; Jia Wang,2 Gong-Ke Li,1 Yong Li,3 Xian-Yao Wan2 1Department of Emergency Intensive Care Medicine, Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People’s Republic of China; 2Department of Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, 116000, People’s Republic of China; 3Department of Critical Care Medicine, Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian-Yao Wan, Department of Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, No. 193 Joint Road, Sha He Kou District, Dalian, 116000, People’s Republic of China, Tel +86 41183635963, Fax +86 41183635025, Email Wan_xianyao23@126.com Yong Li, Department of Critical Care Medicine, Affiliated Hospital of Yangzhou University, No. 368 Hanjiang Middle Road, Hanjiang District, Yangzhou, 225000, People’s Republic of China, Tel/Fax +86 51482981199, Email yzliyong0304@163.comBackground: Guidelines recommend norepinephrine (NE) for the treatment of fatal hypotension caused by trauma. However, the optimal timing of treatment remains unclear.Objective: We aimed to investigate the effect of early versus delayed use of NE on survival in patients with traumatic haemorrhagic shock (HS).Materials and Methods: From March 2017 to April 2021, 356 patients with HS in the Department of Emergency Intensive Care Medicine of the Affiliated Hospital of Yangzhou University were identified using the emergency information system and inpatient electronic medical records for inclusion in the study. Our study endpoint was 24 h mortality. We used a propensity score matching (PSM) analysis to reduce bias between groups. Survival models were used to evaluate the relationship between early NE and 24 h survival.Results: After PSM, 308 patients were divided equally into an early NE (eNE) group and a delayed NE (dNE) group. Patients in the eNE group had lower 24 h mortality rates than those in the dNE group (29.9% versus 44.8%, respectively). A receiver operating characteristic analysis demonstrated that a cut-off point for NE use of 4.4 h yielded optimal predictive value for 24 h mortality, with a sensitivity of 95.52%, a specificity of 81.33% and an area under the curve value of 0.9272. Univariate and multivariate survival analyses showed that the survival rate of patients in the eNE group was higher (p < 0.01) than those in the dNE group.Conclusion: The use of NE within the first 3 h was associated with a higher 24 h survival rate. The use of eNE appears to be a safe intervention that benefits patients with traumatic HS.Keywords: norepinephrine, traumatic haemorrhagic shock, propensity score matching

Haiyan Lan, Weifeng Shan, Yini Wu, Qiaomin Xu, Xiaoli Dong, Peiyi Mei, Gongchen Duan, Minji You, Linfei Jin, Jimin Wu Department of Anesthesiology, Lishui City People’s Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, People’s Republic of ChinaCorrespondence: Jimin Wu, Department of Anesthesiology, Lishui City People’s Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, No. 15, Dazhong Street, Lishui, Zhejiang Province, 323000, People’s Republic of China, Email wujimin2022@163.comObjective: To compare the efficacy and safety of ciprofol and propofol for sedation during hysteroscopy.Methods: A total of 149 patients undergoing hysteroscopy were randomly assigned to a ciprofol (Group C) or propofol group (Group P). All cases received intravenous sufentanil 0.1 μg/kg for analgesic preconditioning. Group C received an induction dose of ciprofol 0.4 mg/kg and a maintenance dosage of 0.6– 1.2 mg/kg/h to maintain BIS value between 40– 60. In Group P, propofol was started at 2.0 mg/kg and then maintained at 3.0– 6.0 mg/kg/h. The primary outcome was the successful rate of hysteroscopy. Secondary outcomes included the change of hemodynamic, respiratory adverse events, injection pain, body movement, recovery time, anesthetist’s satisfaction, time of disappearance of the eyelash reflex and the incidence of nausea and vomiting.Results: The success rate of hysteroscopy in each group was 100%. After drug administration, the incidence of hypotension in Group C was much lower than that in Group P (P< 0.05). The incidence of respiratory adverse events in Group C (4.0%) was much lower than that in Group P (31.1%) (P< 0.05). The incidence of injection pain and body movement in Group C was significantly lower than that in Group P (P< 0.05). The mean eyelash reflex disappearance time was less than 3 minutes in both groups. There was no statistically significant difference between the two groups in awakening times, anesthetist’s satisfaction and the incidence of nausea and vomiting. No serious adverse events occurred in any patients.Conclusion: Ciprofol proved to be a safer alternative to propofol for anesthesia during hysteroscopy. In comparison to propofol, ciprofol does not cause injection pain, exerts less impact on hemodynamics, and results in less respiratory depression.Keywords: ciprofol, propofol, sedation, anesthesia, hysteroscopy

Hexing Ma,1 Hailong Pan,2 Xiangxiang Dong,2 Lingyu Li2 1Department of General Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, 225007, People’s Republic of China; 2Department of Major Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, 225007, People’s Republic of ChinaCorrespondence: Lingyu Li, Department of Major Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, 225007, People’s Republic of China, Tel +86 15861356494, Fax +86 514-87213549, Email 657245733@qq.comObjective: To explore the effect of feedforward control on reducing the incidence of unplanned extubation and improving the quality of catheter nursing.Methods: A total of 186 patients with nasogastric tube after gastrointestinal surgery in the eastern region of our hospital from September 2020 to September 2021 were selected as the control group; 186 patients with nasogastric tube after gastrointestinal surgery in the western region of our hospital at the same period were selected as the experimental group. The influencing factors of unplanned extubation in patients with long-term postoperative nasogastric tube were analyzed, and effective preoperative and postoperative health education was conducted. The ratio of unplanned extubation of nasogastric tube and nursing satisfaction of patients in the two groups were compared.Results: Patient constraint, perceived pressure score, anxiety score, nasal gastrointestinal canal health education feedback score and indwell tube comfort score were independent risk factors for unplanned extubation. The restraint rate and the incidence of unplanned extubation in the experimental group were lower than those in the control group after intervention, with statistical significance (P < 0.05). The nursing satisfaction of the experimental group was significantly higher than that of the control group after feedforward cognitive intervention. After intervention, serum albumin and gastric PH in the experimental group were significantly higher than those in the control group (P < 0.05).Conclusion: The safe nursing management method of feed forward control can effectively reduce the incidence of unplanned extubation in inpatients, which is worth further promoting in nursing work.Keywords: feedforward control, unplanned extubation, nasogastric tube, health education

Chenxing Wei,1,&ast; Jian Chen,1,&ast; Tanveer Muhammad Anwar,2,&ast; Lingling Huang,1 Wenjie Yang,3 Xueyan Dong,1 Qiong Chen,1 Min Yue,2,4,5 Daojun Yu1,3 1Department of Medical Laboratory, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China; 2Department of Veterinary Medicine, Institute of Preventive Veterinary Sciences, Zhejiang University College of Animal Sciences, Hangzhou, 310058, People’s Republic of China; 3Department of Medical Laboratory, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 4Hainan Institute, Zhejiang University, Sanya, 572025, People’s Republic of China; 5State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Yue; Daojun Yu, Email myue@zju.edu.cn; yudaojun98@zju.edu.cnPurpose: Acinetobacter baumannii (A. baumannii or AB) is one of the most opportunistic, nosocomial pathogens threatening public healthcare across countries. A. baumannii has become a primary growing concern due to its exceptional ability to acquire antimicrobial resistance (AMR) to multiple antimicrobial agents which is increasingly reported and more prevalent every year. Therefore, there is an urgent need to evaluate the AMR knowledge of A. baumannii for effective clinical treatment of nosocomial infections. This study aimed to investigate the clinical distribution AMR phenotypes and genotypes, and genomic characteristics of A. baumannii isolates recovered from hospitalized patients of different clinical departments of a sentinel hospital to improve clinical practices.Methods: A total of 123 clinical isolates were recovered from hospitalized patients of different clinical departments during 2019– 2021 to analyze AMR patterns, and further subjected to whole-genome sequencing (WGS) investigations. Multi-locus sequence typing (MLST), as well as the presence of antimicrobial-resistant genes (ARGs), virulence factor genes (VFGs) and insertion sequences (ISs) were also investigated from WGS data.Results: The results highlighted that A. baumannii clinical isolates had shown a high AMR rate, particularly from the intensive care unit (ICU), towards routinely used antimicrobials, ie, β-lactams and fluoroquinolones. ST2 was the most prevalent ST in the clinical isolates, it was strongly associated to the resistance of cephalosporins and carbapenems, with blaOXA-23 and blaOXA-66 being the most frequent determinants; moreover, high carrier rate of VFGs was also observed such as all strains containing the ompA, adeF, pgaC, lpsB, and bfmR genes.Conclusion: Acinetobacter baumannii clinical isolates are mostly ST2 with high rates of drug resistance and carrier of virulence factors. Therefore, it requires measurements to control its transmission and infection.Keywords: Acinetobacter baumannii, antimicrobial resistance, genetic determinants, virulence factors, whole-genome sequencing

Xiaoyu Wu,1,&ast; Danfei Ji,1,&ast; Zefan Wang,1,&ast; Wenhua Yu,2 Quan Du,2 Wei Hu,3 Yongke Zheng,3 Xiaoqiao Dong,2 Fanghui Chen4 1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Neurosurgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Intensive Care Unit, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Emergency Department, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqiao Dong; Fanghui Chen, Email dxqhyy@163.com; wangxiaoleihzsy@163.comBackground: NADPH oxidase 2 (NOX2) is highly expressed in injured brain tissues. We determined serum NOX2 levels of aneurysmal subarachnoid hemorrhage (aSAH) patients and further investigated correlation of serum NOX2 levels with disease severity, delayed cerebral ischemia (DCI) plus prognosis after aSAH.Methods: Serum NOX2 levels were measured in 123 aSAH patients and 123 healthy controls. World Federation of Neurological Surgeons scale (WFNS) score and modified Fisher (mFisher) score were utilized to assess disease severity. Modified Rankin scale (mRS) score was used to evaluate the clinical prognosis at 90 days after aSAH. Relations of serum NOX2 levels to DCI and 90-day poor prognosis (mRS score of 3– 6) were analyzed using multivariate analysis. Receiver operating characteristic curve (ROC) was built to evaluate the prognostic predictive capability.Results: Serum NOX2 levels in aSAH patients, compared with healthy controls, were significantly increased, and were independently correlated with WFNS score, mFisher score and post-stroke 90-day mRS score. Patients with poor prognosis or DCI had significantly higher serum NOX2 levels than other remainders, and serum NOX2 levels independently predicted 90-day poor prognosis and DCI. Serum NOX2 had high prognosis and DCI predictive abilities, and their areas under ROC curve were similar to those of WFNS score and mFisher score.Conclusion: Serum NOX2 levels are significantly associated with hemorrhage severity, poor 90-day prognosis and DCI in aSAH patients. Hence, complement NOX2 may serve as a potential prognostic biomarker after aSAH.Keywords: NADPH oxidase 2, biomarker, aneurysmal subarachnoid hemorrhage, disease severity, delayed cerebral ischemia, prognosis

Bo Feng,1,&ast; Xu Dong,1,&ast; Zhen Liu,2 Jie Zhang,3 Hongyu Liu,1 Yuan Xu1 1Department of Pharmacy, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China; 2Department of Neurology, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China; 3Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongyu Liu; Yuan Xu, Department of Pharmacy, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China, Email liuhongyu@yzu.edu.cn; feebyxuyuan@163.comPurpose: Protein tyrosine phosphatases (PTPs) play an essential way in diseases including cancer, obesity, diabetes and autoimmune disorders. As a member of PTPs, low molecular weight PTP (LMPTP) has been a well-recognized anti-insulin resistance target in obesity. However, the number of reported LMPTP inhibitors is limited. Our research aims to discover a novel LMPTP inhibitor and evaluate its biological activity against insulin resistance.Methods: A virtual screening pipeline based on the X-ray co-crystal complex of LMPTP was constructed. Enzyme inhibition assay and cellular bioassay were used to evaluate the activity of screened compounds.Results: The screening pipeline rendered 15 potential hits from Specs chemical library. Enzyme inhibition assay identified compound F9 (AN-465/41163730) as a potential LMPTP inhibitor with a Ki value of 21.5 ± 7.3 μM. Cellular bioassay showed F9 could effectively increase the glucose consumption of HepG2 cells as a result of releasing insulin resistance by regulating PI3K-Akt pathway.Conclusion: In summary, this study presents a versatile virtual screening pipeline for potential LMPTP inhibitor discovery and provides a novel-scaffold lead compound that is worthy of further modification to get more potent LMPTP inhibitors.Graphical Abstract: Keywords: virtual screening, low molecular weight protein tyrosine phosphatase, LMPTP inhibitor, insulin resistance, molecular docking

Xudong Dong,1,2,&ast; Ailing Ding,2,&ast; Hong Hu,1 Fanping Xu,1 Lingyan Liu,1 Min Wu1,3 1The Obstetrical Department of the First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650500, People’s Republic of China; 2Faculty of Life Science and Technology, Kunming University of Science & Technology, Kunming, 650500, People’s Republic of China; 3Yunnan Provincial Key Laboratory of Carbon Sequestration and Pollution Control in Soils, Faculty of Environmental Science & Engineering, Kunming University of Science & Technology, Kunming, 650500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Wu, Email minwupp@163.comPurpose: As two of the most severe and common medical disorders during pregnancy, gestational diabetes mellitus (GDM) and hypertensive disorder complicating pregnancy (HDCP) cause adverse effects on placental barrier function and thus may lead to a high risk of intrauterine exposure to toxic metals from mother to fetus. This study investigates the impact of the placental barrier on the transfer of cadmium (Cd) from mother to fetus and the relationship between pregnancy complications.Methods: A total of 107 pairs of samples were collected in Kunming, China; 29 were from healthy pregnant women, and 78 were from patients with pregnancy complications. Cd was measured in each mother’s placenta and maternal and umbilical cord blood. The expressions of MT and Cd-MT complex in blood and placental tissue samples were determined by enzyme-linked immunosorbent assay (ELISA).Results: The cesarean section rate in the whole pathological group (60.7%) was higher than that in the normal group (20.7%), and the ratio of the effective barrier (ratio of maternal blood to umbilical cord blood> 1) in the pathological group (74%) was lower than that in the normal group (79%). In addition, the proportion of practical placental barriers in women aged 20– 25 years was 83.3%, 76.3% in women aged 26– 30 years, 74.3% in women aged 31– 35 years, 70% in women aged 36– 40 years, and 71% in women aged 40– 45 years. The Cd content in the placenta of the three pathological groups was significantly higher than that in maternal and umbilical cord blood (P< 0.05), and the distribution of Cd was the same as that in the normal group. However, there was no significant difference between maternal and umbilical cord blood Cd concentrations in the pathological group. The Cd concentration in the normal group’s maternal blood was significantly higher than that in cord blood (P< 0.05). In addition, the expression levels of both metallothionein (MT) and Cd-MT complex in placenta is much higher than in maternal and umbilical blood, and which in normal group are significantly higher than those in pathological group.Conclusion: Both mothers and fetuses are at increased health risk for pregnancy disorders when maternal age, BMI, or body weight increases. Increased maternal age increases the likelihood of Cd transfer from the mother to the fetus. Pregnancy complications may induce lower expression of MT, thus reducing the Cd-MT complex in the placenta, weakening the placental barrier, and increasing the risk of Cd transfer and exposure to the fetus.Keywords: gestational diabetes mellitus, gestational hypertension, maternal blood, placenta barrier, pregnancy complication

Hai Fan,1 Yuesong Wang,1 Xuezhong Wang,1 Xuebin Dong,1 Xuwu Shao,1 Fei Yang2 1Department of Cardiovascular Medicine, People’s Hospital of Maanshan, Maanshan, Anhui, People’s Republic of China; 2Department of Laboratory, People’s Hospital of Maanshan, Maanshan, Anhui, People’s Republic of ChinaCorrespondence: Hai Fan, Tel +86-18255552083, Email 491640302@qq.comPurpose: This study aimed to investigate the effect of emergency percutaneous coronary intervention (PCI) combined with sacubitril-valsartan (Entresto) on the cardiac prognosis in patients with acute myocardial infarction (AMI).Patients and Methods: A total of 78 AMI patients who were treated in our hospital between January 2020 and September 2021 were included and randomly divided into treatment group and control group (n=39 per group). In the control group, patients were treated with primary PCI combined with irbesartan; in the treatment group, patients were treated with primary PCI combined with Entresto; pharmacotherapy lasted for 3 months. The left ventricular remodeling indexes, serum N-terminal B-type natriuretic peptide precursor (NT-proBNP), serum homocysteine (HCY), cystatin C (CysC) and results of 6-minute walk test (6MWT) before and after treatment were compared between two groups. The incidence of major adverse cardiovascular events (MACE) was determined and compared between them.Results: (1) Before treatment, there were no marked differences in the left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness (IVST), NT-proBNP, left ventricular ejection fraction (LVEF), HCY, CysC, and results of 6MWT between two groups (P> 0.05). After treatment, the LVEDS, LVEDD, NT-proBNP, HCY and CysC in the control group were significantly higher than in the treatment group (P< 0.05). The recovery of LVEF and 6MWT in the treatment group was significantly better than in the control group (P< 0.05). After treatment, there was no significant difference in the IVST between two groups (P> 0.05). (2) The incidence of MACE in the control group was significantly higher than in the treatment group (P< 0.05).Conclusion: Compared with irbesartan, Entresto can further improve the cardiac function, prevent ventricular remodeling, and further optimize the clinical efficacy of PCI in AMI patients.Keywords: percutaneous coronary intervention, sacubitril-valsartan, acute myocardial infarction, ventricular remodeling

Zijuan Meng,1 Zhaojun Chen,1 Guangwen Lu,1 Xiaoqi Dong,1 Jun Dai,2 Xiaoding Lou,1 Fan Xia1 1Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, People’s Republic of China; 2Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430034, People’s Republic of ChinaCorrespondence: Jun Dai, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430034, People’s Republic of China, Email dj_hust1987@sina.com; jundai@tjh.tjmu.edu.cnBackground: White-light photodynamic therapy (wPDT) has been used in the treatment of cancer due to its convenience, effectiveness and less painful. However, the limited penetration of white-light into the tissues leads to a reduced effectiveness of solid tumor treatment.Methods: Two short-wavelength aggregation-induced emission (AIE) nanoparticles were prepared, PyTPA@PEG and TB@PEG, which have excitation wavelengths of 440 nm and 524 nm, respectively. They were characterized by UV, fluorescence, particle size and TEM. The ability of nanoparticles to produce reactive oxygen species (ROS) and kill cancer cells under different conditions was investigated in vitro, including white-light, after white-light penetrating the skin, laser. A white-light fiber for intra-tumor irradiation was customized. Finally, induced tumor elimination with fiber-mediated wPDT was confirmed in vivo.Results: In vitro, both PyTPA@PEG and TB@PEG are more efficient in the production ROS when exposed to white-light compared to laser. However, wPDT also has a fatal flaw in that its level of ROS production after penetrating the skin is reduced to 20– 40% of the original level. To this end, we have customized a white-light fiber for intra-tumor irradiation. In vivo, the fiber-mediated wPDT significantly induces tumor elimination with maximized therapeutic outcomes by irradiating the interior of the tumor. In addition, wPDT also has the advantage that its light source can be adapted to a wide range of photosensitizers (wavelength range 400– 700 nm), whereas a laser of single wavelength can only target a specific photosensitizer.Conclusion: This method of using optical fiber to increase the tissue penetration of white light can greatly improve the therapeutic effect of AIE photosensitizers, which is needed for the treatment of large/deep tumors and holds great promise in cancer treatment.Keywords: aggregation-induced emission, photodynamic therapy, photosensitizer, white light, fiber optic

Yumei Ge,1,&ast; Xiaoyu Gou,1,&ast; Xiaoyan Dong,1,2 Yumeng Peng,1,3 Fangfang Yang4 1Department of Laboratory Medicine Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2The Second Medical College, Zhejiang Chinese Medical University, Hangzhou, 310014, People’s Republic of China; 3Department of Clinical Laboratory Diagnostics, Bengbu Medical College, Bengbu, 233030, People’s Republic of China; 4Department of Clinical Laboratory, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, 621000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fangfang Yang, Department of Clinical Laboratory, The Third Hospital of Mianyang (Sichuan mental health center), Mianyang, Sichuan, 621000, People’s Republic of China, Email yhge2159@163.comPurpose: At present, there is no gold standard or unified standard for the diagnosis of neurosyphilis, and the rate of misdiagnosis is high. The diagnosis of neurosyphilis is still challenging. This study compared the clinical indicators between neurosyphilis and latent syphilis infection in the central nervous system. The purpose of this study was to provide evidence for the differential diagnosis and prognosis of patients with neurosyphilis and latent syphilis infection of the central nervous system.Methods: The clinical data of 59 patients with neurosyphilis and 30 patients with latent syphilis infection in the nervous system from 2008 to 2021 were analyzed. The cerebrospinal fluid and serum biochemical markers were evaluated for all patients.Results: CSF-nucleated cells, CSF-TRUST, CSF-totalprotein and CSF-IgG (P< 0.001) were significantly different between neurosyphilis and latent syphilis infection in the central nervous system. CSF-TRUST titer was positively correlated with D-D concentration (r = 0.274, P < 0.05), sodion (r =0.251, P < 0.05), respectively. Glucose concentration is the most unreliable in the diagnosis of neurosyphilis (AUC=0.445, P=0.395), and TRUST combined with nucleated cells and total protein is the most accurate in the diagnosis of neurosyphilis (AUC=0.989, P< 0.001).Conclusion: The combination of TRUST, nucleated cell count and totalprotein detection in CSF can distinguish the patients with neurosyphilis and latent syphilis infection in the central nervous system, which has a significant diagnostic value.Keywords: neurosyphilis, latent syphilis infection, diagnosis, detection index

Yalan Luo,1– 3,&ast; Peng Ge,1– 3,&ast; Haiyun Wen,1– 3,&ast; Yibo Zhang,1– 3 Jin Liu,1,3 Xuanchi Dong,1,3 Bowen Lan,1,3 Guixin Zhang,1– 3 Qi Yang,4 Hailong Chen1– 3 1Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, People’s Republic of China; 3Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 4Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Yang; Hailong Chen, Email dyeyyq1016@163.com; chenhailong@dmu.edu.cnObjective: C/EBPβ, a crucial transcription factor, regulates innate immunity and inflammatory responses. However, the role played by C/EBPβ in alveolar macrophage (AM) inflammatory responses remains unknown. This study aimed to investigate the role and mechanism of C/EBPβ in alveolar macrophages (AMs) from the transcriptional level and to search for natural compounds targeting C/EBPβ.Methods: Rat AMs were infected with Lv-sh-C/EBPβ and treated with LPS, and the expression levels of iNOS, TNF-α, IL-6, and IL-1β were measured by RT-qPCR, Western blotting, and ELISA. Mechanistically, transcriptome sequencing (RNA-seq) revealed changes in gene expression patterns in AMs after LPS stimulation and C/EBPβ knockdown. Functional enrichment analyses and rescue experiments identified and validated inflammation-associated cell signaling pathways regulated by C/EBPβ. Furthermore, virtual screening was used to search for natural compounds that inhibit C/EBPβ with the structure of helenalin as a reference.Results: Following stimulation with LPS, AMs exhibited an increased expression of C/EBPβ. C/EBPβ knockdown significantly decreased the expression levels of inflammatory mediators. A total of 374 differentially expressed genes (DEGs) were identified between LPS-stimulated C/EBPβ knockdown and negative control cells. The NOD-like receptor signaling may be a key target for C/EBPβ, according to functional enrichment analyses of the DEGs. Further experiments showed that the muramyl dipeptide (MDP, NOD2 agonist) reversed the downregulation of inflammatory mediators and the NF-κB pathway caused by the C/EBPβ knockdown. The virtual screening revealed that N-caffeoyltryptophan, orilotimod, and petasiphenone have comparable pharmacological properties to helenalin (a known C/EBPβ inhibitor) and demonstrate a great binding capacity to C/EBPβ.Conclusion: Ablation of C/EBPβ may attenuate LPS-induced inflammatory damage in AMs by inhibiting the NOD2 receptor signaling pathway. Three natural compounds, N-caffeoyltryptophan, orilotimod, and petasiphenone, may be potential C/EBPβ inhibitors.Graphical Abstract: Keywords: C/EBPβ, alveolar macrophage, RNA-seq, NOD-like receptor signaling pathway, IL-1β, virtual screening

Lin-Li Xiang,1,&ast; Qian-Qian Wan,2,&ast; Yi-Min Wang,1 Shao-Jun He,3 Wen-Juan Xu,3 Mei Ding,1,4 Jin-Jin Zhang,1,4 Yuan-Li Sun,1,4 Xiang Dong,1,4 Ying Zhou,5 Yu-Bao Cui,6 Ya-Dong Gao1,4 1Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of Rheumatology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University, Wuhan, People’s Republic of China; 5Department of Pediatrics Laboratory, The Affiliated Wuxi Children’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 6Department of Clinical Laboratory, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ya-Dong Gao, Department of Allergology, Zhongnan Hospital of Wuhan University, Donoghue Road 169, Wuhan, People’s Republic of China, Email gaoyadong@whu.edu.cnBackground: Increased proliferation and hypertrophy of airway smooth muscle cells (ASMCs) contribute substantially to airway remodeling in asthma. Interleukin (IL)-13 regulates ASMC proliferation by increasing Orai1 expression, the pore-forming subunit of store-operated Ca2+ entry (SOCE). The underlying mechanisms of this effect are not fully understood.Methods: Bioinformatic analysis identified an interaction between microRNA 93– 5p (miR-93-5p) and long non-coding RNA (lncRNA) H19, and between miR-93-5p and Orai1. RNA interference was used to investigate H19 knockdown on IL-13-induced proliferation and migration of in vitro cultured human bronchial smooth muscle cells (hBSMCs). Functional relevance of H19 in airway inflammation and airway remodeling was investigated in murine models of acute and chronic asthma.Results: IL-13 concentration-dependently increased the expression of H19 and Orai1 and decreased the expression of miR-93-5p in hBSMCs. H19 knockdown partly reversed the effects of IL-13 on the expression of miR-93-5p and Orai1 and attenuated the proliferation and migration of hBSMCs promoted by IL-13. IL-13-promoted expression of Orai1 was attenuated by miR-93-5p mimic and increased by miR-93-5p inhibitor. IL-13-promoted proliferation of hBSMCs was increased by miR-93-5p inhibitor but not affected by miR-93-5p mimic, whereas IL-13-promoted migration of hBSMCs was increased by miR-93-5p inhibitor and attenuated by miR-93-5p mimic. The inhibiting effect of H19 knockdown on IL-13-induced Orai1 expression and the proliferation and migration of hBSMCs was counteracted by miR-93-5p inhibitor but only marginally or not impacted by miR-93-5p mimic. The expression of H19 and Orai1 was higher in the lungs of asthmatic mice than in control mice. In asthmatic mice, H19 siRNA reduced Orai1 expression, inflammatory cell infiltration, goblet cell hyperplasia, collagen deposition and smooth muscle mass in the lungs.Conclusion: H19 may mediate the effects of IL-13 on Orai1 expression by inhibition of miR-93-5p in hBSMCs. H19 may be a therapeutic target for airway inflammation and airway remodeling.Keywords: IL-13, Orai1, lncRNA H19, microRNA-93-5p, bronchial smooth muscle cells, asthma model

Yongchun Zhou, Jing Chen, XiangHui Dong Department of Orthopedic, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of ChinaCorrespondence: XiangHui Dong, Department of Orthopedic, Shaanxi Provincial People’s Hospital, 256 # You-yi West Road, Xi’an, Shaanxi, 710068, People’s Republic of China, Email donggege-0829@163.comObjective: To evaluate the effect of whole-layer barbed suture for incision closure on the clinical outcome and aesthetic satisfaction of patients with the incision following total knee arthroplasty (TKA).Materials and Methods: A retrospective analysis was conducted on 94 patients (37 men and 57 women, 50– 84 years old) who underwent a first TKA between May 2018 and April 2021. The enrolled patients were divided into two groups according to the suture mode, with 45 cases (group A) receiving closure of the deep tissue with a barbed suture and intradermal suture of the incision with another barbed suture and 49 cases (group B) receiving closure of the deep tissue with absorbable suture and interrupted suture of the incision with nonabsorbable suture. Further comparisons were performed regarding incision length, suture time, postoperative incision complications, Hollander Wound Evaluation Score (HWES), Hospital for Special Surgery (HSS) knee score, American Knee Society (AKS) score, and Patient and Observer Scar Assessment Scale (POSAS). The clinical effects of the two suture modes in TKA and the patients’ aesthetic satisfaction with the incision were also evaluated at 2 weeks, 3 months and 6 months after the operation.Results: Compared with group B, group A had higher HWES at 2 weeks after the operation (P < 0.05), shorter suture times (P < 0.05) and lower POSAS scores at 3 and 6 months after the operation (P < 0.05). However, no significant difference was observed between the two groups in incision length, complication rate, HSS or AKS scores (P > 0.05).Conclusion: Compared with the interrupted suture, the use of whole-layer barbed suture for incision closure after TKA has the advantages of a safe and effective outcome, short operation time, high cosmesis degree of the wound scar and high patient satisfaction.Keywords: barbed suture, knee arthroplasty, interrupted suture, aesthetic satisfaction of incision

Yuhuan Shen,1,&ast; Xiaoyan Dong,2,&ast; Jinlin Liu,1 Huoyang Lv,1 Yumei Ge1,3 1Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 2Department of Clinical Laboratory, Ningbo Blood Centers, Ningbo, Zhejiang, People’s Republic of China; 3Key Laboratory of Biomarkers and in vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumei Ge, Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158, Shang-Tang Road, Gong-Shu District, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-0571-85893264, Email 11218070@zju.edu.cnBackground: Interleukin-26 (IL-26) is an atypical proinflammatory cytokine due to its binding to circulating double-stranded DNA and direct antibacterial activity. Although IL-26 has been confirmed to be involved in the pathophysiology of cancer, chronic inflammatory diseases and infections, the diagnostic and prognostic values of IL-26 levels in syphilis patients are not clear. This study aimed to investigate IL-26 levels in different stages of syphilis progression.Methods: A total of 30 healthy controls and 166 patients with syphilis at different stages of disease progression were enrolled. Serum IL-26 levels were quantified in accordance with the protocols of RayBio® Human Interleukin-26 Enzyme Linked Immunosorbent Assay (ELISA) kits. Clinical laboratory diagnostic parameters and blood analysis data were detected and collected according to clinical medical laboratory standards.Results: The levels of serum IL-26 were significantly higher in neurosyphilis patients than in healthy subjects (6.87 (4.36, 12.14) and 1.67 (0.09, 4.89) pg/μL, respectively; &ast;&ast;&ast;&ast;p < 0.0001), latent syphilis (1.48 (0.40, 2.05) pg/μL, &ast;&ast;&ast;&ast;p < 0.0001), seroresistant syphilis (0.81 (0.20, 2.91) pg/μL, &ast;&ast;&ast;&ast;p < 0.0001) and secondary syphilis (1.66 (0.41, 4.25) pg/μL, &ast;&ast;&ast;&ast;p < 0.0001) with data presented as the median with interquartile range. The concentration of serum IL-26 was most sensitive to serum low-density lipoprotein concentration (r = − 0.438, &ast;&ast;p = 0.004) in latent syphilis, urine epithelial cells (r = 0.459, &ast;&ast;p = 0.003) in seroresistant syphilis, and serum creatinine levels (r = 0.463, &ast;&ast;p = 0.004) and urea creatinine ratio levels (r = 0.500, &ast;&ast;p = 0.008) in secondary syphilis patients. There was no significant correlation with the concentration of IL-26 and toluidine red unheated serum test (TRUST) titers in each type of syphilis patient.Conclusion: Circulating IL-26 in serum displays diagnostic potential in the progression of neurosyphilis and warrants further evaluation in clinical trials.Keywords: neurosyphilis, interleukin-26, IL-26, disease progression, biomarker, diagnosis

Shuguang Xu,1 Jinjing Tu,1 Liang Zhang,1 Yinv Chen,1 Xiaoqi Dong,1 Xiaohui Chi,2,&ast; Hao Xu2,&ast; 1Department of Pulmonary and Critical Care Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Xu; Xiaohui Chi, Email xuhao930523@163.com; chixiaohui@zju.edu.cnPurpose: Nosocomial infections caused by New Delhi metallo-β-lactamase (NDM)-producing bacteria are prevalent worldwide. However, such diseases caused by NDM-producing Aeromonas caviae had never been reported. Our study aimed to elucidate the genomic characteristics of NDM-1-producing A. caviae isolated from hospital patients.Methods: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) and phylogenetic analysis. Subsequent investigations include antimicrobial susceptibility testing and multilocus sequence typing (MLST).Results: We identified here two NDM-1-producing A. caviae isolates from bacteremia. Susceptibility testing showed that two isolates were multi-drug resistant and shared a similar resistance profile and were only sensitive to amikacin and trimethoprim/sulfamethoxazole. Both A. caviae isolates carry the carbapenem resistance gene blaNDM-1 and also have antibiotic resistance genes such as β-lactams, AmpC enzymes, macrolides, aminoglycosides, and quinolones. S1-PFGE and Southern blot analysis were negative. Whole-genome sequencing and comparative analysis revealed that these two isolates shared a close relationship.Conclusion: To the best of our knowledge, this work describes the first detection of non-plasmid encoded blaNDM-1 in A. caviae. The A. caviae isolated in this study has a broad drug resistance spectrum. Phenotypic and molecular analysis indicated the two isolates belong to the same clone. Routine genomic surveillance of this species is now necessary to effectively curb the further dissemination of carbapenem-resistant bacteria in the region.Keywords: Aeromonas caviae, New Delhi metallo-β-lactamase, whole-genome sequencing, SNP, phylogenetic analysis

Jing Wang,1 Xing Dong,2 Hong-Yan Wu,1 Wen-Hua Bu,1 Rong Cong,1 Xin Wang,1 Li-Xin Shang,1 Wen Jiang1 1Department of Obstetrics and Gynecology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wen Jiang, Email jiangwen20110108@163.comBackground: A series of studies has shown that lipoprotein-associated phospholipase A2 (Lp-PLA2) is closely associated with abnormal lipid metabolism and vascular endothelial cell injury, but its role in hypertensive disorders of pregnancy (HDP) remains unclear. This study aims to determine the relationship between placental and serum LP-PLA2 levels and HDP, and to provide a feasible method for predicting HDP.Methods: The placental and serum Lp-PLA2 levels of 63 patients with HDP (20, 25, and 18 cases with gestational hypertension, mild preeclampsia, and severe preeclampsia, respectively) and 20 women with normal pregnancies (control group) were measured via a combination of tissue microarray and immunohistochemistry, real-time quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA).Results: 1) The gene and protein expression levels of placental LP-PLA2: the HDP group had significantly higher levels than those of the control group (P < 0.05). The mild preeclampsia group had significantly higher levels than those of the control group (P < 0.05); the severe preeclampsia group had significantly higher levels than those of the mild preeclampsia group (P < 0.05). 2) Serum levels of Lp-PLA2: the HDP group had significantly higher levels than those of the control group (P < 0.05). The Lp-PLA2 levels increased gradually with the progression of the HDP; there were significant differences in the four groups using pair-wise comparisons (P < 0.05). 3) Serum levels of LP-PLA2 were positively correlated with placental LP-PLA2 levels in the HDP group (r = 0.435, P < 0.05).Conclusion: Elevated Lp-PLA2 levels may be associated with the occurrence of HDP, and changes of Lp-PLA2 levels in the maternal blood may be regarded as a monitoring indicator for this disease.Keywords: hypertensive disorders of pregnancy, preeclampsia, lipoprotein-associated phospholipase A2, placenta, serum

Hong Wu,1 Xuhui Dong,1 Lixian Liao,2 Lihaoyun Huang2 1Department of Pneumology, Yiwu Central Hospital, Yiwu, Zhejiang, People’s Republic of China; 2Department of Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Hong Wu, Department of Pneumology, Yiwu Central Hospital, Yiwu, Zhejiang, People’s Republic of China, Email wuhong19842021@Hotmail.comBackground: RAB40C, a member of the Ras oncogene family, is a protein with GTPase and GTP-binding activity and is also predicted to be important in immunomodulation. However, the link between RAB40C and lung squamous cell carcinoma (LUSC) has not yet been elucidated. Exploring the relationship between RAB40C and LUSC could help expand the repertoire of immunotherapeutic targets for LUSC and provide more effective therapeutic options for LUSC patients, which behalf of our aim for our study.Methods: We analyzed the RAB40C expression in different tumor types and stages based on the TCGA database. Subsequently, we explored the differences in RAB40C expression in LUSC versus paracancerous tissues through immunohistochemical analysis. The prognostic value of RAB40C was assessed by Cox regression and Kaplan-Meier analysis. Gene set enrichment analysis-based RAB40C impact pathways and the correlation between RAB40C expression and immune infiltration were obtained using the TIMER2.0 and the CIBERSORT analytical tools. Tumor mutational load and microsatellite instability (MSI) were assessed by the Spearman correlation analysis. Finally, the close association of RAB40C with LUSC was explored by correlating immune cell infiltration with immunomodulator expression, assessing risk scores in combination with other factors, and analyzing prognostic nomogram.Results: The expression of RAB40C was significantly elevated in LUSC. RAB40C expression was significantly associated with immune factors, immune-related pathways, and MSI. Moreover, RAB40C significantly negatively correlated with LUSC-associated immune infiltrating cells, CD4 memory-activated cells, γδ T cells, M1-like macrophages, and the immune regulator CD28, while it positively associated with the activation of Tregs and natural killer cells. Further, a risk model constructed from RAB40C and its associated immune genes showed that RAB40C might be an independent prognostic factor for LUSC.Conclusion: RAB40C can be used as an effective prognostic biomarker and a potential immunotherapeutic target for the treatment of LUSC.Keywords: RAB40C, LUSC, immune regulator, prognostic model, pan-cancer

Yueting Yao,1,&ast; Yan Liang,2,&ast; Xudong Dong,3 Shuyuan Liu,1 Shao Zhang,4 Weipeng Liu,1 Yu Li,5 Li Shi,1 Zhiling Yan,4 Yufeng Yao1 1Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People’s Republic of China; 2College of Nursing Health Sciences, Yunnan Open University, Kunming, 650223, People’s Republic of China; 3The First People’s Hospital of Yunnan Province & The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, People’s Republic of China; 4Department of Gynaecologic Oncology, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, People’s Republic of China; 5Department of Obstetrics, The First People’s Hospital of Kunming, Kunming, 650011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiling Yan, Department of Gynaecologic Oncology, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, People’s Republic of China, Email yanzhiling2021@126.com Yufeng Yao, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, 650118, People’s Republic of China, Email yufeng_yao@imbcams.com.cnBackground: Long non-coding RNAs (lncRNAs) and their polymorphisms play crucial roles in the development of different cancers.Methods: Eight single-nucleotide polymorphisms (SNPs) in ANRIL and MALAT1 (rs1333045, rs4977574, rs1333048, and rs10757278 in ANRIL and rs11227209, rs619586, rs664589, and rs3200401 in MALAT1) were enrolled and genotyped in a total of 1248 samples, including 587 patients with cervical cancer (CC) and 661 healthy individuals using in TaqMan assay. The association of these SNPs with CC was then evaluated.Results: Our results showed that the allele and genotype frequencies of rs3200401 in MALAT1 were significantly different between the control and CC groups after Bonferroni correction (P = 0.001 and P = 0.004, respectively), indicating that the C allele is a protective factor against CC (OR = 0.70; 95% CI = 0.57– 0.87). In addition, the allele and genotype frequencies of rs4977574 in ANRIL were significantly different between the control and CC groups after Bonferroni correction (P = 0.004 and P = 0.014, respectively), and the A allele might be a protective factor for CC (OR = 0.80; 95% CI = 0.68– 0.93). For subgroup analysis, the alleles of rs3200401 in MALAT1 showed significant differences between the control and adenocarcinoma (AC) and control and squamous cell carcinoma (SCC) groups (P = 0.005 and P = 0.004, respectively). The rs3200401C allele could be a protective factor for AC and SCC development (OR = 0.57; 95% CI = 0.38– 0.85; OR = 0.72; 95% CI = 0.58– 0.90). Moreover, the rs3200401C allele could be a protective factor for cervical cancer stage I development (OR = 0.67; 95% CI = 0.53– 0.86).Conclusion: Our results indicate that rs3200401 in MALAT1 and rs4977574 in ANRIL could play key roles in the CC development.Keywords: cervical cancer, single-nucleotide polymorphisms, long non-coding RNAs, association study

Yusheng Guo,1,2,&ast; Yanqiao Ren,1,2,&ast; Xiangjun Dong,1,2 Xuefeng Kan,1,2 Chuansheng Zheng1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuansheng Zheng, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Tel/Fax +86-27-85726290, Email hqzcsxh@sina.comAbstract: Radiofrequency ablation (RFA) is a commonly used treatment for hepatocellular carcinoma (HCC), however, various complex conditions in clinical practice may lead to insufficient radiofrequency ablation (IRFA), allowing residual HCC to survive. In clinical practice and laboratory models, IRFA plays an important role in rapid tumor progression. Therefore, targeting the residual HCC and avoiding IRFA were worthwhile methods. A deeper understanding of IRFA is required; IRFA contributes to the improvement of proliferative activity, migration rates, and invasive capacity, and this may be due to the involvement of multiple complex processes or proteins, including epithelial mesenchymal transitions (EMTs), cancer stem cells (CSCs), autophagy, heat shock proteins (HSPs), changes of non-tumor cells and extracellular matrix, altered immune microenvironment, hypoxia-inducible factors (HIFs), growth factors, epigenetic alterations, and metabolic reprogramming. We focus on the processes of the above mechanisms and possible therapeutic approach, with a review of the literature. Additionally, we recapitulated the construction methods of various experimental models of IRFA (in vivo and in vitro).Keywords: hepatocellular carcinoma, insufficient radiofrequency ablation, epithelial mesenchymal transitions, residual viable tumors

Xiaofang Dong,1 Sen Yang,2 Yuanli Guo,1 Peihua Lv,1 Yanjin Liu1 1Neurology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2Orthopedics Department, The Seventh People’s Hospital of Zhengzhou, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Yanjin Liu, Neurology Department, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 13523548732, Email luomeiruxue139@sina.com; liu-yanjin@126.comPurpose: To identify latent classes of acute stroke patients with distinct experiences with the symptom clusters of depression, anxiety, fatigue, sleep disturbance, and pain symptoms and assess, if the selected variables determine a symptom-cluster experience in acute stroke patients.Participants and Methods: A sample of 690 participants were collected from July 2020 to December 2020 in a cross-sectional descriptive study. Latent class analysis was conducted to distinguish different clusters of acute stroke participants who experienced five patient-reported symptoms. Furthermore, multinomial logistic regression was selected to verify the influencing indicators of each subgroup, with selected socio-demographic variables, clinical characteristics, self-efficacy, and perceived social support as independent variables and the different latent classes as the dependent variable.Results: Three latent classes, named “all high symptom,” “high psychological disorder,” and “all low symptom,” were identified, accounting for 9.6%, 26.3%, and 64.1% of symptom clusters, respectively. Patients in the “all high symptom” and “high psychological disorder” classes reported significantly lower quality of life (F=40.21, p < 0.05). Female gender, younger age, higher National Institutes of Health Stroke Scale scores, and lower self-efficacy and perceived social support were risk factors associated with the “high psychological disorder” class. Younger patients with lower self-efficacy and perceived social support were more likely to be in the “all high symptom” class.Conclusion: This study identified latent classes of acute stroke patients that can be used in predicting symptom-cluster experiences following a stroke. Also, the ability to characterize subgroups of patients with distinct symptom experiences helps identify high-risk patients. Focusing on symptom clusters in clinical practice can inspire us to create effective targeted interventions for subgroups of stroke patients suffering from the same symptom cluster.Keywords: pain, fatigue, sleep disturbance, anxiety, depression

Xinyi Xu, Xu Liu, Xuecheng Dong, Haibo Qiu, Yi Yang, Ling Liu Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of ChinaCorrespondence: Yi Yang; Ling LiuJiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of ChinaEmail yiyiyang2004@163.com; liulingdoctor@126.comPurpose: Activated alveolar macrophages (AMs) secrete extracellular vesicles and particles to mediate the inflammatory response in the acute respiratory distress syndrome (ARDS) although the underlying mechanisms are poorly understood. This study investigated whether secretory autophagosomes (SAPs) from AMs contribute to the inflammation-mediated lung injury of ARDS.Methods: We first isolated SAPs from cell culture supernatants of RAW264.7 cells and AMs and quantified Interleukin (IL)-1β levels in SAPs. Next, we employed a lipopolysaccharide (LPS)-induced ARDS model to investigate whether SAP-derived IL-1β could exacerbate lung injury. Finally, we used siRNA to knockdown Rab8a, both in vitro and in vivo, to investigate the effect of Rab8a on SAP secretion and lung injury in ARDS.Results: We found that AMs play an important role in ARDS by releasing a novel type of proinflammatory vesicles called SAPs that could exacerbate lung injury. SAPs are characterized as double-membrane vesicles (diameter ∼ 200 nm) with the expression of light chain 3 (LC3). IL-1β in SAPs is the key factor that contributes to the inflammation and lung injury in ARDS. We found that Rab8a is necessary for AMs to release SAPs with IL-1β, and Rab8a knockdown alleviated lung injury in ARDS.Conclusion: This study showed the novel finding that SAPs released from AMs play a vital role in ARDS by promoting an inflammatory response and the underlying mechanism was associated with IL-1β secretion.Keywords: secretory autophagosomes, alveolar macrophages, interlukin-1β, Rab8a, acute respiratory distress syndrome

Hengshuai Zhang, Xingyou Dong, Zhenxing Yang, Jiang Zhao, Qudong Lu, Jingzhen Zhu, Longkun Li, Shanhong Yi, Jie Xu Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of ChinaCorrespondence: Jie Xu; Shanhong YiDepartment of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of ChinaEmail xujie1981@tmmu.edu.cn; 2644057844@qq.comBackground: Cross-sensitization of pelvic organs is one theory for why symptoms of gut sickness and interstitial cystitis/bladder pain syndrome overlap. Experimental colitis has been shown to trigger bladder hyperactivity and hyperalgesia in rats. The chemokine receptor CXCR4 plays a key role in bladder function and central sensitization. We aim to study the role of CXCR4 and its inhibitor AMD3100 in colon-bladder cross-organ sensitization.Methods: The colitis model was established by rectal infusion of trinitrobenzene sulfonic acid. Western blot and immunofluorescence were used to assess the expression and distribution of CXCR4. Intrathecal injection of AMD3100 (a CXCR4 inhibitor) and PD98059 (an ERK inhibitor) were used to inhibit CXCR4 and downstream extracellular signal-regulated kinase (ERK) in the spinal cord and dorsal root ganglion (DRG). Intravesical perfusion of resiniferatoxin was performed to measure the pain behavior counts of rats, and continuous cystometry was performed to evaluate bladder voiding function.Results: Compared to the control group, CXCR4 was expressed more in bladder mucosa and colon mucosa, L6-S1 dorsal root ganglion (DRG), and the corresponding segment of the spinal dorsal horn (SDH) in rats with colitis. Moreover, intrathecal injection of the AMD3100 suppressed bladder overactivity, bladder hyperalgesia, and mastocytosis symptoms caused by colitis. Furthermore, AMD3100 effectively inhibited ERK activation in the spinal cord induced by experimental colitis. Finally, treatment with PD98059 alleviated bladder overactivity and hyperalgesia caused by colitis.Conclusion: Increased CXCR4 in the DRG and SDH contributes to colon inflammation-induced bladder overactivity and hyperalgesia partly via the phosphorylation of spinal ERK. Treatment targeting the CXCR4/ERK pathway might provide a potential new approach for the comorbidity between the digestive system and the urinary system.Keywords: pain, visceral hypersensitivity, sensory afferents, urgency, colitis, ERK

Ye Han,1 Qingsong Yu,2 Xiaoqing Dong,3 Jianxia Hou,1,* Jianmin Han4,* 1Department of Periodontology, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, People’s Republic of China; 2Department of Mechanical and Aerospace Engineering, University of Missouri, Columbia, MO, USA; 3Marketing Department, PlasmaDent Inc., Columbia, MO, USA; 4Department of Dental Materials, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianmin Han; Jianxia Hou, Tel +86-10-82195746; +86-13683696349, Fax +86-10-62164691; +86-10-82195496Email hanjianmin@bjmu.edu.cn; jxhou@163.comPurpose: To evaluate the antibacterial and anti-inflammatory properties of SiOx:H nanocoatings using a plasma-deposition technique.Materials and Methods: Four groups of SiOx:H nanocoatings were prepared by plasma nanocoating technique using different deposition gases and durations, specifically trimethylsilane (TMS) for groups A1 and A2 and a mixture of TMS and oxygen for groups B1 and B2. Changes in surface chemistry and physical properties were measured. Staphylococcus aureus and Streptococcus mutans were cultured on plasma SiOx:H nanocoatings to evaluate antibacterial and antibiofilm formation activities. Human gingival fibroblasts (HGFs) and HaCaT human keratinocytes were cultured and stimulated with tumor necrosis factor-α (TNF-α). Cell viability was measured using a Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to evaluate anti-inflammatory properties, including the mRNA and protein levels of inflammatory mediators and proinflammatory cytokines.Results: The carbon content was dominant in group A nanocoatings and the oxygen and silicon elements were dominant in group B nanocoatings. Groups A2 and B2 were approximately threefold thicker than groups A1 and B1. The plasma SiOx:H nanocoatings decreased bacterial growth and biofilm formation by 30– 70% (p < 0.05). Scanning electron microscopy (SEM) revealed damaged biofilm structures. Moreover, the antibacterial properties of group B were greater than group A, and the antibacterial properties of groups A2 and B2 were more effective than A1 and B1, respectively. CCK-8 assays revealed the plasma SiOx:H nanocoatings had good biocompatibility. Furthermore, under TNF-α-induced inflammation, the mRNA and protein levels of interleukin-6, interleukin-8, cyclooxygenase-2, and monocyte chemoattractant protein-1 were downregulated in the plasma SiOx:H nanocoating groups (p < 0.05).Conclusion: Plasma SiOx:H nanocoatings exerted antibacterial and anti-inflammatory effects with excellent biocompatibility. Therefore, the plasma SiOx:H nanocoating technique has potential for implant materials and other medical devices.Keywords: plasma SiOx:H nanocoating technique, biomaterial-related infection, bacterial adhesion, biofilm formation, anti-inflammation

Cheng Chen,1,2,&ast; Xin Dong,1,&ast; Ping Gu,1 Keyan Chen,1 Qi Wan,1 Haiyue Xie,3 Zhaochun Shi,1 Teng Wang1 1Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241000, People’s Republic of China; 3The First Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Teng Wang; Zhaochun ShiDepartment of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of ChinaTel +86 256 830 6050; +86 256 830 3613Fax +86 258 371 8836Email tengwnjmu@163.com; 290694748@qq.comBackground and Purpose: Migraine suffering is more than the onset of head pain. The broad non-painful clinical symptoms associated with migraine are not well recognized. Recent researches support that migraineurs suffer attention deficits, but these findings are not conclusive. The purpose of our study was to assess whether patients with migraine without aura (MwoA) during the interictal period have attention impairment and to identify the migraine characteristics related to attention deficits.Methods: We enrolled subjects with MwoA during the interictal period and healthy controls matched for age, gender, and education level in this cross-sectional study. The attention network test (ANT) and a battery of neuropsychological tests, including the trail-making test (TMT), the digit span test (DST), and the Stroop test, were administered to the participants during the headache-free period.Results: Forty-four subjects with MwoA (4 males, 40 females) and 20 controls matched for age, gender, and literacy education were included. Patients in MwoA were more anxious (P = 0.007) and depressed (P = 0.001) than healthy subjects. Significant differences between the two groups were detected in the executive network (P = 0.006) but not in the alerting and orienting networks of ANT. Mean reaction time of ANT in the MwoA group was significantly longer than that in the control group (P = 0.028). Patients showed worse performance on DST-forward (P < 0.001), DST-backward (P < 0.001), DS Total (P < 0.001), TMT-A (P < 0.001), TMT-B (P < 0.001) and TMT-d (P = 0.002). Differences found in executive functions between the two groups were unrelated to gender, age, literacy, anxiety, and depression. Multiple regression analysis revealed no relation between clinical characteristics of headache and scores on the executive function with MwoA.Conclusion: Our study suggested that patients in MwoA present worse performances on the executive control of attention networks during the headache-free period, which appear not be associated with measures of migraine severity. Although more studies are needed in this area, our results could be useful to find specific neuropsychological biomarker for migraine pathophysiology.Keywords: migraine without aura, attention, attention network test, executive function, reaction time

Chenyang Li,1 Liang Xie,2 Shaomei Shang,1 Xiaosong Dong,3 Xiaoling Wang,4 Long Zhao,3 Chi Zhang,3 Fang Han3 1Peking University School of Nursing, Beijing, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 4PKU-UPenn Sleep Center, Peking University International Hospital, Beijing, People’s Republic of ChinaCorrespondence: Fang HanSleep Medicine Center, Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaEmail hanfang1@hotmail.comObjective: This study aimed to translate and validate the narcolepsy quality-of-life instrument with 21 questions (NARQoL-21) in Chinese pediatrics with narcolepsy.Methods: NARQoL-21 was translated following the 10 steps of scale translation. The translated version was tested by exploratory factor analysis (EFA), confirmatory factor analysis (CFA), known-group validity, criterion validity, Cronbach’s α and test-rest reliability.Results: The Chinese version of NARQoL-21 consisted of two factors: (psychosocial factors and future outlook factor), including 20 items. EFA yielded 3 domains for psychosocial factors and 1 domain for future outlook factor. The Chinese version had a negative correlation with the overall Modified Epworth Sleepiness Scale (r = − 0.518, p< 0.001) and meaningful difference in score between drug naïve and treated group (p< 0.05). The Cronbach’s α coefficient was higher than 0.7 and intraclass correlation coefficient (ICC) ranged from 0.75 to 0.905, indicating that it had good reliability.Conclusion: The Chinese version of the NARQoL-21 is available and can be used to evaluate the health-related quality of life (HRQoL) of pediatric narcoleptics, despite that there is a shift in factors compared to the English version due to cultural differences. Future studies are recommended to further validate the scale in Chinese pediatrics with narcolepsy.Keywords: narcolepsy, pediatrics, quality of life, validation study

Yu He,1 Lina Guo,1 Yanjin Liu,2 Miao Wei,1 Yuanli Guo,1 Xiaofang Dong,1 Caixia Yang,1 Qing Zhou,3 Xiaoyu Lei,4 Gege Zhang,1 Mengyu Zhang4 1Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Nursing, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Rehabilitation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4College of Nursing, Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Yanjin LiuDepartment of Nursing, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Erqi District, Zhengzhou, People’s Republic of ChinaTel +86 183 9206 1307Email lyjhlb@126.comPurpose: To examine the effectiveness of goal-based health management on health knowledge, health belief and health behavior in people at high risk of stroke.Patients and Methods: This is a two-armed and non-randomized controlled trial from May 31, 2020 to December 31, 2020. Participants were arranged to receive regular health care (n=126) or goal-based health management (n=126). The generalized estimation equation was used to analyze the changes in the participants’ health knowledge, health belief and health behavior at baseline (T0), 1-month (T1), 3-month (T3), and 6-month (T6).Results: A total of 243 participants completed the 6-month study, of which 123 were in the control group and 120 were in the intervention group. After receiving goal-based health management, participants’ health behavior (β= 27.154, p< 0.001), health knowledge (β= 10.504, p< 0.001) and health belief (β= 49.057, p< 0.001) scores increased significantly.Conclusion: Goal-based health management can effectively improve the health knowledge, health belief and health behavior of people at high risk of stroke. We recommend that nurses can provide goal-based health management for people at high risk of stroke with support from hospitals and family members of people at high risk of stroke.Keywords: stroke, prevention, goal setting theory, ecology of health

Yifang Chen,1,&ast; Yang Li,1,&ast; Han Guo,1,2,&ast; Zhaoqi Zhang,1,2 Jiayu Zhang,1,2 Xue Dong,1 Yi Liu,3 Yuan Zhuang,3 Yong Zhao1,4 1Department of State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 3Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of State Key Laboratory of Membrane Biology, Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Zhao; Yuan Zhuang Email zhaoy@ioz.ac.cn; zhuangyuan0215@126.comBackground: Neutrophils present great diverse phenotypes in various microenvironments and play different immune regulatory functions. Neutrophils generally classified into inflammatory phenotype N1 and anti-informatory phenotype N2. Our recent studies showed that IL-23 alone stimulated neutrophils to express IL-17A, IL-17F and IL-22 and displayed a gene transcriptional profile similar to Th17 cells. In the present study, we tried to identify potential cytokines to promote IL-23-induced neutrophil polarization.Methods: Mouse bone marrow-derived neutrophils and human peripheral blood neutrophils were treated with IL-23 (10 ng/mL) plus IL-18 (25 ng/mL) to induce Th17-like subset in vitro and detected by real-time PCR, flow cytometry, ELISA, immunofluorescence and RNA-seq assays. In vivo, collagen-induced arthritis (CIA) mouse model and EL4 tumor-bearing mouse model were used to characterize the potential roles of N(IL-23+IL-18) in inflammation and tumor.Results: Real-time PCR, ELISA and flow cytometry assays showed that IL-18 could significantly enhance IL-23-induced IL-17A, IL-17F and IL-22 expressions in mouse and human neutrophils in a synergistic way, although IL-18 alone failed to induce these cytokines expression. RNA-seq and molecular studies showed that the polarization of N(IL-23+IL-18) is mainly mediated by the JNK/p38-STAT3-BATF signaling pathway. Adoptive transfer of the induced N(IL-23+IL-18) neutrophils significantly accelerated the tumor growth in EL4 tumor-bearing mice and enhanced disease progression in the CIA mouse model. IL-17A-deficient N(IL-23+IL-18) neutrophils failed to enhance the CIA pathogenesis in this model, suggesting that IL-17A may be involved in the N(IL-23+IL-18) neutrophils-promoted arthritis in mice.Conclusion: The Th17-type subpopulation N(IL-23+IL-18) has pro-tumor and pro-inflammatory properties. Recognizing the different functional polarization of neutrophils would significantly help us to understand the distinctive protective/pathological roles of neutrophils in physiological and different pathological situations.Keywords: IL-23, IL-18, neutrophils, polarization, tumor, arthritis