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Liqun Peng,1,2 Shaohua Xu,3 Jian-Liang Xu4 1Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, People’s Republic of China; 3Department of Clinical Laboratory, Center for Gene Diagnosis & Program of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Jian-Liang Xu, Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, People’s Republic of China, Tel +86-13580575810, Fax +8620-85253178, Email xujl6@mail.sysu.edu.cn Shaohua Xu, Department of Clinical Laboratory, Center for Gene Diagnosis & Program of Clinical Laboratory, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, People’s Republic of China, Email xshct4975@163.comIntroduction: Immunogenic cell death (ICD) can enhance the potency of immunotherapy in cancer treatment. Nevertheless, it is ambiguous how ICD-related genes (ICDRGs) contribute to hepatocellular carcinoma (HCC).Methods: Single-cell RNA sequencing (scRNA-seq) data were used to distinguish malignant cells from normal cells in the HCC tumor microenvironment(TME). Bulk RNA sequencing data was employed to acquire the landscape of the 33 ICDRGs. Unsupervised clustering identified two ICD molecular subtypes. The cellular infiltration characteristics and biological behavior in different subtypes were analyzed by ssGSEA. Subsequently, differentially expressed genes (DEGs) between the two subtypes were determined, based on which patients were classified into three gene clusters. Then, the prognostic model was constructed by Lasso-Cox analysis. Finally, we investigated the expression of risk genes in cancer cell line encyclopedia (CCLE) and validated the function of NKX3-2 in vitro experiments.Results: ICD scores and ICDRGs expression in malignant cells were significantly lower than in normal cells by scRNA-seq analysis. ICD-high subtype was characterized by ICD-related gene overexpression and high levels of immune infiltration abundance and immune checkpoints; Three DEGs-related gene clusters were likewise strongly linked to stromal and immunological activation. In the ICD-related prognostic model consisting of NKX3-2, CHODL, MMP1, NR0B1, and CTSV, the low-risk group patients had a better endpoint and displayed increased susceptibility to immunotherapy and chemotherapeutic drugs like 5-Fluorouracil, afatinib, bortezomib, cediratinib, lapatinib, dasatinib, gefitinib and crizotinib. Moreover, NKX3-2 amplification in HCC samples has been verified by experiments, and its disruption suppressed the proliferation and invasion of tumor cells.Conclusion: Our study highlighted the potential of the ICDRGs risk score as a prognostic indicator to aid in the accurate diagnosis and immunotherapy sensitivity of HCC.Keywords: Hepatocellular carcinoma, prognostic model, immunotherapy, immunogenic cell death

Fan Jiang, Lingyi Lu, Sihan Wang, Feng Yuan, Lu Cao, Suling Xu,* Bingjiang Lin* Department of Dermatology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang; National Clinical Medical Research Center for Skin and Immune Diseases, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Suling Xu; Bingjiang Lin, Department of Dermatology, The First Affiliated Hospital of Ningbo University, No. 59 Liuting Street, Ningbo, Zhejiang, 315000, People’s Republic of China, Email linbingjiangnb@163.comPurpose: The purpose of this study was to investigate the comprehensive impact of family history of psoriasis, lesion size, disease severity, and the possibility of joint involvement on patients’ quality of life(QoL).Patients and Methods: Data from 5961 patients with psoriasis recruited from 440 hospitals throughout China were analyzed. The effects of family history of psoriasis, Body Surface Area(BSA), Psoriasis Area and Severity Index(PASI), and Psoriasis Epidemiology Screening Tool(PEST) on their Dermatology Life Quality Index(DLQI) were studied using a moderated chained mediated effects test.Results: A total of 912 patients (15.30%) had a family history of psoriasis, and 5071 patients (85.10%) had plaque psoriasis. In patients with plaque psoriasis, the variables of family history, PASI, PEST, and DLQI were positively correlated with each other. Additionally, in patients with other types of psoriasis, PASI was positively correlated with PEST and DLQI. Age was positively correlated with PASI and PEST and negatively correlated with DLQI in patients with plaque psoriasis; their Body Mass Index(BMI) and disease duration were in positive correlation with PASI and PEST. The mediation effect of PASI and PEST between family history and DLQI was remarkable in patients with plaque psoriasis and not in those with other types of psoriasis. BSA moderated the association between family history and PASI in patients with plaque psoriasis.Conclusion: PASI and PEST play a chain mediating role in the relationship between family history and DLQI in patients with plaque psoriasis, and high levels of BSA increase the ability of family history to positively predict PASI in plaque psoriasis, thereby affecting the patient’s QoL.Keywords: plaque psoriasis, PASI, PEST, quality of life, family history

Jincheng Ma,1– 3,* Jiansong Lin,4,* Xite Lin,1– 3 Yuan Ren,1– 3 Dabin Liu,5 Shuting Tang,1– 3 Leyi Huang,1– 3 Shuxia Xu,4 Xiaodan Mao,1– 3 Pengming Sun1– 3,5 1Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 3Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian Province, People’s Republic of China; 4Department of Pathology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Department of Gynecology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodan Mao; PengMing Sun, Email maodan1985@fjmu.edu.cn; sunfemy@hotmail.comObjective: This study introduced a novel subtype classification method for endometrial cancer (EC) with mismatch repair deficiency (MMRd) by employing immune status and prognosis as the foundational criteria. The goal was to enhance treatment guidance through precise subtype delineation.Methods: Study Cohort: This study encompassed a cohort of 119 patients diagnosed with MMRd-EC between 2015 and 2022. Analyses using t-tests and Mann–Whitney U-tests were performed to assess prognostic markers and peripheral blood immune cell profiles in patients with MutS deficiency (MutS-d) versus those with MutL deficiency (MutL-d). Logistic regression analysis was used to identify independent risk factors. Bioinformatics Analysis: An online database was used to assess the prognostic implications, immune cell infiltration, and immune checkpoint involvement associated with the deficiency of MutS versus MutL in EC.Results: Patients with MutL-d exhibited heightened risk factors, including elevated cancer grade and increased myometrial invasion, leading to poorer prognosis and shorter overall survival and progression-free survival. Regarding systemic immune status, patients with MutL-d demonstrated decreased peripheral blood lymphocyte percentage, lymphocyte count, and CD8+ T cell percentage. For local immunity, the infiltration of natural killer cells, CD8+ T cells, and cytotoxic T lymphocytes in the tumor tissue was reduced in patients with MutL-d. Additionally, patients with MutL-d exhibited lower expression of immune checkpoint markers. The composition of immune subtypes and survival outcomes also indicate that patients with MutL-d have a poorer immune status and prognosis than the patients with MutS-d.Conclusion: Patients with MMRd-EC can be subclassified according to MutS or MutL deficiency. Patients with MutS-d exhibited better immune status, prognosis, and immunotherapy benefits than those with MutL-d. These results can help guide patients to a more precise treatment.Keywords: endometrial cancer, mismatch repair-deficiency, immune, molecular classification, MutL, MutS

Ronglin Ma,1,2,* Chunya Ji,1,* Mengdan Shen,2 Shujuan Xu,2 Guojia Fan,3 Chengcheng Wu,1 Qiang Yu,2 Linliang Yin1 1Center for Medical Ultrasound, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China; 3Center for Cytotoxicity Testing, Sanitation & Environment Technology Institute, Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiang Yu, Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Jiangsu, People’s Republic of China, Tel +86 512 62362045, Email yuqiang0102sz@163.com Linliang Yin, Center for Medical Ultrasound, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Jiangsu, People’s Republic of China, Tel +86 13382183478, Email yllsznthello@hotmail.comBackground: Radionuclides have important roles in clinical tumor radiotherapy as they are used to kill tumor cells or as imaging agents for drug tracing. The application of radionuclides has been developing as an increasing number of nanomaterials are used to deliver radionuclides to tumor areas to kill tumor cells. However, promoting the efficient combination of radionuclides and nanocarriers (NCs), enhancing radionuclide loading efficiency, and avoiding environmental pollution caused by radionuclide overuse are important challenges that hinder their further development.Methods: In the present study, a new small molecule compound (3-[[(2S)-2-hydroxy-3-(4-hydroxyphenyl)-1-carbonyl] amino]-alanine, abbreviation: HN, molecular formula: C12H16N2O5) was synthesized as a linker between radionuclide iodine-125 (125I) and NCs to enable a more efficient binding between NCs and radionuclides.Results: In vitro evidence indicated that the linker was able to bind 125I with higher efficiency (labeling efficiency > 80%) than that of tyrosine, as well as various NCs, such as cellulose nanofibers, metal oxide NCs, and graphene oxide. Single-photon emission computed tomography/computed tomography imaging demonstrated the biological distribution of 125I-labeled NCs in different organs/tissues after administration in mice.Conclusion: These results showed an improvement in radionuclide labeling efficiency for nanocarriers and provided an approach for nanocarrier image tracing.Keywords: nanocarriers, radionuclide labeling, radionuclide 125i, SPECT/CT imaging

Chengying Hong,1 Yihan Xiong,2 Jinquan Xia,3 Wei Huang,4 Andi Xia,1 Shunyao Xu,1 Yuting Chen,1 Zhikun Xu,1 Huaisheng Chen,1 Zhongwei Zhang5 1Department of Critical Care Medicine, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 2Neurology Department, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 3Department of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 4Department of Clinical Microbiology, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 5Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Huaisheng Chen, Department of Critical Care Medicine, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China, Email sunshinic@hotmail.com Zhongwei Zhang, Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Email 716461751@qq.comObjective: The objective of this study was to utilize LASSO regression (Least Absolute Shrinkage and Selection Operator Regression) to identify key variables in septic patients and develop a predictive model for intensive care unit (ICU) mortality.Methods: We conducted a cohort consisting of septic patients admitted to the ICU between December 2016 and July 2019. The disease severity and laboratory index were analyzed using LASSO regression. The selected variables were then used to develop a model for predicting ICU mortality. AUCs of ROCs were applied to assess the prediction model, and the accuracy, sensitivity and specificity were calculated. Calibration were also used to assess the actual and predicted values of the predictive model.Results: A total of 1733 septic patients were included, among of whom 382 (22%) died during ICU stay. Ten variables, namely mechanical ventilation (MV) requirement, hemofiltration (HF) requirement, norepinephrine (NE) requirement, septicemia, multiple drug-resistance infection (MDR), thrombocytopenia, hematocrit, red-cell deviation width coefficient of variation (RDW-CV), C-reactive protein (CRP), and antithrombin (AT) III, showed the strongest association with sepsis-related mortality according to LASSO regression. When these variables were combined into a predictive model, the area under the curve (AUC) was found to be 0.801. The AUC of the validation group was 0.791. The specificity of the model was as high as 0.953. Within the probability range of 0.25 to 0.90, the predictive performance of the model surpassed that of individual predictors within the cohort.Conclusion: Our findings suggest that a predictive model incorporating the variables of MV requirement, HF requirement, NE requirement, septicemia, MDR, thrombocytopenia, HCT, RDW-CV, CRP, and AT III exhibiting an 80% likelihood of predicting ICU mortality in sepsis and demonstrates high accuracy.Keywords: sepsis, mortality, LASSO regression, predictive model, ICU

Xun Qiu,1,2,* Libin Dong,1,2,* Kai Wang,1,2 Xinyang Zhong,1,2 Hanzhi Xu,1,2 Shengjun Xu,2 Haijun Guo,2 Xuyong Wei,1,2 Wei Chen,2,3 Xiao Xu1,2 1Department of Surgery, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China; 2Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, People’s Republic of China; 3Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Chen; Xiao Xu, Email jackweichen@zju.edu.cn; zjxu@zju.edu.cnBackground: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Accumulating evidence indicates that hypoxia and lactate metabolism play critical roles in tumor progression and therapeutic efficacy. This study aimed to construct a hypoxia- and lactate metabolism-related prognostic model (HLPM) to evaluate survival and treatment responses for HCC patients and develop a nomogram integrated with HLPM and clinical characteristics for prognosis prediction in HCC.Methods: Expression profile and clinical data of HCC were obtained from TCGA and ICGC databases. The univariate, LASSO and stepwise multivariate Cox analyses were used to identify the hypoxia- and lactate metabolism-related biomarkers, whose expression levels were then validated in 14 pairs tissue samples and single-cell RNA sequencing dataset. Kaplan–Meier survival curves were utilized to assess the prognostic values of biomarkers or models. Analyses of ImmuCellAI, TIDE and drug sensitivity were conducted to evaluate the therapeutic responses of patients. Furthermore, the nomogram integrated with hypoxic and lactate metabolic characteristics was established through univariate and multivariate Cox analyses. ROC curves, C-index, and calibration curves were depicted to evaluate the performance of the nomogram.Results: Five hypoxia- and lactate metabolism-related biomarkers (KIF20A, IRAK1, ADM, PPARGC1A and EPO) were used to construct HLPM. The expression of five prognostic biomarkers was validated in 14 pairs tissue samples and single-cell RNA sequencing dataset. Analyses of ImmuCellAI, TIDE and drug sensitivity implied that patients with low-risk score were more sensitive to immunotherapy and major chemotherapeutic agents. The nomogram that contained age, histological grade and risk score of HLPM was developed and exhibited a better capacity in prognosis prediction than HLPM only.Conclusion: A novel nomogram integrated with hypoxic and lactate metabolic characteristics was developed and validated for prognosis prediction in HCC, providing insight into personalized decision-making in clinical management.Keywords: hepatocellular carcinoma, nomogram, prognosis, lactate metabolism, hypoxia, immunotherapy

Ruoxin Fang,* Sha Xu,* Jun Gong, Zhengkai Liao Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, Hubei, 430071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengkai Liao, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China, Email zliao@whu.edu.cnAim: BRAF is a pivotal driver gene in cancer development. Based on this, the combination of dabrafenib and trametinib was approved for treating NSCLC patients with BRAFV600E mutations. However, the majority of BRAF mutations in lung cancer are non-V600E variants, particularly class III mutants, which currently lack targeted therapeutic options and result in unfavorable clinical outcomes.Case Presentation: We present a case of advanced lung adenocarcinoma with a class III BRAFG466V mutation. The patient experienced significant pleural and pericardial effusion, leading to chest tightness and an inability to lie flat. Severe pain and limited mobility from lumbar destruction seriously affected the patient’s quality of life. Due to the patient’s intolerance to chemotherapy, dabrafenib and trametinib combination therapy was chosen. After three months of targeted therapy, the patient’s overall condition significantly improved, enabling self-care, and achieving partial response (PR) as an indicator of treatment efficacy.Conclusion: The combination therapy of dabrafenib and trametinib demonstrates remarkable clinical benefits for lung adenocarcinoma patients with the BRAFG466V mutation. Targeted therapy should be considered for patients with BRAF class III mutations, especially those in poor general condition and may not tolerate chemotherapy.Keywords: case report, NSCLC, BRAF G466V, targeted therapy, dabrafenib, trametinib

Yilin Li,1,* Jiaxing Liu,2,* Shun Xu,1 Jiajun Wang1 1Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of General Surgery, The Fourth Hospital of China Medical University, Shenyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shun Xu; Jiajun Wang, Email xushun610539@sina.com; wjj100@163.comAbstract: The tumor microenvironment plays a crucial role in cancer development and treatment. Traditional 2D cell cultures fail to fully replicate the complete tumor microenvironment, while mouse tumor models suffer from time-consuming procedures and complex operations. However, in recent years, 3D bioprinting technology has emerged as a vital tool in studying the tumor microenvironment. 3D bioprinting is a revolutionary biomanufacturing technique that involves layer-by-layer stacking of biological materials, such as cells and biomaterial scaffolds, to create highly precise 3D biostructures. This technology enables the construction of intricate tissue and organ models in the laboratory, which are utilized for biomedical research, drug development, and personalized medicine. The application of 3D bioprinting has brought unprecedented opportunities to fields such as cancer research, tissue engineering, and organ transplantation. It has opened new possibilities for addressing real-world biological challenges and improving medical treatment outcomes. This review summarizes the applications of 3D bioprinting technology in the context of the tumor microenvironment, aiming to explore its potential impact on cancer research and treatment. The use of this cutting-edge technology promises significant advancements in understanding cancer biology and enhancing medical interventions.Keywords: 3D bioprinting, tumor microenvironment research, tumor microenvironment

Wenhua Yu,1 Bo Yang,1 Siting Xu,1 Yun Gao,2 Yan Huang,3 Zhongqun Wang1 1Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 3Department of Ophthalmology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of ChinaCorrespondence: Zhongqun Wang; Yan Huang, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China, Tel +86-15262919468, Email wangtsmc@126.com; wangzhongqun@ujs.edu.cn; 0511syj@163.comAbstract: Diabetic complications can be divided into macrovascular complications such as cardiovascular disease and cerebrovascular disease and microvascular complications such as diabetic retinopathy, diabetic nephropathy and diabetic neuropathy. Among them, cardiovascular disease (CVD) is an important cause of death in diabetic patients. Diabetes retinopathy (DR) is one of the main reasons for the increasing disability rate of diabetes. In recent years, some studies have found that because DR and CVD have a common pathophysiological basis, the occurrence of DR and CVD are inseparable, and to a certain extent, DR can predict the occurrence of CVD. With the development of technology, the fundus parameters of DR can be quantitatively analyzed as an independent risk factor of CVD. In addition, the cytokines related to DR can also be used for early screening of DR. Although many advances have been made in the treatment of CVD, its situation of prevention and treatment is still not optimistic. This review hopes to discuss the feasibility of DR in predicting CVD from the common pathophysiological mechanism of DR and CVD, the new progress of diagnostic techniques for DR, and the biomarkers for early screening of DR.Keywords: diabetic retinopathy, cardiovascular disease, pathophysiological mechanism, optical coherence tomography angiography, biomarkers

Songbai Xu,1 Guangxin Zhang,2 Jiaomei Zhang,1 Wei Liu,2 Yicun Wang,2 Xiying Fu2 1Department of Neurosurgery, Department of Obstetrics, Obstetrics and Gynaecology Center, the First Hospital Jilin University, Changchun, People’s Republic of China; 2Department of Endocrinology, Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, Department of Thoracic Surgery, the Second Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yicun Wang; Xiying Fu, Email wangyicun@jlu.edu.cn; fuxiying@jlu.edu.cnAbstract: Brain tumors, including primary gliomas and brain metastases, are one of the deadliest tumors because effective macromolecular antitumor drugs cannot easily penetrate the blood-brain barrier (BBB) and blood-brain tumor barrier (BTB). Magnetic nanoparticles (MNPs) are considered the most suitable nanocarriers for the delivery of brain tumor drugs because of their unique properties compared to other nanoparticles. Numerous preclinical and clinical studies have demonstrated the potential of these nanoparticles in magnetic targeting, nuclear magnetic resonance, magnetic thermal therapy, and ultrasonic hyperthermia. To further develop and optimize MNPs for the diagnosis and treatment of brain tumors, we attempt to outline recent advances in the use of MNPs to deliver drugs, with a particular focus on their efficacy in the delivery of anti-brain tumor drugs based on magnetic targeting and low-intensity focused ultrasound, magnetic resonance imaging for surgical real-time guidance, and magnetothermal and ultrasonic hyperthermia therapy. Furthermore, we summarize recent findings on the clinical application of MNPs and the research limitations that need to be addressed in clinical translation.Keywords: magnetic nanoparticles, blood-brain tumor barrier, tumor therapy, drug delivery, brain tumor

Nongnong Yang,1,* Haiyan Ma,1,2 Mengyi Huang,1,* Esther Yuet Ying Lau,3– 5 Daniel Yee Tak Fong,6 Meng Wang,7 Pengqiao Wang,1 Siyi Xu,8 Jiale Xu,1 Chen Jiang,1 Yi Luo,9 Runtang Meng1,2,* 1School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 2Engineering Research Center of Mobile Health Management System, Ministry of Education, Hangzhou, Zhejiang, People’s Republic of China; 3Sleep Laboratory, Department of Psychology, The Education University of Hong Kong, Hong Kong, People’s Republic of China; 4Centre for Psychosocial Health, The Education University of Hong Kong, Hong Kong, People’s Republic of China; 5Centre for Religious and Spirituality Education, The Education University of Hong Kong, Hong Kong, People’s Republic of China; 6School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 7Ophthalmology Center, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang, People’s Republic of China; 8School of Nursing, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 9School of Nursing, Ningbo College of Health Sciences, Ningbo, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Runtang Meng; Haiyan Ma, School of Public Health, Hangzhou Normal University, No. 2318, Yuhangtang Road, Yuhang District, Hangzhou, Zhejiang, 311121, People’s Republic of China, Email mengruntang@hznu.edu.cn; mahaiyan@hznu.edu.cnPurpose: The World Health Organization-Five Well-Being Index (WHO-5) is widely used to assess subjective well-being. Nevertheless, measurement invariance and optimal cutoff point of the WHO-5 have not been examined in Chinese samples. We aimed to assess measurement properties of the Chinese version of the WHO-5 (WHO-5-C) among healthcare students.Patients and Methods: A two-wave longitudinal assessment was conducted among 343 Chinese healthcare students from September to November 2022. Measurement properties of the WHO-5-C were assessed through structural validity using confirmatory factor analysis (CFA), measurement invariance using multigroup CFA (MGCFA) and longitudinal CFA (LCFA), convergent validity using correlation analysis with the Self-Rated Health Questionnaire (SRHQ) and Patient Health Questionnaire-4 (PHQ-4), reliability using internal consistency and test–retest reliability, and optimal cutoff point using receiver operating characteristic (ROC) analysis.Results: The WHO-5-C demonstrated satisfactory structural validity with comparative fit index (CFI) of 0.968 at baseline and 0.980 at follow-up, and adequate measurement invariance in different sociodemographic variables at baseline (gender, age, major, home location, being only child, monthly household income, part-time job, physical exercise, hobby, frequency of visiting home, and stress coping strategy) (CFI changes [ΔCFI] = − 0.009– 0.003) and over a week (ΔCFI = − 0.006– 0.000). The WHO-5-C also had good internal consistency (Cronbach’s α = 0.907– 0.934; McDonald’s ω = 0.908– 0.935) and test–retest reliability (intraclass correlation coefficient [ICC] = 0.803). Convergent validity was supported by moderate correlations of the WHO-5-C with the SRHQ and PHQ-4. The optimal cutoff point of the WHO-5-C was found to be 50, with an area under the ROC curve of 0.882 at baseline data, with sensitivity of 0.803 and specificity of 0.762 at follow-up.Conclusion: The WHO-5-C demonstrated adequate measurement properties, especially concerning cross-sectional and longitudinal measurement invariance, with a recommended optimal cutoff point of ≥ 50 for assessing adequate level of psychological well-being in healthcare students.Keywords: WHO-5 Well-Being Index, subjective well-being, measurement properties, diagnostic performance, observational longitudinal design, healthcare students

Longlong Wei,1,2 Yan Zhao,2 Siyue Xu,2 Cuilian Zhang1,2 1Department of Reproductive Medicine Center, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Reproductive Medicine Center, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Cuilian Zhang, Email zclian@zzu.edu.cnBackground: Endometrial polyps (EPs) are one of the most common intrauterine benign tumors, and are an important cause of uterine bleeding and female infertility. Previous studies have suggested that endometritis may contribute to the onset of EPs. This study aims to reveal the causal effect of endometritis on EPs by a two-sample Mendelian randomization (MR) study.Methods: Utilizing summarized statistics from genome-wide association studies (GWAS) in the European population, we conducted a Mendelian randomization study. In order to select suitable instrumental variables (IVs) that were significantly related to the exposures, a number of quality control approaches were used. For endometritis, 2144 cases and 111,858 controls were included, while for EPs, 2252 cases and 460,758 controls. Utilizing the inverse variance weighted (IVW) as the primary analysis, the data were subjected to a two-sample MR analysis, and the weighted median (WM) technique and MR-Egger regression were carried out additionally. The sensitivity analysis revealed neither heterogeneity nor horizontal pleiotropy.Results: Four independent single nucleotide polymorphisms (SNPs) from endometritis GWAS as IVs were selected. The IVW data did not agree to a causal association between endometritis and EPs (β=1.11e-04, standard error [SE] =4.88e-04, P = 0.82). Directional pleiotropy did not affect the outcome, according to the MR-Egger regression (intercept = 0.09, P = 0.10); Additionally, it showed no causation association between endometritis and EPs (β= − 3.28e-03, SE = 3.54e-03, P = 0.45). Similar results were obtained using the weighted-median method (β=8.56e-05, SE=5.97e-04, P = 0.89). No proof of heterogeneity and horizontal pleiotropy between IV estimates was discovered.Conclusion: In conclusion, by large scale genetic data, the results of this MR analysis provided suggestive evidence that the presence of endometritis is not associated with higher EPs risk.Keywords: two-sample Mendelian randomization, GWAS, endometritis, endometrial polyp

Edwin S Meresh,1 Sarah Xu,2 Angelina Palomino,2 Hewa Artin,2 Julia Padiyara,3 Conrad Stasieluk,1 Abid Khurshid4 1Department of Psychiatry, Loyola University Medical Center, Maywood, IL, 60153, USA; 2Loyola Stritch School of Medicine, Maywood, IL, 60153, USA; 3Loyola Medicine Center for Sleep Disorders, Loyola University Medical Center, Maywood, IL, 60153, USA; 4Pulmonary Medicine, Loyola University Medical Center, Maywood, IL, 60153, USACorrespondence: Edwin S Meresh, Email emeresh@lumc.eduBackground: This pilot study measures pain perception, somatosensory amplification and its relationship to health anxiety in patients with fibromyalgia (FM) and patients with FM and obstructive sleep apnea (OSA); this study also examines the effects of OSA on pain perception in patients with FM.Methods: In this pilot study, patients diagnosed with FM or FM and OSA, completed three self-reported questionnaires: Short-Form McGill Pain Questionnaire (SF-MPQ), Somatosensory Amplification Scale (SSAS), and Illness Behavior Questionnaire (IBQ). Sleep study results were analyzed. Scores were summarized using medians and interquartile ranges and are compared using Wilcoxon rank sum tests.Results: Overall FM (n = 25), female n=23 male n=3 mean age, 57.48 years. OSA n=17 (68%) and 8 (32%) were not. The SF-MPQ Sensory sub-scale scores and the SF-MPQ overall scores differed significantly between patients with and without OSA. The SF-MPQ Sensory sub-scale scores were significantly lower for patients with OSA (p=0.03), as were SF-MPQ overall scores (p=0.04). SSAS overall scores and IBQ overall scores did not differ significantly by OSA diagnosis. Correlations of the different dimensions of IBQ with SSAS and mean number of diagnoses in FM and FM+OSA, mean number of diagnoses in problem list of SSAS ≤ 30 was 29.5, mean number of diagnoses in SSAS ≥ 30 was 34.9.Discussion: Developing a better understanding of the effects of OSA on pain perception in patients with FM is needed for improved health status. More research is needed to see if higher pain perception and SSAS score lead to increased health care utilization and to evaluate the relationship between untreated disordered sleeping and pain perception in patients with FM.Conclusion: Our findings highlight the need for more research to evaluate the relationship between treated and untreated disordered sleeping, pain perception, somatization and illness behavior in the health status of individuals with FM.Keywords: fibromyalgia, obstructive sleep apnea, pain perception, symptom amplification, illness behavior

Rong Yin, Shasha Xu, Jing Zhu, Haiou Zhu, Chao He Department of Hepatobiliary Center Ward II, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Rong Yin, Department of Hepatobiliary Center Ward II, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email y13851709399@163.comBackground: Hilar cholangiocarcinoma (HCCA) is a common malignant tumor of the biliary system. Factors such as limited physical function, intractability, and high mortality caused by the tumor lead to negative emotions, such as anxiety and depression in patients. In this study, we investigated the risk factors for negative emotions in patients undergoing radical resection of HCCA during the perioperative period and its effect on prognosis to provide strategies for alleviating the negative emotional disorders of patients and improving prognosis.Methods: From September 2016 to August 2021, we retrospectively examined 205 patients with HCCA who underwent radical resection in our hospital. The incidence of negative emotions and the clinical parameters of patients were compared using Chi-square tests and t-tests. The independent risk factors for unfavorable feelings in patients during the perioperative period were determined using binary logistic regression. The key variables influencing the postoperative survival status of HCCA patients were identified using the log-rank univariate analysis and Cox proportional risk regression analysis.Results: The results of the binary logistic regression analysis showed that perioperative negative emotions were independently influenced by family monthly income (OR = 0.069), medical insurance (OR = 0.089), family care (OR = 0.013), sleep quality (OR = 0.071), TNF-α (OR = 5.851), and bile leakage (OR = 29.412) (P < 0.05). The age of the patient (OR = 2.003), preoperative CA19– 9 (OR = 2.038), lymph node metastases (OR = 2.327), and negative mood (OR = 3.054) were independent risk variables that affected the survival status of patients, as determined by the results of Cox regression analysis (P < 0.05).Conclusion: In this study, we found that anxiety and depression in patients undergoing radical operation of HCCA are related to family monthly income, medical insurance, sleep quality, family care, TNF-α, and bile leakage; also, negative emotions have adverse effects on prognosis.Keywords: hilar cholangiocarcinoma, radical resection, depression, anxiety, risk factors, prognosis

Shuwan Xu,1,2,&ast; Cong Xu,1,&ast; Jiahua Xu,1 Kun Zhang,2 Huanji Zhang1 1Cardiovascular Department, the Eighth Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, People’s Republic of China; 2Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huanji Zhang, Cardiovascular Department, The Eighth Affiliated Hospital of Sun Yat-Sen University, No. 3025 Shennan Middle Road, Shenzhen, 518033, People’s Republic of China, Tel +8613688808979, Email zhanghj65@mail.sysu.edu.cn Kun Zhang, Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, People’s Republic of China, Tel +8613450390268, Email zszhangk@hotmail.comAbstract: The coronary reperfusion following acute myocardial infarction can paradoxically trigger myocardial ischemia-reperfusion (IR) injury. This complex phenomenon involves the intricate interplay of different subsets of macrophages. These macrophages are crucial players in the post-infarction inflammatory response and subsequent myocardial anti-inflammatory repair. However, their diverse functions can lead to both beneficial and detrimental effects. On one hand, these macrophages play a crucial role in orchestrating the inflammatory response, aiding in the clearance of cellular debris and initiating tissue repair mechanisms. On the other hand, their excessive infiltration and activation can contribute to the perpetuation of the inflammatory cascade, leading to additional myocardial injury and adverse cardiac remodeling. Multiple mechanisms contribute to the IR injury mediated by macrophages, including oxidative stress, apoptosis, and autophagy. These processes further exacerbate the damage to the already vulnerable myocardial tissue. To address this delicate balance, therapeutic strategies aiming to target and modulate macrophage polarization and function are being explored. By fine-tuning the immune inflammatory response, such interventions hold promise in mitigating post-infarction myocardial injury and fostering a more favorable environment for myocardial healing and recovery. Through advancements in this area of research, potential anti-inflammatory interventions may pave the way for improved clinical outcomes and better management of patients after acute myocardial infarction.Keywords: ischemia-reperfusion injury, macrophages, inflammatory cascade, cardiac remodeling, oxidative stress

Kunlin Guo,&ast; Mingjie Mao,&ast; Susu Zhang, Shiqin Xu, Liping Zhao, Xian Wang, Shanwu Feng Department of Anesthesiology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian Wang; Shanwu Feng, Department of Anesthesiology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, No. 123, Mochou Road, Tianfei Lane, Nanjing, Jiangsu Province, 210004, People’s Republic of China, Tel +86-25-13770723174 ; +86-25-13921426351, Fax +82-25-52226530, Email wangxian2002@126.com; iamfsw@163.comBackground: Allopregnanolone is a kind of neuroactive steroid or neurosteroid in the central nervous system that acts as an endogenenous GABAA receptor positive modulator. However, at present, no comprehensive bibliometric analysis regarding allopregnanolone research is available. In our study, we intend to analyze the research trends and hot spots related to allopregnanolone in the past 20 years.Methods: We searched for allopregnanolone related articles and reviews between 2004 and 2023 from the Web of Science Core Collection database. Then, the bibliometric analysis was conducted using VOSviewer, CiteSpace, Microsoft Excel 2019, as well as the online bibliometric analysis platform (http://bibliometric.com/).Results: A total of 1841 eligible publications were identified. The number of annual publications and citations was generally on the rise. Among countries, the United States ranked first in overall publications, citations, international cooperation, and the number of research institutions. The University of North Carolina was the most active institution, conducting numerous preclinical and clinical work that focusing on allopregnanolone treatment for diverse psychiatric or neurologic disorders. As for authors, Dr. Frye CA, Morrow AL, and Pinna G were identified as the top three prolific scholars due to their great publications and citations. Based on the publication clusters and citation bursts analysis, the keyword co-occurrence network, the strongest citation bursts, and co-cited references analysis, the hot spots in recent years included “depression”, “postpartum depression”, “GABAA receptor”, and so on.Conclusion: Allopregnanolone is still a popular area of research, and the United States leads the way in this area. Dr. Frye CA, Morrow AL, Pinna G, and their teams contributed greatly to the mechanism study and translation study of allopregnanolone. The use of allopregnanolone for the treatment of psychiatric or neurologic disorders, especially postpartum depression, is the current hot spot. However, the underlying mechanisms of anti-depression are still not clear, deserving more in-depth research.Keywords: allopregnanolone, VOSviewer, CiteSpace, bibliometric analysis, research trend

Qiangjian Mao,1,&ast; Biao Huang,1,&ast; Daocheng Zhu,1 Yuqing Wang,2 Shiqi Xu,2 Desheng Wu,1 Guomin Huang,1 Ziru Li,1 Zhenhai Chi,1 Rixin Chen1 1The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 2Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenhai Chi; Rixin Chen, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China, Email 348916661@qq.com; chenrixin321@163.comBackground: Acupuncture therapy has been widely used in the treatment of musculoskeletal pain (MP) in many countries around the world. However, there are no bibliometric studies on acupuncture therapy for MP. Therefore, the aim of this study was to analyze the current status, frontiers and hot spots in the use of acupuncture therapy for the treatment of MP.Methods: Literature on acupuncture therapy for MP was extracted from the Web of Science Core Collection database from 2003 to 2022. CiteSpace 6.2.R4 (64-bit) software was used to analyze the number and centrality of journals, countries, institutions, authors, references and keywords, and the functions of co-occurrence and clustering were applied to draw a visual knowledge map.Results: Over the past 20 years, the annual journal publications have been on a steady upward trend, with 438 articles published in 143 journals, including Acupuncture in Medicine Journal published the most (28, 6.39%), JAMA-Journal of the American Medical Association was the journal with the highest impact factor (IF = 120.7003), USA dominated with the most publications (140, 31.96%) among 44 countries, and among 196 research organizations Kyung Hee University was the most prolific (19, 4.34%) and Ha, In-Hyuk was the most published author (9, 2.05%). “Acupuncture” is the most popular and highly sought after keywords. “Low back pain” is the keyword with the highest centrality.Conclusion: This article provides the current situation of the use of acupuncture therapy in the treatment of MP in the past 20 years, and statistical analysis reveals that “low back pain”, “knit osteoporosis” and “break cancer” are new research diseases related to acupuncture therapy for MP, and “myobasic trigger point” is a new research direction of acupuncture therapy for MP. Therefore, this study helps researchers grasp the research hotspots and provide certain references for in-depth research and future topic selection.Keywords: musculoskeletal pain, acupuncture therapy, bibliometrics, CiteSpace

Xia Li, Shuang Xu, Liu-Wei Hao, Xiao-Ning Zhou Health Management Discipline of Henan Provincial People’s Hospital, Zhengzhou, Henan Province, 450000, People’s Republic of ChinaCorrespondence: Xia Li, Health Management Discipline of Henan Provincial People’s Hospital, Zhengzhou, Henan Province, 450000, People’s Republic of China, Tel +86 0371-65580070, Email 13213034900@163.comBackground: Breast carcinoma (BC) threatens the physical and mental health of women worldwide, and early diagnosis is important for improving patient outcomes and ensuring successful treatment.Purpose: This research mainly aims to compare and analyze the value of molybdenum target X-ray and high-frequency color Doppler flow imaging (CDFI) in the early diagnosis of BC.Methods: First, 102 patients with suspected early-stage BC (ESBC) admitted to Henan Provincial People’s Hospital were examined by molybdenum target X-ray and CDFI. Based on the pathological findings, the diagnostic efficiency data of the two diagnostic modalities such as positive detection rate (PDR), positive predictive value (PPV), negative predictive value (NPV), sensitivity (SEN), specificity (SPE), and accuracy (ACC), as well as imaging information like masses, microcalcifications (MCs), axillary lymph node (LN) metastases, and blood flow signal or vascular sign abnormalities were analyzed.Results: CDFI contributed to higher PDR, PRV, NPV, SEN, and ACC than molybdenum target X-ray in ESBC diagnosis, but similar SPE. The combined diagnosis of molybdenum target X-ray plus CDFI contributed to even higher PDR, PRV, NPV, SEN, and ACC than molybdenum target X-ray alone and higher ACC than CDFI. Imaging inspection revealed that the number of cases of masses, axillary LN metastases, and abnormalities in blood flow signals or vascular signs detected by CDFI was significantly higher than that by molybdenum target X-ray, while the number of MCs was significantly lower.Conclusion: Molybdenum target X-ray plus CDFI is more effective in the diagnosis of ESBC and plays a complementary role in imaging examination, which can synergistically improve the diagnostic ACC of ESBC and is worthy of clinical promotion.Keywords: molybdenum target X-ray, high-frequency color Doppler flow imaging, breast carcinoma, early diagnosis

Menglong Wang,1– 3,&ast; Wei Pan,1– 3,&ast; Cheng Wei,1– 3,&ast; Jianfang Liu,1– 3 Jishou Zhang,1– 3 Junping Yu,1– 3 Mengmeng Zhao,1– 3 Shuwan Xu,1– 3 Jing Ye,1– 3 Zhen Wang,1– 3 Di Ye,1– 3 Yongqi Feng,1– 3 Yao Xu,1– 3 Jun Wan1– 3 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 2Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People’s Republic of China; 3Hubei Key Laboratory of Cardiology, Wuhan, 430060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Wan; Yao Xu, Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, People’s Republic of China, Tel +86-27-88041911, Fax +86-27-88042293, Email wanjun@whu.edu.cn; whuxuyao@163.comBackground: Increased inflammation contributes to pressure overload-induced myocardial remodeling. 17(R)-Resolvin D1 (17(R)-RvD1), a potent lipid mediator derived from docosahexaenoic acid, possesses anti-inflammatory and pro-resolving properties. However, the association between 17(R)-RvD1 and pressure overload-induced cardiac hypertrophy remains unclear.Methods: Transverse aortic constriction (TAC) surgery was performed to establish a cardiac hypertrophy model. C57BL/6J mice were randomly assigned to the Sham, TAC and TAC+17(R)-RvD1 groups. 17(R)-RvD1 was injected (2 μg/kg, i.p.) before TAC surgery and once every other day after surgery for 4 weeks. The same volume of saline was injected into the mice in both Sham group and TAC group. Then, cardiac function was evaluated and heart tissues were collected for biological analysis.Results: 17(R)-RvD1 treatment attenuated TAC-induced increase in left ventricular diameter and decrease in left ventricular contractility, mitigated increased cardiomyocyte cross-sectional area, and downregulated the expression of hypertrophic genes. Besides, 17(R)-RvD1 attenuated myocardial fibrosis, as indicated by the decreased LV collagen volume and expression of fibrotic genes. In addition, 17(R)-RvD1 ameliorated the inflammatory response in cardiac tissue, as illustrated by the decreased infiltration of CD68+ macrophages and reduced production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. 17(R)-RvD1 treatment significantly suppressed the activation of NLRP3 inflammasome after TAC surgery, which might be responsible for the attenuation of inflammation in cardiac tissue.Conclusion: 17(R)-RvD1 attenuated pressure overload-induced cardiac hypertrophy and fibrosis, and the possible mechanism may be associated with the inhibition of NLRP3 inflammasome. 17(R)-RvD1 may serve as a potential drug for the treatment of cardiac hypertrophy.Keywords: inflammation resolution, resolvin D1, cardiac hypertrophy, NLRP3 inflammasome, transverse aortic constriction

Shengjie Xu,1 Jiaqiu Xi,2 Tao Wu,1 Zhonglin Wang3 1The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, 250000, People’s Republic of China; 2Shandong University of Traditional Chinese Medicine, Jinan, 250000, People’s Republic of China; 3Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of ChinaCorrespondence: Zhonglin Wang, Email zydoctor7@126.comAbstract: Adipose tissue dysfunction plays an important role in metabolic diseases associated with chronic inflammation, insulin resistance and lipid ectopic deposition in obese patients. In recent years, it has been found that under the stimulation of adipocyte endoplasmic reticulum stress (ERS), the over-activated ER unfolded protein response (UPR) exacerbates the inflammatory response of adipose tissue by interfering with the normal metabolism of adipose tissue, promotes the secretion of adipokines, and affects the browning and thermogenic pathways of adipose tissue, ultimately leading to the manifestation of metabolic syndrome such as ectopic lipid deposition and disorders of glucolipid metabolism in obese patients. This paper mainly summarizes the relationship between adipocyte ERS and obese adipose tissue dysfunction and provides an overview of the mechanisms by which ERS induces metabolic disorders such as catabolism, thermogenesis and inflammation in obese adipose tissue through the regulation of molecules and pathways such as NF-κB, ADPN, STAMP2, LPIN1, TRIP-Br2, NF-Y and SIRT2 and briefly describes the current mechanisms targeting adipocyte endoplasmic reticulum stress to improve obesity and provide ideas for intervention and treatment of obese adipose tissue dysfunction.Keywords: endoplasmic reticulum stress, unfolded protein response, obesity, adipose tissue dysfunction

Yicheng Guo,1 Huiqun Gan,1 Shigui Xu,1 Guosheng Zeng,2 Lili Xiao,2 Zhijun Ding,2 Jie Zhu,3 Xinglong Xiong,3 Zhiyuan Fu1 1Department of Pharmacy, Dermatology Hospital of Jiangxi Province, Nanchang, People’s Republic of China; 2Jiangxi Provincial Clinical Research Center for Skin Diseases, Nanchang, People’s Republic of China; 3Candidate Branch of National Clinical Research Center for Skin Diseases, Nanchang, People’s Republic of ChinaCorrespondence: Zhiyuan Fu, Department of Pharmacy, Dermatology Hospital of Jiangxi Province, 388, Yinbing Road, Nanchang, Jiangxi, People’s Republic of China, Tel +86 13970827820, Email fuzhiyuan0774@yeah.netPurpose: This study aims to confirm the efficacy of Xijiao Dihuang decoction (XJDHT), a classic prescription, in treating psoriasis and to explore the potential therapeutic mechanism.Methods: For pharmacodynamic analysis, a mouse model of imiquimod cream (IMQ)-induced psoriasis was constructed. Active ingredients and genes of XJDHT, as well as psoriasis-related targets, were obtained from public databases. Intersecting genes (IGEs) of XJDHT and psoriasis were collected by Venn Diagram. A protein–protein interaction (PPI) network of IGEs is constructed through the STRING database. The Molecular Complex Detection (MCODE) and Cytohubba plug-ins of Cytoscape software were used to identified hub genes. In addition, we conducted enrichment analysis of IGEs using the R package clusterProfiler. Hub genes were validated via external GEO databases. The influence of XJDHT on Hub gene expression was examined by qPCR and ELISA, and molecular docking was used to evaluate the binding efficacy between active ingredients and hub genes.Results: The results revealed that XJDHT possesses 92 potential genes for psoriasis, and 8 Hub genes were screened. Enrichment analysis suggested that XJDHT ameliorate psoriasis through multiple pathways, including AGE-RAGE, HIF-1, IL-17 and TNF signaling pathway. Validation data confirmed the differential expression of IL6, VEGFA, TNF, MMP9, STAT3, and TLR4. Molecular docking revealed a strong affinity between active ingredients and Hub genes. The efficacy of XJDHT in improving psoriatic lesions in model mice was demonstrated by PASI score and HE staining, potentially attributed to the down-regulation of VEGFA, MMP9, STAT3, TNF, and IL-17A, as evidenced by ELISA and qPCR.Conclusion: This study employed network pharmacology and in vitro experiments to identify the potential mechanisms underlying the therapeutic effects of XJDHT on psoriasis, providing a new theoretical basis for its clinical application in the treatment of psoriasis.Keywords: psoriasis, Xijiao Dihuang decoction, network pharmacology, molecular docking, angiogenesis

Jinjuan Duan,&ast; Xia Ju,&ast; Xing Wang, Ning Liu, Siqi Xu, Shengbin Wang Department of Anesthesiology, Affiliated Anqing Medical Centre of Anhui Medical University, Anqing Municipal Hospital, Anqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Siqi Xu; Shengbin Wang, Department of Anesthesiology, Affiliated Anqing Medical Centre of Anhui Medical University, Anqing Municipal Hospital, No. 87 Tianzhushan Road, Anqing, 246000, People’s Republic of China, Tel +86-13865192106 ; +86-13955665151, Email errtg555@163.com; shbw1965@126.comPurpose: The aim of this study was to compare the effects of remimazolam and propofol on emergence agitation (EA) in elderly patients undergoing hip replacement.Methods: A total of 60 elderly patients undergoing hip replacement were recruited for this prospective, single-center, clinical, randomized, controlled study from February to April 2023. They were randomly assigned to two groups: the remimazolam group (group R) and the propofol group (group P). In group R, remimazolam was administered intravenously during the induction and maintenance of anesthesia, In group P, propofol was used during the induction and maintenance of anesthesia. The incidence of EA was recorded as the primary indicator. Secondary indicators included heart rate (HR) and mean arterial pressure (MAP) values at the following moments: 5 min prior to anesthetic induction (T0), 1 min following induction (T1), 5 min after the laryngeal mask was inserted (T2), the beginning of surgery (T3), the moment the laryngeal mask was removed (T4), and the overall incidence of postoperative adverse events (bleeding or splitting of the surgical incision, removal of the intravenous infusion needle, falling off the bed, hypoxemia, and hypertension).Results: The incidence of EA was significantly lower in group R than in group P (10% vs 33%, P < 0.05). At T1, T2, and T3, the HR and MAP values of group R were higher than those of group P (P < 0.05). The overall incidence of postoperative adverse events was significantly lower in group R than in group P (P < 0.05).Conclusion: Remimazolam further reduced the incidence of emergence agitation when compared to propofol during geriatric hip replacement. Moreover, it has a minor hemodynamic effect and lower the incidence of postoperative adverse events.Keywords: remimazolam, propofol, emergence agitation, elderly, hip replacement

Zheng Huang,&ast; Ning Liu,&ast; Shenghong Hu, Xia Ju, Siqi Xu, Shengbin Wang Department of Anesthesiology, Bengbu Medical College, Anqing Municipal Hospital, Anqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Siqi Xu; Shengbin Wang, Email errtg555@163.com; shbw1965@126.comPurpose: This study evaluated the effect of a combined infusion of dexmedetomidine and esketamine on the quality of recovery in patients undergoing modified radical mastectomy.Methods: A total of 135 patients were randomly divided into three groups: dexmedetomidine group (group D) received dexmedetomidine (0.5 μg/kg loading, 0.4 μg/kg/h infusion), dexmedetomidine plus low-dose esketamine group (group DE1) received dexmedetomidine (0.5 μg/kg loading, 0.4 μg/kg/h infusion) and esketamine (0.5 mg/kg loading, 2 μg/kg/min infusion), dexmedetomidine plus high-dose esketamine group (group DE2) received dexmedetomidine (0.5 μg/kg loading, 0.4 μg/kg/h infusion) and esketamine (0.5 mg/kg loading, 4 μg/kg/min infusion). The primary outcome was the overall quality of recovery-15 (QoR-15) scores at 1 day after surgery. The secondary endpoints were total QoR-15 scores at 3 days after surgery, propofol and remifentanil requirement, awaking and extubation time, postoperative visual analogue scale (VAS) pain scores, rescue analgesic, nausea and vomiting, bradycardia, excessive sedation, nightmares, and agitation.Results: The overall QoR-15 scores were much higher in groups DE1 and DE2 than in groups D 1 and D 3 days after surgery (P < 0.05). VAS pain scores at 6, 12, 24 h postoperatively, propofol and remifentanil requirements were significantly lower in groups DE1 and DE2 than in group D (P < 0.05). Compared with group D, awaking time, extubation time, and post-anesthesia care unit (PACU) stay were significantly prolonged in groups DE1 and DE2 (P < 0.05) and were much longer in group DE2 than in group DE1 (P < 0.05). The proportion of postoperative rescue analgesics and bradycardia was higher and the incidence of excessive sedation was lower in group D than in groups DE1 and DE2 (P < 0.05).Conclusion: Dexmedetomidine plus esketamine partly improved postoperative recovery quality and decreased the incidence of bradycardia but prolonged awaking time, extubation time, and PACU stay, especially dexmedetomidine plus 4 μg/kg/min esketamine.Keywords: dexmedetomidine, esketamine, quality of recovery, modified radical mastectomy

Bei Chen,1,2,&ast; Mingzhi Yan,1,2,&ast; Huijing Gao,1,2 Qin Ma,3 Lihua Li,4 Guodong Lü,1,2 Yuehong Gong,1,2 Limei Wen,1,2 Shaoquan Xu,5 Jianhua Wang,1,2 Jun Zhao1,2 1First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3HuaShiDan Pharmaceutical Company Limited, Urumqi, Xinjiang, People’s Republic of China; 4Xinjiang Urumqi Maternal and Child Health Hospital, Urumqi, Xinjiang, People’s Republic of China; 5College of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Zhao; Jianhua Wang, First Affiliated Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Urumqi, Xinjiang, 830011, People’s Republic of China, Email zhaojun700326@163.com; jhw716@sohu.comIntroduction: Cystic echinococcosis (CE) is a chronic zoonotic parasitic disease caused by the larvae of the Echinococcus granulosus sensu lato (s.l.) cluster. The current existing drugs have limited therapeutic efficacy against cystic echinococcosis, and thus, there is an urgent need to develop new drugs.Methods: In this study, 7 harmine (HM) derivatives were screened and the effects of HM derivatives on E. granulosus sensu stricto (s.s.) were evaluated by in vitro and mouse experiments. The safety of the HM derivatives was assessed by cytotoxicity assays, acute toxicity study in animals and subacute toxicity study.Results: These results show that the HM derivatives H-2-168 and DH-004 exhibited more significant antiparasitic effects at an initial concentration of 40 μM. The results of further studies showed that H-2-168 and DH-004 had dose-dependent effects against protoscoleces and had satisfactory therapeutic outcomes in vivo. Electron microscopy observations demonstrated that H-2-168 and DH-004 caused severe disruption of the parasite ultrastructure. Notably, the results of the acute toxicity and subchronic toxicity studies showed that H-2-168 and DH-004 had significantly improved safety. In addition, we found that H-2-168 and DH-004 induced DNA damage in E. granulosus s.s., which may be the mechanism by which these drugs produce their therapeutic effects.Discussion: Overall, the data from this work demonstrate that H-2-168 and DH-004 are highly effective candidate compounds with low toxicity for the treatment of CE and will provide a new therapeutic strategy for CE pharmacological treatment.Graphical Abstract: Keywords: harmine derivatives, β-carboline, Echinococcus granulosus sensu stricto, cystic echinococcosis, DNA damage

Haicheng Wang,1,&ast; Renbin Wang,2,&ast; Jingwen Yang,3– 5 Yuan Feng,6 Shuyu Xu,6 Qing-Guo Pei7 1Department of Pathology, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, People’s Republic of China; 2Department of Gastroenterology, The People’s Hospital of Zhongjiang, Zhongjiang, Sichuan Province, 618100, People’s Republic of China; 3Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, People’s Republic of China; 4National Center of Stomatology & National Clinical Research Center for Oral Diseases, Beijing, 100081, People’s Republic of China; 5National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, People’s Republic of China; 6Department of Oral Implantology, School of & Hospital Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, People’s Republic of China; 7Department of Stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuyu Xu, Department of Oral Implantology, School of & Hospital Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, 399 Yanchang Road, Shanghai, 200072, People’s Republic of China, Tel +86-21-66313725/(8610) ; +8618616308949, Email shuyu_xu0809@163.com Qing-Guo Pei, Department of Stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, People’s Republic of China, Tel +86-21-37798330/(8610) ; +8613764521025, Email dentistpei@126.comBackground: To analyze the fibroblasts subtypes in the gingival tissues of healthy controls, gingivitis and periodontitis patients, as well as the effects of interaction between subtypes on alveolar bone destruction.Methods: Gingival tissues were divided into three groups according to clinical and radiographic examination, and the immunostaining of EDA+FN was assessed. Fibroblasts from gingiva developed colony formation units (CFUs) and induced Trap+MNCs. The expression of osteoclastogenesis-related genes was assessed by real-time PCR. Variances in the gene profiles of CFUs were identified by principal component analysis, and cluster analysis divided CFUs into subtypes. The induction of Trap+MNCs and gene expression were compared among individual or cocultured subtypes. The fibroblast subtypes exerted critical effect on Trap+MNCs formation were selected and edited by CRISPR/Cas to investigate the influence on osteoclastogenesis in the periodontitis in mice.Results: Most periodontitis samples exhibited intensive EDA+FN staining (P < 0.05), and these fibroblasts also induced most Trap+MNCs among three groups; consistently, fibroblasts from periodontitis highly expressed genes facilitating osteoclastogenesis. According to gene profiles and osteoclastogenic induction, four clusters of CFUs were identified. The proportion of clusters was significantly different (P < 0.05) among three groups, and their interaction influenced osteoclastogenic induction. Although Cluster 4 induced less osteoclasts, it enhanced the effects of Clusters 1 and 3 on Trap+MNCs formation (P < 0.05). EDA knockout in Cluster 4 abrogated this promotion (P < 0.05), and decreased osteoclasts and alveolar bone destruction in experimental periodontitis (P < 0.05).Conclusion: Heterogeneous fibroblast subtypes affect the switch or development of periodontitis. A subtype (Cluster 4) played important role during alveolar bone destruction, by regulating other subtypes via EDA+FN paracrine.Keywords: periodontitis, heterogeneity, fibroblast subtype, osteoclastogenesis, alveolar bone destruction

Shuang Xu,1 Yi Fu,2 Dan Xu,1 Shuang Han,1 Mingzhi Wu,3 Xinrong Ju,1 Meng Liu,1 De-Sheng Huang,4,5 Peng Guan4,6 1Library of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2School of Health Management, China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Library of Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China; 4Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, People’s Republic of China; 5Department of Intelligent Computing, School of Intelligent Medicine, China Medical University, Shenyang, Liaoning, People’s Republic of China; 6Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: De-Sheng Huang; Peng Guan, China Medical University, Shenyang, Liaoning, 110122, People’s Republic of China, Email dshuang@cmu.edu.cn; pguan@cmu.edu.cnBackground: Before the COVID-19 pandemic, tuberculosis is the leading cause of death from a single infectious agent worldwide for the past 30 years. Progress in the control of tuberculosis has been undermined by the emergence of multidrug-resistant tuberculosis. The aim of the study is to reveal the trends of research on medications for multidrug-resistant pulmonary tuberculosis (MDR-PTB) through a novel method of bibliometrics that co-occurs specific semantic Medical Subject Headings (MeSH).Methods: PubMed was used to identify the original publications related to medications for MDR-PTB. An R package for text mining of PubMed, pubMR, was adopted to extract data and construct the co-occurrence matrix-specific semantic types. Biclustering analysis of high-frequency MeSH term co-occurrence matrix was performed by gCLUTO. Scientific knowledge maps were constructed by VOSviewer to create overlay visualization and density visualization. Burst detection was performed by CiteSpace to identify the future research hotspots.Results: Two hundred and eight substances (chemical, drug, protein) and 147 diseases related to MDR-PTB were extracted to form a specific semantic co-occurrence matrix. MeSH terms with frequency greater than or equal to six were selected to construct high-frequency co-occurrence matrix (42 × 20) of specific semantic types contains 42 substances and 20 diseases. Biclustering analysis divided the medications for MDR-PTB into five clusters and reflected the characteristics of drug composition. The overlay map indicated the average age gradients of 42 high-frequency drugs. Fifteen top keywords and 37 top terms with the strongest citation bursts were detected.Conclusion: This study evaluated the literatures related to MDR-PTB drug therapy, providing a co-occurrence matrix model based on the specific semantic types and a new attempt for text knowledge mining. Compared with the macro knowledge structure or hot spot analysis, this method may have a wider scope of application and a more in-depth degree of analysis.Keywords: multidrug-resistant tuberculosis, pulmonary tuberculosis, medication trends, specific semantic types, MeSH tree, pubMR

Siqi Xu,&ast; Huide Zhu,&ast; Zhiwei Zheng Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiwei Zheng, Email zhiweizheng@126.comBackground: This study evaluated the value of PNI to predicting relapse-free survival (RFS) and overall survival (OS) in patients with resectable gastroesophageal junction adenocarcinoma (AGE).Methods: Between 2016 and 2020, there were 236 resectable AGE patients underwent a retrospective review via propensity score matched (PSM) analysis. The PNI values were computed for each patient prior to surgery [PNI= 10×albumin (gr/dL) + 0.005×total lymphocyte count (mm3)]. By using disease progression and mortality as the end points, a receiver operating characteristic(ROC) curve was plotted to identify the PNI cut-off value. Kaplan-Meier curves and Cox proportional hazard models were used for survival analysis.Results: The ROC curve indicated that the ideal cutoff value was 45.60. After propensity score matching, there were 143 patients in our retrospective study, which included 58 patients in the low-PNI group and 85 patients in the high-PNI group. When compared to the low PNI group, the high PNI group substantially increased RFS and OS (p< 0.001, p=0.003, respectively) according to the Kaplan-Meier analysis and Log rank test. Advanced pathological N stage (p=0.011) and poor PNI (p=0.004) were also significant risk factors for a shorter OS, according to a univariate analysis. Multivariate analysis revealed that the N0 plus N1 group had an endpoint mortality risk that was 0.39 times lower than the N2 plus N3 group’s (p=0.008). In comparison to the high PNI group, the hazard of endpoint mortality was 2.442 times greater in the low PNI group (p = 0.003).Conclusion: PNI is a simplistic and practical predictive predictor of the RFS and OS time in patients with resectable AGE.Keywords: prognostic nutritional index, resectable adenocarcinoma esophagogastric junction cancer, relapse-free survival, overall survival, prognosis

Jicheng Jia,1,2 Yongchao Ma,3 Shengnan Xu,1 Jiaqi Zheng,2 Xinli Ma,2 Yuzhen Zhang,2 Weijuan Sun,2 Lizhi Liu2 1Department of Education, The National University of Malaysia, Kuala Lumpur, Malaysia; 2Department of Talent Development and Continuing Education, Shandong Shengli Vocational College, Dongying, Shandong, People’s Republic of China; 3Computer Science, North Dakota State University, Fargo, ND, USACorrespondence: Jicheng Jia, Tel +86 15689138097, Email wabajjc@163.comObjective: This study aimed to investigate the impact of academic self-efficacy on test anxiety among higher vocational students, as well as the role of sense of life meaning, fear of failure, and gender difference in mediating this relationship.Methods: A total of 2231 higher vocational students from Shandong Province were surveyed by means of Academic Self-efficacy Questionnaire, Meaning in Life Questionnaire, and Test Anxiety Scale.Results: There were significant negative correlations among academic self-efficacy, sense of life meaning, and test anxiety. Fear of failure was positively correlated with test anxiety. Sense of life meaning and fear of failure played a mediating role in the relationship between academic self-efficacy and test anxiety. The chain mediating effect was significant only in the female group, not in the male group. In contrast, academic self-efficacy indirectly predicted test anxiety by the independent mediating effect of sense of life meaning or fear of failure in the male group.Conclusion: Academic self-efficacy may influence test anxiety through the independent mediating effect of sense of life meaning, fear of failure, and the chain mediating effect, and there is a gender difference in these effects.Keywords: higher vocational students, academic self-efficacy, sense of life meaning, fear of failure, test anxiety

Yibo Zhang,1,&ast; Yichen Wang,1,&ast; Zike Sheng,2,&ast; Qun Wang,1 Dake Shi,1 Shirui Xu,3 Yaping Ai,4 Erzhen Chen,5 Yumin Xu1,2 1Department of Hospital Infection Management, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Clinical Laboratory Medicine, Shanghai Fenglin Clinical Laboratory Co. Ltd, Shanghai, People’s Republic of China; 4Health Economics and Outcome Research, Becton & Dickinson Medical Device (Shanghai) Ltd, Shanghai, People’s Republic of China; 5Department of Emergency Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Erzhen Chen, Department of Emergency Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Tel +86 021-64370045-665599, Email chenerzhen@hotmail.com Yumin Xu, Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Tel +86 021-64370045-600653, Email xym121@163.comPurpose: Indwelling central venous catheters (CVCs) can cause catheter related bloodstream infection (CRBSI). CRBSI occurring in intensive care unit (ICU) patients may lead to the worse outcomes and extra medical costs. The present study aimed to assess the incidence and incidence density, pathogens and economic burden of CRBSI in ICU patients.Patients and Methods: A case-control study was retrospectively carried out in six ICUs of one hospital between July 2013 and June 2018. The Department of Infection Control performed routinely surveillance for CRBSI on these different ICUs. Data of the clinical and microbiological characteristics of patients with CRBSI, the incidence and incidence density of CRBSI in ICUs, the attributable length of stay (LOS), and the costs among patients with CRBSI in ICU were collected and assessed.Results: A total of 82 ICU patients with CRBSI were included into the study. The CRBSI incidence density was 1.27 per 1000 CVC-days in all ICUs, in which the highest was 3.52 per 1000 CVC-days in hematology ICU and the lowest was 0.14 per 1000 CVC-days in Special Procurement ICU. The most common pathogen causing CRBSI was Klebsiella pneumoniae (15/82, 16.67%), in which 12 (80%) were carbapenem resistant. Fifty-one patients were successfully matched with control patients. The average costs in the CRBSI group were &dollar; 67,923, which were significantly higher (P < 0.001) than the average costs in the control group. The total average costs attributable to CRBSI were &dollar;33, 696.Conclusion: The medical costs of ICU patients were closely related to the incidence of CRBSI. Imperative measures are needed to reduce CRBSI in ICU patients.Keywords: CRBSI, prolonged length of stay, cost, CRKP, ICU

Tian QX, Zhang ZH, Ye QL, et al. J Inflamm Res. 2021;14:2253–2265. We, the Editors and Publisher of Journal of Inflammation Research, have retracted the following article. Following publication of the article, the authors raised concerns regarding the duplication of images from Figure 1. Specifically, The images for Figure 1A, PC-3, MT, 12h and 24h have been duplicated. The images for Figure 1B, DU145, MT and Figure 1C, PC-3, Control and MT+LPS have been duplicated. The images for Figure 1C, DU145, MT+LPS and PC-3, MT have been duplicated. The authors explained the incorrect use of images occurred during figure preparation and did provide some of the original data for the study. However, the provided data and the authors explanation regarding the duplicated images did not sufficiently alleviate the journal’s concerns regarding the validity of the findings. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors do not agree with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Gang Xu,1,2 Site Xu,3 Weiwei Gong,2,4 Shihong Dong,2 Hecheng Yu1 1Department of Rehabilitation Medicine, Affiliated Tenth People’s Hospital of Tongji University, Shanghai Tenth People’s Hospital, Shanghai, 20072, People’s Republic of China; 2Department of Rehabilitation Medicine, Tongji University School of Medicine, Shanghai, 200092, People’s Republic of China; 3Division of Information and Statistics, Affiliated Ruijin Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Rehabilitation Medicine, Shanghai First Rehabilitation Hospital, Shanghai, 200090, People’s Republic of ChinaCorrespondence: Gang Xu, Department of Rehabilitation Medicine, Affiliated Tenth People’s Hospital of Tongji University, Shanghai Tenth People’s Hospital, Shanghai, 20072, People’s Republic of China, Tel +8621-66306496, Fax +8621-66301051, Email sykfsci@126.comBackground: Herpes zoster (HZ) is a skin disease that can also cause virus-infectious peripheral neuropathies. Despite this, there is limited information on patient preferences for seeking medical attention for HZ and zoster-associated pain (ZAP). Our study aimed to evaluate how frequently patients with ZAP choose to visit neurologists for their symptoms.Methods: This study conducted a retrospective review of electronic health records in three general hospitals from January 2017 to June 2022. Using association rule mining, the study analyzed referral behaviors.Results: We identified 33,633 patients with 111,488 outpatient visits over 5.5 years. The study found that the majority of patients (74.77– 91.22%) visited dermatologists during their first outpatient visit, while only a small percentage (0.86– 1.47%) preferred to consult a neurologist. The proportion of patients referred to a specialist during their medical visit varied significantly between different specialties within the same hospital (p < 0.05) and even within the same specialty (p< 0.05). There was a weak association (Lift:1.00– 1.17) of referral behaviors between dermatology and neurology. Across the three hospitals, the average number of visits to a neurologist for ZAP was 1.42– 2.49, with an average electronic health record duration of 11– 15 days per patient. After consulting with a neurologist, some patients were referred to other specialists.Conclusion: It was observed that patients with HZ and ZAP tended to visit a variety of specialists, with only a small number seeking the assistance of neurologists. However, from the perspective of neuroprotection, it is the duty of neurologists to provide more means.Keywords: herpes zoster, zoster-associated pain, neuropathy, electronic health records, visit preferences

Guanxiang Huang,1– 3,&ast; Hangjing Gao,1– 3,&ast; Yanlin Chen,1,2 Wenyu Lin,1– 3 Jun Shen,4 Shuxia Xu,5 Dabin Liu,6 Zhihui Wu,7 Xite Lin,1– 3 Tingting Jiang,1– 3 Binhua Dong,1– 3 Pengming Sun1– 3 1Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China; 2Fujian Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital (Fujian Women and Children’s Hospital), Fuzhou, Fujian, 350001, People’s Republic of China; 3Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian, 350001, People’s Republic of China; 4Fujian Provincial Cervical Disease Diagnosis and Treatment Health Center, Fujian Maternity and Child Health Hospital, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 5Department of Pathology, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 6Department of Gynecology, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 7Department of Clinical Laboratory, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengming Sun; Binhua Dong, Laboratory of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-591-87558732 ; +86-13599071900, Fax +86-591-87551247, Email fmsun1975@fjmu.edu.cn; sunfemy@hotmail.com; dongbinhua86@fjmu.edu.cn; dbh18-jy@126.comPurpose: The platelet-to-lymphocyte ratio (PLR) is considered correlated with cancer prognosis including cervical cancer, in addition to high-risk papillomavirus (HR-HPV) infection, of which the predictive value in prognosis of high-grade squamous intraepithelial lesions (HSILs) remains unknown. Here, the prognostic predictive value of PLR in HSIL after loop electrosurgical excision procedure (LEEP) was evaluated.Patients and Methods: This study included 335 nonpregnant participants with histopathologically confirmed HSIL and 3- and 5-year follow-ups from the Fujian Cervical Lesions Screening Cohorts (FCLSCs) between September 2016 and September 2018. PLR and other variables were evaluated to identify the factors related to the recurrence/residual cervical intraepithelial neoplasia (CIN)-free survival (RFS), namely, the time from LEEP at baseline to first detection of recurrence/residual CIN or end of follow-up, by logistic and Cox regression.Results: In the Kaplan‒Meier analysis, HR-HPV infection (p=0.049/0.012), higher PLR (p=0.031/0.038), and gland invasion (p=0.047) had a higher risk for recurrence/residual CIN at the 3-/5-year follow-up. The univariate logistic and Cox regression analyses showed significant differences and a higher cumulative risk in patients with HR-HPV infection (OR=3.917, p=0.026; HR=3.996, p=0.020) and higher PLR (OR=2.295, p=0.041; HR=2.161, p=0.030) at the 5-year follow-up. The findings by multivariate Cox regression analysis were similar, indicating a poor prognosis for patients with HR-HPV infection (HR=3.901, p=0.023) and higher PLR (HR=2.082, p=0.038) at the 5-year follow-up. The calibration plot showed a better model fit for RFS at the 3-year follow-up.Conclusion: Preoperative PLR level and HR-HPV infection could be available markers for predicting recurrence/residual disease of HSIL after LEEP. Clinically, combining PLR with HR-HPV tests may provide novel evaluation method and reference for management in post-treatment patients with cervical precancerous lesions.Keywords: systemic inflammatory response, cervical intraepithelial neoplasia, human papillomavirus, HPV, conization, prognosis

Wei Sun,1,2,&ast; Songyi Xu,3,&ast; Tianlun Shen,1,3,&ast; Guangyao Li,1 Jingfeng Zhang,2 Chunshu Pan,1,2 Wei Lu,1,2 Xiangrui Liu,1 Jianjun Zheng,2 Jun Ling,1,3 Jihong Sun1 1Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Radiology, Ningbo No. 2 Hospital, Ningbo, People’s Republic of China; 3MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Sun, Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Tel +86 13857176538, Email sunjihong@zju.edu.cn Jianjun Zheng, President of Ningbo No. 2 Hospital, Ningbo, People’s Republic of China, Tel +86 574 83870280, Email zhjjnb2@163.comPurpose: Chemotherapy treatments for cancer are always accompanied by a low concentration of drug delivered in the tumor area and severe side effects including systemic toxicity. Improving the concentration, biocompatibility, and biodegradability of regional chemotherapy drugs is a pressing challenge in the field of materials.Methods: N-Phenyloxycarbonyl-amino acids (NPCs) which exhibit significant tolerance to nucleophiles, such as water and hydroxyl-containing compounds, are promising monomers for the synthesis of polypeptides and polypeptoids. Cell line and mouse models were used to comprehensively explore how to enhance the tumor MRI signal and evaluate the therapeutic effect of Fe@POS-DOX nanoparticles.Results: In this study, poly(3,4-dihydroxy-L-phenylalanine)-b-polysarcosine (PDOPA-b-PSar, simplified as POS) was synthesized by the block copolymerization of DOPA-NPC with Sar-NPC. Fe@POS-DOX nanoparticles were prepared in order to utilize the strong chelation of catechol ligands to iron (III) cations and the hydrophobic interaction between DOX and DOPA block to deliver chemotherapeutics to tumor tissue. The Fe@POS-DOX nanoparticles exhibit high longitudinal relaxivity (r1 = 7.06 mM− 1·s− 1) and act as T1-weighted magnetic resonance (MR) imaging contrast agents. Further, the main focus was improving tumor site-specific bioavailability and achieving therapeutic effects through the biocompatibility and biodegradability of Fe@POS-DOX NPs. The Fe@POS-DOX treatment exhibited excellent antitumor effects.Conclusion: Upon intravenous injection, Fe@POS-DOX delivers DOX specifically to the tumor tissues, as revealed by MR, and leads to the inhibition of tumor growth without overt toxicity to normal tissues, thus displaying considerable potential for use in clinical applications.Graphical Abstract: Keywords: poly (α-amino acid)s, polypeptides, polypeptoids, MRI, chemotherapy, nanoparticles

Xin-Yue Yang,1,&ast; Lina Geng,2,&ast; Ronghui Li,2 Ji-Xian Song,1 Cui-Ling Jia,1 Ji-Ren An,1,3 Meng-Fan Sun,1 Shan Xu,1 Ya-Jing Guo,1 Yashuo Zhao,1 En-Sheng Ji1 1Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China; 2College of Chemistry and Material Science, Hebei Normal University, Shijiazhuang, People’s Republic of China; 3The First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yashuo Zhao; En-Sheng Ji, No. 3, Luqian Xingyuan Road, Shijiazhuang, 050200, People’s Republic of China, Email zys870207@126.com; jesphy@126.comBackground: Chronic intermittent hypoxia (CIH) could cause neuronal damage, accelerating the progression of dementia. However, safe and effective therapeutic drugs and delivery are needed for successful CIH therapy.Purpose: To investigate the neuroprotective effect of Huperzine A (HuA) packaged with nanoliposomes (HuA-LIP) on neuronal damage induced by CIH.Methods: The stability and release of HuA-LIP in vitro were identified. Mice were randomly divided into the Control, CIH, HuA-LIP, and HuA groups. The mice in the HuA and HuA-LIP groups received HuA (0.1 mg/kg, i.p.), and HuA-LIP was administered during CIH exposure for 21 days. HuA-LIP contains the equivalent content of HuA.Results: We prepared a novel formulation of HuA-LIP that had good stability and controlled release. First, HuA-LIP significantly ameliorated cognitive dysfunction and neuronal damage in CIH mice. Second, HuA-LIP elevated T-SOD and GSH-Px abilities and decreased MDA content to resist oxidative stress damage induced by CIH. Furthermore, HuA-LIP reduced brain iron levels by downregulating TfR1, hepcidin, and FTL expression. In addition, HuA-LIP activated the PKAα/Erk/CREB/BDNF signaling pathway and elevated MAP2, PSD95, and synaptophysin to improve synaptic plasticity. Most importantly, compared with HuA, HuA-LIP showed a superior performance against neuronal damage induced by CIH.Conclusion: HuA-LIP has a good sustained-release effect and targeting ability and efficiently protects against neural injury caused by CIH.Keywords: huperzine A, nanoliposomes, neuronal damage, chronic intermittent hypoxia, Iron

Jie Shen,1,2,&ast; Xiao Long,3,&ast; Qi Jiang,1 Hao Xu,2 Qinming Wei,1 Qingmiao Shi,2 Yi Liu,2 Shanshan Xu,1 Xiaolu Ma,1 Lanjuan Li2 1Department of Medical Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Orthopedics, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lanjuan Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Tel +86-571-87236458, Fax +86-571-87236459, Email ljli@zju.edu.cnPurpose: In China, vancomycin-resistant enterococci (VRE) was not a common occurrence, and research on the genetic context and transmission mechanism of vanA-plasmid was scarce. The aim of this study was to molecularly characterise a vancomycin-resistant Enterococcus faecium isolate from a bloodstream infection and determine the genetic environment and delivery pattern of the plasmid carrying vancomycin-resistant gene.Materials and Methods: In May 2022, a vancomycin-resistant strain of Enterococci was identified during routine screening for VRE bacteria at the First Affiliated Hospital, Zhejiang University School of Medicine. Utilizing matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), the isolate was accurately identified. Antimicrobial susceptibility and whole-genome sequencing (WGS) were employed to perform phenotypic and genomic analysis, respectively. Further bioinformatics analyses was carried out to characterize the vanA-bearing plasmid.Results: The antimicrobial susceptibility test showed that SJ2 strain was resistant to multiple antimicrobials, including ampicillin, benzylpenicillin, ciprofloxacin, erythromycin, levofloxacin, streptomycin, and vancomycin. Whole-genome analysis revealed that SJ2 strain carries several antimicrobial resistance genes and virulence determinants. MLST analysis found that SJ2 strain belongs to an unknown ST type. Plasmid analysis confirmed that the vanA gene was located on a variant of ~50 kb rep2 plasmid.Conclusion: Our study found that vanA-bearing rep2 plasmid is a potential source of dissemination and outbreak, and continuous surveillance is necessary to control its spread in Hangzhou, China.Keywords: vancomycin-resistant Enterococcus faecium, vanA, whole genome sequencing, rep2

Tianxue Zhao,1 Shaokun Xu,2 Xianfeng Zhang,1 Chenke Xu3 1Department of Endocrinology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Geriatrics, Zhejiang Provincial People’s Hospital, Hangzhou, People’s Republic of China; 3Department of Ultrasound, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Chenke Xu, Department of Ultrasound, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, No. 261 Huansha Road, Hangzhou, 310006, People’s Republic of China, Tel +86-571-56005600, Email muerxck@163.comPurpose: To compare the diagnostic performance and unnecessary ultrasound-guided fine-needle aspiration (US-FNA) biopsy rate of the 2015 American Thyroid Association (ATA), 2016 Korean Society of Thyroid Radiology (KSThR), and 2017 American College of Radiology (ACR) guidelines for patients with and without Hashimoto’s thyroiditis (HT).Patients and Methods: This retrospective study included 716 nodules from 696 consecutive patients, which were classified using the categories defined by the three guidelines: ATA, KSThR, and ACR. The malignancy risk in each category was calculated and the diagnostic performance and unnecessary fine-needle aspiration (FNA) rates of the three guidelines were compared.Results: In total, 426 malignant and 290 benign nodules were identified. Patients with malignant nodules had lower total thyroxine levels and higher thyroid-stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody levels than those without malignant nodules (all P< 0.01). The margin difference was significant in non-HT patients (P< 0.01), but comparable in HT patients (P=0.55). The calculated malignancy risks of high and intermediate suspicion nodules in the ATA and KSThR guidelines and moderately suspicious nodules in the ACR guidelines were significantly lower in non-HT patients compared with HT patients (P< 0.05). The ACR guidelines showed the lowest sensitivity, highest specificity, and lowest unnecessary FNA rates in patients with and without HT. Compared to non-HT patients, HT patients had significantly lower unnecessary FNA rates (P< 0.01).Conclusion: HT was associated with a higher malignancy rate of thyroid nodules with intermediate suspicion according to the ATA, KSThR, and ACR guidelines. The three guidelines, especially ACR, were likely to be more effective and could allow a greater reduction in the percentage of benign nodules biopsied in patients with HT.Keywords: ultrasound-based malignant risk stratification system, Hashimoto’s thyroiditis, thyroid nodules, diagnostic value, papillary thyroid cancer

Shuang Li,1,2,&ast; Yanwen Xu,2,&ast; Yuhang Wu,2,&ast; Heyu Huang,2 Chen Sun,2 Shanshan Xu,2 Huajun Li,2 Xi Zhang,3 Shiyong Zhao,4 Lisu Huang1,2 1Department of Infectious Diseases, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Infectious Diseases, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Clinical Research Unit, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Infectious Diseases, Hangzhou Children’s Hospital, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lisu Huang, Department of Infectious Diseases, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, Zhejiang Province, 310052, People’s Republic of China, Email lisuhuang@zju.edu.cn Shiyong Zhao, Department of Infectious Diseases, Hangzhou Children’s Hospital, 195 Wenhui Road, Hangzhou, Zhejiang Provinve, 310005, People’s Republic of China, Email jhzsyhj@163.comPurpose: Heparin-binding protein (HBP) is a novel biomarker for inflammatory diseases. This study aimed to investigate the role of serum HBP in community-acquired pneumonia (CAP) in children and the association of HBP with the severity and prognosis.Patients and Methods: A total of 125 children with CAP admitted to the hospital were enrolled in this retrospective study. We analyzed the differences in clinical characteristics and examination findings between patients with different levels of HBP. The severe or complicated CAP was defined as having severe radiographic findings and/or systemic manifestations. Receiver operator characteristic (ROC) curves detected the performance of biomarkers in identifying patients with severe or complicated pneumonia. The multivariate logistic regression models assessed the association between HBP levels and the severity and prognosis. Finally, we constructed a predictive model based on HBP.Results: The rate of severe or complicated CAP for patients with upper-quartile HBP concentration (≥ 60 ng/mL) was 54.8%, significantly higher than that of patients with lower HBP concentration (26.6%). The level of HBP is substantially correlated with neutrophil counts, C-reactive protein, erythrocyte sedimentation rate, and serum amyloid A protein (r = 0.31, 0.26, 0.36, and 0.26, respectively). HBP achieved the highest level of discrimination for severe or complicated CAP among the biomarkers. Higher HBP concentration (≥ 60 ng/mL) was associated with a three-fold higher risk of severe or complicated CAP (adjusted odds ratio = 3.11, p < 0.05). A predictive model including four characteristics (HBP, lactate dehydrogenase, age and non-viral infection) for predicting severe or complicated CAP (with area under the ROC curve = 0.75) was built to create a nomogram.Conclusion: Substantially elevated serum HBP is significantly associated with severe or complicated CAP and poor prognosis in children. This finding warrants further investigation of the function of HBP in the pathogenesis of CAP.Keywords: pneumonia, biomarker, heparin-binding protein, children

Shu-xian Xu,1,&ast; Xin-hui Xie,1,&ast; Lihua Yao,1 Li-chang Chen,2 Qirong Wan,1 Zhen-hua Chen,1 Zhongchun Liu1,3 1Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongchun Liu, Department of Psychiatry, Renmin Hospital of Wuhan University, No. 238, Jiefang Road, Wuhan, Hubei, ZIP 430060, People’s Republic of China, Tel +86-8804191181399, Email zcliu6@whu.edu.cnObjective: Little is known about the effectiveness and cognitive side-effects of electroconvulsive therapy (ECT) in young adults with treatment-resistant depression (TRD). The primary aim of this prospective longitudinal observational trial was to examine the clinical features and cognitive outcomes of young adults with TRD undergoing ECT.Methods: Changes in depressive symptoms and objective and subjective cognitive function were assessed using repeated evaluation at baseline, after each ECT session, and at one-month follow-up using the Montgomery-Äsberg Depression Rating Scale (MADRS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Forward Digital Span Test (FDST), and part of the Columbia Subjective Side Effects Schedule.Results: Of 41 inpatients, 35 (85.4%) and 12 (29.3%) met the criteria for response and remission after ECT, respectively. The greatest clinical improvements occurred during the first 3– 4 ECT sessions. While 34 patients reported subjective cognitive impairment increased with ECT, immediate and delayed memory (RBANS) significantly increased after ECT, consistent with FDST results. Objective cognition significantly improved during follow-up, but subjective cognition remained impaired.Conclusion: ECT is effective in young adults with TRD. Although subjective cognitive impairment increased during treatment, objective cognitive impairments were not observed.Keywords: electroconvulsive therapy, young adults, cognitive function, treatment-resistant depression

Zhaolin Li,1,&ast; Qiaojun Zeng,1,&ast; Shuwan Xu,2,&ast; Yuewei Li,1 Tiantian Tang,1 Jianting Shi,1 Xueming Song,1 Wenman He,1 Liang Chen,1 Guirong Liu,1 Boying Gao,3 Jianming Zheng,4 Linjie Huang,1 Ming Chen,1 Shanping Jiang1 1Department of Pulmonary and Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Cardiology, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Cardiovascular Medicine Department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanping Jiang; Ming Chen, Department of Pulmonary and Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Yan-jiang Xi Road 107, Guangzhou, 510120, People’s Republic of China, Tel +86-20-81332441, Email jiangshp@mail.sysu.edu.cn; chenm69@mail.sysu.edu.cnBackground: Although tigecycline is an effective drug against drug-resistant bacteria, it demonstrated a higher all-cause mortality than comparator antibiotics and a high incidence of coagulation disorders which can be accompanied by severe bleeding. At present, a predictive model for tigecycline-related coagulopathy is not readily available, and the prognostic value of coagulopathy in tigecycline-administered patients has not been elucidated. In this paper, we investigate the association between tigecycline-related coagulopathy and in-hospital mortality to develop a nomogram for the prediction of tigecycline-related coagulopathy.Methods: This retrospective cohort study includes 311 adults prescribed with tigecycline from 2018 to 2020. The primary cohort and validation cohort were constructed by dividing the participants in a ratio of 7:3. The endpoint is tigecycline-related coagulopathy, defined as a condition with no abnormality in coagulation prior to tigecycline application but developed the following symptoms upon prescription: activated partial thromboplastin time (APTT) extended by > 10 s than the upper limit of normal (ULN), prothrombin time (PT) prolonged for > 3 s than the ULN or reduced serum level of fibrinogen to < 2.0 g/L. A predictive nomogram based on logistic regression was subsequently constructed.Results: Tigecycline intake for over 7 days, combined other antibiotics, initial PT, initial fibrinogen and estimated glomerular filtration rate (eGFR), are independent prognostic factors of tigecycline-related coagulopathy. The primary and validation cohort each has an area under the receiver operating characteristic curve (AUC) of 0.792 (0.732– 0.851) and 0.730 (0.629– 0.832) for nomogram, respectively. Furthermore, the fitted calibration curve illustrated adequate fit of the model, while the decision curve analysis demonstrated good clinical value. Survival curves showed a high mortality rate among patients with tigecycline-related coagulopathy.Conclusion: This nomogram exhibited helpful clinical value in predicting tigecycline-related coagulopathy that could reduce the high mortality rate of patients prescribed with tigecycline.Keywords: tigecycline, drug-resistant bacteria, coagulopathy, nomogram

Xuanyong Yang,1,* Jiang Xu,1,* Shihai Lan,1 Zhigao Tong,1 Kang Chen,1 Zhizheng Liu,1 Shan Xu2 1Department of Neurosurgery, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shan Xu, Department of Pathology, The First Affiliated Hospital of Nanchang University, No. 17 Yong Wai Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Email xshan2002@126.comBackground: Cerebral ischemia-reperfusion (CI/R) injury is a subtype of complication after treatment of ischemic stroke. It has been reported that exosomes derived from BMSCs could play an important role in CI/R injury. However, whether BMSCs-derived exosomes could regulate CI/R injury via carrying miRNAs remains to be further explored.Methods: RNA sequencing was performed to identify the differentially expressed miRNAs. To mimic CI/R in vitro, SH-SY5Y cells were exposed to oxygen glucose deprivation/reoxygenation (OGD/R). The viability of SH-SY5Y cells was tested by CCK8 assay, and TUNEL staining was performed to detect the cell apoptosis.Results: MiR-133a-3p was identified to be reduced in exosomes derived from the plasma of patients with IS. Upregulation of miR-133a-3p significantly reversed OGD/R-induced SH-SY5Y cell growth inhibition. Consistently, BMSCs-derived exosomal miR-133a-3p could restore OGD/R-decreased SH-SY5Y cell proliferation via inhibiting apoptosis. Meanwhile, DAPK2 was a direct target of miR-133a-3p. In addition, OGD/R notably upregulated the level of DAPK2 and weakened the expressions of p-Akt and p-mTOR in SH-SY5Y cells, whereas exosomal miR-133a-3p derived from BMSCs notably reversed these phenomena. Exosomal miR-133a-3p derived from BMSCs could reverse OGD/R-induced cell apoptosis via inhibiting autophagy. Furthermore, exosomal miR-133a-3p derived from BMSCs markedly alleviated the symptom of CI/R injury in vivo.Conclusion: Exosomal miR-133a-3p derived from BMSCs alleviates CI/R injury via targeting DAPK2/Akt signaling. Thus, our study might shed new light on discovering new strategies against CI/R injury.Keywords: CI/R, BMSC, miR-133a-3p, DAPK2, autophagy

Huifeng Di, Hui Liu, Shuna Xu, Na Yi, Guangchen Wei Jinan City People’s Hospital, Jinan, 271100, People’s Republic of ChinaCorrespondence: Guangchen Wei, Department of Pharmacy, Jinan City People’s Hospital, 001 Xuehu Street, Jinan, 271100, People’s Republic of China, Email wgc0088@126.comBackground: Acne is a highly prevalent skin disease, and inflammation plays an important role. Compound Huangbai Liquid (CHL) is a classical traditional Chinese medicine (TCM) with remarkable clinical therapeutic effects on acne. However, a holistic network pharmacological approach to explain the mechanism of CHL in the treatment of acne has not been explored.Methods: In this study, active components and action targets of Compound Huangbai Liquid were assessed via BATMAN-TCM. The target genes related to acne were extracted from GeneCards, DisGeNet and OMIM databases. Venn diagrams to predict potential targets for the treatment of acne. Protein–Protein interaction (PPI) analysis was proceeded through String database to obtain the core protein, and the protein interaction network was constructed by Cytoscape 3.9.1. Gene Ontology (Go) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on Metascape platforms and bioinformatics.com.cn. TCM-compound-target-disease network and disease-target pathway network were constructed using Cytoscape to give the visual result. Finally, the results were further verified by establishing the mouse acne animal model.Results: This approach identified 165 active compounds, 1117 gene targets, 156 acne-related targets, and 34 potential target proteins for the treatment of acne with CHL. The biological processes were primarily related to cellular response to lipid, response to lipopolysaccharide, and regulation of secretion. The CHL was significantly associated with ten pathways including the Chagas disease and pathways in cancer. Animal experiments showed that CHL could significantly alleviate the levels of inflammatory factors and TLR4/NF-κB/p38 MAPK signaling pathway in acne.Conclusion: This study revealed the multiple active components, multiple targets, and multiple pathways of CHL in the treatment of acne, which provided a new perspective for the study of the mechanism of traditional Chinese medicine in the treatment of acne.Keywords: Compound Huangbai Liquid, acne, network pharmacology, inflammation

Xu Jiang,1,&ast; Yang Pan,1,&ast; Sha Zhu,1 Yaxi Wang,1 Ruxin Gu,1 Yinyin Jiang,1 Bo Shen,1 Jun Zhu,1 Shulan Xu,1 Jun Yan,1 Jingde Dong,1 Wenbin Zhang,2 Chaoyong Xiao,3 Li Zhang1 1Department of Geriatrics, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Radiology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Zhang, Department of Geriatrics, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China, Email jx13773958367@163.comObjective: Patients with rapid eye movement (REM) sleep behavior disorder (RBD) in Parkinson’s disease (PD-RBD) tend to have poor cognitive performance and faster cognitive deterioration, and the potential mechanism is still ambiguous. Therefore, this study aimed to detect the alterations in local brain function in PD-RBD.Methods: Fifty patients, including 23 patients with PD-RBD and 27 patients with PD without RBD (PD-nRBD), and 26 healthy controls were enrolled. All subjects were subjected to one-night polysomnography and underwent resting-state functional magnetic resonance imaging (rs-fMRI). The fMRI images of the three groups were analyzed by regional homogeneity (ReHo) to observe the local neural activity. Correlations between altered ReHo values and chin electromyographic (EMG) density scores and cognitive scores in the PD subgroups were assessed.Results: Compared with the patients with PD-nRBD, the patients with PD-RBD had higher ReHo values in the frontal cortex (the right superior frontal gyrus, the right middle frontal gyrus and the left medial superior frontal gyrus), the right caudate nucleus and the right anterior cingulate gyrus, and compared with the HCs, the patients with PD-RBD had lower ReHo values in the bilateral cuneus, the bilateral precuneus, the left inferior temporal gyrus and the left inferior occipital gyrus. For the patients with PD-RBD, the phasic chin EMG density scores were positively correlated with the ReHo values in the left medial superior frontal gyrus, and the tonic chin EMG density scores were positively correlated with the ReHo values in the right anterior cingulate gyrus.Conclusion: This study indicates that increased ReHo in the frontal cortex, the caudate nucleus and the anterior cingulate gyrus may be linked with the abnormal motor behaviors during REM sleep and that decreased ReHo in the posterior regions may be related to the visuospatial–executive function in patients with PD-RBD.Keywords: Parkinson’s disease, rapid eye movement sleep behavior disorder, resting-state fMRI, regional homogeneity

Min Zhu, Siqi Xu, Xia Ju, Shengbin Wang, Xitong Yu Department of Anesthesiology, The Anqing Medical Center of Anhui Medical University, The Fifth Clinical Medical College of Anhui Medical University, Anqing, People’s Republic of ChinaCorrespondence: Xia Ju, Department of Anesthesiology, The Anqing Medical Center of Anhui Medical University, The Fifth Clinical Medical College of Anhui Medical University, Anqing, 246003, People’s Republic of China, Tel +86 13685563136, Email alcon2006@126.comPurpose: This study aims to investigate the effects of the different doses of esketamine on postoperative quality of recovery in patients undergoing modified radical mastectomy.Methods: Ninety-nine female patients were randomly allocated to three groups: the low-dose esketamine group (group E1) (0.5 mg/kg loading, 2 μg/kg/h infusion), the high-dose esketamine group (group E2) (0.5 mg/kg loading, 4 μg/kg/h infusion), the control group (group C) (received normal saline). The primary outcome was the quality of recovery-15 (QoR-15) scores on postoperative day 1 (POD1) and days 3 (POD3). The secondary outcomes were the sleep quality scores on POD1, bispectral index (BIS) value at 10, 30, and 60 min after operation, numeric rating scale (NRS) pain scores within 24 h after surgery, nausea, vomiting, drowsiness, nightmare, and intraoperative awareness.Results: The total QoR-15 scores were higher in group E1 and group E2 than in group C on POD1 and POD3 (P< 0.05). The sleep quality scores on POD1 and BIS value at 10, 30, and 60 min after operation were higher in group E1 and group E2 than in group C (P< 0.05). The NRS pain scores at 2, 4 and 6 h after surgery in group E1 and at 2, 4, 6, 12 and 24 h after surgery in group E2 were lower than in group C (P< 0.05). The NRS pain scores at 6, 12 and 24 h after surgery in group E2 were lower than in group E1 (P< 0.05). The incidence of drowsiness was higher in group E1 and group E2 than in group C (P< 0.05).Conclusion: Esketamine infusion improved to some extent the quality of recovery on POD1 and POD3 in patients undergoing modified radical mastectomy, especially 4 μg/kg/h esketamine was better, but the BIS value and incidence of drowsiness were significantly increased.Keywords: esketamine, postoperative quality of recovery, radical mastectomy

Yu Li,1 Jinde Zhu,1 Xiaodong Zhao,2 Yi Sun,2,3 Feng Xu,1,2 Song Xu,1,2 Xuejun Shang1,2 1Department of Urology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, People’s Republic of China; 2Department of Urology, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Xuejun Shang, Department of Urology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, No. 305 East Zhongshan Road, Nanjing, 210002, People’s Republic of China, Tel +8613813905418, Email shangxj98@163.comPurpose: Epididymitis histological alterations and related long-term reproductive issues cannot be cured by antibiotics alone. Few studies have been done on the effect of lycopene on epididymitis, despite the fact that it is an efficient antioxidant. The objective of this study was to assess the impact of lycopene on Lipopolysaccharide (LPS)-induced epididymis and lipid metabolism.Methods: Thirty-one 260– 290g rats were separated into the blank control group (n=10), the oil-control group (n=10), the single intraperitoneal injection of 5 mg/kg LPS (n=5), and the continuous intragastric of 5 mg/kg lycopene (n=6). The animals were euthanized after four weeks, and blood and the epididymis were removed for analysis.Results: Lycopene significantly decreased IL-1α, IL-1β, TNF-α, MCP-1, IL-6 and lipid peroxidation product Malondialdehyde in serum and epididymis. It significantly increased the epididymis’s antioxidant enzyme and total antioxidant capacity. According to LC-MS plasma lipidomics, lycopene increased phosphatidylcholine, lysophosphatidylcholine, decreased phosphatidylethanolamine, triacylglycerol, and diacylglycerol levels, changed the composition of lipids, altered metabolic pathways, and these changes were related to the mechanism of anti-inflammatory and oxidative stress. 20 lipids, including PC (20:5e) and LPC (14:0), were identified through additional Spearman correlation analysis as being related to cytokines and oxidation indices. They served as possible lipid markers that may be utilized to gauge the severity of inflammation.Conclusion: Lycopene has anti-inflammatory and antioxidant properties that improve histopathological and functional damage in LPS-induced epididymitis and is an alternate supplement for treating epididymitis. Lipidomics provide new perspectives on the possible mechanism of lycopene in protecting against LPS-induced epididymitis by integrating lipid metabolism and inflammation.Keywords: lycopene, lipidomics, inflammatory, antioxidant, lipids regulation, correlation

Shaoxue Yang1 &ast;, Jie Song2 &ast;, Hong Yang,2 Wei Liu,2 Yuqing Jiang,2 Xiaohui Sun,2 Ding Ye,2 Songxiao Xu,1 Yingying Mao2 1The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Hangzhou, 310022, People’s Republic of China; 2Department of Epidemiology, Zhejiang Chinese Medical University School of Public Health, Hangzhou, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingying Mao, Department of Epidemiology, Zhejiang Chinese Medical University School of Public Health, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email myy@zcmu.edu.cn Songxiao Xu, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Hangzhou, 310022, People’s Republic of China, Email xusx1979@126.comObject: Prostate cancer is one of the leading malignancies in men worldwide. Previous observational studies have linked amino acids and transaminase with altered risk of prostate cancer. However, whether these associations were causal remained unclear. Therefore, we conducted a Mendelian randomization (MR) to assess their potential causal associations.Methods: Summary-level data for prostate cancer were obtained from a meta-analysis of genome-wide association studies (GWAS) including 79,148 prostate cancer cases and 61,106 controls of European descent. Instrumental variables (IVs) of amino acids and alanine aminotransferase (ALT) were obtained from a GWAS of 86,507 European individuals and a GWAS of 312,572 participants from the UK Biobank, respectively. MR analyses were performed using inverse-variance-weighted (IVW), likelihood-based, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test and MR-Egger regression.Results: Genetically predicted circulating concentrations of alanine were associated with an increased risk of prostate cancer (odds ratio (OR): 1.16, 95% confidence interval (CI): 1.01– 1.33, P=0.037 by IVW). Consistently, genetically predicted ALT was inversely associated with the risk of prostate cancer (OR: 0.43, 95% CI: 0.27– 0.68, P=3.28× 10− 4 by IVW). MR-Egger regression did not indicate evidence of directional pleiotropy and sensitivity analyses yielded consistent associations.Conclusion: Our study revealed that genetically predicted circulating alanine and ALT levels were associated with an altered risk of prostate cancer, suggesting their potential roles in the development of prostate cancer. Whether targeting alanine, ALT or its downstream effectors are helpful in reducing prostate cancer incidence warrants further investigation.Keywords: alanine, alanine aminotransferase, amino acids, Mendelian randomization, prostate cancer

Zhen Qin,1– 3 Shuai Xu,1– 3 Ruixia Yuan,4 Zeyu Wang,1– 3 Yongzheng Lu,1– 3 Yanyan Xu,1– 3 Yan Lv,1– 3 Fengyi Yu,1– 3 Jing Bai,1– 3 Hui Zhang,1– 3 Li Zhang,1– 3 Jinying Zhang,1– 3 Junnan Tang1– 3 1Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 2Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan, 450052, People’s Republic of China; 3Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan, 450018, People’s Republic of China; 4Clinical Big Data Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Junnan Tang, Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 15890696166, Email fcctangjn@zzu.edu.cn Jinying Zhang, Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 13503830283, Email jyzhang@zzu.edu.cnObjective: We aimed to investigate the prognostic value of the triglyceride-glucose (TyG) index combined the with Global Registry of Acute Coronary Events (GRACE) score in adult acute coronary syndrome (ACS) patients with type 2 diabetes mellitus (T2DM) who underwent percutaneous coronary intervention (PCI).Methods: The study enrolled total 899 ACS patients with T2DM who underwent PCI. TyG index and the GRACE risk score were calculated and assessed by median. The correlation was analyzed by Spearman’s rank correlation coefficient. The cumulative major adverse cardiovascular event (MACE) curve was generated using the Kaplan–Meier method. Multivariate Cox regression was used to identify predictors of MACEs. Additionally, the receiver operating characteristic curve (ROC), net reclassification index (NRI) and Integrated Discrimination Improvement (IDI) were applied to analyze the performance of each single factor index and combined multivariate index in predicting MACE.Results: In the ACS patients with T2DM after PCI, there were significant differences in the TyG index and GRACE risk score between the MACE group and the MACE-free group (P < 0.001). Kaplan–Meier analysis showed that the TyG index combined with the GRACE risk score was positively correlated with the occurrence of MACEs (log rank P < 0.001). Multivariate Cox regression analyses showed that the TyG index, the GRACE risk score, and the TyG index combined with the GRACE risk score were independent predictors of long-term MACEs (adjusted HR: 1.805; 95% CI: 1.479– 2.203, P < 0.001; adjusted HR: 1.012; 95% CI: 1.009– 1.016, P < 0.001; and adjusted HR: 2.337; 95% CI: 1.805– 3.025, P < 0.001, respectively). Correlation analysis indicated that the TyG index was positively correlated with the GRACE risk score (R = 0.140, P < 0.001). The analysis of AUC, NRI and IDI revealed that the combined multivariate index performed better prognostic role than each single factor index in predicting the occurrence of MACE.Conclusion: Both the GRACE risk score and the TyG index could be significant and independent predictors of clinical outcomes in ACS patients with T2DM after PCI. A combination of them could be enhanced predictions of clinical outcomes in these patients.Keywords: triglyceride-glucose index, GRACE risk score, predictive biomarker, acute coronary syndrome, type 2 diabetes mellitus, percutaneous coronary intervention

Jiangbo Xie,1,2 Tingting Zhang,3 Peichun Li,3 Dong Wang,2 Tao Liu,2 Shunliang Xu1 1Department of Neurology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Neurology, Weifang Traditional Chinese Hospital, Weifang, People’s Republic of China; 3Department of Rehabilitation Medicine, Weifang Traditional Chinese Hospital, Weifang, People’s Republic of ChinaCorrespondence: Shunliang Xu, Department of Neurology, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Road, Jinan, Shandong, 250033, People’s Republic of China, Tel +86 15153169998, Email xushandaeryuan@163.comBackground: Dihydromyricetin (DHM) exerts protective effects in various brain diseases. The aim of this research was to investigate the biological role of DHM in cerebral ischemia reperfusion (I/R) injury.Methods: We generated a rat model of cerebral I/R injury by performing middle cerebral artery occlusion/reperfusion (MCAO/R). The neurological score and brain water content of the experimental rats was then evaluated. The infarct volume and extent of apoptosis in brain tissues was then assessed by 2,3,5-triphenyltetrazolium (TTC) and TdT-mediated dUTP nick end labeling (TUNEL) staining. Hippocampal neuronal cells (HT22) were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) and cell counting kit-8 (CCK-8) assays and flow cytometry were performed to detect cell viability and apoptosis. The levels of lipid reactive oxygen species (ROS) and iron were detected and the expression levels of key proteins were assessed by Western blotting.Results: DHM obviously reduced neurological deficits, brain water content, infarct volume and cell apoptosis in the brain tissues of MCAO/R rats. DHM repressed ferroptosis and inhibited the sphingosine kinase 1 (SPHK1)/mammalian target of rapamycin (mTOR) pathway in MCAO/R rats. In addition, DHM promoted cell viability and repressed apoptosis in OGD/R-treated HT22 cells. DHM also suppressed the levels of lipid ROS and intracellular iron in OGD/R-treated HT22 cells. The expression levels of glutathione peroxidase 4 (GPX4) was enhanced while the levels of acyl-CoA synthetase long-chain family member 4 (ACSL4) and phosphatidylethanolamine binding protein 1 (PEBP1) were reduced in OGD/R-treated HT22 cells in the presence of DHM. Moreover, the influence conferred by DHM was abrogated by the overexpression of SPHK1 or treatment with MHY1485 (an activator of mTOR).Conclusion: This research demonstrated that DHM repressed ferroptosis by inhibiting the SPHK1/mTOR signaling pathway, thereby alleviating cerebral I/R injury. Our findings suggest that DHM may be a candidate drug for cerebral I/R injury treatment.Graphical Abstract: Keywords: dihydromyricetin, ferroptosis, SPHK1, mTOR, cerebral ischemia reperfusion injury

Songchao Xu,1 Yusheng Yi,2 Yanting Wang,1 Pei Wang,1 Yang Zhao,1 Wei Feng1 1Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of China; 2Department of Algology, Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Yang Zhao; Wei Feng, Email zhaoy1979@qdu.edu.cn; fengweisdqd@qdu.edu.cnPurpose: Neuropathic pain is a chronic intractable disease characterized by allodynia and hyperalgesia. Effective treatments are unavailable because of the complicated mechanisms of neuropathic pain. Transient receptor potential canonical 6 (TRPC6) is a nonselective calcium (Ca2+)-channel protein related to hyperalgesia. Dexmedetomidine (Dex) is an alpha-2 (α 2) adrenoreceptor agonist that mediates intracellular Ca2+ levels to alleviate pain. However, the relationship between TRPC6 and Dex is currently unclear. We speculated that the α 2 receptor agonist would be closely linked to the TRPC6 channel. We aimed to investigate whether Dex relieves neuropathic pain by the TRPC6 pathway in the dorsal root ganglia (DRG).Methods: The chronic constriction injury (CCI) model was established in male rats, and we evaluated the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). The expression of TRPC6 and Iba-1 in the DRG were analyzed using quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence assay. The levels of inflammatory cytokines were measured using an enzyme-linked immunosorbent assay.Results: Compared with the CCI normal saline group, both the MWT and TWL were significantly improved after 7 days of Dex administration. Results demonstrated that TRPC6 expression was increased in the DRG following CCI but was suppressed by Dex. In addition, multiple administrations of Dex inhibited the phosphorylation level of p38 mitogen-activated protein kinase and the upregulation of neuroinflammatory factors.Conclusion: The results of this study demonstrated that Dex exhibits anti-nociceptive and anti-inflammatory properties in a neuropathic pain model. Moreover, our findings of the CCI model suggested that Dex has an inhibitory effect on TRPC6 expression in the DRG by decreasing the phosphorylation level of p38 in the DRG.Keywords: neuropathic pain, CCI model, microglia, TRPC6, dexmedetomidine, neuroinflammation

Dawei Shi,1,&ast; Qiulong Zhou,2,&ast; Sihong Xu,1 Yumei Zhu,3 Hui Li,4 Ye Xu2 1National Institutes for Food and Drug Control, Institute of Pathogen Biology at the Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Engineering Research Centre of Molecular Diagnostics of the Ministry of Education, State Key Laboratory of Cellular Stress Biology, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen, People’s Republic of China; 3Shenzhen Center for Chronic Disease Control, Shenzhen, People’s Republic of China; 4Tuberculosis Reference Laboratory, Henan Provincial Centers for Disease Control and Prevention, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Li, Tuberculosis Reference Laboratory, Henan Provincial Centers for Disease Control and Prevention, Zhengzhou, People’s Republic of China, Tel/Fax +86 371-68089049, Email lihui2005yan@126.com Ye Xu, Engineering Research Centre of Molecular Diagnostics of the Ministry of Education, State Key Laboratory of Cellular Stress Biology, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen, People’s Republic of China, Tel +86 592 2187992, Fax +86 592 2187363, Email xuye@xmu.edu.cnPurpose: Pyrazinamide (PZA) is a critical component of standardized chemotherapy for tuberculosis (TB) and is recommended for the treatment of multidrug-resistant (MDR) TB. We aimed to characterize mutations in pncA of M. tuberculosis and evaluate their diagnostic accuracy for PZA susceptibility in China. We also combined genotypic methods with phenotypic susceptibility testing and pyrazinamidase (PZAse) activity to confirm PZA-resistant M. tuberculosis isolates.Results: An evaluation of 82 MDR M. tuberculosis strains revealed that 28.0% (23/82) were phenotypically resistant to 100 mg/L PZA and 15.9% (13/82) showed resistance to 300 mg/L PZA. Mutations in pncA were detected at 33 unique sites, and the majority were point mutations. No evident mutation hotspots or mutations affecting multiple amino acids were found, but the association between pncA mutations and PZA resistance was significant under 100 and 300 mg/L. The sensitivity of pncA mutation detection for predicting PZA susceptibility was 82.6% (19/23), and the specificity was 61.0% (36/59), based on 100 mg/L PZA, whereas the sensitivity was 84.6% (11/13) and the specificity was 55.1% (38/69), based on 300 mg/L PZA. All mutations identified in the highly PZA-resistant (300 mg/L) strains had an 80% loss relative to PZAse activity. No evident PZAse activity loss was observed in one synonymous mutation strain and the loss exceed 60% in all other strains.Conclusion: The association between pncA mutation and PZA resistance was significant. Relatively, the molecular method have shown better reliability than the phenotypic method for the detection of PZA resistance. This provides a theoretical basis for the clinical diagnosis of drug-resistant TB.Keywords: MDR, PZA, pncA, DST, Beijing genotype, enzymatic activity

Shaobo Duan,1 Ye Zhang,1 Shuang Xu,1 Pei Jiang,1 Qinghua Qi2 1Department of Health Management, Henan Provincial People’s Hospital Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Qinghua Qi, Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China, Email qiqinghua333@sina.comObjective: To investigate the predictive role of contrast-enhanced ultrasonography (CEUS) plus D-dimer levels in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).Methods: CEUS was applied to assess lymph nodes in 186 patients with confirmed DLBCL. The clinical data and laboratory indicators were collected from these patients, and a retrospective analysis was conducted on the relationship between the quantitative parameters of CEUS (TTP, PI, AUC, WOT), D-dimer levels, and clinical features of the DLBCL patients. The Cox regression model was used for univariate and multivariate analyses for the risk factors associated with the prognosis.Results: There was an increase of D-dimer levels in advanced DLBCL patients, who were combined with a significant reduction in TTP and WOT and a significant increase in PI and AUC. D-dimer levels and quantitative parameters of CEUS were strongly correlated with the Ann Arbor, B symptoms, International Prognostic Index (IPI), LDH and CRP levels. The results of the Cox regression model indicated that D-dimer levels, TTP and PI, the quantitative parameters of CEUS, were important prognostic factors for DLBCL.Conclusion: CEUS results and D-dimer levels can be used as independent prognostic factors for DLBCL.Keywords: diffuse large B-cell lymphoma, contrast-enhanced ultrasonography, D-dimer, prognosis