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Jiahao Guan,1,* Yihan Dong,1,2,* Wenli Zhang,3 Qiaodi Gui,1 Danxia Luo,4 Hongxia Wen,5 Xiaojun Dang,1 Daoyan Liang,1 Shuling Hu,1 Yaqin Zhang,1 Guimei Liao,2 Lixia Zhang,1 Zifan Lu6 1Department of Clinical Laboratory, Shaanxi Provincial People′s Hospital, Xi ′an, 710068, People’s Republic of China; 2Medical College, Yan’ an University, Yan’ an, Shaanxi, 716000, People’s Republic of China; 3Translational Medicine Center of Shaanxi Provincial People’s Hospital; Shaanxi Province Research Center of Cell Immunological Engineering and Technology, Xi’an, 710068, People’s Republic of China; 4The Gynecology Department of People’s Hospital of Shaanxi Province, Xi’an, 710068, People’s Republic of China; 5Department of Respiratory Medicine II, Shaanxi Provincial People’s Hospital, Xi’an, 710068, People’s Republic of China; 6Translational Medicine Center of Shaanxi Provincial People’s Hospital, Xi’an, 710068, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lixia Zhang; Zifan Lu, Shaanxi Provincial People′s Hospital, No. 256, Youyi West Road, Xi’an, Shaanxi Province, People’s Republic of China, Tel +86 029-85251331, Email 17791735548@163.com; pharmluzifan@163.comBackground: Vaginitis is a common disease of the reproductive system in women, causing discomfort in daily life. Many reports indicate that the causes of vaginitis are related to vaginal microecological disturbances. Therefore, treatment strategies to restore microecological balance have shown promising results in both basic research and clinical settings. Recent studies have highlighted the potential adjuvant role of vitamin D in the treatment of vaginitis while illustrating its role in maintaining microecological balance. Therefore, this study focused on the therapeutic effects of vitamin D on vaginitis.Methods: The study provided a statistical description of 5978 vaginitis patients who visited Shaanxi Provincial People’s Hospital, presenting data in absolute numbers (%) and mean ± standard deviation (median quartiles were used for non-normally distributed variables). The chi-square test and analysis of variance were employed to analyze the distribution of vitamin D levels among patients, factors influencing vitamin D levels, and the association between recurrence rates and vitamin D levels.Results: Vitamin D deficiency (57.74%) or insufficiency (22.20%) is prevalent among patients with vaginitis. Furthermore, vitamin D levels have an impact on the dominant bacterial species in the vagina, as well as catalase, acetylglucosaminidase, and the overall vaginal microecological status. Age and BMI have correlations with vitamin D levels. It is hypothesized that this relationship may be attributed to clinicians utilizing vitamin D as a supplementary treatment.Conclusion: This study examined the statistical findings of vitamin D-related data from 5978 vaginitis patients, revealing a positive correlation between vitamin D deficiency and vaginitis occurrence. Patients with vitamin D deficiency/severe deficiency showed weakly positive levels of catalase and mostly weakly positive levels of acetylglucosaminidase, and most of these vaginitis are trichomonas vaginalis (TV). Furthermore, older individuals and those with higher BMI were found to be more susceptible to symptoms of vitamin D deficiency.Keywords: Vitamin D, vaginal microecology, female reproductive system diseases

Chunxiao Zhou,* Lei Xu,* Mo Geng, Shaoshan Hu Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaoshan Hu, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, 310003, People’s Republic of China, Tel +86 152 6816 6248, Email shaoshanhu421@163.comPurpose: Patients with glioma often fail to achieve satisfactory outcomes despite receiving surgery, radiotherapy, and chemotherapy. Photodynamic therapy (PDT) shows promise in addressing the limitations of traditional treatments. However, the immunological effects of PDT in glioma patients remain underexplored. This study aims to fill this gap by analyzing lymphocyte subpopulations and inflammatory markers in glioma patients undergoing PDT-assisted surgery.Patients and Methods: To enhance our comprehension of the immunobiology of glioma within a clinical framework, we conducted a retrospective analysis of glioma patients from September 2019 to December 2023. Peripheral blood lymphocyte subpopulations (CD3+, CD19+, CD4+, CD8+, CD4+/CD8+) and hematological inflammatory factors were compared among 18 patients who underwent surgery with PDT, 10 patients treated with surgery alone, and healthy controls. Additionally, lymphocyte subpopulations from 48 healthy individuals and hematology inflammatory factors from 38 healthy controls were regarded as controls.Results: PDT-assisted surgery resulted in significant alterations in lymphocyte subpopulations and inflammatory markers before and after treatment, particularly in CD4+ and CD8+ T cells. PDT-treated patients demonstrated a superior therapeutic response compared to surgery alone (P=0.035). Notably, primary glioma patients had more prolonged overall survival than recurrent glioma patients (P=0.039).Conclusion: PDT-assisted surgery significantly affects lymphocyte subpopulations and inflammatory markers, enhancing immune response in glioma patients. These findings support the use of PDT as an effective adjuvant therapy. Monitoring lymphocyte subpopulations and inflammatory markers may be valuable for glioma prognosis and treatment optimization.Keywords: glioma, lymphocyte subpopulations, inflammatory markers, photodynamic therapy

Rong Hong,1,2,* Xiaoxia Ping,2,3,* Yuanying Liu,2 Feiwen Feng,2 Su Hu,2,3 Chunhong Hu2,3 1Department of Radiology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215100, People’s Republic of China; 2Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, People’s Republic of China; 3Institute of Medical Imaging, Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunhong Hu; Su Hu, Department of Radiology, The First Affiliated Hospital of Soochow University; Institute of Medical Imaging, Soochow University, Suzhou, Jiangsu, People’s Republic of China, Email sdhuchunhong@sina.com; husu@suda.edu.cnPurpose: The clinical, pathological, gene expression, and prognosis of invasive mucinous adenocarcinoma (IMA) differ from those of invasive non-mucinous adenocarcinoma (INMA), but it is not easy to distinguish these two. This study aims to explore the value of combining CT-based radiomics features with clinic-radiological characteristics for preoperative diagnosis of solitary-type IMA and to establish an optimal diagnostic model.Methods: In this retrospective study, a total of 220 patients were enrolled and randomly assigned to a training cohort (n = 154; 73 IMA and 81 INMA) and a testing cohort (n = 66; 31 IMA and 35 INMA). Radiomics features and clinic-radiological characteristics were extracted from plain CT images. The radiomics models for predicting solitary-type IMA were developed by three classifiers: linear discriminant analysis (LDA), logistic regression-least absolute shrinkage and selection operator (LR-LASSO), and support vector machine (SVM). The combined model was constructed by integrating radiomics and clinic-radiological features with the best performing classifier. Receiver operating characteristic (ROC) curves were used to evaluate models’ performance, and the area under the curve (AUC) were compared by the DeLong test. Decision curve analysis (DCA) was conducted to assess the clinical utility.Results: Regarding CT characteristics, tumor lung interface, and pleural retraction were the independent risk factors of solitary-type IMA. The radiomics model using the SVM classifier outperformed the other two classifiers in the testing cohort, with an AUC of 0.776 (95% CI: 0.664– 0.888). The combined model incorporating radiomics features and clinic-radiological factors was the optimal model, with AUCs of 0.843 (95% CI: 0.781– 0.906) and 0.836 (95% CI: 0.732– 0.940) in the training and testing cohorts, respectively.Conclusion: The combined model showed good ability in predicting solitary-type IMA and can provide a non-invasive and efficient approach to clinical decision-making.Keywords: computed tomography, invasive mucinous adenocarcinoma, radiomics, machine learning

Zhenghua Cao,1 Shengkun Zhao,1 Shaodan Hu,2 Tong Wu,3 Feng Sun,2 LI Shi2 1Changchun University of Traditional Chinese Medicine, Changchun, Jilin, People’s Republic of China; 2Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin, People’s Republic of China; 3Geriatric Department, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of ChinaCorrespondence: LI Shi, Email shili0648@163.comPurpose: To employ bioinformatics and machine learning to predict the characteristics of immune cells and genes associated with the inflammatory response and ferroptosis in chronic obstructive pulmonary disease (COPD) patients and to aid in the development of targeted traditional Chinese medicine (TCM). Mendelian randomization analysis elucidates the causal relationships among immune cells, genes, and COPD, offering novel insights for the early diagnosis, prevention, and treatment of COPD. This approach also provides a fresh perspective on the use of traditional Chinese medicine for treating COPD.Methods: R software was used to extract COPD-related data from the Gene Expression Omnibus (GEO) database, differentially expressed genes were identified for enrichment analysis, and WGCNA was used to pinpoint genes within relevant modules associated with COPD. This analysis included determining genes linked to the inflammatory response in COPD patients and analyzing their correlation with ferroptosis. Further steps involved filtering core genes, constructing TF-miRNA‒mRNA network diagrams, and employing three types of machine learning to predict the core miRNAs, key immune cells, and characteristic genes of COPD patients. This process also delves into their correlations, single-gene GSEA, and diagnostic model predictions. Reverse inference complemented by molecular docking was used to predict compounds and traditional Chinese medicines for treating COPD; Mendelian randomization was applied to explore the causal relationships among immune cells, genes, and COPD.Results: We identified 2443 differential genes associated with COPD through the GEO database, along with 8435 genes relevant to WGCNA and 1226 inflammation-related genes. A total of 141 genes related to the inflammatory response in COPD patients were identified, and 37 core genes related to ferroptosis were selected for further enrichment analysis and analysis. The core miRNAs predicted for COPD include hsa-miR-543, hsa-miR-181c, and hsa-miR-200a, among others. The key immune cells identified were plasma cells, activated memory CD4 T cells, gamma delta T cells, activated NK cells, M2 macrophages, and eosinophils. Characteristic genes included EGF, PLG, PTPN22, and NR4A1. A total of 78 compounds and 437 traditional Chinese medicines were predicted. Mendelian randomization analysis revealed a causal relationship between 36 types of immune cells and COPD, whereas no causal relationship was found between the core genes and COPD.Conclusion: A definitive causal relationship exists between immune cells and COPD, while the prediction of core miRNAs, key immune cells, characteristic genes, and targeted traditional Chinese medicines offers novel insights for the early diagnosis, prevention, and treatment of COPD.Keywords: bioinformatics analysis, Mendelian randomization, machine learning, COPD, characteristic genes, targeted traditional Chinese medicine, early diagnosis

Shuli Hu, Yaling Li, Xuepeng Fan Department of Intensive Care Unit, Wuhan No. 1 Hospital, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Xuepeng Fan, Email dcbpc888@126.comObjective: To explore how non-surgical esophageal cancer patients can identify high-risk factors for radiation-induced pneumonitis after receiving radiotherapy.Methods: We retrospectively included 228 esophageal cancer patients who were unable to undergo surgical treatment but received radiotherapy for the first time. By retrospective analysis and identifying potential risk factors for symptomatic radiation-induced pneumonitis (ie ≥grade 2), as well as delineating the affected lung as an area of interest on localized CT and extracting radiomics features, along with extracting dosimetric parameters from the affected lung area. After feature screening, patients were randomly divided into training and testing sets in a 7-to-3 ratio, and a prediction model was established using machine learning algorithms. Finally, the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to validate the predictive performance of the model.Results: A total of 54 cases of symptomatic radiation pneumonitis occurred in this study, with a total incidence rate of 23.68%. The results of multivariate analysis showed that the occurrence of symptomatic radiation pneumonitis was significantly correlated with the mean lung dose (MLD), esophageal PTVD90, esophageal PTVV50, V5, V10, V15, and V20 in patients. The machine learning prediction model constructed based on candidate prediction variables has a prediction performance interval between 0.751 (95% CI: 0.700– 0.802) and 0.891 (95% CI: 0.840– 0.942) in the training and validation sets, respectively. Among them, the RFM algorithm has the best prediction performance for radiation-induced pneumonitis, with 0.891 (95% CI: 0.840– 0.942) and 0.887 (95% CI: 0.836– 0.938) in the training and validation sets, respectively.Conclusion: The combination of localization CT radiomics features and diseased lung dosimetry parameters has good predictive value for radiation-induced pneumonitis in esophageal cancer patients after radiotherapy. Especially, the radiation-induced pneumonitis prediction model constructed using RF algorithm can be more effectively used to guide clinical decision-making in esophageal cancer patients.Keywords: esophageal cancer, radiotherapy, radiation pneumonitis, radiomics, prediction model

Danni Song,1 Weiwei Jiang,1 Shuang Hu,1 Rong Zhu,1 Congshan Pu,1 Yiting Wang,1 Chunjian Shan,1 Chun Zhao2 1Department of Obstetrics, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, 210004, People’s Republic of China; 2Reproductive Center, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, 210004, People’s Republic of ChinaCorrespondence: Chunjian Shan, Department of Obstetrics, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, 210004, People’s Republic of China, Email shanchunjian@njmu.edu.cn Chun Zhao Reproductive center, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, 210004, People’s Republic of China, Email zhaochun2008@yeah.netBackground: There are multiple psychological symptoms in women undergoing assisted reproductive technology, which seriously affect health-related quality of life and even cause patients to stop treatment.Aim: This study aimed to identify psychological symptom clusters and their influencing factors in women undergoing assisted reproductive technology.Methods: A cross-sectional survey was conducted from June to November 2023 at the reproductive centers of Nanjing Women and Children’s Healthcare Hospital. Data on demographic and clinical characteristics and Symptom Checklist-90 were collected. Exploratory factor analysis was performed to identify psychological symptom clusters. Univariate logistic regression analysis and multivariate logistic regression analysis were performed to explore influencing factors.Results: A total of 213 patients were recruited. The study found that the included participants scored higher on all SCL scales than the general Chinese females. The three most common were trouble remembering things (81.7%), feeling easily annoyed or irritated (81.2%), and feeling low in energy or slowed down (70.9%). Six symptom clusters were identified: paranoid ideation, depression, obsessive-compulsive disorder, interpersonal sensitivity, somatization, and sleep disorders. Multivariate logistic regression analysis showed that duration of infertility treatment (> 12 months) was identified as a risk factor for sleep disorder cluster (OR=2.833, 95% CI:1.355~5.922), adverse pregnancy history was identified as a risk factor for paranoid ideation cluster (OR=2.961,95% CI:1.406~6.253), depression cluster (OR=2.404,95% CI:1.240~4.660), and obsessive-compulsive cluster (OR=1.810, 95% CI:1.016~3.233), financial burden during treatment was identified as risk factors for all symptom clusters[(OR=5.869, 95% CI:1.717~20.057),(OR=6.490,95% CI:2.210~19.063),(OR=3.034,95% CI:1.560~5.898),(OR=7.078,95% CI:2.420~20.698),(OR=4.532,95% CI:1.845~10.397),(OR=2.151,95% CI:1.129~4.098)].Conclusion: Women undergoing ART experience various psychological symptoms that are interrelated and exist in the form of symptom clusters. More attention should be paid to the psychological status of patients with longer duration of infertility treatment, adverse pregnancy history, and financial burden during treatment. This study guides the development of targeted and effective psychological interventions to facilitate symptom management in women undergoing ART.Keywords: assisted reproductive technology, psychological symptom, symptom clusters, exploratory factor analysis

Shiyu Hu,1,2,* Wenyu Chen,2,* Xiaoli Tan,2,* Ye Zhang,1,2 Jiaye Wang,1,2 Lifang Huang,3 Jianwen Duan4 1Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Respiratory Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 3Health Management Center, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 4Department of Hepatobiliary Surgery, Quzhou People’s Hospital, Quzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lifang Huang, Health Management Center, The Affiliated Hospital of Jiaxing University, No. 1882, Zhonghuan South Road, Nanhu District, Jiaxing, Zhejiang, 314001, People’s Republic of China, Email jxhuanglifang@126.com Jianwen Duan, Department of Hepatobiliary Surgery, Quzhou People’s Hospital, No. 2, Zhongloudi, Quzhou, Zhejiang, 324000, People’s Republic of China, Email 695377686@qq.comPurpose: The purpose of this study is to develop and validate a clinical prediction model for diagnosing Metabolic Syndrome (MetS) based on indicators associated with its occurrence.Patients and Methods: This study included a total of 26,637 individuals who underwent health examinations at the Jiaxing First Hospital Health Examination Center from January 19, 2022, to December 31, 2022. They were randomly divided into training (n = 18645) and validation (n = 7992) sets in a 7:3 ratio. Firstly, the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm was employed for variable selection. Subsequently, a multifactor Logistic regression analysis was conducted to establish the predictive model, accompanied by nomograms. Thirdly, model validation was performed using Receiver Operating Characteristic (ROC) curves, Harrell’s concordance index (C-index), calibration plots, and Decision Curve Analysis (DCA), followed by internal validation.Results: In this study, six predictive indicators were selected, including Body Mass Index, Triglycerides, Blood Pressure, High-Density Lipoprotein Cholesterol, Low-Density Lipoprotein Cholesterol, and Fasting Blood Glucose. The model demonstrated excellent predictive performance, with an AUC of 0.978 (0.976– 0.980) for the training set and 0.977 (0.974– 0.980) for the validation set in the nomogram. Calibration curves indicated that the model possessed good calibration ability (Training set: Emax 0.081, Eavg 0.005, P = 0.580; Validation set: Emax 0.062, Eavg 0.007, P = 0.829). Furthermore, decision curve analysis suggested that applying the nomogram for diagnosis is more beneficial when the threshold probability of MetS is less than 89%, compared to either treating-all or treating-none at all.Conclusion: We developed and validated a nomogram based on MetS risk factors, which can effectively predict the occurrence of MetS. The proposed nomogram demonstrates significant discriminative ability and clinical applicability. It can be utilized to identify variables and risk factors for diagnosing MetS at an early stage.Keywords: metabolic syndrome, risk factors, nomogram, prediction

Shengling Hu,1– 4 Jinqiang Guo,5 Zhe Chen,6 Fengyun Gong,1– 4 Qi Yu1– 4 1Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China; 2Hubei Clinical Research Center for Infectious Diseases, Wuhan, 430023, People’s Republic of China; 3Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences, Wuhan, 430023, People’s Republic of China; 4Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan, 430023, People’s Republic of China; 5Department of Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 6Department of Thoracic Surgery, the Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of ChinaCorrespondence: Qi Yu; Fengyun Gong, Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China, Email fishns123@163.com; 2020jy0008@hust.edu.cnBackground: Multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) with high mortality remains a public health crisis and health security threat. This study aimed to explore the predictive value of nutritional indices for all-cause mortality (ACM) in MDR/RR-TB patients.Methods: We retrospectively recruited MDR/RR-TB patients between January 2015 and December 2021, randomly assigning them to training and validation cohorts. Patients were divided into high nutritional risk groups (HNRGs) and low nutritional risk groups (LNRGs) based on the optimal cut-off value obtained from receiver operating characteristic (ROC) analyses of the hemoglobin-albumin-lymphocyte-platelet (HALP) score, prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score. In the training cohort, Kaplan-Meier survival curves and Log rank tests were used to compare overall survival (OS) between the groups. Cox risk proportion regression analyses were used to explore the risk factors of ACM in patients with MDR/RR-TB. The predictive performance of ACM was assessed using area under the curve (AUC), sensitivity and specificity of ROC analyses.Results: A total of 524 MDR/RR-TB patients, with 255 in the training cohort and 269 in the validation cohort, were included. Survival analyses in the training cohort revealed significantly lower OS in the HNRGs compared to the LNRGs. After adjusting for covariates, multivariate analysis identified low HALP score, low PNI and high CONUT score were independent risk factors for ACM in MDR/RR-TB patients. ROC analyses demonstrated good predictive performance for ACM with AUCs of 0.765, 0.783, 0.807, and 0.811 for HALP score, PNI, CONUT score, and their combination, respectively. Similar results were observed in the validation set.Conclusion: HALP score, PNI, and CONUT scores could effectively predict ACM in patients with MDR/RR-TB. Hence, routine screening for malnutrition should be given more attention in clinical practice to identify MDR/RR-TB patients at higher risk of mortality and provide them with nutritional support to reduce mortality.Keywords: multidrug- and rifampicin- resistant tuberculosis, all- cause mortality, nutrition

Bohai Du,1 Tianlan Li,1 Haoqi He,1 Xun Xu,2 Chunmei Zhang,1 Xianzhu Lu,1 Yuhan Wang,1 Jingyi Cao,1 Yinghan Lu,1 Yiwa Liu,1 Shanshan Hu,1 Juxiao Li,1 Li Li,1 Ming Shi1 1Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, Guangdong Province, 523808, People’s Republic of China; 2Experimental Animal Center, Guangdong Medical University, Dongguan, Guangdong Province, 523808, People’s Republic of ChinaCorrespondence: Li Li; Ming Shi, School of Public Health, Guangdong Medical University, Dongguan, Guangdong Province, 523808, People’s Republic of China, Tel +86-15889530426 ; +86-769-22896568, Email lily2017@gdmu.edu.cn; shiming@gdmu.edu.cnIntroduction: Studies have shown that microplastics (MPs) and nanoplastics (NPs) could accumulate in the human body and pose a potential threat to human health. The purpose of this study is to evaluate the biodistribution and toxicity of MPs/NPs with different particle sizes comprehensively and thoroughly.Methods: The purpose of this study was to investigate the biodistribution and in vivo toxicity of polystyrene (PS) MPs/NPs with different sizes (50 nm, 100 nm, and 500 nm). The BALB/c mice were given 100 μL of PS50, PS100 and PS500 at the dosage of 1 mg/kg BW or 10 mg/kg BW, respectively, by gavage once a day. After 28 consecutive days of treatment, the biodistribution of differently sized PS MPs/NPs was determined through cryosection fluorescence microscopy and fluorescent microplate reader analysis, and the subsequent effects of differently sized PS MPs/NPs on histopathology, hematology and blood biochemistry were also evaluated.Results: The results showed that the three different sizes of PS MPs/NPs were distributed in the organs of mice, mainly in the liver, spleen, and intestine. At the same time, the smaller the particle size, the more they accumulate in the body and more easily penetrate the tissue. During the whole observation period, no abnormal behavior and weight change were observed. The results of H&E staining showed that no severe histopathological abnormalities were observed in the main organs in the low-dose exposure group, while. Exposure of three sizes of PS MPs/NPs could cause some changes in hematological parameters or biochemical parameters related to heart, liver, and kidney function; meanwhile, there were size- and dose-dependencies.Conclusion: The biological distribution and toxicity of plastic particles in mice were more obvious with the decrease of particle size and the increase of concentration of plastic particles. Compared with MPs, NPs were easier to enter the tissues and produce changes in liver, kidney, and heart functions. Therefore, more attention should be paid to the toxicity of NPs.Keywords: microplastics, nanoplastics, polystyrene, size, biodistribution, nanotoxicology

Shengling Hu, Qi Yu, Fenfang Liu, Fengyun Gong Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology; Hubei Clinical Research Center for Infectious Diseases; Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences; Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan, 430023, People’s Republic of ChinaCorrespondence: Fengyun Gong, Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology; Hubei Clinical Research Center for Infectious Diseases; Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences; Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan, 430023, People’s Republic of China, Email 2020jy0008@hust.edu.cnBackground: The development of chronic obstructive pulmonary disease (COPD) following tuberculosis (TB) is known as tuberculosis-associated obstructive pulmonary disease (TOPD). This study aimed to explore the predictive value of inflammatory indicators for TOPD in TB patients.Methods: Data for this cross-sectional study were collected between January 2014 and January 2022 at Wuhan Jinyintan Hospital. The ratio of inflammatory indicators, including Systemic Inflammatory Response Index (SIRI), C-reactive protein-to-lymphocyte ratio (CLR), eosinophil count-to-lymphocyte count ratio (ELR), were calculated. Univariate and multivariate logistic regression analyses were conducted to explore the association between the ratio of inflammatory indicators and TOPD. Furthermore, the relationship between the ratio of inflammatory indicators and TOPD was investigated using propensity score matching (PSM) and receiver operating characteristic (ROC) curve analysis was performed to evaluate their predictive value for TOPD.Results: The present study included a total of 737 patients, of whom 83 participants (11.26%) had TOPD. Sixty-nine TOPD patients and 69 non-TOPD (NTOPD) patients were successfully matched. Univariate and multivariable logistics regression analysis, conducted before and after PSM, revealed that SIRI was independently significantly associated with an increased risk of TOPD. The area under curve (AUC) of SIRI were 0.702 and 0.668 before and after PSM, respectively. Additionally, patients were stratified into four different groups based on SIRI quartiles for further analysis. The prevalence of TOPD in TB patients showed an increase with higher SIRI values, both before and after PSM.Conclusion: Levels of inflammatory indicators were higher in TOPD patients when compared to NTOPD patients. SIRI may be a simple and useful inflammatory index for assessing TOPD, and TB patients with higher values of SIRI are more likely to be high-risk group for TOPD.Keywords: tuberculosis-associated obstructive pulmonary disease, systemic inflammatory response index, ratio inflammatory indicator, propensity score matching

Xianmin Zhu,1 Shuang Dong,1 Jing Tang,1 Rong Xie,1 Huijing Wu,1 Jun Guan,2 Sheng Hu1 1Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Hematology, Wuhan NO.1 Hospital, Wuhan, People’s Republic of ChinaCorrespondence: Sheng Hu, Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, 116 South Road, Wuhan, 430079, People’s Republic of China, Email ehusmn@163.comAbstract: In recent years, there have been limited reports on the efficacy of later-line anti-programmed cell death − 1 (PD-1) therapy in achieving prolonged and complete remission in patients with hepatocellular carcinoma (HCC). Tislelizumab, a humanized anti-PD-1 monoclonal IgG4 antibody, has shown promising results in the treatment of HCC. This report highlights the case of a patient with HCC who experienced the development of lung metastatic lesions following HCC resection and chemotherapy, but achieved a prolonged complete response (CR) after receiving tislelizumab treatment. In April 2017, a 56-year-old male diagnosed with primary HCC underwent hepatectomy and hepatic arterial infusion pump placement. Following the surgery, the patient received adjuvant hepatic arterial infusion chemotherapy (HAIC) with 4 cycles of cisplatin+5-fluorouracil (PF) regimen starting in June 2017. In May 2018, lung metastatic lesions were detected, and the patient underwent 4 cycles of oxaliplatin+leucovorin+5-fluorouracil (FOLFOX) chemotherapy. However, the disease progressed in August 2018, leading to the administration of arsenic trioxide treatment. Despite this, further progression was observed in October 2018, prompting the patient’s enrollment in a clinical trial for tislelizumab therapy. Initially, the patient achieved a partial response (PR) to tislelizumab, which was followed by a CR that lasted for almost 4 years. Unfortunately, tislelizumab treatment had to be discontinued due to immune-related adverse events (AE). Subsequently, the patient received lenvatinib and maintained a CR until July 2023. Tislelizumab monotherapy, when used as a third-line treatment, has demonstrated remarkable efficacy in facilitating patients with advanced HCC to attain a durable CR.Keywords: hepatocellular carcinoma, complete response, immune checkpoint inhibitor, tislelizumab, chemotherapy failure, metastasis

Yimeng Geng,1,* Peifen Zhang,1,* Yanmeng Pan,1,* Huaizhi Wang,2 Yi Chen,1 Jianbo Lai,1,3,4 Shaohua Hu1– 4 1Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Department of Psychiatry, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 3The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, 310003, People’s Republic of China; 4Brain Research Institute of Zhejiang University, Hangzhou, 310003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaohua Hu, Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, The Key Laboratory of Mental Disorder’s Management, Brain Research Institute of Zhejiang University, Hangzhou, 310003, People’s Republic of China, Email dorhushaohua@zju.edu.cnPurpose: Venous thromboembolism (VTE) poses a significant threat to individuals’ health, yet its correlation with mental disorders remains underappreciated. Here, we conducted a retrospective analysis to explore the characteristics of psychiatric patients presenting with VTE.Methods: We retrospectively analyzed psychiatric inpatients with elevated plasma D-dimer levels at the Mental Health Center, First Affiliated Hospital, Zhejiang University School of Medicine, from January 2014 to January 2022. The inclusion criteria comprised comprehensive demographic and clinical profiles, including laboratory and imaging findings.Results: A cohort of 33 eligible patients was included, with plasma D-dimer levels ranging from 880 to 10,700 μg/L FEU. Significantly higher D-dimer levels were observed in patients diagnosed with severe mental disorders (SMD), such as schizophrenia and bipolar disorder, compared to those with mild mental disorders (MMD), including depression and anxiety disorders (p = 0.007). Furthermore, individuals receiving antipsychotic medications for less than one year exhibited elevated D-dimer levels compared to those on treatment for over one year (p = 0.005). However, normalization of D-dimer levels did not demonstrate a significant association with psychiatric diagnosis or treatment duration (p > 0.05).Conclusion: Our findings suggest that patients diagnosed with SMD or those undergoing antipsychotic treatment for less than one year may have elevated D-dimer levels, indicating a potential predisposition to VTE severity. This underscores the importance of recognizing VTE risk in individuals with severe mental disorders and warrants further investigation into the impact of antipsychotic treatment duration on thrombotic risk.Keywords: asymptomatic thromboembolism, D-dimer, psychiatric disorder, risk factors

Ye Zhang,1 Xiaoli Tan,2 Shiyu Hu,3 Zhifang Cui,4 Wenyu Chen2 1Department of General Medicine, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 2Department of Respiratory Medicine, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 3Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Jiaxing, Zhejiang, People’s Republic of China; 4Department of Respiratory Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Wenyu Chen, Department of Respiratory Medicine, Affiliated Hospital of Jiaxing University, No. 1882, Zhonghuan South Road, Nanhu District, Jiaxing City, Zhejiang Province, 314001, People’s Republic of China, Email 00135116@zjxu.edu.cnPurpose: Chronic obstructive pulmonary disease (COPD) concurrent with respiratory failure (RF) is devastating, and may result in death and disability. Systemic immune-inflammation index (SII) is a new prognostic biomarker linked to unfavorable outcomes of acute coronary syndrome, ischemic stroke, and heart failure. Nonetheless, its role in COPD is rarely investigated. Consequently, this study intends to assess the accuracy of SII in predicting the prognosis of COPD.Patients and Methods: The clinical information was retrospectively acquired from the Medical Information Mart for Intensive Care-IV database. The outcomes encompassed the incidence of RF and mortality. The relationship between different SII and outcomes was examined utilizing the Cox proportional-hazards model and restricted cubic splines. Kaplan-Meier analysis was employed for all-cause mortality.Results: The present study incorporated 1653 patients. During hospitalization, 697 patients (42.2%) developed RF, and 169 patients (10.2%) died. And 637 patients (38.5%) died during long-term follow-up. Higher SII increased the risk of RF (RF: HR: 1.19, 95% CI 1.12– 1.28, P< 0.001), in-hospital mortality (HR: 1.22, 95% CI 1.07– 1.39, P=0.003), and long-term follow-up mortality (HR: 1.12, 95% CI 1.05– 1.19, P< 0.001). Kaplan-Meier analysis suggested a significantly elevated risk of all-cause death (log-rank P< 0.001) in patients with higher SII, especially during the short-term follow-up period of 21 days.Conclusion: SII is closely linked to an elevated risk of RF and death in COPD patients. It appears to be a potential predictor of the prognosis of COPD patients, which is helpful for the risk stratification of this population. However, more prospective studies are warranted to consolidate our conclusion.Keywords: systemic immune-inflammation index, chronic obstructive pulmonary disease, respiratory failure, mortality, MIMIC-IV database

Jun Zhang,1,&ast; Xiaoyan Chen,2,&ast; Yan Zhu,1,&ast; Shanshan Wan,1 Shuqiong Hu,3 Yanning Yang1 1Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children, Chongqing, People’s Republic of China; 3Aier Eye Hospital of Wuhan University (Wuhan Aier Eye Hospital), Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanning Yang, Department of Ophthalmology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, Hubei Province, People’s Republic of China, Tel/Fax +86-27-88041911, Email ophyyn@163.comBackground: Although previous studies of sleep-related behaviors in relation to primary open-angle glaucoma (POAG) have been noted, the causal relationship remains unclear. The purpose of our present study was to investigate the relationships of genetically predicted sleep traits with POAG using a two-sample bidirectional Mendelian randomization (MR) method.Methods: Summary-level data collected from publicly available genome-wide association studies (GWAS) of European decent were applied for the bidirectional MR analysis. After quality control steps, independent single-nucleotide polymorphisms for eight sleep behaviors and POAG were selected as the genetic instruments. The inverse-variance weighted (IVW) approach was adopted as the primary method, which was complemented by a series of sensitivity analyses to assess the robustness of the results by estimating heterogeneity and pleiotropy. Multivariable MR (MVMR) was used to assess the direct effect of sleep traits on POAG, after adjusting for several confounding factors.Results: Our investigation revealed a positive correlation between genetically predicted ease of getting up in the morning and sleep duration and POAG using the IVW method (odds ratio (OR)=1.78, 95% confidence interval (CI):1.29– 2.46, P = 4.33× 10− 4; OR = 1.66, 95% CI:1.18– 2.34, P = 3.38× 10− 3, respectively). Other supplementary MR methods also confirmed similar results. Moreover, the MVMR results also revealed that the adverse effects of these two sleep traits on POAG persisted after adjusting for body mass index, smoking, drinking, and education (all P < 0.05). Conversely, the relationships between genetic liability of POAG and different sleep behaviors were not statistically significant in the reverse-direction MR estimate (all P > 0.05).Conclusion: Our study demonstrated that genetic prediction of getting up easily in the morning or sleep duration were associated with a higher risk of POAG, but not vice versa, in a European population. Further validation and clinical interventions are required to offer potential strategies to prevent and manage POAG.Keywords: genome-wide association study, mendelian randomization, sleep behaviors, primary open-angle glaucoma, risk factors

Ming Zhou,1,2,&ast; Peng Liu,1,2,&ast; Xiaoqin Yin,1 Caiting Deng,3,4 Yi Xiao,1 Meng Lei,1 Shuo Hu,1 Feifei An,3 Min Zhao1,5,6 1Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Key Laboratory of Biological, Nanotechnology of National Health Commission, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Science, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 5Department of Nuclear Medicine, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 6National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Zhao; Feifei An, Email mzhao1981@csu.edu.cn; anfeifei@xjtu.edu.cnBackground: Sentinel lymph node (SLN) mapping-guided biopsy is crucial for cancer staging and treatment. Optical/nuclide dual-modality imaging agents for mapping SLN are ideal for preoperative planning and intraoperative biopsy, which are enabled by penetration-depth unlimited nuclide imaging and dynamic real-time optical imaging, respectively. However, commonly reported dual-modality imaging agents are composed of novel but safety-unproven materials, making their quick clinical translation challenging. Herein, we report a novel nanoparticle composed of facile hospital-available drugs and isotope for single-photon emission computed tomography (SPECT)/near-infrared (NIR) fluorescence imaging to detect SLNs.Methods: Indocyanine green-human serum albumin (ICG-HSA) nanoparticles (NPs) were synthesized by ICG-induced HSA self-assembly and further 99mTc-labeling via a one-step, facile hospital-available method. After injecting 99mTc-ICG-HSA into the rats’ forepaw pads, the rats’ draining axillary lymph nodes were visualized by preoperative mapping with SPECT/CT and intraoperative biopsy with NIR fluorescence. The axillary lymph nodes of rats were identified by pathology and fluorescent staining after execution. Additionally, its toxicity testing and comparison with 99mTc-sulfur colloid imaging were also explored.Results: The study reported a self-assembled 99mTc-ICG-HSA with a high radiochemical yield (85.6 ± 3.8%). Compared with conventional 99mTc-sulfur colloid, 99mTc-ICG-HSA NPs showed faster SLN identification, higher renal clearance, and lower hepatic retention. Furthermore, NIRF imaging allowed for the accurate visualization of the SLN and guided SLN biopsy intraoperatively. Notably, the 99mTc-ICG-HSA NPs were composed of hospital-available drugs and isotope, which are safe for acute toxicity evaluation by a certified institute.Conclusion: The proposed 99mTc-ICG-HSA NPs are safe and capable of noninvasive SLN identification and biopsy guidance with multi-modal imaging strategies and could be a promising tool for clinically assisted SLN biopsy. Keywords: image-guided surgery, indocyanine green, albumin, fluorescence imaging, near-infrared, single-photon emission computed tomography

Benjian Gao,1,2,&ast; Fengyi Yang,1,2,&ast; Dongning Zheng,1,2 Shuai Hu,1,2 Jie Liu,1,2 Hong Liu,1,2 Yongfa Liu,1,2 LinXin Liu,1,2 Rui Wang,1,2 Yi Zhao,1,2 Cheng Cui,1,2 Cheng Fang,1,2 Jin Yang,1,2 Song Su,1,2 Yunwei Han,3 Xiaoli Yang,1,2 Bo Li1,2 1Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoli Yang; Bo Li, Email 344920646@qq.com; liboer2002@126.comPurpose: This study aimed to explore the clinical efficacy of transarterial chemoembolization (TACE) in combination with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (triple therapy) compared to TACE alone (monotherapy) for advanced hepatocellular carcinoma (HCC).Material and Methods: Data of consecutive advanced HCC patients receiving triple therapy or monotherapy at our center between January 2019 and December 2022 were collected and retrospectively analyzed. Propensity score matching (PSM) and subgroup analyses were performed to reduce the bias between the two groups. The primary outcomes of the study were the overall survival (OS) and progression-free survival (PFS). The secondary outcomes were the objective response rate (ORR) and disease control rate (DCR).Results: A total of 104 patients were enrolled in this study: 41 in the triple therapy group and 63 in the monotherapy group. After PSM analysis, each group included 37 patients. The median OS and PFS were significantly longer in the triple therapy group than in the monotherapy group in the whole cohort (median OS, 18.8 vs 11.7 months, P = 0.022; median PFS, 10.5 vs 6.4 months, P = 0.012) and after PSM (median OS, 19.6 vs 12.5 months, P = 0.030; median PFS, 10.5 vs 6.7 months, P = 0.008). Furthermore, the treatment modality was an independent prognostic factor for OS (hazard ratio [HR]: 0.449, 95% confidence interval [CI]: 0.240– 0.840, P = 0.012) and PFS (HR: 0.406, 95% CI: 0.231– 0.713, P = 0.002) according to the multivariate cox regression analysis. A greater ORR was also observed in the triple therapy group (ORR: 56.7% vs 32.4%, P = 0.035). No significant difference was observed in DCR between the two groups (83.7% vs 72.9%, P = 0.259).Conclusion: The triple therapy was superior to the monotherapy regarding OS, PFS, and ORR of advanced HCC patients.Keywords: hepatocellular carcinoma, transarterial chemoembolization, tyrosine kinase inhibitors, immune checkpoint inhibitors, efficacy

Dan Pu, Shiyong Zhang, Shoushan Hu, Yuyao Zhang, Xin Xiong, Shufang Du State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Shufang Du; Xin Xiong, Email dushufang@scu.edu.cn; drxiongxin@scu.edu.cnObjective: This study aims to investigate the relationship between oral health-related quality of life (OHRQoL) and emotional distress (ED), including anxiety and depression, in orthodontic patients.Methods: A cross-sectional study was conducted involving 603 orthodontic patients, consisting of 401 females (66.5%) with a mean age of 24.15 ± 7.72 and 202 males (33.5%) with a mean age of 24.16 ± 7.72. A questionnaire containing questions of demographic information, the Oral Health Impact Profile (OHIP-14) and the Huaxi emotional-distress index (HEI) was employed to assess OHRQoL and ED. According to the HEI score, the respondents were divided into ED group (HEI > 8) and non-ED group (HEI ≤ 8). Data were analyzed using Kolmogorov–Smirnov test, Mann–Whitney test and logistic regression analysis with the significance level set at p < 0.05.Results: The prevalence of poor OHRQoL and ED of the study sample was 28.4% and 19.57%, respectively. There was a significantly higher prevalence of ED among poor OHRQoL patients (35.67%) compared to those with good OHRQoL (13.19%) (p < 0.001). Poor OHRQoL and risky drinking behavior addressed higher significant correlation with ED patients than non-ED patients (p < 0.05). There were no statistical differences in other factors such as gender, age, and appliance type (p > 0.05). Poor OHRQoL orthodontic patients were at a higher risk of suffering from anxiety and depression compared to those with good OHRQoL (age-risky drinking behavior-sex-adjusted: OR = 4.00; all p < 0.001).Conclusion: Oral health-related quality of life (OHRQoL) is related to emotional stress. Namely, patients with poor OHRQoL are more likely to experience anxiety and depression. As a result, orthodontists should consistently assess the emotional well-being and OHROoL of patients over the treatment course for better treatment outcomes.Keywords: orthodontic patients, oral health-related quality of life, emotional distress, anxiety, depression, cross-sectional study

Wensi Hao,1,2 Yaqin Gu,1,2 Shuyuan Hu,1,2 Xunming Ji,1,2 Yuping Wang,2 Jiangang Duan1,2 1Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jiangang Duan, Department of Emergency, Xuanwu Hospital, Capital Medical University, No. 45, Changchun St, Xicheng District, Beijing, 100053, People’s Republic of China, Email duanjiangang@xwhosp.orgBackground: Inflammation was associated with the severity of severe cerebral venous thrombosis (CVT) on admission and poor prognosis at discharge. Hereditary protein C/S deficiency (hereditary PCD/PSD) not only promotes thrombosis but also activates the inflammatory response, further inducing venous thrombosis. However, conventional treatments such as standard anticoagulant/endovascular therapy (EVT) do not seem to improve prognosis. Anti-inflammatory therapy may be a new way to treat the disease.Methods: We enrolled five patients with acute/subacute severe CVT with hereditary PCD/PSD from January 2020 to July 2022. In addition to standard anticoagulant therapy, all of them were given short-term methylprednisolone pulse therapy. Neurological deficit, increased intracranial pressure, venous recanalization, serum and cerebrospinal fluid (CSF) inflammatory markers and adverse events were retrospectively described before and after treatment and at 6 months after discharge.Results: Inflammatory indexes of all patients were significantly elevated on admission. After methylprednisolone pulse therapy, serum inflammatory indexes including neutrophil-to-lymphocyte ratio (P=0.043); platelet-to-lymphocyte ratio (P=0.043); systemic immune inflammatory index (P=0.043); interleukin-6 (P=0.043) and hypersensitive C-reactive protein (P=0.022) reduced dramatically compared with baseline. CSF inflammatory indexes had a decreasing trend compared with baseline (P> 0.05). In terms of venous recanalization, one patient achieved complete recanalization, four patients obtained partial recanalization. Compared with baseline on admission, the NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS) and intracranial pressure were all considerably lower at discharge (P=0.029, P=0.041 and P=0.017). At 6-month follow-up, NIHSS and mRS further declined. During hospitalization and 6-month follow-up, none of the five patients experienced severe steroid-related adverse effects such as recurrence of venous thrombosis, spontaneous fracture or osteonecrosis, and gastroduodenal ulcer.Conclusion: Acute/subacute severe CVT with hereditary PCD/PSD has high levels of inflammation. In addition to conventional anticoagulant therapy, early anti-inflammatory therapy using steroids may be necessary. Nevertheless, substantial randomized controlled trials with larger sample sizes are required for further investigation.Keywords: severe cerebral venous thrombosis, hereditary protein C deficiency, hereditary protein S deficiency, thrombosis, inflammation, methylprednisolone pulse therapy

Shanlian Hu,1 Depei Wu,2 Jing Wu,3 Yabing Zhang,4 Mette Bøgelund,5 Johannes Pöhlmann,6 Richard F Pollock6 1School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2First Affiliated Hospital of Soochow University, Soochow University, Suzhou, People’s Republic of China; 3School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People’s Republic of China; 4Shanghai Institute of Technology, Shanghai, People’s Republic of China; 5Incentive Partners ApS, Holte, Denmark; 6Covalence Research Ltd, Harpenden, United KingdomCorrespondence: Richard F Pollock, Covalence Research Ltd, Rivers Lodge, West Common, Harpenden, AL5 2JD, United Kingdom, Tel +44 20 8638 6525, Email pollock@covalence-research.comPurpose: Treatment process attributes can affect health state utilities associated with therapy. For intravenous iron, used to treat iron deficiency and iron deficiency anemia, research into process attributes is still lacking. This study estimated utilities associated with process attributes for intravenous iron infusions.Methods: An online survey including seven health state vignettes and time trade-off tasks was administered to participants, who were not patients living with iron deficiency or iron deficiency anemia, from a Chinese online panel. Vignettes used an identical description of iron deficiency and iron deficiency anemia but differed in the annual number of infusions, infusion duration, and infusion-associated risk of hypophosphatemic osteomalacia. Disutilities and their rate of change as the number of infusions increased were examined using a power model.Results: The survey was completed by 1091 participants. The highest utilities were observed for one annual infusion of 15– 30 minutes or 30– 60 minutes, without risk of hypophosphatemic osteomalacia (0.754 and 0.746, respectively). In comparison, more infusions and infusions with a risk of hypophosphatemic osteomalacia were associated with lower utilities. Utility continued to decrease, but at a diminishing rate, as the annual number of infusions increased, with utility decrements of 0.006 and 0.002, respectively, when going from zero to one and from four to five infusions per year. All marginal disutilities were small (values < 0.01).Conclusion: This study suggested that treatment attributes of intravenous iron infusions affect health state utilities. Using intravenous iron formulations that allow for fewer and shorter infusions without the risk of hypophosphatemic osteomalacia can reduce the number of visits required and increase patients’ quality of life.Plain Language Summary: A lack of iron in the body can be treated successfully using intravenous infusions of iron, but it is not yet known how different intravenous iron formulations affect patients’ quality of life.Intravenous iron formulations differ in how often and for how long (per infusion) they need to be administered; for example, while one available intravenous iron formulation allows most iron deficits to be corrected in a single visit, others can require several visits. Formulations also seem to differ in the risk of complications relating to low phosphate and bone softening.This study presented descriptions of treatment options, differing in the number and duration of infusions as well as in risk, to more than 1000 Chinese respondents. Based on their answers, the differences between intravenous iron administration regimes could be valued and linked to quality of life. Intravenous iron treatment with fewer, shorter infusions and without risk of bone softening was found to come with a better quality of life. Each additional infusion reduced quality of life, but less so if treatment already involved several infusions. These findings can help patients and physicians to make clinical decisions that focus not only on efficacy and safety but also on the quality of life.Keywords: China, disutility, health-related quality of life, intravenous iron, iron deficiency, time trade-off

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

Xin Xiong,1,2,&ast; Xinlin Gao,1,&ast; Jiawei Zhong,1 Shoushan Hu,1 Yijun Li,1 Yunhao Zheng,1 Yang Liu2 1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People’s Republic of China; 2State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Liu, State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, Renmin South Road, Chengdu, 610041, People’s Republic of China, Tel +86 028-85503898, Fax +86 018-85503898, Email liu@scu.edu.cnPurpose: This study conducted a bibliometric analysis that comprehensively described publications on temporomandibular joint and occlusion from 1 January 2000 to 31 October 2022, aiming to reveal hotspots and predict future research trends.Methods: A total of 2985 articles and reviews were retrieved from Web of Science Core Collection (WoSCC). Excel 2019, VOSviewer and CiteSpace software were used for visualizing analysis of research trends, authors, journals, institutions, countries, keywords and cited references.Results: Both the annual publication counts and citation times increased significantly. Wang MQ was the most active author. Moreover, Manfredini D and Okeson JP were the most influential two. Journal of Oral Rehabilitation was the core journal. University of Sao Paulo was the most productive institutions. “Temporomandibular disorders” (TMDs), “temporomandibular joint” and “occlusion” were the top 3 keywords with the most frequencies. Keywords and references with burst showed that the causes of TMDs, diagnosis and treatments for TMDs as well as bruxism may be hotspots currently and in the future.Conclusion: In this study, the research trends, the most productive and influential authors, journals, institutions, countries, in addition to keywords and cited references with burst in the field of temporomandibular joint and occlusion were revealed by a bibliometric analysis, which could help scholars to understand recent hotspots and future trends.Keywords: bibliometric analysis, temporomandibular joint, occlusion, keywords analysis

Wenyu Zhou,1,&ast; Song Hu,1,2,&ast; Yutong Wu,1,&ast; Huan Xu,1,&ast; Lina Zhu,1 Huimin Deng,1 Sheng Wang,1 Yuanli Chen,1 Huanping Zhou,1 Xin Lv,1 Quanfu Li,1 Hao Yang1 1Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, People’s Republic of China; 2Graduate School, Wannan Medical College, Wuhu, AnHui, 241002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Yang, Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Email yanghaozunyi@sina.com Quanfu Li, Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Email quanfuli185@163.comBackground: Mesenchymal stem cell-derived exosomes (MSC-exosomes) have been found to effectively improve the systemic inflammatory response caused by acute lung injury and acute respiratory distress syndrome (ALI/ARDS), regulate systemic immune disorders, and help injured cells repair. The purpose of this study was to take a holistic view of the current status and trends of MSC-exosomes research in ALI/ARDS.Methods: Bibliometrix, Citespace and VOSviewer software were used for bibliometric analysis of the data. We analysed the world trends, country distribution, institution contribution, most relevant journals and authors, research hotspots, and research hotspots related to Coronavirus Disease 2019 (COVID-19) based on the data collected.Results: China possessed the largest number of publications, while the USA had the highest H-index and the number of citations. Both China and the USA had a high influence in this research field. The largest number of publications in the field of MSC-exosomes and ALI/ARDS were mainly from the University of California system. Stem Cell Research & Therapy published the largest number of papers in this scope. The author with the greatest contribution was LEE JW, and ZHU YG published an article in Stem Cell with the highest local citation score. The most frequent keyword and the latest research hotspot were “NF-κB” and “Coronavirus Disease 2019”. Furthermore, our bibliometric analysis results demonstrated that MSC-exosomes intervention and treatment can effectively alleviate the inflammatory response caused by ALI/ARDS.Conclusion: Our bibliometric study suggested the USA and China have a strong influence in this field. COVID-19-induced ALI/ARDS had become a hot topic of research.Keywords: acute respiratory distress syndrome, mesenchymal stem cells, exosome, bibliometrix, Citespace, VOSviewer

Yunbo Chen,1,2 Yuanyuan Dai,3 Yizheng Zhou,4 Ying Huang,5 Yan Jin,6 Yan Geng,7 Bing Ji,8 Rong Xu,9 Wencheng Zhu,10 Shuyan Hu,11 Zhuo Li,12 Jinhua Liang,13 Yonghong Xiao1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People’s Republic of China; 3Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 4Clinical Laboratory, Jingzhou Central Hospital, Jingzhou, People’s Republic of China; 5Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 6Clinical Laboratory, Shandong Provincial Hospital, Jinan, People’s Republic of China; 7Clinical Laboratory, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 8Clinical Laboratory, Affiliated Hospital of Binzhou Medical College, Binzhou, People’s Republic of China; 9Clinical Laboratory, People’s Hospital of Yichun City, Yichun, People’s Republic of China; 10Clinical Laboratory, Lu’an Civil Hospital, Lu’an, People’s Republic of China; 11Clinical Laboratory, People’s Hospital of Qingyang, Qingyang, People’s Republic of China; 12Clinical Laboratory, The First Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China; 13Clinical Laboratory, The Affiliated Hongqi Hospital of Mudanjiang Medicine College, Mudanjiang, People’s Republic of ChinaCorrespondence: Yonghong Xiao, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, People’s Republic of China, Tel/Fax +86 571 87236421, Email xiao-yonghong@163.comPurpose: Blood cultures (BCs) are essential laboratory tests for diagnosing blood stream infections. BC diagnostic improvement depends on several factors during the preanalytical phase outside of innovative technologies. In order to evaluate the impact of an educational program on BC quality improvement, a total of 11 hospitals across China were included from June 1st 2020 to January 31st 2021.Methods: Each hospital recruited 3 to 4 wards to participate. The project was divided into three different periods, pre-implementation (baseline), implementation (educational activities administered to the medical staff) and post-implementation (experimental group). The educational program was led by hospital microbiologists and included professional presentations, morning meetings, academic salons, seminars, posters and procedural feedback.Results: The total number of valid BC case report forms was 6299, including 2739 sets during the pre-implementation period and 3560 sets during the post-implementation period. Compared with the pre-implementation period, some indicators, such as the proportion of patients who had 2 sets or more, volume of blood cultured, and BC sets per 1000 patient days, were improved in the post-implementation period (61.2% vs 49.8%, 18.56 vs 16.09 sets, and 8.0 vs 9.0mL). While BC positivity and contamination rates did not change following the educational intervention (10.44% vs 11.97%, 1.86% vs 1.94%, respectively), the proportion of coagulase negative staphylococci-positive samples decreased in BSI patients (6.87% vs 4.28%).Conclusion: Therefore, medical staff education can improve BC quality, especially increasing volume of blood cultured as the most important variable to determine BC positivity, which may lead to improved BSI diagnosis.Keywords: blood culture, bloodstream infection, medical education, medical staff, quality improvement

Yanghui Jin,1 Shengping Hu,1 Junkai Feng,2 Jianjun Ni3 1Department of Orthopaedics, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Pharmacy, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Jianjun Ni, Department of Pharmacy, Department of Orthopaedics, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China, Email njj19700912@163.comPurpose: To evaluate the accuracy of metagenomic next-generation sequencing (mNGS) for rapid diagnosis of spinal tuberculosis using spinal tissue specimens.Methods: Medical data regarding suspected spinal tuberculosis were retrospectively analyzed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of mNGS were calculated to determine its diagnostic efficacy, and these values were compared with culture and composite reference standard (CRS).Results: Two hundred and three cases of spinal tuberculosis were included for analysis. The sensitivity, specificity, PPV, NPV, and AUC of mNGS compared with culture were all very good. When CRS was used for the comparison, the sensitivity of mNGS and culture were 71.2% and 73.0%; the specificity and PPV were 100% in all cases; the NPV were 74.2% and 75.4%; the AUCs were all 0.86. The sensitivity and NPV of culture were slightly higher than that of mNGS; however, the diagnostic efficacy of mNGS and culture was consistent (P > 0.05).Conclusion: Spinal tissue specimens for mNGS testing had very good accuracy for diagnosing spinal tuberculosis.Keywords: spinal tuberculosis, culture, mNGS, molecular test, diagnostic accuracy

Songhua Hu, Xudan Yang, Yaqin Huang, Zhihao Xu Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, 322000, People’s Republic of ChinaCorrespondence: Zhihao Xu, Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, No. N1, Shangcheng Avenue, Yiwu, Zhejiang, 322000, People’s Republic of China, Email xuzhihao@zju.edu.cnAbstract: Broncholithiasis coupled with Aspergillus infection is a rare disease of the respiratory system with complex pathogenesis and non-specific clinical manifestations that can be easily confused with other types of infectious diseases of the respiratory system. The lack of pertinent clinical manifestations in patients increases the risk of clinical misdiagnosis, omission, and incorrect treatment plan selection, which can result in permanent lung structural alterations and lung function decompensation and ultimately harm the lung. We report a rare case of asymptomatic broncholithiasis coupled with Aspergillus infection that was treated at our hospital and discuss the pathophysiology, diagnosis, differential diagnosis, and prognostic follow-up course. Furthermore, relevant studies from China and other countries, including this case, were reviewed. We gathered eight reports, summarized their significant diagnoses and treatments for broncholithiasis and broncholithiasis coupled with Aspergillus infection, and discussed their clinical features. Our study may help improve physicians’ awareness of these types of diseases and serve as a resource for future diagnosis and treatment.Keywords: broncholithiasis, Aspergillus infection, obstructive pneumonia, infection

Shuqin Zhan,1 Hui Ye,2 Ning Li,1 Yimeng Zhang,1 Yueyang Cheng,1 Yuanqing Wang,1,3 Shimin Hu,1 Yue Hou1 1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 2Ignis Therapeutics (Shanghai) Limited, Shanghai, 200000, People’s Republic of China; 3Department of Neurology, People’s Hospital of Rizhao, Rizhao, 276800, People’s Republic of ChinaCorrespondence: Shuqin Zhan, Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China, Tel +8613801027285, Email shqzhan@hotmail.comPurpose: Narcolepsy is a rare debilitating disorder for which multiple novel pharmacological options have been approved as treatment for the past few years. The current study systematically updates the comparative efficacy and detailed safety analysis of approved wake-promoting agents in narcolepsy.Methods: Randomized controlled trials (RCTs) were searched for diagnosed narcolepsy with approved interventions. Efficacy outcomes included the Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS), Clinical Global Impression of Change (CGI-C), and Patient Global Impression of Change (PGI-C). Safety outcomes including overall adverse event (AE) risk were measured. The study was registered at PROSPERO (CRD 42022334915).Results: The final analysis included 17 RCTs with five drug treatments: modafinil/armodafinil, sodium oxybate, pitolisant, solriamfetol, and lower-sodium oxybate (LXB). For efficacy measures, interventions included in each outcome were effective compared with placebo. Furthermore, the magnitude of solriamfetol effect on MWT (9.11 minutes; 95% CI=7.05– 11.16), ESS (− 4.79; 95% CI=− 6.56 to − 3.01), and PGI-C (9.39; 95% CI= 2.37– 37.19), and LXB effect on CGI-C (9.67; 95% CI=2.73– 34.26) was greater than that of other treatments included in each outcome compared with placebo. For safety measures, all interventions had an acceptable safety profile with LXB having least risk for overall AEs (0.56; 95% CI=0.20– 1.53), serious AEs (0.33; 95% CI=0.09– 1.20), AEs leading to treatment discontinuation (0.11; 95% CI=0.01– 2.04), and all-cause discontinuation (0.04; 95% CI=0.00– 0.67) compared to placebo. Placebo had the lowest risk for exploratory AEs.Conclusion: All approved interventions were effective in controlling the symptoms of narcolepsy at varying degrees with an acceptable safety profile.Keywords: narcolepsy, network meta-analysis, wake-promoting agents, excessive daytime sleepiness, patient-centric scores, safety

Bo Gao,1,&ast; Rui Li,2,&ast; Xiaojia Song,3 Shan Hu,4 Fengmei Yang4 1Departments of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China; 2Departments of Medical office, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China; 3Shiyan Prefecture Center for Disease Control and Prevention, Shiyan, Hubei, 442000, People’s Republic of China; 4Departments of Obstetrics and Gynecology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengmei Yang, Email 29256175@qq.comBackground: Lung squamous cell carcinoma (LUSC) is a type of lung cancer that originates from segmental or subsegmental bronchial mucosa. There is evidence that miRNA plays an important role in the occurrence and progression of tumors.Methods: In this study, plasma samples of patients with early LUSC and healthy volunteers were subjected to miRNA sequencing, and the levels of differentially expressed miRNAs (DEMs) in LUSC tissues were analyzed using R language. Cox regression and Kaplan–Meier (K-M) survival curve analyses were performed to determine the relationship between DEMs and prognosis in LUSC, and PCR method was verified for the plasma expression level of DEMs in patients with LUSC. The levels of CYFRA21-1 and SCC-Ag in plasma were measured, and area under curve (AUC) was used to evaluate the diagnostic value of the DEMs.Results: A total of 21 DEMs were screened out by sequencing. The expression levels of DEMs in tissue samples in the TCGA database were analyzed, and four DEMs with consistent expression levels were further screened from plasma and tissue samples. Regression analysis and K-M curve were performed to select two DEMs (miR-139-5p, miR-451a) that were correlated with the prognosis. PCR verification results showed that the levels of miR-451a and miR-139-5p were low in patients, and the level of miR-139-5p in late stages III & IV with the patients of LUSC was higher than that in stages I & II. The AUC values of the four indicators (SCC-Ag, CYFRA21-1, miR-451a and miR-139-5p) in the diagnosis of LUSC, early and late cases were 0.884, 0.935 and 0.778, respectively.Conclusion: The detection of miR-139-5p and miR-451a levels in plasma has a certain potential in the non-invasive diagnosis, especially in patients with early stages of LUSC.Keywords: miR-139-5p, LUSC, miR-451a, diagnosis, prognosis

Yan Gong,1 Yonghua Wang,2 Wei Wu,3 Ling Li,2 Yunming Li,4 Jie Song,2 Lingli Jiang,5 Shibei Hu,1 Juan Yang,1 Aihua Wang1 1School of Nursing, Chengdu Medical College, Chengdu, People’s Republic of China; 2Department of Nursing, The General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 3Department of Anesthesiology and Pain Medicine, The General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 4Department of Information, Medical Support Center, The General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 5Department of Neurosurgery, The General Hospital of Western Theater Command, Chengdu, People’s Republic of ChinaCorrespondence: Yonghua Wang, Department of Nursing, The General Hospital of Western Theater Command, No. 270 Tianhui Road, Rongdu Avenue, Chengdu, 610083, People’s Republic of China, Tel +86-18180720869, Email 694935018@qq.comPurpose: To explore the relationship between pain intensity, pain resilience, pain catastrophizing, and pain-related activity patterns in older adults with chronic musculoskeletal pain (CMP).Patients and Methods: A total of 220 elderly Chinese with chronic musculoskeletal pain were recruited from a tertiary general hospital. Participants completed several measures including a demographic questionnaire, Brief Pain Inventory (BPI), Pain Resilience Scale (PRS), Pain Catastrophizing Scale (PCS), and Patterns of Activity Measure-Pain (POAM-P). Moreover, Process version 3.5 plug-in SPSS26 was used to test the mediation effect between variables.Results: The scores of POAM-P in older adults with CMP from high to low were: avoidance (27.39 ± 8.10), pacing (24.25 ± 9.48), and overdoing (16.65 ± 10.95). Mediation analysis revealed that pain resilience and pain catastrophizing mediated the relationship between pain intensity and pain-related activity patterns (avoidance and pacing) in older adults with CMP.Conclusion: These results provide evidence for the role of pain resilience and pain catastrophizing in the relationship between pain intensity and pain-related activity patterns. Interventions targeting these factors should be included in activity management programs for elderly CMP patients. It may be possible to reduce the negative impact of pain intensity on activity patterns by improving pain resilience and reducing pain catastrophizing.Keywords: older adults, chronic musculoskeletal pain, avoidance, pacing, overdoing

Yiyi Zhu,1 Lingling Wu,2– 5 Shuling Ye,6– 9 Yaoyang Fu,2– 5 Huimin Huang,1 Jianbo Lai,2– 5 Chuan Shi,6– 9 Shaohua Hu1– 5,10 1School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, People’s Republic of China; 4Brain Research Institute of Zhejiang University, Hangzhou, People’s Republic of China; 5Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, People’s Republic of China; 6Peking University Sixth Hospital, Beijing, People’s Republic of China; 7Peking University Institute of Mental Health, Beijing, People’s Republic of China; 8NHC Key Laboratory of Mental Health (Peking University), Beijing, People’s Republic of China; 9National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, People’s Republic of China; 10Department of Neurobiology, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brian Medicine, and MOE Frontier Science Center for Brain Science and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of ChinaCorrespondence: Shaohua Hu, School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China, Email dorhushaohua@zju.edu.cn Chuan Shi, Peking University Sixth Hospital, Beijing, 100191, People’s Republic of China, Email shichuan@bjmu.edu.cnBackground: Emotional blunting is prevalent in patients with mood disorders and adversely affects the overall treatment outcome. The Oxford Depression Questionnaire is a validated psychometric instrument for assessing emotional blunting. We aimed to evaluate the reliability and validity of the Chinese version of the ODQ (ODQ) in Chinese patients with mood disorders.Methods: 136 mood disorders patients and 95 healthy control participants were recruited at the First Affiliated Hospital of Zhejiang University, School of Medicine. Patients were assessed using the ODQ, Beck Depression Inventory-II (BDI-II), and Montgomery-Asberg Depression Rating Scale (MADRS). Internal consistency reliability and test-retest reliability were analyzed. Confirmatory factor analysis and correlation analysis were used to evaluate construct and convergent validity.Results: A total of 136 patients with mood disorders and 95 healthy controls participated in this study. Cronbach α values were 0.928 (ODQ-20) and 0.945 (ODQ-26). Test-retest reliability coefficients were 0.798 (ODQ-20) and 0.836 (ODQ-26) (p< 0.05); intraclass correlation coefficient values were 0.777 (ODQ-20) and 0.781 (ODQ-26) (p< 0.01). The score of ODQ was positively correlated with BDI-II and MADRS (r=0.326~0.719, 0.235~0.537, p< 0.01). The differences in the ODQ scores between the patient and control groups were statistically significant.Conclusion: The reliability, structural validity, and criterion validity of the ODQ applied to patients with mood disorders meet the psychometric requirements, and the scale can be used to assess emotional blunting in Chinese patients with mood disorders.Keywords: emotional blunting, Chinese, mood disorder, psychometrics, validation

Na Zhu,1,&ast; WeiHua Zhang,2,&ast; Jia Huang,3 Yousong Su,3 JingFang Lu,3 Lu Yang,3 YiFan Shi,3 ShaoHua Hu,4,&ast; Jun Chen,3,5,&ast; Yiru Fang3,5,6,&ast; 1Department of Psychiatry, Shanghai Pudong New Area Mental Health Center, Tong Ji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Psychiatry, Taizhou Second People’s Hospital, Taizhou, People’s Republic of China; 3Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, The Key Laboratory of Mental Disorder Management of Zhejiang Province, Hangzhou, People’s Republic of China; 5Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China; 6State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, CAS, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: ShaoHua Hu; Jun Chen, Email dorhushaohua@zju.edu.cn; doctorcj2010@gmail.comBackground: Cognitive impairment is one of the core features of bipolar depression. A unified, reliable, and valid assessment tool is key to screening and assessing cognitive impairment. The THINC-Integrated Tool (THINC-it) is a simple and quick battery for screening cognitive impairment in patients with major depressive disorder. However, the use of the tool has not been validated in patients with bipolar depression.Methods: The cognitive functions of 120 patients with bipolar depression and 100 healthy controls were evaluated using the THINC-it tool including Spotter, Symbol Check, Codebreaker, Trials, and the only one subjective test (PDQ-5-D) and five corresponding standard tests. A psychometric analysis of the THINC-it tool was performed.Results: The overall Cronbach’s alpha coefficient of the THINC-it tool was 0.815. The intra-group correlation coefficient (ICC) of retest reliability ranged from 0.571 to 0.854 (P< 0.001), while the correlation r of parallel validity ranged from 0.291 to 0.921 (P< 0.001). There were significant differences in the two groups Z-scores of THINC-it total score, Spotter, Codebreaker, Trails, and PDQ-5-D (P< 0.05). Construct validity was analyzed using exploratory factor analysis (EFA). The Kaiser-Meyer-Olkin (KMO) value was 0.749. Using Bartlett’s Sphericity test, the χ2 (10) value was 198.257 (P< 0.001). The factor loading coefficients of Spotter, Symbol Check, Codebreaker, and Trails on the common factor 1 were − 0.724, 0.748, 0.824, and − 0.717, respectively, and the factor loading coefficient of PDQ-5-D on the common factor 2 was 0.957. Results revealed that the correlation coefficient of the two common factors was 0.125.Conclusion: The THINC-it tool has good reliability and validity in assessing patients with bipolar depression.Keywords: bipolar disorder, cognitive impairment, reliability, THINC-it tool, validity

Jisong Yan,1 Hong Luo,1 Qi Nie,1 Shengling Hu,2 Qi Yu,2 Xianguang Wang1 1Department of Respiratory and Critical Care Medicine, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China; 2Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of ChinaCorrespondence: Qi Yu, Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China, Email fishns123@163.com Xianguang Wang, Department of Respiratory and Critical Care Medicine, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China, Email 907395635@qq.comBackground: The growth of antibiotic resistance to Mycobacterium TB represents a major barrier to the goal of “Ending the global TB epidemics”. This study aimed to develop and validate a simple clinical scoring system to predict the unfavorable treatment outcomes (UTO) in multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) patients.Methods: A total of 333 MDR/RR-TB patients were recruited retrospectively. The clinical, radiological and laboratory features were gathered and selected by lasso regression. These variables with area under the receiver operating characteristic curve (AUC)> 0.6 were subsequently submitted to multivariate logistic analysis. The binomial logistic model was used for establishing a scoring system based on the nomogram at the training set (N = 241). Then, another independent set was used to validate the scoring system (N = 92).Results: The new scoring system consists of age (8 points), education level (10 points), bronchiectasis (4 points), red blood cell distribution width-coefficient of variation (RDW-CV) (7 points), international normalized ratio (INR) (7 points), albumin to globulin ratio (AGR) (5 points), and C-reactive protein to prealbumin ratio (CPR) (6 points). The scoring system identifying UTO has a discriminatory power of 0.887 (95% CI=0.835– 0.939) in the training set, and 0.805 (95% CI=0.714– 0.896) in the validation set. In addition, the scoring system is used exclusively to predict the death of MDR/RR-TB and has shown excellent performance in both training and validation sets, with AUC of 0.930 (95% CI=0.872– 0.989) and 0.872 (95% CI=0.778– 0.967), respectively.Conclusion: This novel scoring system based on seven accessible predictors has exhibited good predictive performance in predicting UTO, especially in predicting death risk.Keywords: multidrug- and rifampicin-resistant tuberculosis, treatment outcome, laboratory parameters, scoring system

Hongchen Zhang,1– 3,&ast; Shanshan Hu,1– 3,&ast; Dongchao Xu,1– 3 Hongzhang Shen,1– 3 Hangbin Jin,1– 3 Jianfeng Yang,1– 3 Xiaofeng Zhang1– 3 1The Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Zhejiang, People’s Republic of China; 2Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Zhejiang, People’s Republic of China; 3Hangzhou Institute of Digestive Disease, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofeng Zhang, Department of Gastroenterology, Hangzhou First People’s Hospital, NO. 261 HuanSha Road, Hangzhou, 310006, People’s Republic of China, Tel +86-13588296257, Fax +86-571-56005600, Email moonshadowing@126.comBackground: With the increasing number of critically ill patients in the gastroenterology department (GED), infections associated with Carbapenem resistant gram-negative bacteria (CR-GNB) are of great concern in GED. As the turn-around time (TAT) for a positive screening culture result is slow, contact precaution and pre-emptive isolation, cohorting methods should be undertaken immediately on admission for high-risk patients. Accurate prediction tools for CR-GNB colonization in GED can help determine target populations upon admission. And thus, clinicians and nurses can implement preventive measures more timely and effectively.Objective: The purpose of the current study was to develop and internally validate a CR-GNB carrier risk predictive nomogram for a Chinese population in GED.Methods: Based on a training dataset of 400 GED patients collected between January 2020 and December 2021, we developed a model to predict CR-GNB carrier risk. A rectal swab was used to evaluate the patients’ CR-GNB colonization status microbiologically. We optimized features selection using the least absolute shrinkage and selection operator regression model (LASSO). In order to develop a predicting model, multivariable logistic regression analysis was then undertaken. Various aspects of the predicting model were evaluated, including discrimination, calibration, and clinical utility. We assessed internal validation using bootstrapping.Results: The prediction nomogram includes the following predictors: Transfer from another hospital (Odds ratio [OR] 3.48), High Eastern Cooperative Oncology Group (ECOG) performance status (OR 2.61), Longterm in healthcare facility (OR 10.94), ICU admission history (OR 9.03), Blood stream infection history (OR 3.31), Liver cirrhosis (OR 4.05) and Carbapenem usage history within 3 month (OR 2.71). The model demonstrated good discrimination and good calibration.Conclusion: With an estimate of individual risk using the nomogram developed in this study, clinicians and nurses can take more timely infection preventive measures on isolation, cohorting and medical interventions.Keywords: carbapenem resistant gram-negative bacteria, carrier risk, gastroenterology department, predictive nomogram, screen culture

Chuangang Shen,1 Rui Liu,1 Jing Yang,2 Sanman Hu,1 Peixu He1 1Business School, Huaqiao University, Quanzhou City, Fujian Province, 362021, People’s Republic of China; 2College of Tourism, Huaqiao University, Quanzhou City, Fujian Province, 362021, People’s Republic of ChinaCorrespondence: Jing Yang, College of Tourism, Huaqiao University, Quanzhou, 362021, People’s Republic of China, Tel +86 186-4995-3896, Email jingpsy@hqu.edu.cn Rui Liu, Business School, Huaqiao University, Quanzhou, 362021, People’s Republic of China, Tel +86 175-5418-6578, Email lrecho@foxmail.comPurpose: From the perspective of the work-home resource model, the present research aims to investigate the effect mechanism of family supportive supervisor behaviors (FSSB) on work-family enrichment.Sample and Method: Based on 316 Chinese employees’ samples, this study takes the multiple linear regression technique to test our hypothesis model.Results: Our study reveals that FSSB is positively related to work-family enrichment. In addition, thriving at work can mediate the positive relationship between family-supportive supervisor behaviors and work-family enrichment. Furthermore, the moderating role of intrinsic motivation is also found in this study. Specifically, intrinsic motivation strengthens the positive relationship between FSSB and thriving at work. Facing FSSB, individuals who score high in intrinsic motivation are prone to experience stronger thriving at work, while individuals who score low will hardly experience thriving at work.Conclusion: The current study comprehensively explores how informal organizational support (in our case, family supportive supervisor behaviors) leads to a better family outcome, thus contributing to the work-family interface literature. At the same time, our study also has some guiding significance for practitioners to build a family-friendly environment.Keywords: family supportive supervisor behaviors, thriving at work, work-family enrichment, work-home resource model

Hu L, Wang H, Rao M, et al. Int J Nanomedicine. 2014;9(1):1127–1138. We, the Editors and Publisher of International Journal of Nanomedicine, have retracted the following article. Following publication, the authors raised concerns about the duplication of images within the article. Specifically, The images for Figure 4C and 4F have been duplicated, as have the images for Figure 4D and 4E. The images for Figure 6A and 6B have been duplicated, as have the images for Figure 6C and 6D. It was noted that some images for Figures 2 and 10 may have duplicated regions, however, this was caused by an error during the publication process. When approached for an explanation, the authors were cooperative but wereg unable to provide an adequate explanation for the duplicated images and not all the original data for the study was available. 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 agreed 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’.

Hui Wu, Shen Hu, Jiahao Liu, Dingwen He, Qi Chen, Xigao Cheng Department of Orthopaedics, the Second Affiliated Hospital of Nanchang University, Nanchang city, Jiangxi Province, 330006, People’s Republic of ChinaCorrespondence: Xigao Cheng, Department of Orthopaedics, the Second Affiliated Hospital of Nanchang University, Nanchang city, Jiangxi Province, 330006, People’s Republic of China, Email xigaocheng@hotmail.comObjective: To investigate the risk factors involved in the early and medium-term poor outcomes of percutaneous endoscopic transforaminal discectomy (PETD) treatment of lumbar disc herniation (LDH) at the L4-5 level.Methods: Between January 2015 and May 2020, we recruited 148 LDH patients at the L4-5 level who underwent PETD surgery. The patients were divided into Groups A and B, according to the surgical outcomes. Good and excellent outcomes were categorized into Group A, and generally good and poor outcomes were categorized into Group B. Clinical parameters (age, gender, symptom duration, hospital stay, operation time, blood loss, straight-leg raising (SLR), visual analog scale (VAS), Oswestry Disability Index (ODI) score and modified MacNab criteria) and radiologic parameters (foraminal height (FH), intervertebral height index (IHI), intervertebral angle (IVA), sagittal range of motion (sROM), and lumbar lordosis (LL)) were collected and analyzed using univariate and multiple logistic regression analyses.Results: At the 6-month follow-up post operation, univariate analysis revealed that the symptom duration, SLR, IHI, and sROM were strongly associated with poor outcomes. However, multiple logistic regression analysis demonstrated that prolonged symptom duration, large SLR angel, and large sROM were independent risk factors for poor outcomes. At the 2-year follow-up post operation, univariate analysis suggested that advanced age, prolonged symptom duration, large preoperative VAS score, small FH, small IHI, and large sROM were potential risk factors for poor outcomes. However, multiple logistic regression analysis demonstrated that prolonged symptom duration, small IHI, and large sROM were independent risk factors for poor outcomes.Conclusion: Our study demonstrated that prolonged symptom duration, large SLR angel, and large sROM were independent risk factors for poor outcomes immediately following PETD at the L4-5 level. However, prolonged symptom duration, small IHI, and large sROM were independent risk factors for poor outcomes at medium-term post PETD at the L4-5 level.Keywords: percutaneous endoscopic transforaminal discectomy, risk factors, lumbar disc herniation, early and medium-term, surgical outcomes

Song Hu,1– 3,&ast; Mingxia Wang,2,3,&ast; Siyu Li,2,&ast; Wenyu Zhou,3 Yi Zhang,2 Haobing Shi,2 Pengcheng Ye,2 Jixiong Sun,2 Feng Liu,2 Wei Zhang,2 Li Zheng,3 Qianhao Hou,2 Yue Wang,2 Weixin Sun,2 Yuanli Chen,2 Zhenzhen Lu,4 Zhonghua Ji,2 Lijun Liao,2 Xin Lv,3 Yinglin Wang,2 Xiangrui Wang,2 Hao Yang2,3 1Graduate School, Wannan Medical College, Wuhu, 241002, People’s Republic of China; 2Department of Anesthesiology and Pain Management, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People’s Republic of China; 3Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People’s Republic of China; 4Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Yang; Xiangrui Wang, Department of Anesthesiology and Pain Management, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, People’s Republic of China, Email yanghaozunyi@sina.com; wangxiangruirjyy@sina.comObjective: Propofol-based sedation has been widely used for gastroscopy, but the risk of respiratory suppression in elderly patients should not be overlooked. Intravenous (IV) lidocaine during surgery can reduce the demand for propofol and the incidence of cardiopulmonary complications. We examined whether IV lidocaine reduces the dose of propofol and the occurrence of adverse events during gastroscopy in elderly patients.Methods: We conducted a prospective, single-center, double-blind randomized controlled trial in elderly patients aged ≥ 65 years with ASA I-II. Subjects were randomly assigned to the lidocaine group (Group L, n=70), who received IV 1.5 mg kg− 1 lidocaine followed by a continuous infusion of 4 mg kg− 1 h− 1 lidocaine, or the normal saline group (Group N, n=70), who received an equal volume of saline in the same way.Results: IV lidocaine reduced the total and maintenance propofol dose in Group L (p< 0.001), with no significant effect on the induction dose. The incidence of intraoperative hypoxia (p=0.035), emergency airway management events (p=0.005), duration of gastroscopy (p< 0.05), consciousness recovery time (p< 0.001), and postoperative pain (p=0.009) were all reduced in Group L. Patient (p=0.025) and gastroscopist (p=0.031) satisfaction was higher in Group L. Intraoperative hemodynamic parameters, the respiratory rate, the incidence of sedation-related events and anesthesiologist satisfaction were similar between the two groups.Conclusion: IV lidocaine can significantly reduce the amount of propofol, the incidence of hypoxia and postoperative pain during gastroscopy in elderly patients, with a higher patient and gastroscopist satisfaction.Keywords: lidocaine, propofol, gastroscopy, elderly patient, sedation

Qiwen Dai,1 Yanhong Dai,1 Chunyu Zhang,1 Zhiming Meng,2 Zeyu Chen,1 Senlin Hu3 1School of Economics and Management, Guangxi Normal University, Guilin, People’s Republic of China; 2School of Innovation and Entrepreneurship, Guangxi Normal University, Guilin, People’s Republic of China; 3School of Urban Development Research, East China Normal University, Shanghai, People’s Republic of ChinaCorrespondence: Chunyu Zhang, School of Economics and Management, Guangxi Normal University, Guilin, Guangxi, 541004, People’s Republic of China, Email 468160345@qq.comPurpose: Drawing on the motivation theory, this study investigated the effect and consequences of personal motivation and innovative climate on innovative behavior among university students in mainland China. The study also examined whether the effect of personal motivation and innovative climate on Chinese university students’ innovative behavior is heterogeneous between disciplines and place of residence.Methods: A quantitative study was conducted to test the hypotheses. Data were collected from 245 undergraduate students at Chinese universities with paper-based questionnaires. Self-report scales were used to measure levels of personal motivation, innovative climate, and innovative behaviors. A confirmatory factor analysis was used to test the scale and questionnaire’s reliability and validity. The logistic model was applied to analyze the data and test the hypotheses.Results: Personal motivation and innovative climate have significant effects on Chinese university students’ innovative behavior. The effect of personal motivation and innovative climate on students’ innovative behavior is heterogeneous between disciplines and place of residence. Further, extrinsic motivation serves as a positive incentive. Mentor support, good academic climate, and knowledge sharing affect students’ innovative behavior positively. However, insufficient guaranteed resources has a significant negative influence. The data demonstrated no statistically significant difference between intrinsic motivation and students’ innovative behavior.Conclusion: This study contributes to the empirical literature on mechanisms that influence innovative behavior by testing the relation between personal motivation, innovative climate, and innovative behavior on the part of Chinese university students. In addition, these findings also provide evidence for ways to improve university students’ innovative consciousness and innovative ability, as well as universities’ management practice of innovative education.Keywords: innovative behavior, personal motivation, innovative climate, university students

Feng Gu,1,2,&ast; Shan Hu,3,&ast; Yunjian Wu,4,&ast; Changyu Wu,4 Ying Yang,5 Bing Gu,6 Hong Du1 1Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China; 2Department of Laboratory Medicine, Xuzhou Central Hospital, Xuzhou, 221000, People’s Republic of China; 3Department of Laboratory Medicine, Xuzhou Tumor Hospital, Xuzhou, 221005, People’s Republic of China; 4School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 5Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing, 100850, People’s Republic of China; 6Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Du; Ying Yang, Email hong_du@126.com; y_ying_77@163.comPurpose: Candida infection has a high mortality rate, and the increasing prevalence of non-Candida albicans drug resistance in recent years poses a potential threat to human health. Non-Candida albicans has long culture cycles, and its firm cell walls making it difficult to isolate DNA for sequencing.Materials and Methods: Fe3O4@PEI (PEI, polyvinyl imine) was mixed with clinical samples to form Fe3O4@PEI@non-Candida albicans and enriched them with magnets. Triangular silver nanoplates enhanced the surface-enhanced Raman scattering (SERS) signal. SERS was used to detect the fingerprint spectrum of non-Candida albicans. Then, orthogonal partial least squares discriminant analysis (OPLS-DA) was used to analyze the drug resistance of non-Candida albicans.Results: SERS combined with OPLS-DA could well analyze the drug resistance of non-Candida albicans. Through 10-fold-cross validation, the accuracy of training and test data is greater than 99%, indicating that the model has good classification ability. We used SERS for the first time to detect the drug resistance of non-Candida albicans directly.Conclusion: This approach can be utilized without causing damage to the cell wall and can be accomplished in as little as 90 minutes. It can provide timely guidance for the treatment of patients with good clinical application potential.Keywords: non-Candida albicans, SERS, drug resistance, OPLS-DA

Mingyue Wang, Yan Wu, Yue Zhou, Junqiang Dong, Shenshen Hu, Ping Hou, Jianbo Gao Department of Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Jianbo Gao, Email cjr.gaojianbo@vip.163.comIntroduction: Early detection and treatment of osteoporosis through bone mineral density (BMD) measurement could aid in the prevention of osteoporosis-related fractures. We aimed to assess the parameter of dual-energy spectral CT (DesCT) consistency with BMD determination using quantitative computed tomography (QCT), thereby establishing a basis for further DesCT application for BMD determination.Methods: We subjected the European spine phantom, which contains three vertebral bodies (V1, V2, and V3), to DesCT with different radiation doses. The basis material pairs were hydroxyapatite (water), calcium (water), and hydroxyapatite (fat). Additionally, the medical records of 152 patients who underwent QCT and DesCT for chest scans in a two-month period were reviewed to measure BMD values.Results: No significant differences were found in the basis pair values of the V1, V2, or V3 vertebrae under different radiation doses in the phantom; in particular, the hydroxyapatite (water), hydroxyapatite (fat), relative error values of V1, V2, and V3 under different radiation doses were not significantly different (all p > 0.05). For patients, the hydroxyapatite (water), hydroxyapatite (fat), and hydroxyapatite (average) values measured by DesCT had a significant correlation with BMD measured by QCT Among 242 vertebrae (152 T12 and 90 L1 vertebrae), there was no significant difference between the BMD measured by QCT and the HAP (average) measured by DesCT (p = 0.071). The interclass correlation coefficient (ICC) value was 0.925 between the HAP (average) and HAP (average) with DesCT and BMD measured by QCT (p < 0.001). Bland-Altman diagram indicated that both measurements were in good agreement.Discussion: We showed that BMD values measured by DesCT were stable and repeatable under different radiation doses. DesCT and QCT measurements of human BMD were highly correlated. Thus, DesCT-based BMD assessment of the spine in a clinical setting could be considered feasible.Keywords: dual-energy spectral computed tomography, quantitative computed tomography, bone mineral density, European spine phantom, spine

Multiple second heart field (SHF) transcription factors are involved in cardiac development. In this article we evaluate the relationship between SHF transcription factor polymorphisms and congenital heart disease (CHD). Ten polymorphisms were used for genotyping, and three of these were used for the luciferase assay. The risk of CHD was increased 4.31 times and 1.54 times in the C allele of GATA5: rs6061243 G>C and G allele of TBX20: rs336283 A>G, respectively. The minor alleles of SMYD1: rs1542088 T>G, MEF2C: rs80043958 A>G and GATA5: rs6587239 T>C increased the risk of the simple types of CHD. The minor alleles of GATA5: rs41305803 G>A and MEF2C: rs304154 A>G increased the risk of tetralogy of Fallot (TOF). The minor alleles of TBX20: rs336284 A>G and SMYD1: rs88387557 T>G only increased the risk of a single ventricle (SV). Luciferase assays revealed that the minor alleles of rs304154 and rs336284 decreased the transcriptional levels of MEF2C and TBX20, respectively (p

Runan Zuo,1 Yan Zhang,1 Xiaorong Chen,1 Shiheng Hu,1 Xinhao Song,1 Xiuge Gao,1 Jiahao Gong,1 Hui Ji,1 Fengzhu Yang,1 Lin Peng,1 Kun Fang,2 Yingjun Lv,1 Junren Zhang,1 Shanxiang Jiang,1 Dawei Guo1 1Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, People’s Republic of China; 2The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of ChinaCorrespondence: Dawei Guo; Shanxiang Jiang, Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal, Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, People’s Republic of China, Tel +86 25-84396215, Fax +86-25-84398669, Email gdawei0123@njau.edu.cn; nauvy@sina.comBackground: Halofuginone (HF)-loaded TPGS polymeric micelles (HTPM) were successfully fabricated using the thin-film hydration technique. HTPM via intravenous injection have been demonstrated to exert an excellent anticancer effect against triple-negative breast cancer (TNBC) cells and subcutaneous xenografts. In the present study, we further explored the potential treatment effect and mechanism of orally administered HTPM alone and in combination with surgical therapy on TNBC in subcutaneous and orthotopic mouse models.Methods: Herein, the stability and in vitro release behavior of HTPM were first evaluated in the simulated gastrointestinal fluids. Caco-2 cell monolayers were then used to investigate the absorption and transport patterns of HF with/without encapsulation in TPGS polymeric micelles. Subsequently, the therapeutic effect of orally administered HTPM was checked on subcutaneous xenografts of TNBC in nude mice. Ultimately, orally administered HTPM, combined with surgical therapy, were utilized to treat orthotopic TNBC in nude mice.Results: Our data confirmed that HTPM exhibited good stability and sustained release in the simulated gastrointestinal fluids. HF was authenticated to be a substrate of P-glycoprotein (P-gp), and its permeability across Caco-2 cell monolayers was markedly enhanced via heightening intracellular absorption and inhibiting P-gp efflux due to encapsulation in TPGS polymeric micelles. Compared with HF alone, HTPM showed stronger tumor-suppressing effects in subcutaneous xenografts of MDA-MB-231 cells when orally administered. Moreover, compared with HTPM or surgical therapy alone, peroral HTPM combined with partial surgical excision synergistically retarded the growth of orthotopic TNBC. Fundamentally, HTPM orally administered at the therapeutic dose did not cause any pathological injury, while HF alone led to weight loss and jejunal bleeding in the investigated mice.Conclusion: Taken together, HTPM could be applied as a potential anticancer agent for TNBC by oral administration.Graphical Abstract: Keywords: triple-negative breast cancer, Halofuginone hydrobromide, TPGS polymeric micelles, subcutaneous xenografts, orthotopic xenografts, oral administration

Feng Qian,1– 3,&ast; Song Hu,4,&ast; Yueping Zhu,2,3 Yinling Wang,2,3 Jin Liu,2,3 Jialu Qiao,4 Xiji Shu,4 Yong Gao,5 Binlian Sun,4 Chuanwu Zhu1– 3 1Department of Infectious Diseases, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China; 2Department of Infectious Diseases, The Affiliated Infectious Disease Hospital of Soochow University, Suzhou, 215131, People’s Republic of China; 3Department of Infectious Diseases, The Fifth People’s Hospital of Suzhou, Suzhou, 215131, People’s Republic of China; 4Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, 430056, People’s Republic of China; 5The First Affiliated Hospital, Department of Life Science and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanwu Zhu; Binlian Sun, Tel/Fax +86 512 87806206 ; +86 27 84225149, Email zhuchw@126.com; binlian17@jhun.edu.cnPurpose: To investigate factors involved in T-cell depletion in combination antiretroviral therapy (cART)-treated human immunodeficiency virus 1 (HIV-1)-positive patients.Patients and Methods: 29 HIV-1-positive patients were enrolled. The CD4+, CD8+ T cell subsets and CD56dim NK cells were detected by flow cytometry. The concentrations of cytokines were measured by enzyme-linked immunosorbent assay. Extraction, amplification, and viral load quantification of specimens were performed using the Roche Cobas Ampliprep/Cobas TaqMan HIV-1 test.Results: Compared with IR group, the total number of red blood cells (RBCs) and lymphocytes (LCs) in INR group was significantly reduced, and there was a significant positive correlation between the number of RBCs and that of LCs. The overall production rates of T cells-related cytokines were lower in INR group. However, the cell-surface expression of programmed death-1 (PD-1) on CD4+ T and CD8+ T cells were markedly elevated in INR group. Moreover, it was found that the proportion and the killing ability of CD56dim NK cells significantly increased in INR patients, and significantly correlated with apoptosis of T lymphocytes.Conclusion: A poor immune reconstitution in HIV-positive patients might result from multiple factors, including bone marrow suppression, high PD-1 expression on the surface of CD4+ T cells, and over-activation of T and NK cells. Besides, the activity of NK cells and RBCs count might be important auxiliary indicators for immune reconstitution and provided a reliable guidance for developing strategies to improve immune reconstitution.Keywords: AIDS, T-cells, CD56dim NK cells, antiretroviral therapy, immune reconstitution

Yuting Wang,1 SongNian Hu,2 XinYu Tan,2 Qingqing Sang,3 Peng Shi,3 Chun Wang,3 Daoqian Sang3 1Department of Neurology, The Third Affiliated Hospital of Anhui Medical University, Heifei, People’s Republic of China; 2State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of ChinaCorrespondence: Daoqian Sang, Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, 287, Changhuai Road, Bengbu, 233004, People’s Republic of China, Email sangdaoqian@bbmc.edu.cnPurpose: The aim of this study was to screen the possible pathogenic genes of one family with tuberous sclerosis complexes (TSCs).Patients and Methods: All family members were examined through detailed clinical evaluations, auxiliary examinations and CT. Then, we selected five members from this TSC family as the test samples. They were analysed by a new exon group sequencing method. Single nucleotide polymorphisms (SNPs) were screened by using databases, such as dbSNP and HAPMAP, and then the candidate genes were selected. Genes were analysed, and finally, the most likely mutation sites were screened. The results were examined by Sanger sequencing.Results: In this TSC family, we identified c.913+2T>G, a splicing site mutation in the 9th intron region of TSC1. Family members without TSC did not have this mutation.Conclusion: The mutations in the intron regions cannot be ruled out as a pathogenic factor for TSC.Keywords: pathogenic genes, tuberous sclerosis complex, whole exon sequencing, intron mutation

Tao Wang,1,2,&ast; Fa Long,1,&ast; Zhihui Huang,1 Liang Long,1 Wenting Huang,1 Siyu Hu,1 Fengbo Hu,1 Peng Fu,1 Jingfan Gan,1 Hongbo Dong,1 Guomei Yan1 1University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen, People’s Republic of China; 2The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fa Long, University of Chinese Academy of Sciences Shenzhen Hospital, No. 4253, Songbai Road, Guangming District, Shenzhen, 518106, People’s Republic of China, Tel +86-755-27461986, Email longfa_923@163.comObjective: To investigate the relation of activation site and number with clinical response to bronchial thermoplasty (BT) in refractory asthma patients.Methods: This work included 106 consecutive refractory asthma patients completing three BT sessions in our hospital from May 2016 to May 2019. Procedure details included recording delivery sites and those in BT. Asthma Control Questionnaire (ACQ) scores and spirometric measurements were recorded 1-day before treatment and 6 months post-treatment to explore the effects of BT activation number and site on clinical response.Results: ACQ score (3.19± 1.14 vs 1.26± 0.63), forced expiratory volume in 1 sec (FEV1)% predicted (55.53± 21.66 vs 66.19± 22.50), FEV1 (1.53± 0.74 vs 1.93± 0.82), and forced vital capacity (FVC) (2.49± 0.86 vs 2.92± 0.94) significantly increased after three BT sessions compared with pre-session. Major bronchial ablation did not significantly improve BT response in asthma patients. Multivariate logistic regression identified baseline ACQ score and baseline FEV1% predicted as independent factors affecting the clinical response to BT. Correlation and regression analysis revealed a significant linear relationship between baseline ACQ and ACQ improvement, as well as a linear relationship between the third session activation number and ACQ improvement. Based on subgroup analysis of activation number, cohort C (activations ≥ 200) had better lung function, lower non-responding rate, and better long-term effectiveness than the other two cohorts. The activation number in the third BT session showed the strongest predictive ability compared with the first two sessions.Conclusion: Main bronchial ablation did not markedly affect clinical response to BT. Baseline ACQ and baseline FEV1% predicted were independent factors affecting clinical response to BT. Increasing the activation number might promote the therapeutic efficacy of BT, and the activation number in the third BT session correlated with and predicted the BT response.Keywords: refractory asthma, bronchial thermoplasty, activation, response, correlation

Xiaoxin Li,1 Shen-Long Yang,2 Jing Li,3 Ting-Ting Rao,2 Chuangang Shen,4 Sanman Hu,4 Yongyu Guo5 1Center of Mental Health Education, Huaqiao University, Quanzhou, 362021, People’s Republic of China; 2School of Humanities and Social Science, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 3School of Psychology, Central China Normal University, Key Laboratory of Cyberpsychology and Behavior, Ministry of Education, and Hubei Human Development and Mental Health Key Laboratory, Wuhan, 430079, People’s Republic of China; 4College of Business Administration, Huaqiao University, Quanzhou, 362021, People’s Republic of China; 5School of Psychology, Nanjing Normal University, Nanjing, 210097, People’s Republic of ChinaCorrespondence: Shen-Long Yang; Yongyu Guo, Tel +86 15389428303 ; +86 13397176318, Email yangsl@mail.xjtu.edu.cn; yyguo@njnu.edu.cnBackground: Whether the pandemic can be effectively prevented and controlled depends on the entire population’s adherence to recommendations and preventive behaviors. The present study aimed to investigate the social class differences and internal mechanisms of prevention behaviors in the COVID-19 pandemic.Methods: We conducted an online cross-sectional survey among the general Chinese population at the early stage of the COVID-19 pandemic. The survey website’s subscribers could access the questionnaire through the Tencent online platform, and a total of 1948 participants voluntarily completed it. Most of the participants were female (n = 1257, 64.528%), between the ages of 18– 29 (n = 999, 51.284%), university graduates (n = 1015, 52.105%), and had an annual family income below 100,000 yuan (n = 1119, 57.444%). The differences in COVID-19 prevention behaviors among different social classes, the mediating role of infectious threat perception and the moderating role of perceived epidemic transparency were examined.Results: 1) There were significant differences in prevention behaviors among different social classes. 2) The level of infectious threat perception played a mediating role in the relationship between social class and prevention behavior. When the individuals were from a lower social class, the level of threat perception and the level of COVID-19 prevention behaviors were also lower. 3) Perceived epidemic transparency played a moderating role in the relationship between social class and COVID-19 prevention behavior. It also played a moderating role in the relationship between social class and infectious threat perception.Conclusion: In the implementation of epidemic prevention and control measures, different social classes should be targeted and guided differently. In particular, lower-class individuals can be guided by improving the perceptions of epidemic transparency and infectious threat.Keywords: social class, infectious threat perception, COVID-19 prevention behaviors, perceived epidemic transparency

Qiyun Jiang,1,2 Dan Gong,1,2 Huiqi Li,3 Donglan Zhang,4 Suzhen Hu,5 Qinghua Xia,6 Hong Yuan,7 Peng Zhou,6 Yiying Zhang,7 Xing Liu,8 Mei Sun,1,2 Jun Lv,1,2 Chengyue Li1,2 1Department of Health Policy and Management, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Research Institute of Health Development Strategies, Fudan University, Shanghai, People’s Republic of China; 3School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 4Department of Health Policy and Management, College of Public Health, University of Georgia, Athens, GA, USA; 5Department of Medical Affairs, Liaocheng People’s Hospital, Liaocheng, People’s Republic of China; 6Department of Chronic Disease Prevention and Control, Changning District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 7Department of Chronic Disease Prevention and Control, Jiading District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 8Department of Epidemiology, School of Public Health, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Chengyue Li; Jun Lv, Department of Health Policy and Management, School of Public Health, Fudan University, P.O. Box 177, 130 Dong’an Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-33561022 ; +86-21-33563953, Fax +86-21-33563380, Email lichengyue@fudan.edu.cn; lujun@shmu.edu.cnPurpose: This study aimed to develop a screening tool based on a risk scoring approach that could identify individuals at high risk for hypertension in Shanghai, China.Methods: A total of 3147 respondents from the 2013 Shanghai Chronic Disease and Risk Factor Surveillance were randomly divided into the derivation group and validation group. The coefficients obtained from multivariable logistic regression were used to assign a score to each variable category. The receiver operating characteristic (ROC) curve was used to find the optimal cut-off point and to evaluate the screening performance.Results: Age, family history of hypertension, having diabetes, having dyslipidemia, body mass index, and having abdominal obesity contributed to the risk score. The area under the ROC curve was 0.817 (95% CI: 0.797– 0.836). The optimal cut-off value of 20 had a sensitivity of 83.4%, and a specificity of 64.3%, demonstrating good performance.Conclusion: We developed a simple and valid screening tool to identify individuals at risk for hypertension. Early detection could be beneficial for high-risk groups to better manage their conditions and delay the progression of hypertension and related complications.Keywords: Eastern China, high-risk population, hypertension, risk scoring method, screening tool

Shudong Hu,1,2,&ast; Heng Zhang,1,2,&ast; Yanqi Zhong,3,&ast; Enock Adjei Agyekum,2,&ast; Zongqiong Sun,1 Yuxi Ge,1 Jie Li,4 Weiqiang Dou,5 Junlin He,6 Hong Xiang,7 Yuandong Wang,8 Xiaoqin Qian,2 Xian Wang2 1Department of Radiology, Affiliated Hospital, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Ultrasound, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 3School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 4Department of Interventional Radiology, Affiliated Hospital, Jiangnan University, Wuxi, People’s Republic of China; 5GE Healthcare, MR Research China, Beijing, People’s Republic of China; 6Department of Radiology, Tinglin Hospital of Jinshan District, Shanghai, People’s Republic of China; 7Department of Pediatric, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 8Department of Radiotherapy, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian Wang; Xiaoqin Qian, Tel +86 13952808812 ; +86 13813186750, Email wangxian8812@126.com; yz_tyz1030@126.comPurpose: To explore the separate diagnostic value of preoperative ultrasound (US), magnetic resonance imaging (MRI), and the combination of US and MRI in extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC).Materials and Methods: This retrospective study was approved by the Affiliated People’s Hospital of Jiangsu University review board. A total of 158 PTC patients with ETE received preoperative US and MRI examination and underwent surgery between May 2014 and December 2018 in Affiliated People’s Hospital of Jiangsu University. For each case, the US and MRI features of ETE were retrospectively and independently investigated by two radiologists. The clinical assessment for each case was implemented, respectively, using US imaging only, MRI only, and a combination of both modalities at three different time points with one-month intervals.Results: The diagnostic accuracies of US, MRI, and the combined set for T3 (minimal ETE) were 91.7% (88/96), 74.0% (71/96), and 97.9% (94/96), respectively, indicating a significantly different performance (P < 0.001). The diagnostic accuracies for T4 (extensive ETE) were 62.9% (39/62), 87.1% (54/62), and 93.5% (58/62), respectively. The difference between the three methods for T4 was statistically significant (P = 0.000). The diagnostic accuracies for overall ETE were 80.4% (127/158), 79.1% (125/158), and 96.2% (152/158), respectively. The difference between the three methods for ETE was statistically significant (P = 0.001).Conclusion: This study suggests that ETE can be predicted most accurately by the combination of preoperative US and MRI.Keywords: thyroid cancer, ultrasonography, magnetic resonance imaging, neoplasm staging

Yulan Huang,&ast; Shitong He,&ast; Yitian Chen, Junli Sheng, Yuling Fu, Xialin Du, Yalong Yang, Honglin Liu, Zhenyu Han, Yingqi Huang, Qian Wen, Chaoying Zhou, Xinying Zhou, Shengfeng Hu, Li Ma Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Ma; Shengfeng HuInstitute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email mali_61648322@smu.edu.cn; hushengfeng@smu.edu.cnBackground: As deubiquitinases (DUBs), ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to play a crucial role in regulating diverse biological processes. However, its function in macrophage polarization remains unclear.Methods: We performed in vivo and in vitro experiments to investigate the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a kind of DUBs, in macrophage differentiation by using UCHL1-deficiency mice.Results: We demonstrated that LPS stimulation induced UCHL1 expression in macrophages. The deficiency of UCHL1 expression decreased the expression of CD80 and CD86 but increased the expression of CD206. The expression of TNF-α, IL-6, iNOS, and IL-10 was downregulated, while that of Arg1, Ym1, and Fizz1 was upregulated in UCHL1 deficient macrophages. Moreover, we observed that UCHL1 promoted the degradation of p110α through autophagy, but paradoxically increased the activity of AKT, thereby promoting polarization of macrophages into pro-inflammatory states.Conclusion: In this study, we identified UCHL1 as a positive regulator of M1 macrophage polarization. Our findings may help in developing therapeutic interventions for the treatment of inflammatory diseases and pathogenic infections.Keywords: UCHL1, macrophages, AKT, p110α, autophagy

Sheng Zou,&ast; Jiayue Ye,&ast; Sheng Hu, Yiping Wei, Jianjun Xu Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianjun Xu; Yiping Wei Tel +8613907913526; +8613687919322Email xujianjun3526@163.com; weiyip2000@hotmail.comPurpose: To analyze the relationship between titin (TTN) mutation gene and tumor mutational burden (TMB) and the with prognosis of lung squamous cell carcinomas (LUSC), and to explore the feasibility of TTN as a potential prognostic marker of for LUSC.Methods: We analyzed the somatic mutation landscape of LUSC samples using datasets obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Sequence data were divided into wild and mutant groups, and differences in TMB values between the groups compared using a Mann–Whitney U-test. The Kaplan Meier method was used to analyze the correlation between TTN mutation and LUSC prognosis, whereas CIBERSORT algorithm was used to calculate the degree of relative enrichment degree of among tumor-infiltrating lymphocytes in LUSC.Results: Analysis of both datasets revealed high mutations in the TTN gene, with mutants exhibiting a significantly higher TMB value relative to the wild-type (P < 0.001). Prognosis of the TTN mutant group in LUSC was significantly better than that of wild-type (P = 0.009). Kaplan Meier curves showed that TTN mutation may be an independent prognostic factor in LUSC patients (HR: 0.64, 95% CI 0.48– 0.85, P = 0.001), while GSEA analysis revealed that TTN mutation plays a potential role in the development of LUSC. Finally, analysis of LUSC immune microenvironment revealed that TTN mutation was significantly associated with enrichment of macrophages M1 (p < 0.05).Conclusion: TTN mutation is associated with TMB, and is positively correlated with prognosis of LUSC. Therefore, this mutation may serve as a potential prognostic indicator of LUSC.Keywords: TTN, lung squamous cell carcinomas, tumor mutation burden, prognostic marker, bioinformatics

Xueyao Huang,1,2 Xuan Wei,1 Sijing Qiao,1,2 Xue Zhang,1,2 Rui Li,1 Shunxue Hu,3 Hongluan Mao,1,2 Peishu Liu1,2 1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Peishu Liu; Hongluan MaoDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong University, No. 107 Wen Hua Xi Road, Jinan, Shandong, 250012, People’s Republic of ChinaTel +8618560081988; Tel +8618560082027Email peishuliu@126.com; hongluanmao@126.comPurpose: The efficacy of post-surgery platinum-based chemotherapy, the primary choice for the treatment of ovarian cancer (OC), is greatly reduced by the development of drug-resistance. In this study, we investigated the association of expression low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), two cholesterol metabolism-related proteins, in OC tissues and chemoresistance and patient prognosis.Methods: Survival analysis using LDLR and HMGCR expression in the ovarian cancer patients using the dataset of Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was carried out online. A retrospective study was performed on 65 patients who had undergone surgery for ovarian cancer. In addition, patients were divided into 2 groups: platinum resistance group and platinum sensitivity group. Serum lipid metabolism data were collected and analyzed. Protein expressions of LDLR and HMGCR in ovarian cancer tissue were detected by immunohistochemistry.Results: Online survival analysis showed that patients with higher LDLR expression had poorer prognosis than those with lower LDLR expression in ovarian cancer cells, while a higher HMGCR expression was associated with better OC prognosis. Overall survival (OS) and disease-free survival (DFS) were lower in patients with higher LDLR levels (OS: P=0.046, DFS: P=0.009). Platinum-resistant patients had higher levels of low-density lipoprotein (LDL) and cholesterol in serum as compared with platinum-sensitive patients (P< 0.001). Immunohistochemistry showed that LDLR expression was high and HMGCR was low in platinum-resistant patients.Conclusion: The expression of LDLR and HMGCR proteins, involved in the regulation of cholesterol metabolism and the plasma LDL and cholesterol levels were significantly different in platinum-resistant and platinum-sensitive ovarian cancer patients. We postulate that cholesterol metabolic reprogramming might play a role in platinum resistance in ovarian cancer.Keywords: LDLR, HMGCR, ovarian cancer, platinum resistance, cholesterol metabolism