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Chang-Sheng Ma,1,2,* Ya-Ping Ma,1,3,* Bo Han,1,2,* Wan-Li Duan,1 Shu-Chen Meng,1 Min Bai,1 Hao Dong,1 Li-Ying Zhang,1 Meng-Yuan Duan,1,2 Jing Liu,1 Ai-Jun Deng,2 Mao-Tao He1,2 1Department of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, People’s Republic of China; 3Department of Pathology, The 942Hospital of the People’s Liberation Army Joint Logistic Support Force, Yinchuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Tao He, Department of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China, Tel +86-18209617186, Fax +86-0536-3081201, Email hemaotao@sdsmu.edu.cn Ai-Jun Deng, Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, People’s Republic of China, Email dengaijun@hotmail.comPurpose: Ischemic stroke is a refractory disease wherein the reperfusion injury caused by sudden restoration of blood supply is the main cause of increased mortality and disability. However, current therapeutic strategies for the inflammatory response induced by cerebral ischemia-reperfusion (I/R) injury are unsatisfactory. This study aimed to develop a functional nanoparticle (MM/ANPs) comprising apelin-13 (APNs) encapsulated in macrophage membranes (MM) modified with distearoyl phosphatidylethanolamine-polyethylene glycol-RVG29 (DSPE-PEG-RVG29) to achieve targeted therapy against ischemic stroke.Methods: MM were extracted from RAW264.7. PLGA was dissolved in dichloromethane, while Apelin-13 was dissolved in water, and CY5.5 was dissolved in dichloromethane. The precipitate was washed twice with ultrapure water and then resuspended in 10 mL to obtain an aqueous solution of PLGA nanoparticles. Subsequently, the cell membrane was evenly dispersed homogeneously and mixed with PLGA-COOH at a mass ratio of 1:1 for the hybrid ultrasound. DSPE-PEG-RVG29 was added and incubated for 1 h to obtain MM/ANPs.Results: In this study, we developed a functional nanoparticle delivery system (MM/ANPs) that utilizes macrophage membranes coated with DSPE-PEG-RVG29 peptide to efficiently deliver Apelin-13 to inflammatory areas using ischemic stroke therapy. MM/ANPs effectively cross the blood-brain barrier and selectively accumulate in ischemic and inflamed areas. In a mouse I/R injury model, these nanoparticles significantly improved neurological scores and reduced infarct volume. Apelin-13 is gradually released from the MM/ANPs, inhibiting NLRP3 inflammasome assembly by enhancing sirtuin 3 (SIRT3) activity, which suppresses the inflammatory response and pyroptosis. The positive regulation of SIRT3 further inhibits the NLRP3-mediated inflammation, showing the clinical potential of these nanoparticles for ischemic stroke treatment. The biocompatibility and safety of MM/ANPs were confirmed through in vitro cytotoxicity tests, blood-brain barrier permeability tests, biosafety evaluations, and blood compatibility studies.Conclusion: MM/ANPs offer a highly promising approach to achieve ischemic stroke-targeted therapy inhibiting NLRP3 inflammasome-mediated pyroptosis. Keywords: apelin-13, cerebral ischemia-reperfusion injury, macrophage membrane, ischemic stroke therapy, pyroptosis

Abstract The vertebrate stress response (SR) is mediated by the hypothalamic–pituitary–adrenal (HPA) axis and contributes to generating context appropriate physiological and behavioral changes. Although the HPA axis plays vital roles both in stressful and basal conditions, research has focused on the response under stress. To understand broader roles of the HPA axis in a changing environment, we characterized an adaptive behavior of larval zebrafish during ambient illumination changes. Genetic abrogation of glucocorticoid receptor (nr3c1) decreased basal locomotor activity in light and darkness. Some key HPI axis receptors (mc2r [ACTH receptor], nr3c1), but not nr3c2 (mineralocorticoid receptor), were required to adapt to light more efficiently but became dispensable when longer illumination was provided. Such light adaptation was more efficient in dimmer light. Our findings show that the HPI axis contributes to the SR, facilitating the phasic response and maintaining an adapted basal state, and that certain adaptations occur without HPI axis activity.

Feng Pan,1,* Ai-ting Lu,1,2,* Xiaowei Mao,1,* Fang Hu,1 Hai Zhang,1 Baohui Han1 1Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baohui Han, Email 18930858216@163.comObjective: To investigate the knowledge of pulmonary rehabilitation (PR) among physicians involved in pulmonary disease management.Methods: This multi-regional cross-sectional survey was conducted from December 12, 2019 to January 22, 2020. The participants were enrolled and an electronic questionnaire was exclusively sent to the members of the Lung Cancer Special Committee of the China Medicine Education Association through the WeChat platform. Multivariable logistic regression analysis was performed to explore the associated factors of high PR knowledge scores (≥ 18 points).Results: From the 858 valid questionnaires, the routine implementation of PR was only reported for 16.95% of physicians. The main reason hindering the implementation of PR for patients was the limited knowledge and awareness of PR among the physicians involved (69.1%). A total of 618 and 240 physicians had high and low knowledge scores, respectively. Multivariable analysis suggests that the self-perception of PR knowledge (OR = 1.89, 95% CI: 1.32– 2.771, P = 0.001) was independently associated with high knowledge scores, while having no theoretical knowledge of PR was associated with poor knowledge scores (OR = 0.43, 95% CI: 0.26– 0.72, P = 0.001).Conclusion: Inadequate knowledge of pulmonary rehabilitation is evident among physicians who are involved in pulmonary disease management in China. This underscores the need for more comprehensive and standardized training to bolster their awareness and effective utilization of pulmonary rehabilitation.Keywords: chronic obstructive pulmonary disease, pulmonary rehabilitation, lung cancer, knowledge, oncologists

Yuhan Teng,1 Yining Jian,2 Xinyue Chen,3 Yang Li,4 Bing Han,2 Lei Wang3 1Department of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of Public Health, China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Department of General Practice, the First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 4Department of General Practice, Hunnan Zhujia Community Health Service Center, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Lei Wang, Department of General Practice, The First Hospital of China Medical University, 122 N Nanjing St., Heping District, Shenyang, 110001, People’s Republic of China, Fax +86-24-83283333, Email wanglei_tz@163.comPurpose: To predict the future number of patients with chronic obstructive pulmonary disease (COPD) in China and compare the three prediction models.Methods: A generalized additive model (GAM), autoregressive integrated moving average (ARIMA) model, and curve-fitting method were used to fit and predict the number of patients with COPD in China. Data on the number of patients with COPD in China from 1990 to 2019 were obtained from the Global Burden of Disease (GBD) database. The coefficient of determination (R2), mean absolute error (MAE), mean absolute percentage error (MAPE), root mean squared error (RMSE), relative error of prediction, Akaike Information Criterion (AIC), and Bayesian Information Criterion (BIC) were used to evaluate and compare the fitting effect, prediction effect, and reliability of the three models.Results: The GAM, ARIMA, and curve-fitting methods could predict future trends in COPD in China. The performance of the GAM is the best among the three models, whereas the curve fitting method is the worst, and the ARIMA (0,1,2) model is in between. The prediction results of the three models showed that the number of patients with COPD in China is expected to increase from 2020 to 2025.Conclusion: GAM and AIRMA models are recommended for predicting the future prevalence of COPD in China. The number of patients with COPD in China is expected to increase in the next few years. The prevention and control of COPD in China still needs to be strengthened. Using appropriate models to predict future trends in COPD will provide support for health policymakers.Keywords: generalized additive model, ARIMA model, curve fitting method, COPD, prediction

Yue Cao, Yue-Yue Feng, Wei Du, Jing Li, Ya-Lan Fei, Hao Yang, Meng Wang, Shi-Jie Li, Xian-Jin Li, Bing Han Division of Cardiology, Xuzhou Central Hospital, Xuzhou, People’s Republic of ChinaCorrespondence: Bing Han, Division of Cardiology, Xuzhou Central Hospital, 199 South Jiefang Road, Xuzhou, 221009, People’s Republic of China, Tel +86-516-83985069, Fax +86-516-83956012, Email hbing777@hotmail.comPurpose: To investigate the reasons for elderly atrial fibrillation (AF) patients not continuing their oral anticoagulation (OAC) treatment and the factors that influence this behavior.Methods: Elderly AF patients (aged≥ 75 years) hospitalized from December 2019 to May 2022 were consecutively enrolled. Clinical, demographic, and concomitant medication data were collected. The endpoint was defined as OAC discontinuation for more than 30 days or a switch to an alternative therapy. Predictors of OAC non-persistence were investigated using a multivariable Cox regression model.Results: This study included 560 participants (51.1% men, mean age 80.9± 0.2 years). During a median follow-up of 20 months, medication persistence was observed in 322 patients (57.5%). Non-persistence was found to be significantly higher with warfarin than with NOAC (48.8% vs 33.6%, p = 0.006). In the multivariate analysis, OAC non-persistence was independently predicted by a history of permanent pacemaker implantation, the use of antiplatelet drugs, employee Medicare, living with children, college degree or above, and persistent AF (HR = 1.580, 1.586, 0.604, 0.668, 0.028, 0.769, p < 0.05, respectively). Treatment discontinuation within 3 months of discharge was observed in a large number of patients (81.8%). Medication discontinuation due to bleeding was more frequently observed in patients who continued for longer than 3 months (p < 0.001), while discontinuation due to patient preference was more frequent in those with shorter durations (≤ 3 months) (p = 0.049). Patient preference was the second leading cause of non-persistence in patients, regardless of whether they were taking warfarin or NOAC.Conclusion: OAC non-persistence remains high among elderly AF patients during long-term follow-up, with a significant proportion discontinuing shortly after discharge. This pattern of non-persistence is heavily influenced by demographic factors and patient preference. Further interventions should be developed based on the reasons and risk factors to improve persistence and initiated early in the treatment process.Keywords: atrial fibrillation, the elderly, oral anticoagulants, non-persistence

Guo-Yi Shen,1,&ast; Peng-Jie Yang,2,&ast; Wen-Shan Zhang,1 Jun-Biao Chen,1 Qin-Yong Tian,1 Yi Zhang,1 Bater Han2 1Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, People’s Republic of China; 2Department of Thoracic Surgery, Inner Mongolia Cancer Hospital & Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot, Inner Mongolia Autonomous Region, 010020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Zhang, Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, No. 59, Shengli West Road, Zhangzhou Xiangcheng District, Zhangzhou, 363000, People’s Republic of China, Tel +86-13906969033, Email zhangyi625@126.com Bater Han, Department of Thoracic Surgery, Inner Mongolia Cancer Hospital & Affiliated People’s Hospital of Inner Mongolia Medical University, No. 42, Zhaowuda Road, Saihan District, Huhhot, Inner Mongolia Autonomous Region, 010020, People’s Republic of China, Tel +86-13948120033, Email baterhanhbb@126.comBackground: Dysregulation of lipid metabolism is common in cancer. However, the molecular mechanism underlying lipid metabolism in esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are not well understood. The objective of our study was to construct a lipid metabolism-related prognostic model to improve prognosis prediction in ESCC.Methods: We downloaded the mRNA expression profiles and corresponding survival data of patients with ESCC from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We performed differential expression analysis to identify differentially expressed lipid metabolism-related genes (DELMGs). We used Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses to establish a risk model in the GEO cohort and used data of patients with ESCC from the TCGA cohort for validation. We also explored the relationship between the risk model and the immune microenvironment via infiltrated immune cells and immune checkpoints.Results: The result showed that 132 unique DELMGs distinguished patients with ESCC from the controls. We identified four genes (ACAA1, ACOT11, B4GALNT1, and DDHD1) as prognostic gene expression signatures to construct a risk model. Patients were classified into high- and low-risk groups as per the signature-based risk score. We used the receiver operating characteristic (ROC) curve and the Kaplan-Meier (KM) survival analysis to validate the predictive performance of the 4-gene signature in both the training and validation sets. Infiltrated immune cells and immune checkpoints indicated a difference in the immune status between the two risk groups.Conclusion: The results of our study indicated that a prognostic model based on the 4-gene signature related to lipid metabolism was useful for the prediction of prognosis in patients with ESCC.Keywords: biomarkers, esophageal squamous cell carcinoma, immune microenvironment, lipid metabolism, prognosis

Xiao Han,1 Qianjuan Zhang,2 Chengcheng Wang,3 Bingjuan Han4 1Department of Pediatrics, Jining First People’s Hospital, Jining, Shandong, 272011, People’s Republic of China; 2Department of Children’s Medical Rehabilitation Center, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250001, People’s Republic of China; 3Department of Pediatric Surgery, Jining First People’s Hospital, Jining, Shandong, 272011, People’s Republic of China; 4Department of Children’s Health Prevention, The Second Children & Women’s Healthcare of Jinan City, Jinan, Shandong, 271100, People’s Republic of ChinaCorrespondence: Bingjuan Han, Email hbj208@163.comPurpose: Mowat-Wilson syndrome (MWS) is an autosomal dominant disease caused by a pathogenic variant of the ZEB2 gene. The main clinical manifestations include special facial features, Hirschsprung disease (HSCR), global developmental delay and other congenital malformations. Here, we summarize the clinical characteristics and genetic mutation analysis of three Chinese patients with MWS.Patients and Methods: The clinical characteristics of the patients were monitored and the treatment effect was followed up. DNA was extracted from peripheral blood and analyzed by sequencing. Whole exome sequencing was then performed.Results: Three novel ZEB2 gene mutations were identified in 3 patients (c.1147_1150dupGAAC, p.Q384Rfs&ast;7, c.1137_1146del TAGTATGTCT, p.S380Nfs &ast;13 and c.2718delT, p.A907Lfs&ast;23). They all had special facial features, intellectual disability, developmental delay, microcephaly, structural brain abnormalities and other symptoms. After long-term regular rehabilitation treatment, the development quotient of each functional area of the patient was slightly improved.Conclusion: Our study expanded the mutation spectrum of ZEB2 and enriched our understanding of the clinical features of MWS. It also shows that long-term standardized treatment is of great significance for the prognosis of patients.Keywords: Mowat-Wilson syndrome, ZEB2, gene mutation, rehabilitation treatment, long-term follow-up

Zheyu Zhou,1,&ast; Shuya Cao,2,&ast; Chaobo Chen,3,4,&ast; Jun Chen,5 Xiaoliang Xu,6 Yang Liu,4 Qiaoyu Liu,6 Ke Wang,2 Bing Han,4 Yin Yin6 1Department of General Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, 210008, People’s Republic of China; 2Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Science; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, 210029, People’s Republic of China; 3Department of General Surgery, Xishan People’s Hospital of Wuxi City, Wuxi, 214105, People’s Republic of China; 4Department of Hepatobiliary and Transplantation Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 5Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 6Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yin Yin, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Hefei, 230022, People’s Republic of China, Email jyinjyin@sina.com Bing Han, Department of Hepatobiliary and Transplantation Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321, Zhongshan Road, Nanjing, 210008, People’s Republic of China, Email hanbing_nju@163.comBackground: Edmondson-Steiner (E-S) grade is a pathological indicator of the degree of hepatocellular carcinoma (HCC) differentiation, and E-S grade III–IV is a poor prognostic factor for HCC patients. Predicting poorly differentiated HCC has essential significance for clinical decision-making. Although some studies have developed predictive models based on magnetic resonance imaging (MRI) and radiomics, radiomic features that require specific software for analysis are impractical for clinical work. This study aims to develop a novel and user-friendly nomogram model to predict E-S grade III–IV.Patients and Methods: Medical data on patients meeting the inclusion criteria were obtained from the Nanjing Drum Tower Hospital HCC database (January 2020 to December 2022). Univariate analysis was used to screen for risk factors associated with E-S grade III–IV. A novel nomogram was established based on the subsequent multivariate logistic regression analysis. The performance of the established model was evaluated through diagnostic ability, calibration, and clinical benefits.Results: Overall, 240 HCC patients were included in this study. Among them, 103 were highly differentiated (E-S grade I–II) HCC and 137 were poorly differentiated (E-S grade III–IV) HCC. A nomogram model that integrated alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb), aspartate aminotransferase to lymphocyte ratio index (ALRI), and macrovascular invasion was established. The novel model had a good diagnostic performance with an area under the curve (AUC) value of 0.763. Meanwhile, the model had a diagnostic accuracy of 72.5%, a sensitivity of 78.1%, and a specificity of 65.1%. The calibration curve showed good calibration of the nomogram model (mean absolute error = 0.043), and the decision curve analysis (DCA) demonstrated that the clinical benefit was provided.Conclusion: Our developed nomogram model could successfully predict E-S grade III–IV in HCC patients, which may be helpful in clinical decision-making.Keywords: hepatocellular carcinoma, Edmondson-Steiner grade, nomogram, prediction

Wenjuan Yang,1,2 Bing Han,1 Bei Zheng,1 Ying Li,1 Tiefei Yao,3 Mei Han,3 Gonghua Li,1 Meiling Zhang1 1Department of Pharmacy, Tongde Hospital of ZheJiang Province, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Geriatric Medicine, Tongde Hospital of ZheJiang Province, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Gonghua Li; Meiling Zhang, Department of Pharmacy, Tongde Hospital of ZheJiang Province, Hangzhou, Zhejiang, People’s Republic of China, Tel +86-0571-89972239, Email ligonghua88@163.com; zml9998@sina.comAbstract: Coronavirus disease 2019 (COVID-19) emergence in late 2019, and wide spread quickly in the world. In China, the COVID-19 epidemic situation entered a low level now. With the arrival of flu season, the number of patients with respiratory symptoms is increasing. We reported three cases of patients who co-infected with SARS-CoV-2 and influenza A virus (IAV), and they were all treated with nirmatrelvir-ritonavir (NMV/r) and baloxavir marboxil. Due to the overlapping clinical features between the two diseases, it is important to identified them and gave the antiviral therapy timely.Keywords: COVID-19, influenza, co-infection, baloxavir marboxil, nirmatrelvir-ritonavir

Xiaoyu Pan,1,&ast; Huazheng Zhu,2,&ast; Jinglong Du,1 Guangtao Hu,1 Baoru Han,1 Yuanyuan Jia1 1College of Medical Informatics, Chongqing Medical University, Chongqing, People’s Republic of China; 2College of Intelligent Technology and Engineering, Chongqing University of Science and Technology, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanyuan Jia, Email yyjia@cqu.edu.cnAim: The Coronavirus Disease 2019 (COVID-19) pandemic has increased the public health burden and brought profound disaster to humans. For the particularity of the COVID-19 medical images with blurred boundaries, low contrast and different infection sites, some researchers have improved the accuracy by adding more complexity. Also, they overlook the complexity of lesions, which hinder their ability to capture the relationship between segmentation sites and the background, as well as the edge contours and global context. However, increasing the computational complexity, parameters and inference speed is unfavorable for model transfer from laboratory to clinic. A perfect segmentation network needs to balance the above three factors completely. To solve the above issues, this paper propose a symmetric automatic segmentation framework named MS-DCANet. We introduce Tokenized MLP block, a novel attention scheme that uses a shift-window mechanism to conditionally fuse local and global features to get more continuous boundaries and spatial positioning capabilities. It has greater understanding of irregular lesion contours. MS-DCANet also uses several Dual Channel blocks and a Res-ASPP block to improve the ability to recognize small targets. On multi-modality COVID-19 tasks, MS-DCANet achieved state-of-the-art performance compared with other baselines. It can well trade off the accuracy and complexity. To prove the strong generalization ability of our proposed model, we apply it to other tasks (ISIC 2018 and BAA) and achieve satisfactory results.Patients: The X-ray dataset from Qatar University which contains 3379 cases for light, normal and heavy COVID-19 lung infection. The CT dataset contains the scans of 10 patient cases with COVID-19, a total of 1562 CT axial slices. The BAA dataset is obtained from the hospital and includes 387 original images. The ISIC 2018 dataset is from the International Skin Imaging Collaborative (ISIC) containing 2594 original images.Results: The proposed MS-DCANet achieved evaluation metrics (MIOU) of 73.86, 97.26, 89.54, and 79.54 on the four datasets, respectively, far exceeding other current state-of-the art baselines.Conclusion: The proposed MS-DCANet can help clinicians to automate the diagnosis of COVID-19 patients with different symptoms.Keywords: multi-modality COVID-19 lesion segmentations, laboratory to clinic, multi-scale feature learning, depthwise separable convolution

Ling Sun,1,&ast; Bing Han,2,&ast; Yu Wang,1,&ast; Wenwu Zhu,2 Jianguang Jiang,1 Ailin Zou,1 Boyu Chi,1,3 Lipeng Mao,1,3 Yuan Ji,1 Qingjie Wang,1 Liming Tang4 1Department of Cardiology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213003, People’s Republic of China; 2Department of Cardiology, Xuzhou Central Hospital, Xuzhou Clinical School of Nanjing Medical University, Xuzhou, Jiangsu, 221009, People’s Republic of China; 3Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China; 4Department of Gastrointestinal Disease, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liming Tang, Center of Gastrointestinal Disease, Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, Jiangsu, 213003, People’s Republic of China, Email drtangliming@163.com Yuan Ji, Department of Cardiology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213003, People’s Republic of China, Email jiyuan1213@aliyun.comObjective: In this study, a risk score for ventricular arrhythmias (VA) were evaluated for predicting the risk of ventricular arrhythmia (VA) of acute myocardial infarction (AMI) patients.Methods: Patients with AMI were divided into two sets according to whether VA occurred during hospitalization. Another cohort was enrolled for external validation. The area under the curve (AUC) of receiver operating characteristic (ROC) was calculated to evaluate the accuracy of the model.Results: A total of 1493 eligible patients with AMI were enrolled as the training set, of whom 70 (4.7%) developed VA during hospitalization. In-hospital mortality was significantly higher in the VA set than in the non-VA set (31.4% vs 2.7%, P=0.001). The independent predictors of VA in patients with AMI including Killip grade ≥ 3, STEMI patients, LVEF < 50%, frequent premature ventricular beats, serum potassium < 3.5 mmol/L, type 2 diabetes, and creatinine level. The AUC of the model for predicting VT/VF in the training set was 0.815 (95% CI: 0.763– 0.866). A total of 1149 cases were enrolled from Xuzhou Center Hospital as the external validation set. The AUC of the model in the external validation set for predicting VT/VF was 0.755 (95% CI: 0.687– 0.823). Calibration curves indicated a good consistency between the predicted and the observed probabilities of VA in both sets.Conclusion: We have established a clinical prediction risk score for predicting the occurrence of VA in AMI patients. The prediction score is easy to use, performs well and can be used to guide clinical practice.Keywords: ventricular tachycardia, ventricular flutter and fibrillation, risk stratification, scoring system, acute myocardial infarction

Jun Lu,1– 4,&ast; Yuqing Lou,1,&ast; Yanwei Zhang,1,&ast; Runbo Zhong,1 Wei Zhang,1 Xueyan Zhang,1 Huimin Wang,1 Tianqing Chu,1 Baohui Han,1– 3 Hua Zhong1,3 1Department of Pulmonary Medicine, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Translational Medical Research Platform for Thoracic Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Bio-Bank, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baohui Han; Hua Zhong, Department of Pulmonary Medicine, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China, Email xkyyhan@gmail.com; 18930858216@163.com; eddiedong8@hotmail.comBackground: Nanocarrier platforms have been indicated to have great potential in clinical practice to treat non-small cell lung cancer (NSCLC). Our previous Phase III clinical study revealed that polymeric micellar paclitaxel (Pm-Pac) is safe and efficacious in advanced NSCLC patients. However, the histopathological-toxicological profile of Pm-Pac in mammals remains unclear.Methods: We examined the Pm-Pac-induced antitumour effect in both A549/H226 cells and A549/H226-derived xenograft tumour models.. And then, we evaluated the short-term and long-term toxicity induced by Pm-Pac in healthy Sprague‒Dawley (SD) rats. The changes in body weight, survival, peripheral neuropathy, haematology, and histopathology were studied in SD rats administered Pm-Pac at different dosages.Results: In the A549-derived xenograft tumour model, better therapeutic efficacy was observed in the Pm-Pac group than in the solvent-based paclitaxel (Sb-Pac) group when an equal dosage of paclitaxel was administered. Toxicity assessments in healthy SD rats indicated that Pm-Pac caused toxicity at an approximately 2- to 3-fold greater dose than Sb-Pac when examining animal body weight, survival, peripheral neuropathy, haematology, and histopathology. Interestingly, based on histopathological examinations, we found that Pm-Pac could significantly decrease the incidences of paclitaxel-induced brain and liver injury but could potentially increase the prevalence of paclitaxel-induced male genital system toxicity.Conclusion: This study introduces the toxicological profile of the engineered nanoparticle Pm-Pac and provides a novel perspective on the Pm-Pac-induced histopathological-toxicological profile in a rat model.Graphical Abstract: Keywords: nanomedicine, polymeric micellar paclitaxel, NSCLC, toxicological profile

Hao Wang, Xin Yin, Tianyi Fang, Shenghan Lou, Bangling Han, Jialiang Gao, Yufei Wang, Daoxu Zhang, Xibo Wang, Zhanfei Lu, Junpeng Wu, Jiaqi Zhang, Yimin Wang, Yao Zhang, Yingwei Xue Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of ChinaCorrespondence: Yingwei Xue, Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China, Email xueyingwei@hrbmu.edu.cnBackground: Aging has a negative impact on the immune function of patients. The purpose of this study was to construct an age-related specific immune index according to the immune aging phenomenon of gastric cancer (GC) and explore its prognostic value.Methods: This study retrospectively analyzed patients who underwent radical GC surgery in the Department of Gastrointestinal Surgery, Affiliated Cancer Hospital of Harbin Medical University, from August 2014 to December 2016 and divided them into a training cohort and a validation cohort. A new immune score, the GC-specific immune index (GSII), was developed as a series of lymphocyte subsets associated with the prognosis of patients with GC. Then, the receiver operating characteristic (ROC) curve was used to compare the prediction performance. The Kaplan‒Meier method and Log rank test were used to analyze the overall survival of patients. Cox hazard regression models were used to identify independent risk factors associated with prognosis. Finally, a nomogram model was constructed by combining the GSII and clinicopathological characteristics, and the calibration chart, consistency index, and decision curve were used to test the performance of the model.Results: Aging did not significantly affect CD8 cell counts but decreased CD4 and CD19 cell counts. Based on the Cox analysis, the GSII of patients ≤ 60 years old was 0.079×lg CD4+0.348×lg CD19, and the GSII of patients > 60 years old was 0.058×lg CD4. A decreased GSII was indicative of a poor prognosis and was an independent risk factor associated with patient outcomes. The nomogram constructed based on the GSII and clinicopathological features accurately predicted patient prognosis. Furthermore, the GSII was well validated in the validation cohort.Conclusion: The GSII constructed for the special immune aging phenomenon of GC can accurately predict patient prognosis.Keywords: gastric cancer, lymphocyte subsets, age, prognosis

Yuan Zhang,1,&ast; Hongli Yue,1,&ast; Yirui Qin,1 Jiajing Wang,1 Chenyang Zhao,1 Miao Cheng,1 Bo Han,2 Ruquan Han,1 Weihua Cui1,&ast; 1Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruquan Han; Weihua Cui, Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, No. 119, Nan Si Huan Xi Lu, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +8613701285393 ; Tel +8613701285393, Fax +861059976658, Email ruquan.han@ccmu.edu.cn; weihuacui@ccmu.edu.cnPurpose: Patients undergoing intraspinal tumor resection usually experience severe postoperative pain. Inadequate postoperative analgesia usually leads to severe postsurgical pain, which could cause patients to suffer from many other related complications. Recently, an increasing number of studies have found that gabapentin can relieve hyperalgesia, postoperative pain, and postoperative inflammation. However, there have been no reports on the use of gabapentin combined with sufentanil preoperatively for acute pain following intraspinal tumor resection.Study Design and Methods: This is a protocol for a randomized, placebo-controlled, and double-blinded trial. One-hundred and sixty-eight participants with chronic pain related to the intraspinal tumor will be randomized into the gabapentin and placebo groups in a 1:1 ratio. In the gabapentin group, patients will be given 300 mg gabapentin orally 36 h, 24 h, and 12 h before surgery; the placebo group will receive a placebo orally at the same time points preoperatively. To estimate the efficacy and safety endpoints, all the researchers and patients will be blinded until the completion of this study. The primary outcome will be the consumption of sufentanil within 48 h postoperatively. The secondary outcomes include the visual analog scale pain score and Von Frey mechanical pain threshold 36 h and 24 h before and 24 h and 48 h after surgery, the incidence of postoperative nausea, vomiting, and drowsiness, the length of hospital stay and medical expenses.Discussion: This trial is to evaluate the efficacy and safety of gabapentin combined with sufentanil for postoperative analgesia in patients who complain of pain before intraspinal tumor resection. The findings will provide a new strategy for multimode perioperative analgesia management in these patients.Keywords: gabapentin, intraspinal tumor resection, multimode perioperative analgesia, opiates

Chunxue He,1,2,&ast; Mingqiang Gong,3,4,&ast; Gengxiao Li,1,2 Yunxia Shen,2 Longyin Han,5 Bin Han,6 Mingwu Lou2 1Shenzhen Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Department of Radiology, Longgang District Central Hospital of Shenzhen, Shenzhen, People’s Republic of China; 3The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 4Department of Acupuncture, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China; 5Department of Neurology, Beijing Longfu Hospital, Beijing, People’s Republic of China; 6Department of Rehabilitation Medicine, Longgang District Central Hospital of Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Han; Mingwu Lou, Tel +86 13928488998 ; +86 13808854650, Email hhbb08@163.com; mingwulou@sina.comPurpose: To investigate white matter alterations in post-stroke cognitive impairment (PSCI) patients at the subacute stage employing diffusion kurtosis and tensor imaging.Methods: Thirty PSCI patients at the subacute phase and 30 healthy controls (HC) underwent diffusion kurtosis imaging (DKI) scans and neuropsychological assessments. Based on the tract-based spatial statistics and atlas-based ROI analysis, fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), kurtosis fractional anisotropy (KFA), axial kurtosis (AK), and radial kurtosis (RK) were compared in specific white matter fiber bundles between the groups (with family-wise error correction). Adjusting for age and gender, a partial correlation was conducted between neurocognitive assessments and DKI metrics in the PSCI group.Results: In comparison with the HC, PSCI patients significantly showed decreased MK, RK, and FA and increased MD values in the genu of corpus callosum, anterior limb internal capsule, and left superior corona radiata. In addition, DKI detected more white matter region changes in MK (31/48), KFA (40/48), and RK (25/48) than DTI with FA (28/48) and MD (21/48), which primarily consisted of the right cingulum, right superior longitudinal fasciculus, and left posterior limb of internal capsule. In the left anterior limb of internal capsule, MK and RK values were significantly negatively correlated with TMT-B (r = − 0.435 and − 0.414, P < 0.05), and KFA values (r = − 0.385, P < 0.05) of corpus callosum negatively associated with TMT-B.Conclusion: Combing DTI, DKI, and neuropsychological tests, we found extensive damaged white matter microstructure and poor execution performance in subacute PSCI patients. DKI could detect more subtle white matter changes than DTI metrics. Our findings provide added information for exploring the mechanisms of PSCI and conducting cognitive rehabilitation in the subacute stage.Keywords: diffusion kurtosis imaging, diffusion tensor imaging, subacute ischemic stroke, cognitive impairment

Bin Han,1,&ast; Feng Zang,2,&ast; Juan Liu,2 Songqin Li,2 Weihong Zhang,2 Yongxiang Zhang,2 Zhanjie Li2 1Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China; 2Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongxiang Zhang; Zhanjie Li, Tel +86-13951951616 ; +86-18052106999, Email zyx3019@sina.cn; LZJ070591@163.comPurpose: To improve the ability of infection prevention and control (IPC) of medical staff during the COVID-19 epidemic period, the “four-step” mode of whole staff training and assessment was used.Methods: During the period from March 9 to March 18, 2020, 5425 medical staff from The First Affiliated Hospital of Nanjing Medical University were selected as the objects of this study. There are four stages in the training assessment mode. The first stage is the basic assessment stage; the second stage releases the electronic version of the knowledge point manual; the third stage conducts online exercises; the fourth stage conducts the final assessment.Results: In the first stage, the participation rate of medical staff was 95.04%. In the fourth stage, the participation rate of medical staff was 98.01%. The average score of female medical staff in the first stage and the fourth stage was higher than that of males (P< 0.001). The average score of medical staff under 30 years old in the first stage and the fourth stage was higher than that of other age groups (P< 0.05). In the fourth stage, the correct rate of each part of exercises in the knowledge points of IPC was higher than that in the first stage (P< 0.001). In the two stages, the two parts of “COVID-19 prevention and control” and “multi-drug resistant bacteria prevention and control” had the highest accuracy, while the “disinfection and sterilization” and “infectious disease management” had the lowest accuracy (P< 0.001).Conclusion: The “four-step” infection control training assessment mode has realized “full participation” and “effective training”, and the level of medical staff’s IPC has been significantly improved.Keywords: training and assessment tool, infection prevention and control, COVID-19, four-step, questionnaire

Hai-Juan Zhu,1,2,&ast; Yan He,3,&ast; Sheng-You Wang,2 Bo Han,2 Ye Zhang1 1Department of Anesthesiology and Perioperative Medicine, The Second Hospital of Anhui Medical University, Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Department of Anesthesiology, Anhui Maternal and Child Health Care Hospital, Maternal and Child Health Care Hospital of Anhui Medical University, Hefei, 230001, People’s Republic of China; 3Department of Anesthesiology, Wannan Medical College, Wuhu, Anhui Province, 241002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye ZhangDepartment of Anesthesiology and Perioperative Medicine, The Second Hospital of Anhui Medical University, Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, 230601, People’s Republic of China, Tel +86-551-63869485; +86-13966768081, Fax +86 551-63869400, Email zhangy@ahmu.edu.cnPurpose: This study aimed to explore the efficacy and safety of chloroprocaine for activating labor analgesia and the optimal concentration compared to lidocaine.Patients and Methods: Ninety-six nulliparous parturients were randomly assigned to three groups: LD group, patients received the conventional initial dose of 6 mL of 1% lidocaine; CP1.5 group, patients received 6 mL of 1.5% chloroprocaine as the initial dose; and CP1.2 group, patients received 7.5 mL of 1.2% chloroprocaine as initial dose. Labor analgesia was maintained in all patients via a programmed intermittent epidural bolus (PIEB). The primary outcome was the analgesia onset time. Secondary outcomes included the visual analog scale (VAS) scores, the interval and duration of uterine contractions during the first 12 contractions, failure to reach adequate analgesia, labor and neonatal outcomes, maternal satisfaction and adverse effects.Results: Parturients in the CP1.5 and CP1.2 groups achieved a shorter onset time than those in the LD group (hazard ratio (HR) = 6.540; 95% confidence interval (CI), 3.503– 12.210; P < 0.001 and HR = 3.460; 95% CI, 1.905– 6.282; P < 0.001, respectively). The median time (95% CIs) to adequate analgesia was 12.0 (10.9– 13.1), 7.0 (6.2– 7.8) and 8.0 (7.5– 8.5) minutes in the LD, CP1.5 and CP1.2 groups, respectively. PIEB in the CP1.5 group was associated with lower VAS scores, patient-controlled epidural analgesia (PCEA) boluses, and analgesic consumption; a shorter time from epidural initiation to the first PCEA demand; and higher maternal satisfaction scores than the other two groups (P < 0.01). The interval and duration of uterine contractions, labor and newborn outcomes and adverse effects were comparable among the three groups.Conclusion: Chloroprocaine provided a faster onset of labor analgesia than lidocaine. Thus, 6 mL of 1.5% chloroprocaine might be a superior volume and concentration regimen to 7.5 mL of 1.2% chloroprocaine for activating labor analgesia.Clinical Trial Registration Statement: The study was registered prior to subject enrollment at www.chictr.org.cn (ChiCTR2100049113).Keywords: epidural, labor analgesia, onset time, activation, chloroprocaine, lidocaine

Boyue Han,1,2,&ast; Zhangyuan Gu,3,&ast; Zhebin Liu,1,2 Hong Ling1,2 1Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhebin Liu; Hong Ling, Email zhebinliu@shca.org.cn; linghong98@aliyun.comPurpose: The objective of this study was to compare the demographic characteristics, clinicopathological factors and survival outcomes between infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) using our single-center database.Methods: Seventeen thousand two hundred and three breast cancer patients were treated at Fudan University Shanghai Cancer Center (FUSCC) from January 2000 to December 2017. We identified 365 cases with ILC and 16,838 cases with IDC. The Pearson chi-square test was used to compare tumor characteristics, and the Kaplan–Meier methods were used to perform the survival analysis.Results: ILC had some distinctive characteristics from IDC such as older age (ranged from 61 to 80: ILC 26.8% vs IDC 19.9%, P < 0.001; over 80: ILC 1.6% vs IDC 0.8%, P < 0.001), larger tumor size (ranged from 2 to 5: ILC 45.2% vs IDC 37.1%, P = 0.011), much more hormone receptor expression (ILC 92.9% vs IDC 73.0%, P < 0.001), extremely less HER-2 expression (ILC 7.1% vs IDC 25.9%, P < 0.001). The overall survival and disease-free survival of ILC were worse than IDC (5-year OS, ILC 93.6% vs IDC 94.5%, P < 0.001; 5-year DFS, ILC 88.5% vs IDC 91.6%, P = 0.008). It was worth noting that the ILC patients had a worse overall survival than IDC patients after our propensity score matching study (P = 0.037). The univariate analysis concluded that positive HR (hormone receptor), high expression of Ki-67 and higher pathologic tumor stage were poor prognostic markers of ILC. Multivariate analysis demonstrated that tumor stage was a poor prognostic marker after adjustment for the effects of the above three factors. The most common primary site of metastasis was bone, but the proportion in the ILC group was much higher than that in the IDC group (56.25% vs 36.40%, P = 0.003).Conclusion: Compared with IDC, ILC survived worse and was more prone to bone metastasis. Therefore, a comprehensive understanding of ILC and specific treatments are needed for further research.Keywords: infiltrating lobular carcinoma, infiltrating ductal carcinoma, survival, prognosis

Hongtao Ding, Yong Hai, Yuzeng Liu, Li Guan, Aixing Pan, Xinuo Zhang, Bo Han, Yue Li, Peng Yin Department of Spine Surgery, Beijing Chao-Yang Hospital, Capital Medical University of China, Beijing, People’s Republic of ChinaCorrespondence: Yong Hai; Yuzeng Liu, Department of Spine Surgery, Beijing Chao-Yang Hospital, Capital Medical University of China, Beijing, People’s Republic of China, Tel +86 10-85231229 ; +86 13801221889 ; +86 13811552832, Email prof.haiyong@yahoo.com; yong.hai@ccmu.edu.cn; beijingspine2010@163.comStudy Design: This was a prospective randomized controlled trial study.Objective: To elucidate clinical and radiographic outcomes and complications of cortical bone trajectory (CBT)-screw fixation in patients with osteoporosis at 24-month follow-up and to compare the results with those after transforaminal lumbar interbody fusion (TLIF) using traditional pedicle screw (PS) fixation.Methods: We enrolled 124 patients and randomly assigned them to two groups (each group had 62 participants). The primary outcome was fusion rate. Secondary outcomes were VAS, Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) scores, operation duration, incision length, estimated blood loss, drainage volume, radiological outcomes, and complications.Results: At the 6- and 12-month follow-up points, similar fusion rates were observed based on CT scans in both groups (P=0.583 and 0.583). CBT provided significantly better short-term functional status at 3 months postoperation on ODI and JOA scores (P=0.012 and 0) and similar improvements in pain intensity and functional status at other follow-up points. In addition, CBT resulted in significantly better surgical characteristics. Notably, CBT fixation led to lower incidence of screw loosening (P=0.006).Conclusion: CBT-screw fixation for single-level lumbar fusion in patients with osteoporosis provided improvement in clinical symptoms comparable to that of TLIF using PS fixation. Significantly better lumbar stability was found in the CBT group. We suggest that CBT-screw fixation is a reasonable and superior alternative to PS in TLIF in osteoporosis.Trial Registration Number: ChiCTR1900022658.Date of Registration: April 20, 2019.Keywords: cortical bone-trajectory screw, pedicle screw, lumbar fusion, osteoporosis, randomized controlled trial