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Recent years have witnessed exponential growth in cardiac imaging technologies, allowing better visualization of complex cardiac anatomy and improved assessment of physiology. These advances have become increasingly important as more complex surgical and catheter-based procedures are evolving to address the needs of a growing congenital heart disease population. This state-of-the-art review presents advances in echocardiography, cardiac magnetic resonance, cardiac computed tomography, invasive angiography, 3-dimensional modeling, and digital twin technology. The paper also highlights the integration of artificial intelligence with imaging technology. While some techniques are in their infancy and need further refinement, others have found their way into clinical workflow at well-resourced centers. Studies to evaluate the clinical value and cost-effectiveness of these techniques are needed. For techniques that enhance the value of care for congenital heart disease patients, resources will need to be allocated for education and training to promote widespread implementation.

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

Dynamic Nuclear Polarization (DNP) is a powerful suite of techniques that deliver multifold signal enhancements in nuclear magnetic resonance (NMR) and MRI. The generated athermal spin states can also be exploited for quantum sensing and as probes for many-body physics. Typical DNP methods require the use of cryogens, large magnetic fields, and high power microwave excitation, which are expensive and unwieldy. Nanodiamond particles, rich in Nitrogen-Vacancy (NV) centers, have attracted attention as alternative DNP agents because they can potentially be optically hyperpolarized at room temperature. Here, unraveling new physics underlying an optical DNP mechanism first introduced by Ajoy et al. [Sci. Adv. 4, eaar5492 (2018)], we report the realization of a miniature "optical nanodiamond hyperpolarizer," where 13C nuclei within the diamond particles are hyperpolarized via the NV centers. The device occupies a compact footprint and operates at room temperature. Instrumental requirements are very modest: low polarizing fields, low optical and microwave irradiation powers, and convenient frequency ranges that enable miniaturization. We obtain the best reported optical 13C hyperpolarization in diamond particles exceeding 720 times of the thermal 7 T value (0.86% bulk polarization), corresponding to a ten-million-fold gain in averaging time to detect them by NMR. In addition, the hyperpolarization signal can be background-suppressed by over two-orders of magnitude, retained for multiple-minute long periods at low fields, and deployed efficiently even to 13C enriched particles. Besides applications in quantum sensing and bright-contrast MRI imaging, this work opens possibilities for low-cost room-temperature DNP platforms that relay the 13C polarization to liquids in contact with the high surface-area particles.

The origins of spin lifetimes in quantum systems is a matter of importance in several areas of quantum information. Spectrally mapping spin relaxation processes provides insight into their origin and motivates methods to mitigate them. In this paper, we map nuclear relaxation in a prototypical system of [Formula: see text] nuclei in diamond coupled to Nitrogen Vacancy (NV) centers over a wide field range (1 mT-7 T). Nuclear hyperpolarization through optically pumped NV electrons allows signal measurement savings exceeding million-fold over conventional methods. Through a systematic study with varying substitutional electron (P1 center) and [Formula: see text] concentrations, we identify the operational relaxation channels for the nuclei at different fields as well as the dominant role played by [Formula: see text] coupling to the interacting P1 electronic spin bath. These results motivate quantum control techniques for dissipation engineering to boost spin lifetimes in diamond, with applications including engineered quantum memories and hyperpolarized [Formula: see text] imaging.

The origins of spin lifetimes in quantum systems is a matter of importance in several areas of quantum information. Spectrally mapping spin relaxation processes provides insight into their origin and motivates methods to mitigate them. In this paper, we map nuclear relaxation in a prototypical system of [Formula: see text] nuclei in diamond coupled to Nitrogen Vacancy (NV) centers over a wide field range (1 mT-7 T). Nuclear hyperpolarization through optically pumped NV electrons allows signal measurement savings exceeding million-fold over conventional methods. Through a systematic study with varying substitutional electron (P1 center) and [Formula: see text] concentrations, we identify the operational relaxation channels for the nuclei at different fields as well as the dominant role played by [Formula: see text] coupling to the interacting P1 electronic spin bath. These results motivate quantum control techniques for dissipation engineering to boost spin lifetimes in diamond, with applications including engineered quantum memories and hyperpolarized [Formula: see text] imaging.

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