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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.

Xiaoxi Fan,1,2,&ast; Wenli Zhang,2,3,&ast; Ruihan Zheng,1 Yucong Zhang,1 Xianhui Lai,4 Jibo Han,5 Zimin Fang,1 Bingjiang Han,5 Weijian Huang,1 Bozhi Ye,1,2 Shanshan Dai1,6 1The Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China; 2The Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Cardiology, Yuhuan County People’s Hospital of Zhejiang Province, Taizhou, People’s Republic of China; 5Department of Cardiology, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 6The Key Laboratory of Emergency and Disaster Medicine of Wenzhou, Department of Emergency, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanshan Dai; Bozhi Ye, Email shanshandai137@163.com; fredye2012@163.comAim: Hypertensive nephropathy is a common complication of hypertension. However, no effective measures are currently available to prevent the progression of renal insufficiency. Gasdermin D (GSDMD) is a crucial mediator of pyroptosis that induces an excessive inflammatory response. In the present study, we aimed to determine the effect of GSDMD on the pathogenesis of hypertensive nephropathy, which may provide new insights into the treatment of hypertensive nephropathy.Methods: C57BL/6 (wild-type, WT) and Gsdmd knockout (Gsdmd−/−) mice were subcutaneously infused with angiotensin II (Ang II) via osmotic mini-pumps to establish a hypertensive renal injury model. Recombinant adeno-associated virus serotype 9 (AAV9) carrying GSDMD cDNA was used to overexpress GSDMD. Renal function biomarkers, histopathological changes, and inflammation and fibrosis indices were assessed. Transcriptome sequencing (RNA-seq) and cleavage under targets and mentation (CUT & Tag) experiments were performed to identify the downstream pathogenic mechanisms of GSDMD in hypertensive nephropathy.Results: GSDMD was activated in the kidneys of mice induced by Ang II (P < 0.001). This activation was primarily observed in the renal tubular epithelial cells (P < 0.0001). GSDMD deficiency attenuated renal injury and fibrosis induced by Ang II (P < 0.0001), whereas Gsdmd overexpression promoted renal injury and fibrosis (P < 0.01). Mechanistically, GSDMD increased Ang II–induced GATA binding protein 2 (GATA2) transcription factor expression (P < 0.01). GATA2 also bound to the aquaporin 4 (Aqp4) promoter sequence and facilitated Aqp4 transcription (P < 0.001), leading to renal injury and fibrosis. Moreover, treatment with GI-Y1, an inhibitor of GSDMD, alleviated Ang II–induced renal injury and fibrosis (P < 0.01).Conclusion: GSDMD plays an important role in the development of hypertensive nephropathy. Targeting GSDMD may be a therapeutic strategy for the treatment of hypertensive nephropathy. Keywords: gasdermin D, hypertensive nephropathy, pyroptosis, angiotensin II, aquaporin 4, GATA binding protein 2

Chang-Sheng Ma,1,2,&ast; Ya-Ping Ma,1,3,&ast; Bo Han,1,2,&ast; 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&ast;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,&ast; Ai-ting Lu,1,2,&ast; Xiaowei Mao,1,&ast; 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&ast;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

Background Microorganisms have been used to decompose cellulolytic waste in agriculture for the past many years. However, much of the cellulosic waste including coffee exocarps which are wastes from raw coffee process in Vietnam is often disposed of by biomass burning and discharged into the environment in developing countries, thus causing considerable environmental pollution. Besides, these organic wastes decompose slowly when they are used to produce compost in ordinary conditions. Therefore, using microorganisms to manufacture natural compost from coffee exocarps is considered a useful and environmentally sound alternative. Results In the course of screening for cellulose-degrading bacteria and actinomycetes, 38 bacterial strains and 18 actinomycetes strains were isolated from 15 coffee exocarp samples in coffee-producing areas in Vietnam. The isolates grew with cellulose as the sole sources of carbon and energy. The results of cellulolytic activity determinations were that 13 bacteria ([34 %) and 10 actinomycetes ([56 %) showed enzymatic degradation of cellulose. The isolated strains were identified as belonging to members of the Genus Streptomyces, Actinomycetes, Clostridium and Bacillus. Cellulose-degrading ability of the isolated microorganism strains was mostly 96 % with filter paper; however, for coffee exocarps, it was considerably lower, only about 37 % of the cellulose was digested after 30 days of incubation to coffee exocarps. A medium containing rice husk powder and lactose with pH 7.0 positively affected the cellulolytic activity of A1 and A9 strains. Cellulolytic activity of B4 and B7 strains was also most appropriate when the medium contained peptone, CMC, and with a pH 7.0. Optimal temperature for actinomycetes and bacteria isolate strains was at 25â35 C. Conclusion We concluded that the cellulolytic bacteria and actinomycete could be isolated from coffee exocarps which are normally discharged into the environment in coffee-producing areas. These microorganisms could be used to decompose cellulosic wastes, making compost from coffee exocarps, which could be applied in agriculture in Vietnam and other developing countries.

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.

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