Molecular imaging exhibits remarkable potential in immune cell tracking and advancing personalized clinical management, providing not only diagnostic and prognostic information but also enabling treatment efficacy quantification and therapeutic optimization. Macrophages play an essential role in the pathogenesis and progression of various cardiovascular diseases. This review comprehensively examines the characteristics of diverse molecular imaging modalities and their applications in macrophage imaging, encompassing major cardiovascular conditions, including atherosclerosis, myocardial infarction, and cardiac transplantation. We anticipate that advancements in novel noninvasive molecular imaging technologies for macrophages will ultimately facilitate clinical diagnosis, outcome prediction, treatment strategy formulation, and therapy response monitoring, thereby providing critical technical support for precision medicine practice.

The aim of this study was to establish body surface area (BSA)-dependent Z-score continuous reference intervals of coronary artery diameter measured by Echocardiography in healthy Chinese children population. Echocardiography measured 1221 healthy Chinese children’s coronary artery diameters, including the LMCA, LAD, LCX, RCA-pro, RCA-mid, and RCA-dis. We employed the LMS (Lambda-Mu-Sigma) method for the model and the Haycock equation for the BSA estimation. The coronary artery diameter Z-score continuous reference intervals were established using the LMS method and passed the internal and external validation. Conclusions: The study outcome provides BSA-dependent Z-score continuous reference intervals for the coronary artery diameters in healthy Chinese children. There is a web Z-score calculator with convenient application for clinicians and ultrasound doctors, facilitating subsequent external validations in a larger population.

Lymphatic malformations (LMs), particularly intractable subtypes with diffuse growth, pose significant clinical challenges due to incomplete resection, high recurrence rate, and adverse effects of conventional therapies such as sclerotherapy with bleomycin (BLM). Herein, we developed a multifunctional metal-polyphenol nanoplatform through hyaluronic acid (HA) matrix-regulated biomineralization of Fe3+ and polyphenolic tannic acid (TA), followed by loading with Bleomycin (Fe(Ⅲ)-TA/BLM@HA). This nanoassembly integrates photoacoustic (PA) imaging guidance, targeted delivery, and synergistic photothermal-sclerosis therapy against LMs. The Fe(Ⅲ)-TA/BLM@HA nanoassemblies can specifically target lymphatic endothelial cells (LECs) via HA-LYVE-1 interaction. The nanoassemblies exhibit excellent colloidal stability, remarkable photothermal conversion, and strong PA signals for real-time guided precise intralymphatic injection. Fe(Ⅲ)-TA/BLM@HA binds lymphatic endothelial cells (LECs) in a concentration-dependent manner, and exerts synergistic cytotoxicity, outperforming free BLM and Fe(Ⅲ)-TA@HA. In Balb/c mouse LM models, PA imaging visualized the spatiotemporal distribution of Fe(Ⅲ)-TA/BLM@HA post percutaneous injection. Notably, Fe(Ⅲ)-TA/BLM@HA plus 650 nm NIR laser raised lesion temperature by 13.6 °C, resolving LMs in 1-2 cycles vs 3-4 cycles for free BLM. This study confirms Fe(Ⅲ)-TA/BLM@HA as a safe, effective option for intractable LMs, with substantial translational potential for vascular anomaly management.

Tuberculous pleural effusion (TPE) is a prevalent form of extrapulmonary tuberculosis, and immune abnormalities play a crucial role in promoting its development. However, the dynamic changes and regulatory characteristics of immune cells during TPE progression remain incompletely understood. This study analyzed DNA methylation and transcriptome data from macrophages and CD4+ T cells from pleural lavage fluid of BCG-induced tuberculous pleurisy mouse models at specific time points (Days 0, 1, 7, and 14). The results revealed substantial alterations in DNA methylation patterns associated with inflammatory factors and interferon genes. Notably, macrophages exhibited the most pronounced differences in DNA methylation profiles on Day 1, while CD4+ T cells demonstrated gradual changes over time. The investigation further indicated that DNA methylation primarily regulated the differentiation of Th1, Th17, and Th22 cells but not Th9 cells. Additionally, single-cell RNA sequencing analysis revealed an increasing expression of C1q during infection, which was regulated by DNA methylation. Importantly, C1q+ and C1q- macrophages demonstrated distinct roles in modulating immune responses during infection. This research provides valuable insights into the DNA methylation profile of immune cells during Mycobacterium bovis infection-induced pleurisy in a mouse model, enhancing our understanding of the upstream regulatory mechanisms underlying immune response development in TPE.

Uhl’s anomaly is an exceedingly rare (fewer than 1 in 1,000,000 live births) and often fatal congenital heart disease characterized by the near-complete absence of the right ventricular (RV) myocardium. Although typically considered sporadic, we report a familial case suggesting an inherited etiology. A 12-year-old boy presented with exertional chest pain and a decade-long history of an abnormal cardiac silhouette. Comprehensive imaging revealed apical RV wall thinning, aneurysmal bulging with trabeculations, and severely impaired RV function, with a Tricuspid Annular Plane Systolic Excursion (TAPSE) of 10 mm and a Fractional Area Change (FAC) of 35%. These findings are consistent with a Uhl-like phenotype. Family screening identified similar, though less severe, RV structural anomalies in the patient’s father and sister, supporting an autosomal dominant inheritance pattern. Whole-exome sequencing revealed a rare heterozygous TTN variant (NM_003319:exon154:c.C56156T:p.T18719M) that co-segregated with the disease phenotype. The proband was treated with medical therapy targeting heart failure and remained clinically stable at discharge. To our knowledge, this is the first reported case of familial Uhl’s anomaly associated with a TTN gene mutation. These findings support a possible genetic basis for Uhl’s anomaly and highlight the importance of genetic screening in patients with familial cardiac structural abnormalities.

[This corrects the article DOI: 10.1016/j.heliyon.2024.e38035.].

Purpose:Immune microenvironment plays an important role in aortic dissection (AD). Therefore, novel immune biomarkers may facilitate AD prevention, diagnosis, and treatment. This study aimed at mining key immune-related genes and relevant mechanisms involved in AD pathogenesis.Patients and Methods:Key immune cells in AD were identified by ssGESA algorithm. Next, genes associated with key immune cells were screened by weighted gene coexpression network analysis (WGCNA). Then hub immune genes were picked from protein-protein interaction network of overlapped genes from differential expression and WGCNA analyses by cytohubba plug-in. Their diagnostic potential was evaluated in two independent cohorts from GEO database. In addition, the expressions of hub immune genes were determined by quantitative RT-PCR, immunohistochemistry, and Western blotting in dissected and normal aortic tissues.Results:Activated B cells, CD56dim natural killer cells, eosinophils, gamma delta T cells, immature B cells, natural killer cells and type 17 T helper cells were identified as key immune cells in AD. Thereafter, a gene module significantly correlated with key immune cells were found by WGCNA method. Subsequently, KDR, IGF1, NOS3, PECAM1, GAPDH, FLT1, DLL4, CDH5, VWF, and TEK were identified as hub immune cell related genes by PPI network analysis, which may be potential diagnostic markers for AD, as evidenced by ROC curves. Moreover, the decreased expression of VWF in AD was validated at both mRNA and protein levels, and its expression was significantly positive correlated with the marker of smooth muscle cells, ACTA2, in AD. Further immunofluorescent results showed that VWF was colocalized with ACTA2 in aortic tissues.Conclusion:We identified key immune cells and hub immune cell-related genes involved in AD. Moreover, we found that VWF was co-expressed with the smooth muscle cell marker ACTA2, indicating the important role of VWF in smooth muscle cell loss in AD pathogenesis.

Early detection and treatment of congenital heart disease (CHD) can significantly improve the prognosis of children. However, inexperienced sonographers often face difficulties in recognizing CHD through transthoracic echocardiogram (TTE) images. In this study, 2-dimensional (2D) and Doppler TTEs of children collected from 2 clinical groups from Beijing Children's Hospital between 2018 and 2022 were analyzed, including views of apical 4 chamber, subxiphoid long-axis view of 2 atria, parasternal long-axis view of the left ventricle, parasternal short-axis view of aorta, and suprasternal long-axis view. A deep learning (DL) framework was developed to identify cardiac views, integrate information from various views and modalities, visualize the high-risk region, and predict the probability of the subject being normal or having an atrial septal defect (ASD) or a ventricular septaldefect (VSD). A total of 1,932 children (1,255 healthy controls, 292 ASDs, and 385 VSDs) were collected from 2 clinical groups. For view classification, the DL model reached a mean [SD] accuracy of 0.989 [0.001]. For CHD screening, the model using both 2D and Doppler TTEs with 5 views achieved a mean [SD] area under the receiver operating characteristic curve (AUC) of 0.996 [0.000] and an accuracy of 0.994 [0.002] for within-center evaluation while reaching a mean [SD] AUC of 0.990 [0.003] and an accuracy of 0.993 [0.001] for cross-center test set. For the classification of healthy, ASD, and VSD, the model reached the mean [SD] accuracy of 0.991 [0.002] and 0.986 [0.001] for within- and cross-center evaluation, respectively. The DL models aggregating TTEs with more modalities and scanning views attained superior performance to approximate that of experienced sonographers. The incorporation of multiple views and modalities of TTEs in the model enables accurate identification of children with CHD in a noninvasive manner, suggesting the potential to enhance CHD detection performance and simplify the screening process.

OBJECTIVE:To explore the clinical features and genetic etiology of a child with SPONASTRIME dysplasia (SD).METHODS:A 9-month-old female who had presented at the Linyi People's Hospital in August 2022 for short stature was selected as the study subject. Clinical data of the child were collected, and whole exome sequencing (WES) was carried out. Sanger sequencing was used for validating the candidate variants.RESULTS:The child has manifested short stature, mid-face hypoplasia, joint laxity, internal knee rotation, irregularities in the metaphysis of long bones, and flat and concave lumbar vertebrae. WES revealed that she has harbored compound heterozygous variants of the TONSL gene, namely c.3088G>T (p.Glu1030*) and c.3053G>A (p.Arg1018His), which were inherited from her phenotypically normal parents. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.3088G>T variant was classified as likely pathogenic (PVS1+PM2_Supporting), whilst the c.3053G>A was classified as a variant of uncertain significance (PM2_Supporting+PM3+PP3).CONCLUSION:The c.3088G>T and c.3053G>A compound heterozygous variants of the TONSL gene probably underlay the pathogenesis in this patient. Above finding has facilitated the clinical diagnosis and genetic counseling for her family.

We present a case of a 13-day-old neonate with shock who was diagnosed with congenital variation of aortic arch and critical coarctation of aorta by cardiac point-of-care ultrasound. Finally, surgery confirmed the anomalies. This case demonstrates the value of cardiac point-of-care ultrasound in detecting congenital anomalies of great vessels in neonates and may be beneficial in clinical management.

Background:Studies focused on pregnant women with congenital heart disease (CHD)-associated pulmonary hypertension (PH) are scarce and limited by small sample sizes and single-center design. This study sought to describe the pregnancy outcomes in women with CHD with and without PH. Methods:Outcomes for pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. PH was diagnosed on the basis of echocardiogram or catheterization. The incidence of maternal death, cardiac complications, and obstetric and offspring complications was compared for women with CHD and no PH, mild, and moderate-to-severe PH. Results:A total of 2220 pregnant women with CHD had completed pregnancies. PH associated with CHD was identified in 729 women, including 398 with mild PH (right ventricle to right atrium gradient 30-50 mm Hg) and 331 with moderate-to-severe PH (right ventricle to right atrium gradient >50 mm Hg). Maternal mortality occurred in 1 (0.1%), 0, and 19 (5.7%) women with CHD and no, mild, or moderate-to-severe PH, respectively. Of the 729 patients with PH, 619 (85%) had CHD-associated pulmonary arterial hypertension, and 110 (15%) had other forms of PH. Overall, patients with mild PH had better maternal outcomes than those with moderate-to-severe PH, including the incidence of maternal mortality or heart failure (7.8% versus 39.6%; P<0.001), other cardiac complications (9.0% versus 32.3%; P<0.001), and obstetric complications (5.3% versus 15.7%; P<0.001). Brain natriuretic peptide >100 ng/L (odds ratio, 1.9 [95% CI, 1.0-3.4], P=0.04) and New York Heart Association class III to IV (odds ratio, 2.9 [95% CI, 1.6-5.3], P<0.001) were independently associated with adverse maternal cardiac events in pregnancy with PH, whereas follow-up with a multidisciplinary team (odds ratio, 0.4 [95% CI, 0.2-0.6], P<0.001) and strict antenatal supervision (odds ratio, 0.5 [95% CI, 0.3-0.7], P=0.001) were protective. Conclusions:Women with CHD-associated mild PH appear to have better outcomes compared with women with CHD-associated moderate-to-severe PH, and with event rates similar for most outcomes with women with CHD and no PH. Multimodality risk assessment, including PH severity, brain natriuretic peptide level, and New York Heart Association class, may be useful in risk stratification in pregnancy with PH. Follow-up with a multidisciplinary team and strict antenatal supervision during pregnancy may also help to mitigate the risk of adverse maternal cardiac events.

胜任力评价是胜任力导向医学教育重要的组成部分.在胜任力导向住院医师培训项目中,临床胜任力评估委员会(Clinical Competence Committees,CCCs)是其重要的组成部分.CCCs作为决策小组,定期(通常半年一次)根据住院医师的各种评估数据,遵循程序化评估原则,综合判断住院医师胜任力的成长情况,从而与住院医师项目主任一起,确定住院医师合理的里程碑评级、发展轨迹与进一步改进建议,确保住院医师规范化培训结业时,能够达到独立执业的要求.该文将借鉴国际CCCs经验与现况,介绍北京大学第一医院儿科住院医师项目CCCs的架构、职责和运行经验,讨论存在的问题,提出未来进一步改进的设想.

Background: The heterogeneous morphologic and functional expression of hypertrophic obstructive cardiomyopathy (HOCM) is evidenced by established imaging, multimodality imaging is essential for a comprehensive assessment but may remain uncertain. This study aimed to develop a patient-specific hemodynamics assessment with cardiac computed tomography angiography (CCTA) based computational fluid dynamics (CFD) and prove its usability in cohorts of HOCM patients.Methods: A retrospective study was performed on eight HOCM patients with septal myectomy who had both preoperative and postoperative CCTA as well as transthoracic echocardiography (TTE). The three-dimensional models were reconstructed from CCTA data, following which patient-specific CFD simulations were performed to estimate the blood velocity, pressure gradient, and wall shear stress. The simulation output was compared with TTE. Based on CFD simulations, retrospective and blinded virtual myectomy was also performed, to predict the minimum resected volume for improving obstruction in patients.Result: The complex HOCM anatomy was successfully reconstructed for all 8 patients. The CFD simulation accurately assessed the pressure gradient, flow velocity. There was a good correlation between the peak pressure gradient measured by CFD and TTE in the pre-and post-operative assessments (r = 0.87 and 0.84, respectively), and the flow velocity (r = 0.87 and 0.90, respectively). The volumes of minimal resection myocardium predicted by CFD and virtual myectomy were consistent with the actual resection volumes. Conclusion: CCTA-based CFD for HOCM patients may play a unique role in the assessment of patient-specific morphology and hemodynamics. Combination with virtual myectomy might allow for optimizing therapy planning in septal myectomy.Clinical perspective: CFD based CCTA may emerge as a complement to established imaging strategies, with accurate three-dimensional reconstruction and hemodynamic simulation of the left ventricle in this retrospective study. Combined with virtual myectomy, CFD simulation might allow for predicting the volume of resected myocardium for septal myectomy. Moving forward, this technology may be used by clinicians to better assess the conditions of HOCM patients, and guide the extent and depth of resection during septal myectomy. Therefore, further prospective clinical evaluation is clearly warranted.

目的 在综合医院儿科门诊的实习生带教中,探索案例教学法的应用效果.方法 选择2018年1月—2019年10月来本院儿科进行本科实习的学生126名,通过随机分配方法,分为对照组61名和观察组65名学生.对照组学生采用传统带教方法(普通授课法),观察组选择案例为基础的方法,联合授课法带教.比较两组实习生的临床考核成绩,包括医德医风、临床思维、理论、临床技能操作、临床病历书写等方面的成绩,并进行无记名问卷调查,了解学生对带教方法的满意度.结果 临床考核成绩观察组在临床思维、技能操作、病历书写方面均优于对照组,观察组理论考试成绩分数(88.05±6.26)分,高于对照组的(80.71±6.92)分,且观察组对于带教方法的满意度高达93.8％,高于对照组77.0％,差异均有统计学意义(P<0.05).结论 以案例为基础的教学法可提高儿科门诊实习的效果,且深受欢迎,能提高综合医院儿科门诊实习生的带教质量,提高学生的关爱儿童心理、学习能力、疾病综合分析能力以及沟通技巧和表达能力,能夯实基础知识,更好的理论联系实践.

Background The long-term protective effect of hepatitis B vaccine (HepB), the incidence of hepatitis B virus (HBV) vaccine breakthrough infections (VBIs), and whether a booster HepB is necessary remain to be clarified in children born to mothers with chronic HBV infection. Methods Based on a long-term follow-up prospective cohort of 1177 hepatitis B surface antigen (HBsAg)-positive mothers and their paired infants which was established from 2009 to 2011, total 454 children with immunoprophylaxis success as determined by postvaccination serologic testing (PVST) at 7 months old were included in this study. Among the 454 children, 246 never had a booster HepB, and 208 children received a booster HepB from 1 to 5 years of age. Multivariate logistic regression analysis was used to analyse the risk factors for HBV VBIs. Results The hepatitis B surface antibody (anti-HBs) levels declined sharply from 7 months to 2 years old, and the anti-HBs seronegative rate in the children increased significantly from 2 years old. A total of 31 (6.83%) of the 454 children experienced VBIs, of which 7 had overt and 7 had occult HBV infections. Notably, 14 (45.16%) of the 31 children with VBIs were diagnosed at 2 years old, and all of them had anti-HBs positivity (> 10 mIU/mL) at 1 year old. Maternal hepatitis B e antigen (HBeAg) positivity, higher HBV DNA and HBsAg levels, lower initial infant anti-HBs levels and not receiving a booster HepB were independent risk factors for VBIs. The incidence of VBIs was significantly lower in children with a booster HepB than in nonboosted children (0.50 vs. 11.90%, P < 0.001), and none of the boosted children developed overt or occult HBV infection. The anti-HBs levels of 76.67% for the children with VBIs in the nonboosted group indicated positivity before VBIs was detected. Conclusions After the primary full immunization with HepB, children born to mothers with chronic HBV infection, especially the children with maternal HBeAg positivity, high HBV DNA levels, high HBsAg levels and/or low initial infant anti-HBs levels, were at a high risk of VBIs, and a booster HepB for these children before 2 years old, instead of when their anti-HBs level is < 10 mIU/mL, could reduce the incidence of VBIs.