(1) Background: Exercise intolerance is a nearly ubiquitous consequence among patients who have undergone the total cavopulmonary connection (TCPC) or modified Fontan procedure; however, the specific factors influencing this condition-especially the impact of surgical timing and perioperative management-remain inadequately understood. (2) Methods: From a retrospective cohort of 255 TCPC patients, 99 who had undergone cardiopulmonary exercise testing (CPET) were included. Patients were stratified into a normal exercise tolerance group (ET group, peak VO2 ≥ 80% predicted, n = 45) and an exercise intolerance group (EI group, peak VO2 < 80% predicted, n = 54). Univariate and multivariate logistic regression analyses were performed to identify risk factors for decreased exercise tolerance. (3) Results: Patients in EI group were older at TCPC surgery (4.67 vs. 3.60 years, p = 0.004) and CPET (10.11 vs. 8.65 years, p = 0.01). They had longer operation time (312.14 vs. 267.53 min, p = 0.01), bypass time (122.26 vs. 103.59 min, p = 0.045), and higher rate of prolonged ICU stay (>3 days, 68.9% vs. 31.1%, p = 0.01). ROC analysis determined optimal surgical age cut-off at 3.81 years (AUC = 0.692, p = 0.001). Univariate analysis identified age ≥ 3.8 years, ICU stay > 3 days, longer operation/bypass times, and postoperative atrioventricular valve regurgitation as significant risk factors. Multivariate analysis confirmed age at TCPC ≥3.8 years (OR = 2.54, 95% CI: 1.01-6.42, p = 0.049) and ICU stay >3 days (OR = 2.61, 95% CI: 1.07-6.39, p = 0.04) as independent predictors of exercise intolerance. (4) Conclusions: The delayed completion (beyond 3.8 years of age) of TCPC procedure and the occurrence of early postoperative complications are associated with reduced long-term exercise capacity.

Background:Fulminant myocarditis (FM) in children can progress rapidly to cardiogenic shock, with high risk of mortality. Early recognition of prognostic markers is critical to guide timely escalation of circulatory support. This multicenter study sought to characterize clinical features and identify early predictors of in-hospital mortality in pediatric FM. Methods:We conducted a retrospective cohort study of patients <18 years with FM admitted to eight ECMO-capable pediatric intensive care units between January 2018 and August 2023. Clinical, biochemical, electrocardiographic, and echocardiographic variables were analyzed. Logistic regression was used to identify predictors of mortality, and receiver operating characteristic (ROC) curves were generated to assess discriminatory performance. Results:A total of 187 children were included; 157 (84.0%) required ECMO. In-hospital mortality was 16.6% (31/187). Univariate analysis identified elevated CK-MB, higher peak lactate, and ventricular tachycardia as associated with mortality. In multivariate analysis, peak lactate (AUC 0.791) and CK-MB (AUC 0.774) remained independent predictors. A combined model of peak lactate and ventricular tachycardia demonstrated moderate discrimination (AUC 0.772), whereas a composite model incorporating CK-MB, peak lactate, and ventricular tachycardia achieved the best predictive performance (AUC 0.815). Elevated lactate measured 12 h after initiation of extracorporeal membrane oxygenation or intensive conventional therapy further increased mortality risk (OR 1.219, 95% CI 1.004-1.481). Conclusion:Peak lactate, CK-MB, and ventricular tachycardia are early independent predictors of in-hospital mortality in pediatric FM. Persistent hyperlactatemia within 12 h of advanced support provides additional prognostic value and may assist clinicians in early risk stratification.

Macrophages possess the capacity to degrade extracellular matrix (ECM), but the specific roles of different cytoskeletal structures in controlling this process are incompletely understood. Here, we report that the inward flow of actin stress fibers delivers endocytosed ECM for lysosomal elimination, replenishing the pool of enzymes for extracellular ECM hydrolysis in actin-rich podosomes. Vimentin deficiency disrupted the balance between stress fibers and podosomes, impairing ECM degradation through integrin CD11b in THP-1 macrophages. In lung adenocarcinoma patient samples, M2-type macrophages exhibit a tighter podosome organization, surrounded by compact vimentin filaments, than M1-type. In vitro experiments verified that the invasion ability of A549 lung carcinoma cells was enhanced when accompanied by wild type, but not vimentin knockout M2-type THP-1, macrophages. Subcutaneous injections of macrophages and tumor cells in nude mice showed that vimentin in macrophages can reduce tumor collagen fibers. Together, our findings provide insights into the cytoskeletal dynamics governing macrophage ECM degradation.

Background:The package insert is a key reference and legal basis for clinical medication. However, in the field of rare diseases, advances in diagnosis and treatment often outpace updates to drug labels, resulting in widespread off-label drug use-a practice that is particularly common and often unavoidable in pediatric populations. Inappropriate off-label use, however, carries significant clinical and safety risks. Methods:Under the guidance of the Rare Disease Expert Committee of the Guangdong Pharmaceutical Association, a multidisciplinary panel of experts from clinical medicine, pharmacy, and related specialties developed the "Expert consensus on the off-label use of drugs for pediatric rare diseases in China (2025 edition)". The consensus integrates available evidence, clinical experience, evidence quality, and medication safety profiles, and was finalized after several rounds of rigorous iterative review. Results:The consensus presents 73 recommendations on off-label drug use across 21 rare diseases, organized in a tabular format for clarity and ease of reference. Conclusions:This consensus aims to standardize the management of off-label drug use in pediatric rare diseases. It supports medical institutions in developing off-label drug formularies, promotes rational drug use, and helps address the diagnostic and therapeutic needs of pediatric rare disease patients. Furthermore, it contributes to the establishment of a structured evaluation and management framework for off-label drug use in this clinical context.

BACKGROUND:We had reported that postoperative EEG background including sleep-wake cycle (SWC) and discharge (seizures, spikes/sharp waves) abnormalities were significantly correlated with adverse early outcomes in children after cardiac surgery. We aimed to analyze the relations between these EEG abnormalities and neurodevelopmental outcomes at about 2 years after cardiac surgery. METHODS:We enrolled 121 patients undergoing cardiac surgery at 3.3 months (0.03 ~ 28 months). EEG abnormalities described above during the first postoperative 48 h were evaluated. Griffiths Mental Development Scales-Chinese was used to evaluate the quotients of overall development and 5 subscales of the child's locomotor, language, personal-social, eye-hand coordination and performance skills at 16 ~ 31 months of age. RESULTS:EEG background abnormalities occurred in 59/121 (48.8%) patients and 33 (55.9%) unrecovered to normal by 48 h. Abnormal SWC occurred in 15 (12.4%) patients and 7 (5.8%) unrecovered to normal by 48 h. EEG seizures occurred in 11 (9.1%) patients with frontal lobe seizures in 4. Spikes/sharp waves occurred in 100 (82.6%). EEG background abnormalities, number of spikes/sharp waves and frontal lobe seizures were significantly associated with neurodevelopmental impairment at about 1 ~ 2 year after surgery (Ps ≤ 0.05). CONCLUSIONS:Most parameters of EEG abnormalities were significantly associated with neurodevelopmental impairment after cardiac surgery. IMPACT:Neurodevelopmental impairment in children with congenital heart disease remain poorly understood. Previous studies had reported that either EEG seizures or background abnormalities were associated with worse neurodevelopmental outcomes. Our present study showed that all the EEG background and discharge abnormalities including EEG background, seizures and spikes/sharp waves in the early postoperative period were significantly associated with neurodevelopmental impairment at about 1 ~ 2 years after cardiac surgery. Comprehensive evaluation of early postoperative EEG may provide further insights about postoperative brain injury, its relation with neurodevelopmental impairment, and guide to improve clinical management.

BACKGROUND:Extracorporeal membrane oxygenation (ECMO) is critical for congenital diaphragmatic hernia (CDH), who fails to achieve adequate oxygenation with conventional management. We aim to evaluate initial experiences with ECMO support in a tertiary women and children's medical center in mainland China.METHODS:We retrospectively reviewed the establishment of ECMO for CDH Program in our center and analysis of five CDH neonates, who underwent repair during ECMO between December 2016 and December 2018.RESULTS:The first ECMO for CDH Program in our institution was established and managed by a multidisciplinary team since December 2016. An alert of ECMO was prenatally created for moderate-severe pulmonary hypoplasia. Of sixteen admissions prenatally diagnosed moderate-severe CDH, eight neonates (50%) required ECMO but five (31%) received eventually. Veno-arterial ECMO was established from 3 hours to 41 hours of age (median 20 h). All the five underwent CDH repair after a stabilization period on ECMO, which ranged from 12 h to 122 h (median 58 h). There were no clotting complications, related to coagulating during CDH repair. Bleeding was the most common complication. Cannula malposition was detected in one case. Their median ECMO duration was 437 (range 85-946) hours. Neonatal survival was 80% (4/5) and 3 survived (60%) in the first three months of life.CONCLUSIONS:Multidisciplinary teamwork, precise prenatal evaluation and skillful cannulation assist the successful beginning of ECMO for CDH. Our preliminary results would encourage other institutions, whose ECMO is not well-established.

OBJECTIVES:Certain rhythmic arterial pressure waves in humans and animals have been noticed for over one century. We found the novel and slowest arterial pressure waves in children following surgical repair for CHD, and examined their characteristics and clinical implications. METHODS:We enrolled 212 children with 22 types of CHD within postoperative 48 h. We monitored haemodynamics (blood pressure, cardiac cycle efficiency, dP/dTmax), cerebral (ScO2), and renal (SrO2) oxygen saturation every 6 s. Electroencephalogram was continuously monitored. Mean blood flow velocity (Vm) of the middle cerebral artery was measured at 24 h. RESULTS:We found the waves with a frequency of ∼ 90 s immediately following surgical repair in 46 patients in 12 types of CHD (21.7%), being most prevalent in patients with aortic arch abnormalities (Aorta Group, n = 24, 42.3%) or ventricular septal defect (Ventricular Septal Defect Group, n = 12, 23.5%). In Aorta and Ventricular Septal Defect Groups, the occurrence of the waves was associated with lower blood pressures, dP/dTmax, cardiac cycle efficiency, ScO2, SrO2, Vm, worse electroencephalogram background abnormalities, higher number of electroencephalogram sharp waves, and serum lactate (Ps <0.0001-0.07), and were accompanied with fluctuations of ScO2 and SrO2 in 80.6% and 69.6% of patients, respectively. CONCLUSIONS:The waves observed in children following cardiovascular surgery are the slowest ever reported, occurring most frequently in patients with aortic arch abnormalities or ventricular septal defect. While the occurrence of the waves was associated with statistically worse and fluctuated ScO2 and SrO2, worse systemic haemodynamics, and electroencephalogram abnormalities, at present these waves have no known clinical relevance.

The second edition of the expert consensus on pediatric nutrition was formed based on a global update of pediatric nutrition guidelines or consensus worldwide, the management of congenital heart disease, and the results of multi-center clinical nutrition research for congenital heart disease following the first Chinese consensus edition of 2016. The consensus was also shaped by the results of three discussion sessions and two questionnaires conducted by the 13-member collaboration group. This process was informed by both clinical guidelines and expert consensus. The quality of literature, both in English and Chinese, and the level of recommendations were evaluated using the Grading of Recommendations Assessment, Development, and Evaluations (GRADE) system.

Background: Fulminant Myocarditis and Hemophagocytic Syndrome (HPS) are independent life-threatening diseases. HPS, however, is a rare complication of fulminant myocarditis. It is hard to diagnose HPS in patients with fulminant myocarditis early, but timely identification affects the clinical result. Here is the report of a female who has developed HPS complications after fulminant myocarditis.Case presentation: A 15-year-old Chinese female was admitted to the emergency department with a 3-day history of progressively severe chest pain and then a 1-day history of worsening heart failure needing the veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Interventions: V-A ECMO requiring continuous renal replacement therapy (CRRT) supported critically ill patients with heart failure. The vasoactive drug was used to improve cardiac function, maintain water, electrolyte, and acid-base balance, and nutritional supplements. High-dose methylprednisolone was administered for three days. Etoposide was given two times according to the treatment guideline, followed by cyclosporine. Diagnosis: The definitive diagnosis of the presented case was fulminant myocarditis complicated by hemophagocytic lymphohistiocytosis.Conclusions: For fulminant myocarditis patients suspected of HPS, the functional examination must be considered for early diagnosis. The timely administration of adequate corticosteroids and standard chemotherapy is essential to reduce the risk of HPS mortality.

BACKGROUND:We analysed the characteristics of abnormal electroencephalogram (EEG) patterns before, during, and 48 h after cardiac surgery in patients with heterogeneous congenital heart disease to assess their relationship to demographic and perioperative variables and to early patient outcomes. METHODS:In 437 patients enrolled in a single centre, EEG was evaluated for background (including sleep-wake cycle) and discharge (seizures, spikes/sharp waves, pathological delta brushes) abnormalities. Clinical data (arterial blood pressure, doses of inotropic drugs, and serum lactate concentrations) were recorded every 3 h. Postoperative brain MRI was performed before discharge. RESULTS:Preoperative, intraoperative, and postoperative EEG was monitored in 139, 215, and 437 patients, respectively. Patients with a degree of preoperative background abnormalities (n=40) had more severe intraoperative and postoperative EEG abnormalities (P<0.0001). Intraoperatively, 106/215 (49.3%) patients progressed into an isoelectric EEG. Longer durations of isoelectric EEG were associated with more severe postoperative EEG abnormalities and brain injury on MRI (Ps≤0.003). Postoperative background abnormalities occurred in 218/437 (49.9%) patients, and 119 (54.6%) of them had not recovered after surgery. Seizures occurred in 36/437 (8.2%) patients, spikes/sharp waves in 359/437 (82.2%), and pathological delta brushes in 9/437 (2.0%). Postoperative EEG abnormalities correlated with degree of brain injury on MRI (Ps≤0.02). Demographic and perioperative variables were significantly correlated with postoperative EEG abnormalities, which in turn correlated with adverse clinical outcomes. CONCLUSIONS:Perioperative EEG abnormalities occurred frequently and correlated with numerous demographic and perioperative variables and adversely correlated with postoperative EEG abnormalities and early outcomes. The relation of EEG background and discharge abnormalities with long-term neurodevelopmental outcomes remains to be explored.

Objective:To compare the predictive ability of SpO 2/FiO 2(S/F) and ROX index on the failure of high-flow nasal cannula(HFNC)therapy in children with acute respiratory failure after congenital heart disease surgery, and to identify the best cut-off point. Methods:Through a case-control study, the clinical data of 371 children with acute respiratory failure after congenital heart surgery treated with HFNC admitted to Guangzhou Women and Children′s Medical Center from January 2018 to December 2021 were retrospectively analyzed.The primary outcome was the need for re-intubation within 48 h after extubation of invasive ventilation.The ability of S/F and ROX index to predict HFNC failure was compared, and the optimal cut-off point was determined based on the area under the curve (AUC) of receiver operating characteristic curve.Results:A total of 371 children were included, of whom 27 (7.3%) eventually required mechanical ventilation within 48 h. The S/F prediction accuracy was highest after 6 h of HFNC treatment(AUC=0.712, 95% CI 0.599-0.825, P=0.001), and the best cut-off point for S/F was 178 mmHg(1 mmHg=0.133 kPa)(sensitivity 74.9%, specificity 69.6%). Whereas the prediction accuracy of the ROX index was highest after 12 hours of HFNC treatment, the AUC was 0.737(95% CI 0.623-0.851, P=0.002), and the best cut-off point of the ROX index was 5.865(sensitivity 72.4% specificity 66.7%). The difference in AUC between S/F after 6 h of HFNC treatment and ROX after 12 h was not statistically significant ( P=0.444), with higher sensitivity and specificity, and earlier prediction time(6 hours) in the former. Conclusion:Children with acute respiratory failure after congenital heart surgery have a strong predictive ability of S/F after 6 h of HFNC treatment, and the risk of HFNC treatment failure is higher in children with S/F <178 mmHg.

Objective Balloon angioplasty (BA) has been the treatment of choice for pulmonary artery stenosis (PAS) in children. There remains, however, a significant proportion of resistant lesions. The ultra-high pressure (UHP) balloons might be effective in a subset of these lesions. In this study, we analyzed the safety and efficacy with short- to mid-term follow-up results of UHP BA for PAS in children with congenital heart defects (CHD) in our center. Methods This is a retrospective cohort study in a single tertiary heart center. Children diagnosed with PAS associated with CHD were referred for UHP BA. All data with these children were collected for analysis with updated follow-up. Results A total of 37 UHP BAs were performed consecutively in 28 children. The success rate was 78.4%. A significantly (P = 0.005) larger ratio of the balloon to the minimal luminal diameter at the stenotic waist (balloon/waist ratio) was present in the success group (median 3.00, 1.64–8.33) compared to that in the failure group (median 1.94, 1.41 ± 4.00). Stepwise logistic regression analysis further identified that the balloon/waist ratio and the presence of therapeutic tears were two independent predictors of procedural success. The receiver operating characteristic curve revealed a cut-off value of 2.57 for the balloon/waist ratio to best differentiate success from failure cases. Signs of therapeutic tears were present in eight cases, all of whom were in the success group. Perioperative acute adverse events were recorded in 16 patients, including 11 pulmonary artery injuries, three pulmonary hemorrhages, and two pulmonary artery aneurysms. During a median follow-up period of 10.4 (0.1–21.0) months, nine cases experienced restenosis at a median time of 40 (4–325) days after angioplasty. Conclusions The UHP BA is safe and effective for the primary treatment of PAS in infants and children with CHD. The success rate is high with a low incidence of severe complications. The predictors of success are a larger balloon/waist ratio and the presence of therapeutic tears. The occurrence of restenosis during follow-up, however, remains a problem. A larger number of cases and longer periods of follow-up are needed for further study.

ObjectivesDysnatremia is a common electrolyte disturbance after cardiopulmonary bypass (CPB) surgery for congenital heart disease (CHD) and a known risk factor for adverse neurological events and clinical outcomes. The objective of this study was to evaluate the association of dysnatremia with worse abnormal EEG patterns, brain injuries detected by magnetic resonance imaging (MRI) and early adverse outcomes.MethodsWe monitored continuous EEG in 340 children during the initial 48 h following cardiac surgery. Demographics and clinical characteristics were recorded. Sodium concentrations were measured in the arterial blood gas analysis every 6 h. Hyponatremia and hypernatremia were classified by the average of sodium concentrations over 48 h. Postoperative cerebral MRI was performed before hospital discharge.ResultsIn our patient cohort, dysnatremia was present in 46 (13.5%) patients. Among them, hyponatremia occurred in 21 (6.2%) and hypernatremia in 25 (7.4%). When compared to patients with normonatremia, hyponatremia was not associated with EEG abnormalities and early adverse outcomes (Ps ≥ .14). In hypernatremia group, the CPB time was significantly longer and more frequent use of DHCA (Ps ≤ .049). After adjusting for time, CPB time and the use of DHCA, hypernatremia was significantly associated with worse EEG abnormalities (including background, seizures and pathological delta brushes), more severe brain injuries on MRI (Ps ≤ .04) and trended to be associated with longer postoperative mechanical ventilation time (P = .06).ConclusionHypernatremia and hyponatremia were common in children after cardiac surgery. Hypernatremia, but not hyponatremia, was significantly associated with worse EEG abnormalities and more severe brain injuries on MRI and extended postoperative mechanical ventilation time.

Objective:To summarize the results of surgical treatment for complete atrioventricular septal defect(CAVSD) in early and middle stages.Methods:147 children with CAVSD in Guangzhou Women and Children’s Medical Center from January 2010 to December 2019 were selected, Males 85, females 62, median age of surgery 5 months(1 months-10 years old), median body mass 5.5 kg(2.4-20.9 kg). Complete atrioventricular septal defect was diagnosed by ultrasonic cardiogram before surgery. All the children underwent atrial ventricular valve formation and underwent simultaneous repair.Outpatient follow-up was planned.Ultrasonic cardiogram and electrocardiogram were performed. SPSS 22 statistical software was used for data analysis.Results:All 147 CAVSD patients underwent one-time surgical correction.Early postoperative death occurred in 7 cases(4.76%). The causes of death were: 3 cases of pulmonary hypertension crisis, 3 cases of severe mitral insufficiency(MI), 1 case of postoperative malignant arrhythmia, and the rest of the children were cured and discharged. Permanent pacemaker was installed in 3 patients due to atrioventricular block(AVB). The follow-up time was 1-10 years old, and 2 patients died in late stage: 1 patient did not seek medical treatment in time due to infection, and 1 patient had unknown cause. Five patients underwent secondary surgery: 4 due to severe mitral/tricuspid insufficiency(MI/TI) and 1 due to delayed AVB. The mid-term follow-up showed 9 cases of severe MI and 4 cases of severe TI. Compared with children with surgical age<3 months and ≥3 months, there were statistically significant differences in postoperative ventilator-assisted ventilation time, severe MI before postoperative discharge and total mortality between the two groups( P<0.05). Mid-term follow-up results showed no difference between the two groups. There were statistically significant differences in surgical age, postoperative CICU stay time and total hospital stay between the children with trisomy 21-syndrome and those without trisomy 21-syndrome( P<0.05), and there was no difference between the two groups in mid-term follow-up results. Residual shunt of 1-3 mm VSD was found in 29 cases, 26 cases were closed during follow-up, and 3 cases had smaller residual shunt. Conclusion:Modified single patch technique treatment of CAVSD has good effect, low mortality and low re-operation rate. But age <3 months group, infant mortality was significantly increased, the duration of postoperative mechanical assisted ventilation was prolonged, and the proportion of early postoperative severe MI was high.Severe MI and TI is easy to occur after CAVSD, which requires long-term follow-up and timely treatment. The children with trisomy 21-syndrome were similar to those with normal chromosome except for longer stay in ICU and total hospital stay.

Background Disturbed cerebral autoregulation has been reported in children with congenital heart disease before and during cardiopulmonary bypass surgery, but not after. We sought to characterize the cerebral autoregulation status in the early postoperative period in relation to perioperative variables and brain injuries. Methods and Results A prospective and observational study was conducted in 80 patients in the first 48 hours following cardiac surgery. Cerebral oximetry/pressure index (COPI) was retrospectively calculated as a moving linear correlation coefficient between mean arterial blood pressure and cerebral oxygen saturation. Disturbed autoregulation was defined as COPI >0.3. Correlations of COPI with demographic and perioperative variables as well as brain injuries on electroencephalogram and magnetic resonance imaging and early outcomes were analyzed. Thirty-six (45%) patients had periods of abnormal COPI for 7.81 hours (3.38 hours) either at hypotension (median <45 mm Hg) or hypertension (median >90 mm Hg) or both. Overall, COPI became significantly lower over time, suggesting improved autoregulatory status during the 48 postoperative hours. All of the demographic and perioperative variables were significantly associated with COPI, which in turn was associated with the degree of brain injuries and early outcomes. Conclusions Children with congenital heart disease following cardiac surgery often have disturbed autoregulation. Cerebral autoregulation is at least partly the underlying mechanism of brain injury in those children. Careful clinical management to manipulate the related and modifiable factors, particularly arterial blood pressure, may help to maintain adequate cerebral perfusion and reduce brain injury early after cardiopulmonary bypass surgery. Further studies are warranted to determine the significance of impaired cerebral autoregulation in relation to long-term neurodevelopment outcomes.

A variety of intracellular bacteria modulate the host cytoskeleton to establish subcellular niches for replication. However, the role of intermediate filaments, which are crucial for mechanical strength and resilience of the cell, and in bacterial vacuole preservation remains unclear. Here, we show that Salmonella effector SopB reorganizes the vimentin network to form cage-like structures that surround Salmonella-containing vacuoles (SCVs). Genetic removal of vimentin markedly disrupts SCV organization, significantly reduces bacterial replication and cell death. Mechanistically, SopB uses its N-terminal Cdc42-binding domain to interact with and activate Cdc42 GTPase, which in turn recruits vimentin around SCVs. A high-content imaging-based screening identified that MEK1/2 inhibition led to vimentin dispersion. Our work therefore elucidates the signaling axis SopB-Cdc42-MEK1/2 as mobilizing host vimentin to maintain concrete SCVs and identifies a mechanism contributing to Salmonella replication. Importantly, Trametinib, a clinically-approved MEK1/2 inhibitor identified in the screen, displayed significant anti-infection efficacy against Salmonella both in vitro and in vivo, and may provide a therapeutic option for treating drug-tolerant salmonellosis.

Emerging pathogen infections, such as Zika virus (ZIKV), pose an increasing threat to human health, but the role of mechanobiological attributes of host cells during ZIKV infection is largely unknown. Here, we reveal that ZIKV infection leads to increased contractility of host cells. Importantly, we investigated whether host cell contractility contributes to ZIKV infection efficacy, from both the intracellular and extracellular perspective. By performing drug perturbation and gene editing experiments, we confirmed that disruption of contractile actomyosin compromises ZIKV infection efficiency, viral genome replication and viral particle production. By culturing on compliant matrix, we further demonstrate that a softer substrate, leading to less contractility of host cells, compromises ZIKV infection, which resembles the effects of disrupting intracellular actomyosin organization. Together, our work provides evidence to support a positive correlation between host cell contractility and ZIKV infection efficacy, thus unveiling an unprecedented layer of interplay between ZIKV and the host cell.

Background Congenital heart disease (CHD) is the most common congenital defect in neonates. Infants with CHD often have more nutritional difficulties, but currently, there is no unified Food Frequency Questionnaire (FFQ) for infants and young children aged 7–24 months in China. Therefore, we designed this study to assess the reliability and validity of the FFQ and feeding index for 7-to 24-month-old children after congenital heart disease surgery. Methods From July to October 2018, infants and young children aged 7–24 months after congenital heart disease surgery in Guangzhou were selected. Participants were categorized into two groups, in the first group ( n = 95), the FFQ was completed twice at intervals of 7–10 days to assess reproducibility. In the second group ( n = 98), participants accomplished both the FFQ and the 24-h diet records from 3 consecutive days to assess validity. The score of the Infant and Child Feeding Index (ICFI) and its qualified rate were caculated. Intraclass correlation coefficients (ICC) and Spearman correlation coefficient (SCC) were calculated for reliability and validity, respectively. Results The average intraclass correlation coefficients and spearman correlation coefficient of the FFQ were 0.536 and 0.318, all with statistical significance except the frequency of meat added. The ICFI of the first group was 8.61 (± 3.20), the qualified rate was 0.06% (6/95). The intraclass correlation coefficients of the ICFI ranged from 0.374 to 0.958; and the spearman correlation of the ICFI was -0.066 to -0.834. Conclusions The FFQ possesses satisfactory reliability and moderate validity. The reliability of the ICFI is acceptable, but the validity results are quite different, indicating that the questionnaire is limited in the evaluation of the ICFI.

Objective We aimed to assess the optimal frequency for changing single-use enteral delivery sets during postoperative enteral feeding in infants with congenital heart disease (CHD). Methods We enrolled 120 CHD infants who were fed using an enteral nutrition pump directly connected to a milk bottle with a single-use enteral delivery set in a four-arm randomized controlled trial (ChiCTR2000039544). Patients were randomized into four groups based on the replacement frequency of the enteral delivery set (6 h, 12 h, 18 h, and 24 h groups). The primary outcome was the percentage of contaminated enteral delivery sets (overgrowth of microbiota and colonization of pathogenic bacteria). Secondary outcomes included evidence of infection, gastrointestinal tolerance, intestinal microflora dysbiosis, and healthcare costs. Results The percentages of microbial overgrowth detected in the 6 h, 12 h, 18 h, and 24 h groups were 6.7%, 30.0%, 46.7%, and 80%, respectively (P < 0.001). Significant differences were observed between the 6 h and 18 h groups (P < 0.001), the 6 h and 24 h groups (P < 0.001), and the 18 h and 24 h groups (P = 0.007). Meanwhile, pathogenic bacterial colonization was detected in 0, 4, 6, and 11 delivery sets in the 6 h, 12 h, 18 h, and 24 h groups, respectively (P = 0.002). No difference in clinical symptoms was found among the four groups. The total cost per patient in the 12 h group and the 18 h group was 340.2 RMB and 226.8 RMB, respectively. Conclusion Taking into consideration both microbial overgrowth and cost-effectiveness, the results of this study indicate that for children receiving continuous enteral feeding following CHD surgery, the optimal frequency for changing the single-use enteral delivery set when formula reconstituted from powder is used is 18 hours.

Background & aims: Malnutrition is persistent in 50%-75% of children with congenital heart disease (CHD) after surgery, and early prediction is crucial for nutritional intervention. The aim of this study was to develop and validate machine learning (ML) models to predict the malnutrition status of children with CHD. We used explainable ML methods to provide insight into the model's predictions and outcomes. Methods: This prospective cohort study included consecutive children with CHD admitted to the hospital from December 2017 to May 2020. The cohort data were divided into the training and test data sets based on the follow-up time. The outcome of the study was CHD child malnutrition 1 year after surgery, the primary outcome was an underweight status, and the secondary outcomes were stunted and wasting status. We used five ML algorithms with multiple features to construct prediction models, and the performance of these ML models was measured by an area under the receiver operating characteristic curve (AUC) analysis. We also used the permutation importance and SHapley Additive exPlanations (SHAP) to determine the importance of the selected features and interpret the ML models. Results: We enrolled 536 children with CHD who underwent complete repair. The proportions of children with an underweight, stunted, or wasting status 1 year after surgery were 18.1% (97/536), 12.1% (65/536), and 17.5% (94/536), respectively. All patients contributed to the generation of 115 useable features, which allowed us to build models to predict malnutrition. Five prediction algorithms were used, and the XGBoost model achieved the greatest AUC in all outcomes. The results obtained from the permutation importance and SHAP analyses showed that the 1-month postoperative WAZ-score, discharge WAZ score and preoperative WAZ score were the top 3 important features in predicting an underweight status in the XGBoost algorithm. Regarding the stunted status, the top 3 important features were the 1-month postoperative HAZ score, discharge HAZ score, and aortic clamping time. Regarding the wasting status, the top 3 important features were the hospital length of stay, formula intake, and discharge WHZ-score. We also used a narrative case report as an example to describe the clinical manifestations and predicted the primary outcomes of two children. Conclusions: We developed an ML model (XGBoost) that provides accurate early predictions of malnutrition 1-year postoperatively in children with CHD. Because the ML model is explainable, it may better enable clinicians to better understand the reasoning underlying the outcome. Our study could aid in determining individual treatment and nutritional follow-up strategies for children with CHD. (C) 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.