Objective:To summarize the clinical manifestations, experiences in diagnosis and treatment of arrhythmogenic cardiomyopathy (ACM) in children.Methods:A retrospective analysis of the clinical manifestations, laboratory tests, radiological features, treatment and follow-up results was conducted in 11 children diagnosed with ACM at the center of congenital heart disease, Beijing anzhen hospital from May 2010 to March 2022.Results:A total of 11 patients aged 2 to 16 years, including 5 males and 6 females were diagnosed with ACM. The clinical manifestations included decreased activity tolerance (7 patients), heart failure (4 patients), syncope or sudden death (3 patients), palpitation (3 patients), and chest tightness and pain (3 patients). Electrocardiogram showed right bundle branch block in 9 cases, paroxysmal ventricular tachycardia in 4 cases, frequent premature ventricular contraction in 4 cases, ventricular pre-excitation in 1 case, left bundle branch block in 1 case, and first degree atrioventricular block in 2 cases. Echocardiography showed enlargement of the right heart, widening of the right ventricular outflow tract, and thinning and bulging of the local wall of the right ventricle with reduced pulsation. Ventricular thrombosis was found in 2 cases. Six children underwent cardiac magnetic resonance imaging, which mainly showed severe enlargement of the right heart, thin free wall of the right ventricle, decreased right heart function, enhanced right ventricular myocardium, and formation of right ventricular aneurysm. Two children underwent myocardial biopsy examination and presented with typical pathological changes of ACM. Genetic tests in five patients revealed DSG2 gene mutation in 2 cases, PKP2 gene mutation in 2 cases, and MYH6 gene mutation in 1 case. All patients received anti heart failure treatment and antiarrhythmic drugs. Two children received anticoagulant treatment due to ventricular thrombosis. Radiofrequency ablation was performed in 2 patients. Glenn procedure was performed in 4 patients, and heart transplantation was performed in 1 patient due to progressive heart failure. The follow-up period ranged from 6 months to 12 years. Two cases died of right heart failure, 6 cases had different degrees of heart failure, 1 case had intermittent chest tightness and pain, and 2 cases were stable.Conclusions:ACM is a progressive genetic cardiomyopathy characterized by decreased activity tolerance, cardiac failure and arrhythmia in pediatric patients. The diagnosis is mainly based on clinical manifestations, electrocardiogram, cardiac imaging changes, and genetic testing. Early detection, diagnosis, and personalized treatment can improve the prognosis.

Objective:To analyze the clinical characteristics, treatment, and outcomes of children with complete left bundle branch block (CLBBB) mediated by maternal autoantibodies.Methods:A retrospective analysis was conducted on nine children diagnosed with maternal autoantibody-mediated CLBBB, treated at Beijing Anzhen Hospital and Fujian Provincial Hospital from March 2015 to August 2023. Their clinical characteristics, electrocardiographic and echocardiographic findings before and after treatment were reviewed. Paired sample t-test was used for inter-group comparison. Results:Among the mothers, 6 had positive antinuclear antibodies (ANA), 5 had anti-Sjogren syndrome antigen A antibodies, and 3 had anti-Ro-52 antibodies. The cohort included one female and eight male children, diagnosed with CLBBB at the age of 1 (2, 13) months. The positive autoantibodies in the infants, consisted with maternal antibodies, were detected within the first 3 months of life among 3 cases. Treatments included anti-heart failure therapy, myocardial nutritional support, intravenous immunoglobulin (IVIG) and glucocorticoids. Before treatment, the levels of troponin I (0.175 (0.060, 10.270) μg/L) and N-terminal pro-B-type natriuretic peptide (420 (327, 12 865) ng/L) were elevated, which normalized in most cases after treatment. Post-treatment, the QRS duration significantly shortened compared to pre-treatment ((137±15) vs.(169±25) ms, t=3.76, P<0.001), and the QTc interval significantly decreased ((433±41) vs. (514±27) ms, t=4.95, P=0.001). Before treatment, varying degrees of mitral and tricuspid regurgitation and marked interventricular septal dyskinesia were observed in echocardiography. After treatment, valve regurgitation and ventricular septum motion significantly improved, with a marked increase in left ventricular ejection fraction ((51±13)% vs. (27±6)%, t=-6.66, P<0.001). Conclusions:Maternal autoantibody-mediated CLBBB in children presents with chronic heart failure in infancy. Early treatment with anti-heart failure medications, IVIG and glucocorticoids can improve clinical symptoms.

Objective To observe value of echocardiographic evaluation on infants with pulmonary atresia and intact ventricular septum(PA/IVS)for surgical decision and post operation right ventricle(RV)development.Methods Forty-six PA/IVS infants who underwent pulmonary valve(PV)annuloplasty(group A,n=25),PV annuloplasty and RV outflow tract reconstruction with/without additional systemic-to-pulmonary artery shunt(group B,n=15),and systemic-to-pulmonary artery shunt and atrial septal enlargement(group C,n=6)were retrospectively enrolled.Status of RV developments were compared among groups before operation as well as 1 and 6 months after operation.Results The presentation age in group B was younger than,while in group C was older than that in group A(both P＜0.05).Before operation,tricuspid valve(TV)annulus diameter,TV annulus Z-score and TV/mitral valve(MV)annulus ratio in groups B and C were both smaller than those in group A(all P＜0.05),whereas RV/left ventricle(LV)longitudinal diameter ratio in group B was larger and PV annulus Z-score in group C was smaller than those in group A(both P＜0.05).Meanwhile,preoperative PV annulus Z-score and RV/LV longitudinal diameter ratio in group B were both larger than those in group C(both P＜0.05).One month after operations,TV annulus diameter,TV annulus Z-score and TV/MV annulus ratio in group B and C,as well as PV annulus diameter,PV annulus Z-score and RV/LV longitudinal diameter ratio in group C were all smaller than those in group A(all P＜0.05),while PV annulus diameter,PV annulus Z-score and RV/LV longitudinal diameter ratio in group C were all smaller than those in group B(all P＜0.05).Six months after operations,no significant difference of TV annulus diameter,PV annulus diameter,PV annulus Z-score,TV/MV annulus ratio nor RV/LV longitudinal diameter ratio was found between group A and B(all P＞0.05),but the above indexes in group C were all lower than those in group A and B(all P＜0.05).Besides,no significant difference of TV annulus Z-score was found between group A and B(P＞0.05),which were lower in group C than in group A(P＜0.05).Conclusion Echocardiographic evaluation on PA/IVS infants was helpful to establishment of forward blood flow from RV to pulmonary arteries in time,hence promoting RV development.

Objective:To investigate the role of cardiopulmonary combined diaphragm ultrasound in predicting the weaning from mechanical ventilation in patients of total anomalous pulmonary venous connection after cardiac surgery in children.Methods:105 patients with TAPVC after cardiac surgery were included and admitted to Beijing Anzhen Hospital from January 2020 to September 2023, and median age was 6 months, including 61 males and 44 females. Echocardiography was routinely performed before surgery, clinical indicators such as age, weight, sex, cardiopulmonary bypass, activated coagulation time were recorded at the same time. And bedside cardiopulmonary combined diaphragm ultrasound was performed after the patient successfully passed the spontaneous breathing test. Ultrasound measurements include atrial septal defect diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction, right ventricular area change fraction, tricuspid annular plane systolic excursion, pulmonary venous diameter, pulmonary ultrasound score, and diaphragm thickening fraction, According to whether the offline was successful, patients were divided into two groups: successful extubation group (78 cases) and extubation failure group (27 cases). The t-test was used for mean comparison. The Mann- Whitney U test was used for median comparison. Pearson χ2 test was used for counting data. Univariate analysis was used to determine the parameters with significant statistical differences in predicted weaning failure, and multivariate logistic regression analysis was included to find independent prediction parameters. The statistical parameters between the two groups were used to draw the receiver operating characteristic curves, and then the ROC curves were comprehensively plotted by the combining indexes. Results:The age, weight, left ventricular diastolic diameter, and atrial septal defect diameter of the the failure group were smaller than those in the weaning group, and the differences were statistically significant ( P<0.05). There were statistically significant differences in cardiopulmonary bypass and activated coagulation time in the weaning failure group ( P<0.05). There were no significant differences in gender and preoperative pulmonary venous flow velocity between the two groups ( P>0.05). Multivariate logistic regression analysis showed that postoperative left ventricular ejection fraction, pulmonary venous flow velocity, and pulmonary ultrasound score diaphragm thickening fraction were significantly correlated with weaning failure ( P<0.05), area under the ROC curve( AUC) were 0.736, 0.761, 0.868 and 0.829( P<0.05), and the optimal cut-off values were 0.50, 160 cm/s, 14 scores and 27% respectively. The AUC of cardiopulmonary combined diaphragm with ultrasound index for predicting weaning failure was 0.966, the sensitivity was 96.3%, and the specificity was 89.9%, which was significantly higher than that of other ultrasound indicators. Conclusion:Bedside cardiopulmonary combined diaphragm ultrasound has important clinical value in predicting ventilator evacuation of patients after total anomalous pulmonary venous connection, and its accuracy is higher than that of single-organ ultrasound.

Abstract: Objective To investigate the expression of T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) on the surface of T cells in patients with brucellosis (Bm), as well as the expression of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β) in serum, and to analyze the differential expression of these indicators in patients with acute and chronic brucellosis, in order to provide new approaches for the differential diagnosis of acute and chronic brucellosis. Methods A total of 56 patients diagnosed with brucellosis at the First Affiliated Hospital of Xinjiang Medical University from April 2023 to September 2023 were selected, including 31 patients in the acute phase and 25 patients in the chronic phase. Additionally, 35 healthy individuals underwent routine physical examinations within the same period served as healthy controls. Flow cytometry was used to detect and compare Tim-3 levels on the CD4+ T cells' surface among the groups. Levels of serum IL-10 and TGF-β were measured and compared using CBA and ELISA, respectively, and the relationship of these factors with the staging of brucellosis patients was analyzed. Results The proportions of Tim-3+CD3+CD4+T cells in the control group, acute group, and chronic group were (2.56±1.25)%, (5.14±1.98)%, and (13.66±2.66)%, respectively. The Tim-3 levels in the patients with brucellosis were higher than those in the healthy control group, with the chronic group showing even higher levels, and these differences were statistically significant (P<0.05). The levels of IL-10 and TGF in the patient group were higher than those in the healthy control group, with the chronic group exhibiting significantly higher levels of IL-10 and TGF-β than the acute group, also presenting statistically significant differences (P<0.05). The areas under the ROC curve for predicting chronic brucellosis with Tim-3, IL-10, and TGF-β scores were 0.876, 0.865, and 0.663, respectively. Conclusions There are certain differences in the expression of Tim-3, serum IL-10, and TGF-β among patients with brucellosis, with high expression indicating a potential transition to the chronic phase of the disease. Tim-3 has shown the best diagnostic performance. Therefore, as a diagnostic indicator, Tim-3 may provide new ideas and strategies for the treatment and differential diagnosis of brucellosis.

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*

Objective:To investigate whether stress hyperglycemia (SH) is an independent risk factor for the occurrence and mortality of sepsis-associated encephalopathy (SAE).Methods:From August 2016 to October 2021, sepsis patients admitted to the ICU of Guangdong Provincial People's Hospital were selected as the study subjects. According to whether they developed to SH (RBG>11.1 mmol/L) within 7 days of enrollment, the pat ients were divided into the SH group and the non-SH group for analysis. Logistic regression was used to analyze whether SH was an independent risk factor for SAE occurrence, and ROC curve was used to analyze the predictive value of SH to SAE. Kaplan-Meier curve was used to compare the 90-day survival of SAE patients with or without SH. Cox regression analysis was used to analyze the risk factors of 28-day and 90-day death in SAE patients.Results:A total of 183 sepsis patients were included, including 62 patients in the SH group and 121 in the non-SH group. Logistic regression analysis demonstrated that SH was an independent risk factor for SAE ( OR=4.452, 95% CI: 2.021-9.808, P <0.001). ROC curve demonstrated that SH could accurately predict SAE (AUC=0.831; Sensitivity=78.4%; Specificity=76.8%; and Yoden index=0.553). Kaplan-Meier curve demonstrated that the 90-day survival of SAE patients with SH significantly declined (log-rank test: P<0.01). Cox regression analysis suggested that SH was a risk factor for death at day 28 and day 90 in SAE patients (28 d, HR=2.272, 95% CI: 1.212-4.260, P=0.010; 90 d, HR=2.456, 95% CI: 1.400-4.306, P<0.01). Conclusions:SH is an independent risk factor for SAE and can predict SAE occurrence. SH significantly reduces 90-day survival and increase mortality at 28 and 90 days in SAE patients.

Objective:To investigate the clinical characteristics and pregnancy outcomes in pregnant women with left ventricular non-compaction (LVNC).Methods:The clinical data of seven pregnant women with LVNC from January 2011 to December 2021 in Beijing Anzhen Hospital,Capital Medical University were retrospectively analyzed, including age, gestational age of symptom first occured, LVNC history, clinical symptoms, New York Heart Association (NYHA) cardiac function class, echocardiography, blood brain natriuretic peptide (BNP), treatment and the maternal and fetal outcomes.Results:Five cases were diagnosed before pregnancy, of which there were three women with medication; one case diagnosed in the month of pregnancy; one case diagnosed at 36 weeks of gestation. NYHA cardiac function was grade Ⅰ in four cases and grade Ⅱ in three cases before or during the first trimester of pregnancy. Of the five pregnant women who underwent echocardiography, there were one case of left ventricular insufficiency, three cases of mild left ventricular dysfunction and one case of normal left ventricular function before or during the first trimester of pregnancy. Of the five pregnant women to the second and third trimester of pregnancy, there were one case of grade Ⅳ, one case of grade Ⅲ, two cases of grade Ⅱ-Ⅲ and one case of grade Ⅱ in NYHA class ; three cases of left ventricular insufficiency, two cases of normal left ventricular function by echocardiography four cases had cardiac symptoms at 15-24 weeks of gestation and were treated with medication. In four cases, blood BNP increased to 214-1 197 ng/L during pregnancy, and were 89-106 ng/L after termination of pregnancy. There were 4 cases with arrhythmia. Indications for termination of pregnancy: LVNC complicated with heart failure in two cases, LVNC complicated with decreased cardiac function and threatened preterm birth in one case, complicated with pregnancy at full term in two cases, LVNC complicated with severe pulmonary hypertension in one case, and left ventricular dysfunction in one case. Cesarean section in four cases in the third-trimester, in one case in the second-trimester, and forceps curettage in two cases were taken. Two full-term infants,two preterm infants were born without LVNC.Conclusions:Women diagnosed with LVNC and low left ventricular ejection fraction before pregnancy are more prone to decreased cardiac function during pregnancy. Carrying out pregnancy risk assessment and strengthening the multi-disciplinary team management of high risk factors in pregnancy are conducive to achieve good pregnancy outcomes.

Objective:To investigate the short-term and medium-term changes of the left ventricular ejection fraction (LVEF) and the predictive value of relevant electrocardiogram (ECG) indexes in children with dilated cardiomyopathy (DCM) complicated with complete left bundle branch block (CLBBB).Methods:Children clinically diagnosed with DCM in the Department of Heart Center, Women and Children′s Hospital, Qingdao University and Beijing Anzhen Hospital, Capital Medical University between November 2011 and August 2020 were retrospectively recruited.According to the combination of CLBBB, they were divided into CLBBB group and non-CLBBB group.Echocardiogram and ECG were regularly performed.Short-term and medium-term changes of LVEF based on the 1-5-year follow-up data were compared between groups.COX proportional hazards model and Kaplan-Meier multiplicative limit method were used to analyze the predictive value of ECG indexes of LVEF changes in children with DCM combined with CLBBB.Results:Ninety-four children with DCM were enrolled, including 35 cases in CLBBB group and 59 cases in non-CLBBB group.There was no difference in baseline LVEF between groups.However, significant differences were found in QRS duration, corre-cted QT interval(QTc), R peak time in lead V 5 (T V5R) and QRS notching or slurring between groups ( P<0.05). LVEF of all children showed an upward trend within one year after onset, while the Z value of eft ventricular end diastolic diameter(LVEDd) showed a downward trend, and the two indexes tended to be stable within 1 - 5 years.The Z value of LVEDd in CLBBB group was significantly higher than that of non-CLBBB group, while LVEF was significantly lower (all P<0.05). The mean LVEF of CLBBB group slightly fluctuated around 50%, that of LVEF in non-CLBBB group was 60%.The multivariate COX regression analysis showed that QRS duration ( HR=0.979; 95% CI: 0.960-0.999, P<0.05) and QTc ( HR=0.988; 95% CI: 0.979-0.998, P<0.05) were independent predictors of LVEF recovery in children with DCM.Kaplan-Meier method showed a significant difference of LVEF normalization between DCM children with different QRS durations ( P<0.05), which was also detected in those with QTc interval ( P<0.05). Conclusions:LVEF of children with DCM combined with CLBBB increases in the short term after standard treatment, and then being stable.CLBBB can affect the recovery of left ventricular systolic function in children with DCM.Moreover, QRS duration and QTc interval are independent predictors of LVEF recovery in DCM children.

Objective:To investigate the diagnostic and early-warning value of laboratory test indicators for sepsis-induced myocardial injury (SIMD).Methods:The clinical data of 183 patients with sepsis admitted to the Department of Emergency and Critical Care Medicine of Guangdong Provincial People's Hospital from August 2016 to October 2020 were collected. The patient's age, gender, past medical history, vital signs and pathogen culture results were extracted. Cardiac function, blood routine, liver function, renal function, inflammatory factors, coagulation function, APACHE Ⅱ and SOFA scores were recorded at enrollment and 72 h after admission. SIMD was defined as cTnT ≥300 pg/mL and NT-proBNP ≥1243 pg/mL twice in 72 h intervals between enrolled cases, and the early-warning factors of patients with SIMD were analyzed. The differences in various indicators between the two groups were compared, and Logistic regression analysis was used to explore the diagnostic efficacy of cTnT and NT-proBNP combined for SIMD, and the correlation between PCT/PLT ratio and the occurrence of SIMD.Results:Among 250 patients, 67 patients were excluded for lack of the main indicators, and 183 patients (including 62 patients with history of cardiac disease) were enrolled finally. Among 183 patients with sepsis, 105 patients (57.38%) with cTNT ≥300 pg/mL and NT-proBNP ≥1 243 pg/mL, were diagnosed as myocardial injury; after excluding 62 patients with history of cardiac disease, 59 patients (48.76%) with cTNT ≥300 pg/mL and NT-proBNP ≥1 243 pg/mL were diagnosed as myocardial injury. Logistic regression analysis showed that increased PCT/PLT ratio ( OR=1.585, 95% CI: 1.124-2.237, P=0.009) was an independent risk factor for early-warning of SIMD. The PCT/PLT ratio ( OR= 1.850, 95% CI: 1.103-3.102, P=0.020) could stably predict the occurrence of SIMD in patients without previous history of heart disease. ROC curve analysis showed that PCT/PLT ratio could effectively predict the occurrence of SIMD (AUC=0.693, 95% CI: 0.617-0.769, P<0.001), the optimal cut-off value was 0.177 (sensitivity: 65.7%, specificity: 66.7%). The PCT/PLT ratio was still effective in predicting the occurrence of SIMD after excluding patients with previous history of heart disease (AUC=0.733, 95% CI: 0.643-0.823, P<0.001), and the optimal cut-off value was 0.429 (sensitivity: 55.9%, specificity: 83.9%). Conclusions:The combination of cTnT and NT-proBNP has certain diagnostic value for SIMD, and the PCT/PLT ratio could warn the occurrence of SIMD.