Child, Preschool ; Coronary Aneurysm ; diagnosis ; etiology ; prevention & control ; Diagnosis, Differential ; Early Diagnosis ; Humans ; Immunoglobulins, Intravenous ; administration & dosage ; therapeutic use ; Immunologic Factors ; administration & dosage ; therapeutic use ; Infant ; Mucocutaneous Lymph Node Syndrome ; classification ; complications ; diagnosis ; drug therapy ; Prognosis

Cardiomyopathies ; classification ; genetics ; Humans ; Molecular Biology ; trends

Child ; Humans ; Hypertension, Pulmonary

Humans ; Postural Orthostatic Tachycardia Syndrome

Objective To explore the effect of the ?-blocker —metoprolol on the treatment of vasovagal syncope(VVS) in children.Methods Twenty-nine children with unexplained syncope and positive responses to head-up tilt test(HUT) were included in the study.Sixteen of them took metoprolol(treatment group) and 13 of them took vitamin B or oryzanol (control group) at least 2 weeks and HUT were repeated and syncope episodes were observed.Results In treatment group,9 of 16 patients had no syncope episode while 5 of 16 patients had fewer syncope episodes,1 case had more syncope episodes,and 1 case remained the same.HUT were repeated and 6 of 9 cases had negative outcome.In control group,1 of 13 patients had no syncope episode while 5 of 13 patients had fewer syncope episode,3 cases had more syncope episodes and 4 cases remained the same.HUT were repeated and 3 of 7 cases had ne-(gative) outcome.Conclusion These results indicate that adminstering metoprolol orally may be effective for VVS in children.

Objective To study the characteristics and clinical features of positive response during head - up tilt test (HUT) in children. Methods Forty- nine cases of syncope and aura of syncope were included in the study. All of them underwent HUT (tilt angle 60 degree,lasting 45 minutes). During the test,children' blood pressure,heart rate.electrocardiography and clinical symptoms and signs were dynamically observed. Results The common syncope aura symptoms were headache, dizziness, chest distress, difficulties in breathing, pale, perspiration, blurred vision, auditus depression and symptoms related to digestive symptoms. Among the 28 positive cases, 7 cases were of vaso - inhibitory pattern (25%), with a decrease in blood pressure and an increase in heart rate, 3 cases inhibitory pattern (11%), with a decrease in heart rate but withoilt'blood pressure changes, 4 cases mixed pattern (14 %), with decreases in heart rate and blood pressure obviously, 10 eases POTS (36%), with an increase in heart rate by 30 bpm or up to 120 bpm within 10 minutes while testing, and 4 cases orthostatic hypotension (14%), with a decrease in blood pressure within 3 minutes. Conclusion HUT can be regarded as the main tool in differential diagnosis of unexplained syncope in children.

Objective To discuss the clinical diagnostic method of postural orthostatic tachycarda syndrome(POTS) in children.Methods Thirty-six children with POTS were selected for the research.Among them 15 were boys,21 cases were girls.The age ranged from 5.9 to 16 years,average age 12.3 years.Among them 28 patients(78%) were in between 11-16 years.The age distribution,clinical courses and hemodynamic indexes were analyzed and also the incidence of clinical manifestations and investigation reports were observed.Results Among 81 patients of orthostatic regulation disturbance,36 patients were diagnosed POTS,which was 47% of total.The clinical courses ranged from 1 day to 5 years,average clinical course 10.2 months.The clinical courses of more than half of the total patients were within 6 months(56%).The common clinical features of POTS were chest tightness on standing,vertigo,fatigue,palpitation,syncope,orthostatic regulation disturbance.Ten patients were also associated with gastrointestinal symptoms like nausea,vomiting.The most common feature of POTS patients was tachycardia(HR increased by ≥30 times/min) within 10 min after head-up tilt test(HUT).Average HR increased by 38 times/min.In some patients HR increased up to ≥120 times/min.There were no significant changes in blood.In 23 cases(64%),the T waves were descended by ≥0.2 mV in 2 or more than 2 leads in ECG reading.Investigations reports showed that there were 12 cases whose urine specific gravity was increased.In 11 cases HCO_3~-decreased.Conclusions POTS is commonly seen in schooling female children.The common symptoms are vertigo,chest tightness,fatigue,palpitation.HUT is an important method for the diagnosis of POTS.

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Transmembrane serine protease 2 (TMPRSS2) is a cell surface protease widely present in the human body. It is involved in the infection of various viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and in the cell invasion, tumor growth and metastasis processes of prostate cancer. This study used Boc-Gln-Ala-Arg-AMC as the fluorescent substrate to determine the cleavage activity of TMPRSS2 towards SARS-CoV-2 S protein. Then cell-based screening model for TMPRSS2 inhibitors was established in Vero E6 cells overexpressing TMPRSS2 (Vero E6/TMPRSS2). Seven compounds exhibiting TMPRSS2 inhibitory activities with low toxicity were obtained through high-throughput screening (HTS) from natural and synthetic compound pure product library of National Center for Screening Novel Microbial Drugs. Surface plasmon resonance (SPR) has shown that the obtained inhibitors could bind to TMPRSS2 with moderate affinity in a dose dependent manner. Cell-cell fusion experiments have shown that the obtained inhibitors can inhibit the occurrence of S protein mediated cell-cell fusion by inhibiting TMPRSS2 cleavage of SARS-CoV-2 S protein in a concentration dependent manner. Preliminary pseudovirus experiment showed that the inhibitors may reduce the pseudovirus infection into Opti-HEK-293T-ACE2 cells to varying degrees. In a word, this study successfully established a cell-based HTS model for TMPRSS2 inhibitor and preliminarily confirmed that the seven screened inhibitors possessed in vitro anti-TMPRSS2 activities, providing new structural scaffolds for the development of new drugs against SARS-CoV-2.

OBJECTIVEThe study was designed to explore the value of the New York University Pediatric Heart Failure Index (NYU PHFI) for diagnosing and grading chronic heart failure in children.

METHODSTotally 105 children with chronic heart failure or structural heart disease but without signs and symptoms of heart failure were enrolled. They were diagnosed using modified Ross score, NYU PHFI and NT-proBNP, respectively. According to modified Ross score as the referent criteria, the diagnostic value of NYU PHFI in quantifying chronic heart failure severity in children was studied. Furthermore, according to the grading of heart failure using modified Ross score, the area under the ROC curves of NYU PHFI was examined, respectively, in order to find out the optimal cut-off point.

RESULTSNYU PHFI score was positively correlated with the modified Ross score (r = 0.909, P = 0.000). According to modified Ross score, NYU PHFI scores in different severity of heart failure in children differed significantly (F = 80.034, P = 0.000). A significantly positive correlation was found between plasma NT-proBNP and modified Ross score, and between NT-proBNP and NYU PHFI score. Correlation coefficients between plasma NT-proBNP and modified Ross score, and between plasma NT-proBNP and NYU PHFI score were 0.752 and 0.918, respectively. The correlation between NYU PHFI and plasma NT-proBNP was superior to that between modified Ross score and plasma NT-proBNP. According to modified Ross scores of 0 - 2 as being without heart failure, 3 - 6 as mild degree of heart failure, 7 - 9 as moderate degree of heart failure and 10 - 12 as severe degree of heart failure, the areas under the ROC curve of the NYU PHFI diagnosing if heart failure was present, differentiating moderate from mild and severe from moderate heart failure were 0.982, 0.942 and 0.918, respectively, and the sum of sensitivity and specificity was favorite when 6, 10 and 13 scores were set as cut-off value diagnosing the presence of heart failure, differentiating moderate from mild, and severe from moderate heart failure, respectively. According to above classification of heart failure based on NYU PHFI score, plasma NT-proBNP concentration was significantly different in different degree of heart failure (F = 53.31, P < 0.001). Plasma NT-proBNP concentration in those without heart failure was significantly lower than that of mild heart failure, and it was also significantly lower in mild heart failure than that of severe heart failure.

CONCLUSIONNYU PHFI was highly valuable for diagnosing chronic heart failure in children and 0 - 6 scores as being without heart failure, 7 - 10 scores as mild degree, 11 - 13 scores as moderate degree and 14 - 30 scores as severe degree of heart failure could be used as the reference criteria of different severities of heart failure.

Adolescent ; Child ; Child, Preschool ; Chronic Disease ; Female ; Heart Failure ; diagnosis ; Humans ; Infant ; Male ; Severity of Illness Index