A biomimetic ion channel shortens the QT interval of type 2 long QT syndrome through efficient transmembrane transport of potassium ions.

Potassium ion transport across myocardial cell membrane is essential for type 2 long QT syndrome (LQT2). However, the dysfunction of potassium ion transport due to genetic mutations limits the therapeutic effect in treating LQT2. Biomimetic ion channels that selectively and efficiently transport potassium ions across the cellular membranes are promising for the treatment of LQT2. To corroborate this, we synthesized a series of foldamer-based ion channels with different side chains, and found a biomimetic ion channel of K+ (BICK) with the highest transport activity among them. The selected BICK can restore potassium ion transport and increase transmembrane potassium ion current, thus shortening phase 3 of action potential (AP) repolarization and QT interval in LQT2. Moreover, BICK does not affect heart rate and cardiac rhythm in treating LQT2 model induced by E4031 in isolated heart as well as in guinea pigs. By restoring ion transmembrane transport tactic, biomimetic ion channels, such as BICK, will show great potential in treating diseases related to ion transport blockade. STATEMENT OF SIGNIFICANCE: Type 2 long QT syndrome (LQT2) is a disease caused by K+ transport disorder, which can cause malignant arrhythmia and even death. There is currently no radical cure, so it is critical to explore ways to improve K+ transmembrane transport. In this study, we report that a small-molecule biomimetic ion channel BICK can efficiently simulate natural K+ channel proteins on the cardiomyocyte and cure E4031-induced LQT2 in guinea pig by restoring K+ transport function for the first time. This study found that the potassium transmembrane transport by BICK significantly reduced the QT interval, which provides a conceptually new strategy for the treatment of LQT2 disease.

Nobiletin from citrus peel: a promising therapeutic agent for liver disease-pharmacological characteristics, mechanisms, and potential applications.

Nobiletin (NOB) is a flavonoid derived from citrus peel that has potential as an alternative treatment for liver disease. Liver disease is a primary health concern globally, and there is an urgent need for effective drugs. This review summarizes the pharmacological characteristics of NOB and current in vitro and in vivo studies investigating the preventive and therapeutic effects of NOB on liver diseases and its potential mechanisms. The findings suggest that NOB has promising therapeutic potential in liver diseases. It improves liver function, reduces inflammation and oxidative stress, remodels gut microflora, ameliorates hepatocellular necrosis, steatosis, and insulin resistance, and modulates biorhythms. Nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear transcription factor kappa (NF-κB), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α(PPAR-α), extracellular signal-regulated kinase (ERK), protein kinase B (AKT), toll-like receptor 4 (TLR4) and transcription factor EB (TFEB) signaling pathways are important molecular targets for NOB to ameliorate liver diseases. In conclusion, NOB may be a promising drug candidate for treating liver disease and can accelerate its application from the laboratory to the clinic. However, more high-quality clinical trials are required to validate its efficacy and identify its molecular mechanisms and targets.

Demographics and Clinical Characteristics Assessment of Severe Acute Toxic Ingestions in Pediatric Patients: A Single-Center Study in Jilin Province of China.

OBJECTIVE: This study aimed to describe the demographic and clinical characteristics of severe acute toxic ingestions in children in Jilin Province and provide a reference for seeking effective measures to prevent poisoning accidents. METHODS: The clinical data of patients diagnosed with acute toxic ingestions and who presented with severe life-threatening symptoms or organ dysfunction at the Pediatric Intensive Care Unit of the First Hospital of Jilin University were retrospectively analyzed. Patients with incomplete clinical medical records, unclear toxic substance, and loss to follow-up within 6 months of discharge are excluded. We sorted out these children's demographic characteristics, types of poisoning, clinical manifestations, treatment process, and follow-up, etc. RESULTS: This study enrolled 141 cases with no significant differences in sex and region; adolescents accounted for 44.68%. The most common poisons were pesticides and insecticides for rural areas and internal medication for urban areas. With poisoning details as a grouping variable, there was no statistical difference between sex groupings (χ2 = 6.018, P = 0.198) and no difference between region groups (χ2 = 3.775, P = 0.289). However, there were statistical differences between age groups (χ2 = 28.22, P = 0.001). In this research, patients younger than 6 years are mainly unintentionally poisoned, whereas the suicide rate of the urban group (P < 0.05), adolescents (P < 0.01), and girls (P < 0.01) has increased significantly; moreover, the suicide group is more likely to take more overdose medication or pesticides and insecticides (P < 0.01). In addition, there was a statistical difference between suicide and length of intensive care unit stay (r = 0.268, P < 0.01). A total of 90.78% of the patients were successfully discharged after comprehensive treatment. Children aged younger than 12 years had good psychological and intellectual development during the follow-up period, whereas adolescents diagnosed with depression often required long-term psychological and medication intervention. CONCLUSIONS: This study identified poisoning details in different ages, regions, and sex of acute severe oral poisoning in children from Jilin Province. The results presentation of different prevention priorities should vary among children of different ages and emphasize adolescent suicide being a reality in Jilin Province. There is an urgent need for further culture-specific research in this area.

Current status of diagnosis and treatment of primary benign cardiac tumors in children.

Primary cardiac tumors in children are exceedingly rare overall, which benign account for most part. The onset of the disease is occult, while the clinical manifestations are non-specific-patients may be asymptomatic or show a range of obstructive, arrhythmic, embolic or systemic symptoms. The clinical presentations generally depend on the tumors' size, localization, and pace of growth of the tumor. Moreover, the diagnosis needs comprehensive judgment based on imaging results and pathological examination. With advances in cardiac imagining and the introduction of cardiopulmonary support, the diagnosis and treatment of these rare tumors have improved the prognosis and outlook for benign tumors. To sum up the above, we sought to integrate articles from recent years for the latest comprehensive review of the clinical manifestations, imaging characteristics, clinic pathologic features and treatment of benign cardiac tumors in children to provide a broader idea for pediatricians to recognize and treat such diseases.

Prognosis and clinical characteristics of patients with 3ß-hydroxy-Δ5-C27-steroid dehydrogenase deficiency diagnosed in childhood: A systematic review of the literature.

OBJECTIVES: 3ß-hydroxy-Δ5-C27-steroid dehydrogenase deficiency is a rare autosomal recessive condition. So far fewer than 100 cases have been reported and the factors affecting the prognosis are not yet established. The objective of this study is to explore a possible prediction of the outcome of this rare condition. METHODS: This review was undertaken and reported in accordance with the preferred reporting items for systematic review and meta-analyses guidelines. Demographics, clinical features, gene data, treatment strategies and prognoses at the last follow-up were extracted and summarized. Patients were divided into 2 groups (alive with native liver and liver transplantation/died). Risk factors for the different clinical features were identified. RESULTS: 87 patients that were taken from 7 case reports and 9 case series were included. 38 (38/63, 63.0%) of them presented initial symptoms when they were younger than 1 month and 55 (55/63, 87.3%) less than 1 year. There is a larger proportion of patients younger than 1 month or 1 year at the age of symptom onset in the liver transplantation /died group than patients in alive with the native liver group. The majority of patients (53/62, 85.5%) were diagnosed before the age of 5 year. In all cases, 65 (predicted) pathogenic variants have been identified. Over 70% of patients carried an HSD3B7 variant on exon 1, 4, 5 or 6. 71 (81.6%) were alive at the last follow-up, 16 (18.4%) underwent liver transplantation or died. No significance was found between the group alive with native liver and group liver transplantation /died. CONCLUSION: Age of onset of the symptoms may be a potential factor that determines the outcome of patients with 3ß-HSD deficiency, patients presented with symptoms and signs at an age younger than 1 month or even 1 year may have a worse prognosis. Since there is no difference between clinical outcome and zygosity of gene mutation, we recommend a further study about any possible relationship between mutation site and clinical characteristics or prognosis.

Mycoplasma pneumoniae pneumonia with pulmonary embolism: A study on pediatric cases in Jilin province of China.

Mycoplasma is one of the most common pathogens causing community-acquired pneumonia in pediatric patients. In recent years, the number of refractory or severe cases with drug resistance has been gradually increasing and cases that developed embolism after Mycoplasma pneumoniae (M. pneumoniae) infection have been reported. The present study retrospectively analyzed the clinical features, diagnosis and treatment of M. pneumoniae pneumonia (MPP) combined with pulmonary embolism (PE) in a series of 7 cases encountered between January 1st, 2016 to August 1st, 2019 at the Department of Pediatric Intensive Care Unit of The First Hospital of Jilin University (Changchun, China). Combined with relevant Chinese and international studies published during the last two decades, a comprehensive analysis was performed. All of the pediatric patients of the present study had fever, cough and dyspnea respiratory symptoms at onset and the disease progressed rapidly. Thereafter, PE was confirmed by a series of examinations. Pulmonary CT indicated patchy inflammations and significantly elevated D-dimer levels, accompanied by positive anticardiolipin antibodies. Furthermore, a filling defect in the pulmonary artery branch was observed on CT pulmonary angiography (CTPA) examination. In 2 cases, the condition was improved with anti-infection and anticoagulation treatment with low-molecular-weight heparin and warfarin, respectively, and the pulmonary embolism disappeared after 3-4 months. A total of 5 cases, who were not responsive to the drug treatment, underwent surgical resection. During the operation, the local tissues were determined to be infarcted and the pathological diagnosis was consistent with pulmonary infarction. Among the 5 cases, 2 died of Acute Respiratory Distress Syndrome at 3-8 days after the operation. The remaining patients underwent 6-12 months of follow-up and respiratory rehabilitation and their quality of life is now good. In conclusion, compared with healthy individuals, pediatric patients with critical MPP have an elevated risk of embolism. It is necessary to be vigilant regarding whether MMP is combined with PE and perform timely CTPA examination. Early detection, early treatment and surgical intervention (if necessary) may significantly reduce the risk of mortality and disability.

The Use of Continuous Blood Purification for the Treatment of Malignant Hyperthermia in an Infant.

BACKGROUND: Malignant hyperthermia (MH) is a rare and potentially life-threatening pharmacogenetic disorder encountered during general anesthesia, with the incidence higher in children than in adults. Dantrolene is the specific antagonist of MH, but it is not readily available in China, thus developing alternative treatment protocols is of great practical importance. CASE PRESENTATION: Herein, the authors report a two-month-old infant who underwent holmium laser epiglottis retrofitting through a bronchoscope, but developed limb muscular stiffness, tachypnea, tachycardia, and hyperthermia after sevoflurane exposure. After the diagnosis of MH, corresponding supportive treatment was implemented. Because there was no dantrolene available, continuous blood purification and mechanical ventilation were performed. A few days later, the boy recovered without any complications. CONCLUSION: Based on the authors' successful clinical practice, the authors consider continuous blood purification as a reliable treatment for MH. But its feasibility still needs to be clarified after multicenter clinical observations.

Timing of liver transplantation for pediatric acute liver failure due to mushroom poisoning: a case report and literature review.

BACKGROUND: Pediatric acute liver failure is a rare, life-threatening illness. Mushroom poisoning is a rare etiology. For patients with irreversible pediatric acute liver failure, liver transplantation is the ultimate lifesaving therapy. However, it is difficult to determine the optimal timing of transplantation. Here, we present a case of pediatric acute liver failure due to mushroom poisoning in northeastern China. He was treated with liver transplantation and recovered. To our knowledge, there are few reports about liver transplantation for pediatric acute liver failure caused by mushroom poisoning in mainland China. CASE PRESENTATION: The patient was a previously healthy 9-year-old boy who gradually developed nausea, vomiting, jaundice and coma within 5 days after ingesting mushrooms. He was diagnosed with mushroom poisoning and acute liver failure. He was treated with conservative care but still deteriorated. On the 7th day after poisoning, he underwent LT due to grade IV hepatic encephalopathy. Twenty days later, he recovered and was discharged. A review of the literature revealed that the specific criteria and optimal timing of transplantation remain to be determined. CONCLUSIONS: Patients with pediatric acute liver failure should be transferred to a center with a transplant unit early. Once conservative treatment fails, liver transplantation should be performed.

Increased Serum Levels of Cortisol and Inflammatory Cytokines in People With Depression.

This cross-sectional study aimed at measuring the correlation and association between serum levels of cortisol, inflammatory cytokines, and depression and to measure the detection accuracy of serum levels of cortisol in serum samples. In total, 89 male participants were recruited into this study from June 15, 2017, to September 31, 2017. The Hamilton Depression Rating Scale, Beck Anxiety Inventory, and Pittsburgh Sleep Quality Index were used to investigate the mental health status of the participants. Serum concentrations of cortisol and inflammatory cytokines were determined. The serum cortisol concentration, anxiety level, and sleep quality were included in the final logistic regression model. Serum cortisol was able to accurately distinguish between patients with depression and those without depression. There was a significant positive correlation between serum cortisol levels and Hamilton Depression Rating Scale scores.

The predictive value of diaphragm ultrasound for weaning outcomes in critically ill children.

INTRODUCTION: Multiple studies have shown that diaphragmatic ultrasound can better predict the outcome of weaning in adults. However, there are few studies focusing on children, leading to a lack of sufficient clinical evidence for the application of diaphragmatic ultrasound in children. The purpose of this study was to investigate the predictive value of diaphragm ultrasound for weaning outcomes in critically ill children. METHODS: The study included 50 cases whose mechanical ventilation (MV) time was > 48 h, and all eligibles were divided into either the weaning success group (n = 39) or the weaning failure group (n = 11). Diaphragm thickness, diaphragmatic excursion (DE), and diaphragmatic thickening fraction (DTF) were measured in the zone of apposition. The maximum inspiratory pressure (PImax) was also recorded. RESULTS: The ventilatory treatment time (P = 0.002) and length of PICU stay (P = 0.013) in the weaning failure group was longer than the success group. Cut-off values of diaphragmatic measures associated with successful weaning were ≥ 21% for DTF with a sensitivity of 0.82 and a specificity of 0.81, whereas it was ≥0.86 cm H2O/kg for PImax with a sensitivity of 0.51 and a specificity of 0.82. The linear correlation analysis showed that DTF had a significant positive correlation with PImax in children (P = 0.003). CONCLUSIONS: Diaphragm ultrasound has potential value in predicting the weaning outcome of critically ill children. DTF and PImax presented better performance than other diaphragmatic parameters. However, DE has limited value in predicting weaning outcomes of children with MV. TRIAL REGISTRATION: Current Controlled Trials ChiCTR1800020196, (Dec 2018).

Changes in serum cardiac myosin light chain 1 levels in children with fulminant myocarditis during continuous blood purification.

OBJECTIVE: To investigate the changes in serum cardiac myosin light chain 1 (CMLC-1) levels in children with fulminant myocarditis (FM) during continuous blood purification (CBP), as well as to analyze its correlation with other laboratory indexes. METHOD: Twenty-four (24) children with FM who underwent CBP were enrolled. Before and during treatment (48 and 72 hours after treatment, or death), the optical density value of serum CMLC-1 was measured using enzyme-linked immunosorbent assay, and then the serum CMLC-1 concentration was calculated. The correlations between CMLC-1 OD value change and laboratory indexes including creatine kinase-MB (CK-MB), troponin, myohemoglobin and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analyzed. RESULTS: The serum CMLC-1 concentration significantly increased in the children with FM and decreased obviously during CBP therapy. In the same period, the change of CMLC-1 concentration were positively correlated with creatine kinase-MB (r=0.528), troponin (r=0.726), myohemoglobin (r=0.702), and NT-proBNP levels (r=0.589). CONCLUSION: The serum CMLC-1 concentration increases significantly in children with FM, but CBP therapy can effectively control this increase.

Changes in serum cardiac myosin light chain 1 levels in children with fulminant myocarditis during continuous blood purification

Summary Objective: To investigate the changes in serum cardiac myosin light chain 1 (CMLC-1) levels in children with fulminant myocarditis (FM) during continuous blood purification (CBP), as well as to analyze its correlation with other laboratory indexes. Method: Twenty-four (24) children with FM who underwent CBP were enrolled. Before and during treatment (48 and 72 hours after treatment, or death), the optical density value of serum CMLC-1 was measured using enzyme-linked immunosorbent assay, and then the serum CMLC-1 concentration was calculated. The correlations between CMLC-1 OD value change and laboratory indexes including creatine kinase-MB (CK-MB), troponin, myohemoglobin and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analyzed. Results: The serum CMLC-1 concentration significantly increased in the children with FM and decreased obviously during CBP therapy. In the same period, the change of CMLC-1 concentration were positively correlated with creatine kinase-MB (r=0.528), troponin (r=0.726), myohemoglobin (r=0.702), and NT-proBNP levels (r=0.589). Conclusion: The serum CMLC-1 concentration increases significantly in children with FM, but CBP therapy can effectively control this increase.

Tanshinone IIA inhibits apoptosis in the myocardium by inducing microRNA-152-3p expression and thereby downregulating PTEN.

Progressive loss of cardiac myocytes through apoptosis contributes to heart failure (HF). In this study, we tested whether tanshinone IIA, one of the most abundant constituents of the root of Salvia miltiorrhiza, protects rat myocardium-derived H9C2 cells against apoptosis. Treatment of H9C2 cells with tanshinone IIA inhibited angiotensin II-induced apoptosis by downregulating the expression of PTEN (phosphatase and tensin homolog), a tumor suppressor that plays a critical role in apoptosis. Furthermore, tanshinone IIA was found to inhibit PTEN expression by upregulating the microRNA miR-152-3p, a potential PTEN regulator that is highly conserved in both rat and human. Notably, the antiapoptotic effect of tanshinone IIA was partially reversed when H9C2 cells were transfected with an inhibitor of miR-152-3p. Collectively, our findings reveal a previously unrecognized mechanism underlying the cardioprotective role of tanshinone IIA, and further suggest that tanshinone IIA could represent a promising drug candidate for HF therapy.