A cingulate-hippocampal circuit mediates early depressive-like behavior in the mouse model of Alzheimer disease.

Depressive symptoms usually precede the cognitive decline in Alzheimer disease (AD) and worsen the clinical outcome. However, the neural circuitry mediating early emotional dysfunction, especially depressive symptoms in AD, remains elusive. Anterior cingulate cortex (ACC) is closely related to depression and vulnerable in AD. By quantitative whole-brain mapping and electrophysiological recording, we found that the decreased axonal calcium activity in neurons of ACC and the glutamatergic projection from ACC to the ventral hippocampal CA1 (vCA1) is significantly impaired in 3-month-old 5×FAD mice, which exhibit depressive-like phenotype before cognition defects in early stage. The activation of ACC-vCA1 circuit by chemogenetic manipulation efficiently ameliorated the early depressive-like behaviors in 5×FAD mice. We further identified the upregulated neuregulin-1 (Nrg1) in ACC impaired the excitatory synaptic transmission from the ACC to vCA1 in AD. Our work reveals the role of ACC-vCA1 circuit in regulating AD associated depression symptom in a mouse model of AD.

Effective Manipulation of a Colossal Second-Order Transverse Response in an Electric-Field-Tunable Graphene Moiré System.

The second-order nonlinear transport illuminates a frequency-doubling response emerging in quantum materials with a broken inversion symmetry. The two principal driving mechanisms, the Berry curvature dipole and the skew scattering, reflect various information including ground-state symmetries, band dispersions, and topology of electronic wave functions. However, effective manipulation of them in a single system has been lacking, hindering the pursuit of strong responses. Here, we report on the effective manipulation of the two mechanisms in a single graphene moiré superlattice, AB-BA stacked twisted double bilayer graphene. Most saliently, by virtue of the high tunability of moiré band structures and scattering rates, a record-high second-order transverse conductivity ∼ 510 µm S V-1 is observed, which is orders of magnitude higher than any reported values in the literature. Our findings establish the potential of electrically tunable graphene moiré systems for nonlinear transport manipulations and applications.

Cardiac function evaluation in children with spinal muscular atrophy: A case-control study.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of lower motor neurons, resulting in progressive muscle weakness and atrophy. However, little is known regarding the cardiac function of children with SMA. METHODS: We recruited SMA patients younger than 18 years of age from January 1, 2022, to April 1, 2022, in the First Affiliated Hospital of Sun Yat-sen University. All patients underwent a comprehensive cardiac evaluation before treatment, including history taking, physical examination, blood tests of cardiac biomarkers, assessment of echocardiography and electrocardiogram. Age/gender-matched healthy volunteers were recruited as controls. RESULTS: A total of 36 SMA patients (26 with SMA type 2 and 10 with SMA type 3) and 40 controls were enrolled in the study. No patient was clinically diagnosed with heart failure. Blood tests showed elevated values of creatine kinase isoenzyme M and isoenzyme B (CK-MB) mass and high-sensitivity cardiac troponin T (hs-cTnT) in spinal muscular atrophy (SMA) patients. Regarding echocardiographic parameters, SMA children were detected with lower global left and right ventricular longitudinal strain, abnormal diastolic filling velocities of trans-mitral and trans-tricuspid flow. The results revealed no clinical heart dysfunction in SMA patients, but subclinical ventricular dysfunction was seen in SMA children including the diastolic function and myocardial performance. Some patients presented with elevated heart rate and abnormal echogenicity of aortic valve or wall. Among these SMA patients, seven patients (19.4%) had scoliosis. The Cobb's angles showed a significant negative correlation with LVEDd/BSA, but no correlation with other parameters, suggesting that mild scoliosis did not lead to significant cardiac dysfunction. CONCLUSIONS: Our findings warrant increased attention to the cardiac status and highlight the need to investigate cardiac interventions in SMA children.

Causal links between sedentary behavior, physical activity, and psychiatric disorders: a Mendelian randomization study.

BACKGROUND: Studies suggest a correlation between excessive sedentary behavior, insufficient physical activity, and an elevated likelihood of experiencing psychiatric disorder. Nonetheless, the precise influence of sedentary behavior and physical activity on psychiatric disorder remains uncertain. Hence, the objective of this research was to investigate the possible causal relationship between sedentary behavior, physical activity, and the susceptibility to psychiatric disorder (depression, schizophrenia and bipolar disorder), utilizing a two-sample Mendelian randomization (MR) approach. METHODS: Potential genetic instruments related to sedentary leisure behaviors were identified from the UK Biobank database, specifically a summary-level genome-wide association study (GWAS) involving 422,218 individuals of European descent. The UK Biobank database also provided the GWAS data for physical activity. Primary analysis was performed using inverse variance weighting (IVW) to assess the causal relationship between sedentary behavior, physical activity, and the risk of psychiatric disorder (depression, schizophrenia and bipolar disorder). Sensitivity analysis was conducted using Cochran's Q test, the MR-Egger intercept test, the MR-pleiotropy RESidual sum and outlier test, leave-one-out analysis, and funnel plot analysis. RESULTS: According to the IVW analysis, there was a significant association between genetically predicted leisure television watching and an increased risk of depression (odds ratio [OR] = 1.027, 95% confidence interval [CI]: 1.001-1.053; P = 0.04). The IVW analysis also indicated that there was a decreased risk of depression associated with fraction accelerations of > 425 milligravities, as measured by accelerometers (OR = 0.951, 95%CI: 0.914-0.989; P = 0.013). The other MR methods obtained consistent but non-significant results in the same direction. However, there was no evidence of a causal association between genetic liability for moderate-to-vigorous physical activity, accelerometer-assessed physical activity, computer use, or driving and the risk of depression. Furthermore, IVW analysis has also found that driving has a slight effect in reducing the risk of schizophrenia (OR = 0.092, 95%CI: 0.010-0.827; P = 0.033), while leisure television viewing has a significant protective effect against the onset of bipolar disorder (OR = 0.719, 95%CI: 0.567-0.912; P = 0.006). CONCLUSION: The study provides compelling evidence of a link between depression, bipolar disorder, and excessive TV watching. Furthermore, it suggests that higher accelerometer-assessed fraction accelerations of > 425 milligravities can serve as a genetic protective factor against depression. To mitigate the risk of developing depression, it is advisable to reduce sedentary activities, particularly television watching, and prioritize engaging in vigorous physical exercise.

Association of dietary inflammatory index with obesity among children and adolescents in the United States NHANES cohort: a population-based study.

BACKGROUND: Childhood obesity has become a huge challenge to childhood health, and there is a lack of understanding about the relationship between dietary inflammatory index (DII) and childhood obesity. The main objective of this study was to analyze the potential link between DII and obesity among children and adolescents residing in the United States. METHODS: A cross-sectional analysis was performed using data obtained from the National Health and Nutrition Examination Survey between 2009 and 2018. In total, 12,454 participants were included in the analysis. DII was calculated based on dietary data from the first day of the 24-hour dietary recall. Logistic regression was used to analyze the association between DII and obesity, as well as central obesity defined by the waist-to-height ratio of 0.5 or higher or waist circumference ≥ 90th percentile for age and sex. RESULTS: The mean dietary inflammation index was 2.05 (SE = 0.02), with higher levels in children than in adolescents (P = 0.01). According to our findings, the prevalence of central obesity was higher among adolescents (38.0%) than among children (31.4%). The adolescents in the third quartile of DII have a higher risk of overweight/obesity (OR = 1.46, 95% CI: 1.24-1.71) after adjusting for age, sex, and race. This positive association remained significant even after physical activity was added to the model. Concerning central obesity, the adolescents in the highest quartile of DII have a higher risk, independent of demographic characteristics and physical activity. However, no significant association was observed among children. CONCLUSIONS: The dietary inflammation index was positively associated with overweight/obesity and central obesity among adolescents in the United States after adjusting for confounding factors. These findings highlight the importance of promoting anti-inflammatory diets in adolescents to prevent obesity and its associated complications.

How self-leadership promotes job crafting: Based on the perspective of self-determination theory.

According to self-determination theory, the present study develops a moderated mediation model to investigate how and when self-leadership promotes employees' job crafting, emphasizing the mediating effect of autonomous motivation and the moderating effect of leader empowering behavior. We analyze and test the hypotheses based on 269 valid three-wave data from employees. The findings show that self-leadership has a significantly positive impact on job crafting, and a positive indirect effect on job crafting via autonomous motivation. Furthermore, leader empowering behavior not only enhances the positive impact of self-leadership on autonomous motivation, but also positively moderates the mediating effect of autonomous motivation in the relationship between self-leadership and job crafting. Practically, our study provides insights into how to promote job crafting. We also propose limitations and directions for future research.

Giant Second-Order Nonlinear Hall Effect in Twisted Bilayer Graphene.

In the second-order response regime, the Hall voltage can be nonzero without time-reversal symmetry breaking but inversion symmetry breaking. Multiple mechanisms contribute to the nonlinear Hall effect. The disorder-related contributions can enter the NLHE in the leading role, but experimental investigations are scarce, especially the exploration of the contributions from different disorder sources. Here, we report a giant nonlinear response in twisted bilayer graphene, dominated by disorder-induced skew scattering. The magnitude and direction of the second-order nonlinearity can be effectively tuned by the gate voltage. A peak value of the second-order Hall conductivity reaching 8.76 µm SV^{-1} is observed close to the full filling of the moiré band, four order larger than the intrinsic contribution detected in WTe_{2}. The scaling shows that the giant second-order nonlinear Hall effect in twisted bilayer graphene stems from the collaboration of the static (impurities) and dynamic (phonons) disorders. It is mainly determined by the impurity skew scattering at 1.7 K. The phonon skew scattering, however, has a much larger coupling coefficient, and becomes comparable to the impurity contribution as the temperature rises. Our observations provide a comprehensive experimental understanding of the disorder-related mechanisms in the nonlinear Hall effect.

Superconducting quantum interference effect in NbSe2/NbSe2van der Waals junctions.

Layered materials with exotic properties, such as superconducting, ferromagnetic, and so on, have attracted broad interest. The advances in van der Waals (vdW) stacking technology have enabled the fabrication of numerous types of junction structures. The dangling-bond-free interface provides an ideal platform to generate and probe various physics phenomena. Typical progress is the realization of vdW Josephson junctions with high supercurrent transparency constructed of two NbSe2layers. Here we report the observation of periodic oscillations of the voltage drop across a NbSe2/NbSe2vdW junctions under an in-plane magnetic field. The voltage-drop oscillations come from the interface and the magnitude of the oscillations has a non-monotonic temperature dependence which increases first with increasing temperature. These features make the oscillations different from the modulation of the critical current of a Josephson junction by the magnetic field and the Little-Parks effect. The oscillations are determined to be generated by the quantum interference effect between two superconducting junctions formed between the two NbSe2layers. Our results thus provide a unique way to make an in-plane superconducting quantum interference device that can survive under a high magnetic field utilizing the Ising-paring nature of the NbSe2.

Personalized optimal nutrition lifestyle for self obesity management using metaalgorithms.

Precision medicine applies machine learning methods to estimate the personalized optimal treatment decision based on individual information, such as genetic data and medical history. The main purpose of self obesity management is to develop a personalized optimal life plan that is easy to implement and adhere to, thereby reducing the incidence of obesity and obesity-related diseases. The methodology comprises three components. First, we apply catboost, random forest and lasso covariance test to evaluate the importance of individual features in forecasting body mass index. Second, we apply metaalgorithms to estimate the personalized optimal decision on alcohol, vegetable, high caloric food and daily water intake respectively for each individual. Third, we propose new metaalgorithms named SX and SXwint learners to compute the personalized optimal decision and compare their performances with other prevailing metalearners. We find that people who receive individualized optimal treatment options not only have lower obesity levels than others, but also have lower obesity levels than those who receive 'one-for-all' treatment options. In conclusion, all metaalgorithms are effective at estimating the personalized optimal decision, where SXwint learner shows the best performance on daily water intake.

Duchenne Muscular Dystrophy With Low Acidic α-Glucosidase Activity: Two Case Reports and Literature Review.

Background: Pompe disease is usually considered in children with elevated creatine kinase (CK) levels and decreased acidic α-glucosidase (GAA) enzyme activity. However, there are exceptions, such as GAA pseudo deficiency alleles, which result in lower GAA enzyme activity but do not cause Pompe disease. Here, we report two cases presenting with high CK levels and low GAA activity who were ultimately diagnosed with Duchenne muscular dystrophy (DMD). Case Presentation: Case 1 patient was a 2-month-old boy who presented with an extremely high serum CK level (5,480∼11,880 U/L) and low GAA activity (2.72 nmol/1 h/mg). The whole-exome sequencing did not find the pathogenic GAA gene mutation, however, there was a DMD gene hemizygous variation (c. 7657C > T, p. Arg2553Ter) inherited from his mother, which was verified by the first-generation sequencing. Further genetic analysis of GAA identified two homozygous pseudo deficiency alleles (c.1726G > A, p. Gly576Ser and c.2065G > A, p. Glu689Lys), which were believed to induce the patient's low GAA activity. Therefore, the boy was diagnosed with DMD, although he had extremely low GAA activity. Case 2 patient was also a 2-month-old boy presenting with a significant increase in CK level (12,408∼24,828 U/L). His blood GAA activity (colorimetric method) was 9.02 nmol/1 h/mg. Similarly, his whole-exome sequencing did not find the pathogenic mutation of the GAA gene, but a DMD gene hemizygous variation (c.5571del, p. Lys1857AsnfsTer8), hence he was diagnosed with DMD as well. Regarding GAA activity, the case 2 patient was not as low as the case 1 patient, mainly because his two GAA pseudo deficiency alleles were heterozygous. Conclusion: Pompe disease is usually screened in infants with high CK levels. We should be aware that pseudo deficiency alleles can cause low GAA activities but not Pompe disease. Genetic tests would be helpful to distinguish cases with GAA pseudo deficiency alleles from patients with some muscular disorder diseases such as DMD.

Clinical Characteristics of Hospitalized Pediatric Patients With Hypertensive Crisis-A Retrospective, Single-Center Study in China.

Background: A hypertensive crisis is a medical emergency that causes acute damage to multiple organs. However, the etiology, clinical features, and prognosis of hypertensive crisis in Chinese children remain relatively unknown. The purpose of this study was to analyze the clinical characteristics of pediatric hypertensive crisis patients from a single center in China. Methods: We analyzed data from 70 children with hypertensive crisis between January, 2000, and January, 2022. The patients were divided into two groups: those diagnosed with a hypertensive emergency (n = 46) and those diagnosed with hypertensive urgency (n = 24). Baseline etiologies and risk factors were compared between the two groups. The following data were collected and analyzed: age, sex, weight, height, family history of hypertension, blood pressure, clinical manifestations of hypertensive crisis, underlying causes, biochemical indicators, and antihypertensive drugs. Results: The major symptoms of hypertensive crisis were headache (n = 31, 44.29%), followed by visual symptoms (n = 15, 21.43%), and dizziness (n = 13, 18.57%). Further analysis showed that the incidence of convulsions was significantly higher in patients with hypertensive emergency than those with hypertensive urgency (χ2 = 5.38, p = 0.02). The leading underlying causes were renal disease (n = 34, 48.57%), followed by vascular disease (n = 11, 15.71%), essential hypertension (n = 9, 12.86%), oncological disease (n = 9, 12.86%), central nervous system disease (n = 3, 4.29%), endocrine and metabolic diseases (n = 2, 2.86%), and other (one case with lead poisoning, one case with histiocytosis). End-organ damage occurred in 46 patients with hypertensive crisis, including retinal damage (n = 20, 43.48%), brain damage (n = 19, 41.30%), heart damage (n = 15, 32.61%), and renal damage (n = 3, 6.52%). Hypertensive crisis was most common among children aged 7-12 years. Among children aged 13-18 years, hypertensive urgency was more common than hypertensive emergency. The incidence of dyslipidemia, elevated serum creatinine, and elevated uric acid did not differ significantly between the two groups. Most patients with hypertensive crisis need combined antihypertensive therapy (n = 60, 85.71%). There were no cases of mortality. Conclusions: Hypertensive crisis is caused by secondary diseases, especially renal disease and vascular disease, in the majority of pediatric patients. Combination therapy with antihypertensive agents and treatment of secondary etiology results in a good prognosis.

Silicon Nanoparticles Enhance Ginger Rhizomes Tolerance to Postharvest Deterioration and Resistance to Fusarium solani.

Postharvest deterioration of ginger rhizome caused by microorganisms or wound infections causes significant economic losses. Fusarium solani is one of the important causal agents of prevalent ginger disease soft rot across the world. The massive and continuous use of chemical fungicides in postharvest preservation pose risks to human health and produce environmental contamination. Hence, new alternative tools are required to reduce postharvest deterioration and extend the postharvest life of ginger. In this study, the use of silicon nanoparticles (SiNPs) on the storability of ginger rhizomes during postharvest storage and their resistance to Fusarium solani was investigated. The results showed that 50, 100, and 150 mg L-1 of SiNPs increased the firmness of the ginger rhizome during storage but decreased the decay severity, water loss, total color difference, and the reactive oxygen species (ROS; H2O2 and superoxide anion) accumulation. Specifically, 100 mg L-1 (SiNP100) demonstrated the best effect in the extension of postharvest life and improved the quality of the ginger rhizomes. SiNP100 application increased the activities of antioxidant enzymes (SOD and CAT) and the total phenolics and flavonoid contents, thereby reducing the ROS accumulation and malondialdehyde (MDA) content. Meanwhile, SiNP100 treatment negatively impacts the peroxidase (POD) and polyphenol oxidase (PPO) activities, which may have contributed to the lower level of lignin and decreased total color difference. SiNP100 likely decreased water loss and the transfer of water by altering the expression of aquaporin genes. Moreover, SiNP100 modulated the expression of lignin synthesis and phytopathogenic responses genes including MYB and LysM genes. Furthermore, SiNP100 inhibited Fusarium solani by preventing the penetration of hyphae into cells, thus decreasing the severity of postharvest pathogenic decay. In summary, this study revealed the physiology and molecular mechanisms of SiNPs-induced tolerance to postharvest deterioration and resistance to disease, which provides a foundation for using SiNPs resources as a promising alternative tool to maintain ginger quality and control postharvest diseases.

Haploinsufficiency of A20 in a Chinese child caused by loss-of-function mutations in TNFAIP3: A case report and review of the literature.

Case Presentation: A 3-year-and-6-month-old child was reported to have recurrent high fever with generalized lymph node enlargement and significant elevation of inflammatory markers such as C-reactive protein and procalcitonin in tests. Later, whole exome sequencing determined that the child's disease was haploinsufficiency of A20 (HA20). Results: After immunosuppressive therapy, the child's symptoms improved significantly, and the inflammatory markers dropped to the normal range. Conclusion: Because of the characteristics of HA20, this disease is often underdiagnosed and misdiagnosed in clinical practice. By reporting this case of HA20 in a child, we hope to increase the awareness of this disease in the clinic.

Case Report: Talaromyces marneffei Infection in a Chinese Child With a Complex Heterozygous CARD9 Mutation.

Talaromyces marneffei (TM) infection is rarely seen in clinical practice, and its pathogenesis may be related to deficiency in antifungal immune function. Human caspase recruitment domain-containing protein 9 (CARD9) is a key molecule in fungal immune surveillance. There have been no previous case reports of TM infection in individuals with CARD9 gene mutations. Herein, we report the case of a 7-month-old Chinese boy who was admitted to our hospital with recurring cough and fever with a papular rash. A blood culture produced TM growth, which was confirmed by metagenomic next-generation sequencing. One of the patient's sisters had died of TM septicaemia at 9 months of age. Whole exome sequencing revealed that the patient had a complex heterozygous CARD9 gene mutation with a c.1118G>C p.R373P variation in exon 8 and a c.610C>T p.R204C variation in exon 4. Based on the culture results, voriconazole antifungal therapy was administered. On the third day of antifungal administration, his temperature dropped to within normal range, the rash gradually subsided, and the enlargement of his lymph nodes, liver, and spleen improved. Two months after discharge, he returned to the hospital for a follow-up examination. His general condition was good, and no specific abnormalities were detected. Oral voriconazole treatment was continued. Unexplained TM infection in HIV-negative individuals warrants investigation for immune deficiencies.

Sitosterolemia With Atherosclerosis in a Child: A Case Report.

Introduction: Sitosterolemia is a rare condition in children and is often misdiagnosed as familial hypercholesterolemia. Serious complications can result if not treated promptly and effectively. When pediatric patients are diagnosed with sitosterolemia, vascular, and cardiac studies are important to evaluate for the presence of atherosclerosis. Few cases of severe atherosclerotic heart disease in children with sitosterolemia have been reported, making this case worthy of presentation. Case Presentation: Here, we report a case of sitosterolemia in an 8-year-old child. The patient presented with severe hypercholesterolemia and xanthoma. He was diagnosed two and a half years prior with familial hypercholesterolemia because his father had elevated cholesterol levels. After conventional treatment, the patient was dissatisfied with lipid level control and visited our hospital for further management. Genetic tests of the patient and parents found mutations in intron 7 (NM 022436.2, c.904+1G>A) and intron 9 (NM 022436.2, C. 1324+1de1G) of ABCG5. The 7 intron mutation was from his mother, and the 9 intron mutation was from his father. The patient was diagnosed with sitosterolemia. Results: The child was treated with ezetimibe, a low plant sterol diet, and clopidogrel anticoagulant therapy. After 3 months of treatment, the blood lipid level was significantly lower. Conclusion: Genetic testing should be completed as soon as possible to avoid misdiagnosis in children with abnormally elevated hypercholesterolemia who have a family history of elevated cholesterol. In addition, clinicians should rule out great arterial lesions and be vigilant in evaluating patients for systemic arterial disease and atherosclerosis.

A-kinase interacting protein 1 high expression correlates with advanced tumor stage and poor overall survival in surgical patients with clear cell renal cell carcinoma.

The present study aimed to detect the A-kinase interacting protein 1 (AKIP1) expression in clear cell renal cell carcinoma (ccRCC) tumor tissues and adjacent tissues, and further investigate the correlation of tumor AKIP1 expression with clinicopathological features and survival profile in ccRCC patients.Totally 210 ccRCC patients who underwent resection were retrospectively reviewed, and their tumor and adjacent tissue specimens were acquired for immunohistochemical detection of AKIP1 expression. The survival data of patients were collected for overall survival (OS) assessment.AKIP1 was upregulated in ccRCC tumor tissues compared with adjacent tissues (P < .001). Tumor AKIP1 expression was positively associated with T stage (P = .019), N stage (P = .032), and TNM stage (P = .005) in ccRCC patients. According to AKIP1 expression in tumor tissues, all patients were grouped as AKIP1 low and high expression (AKIP1 high expression were further divided into AKIP1 high+, high++, and high+++ expression). OS was the lowest in the patients with AKIP1 high+++ expression, followed by those with AKIP1 high++ expression and AKIP1 high+ expression, and then patients with AKIP1 low expression (P < .001). Furthermore, multivariate Cox regression exhibited tumor AKIP1 high expression (P = .017), age (>60 years) (P = .030), pathological grade (G2/G3 vs G1) (P = .037), and TNM stage (II/III vs I) (P < .001) were independent predictive factors for decreased OS in ccRCC patients.AKIP1 presents potency to be a novel biomarker for tumor progression and prognosis surveillance in ccRCC.

Beta Blocker Therapy for Congenital Hepatic Arteriovenous Fistula in Two Neonates.

Introduction: Hepatic arteriovenous fistula (HAVF) is an abnormal communication between the hepatic arteries and hepatic veins. This condition is treated mainly using interventional closure and surgery. However, these procedures are associated with many postoperative complications and high mortality. Propranolol and other beta blockers have been used widely and effectively to treat infantile hemangiomas. However, no reports describe the use of these drugs to treat congenital HAVF. Case Description:Here, we present two cases in which beta blocker therapy was used to treat congenital HAVF in neonates. In both cases, antenatal examinations revealed cardiac enlargement and hepatic space-occupying lesions. After birth, both patients rapidly presented with respiratory distress, cyanosis, and heart failure. Echocardiography suggested enlargement of the right heart, widening of the pulmonary artery, and severe pulmonary arterial hypertension, and hepatic examinations revealed HAVF. Results:After admission, the patients were treated with dopamine, milinone, and furosemide for heart failure. However, their conditions worsened, as indicated by nod-like breathing and cyanosis. Endotracheal intubation and ventilator-assisted breathing and a small dose of oral propranolol (1 mg/kg/d) were initiated. The patients' conditions improved, as indicated by decreases in levels of the N-terminal pro-hormone BNP, and the ventilators were removed. The propranolol dose was increased gradually to 2 mg/kg/d. After 2 weeks of propranolol treatment, the neonate in case 2 developed bronchospasm, which improved after propranolol treatment ended and metoprolol treatment was initiated. Liver imaging performed 8-9 months after beta blocker therapy suggested the disappearance of the arteriovenous fistulae in case 2, and close to disappearing of the arteriovenous fistulae in case 1. Conclusion:Propranolol and metoprolol can effectively treat HAVF in infants, an observation consistent with that found in earlier studies that have shown beta blockers are a valid medical treatment option for infantile hemangioma. However, future studies should explore the underlying potential mechanism.

Amiodarone-Related Pure Red Cell Aplastic Anemia and Hypothyroidism in a Child With Total Anomalous Pulmonary Venous Connection.

Introduction: Amiodarone is an effective anti-arrhythmic drug, but there are many clinical side effects that limit its application. There are no case reports of amiodarone-related pure red cell aplastic anemia (PRCA). Case Presentation: Here, we present a case of amiodarone-related PRCA and hypothyroidism in a 7-month-old boy. The patient had a total anomalous pulmonary venous connection (the cardiac type) and had undergone cardiac surgery at the age of 2 months. Eleven days after the operation, atrial tachycardia was observed. Amiodarone was administered orally (15 mg/kg.d), following which the arrhythmia was under control. Subsequently, the patient was prescribed amiodarone (5 mg/kg.d) and discharged. Regular medical consultations were not conducted as required. At 7 months of age (5 months after the operation), the patient returned to the hospital for re-examination. The electrocardiogram showed intermittent sinus bradycardia, occasional junctional escape beats, hemoglobin 7.9 g/DL, and thyroid function-TSH 9.660 uIU/mL. Results: Amiodarone was discontinued. Thyroxine was administered orally. Subsequently, the heart rate improved and TSH returned to normal levels. Nutritional therapy was recommended based on a diagnosis of nutrition-related anemia. A re-visit at 9 months of age showed that the weight was 6 kg, but the routine blood test indicated that hemoglobin was 5.9 g/DL with positive cell anemia and low reticulocyte count. Bone marrow cytology examination suggested PRCA. The hemoglobin level was gradually restored after treatment with prednisone. Conclusion: The use of amiodarone in small infants and young children and its side effects should be carefully monitored. The potential mechanism of amiodarone-related PRCA needs further study.

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathy via the miR-449a/b/Trim11/Mek signaling pathway.

Evidence has shown that long noncoding RNAs (lncRNAs) in the competing endogenous RNA (ceRNA) network are involved in various diseases. However, there is a lack of studies of the ceRNA network in diabetic nephropathy (DN). In this study, we investigated the effect of lncRNAs on mesangial cell (MC) proliferation in DN-related ceRNA networks. Differences in lncRNA and mRNA expression between DN and normal mouse kidney tissues were detected with RNA-seq, and DN-related lncRNA/mRNA/microRNA (miRNA) ceRNA networks were constructed by R3.4.3. Computational analysis was performed, and expression and interactions between the topological RNAs were detected by bioinformatics methods, real-time quantitative PCR (qPCR), and luciferase assay. Cell proliferation ability was measured by 5-ethynyl-2'-deoxyuridine (EdU) in MCs cultured under high- or low-glucose conditions. Moreover, the effect of the topological key lncRNA histocompatibility 2 K region locus 2 (H2k2) H2k2 on MC proliferation via the miRNA (miR)-449a/b/triplet motif 11 (Trim11)/Mek signaling pathway was examined by EdU, flow cytometry analysis, and Western blot. In total, 153 lncRNAs, 428 mRNAs, and 2242 interactions were included in the constructed DN-related ceRNA network. There were 15 RNAs in the top 5% of degree and betweenness. The expression of lncRNA H2k2 and mRNA Trim11 in MCs was increased in DN, which is consistent with the results of RNA-seq and real-time qPCR invivo and in vitro. miR-449a and miR-449b, which were down-regulated in MCs cultured with high glucose, were selected for further analysis. The results of real-time qPCR and luciferase assay revealed the lncRNA H2k2-miR-449a/b-Trim11 interaction in MCs. In addition, the data showed that H2k2 regulates MC proliferation via the miR-449ab/Trim11/Mek signaling pathway. Taken together, these results provide new insight into the association between the topological key lncRNA H2k2 in the DN-related ceRNA network and the miR-449a/b/Trim11/Mek signaling pathway during MC proliferation in DN.-Chen, W., Peng, R., Sun, Y., Liu, H., Zhang, L., Peng, H., Zhang, Z. The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathy via the miR-449a/b/Trim11/Mek signaling pathway.

Long non-coding RNA Rpph1 promotes inflammation and proliferation of mesangial cells in diabetic nephropathy via an interaction with Gal-3.

Diabetic nephropathy (DN) is one of the most significant complications of diabetes and is the primary cause of end-stage kidney disease. Cumulating evidence has shown that renal inflammation plays a role in the development and progression of DN, but the exact cellular mechanisms are unclear. Irregular expression of long non-coding RNAs (lncRNAs) is present in many diseases, including DN. However, the relationship between lncRNAs and inflammation in DN is unclear. In this study, we identified differentially expressed lncRNAs in DN using RNA-sequencing. Among these lncRNAs, we identified seven DN-related lncRNAs in vivo and in vitro using quantitative real-time PCR. One lncRNA in particular, Rpph1 (ribonuclease P RNA component H1), exhibited significantly increased expression. Further, over-expression or knockdown of Rpph1 was found to regulate cell proliferation and the expression of inflammatory cytokines in mesangial cells (MCs). The results revealed that Rpph1 directly interacts with the DN-related factor galectin-3 (Gal-3). Further, over-expression of Rpph1 promoted inflammation and cell proliferation through the Gal-3/Mek/Erk signaling pathway in MCs under low glucose conditions, while knockdown of Rpph1 inhibited inflammation and cell proliferation through the Gal-3/Mek/Erk pathway in MCs under high glucose conditions. These results provide new insight into the association between Rpph1 and the Gal-3/Mek/Erk signaling pathway during DN progression.