Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.

Epidemiological characteristics and trends in postoperative death in children with congenital heart disease (CHD): a single-center retrospective study from 2005 to 2020.

OBJECTIVES: To analyze the epidemiological characteristics and trends in death after thoracotomy in children with congenital heart disease (CHD). METHODS: The clinical data of children with CHD aged 0-14 years who died after thoracotomy in our hospital from January 1, 2005, to December 31, 2020, were retrospectively collected to analyze the characteristics of and trends in postoperative death. RESULTS: A total of 502 patients (365 males; 72.7%) died from January 1, 2005, to December 31, 2020, with an average of 31 deaths per year. For these patients, the median age was 2.0 months, the median length of hospital stay was 16.0 days, the median postoperative time to death was 5.0 days, and the median risk adjustment in congenital heart surgery-1 (RACHS-1) score was 3.0. 29.5% underwent emergency surgery, 16.9% had postoperative ECMO support, and 15.9% received postoperative blood purification treatment. In the past 16 years, the deaths of children with CHD under 1 year old accounted for 80.5% of all deaths among children with CHD aged 0-14 years, and deaths (349 cases) under 6 kg accounted for 69.5% of all deaths. Age at death, weight, and disease type were characterized by annual changes. CONCLUSIONS: The postoperative deaths of children with CHD mainly occurred in infants and toddlers who weighed less than 6.0 kg, and TGA and PA were the most lethal CHDs. The proportion of deaths has been increasing across the years among patients who are young, have a low body weight, and have complex cyanotic CHD.

Diagnosis by metagenomic next-generation sequencing of invasive pulmonary aspergillosis in an infant with chronic granulomatous disease.

Invasive pulmonary aspergillosis (IPA) is a serious fungal infection, with a high degree of mortality in immunocompromised individuals. Diagnosis of IPA is challenging in that clinical manifestations are not specific, with sensitivity of traditional detection procedures low. We report a case of IPA in a chronic granulomatous disease (CGD) infant who was initially suspected to have a lung tumor. Aspergillus fumigatus was identified as the pathogen in bronchoalveolar lavage fluid (BALF) by next-generation sequencing (mNGS). The patient recovered rapidly following a change of appropriate antifungal treatment and was discharged. This case highlights the additional value of BALF-mNGS for the diagnosis of pediatric invasive pulmonary fungal infection in immune-deficient children.

Alagille syndrome associated with total anomalous pulmonary venous connection and severe xanthomas: A case report.

BACKGROUND: Alagille syndrome (ALGS) is an autosomal dominant genetic disorder caused by mutations in the JAG1 or NOTCH2 gene. It is characterized by decreased intrahepatic bile ducts associated with a variety of abnormalities in many other organ systems, such as the cardiovascular, skeletal, and urinary systems. CASE SUMMARY: We report a rare case of ALGS. A 1-month-old male infant presented with sustained jaundice and had a rare congenital heart disease: Total anomalous pulmonary venous connection (TAPVC). Sustained jaundice, particularly with cardiac murmur, caught our attention. Laboratory tests revealed elevated levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, total bilirubin, and total bile acids, indicating serious intrahepatic cholestasis. Imaging confirmed the presence of butterfly vertebra at the seventh thoracic vertebra. This suggested ALGS, which was confirmed by genetic testing with a c.3197dupC mutation in the JAG1 gene. Ursodiol was administered immediately after confirmation of the diagnosis, and cardiac surgery was performed when the patient was 1.5 month old. He recovered well after treatment and was discharged at the age of 3 mo. At the age of two years, the patient returned to our clinic because multiple cutaneous nodules with xanthomas appeared, and their size and number increased over time. CONCLUSION: We report a unique case of ALGS associated with TAPVC and severe xanthomas. This study has enriched the clinical manifestations of ALGS and emphasized the association between JAG1 gene and TAPVC.

Characteristics of in-hospital mortality of congenital heart disease (CHD) after surgical treatment in children from 2005 to 2017: a single-center experience.

BACKGROUND: To evaluate trends in the in-hospital mortality rate for pediatric cardiac surgery procedures between 2005 and 2017 in our center, and to discuss the mortality characteristics of children's CHD after thoracotomy. METHODS: This retrospective data were collected from medical records of children underwent CHD surgery between 2005 and 2017. RESULTS: A total of 19,114 children with CHD underwent surgery and 444 children died, with the in-hospital mortality was 2.3%. Complex mixed defect CHD had the highest fatality rate (8.63%), left obstructive lesion CHD had the second highest fatality rate (4.49%), right to left shunt CHD had the third highest mortality rate (3.51%), left to right shunt CHD had the lowest mortality rate (χ2 = 520.3,P < 0.05). The neonatal period has the highest mortality rate (12.17%), followed by infant mortality (2.58%), toddler age mortality (1.16%), and preschool age mortality (0.94%), the school age and adolescent mortality rate was the lowest (χ2 = 529.3,P < 0.05). In addition, the fatality rate in boys was significantly higher than that in girls (2.77% versus 1.62%, χ2 = 26.4, P < 0.05). CONCLUSIONS: The mortality rate of CHD surgery in children decreased year by year. The younger the age and the more complicated the cyanotic heart disease, the higher the mortality rate may be.

3D Printing of an Oil/Water Mixture Separator with In Situ Demulsification and Separation.

Currently, many meshes, membranes, and fabrics with extreme wettability of superhydrophobicity/superoleophilicity, or superhydrophilicity and underwater superoleophobicity are promising candidates for oil/water mixture separation. Nevertheless, a facile yet effective way to design and fabricate porous mesh still remains challenging. In this work, fused deposition modeling (FDM) 3D printing of Fe/polylactic acid (PLA) composites was employed to fabricate superhydrophilic and underwater superoleophobic mesh (S-USM) with hydrogel coatings via the surface polymerization of Fe(II)-mediated redox reaction. In addition, salt of aluminum chloride was incorporated within the hydrogel coating, which was attributed to strengthening the demulsification of oil-in-water emulsions, resulting in efficient separation of oil-in-water mixtures. The S-USM was efficient for a wide range of oil-in-water mixtures, such as dodecane, diesel, vegetable oil, and even crude oil, with a separation efficiency of up to 85%. In this study, the flexible design and fabrication of 3D printing were used for the facile creation of spherical oil skimmers with hydrogel coatings that were capable of removing the floating oil. Most importantly, this work is expected to promote post-treatment processes using 3D printing as a new manufacturing technology and, in this way, a series of devices of specific shape and function will be expanded to satisfy desired requirements and bring great convenience to personal life.

ECMO as an effective rescue therapeutic for fulminant myocarditis complicated with refractory cardiac arrest.

Fulminant myocarditis (FM) is a life-threatening disease in children. With a rapid, progressive course of deterioration, it causes refractory cardiorespiratory failure even with optimal clinical intervention. We present the case of a 9-year-old girl with FM complicated by cardiogenic shock, malignant arrhythmia, and refractory cardiac arrest. She received effective cardiopulmonary resuscitation, therapeutic hypothermia, and other supportive treatments. However, the patient rapidly worsened into pulseless ventricular tachycardia and refractory cardiac arrest. Therefore, we performed extracorporeal membrane oxygenation (ECMO) to establish spontaneous circulation after the failure of standard resuscitation measures. The girl recovered with intact cardiac and neurocognitive functions after continued ECMO treatment for 221 hours. Therefore, ECMO is an effective rescue therapeutics for FM, especially when complicated with refractory cardiac arrest.

Exome sequencing identified a novel missense mutation c.464G>A (p.G155D) in Ca2+-binding protein 4 (CABP4) in a Chinese pedigree with autosomal dominant nocturnal frontal lobe epilepsy.

The aim of this study was to identify disease-causing gene mutations in a Chinese family affected with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), a 4-generation pedigree of 27 members in the Southern Chinese Han population, including 11 individuals diagnosed with ADNFLE. DNA samples were collected from 15 family members, chinese han people, including seven affected and eight unaffected individuals. None of these patients had night blindness or visual disorders. Four affected individuals were screened for mutations using whole-exome sequencing, and 13 potentially interesting mutations shared by all the four affected individuals were validated using the Sanger sequencing method. Only one novel missense mutation c.464G>A (p.G155D) in the CABP4 gene, encoding the neuronal Ca2+-binding protein 4 (CaBP4), was present in all seven affected individuals in this family as revealed by PCR with blood DNA samples using CABP4 primers. The mutation was also found in one young unaffected family member, but was absent from 300 unrelated control subjects. The p.G155D mutation, located near the Ca2+ binding motif EF-hand 1 and the L-type Ca2+ channel (Cav1.4) binding motif within the N-terminal lobe of CaBP4, is predicted to affect protein function according to the bioinformatics tools PolyPhen-2 and SIFT. These findings suggest that mutations in the CABP4 gene may be linked to ADNFLE.