A de novo novel variant in the MT-TD gene is associated with prominent extra-neurologic manifestations.

Defects in the mitochondrial tRNA genes cause a group of highly clinically and genetically heterogeneous disorders, which poses a challenge for clinical identification and genetic diagnosis. Here, we present a pre-school boy with a novel MT-TD variant m.7560T>C at the heteroplasmy level of 76.53% in blood, 93.34% in urine sediments, and absent in the healthy mother's blood and urine. Besides convulsions, brain magnetic resonance imaging abnormalities and high plasma lactate, the boy presented with the prominent extra-neurologic phenotype including steroid-resistant nephrotic syndrome associated with focal segmental glomerulosclerosis characterized by abnormal mitochondria in podocytes, cortical blindness, and pancreatitis. To our knowledge, this is the unique case with MT-TD m.7560T>C-related multi-organ impairments, which expands the phenotypic and mutational spectrum of primary mitochondrial diseases.

Glomerular basement membrane ultrastructural changes in a patient with COQ2 glomerulopathy: A case report.

Primary coenzyme Q10 deficiency-1, caused by COQ2 disease-causing variants, is an autosomal recessive disorder, and genetic testing is the gold standard for diagnosing this condition. A Chinese boy with steroid-resistant nephrotic syndrome, focal segmental glomerulosclerosis, and progressive kidney insufficiency was included in the study. Electron microscopy revealed the glomerular basement membrane with irregular thickness and lamellation with diffuse effacement of foot processes in the podocytes, and swollen mitochondria with abnormal cristae in the podocytes. Coenzyme Q10 supplementation started about 3 weeks after the onset of mild kidney dysfunction did not improve the proband's kidney outcome. Proband-only whole-exome sequencing and Sanger sequencing revealed two heteroallelic COQ2 variants: a maternally inherited novel variant c.1013G > A[p.(Gly338Glu)] in exon 6 and a variant of unknown origin c.1159C > T[p.(Arg387*)] in exon 7. Subsequent long-read sequencing demonstrated these two variants were located on different alleles. Our report extends the phenotypic and genotypic spectrum of COQ2 glomerulopathy.

[Clinical and genetic analysis of a child with co-morbid progressive IgA nephropathy and COQ8B-associated glomerulopathy].

OBJECTIVE: To explore the genetic etiology and clinical outcome of a child with co-morbid progressive IgA nephropathy and COQ8B-associated glomerulopathy. METHODS: A child who was admitted to Peking University First Hospital on March 2, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples from the child and his parents and sister. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing. This study was approved by the Peking University First Hospital (Ethics No. 2016[1029]). RESULTS: The child, a 7-year-old boy who had developed proteinuria 8 months before, was diagnosed with IgA nephropathy (M1E1S1T1C1). With steroid, cyclophosphamide, cyclosporine and angiotensin-converting enzyme inhibitor therapy, partial remission of proteinuria was achieved. However, his serum creatinine level had increased from 53.8 mol/L at the onset of disease to 86.7 mol/L after 3.9 years, along with massive proteinuria. Kidney biopsy still indicated IgA nephropathy (M0E0S1T0C0). The child was found to harbor a homozygous c.737G>A (p.Ser246Asn) missense variant of the COQ8B gene, for which his parents and sister were heterozygous carriers. The variant was predicted to be pathogenic (PS1+PM2_Supporting+PM3+PP3+PP4) based on the guidelines from the American College of Medical Genetics and Genomics. The child was treated with high-dose coenzyme Q10 in combination with steroid and/or mycophenolate mofetil, though his serum creatinine level still increased to 286 mol/L after 7.3 years, which conformed to a chronic kidney disorder with glomerular filtration rate category of G3b. CONCLUSION: The homozygous c.737G>A missense variants of the COQ8B gene probably underlay the progressive kidney dysfunction in this child. For children with IgA nephropathy presenting with atypical clinical manifestations, unsatisfactory therapeutic effect, and/or early onset of kidney function decline, coexistence of other diseases should be suspected.

Intervention Effect of Time Management Training on Nurses' Mental Health during the COVID-19 Epidemic.

BACKGROUND: The sudden outbreak of COVID-19 has put nurses into a severe test, both physiologically and psychologically. While being required to provide patients with high-quality medical services, nurses also bear the responsibilities and pressures from work, face trauma, disease and even death events, and are thereby more inclined to negative psychological feelings, decline in mental health, and reduction in the quality of their clinical nursing services. Under the background of the COVID-19 epidemic, it is urgent to carry out related intervention in nurses' psychological crisis. SUBJECTS AND METHODS: The mental health of 400 nurses from three tertiary hospitals in Shanghai, China was assessed from September to December 2020. Then, time management training was conducted for 66 nurses who were voluntarily enrolled in the study. They were divided into the intervention group (35 participants) and the control group (31 participants). RESULTS: After the 16-week intervention, (1) there is a significant decrease in the total SCL-90 score of the intervention group and significant decreases in the scores in the 9 dimensions of the scale, suggesting significant improvement in the mental health level; (2) there is a significant increase in the score of the intervention group in subjective well-being, while there is no significant increase in the control group; (3) There is a significant decrease in the score of the intervention group in work stress reaction, but there is no significant decrease in the control group, and there is a significant increase in the physiological reaction of the control group in the measurement after 8 weeks. CONCLUSIONS: It is critical to pay attention to and solve the low mental health level of nurses during the COVID-19 epidemic; Time management training can effectively improve the mental health level of nurses, and it is an effective intervention model to promote nurses' mental health and relieve their work stress.

Effects of Bifidobacterium infantis on cytokine-induced neutrophil chemoattractant and insulin-like growth factor-1 in the ileum of rats with endotoxin injury.

BACKGROUND: The digestive tract is the maximal immunizing tissue in the body, and mucosal integrity and functional status of the gut is very important to maintain a healthy organism. Severe infection is one of the most common causes of gastrointestinal dysfunction, and the pathogenesis is closely related to endotoxemia and intestinal barrier injury. Bifidobacterium is one of the main probiotics in the human body that is involved in digestion, absorption, metabolism, nutrition, and immunity. Bifidobacterium plays an important role in maintaining the intestinal mucosal barrier integrity. This study investigated the protective mechanism of Bifidobacterium during ileal injury in rats. AIM: To investigate the effects of Bifidobacterium on cytokine-induced neutrophil chemoattractant (CINC) and insulin-like growth factor 1 (IGF-1) in the ileum of rats with endotoxin injury. METHODS: Preweaning rats were randomly divided into three groups: Control (group C), model (group E) and treatment (group T). Group E was intraperitoneally injected with lipopolysaccharide (LPS) to create an animal model of intestinal injury. Group T was intragastrically administered Bifidobacterium suspension 7 d before LPS. Group C was intraperitoneally injected with normal saline. The rats were killed at 2, 6 or 12 h after LPS or physiological saline injection to collect ileal tissue samples. The expression of ileal CINC mRNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR), and expression of ileal IGF-1 protein and mRNA was detected by immunohistochemistry and RT-PCR, respectively. RESULTS: The ileum of rats in Group C did not express CINC mRNA, ileums from Group E expressed high levels, which was then significantly decreased in Group T (F = 23.947, P < 0.05). There was no significant difference in CINC mRNA expression at different times (F = 0.665, P > 0.05). There was a high level of IGF-1 brown granules in ileal crypts and epithelial cells in Group C, sparse staining in Group E, and dark, dense brown staining in Group T. There was a significant difference between Groups C and E and Groups E and T (P < 0.05). There was no significant difference in IGF-1 protein expression at different times (F = 1.269, P > 0.05). IGF-1 mRNA expression was significantly different among the three groups (P < 0.05), though not at different times (F = 0.086, P > 0.05). CONCLUSION: Expression of CINC mRNA increased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium reduced CINC mRNA expression. IGF-1 protein and mRNA expression decreased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium prevented the decrease in IGF-1 expression. Bifidobacterium may increase IGF-1 expression and enhance intestinal immune barrier function in rats with endotoxin injury.