NOD1 deficiency ameliorates the progression of diabetic retinopathy by modulating bone marrow-retina crosstalk.

BACKGROUND: Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) plays a pivotal role in inducing metabolic inflammation in diabetes. Additionally, the NOD1 ligand disrupts the equilibrium of bone marrow-derived hematopoietic stem/progenitor cells, a process that has immense significance in the development of diabetic retinopathy (DR). We hypothesized that NOD1 depletion impedes the advancement of DR by resolving bone marrow dysfunction. METHODS: We generated NOD1-/--Akita double-mutant mice and chimeric mice with hematopoietic-specific NOD1 depletion to study the role of NOD1 in the bone marrow-retina axis. RESULTS: Elevated circulating NOD1 activators were observed in Akita mice after 6 months of diabetes. NOD1 depletion partially restored diabetes-induced structural changes and retinal electrical responses in NOD1-/--Akita mice. Loss of NOD1 significantly ameliorated the progression of diabetic retinal vascular degeneration, as determined by acellular capillary quantification. The preventive effect of NOD1 depletion on DR is linked to bone marrow phenotype alterations, including a restored HSC pool and a shift in hematopoiesis toward myelopoiesis. We also generated chimeric mice with hematopoietic-specific NOD1 ablation, and the results further indicated that NOD1 had a protective effect against DR. Mechanistically, loss of hematopoietic NOD1 resulted in reduced bone marrow-derived macrophage infiltration and decreased CXCL1 and CXCL2 secretion within the retina, subsequently leading to diminished neutrophil chemoattraction and NETosis. CONCLUSIONS: The results of our study unveil, for the first time, the critical role of NOD1 as a trigger for a hematopoietic imbalance toward myelopoiesis and local retinal inflammation, culminating in DR progression. Targeting NOD1 in bone marrow may be a potential strategy for the prevention and treatment of DR.

Comparison of the accuracy of two⁃dimensional and three⁃dimensional photography in the facial measuremenof patients with unilateral cleft lip t / 口腔疾病防治

Objective@#To compare the measurement accuracy of two⁃dimensional (2D) photography and three⁃di⁃mensional (3D) photography in the analysis of the asymmetric appearance of children with cleft lip and palate and the influence of the severity of asymmetric deformity on the accuracy of facial measurement to guide clinical measurement work@* Methods@#Children with unilateral cleft lip were enrolled in this prospective study. Seven parameters⁃⁃the devia⁃tion of the pronasale, subnasale, and labrale superius, as well as the cleft/noncleft ratio of the width of nostrils, length and height of lateral lips and height of columella⁃were measured with Vernier calipers as the gold standard. Traditional 2D photography and 3D stereophotogrammetry photos were taken and measured. The extent of cleft malformation is indi⁃cated by the ratio of the cleft side to the noncleft side. The error size is represented by the ratio difference between two⁃dimensional photography or stereophotogrammetry with the ratio of the gold standard@* Results@#Thirteen patients were eventually recruited. The measurement results of the ratio of lateral lip height by 2D photography tended to be larger (P＝0.019), and the measurement results of the ratio of columella height tended to be smaller (P＝0.008). The measure⁃ment results of the deviation of the subnasale by stereophotogrammetry tended to be smaller (P＝0.003). The pronasale deviation (P＝0.022) with two⁃dimensional photography, the deviation of the labrale superius (P＝0.025) and the ratio of lateral lip length (P＝0.036) with stereophotogrammetry had a significant negative correlation with the extent of cleft malformation@* Conclusion@#Both two⁃dimensional photography and stereophotogrammetry have errors and biases that underexaggerate or overexaggerate the extent of cleft malformation, and some errors may increase with the decrease in the extent of cleft malformation. When applying two⁃dimensional and three⁃dimensional photography to analyze cleft lip and palate deformities, these biases should be considered to evaluate the face more objectively

Clinical and molecular characterization of POU3F4 mutations in multiple DFNX2 Chinese families.

BACKGROUND: Many X-linked non-syndromic hearing loss (HL) cases are caused by various mutations in the POU domain class 3 transcription factor 4 (POU3F4) gene. This study aimed to identify allelic variants of this gene in two Chinese families displaying X-linked inheritance deafness-2 (DFNX2) and one sporadic case with indefinite inheritance pattern. METHODS: Direct DNA sequencing of the POU3F4 gene was performed in these families and in 100 Chinese individuals with normal hearing. RESULTS: There are characteristic imaging findings in DFNX2 Chinese families with POU3F4 mutations. The temporal bone computed tomography (CT) images of patients with DFNX2 are characterized by a thickened stapes footplate, hypoplasia of the cochlear base, absence of the bony modiolus, and dilated internal acoustic meatus (IAM) as well as by abnormally wide communication between the IAM and the basal turn of the cochlea. We identified three causative mutations in POU3F4 for three probands and their extended families. In family 1468, we observed a novel deletion mutation, c.973delT, which is predicted to result in a p.Trp325Gly amino acid frameshift. In family 2741, the mutation c.927delCTC was identified, which is predicted to result in the deletion of serine at position 310. In both families, the mutations were located in the POU homeodomain and are predicted to truncate the C-terminus of the POU domain. In the third family, a novel de novo transversion mutation (c.669 T > A) was identified in a 5-year-old boy that resulted in a nonsense mutation (p.Tyr223*). The mutation created a new stop codon and is predicted to result in a truncated POU3F4 protein. CONCLUSIONS: Based on characteristic radiological findings and clinical features, POU3F4 gene mutation analysis will increase the success rate of stapes operations and cochlear implantations, and improve molecular diagnosis, genetic counseling, and knowledge of the molecular epidemiology of HL among patients with DFNX2.

[Clinical analysis and prevention of complications associated with ultrasound-guided percutaneous thick needle biopsy].

OBJECTIVE: To investigate the occurrence of complications in US-guided percutaneous biopsy using core (>19G) gauge cutting needle. METHODS: A retrospective analysis of 5366 US-guided thick needle biopsies was conducted to analyze the incidence of complications after biopsy at different positions. RESULTS: The total incidence of complications was 1.08%, including most frequent hemorrhage, pneumothorax, hemotysis and infection. CONCLUSION: Ultrasound-guided automatic biopsy is easy to operate and safe, and strict execution of the procedures can lower the incidence of the complications.