Fibrodysplasia Ossificans Progressiva: A Case Report.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant genetic disorder characterized by congenital great toe malformations and progressive ectopic ossification. We report a typical case of FOP in a 22-year-old female patient presenting with limited movement of the left knee joint, which began following trauma in 2019. Clinical examination revealed a large mass behind the left knee, bilateral great toe deformities, and no palpable superficial lymph nodes, without systemic pain or other discomfort. Imaging and genetic testing further supported the diagnosis of FOP, demonstrating high-density ossification within soft tissues and a mutation in the ACVR1 gene. Treatment involved a combination of methylprednisolone and alendronate sodium vitamin D3 tablets, which yielded some therapeutic efficacy. The discussion emphasizes clinical diagnosis, pathogenesis, and treatment strategies for FOP, including injury prevention, rehabilitation exercises, and pharmacological interventions. Despite the lack of definitive treatment options, timely diagnosis and comprehensive management can effectively alleviate symptoms and improve the quality of life for affected individuals.

Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis.

BACKGROUND: Intracranial aneurysm (IA) is the most common cerebrovascular disease, and subarachnoid hemorrhage caused by its rupture can seriously impede nerve function. Pyroptosis is an inflammatory mode of cell death whose underlying mechanisms involving the occurrence and rupture of IAs remain unclear. In this study, using bioinformatics analysis, we identified the potential pyroptosis-related genes (PRGs) and performed their inflammatory response mechanisms in IAs. METHODS: The mRNA expression matrix of the IA tissue was obtained from the Gene Expression Omnibus database, and 51 PRGs were obtained from previous articles collected from PubMed. The differentially expressed PRGs (DEPRGs) were performed using R software. Subsequently, we performed enrichment analysis, constructed a protein-protein interaction network, performed weighted gene coexpression network analysis (WGCNA) and external validation using another dataset, and identified a correlation between hub genes and immune cell infiltration. Finally, the expression and tissue distribution of these hub genes in IA tissues were detected using Western blotting and immunohistochemical (IHC) staining. RESULTS: In total, 12 DEPRGs associated with IA were identified in our analysis, which included 11 up-regulated and one down-regulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the DEPRGs were mostly enriched in the NOD-like receptor signaling pathway, interleukin-1 beta production, and the inflammasome complex. Three hub genes, NLRP3, IL1B and IL18, were identified using Cytoscape software and the WGCNA correlation module, and external validation revealed statistically significant differences between the expression of these hub genes in the ruptured and unruptured aneurysm groups (p < 0.05). Furthermore, all AUC values were > 0.75. Immune cell infiltration analysis suggested that the hub genes are related to CD8 T cell, macrophages and mast cells. Finally, IHC staining revealed that the protein levels of these hub genes were higher in ruptured and unruptured IA tissues than in normal tissues (p < 0.05). CONCLUSION: The results of bioinformatics analysis showed that pyroptosis is closely related to the formation and rupture of IA, and identified three potential hub genes involved in the pyroptosis and infiltration ofcells. Our findings may improve the understanding of the mechanisms underlying pyroptosis in IA.

Association between single-nucleotide polymorphism rs145497186 related to NDUFV2 and lumbar disc degeneration: a pilot case-control study.

OBJECTIVE: The association between the single-nucleotide polymorphisms (SNPs) rs28742109, rs12955018, rs987850, rs8093805, rs12965084 and rs145497186 related to gene named NADH dehydrogenase [ubiquinone] flavoprotein 2 (NDUFV2) and lumbar disc degeneration (LDD) was preliminary investigated in a small sample size. METHODS: A total of 46 patients with LDD and 45 controls were recruited at Qilu Hospital of Shandong University, and each participant provided 5 mL peripheral venous blood. NA was extracted from the blood of each participant for further genotyping. The frequency of different genotypes in the case group and control group was determined, and analysis of the risk of LDD associated with different SNP genotypes was performed. The visual analogue scale (VAS) scores of the patients' degree of chronic low back pain were calculated, and the relationship between VAS scores and SNPs was analysed. RESULTS: After excluding the influence of sex, age, height, and weight on LDD, a significant association between SNP rs145497186 related to NDUFV2 and LDD persisted (P = 0.006). Simultaneously, rs145497186 was found to be associated with chronic low back pain in LDD populations. CONCLUSION: NDUFV2 rs145497186 SNP could be associated with susceptibility to LDD and the degree of chronic low back pain.

Long noncoding RNA KCNQ1OT1 inhibits osteoclast differentiation by regulating the miR-128-3p/NFAT5 axis.

Noncoding RNAs play an important role in regulating osteoclast differentiation. We investigated whether and how potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1), a long noncoding RNA, regulates osteoclast differentiation. We found that the expression of KCNQ1OT1 was downregulated in osteoporotic bone tissue. Then transfection of KCNQ1OT1 overexpression vectors or small interfering RNAs showed that the proliferation, migration, and osteoclast differentiation of RAW 264.7 cells were inhibited by KCNQ1OT1 upregulation, while they were promoted by KCNQ1OT1 knockdown. Interestingly, we found and confirmed that miR-128-3p was a target of KCNQ1OT1 using online databases, dual luciferase reporter assays and quantitative real-time polymerase chain reaction, and that it inhibited the expression of miR-128-3p. Moreover, we confirmed that miR-128-3p directly targeted nuclear factor of activated T cell 5 (NFAT5), a protein that combines with osteoprotegerin and thus regulates osteoclastogenesis with the presence of the receptor activator of nuclear factor κB ligand. Furthermore, we demonstrated that both the knockdown of KCNQ1OT1 and the overexpression of miR-128-3p attenuate the expression of NFAT5, while upregulating the osteoclastogenesis markers c-Fos, NFATc1, and Ctsk. The results from overexpression of KCNQ1OT1 and the inhibition of miR-128-3p were contrary to the above. Finally, we found that the inhibition of osteoclast differentiation by KCNQ1OT1 overexpression could be rescued using a miR-128-3p mimic, while the enhancement of migration and osteoclast differentiation by si-NFAT5 could be reversed with a miR-128-3p inhibitor. These results suggested that KCNQ1OT1 regulates the osteoclast differentiation via the miR-128-3p/NFAT5 axis.

Association of Single Nucleotide Polymorphism rs2228570 with Lumbar Disc Degeneration: A Case-Control Study and Meta-Analysis.

OBJECTIVE: To examine the association between single nucleotide polymorphisms (SNPs) rs2228570, rs731236, rs7975232, and rs1544410 and lumbar disc degeneration (LDD) predisposition. METHODS: A search strategy was carried out, and the data were extracted after being chosen by the inclusion and exclusion criteria. Pooled odds ratios and 95% confidence intervals were calculated to assess the association between the aforementioned SNPs and LDD under allelic, dominant, recessive, heterozygous, and homozygous genetic models. In addition, a case-control study involving 46 LDD cases and 45 controls was also performed in the analysis to verify the result. RESULTS: A total of 17 studies were included in this meta-analysis. The pooled results did not show any association between vitamin D receptor (VDR) gene polymorphisms and LDD. But, interestingly, in subgroup analysis, the rs2228570 polymorphism was associated with LDD under the allelic (OR = 0.70, 95% CI = 0.56-0.87, p = 0.002), recessive (OR = 0.60, 95% CI = 0.43-0.84, p = 0.003), and homozygous (OR = 0.47, 95% CI= 0.28-0.79, p = 0.004) genetic models in the Asian population. SNPs rs731236 and rs7975232 still did not show any obvious association. We obtained a similar result from the case-control study: rs2228570 had an obvious relationship with LDD under allelic and homozygous genetic models. At the same time, we found that rs2228570 was also associated with the degree of low back pain (visual analogue scale, VAS score) in LDD population. CONCLUSION: SNP rs2228570 was significantly associated with LDD predisposition and the degree of low back pain in the Asian population.

Thymus­expressed chemokine secreted by breast cancer cells promotes metastasis and inhibits apoptosis.

The aim of the present study was to investigate the underlying mechanisms of thymus­expressed chemokine (TECK) autocrine signaling, and its effect on carcinogenesis and the development of breast cancer. The present study also assessed epithelial­mensenchymal transition (EMT) and cell migration, invasion, proliferation and apoptosis. Breast cancer cell lines MCF­7 and MDA­MB­231 were used in the present study, and TECK basic expression in cancer cells was investigated using western blotting (WB). EMT markers, Akt pathway molecules and apoptosis indicators were detected by reverse transcription­quantitative PCR or WB. In order to assess migration and invasion, wound healing and Matrigel invasion assays were performed. Moreover, flow cytometry was used to assess the rate of proliferation and apoptosis. In vivo experiments were conducted in nude mice to assess cancer growth. It was revealed that breast cancer cells could secrete TECK in an autocrine manner. Furthermore, TECK could increase cell migration and invasion by promoting EMT and inhibit apoptosis via the Akt signaling pathway.