Value of sonographic bidirectional arterial flow combined with elastography for diagnosis of breast imaging reporting and data system category 4 breast masses.

OBJECTIVES: The purpose of this study was to evaluate the role of bidirectional arterial flow combined with ultrasound elastography for differentiation of American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) category 4 masses. METHODS: A total of 116 BI-RADS category 4 breast masses were evaluated with color Doppler sonography, spectral analysis, and elastography. The sensitivity, specificity, accuracy, positive and negative predictive values, and receiver operator characteristic curve were used to estimate the diagnostic performance for each modality and the combination method. RESULTS: The combination method had the best sensitivity (81.1%) but less specificity (94.9%) and the best accuracy (90.5%). The discriminating power of the combined method (area under the curve [AUC], 0.880; 95% confidence interval [CI], 80.0%-96.0%) was significantly higher than that of bidirectional arterial flow (AUC, 0.818; 95% CI, 72.0%-91.6%; P< .01) and elastography (AUC, 0.765; 95% CI, 65.9%-87.0%; P< .01). CONCLUSIONS: Bidirectional arterial flow evaluation, when combined with elastography, could potentially improve diagnostic accuracy for BI-RADS category 4 breast masses.

A Case of Coma Bullae Associated with Brachioradial Artery.

We present the first case of coma bullae observed in a 67-year-old woman due to pressure and ischemia associated with brachioradial artery. A skin biopsy taken from the ulcer border revealed extensive loss of the epidermis, fibrosis of dermis, mild infiltration by lymphocytes and neutrophils, and necrosis of the focal eccrine ducts. CT angiography of the right upper limb showed a high origin of the radial artery, meanwhile both high originating radial artery and the anastomoses were tortuous and were of relatively small caliber. The diagnosis of coma bullae was made. After tissue debridement, the skin lesions gradually recovered, leaving atrophic scars.

miR-146a-5p Modulates Adult Hippocampal Neurogenesis Deficits Through Klf4/p-Stat3 Signaling in APP/PS1 Mice.

Alzheimer's disease (AD) is the most common neurodegenerative disease, and currently, no effective treatment strategies exist for this condition. MicroRNAs (miRNAs) have emerged as promising therapeutic targets of AD. Previous studies have highlighted the significant role of miR-146a-5p in regulating adult hippocampal neurogenesis (AHN). Here, we aimed to investigate whether miR-146a-5p plays a role in the mechanisms of AD. We employed quantitative real-time PCR (qRT-PCR) to assess the expression of miR-146a-5p. Additionally, we examined the expression of Krüppel-like factor 4 (Klf4), Signal transducer and activator of transcription 3 (Stat3), and phosphorylated Stat3 (p-Stat3) using western blot analysis. Furthermore, we validated the interaction between miR-146a-5p and Klf4 using a dual-luciferase reporter assay. Immunofluorescence staining was employed to evaluate AHN. And Contextual fear conditioning discrimination learning (CFC-DL) experiment was used to detect pattern separation. Our findings in the hippocampus of APP/PS1 mice revealed upregulated levels of miR-146a-5p and p-Stat3, while Klf4 levels were downregulated. Interestingly, both miR-146a-5p antagomir and p-Stat3 inhibitor obviously rescued neurogenesis and pattern separation in APP/PS1 mice. Moreover, application of miR-146a-5p agomir reversed the protective effects of Klf4 upregulation. These findings open new avenues for protection against AD through the modulation of neurogenesis and cognitive decline via the miR-146a-5p/Klf4/p-Stat3 pathway.

ALKBH5 Expression could Affect the Function of T Cells in Systemic Lupus Erythematosus Patients: A Case-control Study.

BACKGROUND: N6-methyladenosine (m6A) modification is widespread in eukaryotic mRNA, regulated by m6A demethylase, AlkB homolog 5 (ALKBH5). However, the role of m6A in systemic lupus erythematosus (SLE) is still obscure. We explored ALKBH5 expression in SLE patients and its effects on T cells. METHODS: 100 SLE patients and 110 healthy controls were recruited to investigate the expression of ALKBH5 in peripheral blood mononuclear cells (PBMCs). An additional 32 SLE patients and 32 health controls were enrolled to explore the expression of ALKBH5 in T cells. Then we explored the function of ALKBH5 in T cells by lentivirus. RESULTS: The expressions of ALKBH5 were downregulated in both PBMCs and T cells in SLE patients (all P<0.05). In PBMCs: ALKBH5 mRNA levels were associated with a complement C4 level in plasma (P<0.05). In T cells: ALKBH5 mRNA levels were downregulated in SLE patients with low complement levels, high antidsDNA, anti-Sm, anti-RNP, and proteinuria compared with those without, respectively (all P<0.05); ALKBH5 mRNA levels were negatively related with SLE disease activity index score, erythrocyte sedimentation rate, and anti-dsDNA levels (all P<0.05), and positively correlated with complement C3 and C4 level (all P<0.05). Functionally, the overexpression of ALKBH5 promoted apoptosis and inhibited the proliferation of T cells (all P<0.05). CONCLUSION: ALKBH5 expression is downregulated in SLE patients and could affect the apoptosis and proliferation of T cells, but the exact mechanism still needs to be further explored.

Involvement of N6-methyladenosine modifications of long noncoding RNAs in systemic lupus erythematosus.

BACKGROUND: LncRNAs are potential biomarkers for SLE, but the epigenetic regulatory mechanisms of N6-methyladenosine (m6A) modification in SLE remain largely unclear. METHODS: In this study, we established m6A modification profile and investigated the potential roles of m6A-related lncRNAs in SLE. The m6A modification profile of SLE was established using MeRIP-seq. Four potential m6A related-lncRNAs (linc02446, linc01410, Xist, and PSMB8-AS1) were selected for validation using qRT-PCR, and their expression and association with clinical characteristics with SLE were evaluated. RESULTS: Overall, m6A level was lower in patients with SLE than in controls. Compared with controls, the expression of the two m6A related-lncRNAs (Xist and PSMB8-AS1) was downregulated in patients with SLE (all P < 0.05); the linc02446 was up-regulated in PBMCs of patients with SLE (Z=-2.738, P = 0.006), while it was not differentially expressed in T cells (Z=-0.387, P = 0.699). No significant alteration in linc01410 expression was observed in patients (Z=-0.940, P = 0.347). The lower expression levels of Xist and PSMB8-AS1 were associated with many clinical manifestations in patients with SLE (all P < 0.05). Additionally, mRNAs co-expressed with m6A related-lncRNAs (Xist, linc02446, and PSMB8-AS1) also participated in SLE. CONCLUSION: These results suggest that m6A methylation and m6A related-lncRNAs might be involved in the pathogenesis of SLE. Thus, our findings provide some clues on the potential function of lncRNAs that m6A modification may target in novel therapeutic or diagnostic strategies for SLE.

Comprehensive DNA Methylation-transcriptome Profiles Association Analysis During the Treatment of Acute Myelocytic Leukemia.

BACKGROUND: Epigenetic modifications have recently attracted much attention in the study of the biological mechanisms of Acute Myelocytic Leukemia (AML) for therapy and prognosis. However, studies on DNA methylation changes during AML treatment are limited. OBJECTIVE: The comprehensive DNA methylation-transcriptome profiles association analysis in this study aimed to establish whole-genome DNA methylation profiles and explore DNA methylation-related genes and their potential functions before and after treatment. And more appropriate biomarkers are expected to be identified for therapy strategies in AML. METHODS: Illumina 450K and RNA-Seq data were obtained from the Cancer Genome Atlas. We performed comprehensive DNA methylation-transcriptome profiles association analysis, pathway analysis, correlation analysis, and survival analyses. The StarBase database was utilized to predict interactions between lncRNAs, miRNAs and target mRNAs. RESULTS: In total, 1592 distinct CpG sites and 2419 different expression transcripts were identified between pretreatment and post-treatment AML. The significantly enriched functions of methylated genes were stem cell differentiation, cell population maintenance, and cell development. The expression of UGT3A2, MOG, and VSTM1 was correlated with DNA methylation levels (r2 >0.5). Lastly, we identified 4 lncRNAs, 9 miRNAs and 142 mRNAs to construct a lncRNA-miRNA-mRNA ceRNA network. CONCLUSION: Our results revealed that DNA methylation was altered before and after treatment. Alterations in DNA methylation affected target gene expression and participated in the key biological processes of AML. Therefore, ceRNA networks may provide further insight into the study of favorable therapeutic markers in AML.

Simvastatin delivery on PEEK for bioactivity and osteogenesis enhancements.

A strategy developed for obtaining positive cellular responses remains to be focused in the filed of functional biomimetics. In this study, a hydrogel covered simvastatin-loaded polyetheretherketone (PEEK) bio-composites was constructed with the purpose of bone tissue regeneration therapy. Briefly, a three-dimensional (3D) porous structure was fabricated on PEEK surface; then the substrate was functionalized with the poly(L-lactic acid)/simvastatin porous film and hyaluronic acid hydrogel subsequently. In vitro cell attachment, proliferation, and cytoskeletal observation experiments reveal that our scaffolds show better bio-affinity due to the layer of hyaluronic acid hydrogel compared with control. Furthermore, the alkaline phosphatase activity, calcium mineral deposition evaluation, and gene expression for osteogenic potential all exhibit that the superior osteogenic differentiation of MC3T3-E1 pre-osteoblasts on our scaffolds. Therefore, our PEEK samples loaded with simvastatin and covered with hyaluronic acid hydrogel hold great potential in clinical applications for bone repair.