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The current study was aimed at exploring the potential roles and possible mechanisms of miR-10a-5p in osteoarthritis (OA). We performed RT-qPCR, Western blot, CCK8, EdU Assay, and flow cytometry assay to clarify the roles of miR-10a-5p in OA. Furthermore, the whole transcriptome sequencing together with integrated bioinformatics analyses were conducted to elucidate the underlying mechanisms of miR-10a-5p involving in OA. Our results demonstrated that miR-10a-5p was upregulated in OA and acted as a significant contributing factor for OA. A large number of circRNAs, lncRNAs, miRNAs, and mRNAs were identified by overexpressing miR-10a-5p. Functional enrichment analyses indicated that these differentially-expressed genes were enriched in some important terms including PPAR signaling pathway, PI3K-Akt signaling pathway, and p53 signaling pathway. A total of 42 hub genes were identified in the protein-protein interaction network including SERPINA1, TTR, APOA1, and A2M. Also, we constructed the network regulatory interactions across coding and noncoding RNAs triggered by miR-10a-5p, which revealed the powerful regulating effects of miR-10a-5p. Moreover, we found that HOXA3 acted as the targeted genes of miR-10a-5p and miR-10a-5p contributed to the progression of OA by suppressing HOXA3 expression. Our findings shed insight on regulatory mechanisms of miR-10a-5p, which might provide novel therapeutic targets for OA.

This study was conducted to explore the clinical value of noninvasive assessment of bedside ultrasound in the diagnosis of lung lesions of Coronavirus Disease-19. In this retrospective study, 30 patients with Coronavirus Disease-19 admitted to our hospital from January 18 to February 5, 2020, were selected as the research subjects. All cases were examined by lung ultrasound and CT. Lung lesions were reviewed by blinded observers, with imaging scores being used to analyze the ultrasound findings of lung lesions in patients with Coronavirus Disease-19 and with chest CT being used as the reference standard. The clinical value of ultrasound in the noninvasive assessment of lung lesions was evaluated. Lung ultrasound signs in patients with Coronavirus Disease-19 were mainly manifested as interstitial pulmonary edema (90.0 %, 27/30) and pulmonary consolidations (20.0 %, 6/30). The lung lesions were mainly distributed in the subpleural and peripheral pulmonary zones. The lower lobe and the dorsal region had a greater tendency to be involved. There was moderate agreement (Kappa = 0.529) between the noninvasive assessment of bedside ultrasound for lung lesions in patients with Coronavirus Disease-19 and CT. The ultrasound scores to evaluate mild, moderate and severe lung lesions exhibited sensitivity of 68.8 % (11/16), 77.8 % (7/9), 100.0 % (2/2), specificity of 85.7 % (12/14), 76.2 % (16/21), 92.9 % (26/28), and diagnostic accuracy of 76.7 % (23/30), 76.7 % (23/30), 93.3 % (28/30), respectively. The follow-up dynamic ultrasound examination showed that the condition of all patients worsened gradually, with the ultrasound scores of lung lesions increasing to varying degrees. Though the diagnostic efficacy of bedside ultrasound is relatively low for mild to moderate patients, it is high for severe patients. Bedside ultrasound has important clinical significance for noninvasive assessment and dynamic observation of lung lesions in patients with Coronavirus Disease-19, which is worth further consideration.ZIEL: Diese Studie wurde durchgeführt, um den klinischen Wert der nicht-invasiven Beurteilung von Ultraschall direkt am Krankenbett bei der Diagnose von Lungenläsionen bei COVID-19-Erkrankung zu untersuchen. In dieser retrospektiven Studie wurden 30 COVID-19-Patienten, die vom 18. Januar bis zum 5. Februar 2020 in unser Krankenhaus eingeliefert wurden, als Probanden ausgewählt. Alle Fälle wurden mittels Lungenultraschall und CT untersucht. Die Lungenläsionen wurden von verblindeten Beobachtern überprüft, wobei die sonografischen Befunde der Lungenläsionen bei COVID-19-Patienten mittels Bildgebungs-Scores analysiert wurden und Thorax-CT als Referenzstandard diente. Der klinische Nutzen der Sonografie bei der nicht-invasiven Beurteilung von Lungenläsionen wurde bewertet. Bei COVID-19-Patienten manifestierten sich die Lungenultraschallzeichen in erster Linie als interstitielles Lungenödem (90,0 %, 27/30) und Lungenkonsolidierungen (20,0 %, 6/30). Die Läsionen der Lunge waren überwiegend in den subpleuralen und peripheren Lungenzonen verteilt. Der Unterlappen und die dorsale Region waren tendenziell stärker betroffen. Die Übereinstimmung zwischen der nicht-invasiven Beurteilung des Ultraschalls am Krankenbett und der CT für Lungenläsionen bei COVID-19-Patienten war moderat (Kappa = 0,529). Die Beurteilung mittels Ultraschall von leichten, moderaten und schweren Lungenläsionen ergab eine Sensitivität von 68,8 % (11/16), 77,8 % (7/9), 100,0 % (2/2), eine Spezifität von 85,7 % (12/14), 76,2 % (16/21), 92,9 % (26/28) und eine diagnostische Genauigkeit von 76,7 % (23/30), 76,7 % (23/30) bzw. 93,3 % (28/30). Die anschließende dynamische Ultraschalluntersuchung zeigte, dass sich der Zustand aller Patienten allmählich verschlechterte, wobei die Ultraschall-Scores der Lungenläsionen in unterschiedlichem Maße anstiegen. Ultraschall direkt am Krankenbett hat eine wichtige klinische Bedeutung für die nicht-invasive Beurteilung und die dynamische Beobachtung von Lungenläsionen bei COVID-19-Patienten und sollte weiter in Betracht gezogen werden.

Background/Aims: Previously we have shown that activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-antioxidant response element (ARE) attenuated hyperglycemia-induced damage in podocytes, but the molecular mechanism remains unknown. Methods: Tert-butylhydroquinone (t-BHQ) and small interfering RNAs (siRNAs) were used to regulate Nrf2 expression, while nicotinamide and siRNAs were used to regulate sirtuin 1 (Sirt1) activity and expression, respectively. Mitochondrial superoxide, membrane potential and ATP levels were measured to assess changes in mitochondrial function. Nephrin and synaptopodin expression were measured by western blot analysis. Human podocytes and db/db diabetic mice were used in this study. Results: t-BHQ pretreatment of human podocytes exposed to high glucose (HG) alleviated mitochondrial dysfunction, enhanced the expression of Sirt1, nephrin and synaptopodin and lowered BSA permeability compared with podocytes exposed to HG without t-BHQ pretreatment (p< 0.05). Human podocytes exposed to HG had more severe mitochondrial dysfunction, lower expression of Sirt1, synaptopodin and nephrin and higher BSA permeability than podocytes exposed to HG when Nrf2 expression was downregulated by siRNAs (p< 0.05). The protection provided by activation of the Nrf-ARE pathway in podocytes exposed to HG was partially diminished when Sirt1 expression or activity was decreased by siRNAs or inhibitor compared with podocytes exposed to HG and pretreated with t-BHQ (p< 0.05). When nicotinamide and t-BHQ were both administered to db/db mice, we observed higher levels of urinary albumin/creatinine, lower nephrin and synaptopodin expression, more severe mesangial matrix deposition, collagen deposition on pathological slides and mitochondrial structural damage in podocytes compared to db/db mice treated only with t-BHQ. Conclusions: Our findings suggest that crosstalk between Sirt1 and the Nrf2-ARE anti-oxidative pathway forms a positive feedback loop and that protection provided by t-BHQ activation of the Nrf2-ARE pathway in db/db mice is partly dependent on Sirt1.

To explore the feasibility and value of 3D-CEUS-CT/MR image fusion in evaluating ablative margin (AM) after radiofrequency ablation of hepatocellular carcinoma.There were 49 HCC in 41 patients enrolled in our prospective study. The AM were evaluated with 3D-CEUS-CT/MR image fusion, the results were divided into two groups: in group A, the tumor was completely ablated with a 5 mm AM; in group B, the tumor was completely ablated, but a 5 mm AM was not obtained. The time used in US-CT/MR image fusion and 3 D image post-processing, the technical success rate of 3D-CEUS-CT/MR image fusion and the relation between LTP and AM were observed.The time taken for US-CT/MR image fusion and 3 D image post-processing was 9.2 ± 2.1 min (6 - 12 min), 14.6 ± 2.6 min (9 - 20 min), respectively. The technical success rate of 3D-CEUS-CT/MR image fusion was 81.6 % (40/49). 27 HCC had sufficient AM (group A) and 13 HCC had insufficient AM (group B). The LTP rates in groups A and B were 0/27 and 4/13, respectively. There was a significant difference between groups A and B (P = 0.002). There was a significant negative correlation between LTP and AM (r = -1.000, P 0.001), and the locations of LTP and insufficient AM were concordant.The results suggest that 3D-CEUS-CT/MR image fusion is feasible and useful in evaluating the AM after HCC ablation.ZIEL:: Untersuchung der Durchführbarkeit und des Wertes der 3DCEUS-CT/MR-Bildfusion zur Beurteilung des Ablationsrandes (ablative margin = AM) nach Radiofrequenzablation des hepatozellulären Karzinoms (HCC).In unsere prospektive Studie wurden 49 HCCs von 41 Patienten aufgenommen. Der AM wurde mittels 3D-CEUS-CT/MR-Bildfusion beurteilt und die Ergebnisse in zwei Gruppen aufgeteilt: Gruppe A mit kompletter Ablation des Tumors und einem 5 mm großem AM, Gruppe B mit kompletter Tumorablation ohne Erhalt eines 5 mm AM. Der Zeitaufwand der 3D-CEUS-CT/MR-Bildfusion und der 3D-Bild-Nachbearbeitung, die technische Erfolgsrate der 3D-CEUS-CT/MR Bildfusion sowie das Verhältnis zwischen LTP und AM wurden verfolgt.Der Zeitaufwand für die US-CT/MR Bildfusion betrug 9,2 ± 2,1 min (6 – 12 min) und für die 3D-Bild-Nachbearbeitung 14,6 ± 2,6 min (9 – 20 min). Die technische Erfolgsrate der 3D-CEUS-CT/MR-Bildfusion betrug 81,6 % (40/49). Einen ausreichenden AM (Gruppe A) hatten 27 HCC und einen nicht ausreichenden AM (Gruppe B)13 HCCs. Die LTP-Raten (local tumor progression) in Gruppe A betrugen 0/27 und in Gruppe B 4/13 mit einem signifikanten Unterschied zwischen beiden Gruppen (p = 0,002). Zwischen LTP und AM wurde eine signifikante negative Korrelation beobachtet (r = –1,000, p 0,001) und die Bereiche von LTP und nicht ausreichendem AM stimmten überein.Die Ergebnisse weisen auf die Durchführbarkeit der 3D-CEUS-CT/MR-Bildfusion hin und auf deren Wert für die Beurteilung des AM nach HCC-Ablation.