ADORA3: A Key Player in the Pathogenesis of Intracranial Aneurysms and a Potential Diagnostic Biomarker.

BACKGROUND: The effects of genes on the development of intracranial aneurysms (IAs) remain to be elucidated, and reliable blood biomarkers for diagnosing IAs are yet to be established. This study aimed to identify genes associated with IAs pathogenesis and explore their diagnostic value by analyzing IAs datasets, conducting vascular smooth muscle cells (VSMC) experiments, and performing blood detection. METHODS: IAs datasets were collected and the differentially expressed genes were analyzed. The selected genes were validated in external datasets. Autophagy was induced in VSMC and the effect of selected genes was determined. The diagnostic value of selected gene on the IAs were explored using area under curve (AUC) analysis using IAs plasma samples. RESULTS: Analysis of 61 samples (32 controls and 29 IAs tissues) revealed a significant increase in expression of ADORA3 compared with normal tissues using empirical Bayes methods of "limma" package; this was further validated by two external datasets. Additionally, induction of autophagy in VSMC lead to upregulation of ADORA3. Conversely, silencing ADORA3 suppressed VSMC proliferation and autophagy. Furthermore, analysis of an IAs blood sample dataset and clinical plasma samples demonstrated increased ADORA3 expression in patients with IA compared with normal subjects. The diagnostic value of blood ADORA3 expression in IAs was moderate when analyzing clinical samples (AUC: 0.756). Combining ADORA3 with IL2RB or CCR7 further enhanced the diagnostic ability for IAs, with the AUC value over 0.83. CONCLUSIONS: High expression of ADORA3 is associated with IAs pathogenesis, likely through its promotion of VSMC autophagy. Furthermore, blood ADORA3 levels have the potential to serve as an auxiliary diagnostic biomarker for IAs.

The Median Effective Concentration (EC50) of Epidural Ropivacaine With Different Doses of Oxycodone During Limb Surgery in Elderly Patients.

BACKGROUND: Oxycodone can be used both intravenously and epidurally in elderly patients because of its strong analgesic effect and more slight respiratory inhibition compared with other opioids at the same effect. In this study, we determined the median effective concentration (EC50) of epidural ropivacaine required for great saphenous vein surgery in elderly patients in order to describe its pharmacodynamic interaction with oxycodone. METHODS: One hundred forty-one elderly patients scheduled for high ligation and stripping of the great saphenous vein surgery were allocated into three groups in a randomized, double-blinded manner as follows: Q2.5 group (2.5 mg oxycodone), Q5.0 group (5.0 mg oxycodone), and C group (normal saline). Anesthesia, was achieved with epidural ropivacaine and oxycodone. The EC50 of ropivacaine for surgery with different doses of oxycodone was adjusted by using an up-and-down sequential methods with an adjacent concentration gradient at a factor of 0.9 to inhibit analgesia. Anesthesia associated adverse events and recovery, characteristics were also recorded. RESULTS: The EC50 of ropivacaine for the great saphenous vein surgery in elderly patients was 0.399% (95% CI, 0.371-0.430%) in the Q2.5 group, 0.396% (95% CI, 0.355-0.441%) in the Q5.0 group, and 0.487% (95% CI, 0.510-0.465%) in the C group, respectively (P < 0.05). Specially, the EC50 of ropivacaine in the Q2.5 and Q5.0 groups was lower than that in the C group (P < 0.01), But the difference between the Q2.5 group and the Q5.0 group was not significant (P > 0.05). There was no significant difference in the Bromage score from the motor block examination, heart rate (HR) or mean arterial pressure (MAP) at each observation time point after epidural administration among the three groups (P > 0.05). No serious adverse reactions occurred in any of the three groups. CONCLUSION: Oxycodone combined with ropivacaine epidural anesthesia can reduce the EC50 of ropivacaine required for elderly patients undergoing the great saphenous vein surgery. There was no significant difference in anesthesia associated adverse events among the three groups. The recommended dose of oxycodone is 2.5 mg.