Neuroprotective effect of salidroside on hippocampal neurons in diabetic mice via PI3K/Akt/GSK-3ß signaling pathway.

BACKGROUND: Diabetic encephalopathy is manifested by cognitive dysfunction. Salidroside, a nature compound isolated from Rhodiola rosea L, has the effects of anti-inflammatory and antioxidant, hypoglycemic and lipid-lowering, improving insulin resistance, inhibiting cell apoptosis, and protecting neurons. However, the mechanism by which salidroside alleviates neuronal degeneration and improves learning and memory impairment in diabetic mice remains unclear. OBJECTIVE: To investigate the effects and mechanisms of salidroside on hippocampal neurons in streptozotocin-induced diabetic mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into 4 groups to receive either sham (control group (CON)), diabetes mellitus (diabetes group (DM)), diabetes mellitus + salidroside (salidroside group (DM + SAL)), and diabetes mellitus + salidroside + phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (diabetes mellitus + salidroside + LY294002 group (DM + SAL + LY294002)). After 12 weeks of diabetes onset, the cognitive behaviors were tested using Morris water maze. The number of hippocampal neurons was detected by Nissl staining. The expressions of PI3K, p-PI3K, Akt, p-Akt, GSK-3ß, p-GSK-3ß, cleaved caspase-3, caspase-3, Bax, Bcl-2, MAP2, and SYN in the hippocampus were detected by Western blot. Moreover, the expression of MAP2 and SYN in the hippocampus was further confirmed by immunofluorescence staining. RESULTS: Salidroside increased the time of diabetic mice in the platform quadrant and reduced the escape latency of diabetic mice. Salidroside also increased the expression of p-PI3K, p-Akt, p-GSK-3ß, MAP2, SYN, Bcl-2, while suppressed the expression of cleaved caspase-3, caspase3, and Bax in the DM + SAL group compared with the DM group (P < 0.05). The Nissl staining showed that the number of hippocampus neurons in the DM + SAL group was increased with the intact, compact, and regular arrangement, compared with the DM groups (P < 0.05). Interestingly, the protective effects of salidroside on diabetic cognitive dysfunction, hippocampal morphological alterations, and protein expressions were abolished by inhibition of PI3K with LY294002. CONCLUSIONS: Salidroside exerts neuroprotective properties in diabetic cognitive dysfunction partly via activating the PI3K/Akt/GSK-3ß signaling pathway.

A Multicenter Randomized Trial Assessing ZENFlow Carrier-Free Drug-Coated Balloon for the Treatment of Femoropopliteal Artery Lesions.

Backgrounds and Objectives: Drug-coated balloons (DCBs) have shown promising benefits in improving the outcomes for patients with peripheral artery disease. Several randomized clinical trials have reported that paclitaxel-coated balloon significantly reduce the rates of restenosis and the need for reintervention in comparison with regular balloon angioplasty. Due to the differences in excipients, paclitaxel dose, and coating techniques, variable clinical outcomes have been observed with different DCBs. In this study, we aimed to evaluate the safety and efficacy of a novel ZENFlow carrier-free DCB in the treatment of femoropopliteal artery occlusive disease. Methods: In this randomized controlled trial conducted at 15 sites, 192 patients with Rutherford class 3-5 were randomly assigned into two groups: drug-coated balloon group and percutaneous transluminal angioplasty group. The primary endpoint was a late lumen loss at 6 months based on blinded angiographic core laboratory evaluations, and the secondary endpoints included primary patency rate, binary restenosis, clinically driven target lesion revascularization, ankle-brachial index, Rutherford class change, and major adverse events. Results: In this multicenter trial, 93 patients received DCB angioplasty, whereas 99 patients underwent regular balloon angioplasty. The late lumen loss at 6-month follow-up was 0.50 ± 0.82 and 1.69 ± 0.87 mm in the drug-coated balloon and percutaneous transluminal angioplasty groups, respectively (p < 0.001). During the 12-month follow-up period, the drug-coated balloon group showed a significantly higher primary patency rate (54 vs. 31.3%, p = 0.009) and markedly lower rates of target vessel restenosis (22.1 vs. 64.3%, p < 0.001) and clinically driven target lesion revascularization rate (5.4 vs. 19.2%, p = 0.006) than the percutaneous transluminal angioplasty group. Compared with the percutaneous transluminal angioplasty group, the drug-coated balloon group had significant improvements in the ankle-brachial index and Rutherford class. The all-cause mortality rate was comparable, and no device-related deaths occurred in either groups. Conclusions: Balloon angioplasty using a ZENFlow carrier-free drug-coated balloon is a safe and effective treatment method for femoropopliteal artery lesions. This novel drug-coated balloon catheter achieved satisfactory early and 1-year outcomes in this trial. Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT03844724.

Iodine Distribution Map in Dual-Energy Computed Tomography Pulmonary Artery Imaging with Rapid kVp Switching for the Diagnostic Analysis and Quantitative Evaluation of Acute Pulmonary Embolism.

RATIONALE AND OBJECTIVES: To assess the diagnostic value of dual-energy (DE) computed tomography pulmonary angiography (CTPA) for acute pulmonary embolism (PE) using a helical DE scan mode with rapid kVp switching. MATERIALS AND METHODS: Seventy-six patients with suspected acute PE underwent DE CTPA. Two readers independently assessed and measured the iodine maps. CTPA images were assessed for the presence, location, and degree of PE as the standard of reference. Iodine maps were used to identify the perfusion defect (PD), and the diagnostic accuracy of iodine maps was calculated. The iodine concentrations of PDs and normal lung parenchyma were also measured and compared. RESULTS: A per-patient analysis showed the 84.6% sensitivity and 96.0% specificity of iodine map for PE, and on per-segment analysis, the sensitivity and specificity for PE were 82.9% and 99.6%, respectively. Intraobserver and interobserver variability correlations were excellent, with k values from 0.806 to 1.000. Quantitative analysis showed there was a significant difference for iodine concentration between circumscribed/patchy PDs or wedge-shaped PDs consistent with PE and normal lung parenchyma (P < .05). The intraobserver reliability of reader 1 was from 0.928 to 0.997, and reader 2 was from 0.912 to 0.995. And, the interobserver reliability between two readers was from 0.967 to 0.999. CONCLUSIONS: CTPA based on DE scanning with rapid kVp switching can provide both morphologic analysis and quantitative evaluation of PD related to acute PE in addition to standard CTPA data. Quantification of iodine concentration may be helpful for identifying the presence or absence of PE.

A multicentre retrospective study of transcatheter angiographic embolization in the treatment of delayed haemorrhage after percutaneous nephrolithotomy.

OBJECTIVE: The objective is to determine the timing and indications of transcatheter angiographic embolization (TAE) for delayed haemorrhage after percutaneous nephrolithotomy (PCNL). METHODS: The medical records of 144 patients who underwent arteriography and TAE for delayed post-PCNL haemorrhage at five university hospitals between January 2005 and December 2012 were reviewed retrospectively. RESULTS: The mean time to the onset of post-PCNL haemorrhage was 10.5 days (2 - 30 days). Clinical presentation included sudden onset bleeding in 51 patients (35.4 %), intermittent bleeding in 67 patients (46. 5 %), and continuous slow bleeding in 26 patients (18.1 %). Hemodynamic instability occurred in 32 patients (22.2 %). The mean haemoglobin decrease from the first post-PCNL day to the day of TAE was 49.5 g/L (31.0 - 79.0 g/L). Renal arteriography showed pseudoaneurysms in 69 (47.9 %) patients, arteriovenous fistulas in 28 (19.4 %) patients, mixed arterial and arteriovenous lesions in 17 (11.8 %) patients, arterial lacerations in 23 (16.0 %) patients, and negative angiographic finding in seven (4.9 %) patients. TAE was successful in stopping bleeding in all 137 patients with vascular lesions. There were no major complications associated with TAE. CONCLUSIONS: TAE should be the recommended treatment for delayed post-PCNL haemorrhage in patients with hemodynamic instability and/or corrected haemoglobin decrease >30 g/L following conservative management. KEY POINTS: • Delayed haemorrhage after percutaneous nephrolithotomy occurs more than 24 hours postoperatively. • Angio-embolization is a safe and effective treatment for delayed post-PCNL haemorrhage. • Angio-embolization can treat hemodynamic instability and/or corrected haemoglobin decrease >30 g/L.