Patients with non-disabling middle cerebral artery (MCA) stenosis (ND-MCAS) are at risk for disabling ischemic cerebrovascular events (DICE) despite aggressive medical therapy. In this study, we aimed to verify whether cerebral circulation time (CCT) was a potential predictor of DICE in patients with ND-MCAS. From January 2015 to January 2020, 46 patients with ND-MCAS treated with aggressive medical therapy were enrolled for digital subtraction angiography (DSA) in this convenience sampling study. They were divided into the DICE (–) and DICE (+) groups based on the occurrence of DICE within 3 months after DSA. The CCT was defined as the time from the appearance of the MCA to the peak intensity of the Trolard vein during DSA. The rCCT (relative CCT) was defined as the ratio of the CCT of the stenotic side (sCCT) to the CCT of the healthy side (hCCT). The differences in sCCT, hCCT, and rCCT between the two groups were analyzed with Mann-Whitney U tests. Logistic regression analysis was performed to evaluate the association between the risk factors and DICE. Receiver operating characteristic (ROC) curves were constructed to assess the predictive value of rCCT in identifying DICE in ND-MCAS patients. The results showed that DICE appeared in 5 of the 46 patients within 3 months. rCCT were significantly increased in the DICE (+) group compared with the DICE (–) group [1.08 (1.05, 1.14) vs. 1.30 (1.22, 1.54), p < 0.001]. Logistic regression analysis found that prolonged rCCT was an independent positive prognostic factor for DICE (odds ratio = 1.273, p = 0.019) after adjustment for potential confounders (age, diabetes, antithrombotic use, and stenosis degree). ROC analysis showed that rCCT provided satisfactory accuracy in distinguishing the DICE (+) group from the DICE (–) group among ND-MCAS patients (area under the curve = 0.985, p < 0.001), with an optimal cutoff point of 1.20 (100% sensitivity, 97.6% specificity). In conclusion, prolonged rCCT is independently associated with the occurrence of DICE in ND-MCAS patients and may be used to identify individuals at risk of DICE.

This study aims to investigate the correlation between the enhancement degree of contrast-enhanced ultrasound (CEUS) and the expression of CD147 and MMP-9 in carotid atherosclerotic plaques in patients with carotid endarterectomy and evaluate the diagnostic efficacy of CEUS using pathological results as the gold standard. Thirty-eight patients who underwent carotid endarterectomy (CEA) for carotid stenosis in the Department of Neurovascular Surgery of the Second People’s Hospital of Shenzhen from July 2019 to June 2020 were selected. Preoperatively, two-dimensional (2D) ultrasound scan was performed on all patients to assess the characteristics of the plaque and degree of stenosis, and CEUS was used to evaluate the surface morphology of the plaque and the distribution of neovascularization. Postoperatively, pathological sections and immunohistochemical analysis of CD147 and MMP-9 levels in the plaque were performed on the stripped plaque tissue, and the results were analyzed against the CEUS grading and pathological results. Among the 38 patients, pathological results showed that 10 and 28 were in the stable and vulnerable plaque groups, respectively. There were more smokers in the vulnerable plaque group than in the stable plaque group, with higher intraplaques CD147 and MMP-9. The difference in ultrasound plaque surface morphology grading and CEUS grading between the two groups was statistically significant. There was no significant difference in age, sex, incidence of complications such as hypertension, diabetes, and coronary heart disease between the two groups. CD147 was higher in the CEUS grade IV group than in the grades I (P = 0.040) and II (P = 0.010) groups. MMP-9 was higher in the CEUS grade IV group than in the grade II group (P = 0.017); MMP-9 was higher in the grade III group than in the grade II group (P = 0.015). Intraplaque contrast enhancement intensity was positively correlated with CD147 (r = 0.462, P = 0.003) and MMP-9 (r = 0.382, P = 0.018) levels. There was moderate consistency between the assessment of plaque vulnerability by 2D-ultrasound and by histopathological hematoxylin-eosin (HE) (kappa = 0.457, P > 0.05). 2D diagnosis of vulnerable plaque had a sensitivity of 85.7%, a specificity of 60.0%, a positive predictive value of 85.7%, a negative predictive value of 60.0%, and an accuracy of 78.0%. There was a strong consistency between the assessment of plaque vulnerability by CEUS and histopathological HE (kappa = 0.671, P < 0.01). CEUS had a sensitivity of 89.2%, a specificity of 80.0%, a positive predictive value of 92.6%, a negative predictive value of 72.7%, and an accuracy of 86.8% for the diagnosis of vulnerable plaques; CEUS is a reliable, non-invasive test that can show the distribution of neovascularization within vulnerable plaques, evaluate the vulnerability and risk of intraplaque hemorrhage, with a high consistency with pathological findings. The degree of intraplaque enhancement and the levels of CD147 and MMP-9 in the tissue were positively correlated.

Sepsis is a systemic inflammatory response syndrome, mainly caused by infection or suspected infectious factors. The intestine is not only one of the most easily involved organs in the course of sepsis, but also the dynamic organ for the course of sepsis. The present study investigated the protective effect and mechanism of salidroside on intestinal barrier dysfunction of septic mice. Briefly, C57BL/6 mice were used to establish a septic model and then administered with salidroside. The ileum tissues of mice were examined by histopathological examination. Fluorescein isothiocyanate-dextran concentration was measured. IL-17, IL-6, IL-13 and TNF-α levels in ileum tissues and NF-κB and p38 MAPK activations were detected by ELISA and the expressions of NF-κB p65 and p38 MAPK protein with their phosphorylation and intestinal tight junction proteins were gauged by western blotting. The above assays were performed again to investigate the effect of anti-IL-17A and salidroside (160 mg/kg) alone or in combination. The septic model induced the ileum tissue injury, increased intestinal permeability and TNF-α, IL-17 and IL-6 levels, activated NF-κB and p38 MAPK pathways, promoted the expressions of NF-κB p65 and p38 MAPK and their phosphorylation, while suppressing the levels of IL-13 and intestinal tight junction proteins. Salidroside and anti-IL-17A partially reversed the above effects of septic model, which in combination further strengthened the reversing effect. Collectively, salidroside protected against intestinal barrier dysfunction in septic mice by downregulating IL-17 level to inhibit NF-κB and p38 MAPK signaling pathways, thus providing a new treatment direction.

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Background: Andrographolide is a promising natural substance with numerous pharmacotherapy uses. 14-deoxy-12(R)-sulfo andrographolide (SAP) is the main metabolite of andrographolide in the intestine. Objective: To investigate the pharmacokinetic properties of SAP, a precise and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of SAP concentration in rat plasma was developed and validated in this study. Methods: Chromatographic separation was achieved on an Acpuity UPLC BEH C18 column with gradient elution that consisted of methanol and water at a flow rate of 0.3 mL/min. MS/MS detection was carried out by the multiple reaction monitoring (MRM) mode with a negative electrospray ionization (ESI-) source, with the transitions of m/z 413.2→m/z 287.2 for SAP and m/z 269→m/z 133 for genistein [which was used as an internal standard (IS)]. Results: The calibration curve of SAP was linear over the concentration range of 5-120 ng/mL. The selectivity, precision, accuracy, extraction recovery, matrix effect, and stability of the method were within the acceptable ranges. This SAP quantification method was then successfully applied to a pharmacokinetic study of SAP. The area under the curve (AUC) of SAP in rats treated with SAP at 60 mg/kg by intravenous administration was 7498.53±2405.02 mg/L•min. The AUC of SAP in rats treated with SAP at 60 mg/kg by oral administration was 97.74±39.56 mg/L•min. Thus, the absolute oral bioavailability of SAP was determined to be 1.40%.