ABSTRACT
Objective:To investigate the relationship between intracranial arterial remodeling and imaging markers in patients with cerebral small vessel disease (CSVD).Methods:One hundred and fifty-six patients with CSVD who were admitted to the Department of Neurology of the Second Affiliated Hospital of Zhengzhou University or the Public People′s Hospital of Xinzheng from January 2020 to May 2022 were selected, and their brain artery remodeling (BAR) score was calculated. The patients with BAR score≤-1 standard deviation (SD) were defined as individuals with constrictive remodeling of intracranial arteries, and the patients with BAR score≥1 SD were defined as individuals with dilated remodeling of intracranial arteries. Imaging markers of CSVD [white matter hyperintensities (WMHs), lacune, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy] were quantified, total CSVD load was calculated and patients were divided into low load group (0-2 points, n=91) and high load group (3-4 points, n=65) according to the total CSVD load scores. The correlation between intracranial artery remodeling and various imaging markers of CSVD and total load was analyzed by using univariate analysis and binary Logistic regression analysis. A nomogram prediction model was established and a receiver operating characteristic curve (ROC) was drawn to assess the predictive value of intracranial artery remodeling on high total CSVD load. Results:Dilated intracranial arterial remodeling was an independent influence factor on severe WMHs ( OR=3.66, 95% CI 1.38-9.72, P=0.009), lacune ( OR=3.78, 95% CI 1.17-12.19, P=0.026), cerebral atrophy ( OR=3.11, 95% CI=1.10-8.81, P=0.033), and high total CSVD load ( OR=6.66, 95% CI=2.14-20.77, P=0.001). Age was an independent influencing factor for high total CSVD load ( OR=1.12, 95% CI 1.07-1.16, P<0.01). A nomogram prediction model for high total CSVD load with age and BAR score≥1 SD as dependent variables had a good effect (C-index=0.826) and calibration ( P=0.024). The best cut-off point of ROC curve was 0.50, with an area under the curve of 0.83 (95% CI 0.76-0.89, P<0.01), the sensitivity and specificity of 0.72 and 0.82. Conclusions:Patients with dilated intracranial arterial remodeling may have a heavier CSVD load. Dilated intracranial arterial remodeling may serve as a new biomarker for assessing CSVD, but the mechanism of the association needs further study.
ABSTRACT
OBJECTIVE To prepare Leonurine hydrochloride tablets and evaluate the quality. METHODS The wet granulation technology was adopted ；leonurine hydrochloride was used as the crude drug ，and the types of fillers ，disintegrants，binders and lubricants were screened by single-factor experiments. Combined with orthogonal experiments ，using the cumulative dissolution rate within 15 minutes（using water as dissolution media ）as index ，the proportion of disintegrants ，the mass fraction of binder solution，and the proportion of lubricants were screened and verified. The in vitro dissolution behavior of the prepared Leonurine hydrochloride tablets （dissolution media were hydrochloric acid solution of pH 1.2，acetic acid-sodium acetate solution of pH 4.5， phosphate buffer solution of pH 6.8，water），tablet appearance ，hardness，friability and content uniformity were tested according to the general principles in 2020 edition of Chinese Pharmacopoeia （part Ⅳ）. RESULTS The optimal formulation of Leonurine hydrochloride tablets included leonurine hydrochloride crude drug of 500 mg，dextrin of 9 250 mg，crosslinking polyving y- pyrrolidone of 200 mg，magnesium stearate of 50 mg，1％ hydroxypropyl methyl cellulose solution of 4 mL. The average 15-minute cumulative dissolution rate of the three batches of tablets was 81.25％（RSD＝1.12％，n＝3）. In above 4 dissolution media，the dissolution equilibrium of prepared tablets could be reached within 30 minutes，and the cumulative dissolution rates exceeded 85％. The prepared tablets had uniform beige in color ，smooth surface ，complete edge ，no mottle ，spot，foreign matter ， etc.，hardness of 57.3 N（n＝6），weight loss rate of 0.15％. The content uniformity was in accordance with relevant provisions in 2020 edition of Chinese Pharmacopoeia （part Ⅳ）. CONCLUSIONS Leonurine hydrochloride tablets are successfully prepared ， and the quality comply with relevant regulations.