Cerebral smal vessel disease (CSVD) refers to cerebral smal perforating arteries and arterioles (diameter 40 - 200 μm), capilaries, and venules caused syndromes of clinical, cognitive and pathological manifestations. Its imaging classification includes lacunar infarcts, white matter lesions, cerebral microbleed, and perivascular space enlargement, etc. The pathogenesis of CSVD is stil being explored, and imaging findings can not completely reflect the change process of its pathophysiology, especialy the early lesions. Therefore, the difficulties have increased for the prevention and treatment of CSVD. This article summarizes the progress in research on CSVD biomarkers in recent years in order to provide ideas for its etiology, pathogenesis, and clinical prevention and treatment.

Trimethylamine-N-oxide (TMAO),metabolites of the intestinal microflora,is a newly discovered risk factor for cardiovascular disease.The intestinal flora converted choline and L-carnitine into trimethylamine in the food.Trimethylamine is oxidized to TMAO in liver enzymes.Lowering TMA can stimulate macrophages to reverse cholesterol transport and inhibit atherogenesis.TMAO poietin-monooxygenase 3 (FMO3) is a tool for cholesterol metabolism and reverse cholesterol transpor,lowering FMO3 can slow the gallbladder's secretion of bile,delay intestinal absorption of cholesterol,and limit the synthesis of oxidized cholesterol and cholesterol esters.TMAO in the blood can up regulate scavenger receptors in macrophages,and promote accumulation of cholesterol and formation of foam cells in macrophages,thereby promoting vascular plaque formation and promote the inflammatory response by MAPK and nuclear factor kappa B pathway.TMAO concentrates on affecting cholesterol metabolism,increasing insulin resistance,promoting platelet aggregation,increasing thrombosis,promoting vascular inflammatory response and directly leading to the formation of atherosclerotic plaques.Lowering TMAO levels can potentially prevent or treat atherosclerotic related diseases and reduce the incidence of cardiovascular and cerebrovascular diseases.The intestinal flora of the TMA/FMO3/TMAO pathway is the major pathway regulating lipid metabolism and inflammation.

Objective:To systematically evaluate the clinical efficacy and safety of Xixian Tongshuan Capsules/Pills combined with Western medicine in treating cerebral infarction.Methods:All RCTs about Xixian Tongshuan Capsules/Pills combined with Western medicine in treating cerebral infarction were retrieved from CNKI, Wanfang Database, VIP database, PubMed and CBM. The search period was from the database establishment to December 31, 2021. Two researchers independently extracted the basic literature data and evaluated the methodological quality, then used RevMan5.4 software for meta-analysis.Results:Totally 9 articles were included, involving a total of 988 patients, including 505 cases in the observation group and 483 cases in the control group. Meta-analysis showed that the total effective rate of Xixian Tongshuan Capsules/Pills combined with Western medicine in treating cerebral infarction was higher than that of conventional Western medicine [ RR=1.20, 95% CI (1.13, 1.27), P<0.05]. At the same time, the effect of NIHSS score, Barthel score and FIB were better than those of conventional Western medicine [respectively: MD=-3.21, 95% CI (-4.45, -1.97), P<0.05; MD=11.83, 95% CI (10.66, 13.00), P<0.05; MD=-0.95, 95% CI (-1.36, -0.54), P<0.05]. After treatment with Xixian Tongshuan Capsules/Pills combined with Western medicine, the adverse reactions mainly included dizziness, nausea, indigestion, rash, facial blushing, etc. There was no statistically significant difference in safety between the two groups [ RR=1.50, 95% CI (0.75, 3.01), P>0.05]. Conclusions:Under the treatment of conventional Western medicine, the addition of Xixian Tongshuan Capsules/Pills can improve the clinical efficacy of cerebral infarction treatment, effectively improve the symptoms of neurological impairment, improve the ability of daily life, and promote the prognosis and recovery, and without increasing the incidence of adverse reactions. However, large sample and high quality studies are still needed to support the conclusion.