Stroke is a leading cause of morbidity and mortality in both developed and developing countries all over the world. The only drug for ischemic stroke approved by FDA is recombinant tissue plasminogen activator (rtPA). However, only 2-5% stroke patients receive rtPAs treatment due to its strict therapeutic time window. As ischemic stroke is a complex disease involving multiple mechanisms, medications with multi-targets may be more powerful compared with single-target drugs. Dl-3-n-Butylphthalide (NBP) is a synthetic compound based on l-3-n- Butylphthalide that is isolated from seeds of Apium graveolens. The racemic 3-n-butylphthalide (dl- NBP) was approved by Food and Drug Administration of China for the treatment of ischemic stroke in 2002. A number of clinical studies indicated that NBP not only improved the symptoms of ischemic stroke, but also contributed to the long-term recovery. The potential mechanisms of NBP for ischemic stroke treatment may target different pathophysiological processes, including anti-oxidant, antiinflammation, anti-apoptosis, anti-thrombosis, and protection of mitochondria et al. Conclusion: In this review, we have summarized the research progress of NBP for the treatment of ischemic stroke during the past two decades.

Background The potential effects of pre-pregnancy body mass (BMI) and gestational weight gain (GWG) on pregnancy outcomes remain unclear. Thus, we investigated socio-demographic characteristics that affect pre-pregnancy BMIs and GWG and the effects of pre-pregnancy BMI and GWG on Chinese maternal and infant complications. Methods 3172 women were enrolled in the Chinese Pregnant Women Cohort Study-Peking Union Medical College from July 25, 2017 to July 24, 2018, whose babies were delivered before December 31, 2018. Regression analysis was employed to evaluate the socio-demographic characteristics affecting pre-pregnancy BMI and GWG values and their effects on adverse maternal and infant complications. Results Multivariate logistic regression analysis revealed that age groups < 20 years (OR: 1.97), 25–30 years (OR: 1.66), 30–35 years (OR: 2.24), 35–40 years (OR: 3.90) and ≥ 40 years (OR: 3.33) as well as elementary school or education below (OR: 3.53), middle school (OR: 1.53), high school (OR: 1.40), and living in the north (OR: 1.37) were risk factors in maintaining a normal pre-pregnancy BMI. An age range of 30–35 years (OR: 0.76), living in the north (OR: 1.32) and race of ethnic minorities (OR: 1.51) were factors affecting GWG. Overweight (OR: 2.01) and inadequate GWG (OR: 1.60) were risk factors for gestational diabetes mellitus (GDM). Overweight (OR: 2.80) and obesity (OR: 5.42) were risk factors for gestational hypertension (GHp). Overweight (OR: 1.92), obesity (OR: 2.48) and excessive GWG (OR: 1.95) were risk factors for macrosomia. Overweight and excessive GWG were risk factors for a large gestational age (LGA) and inadequate GWG was a risk factor for low birth weights. Conclusions Overweight and obesity before pregnancy and an excessive GWG are associated with a greater risk of developing GDM, GHp, macrosomia and LGA. The control of body weight before and during the course of pregnancy is recommended to decrease adverse pregnancy outcomes, especially in pregnant women aged < 20 or > 25 years old educated below university and college levels, for ethnic minorities and those women who live in the north of China. Trial registration Registered at Clinical Trials (NCT03403543), September 29, 2017.

Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder that occurs gradually and results in memory, behavior, and personality changes. L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), has been demonstrated to have neuroprotective effects on ischemic, vascular dementia, and amyloid-␤ (A␤)-infused animal models. In the current study, we examined the effects of L-NBP on learning and memory in a triple-transgenic AD mouse model (3xTg-AD) that develops both plaques and tangles with aging, as well as cognitive deficits. Ten-month-old 3xTg-AD mice were given 15 mg/kg L-NBP by oral gavage for 18 weeks. L-NBP treatment significantly improved learning deficits, as well as long-term spatial memory, compared with vehicle control treatment. L-NBP treatment significantly reduced total cerebral A␤ plaque deposition and lowered A␤ levels in brain homogenates but had no effect on fibrillar A␤ plaques, suggesting preferential removal of diffuse A␤ deposits. Furthermore, we found that L-NBP markedly enhanced soluble amyloid precursor protein secretion (␣APPs), ␣-secretase, and PKC␣ expression but had no effect on steady-state full-length APP. Thus, L-NBP may direct APP processing toward a non-amyloidogenic pathway and preclude A␤ formation in the 3xTg-AD mice. The effect of L-NBP on regulating APP processing was further confirmed in neuroblastoma SK-N-SH cells overexpressing wild-type human APP 695 (SK-N-SH APPwt). L-NBP treatment in 3xTg-AD mice also reduced glial activation and oxidative stress compared with control treatment. L-NBP shows promising preclinical potential as a multitarget drug for the prevention and/or treatment of Alzheimer's disease.

Thrombosis and restenosis after vascular reconstruction procedures may cause complications such as stroke, but a clinical means to continuously monitor vascular conditions is lacking. Conventional ultrasound probes are rigid, particularly for postoperative patients with fragile skin. Techniques based on photoplethysmography or thermal analysis provide only relative changes in flow volume and have a shallow detection depth. Here, we introduce a flexible Doppler ultrasound device for the continuous monitoring of the absolute velocity of blood flow in deeply embedded arteries based on the Doppler effect. The device is thin (1 mm), lightweight (0.75 g), and skin conforming. When the dual-beam Doppler method is used, the influence of the Doppler angle on the velocity measurement is avoided. Experimental studies on ultrasound phantoms and human subjects demonstrate accurate measurement of the flow velocity. The wearable Doppler device has the potential to enhance the quality of care of patients after reconstruction surgery.

3-n-butylphthalide (NBP) is a potentially beneficial drug for the treatment of ischemic stroke with multiple actions on different pathophysiological processes. In the present study, the effect of l-, d-, and dl-NBP was investigated on ADP-, collagen-, and AA-induced platelet aggregation. l-NBP was the most potent among l-, d-, and dl-NBP. At higher concentration the effect of dl-NBP on platelet aggregation was greater than that of l- or d-NBP alone. The ex vivo antiaggregatory activity of l-NBP 100mg/kg declined gradually after 2 hours, but a considerable antiplatelet activity was still observed 4h after l-NBP administration. NBP was given orally and resulted in a dose-dependent inhibition of thrombus formation. Of the two isomers, l-NBP was the most potent. It significantly protected mice from a mixture of collagen and epinephrine induced thromboembolic death. When 100 mg/kg of l-NBP were administered orally to rats, the bleeding time increased 2.1-fold compared with the control group. At the same dose, ex vivo platelet aggregation induced by ADP, collagen, and AA was inhibited by l-NBP and the antithrombotic effects of the compound were also observed. Thus, NBP exerts oral anti-platelet and anti-thrombotic efficacy without perturbing systemic hemostasis in rats. l-NBP is more potent than d- and dl-NBP as antiplatelet agent.

3-n-Butylphthalide (NBP) may be beneficial for the treatment of ischemic stroke with multiple actions on different pathophysiological processes. In the present study, we investigated the effect of NBP isomers on learning and memory impairment induced by chronic cerebral hypoperfusion in rats. Male Wistar rats were orally administered 10 and 30 mg/kg l-, d-, or dl-NBP daily for 23 days after bilateral permanent occlusion of the common carotid arteries. Rats receiving 10 mg/kg l-NBP performed significantly better in tests for spatial learning and memory, and they had attenuated cerebral pathology, including neuronal damage, white matter rarefaction, and glial activation compared with controls. Furthermore, 10 mg/kg l-NBP-treated rats had significantly higher choline acetyltransferase activity, decreased cortical lipid peroxide, and reduced hippocampal superoxide dismutase activity, compared with vehicle controls. However, d-and dl-NBP did not show significant beneficial effects. The present findings demonstrate that the beneficial effects of l-NBP on hypoperfusion-induced cognitive deficits may be due to preventing neuropathological alterations, inhibiting oxidative damage and increasing acetylcholine synthesis. Our results strongly suggest that l-NBP has therapeutic potential for the treatment of dementia caused by decreased cerebral blood flow.Senile dementia, a progressive aging-related disease, has become an important medical and social problem due to the increase in the number of elderly. Vascular dementia (VaD), as the second most common form of dementia in the elderly, accounts for approximately 20 to 30% of dementia cases (Giacobini, 2004). VaD is a syndrome presenting with both cognitive and noncognitive symptoms. Cognitive deficits of VaD include memory deficits, executive function damage, slow processing of information, and behavioral and mood abnormalities (Micieli, 2006). The underlying basis of VaD is complicated, because cerebral multi-infarct, cerebrovascular diseases, arterial hypotension, cardiac arrest, and hemorrhagic diseases may all result in VaD (Micieli, 2006). At present, no specific drug exists to prevent, delay, or cure VaD.It is well known that a decrease in cerebral blood flow precedes the onset of VaD (Roman et al., 1993), and chronic cerebral hypoperfusion may be a trigger for VaD and the accompanying cognitive deficits (Kasparova et al., 2005). As well, the decrease in cerebral blood flow relates to the cognitive impairment seen in AD (Kasparova et al., 2005). Bilateral permanent occlusion of the common carotid arteries (BCCAO) in rats results in a significant reduction in cerebral blood flow; therefore, it is a useful model of chronic cerebral hypoperfusion (Tsuchiya et al., 1993). This animal model exhibits learning and memory impairments resembling those found in AD and VaD, accompanied by neuronal degeneration and microvascular abnormalities (Farkas et al., 2004).It has been widely accepted that chronic cerebral hypoperfusion induces oxidative stress damage and brain en...

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