Tight junctions (TJs) are crucial for intercellular connections. The abnormal expression of proteins related to TJs can result in TJ destruction, structural damage, and endothelial and epithelial cell dysfunction. These factors are associated with the occurrence and progression of several diseases. Studies have shown that blood-brain barrier (BBB) damage and dysfunction are the prominent pathological features of stroke. TJs are directly associated with the BBB integrity. In this article, we first discuss the structure and function of BBB TJ-related proteins before focusing on the crucial events that cause TJ dysfunction and BBB damage, as well as the regulatory mechanisms that affect the qualitative and quantitative expression of TJ proteins during ischemic stroke. Multiple regulatory mechanisms, including phosphorylation, matrix metalloproteinases (MMPs), and microRNAs, regulate TJ-related proteins and affect BBB permeability. Some signaling pathways and mechanisms have been demonstrated to have dual functions. Hopefully, our understanding of the regulation of BBB TJs in ischemic stroke will be applied to the development of targeted medications and therapeutic therapies.

Importance: Preclinical and clinical studies have suggested the neuroprotective effect of Panax notoginseng saponins (Xuesaitong soft capsules). However, robust evidence in patients with ischemic stroke is lacking.Objective: To assess the efficacy and safety of Xuesaitong soft capsules in patients with ischemic stroke.Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 67 tertiary health centers in China from July 1, 2018, to June 30, 2020. Included patients were aged 18 to 75 years with a diagnosis of ischemic stroke and a National Institutes of Health Stroke Scale score between 4 and 15.Interventions: Eligible patients were randomly assigned within 14 days after symptom onset to receive either treatment with Xuesaitong soft capsules (120 mg orally twice daily) or placebo (120 mg orally twice daily) for 3 months.Main Outcomes and Measures: The primary outcome was functional independence at 3 months, defined as a modified Rankin Scale score of 0 to 2.Results: Among 3072 eligible patients with ischemic stroke who were randomized, 2966 (96.5%) were included in the modified intention-to-treat cohort (median [IQR] age, 62 [55-68] years; 1982 male [66.8%]). The number of patients who achieved functional independence at 3 months was 1328 (89.3%) in the Xuesaitong group and 1218 (82.4%) in the control group (odds ratio, 1.95; 95% CI, 1.56-2.44; P < .001). In the safety cohort, serious adverse events occurred in 15 of 1488 patients (1.0%) in the Xuesaitong group and 16 of 1482 (1.1%) in the control group (P = .85).Conclusions and Relevance: In this randomized clinical trial, Xuesaitong soft capsules significantly increased the likelihood of functional independence at 3 months in patients with ischemic stroke, indicating that this may be a safe and effective alternative therapy to improve prognosis in this population.Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800016363

Language is an essential higher cognitive function supported by large-scale brain networks. In this study, we investigated functional connectivity changes in the left frontoparietal network (LFPN), a language-cognition related brain network in aphasic patients. We enrolled 13 aphasic patients who had undergone a stroke in the left hemisphere and age-, gender-, educational level-matched controls and analyzed the data by integrating independent component analysis (ICA) with a network connectivity analysis method. Resting state functional magnetic resonance imaging (fMRI) and clinical evaluation of language function were assessed at two stages: 1 and 2 months after stroke onset. We found reduced functional connectivity between the LFPN and the right middle frontal cortex, medial frontal cortex, and right inferior frontal cortex in aphasic patients as compared to controls. Correlation analysis showed that stronger functional connectivity between the LFPN and the right middle frontal cortex and medial frontal cortex coincided with more preserved language comprehension ability after stroke. Network connectivity analysis showed reduced LFPN connectivity as indicated by the mean network connectivity index of key regions in the LFPN of aphasic patients. The decreased LFPN connectivity in stroke patients was significantly associated with the impairment of language function in their comprehension ability. We also found significant association between recovery of comprehension ability and the mean changes in intrinsic LFPN connectivity. Our findings suggest that brain lesions may influence language comprehension by altering functional connectivity between regions and that the patterns of abnormal functional connectivity may contribute to the recovery of language deficits.

Determining an appropriate control for use in acupuncture research remains one of the largest methodological challenges acupuncture researchers face. In general, acupuncture controls fall under one of two categories: (1) sham acupuncture, in which the skin is punctured with real acupuncture needles either fully at nonacupoint locations or shallowly at acupoint locations or both and (2) placebo acupuncture, which utilizes nonpenetrating acupuncture devices. In this study, we will focus on non-penetrating placebo acupuncture devices (blunted-needle and nonneedle devices) that are currently available in acupuncture research. We will describe each device and discuss each device’s validation and application in previous studies. In addition, we will outline the advantages and disadvantages of these devices and highlight how the differences among placebo devices can be used to isolate distinct components of acupuncture treatment and investigate their effects. We would like to emphasize that there is no single placebo device that can serve as the best control for all acupuncture studies; the choice of an acupuncture control should be determined by the specific aim of the study.

Background: Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Songling Xuemaikang capsule (SXC)—a Chinese herbal formula—was effective for essential hypertension. However, the efficacy of SXC monotherapy for hypertension remains unclear. We aimed to compare the blood pressure (BP)–lowering efficacy and safety of SXC versus losartan in patients with essential hypertension. Methods: In this multicenter, randomized, double-blind, noninferiority trial in China, patients 18 to 65 years of age with mild essential hypertension were randomly allocated to receive either SXC or losartan for 8 weeks. The primary outcome was the change in sitting diastolic BP from baseline to 8 weeks, with a predefined noninferiority margin of −2.5 mm Hg. Results: Of the 755 patients who entered a 2-week run-in period, 628 patients (327 women and 301 men; mean [SD] age, 52.6 [9.2] years) were randomly assigned to the SXC (n=314) or losartan (n=314) group. The primary analysis based on the intention-to-treat principle showed that the change in diastolic BP from baseline to 8 weeks was similar between the SXC and losartan groups (−7.9 [8.0] versus −8.1 [7.9]). The lower boundary of 95% CI (mean difference, −0.24 [95% CI, −1.51 to 1.03]) was above the margin of −2.5 mm Hg, showing noninferiority. Results were consistent with per-protocol analysis. SXC produced greater improvements in total hypertension symptom score (−5.7 [4.2] versus −5.0 [4.0]; P =0.020) and total cholesterol (−0.1 [1.0] versus 0.1 [1.2]; P =0.025). There were no differences between groups in the other BP and patient-reported outcomes. Incidence and severity of adverse events were similar between groups. Conclusions: SXC was well tolerated and demonstrated noninferior to losartan in BP lowering in patients with mild hypertension. SXC might be an alternative for mild hypertension, particularly for patients with a preference for natural medicine. Registration: URL: www.chictr.org.cn ; Unique identifier: ChiCTR-IPR-16008108.

The morbidity and mortality rates of ischemic stroke (IS) are very high, and IS constitutes one of the main causes of disability and death worldwide. The pathogenesis of ischemic stroke includes excitotoxicity, calcium overload, oxygen radical injury, inflammatory reactions, necrosis/apoptosis, destruction of the blood-brain barrier (BBB), and other pathologic processes. Recent studies have shown that exosomes are critical to the pathogenesis, diagnosis, and treatment of cerebral infarctions resulting from ischemic stroke; and there is growing interest in the role of exosomes and exosomal miRNAs in the diagnosis and treatment of IS. Exosomes from central nervous system cells can be found in cerebrospinal fluid and peripheral bodily fluids, and exosomal contents have been reported to change with disease occurrence. Exosomes are small membranous extracellular vesicles (EVs), 30–150 nm in diameter, that are released from the cell membrane into the depressions that arise from the membranes of multivesicular bodies. Exosomes carry lipids, proteins, mRNAs, and microRNAs (miRNAs) and transport information to target cells. This exosomal transfer of functional mRNAs/miRNAs and proteins ultimately affects transcription and translation within recipient cells. Exosomes are EVs with a double-membrane structure that protects them from ribonucleases in the blood, allowing exosomal miRNAs to be more stable and to avoid degradation. New evidence shows that exosomes derived from neural cells, endothelial cells, and various stem cells create a fertile environment that supports the proliferation and growth of neural cells and endothelial cells, inhibits apoptosis and inflammatory responses, and promotes angiogenesis. In the present review, we discuss how circulating exosomes—and exosomal miRNAs in particular—may provide novel strategies for the early diagnosis and treatment of ischemic stroke via their potential as non-invasive biomarkers and drug carriers.