Positive association between urinary albumin-creatinine ratio and lower extremity peripheral arterial disease in Chinese diabetes patients: A cross-section study with propensity score matching analysis.

BACKGROUND AND AIMS: Elevated urinary albumin-creatinine ratio (ACR) is an established risk factor for lower extremity peripheral arterial disease (PAD) in non-diabetes individual. This study aimed to determine the relationship between urinary ACR level and PAD in diabetes population. METHODS AND RESULTS: A cross-section study with 1396 hospitalized diabetes participants from department of endocrinology and neurology were performed and the propensity score matching method was applied to reduce the effects of confounding factors between the matched PAD and Non-PAD groups. The relationship between urinary ACR and ankle-brachial index (ABI) was analyzed by linear curve fitting analyses and multiple logistic regression models. Our study showed that the prevalence of PAD (low ABI, ABI<0.9) was 7.09% in our diabetes patients. The ABI level was significantly lower in high ACR group compared with those in normal urinary ACR group (1.11 ± 0.17 vs 1.13 ± 0.15, p = 0.010). The prevalence of PAD was increased with the increased tertile's of log2-transformed ACR in total patients before and after propensity score matching (p < 0.001 and p = 0.007, respectively). The OR (95% CI) between log2-transformed ACR and PAD was 1.0 and 1.70 (1.08-2.69, p = 0.022) respectively in normal and high ACR levels in diabetes patients after adjusting for potential confounders. After propensity score matching, the OR (95% CI) between log2-transformed ACR and PAD was 1.0 and 1.85 (1.05-3.23, p = 0.031) respectively in normal and high ACR levels in diabetes patients after adjusting for potential confounders. CONCLUSION: The elevated urinary ACR level was associated with PAD in Chinese diabetes patients.

Human Umbilical Cord Mesenchymal Stem Cells to Treat Neuromyelitis Optica Spectrum Disorder (hUC-MSC-NMOSD): A Study Protocol for a Prospective, Multicenter, Randomized, Placebo-Controlled Clinical Trial.

Background: Neuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing and disabling autoimmune disease of the central nervous system. Its optimal first-line treatment to reduce relapse rate and ameliorate neurological disability remains unclear. We will conduct a prospective, multicenter, randomized, placebo-controlled clinical trial to study the safety and effectiveness of human umbilical cord mesenchymal stem cells (hUC-MSCs) in treating NMOSD. Methods: The trial is planned to recruit 430 AQP4-IgG seropositive NMOSD patients. It consists of three consecutive stages. The first stage will be carried out in the leading center only and aims to evaluate the safety of hUC-MSCs. Patients will be treated with three different doses of hUC-MSCs: 1, 2, or 5 × 106 MSC/kg·weight for the low-, medium-, and high-dose group, respectively. The second and third stages will be carried out in six centers. The second stage aims to find the optimal dosage. Patients will be 1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 randomized into the optimal dose and the controlled group. The primary endpoint is the first recurrent time and secondary endpoints are the recurrent times, EDSS scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. Endpoint events and side effects will be evaluated every 3 months for 2 years. Discussion: Although hUC-MSC has shown promising treatment effects of NMOSD in preclinical studies, there is still a lack of well-designed clinical trials to evaluate the safety and effectiveness of hUC-MSC among NMOSD patients. As far as we know, this trial will be the first one to systematically demonstrate the clinical safety and efficacy of hUC-MSC in treating NMOSD and might be able to determine the optimal dose of hUC-MSC for NMOSD patients. Trial registration: The study was registered with the Chinese Clinical Trial Registry (CHICTR.org.cn) on 2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial protocol (Protocol version 1.2.1) was released on 16 March 2020.

EGb761 provides a protective effect against Aß1-42 oligomer-induced cell damage and blood-brain barrier disruption in an in vitro bEnd.3 endothelial model.

Alzheimer's disease (AD) is the most common form of senile dementia which is characterized by abnormal amyloid beta (Aß) accumulation and deposition in brain parenchyma and cerebral capillaries, and leads to blood-brain barrier (BBB) disruption. Despite great progress in understanding the etiology of AD, the underlying pathogenic mechanism of BBB damage is still unclear, and no effective treatment has been devised. The standard Ginkgo biloba extract EGb761 has been widely used as a potential cognitive enhancer for the treatment of AD. However, the cellular mechanism underlying the effect remain to be clarified. In this study, we employed an immortalized endothelial cell line (bEnd.3) and incubation of Aß(1-42) oligomer, to mimic a monolayer BBB model under conditions found in the AD brain. We investigated the effect of EGb761 on BBB and found that Aß1-42 oligomer-induced cell injury, apoptosis, and generation of intracellular reactive oxygen species (ROS), were attenuated by treatment with EGb761. Moreover, treatment of the cells with EGb761 decreased BBB permeability and increased tight junction scaffold protein levels including ZO-1, Claudin-5 and Occludin. We also found that the Aß(1-42) oligomer-induced upregulation of the receptor for advanced glycation end-products (RAGE), which mediates Aß cytotoxicity and plays an essential role in AD progression, was significantly decreased by treatment with EGb761. To our knowledge, we provide the first direct in vitro evidence of an effect of EGb761 on the brain endothelium exposed to Aß(1-42) oligomer, and on the expression of tight junction (TJ) scaffold proteins and RAGE. Our results provide a new insight into a possible mechanism of action of EGb761. This study provides a rational basis for the therapeutic application of EGb761 in the treatment of AD.