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BackgroundNeuromyelitis 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.MethodsThe 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.DiscussionAlthough 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 registrationThe 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.

Abstract Background Hepatocellular carcinoma (HCC) is a malignant tumor that threatens global human health. High PKM2 expression is widely reported in multiple cancers, especially in HCC. This study aimed to explore the effects of PKM2 on global gene expression, metabolic damages, patient prognosis, and multiple transcriptional regulation relationships, as well as to identify several key metabolic genes and screen some small-molecule drugs. Methods Transcriptome and clinical HCC data were downloaded from the NIH-GDC repository. Information regarding the metabolic genes and subsystems was collected from the Recon 2 human metabolic model. Drug-protein interaction data were obtained from the DrugBank and UniProt databases. We defined patients with PKM2 expression levels ≥11.25 as the high-PKM2 group, and those with low PKM2 expression (

Objective MicroRNA plays a vital role in gene expression, and microRNA dysregulation is involved in carcinogenesis. The miR-196a-2 polymorphism rs11614913 is reportedly associated with cancer susceptibility. This meta-analysis was performed to assess the overall association of miR-196a-2 with cancer risk.Methods A total of 27 independent case-control studies involving 10,435 cases and 12,075 controls were analyzed for the rs11614913 polymorphism.Results A significant association was found between rs11614913 polymorphism and cancer risk in four genetic models (CT vs. TT, OR=1.15, 95%CI=1.05-1.27; CC vs. TT, OR=1.23, 95%CI=1.08-1.39; Dominant model, OR=1.17, 95%CI=1.06-1.30; Additive model, OR=1.08, 95%CI=1.01-1.14). In the subgroup analysis of different tumor types, the C allele was associated with increased risk of lung, breast, and colorectal cancer, but not with liver, gastric, or esophageal cancer. In the subgroup analysis by ethnicity, a significantly increased risk of cancer was found among Asians in all genetic models, but no associations were found in the Caucasian subgroup.Conclusions The meta-analysis demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility, especially lung cancer, colorectal cancer, and breast cancer among Asian populations.