Objective: To explore effects of repetitive transcranial magnetic stimulation (rTMS) combined with transcranial direct current stimulation (tDCS) on motor function and cortex excitability in subacute stroke patients. Design: Randomized controlled trial. Setting: Inpatient hospitals. Subjects: Sixty-five participants were randomly assigned to four groups: sham, 1Hz rTMS, cathodic tDCS combined with 1Hz rTMS (tDCS-/rTMS-) and anodic tDCS combined with 1Hz rTMS (tDCS+/rTMS-). Interventions: Four interventions were used, including sham, 1Hz rTMS, and cathodal or anodal tDCS, followed by 1Hz rTMS over contralesional motor cortex, which continued for four weeks. Main measures: Outcome measures were motor function and cortical excitability, evaluated by Fugl-Meyer Assessment, National Institutes of Health Stroke Scale and Barthel Index, resting Motion Threshold, Motor Evoked Potentials and Central Motor Conduction Time, assessed at baseline, four weeks and eight weeks. Results: At four weeks after interventions, Fugl-Meyer Assessment lower limb change score in tDCS+/rTMS- group was significantly larger than other three groups ( P < 0.001). There were significant differences in bilateral Motor Evoked Potentials changes between tDCS+/rTMS- group and sham group ( P < 0.05). At eight weeks, compared to other groups, National Institutes of Health Stroke Scale ( P = 0.003), Barthel Index ( P = 0.002), FMA lower limb score ( P < 0.001), and bilateral resting Motion Threshold, Motor Evoked Potentials ( P < 0.05) showed significant changes in tDCS+/rTMS- group. Furthermore, Fugl-Meyer Assessment lower limb change score was associated with increased ipsilesional Motor Evoked Potentials ( r = 0.703 P < 0.001) in tDCS+/rTMS- group. Conclusion: 1Hz rTMS combined with anode tDCS stimulation protocol could be a preferable rehabilitative strategy for motor recovery in subacute stroke patients.
Autoreactive T cells play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). TGF-β type I receptor (TGFβRI) is pivotal in determining T cell activation. Here, we showed that TGFβRI expression in naïve CD4+ T cells was decreased in SLE patients, especially in those with high disease activity. Moreover, IL-6 was found to downregulate TGFβRI expression through JAK/STAT3 pathway in SLE patients. In vitro, the JAK inhibitor tofacitinib inhibited SLE T cell activating by upregulating TGFβRI expression in a dose-dependent manner. In MRL/lpr mice, tofacitinib treatment ameliorated the clinical indicators and lupus nephritis, as evidenced by reduced plasma anti-dsDNA antibody levels, decreased proteinuria, and lower renal histopathological score. Consistently, tofacitinib enhanced TGFβRI expression and inhibited T cell activation in vivo. TGFβRI inhibitor SB431542 reversed the effects of tofacitinib on T cell activation. Thus, our results have indicated that tofacitinib can suppress T cell activation by upregulating TGFβRI expression, which provides a possible molecular mechanism underlying clinical efficacy of tofacitinib in treating SLE patients.
Background: Umbilical cord mesenchymal stem cells (UC-MSCs), which possess potent immunomodulatory effects and low immunogenicity, are considered to be a promising stem cell-based therapy for sepsis. In the current study, we aimed to investigate whether the combined use of UC-MSCs and imipenem has a better effect than imipenem alone in treating Escherichia coli (E. coli)-induced sepsis and to explore the mechanism by which UC-MSCs exert their therapeutic effect in septic mice.Methods: We randomly divided mice into five groups with 10 mice in each group: the normal control group (control group), the sepsis group (vehicle group), the MSCs treatment group (MSCs group), the imipenem treatment group (imipenem group), and the imipenem plus MSCs treatment group (imipenem + MSCs group). We monitored the survival rate in each group every 12 h for 3 days. After observing the survival rate, another 50 mice were also randomly divided into five groups, and the mice were sacrificed after 24 h. Bacterial colonies from the blood and peritoneal lavage fluid were counted in a blinded manner. Organ injury was analyzed by hematoxylin and eosin (HE) staining. Frequencies of myeloid-derived suppressor cells (MDSCs) in the blood, spleen, and bone marrow (BM) were determined by flow cytometry. Plasma levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA).Results: Compared with imipenem treatment, the co-administration of UC-MSCs and imipenem dramatically improved the survival rate, decreased the bacterial load, and ameliorated organ injury.Furthermore, UC-MSCs treatment, either alone or in combination with imipenem, significantly increased plasma levels of IL-10 and the percentage of MDSCs by inducing arginase-1 in septic mice. Conclusions:Our results indicated that UC-MSCs protect mice against sepsis by acting on MDSCs.Combination therapy of UC-MSCs and imipenem may be a new approach for the future clinical treatment of sepsis.
To analyze the changes in liver functions and the relationship between alterations in liver function and mortality risk in young adults with third-degree burn wounds on over 90% of the total body surface area (TBSA).A total of 23 fatally burned factory workers in an inflammable dust explosion and fire were enrolled from 2 intensive care units. Clinical data, particularly the laboratory tests for liver function, were retrospectively analyzed and compared between the survivor and non-survivor groups.Compared to survivors, non-survivors had significantly higher total bilirubin (TBIL), glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase, alkaline phosphatase, prothrombin time, and activated partial thromboplastin time (APTT) at the terminal point of this study (P <.05). In addition, the peak values of TBIL, GPT, and longer APTT were higher in non-survivors than in survivors during hospital course, and the peak values of TBIL was one of major prognostic factors for mortality risk. Furthermore, at the first 2 weeks, the cumulative survival rates were significantly lower in patients with liver dysfunction than those without liver dysfunction (P <.01).Our findings show that the great changes in liver function occurred in first 2 weeks after severe burns. Liver dysfunction may have an effect on clinical outcomes of post-burn. Measures to protect liver function and prevent from deterioration could be beneficial in improvement survival rate, especially during the first 2 weeks.
ObjectivesTo evaluate the efficacy and safety of tacrolimus (TAC) for the treatment of primary Sjögren's syndrome (pSS) with refractory immune thrombocytopenia (RITP). MethodsTwenty-three pSS patients with RITP treated with TAC from June 2018 to June 2021 at the First Affiliated Hospital of Soochow University were enrolled in this retrospective cohort study. Platelet response, clinical and immunological parameters, toxicity and safety were compared and analysed at baseline and different points after TAC treatment. ResultsAt 4 weeks after treatment, 2 patients (8.7%) attained a complete response (CR, platelet count ≥100×10 9 /L and no bleeding), 15 patients (65.2%) achieved a partial response (PR, platelet count ≥ 30×10 9 /L but <100×10 9 /L and no bleeding or a platelet count at least twice that before treatment), and the other 6 patients (26.1%) did not respond to TAC treatment. At 8 weeks after treatment, a CR was seen in 4 patients (17.4%), and the percentage of patients with a PR increased to 78.3% (18 patients). The percentage of patients with a CR increased to 47.8% (11 patients), and 9 patients (39.1%) achieved a PR without relapse at 12 weeks after treatment. At 24 weeks after treatment, 14 patients (60.9%) achieved a CR, and 8 patients (34.8%) achieved a PR. Compared to before treatment, the level of IgG was decreased significantly at 24 weeks after treatment, whereas there was no significant difference in the levels of IgM or IgA between baseline and 24 weeks after treatment. Additionally, the absolute CD3 + T cell count, European SS Disease Activity Index (ESSDAI) score, and levels of IL-2 and INF-γ were significantly decreased at 24 weeks after treatment. Conclusion TAC is effective and well tolerated by pSS patients with RITP, and the mechanism underlying the effect of TAC in thesepatients may be related to reduced Th1 cytokine expression.
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