Objective: To investigate the relationship between the mechanical circulatory support (MCS) combined with immunomodulation and the prognosis of patients with fulminant myocarditis. Methods: This is a retrospective study. A total of 88 patients with fulminant myocarditis admitted to Dongguan Kanghua hospital from Aug. 2008 to Dec. 2020 were included. Medical histories, results of laboratory tests, treatment regimens and clinical outcomes of these patients during their hospitalization were collected from the medical record system. According to the treatment methods, the patients were divided into MCS+immunomodulation group (38 cases), MCS group (20 cases) and traditional treatment group (30 cases). Patients in the MCS+immunomodulation group received intra-aortic balloon pump (IABP) or IABP combined with extracorporeal membrane oxygenation (ECMO) and immunoglobulin or glucocorticoid. Patients in the MCS group only received mechanical circulatory support. Patients in the traditional treatment group received neither mechanical circulatory support nor immunomodulatory therapy, and only used vasoactive drugs and cardiotonic drugs. The in-hospital mortality and length of stay were compared among the three groups. Results: A total of 88 patients with fulminant myocarditis aged (35.0±10.8) years were included, and there were 46 males (52.3%). The mortality of MCS+immunomodulation group (7.9% (3/38) vs. 56.7% (17/30), P=0.001 2) and MCS group (30.0% (6/20) vs. 56.7% (17/30), P=0.002 8) were lower than that of traditional treatment group. Compared with the MCS group, the in-hospital mortality in the MCS+immunomodulation group was lower (P=0.005 4). The most common cause of death was multiple organ dysfunction syndrome (MODS). The constituent ratios of death in MCS+immunomodulation group, MCS group and traditional treatment group were 3/3, 4/6 and 12/17, respectively. The incidence of MODS in the MCS group (20% (4/20)) and the traditional treatment group (40% (12/30)) was significantly higher than that in the MCS+immunomodulation group (7.9% (3/38)) (both P<0.01). In discharged patients, the hospitalization time of MCS+immunomodulation group was shorter than that of traditional treatment group ((13.4±5.5)d vs. (18.5±7.4)d, P<0.05) and MCS group ((13.4±5.5)d vs. (16.9±8.5)d, P<0.05). Conclusion: MCS combined with immunomodulatory therapy is associated with lower in-hospital mortality and shorter hospital stay in patients with fulminant myocarditis.
Adult ; Heart-Assist Devices ; Humans ; Immunomodulation ; Male ; Middle Aged ; Myocarditis/therapy* ; Retrospective Studies ; Treatment Outcome ; Young Adult

Autoimmune diseases are characterized by damage and dysfunction of multiple organs and various complications. Recently, new therapies for autoimmune diseases have been proposed extensively, and there are growing researches focusing on the immunomodulatory abilities of mesenchymal stem cells (MSCs). As a kind of small vesicles secreted by cells, exosomes can be released by MSCs and other cells. Being enriched with protein, mRNA, microRNA, lipids and other cell contents, exosomes participate in the transfer of substances and information between cells, and regulate the biological functions of recipient cells, which may be a potential mechanism of the immunomodulation abilities of MSCs. A growing number of studies have shown that the exosomes secreted by MSCs have similar or even better immunomodulation abilities than MSCs, and their roles in the treatment of several autoimmune diseases have been confirmed in animal models. In this review, we briefly summarize the effects of MSCs and the MSCs-derived exosomes on the immune system and immune cells, especially focusing on the research progress of MSCs-derived exosomes in autoimmune diseases in recent years.
Animals ; Autoimmune Diseases/therapy* ; Exosomes/metabolism* ; Immunomodulation ; Mesenchymal Stem Cells ; MicroRNAs/metabolism*

Epimedii Folium possesses many pharmacological activities including immunomodulation, anti-oxidation, and anti-tumor. Polysaccharides are the main components of Epimedii Folium, and their activities are closely related to the structure. The present study isolated a neutral polysaccharide(EPS-1-1) and an acidic polysaccharide(EPS-2-1) from the aqueous extract of Epimedii Folium through DEAE-52 cellulose anion-exchange chromatography and Sephadex G-100. The structures were characterized by chemical composition analysis, high-performance gel permeation chromatography(HPGPC), Fourier-transform infrared spectrometry(FT-IR), 1-phenyl-3-methyl-5-pyrazolone(PMP) derivatization, scanning electron microscopy(SEM), Congo red test, etc. The immunomodulatory activity of polysaccharides in vitro was determined by investigating the effects on the maturation of bone marrow-derived dendritic cells(BMDCs) and the release of inflammatory cytokines. According to the structural characterization analysis, EPS-1-1 was composed of fructose(Fuc), mannose(Man), ribose(Rib), rhamnose(Rha), glucose(Glc), galactose(Gal), xylose(Xyl), and arabinose(Ara) at 1.90∶0.67∶0.05∶0.08∶3.29∶1.51∶0.05∶0.37(molar ratio), while EPS-2-1 was mainly composed of Fuc, Man, Rha, glucuronic acid(GlcA), galacturonic acid(GalA), Glc, Gal, Xyl, and Ara at 5.25∶0.18∶0.32∶0.13∶1.14∶0.16∶0.55∶0.08∶0.2. EPS-1-1 and EPS-2-1 could promote the maturation and function of BMDCs through up-regulating the expression of MHC-Ⅱ, CD86, CD80, and CD40, and increasing the levels of inflammatory cytokines(IL-6, IL-12, and TNF-α) in vitro experiments, which suggested that EPS-1-1 and EPS-2-1 possessed good immunomodulatory activity.
Cytokines/metabolism* ; Drugs, Chinese Herbal ; Gas Chromatography-Mass Spectrometry ; Humans ; Immunomodulation ; Polysaccharides/chemistry* ; Spectroscopy, Fourier Transform Infrared

Considering the substantial role played by dendritic cells (DCs) in the immune system to bridge innate and adaptive immunity, studies on DC-mediated immunity toward biomaterials principally center on their adjuvant effects in facilitating the adaptive immunity of codelivered antigens. However, the effect of the intrinsic properties of biomaterials on dendritic cells has not been clarified. Recently, researchers have begun to investigate and found that biomaterials that are nonadjuvant could also regulate the immune function of DCs and thus affect subsequent tissue regeneration. In the case of proteins adsorbed onto biomaterial surfaces, their intrinsic properties can direct their orientation and conformation, forming "biomaterial-associated molecular patterns (BAMPs)". Thus, in this review, we focused on the intrinsic physiochemical properties of biomaterials in the absence of antigens that affect DC immune function and summarized the underlying signaling pathways. Moreover, we preliminarily clarified the specific composition of BAMPs and the interplay between some key molecules and DCs, such as heat shock proteins (HSPs) and high mobility group box 1 (HMGB1). This review provides a new direction for future biomaterial design, through which modulation of host immune responses is applicable to tissue engineering and immunotherapy.
Biocompatible Materials/metabolism* ; Dendritic Cells/metabolism* ; Tissue Engineering ; Immunomodulation ; Adaptive Immunity

Objective: To summarize the efficacy of combined treatment strategy of mechanical circulation support devices and immunomodulation therapy for patients with fulminant myocarditis. Method: We retrospectively analyzed the clinical data and outcomes of 37 fulminant myocarditis patients complicating cardiogenic shock, who were hospitalized from October 2017 to December 2019 in our department. Patients received guideline therapy according to "Chinese expert consensus statement on clinical diagnosis and treatment of fulminant myocarditis in adults"issued by Chinese Society of Cardiology of Chinese Medical Association. Patients were divided into IABP group (n=19), ECMO group (n=5) and IABP+ECMO group (n=13) according to different mechanical circulation support regimen. The treatment effectiveness among various groups were compared. The major endpoint was in-hospital mortality. The duration and outcome of mechanical circulation support were also analyzed. Furthermore, relationships between baseline data, proportion of different treatments (including medicine treatment, temporary pacemaker and continuous renal replacement treatment, immunomodulation therapy) and clinical outcome were analyzed. Results: The age of the 37 patients in the cohort was (37.4±17.0) years, and there were 22 male among them. Immunomodulation therapy included glucocorticoid (methylprednisolone) and intravenous immunoglobin. At admission, blood pressure was (70.21±17.37)mmHg(1 mmHg=0.133 kPa),heart rate was(100±30)beat/minutes,there were 10 cases of Ⅲ° atrioventricular block and all received temporary pacemaker implantation, 12 cases of ventricular tachycardia and fibrillation,1 patient received temporary pacemaker implantation due to electronic storm, peak cardiac troponin I level was (18.61±9.55)μg/L, peak B type natriuretic peptide level was 1 670(518,3 410)ng/L,left ventricular ejection fraction (LVEF) was(32.3±10.4)%. Thirty-four out of the 37 patients survived and 3 patients died. Hospital duration was (22.7±8.2)days, LVEF was (50.1±10.5)% at discharge. Lactic acid level was significantly higher in IABP+ECMO group than in IABP group and ECMO group(P<0.001 or =0.005),LVEF was significantly lower in IABP+ECMO group than in IABP group(P=0.004),the proportion of ventilator usage was higher in IABO+ECMO group than in IABP group (P<0.05). Survival rate was similar among the three groups. Conclusion: Comprehensive treatment regimen with combined mechanical circulation support and immunomodulation therapy as the core strategies is effective in the treatment of fulminant myocarditis complicated with cardiogenic shock.
Adult ; Extracorporeal Membrane Oxygenation ; Humans ; Immunomodulation ; Male ; Middle Aged ; Myocarditis/therapy* ; Retrospective Studies ; Shock, Cardiogenic/therapy* ; Stroke Volume ; Treatment Outcome ; Ventricular Function, Left ; Young Adult

BACKGROUND: There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients. METHODS: A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients. RESULTS: After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy. CONCLUSION Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.
Carcinoma, Non-Small-Cell Lung/surgery* ; Chemotherapy, Adjuvant ; Humans ; Immunomodulation ; Lung Neoplasms/surgery* ; Neoplasm Staging ; Propensity Score ; Retrospective Studies ; Thymalfasin

PURPOSE: Allergen immunotherapy (AIT) induces immunological tolerance, and there is increasing evidence of the clinical efficacy of AIT in the treatment of allergic asthma. However, the optimal parameters for asthma control in clinical trials are still unclear. We investigated the efficacy of AIT with respect to changes in the inhaled corticosteroid (ICS) dose in patients with allergic asthma. METHODS: A total of 117 adults with allergic asthma who had used ICS for more than 1 year in a single tertiary hospital in Korea were included in this retrospective study. We compared the clinical parameters and outcomes between the AIT group (ICS with AIT, n = 48) and the non-AIT group (ICS without AIT, n = 69) by applying an inverse probability of treatment weighting method. The patients in the AIT group had received subcutaneous AIT monthly as a maintenance treatment for more than 1 year. The changes in the ICS dose from baseline were evaluated in the 2 groups for 3 years. RESULTS: The proportion of responders who discontinued or decreased in the ICS dose with achieving control status of asthma was significantly higher in the AIT group than in the non-AIT group throughout the study period (at 6 months, 52.1% vs. 24.6%; at 1 year, 70.8% vs. 34.7%; at 2 years, 89.5% vs. 35.6%; at 3 years, 96.3% vs. 51.2%). Treatment responses did not differ significantly by type of allergen (single- or multi-allergens or 3 different products) used throughout the study period. CONCLUSIONS: Irrespective of the type of allergen, long-term maintenance AIT helps to spare ICS dose and achieve better control in patients with allergic asthma in real-world clinical practice.
Adult ; Asthma ; Desensitization, Immunologic ; Humans ; Immunomodulation ; Korea ; Methods ; Retrospective Studies ; Tertiary Care Centers ; Treatment Outcome

Wharton's jelly mesenchymal stem cells (WJ-MSCs) are a class of stem cells with high differentiative potential, an immuno-privileged status and easy access for collection, which raise no legal or ethical issues. WJ-MSCs exhibit several features of embryonic stem cells, both in the phenotypic and genetic aspects, with only a few differences, such as a shorter doubling time and a more extensive ex vivo expansion capacity. WJ-MSCs have immunomodulatory properties, involving both innate and adaptive immune responses. This review focuses on the role of WJ-MSCs in the management of graft-versus-host disease (GvHD), a life-threatening complication of the allogenic transplantation of hematopoietic stem cells. Different studies documented the beneficial effect of the infusion of WJ-MSCs, even when not fully HLA identical, in patients with severe GvHD, refractory to standard treatment. Finally, we summarized current ongoing clinical trials with WJ-MSCs and their potential in regenerative medicine.
Embryonic Stem Cells ; Ethics ; Graft vs Host Disease ; Hematopoietic Stem Cells ; Humans ; Immunomodulation ; Mesenchymal Stromal Cells ; Regenerative Medicine ; Stem Cells ; Umbilical Cord ; Wharton Jelly

Among the three treatment modalities of Graves' disease which include antithyroid drug (ATD), radioactive iodine and surgery, the ATD is most commonly preferred in Korea due to ease of use and definite curative effects on the thyrotoxic symptoms. However, several uncertainties about ATD remain: for example, the mechanism of actions on immune modulation, differences in the effects of drugs among individuals and associated factors in the view of remission. In recent years, long-term ATD treatment has been confirmed as an effective and safe therapy modality in adults, and several treatment guidelines have been released which accept long-term ATD therapy as an acceptable alternative to ablative therapy in Graves' patients. In this review, we summarize the recent progress in understanding the clinical role of ATD and emerging new antithyroid drugs focusing on immunomodulation.
Adult ; Antithyroid Agents ; Graves Disease ; Humans ; Immunomodulation ; Iodine ; Korea

Macrophages play essential roles in innate immune responses by producing various immune mediators. Therefore, modulating macrophage function is an attractive strategy to treat immune disorders. Aralia cordata var. continentalis (AC), known as “Dokwhal” in Korea, possesses various biological and medicinal functions, including immunomodulation. The present study investigated the effect of the hot water extract of AC (HAC) on RAW264.7 murine macrophages. When these cells were treated with HAC, nitric oxide production and inducible nitric oxide synthase expression was induced dose-dependently. In addition, HAC treatment triggered the secretion of innate immune cytokines, such as TNF-α and IL-6. Phagocytosis, measured by FITC-dextran internalization showed that HAC stimulated the phagocytic activity of macrophages. Furthermore, HAC promoted the production of reactive oxygen species in RAW264.7 cells, determined by CM-H2DCFDA. In addition, the immunoblot analysis of intracellular signaling proteins revealed that NF-kB and MAPK signaling pathways, which are important signaling mediators of inflammation, are upregulated by HAC. In conclusion, these findings suggested that HAC can stimulate macrophage activity, and NF-kB and MAPK signaling pathways might be involved in the immunostimulatory effects of HAC.
Aralia ; Cytokines ; Immune System Diseases ; Immunity, Innate ; Immunomodulation ; Inflammation Mediators ; Interleukin-6 ; Intracellular Signaling Peptides and Proteins ; Korea ; Macrophages ; NF-kappa B ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Phagocytosis ; Reactive Oxygen Species ; Water