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Cytokine storm, which is an overreaction of the immune system to external stimulation, is characterized by a rapid increase in cytokine levels and leucocyte counts due to a positive feedback loop, and results in tissue damage and organ dysfunction with a highly inflammatory state. By analyzing the pathogeny, histopathology, disease progression, and clinical manifestation of diseases related to cytokine storm, this article summarizes key information from traditional Chinese medicine for syndrome differentiation. The etiologies of cytokine storm include external causes and causes that are neither internal nor external, and pathologies such as toxin, phlegm, blood stasis, and deficiency are also observed during cytokine storm. The spectrum of diseases covers warm-heat and damp-heat diseases, which could be differentiated using Weifen-Qifen-Yingfen-Xuefen theory; in addition, the fight between vital qi and pathogenic qi can be divided into syndromes with good prognosis and syndromes with unfavorable prognosis. The most commonly injured organs are the lung, heart, spleen, and stomach. However, during the treatment of diseases related to cytokine storm, attention should be paid to the above information to estimate the risk of a cytokine storm occurring, and to adopt appropriate treatment method to prevent its occurrence and improve prognosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Corona Virus Disease 2019 (COVID-19) is a highly contagious, rapidly variable, and dangerous infectious disease. However, no specific and effective treatment for COVID-19 is available until now. The safety and efficacy of mesenchymal stem cells and their exosomes have been well verified in numerous clinical trials. Their immunomodulatory and tissue regeneration capabilities may support them as a prospective therapy for COVID-19 application in the clinic. OBJECTIVE: To focus on the development, pathogenesis and the current treatment status of COVID-19, efficacy and possible immunomodulatory mechanisms of mesenchymal stem cells and their exosomes for COVID-19 so as to provide new insights into the clinical treatment for the disease in the future. METHODS: Articles were searched on PubMed and CNKI with the key words of “SARS-CoV-2, COVID-19, cytokine storm, acute respiratory distress syndrome, mesenchymal stem cells, exosomes, immune regulation, tissue repair” in Chinese and English. Finally, 64 articles were collected for this review. RESULTS AND CONCLUSION: Acute respiratory distress syndrome and acute lung injury caused by cytokine storm are the primary precipitating factors of death in individuals with COVID-19. Mesenchymal stem cells and their exosomes can effectively treat the symptoms of acute respiratory distress syndrome and repair the damaged lung tissue in COVID-19 patients by reducing the cytokine storm and promoting the regeneration of alveolar epithelial cells through the interaction with immune cells and their paracrine effects. All of these investigations confirmed that mesenchymal stem cells and their exosomes can fight the COVID-19 infection, and this might be a promising, safe and effective strategy. However, more preclinical studies and randomized, controlled clinical trials are needed to conduct the biodistribution, metabolic fate, and the potential treatment risks of mesenchymal stem cells and their derived exosomes in vivo to fully exploit their clinical efficacy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the mechanism of Liangge Powder inhibiting cytokine storm in acute lung injury ( ALI) based on network pharmacology and molecular docking. METHODS: The active ingredients and action targets of Liangge Powder were screened from the traditional Chinese medicine systems pharmacology database and analysis platform; the disease targets of ALI were obtained from online mendelian inheritance in man, Gene Cards and other medical databases. Uniprot database was used to query the genes corresponding to the targets, R software and String database were adopted to construct protein-protein interaction ( PPI) network, Cytoscape software was used to construct herbal-compound-target interaction network, R software was used to perform gene ontology (GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes ( KEGG) pathway enrichment analysis, so as to predict the molecular mechanisms. Autodock Vina software was adopted to conduct molecular docking on the core components of Liangge Powder with IL-I~, IL-6, TNF-a receptors and glycogen synthase kinase 3~. RESULTS: Totally 149 active ingredients and 23 7 targets were found in Liangge Powder in the treatment of ALI, the key targets involving AKTI, IL-6 and MAPK3, etc. ; the GO functional enrichment was mainly biological processes, including oxidative stress, lipopolysaccharide response and bacteriogenic molecule, etc. The KEGG pathway mainly involved PI3K-Akt, AGE-RAGE and TNF pathways, etc. ; results of molecular docking showed that the binding forces of core compounds, such as phillyrin, stigmasterol, glabridin, pterocarpin and quercetin, was similar to that of clinically used anti-inflammatory drugs, among which phillyrin was the strongest. CONCLUSIONS: Liangge Powder may act on targets and pathways of AKTl, IL-6, PI3K-Akt and AGE-RAGE through various active ingredients such as phillyrin and and quercetin, and exert therapeutic effects on ALI in terms of anti-inflammatory, antibacterial, antioxidant and immunoregulation. [ABSTRACT FROM AUTHOR]

BACKGROUND: In recent years, tumor immunotherapy has developed rapidly. Most scholars have focused on the single antibody treatment with autologous chimeric antigen receptor T-cell (CAR-T), but poor quality and small number of cultured cells are encountered. Therefore, allogeneic CAR-T cells have a better developmental potential. OBJECTIVE: To investigate the efficacy and safety of allogeneic CAR-T cells in the treatment of recurrent leukemia after allogeneic hematopoietic stem cell transplantation. METHODS: Two patients with relapsed refractory chronic myeloid leukemia in lymphoid blast crisis after allogeneic hematopoietic stem cell transplantation were treated with allogeneic CAR-T cells. Their clinical data were analyzed and relevant literature was reviewed. RESULTS AND CONCLUSION: Case 1 was hospitalized because of fever and fatigue for 5 days, and was diagnosed as chronic myeloid leukemia in lymphoid blast crisis by bone marrow cell morphology, flow cytometry, chromosome analysis, fusion gene and other related examinations. After oral imatinib combined with low dose chemotherapy, HLA10/10 matched haploid transplantation from daughter to mother proceeded smoothly. Three months after transplantation, BCR-ABL (p210) was positive, and chimera: donor cells accounted for 67.4%. After treatment with fludarabine+cyclophosphamide regimen, anti-CD19 CAR-T cells were infused at a dose of 5 ×106 cells/kg. Two weeks later, BCR-ABL (p210) turned negative and chimera: donor cells accounted for 99.62%. During the period, cytokine release syndrome level 1 appeared and symptomatic treatment was performed. The follow-up lasted for 6 months. Case 2 was treated in the local hospital in April 2011 because of left upper abdomen fullness for 1 year and night sweat for 15 days. One year later, it progressed to chronic myeloid leukemia in lymphoid blast crisis with T315I mutation. HLA 7/10 matched haploid stem cell transplantation from little brother to brother was performed after remission by chemotherapy. Anti-CD19 CAR-T cells were transfused at 2×105/kg in the second relapse in 2018. During this period, cytokine release syndrome level 4 appeared. Chronic myeloid leukemia continued to alleviate for over 2 months and then relapsed resulting in death. Thus, the donor-derived CAR-T cells can be considered for the treatment of recurrent chronic myeloid leukemia in lymphoid blast crisis after allogeneic hematopoietic stem cell transplantation. It can be transfused repeatedly. It is safe and effective, and the incidence of Graft-versus-host disease is low. Sequential treatment with anti-CD22 CAR-T cells is safe and effective. [ABSTRACT FROM AUTHOR]