Hu Xiaomei MD, Director Of Research Application Realgar Yang Poison Treatment Of Myelodysplastic Syndrome Academic Experience And Realgar Active Ingredient As 2 S ₂ Mechanism Of Action In Vitro

Background:Myelodysplastic syndrome (MDS) encompasses a heterogeneous group of clonal hematopoietic stem-cell disorders, characterized by ineffective and dysplastic hematopoietic differentiation and variable risk progressed to acute myeloid leukemia. Karyotype abnormality is a sign of abnormal hematopoietic clone, and chromosomal abnormalities are found in40-60%of MDS patients. Meanwhile, dysfunction of T cells in the patients with MDS was observed. On one hand, abnormal T cells in MDS patients directly suppressed hematopoiesis or secreted negative regulator of hematopoiesis, which leaded to excessive apoptosis in normal hematopoietic cells. On the other hand, dysfunction of T cells leaded to abnormal proliferation of malignant clone for escaping from immune surveillance.The disease was not recorded in traditional Chinese medicine (TCM). It was named as "consumptive disease"," blood symptoms " or "mass in the abdomen" in TCM, according to the manifestations such as pale, weak, palpitation, shortness of breath, bleeding, fever and splenomegaly. Now, MDS has been named as "toxin and consumption of bone marrow" in TCM based on the consensus of experts.Chief physician Hu Xiaomei descended academicaly from Zhou Aixiang and Deng Chengshan who are the national famous doctors in TCM. She has had a clinical experience in hematology for27years. She praised highly the "Strengthening Yang School", and has gradually formed her own academic experience based on constantly realizing in clinical practice for many years, especially in the treatment of MDS with TCM. She proposed the theory of strengthening yang for removing toxin, and was good at application of Realgar, a natural drug with pungent and warm. She got some good clinical results and took some measures to protect patients from side effects. Chief physician Hu was distinctive in the treatment of MDS with Realgar to strengthening yang for removing toxin, which is worth to be explored and summarized.Objectives:1. To summarize and extract the academic experience of teacher Hu in the treatment of MDS with Realgar to strengthening yang for removing toxin.2. To investigate in vitro the action mechanisms of Realgar used clinically by teacher Hu in the treatment of MDS. Methods:1. Summaring and extracting the academic experience of chief physician Hu Xiaomei in the treatment of MDS with Realgar to strengthening yang for removing toxin were was performed by following teacher Hu in clinical practice, combing the academic origin, and listing the syndrome differentiation thinking and the features of prescription.2. Investigating in vitro the action mechanisms of Realgar used clinically by teacher Hu in the treatment of MDS were carried out by studying on effects of As2S2, active content of Realgar, on F-36p cell lines and mitogen--activated human peripheral blood mononuclear cells (PBMCs)Results:1. In summary and analysis, chief physician Hu Xiaomei, according to the clinical characteristics of MDS and based on the theories of TCM such as "Yang deficiency leading to cold" and "Extreme cold generating toxin", put forward that the pathogenesis of "toxin and consumption of bone marrow"(MDS) could be described as "Yang deficiency leading to cold accumulation" and the "cold toxin existing for a long time". Strengthening yang for removing toxin was the basic therapeutic principle in the treatment of MDS. Teacher Hu was good at application of Realgar, a natural drug with pungent and warm, to dispelling cold in the treatment of MDS, and got some good clinical results. For reducing the toxicity of Realgar, Teacher Hu took some measures to protect patients from side effects.2. The results studied in vitro showed that As2S2significantly suppressed the proliferation, induced apoptosis and promoted erythroid differentiation on F-36p cell lines. As2S2significantly suppressed cell proliferation, inhibited the expressions of CD4+T lyphocytes, CD8+T lyphocytes, obviously increased the expression of CD4+CD25+Foxp3+Treg cells, and inhibited the production of TNF-a and IL-10in mitogen-activated PBMCs.Conclusions:1. Chief physician Hu was distinctive in the thinking of syndrome differentiation, good therapy outcomes and safety measures to protect from side effects in the treatment of MDS with low-dose Realgar to strengthening yang for removing toxin, which formed her own unique academic experience and enriched the theoretical system of "Strengthening Yang School" in TCM.2. As2S2, active content of Realgar, not only induced apoptosis and erythroid differentiation on F-36p cell lines, but also inhibited mitogen-activated T cells and cytokines, which might be the dominant mechanisms of Realgar in the treatment of MDS.