Hypoxia/ischemia is a common clinical pathophysiological process and cause of death,and it is a common problem in extreme conditions such as high altitude,astronautics and diving.Hamartin is a kind of effective endogenous neuroprotectant and could increase cell tolerance to acute hypoxia or ischemia, thus,is of significance to research.The role of hamartin in hypoxia/ischemia has been a research focus of many scientists.Elucidating the related protective effect and its DNA methylation on hypoxia/ischemia can not only reduce injury,but also lay a basic for further studying the role of hamartin and its DNA methylation in other pathophysiological processes and provide theoretical guidance for the following clinical study.In this paper,we review the structure,mechanism and role of hamartin and the effect of its DNA methylation on hypoxia/ischemia.

OBJECTIVETo explore the mechanism of NK cell dysfunction in patients with multiple myeloma (MM).

METHODSThe expression of inhibitory receptors (CD158a and CD158b) and activating receptors NKG2D and NCRs (NKp30, NKp44 and NKp46) on CD3-CD56+NK cell of 13 MM patients and 30 healthy controls were analyzed by flow cytometry. The concentration of soluble NKG2D ligands (MICA, MICB, ULBP1, ULBP2 and ULBP3) in serum was detected by enzyme- linked immunosorbent assay (ELISA), and the cytotoxicity of NK cell against MM cell line by flow cytometry.

RESULTSThere are no significant differences of percentage and absolute number of NK cells, and the expression level of CD158a and CD158b between MM patients and healthy individuals (P>0.05). No NKp44 expression was detected on fresh isolated NK cells from both groups. There is no difference in inhibitor receptors expression between MM patients and healthy individuals but the expression of NKG2D, NKp30 and NKp46 on NK cells were higher in MM patients as compared with that in healthy individuals. The concentration of soluble NKG2D ligands in serum was higher in MM patients as compared with that in healthy individuals (P<0.05). Cultured healthy individual's NK cells with MM patient's serum could significantly decrease its cytotoxicity against MM cell line U266 cells [(38.5 ± 6.5) % vs (25.4 ± 5.9)%, P=0.044］.

CONCLUSIONThe higher level of soluble NKG2D ligands in serum may be the mechanism of NK cell dysfunction in MM patient.

Cells, Cultured ; Flow Cytometry ; Humans ; Killer Cells, Natural ; metabolism ; pathology ; Multiple Myeloma ; immunology ; metabolism ; NK Cell Lectin-Like Receptor Subfamily K ; metabolism ; Natural Cytotoxicity Triggering Receptor 1 ; metabolism ; Natural Cytotoxicity Triggering Receptor 2 ; metabolism ; Natural Cytotoxicity Triggering Receptor 3 ; metabolism ; Receptors, KIR2DL1 ; metabolism ; Receptors, KIR2DL3 ; metabolism