Tqp cbl YDugc hoc - Tru&ng Bqi hqc YBugc Hue- Tdp 6, si 3- thdng 7/2016 ^ ^ .
NGHIEN CU'U MOI LliN QUAN GIU'A NbNG DQ LIPOPROTEIN-ASSOCIATED PHOSPHOLIPSAE A2 HUYET THANH
v o l BE DAY LOI* N6\ TRUNG MAC O0NG MACH CANH ti BENH N H A N NHdl MAU NAO
Li VSn Tdm', Nguyen PhU&ng Thao Tiin', Nguyin Oinh Todn', Li Thj Yin', Li Thj Pbuvng Anh' (l)Tr&bng Ogi hqc Y Ou&c Hui; (2)Binb viqn Trung uang Hui
Tdm t a t
Co sfr va myc dich: Xo vda mgeh nao la nguyen nhan dan d i n tac nghen eO hpc ddng m i u m i blln cd sau ciing la nhdi m i u n i o . Lipoprotein-associated phospholipase A2 (Lp-PLA2) la mpt chat chi diem sinh hyc viem dgc hifu ddi vdl mach mau, la y l u tfi quan trpng dy b i o mde dfi xo vda dpng mgeh. Nghifn edu nham dinh gia mdi lien quan gida ndng dp Lp-PLA2 huyit thanh vdi be day Idp nfii trung mgc dpng mgeh canh. Odi tuyng va phuong phip nghifn cdu: Nghifn edu md ta cat ngang gdm 37 bfnh nhin nhdi mau nao d i l u trj tgi Khoa Npi Tim mgch Bfnh vifn TrUdng Dgi hpe Y Dupc H u i va Bfnh vifn Trung UOng Huf.
Oanh gii tdn thuang dpng mgeh eanh ngoii sp qua sifu i m bang each do be day Idp npi trung mgc dfing mgch canh chung, xet nghifm ndng dd Lp-PLA2 huyet thanh, bilan lipid, glucose m i u . Kit qui: Bfnh nhin day Idp npi trung mac dfing mgeh eanh cd ndng dp Lp-PLA2 huyit thanh cao hon so vdl nhdm b l day Idp nfii trung mge binh thudng (27,73 lU/ml so vdi 14,35 lU/ml; p < 0,05). Cholesterol toan phan, cholesterol LDL, triglycerid v i Lp-PLA2 l i cae yeu t d ed kha ning dy b i o nhdng thay ddi kich thude be day Idp npi trung mac (p < 0,05). Cd mdi tUOng quan thugn mde dp vda giii'a nong dp Lp-PLA2 huyit thanh vdi be diy Idp ndi trung mge dpng mgch canh (r = 0,47; p < 0,05). Ket lu|n: Nong dp Lp-PLA2 huyit thanh cao cd mdi lien quan "^ nghTa vdi be day Idp nfii trung mgc dpng mgeh eanh d bfnh nhan nhoi mau nao.
T&khda: Dbt quy, xa v&a dbng mgch, viim, chi diim sinh hqc.
Abstract
RELATIONSHIP BETWEEN SERUM LIPOPROTEIN-ASSOCIATED PHOSPHOLIPSAE A2 AND CAROTID INTIMA-MEDIA THICKNESS
WITH CEREBRAL INFARCTION
Le Van Tom', Nguyen Phuong Thao Tien', Nguyen Oinh Toan', Le Thi Yerr', Le Thi Phuong Anh' (l)Hue University of Medicine and Pharmacy; (2)Hue Central Hospital
Background a n d Purpose: Cerebral atherosclerosis is t h e leading cause o f mechanical obstruction of b l o o d f l o w t h a t final event is cerebral i n f a r c t i o n . Lipoprotein-associated p h o s p h o l i p a s e A 2 (Lp-PLA2) is an i n f l a m m a t o r y biomarkers specific f o r b l o o d vessels, is an I m p o r t a n t f a c t o r p r e d i c t e d e x t e n t o f atherosclerosis.
The s t u d y a i m e d t o assess t h e association b e t w e e n s e r u m Lp-PLA2 c o n c e n t r a t i o n w^ith carotid Intima- media thickness (IMT). Materials and M e t h o d : T h e cross - secti'onal study, in 3 7 patients v^ho presented t o D e p a r t m e n t o f Cardiology - Hue University Hospital a n d Hue Central H o s p i t a l . V u l n e r a b i l i t y asessment of t h e external c a r o t i d a r t e r y i n t o t h e skull t h r o u g h u l t r a s o u n d b y m e a s u r i n g c a r o t i d i n t i m a - m e d i a thickness.
Testing s e r u m Lp-PLA2 c o n c e n t r a t i o n , lipid p r o f i l e , b l o o d glucose. Results: Group o f patients w i t h thickness of carotid IMT levels o f serum Lp-PLA2 was 27.73 l U / m l higher t h a n t h e g r a u p w i t h thickness normal carotid IMT was 14,35 l U / m l ; p < 0.05. Total cholesterol, LDL cholestnDl, triglycerid and Lp-PLA2 are t h e factors capable o f predict the changes in size IMT; (p <0.05). There is moderate correlation b e t w e e n Lp-PLA2 levels and canatid intima-media thickness (r = 0.47; p < 0.05). Conclusion: Higher Lp-PLA2 levels is significantly associated w i t h c a r o t i d intima- media thickness in patients w h o have cerebral infarcti'on.
Key words: Stroke, atherosclerosis, inflammation, biomarker.
JnS: Li Van TSm. email: levantan^[email protected] 7n bil: S/5/2016, Ngay ding y ding: 20/5/2016; Ngay A
I 20 ANDPHAHMACY
Tgp chiYDugc hgc - Tru&ng Dgi hgc Y Dugc Hue- Tqp 6, si 3 - thdng 7/2016 1. DAT VAN ot
Tai bien mgch m i u nao (TBMMN) hay dpt quy nao ludn l i van de thdi sy ciia nginh y t l d tat ca eae qufic gia tren t o i n the gldi, vi la bfnh ed ty If mac, ty If t d vong v i tan tgt rat cao, anh hudng khdng chi v l kinh te ma cdn t i c ddng rat ldn d i n tam ly ngudi bfnh, gia dinh va toan xa hpi. Nhdi m i u nao chiem den 87%eua bfnhtai bien mgch miu nao ma nguyfn nhin ehii yeu la do xo vda dpng mgch gay huyet khdi tac nghen ddng chay mgch mau [1], [2], [6].
Lipoprotein-Associated Phospholipase A2 (Lp- PLA2) va vai trd ciia nd duyc biet den la mot chat chi diem sinh hoc mdi trong bfnh 1^ xa v&a dfng mgch va viem mgch mau duye nghien cdu trong vai nam gan day [9], [11], [12].
Sieu am ddng mgch canh la mpt xet nghifm khdng xam nhgp, an toan, d l thyc hifn giup phat hifn va chan doan sdm tfin thuong xa vda dpng mgch, gdp phan rat Idn trong ehan doan can nguyfn bfnh sdm va chinh xic [15].
Muc tifu nghifn edu de tai nham:
1. Khao sdt cdc yeu tddnh hu&ng din be ddy ngi trung mgc dqng mqch canh ngodi sq qua sieu dm &
bqnh nhdn nhoi mdu nao.
2. Ddnh gid mdi liin quan giQ'a nong do Lp-PLA2 huyit thanh vdi be ddy nbi trung mqc dgng mgch cdnh.
1. DOI TirgrNG vA pnycmG PHAP NGHIEN CU'U 2.1. Ooi tuyng: 37 bfnh nhan dU&c chan doan l i nhdl m i u nao duyc dilu tri tgi Khoa Nfii tim mgch BV Trudng Ogi hpe Y Duyc Hui va BVTW Hui.
Tifu ehuan chyn bfnh
Bfnh nhin t r f n 18 tudi bj dpt quy thda man tifu chuan chin doan lam sing ciia Td chdc Y t l The gldi: dptquynaolisyxayra dpt ngpt cac thilu sdt chdc ning t h i n kinh, thudng la khu trii ban l i lan tda, ton tgi qua 24 gid hogc hogc din den t d vong ma khdng cd can nguyfn nao khae ngoai nguyen nhan t d mgch m i u [2]. Bfnh nhan duye ehyp CLVT trong vdng 24 gid ke t d khi nhgp vifn vdi hinh anh d i l n hinh cua nhdi mau nao l i viing giam ty trpng khoang 20 - 30 don vj HU phin bd theo so dd cap mau cua dpng mgeh nio.
Tifu chuan loai t r d
Logi t r d nhdng bfnh nhin bj xult huyft nao, xuat huyft khoang dudi nhfn, tdn thuang mgch m i u nao do chan thuong, cac bilu hifn nhiem
trCing, bfnh mien djch, bfnh i c ti'nh hay phy nd cd thai.
2.2. Phuong phip nghifn cdu Nghien cdu md t i cat ngang
- Khim xet lam sang: Hoi bfnh sd, ti'en sd, each khdi phat bfnh, cic dau hifu kem theo, khim toan difn ve t h i n kinh.
- Cgn lam sang: Chyp nao eat Idp vi ti'nh, nhdi mau nao vung giim ti trpng (20-30 HU).
+ Oinh luyng nfing d f Lp-PLA2 huyit thanh:
Ngudl bfnh khdng can nhjn ddi. Sau khl lay mlu thi be 30 phut dyi co cyc m i u , rdi quay ly tam 3000 vdng/phOt x 10 phut. Tach ngay ra tube va bio quan d -20° C. Khi chgy m i u thi ly t i m lai sau khi lam ra dfing. Ndng dp Lp-PLA2 duye djnh luyng theo phuong phap sandwich: hap phy miln djch gan enzyme (ELISA: Enzyme-Linked ImmunoSorbent-Assay) tren may mifn djch t y dpng ELISA Evolis Twin Plus cua Ddc, hda chit ciia nha san xult Cusabio thyc hifn tgi Khoa Sinh hda Bfnh vifn Trung uong Hui.
+ Xet nghifm Bilan lipid, hs-CRP, Glucose miu.
+ Sifu i m DMCa chung: Oinh gii tdn thuong dpng mgch eanh ngoai sp bang each do be day ldp nyi trung mac (IMT) cua dpng maeh cinh chung.
Dinh gii be diy Idp nfi trung mgc dfing mgch eanh theo hudng dan ciia Hpi Tang huyet ap Chau Au/Hoi Tim mach Chiu Au nim 2007 nhu sau [10], [15]:
IMT < 0,9 mm : binh thudng 0,9 mm < IMT £ 1,49 mm : diy Idp nfii trung mgc 1MT> 1,5 mm : mang xo vda 2.3. X d l y s d lifu
Bang phan mem thdng kf SPSS phien ban 20. Cie biln sd djnh luyng duyc trinh bay bang gia trj trung binh va dp lech ehuan neu dd kifn eiia bien thupc phan phdi ehuan, hogc bang gii tri trung vj v i khoang t d phin vj nlu phan phdi eiia bien khdng ehuan. Cic bien sd djnh ti'nh duyc md ta bang tan sdvi ty If phan tram. So sinh gii trj trung blnh bang kilm dinh tham sd Independent samples t va gia tri trung vj bang kiem djnh phi tham sd Mann-Whitney ddi vdi cac bien sd djnh luyng. So sanh ty If phin tram cho cic biln sd djnh ti'nh bang kilm djnh Chi binh phuang.
Tat ea eic gii tri xac suat duyc phan ti'ch bang kiem dinh hai chieu va duye xem la ed y nghTa thfing ke khi p < 0,05.
211
Tgp chiYDugc bqc • Tru&ng Dgi hqc YDugc Hai- Tgp 6, si 3 - thing 7/2016 3. KET QUA NGHIEN CU'U
3.1. IMT dyng mgeh cinh chung va m§t sd yeu tfi nguy cff
Bing 3.1. Lifn quan b l diy Idp npi trung mge dfing mach canh vdi mpt sdyiu tfi nguy co
Yeutd Tuoi (nam) Huyet ap tam thu (mmHg) HCit thudc la Uong ru'g'u Glucose mau (mmol/l) BMI (kg/m")
Cholesterol toan phan (mmol/l) LDL-C (mmol/l) HDL-C (mmol/l) Triglycerid (mmol/l) LP-PLA2 (lU/ml)
IMT binh thir&ng
< 0,9 mm (n = 8) 56(49,25-72,00) 145 (130,00-182,50)
7 (87,5%) 5 (62,5%) 5,35(4,98-5,50) 22,05(21,09-22,70)
4,69(4,03-5,29) 2,59(1,85-2,69) 1,12(0,71-1,49) 2,50(1,59-3,58) 14,35(9,87-20,96)
IMT day
>0,gmm[n = 2g}
66(58,50-76,00) 150 (120,00-175,00)
14 (48,3%) 5 (17,2%) 5,80(5,10-7,15) 21,77(19,77-22,86)
5,24(4,52-5,62) 3,07(2,47-3,59) 1,21(1,05-1,43) 2,35(1,35-2,85) 27,73(21,55-38,09)
P
>0,05
>0,05
>0,05
<0,05
>0,05
>0,05
>0,05
<0,05
>0,05
>0,05
<0,05 Nhqn xet: Cd sy khae bift y nghTa ve tinh trgng sd dyng ruyu, ve gii trj trung vj ndng dp LDL-C va n&ng dp Lp-PLA2 huyft thanh gida hai nhdm IMT (p < 0,05),
Bing 3.2. Hdi quy tuyen ti'nh da biln be day Idp npi trung mgc dpng mgch cinh vdi mdt sfi yeu td lifn quan
Bien sd Hang sd Tudi Huyet ap tam thu HOt thudc la Udng tutQu Glucose mau BMI
Cholesterol to^n phBn LOL-C HDL-C Triglycerid hs-CRP LP-PLA2
H|sd hdi quy B
3,552 0,007 -0,006 -0,064 -0,737 -0,103 -0,007 -1,252 0,000 1,231 0,468 0,008 0,050
H#sdchu^nhda beta 0,075 -0,139 -0,026 -0,270 -0,180 -0,011 -1,552 0,000 1,448 0,586 0,097 0,727
P 0,174 0,653 0,305 0,878 0,110 0,235 0,941 0,002 0,002 0,998 0,017 0,488
< 0,001
Khoang tin cly 95% ciia B -1,685-8,789 -0,026-0,041 -0,017-0,005 -0,913-0,785 -1,655-0,181 -0,278-0,072 -0,192-0,179 -1,993--0,511 -0,329-0,328 0,479 -1,983 0,091-0,846
•0,015-0,031 0,030-0,071 Nh4in xet: Nhgn thay cholesterol toan phan, LDL-C, triglycerid va Lp-PLA2 la cac yeu tfi ed kha nang dy bao nhdng thay ddi kich thudc be day Idp nfii trung mgc cd 9 nghTa thdng kf vdi p < 0,05.
3.2. Lifn quan gida Lp-PLA2 huyit thanh v i IMT dpng mgch cinh chung
Bing 3.3. Lifn quan ndng dfi Lp-PLA2 huyft thanh vdi be day ldp npi trung mgc dpng mgch canh Gia trj IMT
(mm) X+SD Logarit hda
Trung vj Khoangtdphin vj
Lp-PLA2 binh thudng £ 21,29 lU/ml | Lp-PLA2 tang > 21,29 lU/ml (n = 13) (n = 24) 1,49 ±1,23 2,19 ±1,18 0,07 ± 0,29 0,28 ± 0,25
0,90 2,00 0,70-1,70 1 1,30-2,88
P
>0,05
<0,05
<0,05
I 22 IOURNAL OF MEDICINE At
Tqp chi Y Duqc hqc - Tnt&ng Bgi hgc Y Dugc Hui- Tqp 6, so 3 - thdng 7/2016
Nh^n xet: Gia trj trung binh cung nhu trung vj b l day Idp npi trung mge d nhdm cd ndng dp Lp-PLA2 tang la cao hon so vdi nhdm ndng dp Lp-PLA2 binh thudng. Sy khac bift cd y nghTa thdng kf (p < 0,05).
Bilu dd 3.1. Tuong quan ndng dp Lp-PLA2 huyit thanh vdi be day Idp npi trung mac
dpng maeh canh
Nhqn xet: Cd mdi tuyng quan thugn mdc dd vira giijB ndng dfi Lp-PLA2 huylt thanh vdi be day Idp ndi trung mgc dpng mgch cinh chung (hf sd tuong quan r = 0,47) va mdi tuong quan ed y nghTa thdng kf (p < 0,05).
4. BAN LUAN
4.1. IMT dpng mgch cinh chung v i mdt sfi y l u t d nguy Cff
Dfing mach canh chung la dpng mgeh ndng vdi khau kinh trung binh Idn l i noi dien ra cae bfnh IV xo vaa dpng mgch va la noi de thim dd v i phat hifn cac chi diem ciia xo vda dpng mgch. Vi vgy sieu i m dpng mgch canh ngay nay cang duye sd dyng rpng rai de danh gia miit: dd ngng ciia ton thuong thanh ddng mgch.
Nhilu nghifn cdu da chdng minh mdi lifn quan gida cac y l u td khac nhau cua xa vda dpng mgch vdi be diy Idp nfii trung mgc. Sy gia tang b l diy Idp npi trung mge dpng mach cinh chung la thude do cd gii tri ldn trong vifc dy phdng bfnh 1^ mgch vanh va mgch nio trong tuang Ial [8], [15].
Bang 3.1. Chung tdi thyc hifn sieu am dpng mgeh canh t r f n 37 bfnh nhan nhdi m i u nao, nhdm ed be day Idp ndi trung mge day cd dp tudi trungvj ldn han nhdm cd be diy Idp nfii trung mgc binh thudng (66 tufii so vdl 56 tudi). Chiing tdi ghi nhgn k i t qua: gia trj trung vj ciia cholesterol LDL d nhdm be day Idp npi trung mgc diy cao han d nhdm b l day Idp ndi trung mac binh thudng (3,07 mmol/l so vdi 2,59 mmol/l, khac bift ed y nghTa
thdng ke; p < 0,05). Dllu nay eho thiy ndng dfi cholesterol LDL m i u l i mpt trong nhCi'ng yeu t d gay xo vD-a dpng mgeh.
Nghifn edu ciia Tram Lyi Tram Tifn v i cdng sy (2012), khao sit be diy Idp npi trung mge dpng mgeh canh trfn 40 bfnh nhan nhdi mau nao ed DTD va 50 bfnh nhan nhdl m i u nao khfing ed OTO cOng cd nhgn djnh be diy Idp nfii trung mgc trung binh ciia dpng mgch canh b nhdm nhdi miu nio cd OTD day hon nhdm nhdi miu nao khdng OTO (1,05
± 0,26 mm so vdi 0,81 ± 0,19 mm; p < 0,05) [3].
Nghifn cdu ciia Rosvall M. va cs (2005) tren 86 bfnh nhin dpt quy nao {trong do cd 66 bfnh nhan nhdi miu nao) thl be day Idp ndi trung mac trung binh la 0,814 mm [14]. Theo J. Chlumsky v i Charvast J. (2005) tren 45 bfnh nhan nhfii m i u nao khdng ed rung nhT th1 b l diy Idp nfii trung mgc trung binh l i 0,79 ± 0,10 mm [4].
ChOng tdi cd kit qua be day Idp ndi trung mgc trung binh cao hon, vi trong nghien cdu eua chung tdi ddi tuyng bj nhdi miu nao ed dp tudi trung blnh cao hon v i ti'eh hyp nhieu yeu td nguy co nhu: tang huylt ap, tang glucose mau, Lp-PLA2.
Be day Idp npi trung mgc dyng mgeh eanh da ehdng minh la mpt yeu td du bao sdm ti'en trinh xo vda dpng maeh va cung l i yeu td dye lap dy bao nguy CO cac bien cd tim maeh ndi ehung va nhdi miu nao ndi rifng [5], [15].
4.2. Lifn quan giQ'a Lp-PLA2 huylt thanh va IMT dpng m^ch canh chung
Be day Idp ndi trung mgc ciia dpng mgeh cinh chung khao sat trfn sieu am kieu B l i mpt chisd giup dinh gia tfin thuang xo vda ddng mgeh giai dogn sdm. Ngiy nay cd rat nhilu nghien cdu trfn the gidi da ghi nhgn mdi lien quan gida b l diy Idp nfii trung mac dpng mgch eanh ehung vdi ehi dilm vifm nhu hs-CRP thdng qua mdi lifn hf gida viem va xo vda dyng mgch, nhung vdi Lp-PLA2 chi diem viem dge hieu mgeh mau thi nghien cdu con it.
Nghien cdu eua ehung tdi ghi nhgn ndng dfi Lp- PLA2 huylt thanh trung vj d nhdm be day Idp npi trung mge diy eao hon nhdm b l diy Idp npi trung mac binh thudng (27,73 lU/ml so vdi 14,35 lU/ml, khae bift cd ^ nghTa thfing kf p < 0,05).
Gia tri trung blnh eijng nhU trung vi b l day Idp npi trung mgc d nhdm ed ndng dp Lp-PLA2 tang cao han so vdi nhdm ndng dp Lp-PLA2 blnh thudng (2,00 mm so vdi 0,9 mm; p < 0,05). Cd mdi tuong quan thugn mde dp vda gida nong dp Lp-PLA2 huylt thanh vdi be day Idp npi trung mgc dyng mgch canh chung (r = 0,47; p < 0,05).
IOURNAL OF MEDICINE A( 23|
Tap chi Y Duvc hqc - Tru&ng Dgi hqc Y Duvc Hue- Tqp 6, si 3 - thdng 7/2016
Bang 3.2. Phan t i c h h&i q u y t u y i n t i n h da b l l n be day I d p n p i t r u n g mgc d p n g m a c h c a n h v d l m f i t so y l u t d l i f n q u a n , c h u n g t d i n h g n t h i y : cholesterol t o a n p h a n , cholesterol LDL, triglycerid v i Lp-PLA2 l i c i e y l u t f i cd kha n i n g d y b i o n h d n g t h a y d d i kieh t h u d c be d i y l d p npi t r u n g mac (p < 0,05).
Persson M. va es (2008) nghien edu 6.103 dfii t u y n g (60% la ni?) t u d i t d 4 6 den 69 (trung binh 58 tufii). Tat ea cac dfii t u y n g d u y e t h y c h i f n sieu a m dfing maeh canh ehung phai k i f u B va djnh l u y n g Lp- PLA2. K i t q u i be d i y ldp npi t r u n g mac d d n g mach canh d hai gidi gia t i n g cd y: nghTa ciling v d i s u gia t a n g nong d f i Lp-PLA2 huyet t h a n h [11].
Levi v i cs (2007) ghi n h g n n d n g d p Lp-PLA2 v i lyso-PC t u o n g q u a n v d i suy c h d c nang npi mgc, n d n g d p Lp-PLA2 cao h o n d n h d m b f n h nhan x o v d a mgeh vanh s d m so v d i n h d m c h d n g k h d e m g n h [ 1 0 ] . Jing Liu va es (2014) n g h i f n c d u 913 b f n h nhan t u d i t d 4 5 d i n 7 4 , cho k i t i u f n : nfing d f i Lp-PLA2 cd lien q u a n v d i v d a x o d f i n g m g c h c i n h . Lp-PLA2 d d n g
vai t r d q u a n t r p n g t r o n g b f n h sinh x y v d a dpng m a c h va la m y c tifu tiem n a n g d i f u trj d l ngan ngda s d m b f n h ti'm m g c h [ 9 ] .
N g h i f n c d u eua c h u n g t d i eho t h a y : Lp-PLA2 h u y e t t h a n h cd •i nghTa giai t h i c h s y t h a y d d i be day Idp nfii t r u n g mgc (p < 0,001). N h u vgy, n d n g d f Lp-PLA2 h u y f t t h a n h l i y l u t d d p c lgp t h y c s y ed </
nghTa t r o n g v i f e d u bao n h d n g t h a y d o i kich t h u d e b l day Idp n p i t r u n g mgc eiia d p n g m a c h canh.
N h i f u nghien c d u n u d c n g o i i d e nghj s d dyng sieu i m d d n g mgeh c a n h va d j n h l u y n g ndng d p Lp- PLA2 h u y l t t h a n h d e p h a t h i f n s d m v i d i f u trj xo v d a d f i n g mgeh d l n g i n n g d a b l l n cfi d p t quy nao v i nhfii m a u c o t i m [ 7 ] , [ 1 3 ] , [ 1 5 ] .
S. KET LUAN
N d n g d f Lp-PLA2 h u y e t t h a n h cao cd m d i l i f n q u a n y nghTa v d i be d i y Idp nfii t r u n g mge dpng maeh canh d b f n h n h a n n h d i m i u nao. Chi d i l m sinh hpc v i f m nay ed t h e g d p p h a n t r o n g d y b i o xo v d a d f i n g maeh.
TAI UEU T H A M KHAO 1. Nguyen Van Bang (200S), "Tai bien thieu mau cyc bp nao", Tai bien mgch mau nao, NXB Y hpc, tr.76 - 1 1 3 .
2. Hoang Khanh (2013), "Thieu m i u cyc bd n i o hinh thanh". Than kinh hpc, NX8 Ogi hpc Huf, tr. 241 - 254.
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