• The Journal of Korean Medicine
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• v.34 no.1
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• pp.116-135
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• 2013

Objectives: This study was intended to clarify how Jakyakkamchobuja-tang (hereinafter referred to JKBT) affects mice of C57BL/10 whose osteoarthritis was induced by papain. Methods: Osteoarthritis was induced in mice by injecting papain in the knee joint. Mice were divided into 4 groups (n=6). The normal group were not treated at all whereas the control group (OAC-control) were induced for osteoarthritis by papain and oral medicated with 200 ul of physiological saline per day. The positive comparison group (OAC-$Joins^{(R)}$) were injected with papain and after 7 days, 100 mg/kg of $Joins^{(R)}$ were medicated with 200 ul of physiological saline mixed. The experimental group (OAC-JKBT) were injected with papain and after 7 days were medicated with 400 mg/kg of JKBT mixed with 200 ul of physiological saline. OAC-$Joins^{(R)}$ and OAC-JKBT were oral medicated for each substance for a total of 4 weeks, once per day. After experiments (from 1 week after injection of papain to 4 weeks elapsed), the function of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological variations for knee joint structures were observed. Results: Functions of liver and kidney were not affected. IL-$1{\beta}$ (interleukin-$1{\beta}$), MCP-1 (monocyte chemoattractant protein-1) and TNF-${\alpha}$ (tumor necrosis factor-${\alpha}$) were significantly reduced and IL-6 (interleukin-6) was also reduced but not significantly. After analyzing inflammation cytokine in joints with mRNA (messenger ribonucleic acid), revelation of IL-6, TNF-${\alpha}$, COX-2 (cyclooxygenase-2) and iNOS-II (inducible nitric oxide synthase-II) were all significantly reduced. Revelation of IL-$1{\beta}$ gene was also reduced but not significantly. Neutrophil for WBC (white blood cell) within serum was significantly reduced; monocyte was also reduced but not significantly. PGE2 (prostaglandin E2), TXB2 (thromboxane B2) were significantly reduced and LTB4 (leukotriene B4) was also reduced but not significantly. Destruction of cartilage on micro CT (computed tomography)-arthrography was reduced but had no significant differences. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small (H&E (hematoxylin and eosin), safranine O staining). Conclusions: Based on these results, Jakyakkamchobuja-tang (JKBT) is believed to be useful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.

• Journal of Nutrition and Health
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• v.35 no.1
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• pp.5-14
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• 2002

Alteration in the syntesis or enhanced inactivation of nitric oxide(NO) can induce impairment of endothelial cell function. Insulin dependent diabetes mellitus(IDDM) is characterized by impaired endothelial function and vascular disease. NO is produced through L-arginine pathway To elucidate the hypothesis that the decreased production on NO in IDDM reflects vascular damage and the NO production can be manipulated by either dietary fat(7% of kg diet) or the oral supplementation with L-arginine(2g/kg bw), plasma markers for vascular endothelial damage and plasma lipid profiles were measured in streptozotocin(STZ)-induced diabetic rats. Diabetic or normal Sprague-Dawley rats were fed 6 different experimental diets for 4 weeks(SO : soybean oil, SOA: soybean oil + L-arginine supplementation, BT : beef tallow, BTA_ beef tallow + L-arginine supplementation, OV olive oil, OVA : olive oil + L-arginine supplementation). Plasma glucose, total cholesterel, HDL-cholesterol, LDL-cholesterol and triglyceride were measured. Endothelial markers, plasma von Willebrand factor(vWf), thromboxane B$_2$, and 6-keto PGF1$\alpha$ of aorta were measured by ELISA. Plasma NO production was evaluated through the measurement of nitrite by EIA. Feeding saturated fatty acid(SFA, BT) increased relative liver size(RLS) in diabetic rats compared to either polyunsatunted fatty acid(PUFA, SO) or monounsaturated fatty acid(MUFA, OV) The supplementation of L-arginine inhibited the liver and kidney enlargement in olive oil find diabetic rats. Plasma glucose was lower in diabetic animal find the olive oil compared to fed beef tallow and the supplementation L-arginine decreased it in diabetic rats find beef tallow significantly(p < 0.05). Plasma TXB$_2$ levels were increased due to diabetes and the value of beef tallow group showed highest value. Plasma vWf concentration of beef tallow group was higher value in normal rats and was elevated more in diabetes. In diabetic groups, the vWf concentration of olive oil group was lower than beef tallow or soybean oil group. The supplementation of L-arginine in diabetic rats decreased plasma TXB$_2$ and vWf levels significantly(p < 0.05). NO production was higher in normal olive oil fed rats and was tend to be decreased in diabetic rats and the supplementation of L-arginine recovered to normal value(p < 0.05), Olive oil supplemented with L-arginine tended to lower plasma total cholesterol and LDL-cholesterol after 4 week treatment. These results suggest that generalized vascular endothelial changes based on plasma TXB$_2$and vWf occurs in diabetic rats. and olive oil with L-arginine supplementation contributes to a better control of the hyperglycemia, endothelial changes and hypercholesterolemia accompanying diabetes as compared with beef tallow or soy bean oil in this rat model.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.39-49
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• 1996

In the present study, we observed change in intracellular $Ca^{2+}$$([Ca^{2+}]_i)$ as measured with the fluorescent $Ca^{2+}-indicator$ fura-2 in association with force development of the rat basilar arteries during activation by$K^+$ depolarizing solution and U46619, a thromboxane analogue, in the absence and the presence of calcitonin-gent related peptide (CGRP). CGRP (30 and 100 nM) caused a concentration-dependent inhibition of U46619-induced contraction with decrease in $[Ca^{2+}]_i$, whereas it did not exert any effect on the $K^+$ (90 mM)-induced contraction and increase in $[Ca^{2+}]_i$, Further, $[Ca^{2+}]_i-force$ relationships were determined by plotting the ratio of $F_{340}/F_{380}$ $([Ca^{2+}]_i)$ as a function of the force induced by U46619, and the results were compared with those obtained in the presence of CGRP. The curves obtained in the presence of CGRP (30 and 100 nM) were significantly moved to downward without right shift of the curves suggesting that CGRP inhibited the U46619-induced contraction only by mediation of reduction in $[Ca^{2+}]_i$ with out any change in the sensitivity of contractile apparatus to $Ca^{2+}$. The CGRP-induced attenuation of $[Ca^{2+}]_i$ and force development was significantly inhibited under pretreatment with CGRP $(8{\sim}37)$ fragment (100 nM), a CGRP1 receptor antagonist. Both the reduced contraction and reduction in $[Ca^{2+}]_i$ caused by CGRP were fully reversed by pretreatment with charybdotoxin (100 nM) and iberiotoxin (100 nM), large conductance $Ca^{2+}-activated$ $K^+$ channel blockers, but not by apamin (300 nM), a small conductance $Ca^{2+}-activated$ $K^+$ channel blocker, and glibenclamide ( 1 ${\mu}M$), an ATP-sensitive $K^+$ channel blocker. In conclusion, it is suggested that the CGRP1 receptor, upon activation by CGRP, are coupled to opening of $Ca^{2+}-activated$ $K^+$ channel and cause to decrease in $[Ca^{2+}]_i$, thereby leading to vasodilation of the rat basilar artery. However, it is not defined that the mechanism underlying vasodilation whether the $K^+$ channel blockers, charybdotoxin and iberiotoxin directly block the CGRP receptors and that CGRP-evoked relaxation is dependent on the cyclic AMP or $K^+$ channel opening or both actions.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.7
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• pp.936-942
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• 2012

In the present study, the effects of green tea catechin on microsomal phospholipase $A_2$ ($PLA_2$) activity and the arachidonic acid (AA) cascade in the lungs of microwave exposed rats were investigated. One Sprague-Dawley male rats weighting $100{\pm}10$ g was randomly assigned to the normal group and three were assigned to the microwave exposed groups. The microwave exposed groups were subdivided into three groups according to the levels of dietary catechin supplementation: catechin free diet (MW) group, 0.25% catechin (MW-0.25C) group and 0.5% catechin (MW-0.5C) group. Rats were sacrificed on the 6th day after microwave irradiation (2.45 GHz, 15 min). The lung microsomal $PLA_2$ activity in the MW and MW-0.25C groups was 30% and 15% greater than that of the normal group, respectively, whereas no significant difference between the normal group and MW-0.5C group was observed. The percentage of phosphatidylethanolamine (PE) hydrolyzed in the lung microsome in the MW, MW-0.25C and MW-0.5C group increased by 47%, 18% and 20%, respectively, due to microwave irradiation. The formation of thromboxane $A_2$ ($TXA_2$) in the lung microsome was 50% greater in the MW group than in the normal group. However, the levels of $TXA_2$ in the MW-0.25C and MW-0.5C group were normal. The formation of prostacyclin ($PGI_2$) in the lung microsome was 31% lower in the MW group than in the normal group, while the levels of $PGI_2$ in the MW-0.25C and MW-0.5C group were similar to the normal group. The lung microsomal thiobarbituric acid reactive substances (TBARS) concentration, which can be used as an index of lipid peroxide was 34% greater in the MW group, when compared with the normal group. However, there was no difference between the MW-0.25C, MW-0.5C and normal groups. In conclusion, lung function appeared to be improved by green tea catechin supplementation due to its antithrombus action, which in turn controls the AA cascade system.

• Proceedings of the Ginseng society Conference
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• 1988.08a
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• pp.77-80
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• 1988

The effects of ginseng saponins and some phenolic acids on the in vitro biosynthesis of prostaglandins was examined in order to identify the role of some ginseng components on the regulaion of arachidonic acid metabolism. The productions of prostaglandin $E_2(PGE_2).$ prostaglandin $F_2{\alpha}(PGF_2{\alpha}).$ thromboxane $B_2(TxB_2)$ and 6-keto-prostaglandin $F_1{\alpha}(6-keto-PGF_1{\alpha})$ from $[^3H]-arachidonic$ acid were evaluated with rabbit kidney microsome. human platelet homogenate and bovine aortic microsome. The amounts of the total cyclooxy-genase products from arachidonic acid did't show significant changes in the presence of ginseng saponins. Panaxadiol. panaxatriol and all of the ginsenosides used in these experiments reduced the formation of $TxB_2.$ while increased the $6-keto-PGF_1{\alpha}$ production dose dependently. Ginseng saponins did't inhibit the ADP($10{\mu}M$) induced platelet aggregation. but sodium arachidonate (0.5 mM) induced platelet aggregation. but sodium arachidonate (0.5 mM) induced platelet aggregation was signiticantly inhibited. These findings suggest that ginseng saponins seem to playa role in the regulation of the arachidonate metabolism. probably by affecting the divergent biosynthetic pathway of prostaglandins from endoperoxide.

• Journal of Chest Surgery
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• v.32 no.10
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• pp.863-873
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• 1999

배경: 혈전 생성은 심혈관계 삽입물이나 순환 보조장치의 발전에 있어서 중요한 문제이므로 이러한 장치들의 혈전성에 대한 평가는 필수적이다. 따라서 이러한 장치들의 혈전성 연구를 시행하기 위한 효과적인 생체 외 실험 방식이 개발되어 원심성 순환 펌프의 발전에 큰 도움이 되고 있으며, 최근 엄밀하게 혈액과 공기의 접촉을 차단하는 방식이 믿을 수 있는 생체 외 실험 방식으로 강조되고 있다. 본 논문에서는 모의 순환 회로를 이용하여 기존에 행해진 연구 방법 상의 공기 접촉에 따른 핼액 응고 기전의 활성화 여부를 알아보기 위하여 공기 접촉 여부에 따른 혈액 인자의 변화를 관찰하여 확인하고, 또한 회로 내에서 생성된 혈전을 생체 내에서 형성된 혈전과 비교 분석하여 이 모의 순환 회로를 이용한 생체 외 검사가 새로 고안된 심혈관계 장치들의 혈전성을 평가하는데 있어서 동물실험을 대신할 수 있다는 기존의 주장을 검증하고자 하였다. 연구재료 및 방법: 바이오펌프를 이용한 같은 모의 순환 회로 한 쌍을 준비하고 동일 개체에서 얻은 헤파린을 첨가한(1u/$m\ell$) 신선한 혈액을 공기와 접촉시키지 않도록 한 A-회로와 공기와 접촉시킨 B-회로에 충전시켜 실험을 동시에 진행하여 결과를 얻었으며 총 12번 시행하였다. 회로에 충전한 혈액의 activated clotting time(ACT)은 정상의 3~5배였으며 ACT가 정상 범위의 1.5배가되면 실험을 끝냈고, Hematocrit(HCT), 혈소판, 동맥혈가스분석(ABGA), factor Ⅷ, factor \ulcorner, 섬유소원, thromboxane B2(TXB2), free hemoglobin(fHb) 등을 측정하였다. 실험이 끝난 후 A-회로와 B-회로에서 얻은 각 검사를 평가하고 분석하였으며 생성된 혈전을 생체 내에서 생성된 혈전과 조직 검사로 비교하였다. 본 연구의 자료분석은 SPSS 통계 프로그램을 이용하였고 유의수준 0.05를 기준으로 유의도를 판단하였다. 결과: 정상 ACT는 186.9$\pm$20.5초(평균$\pm$표준편차)이었고, 헤파린을 넣은 초기 ACT는 982.2$\pm$165.5초이었으며, 실험시간은 보통 60분에서 180분 사이였다. HCT, fHb, 혈소판, TXB2, factor Ⅷ, factor \ulcorner, 섬유원소의 초기값은 35.5$\pm$3.2%, 12.4$\pm$6.5 mg/dL, 354$\pm$56($\times$103)/$\mu$L, 72.6$\pm$15.1 mg/dL, 29.3$\pm$1.2%, 137.9$\pm$42.1 mg/dL, 그리고 17.7$\pm$9.7%이었다. 공기 접촉에 따른 차이를 보았을 때 ACT(p=0.398), HCT(p=0.988), fHb(p=0.898), 혈소판 (p=0.904), TXB2(p=0.985), factor Ⅷ(p=0.872), factor \ulcorner(p=0.489), 섬유원소(p=0.973)으로 전 예에서 통계적 유의성이 없었다. 실험 후 양 군에서 생성된 혈전의 현미경 소견은 B-회로의 혈전에 여러 군데 공기 방울이 관찰되는 것 이외에 A-회로에서 생성된 혈전과 차이가 없었고, 생체에서 생성된 혈전과 비교했을 때 그 양상이 같았다. A-회로와 B-회로에서 생성된 혈전의 총 량은 8.4$\pm$3.7 mL와 9.4$\pm$3.1 mL로 통계상 유의성은 없었다. (p=0.624). 결론: 모의 순환 회로를 이용한 혈전성 평가를 위한 생체 외 실험에 있어서 공기와의 접촉 여부는 혈액 응고 기전의 활성화나 혈전 생성에 별다른 영향을 미치지 않는다. 모의 순환 회로에서 형성된 혈전과 문헌에 있는 인체 내에서 형성된 혈전을 비교한 결과 그 형태가 일치하므로 이 모의 순환회로를 이용한 실험이 동물실험을 대신할 수 있다고 판단된다.

• The Korean Journal of Pharmacology
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• v.25 no.1
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• pp.43-51
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• 1989

Responsiveness of muscarinic and alpha adrenoceptor activation on endothelial cells was studied in isolated canine renal artery rings. Ach (10-100 nM), dose dependently, relaxes endothelial intact rings precontracted with phenylephrine ($IC_{50}$ of Ach was 34.5 nM). Selective mechanical destruction of the endothelium transformed the activity of this substance from vasodilatation to vasoconstriction. Acetylcholine induced relaxations could be selectively inhibited competitively by atropine, but could not be inhibited by cyclooxygenase inhibitor. Methylene blue, however, an inhibitor of soluble guanylate cyclase activity, inhibited Ach as well as sodium nitroprusside (SNP) induced relaxation. Relaxation produced by prostacyclin was not modified by methylene blue. On the other hand, alpha adrenoceptor agonist did not relax but contract canine renal artery rings possessing an intact intima precontracted with U-46619. Clonidine, however, selective alpha-2 adrenergic agonist, is more susceptible than phenylepherine, selective alpha-1 adrenergic agonist, to the inhibitory effect of contraction. These results suggest that in canine renal artery rings, 1) muscarinic receptor is responsible for releasing endothelium dependent relaxation factor (EDRF). 2) alpha-1 and alpha-2 adrenergic receptors are present in canine renal artery. 3) relaxation via EDRF is antagonized by methylene blue, providing further evidence that EDRF acts through a cGMP mechanism.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.369-379
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• 1998

Background: Platelet-activating factor(PAF) might play an important role in the development of acute respiratory distress syndrome. Since PAF induced lung injury is similar to changes of acute respiratory distress gyndrome, and abnormalities in surfactant function have been described in acute respiratory distress syndrome, the authors investigated the effects of PAF on the regulation of surfactant protein A, B and C mRNA accumulation Method: The effects of PAF on gene expression of surfactant protein A, B and C in 24 hours after intratracheal injection of PAF in rats. Surfactant protein A, B and C mRNAs were measured by filter hybridization. Results: The accumulation of SP-A mRNA in PAF treated group was significantly decreased by 37.1 % and 41.6%, respectively compared to the control group and the group treated with Lyso-PAF(p<0.025, p<0.01). The accumulation of SP-B mRNA in PAF treated group was decreased by 18.7% and 32.2 %, respectively compared to the control group and the group treated with Lyso-PAF but statistically not significant. The accumulation of SP-C mRNA in PAF treated group was significantly decreased by 30.7% and 38.5%, respectively compared to the control group and the group treated with Lyso-PAF(p<0.l, p<0.01). Conclusion: These findings represent a marked inhibitory effects of platelet-activating factor on surfactant proteins expression in vivo. This supports, in turn, 'platelet-activating factor might be related to pathogenesis of acute respiratory distress syndrome.

• The Journal of Dong Guk Oriental Medicine
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• v.8 no.2
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• pp.115-129
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• 2000

The cause that the increase of animality fat intakes, under exercise, fatness, adding the stress, advanced age etc., the occurrence rate of the circulation system disease has been increased. And the thrombosis importantly came to the front as the risk factor of these circulation system's disease. Nowadays, the ischemic disease has especially discussed, for example the angina or myocardial infarction, originated in thrombosis that came from the platelet aggregation. In the western medicine, as the cure and prevention, using the aspirin or ticlopidine for platelet aggregation suppressant. But in the , the curing method must be used properly according to the pectoralgia or heartache's kind, state, grade. The platelet do not attache to the normal hemangioendothelial cell. But when it stimulated by endothelium peronia and so on, it attache to the injury endothelium or rise aggregation between the platelet. On this time, it secrete the platelet aggregation inducer as like ADP, thromboxane A2 from the inside of platelet. So it has first defensive function through the aggregation augment that prevent the celerity consumption of blood. But the activation of abnormal platelet occur the platelet grume and thrombogenesis. So it bring up the occlusive angiosis, so to speak, cardiovascular disease, cerebrovascular disease, arterial sclerosis. In oriental medicine, the thrombosis in the category of blood stasis and this blood stasis present the generalise or local blood circulation disturbance that generated by all kinds of pathological fact or blood stream retention accompanying with a series of syndrome. As the syndrome, stabbing pain fixed at certain region, squamous and dry skin, fullness and pain of the chest and hypochondrium, firmness and fullness of the lower abdomen, black stool, dark purple tongue or with ecchymoses and petechiae etc.. has been created. And it becomes the pathopoiesis cause that the convulsion and palpitation, severe palpitatiion, tympanites, the symtom complex with a mass or swelling in the abdomen, insanity, stricken by wind etc.. Moreover, it used the drugs for invigorating blood circulation and eliminating blood stasis or drugs for removing blood stasis for all kinds of syndrome through the blood stasis. And the drugs for activating the blood circulation, such as Salviae Radix, Angelicae Sinensis Radix, Persicae Semen, Achyranthis Radix, Cnidii Rhizoma, Carthami Flos are used for that. And it is used to the herbs of insects that has strong effect about the disintergrating blood stasis such as Hirudo, Scolopendrae Corpus, Buthus, Lumbricus etc.. On this study, It used Geijibokryunghwan(GBH) and the consisting herbs to investigate the influence of platelet aggregation about drugs that used to improvement various symptoms created by the thrombosis in oriental medicine. GBH formula has as formula recorded in the , action of 'eleminating the evil and not impairment of healthy energy' and 'promoting the flow of QI and cold and heat, so used for the expel blood stasis herbs from the ancient. Therefore we investigated the restraint effect of GBH and the consisting herbs about the platelet agregation induced to the ADP, AA or collagen. The conclusion is following. 1. When it added the aggregation inducer after that it added GBH and individual consisting herbs in the PRP, GBH showed the (+) inhibition effect on the platelet aggregation and it showed the (+) inhibition effect in the individual consisting herbs as like Paeoniae Radix and Moutan Cortex Radicis. 2. It showed the (+), (+,++) inhibition effect on the platelet aggregation in Paeoniae Radix Hoelen, Paeoniae Radix Moutan Cortex Radicis, Hoelen Moutan Cortex Radicis etc. 3. In the aggregation inhibition activating on the difference of density, GBH showed strong inhibition effect to the aggregation state induced to collagen, and it showed the inhibition effect in the individual consisting herbs as like Paeoniae Radix and Moutan Cortex Radicis about the aggregation induced by the collagen. 4. It showed the strong inhibition effect about the aggregation induced by the collagen in Paeoniae Radix Hoelen, Paeoniae Radix Moutan Cortex Radicis, Hoelen Moutan Cortex Radicis etc Like this, as confirm GBH and the individual consisting herb's inhibition effect of platelet aggregation, We considerated that GBH and the individual consisting herbs have practical applicational value of clinical trial in the thrombosis caused by platelet aggregation.