1.Comparison of the effect of three β-thalassemia prenatal screening strategies using in Guangdong province
Bing LI ; Aihua YIN ; Mingyong LUO ; Li WU ; Yuanzhu MA ; Xionghu WANG ; Xiaozhuang ZHANG ; Qingguo ZHAO
Chinese Journal of Obstetrics and Gynecology 2015;(6):434-440
Objective To compare the effect of three β-thalassemia prenatal screening strategies in Guangdong province. Methods A total of 13 284 hospital-delivered couples and 13 369 newborns were recruited from 91 hospitals in 21 counties or districts of Guangdong province from June to December 2012. Mean cell volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin A2 (Hb A2) were tested for all the couples, and all the couples and newborns were detected by 17 types ofβ-globin gene mutations. The effect of three β-thalassemia prenatal screening strategies were compared as following:(1) MCV/MCH with Hb A2 serial screening(SS):Hb A2 was tested if the woman′s MCV<82 fl and(or)MCH<27 pg. If the woman′s Hb A2>3.5, it meant positive. And if the woman wasβ-thalassemia carrier and her husband′s Hb A2>3.5, it meant couple positive. (2) MCV/MCH with Hb A2 parallel screening(PS):if the woman′s MCV<82 fl and (or) MCH<27 pg and(or) Hb A2>3.5 pg, it meant couple positive. And the husband would be tested forβ-globin gene mutations if the woman was β-thalassemia carrier. (3) MCV/MCH with Hb A2 serial screening for couples(SSC):if one of the couple or both of them had MCV<82 fl and(or) MCH<27 pg, the couple would be tested for Hb A2, and if one of the couple got Hb A2>3.5, it meant couple positive. Results (1) For the SS strategy, the sensitivity was 92.69%(583/629);the specificity was 99.87%(12 638/12 655); the positive predictive value was 97.17%(583/600);and the negative predictive value was 99.64%(12 638/12 684). The results ofβ-globin gene mutations tested showed that the rate ofβ-thalassemia carriers was 4.74%(629/13 284) in the 13 284 pregnant women, and it was 4.29%(570/13 284) in their husbands. (2) The SS strategy detected 27 (0.20%,27/13 284) β-thalassemia carrier couples. For the SS strategy detecting β-thalassemia carrier couples, the missed diagnosis rate was 11.11%(3/27);the sensitivity was 88.89%(24/27);the specificity was 100.00%(27/27); the positive predictive value was 100.00%(24/24); and the negative predictive value was 99.98%(13 257/13 260). (3) When using the SS strategy for 13 369 offsprings, there were 582β-thalassemia carriers (4.35%,582/13 369), including 578 (99.31%,578/582) minorβ-thalassemia, 3 (0.52%,3/582) intermediaβ-thalassemia and 1 (0.17%,1/582) major β-thalassemia. The SS strategy detected 25 fetuses who neededβ-thalassemia prenatal diagnosis. (4) For the PS strategy, the sensitivity was 98.09%(617/629); the specificity was 88.73%(11 229/12 655); the positive predictive value was 30.20%(617/2 043); and the negative predictive value was 99.89%(11 229/11 241). (5) When using the PS strategy for theβ-thalassemia carrier couples, the sensitivity was 100.00%(27/27);the specificity was 95.55%(12 667/13 257);the positive predictive value was 4.38%(27/617);and the negative predictive value was 100.0%(12 667/12 667). (6) The PS strategy detected 28 fetuses who needed β-thalassemia prenatal diagnosis in 13 369 offsprings. (7) For the SSC strategy, the sensitivity was 93.80%(590/629); the specificity was 95.75%(12 117/12 655); the positive predictive value was 52.30%(590/1 128); and the negative predictive value was 99.68%(12 117/12 156). When the SSC strategy was used for the husbands, the sensitivity was 92.28%(526/570); the specificity was 95.27%(12 112/12 714);the positive predictive value was 46.63%(526/1 128); and the negative predictive value was 99.64%(12 112/12 156). (8) When the SSC strategy was used inβ-thalassemia carrier couples, the sensitivity was 100.00%(27/27);the specificity was 91.69%(12 156/13 257);the positive predictive value was 2.39%(27/1 128);and the negative predictive value was 100.00%(12 156/12 156). (9) The SSC strategy detected 28 fetuses who neededβ-thalassemia prenatal diagnosis. Conclusions All the three β-thalassemia prenatal screening strategies had good effect in clinical practice and public health. While in the high-prone area of β-thalassemia, MCV/MCH with Hb A2 parallel screening and MCV/MCH with Hb A2 serial screening for couples stratigies were better.
2.Comparison of three different α-thalassemia prenatal screening strategies used in Guangdong, China
Bing LI ; Aihua YIN ; Mingyong LUO ; Li WU ; Yuanzhu MA ; Xionghu WANG ; Xiaozhuang ZHANG ; Qingguo ZHAO
Chinese Journal of Perinatal Medicine 2015;(7):521-526
Objective To compare the effect and cost of three different α-thalassemia prenatal screening strategies used in Guangdong, China, and to provide evidence for α-thalassemia prevention. Methods In total, 13 284 hospital-delivery couples and 13 369 newborns/fetuses (offspring) from 21 counties or districts of Guangdong Province were included in this study, who were treated from June to December 2012. Mean cell volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin A2 (Hb A2) were detected in the couples, and 6 types ofα-globin gene mutations were found in all couples and newborns. The strategies were MCV/MCH and serum Hb A2 (protocolⅠ) or parallel screening based on pregnant women (protocolⅡ), and serum screening based on couples (protocolⅢ). The validity and reliability of the three strategies were then compared using the Chi-square test. Results The sensitivity and the specificity of pregnant women who wereα-thalassemia carriers in protocolⅠwere 74.82%(1 352/1 807) and 74.11%(8 506/11 477), and were 89.82%(1 623/1 807) and 48.60%(5 578/11 477) in protocol Ⅱ , respectively. And 1.67% (221/13 284) couples were bothα-thalassemia carriers by the gene test. The rate of missed diagnosis in bothα-thalassemia carrier couples in protocolsⅠ,ⅡandⅢwas 50.68%(112/221), 11.76%(26/221) and 11.31%(25/221), respectively. In couples who needed prenatal diagnosis, the rates of missed diagnosis, sensitivity, specificity, positive predictive value, and negative predictive value were 17.46%(11/63), 82.54%(52/63),98.35%(13 003/13 221), 19.26%(52/270) and 99.92%(13 003/13 014) in protocolⅠ;4.76%(3/63), 95.24%(60/63), 88.18%(11 658/13 221), 3.70%(60/1 623) and 99.97%(11 658/11 661) in protocolⅡ;and 3.17%(2/63), 96.83%(61/63), 59.31%(7 842/13 221), 1.12%(61/5 440) and 99.97%(7 842/7 844) in protocol Ⅲ , respectively. The diagnosis of severeα-thalassemia was not missed in all three screening strategies. The mean cost of protocols Ⅰ, Ⅱ and Ⅲ for detecting a couple who needed prenatal diagnosis was 37 049.23, 50 836.00 and 40 321.64 RMB, respectively. Conclusions The three screening protocols have good efficiency in screening forα-thalassemia. However, protocolsⅡandⅢare preferred when financial conditions permit.
3.Investigation of the effect of frozen recombinant staphylokinase on the hemostatic and fibrinolytic systems in healthy volunteers
Hua LU ; Ruilan SHENG ; Wei XU ; Jianfu ZHANG ; Yujie WU ; Fengxiang LU ; Yuanzhu HUANG ; Di XU ; Chun CHEN ; Yanhui SHENG ; Xiaotao WANG
Chinese Pharmacological Bulletin 2001;17(1):47-50
AIM To investigate the effect of frozen recombinant staphylokinase on the hemostatic and fibrinolytic systems in healthy volunteers, in order to obtain reliable evidence for the possibility of further clinical application. METHOD r-Sak had been taken intravenously by 20 cases of healthy volunteers in different dosages (1 mg, 2.5 mg, 5 mg, 10 mg, 15 mg). The clinical hemorrhagic manifestations were observed and a set of hemostatic tests(BT, BPC, ATPP, PT, TT, Fg) and fibrinolytic tests (PL∶A,α2-PI∶A, FDP, D-D) monitored before and after injection. RESULT Four of 20 volunteers showed slight hemorrhagic tendency on mucocutaneous area (3/4 from gingivea and 2/4 at the sites of injection). It stopped spontaneously. None of them showed visceral bleeding. There were no significant changes in hemorrhagic and coagulative phases. Only 4 of them showed slight abnormal changes in D-D. It was supported that r-Sak was a highly selective fibrirolytic agent without significant influence in human hemostatic and coagulatic system. CONCLUSION The specific ranges of doseges, r-Sak is a relatively safe and well tolerated agent for healthy people. Further clinical study is still needed for the suitable dosage for clinical application.
4.Effect of resveratrol on platelet aggregation in vivo and in vitro.
Zhirong WANG ; Jiangang ZOU ; Yuanzhu HUANG ; Kejiang CAO ; Yinan XU ; Joseph M WU
Chinese Medical Journal 2002;115(3):378-380
OBJECTIVELow or moderate consumption of red wine has a greater benefit than the consumption of other beverages in the prevention of atherosclerosis and coronary heart disease and this is increasingly attributed to the polyphenol compounds in red wine, such as resveratrol. In the present study, we investigated the effect of resveratrol on platelet aggregation in vitro and in vivo.
METHODSPlatelet aggregation in rabbits and normal subjects was measured using Born's method.
RESULTSResveratrol, at 10 - 1000 micromol/L, significantly inhibited platelet aggregation in vitro induced by collagen, thrombin, and ADP in healthy subjects. The inhibitory effect was concentration-dependent. Hypercholesterolemia induced by high-cholesterol diet enhanced ADP-induced platelet aggregation. Resveratrol 4 mg x kg(-1) x d(-1) inhibited ADP-induced platelet aggregation in vivo despite no changes in serum lipid levels.
CONCLUSIONSResveratrol inhibits platelet aggregation both in vitro and in vivo. This may be one of the mechanisms by which resveratrol prevents atherosclerosis.
Animals ; Arteriosclerosis ; prevention & control ; Cholesterol, LDL ; blood ; Humans ; Lipids ; blood ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; pharmacology ; Rabbits ; Stilbenes ; pharmacology
5. Distribution of CYP2C9∗3 and VKORC1-1639G>A gene polymorphism in Anhui Han population and their influence on the stable dose of warfarin
Yuanzhu WU ; Jun LIU ; Kui YANG ; Jing PENG ; Jiajie LUAN ; Jun LIU ; Kui YANG ; Jing PENG ; Jiajie LUAN ; Jun WEI ; Dafa ZHANG ; Shuai SONG ; Xiaolong YUAN ; Zhongfang WANG ; Nianbao ZHANG ; Dan XIE ; Peng JIANG ; Jie FAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(6):652-659
AIM: To study the distribution of CYP2C9∗3 and VKORC1-1639G>A gene polymorphism in Han population in Anhui province and their influence on the stable dose of warfarin. METHODS: The blood samples of 1 169 patients from 6 tertiary general hospitals in 5 areas of Anhui province from January 2020 to December 2021 were selected, the genotype of CYP2C9∗3 and VKORC1-1639G>A was detected by fluorescent staining in situ hybridization technique. RESULTS: The distribution of CYP2C9∗3 genotypes in 1 169 patients: the frequencies of AA, AC and CC genes were 90.16%, 9.24% and 0.60%, respectively; The distribution of VKORC1 genotype: the frequencies of AA, AG and GG genes were 84.26%, 14.71% and 1.03% respectively; There was no significant difference between the two genotypes in gender, age and regional distribution (P>0.05). The average daily warfarin dose of CYP2C9∗3 AA genotype in 755 patients with stable warfarin dose was (3.02±0.59) mg/d, which was significantly higher than patients with AC genotype and CC genotype; The average daily warfarin dose of patients with VKORC1-1639AA genotype was (2.72±0.40) mg/d, which was significantly lower than that of patients with AG genotype and GG genotype (P<0.05). And the difference was statistically significant (P<0.05); There are significant differences in gender, age and clinical diagnosis between patients with stable dose of warfarin and those without stable dose (P<0.05). CONCLUSION: CYP2C9 and VKORC1 genotypes are associated with the stable dose of warfarin. Clinical anticoagulation therapy guided by CYP2C9 and VKORC1 genotypes can provide guidance for individualized medication of warfarin.