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OBJECTIVE： To establish the prediction model of steady-state dose of warfarin in patients with renal insufficiency on the basis of CYP2C9＊3（1075A＞C） and VKORC1-1639G＞A gene polymorphism. METHODS： The clinical data of 103 patients with renal dysfunction （involving primary glomerulonephritis， chronic pyelonephritis， hypertensive renal arteriosclerosis， diabetic nephropathy， secondary glomerulonephritis， tubulointerstitial lesions， hereditary kidney diseases） who took warfarin and whose INR was stable at 1.5-3.0 were collected from nephrology department of the First Affiliated Hospital of Xi’an Jiaotong University during Jun. 2016 to Jun. 2019. The CYP2C9＊3（1075A＞C） and VKORC1-1639G＞A genotypes were detected by fluorescence staining in-situ hybridization. The relationship of genotype， gender， age， body mass index （BMI） and glomerular filtration rate （eGFR） with steady-state dose of warfarin were analyzed. The multiple linear regression method was used to establish the prediction model for steady-state dose of warfarin in patients with renal insufficiency. Other 25 patients were involved in validation. RESULTS： The frequencies of CYP2C9＊3（1075A＞C） and VKORC1-1639G＞A genes in 103 patients were in accordance with Hardy-Weinberg equilibrium. The average steady-state dose （3.20±0.88） mg/d of warfarin in CYP2C9＊3 （1075A＞C） AA genotype was significantly higher than that （2.17±0.13） mg/d in CYP2C9＊3 （1075A＞C） AC genotype （P＜0.05）； average steady-state dose （2.89±0.08） mg/d of warfarin in VKORC1-1639G＞A AA genotype was significantly lower than that （4.01±0.17） mg/d in VKORC1-1639G＞A GA genotype （P＜0.05）； steady-state dose of warfarin in male patients （3.16±0.11） mg/d was higher than that in female patients （3.07±0.13） mg/d （P＞0.05）. Age was negatively correlated with steady-state dose of warfarin （P＜0.05）； eGFR was positively correlated with steady-state dose of warfarin （P＜0.05）. BMI had no significant correlation with steady-state dose of warfarin （P＞0.05）. The prediction model for steady-state dose of warfarin included steady-state dose of warfarin＝3.057－0.73* VKORC1-1639G＞A+0.08*eGFR－0.013* age+0.565* CYP2C9＊3（1075A＞C） [VKORC1-1639G＞A：AA＝1，GA＝0，GG＝0；CYP2C9＊3（1075A＞C）：AA＝1，AC＝0；the age was years old； the unit of eGFR was mL/（min·1.73 m2）] （R2＝0.502）. There was no statistical significance between the dose （3.12±0.56） mg/d of prediction model and actual steady-state dose （3.06±0.93） mg/d in 25 validation patients （P＞0.05）. CONCLUSIONS： There are significant differences in steady-state dose of warfarin among different genotype patients with CYP2C9＊3（1075A＞C） AA and VKORC1-1639G＞A. The prediction model of warfarin steady-state dose in patients with renal insufficiency is established successfully.
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Objective To understand the clinic usage of TCM decoction pieces in the First Affiliated Hospital of Xi’an Jiaotong University (hereinafter referred to as our hospital).Methods By using Microsoft Office Excel software, the medicine doses, classification of functions and clinic application of the TCM decoction pieces, which were among the top 50 most frequently used TCM decoction pieces were analyzed.Results In 2014, 60% of the top 50 most frequently used TCM decoction pieces in our hospital exceed the medicine dosage inChinese Pharmacopoeia. According to the functions, the top 3 TCM decoction pieces were medicine for reinforcing deficiency, clearing heat and promoting qi, respectively. Medicine for reinforcing deficiency was mainly used in gastroenteropathy, menopathy and nephropathy. Medicine for clearing heat was mainly used in gastroenteropathy, menopathy and infection of the upper respiratory tract. Medicine for promoting qi was mainly used in gastroenteropathy, tumor and disease of cardiovascular system.Conclusion TCM decoction pieces in our hospital exceed the medicine dosage in Chinese Pharmacopoeia, which requires attention. The top 3 TCM decoction pieces are respectively medicine for reinforcing deficiency, clearing heat and promoting qi, whose clinic applications are basically rational.
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Objective To explore the effects of angelica naphtha on the withdrawal signs and norepinephrine neurotransmitter in uorphine-dependent rats.Methods 72 SD rats were randomly divided into control group,model group,clonidine group and three angelica naphtha groups (80,40 and 20 mg/kg).Rats were received gradualy increasing doses of morphine to produce physical dependence.Withdrawal symptoms were evaluated by Ryuta Tomoji score.The level of norepinephrine and normetanephrine(NMN) were tested by enzyme-linked immunosorbent assay(ELISA).Results The scores of withdrawal signs were (4.00± 3.29),(30.13±4.41),(18.96± 4.43),26.04±4.13),(22.33±4.60) and (19.00±3.47),respectively.The morphine withdrawal signs were reduced by angelica naphtha in a dose-dependent manner(P＜0.01),also significantly reduced the level of NE and NMN and the ratio of NMN/NE in the nucleus ceruleus and prefrontal cortex(all P＜0.01).Conclusion Angelica naphtha alleviates the withdrawal synlptons in morphine-dependent rats,which may be related to the inhibition of excessive turnover of norepinephrine neurotransmitters in the nucleus ceruleus and prefrontal cortex.