1.Toxicity Attenuation Mechanism on Processing Method for Aconiti Lateralis Radix Praeparata in Guilingji Based on Urine Metabolomics
Jiayun XIN ; Jia CHEN ; Xike XU ; Xingrui QI ; Meixin YANG ; Tiantian LIN ; Huibo LEI ; Xianpeng ZU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):166-174
ObjectiveMetabolomics was used to reveal the mechanism of Aconiti Lateralis Radix Praeparata(ALRP) in attenuating toxicity by processing from the aspects of amino acid metabolism, oxidative stress and energy metabolism by analyzing multiple metabolic pathways. MethodTwenty-four rats were randomly divided into control group, raw group and processed group, 8 rats in each group. The raw and processed group were given with 0.64 g·kg-1 of raw ALRP and processed ALRP respectively every day, the control group was given with an equal amount of normal saline once a day. After continuous administration for 7 days, the urine, serum and heart tissue of rats were collected. Pathological examination of the heart was carried out using hematoxylin-eosin(HE) staining, and the activities of lactate dehydrogenase(LDH) and creatine kinase-MB(CK-MB) in serum and cardiac tissues were detected by microplate assay and immunoinhibition assay. The effects of ALRP on rat heart before and after processing were compared and analyzed. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to perform urine metabolomics analysis, and multivariate statistical analysis was used to screen for differential metabolites related to ALRP in attenuating toxicity by processing, and pathway enrichment analysis was carried out to explore the processing mechanism. ResultHE staining showed that no obvious pathological changes were observed in the heart tissue of the control group, while obvious infiltration of inflammatory cells such as plasma cells and granulocytes was observed in the heart tissue of the raw group, indicating that the raw ALRP had strong cardiotoxicity. There was no significant difference in HE staining of heart tissue between the processed group and the control group, indicating that the toxicity of ALRP was significantly reduced after processing. Compared with the control group, the activities of LDH and CK-MB were significantly increased in serum and heart tissue of the raw group, and those were significantly decreased in serum and heart tissue of the processed group, suggesting that the myocardial toxicity of processed ALRP was reduced. A total of 108 endogenous differential metabolites associated with the raw ALRP were screened using multivariate statistical analysis in positive and negative modes, of which 51 differential metabolites were back-regulated by the processed ALRP. Biological analysis of the key regulatory pathways and associated network changes showed that the pathways related to toxicity of ALRP mainly included tryptophan metabolism, arginine and proline metabolism, phenylalanine metabolism, aminoacyl-tRNA biosynthesis, alanine, aspartate and glutamate metabolism, etc. The metabolic pathways related to the attenuation of processed ALRP mainly included aminoacyl-tRNA biosynthesis, tryptophan metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and caffeine metabolism. ConclusionThe processing technology of ALRP in Guilingji can significantly attenuate the cardiotoxicity of raw products, the mechanism mainly involves amino acid metabolism, oxidative stress and energy metabolism, which can provide experimental bases for the research related to the mechanism of toxicity reduction of ALRP by processing and its clinical safety applications.
2.Apatinib mesylate tablets-induced hand-foot skin reaction: report of two cases
Mei HAN ; Ming GE ; Bingtuan LEI ; Huibo YANG
Adverse Drug Reactions Journal 2019;21(2):142-144
Two male patients (patient 1,54 years old;patient 2,63 years old) were treated with apatinib mesylate tablets (apatinib) for adenocarcinoma of cardia and gastric fundus and left lung cancer,respectively.Patient 1 developed erythema and swelling on the extremities,perianal,and perigenital on day 22 after taking apatinib (850 mg/d).Apatinib-induced hand-foot skin reaction (HFSR) was considered.Then apatinib was discontinued,oral vitamin B6 and topical external vitamin E cream were given.After withdrawal of apatinib,his skin symptoms alleviated,and apatinib (750 mg/d) was re-given on day 7 after withdrawal.On day 57 after the resumption of apatinib,the patient's skin symptoms worsened and the medication was discontinued again.Afterwards,apatinib was given and then discontinued for 2 times (first 500 mg/d and then 250 mg/d).Because the symptoms aggravated after medication and alleviated after discontinuation,apatinib treatment was terminated finally.Patient 2 developed skin erythema,swelling,and pain on the palms and soles on day 35 after apatinib treatment at a dose of 500 mg/d.On day 85,he developed skin desquamation and circular keratosis of hands and feet,scattered erythema with desquamation in axilla,perianal region and groin,and increased pain in the skin lesions.Apatinib-induced HFSR was diagnosed.Apatinib was discontinued and symptomatic treatments were given.On day 17 of drug withdrawal,his skin symptoms improved and apatinib (500 mg/d) was given again.About 2 weeks later,the patient's skin symptoms aggravated again,and the drug was discontinued.
3.Apatinib mesylate tablets-induced hand-foot skin reaction: report of two cases
Mei HAN ; Ming GE ; Bingtuan LEI ; Huibo YANG
Adverse Drug Reactions Journal 2019;21(2):142-144
Two male patients (patient 1,54 years old;patient 2,63 years old) were treated with apatinib mesylate tablets (apatinib) for adenocarcinoma of cardia and gastric fundus and left lung cancer,respectively.Patient 1 developed erythema and swelling on the extremities,perianal,and perigenital on day 22 after taking apatinib (850 mg/d).Apatinib-induced hand-foot skin reaction (HFSR) was considered.Then apatinib was discontinued,oral vitamin B6 and topical external vitamin E cream were given.After withdrawal of apatinib,his skin symptoms alleviated,and apatinib (750 mg/d) was re-given on day 7 after withdrawal.On day 57 after the resumption of apatinib,the patient's skin symptoms worsened and the medication was discontinued again.Afterwards,apatinib was given and then discontinued for 2 times (first 500 mg/d and then 250 mg/d).Because the symptoms aggravated after medication and alleviated after discontinuation,apatinib treatment was terminated finally.Patient 2 developed skin erythema,swelling,and pain on the palms and soles on day 35 after apatinib treatment at a dose of 500 mg/d.On day 85,he developed skin desquamation and circular keratosis of hands and feet,scattered erythema with desquamation in axilla,perianal region and groin,and increased pain in the skin lesions.Apatinib-induced HFSR was diagnosed.Apatinib was discontinued and symptomatic treatments were given.On day 17 of drug withdrawal,his skin symptoms improved and apatinib (500 mg/d) was given again.About 2 weeks later,the patient's skin symptoms aggravated again,and the drug was discontinued.
4.Cultivation of health inspection professionals and teaching reform
Huibo XIE ; Zhangheng LEI ; Run CHEN ; Jie LIU ; Li CHEN
Chinese Journal of Medical Education Research 2012;11(1):28-31
The status of health inspection,the setting of courses,teaching reform,requirement of professional and the training pattern of innovative professional were deeply discussed and researched.The pros and cons of several patterns on professional training were summarized.The courses setting and reform emphasis of the innovative professional training were proposed,all of which provided useful view and ideas for training health inspection professionals.

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