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Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances.Here,we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry(UPLC-MS/MS).This enabled simultaneous quantification of 1136 acyl-carnitines(C0-C26)within 10-min with good sensitivity(limit of detection＜0.7 fmol),linearity(cor-relation coefficient＞0.992),accuracy(relative error＜20％),precision(coefficient of variation(CV),CV＜15％),stability(CV＜15％),and inter-technician consistency(CV＜20％,n=6).We also established a quantitative structure-retention relationship(goodness of fit＞0.998)for predicting retention time(tR)of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters(tR,ion-pairs,and collision energy).Furthermore,we quantified 514 acylcarnitines in human plasma and urine,mouse kidney,liver,heart,lung,and muscle.This provides a rapid method for quantifying acyl-carnitines in multiple biological matrices.
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Objective:To analyze the clinical efficacy and pregnancy outcomes of fertility- preserving re-treatment in patients with recurrent atypical endometrial hyperplasia (AEH) and early stage endometrial carcinoma (EEC) after achieved complete remission (CR) of primary fertility-preserving therapy.Methods:There were 104 cases of AEH and EEC collected from 9 hospitals in the multi-center research network platform of fertility-preserving therapy of endometrial carcinoma in China from January 2005 to May 2019. Thirth-one cases of them relapsed from four hospitals mentioned above,who achieved CR after primary fertility-preserving therapy,was analyzed retrospectively. Of the 31 cases, 27 cases chose fertility-preserving re-treatment. The demographic characteristics, re-treatment effect, clinical factors and pregnancy outcomes were observed.Results:(1) There were 16 AEH cases and 11 ECC cases among 27 recurrent patients who chose fertility-preserving therapy again. After re-treatment, CR was found in 13 out of 16 cases of AEH and 9 out of 11 cases of EEC. The overall CR rate was 81% (22/27). (2) After CR of recurrence, 5 cases (23%, 5/22) of re-recurrence were found after with a median time of 33 months (range 21-80 months). There were 4 cases underwent comprehensive surgical staging, and 1 patient chose the third round of fertility preservation therapy with fully informed consent, and CR was reached after 15 months. (3) There were 16 cases with pregnancy intention, with a total of 12 pregnancies, including 5 cases were natural pregnancy and 7 cases were assisted reproductive technology pregnancy. There were 5 live births. The follow-up time was up to May 2019, and the median follow-up time was 73 months (range 0-123 months). All 27 patients had disease free survival.Conclusions:Recurrent patients with AEH and EEC after achieving successful fertility-preserving therapy could choose fertility-preserving therapy again with comprehensive assessment and fully informed consent. After re-treatment, there is a certain tumor CR rate and pregnancy rate, while the close follow-up is required during treatment.
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Objective@#To analyze the clinical efficacy and pregnancy outcomes of fertility- preserving re-treatment in patients with recurrent atypical endometrial hyperplasia (AEH) and early stage endometrial carcinoma (EEC) after achieved complete remission (CR) of primary fertility-preserving therapy.@*Methods@#There were 104 cases of AEH and EEC collected from 9 hospitals in the multi-center research network platform of fertility-preserving therapy of endometrial carcinoma in China from January 2005 to May 2019. Thirth-one cases of them relapsed from four hospitals mentioned above,who achieved CR after primary fertility-preserving therapy,was analyzed retrospectively. Of the 31 cases, 27 cases chose fertility-preserving re-treatment. The demographic characteristics, re-treatment effect, clinical factors and pregnancy outcomes were observed.@*Results@#(1) There were 16 AEH cases and 11 ECC cases among 27 recurrent patients who chose fertility-preserving therapy again. After re-treatment, CR was found in 13 out of 16 cases of AEH and 9 out of 11 cases of EEC. The overall CR rate was 81% (22/27). (2) After CR of recurrence, 5 cases (23%, 5/22) of re-recurrence were found after with a median time of 33 months (range 21-80 months). There were 4 cases underwent comprehensive surgical staging, and 1 patient chose the third round of fertility preservation therapy with fully informed consent, and CR was reached after 15 months. (3) There were 16 cases with pregnancy intention, with a total of 12 pregnancies, including 5 cases were natural pregnancy and 7 cases were assisted reproductive technology pregnancy. There were 5 live births. The follow-up time was up to May 2019, and the median follow-up time was 73 months (range 0-123 months). All 27 patients had disease free survival.@*Conclusions@#Recurrent patients with AEH and EEC after achieving successful fertility-preserving therapy could choose fertility-preserving therapy again with comprehensive assessment and fully informed consent. After re-treatment, there is a certain tumor CR rate and pregnancy rate, while the close follow-up is required during treatment.
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Objective · To investigate the gender-related metabolomic differences in human saliva. Methods · The saliva metabolomic profiles of 5 male and 5 female healthy volunteers with matched age, body mass index (BMI), living and tooth-brushing condition were acquired using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Metabolites were identified using publicly accessible databases and further confirmed individually with standard compounds. Both multivariant and univariate statistics were conducted to find inter-gender differences.Results · Forty-eight metabolites in human saliva were identified including 13 amino acids, 6 choline metabolites, 15 carnitines, 4 sphinganine metabolites,7 lysophosphatidylcholine and 3 organic acids. Levels of phenylalanine, acetylcarnitine, propionylcarnitine, butyrylcarnitine, isobutyrylcarnitine,isovalerylcarnitine and sphinganine were higher in the saliva of females than that of males. Conclusion · Rich metabolic information present in human saliva with significant gender diffference which ought to be taken into consideration in study on the metabonomics of saliva.
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Objective To investigate the effects of baicalin on morphine-induced behavioral sensitization.Methods Locomotor activity was measured for 2h after administration with baicalin in mice.Hyperlocomotion induced by acute morphine (10 mg· kg-1,ip) and behavioral sensitization induced by repeated morphine were established.The level of dopamine of ventral tegmental area(VTA) and prefrontal cortex(PFC) in mice was tested by ELISA assay.Results Baiealin inhibited significantly both locomotor activity in mice (control (1095.8 ± 174.5) times,baicalin (899.6± 187.2),(724.2± 221.4),(609.1 ± 154.6) times ; P＜ 0.01) and hyperlocomotion induced by acute morphine(model (1518.2± 185.8) times,baicalin (1385.4±224.2),(1205.1 ± 174.6),(1100.3±235.1) times ; P＜0.01).Similar inhibition was also seen in the development and expression of morphine-induced behavioral sensitization(model(2096.2±304.6) times,baicalin (2004.2 ± 218.5),(1998.7-± 224.3),(1836.1 ± 233.5) times,P＜ 0.05 ; model (2124.2 ± 189.6) times,baicalin (1922.2± 314.7),(1524.1±289.2),(1477.4± 219.3) times,P＜0.01).Baicalin inhibited dopamine release in VTA and PFC of morphine-sensitized mice(model(457.6± 92.1,589.2 ±102.5) μg · L-1,baicalin(391.1±56.8) μg · L-1,(448.6± 99.3) μg · L-1; (324.5±66.2) μg · L-1,(368.7±45.9) μg · L 1 ; (234.3± 52.6) μg · L-1,(305.3±84.1) μg · L-1 ; P＜0.01,P＜0.01).Conclusion Baicalin inhibits the development and the expression of morphine-induced behavioral sensitization in mice,and this effect is related to the inhibition of dopamine release in VTA and PFC of mice.
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Metabolic characteristics of 39 human brain tumor tissues, including 15 astrocytomas, 13 fibroblastic meningiomas and 11 transitional meningiomas from 39 individual patients, have been studied using high resolution magic-angle spinning (HRMAS) 1H NMR spectroscopy in conjunction with principal component analysis (PCA). With rich metabolite information, 1H NMR spectra showed that the tumor-tissuc metabonome was dominated by lipids, lactate, myo-inositol, ereatine, choline metabolites such as choline, phosphocholine and glycerophosphocholine, amino acids such as alanine, glutamate, glutamine, taurine, N-acetyl-aspartate and glutathione. PCA of the tumor NMR spectra clearly showed metabonomic differences between low-grade astrocytomas and meningiomas whereas such differences were more moderate between fibroblastic and transitional meningiomas. Compared with meningiomas, the low-grade astrocytomas had higher levels of glycerophosphocholine, phosphocholine, myo-inositol and creatine but lower levels of alanine, glutamate, glutamine, glutathione and taurine. The N-acetyl-aspartate level was low but detectable in low-grade astrocytomas whereas it was not detectable in meningiomas. It is concluded that tissue metabonomics technology consisting of HRMAS 1H NMR spectroscopy and multivariate data analysis (MVDA) offers a useful tool (1) for distinguishing different types of brain tumors, (2) for providing the metabolic information for human brain tumors, which are potentially useful for understanding biochemistry of tumor progression.
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Metabonomics is the branch of science concerned with the quantitative understandings of the metabolite complement of integrated living systems and its dynamic responses to the changes of both endogenous factors (such as physiology and development)and exogenous factors (such as environmental factors and xenobiotics). As a holistic approach, metabonomics detects, quantifies and catalogues the time related metabolic processes of an integrated biological system, ultimately, relates such processes to the trajectories of the pathophysiological events. Ever since its birth in 1999, metabonomics has already been described in more than 800 scientific papers and half dozen patents, amongst which almost 700 papers were experimental articles. Now, metabonomics has been established as an extremely powerful analytical tool and hence found successful applications in many research areas including molecular pathology and physiology, drug efficacy and toxicity, gene modifications and functional genomics, and environmental sciences. This holistic approach has thus become an important part of systems biology and has now evolved to be a unique part in global systems biology. The essence of metabonomics and some of the present applications were reviewed to illustrate the rapid development of this extremely exciting new frontier.