Association between ambient temperature exposure and pregnancy outcomes in patients undergoing in vitro fertilization in Shanghai, China: a retrospective cohort study.

STUDY QUESTION: Does ambient temperature exposure affect outcomes including clinical pregnancy and live birth in women undergoing IVF? SUMMARY ANSWER: Both extreme cold and hot ambient temperatures were significantly associated with adverse pregnancy outcomes of IVF cycles. WHAT IS KNOWN ALREADY: Heat exposure has been linked to adverse pregnancy outcomes worldwide. However, the effect of ambient temperature on infertile women undergoing IVF treatment is unclear. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study was conducted from a database of 3452 infertile women who underwent their first fresh or frozen embryo transfer in the Shanghai First Maternity and Infant Hospital from April 2016 to December 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Daily mean ambient temperature exposure for each patient was obtained based on their residential address. Temperature-stratified multiple logistic regression analysis was performed to investigate associations between temperature exposure and pregnancy outcomes after controlling for confounders. Vulnerable sub-groups were identified using forest plots. MAIN RESULTS AND THE ROLE OF CHANCE: The clinical pregnancy rate and live birth rate were 45.7% and 37.1%, respectively. Regarding clinical pregnancy, a higher temperature during cold weather was significantly associated with a higher pregnancy rate in the period about 11 weeks before ovarian stimulation (adjusted odds ratio (aOR) = 1.102, 95% CI: 1.012-1.201). Regarding live birth, an increased temperature during cold weather was significantly related to a higher live birth rate in the period after confirmation of clinical pregnancy or biochemical pregnancy, with the aORs of 6.299 (95% CI: 3.949-10.047) or 10.486 (95% CI: 5.609-19.620), respectively. However, a higher temperature during hot weather was negatively associated with the live birth rate in the periods after confirmation of clinical pregnancy or biochemical pregnancy, with the aORs at 0.186 (95% CI: 0.121-0.285) or 0.302 (95% CI: 0.224-0.406), respectively. Moreover, the decline in live birth rates during cold and hot weather was accompanied by increased rates of early miscarriage (P < 0.05). Stratified analyses identified susceptibility characteristics among the participants. LIMITATIONS, REASONS FOR CAUTION: Climate monitoring data were used to represent individual temperature exposure levels according to the patient's residential address in the study. We were not able to obtain information of personal outdoor activity and use of indoor air conditioners in this retrospective study, which may affect actual temperature exposure. WIDER IMPLICATIONS OF THE FINDINGS: This study highlights that the ambient temperature exposure should be taken into account during IVF treatment and afterwards. There is a need to be alert to extremes in cold and hot ambient temperatures, especially during the period of follicle development and pregnancy. With this knowledge, clinicians can scientifically determine the timing of IVF treatment and reinforce patients' awareness of self-protection to minimize adverse pregnancy outcomes associated with extreme temperatures. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a grant from the Clinical Research Plan of Shanghai Hospital Development Center [SHDC2020CR4080], a grant from the Science and Technology Commission of Shanghai Municipality [19411960500], and two grants from the National Natural Science Foundation of China [81871213, 81671468]. B.W.M. is supported by a NHMRC Investigator grant (GNT1176437). B.W.M. reports consultancy for ObsEva, and research grants from Merck KGaA, Ferring and Guerbet. The other authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Clinical outcomes after fresh versus frozen embryo transfer in women with advanced reproductive age undergoing in vitro fertilization: a propensity score-matched cohort study.

This retrospective cohort study aimed to compare clinical outcomes following fresh or frozen embryo transfer (FET) in women with advanced reproductive age (ARA). Women aged 35-45 years who underwent their first autologous fresh or frozen cleavage stage embryo transfer cycle in the Centre for Assisted Reproduction of Shanghai First Maternity and Infant Hospital between January 2016 and December 2020 were included. The primary outcome was live birth after the first embryo transfer of the in vitro fertilization (IVF) cycle. Multiple covariates were used for propensity score matching (PSM) and generalized estimating equations were performed to examine the independent association between FET and live birth. Of the total 1453 patients, 327 patients had FET and 1126 patients had fresh ET. After the PSM procedure, 274 patients were included in each group. The live birth rate was 24.8% in the FET group and 25.2% in the fresh ET group (OR 0.98, 95% CI: 0.67-1.44, P = 0.92). Other pregnancy, perinatal and neonatal outcomes were all comparable between the two groups. This study showed that FET did not improve live birth and other clinical outcomes as compared with fresh embryo transfer in women with ARA who underwent their first IVF cycle.

Whole-Transcriptome Analysis Identifies Gender Dimorphic Expressions of Mrnas and Non-Coding Rnas in Chinese Soft-Shell Turtle (Pelodiscus sinensis).

In aquaculture, the Chinese soft-shelled turtle (Pelodiscus sinensis) is an economically important species with remarkable gender dimorphism in its growth patterns. However, the underlying molecular mechanisms of this phenomenon have not been elucidated well. Here, we conducted a whole-transcriptome analysis of the female and male gonads of P. sinensis. Overall, 7833 DE mRNAs, 619 DE lncRNAs, 231 DE circRNAs, and 520 DE miRNAs were identified. Some "star genes" associated with sex differentiation containing dmrt1, sox9, and foxl2 were identified. Additionally, some potential genes linked to sex differentiation, such as bmp2, ran, and sox3, were also isolated in P. sinensis. Functional analysis showed that the DE miRNAs and DE ncRNAs were enriched in the pathways related to sex differentiation, including ovarian steroidogenesis, the hippo signaling pathway, and the calcium signaling pathway. Remarkably, a lncRNA/circRNA-miRNA-mRNA interaction network was constructed, containing the key genes associated with sex differentiation, including fgf9, foxl3, and dmrta2. Collectively, we constructed a gender dimorphism profile of the female and male gonads of P. sinensis, profoundly contributing to the exploration of the major genes and potential ncRNAs involved in the sex differentiation of P. sinensis. More importantly, we highlighted the potential functions of ncRNAs for gene regulation during sex differentiation in P. sinensis as well as in other turtles.

Transcriptome analysis reveals key genes and pathways related to sex differentiation in the Chinese soft-shelled turtle (Pelodiscus sinensis).

Most vertebrates exhibit sexual dimorphisms in size, colour, behaviour, physiology and many others. The Chinese soft-shelled turtle (Pelodiscus sinensis) male individuals reach a larger size than females which produce significant economic implications in aquaculture. However, the mechanisms of sex determination and plastic patterns of sex differentiation in P. sinensis remain unclear. Here, comparative transcriptome analysis on male and female embryonic gonads prior to gonad formation and stages mediated gonadal differentiation of P. sinensis were performed to characterize the potential sex-related genes and their molecular pathways in P. sinensis. A total of 6369 differentially expressed genes (DEGs) were identified from day 9 and day 16 and assigned to 626 GO pathways and 161 KEGG signalling pathways, including ovarian steroidogenesis pathway, steroid hormone biosynthesis pathways, and the GnRH signalling pathway (P < 0.05). Moreover, protein interaction network analyses revealed that Akr1c3, Sult2b1, Sts, Cyp3a, Cyp1b1, Sox30 and Lhx9 might be key candidate genes for sex differentiation in P. sinensis. These data provide a genomic rationale for the sex differentiation of P. sinensis and enrich the candidate gene pool for sex differentiation.

Correlation between menopausal symptoms and everyday cognition in Chinese (peri)menopausal women.

OBJECTIVE: The aim of this study was to evaluate the relationship between the severity of menopausal symptoms and everyday cognitive decline in Chinese peri and postmenopausal women. METHODS: The peri and postmenopausal Chinese Han female who first visited the menopausal clinic of Shanghai Jiao Tong University Affiliated Sixth People's Hospital was selected as the study participants. The general questionnaire was used to obtain the sociodemographic characteristics of the study participants. The menopausal rating scale (MRS) was used to assess the severity of menopausal symptoms. The short version of the Everyday Cognition (ECog-12) scales was used to assess everyday cognitive performance. RESULTS: A total of 295 women were included, with an average age of 51.12 ± 5.15 years. The average ECog scores were 1.51 ± 0.49 and the average MRS scores were 6.89 ± 4.77. In multiple linear regression analysis, after adjusting for confounding factors age, body mass index (BMI), monthly income, occupational status, education level, menopausal status, parity, regular exercise, and history of chronic diseases, complaints of anxiety and physical/mental fatigue were positively correlated with everyday cognitive decline. CONCLUSIONS: Menopausal anxiety and physical/mental fatigue were the independent predictors of everyday cognition.

Effect of Menopausal Hormone Therapy on the Vaginal Microbiota and Genitourinary Syndrome of Menopause in Chinese Menopausal Women.

Genitourinary syndrome of menopause (GSM) is a chronic and progressive condition with a series of vulvovaginal, sexual, and lower urinary tract discomforts, mainly due to hypoestrogenism. Menopausal hormone therapy (MHT) has generally been considered as the most effective treatment for GSM. In addition, vaginal microbiota is of particular significance to gynecological and reproductive illnesses and potentially has some intimate connections with GSM. Consequently, we sought to evaluate how MHT impacts the composition and structure of vaginal microbiota while alleviating GSM in Chinese menopausal women aged 45-65 years, which has not been investigated previously. 16S rRNA gene sequencing was performed to analyze microbial diversity and composition using vaginal swabs obtained from 100 menopausal women, classified as MHT women who have been taking tibolone regularly (n = 50) and non-treated women who never received any treatment (n = 50). Vaginal Health Index Score (VHIS) and GSM symptoms inquiry were also performed. We found that the vaginal microbial diversity decreased and that the abundance of Lactobacillus increased to be the dominant proportion significantly in the MHT group, in considerable contrast to vaginal microbiota of the non-treated group, which significantly comprised several anaerobic bacteria, namely, Gardnerella, Prevotella, Escherichia-Shigella, Streptococcus, Atopobium, Aerococcus, Anaerotruncus, and Anaerococcus. In this study, women without any MHT had significantly more severe GSM symptoms than those receiving tibolone, especially with regard to vulvovaginal dryness and burning, as well as decreased libido (P < 0.01). However, there was no significant difference in the severity of urological symptoms between the groups (P > 0.05). Furthermore, Lactobacillus was demonstrated to be associated with VHIS positively (r = 0.626, P < 0.001) and with GSM negatively (r = -0.347, P < 0.001). We also identified Chlamydia (r = 0.277, P < 0.01) and Streptococcus (r = 0.270, P < 0.01) as having a prominent association with more serious GSM symptoms. Our study provided an elucidation that MHT could notably alleviate GSM and conspicuously reshape the composition of the vaginal microbiota, which is of extreme importance to clinical practice for the management of GSM.

Association of snoring and body composition in (peri-post) menopausal women.

BACKGROUND: Little attention has been paid to whether snoring frequency is associated with body composition in menopausal women, particularly in China. This study objected to investigate the association between self-reported snoring and body composition in (peri-post) menopausal Chinese women as well as metabolic indicators. METHODS: This cross-sectional study enrolled 715 participants aged 40-67 years from the Menopause Clinic in the Shanghai Sixth People's Hospital. Participants were categorized into four subgroups stratified by self-reported snoring frequency: never, rarely (< 1 night per week), occasionally (1-2 nights per week), regularly (≥3 nights per week), while body composition was measured using bioelectrical impedance analysis (BIA). Besides, blood sample were collected to test the glycolipid indicators. RESULTS: In our sample of investigation, regular snoring (≥3 nights per week) was found to be an independent risk factor for higher fat mass (total, upper limbs, trunk), with the highest risk of 2.4 times for fat mass of trunk after adjusting for metabolic confounders(p = 0.003). Meanwhile, regular snoring was independently associated with higher fat mass (total and each segment) only in menopausal transition (p = 0.023). CONCLUSIONS: We suggested that self-reported regular snoring may be taken as a simple alternative to predict higher fat mass (≥17.11 kg, upper quartile) in menopausal women. Similarly, body composition should be attached to the great importance to those who in menopausal transition in order to help to prevent obstructive sleep apnea (OSA).

Fetal sex influences maternal fasting plasma glucose levels and basal ß-cell function in pregnant women with normal glucose tolerance.

AIMS: Fetal sex has recently emerged as a new factor that is related to maternal glucose homeostasis during pregnancy. The present study aimed to investigate the effect of fetal sex on maternal glucose metabolism in women with normal glucose tolerance (NGT) during pregnancy in the Chinese population. METHODS: A total of 877 pregnant women with NGT were recruited at 24-28 weeks of gestation and underwent a 75-g oral glucose tolerance test (OGTT). Pregnant women were divided into two groups according to fetal sex. Physical examinations and laboratory tests were performed. Pancreatic ß-cell function and insulin sensitivity were evaluated using OGTT-derived indices. RESULTS: Compared with women bearing female fetuses, women who delivered male fetuses had higher fasting plasma glucose (FPG) concentrations [4.5 (4.2-4.8) vs. 4.4 (4.2-4.7) mmol/L, P < 0.05], but lower HOMA-ß [161.9 (118.2-238.8) vs. 181.0 (131.7-260.9), P < 0.05] and Stumvoll first phase of insulin secretion [1230.2 (1077.9-1433.7) vs. 1290.9 (1134.0-1493.2), P < 0.05]. Multiple linear regression analysis indicated that the sex of the fetus was independently associated with maternal FPG and HOMA-ß. Further binary logistic regression analyses revealed that the presence of a male fetus was significantly associated with elevated FPG [odds ratio (OR) 1.50; 95% confidence interval (CI) 1.12-2.00; P = 0.006] and lower HOMA-ß (OR 0.70; 95% CI 0.52-0.94; P = 0.018) even after adjustment for potential confounders. CONCLUSIONS: This study provided evidence that maternal glucose metabolism could be affected by fetal sex even in NGT pregnant women. Our results suggest that the presence of male fetuses was independently associated with maternal elevated FPG and lower basal ß-cell function.

Cardiac-protective effects and the possible mechanisms of alatamine during acute myocardial ischemia.

Alatamine is a constituent in the extract of a traditional herbal medicine Ramulus euonymi widely used for cardiac protection. However, its precise effects remain unclear. In the present study, we found that alatamine was able to reduce acute myocardial ischemia (AMI)-induced cardiac dysfunction in a rat model, as reflected by significantly restored electrocardiograms, M-mode echocardiograms, and left ventricular hemodynamics. Also, Nagar Olsen staining revealed that alatamine markedly reduced AMI-induced cardiac injury and cardiac myocyte apoptosis. TUNEL and caspase-3 activity assay showed that cardiac myocytes underwent significant apoptosis during AMI, and levels of LDH and CK-MB increased in the serum. However, such changes were significantly inhibited by pre-administration of alatamine. Furthermore, such anti-apoptotic effects of alatamine was also confirmed in a cardiac myocyte model of isoproterenol (ISO)-induced damage. Mechanistically, it was also found that alatamine improved the expression and activity of sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA), which were inhibited during AMI, promoting contractility and relaxation. Meanwhile, alatamine decreased Bax and increased Bcl-2 expressions both in vivo and in vitro, therefore inhibiting cardiac myocyte apoptosis and preventing cardiac dysfunction caused by AMI at the cellular level. The present study revealed the beneficial role of alatamine in cardiac protection and highlighted it as a potential therapeutic reagent for reduction of AMI-induced cardiac injury.

Use of the local false discovery rate for identification of metabolic biomarkers in rat urine following Genkwa Flos-induced hepatotoxicity.

Metabolomics is concerned with characterizing the large number of metabolites present in a biological system using nuclear magnetic resonance (NMR) and HPLC/MS (high-performance liquid chromatography with mass spectrometry). Multivariate analysis is one of the most important tools for metabolic biomarker identification in metabolomic studies. However, analyzing the large-scale data sets acquired during metabolic fingerprinting is a major challenge. As a posterior probability that the features of interest are not affected, the local false discovery rate (LFDR) is a good interpretable measure. However, it is rarely used to when interrogating metabolic data to identify biomarkers. In this study, we employed the LFDR method to analyze HPLC/MS data acquired from a metabolomic study of metabolic changes in rat urine during hepatotoxicity induced by Genkwa flos (GF) treatment. The LFDR approach was successfully used to identify important rat urine metabolites altered by GF-stimulated hepatotoxicity. Compared with principle component analysis (PCA), LFDR is an interpretable measure and discovers more important metabolites in an HPLC/MS-based metabolomic study.

[Screening of hepatotoxicity fraction of Genkwa Flos and study on UPLC fingerprint of hepatotoxicity fraction].

OBJECTIVE: To look for the active fraction of ethanol extract of Genkwa Flos (EGF) induced hepatotoxicity and develop an UPLC fingerprint of the active fraction. METHOD: Target fraction of EGF induced hepatotoxicity was guided by the serum biochemical and histopathology methods. The UPLC method was applied to establish the chromatographic fingerprint. The separation was achieved on a BEH C18 column (2.1 mm x 50 mm, 1.7 microm) with a mobile phase consisting of acetonitrile and water containing 0.05% phosphate acid running gradient elution. The detection was carried out at 210 nm and the analysis was finished within 10 min. RESULT: The chloroform phase of EGF could be responsible for the hepatotoxicity of this herb. The common mode of the UPLC fingerprint was set up under the established condition. There were 17 common peaks in fourteen batches of herbs, eight of which were identified, and the similar degrees of the fourteen batches to the common mode were between 0.890-0.999. CONCLUSION: It is easy to locate the chloroform extraction of EGF with hepatotoxicity. And the UPLC fingerprint was developed for the above fraction, which could provide valuable references for safe and effective clinical use of EGF.

Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel-loaded microsphere with larotaxel-solution.

PURPOSE: Larotaxel is a new taxane compound with poor solubility. The aim of this study is to develop a new formulation to locate the poorly soluble drug and compare the pharmacokinetics and tissue distribution of larotaxel-loaded microsphere (LTX-LM) with the solution form larotaxel-solution (LTX-solution). METHODS: A sensitive and efficient UPLC-MS/MS method was developed and validated for determination of larotaxel in rat plasma and tissues and applied to assess the plasma protein binding, pharmacokinetics, and tissue distribution. RESULTS: Pharmacokinetic study indicated that larotaxel plasma disposition was triphasic, and LTX-LM group had markedly higher AUC, smaller clearance, and lower apparent volume of distribution than the LTX-solution group. The tissue distribution exhibited significant lower uptake of LTX-LM in lung, kidney, heart, muscle, and brain among all the tissues, indicating the advantage of LTX-LM over the solution form in reducing drug precipitation in vivo and toxicity in cardiovascular system and central nervous system. CONCLUSIONS: These results suggest that lipid microsphere could be an effective parenteral carrier for LTX delivery in cancer treatment.

Development of a UFLC-MS/MS method for simultaneous determination of six lignans of Schisandra chinensis (Turcz.) Baill. in rat plasma and its application to a comparative pharmacokinetic study in normal and insomnic rats.

Schisandra chinensis (Turcz.) Baill., a traditional Chinese medicine, has been used for treating insomnia for centuries. This paper was designed to study on the plasma pharmacokinetic for its absorption process, and to compare the pharmacokinetics of its active ingredients in normal and insomnic rats orally administrated with the prescription. Therefore, an efficient, sensitive and selective ultra fast liquid chromatography/tandem mass spectrometry (UFLC-MS/MS) method for the simultaneous determination of six sedative and hypnotic lignans (schisandrin, schisandrol B, schisantherin A, deoxyshisandrin, γ-schisandrin and gomisin N) of Schisandra chinensis (Turcz.) Baill. in rat plasma has been developed and validated. The analysis was performed on a Shim-pack XR-ODS column (75mm×3.0mm, 2.2µm) using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid waterat a flow rate of 0.4ml/min. The detection of the analytes was performed on 4000Q UFLC-MS/MS system with turbo ion spray source in the positive ion and multiple reaction-monitoring mode. The method was validated in plasma samples, which showed good linearity over a wide concentration range (r(2)>0.99), and obtained lower limits of quantification were 10, 1.2, 1.2, 1.2, 1.0 and 1.2ngmL(-1) for the analytes. The intra- and inter-day assay variability was less than 15% for all analytes. The mean extraction recoveries of analytes and IS from rats plasma were all more than 85.0%. The validated method has been successfully applied to comparing pharmacokinetic profiles of analytes in rat plasma. The results indicated that significant difference in pharmacokinetic parameters of the analytes was observed between two groups, while absorptions of these analytes in insomnic group were all significantly higher than those in normal group.

Metabonomic study of genkwa flos-induced hepatotoxicity and effect of herb-processing procedure on toxicity.

A urinary metabonomic approach based on ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS) was developed to study the metabolic disturbances caused by the administration of Genkwa Flos (GF) to rats. Potential biomarkers of GF-induced toxic effects were screened out and identified, and the underlying toxicological mechanism as well as the detoxification of vinegar-processing procedure on this herb was discussed. Urine samples were analyzed by the established UPLC-MS method. With the help of serum biochemistry and histopathology results, metabolic disturbances induced by the exposure to GF and the detoxification of processing procedure were confirmed. The differences in the metabolic profiles of healthy and treated rats were clearly discriminated with the principal component analysis of the chromatographic data. Eight significantly changed metabolites were identified and interpreted as biomarkers for the hepatotoxicity and detoxification of processing procedure. This study indicated that a UPLC-MS-based metabonomic analysis of urine samples could be considered as a promising tool to predict the hepatotoxicity induced by the GF and the detoxification of traditional vinegar-processing procedure on this herb.

Discrimination of raw and vinegar-processed Genkwa Flos using metabolomics coupled with multivariate data analysis: a discrimination study with metabolomics coupled with PCA.

In this paper, a novel approach using UPLC-MS (Ultra performance liquid chromatography tandem mass spectrometry) coupled with multivariate statistic analysis was established for the profiling and discrimination of raw and processed herb using Genkwa Flos as a model herb. A batch of raw and processed samples was analyzed, and the datasets of t(R)-m/z pairs, ion intensities and sample codes were subjected to the principal component analysis (PCA). Raw and processed herb showed a clear classification of the two groups on the score plot. Loading plot was performed, and the chemical markers having great contributions to the differentiation were screened out. The identities of the chemical markers were identified by comparing the mass spectra and retention times with those of reference compounds and/or tentatively assigned by matching empirical molecular formulae and mass fragments with those of the known compounds published in the literatures. Based on the proposed strategy, yuanhuacine, genkwadaphnin, genkwanin-5-O-ß-d-primeveroside, genkwanine N, genkwanin, 3'-hydroxy-genkwanin and apigenin were explored as representative markers in distinguishing the raw from the processed herbs. The method has been successfully applied in the distinguishing raw from processed herbs. Furthermore, the underlying detoxification mechanism of traditional processing procedure on the herb was predicted, and was related to the changes in the metabolic profiling. This research could be valuable to explore the chemical markers, investigate the mechanism underlying the processing procedure, and promote the quality control and safety application of traditional Chinese herbs.

Simultaneous determination of 20 components in red wine by LC-MS: application to variations of red wine components in decanting.

The decanting of red wines has a long tradition in red wine service from the perspective of modifying the aroma or taste of a wine. A simple and sensitive liquid chromatography-mass spectrometry method was developed for the simultaneous determination of 20 organic acids and polyphenols in decanting red wine. The separation was performed on a Diamonsil C(18) column (250 mm × 4.6 mm, 5 µm) using a mobile phase composed of methanol-0.1% acetic acid under gradient elution. Analysis was performed in selected ion monitoring mode with negative electrospray ionization interface. All the linear regressions showed good linear relationships (r(2) > 0.9973) between the peak area and concentration of each marker. The assay was reproducible with overall intra and interday variation of less than 5.0%. The recoveries for the quantified compounds were observed over the range of 92.1-108.3% with RSD values less than 5.7%. The method developed was successfully applied to determine the variations of the 20 components in red wine after decanting in different conditions. Concentrations of most organic acids and polyphenols investigated in the red wine were decreased in decanting. In addition, increment of duration, temperature, and light intensity would intensify the changes.

Bioequivalence and population pharmacokinetic modeling of two forms of antibiotic, cefuroxime lysine and cefuroxime sodium, after intravenous infusion in beagle dogs.

To investigate the bioequivalence and the population pharmacokinetics of cefuroxime lysine and cefuroxime sodium in healthy beagle dogs. A randomized 2-period crossover design in 18 healthy beagle dogs after receiving 20, 40, and 80 mg/kg of cefuroxime lysine or cefuroxime sodium was conducted. A 3-compartment open model was used as the basic model for the population pharmacokinetic study. Both of the antibiotics exhibited dose-proportional pharmacokinetics over the dose range of 20-80 mg/kg. The mean relative bioavailability of cefuroxime lysine versus cefuroxime sodium was 1.05 (range, 0.71 to 1.42), with a significant difference between males and females. The estimates of population pharmacokinetic of CL, V(1), Q(2), V(2), Q(3), V(3) were 3.74 mL/h, 1.70 mL, 29.5 mL/min, 3.58 mL, 0.31 mL/min, and 158 mL for cefuroxime lysine and 4.10 mL/h, 1.00 mL, 38.5 mL/min, 4.19 mL, 0.06 mL/min, and 13.6 mL for cefuroxime sodium, respectively. The inter-individual variability was determined to be less than 29.1%. A linear pharmacokinetic was revealed for cefuroxime lysine and cefuroxime sodium in dogs after intravenous infusion, and the bioequivalence of these forms of the antibiotic was observed with the significant gender-related differences in mean relative bioavailability of cefuroxime lysine versus cefuroxime sodium.

Development of an LC-MS method for determination of three active constituents of Shuang-huang-lian injection in rat plasma and its application to the drug interaction study of Shuang-huang-lian freeze-dried powder combined with levofloxacin injection.

A sensitive and specific high performance liquid chromatography coupled with mass spectrometric (LC-MS) method was developed and validated for the simultaneous determination of three main active constituents of Shuang-huang-lian injection with and without the combination use of levofloxacin injection in rat plasma. After addition of the internal standard rutin, plasma samples were protein precipitated with acetonitrile, the chromatographic separation was achieved on a Kromasil C18 column (250 mm × 4.6 mm, 5 µm), using a gradient mobile phase system of acetonitrile-water containing 0.05% formic acid. The analytes were detected without interference in the selected ion monitoring (SIM) mode with positive electrospray ionization. The linear range was 0.04-20 µg/mL for chlorogenic acid, 0.8-400 µg/mL for baicalin and 0.01-5.0 µg/mL for phillyrin, respectively. The accuracy (relative error, R.E.%) were between -2.7 and 3.4%, while the intra-day and inter-day precisions were less than 9.2 and 9.6% for the three analytes, respectively. This method was successfully applied to the drug interaction study of Shuang-huang-lian freeze-dried powder combined with levofloxacin injection after intravenous administration to rats. The results indicated that there were obvious differences in the pharmacokinetic behaviors after combination compared with only administration of Shuang-huang-lian injection.

Pharmacokinetic analysis of alpha and beta epimers of glycyrrhetinic acid in rat plasma: differences in singly and combined administrations.

An HPLC method for the determination of 18alpha-glycyrrhetinic acid and 18beta-glycyrrhetinic acid in rat plasma was established, which was used subsequently to determine the pharmacokinetic profiles of both epimers of glycyrrhetinic acid in rats. alpha-glycyrrhetinic acid, beta-glycyrrhetinic acid, and a mixture of alpha-glycyrrhetinic and beta-glycyrrhetinic acids were administered to rats via gastric infusion. Blood samples were collected at different time intervals and extracted by liquid-liquid extraction. Separation was achieved by using a Kromasil C18 column (150 mm x 4.6 mm, 5 microm) with the mobile phase composed of acetonitrile--4 mmol x L(-1) ammonium acetate solution (46 : 54, v/v) at a flow rate of 1.0 mL x min(-1), and the detection wavelength was set at 250 nm. The pharmacokinetic parameters were calculated using the software DAS 2.0. In a combined administration, the main pharmacokinetic parameters of beta-glycyrrhetinic acid are significantly different from that of alpha-glycyrrhetinic acid (P < 0.05), while no significant difference was obtained when administrated individually. Compared to the single administration, significant differences (P < 0.05) on the values of AUC(0-t) and AUC(0-infinity) of beta-glycyrrhetinic acid were observed when this chemical was administrated together with alpha-glycyrrhetinic acid. In contrast, the pharmacokinetic parameters of alpha-glycyrrhetinic acid were not affected even under the co-administration. Here, a sensitive, specific, rapid and reproducible HPLC method was developed for the pharmacokinetic studies of alpha-glycyrrhetinic acid and beta-glycyrrhetinic acid in rat plasma.

Development of a UPLC-ESI-MS/MS method for the determination of larotaxel in beagle dog plasma: application to the pharmacokinetic study.

A UPLC-ESI-MS/MS method has been developed and validated for the determination of larotaxel in beagle dog plasma. After addition of the internal standard, plasma samples were extracted by liquid-liquid extraction with methyl tert-butyl ether and separated on a 50×2.1 mm ACQUITY 1.7 µm C18 column (Waters, USA), with acetonitrile and 5 mM ammonium acetate as mobile phase, within a runtime of 3.0 min. The analytes were detected without interference in Multiple Reaction Monitoring mode with positive electrospray ionization. The linear range was 2.5-5,000 ng/mL. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 9.3% and 10.2%, respectively, and the accuracy (relative error, RE, %) was less than 11.5%. The validated method was successfully applied to a pharmacokinetic study of larotaxel in beagle dogs after intravenous administration of larotaxel-loaded lipid microsphere with different doses of 0.4, 0.8, and 1.6 mg/kg. The area under the concentration-time curve and the peak concentration of larotaxel seemed to increase with increasing dose proportionally, suggesting linear pharmacokinetics.