ABSTRACT
OBJECTIVE To investigate the efficacy of Methotrexate （MTX） injection combined with Mifepristone tablets in the treatment of ectopic pregnancy. METHODS A retrospective cohort study method was used to collect data on patients with ectopic pregnancy who visited the Affiliated Hospital of Chengdu University from January 1， 2013 to December 31， 2021. Control group was given MTX injection alone， and exposure group was given MTX injection combined with Mifepristone tablets. Baseline variables were balanced between the two groups using a propensity score matching （PSM）， and the outcomes of the matched cohorts were compared. RESULTS A total of 125 patients were included， involving 68 in the control group and 57 in the exposure group. After PSM， 46 cases in each group were successfully matched. There was no significant difference in the treatment response rate and the incidence of adverse drug reaction （ADR） between the exposure group and the control group， which were 73.91% and 63.04%， 21.74% and 13.04% （P＞0.05）. Compared with before treatment， serum levels of β-HCG were all significantly decreased in 2 groups after treatment （P＜0.05）； there was no significant difference in the serum level of β-HCG after treatment， the time to return to normal， the interval time of second pregnancy， second ectopic pregnancy and second intrauterine pregnancy between 2 groups （P＞0.05）. The mean diameter difference of B-ultrasound pregnancy mass before and after treatment， duration of clinical symptom remission and length of hospital stay in the exposure group were significantly higher than those in the control group （P＜ 0.05）， but drug costs during hospitalization and total hospitalization costs were not significantly increased （P＞0.05）. There were no significant difference between single-dose group and multi-dose group of MTX in the treatment response rate and the incidence of ADR （P＞0.05）. The hospitalization time， drug cost and total cost of the single dose group were significantly less than those of the multi-dose group （P＜0.05）. CONCLUSIONS MTX injection combined with or without Mifepristone tablet can both effectively treat ectopic pregnancy， with comparable efficacy and safety. MTX single-dose regimen is similar to the multi-dose regimen in efficacy， but the multi-dose regimen increases the hospital stay and hospitalization costs.
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Background The increasing threats of air pollution and extreme weather have been widely recognized in recent years in China, but their individual and joint effects on cardio-cerebrovascular mortality are unclear. Objective This study aims to investigate the individual effects of and potential interactions between oxidant pollutants and ambient temperature on cardio-cerebrovascular mortality risks. Methods We collected daily data on death counts of cardio-cerebrovascular diseases, concentrations of ambient air pollutants, and meteorological parameters in Guangzhou, Chinabetween 1 January 2006 and 31 December 2016. A generalized additive model with a Poisson distribution was conducted to assess the associations of oxidant pollutants and ambient temperature with cardio-cerebrovascular mortality risks. Bivariate response surface models and stratified analyses were further adopted to qualitatively and quantitatively examine the potential interactions between oxidant pollutants and ambient temperature on cardio-cerebrovascular mortality risks. Results During the study period, the daily averages were 60.3 μg·m−3 for ozone (O3), 50.9 μg·m−3 for combined atmospheric oxidant capacity (Ox), 32.5 μg·m−3 for nitrogen dioxide (NO2), and 22.3℃ for ambient temperature. The average daily death counts of coronary and stroke diseases were 20 and 15, respectively. Per 10 μg·m−3 increment in O3, Ox, and NO2 were associated with increased coronary mortality risks (excess risk, ER) of 1.26% (95%CI: 0.79%-1.74%), 1.61% (95%CI: 0.99%-2.23%), and 1.33% (95%CI: 0.59%-2.07%), and with increased stroke mortality risks of 1.56% (95%CI: 1.04%-2.09%), 2.30% (95%CI: 1.60%-3.01%), and 2.93% (95%CI: 2.07%-3.79%) over cumulative lags of 2-5 days, respectively. The exposure-response relationships between ambient temperature and coronary and stroke mortality risks exhibited an inverse "J" shape, with the minimum mortality at temperatures of 25.7℃ for coronary disease and 27.3℃ for stroke. Our results further showed potentially synergic effects of higher temperatures and higher levels of O3 and Ox exposures on coronary mortality risks, and the relative ER due to interactions was 0.103 (95%CI: 0.028-0.178) for O3 and 0.079 (95%CI: 0.004-0.154) for Ox. We didn't find evidence of an interaction between oxidant pollutants and low temperature. Conclusion Short-term exposures to oxidant pollutants are associated with increased cardio-cerebrovascular mortality risks, and the interactive effects of high temperature and oxidant pollutants are synergistic in relation to cardio-cerebrovascular mortality risks.
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OBJECTIVE： To study the efficacy enhancing effect of compatibility of Aconitum carmichaeli liposoluble alkaloids and total glucosides of peony in the treatment of wind-cold-dampness type bi-syndrome model rats. METHODS： Totally 100 SD male rats were randomly divided into blank group （water）， model group （water）， rotundine group [positive control， 10.0 mg/（kg·d）]， dexamethasone group [positive control， 0.3 mg/（kg·d）]，A. carmichaeli alkaloids low-dose and high-dose groups [A. carmichaeli liposoluble alkaloid extract 12.5， 25.0 mg/（kg·d）]， total glucosides of peony low-dose and high-dose groups [total glucosides of peony powder 200.0，400.0 mg/（kg·d）]， compatibility low-dose and high-dose groups [A. carmichaeli liposoluble alkaloid+total glucosides of peony powder were 12.5 mg/（kg·d）+400.0 mg/（kg·d）， 25.0 mg/（kg·d）+800.0 mg/（kg·d） respectively]， with 10 rats in each group. Except for blank group， other groups were given complete Freund’s adjuvant 0.1 mL on the right hind paw and wind-cold-dampness stimulation to induce wind-cold-dampness type bi-syndrome model. Nineteen days after modeling， they were given relevant medicine or water intragastrically， once a day， for consecutive 14 d. The joint tenderness threshold （except for dexamethasone group） and joint swelling index （except for rotundine group） were measured at 0 （before medication）， 3rd and 6th day after administration respectively. HE staining was used to observe the pathological changes of synovial membrane of ankle joint in rats （except for rotundine group）. ELISA assay was used to determine anti-cyclic citrullinated peptide （CCP） antibody in serum of rats （except for rotundine group）， and compatibility index （CI） were calculated. RESULTS： Compared with blank group， joint tenderness threshold of rats were decreased significantly in model group at different time points， while joint swelling index was increased significantly （P＜0.01）. Inflammatory lesions in synovial tissue were obvious， and the content of anti-CCP antibody in serum was significantly increased （P＜0.01）. Compared with model group， the joint tenderness threshold， joint swelling index， synovial tissue pathological changes and anti-CCP antibody content in serum of rats in medication groups were improved in varying degrees， most of the indicators had significant difference （P＜0.05 or P＜0.01）， and the improvement effect of the compatibility groups was better than single component treatment groups. CI value calculated based on anti-CCP antibody content was 0.213，suggesting that the compatibility of the two components had synergistic effect. CONCLUSIONS： The compatibility of A. carmichaeli liposoluble alkaloids and total glucosides of peony in the treatment of wind-cold-dampness type bi-syndrome model rats has analgesia，anti-inflammation and synovial tissue protection， with synergistic efficacy-enhancing effect.
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OBJECTIVE：To study the toxicity mechanism of lipid-soluble alkaloids of Aconitum carmichaeli to adjuvant-induced arthritis （AIA） model rats. METHODS： Totally 40 rats were randomly divided into blank group （ultrapure water）， model group （ultrapure water） and A. carmichaeli lipid-soluble alkaloids low-dose and high-dose groups （12.5， 35 mg/kg）， with 10 rats in each group. Except for blank group， rats in other groups were given complete Freund’s adjuvant 0.1 mL on the right hind paw to induce AIA model. 19 d after modeling， they were given relevant medicine intragastrically， once a day. After 14 d of administration， endogenous metabolites were separated and identified from plasma by UPLC-LTQ/Orbitrap MS. Then， the collected data were analyzed by principal component analysis （PCA） and partial least squares-discriminant analysis （PLS-DA）. Variable importance projection （VIP）＞1 and P value （＜0.05） were used to screen differential metabolites in plasma. Retrieving the database of Kyoto Encyclopedia of Genes and Genomes according to the differential metabolites，the toxic mechanism of A. carmichaeli liposoluble alkaloids to AIA rats were speculated. RESULTS： A total of 57 plasma metabolites were indentified， and 11 differential metabolites such as L-proline， 6-hydroxynicotinic acid and adenosine were identified. After inducing AIA model， the plasma contents of L-proline and uridylic acid were decreased significantly （P＜0.05 or P＜0.01）， and the content of deoxycytidine was increased significantly （P＜0.01）. Low dose of A. carmichaeli lipid-soluble alkaloids could decrease the plasma contents of adenosine and L-proline in rats （P＜0.05 or P＜0.01）， while the plasma contents of deoxycholic acid was increased significantly （P＜0.05）. High dose of A. carmichaeli lipid-soluble alkaloids could decrease the plasma contents of 6-hydroxynicotinic acid， adenosine， carnitine， L-proline， N-formylaminobenzoic acid were decreased significantly （P＜0.05 or P＜0.01）， while the plasma contents of deoxycholic acid， L-arginine， deoxycytidine and L-lysine were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： The toxicity of low-dose of A. carmichaeli lipid-soluble alkaloids to AIA model rats is less； the toxicity of high-dose of A. carmichaeli lipid-soluble alkaloids to AIA model rats may be related to abnormal bile secretion， lysine biosynthesis and metabolic disorders of purine， pyrimidine， tryptophan， proline and arginine.