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OBJECTIVE To provide a reference for the dose adjustment of tacrolimus in patients who underwent lung transplantation after combined use of voriconazole. METHODS The clinical data of lung transplantation patients who used voriconazole and tacrolimus in our hospital from January 2020 to December 2022 were collected retrospectively. The effects of voriconazole on the valley concentration， daily dose and standardized blood concentration of tacrolimus were analyzed by using SPSS 21.0 software； multiple linear regression analysis was conducted for the factors that may affect the standardized blood concentration of tacrolimus. RESULTS A total of 153 lung transplantation patients were included. After the combination of voriconazole， the average daily dose of tacrolimus decreased from 3.37 mg to 0.76 mg， and valley concentration and standardized blood concentration were increased significantly （P＜0.000 1）. The average daily dose of voriconazole was negatively correlated with the standardized blood drug concentration of tacrolimus （P＝0.000 1，r＝－0.224）. The valley concentration of voriconazole was positively correlated with valley concentration （P＜0.000 1，r＝0.316） and standardized blood concentration （P＜0.000 1，r＝ 0.249） of tacrolimus. After combination with voriconazole， the standardized blood drug concentration of patients who underwent single lung transplantation was significantly higher than those who underwent double lung transplantation， and the standardized blood concentration of tacrolimus after oral administration of voriconazole was significantly higher than after intravenous drip of voriconazole （P＜0.05）. Most liver and kidney function indicators showed no significant changes. The results of multiple factor regression analysis showed that the valley concentration of voriconazole had a significant impact on the standardized blood concentration of tacrolimus （P＜0.001）. CONCLUSIONS The valley concentration of voriconazole has greatest influence on the blood concentration and dose adjustment of tacrolimus， which is an independent influencing factor. In clinical practice， the dose of tacrolimus should be reduced in combination with voriconazole， and therapeutic drug monitoring should be conducted for both drugs.
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Phytoremediation plays an important role in the treatment of heavy metal pollution in soil. In order to elucidate the mechanism of salicylic acid (SA) on copper absorption, seedlings from Xuzhou (with strong Cu-tolerance) and Weifang Helianthus tuberosus cultivars (with weak Cu-tolerance) were selected for pot culture experiments. 1 mmol/L SA was sprayed upon 300 mg/kg soil copper stress, and the photosynthesis, leaf antioxidant system, several essential mineral nutrients and the changes of root upon copper stress were analyzed to explore the mechanism of copper resistance. The results showed that Pn, Tr, Gs and Ci upon copper stress decreased significantly compared to the control group. Meanwhile, chlorophyll a, chlorophyll b and carotenoid decreased with significant increase in initial fluorescence (F0), maximum photochemical quantum yield of PSⅡ (Fv/Fm), electron transfer rate (ETR) and photochemical quenching coefficient (qP) content all decreased. The ascorbic acid (AsA) content was decreased, the glutathione (GSH) value was increased, the superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity in the leaves were decreased, and the peroxidase (POD) activity was significantly increased. SA increased the Cu content in the ground and root system, and weakened the nutrient uptake capacity of K, Ca, Mg, and Zn in the root stem and leaves. Spray of exogenous SA can maintain the opening of leaf stomata, improve the adverse effect of copper on photosynthetic pigment and PSⅡ reaction center. Mediating the SOD and APX activity started the AsA-GSH cycle process, effectively regulated the antioxidant enzyme system in chrysanthemum taro, significantly reduced the copper content of all parts of the plant, and improved the ion exchange capacity in the body. External SA increased the content of the negative electric group on the root by changing the proportion of components in the root, promoted the absorption of mineral nutrient elements and the accumulation of osmoregulatory substances, strengthened the fixation effect of the root on metal copper, and avoided its massive accumulation in the H. tuberosus body, so as to alleviate the inhibitory effect of copper on plant growth. The study revealed the physiological regulation of SA upon copper stress, and provided a theoretical basis for planting H. tuberosus to repair soil copper pollution.
Subject(s)
Antioxidants , Copper , Helianthus/metabolism , Salicylic Acid/pharmacology , Chlorophyll A/pharmacology , Spectroscopy, Fourier Transform Infrared , Chlorophyll/pharmacology , Ascorbic Acid , Superoxide Dismutase/metabolism , Photosynthesis , Glutathione , Plant Leaves , Stress, Physiological , SeedlingsABSTRACT
OBJECTIVE：To analyze the occurrence of acute kidney injury （AKI）after lung transplantation and its possible influential factors . METHODS ：Medical records of 64 patients who received lung transplantation in our hospital from April 2017 to June 2018 were included in this retrospective study. Patients were divided into AKI group （44 cases）and non-AKI group （20 cases），according to whether AKI occurred after operation. According to diagnostic criteria for lung transplantation in our hospital ， all patients were given Methylprednisolone sodium succinate for injection or Methylprednisolone sodium succinate for injection combined with Basiliximab for injection ，and triple immunosuppressive therapy of Tacrolimus capsules+Mycophenolate mofetil dispersible tablets or Mycophenolate mofetil capsules or Mycophenolate sodium enteric-coated tablets+Methylprednisolone tablets or Prednisone acetate tablets were given after operation. The occurrence of AKI in AKI group within a week after operation were recorded. Intraoperative influential factors （operation type ， operation duration ， ECMO support ， immune inhibitor use ， intraoperative blood loss ），postoperative influential factors [days of ICU ，mechanical ventilation and ECMO support ，median value of Scr within one week after operation ，median tacrolimus concentration and the use of potential nephrotoxic drugs （≥4 kinds）， hospitalization days] and survival rate one year after operation were observed in 2 groups. RESULTS ：Within one week after lung transplantation，44 patients（68.8％）had experienced at least one episode of AKI ，among which 19 cases（29.7％）were stage 1， 17 cases（26.5％）were stage 2 and 8 cases（12.5％）were stage 3. The incidence of AKI was the highest on post-operative day 4 （57.4％）. The incidence of AKI at stage 3 exhibited growth trend within the first week after operation ，and reached the highest on median post-operative day 5（8.7％）. Operation duration ，median value of Scr within one week after operation ，median tacrolimus concentration in non-AKI group were significantly shorter or lower than AKI group ；there was no significant difference in operation type， ECMO support ， use of immunosuppressive agents ， intraoperative blood loss ，ICU days ，mechanical ventilation days，ECMO support days ，the utilization rate of potential nephrotoxic drugs （ ≥4 kinds） and hospitalization days between 2 groups （P＞0.05）. There was no statistical significance in the survival rate at stage 1 and 2 one year after operation between AKI group and non-AKI group （P＞0.05）. One year after operation ，survival rate of AKI group at stage 3 was significantly lower than that of non-AKI group （P＜0.05）. CONCLUSIONS：The incidence of AKI is high after lung transplantation. Operation duration ，median value of Scr within one week after operation ，median tacrolimus concentration were possible factors for the occurrence of AKI after operation.
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Extracorporeal membrane oxygenation (ECMO) is a viable ultimate support therapy for patients with severe cardiorespiratory failure. Antimicrobial agents are commonly prescribed in critically ill patients with ECMO. However, an increasing number of studies have shown that ECMO circuit is associated with significant pharmacokinetic (PK) alterations, including the increased volume of distribution and reduced the clearance. In addition, the critical illness pathophysiology can also influence PK of antimicrobial, such as systemic inflammation, excessive fluid resuscitation, hypo-albuminemia, worsening hepatic or renal function. These PK alterations may increase the possibility of therapeutic failure or toxicity. Therefore, this study reviews published studies of the effects of ECMO on PK of antimicrobial agents in adults and makes preliminary recommendations on possible dosing regimen.
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OBJECTIVE： To study the correlation of tacrolimus concentrations among transplant patients’ whole blood， plasma and blood cells， analyze the effects of transplant types and ages on the their correlation， and to provide reference for rational drug use in clinic. METHODS： Totally 20 patients receiving tacrolimus anti-rejection therapy after transplantation and undergoing therapeutic drug monitoring （TDM） were randomly selected. According to the type of transplantation， they were divided into renal transplantation group and lung transplantation group （10 cases for each group）. According to age， they were divided into three groups： 20-40 years old group， 41-60 years old group and 61-80 years old group （4， 9， 7 cases for each group）. Their residual blood after TDM was collected. Chemiluminescence microparticle immuno assay （CMIA） was used to detect the concentration of tacrolimus in whole blood. UPLC-MS/MS was used to measure the concentrations of tacrolimus in plasma and blood cells. Pairs plots and Spearman rank correlation analysis were used to analyze the correlation of tacrolimus between whole blood and plasma， between whole blood and blood cells， between plasma and blood cells as well as the effects of transplant types and ages on tacrolimus concentrations among tansplant patient’s whole blood， plasma and blood cells. RESULTS： The correlation of tacrolimus concentrations in whole blood and plasma （r＝0.623，P＜0.01） was slightly stronger than that of whole blood and blood cells （r＝0.591， P＜0.01）； while the correlation of tacrolimus concentration in plasma and blood cells was relatively weak （r＝0.497，P＜0.05）. Transplant type and age had an effect on the correlation of tacrolimus concentrations among patients’ whole blood， plasma， blood cells. The correlation of tacrolimus concen- tration in whole blood， blood cells and plasma in renal transplantation group was also weak （all r＜0.5）， and was weaker than that in lung transplantation group. The correlation of tacrolimus concentration among whole blood， plasma and blood cells was weak in patients of aged 20-40 years old group （all r＜0.3）， and was weaker than that of patients of aged 41-60 years old group and 61-80 years old group. CONCLUSION： Post-transplantation patients’ tacrolimus concentrations in whole blood， plasma and blood cell have a weak correlation. Rejections and adverse effects should be monitored in these patients， especially those renal transplantation patients or those patients aged 20 to 40.
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OBJECTIVE:To investigate the effects of blood concentration monitoring of cylosporin A(CsA) in patients with nephrotic syndrome(NS)on efficacy and safety. METHODS:The medical records of 154 NS patients receiving CsA and blood concentration monitoring in nephrology department of China-Japan Friendship Hospital during Jan. 2014-Aug. 2017 were analyzed retrospectively. The results of blood concentration monitoring in 63 adult inpatients with refractory NS receiving CsA for the first time within 6 months of initial treatment were analyzed statistically. The relationship of blood concentration monitoring with efficacy and safety was analyzed. RESULTS:The blood concentration of CsA in 154 patients were monitored for 512 times with an average of 3.32 times/person,and average blood concentration was(125.98±105.13)ng/mL. The patients with blood concentration of CsA＜100 ng/mL accounted for 44.14%. There was no statistical significance in average monitoring times or average blood concentration between male and female,average blood concentration of CsA among different age groups (P＞0.05). The blood concentration was monitored for 237 times in 63 adult inpatients with refractory NS receiving CsA for the first time within 6 months of initial treatment(induction period). Average blood concentration of effective group were significantly higher than ineffective group;the proportion of effective group with blood concentration＜100 ng/mL was significantly lower than that of ineffective group,with statistical significance (P＜0.05). Among 63 patients,17 patients suffered from ADR (the incidence of ADR was 26.98%). The average blood concentrations of ADR patients were significantly higher than those without ADR;the monitoring times of ADR patients with blood concentration＞150 ng/mL was significantly higher than those without ADR,with statistical significance(P＜0.05). There was no statistical significance in the incidence of ADR between effective group and ineffective group (P＞0.05). Among effective group,there was no statistically significance in average blood concentration between ADR patients and patients without ADR(P＞0.05);the monitoring times of ADR patients with blood concentration＞150 ng/mL was significantly higher than patients without ADR,with statistical significance(P＜0.05). With the increase of monitoring times,the incidence of ADR decreased gradually. There was no statistical significance in the incidence of ADR among patients who were monitored for different times (P＞0.05). CONCLUSIONS:The pharmacokinetics of CsA varies in different patients and many factors affect its blood concentration. The changes of blood concentration affect the efficacy and safety of CsA. It is difficult to determine the dosage of CsA based on experience in the treatment of NS with CsA. Great importance should be attached to blood concentration monitoring of CsA and the implementation of individualized dosage regimen based monitoring results so as to improve therapeutic efficacy and reduce the occurrence of ADR.
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OBJECTIVE:To explore the necessity of developing therapeutic drug monitoring of vancomycin in our hospital and its existing problems,and provide a reasonable basis for the clinical rational use of vancomycin. METHODS:The cross-sectional survey was designed to collect the clinical data of 92 patients with therapeutic drug monitoring of vancomycin and statistically ana-lyze 192 cases of plasma concentration monitoring data. RESULTS:The average plasma trough concentration was (15.96 ± 8.06) mg/L;with the increase of age,the plasma trough concentration was increasing,there was no significant difference in the plasma trough concentration among different age groups (P=0.000);there were only 13 cases (6.77%) that obtained the plasma trough concentration within 30 min before the fourth dose;after using wancomycin,clearance rates of Cr and the endogenous creatinine were slightly higher than before,but there was no significant difference(P=0.722);36 cases(39.13%)showed vancomycin sus-ceptible gram positive cocci;after using wancomycin,the body temperature,white blood cell count and neutrophil percentage were lower than before,the differences were statistically significant (P=0.006,P=0.000,P=0.000);48 cases (52.17%) in treatment received initial loading dose,and only 15 cases (16.30%) did not use in combination with other anti infective drugs. CONCLU-SIONS:The results showed there are still a lot of problems in the treatment of vancomycin in our hospital,for example,the stan-dard rate of the plasma trough concentration is about 50%;most of the time of blood sampling is not reasonable;the detection rate of the pathogen is low;only about half of the cases are given the loading dose,etc. Therefore clinical pharmacists’intervention for blood sampling is an important part to promote rational drug therapy monitoring. Meanwhile,data interpretation of the monitoring results of serum drug concentration of vancomycin is a basic method for clinical pharmacists in clinical monitoring to correct the un-reasonable operations,and also the necessary measures for preventing the drug renal toxicity,it is a very important significance for the medication safety and effectiveness especially in severe infection patients,the elderly,the children and the people with renal function insufficiency.
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Objective To investigate the risk of postpartum haemorrhage in HBV-infected pregnant women. Methods Cohort or case-control studies that discussed the relationship between hepatitis b virus infection and pregnancy outcome were searched in PubMed , EMBASE , Wiley Online Library , Cochrane Library , Google Scholar, CBM, WanFang database and CNKI etc. (till August 2015). The quality of included Cohort or case-control studies was evaluated , and Meta-analysis was performed with Rev Man5.2 software. Results Four observational case-control studies and 17 cohort studies , involving 19 549 women in observation , were identifled. Meta-Analysis results displayed that the incidence of postpartum haemorrhage in HBV-infected women was 9.3%, while 2.8% in women without HBV [RR = 2.97, 95% CI (2.25 ~ 3.92),P < 0.01]. Compared with normal-risk women , the incidence of postpartum haemorrhage of HBV-infected women with normal hepatic function was also higher [RR = 2.56, 95% CI (2.01 ~ 3.25),P < 0.01]. HBV-infected women with hepatic dysfunction had higher incidence of postpartum haemorrhage than those with normal hepatic function [RR = 2.67, 95% CI (2.17~ 3.28),P < 0.01]. Conclusions HBV-infected women are at higher risk of postpartum haemorrhage than normal pregnancy women and further hepatic dysfunction would lead to a continuing increase of the risk.
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Objective To study changes of AMPA receptors expression in nucleus accumbens and hypothalamus of methamphetamine dependent rats,and the therapeutical effect of rhynchophylline.Methods SPF male rata were randomly divided into normal control group,model group of methamphetamine,low dose of rhynchophylline group and high dose of rhynchophylline group(n=8 in each group).Experiment of conditioned place preference(CPP)was used to build the model of methamphetamine dependent rata.Western blotting was used to examine the changes of GluR2/3 subunits expression.The time of staying in drug-paired compartment of rats was used independent-samples t test to gather statistics,and the photodensity of proteinum strap was used One-Way ANOVA to gather statistics.Results Compare with rats in normal control group(the time of staying in drug-paired compartment of rats was(383.00±38.20)s),the rats produced CPP after treated with methamphetamine(the time of staying in drug-paired compartment of rats was(536.20±57.49)s),and low(30mg/kg) and high (60 ms/kg)dose of rhynchophylline(the time of staying in drug-paired compartment of rats were(299.80±15.96)s and(189.40±59.02)s)both could eliminate CPP effect.Compare with rats in normal control group (the ratio of value of average gray scale were(0.54±0.04)INT·mm~2 and (0.70±0.04)INT·mm~2),GluR2/3 subunits expression in nucleus aecumbens increased significantly in model group(the ratio of value of average gray seale was(0.89±0.03)INT·mm~2)and low dose of rhynchophylline group(the ratio of value of average gray seale was (0.93±0.03)INT·mm~2,P<0.01),which decreased significantly in hypothalamus(the ratio of value of average gray scale were (0.53±0.03)INT·mm~2 and (0.52±0.02)INT·mm~2,P<0.01).But GluR2/3 subunits expression in nucleus accumbens and hypothalamus of rats in high dose of rhynchophylline group(the ratio of value of average gray scale were (0.57±0.06)INT·mm~2 and (0.65±0.01)INT·mm~2) just liked the expression of normal control group(P>0.05).Conclusion GluR2/3 subunits expression of methamphetamine-induced CPP rats increased in nucleus accumbens but decreased in hypothalamus.High dose of rhynchophylline can reverse such changes and rebound the expression to normal level.
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To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin and ferulic acid. METHODS: Drug concentrations of rat plasmas after intravenous injection of paronia pall (PPE) or ferulic acid (FA) extract solution, as well as oral administration of PPE and FA solution, and different kinds of decoctions based on Guanxin Ⅱ prescription were determined by an HPLC system. NONMEM (nonlinear mixed-effect modeling) method was used to analyze the population pharmacokinetics of PF and FA. RESULTS: A two-compartment model with first order degradation in absorption phase, and an ordinary two-compartment model were adequately describe PF and FA pharmacokinetic profiles, respectively. The mean of PF population parameters, CL1, V1, CL2, V2, Ka0, and Ka1, were 0.509 L/h, 0.104 L, 0.113 L/h, 0.123 L, 0.135 /h, and 0.0135 /h, respectively, while the typical values of CL1, V1, CL2, V2, Ka1, and F in FA model were 0.295 L/h, 0.025 L, 0.0331 L/h, 0.0518 L, 0.110 /h, and 0.40, respectively. Inter-individual variabilities were estimated and dose formulation (DF) was identified as a significant covariate in the model. CONCLUSION: The results indicate that the pharmacokinetic behaviors of index components in Guanxin Ⅱ prescription can be influenced by different dose formulations administrated in rats.