最新刊期
卷 35 ， 期 1 ， 2024
- 摘要：OBJECTIVETo explore the whole-process pharmaceutical care model of iodine contrast medium and promote the rational clinical use of iodine contrast medium.METHODSClinical Professional Committee on Rational Drug Use of China Medical Education Association and Expert Committee on Drug Evaluation and Clinical Research of Guangdong Pharmaceutical Association organized domestic experts to establish a working group on the Consensus on the whole-process pharmaceutical care for iodine contrast medium. The working group conducted literature searches， evidence-based analysis， and discussions on the development process， indications， contraindications， adverse drug reactions， drug interactions， drug use for special population， pharmaceutical care， and other key topics to summarize the content and process of the whole-process pharmaceutical care for iodine contrast medium. This consensus was ultimately formed.RESULTSThe consensus on whole-process pharmaceutical care for iodine contrast medium included an evaluation of the patient， renal function， combined drug use， and hydration regimen before examination， the presence of contrast agent extravasation or suspected acute adverse reactions during examination， observation time points and follow-up after examination， and the presentation of specific work in each stage through pharmaceutical care flowchart. The medication monitoring record form was also formed to record the work situation.CONCLUSIONSThe consensus has established a whole-process pharmaceutical care system for iodine contrast medium， providing scientific evidence for clinical physicians and nursing staff in the rational use of such special drugs， and also serving as a reference for pharmacists in providing related pharmaceutical care.关键词：rational drug use;adverse drug reactions;pharmaceutical care;whole-process;consensus
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发布时间：2024-01-11 - 摘要：On-site supervision is a risk-based regulatory system that requires the scientific development of supervision plans for quality risks and hidden dangers in pharmaceutical enterprises， the rational allocation of supervision resources based on their risk levels， and the implementation of classified supervision measures. In this study， the quality risk monitoring business support system is set up for pharmaceutical enterprises by establishing the quality risk expert database and quality risk monitoring index system for pharmaceutical enterprises based on the difficulty analysis of on-site drug supervision. Based on this support system， the quality risk classification method， the differentiated spot check strategy and business auxiliary visualization system are established. This support system is used to learn the risk level of pharmaceutical enterprises， so as to innovate supervision methods and optimize monitoring strategies. Taking Jiangxi Province as an example， it is verified that the support system can guide the risk assessment of sample enterprises， can improve the targeting of on-site drug supervision in the process of technical review， scheme editing， on-site implementation and comprehensive evaluation， and can effectively improve the quality and efficiency of supervision.关键词：drug supervision;quality risk;big data;on-site supervision;strategy optimization
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发布时间：2024-01-11 - 摘要：OBJECTIVETo investigate the mechanism of catalpol affecting the differentiation of helper T cell 17 （Th17） by interfering the expressions of pyruvate kinase M2 （PKM2） and lactate dehydrogenase A （LDHA）.METHODSThe naive CD4+ T cells were selected from the spleen of C57BL/6 mice， and were differentiated into Th17 cells by adding directional differentiation stimulants for 72 hours. At the same time， the cells were treated with 0 （directed control）， 20， 40 and 80 μg/mL catalpol. The flow cytometry was used to detect the proportion of Th17 cell differentiation in cells； the colorimetric method was adopted to detect the levels of pyruvate and lactate in cell culture supernatant； mRNA expressions of retinoid-related orphan nuclear receptor gamma t （RORγt）， PKM2 and LDHA were detected by qRT-PCR method； Western blot was used to detect the expression levels of PKM2， LDHA， signal transducer and activator of transcription 3 （STAT3）， and phosphorylated STAT3 （p-STAT3） proteins in cells.RESULTSCompared with the directed control group， after 72 hours of treatment with 20， 40， 80 μg/mL catalpol， the differentiation ratio of Th17 cells were decreased by 6.74%， 8.41%， 9.24%， and the levels of pyruvate and lactate in the cell culture supernatant， the mRNA expressions of PKM2， LDHA and RORγt as well as the protein expressions of PKM2 and LDHA and the phosphorylation of STAT3 were significantly reduced （P＜0.05）.CONCLUSIONSCatalpol can reduce the glycolysis level by down-regulating the expressions of PKM2 and LDHA， thereby inhibiting the differentiation of Th17 cells.关键词：glycolysis;helper T cell 17;pyruvate kinase M2;lactate dehydrogenase A
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发布时间：2024-01-11 - 摘要：OBJECTIVETo establish the quality control method for the roots and rhizoma of Toricellia angulata.METHODSThe properties of the roots and rhizoma of T. angulata were observed and microscopic identification was conducted. The moisture， total ash， acid-insoluble ash and ethanol-soluble extract were examined according to the method stated in the 2020 edition of Chinese Pharmacopoeia （part Ⅳ）. HPLC fingerprints of 11 batches of the roots and rhizoma of T. angulata were established， common peaks were identified and the similarity was evaluated by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition）. The contents of coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D-glucopyranoside and syringaresinol were determined by HPLC.RESULTSThe properties and microscopic identification of the roots and rhizoma of T. angulata were obvious. The average contents of moisture， total ash， acid-insoluble ash and ethanol-soluble extract were 7.54%， 2.18%， 0.15% and 7.81%， respectively. There were 16 common peaks marked in the HPLC fingerprints of 11 batches of the roots and rhizoma of T. angulata， with similarities of 0.856-0.960； five of them were identified， such as coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D-glucopyranoside and syringaresinol. The contents of the above five components were 0.047 2-0.401 6， 0.836 8-8.697 9， 1.245 3-10.950 0， 0.139 0-0.437 8 and 0.016 4-0.635 3 mg/g， respectively.CONCLUSIONSThe established method is stable and accurate， which can be used for the quality control of the roots and rhizoma of T. angulata. It is preliminarily proposed that the moisture in the roots and rhizoma of T. angulata is not more than 11.0%， the total ash is not more than 4.0%， the ethanol-soluble extract is not less than 5.0%， the contents of coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D-glucopyranoside and syringaresinol are not less than 0.04， 0.83， 1.24， 0.13， 0.01 mg/g， respectively.关键词：rhizoma of Toricellia angulata;property identification;microscopic identification;fingerprint;content determination;quality control
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发布时间：2024-01-11 - 摘要：OBJECTIVEOptimizing the water extraction technology of Xiangqin jiere granules.METHODSThe orthogonal test of 3 factors and 3 levels was designed， and comprehensive scoring was conducted for the above indexes by using G1-entropy weight to obtain the optimized water extraction technology of Xiangqin jiere granules with water addition ratio， extraction time and extraction times as factors， using the contents of forsythoside A， baicalin， phillyrin， oroxylin A-7-O-β-D-glycoside， wogonoside， baicalein and wogonin， and extraction rate as evaluation indexes. BP neural network modeling was used to optimize the network model and water extraction process using the results of 9 groups of orthogonal tests as test and training data， the water addition multiple， decocting time and extraction times as input nodes， and the comprehensive score as output nodes. Then the two analysis methods were compared by verification test to find the best water extraction process parameters.RESULTSThe water extraction technology optimized by the orthogonal test was 8-fold water， extracting 3 times， extracting for 1 h each time. Comprehensive score was 96.84 （RSD＝0.90%）. The optimal water extraction technology obtained by BP neural network modeling included 12-fold water， extracting 4 times， extracting for 0.5 h each time. The comprehensive score was 92.72 （RSD＝0.77%）， which was slightly lower than that of the orthogonal test.CONCLUSIONSThe water extraction technology of Xiangqin jiere granules is optimized successfully in the study， which includes adding 8-fold water， extracting 3 times， and extracting for 1 hour each time.关键词：water extraction technology;G1-entropy weight;orthogonal test;BP neural network
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发布时间：2024-01-11 -
Repair effect of ephedrine on lipopolysaccharide-induced microglia function injury and its mechanism
摘要：OBJECTIVETo study the repair effect of ephedrine on lipopolysaccharide （LPS）-induced microglia function injury and its mechanism.METHODSHuman microglia cells （HMC3） were used as research objects to investigate the effects of different concentrations of ephedrine （75， 150， 300， 600 μg/mL） on the viability and apoptosis of HMC3 cells. HMC3 cells were divided into control group （without drug intervention）， LPS group （1 μg/mL）， ephedrine group （1 μg/mL LPS+300 μg/mL ephedrine）， BAY11-7082 group [1 μg/mL LPS+5 μmol/L nuclear factor-κB （NF-κB） pathway inhibitor BAY11-7082]， inhibitor group （1 μg/mL LPS+300 μg/mL ephedrine+5 μmol/L BAY11-7082） and activator group （1 μg/mL LPS+300 μg/mL ephedrine+1 μmol/L NF-κB pathway activator Prostratin）. After 24 hours of drug treatment， cell migration， the levels of soluble interleukin-6（sIL-6）， interleukin-10（IL-10）， superoxide dismutase（SOD）and malondialdehyde（MDA）， and the expressions of NF-κB pathway-related proteins were all detected.RESULTSThe viability of HMC3 cells could be increased significantly by 300 μg/mL ephedrine， while the apoptotic rate was decreased significantly （P＜0.05）. Compared with the control group， the number of migrating cells was increased significantly in the LPS group； the levels of sIL-6 and MDA， the phosphorylation of NF-κB protein were increased significantly， while the levels of IL-10 and SOD were decreased significantly （P＜0.05）. Compared with the LPS group， the above indexes were reversed significantly in the ephedrine group and BAY11-7082 group （P＜0.05）. Compared with the ephedrine group， the number of migrating cells was decreased significantly in the inhibitor group； the levels of sIL-6 and MDA， the phosphorylation of NF-κB protein were decreased significantly， while the levels of IL-10 and SOD were increased significantly （P＜0.05）. The above indexes were reversed significantly in the activator group （P＜0.05）.CONCLUSIONSEphedrine can repair cell injury by inhibiting LPS induced apoptosis， migration， inflammation and oxidant stress of HMC3 cells， the mechanism of which may be associated with inhibiting the activity of the NF-κB signaling pathway.关键词：ephedrine;lipopolysaccharide;nuclear factor-κB signaling pathway;cell function injury- 3
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发布时间：2024-01-11 - 摘要：OBJECTIVETo study the effects of the Mongolian medicine Sugemule-4 on the metabolism of insomnia rats， and to preliminarily explore its possible mechanisms for improving insomnia.METHODSThe rat model of chronic stress insomnia was established by tail clipping stimulation and intraperitoneal injection of p-chlorophenyl alanine solution. Twenty-four male rats were randomly divided into the normal group， model group， diazepam group （positive control， 0.92 mg/kg）， and Sugemule-4 group （5.2 g/kg）， with 6 rats in each group. Since the 7th day of tail clipping stimulation， the Sugemule-4 group and diazepam group began to be intragastrically administered with relevant medicine； the normal group and model group were intragastrically administered with an equal volume of distilled water， once a day， for 14 consecutive days. The learning and memory abilities of rats were tested using a water maze experiment， and the non-invasive sleep activity monitoring system was used to monitor the 24-hour sleep time of rats. A metabolomics study was conducted on rat serum and hippocampal tissue by using ultra-high-performance liquid chromatography-tandem mass spectrometry. The multivariate statistical analysis method was adopted to analyze the differential metabolites in serum and hippocampal tissue of rats， and screen for differential metabolites and metabolic pathways among those groups.RESULTSCompared with the normal group， the escape latency of rats in the model group was significantly increased， the times of crossing platforms were significantly reduced， and the percentage of average 24-hour sleep time was significantly reduced （P＜0.05）. Compared with the model group， the levels of the above indicators were significantly reversed in the diazepam group and Sugemule-4 group （P＜0.05）. Metabolomics studies found that a total of 9 differential metabolites were identified in rat serum and hippocampal tissue， including 5-hydroxyindoleacetic acid， canine urate， canine urinary quinolinic acid， 5-hydroxytryptamine， phenol sulfate， 1-carboxyethyltyrosine， 3-（4-hydroxyphenyl） lactate， N-acetyl tyrosine， tyrosine and phenol sulfate， mainly involving 2 metabolic pathways of tryptophan and tyrosine.CONCLUSIONSSugemule-4 can improve the sleep time and behavioral performance of insomnia rats， and its mechanism may be associated with affecting amino acid metabolic pathways such as tryptophan and tyrosine.关键词：Sugemule-4;insomnia;metabolomics;amino acid metabolism
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发布时间：2024-01-11 - 摘要：OBJECTIVETo study the mechanism of oxymatrine inducing apoptosis of osteosarcoma MG63 cell line based on mitophagy mediated by cyclooxygenase-2 （COX-2）/PTEN-induced putative kinase-1 （PINK1）/Parkinson disease protein-2 （Parkin） signaling pathway.METHODSMG63 cells were treated with 2.0， 4.0， 8.0 mg/mL oxymatrine and 6 μmol/L 5-fluorouracil， then the apoptotic rate， the expression of apoptosis-related proteins [B-cell lymphoma-2 （Bcl-2）， Bcl-2 related X protein （Bax）]， the proportion of decrease in mitochondrial membrane potential， the level of mitophagy as well as the protein expressions of PINK1， Parkin， and microtubule-associated protein 1 light chain-3Ⅱ （LC3-Ⅱ） were detected. PINK1 small interfering RNA （siRNA） was adopted to intervene in the expression of PINK1， the cells were divided into control group， PINK1 siRNA group， oxymatrine group， and PINK1 siRNA+oxymatrine group； the protein expressions of PINK1， Parkin， and LC3-Ⅱ， the proportion of decrease in mitochondrial membrane potential （MMP） as well as apoptotic rate were detected. The lentivirus infection technique was used to overexpress COX-2， the cells were divided into control group， oxymatrine group， COX-2 group， and COX-2+oxymatrine group. The protein expressions of COX-2， PINK1， and Parkin， as well as the proportion of decrease in MMP were detected.RESULTSAfter being treated with oxymatrine， the apoptotic rate， the protein expressions of Bax， PINK1， Parkin， and LC3-Ⅱ， the level of mitophagy as well as the proportion of decrease in MMP were significantly increased （P＜0.05）， while the protein expression of Bcl-2 was significantly decreased （P＜0.05）. Compared with the oxymatrine group， the protein expressions of PINK1， Parkin， and LC3-Ⅱ， apoptotic rate and the proportion of decrease in MMP were significantly decreased in PINK1 siRNA+oxymatrine group （P＜0.05）. Compared with the oxymatrine group， the protein expression of COX-2 in the COX-2+oxymatrine group was increased significantly （P＜0.05）， while the protein expressions of PINK1 and Parkin as well as the proportion of decrease in MMP were decreased significantly （P＜0.05）.CONCLUSIONSOxymatrine can mediate the overactivity of mitophagy based on the PINK1/Parkin signaling pathway by inhibiting COX-2 expression， thus promoting the apoptosis of the MG63 osteosarcoma cell line.关键词：osteosarcoma;cell apoptosis;mitophagy;cyclooxygenase-2;PTEN-induced putative kinase protein-1;Parkinson disease protein-2
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发布时间：2024-01-11 - 摘要：OBJECTIVETo investigate the improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis （UC） and its mechanism.METHODSUC rat models were established， and 70 rats with successful modeling were randomly divided into model group， limonin low-， medium-， and high-dose groups （12.5， 25， 50 mg/kg）， and sulfasalazine group （positive control group，500 mg/kg）， with 14 rats in each group. Another 14 rats were selected as the control group. After modeling， each group was given the corresponding drug or equal amount of normal saline， once a day， for 2 weeks. Twenty-four hours after the last administration， the general condition of rats was observed and the body weight was measured， and colon tissue was collected for colonic mucosal damage index （CMDI） scoring； the levels of interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in colon tissue were detected； the pathological changes of colon tissue were observed； the protein expressions of Claudin-1， Occludin， ZO-1， high mobility group protein B1 （HMGB1） and receptor for advanced glycation end products （RAGE） in colon tissue were detected； fecal 16S rRNA sequencing was used to detect the relative abundance of intestinal microbiota in rats.RESULTSCompared with the control group， the rats in the model group were in poor mental state， with darker fur， irritable mood， disordered arrangement of colon glands， inflammatory cell infiltration， cell necrosis and edema； CMDI score， the levels of IL-1β， IL-6 and TNF-α， protein expressions of HMGB1 and RAGE in colon tissue， the relative abundance of Proteobacteria and Bacteroidetes were significantly increased （P＜0.05）； body weight， the protein expressions of Claudin-1， Occludin and ZO-1 in colon tissue， the relative abundance of Firmicutes in the intestine were significantly decreased （P＜0.05）. Compared with the model group， general situation and pathological damage of colonic tissue in limonin groups were improved， the levels of the above indicators were significantly reversed （P＜0.05）， and in a dose-dependent manner （P＜0.05）； there was no significant difference in various indexes between sulfasalazine group and limonin high-dose group （P＞0.05）.CONCLUSIONSLimonin can improve intestinal injury and intestinal flora disturbance in UC model rats， the mechanism of which may be associated with the down-regulation of HMGB1/RAGE signaling pathway.关键词：ulcerative colitis;intestinal injury;intestinal flora;HMGB1/RAGE signaling pathway
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发布时间：2024-01-11 - 摘要：OBJECTIVETo study the improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome （PCOS） and its mechanism.METHODSOne hundred and twenty-six female rats were randomly separated into blank group， PCOS group， poria acid low-dose group （8.33 mg/kg）， pachymic acid high-dose group （33.32 mg/kg）， ethinylestradiol cyproterone group （positive control group， 0.34 mg/kg）， recombinant rat high mobility group protein B1 protein （rHMGB1） group （8 μg/kg）， and poria acid high dose+rHMGB1 group （33.32 mg/kg poria acid+8 μg/kg rHMGB1）， with 18 rats in each group. Except for the blank group， the rats in all other groups were given Letrozole suspension intragastrically to construct the PCOS model. After successful modeling， administration was performed once a day for 4 weeks. After medication， the fasting blood glucose and fasting insulin levels， and insulin resistance index （HOMA-IR） were measured in rats； the levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH） and testosterone （T） in rat serum， and the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in ovarian tissue were detected； ovarian coefficients of rats were calculated； the pathological changes of ovarian tissue were observed； the expressions of HMGB1， receptor for advanced glycosylation end product （RAGE） and phosphorylated nuclear factor κB p65 （p-NF-κB p65） proteins were determined in ovarian tissue of rats.RESULTSCompared with the blank group， the pathological injury of ovarian tissue of rats in the PCOS group was serious， the levels of fasting blood glucose and fasting insulin， HOMA-IR and ovarian coefficient were increased， the levels of serum LH and T were increased， while the levels of FSH were decreased； the levels of IL-1β and TNF-α， the expressions of HMGB1， RAGE and p-NF-κB p65 protein in ovarian tissue were increased， with statistical significance （P＜0.05）. Compared with the PCOS group， pathological damage of ovarian tissue was reduced in poria acid low-dose and high-dose groups and ethinylestradiol cyproterone group， and fasting blood glucose， fasting insulin levels， HOMA-IR and ovarian coefficient were decreased； serum LH and T levels were decreased， while FSH levels were increased； the levels of IL-1β and TNF-α and the expressions of HMGB1， RAGE and p-NF-κB p65 protein in ovarian tissue were decreased， with statistical significance （P＜0.05）. The trend of corresponding indexes in rHMGB1 group was opposite to the above （P＜0.05）. Compared with poria acid high-dose group， the changes of the above indexes were reversed significantly in poria acid high-dose+rHMGB1 group （P＜0.05）.CONCLUSIONSPoria acid may improve insulin resistance and inhibit inflammatory reaction in PCOS rats by inhibiting HMGB1/RAGE pathway.关键词：polycystic ovary syndrome;HMGB1/RAGE pathway;insulin resistance;inflammation response
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发布时间：2024-01-11 - 摘要：OBJECTIVETo evaluate the cost-effectiveness of ivabradine in the treatment of chronic heart failure （CHF） in the context of “Quadruple Therapy” from the perspective of the health system.METHODSBased on real-world cohort data， the Markov model was constructed according to the natural progression of CHF， with a cycle time of 3 months， a study timeframe of 20 years， and a discount rate of 5%. Using quality-adjusted life year （QALY） and incremental cost-effectiveness ratios （ICER） as the output indexes， the cost-utility analysis was used to evaluate the cost-effectiveness of ivabradine in combination with the “Quadruple Therapy” regimen， compared with the “Quadruple Therapy” regimen for the treatment of CHF， and the robustness of the results of the base analysis was verified by univariate sensitivity analysis and probabilistic sensitivity analysis.RESULTSThe results of the base analysis showed that the ICER of ivabradine combined with the “Quadruple Therapy” regimen was 165 065.54 yuan/QALY， compared with the “Quadruple Therapy” regimen， which was lower than the willingness-to-pay （WTP） threshold （257 094 yuan/QALY） based on 3 times of China’s gross domestic product （GDP） per capita in 2022. The results of the univariate sensitivity analysis showed that the discount rate had the greatest impact on the robustness of the model. The probabilistic sensitivity analysis showed that the probability that the ivabradine combined with the “Quadruple Therapy” regimen was cost-effective under the WTP threshold in this study was 59.50%.CONCLUSIONSWhen using 3 times China’s 2022 GDP per capita （257 094 yuan/QALY） as the WTP threshold， the combination of ivabradine and the “Quadruple Therapy” regimen for treating CHF is cost-effective.关键词：ivabradine;Quadruple Therapy;Markov model;pharmacoeconomics
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发布时间：2024-01-11 - 摘要：OBJECTIVETo develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy.METHODSRetrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model.RESULTSThe pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance.CONCLUSIONSThe PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.关键词：mycophenolic acid;children;population pharmacokinetics
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发布时间：2024-01-11 - 摘要：OBJECTIVETo construct a risk prediction model for bloodstream infection （BSI） induced by carbapenem-resistant Klebsiella pneumoniae （CRKP）.METHODSRetrospective analysis was conducted for clinical data from 253 patients with BSI induced by K. pneumoniae in the First Hospital of Qinhuangdao from January 2019 to June 2022. Patients admitted from January 2019 to December 2021 were selected as the model group （n＝223）， and patients admitted from January 2022 to June 2022 were selected as the validation group （n＝30）. The model group was divided into the CRKP subgroup （n＝56） and the carbapenem-sensitive K. pneumoniae （CSKP） subgroup （n＝167） based on whether CRKP was detected or not. The univariate and multivariate Logistic analyses were performed on basic information such as gender， age and comorbid underlying diseases in two subgroups of patients； independent risk factors were screened for CRKP-induced BSI， and a risk prediction model was constructed. The established model was verified with patients in the validation group as the target.RESULTSAdmissioning to intensive care unit （ICU）， use of immunosuppressants， empirical use of carbapenems and empirical use of antibiotics against Gram-positive coccus were independent risk factors of CRKP-induced BSI （ORs were 3.749， 3.074， 2.909， 9.419， 95%CIs were 1.639-8.572， 1.292-7.312， 1.180-7.717， 2.877-30.840， P＜0.05）. Based on this， a risk prediction model was established with a P value of 0.365. The AUC of the receiver operating characteristic （ROC） curve of the model was 0.848 [95%CI （0.779， 0.916）， P＜0.001]， and the critical score was 6.5. In the validation group， the overall accuracy of the prediction under the model was 86.67%， and the AUC of ROC curve was 0.926 [95%CI （0.809， 1.000]， P＜0.001].CONCLUSIONSAdmission to ICU， use of immunosuppressants， empirical use of carbapenems and empirical use of antibiotics against Gram-positive coccus are independent risk factors of CRKP-induced BSI. The CRKP-induced BSI risk prediction model based on the above factors has good prediction accuracy.关键词：bloodstream infection;risk factors;risk prediction model
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发布时间：2024-01-11 - 摘要：OBJECTIVETo explore the effects of 5，10-methylenetetetrahydrofolate reductase （MTHFR） gene polymorphism on the adverse reactions in patients with osteosarcoma after the first high-dose methotrexate （HD-MTX） treatment.METHODSA prospective study was conducted to include 53 patients with osteosarcoma treated with HD-MTX at the first admission in General Hospital of Eastern Theater Command. The dose of MTX was evaluated according to the polymorphism of rs1801133 in the METHFR gene and demographic factors， then whole pharmaceutical monitoring was conducted. The data on liver toxicity， renal toxicity， hematological toxicity， and gastrointestinal reaction were collected after the first chemotherapy cycle. Single factor analysis and binary Logistic regression analysis were used to analyze the correlation between MTX dose， 24 h blood drug concentration， and rs1801133 locus genotype with four adverse reactions.RESULTSThe MTX dosage in patients with CC wild type was significantly higher than that in TT mutant type （7.97 g/m2 vs. 6.98 g/m2， P＝0.030）， but this difference did not affect the 0 h and 24 h blood drug concentrations of MTX. The above four adverse reactions were not related to the dose of MTX. The results of binary Logistic regression analysis showed that carrying one T allele increased the risk of developing hematological toxicity by 4.13 times（95% confidence interval：1.35-12.62，P＝0.013）. When 24 h plasma concentration threshold of MTX was set to 2.65 µmol/L， the sensitivity and specificity of predicting liver function damage were 53.33% and 86.96%， respectively； when the threshold was set to 7.28 μmol/L， the sensitivity and specificity of predicting renal damage were 100% and 81.63%.CONCLUSIONSThe polymorphism of the rs1801133 in the MTHFR gene is associated with hematological toxicity of MTX. Patients who take HD-MTX for the first time and carry the T allele have a high risk of hematological toxicity. The 24 h plasma concentration of MTX is related to liver toxicity and renal toxicity. In addition， monitoring the 24 h blood drug concentration can predict liver and renal toxicity， and take early intervention measures.关键词：high-dose;5，10-methylenete- trahydrofolate reductase;rs1801133 locus;adverse reactions;genetic polymorphism
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发布时间：2024-01-11 - 摘要：OBJECTIVETo determine the optimal therapeutic plan for metastatic hormone-sensitive prostate cancer （mHSPC）， and to provide reference for clinical decision-making.METHODSRetrieved from Medline， Embase， BIOSIS preview， the Cochrane Library and ClinicalTrials.gov systematically， randomized controlled trials about mHSPC therapy， with overall survival （OS） and radiographic progression-free survival （rPFS） as efficacy outcomes and the incidence of serious adverse events （SAEs） as safety outcome， were collected during the inception-Mar. 2022. Two researchers independently screened the literature， extracted data， and evaluated the risk of bias for the included study before conducting a Bayesian network meta-analysis.RESULTSEight studies with 9 437 patients were finally included. The effectiveness and safety of 7 therapy plans were compared [abiraterone acetate， apalutamide， darolutamide+docetaxel， docetaxel， enzalutamide， standard non-steroidal antiandrogen （SNA） in addition to ADT， and ADT alone]. In terms of efficacy index， the most beneficial regimen （except for ADT+SNA） for OS was ADT+darolutamide+docetaxel （HR＝0.54， 95%CI of 0.44-0.66）， followed by ADT+abiraterone acetate （HR＝0.64，95%CI of 0.57-0.71）， apalutamide （HR＝0.65， 95%CI of 0.53-0.79）， enzalutamide （HR＝0.66， 95%CI of 0.53-0.82）； the least beneficial regimen for OS was ADT+docetaxel （HR＝0.79， 95%CI of 0.71-0.88）. The most beneficial regimen （except for ADT+SNA） for rPFS was ADT+enzalutamide （HR＝0.39， 95%CI of 0.30-0.50）， followed by ADT+apalutamide （HR＝0.48， 95%CI of 0.39-0.60）， abiraterone acetate （HR＝0.57， 95%CI of 0.51-0.64）， docetaxel （HR＝0.62， 95%CI of 0.56-0.69）. The results of the tumor-loading subgroup analysis were the same. In terms of safety， ADT+darolutamide+docetaxel （OR＝25.86， 95%CI of 14.08-51.33）， and ADT+docetaxel （OR＝23.35， 95%CI of 13.26-44.81） were associated with markedly increased SAEs； the incidence of SAEs caused by ADT+abiraterone acetate （OR＝1.42， 95%CI of 1.10-1.82） was slightly increased， and those of other therapy plans had no significant difference.CONCLUSIONSCompared with ADT alone， ADT+darolutamide+docetaxel may provide the most significant OS benefit， but the incidence of SAEs is increased greatly； compared with ADT+docetaxel， ADT+abiraterone acetate， apalutamide or enzalutamide provide more OS benefits. ADT+enzalutamide provide optimal rPFS benefits with no increased SAEs.关键词：androgen deprivation therapy;pharmacotherapy plan;network meta-analysis
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发布时间：2024-01-11 - 摘要：OBJECTIVETo investigate the preferences of patients who underwent solid organ transplantation regarding therapeutic drug monitoring （TDM） of mycophenolic acid （MPA） and explore the factors influencing patients’ decision-making process， so as to provide support for the development of individualized medication guidelines for MPA and improvement of clinical decision-making.METHODSThe cross-sectional study was used to design the questionnaire on the patients’ preferences to accept MPA TDM， and involved patients who underwent solid organ transplantation and received MPA treatment at two tertiary hospitals in Beijing from April 14， 2022， to June 27， 2022. The Likert 5-level scoring method was used to score the patients’ preferences to accept MPA TDM， the influencing factors and their correlation of the patients’ preferences to accept MPA TDM were analyzed by Pearson correlation analysis and binary Logistic regression analysis， and the nonparametric test and chi-square test were used to rank and analyze the consistency of the factors affecting patients’ preference decision.RESULTSA total of 140 questionnaires were collected， and the effective recovery rate was 77.35%. The average preference score of 140 patients to receive MPA TDM was （4.01±0.65）， and the overall preference value was high. There were 116 （82.86%） patients agreed or strongly agreed with MPA TDM. Significant differences were observed in preference scores between patients who had previously undergone MPA TDM and those who had never undergone it [（4.30±0.53） scores vs. （3.80±0.65） scores， P＜0.001]. Additionally， patients’ preference scores were significantly influenced by their understanding level and attention level （P＜0.001）. The ranking of factors contributing to decision-making exhibited consistency （P＜0.001）. The factors were ranked in descending order of clinical efficacy， safety， comfortability， economy and time cost.CONCLUSIONSThe patients who underwent solid organ transplantation hold high preferences towards MPA TDM. The primary factors influencing their decisions are their prior experience， understanding level， and attention level.关键词：therapeutic drug monitoring;patient’s preferences;solid organ transplantation;questionnaire survey
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发布时间：2024-01-11 - 摘要：OBJECTIVETo provide reference for improving the rational use of antimicrobial drugs in primary township medical institutions.METHODSBased on the county prescription pre-review center， a team led by anti-infective clinical pharmacists constructed the management mode for the use of antimicrobial drugs in county-level medical communities with clinical pharmacists as the main team by finding out the main problems in the use of antimicrobial drugs in primary township medical institutions， providing feedback on the problems， organizing relevant training for the problems， improving the customization rules of the prescription pre-review software， implementing the automatic interception and pharmacist online prescription review and other measures. Data on the use of antimicrobial drugs were collected and compared in the 15 primary township medical institutions between January-June in 2022 （before the implementation of the mode） and January-June in 2023 （after the implementation of the mode）.RESULTSCompared with before the implementation of the mode， the utilization rate of antimicrobial drugs in outpatients of primary township medical institutions decreased from 24.97% before the implementation of the mode to 19.39% after the implementation of the mode； the utilization rate of antimicrobial injection in outpatients decreased from 66.10% to 46.80%； the utilization rate of intravenous drip of antimicrobial drugs in outpatients decreased from 52.33% to 40.35%； the rates of combined use of antimicrobial drugs in outpatients decreased from 12.70% to 8.19%； the reasonable rate of antimicrobial prescribing in outpatients increased from 55.28% to 73.93%. After the implementation of the mode， the proportion of antimicrobial prescriptions for each diagnosis was basically the same as before； the defined daily dose system （DDDs） and proportion of a few antimicrobial drugs changed compared with before according to the anatomical therapeutic chemical classification of drugs， among which DDDs of lincomycin， gentamicin and other drugs declined significantly； DDDs of antimicrobial drugs for each classification was basically the same as before according to AWaRe classification.CONCLUSIONSThe management mode of the use of antimicrobial drugs led by anti-infective clinical pharmacists is constructed in the prescription pre-reviewing center of county-level medical communities， which can effectively improve the rational use of antimicrobial drugs in the primary township medical institutions.关键词：antimicrobial drugs;primary township medical institutions;clinical pharmacists;rational drug use
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发布时间：2024-01-11 - 摘要：OBJECTIVETo provide reference for the adjustment of antibiotic treatment regimens， identification of adverse reactions， and individualized pharmaceutical care for melioidosis sepsis （MS）.METHODSClinical pharmacists participated in the intensive and eradicating therapeutic processes for an MS patient by using blood concentration and gene detection. Based on the literature， antibiotic treatment regimens of MS were adjusted by determining the blood concentrations of β-lactam and trimethoprim/sulfamethoxazole （TMP/SMZ） and calculating PK/PD parameters. The causes of adverse drug reactions were analyzed and addressed by detecting drug-related gene polymorphisms through high-throughput sequencing.RESULTSClinical pharmacists used blood concentration and genetic testing methods to propose adjustments to imipenem-cilastatin sodium dosage and analyze the causes of various adverse drug reactions. PK/PD targets were calculated by measuring the blood concentrations of β-lactam and TMP/SMZ. Clinical pharmacists explained to clinical doctors the compliance status of patients with melioidosis in sepsis and non-sepsis stages through reviewing guidelines and literature； the results of blood concentration and genetic test were used to analyze the correlation of neurotoxicity of MS patients with IMP cmin， and it was found that nephrotoxicity was not related to the cmax of TMP/SMZ， but to the patient’s water intake. After whole-process antibiotic treatment， the patient’s condition improved and was discharged， and the adverse reactions were effectively treated.CONCLUSIONSClinical pharmacists use blood concentration and genetic tests to assist clinicians in formulating MS treatment regimens， and provide whole-course pharmaceutical care for a MS patient. This method has improved the safety and effectiveness of clinical drug therapy.关键词：β-lactam antibiotic;trimethoprim/sulfamethoxazole;blood concentration;genetic test;pharmaceutical care
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发布时间：2024-01-11 - 摘要：OBJECTIVETo construct the “school-enterprise-community” linkage community pharmaceutical care mode based on the WeChat mini program， upgrade the content and mode of community pharmaceutical care， and improve the quality of healthy life of the residents.METHODSFocusing on the pharmaceutical care needs of community residents， by integrating school， enterprise and community pharmaceutical resources， the WeChat mini program of “drug enjoying health” was created and the “online+offline” community pharmaceutical care mode was built. Using classified random sampling， mini program users were randomly selected as the observation group， and offline pair-assisted community residents as the control group. The intervention effects of the two groups were compared around the three aspects of medication health knowledge mastery， medication compliance and medication behavior.RESULTSThe “drug enjoying health” mini program consisted of four modules： “drug for health”， “drug for warmth”， “drug for safety”， and “personal information”. The “school-enterprise-community” linkage community pharmaceutical care mode based on the “drug enjoying health” mini program began to be applied in July 2022， with 6 185 users， 2 732 recovery records of expired drugs， 941 times of pharmaceutical care， and 3 354 consultation orders. After the intervention， the qualified rate of medication health knowledge mastery， complete compliance rate， and the correct rate of medication behavior in the observation group increased from 33.53% to 76.87%， 20.23% to 46.26%， and 49.71% to 89.80%， respectively； the proportion of the increase after the intervention was higher than that of the control group （P＜0.05）.CONCLUSIONSThis mode has effectively improved the quality of community pharmaceutical care， improves the health awareness of community residents in drug use， and promotes the standardization， rationalization and safety of residents’ drug use.关键词：WeChat mini program;school;enterprise;society
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发布时间：2024-01-11 - 摘要：In recent years， data mining algorithms have been widely employed in scientific research within the field of traditional Chinese medicine （TCM）. The data mining algorithms are used to effectively handle and analyze the complex data in TCM formulas， providing a rational explanation for the mechanism of action. This method has proven particularly useful in uncovering patterns of compatibility and frequent combinations of herbs in TCM， thereby enhancing the reliability and accuracy of clinical diagnosis， target screening， and the study of new drugs. This paper reviews and analyzes 147 papers on TCM formula research that utilize data mining algorithms. The results indicate that data mining algorithms play a unique advantage in six sub-areas， including the study on the mechanism of action in TCM formula， the dose-efficacy of TCM formulas， the identification of core drugs pairs/groups， mining the relationships among “formulas-drug-symptom”， the discovery of new formulas， and mining the compatibility law. Notably， association rules and clustering algorithms are the most representative.关键词：traditional Chinese medicine formula;bibliometrics analysis;application
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发布时间：2024-01-11 - 摘要：Yigongsan， derived from QIAN Yi’s Key to Therapeutics of Children’s Diseases in the Song Dynasty， is a classic pediatric prescription that is included in the Catalogue of Ancient Classic Prescriptions （the Second Batch of Pediatrics） released by the National Administration of Traditional Chinese Medicine in 2022. This paper verifies and analyzes the historical origin， composition， dosage， processing， decoction method and efficacy of Yigongsan by systematically combing ancient books and modern documents. As a result， Yigongsan is composed of five herbs： Panax ginseng， Poria cocos， Atractylodes macrocephala， Citrus reticulata and Glycyrrhiza uralensis， of which P. cocos should be peeled， A. macrocephala is fried with soil， G. uralensis is roasted with honey while P. ginseng and C. reticulata are raw products. According to the dosage of ancient and modern times， each medicinal herb must be ground into fine powder， 1.6 g for each， added with 300 mL of water， 5 pieces of Zingiber officinale， and 2 Ziziphus jujuba， decocted together to 210 mL， and taken before meals. In ancient books， Yigongsan is used to treat vomiting， diarrhea， spleen and stomach deficiency， chest and abdominal distension， and lack of appetite， etc. Modern research showed that Yigongsan could also be used in the diseases of immune system， respiratory system， blood system， etc.， involving infantile anorexia， asthma， anemia， tumors and so on.关键词：Yigongsan;literature research;efficacy
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发布时间：2024-01-11 - 摘要：Myocardial ischemia-reperfusion injury （MIRI） is a serious complication of revascularization in patients with myocardial infarction. The nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway plays an important role in the pathological process of MIRI. Currently，research has found that traditional Chinese medicine has a good effect on myocardial injury caused by ischemia-reperfusion. Based on the Nrf2/HO-1 signaling pathway，this article summarizes the action mechanism of traditional Chinese medicine formulas and monomers in intervening with MIRI. It is found that traditional Chinese medicine formulas （Yixin formula，Wenyang tongmai formula，Dingxin formula Ⅰ），monomers such as terpenoids （ginkgolides，astragaloside Ⅳ，ginsenosides），phenols （brazilin，hematoxylin A，resveratrol） and quinones （aloe，emodin） can alleviate MIRI by activating the Nrf2/HO-1 signaling pathway，inhibiting oxidative stress and inflammatory reactions，etc.关键词：myocardial ischemia-reperfusion injury;nuclear factor erythroid 2-related factor 2;heme oxygenase-1;signaling pathway
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发布时间：2024-01-11
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