Ready to administer infusion solutions is a sterile preparation that can be used directly for intravenous infusion of patients by compound one or more intravenous medications through aseptic operation technology.During the process of dissolution,dilution,preparation,storage,and use of intravenous drugs,the stability and compatibility of the infusion solutions may be affected by various factors,posing risks to medication safety.Currently,there is no unified technology,quality standards,or corresponding guidance documents for controlling the stability and compatibility of ready to administer infusion solutions.In order to improve the quality of ready to administer infusion solutions,ensure the safety and efficacy of intravenous medication,and reduce medication risks for patients,the Pharmacy Intravenous Admixture Services Professional Committee of Anhui Pharmacists Association has compiled the "Expert consensus on physical stability and compatibility inspection indicators for ready to administer infusion solutions".This consensus is based on experimental research,literature reviews,and expert consultations,as well as domestic practices in intravenous admixture services.The aim is to provide scientific,simple,quick,and feasible inspection methods for the quality inspection and research of ready to administer infusion solutions.
In January 2023,the American Heart Association (AHA) released A Scientific Statement:Cancer Therapy Related Hypertension,provided an overview of the mechanisms and clinical management of anticancer therapy related hypertension.Contemporary anticancer drugs are mostly at the expense of cardiovascular toxicities,one of the most common side effects is hypertension,especially vascular endothelial growth factor inhibitors,as well as tyrosine kinase inhibitors and proteasome inhibitors.Cancer therapy related hypertension is often dose limiting,and is usually reversible after interruption or discontinuation of treatment.The exact molecular mechanisms underlying hypertension are unclear,recent discoveries indicate an important role for decreased nitric oxide,increased endothelin-1,endothelial dysfunction,increased sympathetic outflow,and microvascular rarefaction.Based on the International Cardio Oncology Society (IC-OS),this article provides an interpretation of the diagnosis and management of hypertension related to cancer treatment.Insufficient evidence exists supporting an antihypertensive medication strategy specific to patients with anticancer therapy induced hypertension,therefore,antihypertensive management should follow current guidelines for the general population..Multidisciplinary cooperation is needed to optimize management to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.
Objective To study the protective effect of Wedelolactone (WEL) against inflammatory injury in human umbilical vein endothelial cells (HUVECs) and its molecular mechanism by inducing PI3K/Akt/mTOR. Methods The model of atherosclerosis (AS) oxidative stress injury in HUVECs was induced with 200 μmol·L-1 of hydrogen peroxide for 24 h.The experimental groups were as follows:normal control group,DMSO (dimethyl sulfoxide) group,H2O2 group,and WEL group.MTT was used to measure the cell survival rate of each group;flow cytometry was used to assess intracellular ROS levels;fluorescence microscopy was used to detect the expression of p62 protein;immunoblotting assay was used to determine the protein expression levels for apoptosis-related proteins associated with PI3K/Akt/mTOR signaling pathway and autophagy-related proteins. Results Compared with the H2O2 group,the HUVEC cell survival rate was significantly inhibited in the WEL group (P<0.05).ROS production was significantly lower,and the protein expressions of SOD1 and p62 were significantly increased in the WEL group as compared to the hydrogen peroxide group.The protein expression of p-mTOR,p-Akt,and p-PI3K was significantly decreased in hydrogen peroxide (P<0.01);In the WEL experiment,p-mTOR,p-Akt,and p-PI3K were increased significantly in the post-injury HUVECs (P<0.01). Conclusion Wedelolactone inhibits HUVECs' autophagy by suppressing H2O2-induced inflammatory damage in HUVECs,which may be related to the fact that WEL promotes the phosphorylation of PI3K,Akt,and mTOR proteins,inhibits autophagy and thus resists oxidative stress damage in HUVECs cells.
Objective To study the effect of curcumin on wound healing in diabetic mice. Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species (ROS) in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin (HE) and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression. Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin (15,30 mg·mL-1) group after 7 d and 14 d of wound perforation (P<0.01).Hematoxylin-eosin (HE) and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin (15,30 mg·mL-1) group.Immunofluorescence assay showed significantly higher expression of CD206 (P<0.01) and significantly reduced expression of CD86 (P<0.01) in the skin wounds of curcumin (15,30 mg·mL-1) for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin (30 mg·mL-1) group was significantly higher than that of the low-dose curcumin group (P<0.01). Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.
Objective To investigate the effects of harmine (HM) on the expression level of mitochondrion fusion related proteins and mitochondrial function injury in PC12 cells. Methods PC12 cells were divided into cell control group,HM group,mitochondrion mitosis inhibitor Mdivi-1 group,HM+Mdivi-1 group,mitochondrion fission agonist WY14643 group,HM+WY14643 group,with drug concentrations of 1,10,25,50,100 μmol·L-1.After 24 h treatment,the MTT method was used to detect the cell survival rate,and a microscope was used to observe the cell morphology,MitoTracker Red probe staining was used to observe the mitochondrial morphology and the length ratio of vertical and horizontal axes,JC-1 staining was used to detect the mitochondrial membrane potential,and a kit was used to detect ATP level and lactate dehydrogenase (LDH) activity.Immunofluorescence staining and Western blotting were used to assess the expression levels of caspase-3,apoptosis-promoting protein (Bax) cytochrome C (cyt-c),mitochondrial fusion protein (Mfn2) and mitochondrial mitotic protein (Drp-1).The interference sequence of Drp1 was transfected by electroporation,and the siRNA sequence with good transfection effect was screened.The related indicators were detected by fluorescence method,MTT method,and immunoblotting method in cooperation with drug intervention. Results MTT results showed that compared with the cell control group,the survival rate of HM group,Mdivi-1 group,HM+Mdivi-1 group,WY14643 group and HM+WY14643 group decreased significantly (P<0.01),and the EC50were (11.48±2.32),(12.35±1.67),(14.88±2.07),(39.14±3.25),(20.09±1.97),respectively.According to this,subsequent experiments selected 20 μmol·L-1for HM,WY14643 and HM+WY14643 as working concentrations to construct PC12 cell model.Microscopic observation and MitoTracker Red probe staining showed that the cell density in the drug group decreased in varying degrees,and a transition from branched to round morphology in the drug-treated groups was observed.The morphology of mitochondria tended to be round,and the ratio of the length of the longitudinal axis to transverse axis was (3.33±0.72) in the cell control group,(2.19±0.58) in the HM group,(2.45±0.44) in Mdivi-1 group,and (1.43±0.62) in HM+Mdivi-1 group,respectively.The results of JC-1 staining showed that compared with the cell control group,the mitochondrial mode potential of the HM group significantly decreased (P<0.01).ROS significantly increased (P<0.01) and ATP levels decreased (P<0.01),and LDH enzyme activity increased (P<0.01).Immunofluorescence staining and Western blotting results showed that compared with the cell control group,the expression levels of proapoptotic proteins Bax,cytochrome C,and caspase-3 in the HM group were significantly increased (all P<0.01).Compared with the cell control group,the expression level of mitochondrial fission related protein Drp1 in HM group was significantly higher(P<0.01).The expression level of mitochondrial fusion related protein Mfn2 significantly decreased (P<0.01).After specific interference with Drp1 and synergistic intervention with HM,the survival rate of PC12 cells in each interference group decreased compared to each drug intervention group.The expression of Drp1 and Mfn2 was downregulated,and the differences were statistically significant (P<0.05 or P<0.01). Conclusion HM can reduce the mitochoudrial membrane potential and ATP levels by accumulating ROS,there by activating the caspase-3 apoptosis pathway and promoting cell apoptosis.Mitochondrial fusion division may be involved in the damage of PC12 cells caused by HM,initiating apoptosis through the mitochondrial pathway.
Objective To analyze the achievement of target vancomycin concentration and the risk factors affecting the concentration to reach the target,providing a reference for the rational use of vancomycin and the implementation of therapeutic drug monitoring (TDM). Methods Patients who were hospitalized and received vancomycin TDM from January 2016 to June 2019 at Zhongshan Hospital,Fudan University were selected.Clinical data,vancomycin blood concentrations,and occurrences of acute kidney injury (AKI) during the hospitalization were collected.Factors affecting the attainment of target vancomycin concentrations were analyzed using logistic regression and grouped according to whether the target concentrations were attained.The correlation between drug concentration and the occurrence of AKI was analyzed. Results A total of 1 106 patients were included,with 70.7% being males and a median age of 60.0 (IQR=20) years.Surgical departments accounted for 76.4% of the distribution.The median duration of vancomycin therapy was 10.8 d (IQR=9.0).A total of 21.6% of patients had their first concentration monitored before administration of doses 4 and 5.The drug concentration monitoring results of 46.8% (518/1 106) of patients were in the range between 10-20 μg·mL-1,reaching the target concentration range.The incidence of vancomycin-associated AKI was 25.9%.The incidence of AKI varied among patients with different vancomycin concentrations:when the concentrations are <10,10-<15,15-20,and >20 μg·mL-1,the AKI rates are 15.8%,20.5%,25.8%,and 39.4%,respectively.Multivariate logistic regression analysis showed that target concentrations were more likely to be reached with a dosing course of >7-14 d (OR=1.688,P=0.001) and >14 d (OR=1.744,P=0.002) than with a dosing course of ≤7 d. Patients receiving conventional daily doses were more likely to achieve target concentrations than those receiving the non-conventional daily dose (OR=1.540,P=0.003). Conclusion The current status of vancomycin TDM in China still suffers from deficiencies,such as delayed timing of monitoring and low rate of target concentration attainment.Higher vancomycin concentrations are significantly associated with AKI,and the factors affecting the vancomycin concentration to reach the target mainly include treatment duration and the complexity of the dosing regimen.
Objective To establish a highly sensitive,stable,and universally applicable ultra-high-performance liquid mass spectrometry tandem method (UPLC-MS/MS) for simultaneous determination of nirmatrelvir and ritonavir blood concentrations in human plasma. Methods The separation was performed on an ACQUITY UPLC BEH C18 column (2.1 mm×50 mm,1.7 μm) with gradient elution,and the mobile phase consisted of 0.1% formic acid-water and 100% acetonitrile at the flow rate of 0.3 mL·min-1.The column temperature was 45 ℃,and the injection volume was 2 μL.Electrospray ionization as ion source (ESI+) was used as the ion source and multiple reactions monitoring mode (nirmatrelvir m/z 500.20→319.10,nirmatrelvir-D9 m/z 508.59→328.10,ritonavir m/z 721.30→426.10,13C,2H3-ritonavir m/z 725.30→426.10) was adopted.Thirty patients with coronavirus disease 2019(COVID-19) treated with nirmatrelvir and ritonavir at the People's Hospital of Changxing County in Jan.2023 were selected to measure their steady-state trough concentrations of nirmatrelvir and ritonavir after 3 days of treatment. Results The linear range of nirmatrelvir was 0.100-10.0 μg·mL-1 (R2=0.997 2),and the linear range of nirmatrelvir was 0.050-5.00 μg·mL-1 (R2=0.995 2).The recovery rates of nirmatrelvir and lopinavir were both >90% and the intra-batch and inter-batch precision relative standard deviations (RSDs) were both <10%.Additionally,the recovery ranges for nirmatrelvir and lopinavir were 91.5%-97.0%,and the matrix effects ranged from 92.4% to 97.7%.The results of clinical samples showed that the plasma concentrations of nirmatrelvir and ritonavir in patients with COVID-19 varied greatly among individuals. Conclusion The method for simultaneous determination of nirmatrelvir and ritonavir concentrations in human plasma established in this study is convenient,highly specific,highly accurate,with high precision,which is suitable for monitoring the concentrations of nirmatrelvir and ritonavir in patients.
Objective To establish a quality control method for monitoring the blood concentrations of cyclosporin A and tacrolimus by HPLC-MS/MS,and to evaluate the quality control samples using the Westgard multi-rule theory. Methods HPLC-MS/MS was used to determine the concentration of cyclosporin A and tacrolimus in human whole blood.The quality control samples of low,medium and high concentration levels in the therapeutic drug monitoring process were statistically analyzed,Levery-Jennings and Z-score quality control charts were drawn,and the Westgard multi-rule theory was applied for in-house quality control evaluation. Results The established method was fully validated with linear ranges of 10.40-1 040.00 ng·mL-1and 0.50-49.50 ng·mL-1,the quantification limits were 10.40 and 0.50 ng·mL-1,respectively.The extraction recoveries were 108.61%-113.24%and 101.99%-109.37%,respectively.The matrix factors normalized by internal standard were 106.68%-111.27%and 95.70%-97.81%for cyclosporin A and tacrolimus,respectively.The intra-day and inter-day accuracy and precision were less than 15.0%.Other parameters were also validated and met the acceptance criteria.Levery-Jennings and Z-score quality control charts showed that there were 4 warnings (violation of the 12s rule) in the results of the 26 groups of quality control samples in the third quarter of 2022,and no phenomenon was observed to be out of control. Conclusion The established in-house quality control system for therapeutic drug monitoring of cyclosporin A and tacrolimus can effectively ensure the accuracy of blood drug concentration detection.
Objective To assess the pharmacokinetic characteristics of two types of tofacitinib citrate tablets in healthy individuals and evaluate their bioequivalence and safety. Methods A randomized,two-period,self-crossing design was used with 36 subjects in two groups in both fasting and postprandial conditions.Each group received 5 mg tofacatile citrate tablets of either generic tofacitinib citrate tablets (T) or the reference product (R) per period,and the plasma concentration of tofacatile tablets was detected by LC-MS/MS.Phoenix WinNonlin software was used to calculate pharmacokinetic parameters and evaluate its bioequivalence. Results After single oral administration of test and reference preparations,the main pharmacokinetic parameters were as follows:Cmax values in fasting group were (57.54±13.95) and (59.17±12.31) ng·mL-1,respectively;AUC0-t values were (143.83±34.58) and (142.13±33.00) ng·h·mL-1,respectively;AUC0-∞ values were (147.39±35.27) and (146.15±34.64) ng·h·mL-1,respectively;tmax was 0.5 h for both;Cmax values in the postprandial group were (57.16±17.56) and (55.19±21.98) ng·mL-1;AUC0-t values were (165.47±41.63) and (162.04±41.84) ng·h·mL-1;AUC0-∞ values were (171.88±44.15) and (168.05±44.21) ng·h·mL-1;The t max was 1.0 h for both.The 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ in fasting group and postprandial group were 96.35% (90.11%-103.03%) and 105.91% (95.20%-117.83%),101.02% (98.76%-103.34%) and 102.23% (99.67%-104.86%),100.77% (98.53%-103.06%) and 102.40% (99.81%-105.06%),all within the range of 80.00%-125.00%. Conclusion Both types of generic tofacitinib citrate tablets are bioequivalent and safe in Chinese healthy individuals.
Objective To develop an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS /MS) method for the simultaneous quantification of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in human plasma and to apply it to the therapeutic monitoring. Methods Dolutegravir-D5,raltegravir-D4,efavirenz-D5,lamivudine-13C-15N2and tenofovir-D7 were used as internal standard,respectively.All samples were extracted using the protein precipitation method with acetonitrile and then diluted for analysis.Chromatographic separation was performed on Shim-pack XR-ODS Ⅲ(2.0 mm×50 mm,1.6 μm)column.Mobile phases A and B consisted of 0.1% formic acid in water and acetonitrile respectively.A programmed mobile phase gradient was used at a flow rate of 0.3 mL·min-1and column temperature of 40 ℃.The tandem mass spectrometer was equipped with an electrospray ionization (ESI) source operating in multiple reaction monitoring (MRM) modes.After methodological validation,it can be used for therapeutic drug monitoring in HIV patients. Results There was good linearity in the validated concentration ranges of 62.5-3 000 ng·mL-1for dolutegravir,10-500 ng·mL-1for raltegravir,125-6 000 ng·mL-1for efavirenz,10-500 ng·mL-1for lamivudine and 10-500 ng·mL-1for tenofovir with the linear correlation coeffificients of determination(R2) of all higher than 0.998.The accuracy of both intra-day and inter-day studies ranged from 94.0%-109.3%,and the relative standard deviations were less than 7%.The IS-normalized matrix factor and extraction recoveries of all analytes were 95.7%-106.0%and 98.7%-104.5%at all concentrations.All analytes were stable in plasma at a certain storage environment.The trough blood concentrations of dolutegravir,efavirenz,lamivudine and tenofovir were 107.7-2 366.0,740.0-3 410.0,38.5-1 229.3,31.6-224.4ng·mL-1in HIV patients,respectively. Conclusion The method is highly aceurate,easy to perform,low-cost,and suitable for therapeutic drug monitoring of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in HIV patients.
Originally used as an antimalarial drug,hydroxychloroquine is now widely used in the treatment of rheumatic immune diseases due to its cost-effectiveness,safety,and efficacy.In addition to its immunomodulatory effects,hydroxychloroquine also exhibits antithrombotic,anti-hypolipidemic,and anti-hypoglycemic properties.Hydroxychloroquine blood levels are correlated with clinical outcomes and adverse reactions,and can reflect patient compliance.However,due to the complex pharmacokinetic profile of hydroxychloroquine,significant inter-individual differences in blood concentration exist even with the administration of the same dosage.This study investigates the factors affecting the blood concentration of hydroxychloroquine in terms of physiological factors,pathological factors,metabolic enzyme gene polymorphisms,and drug-related factors.The aim is to provide a reference for rational clinical use and the development of individualized dosing.
Objective To explore the clinical effect of clinical observation of supplemented wendan decoction combined with Western medicine in treating insomnia accompanied by anxiety and depression in phlegm-heat internal disturbance syndrome. Methods A total of 120 cases of insomnia with anxiety and depression comorbiditis with phlegm heat disturbance syndrome were randomly divided into control group and treatment group,60 cases in each group.The control group was given escitalopram oxalate tablet combined with dexzopiclonone tablet,and the observation group was given added Wendan decoction on the basis of the control group.Both groups were treated continuously for 6 weeks.Polysomnography monitoring parameters and heart rate variability were compared between the two groups during baseline period and visit 2 (baseline period+3 months).Scale scores of the two groups were compared during baseline period,visit 1 (baseline period+6 weeks) and visit 2.The content of heart rate variability includes:time domain analysis (standard deviation of normal interval (SDNN),square root of the square sum of the mean of the difference between adjacent normal interval (RMSSD) and frequency domain analysis (LF,HF,LF/HF).The scale scores included the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) to assess sleep status,and the Hamilton Depression Scale (HAMD),Hamilton Anxiety Scale (HAMA),Self-assessment Scale for Depression (PHQ-9) and Generalized Anxiety Disorder Scale (GAD-7) to assess anxiety and depression status. Results (1) Polysomnography monitoring:the wake time of observation group was significantly shorter than that of control group,the number of awakenings was significantly less than that of control group,and the percentage of N3 and REM was significantly higher than these of control group (P<0.05).(2) Heart rate variability:RMSSD and HF values in the observation group were significantly higher than those in the control group,and LF/HF values were significantly lower than those in the control group (P<0.05).(3) In terms of sleep:during the interview,PSQI total score,sleep quality,hypnotic drugs and daytime dysfunction in the observation group were significantly lower than those in the control group (P<0.05);At the 3 months,the sleep quality,hypnotic drugs and daytime dysfunction in the observation group were significantly lower than those in the control group (P<0.05).In terms of emotion:HAMA,HAMD and GAD-7 scores were significantly lower than those of control group at 6 weeks (P<0.05);At the 3 months,HAMA and GAD-7 scores were significantly lower than those of control group (P<0.05). Conclusion Supplemented Wendan decoction combined with western medicine can obviously optimize the sleep structure of insomnia patients with anxiety and depressionof phlegm-heat disturbance syndrome,improve sleep continuity and deepen sleep depth,and improve parasympathetic functional activities,contribute to sympathetic parasympathetic balance,can improve insomniaand depression symptoms recently,and significantly improve anxiety symptoms in the short term,with good safety.
Patients with gastric cancer are at high risk for venous thromboembolism (VTE) and bleeding,and patients who develop VTE are often associated with poor outcomes,making it clinically challenging to identify and manage the risk of thrombosis in patients with gastric cancer.Risk factors for VTE in gastric cancer patients include age,obesity,surgery,chemotherapy,etc.It is essential to identify high-risk patients and adopt aggressive prevention strategies.The main strategy to prevent and treat VTE is the use of anticoagulant drugs.This article discusses guidelines and recent studies for the prevention and treatment of VTE in patients with gastric cancer to help clinicians make individualized decisions for their patients and maximize clinical outcomes for their patients.
Alzheimer's disease (AD) is a disease with clinical manifestations of learning and memory impairment,cognitive dysfunction,and language dysfunction,the pathogenesis of AD is complex,of which Aβ theory covers various mechamisms such as oxidative stress,inflammation,apoptosis and other mechanisms.Based on the Aβ mechanism and related signaling pathways,this study discusses the overview of typical Chinese medicines and their active ingredients in the prevention and treatment of AD.The aim is to provide insights and references for the development of traditional Chinese medicines for the prevention and treatment of AD.
Coronavirus disease 2019 (COVID-19) has been one of the most concerning public health events in recent years,seriously threatening the lives and health of people worldwide.COVID-19 vaccines are the most cost-effective measure to reduce the influence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) to the population.Therefore,countries actively develop and vaccinate COVID-19 vaccines,including recombinant protein vaccines,viral vector vaccines,inactivated vaccines,and mRNA vaccines,which occupy the primary market.With the enhancement of variants transmission ability and evasion immunity,the protective effect and durability of COVID-19 vaccines have become the current research hotspots.This paper presents a brief review of the progress of COVID-19 vaccines,intending to provide a reference for the development of COVID-19 vaccines.
Phytoestrogens refer to a class of compounds in plants that can bind to and activate estrogen receptors in mammalian organisms,exerting varying degrees of protective and improvement effects on the body.Modern pharmacological studies have found that phytoestrogens have therapeutic effects on the cardiovascular system,nervous system,endocrine system,immune system,and so on.It is worth noting that the binding of phytoestrogens to estrogen receptors in the brain can produce central neuroprotective effects and improve learning and cognitive impairment in Alzheimer's pectients through multiple targeted pathways.This paper describes the research progress and related mechanisms of phytoestrogen-like monomers,Chinese herbal medicine,and compound formulations in Alzheimer's disease.The aim is to provide new drug design ideas and solutions for the effective treatment of senile dementia with traditional Chinese medicine.
Small molecule drug screening technology is continuously evolving and expanding along with drug discovery,and the innovation in drug screening technology can improve the research and development efficiency and success rate,shorten the cycle time,and reduce the cost.From traditional screening technologies based on known active compounds and high-throughput screening (HTS) to new technologies such as structure-based drug discovery (SBDD),fragment-based drug discovery (FBDD),DNA encoded compound library (DEL) and proteolysis targeting chimeras (PROTAC),small molecule drug screening technologies are continuously broadening the market potential for small molecule drugs.This article will provide an overview of the current status of small molecule drug screening technology,systematically review each technique along with their advantages and disadvantages,and offer essential insights for the development of new small molecule drug screening technologies.
Pulmonary hypertension has a high mortality rate,and although targeted therapy is available,it is still incurable,and the long-term prognosis for patients is poor.As a tyrosine kinase inhibitor,imatinib was approved for marketing in China in 2002 for the treatment of chronic myelogenous leukemia and other tumor diseases.In addition to the antitumor effects,imatinib was found to improve hemodynamics and exercise tolerance in patients with severe pulmonary arterial hypertension,but the safety was suboptimal.With the emergence of new formulations of imatinib targeted at the lungs,it is expected to become a new targeted drug for pulmonary arterial hypertension.
Objective Based on HPLC fingerprinting and chemometrics,to evaluate the quality of Schefflera kwangsiensis Merr. from Guangxi. Methods HPLC was used to establish fingerprints of Schefflera kwangsiensis Merr.from ten different origins,and gradient elution was carried out with methanol-0.1% phosphoric acid aqueous solution as mobile phase.Cluster analysis (CA),principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to evaluate quality. Results The fingerprints of Schefflera kwangsiensis Merr.from ten different origins were established by HPLC,a total of 22 common peaks were calibrated,with a similarity range of 0.922-0.999.Four chromatographic peaks were identified as rhodopsin,4,5-bis-O-caffeoylquinic acid,caffeic acid,and naringin.The samples were classified into four types according to the CA and OPLS-DA. PCA identified four principal components with a cumulative contribution rare of 95.39%. Conclusion The quality of Schefflera kwangsiensis Merr. can be comprehensively evaluated by fingerprinting combined with CA,PCA and OPLS-DA analysis.The Study can provide a reference for improving the quality control and assessment of Schefflera kwangsiensis Merr.
Objective A comprehensive evaluation of oral anticoagulants (OACs) was conducted using the A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions (the Second Edition),to provide a reference for drug selection and clinical medication decisions in medical institutions. Methods Evaluation evidence was collected,and the drugs included in the evaluation were quantified on four dimensions of clinical properties (efficiency and safety),pharmaceutical properties,economy and others. Results All oral anticoagulants included in the evaluation had a score of 70 or higher in the comprehensive evaluation,while warfarin had the highest overall score.Clinical properties and pharmacologic properties were identified as the core attributes for drug selection evaluation. When considering only these factors,edoxaban received the highest score. Conclusion OACs are the preferred option for patients requiring long-term anticoagulation therapy.Various OACs offer distinct clinical advantages.Utilizing the Guidelines (Second Edition) for oral anticoagulant selection and evaluation can offer visual evidence for drug selection and promote the scientific,rational,and safe use of drugs in clinical management.
Objective To investigate the pathogenic characteristics and use of antibiotics in children with acute osteomyelitis,and to provide evidence for rational drug use in the clinic. Methods The clinical data of 266 children with acute osteomyelitis admitted to the Department of Orthopedics,Children's Hospital Affiliated to Zhengzhou University from January 2019 to December 2022 were retrospectively analyzed,and the basic information,pathogenic microorganisms,drug sensitivity test results,and antibacterial drug use of the children were statistically analyzed. Results In 266 cases of pediatric acute osteomyelitis,all underwent pathogen examination,and 148 cases were cultured for pathogens with a positive detection rate of 55.64%.A total of 154 strains of bacteria were detected.The top three pathogens were Staphylococcus aureus (104 strains,67.53%),Staphylococcus epidermidis (8 strains,5.19%),and Staphylococcus hominis (7 strains,4.55%).The detection rate of methicillin-resistant Staphylococcus aureus (MRSA) was 33.65%.Compared with methicillin-sensitive Staphylococcus aureus (MSSA),there was no significant difference in disease severity and prognosis of infection with MRSA.The utilization rate of antibiotics was 100.00%;227 cases of empirical antibiotics were used alone,accounting for 85.34%,primarily using ceftriaxone.Combination therapy was used in 39 cases,accounting for 14.66%,mainly ceftriaxone combined with vancomycin;the average course of intravenous drugs was 40.20 days.After receiving the drug sensitivity test results in 148 cases,76 cases (51.35%) continued the original treatment plan due to effective treatment.In 37 cases (25.00%),treatment was adjusted based on the drug sensitivity results due to poor treatment outcomes;the drug sensitivity results indicated sensitivity,but the clinical effect was not good in 25 cases accounting for 16.89%,which changed the drug treatment.In 10 cases (6.76%),clinical treatment was effective,leading to a switch to narrow-spectrum antibiotics or a change from combination therapy to monotherapy based on drug sensitivity results. Conclusion Empiric antibacterial therapy can cover common pathogens in children with acute osteomyelitis,and medication regimens can be adjusted according to clinical efficacy and drug sensitivity.However,the course of intravenous antibiotic treatment is too long,so it is necessary to further optimize the timing of transitioning from intravenous to oral administration.
Objective To analyze the pathogenic bacteria and drug resistance of peritoneal dialysis-associated peritonitis(PDAP),and provide a clinical reference for the rational use of antibiotics. Methods The demographic data of PDAP patients admitted to the peritoneal dialysis(PD) Center of the First Affiliated Hospital of Soochow University from July 1,2015 to December 30,2021 were collected,and the pathogens,drug resistance and prognosis were retrospectively analyzed. Results A total of 150 episodes of PDAP occurred in 92 patients.The positive rate of PD fluid culture was 61.33%,including 65 cases(70.65%) of Gram-positive(G+) bacteria,mainly Staphylococcus and Streptococcus.Gram-negative(G-) bacteria were in 16 cases(17.39%),mainly Escherichia coli and Enterobacter cloacae.There were 11 cases(11.96%) of multiple infections,including 5 cases of combined fungal infection.From 2016 to 2021,the incidence of G+ bacteria-related PDAP decreased from 14 to 8 cases.G+ strains were resistant to methicillin(35.00%),and were sensitive to linezolid(100.00%),teicoplanin(100.00%) and rifampicin(100.00%).The sensitivity rate to vancomycin was 98.59%.G- strains were sensitive to ceftazidime(86.36%),ceftizoxime(88.89%) and amikacin(100.00%).The MIC of vancomycin against Staphylococcus showed an upward trend in 2019-2021.The overall cure rate of PDAP was 81.33% in patients who responded to antibiotic treatment,and the cure rate of G+ bacteria was higher than that of multiple infections(89.23% vs. 36.36%,P<0.01).The outcome of patients with multiple infections,especially those with concurrent fungal infection was poor. Conclusion The incidence of PDAP in the PD center has shown a decreasing trend in recent years.G+ bacteria are still the main pathogenic bacteria causing PDAP,and they are highly resistant to methicillin,so vancomycin should be used as empirical therapy.For G-bacteria,cefotaxime and amikacin can be chosen as empirical therapy.There is a drift in the MIC values of vancomycin against Staphylococcus in the study period,so it is necessary to monitor the MIC of vancomycin against Staphylococcus and its changing trend.
Objective To present a pharmaceutical care case of a pediatric patient with nephrotic syndrome developing tacrolimus-inducedposterior reversible encephalopathy syndrome (PRES) during tacrolimus treatment,and to accumulate experience for the treatment and pharmaceutical services of related diseases. Methods Clinical pharmacists conduct an analysis and evaluation of the correlation of drug-induced PRES caused by tacrolimus in a pediatric patient.Simultaneously,regarding the latest evidence-based information,they propose optimized drug therapy recommendations and provide personalized pharmaceutical services. Results After treatment with antispasmodics,blood pressure control,intracranial pressure reduction,and tapering of tacrolimus,the clinical symptoms of the child improved.Follow-up cranial MRI demonstrated partial absorption of abnormal signals in the brain,and the lesions were significantly smaller than before. Conclusion For tacrolimus-related PRES,clinical pharmacists can enhance the long-term safety and effectiveness of patient medication through aspects such as choosing antihypertensive drugs,adjusting treatment plans based on drug concentration monitoring,and implementing targeted pharmaceutical monitoring and educatio.
Objective To investigate the characteristics of clopidogrel-associated thrombocytopenia to provide references for clinically safe drug use. Methods The case reports of thrombocytopenia induced by clopidogrel published in PubMed,Embase,CNKI,Wanfang and VIP were searched from the establishment of each database to November 2022,and their occurrence was collated and analysed. Results A total of 44 cases from 43 articles were identified and included in the analysis.There were 30 males (68.2%) and 14 females (31.8%).Ages ranged from 37 to 88 (65.0±11.4) years,of which 30 (68.2%) were ≥60 years old.Thrombocytopenia was found from 8 h to 9 months after medication,of which 29 cases (65.9%) appeared within two weeks.There were 31 cases (70.5%) with severe thrombocytopenia and 38 cases (86.4%) with complications,of which 24 cases (63.2%) with bleeding and 19 cases (50.0%) with thrombotic thrombocytopenic purpura (TTP).The platelet count of 41 cases (93.2%) returned to normal after drug withdrawal and symptomatic treatment,and 3 cases (6.8%) died finally. Conclusion Clopidogrel related thrombocytopenia is mainly severe thrombocytopenia,and often accompanied by bleeding or thrombotic thrombocytopenic purpura (TTP),but the overall outcome is good.Platelet count should be regularly monitored within the first two weeks after medication.Clopidogrel should be stopped and symptomatic treatment should be given in case of any abnormality.
Objective To investigate the current situation,problems and suggestions of pharmacovigilance activities conducted by drug marketing authorization holders(MAH) and pharmacovigilance inspections carried by regulatory authorities. Methods A questionnaire survey was conducted on relevant institutions and personnel responsible for pharmacovigilance inspections in 31 provinces, autonomous regions, municipalities and the Xinjiang Production and Construction Corps. The MAH pharmacovigilance activities were rated from 5 aspects (5 major items and 27 specific items). Results The average overall score for 5 major items was 3.46;The average score for 27 specific activities was 3.50.The MAH scored the highest in terms of pharmacovigilance organization,personnel,and resources,and scored the lowest in terms of drug risk identification and assessment. Conclusion MAH needs to further strengthen their awareness of primary responsibility,gradually improve the pharmacovigilance system,and constantly improve the ability and level of pharmacovigilance;The drug regulatory department should also provide guidance to enterprises,establish and improve the team of inspectors,and systematically advanced various aspects of pharmocovigilance inspection.
Objective To provide a reference for biopharmaceutical enterprises in China to improve innovation efficiency and the government to formulate relevant policies. Methods Research and development-related data and regional environmental data of 32 listed biopharmaceutical companies from 2015 to 2021 were selected to measure the innovation efficiency of listed biopharmaceutical companies with the three-stage data envelopment analysis (DEA) model,excluding the impact of environmental factors and random disturbances. Results After excluding the impact of environmental factors and random disturbances,the average innovation efficiency of listed biopharmaceutical enterprises was 0.46.The average pure technology efficiency and scale efficiency were 0.99 and 0.46,respectively. The regression coefficients among economic development level,government support intensity,degree of competition,opening-up level,and the slack value of R & D personnel were 185.97(P<0.05),105.67(P>0.10),385.81(P<0.01),-121.64(P<0.05),respectively.The regression coefficients between economic development level,government support,degree of competition,opening-up level,and the slack value of R & D investment were 136.13(P>0.10),258.61(P<0.01),285.33(P<0.01),-30.52(P>0.10),respectively. Conclusion The innovation efficiency of listed biopharmaceutical enterprises in China is at a relatively low level.Scale efficiency is the main factor restricting the improvement of innovation efficiency.The regional opening-up level contributes to the improvement of innovation efficiency of listed biopharmaceutical companies,while the level of competition,government support and economic development level constrain improvements in innovation efficiency. The external environment hinders the improvement of the concentration degree of the biopharmaceutical industry,which hurts exerting the scale effect for enterprises.