最新刊期
卷 35 ， 期 18 ， 2024
- 摘要：OBJECTIVETo establish a research indicator evaluation system suitable for pharmaceutical personnel in children’s hospitals， and provide technical support and reference basis for the evaluation of scientific research capabilities of pharmacy personnel.METHODSThe literature/text research methods were adopted to search related literature， policies， regulations and research reports of scientific research management； brainstorming method was used to sort out the key elements and decompose the indicators at all levels step by step. On this basis， using the method of expert interview， the key elements were clarified， the three-level index evaluation system was preliminarily drawn up， and the letter inquiry paper was made accordingly. Finally， Delphi method was used to establish the evaluation system of scientific research indicators for pharmacists through three screening criteria [importance assignment＞3.5， coefficient of variation＜25%， and unimportant percentage （including unimportant and very unimportant）＜50%].RESULTSOverall 36 questionnaires were distributed by two rounds of expert letters， and 36 questionnaires were recovered， with a recovery rate and an effective rate of 100% for both rounds. The average expert judgment coefficient was 0.912， the average expert familiarity level was 0.747， and the average expert authority coefficient was 0.830. After the second round of letters and inquiries， the values of Kendall’s W of the first-level， the second-level and the third-level indicators were 0.269， 0.379 and 0.460， which were significantly higher than the results of the first round of inquiry （P＜0.01）. Finally， the evaluation system of scientific research indicators for pharmacists was determined with 4 first-level indicators， 18 second-level indicators and 62 third-level indicators.CONCLUSIONSThe pharmaceutical experts from the children’s hospital selected in this study have high authority and wide professional coverage； the evaluation system of scientific research indicators for pharmacists has certain standards and norms， which can provide a powerful reference for the professional level assessment and scientific research ability evaluation of pharmacists.关键词：evaluation indicator system;children’s hospital;pediatric pharmacist
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发布时间：2024-09-25 - 摘要：OBJECTIVETo know about the working mode and human resource status of pharmacy intravenous admixture services （PIVAS） in national medical institutions.METHODSThrough questionnaire survey， the national PIVAS was invited to fill out questionnaire and statistical analysis was performed on the effective sample data related to PIVAS working mode and human resources in the questionnaire.RESULTSIn this study， 761 PIVAS from 722 medical institutions of 29 provinces were involved in the questionnaire survey， with 471 valid questionnaires for working mode and 441 valid questionnaires for human resources survey. In terms of working mode， among 471 PIVAS， 292 PIVAS （62.0%） were in pharmacist-alone mode， and 176 PIVAS （37.4%） were in pharmacist-nurse cooperative mode； there was no significant difference in the types of medical orders received by PIVAS between these two working modes except for the other medical orders （P＞0.05）. In terms of human resource setting， among 441 PIVAS， the average number of total staff of single PIVAS was 24（16，33）， including 11（6，19） pharmacists， 7（2，13） nursing staff， and 3（1，5） workers； there was a statistically significant difference in the number of personnel among three groups （P＜0.01）. The per capita income of PIVAS respondents in 2019 was [7.9（4.8，10.7）]×104 yuan， and in 2021 it was [8.8（5.8，11.7）]×104 yuan， with an increase of 9.0% compared to 2019. The difference between the two groups was statistically significant （P＜0.01）.CONCLUSIONSMedical institutions’ PIVAS in China had not fully implemented the pharmacist-alone work model， and some medical institutions had chosen a pharmacist-nurse cooperative mode. It is suggested that relevant departments formulate corresponding qualification requirements and training standards for nursing personnel as soon as possible based on sufficient research on PIVAS’s demand for nursing professionals.关键词：working mode;human resources;cross-sectional study
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发布时间：2024-09-25 - 摘要：OBJECTIVETo assess the blending types and workload of pharmacy intravenous admixture services （PIVAS） in China.METHODSBy questionnaire survey， the working status of PIVAS in different levels of hospitals nationwide was investigated， involving the types of blending infusion， daily blending volume of hazardous drugs infusion， parenteral nutrition solution， general and antibacterial drug infusion， intravenous bolus drugs， skin test solution and intravenous agents， as well as the daily packing volume.RESULTSA sample of 750 PIVAS in 30 provinces （autonomous regions， municipalities） across China were surveyed by questionnaire， involving 621 tertiary hospitals and 90 secondary hospitals. The main types of liquid preparation were intravenous infusion， followed by parenteral nutrition solution， and chemotherapy pump （including chemotherapy infusion）， accounting for 99.73%， 79.47% and 43.33%， respectively. The daily blending volume of hazardous drugs infusion， parenteral nutrition solution， general and antibacterial drug infusion， intravenous bolus drugs， skin test solution and intravenous agents in PIVAS of tertiary hospitals were 23.00 （9.00， 56.50） sets， 31.00 （13.97， 74.00） bags， 813.00 （375.00， 2 061.75） bags， 426.00 （210.00， 987.00） bags， 30.00 （6.00， 155.00） ampoules， 30.00 （7.13， 136.84） ampoules， 3 200.00 （1 684.50， 5 554.50） ampoules respectively， while the daily packing volume was 218.50 （52.26， 559.00） bags； above indexes of PIVAS in secondary hospital were 4.00（2.00，12.00）sets， 8.90（3.00，23.00）bags， 270.50（108.00， 2 061.75）bags， 157.00（71.00，987.00）bags， 5.85（3.75，141.00） ampoules， 0 ampoule， 1 349.00（548.10，2 408.00）ampoules， 107.50（33.25，207.00）bags.CONCLUSIONSThe scope of blending types of PIVAS has been significantly expanded， and tertiary hospitals are significantly higher than secondary hospitals in the blending and packing volumes of all types of intravenous fluids and drugs dispensed， showing obvious advantages in dealing with complex medications and high-risk treatments.关键词：blending types;blending volume;packing volume
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发布时间：2024-09-25 - 摘要：OBJECTIVETo investigate the mechanism of Yifei xuanfei jiangzhuo formula （YFXF） against vascular dementia （VD）.METHODSThe differentially expressed genes of YFXF （YDEGs） were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear， support vector machine， extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion， and were randomly divided into model group and YFXF group （12.18 g/kg， by the total amount of crude drugs）， and sham operation group was established additionally， with 6 rats in each group. The effects of YFXF on behavior （using escape latency and times of crossing platform as indexes）， histopathologic changes of cerebral cortex， and the expression of proteins related to the secreted phosphoprotein 1 （SPP1）/phosphoinositide 3-kinase （PI3K）/protein kinase B （aka Akt） signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated.RESULTSA total of 6 YDEGs were obtained， among which SPP1， CCL2， HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy （area under the curve of 0.954）. Compared with the model group， YFXF could significantly shorten the escape latency of VD rats， significantly increase the times of crossing platform （P＜0.05）； improve the pathological damage of cerebral cortex， such as neuronal shrinkage and neuronal necrosis； significantly reduce the expressions of SPP1 protein and mRNA （P＜0.05）， while significantly increase the phosphorylation levels of PI3K and Akt （P＜0.05）.CONCLUSIONSVD high-risk genes SPP1， CCL2， HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.关键词：vascular dementia;network pharmacology;nomogram model;machine learning model;SPP1/PI3K/Akt signaling pathway
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发布时间：2024-09-25 - 摘要：OBJECTIVETo investigate the effects of polydatin （PD） on the inflammatory response in dry eye disease （DED） rats and its potential mechanism based on protein kinase A （PKA）/cyclic adenosine monophosphate response element binding protein （CREB） signaling pathway.METHODSMale SD rats were randomly divided into blank control group （normal group）， model group （simple DED group）， 0.05%PD group， 0.5%PD group and 0.5%PD+PKA inhibitor H-89 group （0.5%PD+H-89 group）， with 15 rats in each group. Except for the normal group， the rats in other groups were prepared with a DED model by injecting scopolamine hydrobromide 12.5 mg/d onto the surface of eyeball. At the same time， each drug group was given corresponding liquid medicine （0.5% or 0.05% PD， eye drip， 3 times a day； 1 mg/kg H-89， intraperitoneal injection， once a day） for 7 d in total. The tear secretion， corneal fluorescein staining score and conjunctival goblet cell density of rats were detected in each group； the pathological changes of corneal tissues were observed， and the levels of inflammatory factors （tumor necrosis factor-α， interleukin-1β， interleukin-6） and the expression of PKA/CREB signaling pathway-related proteins were detected in corneal tissues.RESULTSCompared with normal group， the corneal epithelium of rats in the simple DED group was thickened， stromal layer cells were disordered and partially absent， nuclear spacing was larger， and a large number of inflammatory cells infiltrated； the tear secretion， conjunctival goblet cell density and the phosphorylation levels of PKA and CREB in corneal tissues were reduced significantly， while the corneal fluorescein staining score and the levels of inflammatory factors in corneal tissue were increased significantly （P＜0.05）. Compared with the simple DED group， the pathological injuries of corneal tissues of rats in 0.05%PD and 0.5%PD groups were alleviated， each quantitative index was significantly improved， and the improvement effect of 0.5%PD group was more obvious （P＜0.05）. H-89 could reverse the improvement effect of PD on each index significantly （P＜0.05）.CONCLUSIONSPD can increase tear secretion and the conjunctival goblet cell density， and reduce the inflammatory response and pathological injury of corneal tissue in DED rats. The above effects are related to the activation of PKA/CREB signaling pathway.关键词：dry eye disease;inflammatory response;PKA/CREB signaling pathway
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发布时间：2024-09-25 - 摘要：OBJECTIVETo explore the effects and mechanism of Bielong ruangan decoction on liver cancer model rats.METHODSThirty-two male SD rats were randomly divided into control group， model group， and Bielong ruangan decoction low-dose and high-dose groups [6.84， 27.36 g/（kg·d）， by raw material]， with 8 rats in each group. Except for the control group， other groups were intraperitoneally injected with diethylnitrosamine （DEN） 50 mg/kg （once a week， for 16 consecutive weeks） to induce liver cancer model. At the 8th week of DEN injection， Bielong ruangan decoction low-dose and high-dose groups were orally administered with the corresponding medication， twice a day， until the 16th week. The general condition of rats in each group was observed during the experimental period. After the final administration， the body weight and liver mass were weighed， and the liver indexes were calculated； serum contents of alanine transaminase （ALT） and aspartate transaminase （AST） were determined； the appearance， pathological morphology and degree of fibrosis of liver were observed； Ishak scoring for liver fibrosis was performed； the mRNA and protein expressions of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）， caspase-1， gasdermin D （GSDMD）， interleukin-18 （IL-18）， IL-1β in liver tissue were detected.RESULTSCompared with the model group， the general condition of rats （except for the low-dose group）， liver texture， surface nodules and tumors， inflammatory cell infiltration and abnormal cell amount were all improved in Bielong ruangan decoction low-dose and high-dose groups. Liver index （except for low-dose group）， Ishak score （except for low-dose group）， the serum contents of ALT and AST， as well as the mRNA and protein expressions of NLRP3， caspase-1， GSDMD， IL-18 and IL-1β in liver tissue were reduced significantly （P＜0.05）， with some of above indicators in high-dose group being significantly lower than those in low-dose group （P＜0.05）.CONCLUSIONSBielong ruangan decoction can inhibit the progression of liver cancer in rats and reduce liver damage. Its mechanism of action may be related to the inhibition of the NLRP3/caspase-1/GSDMD signaling pathway and the improvement of inflammatory response.关键词：liver cancer;NLRP3/caspase-1/GSDMD signaling pathway;inflammatory response
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发布时间：2024-09-25 - 摘要：OBJECTIVETo identify the chemical constituents of the modified Yupingfengsan formula.METHODSUPLC-Q-Exactive Orbitrap-MS technology was adopted. The separation was performed on Waters BEH C18 column with acetonitrile （A）-0.1% formic acid solution （B） as mobile phase for gradient elution. The heating electrospray ionization was used for positive and negative ion mode scanning. The scanning range was m/z 50-1 500， and the spray voltage was 2 kV （positive ion mode） and 1.5 kV （negative ion mode）. The information of chemical constituents of modified Yupingfengsan formula was collected through literature review to establish a database； the structure of the constituent was identified based on the above database， relevant literature， and chromatography and mass spectrometry information of reference standards. RESULTS &CONCLUSIONSTotally 114 chemical constituents were identified from modified Yupingfengsan formula， including 31 flavonoids， 39 phenylpropanoids， 5 saponins， 8 terpenoids， 3 chromones， 3 curcuminoids， etc. Based on the comparison of reference standards， 8 constituents were ultimately determined， including magnoflorine， calycosin， calycosin glycoside， cimifugin， 5-O-methylvisammioside， sec-O-glucosylhamaudol， luteolin and mangiferin. These constituents mainly involved glycosylation cleavage， retro Diels-Alder fragmentation， glycosylation loss， neutral molecule loss and other fragmentation pathways.关键词：chemical constituents;flavonoids;phenylpropanoids;fragmentation pattern
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发布时间：2024-09-25 - 摘要：OBJECTIVETo investigate the effects of Yiqi tongmai formula on atherosclerosis （AS） in ApoE－/－ mice and its mechanism.METHODSForty ApoE－/－ mice were randomly divided into model group， positive control group [atorvastatin calcium， 2.6 mg/（kg·d）]， and low-dose， medium-dose and high-dose groups of Yiqi tongmai formula [0.46， 0.91， 1.82 g/（kg·d）， by raw material]， with 8 mice in each group. Eight C57BL/6J mice were selected as the normal group. Except for the normal group， the other groups were given a high-lipid diet and relevant drug or normal saline intragastrically， once a day， for 12 consecutive weeks. After the last medication， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） as well as the contents of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and monocyte chemoattractant protein-1 （MCP-1） were measured in mice. The proportion of aortic plaque area in each group of mice was detected and calculated， and the pathological morphological changes of the aortic sinus were observed； the protein phosphorylation levels of aortic phosphoinositide 3-kinase （PI3K）， protein kinase B （aka Akt） and mammalian target of rapamycin （mTOR） were examined.RESULTSCompared with the model group， the serum levels of TC， TG and LDL-C and the contents of TNF-α， IL-1β and MCP-1 （including low-dose group） were decreased significantly in medium-dose and high-dose groups of Yiqi tongmai formula， while the content of HDL-C in high-dose group was increased significantly （P＜0.05 or P＜0.01）； aortic plaques of the mice were reduced in Yiqi tongmai formula groups to different extents， and pathological changes such as lipid deposition and inflammatory cell infiltration were relieved to different extents； the proportion of aortic plaque area， the protein phosphorylation levels of PI3K， Akt and mTOR in aortic tissue were significantly reduced in medium-dose and high-dose groups of Yiqi tongmai formula （P＜0.05 or P＜0.01）.CONCLUSIONSYiqi tongmai formula can improve lipid metabolism， reduce inflammatory response， and delay plaque development in AS mice. Its effect may be related to the inhibition of PI3K/Akt/mTOR signaling pathway activation.关键词：atherosclerosis;inflammation response;PI3K/Akt/mTOR signaling pathway
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发布时间：2024-09-25 - 摘要：OBJECTIVETo investigate the effects of Tongxie yaofang （TXYF） on the symptoms of rats with irritable bowel syndrome with diarrhea （IBS-D） by regulating colonic tryptophan hydroxylase 1 （TPH1）， serotonin transporter （SERT） and intestinal flora.METHODSForty-two SD rats were randomly divided into control group （7 rats） and modeling group （35 rats）. In modeling group， rat model of IBS-D was established by intragastrical administration of 0.45 g/L senna leaf solution [10 mL/（kg·d）] combined with chronic unpredictable stimulation. Thirty-five successfully modeled rats were randomly divided into model group， pinaverium bromide group [15 mg/（kg·d）] and TXYF low-dose， medium-dose and high-dose groups [3.75、7.5、15 g/（kg·d）， calculated by crude drug]， with 7 rats in each group. Each administration group was orally administered the corresponding drug， once a day， for 10 consecutive days. The general condition and weight changes of each group of rats were compared before modeling， after modeling and before administration， after the last drug intervention； the diarrhea index and visceral sensitivity were detected， and pathological changes of colon tissue were observed after modeling and before administration， after the last drug intervention. The level and expression of 5-hydroxytryptamine （5-HT）， protein and mRNA expressions of TPH1 and SERT were determined in colon tissue. The diversity and structural changes of fecal intestinal flora of rats were analyzed.RESULTSThere was no significant change in colon histopathology in each group. Compared with model group， the general condition of rats in each medication group improved. The daily body weight gain of rats was significantly increased， while diarrhea index， visceral sensitivity， the expressions of 5-HT and TPH1 in colon tissue were significantly decreased； SERT expression of colon tissue was significantly increased in TXYF medium-dose and high-dose groups （P＜0.05 or P＜0.01）. The diarrhea index， colon TPH1 protein expression and colon 5-HT protein positive rate in the TXYF low-dose group decreased while the mRNA expression of SERT increased significantly （P＜0.05）. There was a dose-dependent trend in the effect of TXYF. Compared with model group， Chao1 index and Shannon index of the rats in TXYF high-dose group were significantly decreased （P＜0.05 or P＜0.01）， the beneficial bacteria such as Firmicutes and Lactobacillus increased significantly， while the pathogenic bacteria such as Proteobacteria， Escherichia-Shigella and Rikenellaceae_RC9_gut_group decreased significantly （P＜0.05 or P＜0.01）.CONCLUSIONSTXYF can decrease the level of 5-HT and improve intestinal flora disorder by inhibiting the expression of TPH1 and up-regulating the expression of SERT in colon tissue， thus promoting the symptoms of IBS-D rats.关键词：irritable bowel syndrome with diarrhea;5-hydroxytryptamine;tryptophan hydroxylase 1;serotonin transporter;intestinal flora
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发布时间：2024-09-25 - 摘要：OBJECTIVETo investigate the effects and mechanism of galangin （GAL） on hepatocyte apoptosis in rats with obstructive jaundice （OJ） based on the Janus kinase 2 （JAK2）/signal transduction and activator of transcription 3 （STAT3） signaling pathway.METHODSTaking male SD rats as the object， the OJ model was established by double ligation of common bile duct， and 48 rats with successful modeling were randomly separated into OJ model group （model group）， low-dose GAL group （GAL-L group）， high-dose GAL group （GAL-H group） and high-dose GAL+JAK2 activator colivelin group （GAL-H+colivelin group）， with 12 rats in each group； another 12 SD rats with laparotomy/abdominal closure without ligation were selected as sham operation group （sham group）. Each administration group was given relevant medicine intragastrically and/or intraperitoneally， once a day， for 7 consecutive days. After the last medication， the morphology of liver tissue in rats was observed； the serum levels of total bilirubin （TBIL）， direct bilirubin （DBIL）， alanine transaminase （ALT） and γ-glutamyltransferase （GGT）， as well as the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in liver tissue were detected. The apoptotic rate of liver tissue cells， the expression levels of signaling pathway-related proteins （phosphorylated JAK2， JAK2， phosphorylated STAT3， STAT3） and apoptosis-related proteins [B cell lymphoma 2 （Bcl-2）， Bcl-2 related X protein （Bax）] were determined.RESULTSCompared with sham group， congestion of liver sinusoids， damage to liver lobules， disordered arrangement and swollen morphology of liver cells， the disappearance of nucleoli， and significant infiltration of inflammatory cells and fibrous tissue proliferation were observed in model group； the serum levels of TBIL， DBIL， ALT and GGT， the level of MDA in liver tissue， the apoptosis rate of liver cells， the protein expression of Bax， and the protein phosphorylation levels of JAK2 and STAT3 in liver tissue of model group were increased significantly （P＜0.05）； the level of SOD and the protein expression of Bcl-2 in liver tissue were decreased significantly （P＜0.05）. Compared with the model group， the pathological injuries of liver tissue were relieved in GAL-L group and GAL-H group， all quantitative indicators had significantly improved， and the effect of GAL-H group was more significant （P＜0.05）. Colivelin could significantly reverse the improvement effects of GAL on liver injury and related indicators of OJ rats （P＜0.05）.CONCLUSIONSGAL may inhibit liver cell apoptosis in OJ rats， improve liver function and alleviate oxidant stress， the mechanism of which may be associated with inhibiting JAK2/STAT3 signaling pathway.关键词：obstructive jaundice;hepatocytes;apoptosis;JAK2/STAT3 signaling pathway
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发布时间：2024-09-25 - 摘要：OBJECTIVETo explore the effects of ursolic acid （UA） on the growth， invasion， apoptosis and metastasis of human colorectal cancer cells SW620 and find out the underlying molecular mechanisms.METHODSThe effects of different concentrations （0， 5， 10， 15， 20， 25， 30 μmol/L） of UA on the proliferation of SW620 cells for different durations （24， 48， 72 h） were detected by CCK-8 assay； the clone formation was detected by clone formation assay after SW620 cells were treated with different concentrations of UA （0，10，15，20 μmol/L） for 10 days. After SW620 cells were treated with different concentrations of UA （0， 10， 15， 20 μmol/L） for 24 hours， flow cytometry， Transwell invasion assay and Western blot assay were adopted to detect apoptosis and invasion of SW620 cells， and the expressions of B cell lymphoma 2 （Bcl-2）， cleaved-poly （ADP-ribose） polymerase （cleaved-PARP）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， p38 MAPK， E-cadherin， N-cadherin and zinc finger transcription factor Snail. The effects of p38 MAPK inhibitor （SB203580） combined with UA on the protein expressions of p-p38 MAPK， Bcl-2 and N-cadherin were investigated.RESULTSCompared with 0 μmol/L UA， the survival rates of SW620 cells treated with 5-30 μmol/L UA for 24， 48 and 72 h were significantly decreased （P＜0.05）. The clone formation rate of cells treated with 15 μmol/L and 20 μmol/L UA was significantly decreased （P＜0.05）. After being treated with 15 μmol/L and 20 μmol/L UA， the cell apoptosis rate， the protein expressions of cleaved-PARP and E-cadherin， and the phosphorylation of p38 MAPK protein were increased； but the number of transmembrane cells， and the protein expressions of Bcl-2， Snail and N-cadherin were decreased； there was statistical significance in difference of most indexes （P＜0.05）. Some indexes changed in a concentration-dependent manner （P＜0.05）. SB203580 could significantly inhibit the upregulation of p38 MAPK by UA and reverse the inhibitory effect of UA on the protein expressions of Bcl-2 and N-cadherin （P＜0.05）.CONCLUSIONSUA can inhibit the growth， invasion and metastasis of SW620 cells， and induce cell apoptosis， the mechanism of which may be attributed to the activation of p38 MAPK signaling pathway.关键词：human colorectal cancer;growth;invasion;metastasis;apoptosis;p38 MAPK
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发布时间：2024-09-25 - 摘要：OBJECTIVETo provide a reference for the improvement of pharmacoeconomic evaluation and health economic decision-making in China.METHODSFrom the perspective of China’s healthcare system， a three-state partitioned survival model was constructed based on the BECOME study， the quality-adjusted life year （QALY） and equal value of life-year gained（evLYG） were used as the health gain measures respectively， and the cost-utility analysis was used to evaluate the cost-effectiveness of bevacizumab combined with chemotherapy regimen versus chemotherapy alone in the first-line treatment of RAS-mutant metastatic colorectal cancer （mCRC）. The cycle length was 2 weeks， the time horizon was the patients’ lifetime， the discount rate was 5%， and the willingness-to-pay threshold was 1 to 3 times China’s gross domestic product per capita in 2023 （89 358-268 074 yuan）. One-way sensitivity analysis and probabilistic sensitivity analysis were used to assess the robustness of the results.RESULTSCompared to the chemotherapy alone， the incremental cost-effectiveness ratio （ICER） of the bevacizumab combined with chemotherapy regimen was calculated to be 330 311.33 yuan/QALY based on QALY， which exceeded the willingness-to-pay threshold （268 074 yuan）. However， when the ICER was calculated based on evLYG， it was determined to be 254 085.64 yuan/evLYG， which fell below the willingness-to-pay threshold （268 074 yuan）. The results of the one-way sensitivity analysis showed that the price of bevacizumab had the greatest impact on the ICER value. The results of the probabilistic sensitivity analysis showed that the probability of the bevacizumab combined with chemotherapy regimen being more cost-effective was approximately 3% when assessed by QALY； the probability of the regimen being more cost-effective rose to 56% when assessed by evLYG.CONCLUSIONSWhen evaluating the cost-effectiveness of interventions for RAS-mutant mCRC， ICER values based on evLYG may provide a fairer measure compared to ICER values calculated by QALY. It is recommended that when pharmacoeconomic evaluations are conducted for special populations， both QALY and evLYG can be used as health outcome indexes for evaluation to achieve a better allocation of healthcare resources and improve the fairness of decision-making.关键词：quality-adjusted life year;RAS-mutant metastatic colorectal cancer;pharmacoeconomics
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发布时间：2024-09-25 - 摘要：OBJECTIVETo explore the characteristics of adverse drug reaction （ADR） induced by semaglutide and provide a reference for clinically safe medication.METHODSUsing search terms such as “semaglutide” and “adverse reactions” in both Chinese and English， the case reports about ADRs caused by semaglutide were searched and analyzed from PubMed， Web of Science， SpringerLink， CNKI， Chinese Medical Journal Full-text Database， Wanfang Medical Network and VMIS.RESULTSOverall 14 literature were included， involving 17 patients. Among 17 patients， 9 were female and 8 were male， with the age ranging from 25 to 80 years. Eight patients were given two or more drugs， and eight patients took 0.25 mg as the initial dose； the ADR occurred most frequently within 6 months （94.12%）. Sixteen patients’ symptoms improved or recovered after drug withdrawal and symptomatic treatment. Eleven patients did not mention whether to continue to use semaglutide in the future. Nine patients underwent ADR correlation evaluation， and 1， 3， 1 and 4 cases were determined to be “definite”， “probable”， “possible”， and “doubtful” respectively. Semaglutide-induced ADRs involved multiple organs or systems， most of which were the digestive system （35.29%）， followed by skin tissue （29.41%）. Among them， acute gastric dilation， severe liver injury， calculous cholecystitis， bullous pemphigoid， eosinophilic fasciitis， acute kidney injury， acute interstitial nephritis， depression and acute hemolytic anemia were not mentioned in the instruction.CONCLUSIONSADRs caused by semaglutide can occur in all ages， mainly within 6 months after medication， and mainly involve the digestive system， skin tissue， etc. Great attention should be paid to pharmaceutical care for those patients with liver and kidney dysfunction， neuropsychiatric diseases， glucose-6-phosphate dehydrogenase deficiency， etc. When ADR occurs， drug withdrawal and symptomatic treatment should be performed promptly to ensure patients’ medication safety.关键词：adverse drug reaction;case report;literature analysis
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发布时间：2024-09-25 - 摘要：OBJECTIVETo analyze the influential factors for rivaroxaban-induced bleeding events in patients with non-valvular atrial fibrillation （NVAF） and coronary heart disease.METHODSA total of 64 hospitalized patients with NVAF complicated with coronary heart disease who were treated with rivaroxaban and admitted to the Fuzhou University Affiliated Provincial Hospital from November 2021 to May 2023 were included in this retrospective study. The demographic data， laboratory test indexes and other general clinical data， and steady-state trough concentration of rivaroxaban were collected， and the dose-adjusted trough concentration was calculated. The occurrence of bleeding events within 6 months after discharge was recorded. The univariate analysis and binary Logistic regression analysis were adopted to determine the independent risk factors of rivaroxaban-related bleeding events. The binary Logistic regression equation was constructed to predict the probability of bleeding events. The area under the receiver operator characteristic （ROC） curve （AUC） was used to analyze the predictive value of the regression equation.RESULTSAmong 64 patients， 19 patients had 24 case-times bleeding events， most of which were mild bleeding （19 case-times， 79.2%）， and mainly gastrointestinal bleeding （17 case-times， 70.8%）. After symptomatic treatment and adjustment of the anticoagulant regimen， most of them were improved or cured. In the univariate analysis， the proportion of patients with a history of anemia， platelet count， urea nitrogen content， steady-state trough concentration of rivaroxaban， dose-adjusted trough concentration and coagulation indexes [international normalized ratio， prothrombin time （PT）， activated partial thromboplastin time] in bleeding group were significantly more or higher than those in non-bleeding group， while the albumin level was significantly lower than that in non-bleeding group （P＜0.05）. In binary Logistics regression analysis， high PT level （odds ratio＝1.473， 95% confidence interval＝1.103-1.967， P＝0.009） and high rivaroxaban dose-adjusted trough concentration （odds ratio＝1.174， 95% confidence interval＝1.018-1.355， P＝0.027） were independent risk factors for rivaroxaban-related bleeding events. The binary Logistic regression equation of bleeding event prediction probability （P） was LogitP＝－6.975+0.387×PT level+0.161×dose-adjusted trough concentration， and the AUC of the ROC curve was 0.825 （95% confidence interval was 0.708-0.909， P＜0.001）.CONCLUSIONSThe risk factors of rivaroxaban-related bleeding events in patients with NVAF and coronary heart disease include previous anemia history， high platelet count， high urea nitrogen content， high rivaroxaban steady-state trough concentration， high dose-adjusted trough concentration， high coagulation indexes and low albumin level. High PT level and high dose-adjusted trough concentration are independent risk factors that can be used to predict the risk of rivaroxaban-induced bleeding events. The regression equation has good predictive value.关键词：non-valvular atrial fibrillation;coronary heart disease;bleeding events;prothrombin time;dose-adjusted trough concentration;independent risk factor
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发布时间：2024-09-25 - 摘要：OBJECTIVETo mine the cardiovascular safety signal of relugolix， and provide a reference for the listing of this drug in China and future clinical safety drug evaluation.METHODSThe adverse event （AE） report data of relugolix， as the primary or secondary suspected drug， was collected from the FDA Adverse Event Reporting System （FAERS） from the first quarter of 2021 to the third quarter of 2023. The reporting odds ratio （ROR） method was used for data mining. The AEs in the FAERS database were identified and coded using preferred terms （PT） stated in version 24.0 of the Medical Dictionary for Drug Regulatory Activities （MedDRA）. The AEs of the target drug were identified by the narrow standardized MedDRA query （SMQ） terms and high-level term （HLT）. Sensitivity analysis was conducted using AEs suspected to be primarily or secondarily related to relugolix or related to drug interaction and concomitant drug， and broad SMQ terms.RESULTSA total of 4 354 relugolix-related AE reports were extracted. In the primary analysis， nine SMQ terms were analyzed， involving 2 positive signals such as dyslipidemia and hyperglycemia/new onset diabetes mellitus. Eleven HLTs were analyzed， and three positive signals were detected for three terms including cholesterol analyses， triglyceride analyses and hyperglycemia conditions （non-alternative analysis）. Sensitivity analysis results indicated the reliability of the study findings.CONCLUSIONSRelugolix may induce risk signals related to high blood lipids and high blood glucose， but no moderate risk signals such as hypertension， heart disease， and stroke are found. During relugolix treatment in clinical practice， attention must be paid to hyperlipidemia and hyperglycemia-related AE.关键词：gonadotropin-releasing hormone antagonist;adverse event;cardiovascular event;hyperlipidemia;hyperglycemia
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发布时间：2024-09-25 - 摘要：OBJECTIVETo explore the therapeutic effect and safety of tolvaptan in the treatment of heart failure with preserved ejection fraction （HFpEF） complicated with hyponatremia.METHODSOverall 106 patients with HFpEF complicated with hyponatremia were collected from the Department of Cardiology in the First Affiliated Hospital of Nanyang Medical College from January 1， 2020 to June 1， 2023. According to the random number table， the patients were divided into conventional treatment group （n＝53） and tolvaptan group （n＝53）. The conventional treatment group was given conventional treatment. Tolvaptan group additionally received Tolvaptan tablets 15 mg on the basis of conventional treatment group， increasing to 30 mg after 24 h， and then adjusting the dosage according to the levels of serum sodium； the maximum dose should not exceed 60 mg/d， and the medication should be stopped when the serum sodium level was≥150 mmol/L. Both groups of patients were treated for 6 months. The levels and changes of cardiac function indexes [left ventricular ejection fraction （LVEF）， left ventricular end systolic diameter （LVESD）， left ventricular end diastolic diameter （LVEDD）， N-terminal pro-brain natriuretic peptide （NT-proBNP）]， 24 h urine output， serum sodium， blood creatinine and urea nitrogen were compared between 2 groups before and after treatment. The occurrence of adverse drug reaction （ADR） was recorded.RESULTSBefore treatment， there was no statistically significant difference in those indexes between 2 groups （P＞0.05）. After treatment， the levels of LVEF， 24 h urine output and serum sodium in 2 groups were significantly higher than before treatment， and the tolvaptan group was significantly higher than the conventional treatment group； the levels of LVESD， LVEDD and NT-proBNP were significantly lower than before treatment， and the tolvaptan group was significantly lower than the conventional treatment group （P＜0.05 or P＜0.01）. The changes in cardiac function indexes， 24 h urine output and serum sodium levels in the atorvastatin group were more significant than the conventional treatment group （P＜0.05）. There was no statistically significant difference in the levels and changes of blood creatinine and urea nitrogen before and after treatment， as well as the incidence of nausea and vomiting， dizziness， hypernatremia and frequent urination between 2 groups （P＞0.05）.CONCLUSIONSTolvaptan can improve cardiac function and increase the blood sodium levels in patients with HFpEF complicated with hyponatremia， without affecting their renal function or increasing the risk of ADR.关键词：heart failure with preserved ejection fraction;hyponatremia;cardiac function
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发布时间：2024-09-25 - 摘要：OBJECTIVETo evaluate the efficacy and safety of camrelizumab combined with apatinib in first-line treatment of unresectable advanced hepatocellular carcinoma.METHODSBased on real-world data， 67 patients with unresectable advanced hepatocellular carcinoma admitted to our hospital from January 2020 to January 2023 were retrospectively selected as the subjects. According to their different medication regimens， they were divided into two groups： camrelizumab combined with apatinib group （32 cases） and camrelizumab combined with oxaliplatin group （35 cases）. Both groups of patients were treated for more than 12 months， with a follow-up period of 12 months from the start of treatment. The therapeutic effects of two groups， as well as the levels of tumor markers， liver and kidney function indicators， and blood routine indicators before and after treatment were compared； Kaplan-Meier method was used to draw survival curves， and Log-rank test was used to analyze the differences in survival between two groups. Multivariate Cox regression analysis was used to identify factors that affect patient survival.RESULTSAfter treatment， the disease control rate of patients in camrelizumab combined with apatinib group was 68.8%， significantly higher than 45.7% in camrelizumab combined with oxaliplatin group （P＜0.05）； the levels of alpha-fetoprotein， carbohydrate antigen 19-9 （except for camrelizumab combined with oxaliplatin group） and carbohydrate antigen 15-3 in both groups were significantly reduced， and the decrease in alpha-fetoprotein， carcinoembryonic antigen and carbohydrate antigen 15-3 was more significant in camrelizumab combined with apatinib group （P＜0.05）； the levels of aspartate transaminase were significantly increased in camrelizumab combined with apatinib group （P＜0.05）. Compared with camrelizumab combined with oxaliplatin group， camrelizumab combined with apatinib group had significantly prolonged overall survival （hazard ratio of 2.97， 95% confidence interval of 1.305-6.749， P value of Log-rank test of 0.006）； the treatment plan and stage of hepatocellular carcinoma at the time of diagnosis were important factors affecting patient survival （hazard ratios of 2.97 and 5.16， 95% confidence intervals of 1.305-6.749 and 2.261-11.780， respectively， P＜0.05）.CONCLUSIONSCamrelizumab combined with apatinib as first-line treatment for unresectable advanced hepatocellular carcinoma has good clinical efficacy and overall controllable safety， but attention should be paid to monitoring patients’ liver function indicators during medication.关键词：apatinib;oxaliplatin;hepato-cellular carcinoma;therapeutic efficacy;safety;real-world study
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发布时间：2024-09-25 - 摘要：OBJECTIVETo evaluate the safety， efficacy and economics of dapagliflozin in the treatment of type 2 diabetes mellitus （T2DM） combined with cardiovascular disease （CVD）， and provide an evidence-based basis for clinical treatment decisions.METHODSPubMed， the Cochrane Library， Embase， Web of Science， CNKI， Wanfang data， VIP， SinoMed and official websites of domestic and foreign health technology assessment （HTA） organizations were systematically searched. HTA reports， systematic evaluations/meta-analyses， and pharmacoeconomic studies of dapagliflozin in the treatment of T2DM combined with CVD were searched. After data extraction and quality assessment， the results of the included studies were analyzed descriptively.RESULTSA total of 13 papers were included， of which 10 were systematic evaluations/meta-analyses and 3 were pharmacoeconomic studies. In terms of efficacy， dapagliflozin significantly reduced patients’ glycosylated hemoglobin， body weight， body mass index and blood pressure levels compared with placebo， without increasing the risk of all-cause mortality； in terms of safety， dapagliflozin did not increase the risk of overall adverse events， major adverse cardiovascular events， cardiovascular death， hospitalization for heart failure， myocardial infarction， stroke， bone fracture and renal hypoplasia； in terms of economics， the UK and Chinese studies found an economic advantage for dapagliflozin， the Thai study did not.CONCLUSIONSDagliflozin has better efficacy and safety in the treatment of T2DM combined with CVD， and its economic findings are still controversial in different countries， with economic advantages in the context of current Chinese healthcare policies and drug prices.关键词：type 2 diabetes mellitus;cardiovascular disease;rapid health technology assessment;effectiveness;safety;economics
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发布时间：2024-09-25 - 摘要：OBJECTIVETo provide a reference for medical staff to timely identify and treat perinatal anaphylactic shock.METHODSThe clinical pharmacists participated in the rescue process of anaphylactic shock caused by esketamine during cesarean section anesthesia in a full-term pregnant patient at the Department of Obstetrics and Gynecology of Sichuan Provincial Maternity and Child Health Care Hospital. By consulting the relevant drug instructions and searching the relevant literature， clinical pharmacists assisted physicians in identifying anaphylactic shock and amniotic fluid embolism， analyzing the correlation between the drugs used and adverse reactions， and providing medication education.RESULTSThe patient developed hypoxemia and hypotension after anesthesia， and there was no coagulation dysfunction. After symptomatic treatment with adrenaline， the condition rapidly improved， so it was diagnosed as anaphylactic shock. Based on the patient’s medication use and the characteristics of adverse reactions， combined with the National Adverse Drug Reaction Monitoring Center’s criteria for determining the association between drugs and adverse reactions and Naranjo’s evaluation scale， it was comprehensively determined that the suspected allergenic drug causing anaphylactic shock was esketamine. The clinical pharmacist informed the patient that she must inform the physician of the relevant medications for this severe allergic reaction during her later visits. The patient recovered and was discharged on the 6th day after cesarean section.CONCLUSIONSThe clinical manifestations of anaphylactic shock and amniotic fluid embolism are similar， and careful differentiation is needed in clinical practice； if a patient experiences a systemic allergic reaction caused by drugs， the suspected drugs should be stopped promptly and effective symptomatic treatment should be taken immediately to delay or terminate disease progression and ensure the patient’s life safety.关键词：anaphylactic shock;perinatal period;narcotic drugs
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发布时间：2024-09-25 - 摘要：OBJECTIVETo provide a reference for the safe clinical use of meropenem.METHODSThe relationship of adverse reactions was analyzed based on a case of febrile neutropenia after using meropenem in an infant after congenital heart surgery by clinical pharmacists. By retrieving Chinese and English databases， case reports of adverse reactions induced by meropenem in blood system were summarized and analyzed. Relevant risk signals of adverse events were excavated from the FDA Adverse Event Reporting System， and the characteristics of meropenem-induced hematologic adverse reactions were summarized.RESULTSThis case was assessed as “very likely” according to the Naranjo’s assessment scale by clinical pharmacists. A total of 16 patients were included in the literature analysis， of which one was febrile neutropenia， 13 patients had grade 4 serious adverse reactions that were life-threatening or required urgent treatment. All adverse reactions improved after drug withdrawal. Data mining revealed that the median occurrence time of hematologic adverse events induced by meropenem was 6 d； neonatal thrombocytopenia， intravascular hemolysis and neutrophil count decrease were the top 3 signals of risk intensity for adverse events.CONCLUSIONSEarly use of meropenem may induce serious life-threatening hematological adverse reactions， especially in infants and elderly， those who use higher doses of meropenem， those who have previous antibiotic allergies， those with complex underlying diseases， those who use multiple antibiotics in combination， and those who experience high fever and bleeding after medication. Close monitoring should be provided in clinical practice.关键词：febrile neutropenia;hematologic system;adverse event;pharmaceutical monitoring;FAERS;data mining
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发布时间：2024-09-25 - 摘要：OBJECTIVETo provide a reference for clinically rational drug use and pharmaceutical care for patients with diabetes complicated with hyperlipidemia induced by immunosuppressive agents after liver transplantation.METHODSClinical pharmacists participated in the treatment of a patient with diabetes complicated with suspected hyperlipidemia induced by immunosuppressive agents after liver transplantation. Due to the poor glucose control of the patient， the clinical pharmacists assisted the doctor in adjusting the glycemic control plan： subcutaneous injection of 18， 12 and 16 units of Insulin lispro injection before meals， and subcutaneous injection of 16 units of Insulin glargine injection before bedtime. Due to the occurrence of hyperlipidemia in the patient， clinical pharmacists clarified the possible cause of abnormal blood lipid elevation was using immunosuppressants by reviewing the timeline of dose adjustment of immunosuppressive agents and changes in blood lipid levels based on relevant guidelines. Clinical pharmacists suggested using Rosuvastatin calcium tablets 5 mg， qd for lipid-lowering treatment， reducing the dosage of Mycophenolate mofetil capsules and Tacrolimus capsules to 500 mg， bid and 2 mg， bid， respectively. Medication education and pharmaceutical care were also carried out.RESULTSThe doctor adopted the advice of the clinical pharmacists. After treatment， the levels of blood glucose and blood lipid in the patient improved， and he was allowed to be discharged with medication.CONCLUSIONSClinical pharmacists provide pharmaceutical services such as recommending the addition of statins， adjusting the dosage of immunosuppressive agents， and conducting pharmaceutical care to optimize individualized medication plans for patients and ensure the safety and effectiveness of medication.关键词：after liver trans-plantation;hyperlipidemia;diabetes;clinical pharmacist;pharmaceutical care
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发布时间：2024-09-25 - 摘要：Gastroesophageal reflux disease （GERD） is a gastrointestinal motility disorder characterized by the reflux of gastric contents into the esophagus， leading to symptoms such as acid reflux and heartburn. The incidence of GERD is closely associated with psychological disorders， including anxiety and depression. The brain-gut axis， serving as a mediator of the bidirectional connection between the brain and the gastrointestinal tract， plays a crucial role in the occurrence and development of GERD with anxiety and depression. Various therapeutic approaches， including compound Chinese medicine internal therapy （such as Pingchong jiangni decoction， Tiaozhong huashi decoction， etc.）， combination therapy of internal and external Chinese medicine （such as Lianzhi xiere decoction combined with acupoint application， acupuncture at the back segment of governor vessel plus Chinese medication of soothing the liver and gallbladder， etc.）， and combination therapy of internal Chinese and western medicine （including Jianpi shugan decoction combined with rabeprazole， rabeprazole combined with Jianzhong jiangni decoction， etc.）， have been shown to regulate brain-gut peptides， intestinal flora， inflammatory factors and gastrointestinal hormones， thereby effectively alleviating GERD symptoms， anxiety and depression， and enhancing patients’ quality of life.关键词：anxiety;depression;brain-gut axis;traditional Chinese medicine;integration of traditional Chinese and western medicine
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发布时间：2024-09-25
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