最新刊期
卷 34 ， 期 20 ， 2023
- 摘要：In order to strengthen the supervision of the use of drugs in hospitals，the Sichuan Academy of Medical Sciences·Sichuan Provincial People’s Hospital took the lead in compiling the Principles for the Rational Use of National Key Monitoring Drugs （the Second Batch） with a number of experts from multiple medical units in accordance with the Second Batch of National Key Monitoring Rational Drug Use List （hereinafter referred to as “the List”） issued by the National Health Commission. According to the method of the WHO Guidelines Development Manual， the writing team used the Delphi method to unify expert opinions by reading and summarizing the domestic and foreign literature evidence of related drugs， and applied the evaluation， formulation and evaluation method of recommendation grading （GRADE） to evaluate the quality of evidence formed， focusing on more than 30 drugs in the List about the evaluation of off-label indications of drugs， key points of rational drug use and key points of pharmaceutical monitoring. It aims to promote the scientific standardization and effective management of clinical medication， further improve the quality of medical services， reduce the risk of adverse drug reactions and drug abuse， promote rational drug use， and improve public health.关键词：rational drug use;guidelines;medical institutions
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发布时间：2023-10-25 - 摘要：OBJECTIVETo study the protective effects of mangiferin against oxidative stress injury of myocardial cells induced by hydrogen peroxide （H2O2）， and its effects on the expression of nuclear factor of activated T cell cytoplasmic 4（NFATc4）.METHODSH9c2 myocardial cells were cultured in vitro and divided into blank group， H2O2 group， and 50， 100， 150 μmol/L mangiferin groups. Mangiferin groups were treated with different concentrations of mangiferin for 12 h， and then were subjected to H2O2 （200 μmol/L） stimulation for 12 hours together with the H2O2 group； relative survival rate was detected in each group， and the levels of superoxide dismutase （SOD）， catalase （CAT） and malondialdehyde （MDA） in cell supernatant and reactive oxygen species （ROS） in H9c2 cells were measured. Meanwhile， the expressions of apoptosis-related proteins [B cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax）， cleaved caspase-3] and nuclear protein NFATc4 were determined. Furthermore， the NFATc4 interference sequence was transfected， and the effects of NFATc4 on oxidant stress indexes and apoptosis-related proteins in H2O2-induced myocardial cells were investigated.RESULTSCompared with blank group， relative cell viability， the levels of SOD and CAT， relative expression of Bcl-2 were decreased significantly， while the levels of MDA and ROS， relative expressions of Bax， cleaved caspase-3 and nuclear protein NFATc4 were increased significantly （P＜0.05 or P＜0.01）. Compared with the H2O2 group， the above indexes of 100 and 150 μmol/L mangiferin groups were reversed significantly （P＜0.05）. After the transfection of the NFATc4 interference sequence， the expression of nuclear protein NFATc4 was down-regulated significantly； the levels of MDA and SOD， the protein expressions of Bax and cleaved caspase-3 were all decreased/down-regulated significantly， while the levels of SOD and CAT， and the protein expression of Bcl-2 were all increased/up-regulated significantly， compared with H2O2 group （P＜0.05）.CONCLUSIONSMangiferin can relieve H2O2-induced oxidative stress of H9c2 cells， reduce the apoptosis and inhibit the nuclear translocation of NFATc4， thereby alleviating myocardial cell damage； reducing the nuclear level of NFATc4 protein is related to reducing H2O2-induced oxidative stress and cell apoptosis.关键词：H9c2 cells;oxidative stress;apoptosis;nuclear factor of activated T cells cytoplasmic 4
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发布时间：2023-10-25 - 摘要：OBJECTIVETo investigate the effect and mechanism of anwulignan on improving hepatic fibrosis in rats.METHODSFifty SD rats were randomly divided into the normal group， model group， colchicine tablet group （0.1 mg/kg）， and anwulignan high-dose and low-dose groups （2.8 and 0.7 mg/kg）， with 10 rats in each group. Except for the normal group， all groups of rats were intraperitoneally injected with 50% CCl4 olive oil mixed solution to replicate the rat model of liver fibrosis. At the end of the modeling， rats in each group were given the corresponding drugs or distilled water intragastrically from the 9th week， once a day， for 4 weeks consecutively. During the experimental period， the general condition of the rats was observed； the liver index was calculated； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， superoxide dismutase （SOD） and malondialdehyde （MDA） were detected by colorimetric assay； the pathomorphology of the liver tissues and liver fibrosis were observed by HE staining and Masson staining； Western blot was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway and apoptosis-related proteins in liver tissues.RESULTSCompared with the normal group， the dietary amount of rats in the model group decreased， with sparse and disheveled fur， slow response， and a slower rate of weight growth or weight loss； the liver index was significantly increased （P＜0.01）； the serum levels of ALT， AST and MDA were significantly increased， and the SOD level was significantly decreased （P＜0.01）； HE and Masson staining showed that a large amount of fibrous proliferation was present in the liver tissues of the rats， and the collagen volume fraction was significantly increased （P＜0.01）； the protein expressions of PI3K， Akt， phosphorylated Akt and B-cell lymphoma （Bcl-2） were down-regulated significantly， while the protein expression of Bcl-2-associated X protein was increased significantly （P＜0.01）. Compared with the model group， the above indexes of the anwulignan high-dose and low-dose groups and the colchicine tablets group were all reversed significantly（P＜0.01 or P＜0.05）.CONCLUSIONSAnwulignan may reduce oxidative stress and inhibit hepatocyte apoptosis by activating the PI3K/Akt signaling pathway， and play the role of anti-hepatic fibrosis.关键词：hepatic fibrosis;PI3K/Akt pathway;oxidative stress;apoptosis
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发布时间：2023-10-25 - 摘要：OBJECTIVETo establish the fingerprint of the ethanol extract from Callicarpa nudiflora， analyze its anti-respiratory syncytial virus （RSV） activity in vitro， and study the relationship between spectrum and effect.METHODSUsing 10%， 30%， 50%， 70% and 90% ethanol as solvent， 20 batches of ethanol extracts from 4 batches of C. nudiflora were prepared. The fingerprints for 20 batches of ethanol extracts from C. nudiflora were mapped by ultra-high-performance liquid chromatography （UPLC）， and the similarity evaluation was conducted by using the Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprints （2012 edition）. The cytopathic effect method and MTT method were used to investigate the in vitro inhibitory activity of the ethanol extracts from C. nudiflora on RSV. Pearson correlation analysis， grey correlation degree and orthogonal partial least squares （OPLS） analysis were used to study the spectrum-effect relationship.RESULTSThere were 25 common peaks in 20 batches of ethanol extracts from C. nudiflora， and the similarities ranged from 0.912 to 0.998， and the RSDs of common peak areas were 33.54%-162.28%. The average values of IC50 for RSV of 20 batches of ethanol extracts from C. nudiflora were 9.55-272.23 μg/mL. The results of Pearson correlation analysis， grey correlation analysis and OPLS analysis showed that the Pearson correlation coefficients （P＜0.05） of the common peaks 8， 10， 12， 16， 18-19， 22-24 with pharmacodynamic indicators and regression coefficients were all negative， the correlation coefficients were all greater than 0.6， and the values of variable importance in projection were all greater than 1.CONCLUSIONSTwenty batches of ethanol extracts from C. nudiflora have similar components but significant differences in content， and exhibit different degrees of anti-RSV activity in vitro. The corresponding components of common peaks 8， 10， 12， 16， 18-19， 22-24 may be the characteristic components of anti-RSV of C. nudiflora.关键词：ethanol extract;respiratory syncytial virus;fingerprint;anti-virus;spectrum-effect relationship
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发布时间：2023-10-25 - 摘要：OBJECTIVETo investigate the effects and mechanism of ginsenoside Rh2 on the proliferation and apoptosis in human glioma U87 and U251 cells.METHODSUsing human glioma U87 and U251 cells as subjects， the proliferation and apoptosis， as well as the expression of histone deacetylase 1 （HDAC1） protein and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax） and cleaved caspase-3] were detected after being treated with different concentrations of ginsenoside Rh2.RESULTSThe concentrations of 10， 20， 30， 40， 50， 60， 70， 80 μmol/L ginsenoside Rh2 could generally significantly increase the proliferation inhibition rate of U87 and U251 cells （P＜0.05 or P＜0.01）， and the half inhibitory concentrations of this component after 48 hours of action were 51.34 and 55.84 μmol/L， respectively； 30， 50 μmol/L ginsenoside Rh2 could increase the total apoptotic rate of both types of cells， reduced the protein expressions of HDAC1 and Bcl-2， and increased the protein expressions of Bax and cleaved caspase-3 significantly （P＜0.05 or P＜0.01）.CONCLUSIONSGinsenoside Rh2 has a significant inhibitory effect on the proliferation of glioma cells and promotes the apoptosis of cells， which may be through reducing the expression of HDAC1 protein and activating the Bcl-2 family protein-mediated apoptosis pathway.关键词：ginsenoside Rh2;glioma;histone deacetylase 1;U87 cells;U251 cells;Proliferation;Apoptosis
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发布时间：2023-10-25 - 摘要：OBJECTIVETo explore the improvement effect and potential mechanism of Baicao fuyanqing suppository on bacterial vaginitis （BV） in rats.METHODSThe female SD rats were randomly divided into normal group， model group， metronidazole group （positive control， 0.03 g/kg）， Baicao fuyanqing suppository low-dose， medium-dose and high-dose groups （0.18， 0.36， 0.72 g/kg）， with 8 rats in each group. Except for the normal group， the rats in other groups were injected subcutaneously with 0.2 g of Estradiol benzoate injection+20 μL of Escherichia coli suspension （2×108～3×108 cfu/mL） through the vaginal opening to establish the BV rat model. Administration groups were given relevant medicine vaginally， while the normal group and the model group were given normal saline， once a day， for 6 consecutive days. Twenty-four hours after the last administration， the vaginal appearance score and vaginal pH were measured for each group of rats. The levels of cytokines [interleukin-1β （IL-1β）， IL-2， IL-13， immunoglobulin A （IgA）] in vaginal lavage fluid were determined. The morphology of the uterus and accessories， and pathological changes in the vaginal tissue were observed. The expressions of Toll-like receptor 2 （TLR2）， TLR4 and nuclear factor-κB （NF-κB） in vaginal tissues were determined.RESULTSCompared with the normal group， the uterus edema， the irregular shape of uterus and accessories， the vaginal mucosa hyperplasia， and the massive desquamation of epithelial cells were observed in the model group， complicating with massive infiltration of inflammatory cells； vaginal opening redness and swelling score and secretion score， vaginal pH， the levels of proinflammatory cytokine IL-1β and IL-2， the protein expressions of TLR2， TLR4 and NF-κB were all increased or up-regulated， while the levels of IgA and anti-inflammatory cytokine IL-13 decreased significantly （P＜0.05 or P＜0.01）. Compared with the model group， varying degrees of improvement in uterine and accessories， and vaginal tissue lesions in rats were observed in administration groups， and most of the quantitative indicators mentioned above showed significant improvement （P＜0.05 or P＜0.01）.CONCLUSIONSBaicao fuyanqing suppository has a certain improvement effect on inflammatory symptoms in BV rats， and its mechanism may be related to the inhibition of the TLR/NF-κB signaling pathway.关键词：bacterial vaginitis;inflammation;Toll-like receptor/nuclear factor-κB signaling pathway
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发布时间：2023-10-25 - 摘要：OBJECTIVETo explore the potential targets and mechanisms of the modified Baihe dihuang decoction （MBD/BDD） applied in post-stroke depression （PSD）.METHODSNetwork pharmacology was used to mine the potential targets and key pathways of MBD/BDD in the treatment of PSD. PSD model rats were induced by focal cerebral ischemia surgery combined with chronic unforeseen mild stress， and then were randomly divided into PSD model group， MBD/BDD group （12.6 g/kg， by raw drug）， and fluoxetine hydrochloride （FLX） group （positive control， 2.3 mg/kg）； a blank control group was also set up， with 8 rats in each group. Each administration group was given a corresponding medication solution by gavage once a day for 21 consecutive days. The intervention effect of MBD/BDD on depression-like symptoms in model rats was evaluated by open field and forced swimming tests. The brain tissues of rats in each group were dissected and total RNA was extracted for transcriptome sequencing and bioinformatics analysis. The mRNA and protein expressions of genes with significant changes and common neurotrophic factors were verified based on the above results.RESULTSA total of 131 MBD/BDD antidepressant-related target genes were obtained （such as IL1B and AKT1， etc.）， which were closely related to neural active ligand-receptor interactions and cyclic adenosine monophosphate signaling pathway. MBD/BDD could significantly prolong or increase the total time spent and distance traveled in the central grid of PSD model rats， and significantly shorten the cumulative immobility time （P＜0.05）. After treatment with MBD/BDD， the number of genes that changed in rat brain tissue was much higher than that in the FLX group， and there were significant differences in gene profiles among the PSD model group， MBD/BDD group， and FLX group. There were 1 351 differentially expressed genes （DEGs） between the MBD/BDD group and the PSD model group， of which 178 were significantly down-regulated and 1 173 were significantly up-regulated （P＜0.05）. Above 1 351 DEGs were involved in neuronal differentiation， chemical synaptic transmission regulation. They were significantly enriched in axonal guidance， cholinergic synapses and neuroactive ligand-receptor interactions. The top 30 genes in terms of up-regulation in the brain tissue of rats of MBD/BDD group were all associated with neuronal proliferation， development， differentiation， and migration. After MBD/BDD intervention， the expressions of Fezf2， Arx， Ostn， Nrgn genes， brain-derived neurotrophic factor and tyrosine kinase receptor B protein in brain tissue of rats were significantly increased （P＜0.05）.CONCLUSIONSThe anti-PSD effect of MBD/BDD may be related to the up-regulation of the expression of genes related to neuronal proliferation， development， differentiation and migration， as well as the promotion of neural structural and functional repair.关键词：post-stroke depression;network pharmacology;transcriptomics;neuroprotection
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发布时间：2023-10-25 - 摘要：OBJECTIVETo investigate the effects of astaxanthin on oxidative stress and inflammatory reaction in rats with traumatic brain injury （TBI）.METHODSMale SD rats were randomly divided into sham operation group， model group， astaxanthin low-dose group （20 mg/kg）， astaxanthin high-dose group （40 mg/kg）， astaxanthin+ML385 group [astaxanthin 40 mg/kg+nuclear factor-erythroid 2-related factor 2 （Nrf2） inhibitor ML385 30 mg/kg]， with 14 rats in each group. Except for the sham operation group， TBI model was induced by the modified Feeney free-fall impact method in other groups. The rats in each drug group were given the corresponding drug intragastrically or intraperitoneally， and the rats in the sham operation group and model group were intragastrically given a constant volume of normal saline. The neurological function of rats in each group was scored on the 1st， 3rd and 7th day after drug intervention； on the 7th day of drug intervention， the changes of cerebral histomorphology and inflammatory infiltration score were observed in each group， and the ultrastructure of nerve cells in brain tissue was also observed. The contents of oxidative stress indexes [superoxide dismutase （SOD）， catalase （CAT）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， nitric oxide （NO）] and inflammatory reaction indexes [tumor necrosis factor-α， interleukin-1β （IL-1β）， IL-6， inducible nitric oxide synthase] as well as protein and mRNA expressions of Nrf2， heme oxygenase-1 （HO-1） and NAD（P）H： quinone oxidoreductase 1 （NQO1） were detected in cerebral tissue.RESULTSCompared with the sham operation group， the brain edema of rats in the model group was obvious， accompanied by a large number of inflammatory cells infiltrated， the shape of organelles was damaged and their number was reduced， and the ultrastructure of nerve cells was seriously damaged. The neurological function score， the contents of SOD， CAT， GSH-Px and NO and the relative expression levels of Nrf2， HO-1 and NQO1 protein and mRNA in brain tissue were significantly decreased， while the inflammatory infiltration scores， the contents of MDA and inflammatory reaction indexes were significantly increased （P＜0.05）. Compared with the model group， low-dose and high-dose astaxanthin could significantly improve the pathological status of brain tissue and nerve cells and neurological function scores （except for the first day of drug intervention in the astaxanthin low-dose group）， increase the contents of SOD， CAT， GSH-Px and NO and the relative expression levels of Nrf2， HO-1， NQO1 protein and mRNA in brain tissue in a dose-dependent manner， and reduce inflammatory infiltration scores， the contents of MDA and inflammatory reaction indexes （P＜0.05）. ML385 could significantly inhibit the above effects of astaxanthin （P＜0.05）.CONCLUSIONSAstaxanthin may reduce the oxidative stress of TBI model rats， alleviate the neurological damage and reduce the level of inflammation reaction by activating the Nrf2/HO-1 signaling pathway.关键词：traumatic brain injury;oxidative stress;inflammatory reaction;Nrf2/HO-1 signaling pathway
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发布时间：2023-10-25 - 摘要：OBJECTIVETo optimize the formulation of a porcine fibrin patch （abbreviated as “DBT”）.METHODSBased on single-factor tests， with the contents of fibrinogen， thrombin and collagen before freeze-drying as the factors， with the overall desirability （OD） value of adhesion strength， holding viscosity and water absorption as response value， the formulation of DBT was optimized by Box-Behnken-response surface methodology， and the verification tests were conducted.RESULTSAccording to the results of the single factor tests and Box-Behnken-response surface methodology， combined with the actual production， the optimal formulation of DBT was 6.5 mg/cm2 of fibrinogen， 8.0 IU/cm2 of thrombin and 5.6 mg/mL of collagen. The average OD value of 3 validation tests was 0.726 6 （RSD＝0.58%， n＝3）， and the relative error of which with the predicted value （0.733 0） was －0.87%.CONCLUSIONSThe optimal formulation of DBT is stable and feasible.关键词：formulation optimization;fibrinogen;thrombin;collagen;Box-Behnken-response surface methodology
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发布时间：2023-10-25 - 摘要：OBJECTIVETo establish the method for determination of bile acid active constituents （cholic acid， hyodeoxycholic acid and sodium taurocholate） in Babao jingfeng powder， and to compare the differences of 3 constituents in Babao jingfeng powder from different manufacturers.METHODSUPLC-MS method was adopted to determine the contents of cholic acid， hyodeoxycholic acid and sodium taurocholate in 9 batches of Babao jingfeng powder from 3 manufacturers. The separation was performed on a Phenomenex Luna® C18 column with mobile phase consisted of acetonitrile-water （gradient elution） at a flow rate of 0.5 mL/min. The column temperature was 40 ℃ and the sample size was 2 μL. MS system was operated in a negative ion single quadrupole mode， and the m/z of cholic acid， hyodeoxycholic acid and sodium taurocholate were 407.2， 392.2 and 514.2， respectively. With the contents of three components as the index， cluster analysis and principle component analysis were performed on 9 batches of samples.RESULTSThe linear ranges of cholic acid， hyodeoxycholic acid and sodium taurocholate were 5.48-548.40， 5.38-538.40， 4.74-474.05 ng/mL， respectively （r≥0.999 3）. RSDs of precision， repeatability and stability tests （24 h） were all lower than or equal to 3.7% （n＝6）， and the average recoveries were 103.3%， 103.3% and 101.6% with RSDs of 3.3%， 3.4%， 4.2% （n＝6）， respectively. The contents of cholic acid ranged 0.702-1.711 mg/g， those of deoxycholic acid ranged 0.599-2.049 mg/g， and those of sodium taurocholate ranged 0.664-1.752 mg/g in 9 batches of samples. The average content of 3 components in samples from manufacturer A was high， and the difference between batches was the smallest； the average content of 3 components from manufacturer C was the lowest， and the difference between batches was large. Cluster analysis could basically distinguish samples from different manufacturers； cluster analysis was conducted by using the comprehensive score of principal components as an indicator， the results of which were basically consistent with those of cluster analysis for content.CONCLUSIONSThe method is established successfully for the content determination of the 3 bile acid active constituents of artificial bezoar in Babao jingfeng powder. The contents of 3 components in Babao jingfeng powder from 3 manufacturers are significantly different.关键词：cholic acid;hyodeoxycholic acid;sodium taurocholate;artificial bezoar;content determination
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发布时间：2023-10-25 - 摘要：OBJECTIVETo evaluate the efficacy of the functional dressing of Polygonum capitatum nanofibers （P-PVP-PCL）.METHODSP-PVP-PCL were prepared by electrospinning technology， and the microstructure of P-PVP-PCL was observed. The antibacterial activity and antioxidant activity of P-PVP-PCL and its effects on the survival rate， adhesion and migration rate of mouse fibroblast L929 cells were investigated. The effects of medical gauze dressing， blank nanofiber dressing （PVP-PCL） and P-PVP-PCL on the healing rate of the wound were investigated by establishing the back skin wound model of rats. The pathological changes of the wound tissue and collagen fiber deposition were observed， as well as the number of platelet endothelial cell adhesion molecule-1 （CD31） positive blood vessels and the expression of transforming growth factor-β （TGF-β） protein in wound tissue.RESULTSP-PVP-PCL had a smooth surface and a double-layer structure at the cross-section. The inhibition rates of P-PVP-PCL against Staphylococcus aureus and Escherichia coli were （98.88±0.66）% and （94.75±1.41）%， respectively. The antioxidant activity of P-PVP-PCL was （83.69±1.56）%， and the cell activity of the P-PVP-PCL group was significantly higher than those of the control group and PVP-PCL group （P＜0.05）. Compared with medical gauze dressings， P-PVP-PCL was more conducive to L929 cell adhesion； at 48 hours， the cell scratches in this group had basically healed. Compared with the medical gauze dressing group， the wound healing rates of the PVP-PCL group and the P-PVP-PCL group were significantly increased （P＜0.05）. On the 14th day of intervention， the wounds in the P-PVP-PCL group had basically healed， there was no dermal necrosis in the wound tissue， and the collagen fibers were arranged relatively neatly and the density was relatively uniform. The number of CD31 positive blood vessels and the expression of TGF-β protein showed a downward trend compared with the 7th day of intervention， and the number of CD31 positive blood vessels was significantly lower than those of the medical gauze dressing group and PVP-PCL group （P＜0.05）， but the protein expression of TGF-β was significantly higher than those of the medical gauze dressing group and the PVP-PCL group （P＜0.05）.CONCLUSIONSP-PVP-PCL has good antibacterial and antioxidant activity in vitro， and can promote the proliferation， adhesion and migration of L929 cells. It can promote wound healing of rats in vivo.关键词：wound dressing;electrospinning;pharmacodynamic evaluation;antibacterial;antioxidant;wound healing
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发布时间：2023-10-25 - 摘要：OBJECTIVETo provide references for the safe use of lorlatinib in clinical practice.METHODSThe reporting odds ratio （ROR） method， Medicines and Healthcare Products Regulatory Agency comprehensive standard method （referred to as “MHRA method”） and the Bayesian confidence propagation neural network （BCPNN） method were used to detect adverse drug events （ADEs） signals of lorlatinib in the FDA Adverse Event Reporting System from the first quarter of 2019 to the fourth quarter of 2022. RESULTS &CONCLUSIONSTotally 114 overlapping ADEs signals of lorlatinib were detected by the three methods， among which there were 73 new suspicious ADEs signals which were not covered in the instruction of lorlatinib. When using loratinib in clinical practice， special attention should be paid to ADEs with a high number of cases and signals， such as various neurological diseases， psychiatric diseases， respiratory system， thoracic and mediastinal diseases； clinical manifestations included cerebral edema， cerebral infarction， pulmonary hypertension， mutism， decreased sexual desire， pleural effusion. The signals of mobile thrombophlebitis， radiation necrosis， mutism， vesicoureteral reflux not mentioned in the instructions were all strong in BCPNN detection with high specificity， to which we should pay attention in clinical application.关键词：adverse drug event;signal mining
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发布时间：2023-10-25 - 摘要：OBJECTIVETo provide a reference for the dose adjustment of tacrolimus in patients who underwent lung transplantation after combined use of voriconazole.METHODSThe clinical data of lung transplantation patients who used voriconazole and tacrolimus in our hospital from January 2020 to December 2022 were collected retrospectively. The effects of voriconazole on the valley concentration， daily dose and standardized blood concentration of tacrolimus were analyzed by using SPSS 21.0 software； multiple linear regression analysis was conducted for the factors that may affect the standardized blood concentration of tacrolimus.RESULTSA total of 153 lung transplantation patients were included. After the combination of voriconazole， the average daily dose of tacrolimus decreased from 3.37 mg to 0.76 mg， and valley concentration and standardized blood concentration were increased significantly （P＜0.000 1）. The average daily dose of voriconazole was negatively correlated with the standardized blood drug concentration of tacrolimus （P＝0.000 1，r＝－0.224）. The valley concentration of voriconazole was positively correlated with valley concentration （P＜0.000 1，r＝0.316） and standardized blood concentration （P＜0.000 1，r＝0.249） of tacrolimus. After combination with voriconazole， the standardized blood drug concentration of patients who underwent single lung transplantation was significantly higher than those who underwent double lung transplantation， and the standardized blood concentration of tacrolimus after oral administration of voriconazole was significantly higher than after intravenous drip of voriconazole （P＜0.05）. Most liver and kidney function indicators showed no significant changes. The results of multiple factor regression analysis showed that the valley concentration of voriconazole had a significant impact on the standardized blood concentration of tacrolimus （P＜0.001）.CONCLUSIONSThe valley concentration of voriconazole has greatest influence on the blood concentration and dose adjustment of tacrolimus， which is an independent influencing factor. In clinical practice， the dose of tacrolimus should be reduced in combination with voriconazole， and therapeutic drug monitoring should be conducted for both drugs.关键词：tacrolimus;lung transplantation;blood concentration;therapeutic drug monitoring
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发布时间：2023-10-25 - 摘要：OBJECTIVETo compare the short-term therapeutic effect and safety of bevacizumab versus anlotinib respectively combined with chemotherapy drug in the treatment of epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKI） acquired resistant advanced lung adenocarcinoma.METHODSThe information of 84 patients with EGFR-TKI acquired resistant advanced lung adenocarcinoma in the Third People’s Hospital of Chengdu was analyzed retrospectively during Jun. 2019-Oct. 2021. The patients were divided into chemotherapy group （32 cases）， anlotinib combined chemotherapy group （24 cases） and bevacizumab combined chemotherapy group （28 cases）. Patients in the chemotherapy group were given Pemetrexed disodium for injection and Carboplatin injection， and symptomatic treatment was given for adverse reactions. On the first day of chemotherapy， patients in the anlotinib combined chemotherapy group received Anlotinib hydrochloride capsules 10 mg orally， once a day， for 14 consecutive days and 7 days of discontinuation， based on the treatment of the chemotherapy group. Patients in the bevacizumab combined chemotherapy group were given Bevacizumab injection of 15 mg/kg intravenously 1 day before chemotherapy， based on the treatment of the chemotherapy group. Three groups of patients were treated for a total of four cycles， with one cycle every three weeks. The overall response rate （ORR）， disease control rate （DCR）， median progression-free survival （mPFS）， and the changes of serum tumor markers were compared among three groups before and after treatment； meanwhile， the occurrence of adverse drug reactions was recorded， and the 1-year survival rate was followed up.RESULTSAfter 4 treatment cycles， ORR and DCR of bevacizumab combined chemotherapy group and anlotinib combined chemotherapy group were higher than chemotherapy group （P＜0.05）； mPFS of the two groups were significantly longer than chemotherapy group， and DCR of anlotinib combined chemotherapy group was significantly higher than bevacizumab combined chemotherapy group （P＜0.05）. After 4 treatment cycles， the serum levels of tumor markers in three groups were significantly lower than before treatment， and both combined chemotherapy groups were significantly lower than chemotherapy group （P＜0.05）. There was no statistically significant difference in the incidence of adverse reactions such as nausea， vomiting， bone marrow suppression， and 1-year survival rate among the three groups of patients （P＞0.05）.CONCLUSIONSBevacizumab and anlotinib combined with chemotherapy drug are effective and safe in the treatment of advanced lung adenocarcinoma with acquired EGFR-TKI resistance.关键词：anlotinib;epidermal growth factor receptor-tyrosine kinase inhibitors;lung adenocarcinoma
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发布时间：2023-10-25 - 摘要：OBJECTIVETo establish the estimation model for the exposure of mycophenolic acid （MPA） in early renal transplant recipients [calculated by the area under the plasma concentration-time curve with 12 h （AUC0－12 h）].METHODSTwenty kidney transplant recipients， who received triple immunosuppressive therapy of mycophenolate mofetil （MMF）+tacrolimus+methylprednisolone， were selected and given MMF dispersible tablets （750 mg， q12 h） on the 15th day after the operation； the blood samples were collected from the patients before and 0.5， 1.0， 1.5， 2.0， 3.0， 4.0， 6.0， 8.0， 12.0 hours after the administration， respectively. The blood concentration of MPA was determined， and the pharmacokinetic parameters of MPA were calculated. The multivariate linear stepwise regression analysis method was used to fit an estimation formula for the finite sampling method suitable for MPA-AUC0－12 h of the recipients. Bland-Altman analysis was used to evaluate the agreement between the estimation formula and the classical pharmacokinetic method.RESULTSThe main pharmacokinetic parameters of MPA in 20 renal transplant recipients： c0 was （1.53±0.84） μg/mL， cmax was （12.07±5.97） μg/mL， t1/2 was （5.41±3.67） h， tmax was （1.58±0.75） h， and the average AUC0－12 h calculated by the classical pharmacokinetic method was （33.95±13.40） μg·h/mL. MPA-AUC0－12 h was estimated with sampling points of “4.0， 8.0， 12.0 h”； the simplified calculation formula was AUC0－12 h＝12.058+2.819c4.0+7.045c8.0+3.879c12.0 （R 2＝0.934）. The predicted value had a good correlation and consistency with the measured value， and 95.0% of predicted values did not exceed the x±1.96SD （standard deviation） range.CONCLUSIONSThe estimation model is established successfully for the exposure of MPA in early renal transplant recipients； the model has better prediction accuracy and fewer sampling points.关键词：exposure;renal transplantation;pharmacokinetics;limited sampling strategy;estimation model
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发布时间：2023-10-25 - 摘要：OBJECTIVETo investigate the association between the functional GLCCI1 gene rs37973 polymorphism and inhaled corticosteroids （ICSs） response in patients with asthma-chronic obstructive pulmonary disease overlap （ACO）.METHODSTotally 173 newly diagnosed ACO patients were recruited from Shanghai Pudong New Area People’s Hospital during April 1st， 2019 to December 31st， 2020. All patients were treated with Salmeterol fluticasone inhalation powder， twice a day， for 24 weeks. The genotype of rs37973 locus was determined， and lung function indicators [forced expiratory volume in one second （FEV1）， FEV1/forced vital capacity （FVC）， the percentage of FEV1 to expected value （FEV1%pred）]， and lung function improvement （ΔFEV1 and ΔFEV1%pred） were all detected.RESULTSTotally 111 patients completed the whole 24-week follow-up and lung function detection. Among them， there were 42 cases of AA genotype， 52 cases of AG genotype， and 17 cases of GG genotype. After 12， 24 weeks of treatment， lung function indexes of patients were significantly better than baseline lung function indexes before treatment （P＜0.05）. After 24 weeks of treatment， ACO patients with AA and AG genotypes showed significantly better lung function improvement than GG genotype， and ΔFEV1%pred of AA genotype was significantly better than AG genotype （P＜0.05）. After 12， 24 weeks of treatment， the improvement of lung function in patients with a smoking history ≤20 pack year was significantly better than those with a smoking history ＞20 pack year， and among patients with a smoking history ≤20 pack year， only AA genotype had significantly better FEV1%pred than AG genotype （P＜0.05）. After 12 weeks of treatment， among patients with a smoking history ＞20 pack year， the improvement of lung function in AA genotype and AG genotype was significantly better than GG genotype， and the FEV1%pred in AA genotype was significantly better than AG genotype （P＜0.05）. After 24 weeks of treatment， the improvement of lung function of AA genotype and AG genotype was significantly better than GG genotype （P＜0.05）.CONCLUSIONSGG genotype of GLCCI1 gene rs37973 locus is associated with the poor treatment response to ICSs in patients with ACO， especially in patients with smoking history ＞20 pack year.关键词：glucocorticoid-induced transcript 1;single nucleotide polymorphisms;inhaled corticosteroids
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发布时间：2023-10-25 - 摘要：OBJECTIVETo evaluate the efficacy and safety of antibody-drug conjugates （ADC） in the treatment of breast cancer， so as to provide an evidence-based reference for clinical medication.METHODSRetrieved from CNKI， Wanfang database， VIP， PubMed， the Cochrane Library， Embase， and Web of Science， randomized controlled trials （RCTs） about trastuzumab emtansine， trastuzumab deruxtecan and sacituzumab govitecan （trial group） versus chemotherapy or other anti-tumor drugs （control group）， were collected during the inception to April 2023. After screening the literature， extracting data， and evaluating the quality of the literature， a meta-analysis was conducted by using RevMan 5.4.1 software.RESULTSA total of 8 RCTs were included， with a total of 5 577 patients. The results of the meta-analysis showed that the progression-free survival （PFS） [HR＝0.76， 95%CI （0.69， 0.83）， P＜0.000 01]， overall survival （OS） [HR＝0.87， 95%CI （0.81， 0.93）， P＜0.000 1]， and clinical benefit rate （CBR） [OR＝2.70， 95%CI （1.15， 6.33）， P＝0.02] of the trial group were significantly higher than control group. There was no statistically significant difference in objective response rate （ORR） between the two groups [OR＝2.34， 95%CI （0.59， 9.33）， P＝0.23]. The results of subgroup analysis showed that the PFS of HER2-positive patients and HER2-negative patients， and the OS of HER2-positive patients in the trial group were significantly higher than control group （P＜0.05）. The incidence of anemia and increase of aspartic acid transaminase （AST） in the trial group was significantly higher than control group （P＜0.05）. The results of sensitivity analysis showed that the results obtained with PFS， OS， and ORR as indicators were relatively robust， while the results obtained with CBR as indicators lacked robustness.CONCLUSIONSADC drugs have significant effects on breast cancer， but will increase the risk of anemia and elevated AST.关键词：trastuzumab emtansine;trastuzumab deruxtecan;sacituzumab govitecan;breast cancer;efficacy;safety
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发布时间：2023-10-25 - 摘要：OBJECTIVETo predict the development trends of licensed pharmacist staffing in retail pharmacies within the western China and provide reference for the formulation of policies related to licensed pharmacists.METHODSBased on the data of retail pharmacies and licensed pharmacists in the western China from 2016 to 2022， a grey model was constructed to analyze and predict the number development trends of retail pharmacies and licensed pharmacists in the western China from 2023 to 2026.RESULTSCurrently， the 1∶1 staffing requirement for licensed pharmacists and retail pharmacies had been met in Shaanxi， Guangxi and Gansu. Based on current trends， Inner Mongolia， Chongqing， Yunnan， and Qinghai were expected to meet the 1∶1 staffing requirement for licensed pharmacists and retail pharmacies between 2023 and 2026. Sichuan and Xinjiang were also expected to meet this requirement in the future. However， there was still a significant gap in Guizhou， Xizang， and Ningxia towards achieving the above goals.CONCLUSIONSThere is still a discrepancy between the deployment of licensed pharmacists and the national requirements in certain western provinces. Local authorities should formulate relevant policies according to local circumstances. Regions that have already met or will soon achieve the staffing requirement for licensed pharmacists should continue to enhance the quantity and quality of their licensed pharmacist workforce. In areas where meet this criterion in the short term is not feasible， it is necessary to strengthen the development of the licensed pharmacist workforce， and control the number of new retail pharmacies.关键词：retail pharmacies;western region;grey model;forecast
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发布时间：2023-10-25 - 摘要：Autoimmune diseases（ADs） are diseases in which the body’s immune tolerance is impaired， causing damage to its tissues. The pro-inflammatory helper T cell 17 （Th17） and anti-inflammatory regulatory T cell （Treg） are functionally antagonistic to each other， and the immune imbalance between them and the imbalance of related inflammatory factors are closely related to the occurrence of a variety of ADs. Plenty of evidence has shown that gut microbiota can regulate Th17/Treg differentiation， rebuild immune tolerance and delay the ADs process through regulating cytokine production， transcription factor expression and energy metabolism. This paper reviews the intervention effects of traditional Chinese medicine（TCM） monomers on the common ADs by regulating Th17/Treg differentiation balance based on intestinal flora： ulcerative colitis，rheumatoid arthritis and diabetes mellitus type 1. It is found that its mechanism of action may be to restore the balance of pro-inflammatory factors and anti-inflammatory factors to alleviate intestinal mucosal barrier damage， reduce synovial angiogenesis and improve pancreatic β cell destruction， which provides some ideas for the prevention and treatment of ADs with integrated traditional Chinese and western medicine.关键词：autoimmune diseases;gut microbiota;helper T cell 17;regulatory T cell
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发布时间：2023-10-25 - 摘要：Osteoporosis， as a systemic bone disease with high incidence rate and high disability rate， has become a research hotspot in recent years. The daidzein in soybean isoflavones can bind with estrogen receptors， simulating the prevention and treatment of osteoporosis with estrogen-like effect. Its mechanism of action includes promoting osteoblast formation and differentiation by activating the Wnt signaling pathway， increasing bone density， and improving bone tissue health； inhibiting osteoclast differentiation and slowing down bone resorption by reducing receptor activator of nuclear factors κB ligand/osteoprotegerin ratio， downregulating the expression of macrophage colony-stimulating factor （M-CSF）； collaborating antioxidant and immune regulation to achieve the goal of preventing and treating osteoporosis. In addition， different doses of daidzein have different effects on bone density and osteoporosis， which may be related to factors such as study design， sample selection， and individual differences.关键词：osteoporosis;estrogen-like effect;mechanism
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发布时间：2023-10-25
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