最新刊期
卷 35 ， 期 12 ， 2024
- 摘要：OBJECTIVETo design the implementation path around the key links of the management in the clinical comprehensive evaluation of drug in China， and to provide suggestions for optimizing and perfecting the management in the clinical comprehensive evaluation of drug.METHODSBased on the relevant experience of drug evaluation management in typical countries regions at home and abroad， the discussion was performed and the management mechanism was designed from seven aspects， such as funding source， selection of topics， staff management， information management， data management， evaluation process and quality assessment. RESULTS &CONCLUSIONSIn terms of funding sources， the financial department can provide funding guarantees or other alternative forms such as performance evaluations to encourage all parties to undertake the clinical comprehensive evaluation of drug projects. In terms of the selection of topics， a “top-down” or “bottom-up” selection mode can be determined according to the project’s nature and actual situation， and a selection process of “forming alternatives-setting up theme selection list-demonstrating and publishing theme selection list” can be formed. In terms of staff management， the specialty of team members should be specified， and the expert team should be established to provide clinical comprehensive evaluation of drug. In terms of information management， the national/provincial basic informational platform should be established， and the registration system should be established. In terms of data management， a regional health data-sharing platform should be formed and the “application-checking-utilization” mechanism should be conducted. In terms of the evaluation process， the evaluation procedures that concern on project implementation plan demonstration system and project closing review system should be constructed. In terms of quality assessment， quality assessment and reward and punishment mechanism for project completion， that consider the quality of management first while focusing on the technical quality， can be established. The management mechanism based on the standardized implementation of the seven key links will standardize the development of clinical comprehensive evaluation of drugs in China to some extent， and help improve the quality of clinical comprehensive evaluation projects for drugs.关键词：management mechanism;procedure;key links
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发布时间：2024-06-25 - 摘要：OBJECTIVETo comprehensively evaluate the three oral Janus kinase inhibitors （JAKi） such as upadacitinib， abrocitinib and baricitinib in the treatment of atopic dermatitis.METHODSThe six dimensions of safety， efficacy， economy， appropriateness， accessibility and innovativeness were used for evaluation. Meta-analysis was conducted to evaluate the safety and efficacy of three oral JAKi； pharmacoeconomic studies were searched， and the treatment costs were calculated to evaluate the economy of each JAKi. Appropriateness was described based on literature review and drug labels. Accessibility of three oral JAKi was assessed by using a questionnaire survey. The innovation of JAKi was elucidated from the perspective of its mechanism of action.RESULTSIn terms of safety， the incidence of upper respiratory tract infection （OR＝1.47， 95%CI of 1.04-2.08， P＝0.03） and nasopharyngitis （OR＝1.44， 95%CI of 1.06-1.95， P＝0.02） in the upadacitinib 30 mg group was significantly higher than that in the placebo group； the incidence of nasopharyngitis in baricitinib 4 mg group was significantly higher than that in the placebo group （OR＝2.24， 95%CI of 1.39-3.61， P＝0.000 8） and baricitinib 2 mg group （OR＝0.48， 95%CI of 0.31-0.74，P＝0.001）. In terms of efficacy， regardless of the dosage， all three JAKi groups were superior to the placebo group， and the high-dose groups of upadacitinib and abrocitinib were superior to the low-dose groups （P＜0.000 1）. In terms of economy， the annual treatment cost of baricitinib was the lowest （13 870.0 yuan）， but it has not been approved for atopic dermatitis indication in China； next was upadacitinib （27 192.5 yuan）. In terms of appropriateness， the overall appropriateness of the three JAKis was good， but none of them was suitable for patients with severe liver injury. In terms of accessibility， baricitinib had the highest availability rate （59.4%）， but the affordability of upadacitinib was relatively good under China’s medical insurance system. In terms of innovation， among the three types of JAKi， upadacitinib and abrocitinib had better innovation.CONCLUSIONSThree oral JAKi treatments for atopic dermatitis have controllable safety and good efficacy. Considering the issue of medical insurance reimbursement， it is recommended that Chinese patients use upadacitinib.关键词：atopic dermatitis;clinical comprehensive evaluation;upadacitinib;abrocitinib;baricitinib
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发布时间：2024-06-25 - 摘要：OBJECTIVETo provide reference for improving the disease diagnosis related groups （DRG） payment reform， promoting refined hospital operation and management and rational drug use.METHODSTaking the orthopedic department of our hospital （the Third Affiliated Hospital of Anhui Medical University） as the research object， based on evidence-based medicine， a medication clinical pathway （hereinafter referred to as medication pathway） for DRG diseases in this department was constructed and implemented. All patients who met the DRG disease were included in the medication path management， and the patients in the same DRG disease group were treated with the same treatment method. Segmented regression model （SRM） was adopted to analyze the effects of medication pathway on the medical service capacity， efficiency and quality of our hospital.RESULTSDuring the implementation of medication pathway， significant decreases were observed in average length of hospital stay， cost per hospitalization， the proportion of medication expenses， medication cost per hospitalization and defined daily dose； the proportion of medical service revenue and the qualified rate of medical orders significantly increased （P＜0.05）. After the implementation of medication pathway， the average length of hospital stay and defined daily dose continued to decrease， and the qualified rate of medical orders also continued to significantly increase （P＜0.05）.CONCLUSIONSThe implementation of medication pathway enhances the quality of medical services， improves operational efficiency， reduces medical expenses， and contributes to the development of a refined hospital management system.关键词：disease diagnosis related groups;segmented regression model;interrupted time series analysis;orthopedic department
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发布时间：2024-06-25 - 摘要：OBJECTIVETo study the effects of transferrin-targeting peptide T7 （7pep） on intracellular transportation of polyethylene glycol-polycaprolactone （PEG-PCL） micelles in human cervical cancer HeLa cells.METHODSUsing coumarin-6 （C6） as fluorescent indicator probe， both coumarin-6 （C6）-loaded PEG-PCL （PEG-PCL-C6） micelles and 7pep-modified PEG-PCL （7pep-PEG-PCL-C6） micelles were prepared by film-dispersion method. The particle size， polydispersity index and appearance morphology were compared between two types of micelles； the real-time uptake of two types of micelles by HeLa cells was compared， and the colocalization of two types of micelles with early endosomes （EE）， endocytic recycling compartments （ERC） and late endosomes （LE） after entry into the cells was observed.RESULTSThe particle sizes of PEG-PCL-C6 and 7pep-PEG-PCL-C6 micelles were（75.0±2.3）and（82.0±1.5）nm； the polymer dispersity indexes were 0.17±0.20 and 0.17±0.32， respectively， with a regular spherical appearance. The colocalization results showed that entry speed and amount of 7pep-PEG-PCL-C6 micelles were significantly faster/more than those of PEG-PCL-C6 micelles. 7pep-PEG-PCL-C6 micelles entered EE faster than PEG-PCL-C6 micelles， while PEG-PCL-C6 micelles entered ERC at a faster rate than 7pep-PEG-PCL-C6 micelles， and both PEG-PCL-C6 micelles and 7pep-PEG-PCL-C6 micelles tended to accumulate gradually in LE； Pearson coefficient， signal overlap ratio， and colocalization ratio of 7pep-PEG-PCL-C6 micelles with LE were significantly lower 60 minutes after entering the cell than those 30 minutes after entering the cell （P＜0.05 or P＜0.01）.CONCLUSIONSTargeting 7pep modification can increase the entry speed and amount of PEG-PCL-C6 micelles， and also alter their intracellular transportation behavior.关键词：micelle;transferrin receptor;targeting drug delivery system;cellular transport
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发布时间：2024-06-25 - 摘要：OBJECTIVETo explore the effects and mechanism of Huayu qutan formula on atherosclerosis （AS） in ApoE－/－ mice.METHODSThirty ApoE－/－ mice were randomly divided into model group， Huayu qutan formula group [20 g/（kg·d）]， rosuvastatin group [1.55 mg/（kg·d）]， with 10 mice in each group. Another 10 C57BL/6J mice were selected as normal control group. ApoE－/－ mice were given high-lipid diet for 12 weeks to induce AS model. After modeling， each group was given relevant medicine or normal saline intragastrically， once a day， for 4 consecutive weeks. After the last administration， the levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， 5，6-epoxyeicosatrienoic acid （5， 6-EET）， 8，9-EET， 11，12-EET， 14，15-EET， interleukin-1β （IL-1β） and IL-18 in serum were detected； mRNA expressions of inhibitor of nuclear factor κB （IκB）， nuclear factor κB （NF-κB）， NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， Caspase-1， IL-1β and IL-18 in the aortic tissue of mice were detected； protein expression levels of IκB， NF-κB， NLRP3， apoptosis-associated speck-like protein containing CARD （ASC）， Caspase-1， gasdermin D （GSDMD）， IL-1β and IL-18 in the aortic tissue of mice were detected. The morphological changes of the aortic tissue were observed.RESULTSCompared with model group， the serum levels of TC， TG， LDL-C， IL-1β and IL-18， the mRNA expressions of IκB， NF-κB， NLRP3， Caspase-1， IL-1β and IL-18 in aortic tissue， and the protein expressions of IκB， NF-κB， NLRP3， ASC， Caspase-1， GSDMD， IL-1β and IL-18 were all decreased significantly in Huayu qutan formula group and rosuvastatin group （P＜0.05）， while the serum levels of 5，6-EET， 8，9-EET， 11，12-EET and 14，15-EET were increased significantly （P＜0.05）. The aortic atherosclerotic plaques were alleviated significantly.CONCLUSIONSHuayu qutan formula can play role of anti-AS through EETs-mediated pyroptosis.关键词：atherosclerosis;pyroptosis;epoxyeicosatrienoic acid
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发布时间：2024-06-25 - 摘要：OBJECTIVETo investigate the in vitro inhibitory mechanism of berberine on the proliferation of tumor stem cells and evaluate its in vivo safety.METHODSFlow cytometry was used to select tumor stem cells from mouse skin melanoma B16F10 cells； CD44， CD133， Nanog homologous box protein （NANOG） and octamer-binding transcription factor 4 （OCT4） were used as indicators to characterize tumor stem cells. Tumor stem cells were divided into control group， all-trans retinoic acid （ATRA） group， and berberine group， and the CCK-8 method was used to detect the effects of berberine on the viability of tumor stem cells； flow cytometry was adopted to detect cell apoptotic rate， the proportion of CD44+/CD133+ and the positive cell rate of sex determining region Y box protein 2 （SOX2）； the morphological changes of tumor balls were recorded after treatment with berberine； the morphology of cell pyroptosis in each group was recorded， and the release rate of lactate dehydrogenase （LDH） was detected； Western blot assay was adopted to detect the expressions of pyroptosis-related protein gasdermin E （GSDME）， GSDME-N， caspase-3 and cleaved caspase-3. Preliminary evaluation of in vivo safety of berberine was conducted by using zebrafish embryo toxicity experiments.RESULTSCompared with B16F10 cells， the proportion of CD44+/CD133+ cells in tumor stem cells and the fluorescence intensity of NANOG and OCT4 were significantly increased （P＜0.000 1）. The half-inhibitory concentration of berberine to tumor stem cells was 50.98 μmol/L. Compared with the control group， the apoptotic rate of cells in the berberine group was significantly increased， while the proportion of CD44+/CD133+ cells and the rate of SOX2 positive cells were reduced significantly （P＜0.000 1）； tumor stem cell spheroids were atrophied， with partial cell death. After treatment with berberine， tumor stem cells exhibited swelling in their outermost layer， the release rate of LDH of cells was significantly increased and the release rate of LDH increased with increasing dose； the protein expressions of GSDME-N and cleaved-caspase-3 of cells in berberine 20， 40 μmol/L groups were significantly increased， and the protein expressions of GSDME and caspase-3 were significantly reduced （except for berberine 20 μmol/L group， P＜0.05）. The embryonic development of zebrafish treated with berberine was almost unaffected， and the survival rate of embryo reached 100%， with no obvious abnormalities observed.CONCLUSIONSBerberine has good activity against the proliferation of tumor stem cells， and its mechanism of action may be related to activating GSDME and promoting cell pyroptosis； berberine has good in vivo safety.关键词：tumor stem cells;pyroptosis;gasdermin E;safety
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发布时间：2024-06-25 - 摘要：OBJECTIVETo compare the chemical components contained in Artemisiae Scopariae Herba （ASH） standard decoction and its decoction pieces， and provide foundation of their pharmacological substances.METHODSASH standard decoction and its decoction pieces were prepared； UFLC-Q-TOF-MS/MS method was used for the detection in the negative ion mode， and the total ion chromatogram was extracted by the PeakView 1.6 software. By comparing with reference substances， literature data， and online search of compound database such as PubChem， the chemical components contained in ASH standard decoction and its decoction pieces were identified and analyzed for the differences.RESULTSA total of 125 chemical components were identified in ASH standard decoction and its decoction pieces， including 50 organic acids， 39 flavonoids， 3 coumarins， 2 amino acids， 5 lignans， and 26 others. 3-methoxy-caffeic acid-4-O-β-D-glucoside， p-hydroxybenzoic acid， caffeic acid 4-O-glucoside， spiraeoside， and phenyl β-D-glucoside in ASH standard decoction were not detected in its decoction pieces， while 6′-6′ chlorogenic acid dimer， quercetin-5-glucoside， apigenin 7-methyl ether 5-（6″-malonylglucoside）， quercetin-3-O-arabinoside， 6″-caffeoylhyperin and 6-O-caffeoyl-D-glucoside in decoction pieces were not detected in the standard decoction.CONCLUSIONSMost components in ASH decoction pieces are transferred to its standard decoction， but a few components undergo chemical reactions in whole or in part during the boiling process， transforming into other or new components in the standard decoction.关键词：standard decoction;decoction pieces;differential component analysis;UFLC-Q-TOF-MS/MS
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发布时间：2024-06-25 - 摘要：OBJECTIVETo establish high performance liquid chromatography （HPLC） fingerprint of Xiaohe syrup and determine the contents of 10 effective ingredients in them.METHODSWith 12 batches of Xiaohe syrup as samples， ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was adopted with Athena C18 （250 mm×4.6 mm， 5 μm） as the chromatographic column， acetonitrile-0.1% phosphoric acid aqueous solution as mobile phase for gradient elution. The flow rate was 1.0 mL/min， and the detection wavelength was 210 nm. Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprint （2012A version） was imported to establish the fingerprint of Xiaohe syrup and evaluate the similarity. The content determination was performed on ACQUITY UPLC BEH C18 （100 mm×2.1 mm， 1.7 μm） chromatographic column， with 0.01% formic acid acetonitrile-0.01% formic acid water as mobile phase for gradient elution at a flow rate of 0.4 mL/min； combined with high-resolution mass spectrometer， positive and negative ions were scanned with an electric spray ion source to determine the content of each main component in 12 batches of Xiaohe syrup.RESULTSA total of 33 common peaks were calibrated in 12 batches of samples， with similarities greater than 0.97； 10 chromatographic peaks were confirmed， namely flavonoid glycosides， paeoniflorin， ferulic acid， naringin， rosmarinic acid， neohesperidin， salvianolic acid B， tetrahydropalmatine， saikosaponin A， and saikosaponin D. The results of content determination showed that the above 10 components had good linear relationships within their respective mass concentration ranges （all R 2＞0.999）， with contents ranging from 0.35 to 0.64， 3.15 to 5.61， 0.11 to 0.17， 1.68 to 3.17， 1.59 to 1.90， 1.15 to 1.64， 0.78 to 1.48， 0.11 to 0.26， 0.06 to 0.13， and 0.33 to 0.61 mg/mL， respectively.CONCLUSIONSThe main components of 12 batches of Xiaohe syrup are similar， but the contents vary； HPLC fingerprint and UPLC-MS/MS content determination method established in this study can be used for comprehensive quality evaluation of Xiaohe syrup.关键词：fingerprint;quality control;content determination;UPLC-MS/MS
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发布时间：2024-06-25 - 摘要：OBJECTIVETo investigate the impact of evodiamine on the proliferation， migration and invasion abilities of trophoblastic cells induced by high glucose and its potential mechanism based on advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway.METHODSHuman trophoblastic cells HTR-8/SVneo were divided into control group， high glucose group， evodiamine low-dose group （2 μmol/L）， evodiamine high-dose group （4 μmol/L）， pc-NC group （transfected with pc-NC plasmid+4 μmol/L evodiamine）， and pc-RAGE group （transfected with pc-RAGE plasmid+ 4 μmol/L evodiamine）. Cells in all groups except for the control group were cultured in a high sugar （25 mmol/L glucose） environment， and cells in all groups except for the control group and the model group were transfected with the corresponding plasmids and/or received the corresponding drug interventions. The survival rate， apoptotic rate， scratch healing rate， and invasion number， as well as the protein and mRNA expressions of AGE， RAGE， nuclear factor-κB p65 （NF-κB p65）， matrix metalloproteinase-2 （MMP-2）， and MMP-9 were examined in each group.RESULTSCompared with the control group， the cell survival rate， scratch healing rate， invasions number， and the mRNA and protein expressions of MMP-2 and MMP-9 in the high glucose group significantly decreased （P＜0.05）， while the apoptotic rate， the mRNA and protein expressions of AGE and RAGE， the mRNA expression of NF-κB p65， and the phosphorylation level of NF-κB p65 protein significantly increased （P＜0.05）； compared with the high glucose group， the above indexes of cells in evodiamine low-dose and high-dose groups were significantly improved， and the effect of the high-dose group was significantly better than that of the low-dose group （P＜0.05）； overexpression of RAGE attenuated the ameliorative effect of evodiamine on the above indexes in high glucose-induced trophoblast cells （except for AGE mRNA and protein） （P＜0.05）.CONCLUSIONSEvodiamine can promote the proliferation， migration and invasion of high glucose-induced trophoblast cells and ameliorate their functional impairment， and the above effects are associated with the inhibition of the AGE/RAGE signaling pathway.关键词：high glucose;trophoblast cells;proliferation;migration;invasion;AGE/RAGE signaling pathway
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发布时间：2024-06-25 - 摘要：OBJECTIVETo investigate the neuroprotective effect of curculigoside （CUR） on rats with spinal cord injury （SCI） based on phosphatase and tensin homologue deleted on chromosome ten gene-induced putative kinase 1 （PINK1）/E3 ubiquitin ligase Parkin signaling pathway.METHODSTaking male SD rats as subjects， 15 rats were randomly selected as sham operation group； the rest rats were chosen to establish SCI model by spinal cord impact method， and then were divided into model group， CUR low-dose group （36 mg/kg CUR， gavage）， CUR high-dose group （72 mg/kg CUR， gavage） and CUR high-dose+3-methyladenine （3-MA） group （72 mg/kg CUR， gavage+20 mg/kg autophagy inhibitor 3-MA， intraperitoneal injection）， with 15 rats in each group. Rats in each group were given corresponding liquid/normal saline， once a day， for 28 consecutive days. Basso-Beattie-Bresnahan （BBB） score and Rivlin inclined plate experiment were performed on the 14th and 28th day after administration； the pathological changes of spinal cord tissue in rats were observed in each group； the apoptosis of spinal cord tissue， the levels of oxidative stress factors [malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）]， and the protein expressions of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， PINK1， Parkin， p62 and microtubule-associated protein light chain 3 （LC3） were all determined.RESULTSCompared with the sham operation group， obvious edema and bleeding in the spinal cord tissue of rats were observed in the model group， accompanied by a large number of inflammatory cell infiltration； BBB score and inclined plate angle， SOD and GSH levels， the protein expressions of BDNF， PINK1 and Parkin， and LC3Ⅱ/Ⅰ ratio were significantly reduced； the apoptosis rate， MDA level， the protein expressions of GFAP and p62 in spinal cord tissue were significantly increased （P＜0.05）. Compared with the model group， the edema， bleeding and infiltration of inflammatory cells in the spinal cord tissue of rats were reduced in the administration groups， and the above quantitative indicators had been significantly improved （P＜0.05）； 3-MA could significantly reverse the improvement effects of the above indexes by CUR （P＜0.05）.CONCLUSIONSCUR can promote the recovery of neurological and motor functions in SCI rats， improve the pathological injury of the spinal cord and inhibit apoptosis， which may be related to mitochondrial autophagy mediated by activating the PINK1/Parkin signaling pathway.关键词：spinal cord injury;neuroprotection;PINK1/Parkin signaling pathway;mitochondrial autophagy
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发布时间：2024-06-25 - 摘要：OBJECTIVETo explore the effect of paeoniflorin on glucose metabolism， inflammation and oxidative stress in rats with gestational diabetes mellitus （GDM） and its potential mechanism based on nuclear factor-erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/nicotinamide adenine dinucleotide phosphate：quinone oxidoreductase 1 （NQO1） signaling pathway.METHODSThe female rats fed with high fat and high sugar diet and the male rats fed with an ordinary diet were caged， the successfully conceived rats were collected， and streptozotocin was injected intraperitoneally once to induce the GDM model. The successfully modeled rats were randomly divided into the model group， metformin hydrochloride group （200 mg/kg metformin by gavage）， paeoniflorin low-， high-dose groups （45， 90 mg/kg paeoniflorin by gavage， respectively）， paeoniflorin+ML385 group （90 mg/kg paeoniflorin by gavage and intraperitoneal injection of 30 mg/kg Nrf2 inhibitor ML385）， with 12 rats in each group； in addition， another 12 conceived rats fed with an ordinary diet were selected as the control group. The rats in each drug group were given the corresponding drug/normal saline， once a day， for 2 consecutive weeks. Glucose metabolism indexes [fasting blood glucose （FBG）， fasting insulin （FINS）， insulin resistance index （HOMA-IR）]， serum inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）] and renal tissue oxidative stress indexes [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）] were detected； the pathological changes of renal tissue were observed， and the protein expressions of Nrf2， HO-1 and NQO1 in renal tissue were detected.RESULTSCompared with the control group， the renal tissue lesions of the model group were obvious， including glomerular atrophy， edema degeneration of renal tubular epithelial cells and a large number of inflammatory cell infiltration； the levels of FBG and FINS， HOMA-IR， the levels of IL-6 and TNF-α in serum， and the level of MDA in renal tissue were significantly increased （P＜0.05）， while the levels of SOD and GSH-Px and the protein expressions of Nrf2， HO-1 and NQO1 in renal tissue were significantly decreased （P＜0.05）. Compared with the model group， the renal tissue lesions of rats in paeoniflorin low-dose and high-dose groups were reduced， the above quantitative indexes were significantly improved， and the improvement effect was better in high-dose group （P＜0.05）， while ML385 could significantly reverse the improvement effect of paeoniflorin on the above indexes （P＜0.05）.CONCLUSIONSPaeoniflorin can improve the abnormal glucose metabolism， inflammation and oxidative stress damage of renal tissue in GDM rats， which may be related to the activation of Nrf2/HO-1/NOQ1 signaling pathway.关键词：gestational diabetes mellitus;inflammation;oxidative stress;Nrf2/HO-1/NQO-1 signaling pathway
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发布时间：2024-06-25 - 摘要：OBJECTIVETo study the protective effect and possible mechanism of soybean isoflavones against threatened miscarriage rats.METHODSFemale mice were selected to promote estrus and mate with male mice. After pregnancy， they were randomly divided into normal group （purified water， i.g.， n＝10）， model group （purified water， i.g.， n＝9）， positive control drug group （progesterone 4 mg/kg， i.m.， n＝9）， low-， medium- and high-dose soybean isoflavone groups （25， 50 and 100 mg/kg， i.g.， n＝10）. Except for the normal group， the rest were given mifepristone+misoprostol on the 8th day of pregnancy to establish threatened miscarriage model， and then given purified water or drugs， once a day， on days 1-7 and 9-12 of pregnancy， respectively. At 14 days of pregnancy， the rates of fetal protection were counted. Serum levels of β-human chorionic gonadotrophin （β-HCG） and progesterone （P） in rats were detected. Pathological and morphological changes in rat placenta and decidua tissues were observed， and the apoptosis indexes of cells were detected； mRNA and protein expressions of factor of apoptosis related （Fas）， factor of apoptosis related ligand （FasL）， proliferating cell nuclear antigen （PCNA） and heparin binding epidermal growth factor （HB-EGF） were determined in placenta tissues， and mRNA and protein expressions of Fas， PCNA and HB-EGF in decidua tissues were detected.RESULTSIn the model group， the placental tissues of rats were hyperemia and dilatation， with fewer and irregular blood vessels； severe stromal edema， inflammatory cell infiltration and iron-choledrin deposition were observed. Compared with model group， the fetal survival rates， serum levels of β-HCG and P， the expressions of PCNA and HB-EGF mRNA and proteins in the placenta and decidua tissue of soybean isoflavone groups increased significantly （P＜0.05）， while pathological changes were improved significantly； cell apoptosis index in the placenta and decidua tissue， the expressions of Fas， FasL mRNA and proteins in the placenta and Fas mRNA and protein in the decidua tissue decreased significantly （P＜0.05）. The effect of soybean isoflavones was dose-dependent （P＜0.05）.CONCLUSIONSSoybean isoflavone has protective effect on threatened miscarriage， the mechanism of which is related to down-regulating the expressions of Fas and FasL mRNA and protein at the maternal-fetal interface， and up-regulating the expressions of mRNA and protein of PCNA and HB-EGF.关键词：threatened miscarriage;maternal-fetal interface;factor of apoptosis related;factor of apoptosis related ligand;proliferating cell nuclear antigen;heparin binding epidermal growth factor
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发布时间：2024-06-25 - 摘要：OBJECTIVETo investigate the effect of pachymic acid （PA） on renal function and fibrosis in chronic renal failure （CRF） rats and its potential mechanism based on the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway.METHODSUsing male SD rats as subjects， the CRF model was established by 5/6 nephrectomy； the successfully modeled rats were divided into model group， PA low-dose， medium-dose and high-dose groups （5， 10， 20 mg/kg PA）， high-dose PA+ROCK pathway activator lysophosphatidic acid （LPA） group （20 mg/kg PA+1 mg/kg LPA）， with 15 rats in each group. Another 15 rats were selected as the sham operation group with only the kidney exposed but not excised. The rats in each drug group were gavaged and/or injected with the corresponding liquid via the caudal vein， once a day， for 12 consecutive weeks. During the experiment， the general condition of rats was observed in each group. After the last administration， the serum renal function indexes （blood urea nitrogen， serum creatinine， uric acid） of rats in each group were detected， the renal histopathological changes were observed； the renal tubule injury score and the area of renal fibrosis were quantified. The levels of oxidative stress indexes [malondialdehyde （MDA）， superoxide dismutase （SOD）] and inflammatory factors （tumor necrosis factor-α， interleukin-1β， interleukin-6）， the positive expression rates of connective tissue growth factor （CTGF） and collagen Ⅰ were detected as well as the expression levels of pathway-related proteins （RhoA， ROCK1） and fibrosis-related proteins （transforming growth factor-β1， bare corneum homologs 2， α-smooth muscle actin） were determined.RESULTSCompared with the sham operation group， the rats in model group had reduced diet， smaller body size， listless spirit and sluggish response， reduced and atrophied glomeruli， dilated renal tubules with chaotic structure， and a large number of inflammatory cells infiltrated interstitium； the serum levels of renal function indexes， renal tubule injury score， renal fibrosis area proportion， the levels of MDA and inflammatory factors， the positive expression rates of CTGF and collagen Ⅰ， and the expression levels of pathway-related proteins and fibrosis-related proteins in renal tissues were significantly increased， while SOD level was significantly decreased （P＜0.05）. Compared with the model group， the general condition and pathological injuries of kidney tissue of rats in PA groups were improved to varying degrees， and the above quantitative indexes were significantly improved in a dose-dependent manner （P＜0.05）. LPA could significantly reverse the improvement effect of PA on the above indicators （P＜0.05）.CONCLUSIONSPA can improve renal function and alleviate renal fibrosis in CRF rats， which may be related to inhibiting the activation of RhoA/ROCK signaling pathway.关键词：chronic renal failure;renal function;fibrosis;RhoA/ROCK signaling pathway
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发布时间：2024-06-25 - 摘要：OBJECTIVETo provide reference for the rational use of antiemetic drugs in tumor chemotherapy patients.METHODSThe data of tumor patients who were given antiemetic drugs were collected from 9 departments of our hospital with hospital information system from Oct. 1st to Nov. 30th in 2022， such as oncology department， radiotherapy department， gynecology department， and gastroenterology department. The application of chemotherapy drugs and the use of antiemetic drugs were analyzed statistically， and the irrational use of antiemetic drugs was analyzed.RESULTSA total of 520 patients were included， involving 248 （47.69%） using chemotherapy drugs with a moderate emetogenic risk level and 135 （25.96%） with a high emetogenic risk level. A total of 461 cases （73.06%） of 5-hydroxytryptamine 3-receptor antagonists were used， including palonosetron in 333 cases， ondansetron in 106 cases， tropisetron in 15 cases and granisetron in 7 cases， and only 148 cases of patients were prioritized for the use of nationally procured medicines and national essential medicines （32.10%）. Neurokinin-1 receptor antagonists were used in 170 cases （26.94%）， including fosaprepitant in 112 cases and aprepitant in 58 cases. The use of antiemetic drugs was unreasonable in 162 patients （31.15%）； among the types of irrational drugs， the antiemetic regimen was unreasonable in the largest number of cases （22.40%）， followed by the irrational pharmacoeconomics （19.13%）.CONCLUSIONSThe emetogenic risk levels of chemotherapy drugs used for tumor patients in our hospital are primarily moderate to high， and there is irrational use of antiemetic regimen and pharmacoeconomics. Clinicians， nurses， pharmacists and hospital departments should collaborate as multiple teams to strengthen full supervision of the standardization of antiemetic drugs， reasonably select antiemetic drugs based on emetogenicity rating， and improve the compliance of doctors with the guidelines to ensure the safety， effectiveness， and cost-effective of patient medication.关键词：emetogenicity rating;rational drug use;chemotherapy-induced nausea and vomiting;tumor
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发布时间：2024-06-25 - 摘要：OBJECTIVETo establish a method for determining the blood concentration of apatinib and apply it clinically.METHODSUltra-high performance liquid chromatography （UPLC） was used for the determination of blood concentration. The chromatographic column was ACQUITY UPLC BEH C18 with the mobile phase consisted of acetonitrile-0.1% formic acid aqueous solution （gradient elution） at the flow rate of 0.2 mL/min； the column temperature was 40 ℃， and the injection volume was 5 μL. The data of 26 cancer patients taking apatinib were collected， and their blood concentrations were measured. The correlation between patient’s blood concentration and age， dosage， adverse reactions， and combination therapy were analyzed； the levels of serum kidney injury-related factors [cystatin C （CysC）， kidney injury molecule 1 （KIM-1）， interleukin-18 （IL-18）， tumor necrosis factor-α （TNF-α）] were determined before and after treatment.RESULTSThe linear range of apatinib was 500-2 000 ng/mL， with a precision RSD of 3.7%， stability RSD of 4.9%， and an average sample recovery rate of 96.0% （RSD was 2.1%）. The lowest blood concentration of apatinib was 103 ng/mL and the highest was 1 932 ng/mL among 26 patients. The blood concentration of apatinib in patients showed a fluctuating downward trend with age. At a dosage of 0.125 or 0.25 g， the blood concentration of patients taking apatinib was concentrated within the range of 1 000-2 000 ng/mL. Among 26 cancer patients， 13 experienced adverse reactions， and no adverse reaction was observed in those with blood concentrations ranging from 500 to ＜1 000 ng/mL. Twenty patients were simultaneously treated with other drugs， resulting in varying blood concentration. After treatment， the levels of serum CysC， KIM-1， IL-18 and TNF-α were significantly higher than before treatment （P＜0.05）.CONCLUSIONSThe established UPLC method can quickly detect the blood concentration of apatinib. When using apatinib in clinical practice， comprehensive consideration should be given to the patient’s age， drug combination， and the attention should be paid to preventing possible acute kidney damage caused by apatinib.关键词：blood concentration monitoring;ultra-high performance liquid chromatography;kidney injury;adverse drug reactions
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发布时间：2024-06-25 - 摘要：OBJECTIVETo explore the risk signals of Fluocinolone acetonide intravitreal implants and promote safe and rational drug use for patients.METHODSBased on the data from the Hainan Province Franchised Drug Adverse Reaction Monitoring Subsystem （hereinafter referred to as the “Franchised Drug Monitoring System”） and the FDA Adverse Event Reporting System （FAERS）， the adverse drug reaction （ADR）/adverse drug event （ADE） reports of Fluocinolone acetonide intravitreal implants were coded by using system organ classification and preferred terminology， and relevant patient information was collected. Risk signal mining was carried out by using the reporting odds ratio （ROR） method and the comprehensive standards method of the UK Medicines and Healthcare Products Regulatory Agency （hereinafter referred to as the “MHRA method”）.RESULTSAmong the 72 reports of Fluocinolone acetonide intravitreal implants received by the Franchised Drug Monitoring System， the ratio of male to female was 1∶1.4， the patient’s age was mainly distributed between 18 and 64 years old； ADR/ADE affected 5 systemic organs， with eye organ diseases accounting for 87.7%； among them， there were 9 new and general ADR reports （12.5%） and 4 severe ADR reports （5.6%）； ROR method and MHRA method both identified three risk signals： cataracts， glaucoma， and high intraocular pressure. Among the 244 reports received by the FAERS database， the ratio of male to female was 1∶1.5； ADR/ADE damage affected 10 systemic organs， with 46.1% suffering from various injuries， poisoning， and operational complications， and 32.0% suffering from product problems； there were 20 severe ADR reports （8.2%）； ROR method and MHRA method both identified 19 risk signals， including implantation complications， medication system issues， etc.CONCLUSIONSWhen using Fluocinolone acetonide intravitreal implants in clinical practice， in addition to paying attention to eye ADR/ADE such as high intraocular pressure， cataracts， and glaucoma， attention should also be paid to the potential risks caused by ADE due to product quality and unreasonable use.关键词：uveitis;adverse reaction;adverse event;risk signals;reporting odds ratio;UK Medicines and Healthcare Products Regulatory Agency
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发布时间：2024-06-25 - 摘要：OBJECTIVETo provide reference for safe drug use in the clinic by mining the adverse drug event （ADE） signals of 4 kinds of biological agents for the treatment of inflammatory bowel disease （IBD）.METHODSADE data of infliximab， adalimumab， ustekinumab and vedolizumab were collected from the FDA adverse event reporting system between the first quarter in 2004 and the fourth quarter in 2022， and were mined by using reporting odds ratio （ROR） method and proportional reporting ratio （PRR） method. The system organ class （SOC） was used for the classification and statistics of drug ADE terminology. RESULTS &CONCLUSIONSA total of 65 173， 247 894， 37 596 and 6 134 ADE reports were retrieved for the above 4 biologic agents， involving 1 664， 1 731， 588， 303 ADE signals and 27， 27， 24， 26 SOC， respectively. The largest number of ADE reported of infliximab were various musculoskeletal and connective tissue diseases， and the signal intensity of disseminated tuberculosis was stronger. The largest number of ADE reported of adalimumab were systemic disease and various reactions at the administration site， and the signal intensity of papular at the injection site was stronger. The largest number of ADE reported of ustekinumab were various injuries， poisoning and operation complications， and the signal intensity of latent tuberculosis was slightly stronger. The largest number of ADE reported of vedolizumab were systemic diseases and various reactions at the administration site， and the signal intensity of shorter treatment response time was stronger. When clinically administering the four drugs， it is crucial to pay close attention to common ADEs and other ADE not mentioned in the drug label. For infliximab， clinicians should exercise caution due to the potential risk of synovitis and basal cell carcinoma； when prescribing adalimumab， caution should be exercised due to ADEs related to synovitis and hernia； for ustekinumab， the ADE associated with hepatobiliary diseases should be vigilant； for vedolizumab， clinicians should be vigilant for blood in the stool， increasing frequency of defecation. Except for ustekinumab， the other 3 biological agents also require attention for ADE associated with pregnancy.关键词：biological agents;infliximab;adalimumab;ustekinumab;vedolizumab;adverse events
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发布时间：2024-06-25 - 摘要：OBJECTIVETo investigate the efficacy and safety of Wuling capsules combined with low-dose quetiapine in the treatment of oldest-old patients with insomnia accompanied by anxiety and depression.METHODSThe clinical data of 96 oldest-old patients （aged≥80 years） with insomnia accompanied by anxiety and depression who were attending outpatient clinics or hospitalized in our hospital from June 2020 to December 2022 were retrospectively analyzed. According to the different drug treatments， the patients were divided into Wuling capsules group （0.99 g， tid， 34 cases）， quetiapine group （25-50 mg， qn， 30 cases） and combination group （using Wuling capsules and quetiapine simultaneously， same as the single drug groups， 32 cases）. Before and after 8 weeks of treatment， the patients of three groups were compared in terms of photoplethysmography sleep monitoring indexes （total sleep duration， sleep efficiency， sleep latency， and the number of awakening）， Pittsburgh sleep quality index （PSQI） score， 14-item Hamilton anxiety scale （HAMA-14） score， 17-item Hamilton depression scale （HAMD-17） score， mini-mental state examination （MMSE） score， and serum levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）； the therapeutic effects and adverse drug reactions of the three groups were observed and compared.RESULTSCompared with before treatment， the total sleep time， sleep efficiency and MMSE scores of the three groups were significantly longer or higher after treatment （P＜0.05）， while the sleep latency， number of awakening， PSQI score， HAMA-14 score， HAMD-17 score， serum IL-1β and TNF-α levels were significantly shorter or lower after treatment （P＜0.05）. Sleep latency， number of awakening， HAMA-14 score， HAMD-17 score and serum TNF-α level in quetiapine group were significantly shorter or lower than Wuling capsules group after treatment （P＜0.05）. Moreover， the above indexes in the combination group were significantly better than quetiapine group and Wuling capsules group （P＜0.05）. The total effective rate of treatment in the combination group was significantly higher than the other two groups （P＜0.05）. There was no significant difference in the incidence of adverse drug reactions among the three groups （P＞0.05）.CONCLUSIONSThe therapeutic effect of Wuling capsules combined with low-dose quetiapine is better than that of individual drugs for oldest-old patients with insomnia accompanied with anxiety and depression， not increasing the risk of adverse reactions.关键词：low-dose quetiapine;insomnia;anxiety;depression;oldest-old patients
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发布时间：2024-06-25 - 摘要：OBJECTIVETo observe the clinical efficacy and safety of camrelizumab combined with sorafenib in the treatment of advanced liver cancer.METHODSSixty patients with advanced liver cancer who were treated in our hospital from March 2020 to November 2021 were selected as the study subjects， and then were randomly divided into study group and control group， with 30 cases in each group. The control group was treated with Sorafenib tosylate tablets orally （0.4 g，bid）， and the study group was additionally given Camrelizumab for injection intravenously （200 mg， every 3 weeks） based on the control group； for all patients， the treatment was stopped until disease progression or intolerable side effects occurred. The clinical efficacy， progression-free survival （PFS）， total survival （OS） and 1-year survival rate of the two groups were compared， and the incidence of adverse reactions in two groups， and immune-related adverse reactions in the study group during treatment were recorded.RESULTSThe objective remission rate of the study group was significantly higher than the control group （36.7% vs. 13.3%， P＜0.05）， and the median OS and median PFS were significantly longer than the control group （OS： 12.6 months vs. 7.9 months； PFS： 8.2 months vs. 5.3 months， P＜0.05）. There was no significant difference in the 1-year survival rate and the incidence of elevated aspartate aminotransferase and alanine aminotransferase， rash or pruritus， anorexia， diarrhea， fatigue and hypertension between the two groups （P＞0.05）. The adverse events immune-related in the study group mainly included 21 cases of reactive capillary hyperplasia （70.0%）， 6 cases of hypothyroidism （20.0%）， and 1 case of immune-associated pneumonia （3.3%）， which were improved or tolerable after symptomatic treatment.CONCLUSIONSCamrelizumab combined with sorafenib in the treatment of advanced liver cancer can effectively control and delay the disease progression， prolong the survival period of patients， and the adverse reactions can be tolerated.关键词：camrelizumab;liver cancer;advanced;survival period;therapeutic effect;safety
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发布时间：2024-06-25 - 摘要：OBJECTIVETo explore the pharmaceutical care of reactivating anthracycline chemotherapy in patients with advanced breast cancer complicated with thyroid cancer.METHODSClinical pharmacists participated in the whole treatment process of a patient with advanced breast cancer complicated with thyroid cancer and provided personalized medication recommendations. Considering that the patient currently has multiple primary anti-tumor drug resistance， clinical pharmacists recommend reactivating the EC rescue protocol （intravenous infusion of epirubicin hydrochloride 140 mg+cyclophosphamide 1 g， d1， 21 days for a cycle）. The cumulative lifetime dose of epirubicin and the optimal course of chemotherapy was estimated according to the body weight change of the patient. Given the issue that abnormal fluctuation of thyroid stimulating hormone （TSH） level during chemotherapy may increase the risk of cardiac toxicity， clinical pharmacists suggest adopting a dose adjustment strategy of “fast first and slow later” for Levothyroxine sodium tablet according to the target range of TSH and test results.RESULTSThe doctors adopted the pharmacists’ suggestion； the clinical pharmacists assisted the doctors in reactivating the anthracycline-based 7-cycle combination regimen， during which the patient had no significant cardiac adverse events and was repeatedly evaluated as stable. TSH decreased steadily after Levothyroxine sodium tablets were added， and no adverse reaction related to TSH inhibition was observed.CONCLUSIONSPatients with primary drug-resistant breast cancer complicated with thyroid cancer may be reactived anthracyclines if necessary， but baseline cardiac function and thyroid hormone levels should be tested before initiation， and cardiac toxicity risk assessment should be performed in combination with the patient’s history. Clinical pharmacists should actively exert their professional advantages to carry out whole-process pharmaceutical care for such patients， so as to ensure the safety of drug use for patients.关键词：breast cancer;thyroid cancer;pharmaceutical care;clinical pharmacist
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发布时间：2024-06-25 - 摘要：OBJECTIVETo provide ideas for clinical diagnosis， treatment and pharmaceutical care of rhino-orbito-cerebral mucormycosis （ROCM）.METHODSThe diagnosis and treatment of 1 case of ROCM in which clinical pharmacists participated were analyzed. Combined with treatment guidelines， the actual situation of drug accessibility and economy， clinical pharmacists recommend amphotericin B colloidal dispersion in combination with posaconazole to treat fungal infections. The clinical efficacy， liver and kidney function and electrolytes were monitored. To increase the local concentration of amphotericin B deoxycholate （AmB-D）， clinical pharmacists assisted physicians in determining the dosage and formulation of AmB-D for intrathecal injection， intranasal and eye drops based on the results of blood and cerebrospinal fluid examinations. In response to the situation that the plasma trough concentration of posaconazole had not reached the target， clinical pharmacists recommended that Posaconazole oral suspension was replaced with Posaconazole enteric-coated tablets， and provided the patient with therapeutic drug monitoring （TDM）， individualized medication guidance， and long-term follow-up after discharge.RESULTSThe clinician adopted the advice of the clinical pharmacists. After treatment， the patient was discharged from the hospital with medicine after her condition improved.CONCLUSIONSClinical pharmacists develop individualized treatment protocols for ROCM patients by adjusting dose and dosage forms， providing medication monitoring and TDM to ensure the safety of drug use for patients.关键词：amphotericin B colloidal dispersion;posaconazole;therapeutic drug monitoring;clinical pharmacist
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发布时间：2024-06-25 - 摘要：Glucagon-like peptide-1 receptor agonists （GLP-1RAs） have been widely used in diabetes and obese people in recent years， and they have also caused a series of adverse reactions， the most important of which is digestive system-related adverse reactions. The adverse reactions of the digestive system associated with GLP-1RAs involve the gastrointestinal， pancreatic， and biliary tracts； among them， nausea， vomiting， constipation， and diarrhea are the most common adverse reactions， which are the main reasons for drug withdrawal. The incidence of pancreatic and biliary system diseases is low， but there is no research evidence to exclude their association with GLP-1RAs. Tirzepatide appears on the market relatively late， and its safety still lacks sufficient real-world data. Medical staff should adopt active dietary guidance strategies for patients and strengthen medication education to help patients actively prevent and scientifically respond to adverse reactions in the digestive system.关键词：digestive system;adverse reaction
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发布时间：2024-06-25
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