摘要:OBJECTIVETo compare the clinical comprehensive value of 15 Chinese patent medicines for the treatment of chronic hepatitis B, in order to provide reference for clinical rational drug use.METHODSAccording to the Management Guidelines for Clinical Comprehensive Evaluation of Pharmaceuticals (2021 Version for Trial Implementation), systematic literature review, meta-analysis and other related data analysis methods were used to perform qualitative and quantitative analysis for the safety, efficacy, economy, suitability, accessibility and innovation of 15 Chinese patent medicines.RESULTSIn terms of safety, most of the adverse drug reactions of chronic hepatitis B Chinese patent medicines before the market were unobserved or unclear; post-marketing safety took nucleoside analogs as the intermediate bridge for meta-analysis, there was no significant difference in the incidence of adverse drug reactions among the combined regimens of Chinese patent medicines (P>0.05), except that the combination regimen of Fuzheng huayu capsule, Compound yiganling capsules versus combination regimen of Jiuwei gantai capsules showed statistically significant differences (P<0.05). In terms of effectiveness, the results of network meta-analysis showed that most Chinese patent medicines, such as Fuzheng huayu capsules combined regimens, had no significant differences in effective rate, HBeAg negative conversion rate and HBV-DNA negative conversion rate (P>0.05); however, in reducing the liver elastic hardness value, the combined regimen of Dangfei liganning tablet (capsule) was better than the other combined regimens (P<0.05). In terms of economy, the highest cost was the Shuganning injection, and the lowest was Hepatitis B qingre jiedu granules. In terms of suitability, most of the medicines were capsules, tablets and granules, which only needed to be sealed to store and taken orally or taken with boiling water. Compared with injections and some similar products that required strict control of storage temperature, its suitability was better. In terms of accessibility, from the perspective of drug price and affordability, Shuganning injection had the highest average daily cost, the number of days that needed to be borne by the average daily wage was the highest; the average daily cost of Compound yiganling tablets was the lowest, and the number of days required to be borne by the average daily wage was the lowest. From the perspective of availability, Compound biejia ruangan tablets, Dangfei liganning capsules and Wuzhi granules were easier to obtain. In terms of innovation, the 15 Chinese patent medicines included in the study were all domestically produced medicines with a relatively long-term theoretical basis of traditional Chinese medicine and experience in human medicine, and had good industrial innovation. Among them, Compound huayu tablets (capsules) and Anluo huaxian pills were protected varieties of traditional Chinese medicine; Fuzheng huayu tablets (capsules) with more patents had 6 valid patents, all of which were patents for invention.CONCLUSIONSWuzhi capsule, Sedum sarmentosum granules, Compound yiganling tablets, Rhubarb buchong pills and Dangfei liganning capsules have high clinical comprehensive value.
关键词:Chinese patent medicine;clinical comprehensive evaluation;rational drug use
摘要:OBJECTIVETo analyze the difference between the payment limitations of anti-cancer drugs and application scope of drug instructions, so as to better implement the payment policy of medical insurance drugs.METHODSThe differences between the payment limitations of anti-cancer drugs and application scope of drug instructions in the National Catalogue of Drugs for Basic Medical Insurance, Industrial Injury Insurance and Maternity Insurance (2022) were compared and analyzed; the evidence-based basis of the difference was discussed, and the scope of limited payment was interpreted.RESULTSTotally 118 drugs had payment limitations; limitations scope mainly included limited evidence of gene detection results, limited indications, limited second-line and above treatment, limited payment duration, limited specialist prescription, limited medical institution grade, etc. Among them, 43 drugs had differences between the payment limitations and drug instructions, and the indications of 31 drugs were greater than payment limitations; for seven drugs, the drug indications beyond the payment limitations were recommended by the guidelines. The payment limitations of 75 drugs were consistent with drug instructions. The second-line and multi-line treatment was ineffective or intolerable with first-line drugs. There was a certain relationship between locally advanced, advanced or metastatic tumor and tumor stage, but different tumors had different criteria. Systemic treatment mainly referred to systemic treatment with drug. The results of limited genetic test required that the result was positive or negative. In addition, six kinds of TCM injections were limited to the level of medical institutions; the payment of two drugs did not exceed 12 months; when lenalidomide was combined with isazomide citrate, the medical insurance only paid for one of the drugs.CONCLUSIONSThe payment limitations of some anti-cancer drugs are inconsistent with the drug indications. The drug payment limitations should be expanded according to the actual situation of clinical medication and the recommendations of guidelines. At the same time, the payment limitations should be formulated accurately and in detail, thus clinical and medical insurance staff can understand it and fully protect the interests of patients.
摘要:OBJECTIVETo investigate the effect of raw and wine-processed Schisandra chinensis on neuro-immune-endocrine network in insomnia mice and its mechanism.METHODSFifty mice were randomly divided into blank group, model group, diazepam group, raw S. chinensis group and wine-processed S. chinensis group, with 10 mice in each group. Except for blank group, the mice in the other groups were intraperitoneally injected with thyroxine solution to establish mice model of insomnia; at the end of each day’s modeling, the corresponding doses of diazepam,raw and wine-processed S. chinensis were given by gavage. The blank group and model group were given constant volume of normal saline. The general state of the mice was observed and recorded, and the total activity distance and upright times of the mice were detected; the EEG and EMG signals of mice were recorded, and the time ratio of sleep wake time (wake), non-rapid eye movement (NREM) and rapid eye movement (REM) was analyzed; the contents of neurotransmitters [γ-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), cortisol (CORT)] in brain suprachiasmatic nucleus (SCN) were detected; and the expressions of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were detected; the mRNA expressions of clock gene Bmal1, circadian clock gene Clock and cycle gene Per2 were all detected.RESULTSCompared with the blank group, the mental state of the model group mice was relatively depressed, the amount of food and water increased, the body mass decreased, the hair was rough and shiny, and the circadian rhythm was irregular; the total activity distance and upright times decreased significantly; the time ratio of wake increased significantly, while the time ratios of REM and NREM decreased significantly; the content of 5-HT in brain SCN decreased significantly, while the content of NE, DA and CORT increased significantly; the fluorescence intensity of IL-1β and TNF-α was significantly increased; the relative expression level of Bmal1 and Clock mRNA was significantly increased, while the relative expression level of Per2 mRNA was significantly decreased (P<0.05 or P<0.01). Compared with the model group, the general state of mice in diazepam group, raw S. chinensis group and wine-processed S. chinensis group was improved obviously, and most of the above index levels were significantly reversed (P<0.05 or P<0.01).CONCLUSIONSRaw and wine-processed S. chinensis have a certain therapeutic effect on insomnia mice, the mechanism of which may be related to the regulation of neuro-endocrine-immune system related biological indicators in insomnia mice.
摘要:OBJECTIVETo investigate the improvement mechanism of caudatin on liver injury of rats.METHODSSD rats were randomly divided into blank group, model group, caudatin low-dose and high-dose groups (25, 50 mg/kg), with 6 rats in each group. Diethylnitrosamine (DEN) was injected intraperitoneally three times per week for eight weeks to establish liver injury model of rats. At 5th week of modeling, the rats received relevant medicine or 0.5% sodium carboxymethylcellulose intragastrically for 4 weeks. The levels of liver function indexes [alanine transaminase (ALT), aspartate transaminase (AST), total protein (TP) and total bilirubin (TBI)] and inflammatory factors [interleukin (IL-6), tumor necrosis factor α (TNF-α), IL-1β] in serum were detected; the histopathological morphological changes of rat liver were observed; the positive protein expressions of nuclear factor κB (NF-κB) and 78 kDa glucose regulatory protein (Grp78) in liver tissue were also determined; the expressions of endoplasmic reticulum stress-related protein Grp78, C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6) and inositol requiring enzyme 1α (IRE1α) and the level of protein kinase R-like endoplasmic reticulum kinase (PERK) in liver tissue were detected.RESULTSCompared with blank group, serum levels of ALT, AST, TBI, IL-6, TNF-α and IL-1β and positive expressions of NF-κB and Grp78 in liver tissue as well as protein expressions of Grp78, CHOP, ATF6 and IRE1α, PERK protein phosphorylation level were all increased significantly in model group (P<0.05), while the serum level of TP was decreased significantly (P<0.05). The disordered structure of liver lobule, swollen liver cells, unclear intercellular boundary were observed and accompanied by inflammatory cell infiltration. Compared with model group, most of the above indexes were significantly reversed in caudatin groups (P<0.05); the structure of hepatic lobule was relatively complete and clear, the cells were arranged orderly, and the infiltration of inflammatory cells was also reduced.CONCLUSIONSCaudatin has a significant improvement effect against DEN-induced liver injury in rats, the mechanism of which may be associated with inhibiting endoplasmic reticulum stress and inflammatory reaction.
摘要:OBJECTIVETo investigate the protective effects and mechanism of ziyuglycoside Ⅰ on acute lung injury in sepsis rats based on network pharmacology, and conduct experimental verification.METHODSThe network pharmacology was used to predict the potential target of ziyuglycoside Ⅰ in the treatment of acute lung injury following sepsis. The rat model of sepsis was reproduced by cecum ligation and puncture for experimental verification. Totally 192 SD rats were randomly divided into the sham operation group (Sham group), sepsis group (Sep group), conventional therapy group (CT group) and ziyuglycoside Ⅰ group (ZgⅠ group), respectively. Sham group and Sep group were given sterile normal saline, and CT group and ZgⅠ group were given relevant volume of Ringer’s solution and ziyuglycoside Ⅰ. The arterial blood gas, serum inflammatory factors, lung wet/dry mass ratio, pathological changes of lung tissue, pulmonary vascular permeability, the expressions of pulmonary vein tight junction protein 1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) protein and 72-hour survival were observed in each group.RESULTSResults of network pharmacology showed that there were 47 potential targets of ziyuglycoside Ⅰ in the treatment of sepsis. The results of gene ontology function enrichment analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that the mechanism could be correlated with biological processes such as positive regulation of reactive oxygen species metabolism, wound healing, regulation of endothelial cell proliferation, cell activation, blood vessel development, response to oxidative stress, etc., and with signaling pathway such as apoptosis, tight junction, HIF-1 signaling pathway, etc. The results of experimental verification showed that compared with Sham group, pH value and the level of partial arterial oxygen pressure were decreased significantly in Sep group (P<0.05), while the level of partial pressure of carbon dioxide, serum levels of tumor necrosis factor α, interleukin 6 were increased significantly (P<0.05); the ratio of lung wet/dry mass was increased significantly (P<0.05); the protein expressions of ZO-1 and VE-cadherin were decreased significantly (P<0.05); 72 h survival rate decreased,the survival time was significantly shortened (P<0.05); the results of pathological observation of lung tissue showed that the rats’ alveoli were extensively ruptured, the alveolar wall was thickened and accompanied with edema, and there was obvious inflammatory cell infiltration; the results of pulmonary vascular permeability observation showed that the lung surface of rats was dark, with a large amount of Evans blue exudation, and the left lower lung was obviously dark blue. Compared with Sep group, the levels of above indexes almost were reversed significantly in CT group and ZgⅠ group (P<0.05); the lung histopathology and pulmonary vascular permeability were significantly improved, and the recovery degree of ZgⅠ group was greater than that of CT group, which was close to the results of Sham group.CONCLUSIONSZiyuglycoside Ⅰ can significantly reduce inflammatory reaction and acute lung injury in septic rats, which is related to vascular function and tight junction signal pathway.
摘要:OBJECTIVETo study the extraction and enrichment technology of chrysosplenides A (CA) and I (CI) in Tibetan medicine Chrysosplenium axillare.METHODSHPLC method was used to determine the contents of CA and CI. The orthogonal experiment was used to optimize the extraction technology of CA and CI in C. axillare using total transfer rate of CA and CI as evaluation indexes, with volume fraction of ethanol, extraction temperature, extraction times and solid-liquid ratio as factors. The validation test was also performed. The enrichment technology of CA and CI in C. axillare was optimized using D101 macroporous adsorption resin as adsorbent, total contents of CA and CI as evaluation indexes, with the volume fraction and dosage of eluent for impurities and target components. The validation test was also performed.RESULTSThe optimum extraction conditions of CA and CI from C. axillare were as follows: the medicinal powder of C. axillare was extracted by ultrasound at room temperature for 45 min at one time with 8 times of 50% ethanol. Results of validation tests showed that total transfer rate of CA and CI in C. axillare was 95.43% in average (RSD=1.02%, n=3). The optimal enrichment technology was as follows: the sample solution was added into D101 macroporous adsorption resin column and stood for 1 hour; the impurities were eluted with 20% ethanol 4 BV (column volume), and CA and CI were eluted with 50% ethanol 4 BV. The results of validation tests showed that total content of CA and CI was 322.7 mg/g in average (RSD=1.05%, n=3), with average enrichment multiple of 11.61 times.CONCLUSIONSThe study has successfully optimized the extraction and enrichment technology of CA and CI from C. axillare, and can provide reference for the development and utilization of CA and CI.
关键词:extraction;enrich- ment;technology optimization;chrysosplenoside A;chrysos- plenoside I
摘要:OBJECTIVETo study the anti-inflammatory effect and mechanism of the ethanol extract and the drug-containing serum of Zhuang medicine Stahlianthus involucratus on lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation.METHODSThe drug-containing serum or blank serum was obtained by intragastrical administration of ethanol extract of S. involucratus (75.35 g/kg) or purified water. Using RAW264.7 cells as objects, RAW264.7 cells were divided into normal control group, LPS group (1 μg/mL), S. involucratus ethanol extract high-dose, medium-dose and low-dose groups (50, 25, 12.5 μg/mL), 4% or 15% blank serum groups, 4% or 15% blank serum+LPS groups, 4% or 15% drug-containing serum groups, 4% or 15% drug-containing serum+LPS groups. After culturing for 24 h, cell viability, the contents of nitric oxide (NO), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and IL-6 as well as mRNA expressions of Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) and protein expressions of nitric oxide synthase (NOS) and cyclooxygenase 2 (COX-2) were all detected in each group.RESULTSAfter culturing for 24 h, there was no statistical significance in the difference of cell viability. Compared with normal control group, the contents of NO, TNF-α, IL-1β and IL-6, mRNA expressions of TLR4 and NF-κB, and protein expressions of NOS and COX-2 were increased significantly in LPS group (P<0.05). Compared with 4% or 15% blank serum groups, the levels of above indexes were increased significantly in 4% or 15% blank serum+LPS groups (P<0.05). Compared with LPS group, the levels of above indexes were decreased significantly in S. involucratus ethanol extract groups (P<0.05). Compared with 4% or 15% blank serum+LPS groups, the levels of above indexes were decreased significantly in 4% or 15% drug-containing serum+LPS groups (P<0.05).CONCLUSIONSThe ethanol extract and the drug-containing serum of S. involucratus can significantly alleviate LPS-induced inflammatory reaction, the mechanism of which may be associated with inhibiting the activity of TLR4/NF-κB signaling pathway, down-regulating the protein expressions of COX-2 and NOS, and reducing the release of inflammatory factors.
摘要:OBJECTVE To study the improvement effects of obacunone on renal interstitial fibrosis (RIF) in unilateral ureteral obstruction (UUO) model mice, and to investigate its mechanism based on ferroptosis mediated by nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4 (GPx4) signaling pathway.METHODSThirty mice were randomly divided into sham operation group, model group, irbesartan group (positive control, 20 mg/kg), obacunone low-dose and high-dose groups (10, 40 mg/kg), with 6 mice in each group. Except for sham operation group, UUO model was established by ligation of unilateral ureter in other groups. After operation, administration groups were given intraperitoneal injection of relevant medicine, and sham operation group and model group were given intraperitoneal injection of constant volume of normal saline, once a day, for 7 consecutive days. The levels of creatinine (Cr) and blood urea nitrogen (BUN), the content of malondialdehyde (MDA) and the activities of total superoxide dismutase (T-SOD) in serum and the concentration of Fe2+ in renal tissue were all detected. HE staining and Masson staining were performed to observe the morphology and the fibrosis of renal tissues. Immunohisto- chemical staining was used to determine expressions of the fibronectin (Fn), α-smooth muscle actin (α-SMA), GPx4 and Nrf2 in renal tissue. Western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the protein and mRNA levels of Fn, α-SMA, Nrf2, GPx4 and SLC7A11 in the renal tissues.RESULTSCompared with sham operation group, serum levels of Cr and BUN, the concentration of Fe2+ in renal tissue, the protein and mRNA levels of Fn and α-SMA in model group were increased significantly (P<0.05), while the activity of T-SOD in serum, protein and mRNA expressions of Nrf2, GPx4, SLC7A11 in kidney tissue were significantly decreased (P<0.05); in the kidney tissue, the renal tubules were dilated, the collagen deposition was obvious, the fibrous bands were thicker and darker, and the renal interstitial inflammatory cells infiltrated significantly. After intervened with obacunone, the levels of above indexes (except for mRNA expression of SLC7A11 in obacunone low-dose group) in serum and renal tissue were reversed significantly (P<0.05), and pathological damage and collagen deposition of kidney tissue were alleviated.CONCLUSIONSObacunone can improve renal interstitial fibrosis of UUO model mice, the mechanism of which may be associated with activating the Nrf2/GPx4 pathway and then inhibiting ferroptosis to relieve RIF in UUO model mice.
摘要:OBJECTIVETo establish the quality control method of Flueggea suffruticosa.METHODSThe microscopical identification and thin layer chromatography (TLC) of F. suffruticosa were carried out, and the mass fractions of moisture, total ash, acid-insoluble ash and alcohol-soluble extracts in F. suffruticosa were measured based on the 2020 version of Chinese Pharmacopoeia (part Ⅳ). The content of securinine in medicinal materials was determined by high performance liquid chromatography.RESULTSThe powder of F. suffruticosa was gray-green, with obvious microscopic characteristics such as pores, pollen grains, calcium oxalate cluster crystals, ducts. The results of TLC identification showed that in the chromatograms of 16 batches of medicinal samples, the same color spots were found on the corresponding positions of the chromatograms of securinine, rutin, quercetin and F. suffruticosa control. The average mass fractions of moisture, total ash, acid-insoluble ash and alcohol-soluble extracts in 16 batches of medicinal materials were 9.26%, 6.96%, 1.17% and 28.89%, respectively. The injection volume of securinine in the range of 0.052 4-0.524 0 µg had a good linear relationship with the peak area (R2=0.999 8). RSDs of precision, repeatability and stability (24 h) test were all less than 3% (n=6 or 7). The average recovery of sample was 97.47%, RSD was 1.63% (n=6). The content of securinine in 16 batches of medicinal materials was 1.003-6.872 mg/g.CONCLUSIONSThe quality control method of F. suffruticosa is established, and the mass fractions of moisture, total ash and acid-insoluble ash should not exceed 12.0%, 9.0% and 2.0%, respectively; the alcohol-soluble extract should not be less than 20%, and the content of securinine should not be less than 1.00 mg/g.
摘要:OBJECTIVETo compare characteristic chromatogram and the contents of multiple indicator components of Morus alba decoction powder and decoction at different decoction time, and to provide experimental basis for the development of M. alba decoction.METHODSTaking decoction powder and decoction at different decoction time as subject, HPLC characteristic chromatogram of 2 kinds of samples were established with Similarity Evaluation Software System of TCM Chromatographic Fingerprint (2012 version), and similarity evaluation was performed. The contents of mulberroside A, geniposide, berberine, baicalin, quercetin and luteolin in decoction powder and decoction were determined by HPLC. The contents of each indicator component and the change of total content were as the evaluation indexes to compare the difference between the two substances during decoction.RESULTSThe similarities of characteristic chromatogram of the two substances ranged from 0.943 to 1.000 and 0.975 to 0.998 at different decoction time, respectively. Six indicator components of the decoction powder dissolved faster and had higher contents. The contents of each indicator component in the decoction powder when decocting at 20 minutes was 1.1-1.5 times of the decoction when decocting at 50 min, and the total content in the decoction powder was 1.2 times of the decoction.CONCLUSIONSCompared with decoction, M. alba decoction powder has the advantages of shortening the decoction time and saving traditional Chinese medicine resources. The results of this study lay a research foundation for “Zungu” to develop its preparation.
摘要:OBJECTIVETo screen the active ingredient with estrogenic effect from total flavonoids of Cuscutae Semen.METHODSThe estrogenic effect of total flavonoids from 10 batches of Cuscutae Semen was evaluated with mouse uterus coefficient and endometrial thickness as evaluation indexes, establish its fingerprint and calibrate the common peak. Common peak and spectrum-effect relationship of the above two indicators were analyzed by bivariate relationship analysis and grey correlation analysis to screen active components with estrogenic effect. UPLC-Q-TOF-MS technology was used to characterize the active components.RESULTSThe estrogenic effect of total flavonoids from 10 batches of Cuscutae Semen was good. Twenty-eight and thirty-three common peaks of total flavonoids in Cuscutae Semen were obtained in the positive and negative ion modes respectively. The constituents represented by peaks 7,10,12-16,26 in positive ion mode and peaks 2,5,8,9,12,16,19,22-26 in negative ion mode were highly correlated with the estrogenic effect of total flavonoids from Cuscutae Semen. Further identification showed that the active substances with estrogenic effect from the total flavonoids of Cuscutae Semen were 5,7,3′, 4′-tetramethoxyflavone, 6-O-(trans) p-coumarin-furanfructose-(2→1)-glucopyranoside, rutin, kaempferol-3,7-diglucoside, apigenin-7-O-glucoside, hyperoside, baicalin, quercitin, quercetin, apigenin, kaempferol, isorhamnetin, rhododendron, isoquercetin, kaempferol-3-furan arabinoside, 2,6-octadecanediacetylic acid.CONCLUSIONSA total of 16 chemical components with estrogenic effect are screened from total flavonoids of Cuscutae Semen in the study, which can provide reference for the development of phytoestrogens.
摘要:OBJECTIVETo systematically evaluate pharmacoeconomic studies (modeling approach) based on the Chinese acute ischemic stroke (AIS) population, and to provide the suggestions for improving the pharmacoeconomic evaluation method of AIS.METHODSRetrieved from CNKI, Wanfang Data Knowledge Service Platform, VIP, PubMed, Embase, the Cochrane Library, ScienceDirect, and Web of Science databases, relevant literature on pharmacoeconomic evaluation of AIS were collected from January 2014 to February 2022. Basic information of included study, basic information and outcome indicators of the model were analyzed statistically. The quality of the included literature was evaluated using CHEERS 2022, and problems in the existing literature were identified and suggestions were made.RESULTSTwelve papers were finally included, involving five in Chinese and seven in English. All studies reported the study perspective, mainly from the perspective of health system; the age of the target population was mainly distributed around 60 years old; the main interventions in the included studies were pharmacotherapy, including single-drug regimens and combination drug regimens; nine papers used decision trees combined with Markov models, and three papers used Markov models alone, but the classification of health status was inconsistent; all papers reported study time frame and cycle period, with most studies choosing a study time frame of 30 years and a cycle period of 1 year; all studies used modified Rankin scale scores as an indicator of clinical effectiveness, which were mainly derived from clinical trials; utility values in most literature were derived from published studies, and costs were mainly direct medical costs; all studies performed cost-utility analyses using quality-adjusted life years and/or incremental cost-effectiveness ratios as outcome indicators, and single-factor sensitivity analyses and probabilistic sensitivity analyses were performed, but no contextual analyses were conducted for the different model structures that may exist.CONCLUSIONSThe overall report of the included studies is relatively complete, but the methodology is relatively uniform, and there are still deficiencies in terms of study perspective, study time frame, parameter sources, and contextual analysis. Future AIS pharmacoeconomic evaluations should further improve the report content in accordance with the CHEERS list entries, conduct contextual analysis of multiple health state classification approaches from a society-wide perspective, while using data from real-world sources and standardizing the uncertainty analysis process of the study results to increase the authenticity and reliability of the study results.
摘要:OBJECTIVETo evaluate the cost-effectiveness of tislelizumab monotherapy in the second-line treatment of advanced or metastatic esophageal squamous cell carcinoma (ESCC),so as to provide reference for rational use of drug in clinic.METHODSA three-state partitioned survival model was constructed from the perspective of China’s health system, based on the data of RATIONALE-302 study,with simulation time limit of 10 years, cycle period of 1 month. The incremental cost-effectiveness ratio (ICER) was calculated with quality-adjusted life year (QALY) as utility index. The cost-effectiveness of tislelizumab monotherapy was compared with that of chemotherapy for second-line treatment of advanced or metastatic ESCC by cost-utility analysis. The stability of basic analysis results was validated through sensitivity analysis and scenario analysis.RESULTSThe results of basic analysis showed that compared with chemotherapy group, incremental cost per capita of tislelizumab group was 35 025.32 yuan,and incremental utility per capita was 0.23 QALYs; ICER was 154 707.71 yuan/QALY, which was far lower than the willingness-to-pay (WTP) threshold of 3 times of China’s per capita gross domestic product (GDP) 242 928 yuan in 2021. The results of univariate sensitivity analysis showed that parameters such as the cost of apatinib, the utility value of disease progression status and the cost of adverse reactions in the chemotherapy group had a great impact on the ICER value, but these parameters could not cause the reversal of the basic analysis results. Probabilistic sensitivity analysis showed that WTP threshold was 242 928 yuan/QALY,the probability of tislelizumab monotherapy possessed cost-effectiveness was 81%. Results of scenario analysis showed that in which model simulation time lasted for 5 or 20 years,ICER of tislelizumab was 99 973.60 yuan/QALY and 155 773.22 yuan/QALY, which were less than 3 times of China’s per capita GDP in 2021 as WTP threshold.CONCLUSIONSWhen three times of China’s GDP per capita in 2021 is taken as the WTP threshold, the second-line treatment of tirelizumab monotherapy for advanced or metastatic ESCC is more cost-effective than chemotherapy.
摘要:OBJECTIVETo discuss the factors affecting the blood concentration of high-dose methotrexate (HD-MTX) and the occurrence of adverse drug reactions (ADR) when treating lymphoma with HD-MTX.METHODSFrom July 2020 to November 2021, the information of HD-MTX patients who had been monitored for HD-MTX blood drug concentration in the First Affiliated Hospital of Guangdong Pharmaceutical University was collected by retrospective analysis, such as medical record number, age, sex, height, body mass, chemotherapy plan, dosage; test indexes such as alanine transaminase, aspartate transaminase, total bilirubin, creatinine clearance (CrCl), albumin (ALB) and other indexes were also collected before and after administration. The blood concentrations (c6 h, c24 h, c48 h) of HD-MTX were recorded, drug information of proton pump inhibitors (PPIs) was extracted and used, and ADR occurring within 48 h after administration were all evaluated. Single factor analysis, multiple linear regression and χ2 test were used to analyze the influential factors.RESULTSA total of 133 patients were included in this paper. The results of the single factor analysis of HD-MTX blood drug concentration showed that age, CrCl had an effect on c 6 h (P<0.05); age, CrCl and ALB had an effect on c24 h (P<0.05); age, body mass index (BMI), CrCl, combined use of PPIs and ALB had an effect on c48 h (P<0.05). The results of multiple linear regression analysis showed that age and CrCl had no effect on c 6 h (P>0.05), age was the main influential factor of c 24 h (P<0.05), and CrCl and combined use of PPIs were the main influential factors of c48 h (P<0.05); the coefficient of variance expansion was between 1 and 3.5, indicating that the analysis results were acceptable. The overall incidence of adverse reactions was 51.13%, of which the blood and lymphatic system reactions were the most common. The results of the influential factors of ADR showed that age, BMI, liver function and CrCl had effect on the incidence of ADR (P<0.05).CONCLUSIONSDuring the process of HD-MTX in the treatment of lymphoma, the patient’s age, CrCl and combined use of PPIs should be considered, and the patient’s blood concentration should be monitored; at the same time, the age of patients, BMI, liver function and CrCl have an impact on the incidence of ADR.
关键词:blood concentration;lymphoma;influential factor;adverse drug reaction
摘要:OBJECTIVETo carry out data mining on the prescriptions of traditional Chinese medicine (TCM) for the treatment of renal anemia, and to explore the medication rules of TCM in the treatment of renal anemia.METHODSThe Chinese and English databases including PubMed, the Cochrane Library, Web of Science, CNKI, Wanfang, VIP and CBM were searched by computer to screen the related literature about TCM in the treatment of renal anemia. Excel software was used to extract prescription information, including frequency of use, property and flavor, meridian tropism and efficacy of single TCM. Association rule analysis and hierarchical clustering analysis were performed for each ingredient of TCM with R language.RESULTSA total of 268 literature were included, involving 169 ingredients with a total use frequency of 3 919 times. Among them, Astragalus memeranaceus, Angelica sinensis, Atractylodes macrocephala, Rheum officinale, Poria cocos, Radix Rehmanniae Praeparata, Radix Codonopsis, Salvia miltiorrhiza and Ligusticum chuanxiong were used more than 100 times. The properties and flavors of the drugs were mainly warm and sweet; meridian tropism mainly targeted spleen, liver and kidney; the function was mainly in replenishing qi, nourishing blood, promoting blood circulation and removing blood stasis, and clearing damp and promoting diuresis, purgation. The result of association rule analysis showed that the core ingredients were A. memeranaceus, A. sinensis, A. macrocephala, P. cocos and S. miltiorrhiza. Hierarchical cluster analysis showed that the clustering results were divided into grade 1, 2 and 3, and the cluster classification of A. memeranaceus and A. sinensis was always the same.CONCLUSIONSThe core prescription for treating renal anemia includes A. memeranaceus, A. sinensis, A. macrocephala, P. cocos and S. miltiorrhiza; among them, A. memeranaceus and A. sinensis are at the center of the core prescription and indispensable. The medication rule is mainly guided by drugs for invigorating qi, nourishing blood, strengthening spleen, and removing dampness. According to the characteristics of different symptoms of patients, dialectical treatment is made, and other TCM is added or subtracted on the basis of the core prescription.
关键词:data mining;R language;traditional Chinese medicine;medication rules
摘要:OBJECTIVETo explore the way to re-use epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) in patients with EGFR-TKI-induced interstitial pneumonia (IP), using osimertinib as an example.METHODSThe IP treatment regimen and re-use of EGFR-TKI regimen in a patient who developed IP after the use of osimertinib were analyzed. And a literature review was made by combining the characteristics of the cases which reported in the literature and the characteristics of this case.RESULTSThe patient’s IP symptoms due to treatment with osimertinib had resolved after treatment. The patient’s IP symptoms also did not worsen after using almonertinib in combination with hormones as re-use of EGFR-TKI regimen. However, almonertinib was discontinued as the patient experienced disease progression. The adverse reactions of IP needed to be dealt with in time, the EGFR-TKI should be discontinued and symptomatic treatment should be given.CONCLUSIONSEGFR-TKI targeted therapy could be re-selected by replacing EGFR-TKI, adjusting the dose of EGFR-TKI, and using hormones in combination. EGFR-TKI-induced adverse drug reactions of IP are rare, but need to be observed closely. If other EGFR-TKI is used, close monitoring of adverse reactions and curative effects are also required in order to adjust the patient’s treatment plan in time.
关键词:interstitial pneumonia;epidermal growth factor receptor-tyrosine kinase inhibitors;adverse drug reactions
摘要:OBJECTIVETo systematically evaluate the difference of efficacy and safety of four kinds of commonly used haemocoagulases combined with proton pump inhibitor (PPI) for nonvariceal upper gastrointestinal bleeding (NVUGIB), and to provide evidence-based basis for clinical decision-making.METHODSRetrieved from PubMed, Web of Science, Wanfang data, VIP and CNKI databases, randomized controlled trials (RCTs) or cohort studies about Hemocoagulase agkistrodon blomhoffii, Haemocoagulase agkistrodon, hemocoagulase and Hemocoagulase bothrops atrox combined with PPI were collected during the inception to Dec. 2021. Two researchers independently screened the literature, extracted data and evaluated the quality of included studies. ADDIS 1.16.8 software was used to conduct a Bayesian network meta-analysis.RESULTSA total of 33 studies were included, involving 3 602 patients. Results of network meta-analysis showed that: in terms of hemostatic efficacy, compared with PPI monotherapy, four kinds of haemocoagulases combined with PPI could significantly improve the hemostatic efficacy of patients (P<0.05); there was no statistical significance in the pairwise comparison of different hemocoagulases (P>0.05). The optimal probabilistic ranking of network meta-analysis was as follows: Hemocoagulase agkistrodon blomhoffii combined with PPI>Hemocoagulase bothrops atrox combined with PPI>Haemocoagulase agkistrodon combined with PPI>hemocoagulase combined with PPI>PPI alone. In terms of the incidence of adverse drug reactions (ADR), compared with PPI monotherapy, there was no statistical difference in the incidence of ADR among four kinds of haemocoagulases combined with PPI (P>0.05). There was no statistical significance in the pairwise comparison of different hemocoagulases (P>0.05). The optimal probabilistic ranking of network meta-analysis was as follows: hemocoagulase combined with PPI>Hemocoagulase bothrops atrox combined with PPI>Hemocoagulase agkistrodon blomhoffii combined with PPI>Haemocoagulase agkistrodon combined with PPI>PPI alone.CONCLUSIONSCompared with PPI monotherapy, four different sources of hemocoagulases combined with PPI have better efficacy and similar safety in the treatment of NVUGIB. There is no significant difference in efficacy and safety among different hemocoagulases.
摘要:OBJECTIVETo indirectly compare and evaluate the efficacy and safety of rituximab, tocilizumab, eculizumab, inebilizumab and satralizumab in preventing the relapse of neuromyelitis optica spectrum disorders, so as to provide reference for clinical drug use.METHODSRetrieved from Embase, Medline, PubMed, CNKI, ClinicalTrials.gov, UMIN Clinical Trials Registry and Chinese Clinical Trial Registry, randomized controlled trials (RCTs) about five monoclonal antibodies (trial group) versus placebo or other therapeutic scheme (control group) were collected during the inception to Apr. 2022. Two reviewers independently screened literature, extracted data, and assessed the quality of included literature with Cochrane risk bias assessment tool. OpenBUGS software was used for network meta-analysis. In terms of safety, Chi-square test was performed for adverse events (AEs) in trial group and control group.RESULTSA total of 7 RCTs were included, involving 793 patients. The results of surface under the cumulative ranking curve (SUCRA) showed the order of capabilities decreasing relapse risk was: eculizumab>rituximab>inebilizumab>satralizumab; the order of capabilities reducing the annual recurrence rate was: eculizumab>satralizumab; the order of capabilities improving the progress of disability was: eculizumab>satralizumab>inebilizumab>rituximab>tocilizumab. In terms of safety, the results of χ2 test showed that there were no statistically significant differences in the risk of total AEs and serious AEs in each study between trial groups and control groups (P>0.05); the incidence of infusion reaction, nausea and vomiting in rituximab group, and that of upper respiratory tract infection in eculizumab group were significantly higher than placebo group (P<0.05).CONCLUSIONSThe effect of eculizumab is more optimal in three outcomes; in terms of improving the progress of disability, eculizumab, satralizumab and inebilizumab are more effective than the other two drugs; in terms of safety, there are significant differences in some AEs with different grades and individual AEs, but it is not found that they are inconsistent with the reported results of the existing literature and drug instructions.
摘要:OBJECTIVETo systematically evaluate the efficacy and safety of vonoprazan (VPZ) for Helicobacter pylori (Hp) eradication therapy.METHODSRetrieved from The Cochrane Library, Embase, PubMed, CNKI, VIP and Wanfang database, randomized controlled trials about VPZ for Hp eradication therapy (trial group) versus proton pump inhibitor (PPI) (control group) were collected during the inception to July 2022. After data extraction and quality evaluation with bias risk assessment tool recommended by Cochrane System Evaluation Manual 5.1.0, meta-analysis was performed by using RevMan5.3 software.RESULTSNine studies with 2 134 patients were included. Compared with control group, the overall Hp eradication rate of trial group increased significantly in either the ITT analysis or PP analysis, being 87.5% vs. 76.2% [RR=1.14, 95%CI (1.06,1.21), P<0.001] and 92.4% vs. 80.5% [RR=1.11, 95%CI (1.03,1.21), P<0.01], respectively. According to ITT and PP analysis of primary treatment subgroup, compared with control group, the overall Hp eradication rate of trial group increased significantly, being 88.4% vs. 76.5% [RR=1.15, 95%CI (1.09,1.22), P<0.000 01] and 92.8% vs. 80.9% [RR=1.12, 95%CI(1.03,1.23), P<0.05]; according to ITT and PP analysis of rescue therapy subgroup, there was no significant difference in the overall Hp eradication rate between control group and trial group (P>0.05). According to ITT and PP analysis of triple therapy subgroup, compared with control group, overall Hp eradication rate of trial group increased significantly, being 88.3% vs. 75.6% [RR=1.16, 95%CI (1.08, 1.25), P<0.000 1] and 92.6% vs. 77.6% [RR=1.15, 95%CI (1.04, 1.28), P<0.01]; according to ITT and PP analysis of quadruple therapy subgroup, there was no significant difference in the overall Hp eradication rate between control group and trial group (P>0.05). Compared with control group, the incidence of adverse events in trial group decreased significantly, being 34.2% vs. 40.9% [RR=0.84, 95%CI(0.70,0.99), P<0.05]. There was no statistical significance in the incidence of serious adverse events between 2 groups (P>0.05).CONCLUSIONSCompared with PPI therapy, the efficacy of VPZ-based triple therapy is better, particularly in primary treatment patients. However, VPZ has no significant advantage in rescue treatment and bismuth-containing quadruple regimen. And the safety and tolerance of VPZ for Hp eradication therapy are well, even better than PPI.
摘要:OBJECTIVETo compare the similarities and differences of the two methods in analyzing the use of opioids in third grade class A medical institutions and provide a reference for the management of opioids in medical institutions.METHODSTwo methods, Defined Daily Dose (DDD) and Oral Morphine Equivalent (OME), were used to count the opioid prescription data of five comprehensive medical institutions of third grade class A (named H1-H5) in Shanxi province in 2020, calculate consumption sum of opioid, annual per capita consumption sum, patient cost burden and drug consumption sum ratio, compare the index results presented by the two analysis methods, and explore the application scenarios of the advantages of each of the two evaluation methods.RESULTSThe ranking of consumption sum of opioid and patient cost burden calculated by the two methods was the same in the five sample medical institutions, but the ranking of per capita consumption sum was different. Taking the 5 medical institutions as a whole, the top 4 rankings of consumption sum ratio for each species of opioid compared by both methods were the same, i.e. remifentanil>sufentanil>oxycodone>morphine. The ratio of remifentanil was close to 50%. When comparing the ranking of consumption sum ratio in each medical institution, the ranking calculated by the two methods was different for those medical institutions except for H1 medical institutions. The consumption sum ratio of fentanyl calculated by DDD method was significantly higher than that of OME method; whereas consumption sum ratio of remifentanil calculated by OME method was significantly higher than that of DDD method. Perioperative patients had the highest consumption sum ratio, about 50%. The consumption sum ratio of critically ill patients in H3 medical institutions and inpatient patients with cancer pain and other patients in H5 medical institutions calculated by DDD method was significantly higher than that by OME method. There were differences in the order of cost burden of different types of patients calculated by two methods.CONCLUSIONSDDD method can accurately reflect the dosage of opioid drugs and facilitate the monitoring and management of the dosage; OME method can more reflect the analgesic effect and compare the cost burden of patients.
关键词:oral morphine equivalent;defined daily dose;consumption sum ratio;rational use of drugs
摘要:Hypertension is a common cardiovascular disease. At present, the prevalence and mortality of hypertension in China continue to rise, the morbidity and mortality of complications remain high. The continuous increase of blood pressure can cause damage to multiple target organs such as heart, brain, kidney and blood vessels. This article reviews the research progress of signal pathways related to the prevention and treatment of hypertension target organ damage by traditional Chinese medicine, and summarizes six signal pathways related to RhoA/ROCK, renin-angiotensin-aldosterone system, endothelin-1/nitric oxide, transforming growth factor-β1/Smads, phosphatidylinositide 3-kinases/protein kinase B, and Toll-like receptor 4/nuclear transcription factor-κB, in order to provide theoretical evidence for further research on clinical diagnosis and treatment of hypertension and its target organ damage.
关键词:hypertension;target organ damage;signal pathway
摘要:Bilirubin has good anti-inflammatory, antioxidant and immunomodulatory effects, but its poor water solubility and low bioavailability greatly limit its clinical application. Researchers have developed bilirubin into various nanoparticles, which effectively eliminate the limitation of low solubility of bilirubin with the advantage of dosage form, so that they can maximize its pharmacological activities such as anti-inflammatory, anti-oxidation and immune regulation. Bilirubin nanoparticles have great application potential in a variety of gastrointestinal diseases, liver and kidney diseases, skin diseases, autoimmune diseases, islet transplantation and targeted therapy of tumors (both as a direct anti-tumor drug and as a drug delivery system). The study of bilirubin nanoparticles will promote the clinical application of bilirubin and the development of related new drugs.
摘要:Linezolid is an antibacterial agent for the treatment of multi-resistant Gram-positive bacterial infections, which is widely used in clinical practice. However, there are large individual differences in the pharmacokinetic characteristics of the drug in patients, and it is difficult to obtain the optimal therapeutic effect when the drug is administered according to the conventional dose in the instructions. Therefore, it is necessary to carry out therapeutic drug monitoring (TDM) for linezolid, and guide and optimize its antibacterial treatment plan by using population pharmacokinetics (PPK) and pharmacodynamics principles. This paper summarizes the PPK changes and the research progress of individualized administration of linezolid in various populations, and recommends that the patient’s steady-state blood concentration is kept at 2-8 mg/mL through TDM when using linezolid clinically. It is recommended to appropriately reduce the dosage for patients with liver and kidney dysfunction, appropriately increase the dosage for obese, burned and children patients, and provide pharmaceutical monitoring during the medication process to promote rational drug use.