Objective To manage off-label medication use scientifically and standardizedly in Yunnan province, to provide reference for decision-makers in medical institutions, and to construct the evaluation methods, catalogs and management plan for off-label medication use according to the latest regulations and discipline progress. Methods Using the Delphi methodology to solicit expert opinions, the panel established a consensus, evaluation standards. And 368 off-label medication use of 35 medical institutions were evaluated by the standards from four dimensions: the reliability of evidence sources, safety, effectiveness and the necessity. Results The panel formed the recommendations and catalogue for the management of off-label medication use in Yunnan Province. The recommendations in the catalogue are divided into strong recommendation, recommendation, cautious recommendation and temporary dis-recommendation. Conclusion Based on the research and demand-oriented study, the Expert Consensus on the Off-label Meddication Use in Medical Institutions of Yunnan Province was formed, which provided a basis for the rational use and management off-label medication use.

Objective To construct a set scoring criteria for the evaluation and selection of oral nonsteroidal anti-inflammatory drugs( NSAIDs)for clinical analgesia,to ensure the scientific and standardized development of the comprehensive clinical evaluation on oral NSAIDs,to the foundation for the comprehensive clinical evaluation on other drugs. Methods According to authoritative guidelines and drug instructions,the Delphi expert consultation method was subjected to seek expert opinions and establish an expert consensus on the evaluation and selection scoring criteria of oral NSAIDs,and use this criteria to score 6 oral NSAIDs. Results This study quantitatively scored from six dimensions: safety,efficacy,economy,accessibility,innovation,and suitability.The total scores from high to low were celecoxib capsules,meloxicam tablets,etoricoxib tablets,diclofenac sodium sustained-release tablets,ibuprofen sustained-release capsules,and imrecoxib tablets. Conclusion Guided by clinical value,a scientific and standardized evaluation and selection criteria of oral NSAIDs for clinical analgesia has been established to strengthen pharmaceutical management in medical institutions,while promoting the rational use of drugs.

In April 2022,the American College of Cardiology (ACC)/ American Heart Association (AHA)/ Heart Failure Society of America (HFSA)released the guideline for the management of heart failure (HF),updating and integrating the 2013 and 2017 versions of the guidelines.Based on the latest research evidence,the guideline for the management of heart failure 2022 provided clinicians with comprehensive recommendations for the prevention,diagnosis and management of patients with HF,redefined the stage and classification of HF,comprehensively updated the management strategy,and put more emphasis on the prevention of HF and the management coordination of the professional team of HF.This article interpreted the guideline for the management of heart failure 2022 from the perspective of medical therapy,in order to provide references for the medical therapy of patients with HF in China.

Objective A simulated annealing algorithm appropriately assembled the systemic physiological pharmacokinetic model of theophylline to simplify the systemic physiological pharmacokinetic model,and the feasibility of the simplified model was evaluated. Methods Using the published systemic physiological pharmacokinetic model of theophylline,using the simulated annealing algorithm (SA) appropriate lumped algorithm to search for the optimal lumped matrix,the whole body physiological pharmacokinetic model of theophylline is lumped and simplified,and evaluate the lumped simplified model with the original model. Results The 13-state of the original model are lumped into seven states.After evaluation,the lumped and simplified model has well accuracy and applicability.The value of ARD% is less than 0.002%,and the concentration-time distribution diagram of the original model and the lumped-reduced model are good coincidences,with less error. Conclusion The simulated annealing (SA) lumped reduction of the physiological pharmacokinetic model of theophylline is robust and efficient,and this approach can be considered for the simplification of physiological pharmacokinetic models for other drugs.

Objective To explore early plasma differential metabolites in patients with acute paraquat poisoning based on the metabolomics approach,and to find the important biomarkers for the prognosis evaluation and the therapeutic targets. Methods Plasma samples of 12 patients with paraquat poisoning and 12 healthy people were analyzed using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS).Plasma differential metabolites between paraquat poisoning patients and healthy controls were screened by multivariate statistical method,and their levels in the death and survival subgroups of paraquat poisoning patients were further analyzed. Results A total of 48 differential metabolites,including phospholipids,amino acids,and saturated or unsaturated fatty acids,were screened in the poisoned patients compared to the healthy controls.Among them,the plasma levels of LysoPE (22:6) and LysoPC (20:1) showed the most significant changes in the poisoned patients,which were 16.2 times (P<0.05) and 17.9 times (P<0.05) higher than those in the healthy controls,respectively.Plasma levels of seven metabolites,including LysoPE,LysoPC,L-lactic acid,eicosadienic acid,and 4-hydroxybutyric acid were significantly higher in the patients who died after poisoning than in the surviving patients (P<0.05).LysoPE (22:6) and LysoPC (20:1) similarly varied most significantly.In addition,plasma phenyl alanyl phenylalanine level was significantly lower in the patients who died after poisoning than in the surviving patients (P<0.01). Conclusion Those screened metabolites may participate in the pathological process of paraquat poisoning injury and may have potential application value for the prognosis evaluation.

Objective To explore the effects of palmitate acid(PA) on autophagy and lipid metabolism in human ovarian granulosa cells (KGN cell lines). Methods The KGN cells were pretreated with different concentrations of PA alone or in combination with 3-methyladenine (3-MA).Cell lipid deposition was detected by oil red O staining experiment. KGN cells were determined by cell counting kit(CCK-8) assay. Reactive oxygen species (ROS) content was measured by DCFH-DA fluorescent probe. Western blotting was used to detect sterol regulatory element-binding protein 1 (SREBP1),microtubule-related protein 1 light chain 3 (LC3-Ⅰ and LC3-Ⅱ),ubiquitin-binding proteins p62 and PTEN-induced putative kinase 1 (PINK1),Parkin. Results In the range of 0-400 μmol·L^-1 concentration of PA,with the concentration increased,the number of intracellular lipid droplets was increased,the expression of SREBP1 was up-regulated,and the cell viability was decreased significantly (P<0.05).Compared with the control group,PA in the concentration of 400 μmol·L^-1 increased the intracellular ROS content,LC3-Ⅱ/LC3-Ⅰ ratio (P<0.05),and increased the relative expression of p62,PINK1,and Parkin proteins (P<0.05).After being pretreated with autophagy inhibitor 3-MA,the cell viability of 3-MA+PA group was increased (P<0.05),the ROS content,LC3-Ⅱ/LC3-Ⅰ ratio were decreased (P<0.05),and the relative expression of p62,PINK1 and Parkin protein were decreased (all P<0.05). Conclusion PA is lipotoxic to ovarian granulosa cells and may activate autophagy in ovarian granulosa cells via PINK1/Parkin,which can be reversed by 3-MA.

Objective To investigate the inhibitory effect of evodiamine on tumor vascular proliferation and its mechanism. Methods Human umbilical vein endothelial cells (HUVECs) and human hepatocellular carcinoma cells (HepG2) were treated with evodiamine and cobalt dichloride (CoCl₂) in different concentrations alone or together for 24 h.The cell proliferation level was detected by thiazole blue (MTT) assay;the effect of evodiamine on apoptosis of HUVECs was detected by Annexin V/PI double staining flow cytometry;the hypoxia model of HUVECs in vitro was established by chemical induction of CoCl₂;the protein expression levels of hypoxia-inducing factor -1α (HIF-1α),glycolytic key enzyme (PFKFB3) and vascular endothelial growth factor receptor 2 (VEGFR2) in HUVECs were detected by Western blotting. Results MTT results showed that the inhibitory effect of evodiamine on the proliferation of HUVECs and HepG2 cells was significant (P<0.05 or P<0.01).The IC₅₀ values were 1.15 μmol·L^-1 and 1.07 μmol·L^-1,respectively.Flow cytometry results showed that the apoptosis of HUVECs could be induced by evodiamine (P<0.01).The inhibition of HIF-1α and PFKFB3 proteins in HUVECs was not significant,but the protein expression level of VEGFR2 was significantly down-regulated by the treatment of evodiamine under normoxic conditions (P<0.01).When the concentration of CoCl₂ was 5-50 μmol·L^-1,the expression levels of HIF-1α and PFKFB3 protein were significantly increased (P<0.01),and both increased with the increase of CoCl₂ concentration,while the proliferation level of HUVECs was not significantly changed.However,the cell survival rate was significantly increased.The cell survival rate significantly increased when 100-400 μmol·L^-1 CoCl₂ was used. The cell survival rate significantly decreased at 800 μmol·L^-1 CoCl₂ (P<0.01).Under high expression of HIF-1α in HUVECs induced by CoCl₂,Compared with the CoCl₂ group,evodiamine(0.4 μmol·L^-1) could significantly down-regulated the protein expression levels of HIF-1α,PFKFB3 and VEGFR2 and survival rate (P<0.01).The HIF-1α and PFKFB3 protein levels and survival rate of the EVO+CoCl₂ group were up-regulated compared with that of the evodiamine group (P<0.05),and VEGFR2 was not up-regulated. Conclusion Evodiamine significantly inhibited the proliferation of HUVECs and HepG2 cells and induced the apoptosis of HUVECs;Evodiamine can significantly down-regulate the glycolysis (Warburg effect) of HUVECs under the condition of CoCl₂ simulated hypoxia,and the mechanism may be related to the independent down-regulation of HIF and VEGFR signaling pathways.

Objective To investigate the effect of guangchenpi on gastrointestinal motility in functional dyspepsia (FD) rats and its mechanism. Methods Fourty-two SPF rats were randomly divided into normal control group(7) and model group(35).The FD model was induced by Guo's tail clipping method,irregular feeding,and intragastric administration with 0℃ and 0.9% sodium chloride solution.After modeling,the FD rats were randomly divided into model control group,domperidone group,new guangchenpi group,10-year aging guangchenpi group,and simulated aging guangchenpi group with seven rats in each group according to body weight and behavioral score.The rats were intragastrically administered for seven days.The general condition and body weight of rats were observed and recorded.The autonomic activity ability of rats was observed by an open field test.The residual gastric rate and small intestinal propulsion rate of rats were observed by the gastrointestinal motility test.The pathological morphology of gastric antrum was observed by HE staining.ELISA measured the contents of motilin and 5-hydroxytryptamine(5-HT) in serum.The expression of 5-HT4R protein in the duodenum was observed by Western blotting. Results Compared with the model control group,the general conditions of the three guangchenpi groups were clearly better,with a noticeable increase in body weight and behavioral score.The gastric residual rate of guangchenpi groups showed a significant decreasing trend,with a significant increasing trend in small intestinal propulsion rate.The contents of motilin and 5-hydroxytryptamine in serum significantly increased,with a significant increase in the expression of 5-HT4R protein in the duodenum. Conclusion Guangchenpi can promote gastrointestinal motility in FD rats,and its mechanism may be related to motilin and the 5-HT system(5-HT,5-HT4R).The effect of guangchenpi aging time on gastrointestinal motility in FD rats is not obvious.

Objective To evaluate the antioxidant activity of four active ingredients from Bupleurum in vitro. Methods DPPH (1,1-diphenyl-2-trinitrophenyl hydrazine) and ABTS [2,2-biazo-bis (3-ethyl-benzothiazole-6-sulfonic acid)] were used to detect the free radical scavenging activity of four active ingredients of Bupleurum by UV spectrophotometry.The model of H₂O₂-induced injury in normal human hepatocytes (LO2) was established.The survival rate,GSH-Px,SOD activity,and MDA of the model cells were used as indexes to detect and screen the antioxidant effects of three active ingredients of Bupleurum. Results The clearance rates of DPPH by Bupleurum polysaccharides,Bupleurum flavonoids,Bupleurum saponins,and Bupleurum volatile oil were 38.718 μg·mL^-1,51.297 μg·mL^-1,3.149 mg·mL^-1 and 2.426 g·mL^-1,respectively.The clearance rates of ABTS by Bupleurum polysaccharides,Bupleurum flavonoids,Bupleurum saponins and Bupleurum volatile oil were 130.931 μg·mL^-1,351.484 μg·mL^-1,5.422 mg·mL^-1 and 2.241 g·mL^-1,respectively.Bupleurum saponins (60 μg·mL^-1) increased the cell viability to 67.47%(P<0.05),significantly increased the activities of GSH-Px and SOD to 17.06 U·mg^-1 and 52.05 U·mg^-1(P<0.05),and significantly reduced MDA content to 2.11 μmol·g^-1(P<0.05). Conclusion Bupleurum polysaccharides,flavonoids,and saponins have antioxidant effects in vitro,which provides a theoretical basis for the clinical application of Bupleurum in soothing the liver and relieving depression.

Objective To investigate the effects of Allium cepa var.aggregatum extract (ACAE) on lipid metabolism of oleic acid-induced HepG2 cells and its underlying mechanism. Methods MTT was used to select the appropriate experimental concentration of ACAE,enzyme-linked immunosorbent assay (ELISA) was used to detect the effects of different concentrations of ACAE on the production of TG and ROS in oleic acid-induced HepG2 cells,and Griese reagent was used to analyze the difference of NO production in each group.Real-time PCR was used to observe the relative contents of PNPLA3 and PPARα mRNA in each group.Western blot was used to observe the relative production of PNPLA3,SREBP-1C,PPARα,Nrf2,CYP1A1,and GP78 in each group. Results In the concentration of 5-20 mg·L^-1, ACAE significantly decreased the relative production of TG,NO,PNPLA3 mRNA and its corresponding protein,SREBP-1C,CYP1A1,GP78,and up-regulated the relative contents of ROS,PPARα mRNA and its corresponding protein,and Nrf2 in oleic acid-induced HepG2 cells. Conclusion ACAE could effectively regulate the lipid metabolism of oleic acid-induced HepG2 cells,and the mechanism might be related to reducing lipid accumulation by inhibiting key proteins such as PNPLA3 and promoting lipid oxidation by activating signaling pathways such as Nrf2.

ObjectiveTo investigate the potential effect of Panax ginseng polysaccharide on the permeability,the expression of adhesion junction proteins,and calcium ion level in rat small intestinal epithelial cells (IEC-6),and to explore the mechanism of Chinese herbs with the actions of strengthening qi and invigorating spleen in intestinal mucosal protection. Methods Different experimental conditions [normal Ca²⁺-containing culture,Ca²⁺-containing +DFMO (difluoromethylornithine,polyamine synthesis inhibitors) culture,and Ca²⁺-free culture] were set to investigate the effect of Panax ginseng polysaccharide;the transwell cell phenol red permeability was measured to observe the intercellular permeability;Western blotting was used to determine the expression of adhesion junction proteins(E-cadherin,α-catenin,and β-catenin);laser confocal microscopy was used to observe the level of intracellular calcium. Results ①When cultured in normal Ca²⁺-containing medium,the result showed that Panax ginseng polysaccharide (40,80 or 160 mg·L^-1,below) can reduce intercellular permeability,improve the expression of adhesion junction proteins (E-cadherin,α-catenin and β-catenin) and the level of intracellular calcium (P<0.05 or P<0.01);②In Ca²⁺-containing +DFMO culture,the intercellular permeability increased and the expression of adhesion junction proteins (E-cadherin,α-catenin)and the level of intracellular calcium decreased (P<0.05 or P<0.01),Panax ginseng polysaccharide could ameliorate the increase of intercellular permeability and the reduction of adhesion junction proteins(E-cadherin,α-catenin)and the level of intracellular calcium induced by DFMO (P<0.05 or P<0.01);③In Ca²⁺-free culture,the intercellular permeability increased and the expression of adhesion junction proteins (E-cadherin、α-catenin and β-catenin)and the level of intracellular calcium decreased (P<0.05),Panax ginseng polysaccharide could ameliorate the increase of intercellular permeability and decrease of adhesion junction proteins (E-cadherin,α-catenin and β-catenin,P<0.05 or P<0.01 compared with the model group). Conclusion Panax ginseng polysaccharide can enhance the intestinal epithelial barrier,and the mechanism is related to its improvement on the level of intracellular calcium and the expression of adhesion junction proteins.

Plants of the genus Stauntonia DC.in the Lardizabalaceae family mainly contain pentacyclic triterpenoids and their glycosides,pentacyclic nortriterpenoids and their glycosides,phenylpropanoids,flavonoids,and other compounds.Triterpenoid saponins as the main compounds and active components of Stauntonia DC.have various biological activities,including analgesic,anti-inflammatory,antitumor,and antioxidant activities.Stauntonia chinensis DC.,the intensively studied plant,has been widely used to treat trigeminal neuralgia,sciatica,neuropathic headache,rheumatic joint pain,and other diseases.The chemical constituents and pharmacological activities of the plants of Stauntonia DC.are summarized in this paper to provide a reference for further research and development of Stauntonia DC.plants.

Objective To observe Buzhong Yiqi granule's clinical efficacy in treating lung cancer-related fatigue of lung-spleen qi deficiency. Methods Sixty patients with cancer-related fatigue of lung cancer who met the diagnostic criteria of lung-spleen deficiency were randomly divided into a treatment group and a control group, 30 patients in each group. The control group received non-medicine treatment (physical activities, psychological and nutritional counseling, and sleep guidance). The treatment group received Buzhong Yiqi granules based on the control group,one bag each time, t.i.d., taken with water. All the patients were treated for 30 days. The improvements of indications, such as fatigue symptom inventory (FSI) scale scores, Karnofsky performance status(KPS)scale scores, functional assessment of chronic illness therapy-fatigue (FACIT-F) scale scores, the scores and efficacy for traditional Chinese medicine (TCM) syndromes, immunity function and adverse reactions were compared between the two groups. Results After treatment, the scores of FSI in the patients of the two groups were lower than those before treatment (P<0.05), and the scores of the treatment group were lower than those of the control group (P<0.05). The scores of KPS in the two groups were significantly increased compared with those before treatment (P<0.05), and the scores of the treatment group were higher than those of the control group (P<0.05). After treatment, the scores of FACIT-F in the two groups were higher than before (P<0.05). There was no significant difference between the two groups regarding social and family status (P>0.05). The scores of other dimensions in the treatment group were higher than those in the control group (P<0.05). After treatment, the scores of TCM syndromes in the 2 groups decreased compared with those before treatment (P<0.05), and the scores of treatment group were lower than those of the control group (P<0.05). The effective rate of TCM syndromes in the treatment group was higher than that of the control group (P<0.05). After treatment, the counts of CD₃⁺ and CD₄⁺ in the two groups were significantly higher than those before treatment, and the counts of CD₃⁺ and CD₄⁺ of the treatment group were higher than those in the control group (P<0.05). During the study, 1 patient developed abdominal distension. Conclusion Buzhong Yiqi granule in treating lung cancer-related fatigue of lung-spleen qi deficiency could improve fatigue, the quality of life, and immunity function with fewer adverse reactions, which is worthy of clinical application.

Objective To analyze the data of screening electrocardiogram(ECG) and the common reasons for ECG screening failures in early phase clinical drug trials,and to discuss the precautions and improvement strategies of ECG screening in early drug clinical trials. Methods ECGs were collected from volunteers who participated in early drug clinical trial screening in the Phase I clinical research center of a grade Ⅲ general hospital from May 2021 to April 2022,and the main index data and reasons for screening failure were analyzed. Results Nine early drug trials were included in this study.One thousand one hundred and fifty-nine volunteers participated in ECG screening,including 795 males and 364 females aged 18 to 57[(32.62±7.96) years].The average heart rate was (68.06±9.90) bpm,the average PR interval was (155.24±19.32) ms,the average QRS interval was (94.98±9.66) ms,the average QTcF interval was (403.54±19.68) ms.Sixty-one patients (5.26%) failed to be screened directly by ECG.Among them,significantly shortened PR interval (< 110 ms),sinus bradycardia,first-degree atrioventricular block,and delayed intraventricular conduction were the most common causes of screening failure.The rate of screening failure was higher in males than in females (6.16% vs. 3.30%). Conclusion ECG is an important method for screening subjects in early drug clinical trials.Researchers should standardize the operation,collect ECG data accurately,and develop scientific and unified screening criteria to ensure the safety of subjects and the quality of clinical trial safety data.

Most opioids suppress the immune system, but recent studies suggest they may play a dual role;one opinion showed that it could downregulate immunity, leading to tumor progression, while the other is to upregulate immunity by reducing pain, thereby controlling tumors. In recent years, with the widespread use of immunotherapy, the impact of opioids on immunotherapy for cancer pain patients has also attracted more and more attention. However, the relationship between opioids and the efficacy of immunotherapy is inconclusive. Therefore, this review will discuss the links between opioids, immunotherapy, and immune function.

Acanthamoeba is an opportunistic protozoa that is widely distributed in the natural environments and can cause serious, even fatal infections after invading the human body. At present, drug therapy is still the first choice of treatment. However, the drug-resistant trophozoites and cysts that are changed from trophozoites cause the recurrence of infection, and it has also become a problematic challenge to treat. With the development of science and technology, traditional medicine is improved, and novel drugs continue to be developed that provide broad prospects for the accurate and efficient drug treatment of Acanthamoeba infection. This paper focuses on the research status of anti-acanthamoeba drugs in recent years, which reviewed from four aspects: antibacterial drugs, antifungal drugs, biguanides, and new preparations(nanoparticles and dendrimers), in order to guide the effective treatment of Acanthamoeba infection and ideas for the development of new drugs.

Clinical drug evaluation is of great significance to ensure the safety of drug use by the public, promote the rational use of drugs,solve the limitations of clinical research and expand the scope of drug use.Pharmacoepidemiological study methods such as randomized controlled trial,cohort studies, and pharmacoeconomic studies have been widely used in clinical drug evaluation.These methods have significant advantages and application values.In the process of clinical drug evaluation,the relevant research methods of pharmacoepidemiology can be fully utilized to contribute to drug efficacy,safety,economy,and clinical decision-making,and to ensure the safe and rational use of drugs by the public.

Objective To explore the effect of interleukin-6(IL-6) and CYP2C19 polymorphism on voriconazole blood trough concentration (VCZ-C_min). Methods A total of 223 patients with invasive pulmonary fungal infection who were treated with voriconazole were admitted to the prospective study.The VCZ-C_min was measured by reversed-phase high-performance liquid chromatography(RP-HPLC)and the CYP2C19 genotype was detected by real-time polymerase chain reaction (RT-PCR).The correlation between IL-6 and VCZ-C_min was analyzed by Pearson's method.The differences were compared for IL-6 levels in different ranges of VCZ-C_min and VCZ-C_min in different stratification of IL-6.The risk was predicted for VCZ-C_min≥5.0 mg·L^-1 in high IL-6 stratification,and the influence was compared for IL-6 on VCZ-C_min under different CYP2C19 genotypes. Results There was a positive correlation between IL-6 and VCZ-C_min(P<0.001).77.14% (27/35) of VCZ-C_min and its corresponding IL-6 were similar in the same patient.There were significant differences in IL-6 levels in the sub-treatment range,treatment range and ultra-therapeutic range,respectively(P<0.001).VCZ-C_min was significantly different in the three different strata of IL-6(P<0.001).IL-6 had a significant effect on VCZ-C_min in patients with CYP2C19 ultra metabolism, extensive metabolism (UM+EM) and intermediated metabolism (IM) genotypes(P<0.05),but not in patients with poor metabolism (PM)(P>0.05). Conclusion During the application of VCZ in clinical patients,physicians should pay special attention to the effect of IL-6 on VCZ-C_min,especially on CYP2C19 UM+EM and IM patients,and should monitor VCZ-C_min frequently.

Objective To assess the safety of Brodsky oral solution. Methods This study extensively investigated several Chinese databases (China National Knowledge Infrastructure,Wanfang Database, and VIP Database for Chinese Technical Periodicals) and international databases (Pubmed, Web of Science, and ADIS), and systematically analyzed Brodsky oral solution. The pharmacological effects and adverse reactions of the oral solution and its prescription components, combined with the clinical case data on the prevention and treatment of epilepsy with the Brodsky oral solution since 2000. Results The analysis results show no obvious adverse events associated with the Brodsky oral solution, very few gastrointestinal reactions such as nausea and vomiting occurred in patients, and the reactions disappeared after drug withdrawal. Conclusion There are few obvious adverse events associated with the Brodsky oral solution, it is safe for patients. The prescription and safety of Brodsky oral solution are comprehensively examined in this article, which also offers references and recommendations for responsible drug usage and relevant studies on Brodsky oral solution.

Objective To verify the short-term effect of management mode for "monitoring-comment-notification-education-improvement" (MCNEI) by comments on the medical advice of antibiotics for inpatients with cancer. Methods Three hundred and thirty medical records containing antibiotics and medical advice for inpatients with cancer between April and September 2021 from the oncology-related departments of our hospital were randomly collected month by month.According to the standards stipulated by Management Practices of Hospital Prescription Comments (Trial),the medication rationality of inpatients was analyzed,and improvement measures were provided. Results From April to September 2021,the overall qualified rate for rational use of antibiotics increased month by month,which were 48.00%,56.67%,81.25%,88.33%,83.33%,and 88.00%,respectively (P< 0.01). Conclusion Actively carrying out the MCNEI management mode of antibiotics,and intervening after the comments of antibiotics medical advice for patients with cancer,can significantly improve the rational use of antibiotics.

Objective To evaluate the efficacy,safety,and pharmacoeconomics of fluticasone furoate/umeclidinium/vilanterol powder for inhalation in the treatment of moderate to severe chronic obstructive pulmonary disease by rapid health technology assessment (HTA) to provide a basis for clinical decision-making. Methods The databases of PubMed,Cochrane Library,Embase,ScienceDirect,Medline,CNKI,and the HTA-related websites,such as INAHTA and HTAi,were systematically searched from their inception dates to April 2022 for collecting the health technology evaluation,systematic review/Meta-analysis and pharmacoeconomic research on treating moderate to severe chronic obstructive pulmonary disease with fluticasone furoate/umeclidinium/vilanterol.Two reviewers independently screened the literature,extracted the required data,and conducted a comprehensive analysis. Results Four HTA reports,seven systematic review/Meta-analyses and seven pharmacoeconomic studies were included.The results of effectiveness studies showed that compared with other treatment groups,fluticasone furoate/umeclidinium/vilanterol reduced the incidence of acute exacerbations,slowed the rate of decline in lung function and improved St.George's Respiratory Questionnaire score.The safety studies showed that fluticasone furoate/umeclidinium/vilanterol reduced mortality without an increase in serious adverse events or specific adverse cardiovascular events compared to other treatment groups.However,they increased the risk of pneumonia compared to the umeclidinium bromide/vilanterol [RR=1.78,95%CI=(1.13,2.82)].Pharmacoeconomic studies showed that fluticasone furoate/umeclidinium/vilanterol had better economic and cost-effectiveness results in China,European and American countries,increasing life years saved (0.145-0.764 LYs) and quality-adjusted life years (0.118-0.492 QALYs) compared to other treatment groups. Conclusion Fluticasone furoate/umeclidinium/vilanterol can achieve great effectiveness,safety,and economy in treating moderate to severe chronic obstructive pulmonary disease.

Objective To evaluate the cost-utility of the combination of darolutamide,androgen-deprivation therapy (ADT),and docetaxel for treating metastatic hormone-sensitive prostate cancer (mHSPC). Methods A partitioned survival model was constructed to simulate total cost,quality-adjusted life years (QALYs),and incremental cost-utility ratio (ICUR) over a 25-year lifetime horizon.One-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the model. Results The base-case results showed that darolutamide yielded an additional 1.93 QALYs and an incremental cost of 443 434.97 CNY.The ICUR was 230 204.49 CNY/QALY,which was slightly lower than 3 times the GDP per capita.Scenario analysis showed that when the price of darolutamide fell by 30%,the ICUR was lower than two times the GDP per capita.According to the one-way sensitivity analyses,the utility of the mHSPC state and the cost of darolutamide had the most significant impact on the final result.In the probabilistic sensitivity analyses,at a willingness-to-pay threshold of 242 928 CNY/QALY,the probability of darolutamide being cost-effective was 63.30%. Conclusion From the perspective of the Chinese healthcare system,the combination of darolutamide,ADT,and docetaxel was a more cost-effective treatment regimen in the treatment of mHSPC patients.

Objective To investigate the stability of etoposide infusion under different storage conditions,and to provide a basis for clinical rational drug use. Methods The compatible concentrations of etoposide infusion were set as 0.04,0.1,0.2,0.25,and 0.4 mg·mL^-1,respectively.Under the conditions of room temperature without light,room temperature with light,and 2-8 ℃,the appearance of etoposide infusion was observed at each time point,and the pH value and content were determined by pH meter and high-performance liquid chromatography (HPLC),respectively. Results When the compatible concentration was not more than 0.25 mg·mL^-1,etoposide infusion's appearance,pH value and content had no significant changes in 24 h under three storage conditions.When the compatible concentration of etoposide infusion was 0.4 mg·mL^-1,precipitation all occurred,and the content decreased to 67.07%,61.00%,and 38.29% at 24 h under the conditions of room temperature without light,room temperature with light,and 2-8 ℃,respectively. Conclusion When the compatible concentration does not exceed 0.25 mg·mL^-1,etoposide infusion can stabilize in 24 h under the conditions of room temperature without light,room temperature with light,and 2-8 ℃.When the compatible concentration is 0.4 mg·mL^-1,considering the poor stability of the etoposide infusion under three storage conditions,the compatibility concentration of etoposide infusion exceeds 0.25 mg·mL^-1 is not recommended unnecessarily.

Objective To conduct data mining on adverse events (AEs) of lorlatinib, and to explore the risk factors of serious AEs. Methods The FAERS database was searched,and the openFDA data platform was used to collect the report information of AEs induced by lorlatinib from listing to March 31,2022.Grouped according to severity,the risk factors of severe AEs caused by lorlatinib were analyzed by univariate analysis and a modified Poisson regression model. Results A total of 1 986 lorlatinib AEs were reported,including 1 468 serious AEs (73.92%).One hundred and three AEs signals were detected.According to the frequency of occurrence,the number of edema reports was the most (49 cases),and according to the signal intensity,the signal of migratory superficial thrombophlebitis was the strongest [ROR=214.689,95%CI=(88.065,523.376)],moreover,none of them was mentioned in drug instructions.Modified Poisson regression analysis showed that the risk factors for the development of severe AEs were the combination of drugs with CYP3A enzyme system interactions [RR=1.148,95%CI=(1.009,1.305)],and low body weight [RR=0.997,95%CI=(0.994,1.000)],however,other symptomatic medications were the protective factors [RR=0.680,95%CI=(0.493,0.938)]. Conclusion It was recommended that clinicians and pharmacists should pay more attention to the signals not mentioned in the instructions of lorlatinib,strengthen the management of patient combination drugs and nutrient metabolism,avoid the occurrence of serious AEs,and ensure the safety of the patient's medication.