OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

OBJECTIVE To compare the efficacy and safety of infliximab（IFX）， ustekinumab（UST） and vedolizumab（VDZ） in the treatment of active Crohn’s disease （CD）. METHODS The patients with active CD who were diagnosed and initially received any of the aforementioned biologics at the First Affiliated Hospital of the USTC （Anhui Provincial Hospital） from January 2020 to December 2023 were selected as the study subjects. They were divided into the IFX group （34 cases）， the UST group （37 cases）， and the VDZ group （15 cases） based on their treatment regimens. Patients in all three groups received induction and maintenance therapy with IFX， UST or VDZ for at least 12 months. The CD Activity Index （CDAI） scores and their changes from baseline （ΔCDAI）， clinical remission rates， clinical response rates， nutritional indicators [body mass index （BMI）， albumin （ALB）， hemoglobin （HGB）]， and inflammatory markers [C-reactive protein （CRP）， erythrocyte sedimentation rate （ESR）] of three groups after the induction phase （9th week of treatment） and during the maintenance phase （12th month of treatment） were compared. Additionally， the cumulative clinical remission rates at 1 year of treatment and the incidence of adverse events （AEs） were compared. RESULTS There were no statistically significant differences in the aforementioned baseline indicators among the three groups （ P ＞0.05）. In all three groups， the CDAI scores were significantly lower after the induction phase and during the maintenance phase， compared to the baseline （ P ＜0.05）. In the IFX group， CDAI scores at the above time points were significantly lower than those in the UST and VDZ groups during the same periods （ P ＜0.05）， and the absolute value of ΔCDAI during the maintenance phase was significantly higher than that in the VDZ group （ P ＜0.05）. The clinical remission rate in the IFX group during the maintenance phase was significantly higher than that in the UST and VDZ groups during the same period， and the clinical response rate was significantly higher than that in the VDZ group during the same period （ P ＜0.05）. The levels of ALB， HGB， CRP and ESR in the IFX group after the induction phase and during the maintenance phase， as well as the levels of CRP and ESR in the UST group after the induction phase， all improved significantly compared to the baseline. Furthermore， the levels of ALB and HGB in the IFX group were significantly higher than those in the UST and VDZ groups during the same period （ P ＜0.05）. The cumulative clinical remission rates among the three groups were significantly different （ P ＜0.05）， with patients in the IFX group achieving remission more rapidly and at a higher proportion. There was no statistically significant difference in the incidence of AEs among IFX， UST and VDZ groups （14.71%， 8.11% and 20.00%， respectively； P ＞0.05）； infusion reactions were the most common AEs in the IFX group （8.82%）. CONCLUSIONS Compared with UST and VDZ， IFX demonstrates a higher clinical remission rate during the maintenance phase， more effectively improves active CD patients’ nutritional status， and continuously reduces systemic inflammatory responses. However， clinicians should be mindful of the risk of adverse events， such as infusion reactions， associated with this drug.

OBJECTIVE To comprehensively evaluate the quality of adverse drug reaction （ADR） reports in clinical departments or ward （hereinafter referred to as “department”） based on game theory combinatorial weighting-technique for order preference by similarity to ideal solution （TOPSIS）-rank-sum ratio （RSR） method， providing a reference for the further standardization of ADR reporting. METHODS Based on relevant documents and scoring criteria， the ADR report quality evaluation standards previously developed by our team were modified. Using game theory principles， the fusion of subjective and objective weights for each indicator was determined. A game theory combinatorial weighting-TOPSIS-RSR model was developed to evaluate and categorize the quality of raw ADR reports submitted by departments to the pharmacy department at Bozhou Hospital of Anhui Medical University. RESULTS A total of 222 ADR reports from 23 departments were included. The game theory combinatorial weighting method identifies weak points in management， such as ADR symptoms and signs， the description of underlying diseases， timing of ADR， by optimizing the weightings of the indicators. The TOPSIS-RSR method calculates that the mean relative closeness of the departments was 0.401 7， indicating that the overall report quality ranged from moderate to substandard. 20095） Three departments， including neurosurgery， demonstrated medium reporting quality [estinate closeness （Ĉ）i ≥0.506]， while two departments， such as the respiratory department，were rated as unqualified （Ĉi＜0.278）. The remaining departments were all deemed qualified （0.278≤ Ĉi＜0.506）. CONCLUSIONS The developed game theory combinatorial weighting-TOPSIS-RSR method provides an effective approach for the quality evaluation of ADR reports， which not only balances subjective and objective weights but also facilitates comparisons among different departments. There is still room for improvement in the ADR report quality at the hospital.

Objective: To investigate the potential mechanisms of Xanthatin in inhibiting the proliferation of laryngeal squamous cell carcinoma(LSCC) cells by integrating network pharmacology and in vitro experiments. Methods: The targets of Xanthatin were identified using databases such as PharmMapper, while disease-related targets for LSCC were obtained from databases such as DisGeNET. The overlapping targets between Xanthatin and LSCC were determined by intersecting these datasets. A protein-protein interaction(PPI) network was constructed based on the overlapping targets, and key targets were identified. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analyses of the overlapping targets were performed using R software. A "Xanthatin-target-pathway" network was visualized using Cytoscape 3.8.0 software. The preliminary validation of the aforementioned results was performed using molecular docking and transcriptomics. The effects of Xanthatin on the proliferation of TU177 cells were assessed using CCK-8 and colony formation assays. Additionally, Western blot analysis was employed to measure the expression levels of PI3K, p-PI3K, Akt, and p-Akt proteins. Results: A total of 159 overlapping targets between Xanthatin and LSCC were identified, and seven key targets, including AKT1, were screened. GO enrichment analysis yielded 2 455 entries, and KEGG enrichment analysis identified 172 pathways, such as the PI3K-Akt signaling pathway. Xanthatin exhibited favorable binding activity with the core target proteins of LSCC in molecular docking experiments. The transcriptomics results showed high consistency with the predictions from network pharmacology. CCK-8 and colony formation assays demonstrated that Xanthatin at concentrations of 1, 2, and 4 μmol/L significantly inhibited the proliferation of TU177 cells in a dose-dependent manner. The expression levels of p-PI3K and p-Akt proteins decreased with increasing concentrations of Xanthatin. Conclusion Xanthatin may exert an inhibitory effect on the proliferation of LSCC cells by modulating the PI3K-Akt signaling pathway.

Objective In order to provide a better reference and basis for the selection of reasonable hypoglycemic drugs for clinical treatment,the study conducted a comprehensive clinical evaluation of the innovator sodium-glucose transporters 2(SGLT-2)inhibitors,based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition).Methods The real-world studies,randomized controlled trials,Meta-analysis/systematic review,drug clinical use guidelines,expert consensus and drug description evaluation evidence were collected,and the included drugs were assigned and evaluated from five dimensions:pharmaceutical characteristics,efficacy,safety,economy and other attributes.Results All SGLT-2 inhibitors had evaluation scores above 75,with dagaglifloztin tablets having the highest score of 84.6,and canaglifloztin having the lowest score of 75.1.Conclusions All five original SGLT-2 inhibitors showed good clinical utility,the difference is that the participating original drugs have different advantageous intervals in clinical use.The results show that dagliflozin has the most ideal clinical utility,and its clinical use should be safer and more effective.Due to the short time on the market and insufficient evidence-based reasons,the advantages of clinical use of proline hemegliflozin are not obvious compared with other evaluated drugs.

Objective To analyze the effect of diltiazem on blood concentration of tacrolimus(TAC)retrospectively,and to provide reference for individual administration of tacrolimus in patients with nephrotic syndrome(NS).Methods The patients with NS who were treated in the outpatient/inpatient department of our hospital from January 2018 to December 2022 were collected,and the general information,combined drug use,blood drug concentration and other information of the patients were recorded.The patients were divided into two groups according to whether diltiazem was used or not:TAC group alone and TAC group combined with diltiazem.The effect of diltiazem on tacrolimus concentration was analyzed.Results A total of 45 patients with NS were included in this study,and 21 patients in the TAC group were treated with TAC alone.The mean blood concentration of TAC after medication was(5.77±2.87)ng·mL-1,which reached the effective therapeutic concentration range.The average blood concentration of TAC+Diltiazem group in the 24 patients was(2.90±1.29)ng·mL-1 before combined treatment,and increased to(5.74±2.46)ng·mL-1 after combined with diltiazem,with a growth rate of(127.34±119.57)％.The increase range was from 10％to 288％,and there was significant difference(P＜0.05).According to the observation within 6 months after the combination of the two drugs,the average blood concentration of TAC continued to increase,especially in the 5th month after the administration of TAC,and the concentration tended to be stable after 5 months.By compare with the effect of diltiazem dosage on the blood concentration of TAC,90 mg·d-1 and 180 mg·d-1 had little difference in improving the blood concentration of TAC.At the same time,the combination of the two drugs did not cause adverse reactions.Conclusion A daily dose of 90 mg of Diltiazem can significantly increase the TAC blood concentration in patients with NS who cannot reach the effective therapeutic concentration with conventional doses.It can reach the effective clinical therapeutic concentration without increasing the dose of tacrolimus.The combination of the two drugs were generally safe and effective.

Objective In order to provide a better reference and basis for the selection of reasonable hypoglycemic drugs for clinical treatment,the study conducted a comprehensive clinical evaluation of the innovator sodium-glucose transporters 2(SGLT-2)inhibitors,based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition).Methods The real-world studies,randomized controlled trials,Meta-analysis/systematic review,drug clinical use guidelines,expert consensus and drug description evaluation evidence were collected,and the included drugs were assigned and evaluated from five dimensions:pharmaceutical characteristics,efficacy,safety,economy and other attributes.Results All SGLT-2 inhibitors had evaluation scores above 75,with dagaglifloztin tablets having the highest score of 84.6,and canaglifloztin having the lowest score of 75.1.Conclusions All five original SGLT-2 inhibitors showed good clinical utility,the difference is that the participating original drugs have different advantageous intervals in clinical use.The results show that dagliflozin has the most ideal clinical utility,and its clinical use should be safer and more effective.Due to the short time on the market and insufficient evidence-based reasons,the advantages of clinical use of proline hemegliflozin are not obvious compared with other evaluated drugs.

Objective To analyze the effect of diltiazem on blood concentration of tacrolimus(TAC)retrospectively,and to provide reference for individual administration of tacrolimus in patients with nephrotic syndrome(NS).Methods The patients with NS who were treated in the outpatient/inpatient department of our hospital from January 2018 to December 2022 were collected,and the general information,combined drug use,blood drug concentration and other information of the patients were recorded.The patients were divided into two groups according to whether diltiazem was used or not:TAC group alone and TAC group combined with diltiazem.The effect of diltiazem on tacrolimus concentration was analyzed.Results A total of 45 patients with NS were included in this study,and 21 patients in the TAC group were treated with TAC alone.The mean blood concentration of TAC after medication was(5.77±2.87)ng·mL-1,which reached the effective therapeutic concentration range.The average blood concentration of TAC+Diltiazem group in the 24 patients was(2.90±1.29)ng·mL-1 before combined treatment,and increased to(5.74±2.46)ng·mL-1 after combined with diltiazem,with a growth rate of(127.34±119.57)％.The increase range was from 10％to 288％,and there was significant difference(P＜0.05).According to the observation within 6 months after the combination of the two drugs,the average blood concentration of TAC continued to increase,especially in the 5th month after the administration of TAC,and the concentration tended to be stable after 5 months.By compare with the effect of diltiazem dosage on the blood concentration of TAC,90 mg·d-1 and 180 mg·d-1 had little difference in improving the blood concentration of TAC.At the same time,the combination of the two drugs did not cause adverse reactions.Conclusion A daily dose of 90 mg of Diltiazem can significantly increase the TAC blood concentration in patients with NS who cannot reach the effective therapeutic concentration with conventional doses.It can reach the effective clinical therapeutic concentration without increasing the dose of tacrolimus.The combination of the two drugs were generally safe and effective.

Objective To evaluate the predictive ability and influencing factors of individualized drug administration adjuvant decision-making system Java PK? for Desktop(JPKD)for tacrolimus blood concentration in kidney transplant recipients.Methods The monitoring data of tacrolimus blood concentration from 149 recipients early after kidney transplantation were collected.The trough blood concentration of tacrolimus was predicted by JPKD.The absolute weighted deviation and relative prediction deviation between the actual and predicted concentration were calculated.The influencing factors of the absolute weighted deviation were analyzed by univariate and multivariate logistic regression analyses,and the predictive values of these influencing factors on the accuracy of software prediction were assessed by delineating the receiver operating characteristic(ROC)curve.Results Two hundred and sixty-six samples of tacrolimus blood concentration data were collected from 149 patients.The measured blood concentration of tacrolimus was(6.5±3.0)ng/mL(1.1-16.6 ng/mL),and the predicted value calculated by JPKD was(5.6±2.5)ng/mL(1.4-14.4 ng/mL).The absolute weighted deviation of the calculated data was 28.38％,and the relative prediction deviation was-13.55％.Univariate analysis showed that gender,albumin,changes in hematocrit,cytochrome P450(CYP)3A5*3 genotype and C3435T genotype were associated with the inaccurate prediction results.Multivariate logistic regression analysis found that CYP3A5*3 genotype of AA and the changes in hematocrit were the independent risk factors affecting the accuracy of tacrolimus blood concentration predicted by JPKD.ROC curve analysis showed that when the changes in hematocrit exceeded 2.25％,the risk of inaccurate software prediction was increased.Conclusions JPKD possesses certain accuracy in predicting the blood concentration of tacrolimus in kidney transplant recipients,which may improve the qualified rate of tacrolimus blood concentration.Nevertheless,CYP3A5*3 genotype and the changes of hematocrit may affect the accuracy of predictions.

OBJECTIVE To evaluate the cost-effectiveness of bevacizumab combined with erlotinib in the first-line treatment of advanced EGFR mutant non-squamous non-small cell lung cancer （NSCLC） from the perspective of China’s health system. METHODS A dynamic Markov model was established based on BEVERLY study data， with a cycle of 3 weeks， a research deadline until 99% of patients die， and an annual discount rate of 5%. The model outputs were total cost， quality-adjusted life year （QALY）， and incremental cost-effectiveness ratio （ICER）. Taking 3 times China’s per capita gross domestic product （GDP） in 2023 as the willingness-to-pay （WTP） threshold， the cost-utility analysis was used to evaluate the cost-effectiveness of bevacizumab combined with erlotinib （observation group） versus erlotinib alone （control group） in the first-line treatment of advanced EGFR mutant non-squamous NSCLC， and the single factor sensitivity analysis and probability sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The results of the basic analysis showed that compared with the erlotinib therapy plan， ICER of bevacizumab combined with erlotinib was 1 452 243.01 yuan/QALY， which was more than 3 times China’s per capita GDP in 2023 （268 074 yuan/QALY） as the WTP threshold， indicating that bevacizumab combined with erlotinib was not cost-effective. The results of single factor sensitivity analysis showed that the cost of bevacizumab， the utility value of progression-free survival and progressed disease status had a great influence on the results. The results of probability sensitivity analysis showed that when the WTP threshold was 1 740 000 yuan/QALY， the probability of cost-effective of bevacizumab combined with erlotinib plan was 50%. CONCLUSIONS Compared with erlotinib alone， bevacizumab combined with erlotinib is not cost-effective in the first-line treatment of advanced EGFR mutant non-squamous NSCLC， when using 3 times China’s per capita GDP in 2023 as the WTP threshold.