Objective:To review the Minimal Clinically Important Difference(MCID)of EQ-5D-3L calculated by anchor-based method,evaluate the reliability of existing MCID,and provide reference thresholds for the interpretation of clinical research results.Methods:CNKI,PubMed,Embase and others were searched from inception to June 30,2023.The nonparametric tests were used to analyze the impact of statistical methods and sample size on MCID.Results:A total of 51 studies were eventually included.Studies were primarily prospective in design,32 studies focused on musculoskeletal disorders,37 studies used a single anchor,45 studies adopted patient-perspective anchor,and the Receiver Operating Characteristic(ROC)curve was the main statistical analysis method.A total of 160 MCID were obtained from 51 studies,ranging from 0.003 to 0.540,and only 3 MCID from 2 studies were rated as"high reliability"across all core items of the evaluation instrument.It is found that statistical analysis methods,sample size,and measurement time interval all significantly affect MCID.Conclusion:The disease type in EQ-5D-3L MCID studies were not abundant and unbalanced,and the heterogeneity of MCID measured in the included studies was high.The reliability evaluation results showed that the existing MCID has poor reliability in all items except the first and second items of the evaluation instrument.

Objective:To explore the expression and mechanism of lncRNA MALAT1 in negative sputum for tuberculous bac-terium.Methods:Expression of lncRNA MALAT1 in peripheral blood mononuclear cells(PBMC)of patients with positive sputum bacteria(Positive group)and negative sputum bacteria(Negative group)and healthy volunteers(HC group)was detected by RT-PCR.ELISA was used to detect expression levels of TNF-α,IL-1β and IL-6 in plasma.Expression of lncRNA MALAT1 in mice macro-phages RAW264.7 was silenced by siRNA interference,and RAW264.7 cells were infected with mycobacterium tuberculosis(MTB)H37Rv.Cells were divided into four groups:Control group,Control+MTB group,MTB+si-NC group and MTB+si-MALAT1 group.Proliferation activity of RAW264.7 cells in each group was detected by CCK-8 method.The number of MTB in each group was detected by CFU.Expressions of TNF-α,IL-1β and IL-6 in supernatant of RAW264.7 cells were detected by ELISA.Results:Compared with HC group,expressions of lncRNA MALAT1 in PBMC,and TNF-α,IL-1β and IL-6 in plasma were significantly increased in Positive group and Negative group(P<0.01).Compared with Control group,expression level of lncRNA MALAT1,proliferation activity,CFU value,and concentrations of TNF-α,IL-1β and IL-6 in supernatant of Control+MTB group,MTB+si-NC group and MTB+si-MALAT1 group were significantly increased(P<0.05).Compared with MTB+si-NC group,the above detection indexes in MTB+si-MALAT1 group were significantly decreased(P<0.05),while there was no significant difference in Control+MTB group(P>0.05).Conclusion:The significantly increased expression of MALAT1 in patients with negative sputum for tuberculous bacterium is positively correlated with expression of plasma inflammatory factors,while the silence of MALAT1 expression can reduce MTB induced inflammatory response by inhibiting the proliferation and phagocytosis of MTB infected macrophages.

Objective To evaluate the cost-effectiveness of toripalimab plus axitinib compared to sunitinib in the first-line treatment of advanced renal cell carcinoma patients.Methods Based on the RENOTORCH trial,constructed a partitioned survival model to evaluate the long-term costs and health outcomes of toripalimab plus axitiniband sunitinib in the first-line treatment of advanced renal cell carcinoma(RCC)patients from the Chinese healthcare system perspective.The cycle length of the model was 3weeks,simulating the total cost,quality adjusted life years(QALYs),and incremental cost-effectiveness ratio(ICUR)for patients over 25 years.The costs were derived from the average bidding price of Yaozhi database in 2023 and published literature.The health state utility values were derived from clinical trials.The discount rate was 5%,and the willingness to pay(WTP)threshold was 3 times the per capita gross domestic product(GDP)in 2022.One-way and probability sensitivity analyses were used to test the robustness of the model.Results Based on the progression free survival(PFS)evaluated by the Independent Review Committee(IRC)and Investigator(IA),the ICUR values were 239 436.39 yuan/QALY and 175 440.39 yuan/QALY,respectively,both lower than the WTP threshold.One-way sensitivity analysis showed that the health state utility values of PFS status and the price of axitinib had a significant impact on the model.Probability sensitivity analysis showed that the probability of toripalimab plus axitinib being cost-effective was 63.64%and 98.03%according to the IRC and IA assessments,respectively.Conclusion Toripalimab plus axitinib was cost-effective in the first-line treatment of advanced RCC patients.

Objective:Time trade-off was employed to measure health state utilities associated with treatment attributes of hemophilia A patients to provide parameters for economic evaluations.Methods:Patients were recruited through patient organization and blood center of Shandong to measure health state utility values for 10 health states.Results:The utility values of preventive treatments for severe,moderate,and mild hemophilia A were 0.644,0.738,and 0.815,respectively.Compared with injections at 2-day intervals,the utility values were increased by 0.044 and 0.092 at 3-and 4-day intervals,respectively.Taking"severe hemophilia A patients injected every 2 days"as the base state,the disutility values for spontaneous bleeding and traumatic bleeding were 0.226 and 0.172.The disutility values for mild,moderate,and severe bleeding were 0.052,0.159,and 0.476,respectively,and the magnitude of the decrease gradually increased.Conclusion:Treatment attributes have an impact on patient preferences and more attention should be paid in pharmacoeconomic evaluations.

Objective:To review the Minimal Clinically Important Difference(MCID)of EQ-5D-3L calculated by anchor-based method,evaluate the reliability of existing MCID,and provide reference thresholds for the interpretation of clinical research results.Methods:CNKI,PubMed,Embase and others were searched from inception to June 30,2023.The nonparametric tests were used to analyze the impact of statistical methods and sample size on MCID.Results:A total of 51 studies were eventually included.Studies were primarily prospective in design,32 studies focused on musculoskeletal disorders,37 studies used a single anchor,45 studies adopted patient-perspective anchor,and the Receiver Operating Characteristic(ROC)curve was the main statistical analysis method.A total of 160 MCID were obtained from 51 studies,ranging from 0.003 to 0.540,and only 3 MCID from 2 studies were rated as"high reliability"across all core items of the evaluation instrument.It is found that statistical analysis methods,sample size,and measurement time interval all significantly affect MCID.Conclusion:The disease type in EQ-5D-3L MCID studies were not abundant and unbalanced,and the heterogeneity of MCID measured in the included studies was high.The reliability evaluation results showed that the existing MCID has poor reliability in all items except the first and second items of the evaluation instrument.

Objective:Time trade-off was employed to measure health state utilities associated with treatment attributes of hemophilia A patients to provide parameters for economic evaluations.Methods:Patients were recruited through patient organization and blood center of Shandong to measure health state utility values for 10 health states.Results:The utility values of preventive treatments for severe,moderate,and mild hemophilia A were 0.644,0.738,and 0.815,respectively.Compared with injections at 2-day intervals,the utility values were increased by 0.044 and 0.092 at 3-and 4-day intervals,respectively.Taking"severe hemophilia A patients injected every 2 days"as the base state,the disutility values for spontaneous bleeding and traumatic bleeding were 0.226 and 0.172.The disutility values for mild,moderate,and severe bleeding were 0.052,0.159,and 0.476,respectively,and the magnitude of the decrease gradually increased.Conclusion:Treatment attributes have an impact on patient preferences and more attention should be paid in pharmacoeconomic evaluations.

Objective:To explore the expression and mechanism of lncRNA MALAT1 in negative sputum for tuberculous bac-terium.Methods:Expression of lncRNA MALAT1 in peripheral blood mononuclear cells(PBMC)of patients with positive sputum bacteria(Positive group)and negative sputum bacteria(Negative group)and healthy volunteers(HC group)was detected by RT-PCR.ELISA was used to detect expression levels of TNF-α,IL-1β and IL-6 in plasma.Expression of lncRNA MALAT1 in mice macro-phages RAW264.7 was silenced by siRNA interference,and RAW264.7 cells were infected with mycobacterium tuberculosis(MTB)H37Rv.Cells were divided into four groups:Control group,Control+MTB group,MTB+si-NC group and MTB+si-MALAT1 group.Proliferation activity of RAW264.7 cells in each group was detected by CCK-8 method.The number of MTB in each group was detected by CFU.Expressions of TNF-α,IL-1β and IL-6 in supernatant of RAW264.7 cells were detected by ELISA.Results:Compared with HC group,expressions of lncRNA MALAT1 in PBMC,and TNF-α,IL-1β and IL-6 in plasma were significantly increased in Positive group and Negative group(P<0.01).Compared with Control group,expression level of lncRNA MALAT1,proliferation activity,CFU value,and concentrations of TNF-α,IL-1β and IL-6 in supernatant of Control+MTB group,MTB+si-NC group and MTB+si-MALAT1 group were significantly increased(P<0.05).Compared with MTB+si-NC group,the above detection indexes in MTB+si-MALAT1 group were significantly decreased(P<0.05),while there was no significant difference in Control+MTB group(P>0.05).Conclusion:The significantly increased expression of MALAT1 in patients with negative sputum for tuberculous bacterium is positively correlated with expression of plasma inflammatory factors,while the silence of MALAT1 expression can reduce MTB induced inflammatory response by inhibiting the proliferation and phagocytosis of MTB infected macrophages.

Objective To evaluate the cost-effectiveness of toripalimab plus axitinib compared to sunitinib in the first-line treatment of advanced renal cell carcinoma patients.Methods Based on the RENOTORCH trial,constructed a partitioned survival model to evaluate the long-term costs and health outcomes of toripalimab plus axitiniband sunitinib in the first-line treatment of advanced renal cell carcinoma(RCC)patients from the Chinese healthcare system perspective.The cycle length of the model was 3weeks,simulating the total cost,quality adjusted life years(QALYs),and incremental cost-effectiveness ratio(ICUR)for patients over 25 years.The costs were derived from the average bidding price of Yaozhi database in 2023 and published literature.The health state utility values were derived from clinical trials.The discount rate was 5%,and the willingness to pay(WTP)threshold was 3 times the per capita gross domestic product(GDP)in 2022.One-way and probability sensitivity analyses were used to test the robustness of the model.Results Based on the progression free survival(PFS)evaluated by the Independent Review Committee(IRC)and Investigator(IA),the ICUR values were 239 436.39 yuan/QALY and 175 440.39 yuan/QALY,respectively,both lower than the WTP threshold.One-way sensitivity analysis showed that the health state utility values of PFS status and the price of axitinib had a significant impact on the model.Probability sensitivity analysis showed that the probability of toripalimab plus axitinib being cost-effective was 63.64%and 98.03%according to the IRC and IA assessments,respectively.Conclusion Toripalimab plus axitinib was cost-effective in the first-line treatment of advanced RCC patients.

Purpose To design PCR combined probes u-sing TaqMan technology to detect the expression of major driver genes in a variety of soft tissue sarcomas at one time,and to dis-cuss whether the combined probes can better assist clinicopatho-logical diagnosis based on histological features and FISH results.Methods Our research group designed 32 pairs of fusion gene probes related to soft tissue sarcoma based on TaqMan tech-nique,involving 10 types of sarcoma.The histopathological specimens of 70 patients with common fusion gene soft tissue sarcoma in our hospital were examined by fusion gene combina-tion,and the histopathological specimens of 30 patients with oth-er soft tissue sarcoma without fusion gene were set as controls.Individual common sarcoma types were analyzed with FISH probe detection.At the same time,the detection performance of the combined probe was evaluated by various methods.Results The soft tissue sarcoma-related fusion gene probe designed by our research group was used to detect the confirmed soft tissue sarcomas,and the results showed that the highest sensitivity was 100％.Among the three types of tumors,protuberant dermatofi-brosarcoma,synovial sarcoma and mucinous liposarcoma were verified by FISH,and the coincidence rate of the two methods was high,with no statistical significance(P＞0.05).The re-sults of interlot and intralot reproducibility of protuberous derma-tofibrosarcoma,mucinous liposarcoma and synovial sarcoma were consistent.Three different concentration limits were used to de-tect the positive plasmid of all the fused gene RNA,and 25 cop-ies/μL was the lowest concentration limit.Conclusion Com-bined with the pathological diagnosis results,TaqMan technology can be used to design PCR combined probes for soft tissue sarco-ma,which have high sensitivity and high specificity and good methodological performance,and meet the needs of primary medical institutions for one-time and rapid auxiliary pathological diagnosis of common soft tissue sarcoma.It provides a rapid and reliable method for the detection of multiple fusion genes in clin-ical soft tissue sarcoma.

Objective:Evaluating the impact of various hypoglycemic events on the Health-Related Quality of Life(HRQoL)of diabetes patients to provide empirical data for health technology assessment.Methods:The data was collected from a tertiary hospital in Jinan,Shandong Province,China.Health utility was measured using the Time Trade-off(TTO)method,and disutility was calculated based on the formula.Subsequently,the intergroup differences among various hypoglycemic event groups were analyzed.Results:The hypoglycemic events'average utility was all lower than the average utility for diabetics without hypoglycemic events(baseline status).Severe hypoglycemic events(0.108)had higher disutility compared to non-severe hypoglycemic events(0.008).Furthermore,nocturnal severe/non-severe hypoglycemic events(0.118/0.008)exhibited higher average disutility than daytime severe/non-severe hypoglycemic events(0.098/0.007).Conclusion:Optimal diabetes management demands prioritizing the prevention of both severe hypoglycemic events and nocturnal hypoglycemic events.