OBJECTIVE To provide direction and reference for the adjustment of the discount rate （DR） in China’s pharmacoeconomic guidelines. METHODS Search was conducted on the official websites of the International Society for Pharmacoeconomics and Outcomes Research， health technology assessment agencies in various countries/regions， as well as relevant websites of other upper-middle-income or high-income countries/regions. The recommended DR， adjustment trends， and setting rationales in pharmacoeconomic evaluation guidelines across different countries/regions were then summarized and compared. Based on theoretical derivation and literature analysis， the effects of different DR on the incremental cost-effectiveness ratio （ICER） were examined. RESULTS & CONCLUSIONS Among the 40 included guidelines， the base-case DR ranged from 1.5% to 5%， with 5% being the most common value； the range for sensitivity analysis was 0 to 12%. Thirty-six countries/regions applied the same DR to both costs and health outcomes， while in the Netherlands， Belgium， Poland and Czech Republic， DR for costs was higher than for health outcomes. In recent years， Korea， France and Ireland had lowered their DR in response to economic changes， whereas the Netherlands and Czech Republic had raised their DR for cost. The setting of the DR was primarily based on the public project investment interest rate or referred to recommendations from internationally authoritative institutions and other relevant guidelines. The direction and magnitude of the impact of different DR on the ICER largely depended on the distribution of costs and health outcomes between the intervention and reference measure. The setting and adjustment of DR were closely associated with the economic environment. Based on international experience, the DR in China can be lowered by 0.5% to 1.5%， and localized empirical research can be conducted using internationally common estimation methods.

Objective To observe hierarchical differences in brain functional networks in unilateral mesial temporal lobe epilepsy(mTLE)patients with different outcomes after surgery.Methods A total of 69 unilateral mTLE patients who underwent resection of epileptogenic lesion on the affected side were retrospectively enrolled.Based on Engel classification 1 year after surgery,the patients were divided into seizure free(SF)group and non-seizure free(NSF)group.Functional connectivity gradient analysis was employed to extract principal gradient explaining the highest variance on preoperative resting-state functional MRI(rs-fMRI),then the whole-brain gradient characteristics and principal gradient values within specific functional networks were compared between groups.Results Principal gradient connected default mode network(DMN)with sensorimotor network(SMN)along a continuous axis.Compared to SF group,NSF group showed a contracted gradient range at both ends(DMN and SMN)of the functional network and weakened hierarchical differentiation,and principal gradient value of DMN was higher,while that of SMN was lower than those in SF group(both P＜0.05).Conclusion Hierarchical differences in brain functional networks in unilateral mTLE patients with different outcomes after surgery mainly present as enhanced DMN and weakened SMN in NSF ones,and the latter two might serve as important neuroimaging markers for evaluating postoperative seizure recurrence.

Objective To investigate the relationship between serum peroxiredoxin 6(PRDX6)and annexin A1(ANXA1)levels and the severity and prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)compli-cated with type II respiratory failure.Methods A total of 257 patients with AECOPD complicated with type II respiratory failure(respiratory failure group),130 patients with stable COPD(stable COPD group)and 130 healthy subjects(control group)were selected from the Panzhihua University Affiliated Hospital from December 2021 to December 2023.According to the oxygenation index,AECOPD patients with type II respiratory failure were divided into mild respiratory failure group(n=101),moderate respi-ratory failure group(n=80)and severe respiratory failure group(n=76).According to the 28-day prognosis,they were divided into death group(n=62)and survival group(n=195).Serum PRDX6 and ANXA1 levels were detected by enzyme-linked immu-nosorbent assay(ELISA).The correlation between serum PRDX6,ANXA1 levels and oxygenation index in AECOPD patients with type II respiratory failure was analyzed by Spearman correlation coefficient.Multivariate Logistic regression model was used to analyze the influencing factors of poor prognosis in patients with AECOPD complicated with type II respiratory fail-ure,and receiver iperating characteristic(ROC)curve was drawn to evaluate the predictive value of serum PRDX6 and ANXA1.Results The serum PRDX6 level in the respiratory failure group(41.54±4.28 pg/ml)was lower than that in the stable COPD group(61.38±4.94 pg/ml)and the control group(80.65±8.93 pg/ml),and the ANXA1 level(3.35±0.69 μg/L)was higher than that in the stable COPD group(2.13±0.61 μg/L)and the control group(1.03±0.14 μg/L),the differences were statistically sig-nificant(t=-33.894～21.727,all P<0.001).The serum level of PRDX6 in severe respiratory failure group(34.54±5.05 pg/ml)was lower than that in moderate respiratory failure group(43.90±4.72 pg/ml)and mild respiratory failure group(54.28±6.34 pg/ml),the serum level of ANXA1 in severe respiratory failure group(3.94±0.43 μg/L)was higher than that in moderate respi-ratory failure group(3.57±0.46 μg/L)and mild respiratory failure group(2.70±0.43 μg/L),the differences were statistically sig-nificant(t=-19.018～22.338,all P<0.001).Oxygen index was positively correlated with serum PRDX6(r=0.815,P<0.001)and negatively correlated with ANXA1(r=-0.781,P<0.001)in AECOPD patients with type II respiratory failure.The mortality rate of 257 AECOPD patients with type II respiratory failure was 24.12%(62/257)after 28 days of follow-up.Increase forced expi-ratory volume in the first second(FEV1)as a percentage of the predicted value,increased oxygenation index and increased PRDX6 were independent protective factors for the poor prognosis of AECOPD patients with type II respiratory failure(Wald χ2=-0.154,-0.014,-0.173,all P<0.05),increased ANXA1 was an independent risk factor(Wald χ2=0.250,P<0.05).The area un-der the curve of serum PRDX6 and ANXA1 combined to predict the poor prognosis of AECOPD patients with type II respiratory failure was 0.906,which was greater than 0.788 and 0.781 predicted by the two indicators alone,and the differences were statisti-cally significant(Z=4.243,4.224,all P<0.001).Conclusion The decrease of serum PRDX6 level and the increase of ANXA1 level are related to the aggravation and poor prognosis of AECOPD patients with type II respiratory failure.The value of serum PRDX6 combined with ANXA1 in predicting the prognosis of AECOPD patients with type II respiratory failure is high.

Objective:To screen the evidence related to perioperative pain management in thoracic surgery and summarize the best evidence, so as to provide evidence-based basis for clinical nursing practice.Methods:Databases such as Cochrane Library, International Association for the Study of Pain, American Pain Society, Wanfang Database, and China National Knowledge Infrastructure were systematically searched for guidelines, clinical decisions, evidence summaries, best practices, systematic reviews, and expert consensus related to perioperative pain management in thoracic surgery patients. The retrieval time limit was from the establishment of the database to December 31, 2023. Two researchers conducted quality evaluation and evidence extraction.Results:A total of 12 articles were included, including 6 guidelines, 4 systematic reviews, and 2 expert consensuses. Thirty pieces of evidence covering six aspects including organizational management, planning, education, assessment, implementation, and evaluation were summarized.Conclusions:The best evidence summarized in this study can provide evidence-based basis for standardizing the perioperative pain management of thoracic surgery patients.

Objective To investigate the relationship between serum peroxiredoxin 6(PRDX6)and annexin A1(ANXA1)levels and the severity and prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)compli-cated with type II respiratory failure.Methods A total of 257 patients with AECOPD complicated with type II respiratory failure(respiratory failure group),130 patients with stable COPD(stable COPD group)and 130 healthy subjects(control group)were selected from the Panzhihua University Affiliated Hospital from December 2021 to December 2023.According to the oxygenation index,AECOPD patients with type II respiratory failure were divided into mild respiratory failure group(n=101),moderate respi-ratory failure group(n=80)and severe respiratory failure group(n=76).According to the 28-day prognosis,they were divided into death group(n=62)and survival group(n=195).Serum PRDX6 and ANXA1 levels were detected by enzyme-linked immu-nosorbent assay(ELISA).The correlation between serum PRDX6,ANXA1 levels and oxygenation index in AECOPD patients with type II respiratory failure was analyzed by Spearman correlation coefficient.Multivariate Logistic regression model was used to analyze the influencing factors of poor prognosis in patients with AECOPD complicated with type II respiratory fail-ure,and receiver iperating characteristic(ROC)curve was drawn to evaluate the predictive value of serum PRDX6 and ANXA1.Results The serum PRDX6 level in the respiratory failure group(41.54±4.28 pg/ml)was lower than that in the stable COPD group(61.38±4.94 pg/ml)and the control group(80.65±8.93 pg/ml),and the ANXA1 level(3.35±0.69 μg/L)was higher than that in the stable COPD group(2.13±0.61 μg/L)and the control group(1.03±0.14 μg/L),the differences were statistically sig-nificant(t=-33.894～21.727,all P<0.001).The serum level of PRDX6 in severe respiratory failure group(34.54±5.05 pg/ml)was lower than that in moderate respiratory failure group(43.90±4.72 pg/ml)and mild respiratory failure group(54.28±6.34 pg/ml),the serum level of ANXA1 in severe respiratory failure group(3.94±0.43 μg/L)was higher than that in moderate respi-ratory failure group(3.57±0.46 μg/L)and mild respiratory failure group(2.70±0.43 μg/L),the differences were statistically sig-nificant(t=-19.018～22.338,all P<0.001).Oxygen index was positively correlated with serum PRDX6(r=0.815,P<0.001)and negatively correlated with ANXA1(r=-0.781,P<0.001)in AECOPD patients with type II respiratory failure.The mortality rate of 257 AECOPD patients with type II respiratory failure was 24.12%(62/257)after 28 days of follow-up.Increase forced expi-ratory volume in the first second(FEV1)as a percentage of the predicted value,increased oxygenation index and increased PRDX6 were independent protective factors for the poor prognosis of AECOPD patients with type II respiratory failure(Wald χ2=-0.154,-0.014,-0.173,all P<0.05),increased ANXA1 was an independent risk factor(Wald χ2=0.250,P<0.05).The area un-der the curve of serum PRDX6 and ANXA1 combined to predict the poor prognosis of AECOPD patients with type II respiratory failure was 0.906,which was greater than 0.788 and 0.781 predicted by the two indicators alone,and the differences were statisti-cally significant(Z=4.243,4.224,all P<0.001).Conclusion The decrease of serum PRDX6 level and the increase of ANXA1 level are related to the aggravation and poor prognosis of AECOPD patients with type II respiratory failure.The value of serum PRDX6 combined with ANXA1 in predicting the prognosis of AECOPD patients with type II respiratory failure is high.

Objective To observe hierarchical differences in brain functional networks in unilateral mesial temporal lobe epilepsy(mTLE)patients with different outcomes after surgery.Methods A total of 69 unilateral mTLE patients who underwent resection of epileptogenic lesion on the affected side were retrospectively enrolled.Based on Engel classification 1 year after surgery,the patients were divided into seizure free(SF)group and non-seizure free(NSF)group.Functional connectivity gradient analysis was employed to extract principal gradient explaining the highest variance on preoperative resting-state functional MRI(rs-fMRI),then the whole-brain gradient characteristics and principal gradient values within specific functional networks were compared between groups.Results Principal gradient connected default mode network(DMN)with sensorimotor network(SMN)along a continuous axis.Compared to SF group,NSF group showed a contracted gradient range at both ends(DMN and SMN)of the functional network and weakened hierarchical differentiation,and principal gradient value of DMN was higher,while that of SMN was lower than those in SF group(both P＜0.05).Conclusion Hierarchical differences in brain functional networks in unilateral mTLE patients with different outcomes after surgery mainly present as enhanced DMN and weakened SMN in NSF ones,and the latter two might serve as important neuroimaging markers for evaluating postoperative seizure recurrence.

Objective:To screen the evidence related to perioperative pain management in thoracic surgery and summarize the best evidence, so as to provide evidence-based basis for clinical nursing practice.Methods:Databases such as Cochrane Library, International Association for the Study of Pain, American Pain Society, Wanfang Database, and China National Knowledge Infrastructure were systematically searched for guidelines, clinical decisions, evidence summaries, best practices, systematic reviews, and expert consensus related to perioperative pain management in thoracic surgery patients. The retrieval time limit was from the establishment of the database to December 31, 2023. Two researchers conducted quality evaluation and evidence extraction.Results:A total of 12 articles were included, including 6 guidelines, 4 systematic reviews, and 2 expert consensuses. Thirty pieces of evidence covering six aspects including organizational management, planning, education, assessment, implementation, and evaluation were summarized.Conclusions:The best evidence summarized in this study can provide evidence-based basis for standardizing the perioperative pain management of thoracic surgery patients.

The Qa-1 in mice is homologous to human leukocyte antigen E(HLA-E), and both of them belong to the non-classical major histocompatibility complex I b(MHC-I b) molecules. Qa-1 is capable of presenting self or exogenous antigen peptides to interact with two distinct receptors, namely T cell receptor (TCR) and natural killer cell group 2 member A (or C) (NKG2A/C), thus playing an important role in immune response and regulation. Qa-1-restricted regulatory CD8⁺ T cell (CD8⁺ Treg) is one of the most studied CD8⁺ Treg subgroups, which can maintain immune homeostasis and autoimmune tolerance by exerting immunosuppressive effects. Consequently, Qa-1-restricted CD8⁺Treg cells are closely associated with the occurrence and development of various clinical diseases, such as tumors, infections, autoimmune diseases, and transplant rejections. This paper provides a comprehensive review of the phenotypic characteristics, functional effects, regulatory mechanisms of Qa-1-restricted CD8⁺ Treg cells, as well as the latest research progresses of Qa-1-restricted CD8⁺ Treg cells involved in the pathogenesis of infectious diseases.
Humans ; Animals ; T-Lymphocytes, Regulatory/immunology* ; Histocompatibility Antigens Class I/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Communicable Diseases/immunology*

Objective:To investigate the impact of Tai Chi on brain network topology in patients with type 2 diabetes mellitus(T2DM)and mild cognitive impairment(MCI).Method:Patients with T2DM and MCI were recruited and randomly assigned to three groups:Tai Chi group(n=33),fitness walking group(n=31),and health education control group(n=35).Cognitive function was as-sessed using the Montreal Cognitive Assessment(MoCA)at baseline and after 24 weeks of intervention.Mag-netic resonance imaging(MRI)and graph theory methods were used to analyze characteristic path length,be-tweenness centrality,and nodal efficiency to evaluate brain network topology.Result:After 24 weeks,the MoCA score of the Tai Chi group significantly improved compared to the con-trol group(P=0.016),but there was no significant difference compared to the fitness walking group.No signif-icant changes in characteristic path length were observed among the three groups.Compared to the control group,the betweenness centrality in the Tai Chi group significantly increased in the right precentral gyrus,right middle temporal gyrus(temporoccipital part),and left angular gyrus.Additionally,the betweenness cen-trality in the bilateral middle temporal gyri(temporoccipital part)was higher in the Tai Chi group than in the fitness walking group.Nodal efficiency in the right supramarginal gyrus(posterior part)significantly increased in the Tai Chi group compared to the control group.Correlation analysis showed that the change in between-ness centrality of the left middle temporal gyrus in the Tai Chi group was positively correlated with the change in MoCA score(r=0.642,P＜0.001),and the nodal efficiency of the right supramarginal gyrus was also positively correlated with the change in MoCA score(r=0.372,P=0.033).Conclusion:This study preliminarily reveals that Tai Chi may improve cognitive function in patients with T2DM and MCI by modulating the local topological properties of brain networks,particularly in the left mid-dle temporal gyrus and right supramarginal gyrus.

AIM:To investigate the oncolytic effect of human umbilical cord mesenchymal stem cells(hUMSCs)delivering reovirus type 3(Reo3)on chronic myeloid leukemia(CML)K562 cells.METHODS:The expression of junc-tional adhesion molecule-A(JAM-A),a receptor susceptible to Reo3,on the surface of hUMSCs and K562 cells was as-sessed by flow cytometry.Intracellular viral inclusion body distribution 72 h after Reo3 infection in hUMSCs was observed by electron microscopy.The hUMSCs were infected with various multiplicities of infection(MOI)of Reo3(MOI=0,1,2 and 3)for 24,48,72,96 and 120 h,and the most suitable MOI was identified by CCK-8 assay.Subsequently,hUMSCs were infected with the optimal titer of Reo3 for the same durations,and supernatants were collected.The titer of Reo3 in the supernatant from each group was measured using mouse fibroblast L929 cells combined with median tissue culture in-fectious dose(TCID50)method,determining the optimal infection time.The K562 cells were divided into 4 groups:con-trol group,hUMSCs group,Reo3 group,and hUMSCs-Reo3 group.Ratios of hUMSCs to K562 cells in hUMSCs group and hUMSCs-Reo3 group were set at low,medium and high(5∶1,10∶1 and 20∶1).The changes of K562 cell viability af-ter co-cultured with hUMSCs-Reo3 for 24,48 and 72 h were analyzed by CCK-8 assay.The apoptosis of K562 cells was evaluated by flow cytometry.The half maximal effective concentration(EC50)of anti-Reo3 monoclonal antibody was deter-mined using L929 cells.The oncolytic effect of hUMSCs-Reo3 on K562 cells with antibody present in vitro was verified.Western blot analysis was used to detect the protein levels of Bcl-2,Bax,survivin and cleaved caspase-3 in K562 cells af-ter treatment.A BALB/c nude mouse subcutaneous tumor model was constructed with K562 cells(n=6)to analyze the in vivo anti-tumor effect of hUMSCs-Reo3.RESULTS:The expression levels of JAM-A on the surfaces of hUMSCs and K562 cells were found to be 11.0%and 99.0%,respectively.Electron microscopy revealed a significant presence of viral inclusion bodies within hUMSCs 72 h following infection with Reo3.Within 120 h,no statistically significant difference was observed in the viability of hUMSCs between Reo3(MOI=1)group and uninfected group,establishing the optimal MOI.The TCID50 results indicated that the highest virus titer in the lysate of hUMSCs in Reo3(MOI=1)group occurred 48 h after infection,determining 48 h as the optimal infection time.The K562 cells co-cultured with hUMSCs-Reo3 for 24,48 and 72 h showed a dose-and time-dependent inhibition of cell viability.The EC50 of the anti-Reo3 monoclonal antibody was found to be 1∶34.Even in the presence of antibodies at various concentrations(1∶34,1∶300 and 1∶600),hUMSCs were capable of transporting Reo3 to inhibit K562 cell viability and induce apoptosis in vitro.Compared with control group,significant down-regulation of Bcl-2 and survivin expression levels in K562 cells was noted after 48 h of co-culture with hUMSCs-Reo3(P<0.05),while Bax and cleaved caspase-3 expression levels were significantly up-regulated(P<0.05 or P<0.01).In the BALB/c nude mouse tumor-bearing model,determination of tumor volume changes,pathological examination of tumor tissue and major organs,and assessment of cathepsin B/L activity using a small animal live imaging system confirmed the oncolytic effect of hUMSCs-Reo3 on K562 cells in vivo without adverse effects on normal tissues.CONCLUSION:The hUMSCs are effective in transporting Reo3,and this delivery system is capable of releasing suffi-cient quantities of Reo3 in both in vivo and in vitro settings to inhibit the malignant proliferation of K562 cells and promote apoptosis,thereby exerting an oncolytic effect.