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 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 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 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.

OBJECTIVE To provide a reference for the early diagnosis， drug treatment and medication monitoring for patients with Lemierre’s syndrome. METHODS The doctors confirmed the diagnosis of the patient as having Lemierre’s syndrome based on the patient’s condition and the results of metagenomic next-generation sequencing （mNGS）， and the clinical pharmacists participated in the treatment process of the patient. During the treatment process， the clinical pharmacists suggested using piperacillin sodium and tazobactam sodium combined with metronidazole for anti-infective treatment against Fusobacterium necrophorum infection； clinical pharmacists recommend anticoagulant treatment with Enoxaparin sodium injection for left internal jugular vein thrombophlebitis. RESULTS The doctors accepted the suggestion of the clinical pharmacists， and the patient’s condition improved after treatment and was allowed to be discharged with medication. CONCLUSIONS By interpreting the results of mNGS， combined with the patient’s condition， the clinical pharmacists assist doctors in formulating individualized anti-infective and anticoagulant plans for the patient and provide medication monitoring， ensuring the safety and effectiveness of the patient’s medication.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

AIM:To explore the synergistic sensitization effect of human umbilical cord mesenchymal stem cell culture supernatant(hUMSC-CM)combined with temozolomide(TMZ)on various glioma cell lines,and to elucidate the underlying mechanisms.METHODS:The hUMSC-CM was harvested using two different serum deprivation tech-niques at 24 and 48 h,and was converted into freeze-dried powder,which was then given to rat malignant glioma cell line RG-2,human astrocytoma cell line U251 and human glioblastoma cell line LN-428 at 5 concentrations(0,1,3,6 and 9 g/L).The effectiveness and sensitivity of hUMSC-CM for inhibiting growth of glioma cells at 24,48 and 72 h were as-sessed using CCK-8 assay.Hematoxylin-eosin(HE)staining combined with CCK-8 assay was employed to evaluate the chemotherapy sensitivity of glioma cells after 48 h of treatment with TMZ at 6 concentrations(0,25,50,100,200 and 400 μmol/L).Two concentrations(3 and 9 g/L)of hUMSC-CM and 3 concentrations(50,100 and 200 μmol/L)of TMZ were chosen for concurrent treatment of glioma cells to assess the proliferation and pathological alterations.TUNEL staining was utilized to detect apoptosis.Flow cytometry was utilized to analyze cell cycle modifications.The expression alterations of apoptosis-inducing proteins,cleaved caspase-3,cleaved caspase-8 and cleaved PARP1,as well as autophagy-inducing proteins beclin-1 and LC3,were examined using Western blot to investigate the synergistic sensitization mechanism of hUMSC-CM combined with TMZ in vitro.RESULTS:The susceptibility of glioma cell lines to hUMSC-CM and TMZ varied,with RG-2 showing the highest sensitivity,followed by U251,and then LN-428.The inhibitory effect of hUMSC-CM(3 and 9 g/L)and TMZ(50,100 and 200 μmol/L)combined treatment on glioma cells was significantly greater than that that of single-agent treatments(P＜0.05),demonstrating a dose-and concentration-dependent enhancement.Notably,the combination of 9 g/L hUMSC-CM(C9)with 50 μmol/L TMZ(T50)effectively suppressed glioma cell growth.CCK-8 as-say indicated a significant reduction of cell viability in C9+T50 group compared with either C9 or T50 alone(P＜0.05).HE staining and TUNEL staining revealed pronounced morphological changes and significant apoptotic features in glioma cells treated with C9+T50.Flow cytometric analysis confirmed that C9+T50 induced cell cycle arrest in glioma cells.Fur-thermore,compared with control group,the levels of cleaved caspase-3,cleaved caspase-8,cleaved PARP1,beclin-1,and LC3-Ⅱ/LC3-Ⅰ were significantly elevated in the C9+T50-treated glioma cells(P＜0.01).CONCLUSION:(1)The concomitant administration of hUMSC-CM and TMZ exerts a broad inhibitory effect on glioma cells,with a synergistic sen-sitization observed across different cell lines.(2)The enhancement of glioma cell sensitivity to TMZ by hUMSC-CM may be attributed to the modulation of caspase-8/caspase-3/PARP1 signaling pathway and the induction of both apoptosis and autophagy in glioma cells.