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 evaluate the effect of comprehensive warming measures on reducing the inci-dence of inadvertent perioperative hypothermia(IPH)in patients with extensive burns.Methods A total of 82 patients with extensive burns who underwent escharectomy between January 2020 and January 2024 were selected as the study subjects.They were randomly divided into a control group and an observation group,with 41 patients in each group.The control group received conventional warming measures,while the observation group received comprehensive warming measures in addition to the conventional measures.Body temperature was monitored at the following time points:preoperatively,at the start of anesthesia,at the start of surgery,60 minutes after surgery,120 minutes after surgery,and at the end of surgery.The time to anesthesia recovery,intraoperative fluid infusion volume,blood transfusion volume,urine output,incidence of postoperative shive-ring,and length of hospital stay were recorded.Hemoglobin(HB),platelet count(PLT),prothrombin time(PT),activated partial thromboplastin time(APTT),and blood lactate levels were measured before and after surgery.Results Statistically significant differences were observed between the two groups in intraoperative blood transfusion volume,postoperative blood lactate levels,incidence of IPH,incidence of postoperative shive-ring,and length of hospital stay(P＜0.05).No statistically significant differences were found in intraopera-tive fluid infusion volume,urine output,time to anesthesia recovery,or postoperative levels of HB,PLT,PT,and APTT(P＞0.05).The body temperature of patients in both groups showed a decreasing trend as surgery progressed.The body temperature in the control group was significantly lower than that in the observation group at 60 minutes after surgery,120 minutes after surgery,and at the end of surgery(P＜0.05).Conclusion Comprehensive perioperative warming measures can reduce the incidence of intraoperative hypothermia and decrease intraop-erative bleeding in patients with extensive burns.

Objective:To investigate the correlation between serum NOD-like receptor protein 3 (NLRP3) levels and serum lipids in metabolic-associated fatty liver disease (MAFLD) before and after a single high-fat meal.Methods:A retrospective cohort study was conducted. Sixty-three MAFLD patients (MAFLD group) and fifty-four healthy subjects (CON group) recruited from February 2019 to December 2019 at Hebei Provincial People's Hospital were included. The baseline data were compared between the two groups, and a single high-fat meal trial was conducted. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and NLRP3 were measured at 2 h, 4 h, and 6 h after fasting and a high-fat meal. Multiple linear regression analysis was used to evaluate the influencing factors of area under the operating curve (AUC NLRP3) of serum NLRP3 subjects. Logistic regression analysis was used to evaluate the correlation between serum AUC NLRP3 and the risk of MAFLD. Results:The levels of TC, TG, LDL-C, and NLRP3 were significantly higher in the fasting group than the CON group at 2 h, 4 h, and 6 h after a meal [TC (mmol/L), fasting: (5.29±1.01) vs. (4.28±0.62), 2 h: (5.24±0.98) vs. (4.25±0.62), 4 h: (5.38±1.04) vs. (4.26±0.63), 6 h: (5.54±1.07) vs. (4.41±0.65); TG (mmol/L), fasting: (2.67±0.96) vs. (0.92±0.33), 2 h: (3.91±1.35) vs. (1.69±0.59), 4 h: (5.09±1.7) vs. (1.91±0.93), 6 h: (5.36±2.27) vs. (1.75±1.03); LDL-C (mmol/L), fasting: (3.47±0.74) vs. (2.65±0.49), 2 h: (3.36±0.71) vs. (2.58±0.49), 4 h: (3.30±0.71) vs. (2.55±0.47), 6 h: (3.36±0.74) vs. (2.63±0.48); NLRP3 (ng/L), fasting: (84.63±12.96) vs. (56.71±11.37), 2 h: (106.06±17.76) vs. (69.12±14.92), 4 h: (89.78±15.98) vs. (57.74±12.34), 6 h: (80.03±13.61) vs. (54.06±10.35); P<0.001], while the HDL-C level was significantly lower than the CON group [HDL-C (mmol/L), fasting: (1.14±0.24) vs. (1.33±0.29), 2 h: (1.14±0.24) vs. (1.33±0.29), 4 h: (1.09±0.24) vs. (1.27±0.28), and 6 h: (1.05±0.26) vs. (1.29±0.30); P<0.001]. Serum AUC NLRP3 was significantly correlated with AUC TG and AUC LDL-C (AUC TG: B=7.391, 95% CI:5.662-9.12; AUC LDL-C: B=6.559, 95% CI:3.052-10.065; P<0.001) after adjusting for confounding factors, and it was identified as an independent influencing factor for MAFLD ( OR=1.039, 95% CI:1.007-1.071; P=0.015). Conclusion:The serum NLRP3 levels before and after a single high-fat meal are significantly associated with elevated TG and LDL-C levels, and may influence the progression of MAFLD.

Objective:To investigate the correlation between serum NOD-like receptor protein 3 (NLRP3) levels and serum lipids in metabolic-associated fatty liver disease (MAFLD) before and after a single high-fat meal.Methods:A retrospective cohort study was conducted. Sixty-three MAFLD patients (MAFLD group) and fifty-four healthy subjects (CON group) recruited from February 2019 to December 2019 at Hebei Provincial People's Hospital were included. The baseline data were compared between the two groups, and a single high-fat meal trial was conducted. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and NLRP3 were measured at 2 h, 4 h, and 6 h after fasting and a high-fat meal. Multiple linear regression analysis was used to evaluate the influencing factors of area under the operating curve (AUC NLRP3) of serum NLRP3 subjects. Logistic regression analysis was used to evaluate the correlation between serum AUC NLRP3 and the risk of MAFLD. Results:The levels of TC, TG, LDL-C, and NLRP3 were significantly higher in the fasting group than the CON group at 2 h, 4 h, and 6 h after a meal [TC (mmol/L), fasting: (5.29±1.01) vs. (4.28±0.62), 2 h: (5.24±0.98) vs. (4.25±0.62), 4 h: (5.38±1.04) vs. (4.26±0.63), 6 h: (5.54±1.07) vs. (4.41±0.65); TG (mmol/L), fasting: (2.67±0.96) vs. (0.92±0.33), 2 h: (3.91±1.35) vs. (1.69±0.59), 4 h: (5.09±1.7) vs. (1.91±0.93), 6 h: (5.36±2.27) vs. (1.75±1.03); LDL-C (mmol/L), fasting: (3.47±0.74) vs. (2.65±0.49), 2 h: (3.36±0.71) vs. (2.58±0.49), 4 h: (3.30±0.71) vs. (2.55±0.47), 6 h: (3.36±0.74) vs. (2.63±0.48); NLRP3 (ng/L), fasting: (84.63±12.96) vs. (56.71±11.37), 2 h: (106.06±17.76) vs. (69.12±14.92), 4 h: (89.78±15.98) vs. (57.74±12.34), 6 h: (80.03±13.61) vs. (54.06±10.35); P<0.001], while the HDL-C level was significantly lower than the CON group [HDL-C (mmol/L), fasting: (1.14±0.24) vs. (1.33±0.29), 2 h: (1.14±0.24) vs. (1.33±0.29), 4 h: (1.09±0.24) vs. (1.27±0.28), and 6 h: (1.05±0.26) vs. (1.29±0.30); P<0.001]. Serum AUC NLRP3 was significantly correlated with AUC TG and AUC LDL-C (AUC TG: B=7.391, 95% CI:5.662-9.12; AUC LDL-C: B=6.559, 95% CI:3.052-10.065; P<0.001) after adjusting for confounding factors, and it was identified as an independent influencing factor for MAFLD ( OR=1.039, 95% CI:1.007-1.071; P=0.015). Conclusion:The serum NLRP3 levels before and after a single high-fat meal are significantly associated with elevated TG and LDL-C levels, and may influence the progression of MAFLD.

Diabetic Retinopathy (DR) is a chronic, progressive and potentially harmful retinal microvascular disease that is associated with persistent hyperglycemia.Without timely and effective treatment, it will seriously damage the vision of patients and bring great inconvenience to their lives.The development of DR involves various mechanisms such as blood-retinal barrier damage, inflammation and neurodegeneration.Intraocular fluids, including aqueous humor and vitreous fluid, can directly reflect the changes in the intraocular environment and have a good indication of the progress of intraocular lesions.In recent years, the changes of various cytokines in intraocular fluid during the occurrence of DR and their influence on the disease course and their changes after treatment have been widely studied.This article focuses on the changes in angiogenesis-related cytokines such as vascular endothelial growth factor, placental growth factor, galectin-1, angiotensin 1 (Ang1), Ang2 and inflammation-related cytokines such as tumor necrosis factor-α, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, transforming growth factor-β, interleukin (IL)-1β, IL-6, IL-8, IL-10 in the intraocular fluid of DR patients, and the changes of these cytokines and the significance after treatment in patients with diabetic macular edema and proliferative DR to provide potential targets for exploring new and personalized clinical treatment and theoretical basis to improve the prognosis of patients with DR.

Objective:To study the clinicopathological features of adrenocortical oncocytic tumors (ACOT) and to compare the diagnostic values of Lin-Weiss-Bisceglia (LWB) score and Helsinki score.Methods:Forty-four cases of ACOT diagnosed at Beijing Friendship Hospital, China from March 2008 to July 2019 were histologically analyzed to evaluate their malignant potential (benign versus malignant) according to two scoring criteria. Immunohistochemical studies (EnVision method) were also used.Results:There were 23 males and 21 females with an average age of 46 years. Histologically, the tumor cells were arranged in trabecular, chrysanthemum-shaped, glandular and microcapsule structures, while clear cells were rare or absent. Most of the tumor cells were moderately atypical, and intranuclear inclusion bodies were conspicuous. Immunohistochemical staining showed that tumor cells were positive for Melan A, inhibin, Syn and calretinin. The average proliferation index was 3% in benign ACOT, about 5% in ACOT of malignant potential, and>20% in malignant ACOT. According to the LWB score, 61.4% (27/44) of the tumors were on the left side and had multiple lesions. The percentage of benign ACOT was 59.1% (26/44), malignant potential 6.8% (3/44), malignant 34.1% (15/44), respectively. Among the 15 malignant ACOT, the mitotic figures>5/50 HPF were found in 13 cases, necrosis in 11 cases and capsule invasion in 10 cases. According to the Helsinki score, 65.9% (29/44) of the tumors were benign, and 34.1% (15/44) were malignant. There was no significant difference between the two scoring standards ( P>0.05). During the follow-up of 9 to 144 months, 31 patients survived without disease and 13 patients relapsed or had metastasis. Conclusions:ACOT more likely be benign than malignant. The left side is more common. Malignant tumors are prone to recurrence and metastasis. The morphological parameters (high mitotic index, necrosis, and capsular invasion) in the LWB scoring standards combined with immunohistochemical parameters (Ki-67) in the Helsinki score are helpful for the diagnosis of malignant ACOT and are important predictors of poor prognosis.

Objective To analyze the echocardiographic findings , associated anomalies and chromosomal characteristics in fetuses with pulmonary atresia with ventricular septal defect ( PA/VSD ) . Methods T he echocardiographic data and follow‐up materials were retrospectively reviewed in 30 256 fetuses from December 2012 to M arch 2018 in the consultation center of fetal heart disease in maternal‐fetal medicine in Anzhen hospital . Of all the fetuses ,59 cases ( 0 .19% ) had PA/VSD . T he echocardiographic findings ,associated anomalies and chromosomal characteristics were retrospectively analyzed in all the 59 fetuses with PA/VSD . Based on w hether the presence of the native pulmonary arteries and the major aortopulmonary collateral arteries ( M APCAs) or not ,the PA‐VSD was classified into type A ,type B ,and type C . Results A large ventricular defect was demonstrated in five‐chamber view with 61 .7% of the mean ratio of the aortic overriding . O ther fetal echocardiographic features of all the 59 fetuses with PA/VSD included :the right aortic arch ( n ＝19 ) ,reversal flow in the ductus arteriosus ( n ＝40 ) ,M APCAs ( n ＝24) . T he classification of the PA/VSD included :type A ( n ＝35) ,type B ( n ＝5) and type C ( n ＝19) . Associated anomalies :persistent left superior vena cava ( n ＝ 13 ) ,anomalous pulmonary vein connection ( n＝5 ) ,complete atrioventricular septal defect ( n ＝ 5 ) ; single umbilical artery ( n ＝ 3 ) ,right atrial isomerism ( n ＝3) . Of all the 30 cases performed chromosomal test ,3 cases had aneuploidy and 7 cases had microdeletion of chromosome . Conclusions The fetal echocardiographic findings of the PA/VSD are characteristic . For prenatal diagnosis of PA/VSD ,the type of PA/VSD should be defined and chromosomal test should be performed ,w hich can be helpful for prenatal consulting .

Objective To detect the expression levels of RAD21(S.Pombe RAD21 homolog)in lung cancer,and assess its clinical significance and potential functions. Methods The expression level of RAD21 in lung cancer was determined by Western blot and immunohistochemistry meth?ods;the RAD21 mRNA expression in lung cancer was analyzed through Oncomine database;the relationship between the RAD21 expression levels and prognosis in patients with lung cancer was studied by Kaplan Meier curve;the RAD21 functions in lung cancer were predicted by using gene set enrichment analysis. Results Compared with adjacent normal tissue,the protein level of RAD21 in lung tissues were upregulated . The data from Oncomine database showed that RAD21 mRNA levels were significantly higher than the normal control groups in multiple lung cancer datasets(P<0.01);in addition,Kaplan?Meier survival curves showed that the RAD21 expression levels was correlated with the survival of patients with lung can?cer(P<0.05);gene set enrichment analysis indicated that RAD21 was mainly enriched in apoptotic signaling pathways and cell cycle regulation gene sets. Conclusion The downregulated RAD21 could be used as a biomarker to assess the prognosis of lung cancer patients. In addition, RAD21 may be involved in the regulation of cell cycle and apoptosis,which affects the development and progression of lung cancer.

Objective To analyze the effects of individualized lifestyle intervention on compliance and metabolic status of patients with type 2 diabetes mellitus (T2DM).Methods Two hundred T2DM patients were selected and randomly divided into experimental and control groups of 100 patients respectively.The experimental group was given individualized lifestyle intervention for 6 months in addition to conventional oral medications.The intervention was to prescribe diet control and exercise therapy according to the patients' individual conditions.The control group was given conventional treatment and verbal lifestyle intervention for 6 months.Comparison was made in patients compliance and various metabolic markers between the two groups.Results The percentage of conduction of diet control and exercise therapy in experimental group was significantly higher than control group ( Diet control:80 vs.52,x2=7.08,P=0.029;Exercise therapy:78 vs.44,x2=11.207,P=0.004).After intervention,the fasting plasma glucose (FPG),2-hour postprandial blood glucose (2hPG),glycated hemoglobin ( HbA1c),body mass index ( BMI),triglyceride ( TG),total cholesterol (TC),low-density lipoprotein ( LDL-C ),and insulin resistance index ( HOMA-IR ) in experimental group decreased significantly,and high-density lipoprotein ( HDL-C ) increased significantly [FPG:( 8.45 ± 1.46 ) mmol/L vs.(6.66 ± 0.67) mmol/L,P=0.000;2hPG:( 12.76 ± 2.25 ) mmol/L vs.(8.22 ± 1.79) mmol/L,P=0.000;HbA1c:(7.68 ± 1.06 ) ％ vs.( 6.48 ± 0.69 ) ％,P=0.000;BMI:( 25.90 ± 1.72 ) kg/m2 vs.( 22.81 ±1.41 ) kg/m2,P=0.016;TG:(2.57 ±0.68) mmol/Lvs.( 1.88 ±0.35) mmol/L,P=0.006;TC:(5.72 ±0.13) mmol/L vs.(5.14 ± 1.38) mmol/L,P=0.043;LDL-C:(3.28 ±0.10)mmol/L vs.(2.81 ±0.57)mmol/L,P=0.009;HOMA-IR:7.58 ± 0.19 vs.4.58 ± 1.98,P=0.000;HDL-C:( 1.29 ± 0.04) mmol/L vs.( 1.62 ± 0.27 ) mmol/L,P=0.003].The levels of FPG,2hPG,HbA1c,BMI,TG,HOMA-IR also decreased in control group after intervention compared with before intervention [FPG:( 8.67 ± 2.71 ) mmol/L vs.( 7.26 ± 1.21 ) mmol/L,P=0.001;2hPG:( 12.82 ± 2.15 ) mmol/L vs.( 10.85 ± 1.98 ) mmol/L,P=0.000,HbA1c:( 7.75 ± 1.08 ) ％ vs.( 7.01 ± 0.87 ) ％,P=0.002;BMI:( 25.82 ± 1.74 ) kg/m2 vs.( 24.23 ± 1.36 ) kg/m2,P=0.024;TG:(2.47 ±0.75) mmol/L vs.(2.13 ± 0.43 ) mmol/L,P=0.018;HoMA-IR:7.88 ± 0.20 vs.6.15 ± 2.01,P=0.042].No significant difference was found on the values of TC,HDL-C and LDL-C before and after intervention in control group (P ＞ 0.05).The effect of intervention of experimental group was more obvious when compared with control group ( FPG:P=0.036;2hPG:P=0.000;HbA1c:P=0.045;BMI:P=0.037;TG:P=0.022;HoMA-IR:P=0.000).Conclusion Individualized lifestyle intervention can improve the compliance of T2DM patients,and was in favor of control metabolic status of T2DM patients to delay the occurrence and development of complications.

Objective To detect the methylation status of p16 gene promoter in CD4~+ T cells of patients with systemic lupus erythematosus(SEE),and its significance in the pathogenesis of SLE.Methods The pl 6 gene promoter methylation in peripheral CD4~+ T cells was detected with the Taqman probe-based realtime PCR(Methylight)technology in 28 patients with SLE and 20 healthy human controls.Results The methylation rate of p16 gene promoter in peripheral CD4~+ T cells was higher in patients with SLE than that in the controls(35.7%VS 10%,x~2=4.11,P<0.05).There was no correlation between SLE disease activity index (SLEDAI)and the normalized index of methylation(NIM)of p16 gene promoter(r_s=-0.29,P>0.05).Conclusion The methylation status of p16 gene promoter is aberrant in CD4~+ T,:ells of SLE patients,suggesting that the hypermethylation of p16 gene plays a certain role in the pathogenesis of SLE.