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 the value of nomogram model based on clinical and ultrasonic characteristics for diagnosing lymphoma.Methods Data of 176 patients with suspected lymphoma due to enlarged superficial lymph nodes were retrospective analyzed.The patients were divided into lymphoma group(n=90,invasive subgroup[n=40]and non-invasive subgroup[n=50])or non-lymphoma group(n=86)based on pathological results.Clinical and ultrasonic data were compared between groups and subgroups.Multivariate logistic regression was used to screen the independent risk factors of lymphoma,and then a nomogram was constructed.Receiver operating characteristic curves were drawn to evaluate the efficacy of conventional ultrasound,conventional contrast-enhanced ultrasound(C-CEUS),high-frame-rate contrast-enhanced ultrasound(H-CEUS)and nomogram for diagnosing lymphoma.Results Multivariate logistic regression analysis revealed that age＞59 years,cortical stripe/reticular hyperecho of lymph nodes and"centrifugal firework"enhancement pattern showed with H-CEUS were all independent risk factors of lymphoma(all P＜0.05).Taken 59 years as the best cut-off value of patients'age,the sensitivity,specificity,accuracy and the area under the curve(AUC)for diagnosing lymphoma was 67.78%,58.10%,63.06%and 0.630,respectively.The sensitivity,specificity,accuracy and AUC of cortical stripe/reticular hyperecho of lymph nodes for diagnosing lymphoma was 73.33%,58.10%,65.91%and 0.657,respectively,while of"centrifugal firework"pattern enhancement in H-CEUS was 77.78%,69.80%,73.86%and 0.738,respectively.AUC of conventional ultrasound,C-CEUS,H-CEUS and nomogram for diagnosing lymphoma was 0.657,0.540,0.738 and 0.844,respectively.Conclusion Nomogram model based on clinical and ultrasonic characteristics had good diagnostic efficacy for lymphoma,and"centrifugal firework"pattern enhancement in H-CEUS could be regarded as the specific characteristic of lymphoma.

Objective To identify the exact locations of the brain being irradiated in advanced nasopharyngeal carcinoma(NPC)patients during radiotherapy,and to analyze the differences in brain dose distribution between advanced NPC patients treated with intensity-modulated radiotherapy(IMRT)and volumetric modulated arc therapy(VMAT).Methods Based on the CT brain template provided by the Montreal Neurological Institute,the brain dose distribution was analyzed with voxel-based method.Results For advanced NPC patients,VMAT plans did not demonstrate superiority in normal brain tissue sparing,while IMRT performed better,with advantages observed in regions such as the brainstem,the posterior lobe of the cerebellum,the anterior lobe of the cerebellum,temporal lobes,occipital lobes,limbic lobes,and certain areas of the subcortical regions.Conclusion IMRT is advantageous over VMAT in protecting the normal brain tissues in advanced NPC patients.

Objective To understand cognition level and treatment intention of patients with endometriosis(EMs);To evaluate the effects of TCM chronic disease management on EMs patients.Methods The disease cognition level and treatment intention of 1 895 EMs patients from October 2020 to December 2021 in 19 provinces,autonomous regions and municipalities were analyzed through cross-sectional investigation.The cognitive effect of chronic disease management of TCM on 801 patients with EMs from 6 Grade A hospitals in Beijing was evaluated by self-control study.Results The cognition level of EMs patients for the disease was improved with the increase of educational background.Patients generally believed that EMs was a chronic disease,requiring regular review and long-term management.The proportion of patients with high school education or below,junior college education,bachelor degree or above who knew the possibility of malignant changes in EMs was less,only 32.3%,41.6%and 47.7%,respectively.The awareness rate of patients with high school education or below for recurrence after EMs conservative surgery was 46.9%,lower than that of those with junior college education(66.8%)and bachelor degree or above(72.7%).Among the patients with dietary contraindications,the proportion of patients with high school education or below,junior college education,bachelor degree or above who knew the contraindication of the forest frog oil was less,only 20.7%,30.3%and 32.9%,respectively.In the aspect of life adjustment,the awareness of patients was generally high.EMs patients mainly recognized the disease through face-to-face communication with gynecologists.Only 34.4%of patients with high school education or below learned about EMs through WeChat public accounts,APPs and other new media,which was lower than those with junior college education(48.6%)and bachelor degree or above(55.4%).EMs patients generally tend to be treated in comprehensive hospitals,with high acceptance of TCM treatment,mainly TCM decoction,and low acceptance of TCM appropriate technology.After 1 year of TCM chronic disease management,the disease awareness of EMs patients was significantly improved compared with before management,with statistical significance(P<0.05).Conclusion EMs patients with different educational backgrounds have different cognition of the disease,and each has different emphasis.Education and popularization should be carried out according to their knowledge blind spots.Chronic disease management of TCM can improve the disease cognition level of EMs patients.

Objective To investigate the mechanism of Yes-associated protein 1(YAP1)ameliorating aristolochic acid 1(AAI)-induced liver injury in mice based on untargeted metabolomics techniques.Methods There were 83-week-old male hepatocyte-specific Yap1 gene knockout mice(genotyped as Yap1Flox/Flox,Albumin-Cre,aka.Yap1LKO)were randomly selected as the Yap1LKO+AAI group,and 8 Yap1Flox control mice as the Yap1Flox+AAI group.Both groups were injected intraperitoneally with AAI at a dose of 2.5 mg·kg-1·d-1 for 14 consecutive days.Genotypes were identified by tail PCR;serum alanine transaminase(ALT)and aspartate transaminase(AST)activities were determined by microplate assay;histopathological changes of liver tissue were observed by HE staining;and the protein expression of YAP1 in liver tissue was determined by immunohistochemistry.The untargeted metabolomics approach was used to analyze the liver tissue differential metabolites,and the samples were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbit trap high-resolution mass spectrometry,and the differential metabolites were screened by principal component analysis(PCA),Partial least square-discriminant analysis(PLS-DA),and orthogonal partial least squares-discriminant analysis(OPLS-DA);using HMDB database and METLIN database to identify metabolites,and the pathway enrichment of differential metabolites was analyzed by KEGG database.Results(1)After 14 days of AAI induction,the increase of body mass in Yap1LKO mice was lower than that in Yap1Flox mice,but there was no statistical significance(P＞0.05).On day 14,compared with the Yap1Flox+AAI group,the serum ALT and AST enzyme activities in the Yap1LKO+AAI group of mice were significantly increased(P＜0.05),and the histopathological damage of the liver was significantly aggravated.The livers of the Yap1Flox mice had a positive protein expression of YAP1,whereas the Yap1LKO mice did not have a positive protein expression of YAP1.(2)A total of 139 differential metabolites with significant changes(VIP＞1 and P＜0.05)were screened by metabonomic analysis;compared with Yap1LKO+ AAI group,62 liver metabolites in Yap1Flox+AAI group were up-regulated,including choline,taurine,hypotaurine,α-linolenic acid,eleostearic acid,chenodeoxycholic acid and so on.Seventy-seven metabolites were down-regulated including glycerophosphocholine,L-phosphatidylcholine,L-glutamine,L-serine,L-glutathione,5-methionine,phenylalanine,glucose 6-phosphate,lactic acid,uric acid glycosides,etc..KEGG-enriched pathways were mainly choline metabolism,glycerophospholipid metabolism,insulin resistance,glutathione metabolism,etc..Conclusion Hepatocyte-specific Yap1 gene knockout exacerbated AAI-induced liver injury in mice,and YAP1 was involved in the regulation of choline metabolism and glycerophospholipid metabolism through the up-regulation of unsaturated fatty acids,such as choline and taurine,which ameliorated AAI-induced liver injury in mice.

BACKGROUND:In clinical application,simple interspinous fixation without additional interbody fusion has similar fixation effects to pedicle screw and rod fusion internal fixation,and can effectively reduce the range of motion of the responsible segment and the stress of the articular process.However,after simple placement of the new interspinous fusion fixation device BacFuse,the stress at the root of the spinous process is relatively concentrated,and the spinous fracture is prone to occur.If an intervertebral fusion cage is inserted in conjunction with interspinous fixation,Von Mises stress can theoretically be dispersed to reduce the risk of spinous fracture.However,there are few studies on biomechanics and finite element analysis. OBJECTIVE:To observe the biomechanical stability of interspinous fixation-assisted endoscopic interbody fusion in the treatment of severe lumbar spinal stenosis. METHODS:The normal finite element model M0 of the L4-L5 segment of the lumbar spine was established by Mimics,Geomagic,Solidworks,and ANSYS software based on the lumbar CT images of a 26-year-old adult male volunteer excluding spinal diseases.On the basis of M0,the immediate model M1 after endoscopic decompression combined with interbody fusion,the interspinous fixation device(BacFuse)model M2 after endoscopic decompression,and the interspinous fixation(BacFuse)model M3 after endoscopic-assisted interbody fusion were established.The same stress was applied to the upper surface of the L4 vertebral body in the four groups,and the lower surface of the L5 vertebral body was fixed and supported.The range of motion and the extreme Von Mises stress of the endplate bone and the posterior ligament complex of the vertebral body were analyzed under six working conditions of flexion,extension,left/right bending,and left/right rotation. RESULTS AND CONCLUSION:(1)Compared with model M0,the range of motion value of model M1 increased significantly under six working conditions.Model M2 and model M3 had a significant reduction in range of motion.(2)Compared with model M0,the maximum stress of the vertebral body in model M1 did not change significantly under the six working conditions.The maximum stress at the rear of the M2 vertebral body increased significantly.(3)Compared with model M1,the maximum stress of model M3 did not change significantly under the six working conditions.Compared with model M2,the maximum stress of model M3 decreased significantly.(4)Compared with the model M0,the extreme Von Mises stress of the L4 and L5 endplates of the model M1 was significantly increased.The extreme Von Mises stress in L4 and L5 endplates of models M2 and M3 decreased slightly.Compared with model M1,the Von Mises stress of the bone under the L4 and L5 endplate of models M2 and M3 was significantly reduced.(5)It is concluded that the implantation of BacFuse can effectively reduce the bone stress under the endplate during simple interbody fusion,decrease the risk of cage subsidence,diminish the risk of facet joint fracture on the decompression side,and provide a good stable environment for interbody fusion.The placement of an intervertebral fusion cage can reduce the stress of the root of the spinous process,which is beneficial to decrease the risk of fracture of the root of the spinous process.

AIM:This study aimed to investigate the effects of hsa-miR-204-5p on the viability,migration,cell cycle,and apoptosis of human vascular endothelial cells.METHODS:We established a model using the hsa-miR-204-5p mimic in the human umbilical vein endothelial cell line EA.hy926.We evaluated the effects of hsa-miR-204-5p on endothelial cell functionality through various analyses,including cell scratch,Transwell,CCK-8,cell cycle,and apopto-sis assays.Subsequently,we employed RNA sequencing and RT-qPCR to predict and verify the downstream target genes of hsa-miR-204-5p.Genes meeting the criteria of log2FC≤-0.5 and P＜0.05 in RNA sequencing and those predicted as downstream target genes of hsa-miR-204-5p by the miRWalk database were intersected.Furthermore,we conducted Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.RESULTS:Overexpres-sion of hsa-miR-204-5p inhibited the viability and migration of EA.hy926 cells,and reduced their apoptotic rate and the proportion of cells in S phase.Enrichment analyses showed that downstream target genes of hsa-miR-204-5p,including MAPT,PPP3R1,PRKACB,PTPRR,MAP2K4,CACNA2D2 and RPS6KA6,exhibited enrichment in MAPK signaling pathway.RT-qPCR results revealed that the mRNA expression levels of MAPT and MAP2K4,especially MAPT,were sig-nificantly down-regulated after overexpression of hsa-miR-204-5p.CONCLUSION:The findings suggest that hsa-miR-204-5p suppresses the biological behaviors of endothelial cells,such as viability,migration,and apoptosis,likely through the inhibition of MAPT/MAPK signaling pathway.

As a common clinical disease, fracture is often accompanied by pain, swelling, bleeding as well as other symptoms and has a high disability rate, even threatening life, seriously endangering patients' physical and psychological health and quality of life. Medical practitioners take many strategies for the treatment of fracture healing, including Traditional Chinese Medicine (TCM). In the early stage of fracture healing, the local fracture is often in a state of hypoxia, accompanied by the expression of hypoxia inducible factor-1α (HIF-1α), which is beneficial to wound healing. Through literature mining, we thought that hypoxia, HIF-1α and downstream factors affected the mechanism of fracture healing, as well as dominated this process. Therefore, we reviewed the local characteristics and related signaling pathways involved in the fracture healing process and summarized the intervention of TCM on these mechanisms, in order to inspirit the new strategy for fracture healing, as well as elaborate on the possible principles of TCM in treating fractures based on the HIF molecular mechanism.

Objective:To determine the content of the released nickel ion through the 7 extraction media to extract the Ni-Ti wires and to plot the curve of the released nickel ion so as to identify a leaching medium that can be substituted for blood for in vitro Ni release evaluation. Methods:The release of Ni through microwave digestion/inductively coupled plasma mass spectrometry (ICP-MS) in the goat serum was determined. Because of the high content of Ni release, it could be determined by diluting the extraction medium, and other extraction media could be determined directly. Ni release standard curves were plotted by the release amount and different time point variables. Though the different extraction media Ni release curves confirm the specificity of extraction media instead of blood.Results:By analyzing the Ni release curves of seven leaching media, it was found that none of these seven extraction media was suitable for the evaluation of Ni release in in vitro leaching media. Considering the safety of the leaching medium and the simplicity of preparation, hydrochloric acid solution was chosen as the leaching medium, but the concentration needed to be diluted accordingly. Finally, a hydrochloric acid solution was created as an alternative to blood for the in vitro study of Ni release from Ni-Ti alloy cardiovascular products, with a volume fraction of 0.005%. Conclusions:The in vitro leaching medium that can replace blood was found to be hydrochloric acid for the time being, but its concentration was too high, resulting in too much Ni release as well, which deviated from the actual situation. Therefore, the hydrochloric acid solution was diluted step by step, and the Ni release curve was examined until it was close to the clinical release level, and the actual concentration was determined, thus laying a solid foundation for the subsequent evaluation of the safety and risk.

Objective:To explore the clinical warning value of ischemic modified albumin (IMA) and IMA to human serum albumin (HSA) ratio (IMAR) in the development of pre-eclampsia (PE) and its severity.Methods:A total of 156 pregnant women with PE admitted to the Haidian District Maternal and Child Health Hospital of Beijing from April 2022 to March 2023 were collected as the PE group, and 156 healthy pregnant women with the same age and gestational age were matched as the control group. PE pregnant women were further divided into severe PE group (78 cases) and non-severe PE group (78 cases). Severe PE pregnant women were divided into emergency group (42 cases) and non-emergency group (36 cases) according to the disease progression time.All pregnant women were stratified according to their HSA levels (<30 g/L, 30-32 g/L, ≥32 g/L), and the peripheral blood IMA, HSA, and IMAR of pregnant women in different periods and subgroups were compared, and also the difference of IMA levels in umbilical artery blood. Bivariate correlation analysis was used to explore the correlation between severe PE and IMA or IMAR, and receiver operating characteristic (ROC) curves was used to analyze the diagnostic value of IMA, HSA, and IMAR for PE and severe PE.Results:(1) The IMA level and IMAR in peripheral serum of pregnant women in the PE group at diagnosis, and the IMA level in umbilical artery blood at delivery, and peripheral serum at 2 days after delivery were higher than those in the control group. The HSA level in peripheral serum was lower than that in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (2) The IMA level and IMAR in the peripheral serum of pregnant women with severe PE were higher than those in the non-severe PE group at diagnosis, while the HSA level were lower than those in the non-severe PE group. The differences were statistically significant (all P<0.05). At diagnosis, the IMA level and IMAR in peripheral serum of pregnant women in the emergency group were higher than those in the non-emergency group, while the HSA level was lower than that in the non-emergency group. The differences were statistically significant (all P<0.05). When diagnosed, the peripheral serum IMA levels of pregnant women in the PE group were compared between subgroups with HSA<30 g/L, 30-32 g/L, ≥32 g/L, and there was no statistically significant difference ( F=0.366, P=0.694). However, the IMAR was compared between the three subgroups, and the difference was statistically significant ( F=28.544, P<0.001), which increased with the decrease of HSA levels. In the subgroup with HSA≥32 g/L, the peripheral serum IMA level and IMAR of pregnant women in the PE group were higher than those in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (3) The severe PE manifestations positively correlated with peripheral serum IMAR at diagnosis include systolic blood pressure ( r=0.279), mean arterial pressure ( r=0.212), and urinary protein quantification ( r=0.277), while the severe PE manifestations negatively correlated include HSA levels ( r=-0.644) and newborn birth weight ( r=-0.305), all of which were significantly correlated ( P<0.05). (4) The area under curve (AUC) for IMAR diagnosis of PE was 0.875 (95% CI: 0.833-0.916), with the highest diagnostic efficiency at a cutoff value of 2.06, sensitivity of 72.5%, and specificity of 85.1%. The AUC for diagnosing severe PE was 0.871 (95% CI: 0.822-0.919), with the highest diagnostic efficacy at a cutoff value of 2.18, sensitivity of 72.3%, and specificity of 88.3%. The diagnostic efficacy of IMAR for PE and severe PE were higher than those of IMA and HSA levels. Conclusions:The level of IMA and IMAR in pregnant women with PE are higher than those in normal pregnant women. IMA and IMAR are correlated with the severity of PE, with IMAR changes occurring earlier and more significantly. IMAR could be considered as one of the evaluation indicators for the development of PE, or as a more sensitive PE severity warning indicator than HSA.