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 examine the association between incidence of hand-foot-mouth disease (HFMD) and meteorological factors, so as to provide the basis for the prevention and control of HFMD. Methods: The number of HFMD cases in Jiading District, Shanghai Municipality from 2016 to 2023 were collected through the Chinese Disease Prevention and Control Information System, and meteorological data were obtained from the Shanghai Meteorological Bureau. The associations of daily average temperature, daily average relative humidity, and daily average atmospheric pressure with the daily number of HFMD cases were analyzed using a distributed lag non-linear model (DLNM). Results: A total of 21 555 HFMD cases were reported in Jiading District from 2016 to 2023, with an average annual incidence of 132.57/100 000. There were 12 762 male cases (59.21%) and 8 793 female cases (40.79%). The main peak of incidence occurred from June to August, and the secondary peak was from October to December. DLNM analysis showed that the incidence risk of HFMD first increased and then decreased with the increase of daily average temperature, and first decreased and then increased with the prolongation of the lag time. The cumulative lag risk was higher when the daily average temperature ranged from 18.4 to 35.1 ℃, and the maximum cumulative lag effect was observed at 27.8 ℃ (RR=5.522, 95%CI: 4.751-6.370). The incidence risk of HFMD first increased and then decreased with the increase of daily average relative humidity, and first decreased, then increased and then decreased again with the prolongation of the lag time. The cumulative lag risk was higher when the daily average relative humidity ranged from 71.7% and 90.8%, and the maximum cumulative lag effect was observed at 81.8% (RR=1.603, 95%CI: 1.321-1.995). The incidence risk of HFMD decreased with the increase of daily average atmospheric pressure, and decreased with the prolongation of the lag time when the daily average atmospheric pressure was greater than 1 015.80 hPa. When the daily average atmospheric pressure was less than 1 015.80 hPa, the incidence risk of HFMD increased with the prolongation of the lag time. The maximum cumulative lag effect was observed at 986.80 hPa (RR=8.513, 95%CI: 1.401-36.625). Conclusion The incidence risk of HFMD in Jiading District initially increases and then decreases with increasing temperature and relative humidity, while it decreases with increasing atmospheric pressure, and these effects exhibit a lagged response.

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

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.

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.

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.

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.