OBJECTIVE To establish a hospital preparation cost item library， providing a reference for the refined accounting management of preparation costs in medical institutions. METHODS Based on literature analysis and practical work experience， a preliminary list of cost items was drafted. The Delphi method was employed to screen and optimize the items by analyzing the questionnaire recovery rate， expert authority coefficient， item importance score， coefficient of variation， and Kendall’s W of concordance. RESULTS The questionnaire recovery rates for the two rounds of expert consultation were 95.7% and 100%， respectively； the expert authority coefficients were 0.937 and 0.939， respectively； Kendall’s W of concordance were statistically significant （ P ＜0.001）. The finally established hospital preparation cost item library included 6 first-level items （such as raw material and packaging material costs， human resource costs， and production operation costs） and 29 second-level items （including main drug raw material costs， production personnel compensation， and finished product full-item testing costs）， comprehensively covering dimensions such as raw materials and packaging materials， fixed asset depreciation and equipment maintenance， human resources， production operations， energy and environment， and R & D and other costs. CONCLUSIONS This study successfully establishes a scientific and reliable cost item library for medical institution preparations， which can guide institutions to itemize actual expenditures， provide structured evidence for autonomous pricing， and support data needs for the formulation of insurance access and payment policies for innovative preparations.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Dorsal pancreatic artery (DPA) is one of the most commonly studied arteries in the pancreas. The management of DPA during pancreatic standard resection/radical surgery (pancreaticoduodenectomy, distal pancreatectomy, and total pancreatectomy) is closely related to complications such as late bleeding caused by pancreatic fistula erosion after surgery. This article collected data from patients who underwent open/minimally invasive standard pancreatic resection/radical surgery from August 2024 to July 2025, displayed different origins of DPA, and discussed the management of DPA during standard pancreatic resection/radical surgery. This article updated and improved the latest classification of DPA, and highlighted the importance of programmatic management of DPA in pancreatic surgery to reduce the risk of late postoperative bleeding.

Objective To investigate the effect of obstructive sleep apnea(OSA)on behavioral problems in children and the association between them.Methods A simple random sampling method was used to select 100 children aged 4 to 12 years for the case group.All of them were diagnosed with OSA through overnight polysomnography at the Sleep Medicine Center,West China Fourth Hospital,Sichuan University between October 2022 and October 2023.An additional 100 children without snoring symptoms and clinically evaluated and confirmed as not having OSA were enrolled as the control group.General demographic data of the participants were collected.The Caregiver Report Form of the Achenbach Child Behavior Checklist(CBCL)was used for behavioral problem assessment,and polysomnography data were collected.The chi-square/t test was used to analyze the inter-group differences in general data,the total score of behavioral problems,and scores for each dimension.Linear regression was performed to analyze the relationship between OSA and the total score for children's behavioral problems and those for the different dimensions.Logistic regression was applied to analyze the relationship between the obstructive apnoea-hypopnea index(OAHI)and behavioral problems in children with OSA.A logistic regression model integrating the OAHI×sex interaction term was constructed to evaluate the moderating effect of sex on the association between OAHI and behavioral problems.Results No significant differences were observed in general demographic data between the case and control groups.The total score for behavioral problems and those for each dimension were higher in the case group than those in the control group,with the total score of the case group being 24.60±1.55 and that of the control group being 8.85±0.75(P<0.001).The results of the linear regression analysis showed a positive association between OSA and both the total score for behavioral problems(b=16.01;95%CI,12.56-19.47)and those for each dimension.The results of the logistic regression analysis showed that,after adjusting for covariates,OAHI was a risk factor for behavioral problems in children with OSA(odds ratio[OR]=1.17;95%CI,1.04-1.31).After stratification by sex and adjustment for covariates,the OR value of the effect of OAHI on behavioral problems was slightly higher in female participants(1.57)than that in male participants(1.21).The interaction effect analysis showed that sex moderated the association between OAHI and behavioral problems(OR=1.64;95%CI,1.02-2.64;P=0.04).Conclusion Children with OSA are prone to developing behavioral problems.OAHI is a risk factor for behavioral problems in children with OSA,with a potentially greater effect observed in girls.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Stress granules are highly dynamic, membrane-free organelles that form in cells under stress conditions through liquid-liquid phase separation.Their main components are RNA and proteins, and they play a role in RNA metabolism, among other functions.The formation, dispersion, and removal of stress granules are regulated by the rapamycin pathway, the eukaryotic translation initiation factor pathway, and modifications of RNA-binding proteins.While physiological stress granules are typically transient, chronic stress associated with aging can lead to homeostatic imbalance and persistence of these granules.This aberrant RNA metabolism can result in the pathological aggregation of RNA-binding proteins, cellular damage, and the formation of pathological stress granules, which may accelerate the progression of aging-related diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, and tumors.In this paper, we will summarize the connection between stress granules and aging-related diseases to provide new insights for disease diagnosis and research.

Extrachromosomal circular DNA(eccDNA)is a special kind of circular DNA molecules in nucleus of eukaryotes.These molecules are derived from chromosome genomes,and can independently participate in a variety of cell physiological or pathological processes,which are closely associated with the occurrence and development of tumors.The discovery of eccDNA can be traced back to the 1970s,and with the development of molecular biology technology,researchers have gradually revealed its impor-tant function in cancer.The formation of eccDNA is a complex process involving multiple mechanisms,including breakage-fusion-bridge cycle,chromothripsis,translocation-deletion-amplification,episome model and fork stalling and template switching,etc.eccDNA,especially large molecular weight eccDNA(＞1 Mb,also known as ecDNA),plays an important role in promoting the amplification and activation of oncogenes,driving tumor heterogeneity and drug resistance,and has shown broad application potential as a molecular marker for tumor liquid biopsy.This review summarizes the exploration history,biogenesis,functions in tumor biology and detection,specificity in different types of tumors and analysis methods of eccDNA,and also discusses its application value in clinical diagnosis and treatment of tumors,so as to provide reference for further exploration of eccDNA in basic research and clinical practice of tumors.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

This study examines the effects of zearalenone(ZEA)on the survival and function of lu-teinized granulosa cells,and studies the role of activating transcription factor 6(ATF6)in regula-ting apoptosis and functional abnormalities of luteinized granulosa cells induced by ZEA.An in vitro model of luteinized granulosa cells was utilized to examine the effects of ZEA treatment on apoptosis,hormone secretion,and the expression of relevant proteins.Furthermore,the expression of ATF6 was manipulated using siRNA to elucidate its regulatory function in the ZEA-induced damage of luteinized granulosa cells in mice.Our findings revealed that ZEA inhibited the activity of luteinized granulosa cells and reduced the secretion of estradiol(E2)and progesterone(P4)in a dose-dependent manner.The expression levels of p-IRE1,ATF6 and StAR in both low(20 pmol/L)and high(40 μmol/L)ZEA groups were significantly increased after 24 h(P＜0.05).GRP78 had no significant change at low concentration treatment(P＞0.05),but significantly increased at high concentration treatment(P＜0.05).Similarly,ATF4 and p-EIF2α had no significant change at low concentration treatment(P＞0.05),but significantly decreased at high concentration treat-ment(P＜0.05).HSD3B2 and CYP19A1 were significantly decreased in both low and high concentration treatments(P＜0.05).After 48 h of treatment,ATF6 and GRP78 were significantly increased in both low and high concentration treatments(P＜0.05).p-IRE1 was significantly de-creased at low concentration treatment(P＜0.05),but remained unchanged at high concentration treatment(P＞0.05).ATF4,p-EIF2α,HSD3B2 and CYP19A1 were significantly decreased in both low and high concentration treatments(P＜0.05).St AR was significantly increased in both low and high concentration treatments(P＜0.05).Interference with the expression of ATF6 could sig-nificantly reduce the apoptosis induced by low concentration group(P＜0.05),and enhanced the hormone secretion in both high and low concentration groups(P＜0.05).In conclusion,ZEA can cause damage to luteinized granulosa cells and activate ATF6 signaling pathway.Interference with ATF6 can alleviate apoptosis and hormone secretion disturbance induced by low concentration ZEA,but has limited effect on damage caused by high concentration ZEA.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.