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

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.

Objective:To investigate the effect of "four-staff co-management" follow-up mode on risk factor control and medium-term prognosis improvement in patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:This was a intervention study. Patients with coronary heart disease who were admitted to the Xiamen Cardiovascular Hospital of Xiamen University from June 2021 to January 2022 and successfully discharged after PCI were included. According to the different types of follow-up after discharge, patients were divided into the traditional follow-up group and the "four-staff co-management" follow-up group. The "four-staff co-management" follow-up mode means that specialists, specialist managers in third-level A hospitals and general practitioners and health managers in basic hospitals were jointly responsible for post-discharge follow-up of PCI patients. Baseline clinical data were collected. The primary endpoints were the rate of compliance of coronary heart disease risk factor control at 12 months after surgery, the rate of secondary surgery, and the incidence of mid-term major adverse cardiovascular and cerebrovascular events (MACCE). Unplanned secondary PCI included symptom-driven secondary PCI and asymptomatic secondary PCI. MACCE includes myocardial infarction, hospitalization for heart failure, stroke, major bleeding, all-cause death, and composite endpoints including these events.Results:A total of 2 181 patients were enrolled, including 1 097 patients in the traditional follow-up group and 1 084 patients in the "four-staff co-management" follow-up group. At baseline, there were no statistically significant differences in gender, age, discharge diagnosis, co-existing diseases, echocardiographic indexes, and coronary artery lesions between the two groups (all P>0.05). There were no significant differences between the two groups in total PCI stent length, maximum internal diameter of stent, proportion of patients using drug balloon, proportion of patients with a planned second surgery during hospitalization, and discharge with drugs (all P>0.05). Twelve months after PCI, the reduction in HbA1c and low-density lipoprotein cholesterol was greater in the "four-staff co-management " follow-up group than that in the traditional follow-up group (all P<0.05), and the rate of reaching the standard for low-density lipoprotein cholesterol was higher than that in the traditional follow-up group ( P=0.001), but there was no statistical significance between the two groups for blood pressure and blood glucose (all P>0.05). During the follow-up period, the proportion of symptom-driven second operation patients was lower in the "four-staff co-management" follow-up group than that in the traditional follow-up group ( P<0.001), and there was no significant difference in the proportion of asymptomatic second operation patients between the two groups ( P=0.191). The proportion of hospitalized patients with heart failure in the "four-staff co-management" follow-up group was lower than that in the traditional follow-up group ( P=0.029), and there was no significant difference in the proportion of myocardial infarction, cerebral infarction, cerebral hemorrhage, massive hemorrhage, death and complex endpoint events between the two groups (all P>0.05). Conclusion:The "four-staff co-management" follow-up mode can effectively improve the control of risk factors and medium-term prognosis in patients with coronary heart disease after PCI.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Treatment-resistant depression (TRD) remains a major challenge in psychiatric clinical practice. However, there is still substantial controversy in the academic community regarding how to define and assess it, and treat and manage these patients effectively. This paper reviews the evolution of the concept of "treatment resistance"in depression with a particular focus on comparing the conventional concept of TRD with the recently proposed concept of "Difficult-to-Treat Depression (DTD)". It explores the underlying rationale and logic behind this conceptual shift, and discusses the practical challenges associated with implementing the "DTD" framework in clinical practice. Finally, the paper provides targeted recommendations to address these challenges, aiming to serve as a reference for psychiatric clinicians and researchers in China.

Anticipatory anxiety is a negative emotion that arises when individuals encounter potential threats or uncertainties in the future. It is the core symptom of a variety of anxiety disorders, and is closely associated with the occurrence, severity, treatment outcome, and prognosis of anxiety disorders, which has garnered a growing amount of focus in clinical practice. Nevertheless, scientific research on anticipatory anxiety continues to face obstacles such as unclear pathological mechanisms, the absence of simple and consistent self-assessment tools, and effective interventions. To improve understanding of the role of anticipatory anxiety in the diagnosis and treatment of anxiety disorders, this study reviews pertinent domestic and international literature, and briefly introduces the concept, assessment and measurement, activation paradigm, pathological mechanisms, and interventions of anticipatory anxiety.

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.

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.