ObjectiveTo investigate the effects and potential mechanisms of morning and evening fasting on postprandial lipid responses, a post hoc analysis based on a crossover randomized controlled trial was conducted to assess the effects of different fasting strategies on postprandial lipid metabolism in community residents in Shanghai. MethodsA total of 23 participants took part in a randomized crossover trial involving two intervention days: morning fasting and evening fasting, with a washout period of 6 days between intervention days. Two-way analysis of variance was used to test the differences in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the relative expression of circadian clock genes before and after the next meal under fasting. Wilcoxon rank sum tests were used to analyze the different metabolites between the two groups. Principal component analysis and Orthogonal partial least squares-discriminant analysis were conducted to evaluate the ability of metabolites to differentiate between morning fasting and evening fasting and identify the important differential metabolites. After adjusting for age, sex, and BMI, a partial correlation analysis was performed to identify metabolites associated with plasma lipids. In addition, important metabolites associated with plasma lipids were computed by pathway enrichment analysis. ResultsAfter evening fasting intervention, fasting TG level [(0.37±0.29) vs (0.27±0.18)] mmol·L^-1, fasting and postprandial change values in TC [(2.74±0.47) vs (2.51±0.27)] mmol·L^-1 and LDL-C [(1.32±0.38) vs (0.99±0.27)] mmol·L^-1 were significantly lower than those after morning fasting (P<0.05). While, change values of fasting LDL-C [(0.89±0.37) vs (1.14±0.37)] mmol·L^-1 and TG [(1.14±0.19) vs (1.28±0.17)] mmol·L^-1 were significantly higher than those after morning fasting intervention (P<0.05). After fasting intervention, the relative expression of AMPK, CRY1, CLOCK, MTNR1B, AANAT, and ASMT was correlated with the amount of plasma lipid changes (P<0.05). Specifically, CLOCK and AANAT were upregulated following evening fasting and downregulated after morning fasting. Among the 217 important differential metabolites, 111 were correlated with plasma lipids, and which were primarily enriched in the cysteine and methionine metabolism pathways (P<0.05). ConclusionCompared to morning fasting, evening fasting was more effective in improving postprandial lipid responses, indicating that an evening fasting window during intermittent fasting could be conducive to cardiovascular disease prevention in adults. Meanwhile, it is suggested that morning and evening fasting may affect lipid responses through circadian rhythm oscillations and the cysteine and methionine metabolism pathways.

Programmed cell death (PCD) is characterized as a cell death pathway governed by specific gene-encoding requirements, plays crucial roles in the homeostasis and innate immunity of organisms, and serves as both a pathogenic mechanism and a therapeutic target for a variety of human diseases. Z-DNA-binding protein 1 (ZBP1) functions as a cytosolic nucleic acid sensor, utilizing its unique Zα domains to detect endogenous or exogenous nucleic acids and its receptor-interacting protein homotypic interaction motif (RHIM) domains to sense or bind specific signaling molecules, thereby exerting regulatory effects on various forms of PCD. ZBP1 is involved in apoptosis, necroptosis, pyroptosis, and PANoptosis and interacts with molecules, such as receptor-interacting protein kinase 3 (RIPK3), to influence cell fate under various pathological conditions. It plays a crucial role in regulating PCD during infections, inflammatory and neurological diseases, cancers, and other conditions, affecting disease onset and progression. Targeting ZBP1-associated PCD may represent a viable therapeutic strategy for related pathological conditions. This review comprehensively summarizes the regulatory functions of ZBP1 in PCD and its interactions with several closely associated signaling molecules and delineates the diseases linked to ZBP1-mediated PCD, along with the potential therapeutic implications of ZBP1 in these contexts. Ongoing research on ZBP1 is being refined across various disease models, and these advancements may provide novel insights for studies focusing on PCD, potentially leading to new therapeutic options for related diseases.

Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.
Neoplasms/metabolism* ; Receptors, Notch/metabolism* ; Disease Resistance/physiology* ; Signal Transduction/physiology* ; Humans ; Drug Resistance, Neoplasm/physiology* ; Molecular Targeted Therapy/methods*

Background Per- and polyfluoroalkyl substances (PFAS), a group of persistent organic pollutants associated with adverse health effects including hepatotoxicity, immunosuppression, and carcinogenicity, have undergone risk assessments by multiple international organizations, with dietary exposure being the primary pathway. Objective To characterize the exposure to PFAS from food and drinking water sources of elderly residents in Songjiang District of Shanghai and to evaluate associated health risk and health effects. Methods A cross-sectional study was conducted from May to July 2024 in Songjiang District based on the Shanghai Suburban Adult Cohort and Biobank (SSACB) cohort. Dietary surveys were administered via face-to-face interviews among older adults aged 65 years and above, yielding 4 583 valid questionnaires. The estimated daily intake (EDI) of PFAS was calculated by integrating data from the Sixth National Dietary Survey and recent literature on PFAS concentrations in food and drinking water in Shanghai. Health risk assessment was performed using health-based guideline values (HBGV) proposed by various institutions and studies. Additionally, correlation analysis and linear regression modeling of EDI and biochemical indicators in the elderly were conducted to evaluate potential adverse health effects. Results The elderly population in Songjiang District exhibited dietary characteristics consistent with the Eastern Healthy Diet Pattern. Among PFAS compounds, PFOA showed the highest level of oral exposure [mean: 1.495 ng·(kg·d⁻¹)], followed by PFOS [mean: 0.637 ng·(kg·d⁻¹)], PFHxS [mean: 0.636 ng·(kg·d⁻¹)], and PFBS [mean: 0.273 ng·(kg·d⁻¹)]. Specifically, drinking water was the primary source of PFOA [1.415 ng·(kg·d⁻¹), accounting for 94.60%], while aquatic products were the major source of PFOS [0.278 ng·(kg·d⁻¹), accounting for 43.66%]. Using the HBGV derived by China's epidemiological studies, the mean hazard index (HI) for PFAS exposure was 1.39, indicating 54.35% of the population had potential health risks (HI>1). Following the 2024 standard established by the Food Safety Commission of Japan (FSCJ), the HI value dropped to 0.11, suggesting negligible risk. PFAS exposure was negatively associated with triglyceride levels and the indicators of liver and kidney function, but positively associated with low-density lipoprotein cholesterol (LDL-C) and lung cancer markers in the elderly residents. Conclusion PFAS exposure among the elderly residents in Songjiang District is predominantly attributed to PFOA, PFOS, PFHxS, and PFBS, with drinking water and aquatic products identified as primary exposure sources. Current exposure levels demonstrate significant associations with biomarkers of lipid metabolism and lung cancer markers, suggesting potential population health risks. These findings underscore the urgent need to establish HBGV for PFAS compounds based on Chinese population-specific metabolic characteristics.

Abstract Prenatal stress is a common, systemic, nonspecific stress response that occurs during pregnancy. The gut microbiota, which is known as the “second genome” of the human body, interacts with all major systems of the body. Changes in the gut microbiota can impact the development and health of infants and young children. Advances in research technology have allowed us to uncover the relationship between prenatal stress and imbalances in offspring intestinal microbiota, as well as the development of multiple systemic diseases. However, the exact mechanisms through which prenatal stress disrupts the gut microbiota of offspring remain incompletely understood. This review summarizes the existing research on diseases caused by prenatal stress disrupting the offspring intestinal flora, and seeks future research directions to expand the understanding of the pathogenesis of infant diseases.

Abstract Asthma is a well-characterized heterogeneous disease marked by airway remodeling and chronic airway inflammation. Clinically, the treatment of asthma primarily relies on hormonal drugs. However, the long-term use of these medications can lead to significant side effects. Mitophagy is a biological process that selectively transports damaged mitochondria to lysosomes for degradation. Recent research has revealed the crosstalk between mitophagy and asthma. Accordingly, taking mitophagy as an entry point, summarizing the key molecular mechanisms and regulators of mitophagy in asthma will facilitate the development of novel intervention targets and strategies for asthmatic treatment.

Background Lifestyle intervention or dietary modification has been the cornerstone of primary prevention and management of type 2 diabetes (T2D). Objective To investigate the associations of plant foods intake with the risk of incident T2D. Methods Based on a general population cohort, the Shanghai Suburban Adult Cohort and Biobank (SSACB), dietary data were collected for each participant in Songjiang District of Shanghai at enrollment with a validated Food Frequency Questionnaire (FFQ), and plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI) were calculated. Incident T2D cases were identified according to physician diagnosis (fasting blood glucose ≥7.0 mmol·L⁻¹, or 2 h value during a 75-g oral glucose tolerance test ≥11.1 mmol·L⁻¹, or glycosylated hemoglobin ≥6.5%, or with typical symptoms of hyperglycemia or hyperglycemic crisis, accompanied by a random plasma glucose ≥11.1 mmol·L⁻¹) or medication records, obtained from the electronic information system for residents' medical insurance. Multivariable-adjusted Cox proportional hazards models and restricted cubic splines were used to evaluate the associations of foods from different sources with the risk of incident T2D. Results A total of 29016 participants [age at baseline (55.3±11.6) years] with a median follow-up duration of 5.688 years until 21 September 2022 were included. Plant foods (unprocessed) intake was associated with a decreased risk of incident T2D [HR (95%CI): 0.983 (0.969, 0.998)]. In comparison with participants in the highest quartile (≥859.3 g) of plant foods daily intake, the risk of incident T2D for those in the lowest quartile (<500.9 g) was higher [HR (95%CI): 1.250 (1.012, 1.544)]. No significant associations of animal foods [HR (95%CI): 1.006 (0.987, 1.026)] and processed foods [HR (95%CI): 0.978 (0.944, 1.014)] intakes were found with the risk of incident T2D. Replacing 50 g animal foods [HR (95%CI): 0.982 (0.968, 0.996)] or processed foods [HR (95%CI): 0.983 (0.969, 0.998)] with 50 g plant foods was associated with significantly decreased risks of incident T2D. Additionally, non-linear associations of PDI (P_nonlinear=0.023) and hPDI (P_nonlinear=0.016) with the risk of incident T2D were found in the SSACB. Conclusion Plant foods intake, especially healthful plant foods intake, is significantly associated with a decreased risk of incident T2D.

Objective:To investigate the internal structure and determinants of hospitalization expenses for uterine leiomyoma patients in DRG pilot and non-DRG pilot hospitals in Beijing,to fumish insights for the forthcoming phase of public hospital reform.Methods:The statistical data of 5 DRG pilot hospitals and 124 non-DRG pilot hospitals in Beijing from 2015 to 2021 were collected to analyze the correlation degree between each detail expense and the average hospitalization expense by using grey correlation analysis,and the influencing factors of the average hospitalization expense of hospitalized patients by using random forest model.Results:The results of the grey correlation analysis revealed that the highest correlations affecting hospitalization expense in the DRG pilot hospital group and the non-DRG pilot hospital group were the average expense in each surgical treatment and the average drug costs for each patient,respectively,and the lowest was the average expense of inspection and test in each patient.The results of random forest model showed that the top two influencing factors of DRG pilot hospital group were consumption ratio and the average length of hospitalization,while the average length of hospitalization,surgical treatment expense ratio and consumption ratio are more important than other influential factors of non-DRG pilot hospital group.Conclusion:DRG payment is conducive to optimizing the hospitalization expense structure of uterine leiomyoma hospitalized patients.The average length of hospitalization,consumption ratio,and surgical treatment expense ratio are important factors affecting the hospitalization expense of uterine leiomyoma hospitalized patients.Public hospitals should continue to optimize the expense structure in the future,pay equal attention to"reducing expenditure"and"open source",implement DRG payment and its supporting measures to enhance the efficiency of medical services,reinforce the comprehensive management of consumables,and empower hospitals and medical personnel.

Objective:To investigate the internal structure and determinants of hospitalization expenses for uterine leiomyoma patients in DRG pilot and non-DRG pilot hospitals in Beijing,to fumish insights for the forthcoming phase of public hospital reform.Methods:The statistical data of 5 DRG pilot hospitals and 124 non-DRG pilot hospitals in Beijing from 2015 to 2021 were collected to analyze the correlation degree between each detail expense and the average hospitalization expense by using grey correlation analysis,and the influencing factors of the average hospitalization expense of hospitalized patients by using random forest model.Results:The results of the grey correlation analysis revealed that the highest correlations affecting hospitalization expense in the DRG pilot hospital group and the non-DRG pilot hospital group were the average expense in each surgical treatment and the average drug costs for each patient,respectively,and the lowest was the average expense of inspection and test in each patient.The results of random forest model showed that the top two influencing factors of DRG pilot hospital group were consumption ratio and the average length of hospitalization,while the average length of hospitalization,surgical treatment expense ratio and consumption ratio are more important than other influential factors of non-DRG pilot hospital group.Conclusion:DRG payment is conducive to optimizing the hospitalization expense structure of uterine leiomyoma hospitalized patients.The average length of hospitalization,consumption ratio,and surgical treatment expense ratio are important factors affecting the hospitalization expense of uterine leiomyoma hospitalized patients.Public hospitals should continue to optimize the expense structure in the future,pay equal attention to"reducing expenditure"and"open source",implement DRG payment and its supporting measures to enhance the efficiency of medical services,reinforce the comprehensive management of consumables,and empower hospitals and medical personnel.

Objective:To investigate the internal structure and determinants of hospitalization expenses for uterine leiomyoma patients in DRG pilot and non-DRG pilot hospitals in Beijing,to fumish insights for the forthcoming phase of public hospital reform.Methods:The statistical data of 5 DRG pilot hospitals and 124 non-DRG pilot hospitals in Beijing from 2015 to 2021 were collected to analyze the correlation degree between each detail expense and the average hospitalization expense by using grey correlation analysis,and the influencing factors of the average hospitalization expense of hospitalized patients by using random forest model.Results:The results of the grey correlation analysis revealed that the highest correlations affecting hospitalization expense in the DRG pilot hospital group and the non-DRG pilot hospital group were the average expense in each surgical treatment and the average drug costs for each patient,respectively,and the lowest was the average expense of inspection and test in each patient.The results of random forest model showed that the top two influencing factors of DRG pilot hospital group were consumption ratio and the average length of hospitalization,while the average length of hospitalization,surgical treatment expense ratio and consumption ratio are more important than other influential factors of non-DRG pilot hospital group.Conclusion:DRG payment is conducive to optimizing the hospitalization expense structure of uterine leiomyoma hospitalized patients.The average length of hospitalization,consumption ratio,and surgical treatment expense ratio are important factors affecting the hospitalization expense of uterine leiomyoma hospitalized patients.Public hospitals should continue to optimize the expense structure in the future,pay equal attention to"reducing expenditure"and"open source",implement DRG payment and its supporting measures to enhance the efficiency of medical services,reinforce the comprehensive management of consumables,and empower hospitals and medical personnel.