ObjectiveTo investigate the contamination status of ochratoxin A (OTA) in commercially available food products in Shanghai, and to assess OTA exposure levels and the associated non-carcinogenic and carcinogenic risks among pregnant women by integrating dietary consumption data of this population. MethodsThe levels of OTA contamination in 1 520 food samples collected in Shanghai from 2022 to 2023 were determined using liquid chromatography-tandem mass spectrometry. An exposure assessment model was developed based on the dietary consumption levels of pregnant women from the 2016‒2017 Shanghai Pregnant Women Dietary Monitoring Survey to calculate the estimated daily intake (EDI) of OTA, the margin of exposure for non-carcinogenic toxicity (MOE₁), and the margin of exposure for carcinogenic toxicity (MOE₂). An MOE₁ greater than 200 and an MOE₂ greater than 10 000 indicate that the non-carcinogenic toxicity and carcinogenic toxicity resulting from exposure are negligible, respectively. For samples with OTA contamination levels below the limit of detection (LOD), which accounted for more than 80% of the samples, the OTA levels were assigned values of 0 and LOD, respectively, for subsequent calculations. ResultsThe detection rates of OTA in cereals, nuts, dried fruits, and alcohol samples collected in 2022 were 2.03%, 0, 0, and 0, respectively. The OTA detection rates in cereals, nuts, dried fruits, beans, and alcohol samples collected in 2023 were 2.50%, 0.39%, 2.47%, 1.67%, and 13.33%, respectively. For pregnant women in Shanghai in 2022, simulation results indicated that when assigning a value of 0 and the LOD, theP₅₀ values of EDI for dietary OTA exposure were 0.05 and 0.72 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.25 and 2.40 ng·(kg·d)^-1, respectively. For pregnant women in Shanghai in 2023, the P₅₀ values of EDI for dietary OTA exposure were 0.04 and 1.00 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.23 and 2.67 ng·(kg·d)^-1, respectively, both substantially below the tolerable daily intake (TDI) for OTA [17 ng·(kg·d)^-1]. The EDI for dietary OTA exposure in 100.0% of Shanghai pregnant women was lower than the TDI, indicating an overall low level of dietary OTA exposure among this population. For 100.0% of pregnant women, the MOE₁ for dietary OTA exposure exceeded 200. When assigned a value of 0, the MOE₂ for 100.0% of pregnant women in both 2022 and 2023 exceeded10 000. When assigned the LOD value, 72.3% and 81.8% of pregnant women in 2022 and 2023, respectively, had an MOE₂ exceeding 10 000. ConclusionFrom 2022 to 2023, samples of cereals, nuts, dried fruits, beans, and alcohol sold in Shanghai exhibited varying degrees of OTA contamination. The overall EDI of OTA exposure among pregnant women in Shanghai remained at a low level. The non-carcinogenic and carcinogenic risks associated with OTA exposure were generally low and at controllable levels.

Objective:To select low-dose radiation-activated genes with intrinsic radiation protection by developing a model for adaptive responses to low-dose ionizing radiation, in order to explore the mechanisms behind the radiation resistance of the candidate genes.Methods:The cells were divided into adaptive response induction group and whole transcriptome sequencing group. The level of DNA damage was assessed using the γ-H2AX immunofluorescence assay. The low-dose radiation-activated candidate genes with radiation protection were selected through whole transcriptome sequencing and quantitative reverse transcription PCR (RT-qPCR)-based validation. The anti-radiation effect of candidate gene CCND1 was assessed based on CCK-8 cell proliferation and γ-H2AX immunofluorescence assay. After up- and down-regulation of CCND1 expression, the anti-radiation mechanism of CCND1 was preliminarily explored through transcriptome sequencing analysis.Results:A model for low-dose ionizing radiation-induced adaptive responses of lymphocytes was constructed. Using this model, six candidate genes with radiation protection, including CCND1, ZMAT3, MGAT3, DFFB, CYP4F2, ITGA6, were selected. Compared to the control group, overexpressed CCND1 led to significantly enhanced proliferation ability of AHH-1 cells ( t = 7.92-14.76, P < 0.05) and distinctly lowered level of DNA damage ( t = 2.79-9.68, P < 0.05) after 2 Gy of X-ray irradiation. Furthermore, compared to the control group, the CCND1 knockdown caused significantly decreased cell proliferation ability ( t = 13.58-26.25, P < 0.05) and notably elevated level of DNA damage of cells ( t = 2.87-7.61, P < 0.05). Transcriptome sequencing revealed that up- and down-regulation of CCND1 expression resulted in the activation of pathways related to cell growth, death, and damage repair. Conclusions:By selecting six low-dose-activated candidate genes with radiation protection and revealing the function of CCND1 in radiation protection, this study provides a new perspective for the development of radiation protection agents from the perspective of adaptive responses to low-dose radiation.

Objective To investigate the value of artificial intelligence iterative reconstruction(AIIR)in preoperative low-dose CT of ovarian tumor.Methods Seventy patients with ovarian tumor were prospectively enrolled.Routine-dose(120 kVp,200 mAs)and low-dose(120 kVp,40 mAs)contrast-enhanced abdominopelvic CT scanning at portal venous phase were sequentially performed.The routine-dose images were reconstructed with hybrid iterative reconstruction(HIR)(group A),while low-dose images were reconstructed with HIR(group B)and AIIR(group C),respectively.Subjective and objective evaluation of image quality were compared among groups,and the diagnostic accuracy of peripheral organ invasion and peritoneal metastasis based on group A,B and C,as well as radiation dose of routine-and low-dose scanning were recorded.Results In group B,A and C,the subjective scoring of definition of tumor margin and septation,boundary between tumor and surrounding organ,as well as the signal-to-noise ratio and contrast-to-noise ratio of ovarian tumor and psoas muscles,increased successively(all P＜0.017).No significant difference of subjective scoring of tumor feeding vessel clarity was found between group A and C(P=0.435),which were both higher than that in group B(P＜0.017).The accuracy for diagnosing peripheral organ invasion based on group A,B and C was 83.87％ (52/62),72.58％ (45/62)and 83.87％ (52/62),for diagnosing peritoneal metastasis was 85.71％ (60/70),78.57％ (55/70)and 84.29％ (59/70),respectively.Compared to routine-dose CT,the effective dose of low-dose CT was reduced by 79.70％ (2.60 mSv vs.12.81 mSv,P＜0.001).Conclusion AIIR could improve image quality and metastasis diagnostic efficacy in low-dose CT of ovarian tumors.

To satisfy the growing healthcare demands of the public, it is essential to develop a public service platform for vaccination. This initiative aligns with national policies, optimizes resource allocation, innovates service models, enhances service efficiency, and reduces service costs. Drawing on relevant national policies and regulatory requirements, as well as the notable achievements and practical experiences gained through the exploration and innovation of vaccination service models across various regions, this paper proposes expert recommendations. It defines the essential components and functional specifications for public service platforms, focusing on public needs such as electronic vaccination record management, appointment management, the promotion of electronic vaccination certificates, vaccination certificate verification for school enrollment, vaccination site navigation, and science communication and public engagement. The recommendations aim to serve as a reference for the development of vaccination public service platforms nationwide.

The water-sediment interface is an important zone for the migration and transformation of chemical substances,but traditional sampling methods make in situ sampling challenging,thus it is difficult to capture information on environmental processes at the micro-scale.In this study,diffusive gradients in thin films(DGT)probe technique was used as in situ tool to detect 18 kinds of typical per-and polyfluoroalkyl substances(PFAS)in the water-sediment system,elucidating their vertical distribution characteristics and patterns.The results showed that different PFAS exhibited distinct variation patterns with depth in water and sediment.Short-chain PFAS exhibited greater mobility,while the migration of long-chain PFAS was restricted in sediment and pore water due to their strong hydrophobicity and adsorption capacity,resulting in relatively small concentration changes in the sediment column.The PFAS concentrations measured by DGT ranged from 11.2 μg/L to 1305 μg/L.For long-chain PFAS,the concentrations measured by DGT were higher than those obtained from direct measurement of water and pore water,while the opposite results were obtained for short-chain PFAS.The DGT results indicated that although long-chain PFAS exhibited strong adsorption to sediment particles,the adsorbed PFAS were still bioavailable.DGT probe technique,with its advantages of in situ sampling and high spatial resolution,provides deep insights into the complex environmental processes occurring at the microscale in the water-sediment systems.DGT offers important technical support and scientific evidence for assessing the adsorption-desorption behavior,bioavailability,and ecological risks of these emerging pollutants in aquatic environment.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

Objective To explore the influencing factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial internal carotid artery(ICA)stenosis and to construct a nomogram prediction model.Methods This study retrospectively and consecutively enrolled patients diagnosed with unilateral moderate-to-severe extracranial ICA stenosis and exhibited indications for carotid endarterectomy(CEA)hospitalized in the Department of Neurosurgery at the First Affiliated Hospital of Soochow University,between August 2019 and September 2024.The patients were divided into a stroke group and a non-stroke group,based on their clinical presentation and head MRI results.Baseline characteristics and clinical data including age,sex,body mass index,blood pressure(systolic and diastolic pressure[＜140 mmHg,140-＜160 mmHg,≥160 mmHg]),hypertension,diabetes,smoking and alcohol consumption history,use of statin and antiplatelet medication,fasting blood glucose,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglycerides(TG),total cholesterol(TC)were collected and ratios between LDL-C/HDL-C,TG/HDL-C,non-HDL-C(calculated according to equation:non-HDL-C=TC-HDL-C),and non-HDL-C/HDL-C(nHHR)were calculated based on aforementioned data.The clinical and baseline data were then compared between two groups.Imaging data included side of carotid artery stenosis(identified through neck vascular ultrasound,CT angiography and/or DSA),degree of carotid stenosis(with 50％-69％categorized as moderate stenosis,and,70％-99％as severe stenosis),plaque echogenicity(predominantly low,medium or high),plaque calcification(surface and basal calcification),plaque ulceration(exists or not),bilateral middle cerebral artery(MCA)hemodynamic parameters measured by transcranial Doppler ultrasound(including,mean flow velocity[Vm],peak systolic velocity[Vs],end-diastolic velocity[Vd]),and the pulsatility index(PI,calculated via formula:PI=[Vs-Vd]/Vm).The hemodynamic parameter differences(△Vm,△Vs,△Vd,△PI)between the healthy and affected MCA were calculated.The baseline,clinical and imaging data with P＜0.05 in univariate analysis were included in multivariate Logistic regression analysis using forward stepwise selection to identify influencing factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis,and a nomogram prediction model was then constructed base on the analyzed results.Receiver operating characteristic curves were plotted,and the area under the curve(AUC)was calculated to evaluate the predictive performance of the nomogram.Delong's test was used to compare AUC differences between single indicators and the combined model.Results A total of 166 patients with unilateral moderate-to-severe extracranial ICA stenosis and CEA indication were included.In which,99 patients were in the stroke group and 67 patients were in the non-stroke group.The stroke group had a significantly higher proportion of hypertension patients(78.8％[78/99]vs.59.7％[40/67],P=0.008),higher systolic blood pressure([152±15]mmHg vs.[137±18]mmHg,P＜0.01),higher diastolic blood pressure([84±10]mmHg vs.[80±10]mmHg,P=0.042),higher TG(1.33[0.95,1.77]mmol/L vs.1.10[0.87,1.48]mmol/L,P=0.019),higher TG/HDL-C(1.35[0.97,2.08]vs.1.07[0.81,1.52],P=0.003),and higher nHHR(2.89[2.25,3.61]vs.2.48[1.93,3.27],P=0.027)than the non-stroke group.The HDL-C was significantly lower in the stroke group(0.96[0.80,1.15]mmol/L vs.1.03[0.91,1.16]mmol/L,P=0.014).Statistically significant differences were also observed in the distribution of systolic blood pressure between the groups(P＜0.01).No significant differences were found in other clinical data(all P＞0.05).The proportion of patients with carotid plaque ulceration was higher in the stroke group(35.4％[35/99]vs.16.4％[11/67],P=0.007),while stenosis side,stenosis degree,plaque echogenicity,and plaque calcification type showed no significant differences between the groups(all P＞0.05).△Vm(19[4,32]cm/s vs.10[-3,21]cm/s,P=0.001),△Vs(32[9,55]cm/s vs.24[3,40]cm/s,P=0.005),and △Vd(10[-1,19]cm/s vs.6[-3,12]cm/s,P=0.006)were significantly higher in the stroke group.No significant difference was found in △PI(P=0.076).Multivariate Logistic regression analysis identified high systolic blood pressure(OR,1.063,95％CI 1.036-1.090,P＜0.01),high TG/HDL-C(OR,2.802,95％CI 1.551-5.061,P=0.001),high △Vm(OR,1.032,95％CI 1.010-1.055,P=0.004),and plaque ulceration(OR,2.777,95％CI 1.123-6.871,P=0.027)as independent risk factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis.Systolic blood pressure,TG/HDL-C,△Vm and plaque ulceration were involved in the construction of a combined predictive model for ischemic stroke in the targeted patient group(with unilateral moderate-to-severe extracranial ICA stenosis).The AUC of the combined prediction model was 0.828(95％CI 0.765-0.892,P＜0.01),which was significantly higher than the predictive efficacy of any single factor(all P＜0.01).Conclusions High systolic blood pressure,high TG/HDL-C ratio,high △Vm,and plaque ulceration are independent risk factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis.The nomogram prediction model based on these factors demonstrates good predictive value for assessing ischemic stroke risk in this patient population.

The cribriform fascia is formed by the fusion of deep and superficial fascias in the axilla,and it forms the base of the axilla together with the subcutaneous tissue and skin,which is a key part of the system of the membranous anatomy of breast surgery.The loose anatomical structure of the cribriform fascia makes it an important anatomical landmark in the axillary region,which plays an important role in accurate localization of lymph nodes.The sentinel lymph node biopsy through cribriform fascia has less intraoperative blood loss and shorter catheterization time compared with the traditional axillary fold approach.However,the anatomical structure of the cribriform fascia and its significance in the membranous anatomy of breast surgery have not been fully elucidated.This article analyzes the anatomical structure of the cribriform fascia and its adjacent tissues,and emphasizes the anatomical structure that needs to be paid attention to in sentinel lymph node biopsy through the axillary cribriform fascia,so as to provide a reference for clinicians to fully understand the cribriform fascia structure.