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.

Background Pyrethroid pesticides (PYRs) can cross the placental barrier to cause intrauterine fetal exposure, which may lead to developmental immunotoxicity (DIT). However, the specific effect of maternal PYR exposure during pregnancy on the cellular immune function of 1-year-old children remains unclear. Objective To explore the effect of PYRs exposure throughout the entire pregnancy on peripheral blood lymphocytes in 1-year-old children and potential sensitive window period of PYRs exposure. Methods A birth cohort was established by enrolling pregnant women in their first trimester and following them and their infants until one year of age. Ultra-high performance liquid chromatography-tandem mass spectrometry was used to detect the levels of PYRs metabolites, including 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylic acid (cis-DBCA), in the urine of pregnant women during the first trimester (gestational weeks 6-12), the second trimester (gestational weeks 21-24), and the third trimester (gestational weeks 33-36). Peripheral blood leukocyte and lymphocyte counts were measured in children at 12 months of age using the Coulter principle combined with flow cytometry. Exposure levels of PYRs metabolites in each trimester were divided into low, moderate, and high exposure groups based on the 25th (P₂₅) and 75th (P₇₅) percentiles. Meanwhile, participants were classified as having repeated high or low exposure if their metabolite levels were > P₇₅ or <P₂₅ in at least two trimesters, respectively, while all others were categorized as having repeated moderate exposure. Generalized linear models were used to analyze the associations between trimester-specific and repeated PYRs metabolite exposure levels and the peripheral blood white blood cell (WBC) and lymphocyte counts in children aged 1 year. Results A total of 336 mother-child pairs were included in this study. For the pregnant women, the total detection rates of maternal urinary 3PBA, 4F3PBA, and cis-DBCA across the three trimesters of pregnancy were 80.5%, 100.0%, and 81.3%, respectively; and median creatinine-corrected concentrations were 0.24, 0.36, and 0.42 μg·g⁻¹, respectively. In children aged 1 year, the mean WBC and lymphocyte counts in peripheral blood were (8.9±2.0)×10⁹·L⁻¹ and (5.7±1.6)×10⁹·L⁻¹, respectively. The results of the generalized linear model analysis indicated that compared to the low exposure group, the high cis-DBCA exposure group during the third trimester of pregnancy had significantly lower peripheral blood WBC count (β=−0.87, 95%CI: −1.51, −0.23) and lymphocyte count (β=−0.64, 95%CI: −1.15, −0.13); and the repeated high-exposure group of cis-DBCA had significantly lower peripheral blood WBC count (β=−1.34, 95%CI: −2.34, −0.34) and lymphocyte count (β=−0.80, 95%CI: −1.60, −0.01) than the repeated low exposure group. Similarly, the repeated moderate-exposure group of cis-DBCA had a significantly lower peripheral blood WBC count (β=−0.83, 95%CI: −1.59, −0.07) than the repeated low exposure group. Conclusion High maternal exposure to PYRs with cis-DBCA as the major metabolite exposure is associated with decreased peripheral leukocyte and lymphocyte counts in children aged 1 year, and repeated high-level exposure throughout gestation appears to exacerbate DIT in offspring. The third trimester of pregnancy maybe a sensitive window for children's DIT induced by exposure to PYRs during pregnancy.

Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

OBJECTIVE To explore the efficacy and safety of toludesvenlafaxine in the treatment of patients with major depressive disorder （MDD） with anhedonia. METHODS This retrospective study included 160 patients with MDD with anhedonia who were treated at Hebei Mental Health Center from May 2023 to August 2025. These patients were divided into a control group （ n ＝81） and an observation group （ n ＝79） according to treatment regimens. All patients received transcranial magnetic stimulation therapy. On this basis，the control group was treated with Sertraline Hydrochloride Tablets， while the observation group received Toludesvenlafaxine Hydrochloride Sustained-Release Tablets，with an 8-week continuous treatment course.To compare t he clinical total effective rate， anhedonia remission rate，the severity of depressive symptoms，degree of anhedonia，cognitive function，social function and quality of life between the two groups before and after treatment， the incidence of adverse reactions during treatment was recorded simultaneously. RESULTS After treatment，the total effective rate and anhedonia remission rate of the observation group were significantly higher than the control group （ P ＜0.05）. At the 4th and 8th weeks of treatment， the scores of Snaith-Hamilton Pleasure Scale， Hamilton Depression Rating Scale-17 Items， and Sheehan Disability Scale of both groups were significantly lower than those before treatment in the same group， and the observation group was significantly lower than the control group （ P ＜0.05）； the scores of Montreal Cognitive Assessment and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form were significantly higher than those before treatment in the same group， and the observation group was significantly higher than the control group （ P ＜0.05）. There was no statistically significant difference in the overall incidence of adverse reactions between the two groups （ P ＞0.05）. CONCLUSIONS Toludesvenlafaxine can significantly improve depressive symptoms， cognitive function， and social function in MDD patients with anhedonia，with good safety.

Objective To evaluate the feasibility of intravesical instillation of urokinase and heparin sodium in the treatment of bladder clot irrigation.Methods This report discusses the diagnosis and treatment of three patients with bladder blood clot tamponade confirmed by abdominal and pelvic computed tomography(CT)scans enrolled from our hospital during Jun. to Sep. 2024, and discuss the relevant literature.Results A solution containing urokinase(20 000 IU)and heparin sodium(125 000 U)was instilled through a three-way catheter and retained for 30 minutes before drainage. Complete clot dissolution was achieved in all cases, with immediate relief of hypogastric distension and pain. Post-procedural CT showed restored bladder lumen patency. Hemoglobin levels decreased by 2-5 g/L without complications.Conclusion This preliminary trial demonstrated that intravesical instillation of urokinase-heparin provides a safe and effective minimally invasive alternative for bladder clot in irrigation cases.

Tumor angiogenesis is a core pathological driver of malignant growth, invasion, and metastasis, and represents a major obstacle to effective anticancer therapy. Conventional antiangiogenic agents, including neutralizing monoclonal antibodies and small-molecule tyrosine kinase inhibitors, are constrained by drug resistance, on-target toxicity, and the compensatory activation of alternative pro-angiogenic pathways. Targeted protein degradation (TPD) has emerged as a promising strategy that may overcome these limitations. Unlike traditional inhibitors that operate through an occupancy-driven mechanism, degraders function through an event-driven catalytic mechanism in which a single degrader molecule can catalytically promote the ubiquitination and subsequent proteasomal or lysosomal degradation of multiple molecules of the same target protein, thereby eliminating the target protein together with all of its functions rather than merely blocking a single active site. This review systematically delineates the pathophysiological basis of tumor angiogenesis, encompassing the angiogenic switch driven by hypoxia-inducible factor-1α (HIF-1α), the aberrant structural and functional features of the tumor vasculature, and the self-reinforcing vicious cycles that sustain malignant progression. We then categorize the principal TPD modalities, with particular emphasis on proteolysis-targeting chimeras (PROTACs) and lysosome-targeting chimeras (LYTACs), and describe their design principles and mechanisms of action. PROTACs recruit E3 ubiquitin ligases to direct intracellular targets to the ubiquitin-proteasome system for degradation, whereas LYTACs engage lysosome-targeting receptors to route extracellular and membrane proteins to the lysosome, thereby expanding the degradable target space beyond the intracellular proteome. We further summarize recent advances in the application of TPD to antiangiogenic intervention at four distinct levels. First, at the signaling initiation level, degradation of vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) by aptamer-engineered PROTACs, antibody-based LYTACs, and small-molecule VEGFR2 degraders blocks the upstream trigger of the angiogenic cascade. Second, at the signal transduction level, degradation of focal adhesion kinase (FAK), B-Raf proto-oncogene serine/threonine kinase (BRAF), phosphodiesterase 4 (PDE4), and bromodomain-containing protein 4 (BRD4) interrupts intracellular signaling cascades and transcriptional responses. Third, at the microenvironment level, degradation of proviral integration site for Moloney murine leukemia virus (PIM) kinases curtails the pro-angiogenic signals secreted by tumor-associated macrophages. Fourth, multi-target synergistic strategies, exemplified by bispecific degraders that simultaneously target human epidermal growth factor receptor 2 (HER2) and VEGF-A, represent a preliminary exploration of cooperative intervention. Representative degraders reviewed herein elicit diverse antiangiogenic phenotypes, ranging from the direct inhibition of endothelial cell proliferation, migration, and tube formation to reductions in microvessel density and the suppression of vasculogenic mimicry. Finally, we discuss the major challenges that remain, including the precise matching of degradation kinetics with the vascular normalization window, target selectivity and tissue specificity, and the activation of compensatory networks and the emergence of resistance. Since the application of TPD in this setting remains at an early stage, the clinical translation of these approaches will require careful optimization of degradation efficiency, spatiotemporal control, and delivery strategies. We also envision future directions toward immunotherapy-based combination regimens and precision-degradation approaches guided by single-cell and spatial transcriptomics. In our view, TPD should not be regarded merely as a substitute for conventional antiangiogenic drugs, but rather as a molecular tool capable of systematically remodeling the tumor vascular microenvironment. When precise control of degradation efficiency and spatiotemporal regulation are integrated with a thorough understanding of the heterogeneity and compensatory capacity of tumor vessels, the full clinical potential of this strategy can be realized.

Objective: To explore the associations of sedentary behavior and physical activity with next day affective states in junior and senior high school students, so as to provide a reference for promoting affective health in the population. Methods: From March to April 2026, 137 junior and senior high school students aged 12-17 years were recruited from two junior and senior high schools in Tianjin using convenience sampling. The ActiGraph wGT3X-BT accelerometer was used to continuously monitor 24 hour activity behaviors, and screen sedentary time (SST) and non-screen sedentary time were distinguished in combination with daily time use diaries. Daily affect levels in junior and senior high school students were collected via the Positive and Negative Affect Schedule-Expanded Form, with moods classified into high /low arousal positive affect and high /low arousal negative affect. Bayesian multilevel compositional data analysis and isotemporal substitution analysis were employed to explore the associations and substitution effects of sedentary behavior and 24 hour activity behaviors with next day affective states in junior and senior high school students. Results: Bayesian multilevel modeling showed that the associations between 24 hour movement behaviors and nextday affect in junior and senior high school students were mainly evident at the within person level. SST was associated with lower next day high arousal positive affect ( β =-0.15) and low arousal positive affect ( β = -0.11 ), and with higher high arousal negative affect ( β =0.12); light physical activity (LPA) was associated with higher high arousal positive affect ( β =0.13), and moderate to vigorous physical activity (MVPA) was associated with lower low arousal negative affect ( β =-0.06) (all P <0.05). Dose response analysis showed that, at the within person level, the substitution effect between SST and LPA was the most pronounced. As the duration of reallocating SST to LPA increased from 10 min to 60 min, high arousal positive affect ( β =0.020-0.123) and low arousal positive affect ( β =0.010-0.061) showed upward trends, while high arousal negative affect ( β =-0.061 to -0.010) showed a downward trend (all P <0.05); although low arousal negative affect presented a decreasing trend, it did not reach statistical significance at any time point ( β =-0.041 to -0.007, all P >0.05). Among the other substitution relationships, reallocating SST to MVPA was accompanied by a decrease in low arousal negative affect ( β =-0.033 to -0.005 ), and reallocating SST to sleep was accompanied by a decrease in high arousal negative affect ( β =-0.029 to -0.005) (all P < 0.05). Conclusions The associations between 24 hour activity behaviors and next day affect in junior and senior high school students are mainly evident at the within person level. Reallocating an individual s daily SST to LPA or MVPA can improve next day affective states in junior and senior high school students.

Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.

Objective:To investigate the association between blood selenium levels and sex hormones in Chinese men aged 18-79 years.Methods:Data were derived from the China National Human Biomonitoring survey conducted in 2017-2018, with a final sample size of 5 414 men. General demographic characteristics, behavioral habits, and dietary frequency were collected through questionnaires and physical examinations. Fasting blood samples were collected to measure blood lead, serum testosterone, and estradiol levels. Complex sampling linear regression models were used to analyze the associations between blood selenium levels and testosterone, estradiol, and the testosterone/estradiol ratio, adjusting for confounding factors including age, education level, marital status, smoking status, alcohol consumption, seafood intake, soy product intake, protein supplement intake, BMI, and diabetes status.Results:The mean age of the 5 414 participants was (46.85±27.91) years; 4 774 (91.65%) were of Han ethnicity and 4 505 (86.68%) were married. The median ( Q1, Q3) blood selenium concentration in men was 97.80 (80.64, 116.99) μg/L. After adjusting for confounding factors, the complex sampling linear regression model revealed negative associations between blood selenium levels and both testosterone levels and the testosterone/estradiol ratio, with a significant linear trend ( Ptrend<0.05). Compared with the Q1 group, the β (95% CI) values for testosterone in the Q2, Q3, and Q4 groups were -0.02 (-0.06 to 0.02), -0.03 (-0.08 to 0.01), and -0.06 (-0.09 to -0.02), respectively. Similarly, the β (95% CI) values for the testosterone/estradiol ratio in the Q2, Q3, and Q4 groups were -0.01 (-0.03 to 0.02), -0.01 (-0.04 to 0.04), and -0.03 (-0.06 to -0.01), respectively. Subgroup analysis indicated stronger associations between blood selenium levels and testosterone/estradiol levels in non-smoking and obese men (BMI≥28 kg/m2). Conclusion:Blood selenium levels are negatively associated with testosterone levels and the testosterone/estradiol ratio in Chinese adult males.

As a serine protease,thrombin can convert soluble fibrinogen into insoluble fibrin and plays a pivotal role in the coagulation cascade.Therefore,the accurate quantitative assay of thrombin levels is of great value in the evaluation of coagulation function,clinical screening and prognostic monitoring of coagulation-related diseases,and screening of drugs for targeted therapy.Existing methods for thrombin detection can be divided into two categories,e.g.,the assay of concentration levels using nucleic acid aptamers as the affinity elements and the assay of activity levels based on the hydrolytic cleavage of substrate peptides.In recent years,electrochemical biosensors have attracted much attention in thrombin detection due to high sensitivity,high selectivity,simple instrument,fast response,and good portability.In this review,the latest research progress in methods for electrochemical detection of thrombin was summarized,focusing on the detection principles and the applied signal amplification strategies of related electrochemical biosensors.In addition,the challenges with respect to the practical use of electrochemical thrombin biosensors and the prospects were discussed.