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.

In the strategic context of "healthy China"， the concept of "medicine and food homology"， rooted in the culture of traditional Chinese medicine （TCM）， has received unprecedented attention. In response to population aging in China， the health of the elderly has become the focus of public health attention， and proactive health is the key to healthy aging. From the perspective of the application of medicinal and edible materials in proactive health and technological responses to population aging for the first time， this paper firstly provided a systematic overview of medicinal and edible materials and the policies related to proactive health. Second， it summarized the situation of modern technology that accelerates the research and development of medicinal and edible products， as well as the current situation of various modern biotechnologies that reveal the mechanism of action of medicinal and edible materials. Third， it discussed the application scenarios of medicinal and edible materials in proactive health and technological responses to population aging， as well as the future research and development of medicinal and edible materials. By exploring in depth the unique value and importance of medicinal and edible materials， the paper lays a theoretical foundation for improving the health care capabilities of TCM and contributes new strategies derived from TCM to healthy aging.

ObjectiveTo investigate the risk factors for pyogenic liver abscess （PLA） comorbid with sepsis by analyzing clinical features， and to construct a predictive model. MethodsA retrospective analysis was performed for 489 patients who were hospitalized and diagnosed with PLA in The Affiliated Hospital of Xuzhou Medical University from January 2019 to December 2023， and according to the presence or absence of sepsis， they were divided into sepsis group with 306 patients and non-sepsis group with 183 patients. Related data were collected， including general information， laboratory markers， and outcome measures. The patients were further divided into a training set of 342 patients and a validation set of 147 patients at a ratio of 7∶3， and the training set was used for screening of variables and construction of a predictive model， while the validation set was used to test the performance of the model. An LASSO regression analysis was used for the screening of variables， and a multivariate Logistic regression analysis was used to construct the predictive model and plot a nomogram. The calibration curve， the receiver operating characteristic （ROC） curve， and the decision curve analysis were used for the validation of the model， and internal validation was performed for assessment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical variables between groups. ResultsThere were significant differences between the sepsis group and the non-sepsis group in pulse rate， mean arterial pressure， duration pf symptoms， comorbidity of liver cirrhosis or malignant tumor， leukocyte count， neutrophil count， lymphocyte count， platelet count （PLT）， activated partial thromboplastin time， fibrinogen， C-reactive protein， aspartate aminotransferase， alanine aminotransferase， albumin， total bilirubin （TBil）， creatinine， potassium， and prognostic nutritional index （PNI） （all P<0.05）. In the training set， the LASSO regression analysis identified four predictive factors of pulse rate， PLT， TBil and PNI， and the multivariate Logistic regression analysis showed that pulse rate （odds ratio ［OR］=1.033， 95% confidence interval ［CI］： 1.006‍ ‍—‍ ‍1.061， P=0.018）， PLT （OR=0.981， 95%CI： 0.975‍ ‍—‍ ‍0.987， P<0.001）， TBil （OR=1.086， 95%CI： 1.053‍ ‍—‍ ‍1.125， P<0.001）， and PNI （OR=0.935， 95%CI： 0.882‍ ‍—‍ ‍0.988， P=0.019） were independent influencing factors for the risk of sepsis in patients with PLA. The model constructed based on these factors showed a good predictive ability， with an area under the ROC curve of 0.948 （95%CI： 0.923‍ ‍—‍ ‍0.973） in the training set and 0.912 （95%CI： 0.848‍ ‍—‍ ‍0.976） in the validation set. The decision curve analysis showed that the model has a good net benefit within the range of 0.3‍ ‍—‍ ‍0.9 for threshold probability. ConclusionThe nomogram prediction model constructed based on pulse rate， PLT， TBil， and PNI has a certain clinical value and can well predict the risk of sepsis in patients with PLA.

Objective: To explore the correlation between traditional Chinese medicine (TCM) constitution and depressive symptom among school aged children and adolescents, so as to provide evidences for informing constitution based regulation and prevention of depressive symptom. Methods: From June to December 2024, a total of 4 729 students aged 6-14 were recruited by cluster random sampling from 10 primary schools in Baoding (Hebei Province), Heze and Liaocheng (Shandong Province). General information, TCM constitution and depressive symptom were collected. Restricted cubic spline (RCS) models were used to analyze related factors and threshold effects of depressive symptom. Binary Logistic regression was applied to examine the association between depressive symptom and TCM constitution, with subgroup analyses conducted. Results: The detection rate of depressive symptom among the included children and adolescents was 25.82%. RCS analyses indicated non linear associations between depressive symptom and age (inflection point at 10 years old), bedtime (inflection point at 22:00), and wake up time (inflection point at 6:30 ) (all P non linearity <0.01). Linear associations were observed with body mass index (BMI) and sleep duration (all P non linearity > 0.05 ). After adjusting for covariates such as age, BMI and sleep status, binary Logistic regression analyses showed that Yin deficient constitution ( OR =1.26, 95% CI =1.09-1.45) and Phlegm-dampness constitution ( OR =1.42, 95% CI =1.11-1.82) were significantly associated with depressive symptom among children and adolescents (all P <0.05). Conclusions Depressive symptom among school aged children and adolescents is primarily associated with Yin deficiency and Phlegm dampness constitutions in TCM constitution. Active attention should be paid to susceptible TCM constitution among children and adolescents. Targeted health guidance and interventions should be implemented to improve TCM constitution health status for preventing the occurrence of depressive symptom.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

OBJECTIVE To explore the effect and mechanism of Zexie tang （ZXT） on reducing lipid accumulation through network pharmacology， and compare the difference of traditional decoction versus formula granules. METHODS The active components and targets of ZXT were identified using TCMSP and SwissTargetPrediction databases. GeneCards， OMIM， DisGeNET and TTD databases were used to analyze the related targets of non-alcoholic fatty liver disease （NAFLD）； protein-protein interaction network model was constructed by String database；“ ZXT-NAFLD target-pathway” network diagram was constructed by using CytoScape software； target enrichment analysis was performed by using Metascape platform. Fat accumulation model of human hepatocellular carcinoma HepG2 cells was established to observe the effects of traditional decoction and formula granules of ZXT on lipid accumulation of cells. RESULTS Alisol B， alisol C， 1-monolinolein and alisol B monoacetate were the key active components of ZXT in the treatment of NAFLD. The core targets included MDM2， MAPK1， PIK3CB， PRKCQ and MAPK14， etc. The core signaling pathways included endocrine resistance， insulin resistance and Th17 cell differentiation. Compared with model group， except for the Zexie formula granules group and Baizhu formula granules group， the absorbance values in all other administration groups were significantly decreased （P＜0.01）； the absorbance value of Baizhu traditional decoction group was significantly higher than that of ZXT traditional decoction group （P＜0.01）； the absorbance values of Zexie formula granule group and Baizhu formula granule group were significantly higher than that of ZXT formula granule group （P＜0.01）； the absorbance value of Zexie formula granule group was significantly higher than that of Zexie traditional decoction group （P＜0.01）； the absorbance value of Baizhu formula granule group was significantly higher than that of Baizhu traditional decoction group （P＜0.01）. CONCLUSIONS ZXT reduces lipid accumulation of human hepatocellular carcinoma cells through multiple components， multiple target and multiple pathways， and its traditional decoction and formula granules exhibit slightly different lipid-lowering effects.

Objective:This study investigated the expression level of phosphatidylserine-specific phospholipase A1(PLA1A)in colorectal can-cer(CRC)and analyzed its correlations with clinicopathological features,prognosis,and immune infiltration.Methods:The expression level of PLA1A in CRC was screened,and the influence of this expression level on patient prognosis was analyzed using bioinformatics methods.A cohort of 192 patients diagnosed with CRC at Shanxi Province Cancer Hospital from January to December 2020 were selected.The PLA1A ex-pression level in those with CRC was determined using immunohistochemistry(IHC)and real-time quantitative reverse transcription PCR(RT-qPCR).The relationship between PLA1A level and the clinicopathological features of the patients with CRC was analyzed using the chi-square test.The expression levels of immune cell markers CD4 and CD8 as well as immunosuppressive checkpoints PD-1,TIM-3,and CTLA-4 in CRC were detected via IHC,and their correlations with PLA1A level were analyzed using the chi-square test.Results:The results of bioinformatics analysis showed that the expression level of PLA1A in CRC tissue was higher than paracancerous tissue,which correlated with overall surviv-al(OS)(P<0.05).The IHC and RT-qPCR results showed that PLA1A expression level was significantly upregulated in CRC tissiue(P<0.05).High PLA1A level was closely associated with the TNM stage,degree of differentiation,and lymph node metastasis(P<0.05).The IHC results demonstrated that PLA1A positively correlated with the infiltrating CD8+T cell level(P<0.05).In addition,the elevated PLA1A levels upregu-lated the expressions of immunosuppressive checkpoints PD-1,TIM-3,and CTLA-4(P<0.05).Conclusions:PLA1A is highly expressed in CRC,which is closely related to immune infiltrating cells and immunosuppressive checkpoints,suggesting that PLA1A plays an important role in immune infiltration in CRC,a finding that provides guidance in the treatment of CRC.

Objective:To understand the pathogenic composition and epidemiological characteristics of febrile respiratory syndrome (FRS) in elderly people aged 60 and above in China, and to provide a reference basis for the scientific and precise prevention and control of FRS in the elderly.Methods:Based on FRS cases surveillance data from information management system of National Technical Platform for Infectious Disease Surveillance, National Science and Technology Major Project of China, the surveillance pathogens included 8 viruses, including influenza virus (IFV), respiratory syncytial virus (RSV), adenovirus (HAdV), parainfluenza virus (HPIV), metapneumovirus (HMPV), coronavirus (HCoV), bocavirus and rhinovirus (HRV); 7 bacterias, namely Streptococcus pneumoniae ( S.pneumoniae), Staphylococcus aureus ( S.aureus), Klebsiella pneumoniae ( K.pneumoniae), Pseudomonas aeruginosa ( P.aeruginosa), Group A Streptococcus ( GAS), Haemophilus influenzae ( H.influenzae) and Legionella pneumophila ( L. pneumophila), in addition to Chlamydia pneumoniae ( C. pneumoniae) and Mycoplasma pneumoniae ( M. pneumoniae). A descriptive epidemiological approach was used to analyze the pathogenic composition and major epidemiological characteristics of FRS cases aged 60 years and older nationwide from 2009 to 2021. Results:The predominant viruses of FRS cases aged≥60 years accounted for 87.93% of the pathogen spectrum in China, including IFV (42.42%), HRV (16.71%), HPIV (11.53%), HCoV (9.52%), and RSV (7.75%), while the pathogen spectrum of the major bacteria accounted for 94.60%, including S. pneumoniae (25.71%), P. aeruginosa (24.97%), K. pneumoniae (22.47%), H. influenzae (12.23%), and S. aureus (9.22%). Influenza viruses have always been at the top of the viral pathogen spectrum, and P. aeruginosa, K. pneumoniae and S. pneumoniae, ranked high in the bacterial pathogen spectrum. Among them, the proportions of HRV, HPIV, RSV, K. pneumoniae, and H. influenzae fluctuated and increased during the 13 years of observation. The positive rate of any pathogen in FRS cases was higher in out patient emergencies (32.83%) than in hospitalized cases (27.26%) ( χ2 =125.89, P<0.001). The positive rate of IFV was higher in cases aged 60-74 years (13.66%). The positive rate of P. aeruginosa and K. pneumoniae were higher in cases aged ≥90 years (10.71%, 9.40%) and in northern regions (8.32%, 7.30%). The positive rate of any pathogen in FRS cases was higher in winter (33.82%) than in other seasons ( χ2=212.03, P<0.001). The positive rate of IFV and HRV were higher in winter (22.87%) and autumn (5.98%) and the positive rate of P.aeruginosa (8.11%) and K.pneumoniae (8.30%) were higher in summer. Conclusions:IFV, HRV, HPIV, S. pneumoniae, P. aeruginosa and K. pneumoniae were respectively the top three pathogens in the viral and bacterial pathogen spectrum of FRS cases aged 60 years and above in China from 2009 to 2021, and the positive rate of these main pathogens showed differences between age groups, seasons, and geographic regions. In the future, the dynamic surveillance of various pathogens in the elderly with respiratory tract infections should be continuously strengthened.

Objective:To explore the association between the systemic immune-inflammation index (SII) and obesity metabolic phenotypes, as well as metabolic features in children and adolescents.Methods:A cross-sectional study was conducted using the random cluster sampling method from March 2023 to May 2024. Children and adolescents aged 9-17 years in Guangzhou were surveyed through questionnaires, physical measurements, and blood tests. According to BMI and metabolic status, participants were classified into normal-weight groups [metabolically healthy normal weight (MHNW) and metabolically unhealthy normal weight (MUNW)] and overweight/obese groups [metabolically healthy overweight/obese (MHO/O) and metabolically unhealthy overweight/obese (MUO/O)]. After natural log-transformation of SII values (lnSII), multinomial logistic regression was used to assess the association between SII and obesity metabolic phenotypes, while binary logistic regression was applied to assess the relationship between SII and metabolic phenotypes in the overweight/obese subgroup. Linear regression model and restricted cubic spline (RCS) were employed to examine the relationship between SII and metabolic features among the entire population.Results:A total of 3 749 participants were included. After adjusting for covariates, for every unit increase in lnSII, the risk of MHO/O and MUO/O increased by 93% ( OR=1.93, 95% CI: 1.56-2.40, P<0.001) and 156% ( OR=2.56, 95% CI: 2.02-3.25, P<0.001), respectively. In the overweight/obesity subgroup, for every unit increase in lnSII, the risk of MUO/O increased by 37% ( OR=1.37, 95% CI: 1.01-1.87, P=0.045). Linear regression model and RCS showed that lnSII was positively correlated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (SBP: β=1.39, 95% CI: 0.67-2.11, P<0.001; DBP: β=1.27, 95% CI: 0.79-1.75, P<0.001). lnSII also had a non-linear relationship with triglyceride ( Pnonlinear=0.032) and high-density lipoprotein cholesterol ( Pnonlinear=0.002). Conclusion:Elevated SII levels are associated with unfavorable obesity metabolic phenotypes, higher blood pressure, and altered lipid profiles in children and adolescents. SII may be a potential driving factor for metabolic heterogeneity in children and adolescents.

Objective:To evaluate the role of interferon regulatory factor 3 (IRF3) in renal fibrosis in a mouse model of renal ischemia-reperfusion injury.Methods:Twelve male C57BL/6J wild-type mice and 12 macrophage IRF3 conditional knockout C57BL/6J mice, aged 8-10 weeks, weighing 20-25 g, were divided into 2 groups ( n=6 each) using a random number table method: wild-type sham operation group (WT-Sham group) and wild-type renal ischemia-reperfusion injury group (WT-I/R group); IRF3 conditional knockout sham operation group (cKO-Sham group) and IRF3 conditional knockout I/R group (cKO-I/R group). The model of renal I/R injury was established by occluding bilateral renal pedicles for 45 min followed by reperfusion in anesthetized animals. The orbital blood samples and renal tissues were collected at 14 days of reperfusion for determination of the concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in serum, expression of fibronectin, collagen-I, alpha-smooth muscle actin (α-SMA) (by immunofluorescence), F4/80-α-SMA double positive cell count, and mRNA expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in renal tissues (by real-time polymerase chain reaction) and for observation of pathological changes which were scored. The area of renal fibrosis was measured. Results:For two types of mice, compared with group Sham, the levels of serum BUN and Cr, area of renal fibrosis and renal injury score were significantly increased, the expression of fibronectin, COL-Ⅰ and α-SMA protein and IL-6, IL-1β, TNF-α and TGF-β1 mRNA was up-regulated, and the F4/80-α-SMA dual positive cell count was increased in group WT-I/R ( P<0.05). Compared with group WT-I/R, the concentrations of BUN and Cr in serum, area of renal fibrosis and renal injury score were significantly decreased, the expression of fibronectin, COL-Ⅰ and α-SMA protein and IL-6, IL-1β, TNF-α and TGF-β1 mRNA was down-regulated, and the F4/80-α-SMA dual positive cell count was decreased in cKO-I/R group ( P<0.05). Conclusions:IRF3 is involved in the process of renal fibrosis in a mouse model of renal ischemia-reperfusion injury, and the mechanism may be associated with the promotion of inflammatory responses and the transformation of macrophages into myofibroblasts.