Objective To investigate the status and influencing factors of overweight and obesity among primary and secondary school students in Pudong New Area of Shanghai, and to provide reference for formulating obesity-related intervention strategies for school-age children. Methods Stratified cluster random sampling method was used to conduct a questionnaire survey among primary and secondary school students in Pudong New Area. The overweight and obesity rate was calculated according to the Chinese health industry standard, and the risk factors of overweight and obesity in children and adolescents of different school age groups were analyzed by logistic regression. Results The overweight and obesity rate (25.3%) of primary and secondary school students in Pudong New Area exceeded the national average level. In primary school group, male, sleep time ≥ 8h per day, water intake ≥ 1200 mL per day, and the presence of mobile food stalls around the school were the risk factors for overweight and obesity. Daily extracurricular exercise time of 30 minutes to 2 hours was a protective factor. In junior high school group, male and electronic product use time of ≥ 2h per day were the risk factors for overweight and obesity. The daily extracurricular exercise time of 1 to 2 hours was a protective factor. In high school group, drinking water ≥1200mL per day was a risk factor for overweight and obesity. Eating breakfast every day for the past week was a protective factor. Conclusion Group intervention targeting overweight and obese school-age children, while changing corresponding unhealthy habits according to different school age groups, is crucial for weight loss in school-age children.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

OBJECTIVE To screen the potential active components of Polygonum orientale flower against myocardial ischemia- reperfusion injury （MIRI） in rats based on physiological and pathological states. METHODS SD rats were divided into normal control group， normal administration group， MIRI control group and MIRI administration group， with 5 rats in each group. After drug intervention or modeling and drug intervention， chromatographic separation plasma samples were collected， and chromatographic separation and mass spectrometry data collection were performed by using UPLC-Q-TOF/MS. The prototype components and metabolites were analyzed by comparing the reference substance maps， the maps of each plasma sample， and the relevant literature. At the same time， the common peaks in plasma samples of rats in normal administration group and MIRI administration group were identified. Combined with principal component analysis and orthogonal partial least square-discriminant analysis， the differential transitional components were screened out according to the value of variable importance in the projection （VIP）＞1， to speculate the potential active components of P. orientale flower in rats under physiological and pathological states. The SD rats were divided into control group， MIRI group， positive control group （Compound danshen tablets 0.2 g/kg， 3 times a day）， and potentially active compound groups （10 mg/kg， twice a day）， with 5 rats in each group. The rats in administration groups were given relevant medicine intragastrically， for 3 consecutive days. The activity of superoxide dismutase （SOD）， the leakages of lactate dehydrogenase （LDH）， creatine kinase isoenzyme-MB （CK-MB） and cardiac troponin Ⅰ （cTnⅠ） in plasma were detected after the last administration. RESULTS Twenty-six main chromatographic peaks were obtained from the total ion chromatogram of the extract of P. orientale flower， and 14 of them were determined， including gallic acid， catechin， protocatechuic acid and so on. There were fifteen （including 6 absorbed prototype components and 9 metabolites） and nineteen transitional components （including 6 absorbed prototype components and 13 metabolites） in the plasma sample of normal rats and MIRI rats. Eight transitional components were detected in both normal rats and MIRI rats， and the VIP values of kaempferol glucuronidation metabolites， quercetin carbonylation metabolites and N-p-paprazine to the corresponding peak were higher than 1. Compared with MIRI group， the activities of SOD were increased significantly in the plasma of MIRI rats in each potential active compound group （P＜0.01）， and the leakages of LDH， CK-MB， and cTnⅠ in the plasma of MIRI rats were reduced significantly （P＜0.01）. CONCLUSIONS The potential anti-MIRI active components in extract of P. orientale flower are N-p-paprazine， quercetin， kaempferol and kaempferol-3-O-β-D-glucoside.

OBJECTIVE To investigate the mechanism by which Ginkgo flavone aglycone （GA） reduces the cardiotoxicity of doxorubicin （DOX） based on transcriptomics and proteomics. METHODS Thirty-six mice were randomly assigned to control group （CON group， tail vein injection of equal volume of physiological saline every other day+daily intragastric administration of an equal volume of physiological saline）， DOX group （tail vein injection of 3 mg/kg DOX every other day）， and GDOX group （daily intragastric administration of 100 mg/kg GA+tail vein injection of 3 mg/kg DOX every other day）， with 12 mice in each group. The administration of drugs/physiological saline was continued for 15 days. Mouse heart tissues were collected for RNA-Seq transcriptomic sequencing and 4D-Label-free quantitative proteomic analysis to screen differentially expressed genes and proteins， which were then subjected to Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. The expression levels of Apelin peptide （Apelin）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） mRNA and protein in mouse heart tissues， as well as the phosphorylation levels of PI3K and Akt proteins， were verified. H9c2 cardiomyocytes were divided into control group （CON group）， DOX group （2 μmol/L）， and GDOX group （2 μg/mL GA+2 μmol/L DOX） to determine cell viability and the levels of key glycolytic substances in the cells. RESULTS Six common pathways were identified from transcriptomics and proteomics， including the Apelin signaling pathway， the PI3K-Akt signaling pathway， and insulin resistance. Among them， the Apelin and PI3K-Akt signaling pathways were the most enriched in terms of gene numbers. Target validation experiments showed that compared to the CON group， the relative expression of Apelin， PI3K and Akt mRNA and protein levels， as well as the phosphorylation levels of PI3K and Akt proteins， were significantly decreased in the DOX group （P＜0.05 or P＜0.01）. The relative expression of Apelin， PI3K and Akt mRNA and the phosphorylation levels of PI3K and Akt proteins were significantly increased in the GDOX group as compared with the DOX group （P＜0.05 or P＜0.01）. Cellular experiments indicated that compared to the CON group， cell viability in the DOX group was significantly decreased （P＜0.05）， the relative uptake of glucose and the relative production of pyruvate and lactate were significantly increased （P＜0.05）， and the relative production of ATP was significantly reduced （P＜0.05）. Compared to the DOX group， cell viability in the GDOX group was significantly increased （P＜ 0.05）， and the relative production of pyruvate and lactate was significantly reduced （P＜0.05）. CONCLUSIONS GA may alleviate DOX-induced cardiotoxicity by upregulating the mRNA and protein expression of Apelin， PI3K， and Akt in heart tissues， and regulating glycolytic processes.

Previous research on traditional Chinese medicine tongue inspection has mainly focused on its development,clinical application,and objectification,ignoring the fundamental question of "why tongue inspection is important in traditional Chinese medicine diagnosis" and neglecting the dominant role of traditional Chinese medicine brain thinking activities during diagnosis. Therefore,applying modern cognitive neuroscience technology to explore the impact of tongue inspection information on traditional Chinese medicine diagnostic thinking from an empirical research perspective may open up a new path for future tongue inspection research. This article proposes the combined application of eye tracking and event-related potential technology,drawing on the experimental paradigm of text reading inference correction in cognitive psychology,to collect eye movement and electroencephalogram data of participants induced by changes in tongue information during the reading process of traditional Chinese medicine medical records. This method can achieve synchronous observation of the focus areas and electroencephalogram signals of the subjects during the reading process,and provide cognitive scientific evidence for "why tongue inspection is important in traditional Chinese medicine diagnosis" through statistical data analysis. This research approach integrates the theories,techniques,and methods of traditional Chinese medicine and cognitive science,and is of great significance for developing cognitive thinking research in traditional Chinese medicine.

Objective To investigate the regulatory effect of Xuebijing injection on inflammatory reaction during the preservation of isolated empty beating pig hearts with extracorporeal membrane oxygenation.Methods Twelve healthy Guangxi Bama miniature pigs were randomly divided into the Xuebijing group(n=6)and normal saline group(n=6).After the models were established in the Xuebijing group,Xuebijing injection was given at a dose of 5 mL/h through micropump in membrane oxygenator.In the normal saline group,an equivalent amount of 0.9％sodium chloride injection was pumped.Continuous pumping was performed for 8 h in both groups.The time of cardiac resuscitation and perfusion pressure,heart rate,perfusion flow rate after 8 h preservation were recorded in two groups.Pathological and ultrastructural changes of myocardial tissues in the left ventricular wall of hearts with cardiac arrest were observed after 8 h preservation.Serum levels of myocardial injury markers and inflammatory cytokines were detected in two groups at the beginning(T0),2 h(T2),4 h(T4),6 h(T6)and 8 h(T8)after model establishment,respectively.The expression levels of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate specific proteinase-1(Caspase-1),apoptosis-associated speck-like protein containing a CARD(ASC)messenger RNA(mRNA)in myocardial tissues were measured at T0,T2,T4,T6 and T8,respectively.Results There were no significant differences in the time of cardiac resuscitation and perfusion pressure,heart rate,perfusion flow rate after 8 h preservation between two groups(all P＞0.05).Compared with the normal saline group,the levels of lactate dehydrogenase(LDH)at T4,creatine kinase(CK),LDH and α-hydroxybutyrate dehydrogenase(α-HBDH)at T6 and T8,tumor necrosis factor(TNF)-α at T4,T6 and T8,and interleukin(IL)-6,IL-18 and IL-1 β at T0,T2,T4,T6 and T8 were lower,and the mRNA relative expression levels of NLRP3 and Caspase-1 at T2,T4 and T6,and Caspase-1 and ASC at T8 were lower in the Xuebijing group,respectively(all P＜0.05).Hematoxylin-eosin staining and transmission electron microscopy showed that the degree of myocardial injury in the Xuebijing group was slighter than that in the normal saline group.Conclusions Xuebijing injection may effectively mitigate inflammatory response and exert certain myocardial protection effect during the ECMO preservation of isolated empty beating pig hearts.

Objective·To identify the functional motifs of mucin 1(MUC1)involved in regulating tumor cell proliferation,migration,and stemness maintenance.Methods·Mutational characteristics of the MUC1 gene across different cancers were identified from The Cancer Genome Atlas(TCGA)database.Various MUC1 mutation sites were analyzed and localized,followed by ranking based on mutation frequency.Western blotting was used to screen high-frequency MUC1 mutants with stable protein expression.BT549 cell line with MUC1 knocked out and MCF-10A cell line were used to stably overexpress MUC1 wild-type(MUC1-WT)and mutants by using lentiviral technology.Immunofluorescence was used to detect the cellular localization of MUC1 mutants.Using MUC1-WT as a positive control and MUC1-AQA,a loss-of-function mutant,as a negative control,the biological functions of different MUC1 mutant cells were analyzed:cell proliferation ability was assessed by cell counting kit-8(CCK-8)assay and colony formation assay;cell migration ability was evaluated by wound-healing and Transwell assays;cell stemness was examined by sphere formation assay.Structural localization of MUC1 mutants was analyzed by using PyMOL software,and molecular docking analysis was performed by using a protein docking software(ZDOCK Server).Results·A total of 102 mutations located in the MUC1 coding region were identified in the TCGA database,among which five missense mutations(P418S,S251R,V359I,N271S,and N465H)exhibited higher frequencies and were located in the non-variable number of tandem repeats(non-VNTR)region.Further examination revealed that the MUC1-S251R,N271S,and V359I mutants could be stably expressed.The cellular localization assay indicated that these three mutants predominantly localized in the cytoplasm,but were also presented in the nucleus.The nuclear-to-cytoplasmic ratio showed minimal differences between MUC1-WT and the mutants.Analysis of the tumorigenic biological functions of the cells expressing different MUC1 mutants revealed that:① High expression of MUC1-WT significantly enhanced the proliferation ability of both BT549 and MCF-10A cells;the proliferation of MUC1-AQA,S251R,and N271S mutant cells was decreased compared to MUC1-WT cells,while MUC1-V359I mutant cells exhibited a similar proliferative profile to MUC1-WT cells.② The migration ability of MUC1-WT high-expressing cells was significantly enhanced,whereas MUC1-AQA cells demonstrated attenuated migration.In the BT549 cells,the migration ability of MUC1-S251R and V359I cells was similar to that of MUC1-WT cells,whereas MUC1-N271S cells showed reduced migration.In the MCF-10A cells,the migration ability of MUC1-N271S and MUC1-V359I cells was similar to that of MUC1-WT cells,whereas MUC1-S251R cells exhibited significantly decreased migration.③ Stemness was enhanced in both cell types with high MUC1-WT expression,while MUC1-AQA cells lost stemness;the cells with MUC1-N271S,V359I and MUC1-WT showed comparable maintenance of stemness,whereas MUC1-S251R cells demonstrated compromised stemness.PyMOL software analysis unveiled that MUC1-N271S and V359I were located in or around the sperm protein-enterokinase-agarin(SEA)region,specifically in the loop region and the β-sheet,respectively.The molecular docking analysis revealed that the stability of the complex formed by MUC1-WT or V359I with the extracellular domain of epidermal growth factor receptor(EGFR)surpassed that of MUC1-N271S or S251R,indicating a stability hierarchy of V359I>WT>N271S>S251R.Conclusion·MUC1 mutants exhibit diverse impacts on the biological functions of tumor cells,with their effects on proliferation correlating with the EGFR signaling pathway.MUC1-V359I is similar to MUC1-WT,indicating a negligible effect on tumor cell proliferation,migration,and stemness maintenance.Conversely,MUC1-S251 and N271 sites may be involved in the regulation of signaling pathways governing cell proliferation and migration and the MUC1-S251 site plays a critical role in maintaining cell stemness.

Objective:To establish and validate reference intervals of serum vitamin K for healthy children in China.Methods:A cross-sectional study was conducted from January 2020 to May 2023, involving 807 healthy children aged 0 to 14 years, selected by stratified random sampling based on the population distribution of children in eastern, central, western, and northeastern China. Sample collection was carried out in 16 hospitals across 12 provinces, autonomous regions, and municipalities. Basic information of the children was collected using a standardized self-design questionnaire. Serum levels of vitamin K 1 and vitamin K 2 (menaquinone-4 (MK-4), menaquinone-7 (MK-7)) were measured using liquid chromatography-tandem mass spectrometry. The reference intervals was established by direct approach. The children were divided into different groups by age. Inter-group comparisons were conducted using the Kruskal-Wallis non-parametric test, and the reference intervals ( P2.5- P97.5) were determined using non-parametric methods. Screening 40 healthy children for small sample validation based on age groups within the reference range(25 from eastern, 10 from central, and 5 from western regions). Results:The age of the 807 children was 5.00 (2.00, 9.81) years, and 495 (61.3%) were males and 312 (38.7%) females. Reference intervals were established for 795 children, of whom 303 children were aged 1 month to 3 years and 492 were aged 4 to 14 years. The reference intervals for serum vitamin K 1 were 0.09-4.54 μg/L for children aged 1 month to 3 years, and 0.10-1.73 μg/L for 4-14 years. For MK-7, the intervals were 0.07-1.42 μg/L for 1 month to 3 years and 0.19-2.03 μg/L for 4-14 years. The reference intervals for MK-4 in children aged 1 month to 14 years were 0-0.42 μg/L. The measured values of serum vitamin K 1, MK-4, and MK-7 in the validation samples did not exceed the reference limit in more than 2 samples. Conclusion:Reference intervals for vitamin K 1, MK-4, and MK-7 in healthy children aged 1 month to 14 years have been established and validated, and can be used to assess vitamin K nutritional status in children.

Objective To assess the feasibility of utilizing the ExacTracDynamic surface monitoring system(ETD)for setup and body surface monitoring in patients with thoracic tumors undergoing intensity-modulated radio-therapy(IMRT).Methods Patients receiving IMRT for thoracic tumors were included in this study.The enrolled patients were alternatively assigned to either conventional cross curve positioning(control group)or surface monitoring system-assisted positioning(experimental group).ETD X-ray images were utilized for calibration purposes prior to radiotherapy,enabling the determination of setup errors.A region of interest(ROI)was delineated on the body surface above the sternum,and real-time body surface monitoring was performed based on this ROI during radiotherapy.Post-radiotherapy X-ray images were obtained to verify patient position.Data regarding left-right(X),head-foot(Y),abdomen-back(Z),pitch,roll,and yaw directions were recorded and analyzed.Results A total of 60 patients were enrolled,with 754 fractions of radiotherapy in the control group and 718 fractions in the experimental group.The setup errors in the X and Z directions were significantly smaller in the experimental group compared to the control group(P<0.05).Moreover,there was a significant reduction in the number of setup errors≤0.50 cm for X,Y,and Z directions,as well as≤1.00° for Roll angle in the experimental group compared to the control group(P<0.05).Additionally,differences were observed between surface monitoring and X-ray image verification regarding position deviation along Y and Z directions(P<0.05),although these deviations remained within submillimeter levels on average.Conclusion Surface monitoring system-assisted positioning can enhance radiotherapy setup accuracy among thoracic tumor patients,particularly along X and Z directions.Furthermore,when setting ROI above sternum on body surface area,surface monitoring provides better reflection of target area's position deviation.