Objective To investigate the microbial contamination and its influencing factors of indoor air in public places in Xi'an City, to assess the health risk of employees, and to provide a scientific basis for improving the indoor environment of public places. Methods Total bacterial count and total fungal count in indoor air were monitored in hotels/inns, shopping malls/supermarkets, gyms, and waiting rooms in Xi'an from 2023 to 2024. The health risk assessment of employees was evaluated according to the Chinese Population Exposure Parameters Manual (Adult Volume). Results Overall, the standard-exceeding rate of total bacterial count in Xi'an was 3.85%, and the median values of total bacterial count and total fungal count were 350 CFU/m3 and 300 CFU/m3, respectively. The results of the generalized linear model showed that high indoor temperature and PM10 levels were associated with increased indoor bacterial concentrations (β>0, P<0.05), while high daily passenger flow, and high indoor relative humidity and PM₁₀ levels were associated with increased indoor fungal concentrations (β>0, P<0.05). The multivariate logistic regression showed that high levels of indoor bacterial and fungal concentrations were risk factors for respiratory discomfort among employees. The hazard quotient (HQ) values for all types of public places were less than 1, indicating that the health risk of microbial aerosol exposures for employees was relatively low. Conclusion The indoor microbial pollution in public places in Xi'an is relatively mild, but countermeasures still need to be taken to reduce indoor air microbial contamination.

Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

BackgroundPrenatal depression has an important impact on maternal health and pregnancy outcomes. Previous studies have shown that maternal prenatal depression is associated with social support， and social support is related to fear of childbirth. However， there is limited research on the relationship among maternal prenatal depression， social support and fear of childbirth， and no studies have specifically explored the influence of social support and fear of childbirth on prenatal depression in primiparous women. ObjectiveTo investigate the current status of prenatal depression among primiparous women， and to analyze the correlation between social support and fear of childbirth， and to further explore the influence of social support and fear of childbirth on prenatal depression in this population， so as to provide references for improving their mental health. MethodsA total of 380 primiparous women admitted to the inpatient department of Chengdu Wenjiang District People's Hospital from December 2022 to September 2023 were enrolled as study subjects. A self-made questionnaire， Edinburgh Postnatal Depression Scale （EPDS）， Social Support Rating Scale （SSRS） and Childbirth Attitudes Questionnaire （CAQ） were used to conduct the survey. Pearson correlation analysis was employed to examine the relationships between scale scores. Multiple linear regression analysis was conducted to identify influencing factors of prenatal depression. ResultsA total of 380 questionnaires were distributed， with 372 （97.89%） valid responses collected. Among the participants， 222 cases （59.68%） were identified with prenatal depression. Pearson correlation analysis revealed that EPDS score was negatively correlated with SSRS score （r=-0.283， P<0.01） and positively correlated with CAQ score （r=0.341， P<0.01）. Multiple linear regression analysis indicated that social support （β=-0.166， P<0.01） and fear of childbirth （β=0.269， P<0.01） were influencing factors of prenatal depression in primiparous women. ConclusionThe prevalence of prenatal depression among primiparous women is concerning， with depression levels showing significant associations with both social support and fear of childbirth.

Elucidate the influence of RFRP-3 on follicular development and steroid hormone synthe-sis in mice.Forty 6-week-old female KM mice were randomly allocated into four groups,namely the 0(control),100,500 and 2 000 ng/d treatment groups.Each group received daily intraperitoneal injections of RFRP-3 for a duration of 7 days.The ovarian coefficients were calculated and recorded by measuring the wet weight of the ovaries.The effects of RFRP-3 at different concentrations on follicular maturation in mice were investigated through HE staining.Western blot analysis was em-ployed to assess the expression of apoptosis-related proteins,steroidogenic enzymes,and oocyte se-cretion factors within the mouse ovaries.The concentrations of progesterone(P4)and estradiol(E2)in the serum of the mice were determined using radioimmunoassay techniques.The results re-vealed no significant differences in body weight between the experimental groups and the control.However,the ovarian coefficients in the 500 and 2 000 ng/d treatment groups were significantly re-duced when compared to the control(P＜0.01).A marked decrease in the numbers of secondary and antral follicles was observed in the 500 ng/d and 2 000 ng/d groups(P＜0.01),concomitant with a substantial increase in atretic follicles(P＜0.01).A significant decline in follicle count was also noted in these groups(P＜0.01).Compared to the control,the protein expression of Bax and Caspase3 was substantially upregulated in the 500 and 2 000 ng/d treatment groups(P＜0.05),while the expression of Bcl-2 protein was significantly downregulated(P＜0.01).Similarly,the protein expression of 3βHSD,StAR,CYP11a1,and CYP17a1 was significantly decreased at the 500 and 2 000 ng/d groups(P＜0.01).E2 concentrations were moderately reduced in the 500 ng/d group(P＜0.05)and significantly decreased in the 2000 ng/d group(P＜0.01),whereas P4 levels remained unchanged across all experimental groups.Notably,the expression of BMP15 and GDF9 at both the gene and protein levels was markedly attenuated in the 500 and 2 000 ng/d treatment groups compared to the control(P＜0.05).In conclusion,RFRP-3 appears to inhibit follicular de-velopment and steroid hormone secretion in mice by modulating the expression of apoptotic fac-tors,oocyte secretion factors,and steroidogenic enzymes within the ovaries.This study provides a theoretical foundation for understanding the regulatory mechanisms of RFRP-3 on mammalian follicular development and steroid hormone synthesis.

Objective:To explore the features of levels of lung cancer biomarkers in peripheral blood of adults in Beijing and surrounding areas, and establish personalized reference intervals for these biomarkers.Methods:A cross sectional study was conducted. The lung cancer biomarker data, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), neuron specific enolase (NSE), progastrin-releasing peptide (ProGRP), and squamous cell carcinoma antigen (SCC-Ag), collected from adults who underwent cancer prevention examinations at the Cancer Hospital of the Chinese Academy of Medical Sciences from July 2021 to July 2022 were retrospectively analyzed. The interquartile range method was used to eliminate outliers, and the P95 value was calculated. Upper limit of 5 lung cancer biomarkers in different gender and age groups were obtained by referring to the reference intervals of quantitative analytes in the clinical laboratory (WS/T 402-2024). By analyzing the data of 208 adults who underwent cancer prevention physical examinations at the same center in June 2021 and 140 patients with benign lung masses confirmed by surgical resection pathology from January 2016 to June 2022, the established reference intervals for biomarkers were validated. Results:Two thousand six hundred and twenty-six cases of apparently healthy physical examiners were included for constructing reference intervals, including 1 456 males (55.4%) and 1 170 females (44.6%); the age range was 20-88 years old. The serum levels [ M ( Q1, Q3)] of CEA, NSE, ProGRP, SCC-Ag and CYFRA21-1 in 2 626 cases were 1.63 (1.07, 2.43) ng/ml, 13.08 (11.44, 14.77) ng/ml, 34.93 (29.02, 42.19) pg/ml, 0.80 (0.60, 1.00) ng/ml and 1.96 (1.48, 2.63) ng/ml, respectively. The serum levels of CEA [1.88 (1.22, 2.76) ng/ml vs. 1.41 (0.93, 2.02) ng/ml], NSE [13.31 (11.87, 15.00) ng/ml vs. 12.69 (10.96, 14.53) ng/ml], SCC-Ag [0.9 (0.7, 1.1) ng/ml vs. 0.7 (0.6, 0.9) ng/ml], and CYFRA21-1 [2.02 (1.53, 2.71) ng/ml vs. 1.87 (1.40, 2.51) ng/ml] in males were higher than those in females, and ProGRP [34.00 (28.25, 41.55) pg/ml vs. 36.12 (29.97, 42.98) pg/ml] was lower than that in females, and the differences were statistically significant (all P < 0.001). There were statistically significant differences in serum CEA levels between the groups of ≤ 40 years old (458 cases), >40-50 years old (827 cases), >50-60 years old (783 cases), >60-70 years old (412 cases), and >70 years old (146 cases) in pairwise comparison (all P < 0.05). Except for the age groups of ≤ 40 years old and >40-50 years old and the age groups of >60-70 years old and >70 years old, there were statistically significant differences in serum NSE levels among the other age groups in pairwise comparison (all P < 0.05). There were statistically significant differences in serum ProGRP levels between the 5 age groups (all P < 0.05). There were statistically significant differences when comparing the serum SCC-Ag level in the >40-50 age group, >50-60 age group and >60-70 age group with that in the ≤40 age group and >70 age group, respectively (all P < 0.05). However, there was no statistically significant difference between the other age groups in pairwise comparison (all P > 0.05). There were statistically significant differences in serum CYFRA21-1 levels between the 5 age groups (all P < 0.05). When gender and age were not distinguished, the P95 values of serum CEA, NSE, ProGRP, SCC-Ag and CYFRA21-1 levels were 4.44 ng/ml, 16.61 ng/ml, 57.65 pg/ml, 1.50 ng/ml, and 4.21 ng/ml, respectively. Considering gender and age, except for the >70 age group with no statistically significant difference in the P95 value of serum CEA level between males and females ( P > 0.05), the P95 value of serum CEA level in males was higher than that in females in all other age groups (all P < 0.001); the P95 values of serum CEA level in both males and females increased with age, but showed a decreasing trend in males over the age of 70. The P95 value of serum NSE level in males was higher than that in females in the age groups of ≤ 40 years and >40-50 years (both P < 0.05), while there was no statistically significant difference in the P95 value of serum NSE level between males and females in other age groups (all P > 0.05). The P95 values of serum NSE level in both males and females decreased firstly and increased later with age, reaching their highest levels at the age of >70. The P95 values of serum ProGRP level in females aged ≤ 40 and >50-60 were higher than those in males (both P < 0.05), while there was no statistically significant difference in the P95 value of serum ProGRP level between genders in other age groups (all P > 0.05); the P95 values of serum ProGRP level in both males and females increased with age. There was no statistically significant difference in the P95 value of serum SCC-Ag level between males and females in the ≤ 40 age group ( P > 0.05), while the P95 value of serum SCC-Ag level in males was higher than that in females in all other age groups (all P < 0.05). The P95 values of serum SCC-Ag level in males increased with age, while they were stable in females. There was no statistically significant difference in the P95 value of serum CYFRA21-1 level between males and females in the >60-70 age group ( P > 0.05), while the P95 value of serum CYFRA21-1 level in males was higher than those in females in all other age groups (all P < 0.05); the P95 values of serum CYFRA21-1 level in both males and females increased with age. Based on data from 2 626 apparently healthy physical examiners, reference intervals for the levels of 5 lung cancer biomarkers were constructed in different age groups of different genders. Validation was conducted on 208 physical examiners and 140 patients with benign lung lesions, and it was found that the compliance rate of using newly created reference intervals for different gender and age groups to interpret detection results was >90%, and the validation was passed. Conclusions:There are gender and age differences in the reference intervals of CEA, CYFRA21-1, NSE, ProGRP, and SCC-Ag in peripheral blood of adults in Beijing and surrounding areas. The constructed reference intervals of gender and age for biomarkers have been validated and shown good results, providing reference for optimizing the clinical application of lung cancer-related biomarkers.

Ischemic stroke and hemorrhagic stroke have different pathogenic mechanisms,but share similarities in metabolic dysregulation,inflammatory responses and oxidative stress.This paper summarized 28 metabolic markers shared between ischemic stroke and hemorrhagic stroke with consistent trends through literature review.It also provided an overview of their involvement in abnormal energy metabolism,inflammatory responses,blood-brain barrier disruption,and neural damage in relation to stroke.The aim is to provide a scientific basis for future prognosis,curative efficacy evaluation and future homotherapy of ischemic stroke and hemorrhagic stroke,and provide insights for the development of new therapies and new drugs.