ObjectiveTo analyze the epidemiological trends and characteristics of brucellosis in humans (hereinafter referred to as brucellosis) in Tangshan City, Hebei Province from 2016 to 2023, and to provide a scientific basis for formulating brucellosis prevention and control strategies in the region. MethodsThe incidence data of human brucellosis in Tangshan City from 2016 to 2023 were collected from the China Disease Prevention and Control Information System. The diagnosis time, infection route, and clinical characteristics of the cases were obtained from the case investigation reports. Descriptive epidemiological methods were used to analyze the temporal, spatial, demographic distributions, and clinical characteristics of human brucellosis. Brucella species were identified using agglutination tests with bacterial suspension and A/M antigen-positive serum. ResultsA total of 2 193 cases of human brucellosis were confirmed and clinically diagnosed in Tangshan City from 2016 to 2023, with the peak incidence occured from March to August, and which exhibited distinct geographic distribution patterns. The highest incidence rate was found in people aged 60‒<70 years. The occupation of cases were primarily farmers. The incidence rate in males (528/100 000) was higher than that in females (184/100 000). All cases had confirmed exposure to infected animals or contaminated animal products. ConclusionThe epidemic of human brucellosis in Tangshan exhibited an overall steady downward trend from 2016 to 2023, except for a slight increase in 2016 and 2021, with the incidence rate controlled at 289/100 000‒335/100 000. The prevention and control situation of human brucellosis still remains severe, with the highest incidence rate in the eastern region of Tangshan, which are characterized by the breeding, slaughtering, and processing of cattle and sheep. Therefore, it it is necessary to enhance the prevention and control of human brucellosis among the personnel engaged in these industries in the eastern areas.

Five new flavan-4-ol glycosides jixueqiosides A-E (1-5) and two new flavan glycosides jixueqiosides F and G (6 and 7), along with twelve known flavan-4-ol glycosides (8-19), were isolated from the roots of Pronephrium penangianum. Comprehensive spectral analyses, X-ray single-crystal diffraction, and theoretical electronic circular dichroism (ECD) calculations established structures and absolute configurations. A single crystal structure of flavan-4-ol glycoside (14) was reported for the first time, while the characteristic ECD and NMR data for all isolated flavan-4-ol glycosides (1-5 , 8-19) were analyzed, establishing a set of empirical rules. Activity screening of these isolates showed that 8 and 9 could inhibit the proliferation of MDA-MB-231 and MCF-7 cells with IC₅₀ values of 7.93 ? 2.85 ?mol?L^-1 and 5.87 ? 1.58 ?mol?L^-1 (MDA-MB-231), and 2.21 ? 1.38 ?mol?L^-1 and 3.52 ? 1.55 ?mol?L^-1 (MCF-7), respectively. Western blotting and flow cytometry analyses demonstrated that 8 and 9 dose-dependently induced apoptosis in MDA-MB-231 cells by up-regulating BAX, activating caspase-3 and down-regulating BCL-2. Additionally, compound 8 affected autophagy-related proteins, increasing the ratio of LC3-II/LC3-I and Beclin-1 levels to inhibit MDA-MB-231 cell proliferation. Moreover, anti-inflammatory studies indicated that 2, 3, 7, 13, 14, and 18 moderately inhibited tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and nitric oxide (NO) release.
Humans ; Plant Roots/chemistry* ; Glycosides/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Flavonoids/isolation & purification* ; Cell Proliferation/drug effects* ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Molecular Structure ; Apoptosis/drug effects* ; Cell Line, Tumor ; Tumor Necrosis Factor-alpha/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Interleukin-6/immunology* ; Animals ; Mice

Objective To explore the effects of miR-373 and Janus kinase 2/signal transducer and activator of transcription 6 (JAK2/STAT6) signaling pathways on the M2 polarization of tumor associated macrophages (TAM) in rectal cancer. Methods THP-1 cells were induced into M0/M1/M2 macrophages, M0 macrophages were cocultured with Caco-2 cells to obtain TAM, Flow cytometry was used to detect the expression of CD86 and CD206, Real-time quantitative qPCR and Western blot were used to detect miR-373, inducible nitric oxide synthase (iNOS), toll-like receptor 4 (TLR-4), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), arginase 1 (Arg1), chitinase 3-like 1 (Ym1), resistin like α (Fizz1), IL-10 mRNA and protein levels. TAM were transfected and divided into overexpressing miR-373 group (miR-373-TAM) and control group (miR-NC-TAM), overexpressing miR-373+JAK2-TAM group (miR-373 combined with JAK2-TAM) and control group (miR-373 combined with NC-TAM), and then cocultured with Caco-2 cells. Flow cytometry was used to detect the expression of CD206 in TAM; Real-time quantitative PCR and Western blot were used to detect miR-373, Arg1, Ym1, Fizz1, IL-10, JAK2, STAT6 mRNA and protein levels in TAM; CCK-8 assay, colony formation assay, and Transwell assay were used to detect the proliferation, migration, and invasion ability of Caco-2 cells. Thirty nude mice were randomly divided into Caco-2 cells group, Caco-2 cells combined with miR-NC-TAM group, and Caco-2 cells combined with miR-373-TAM group, with 10 mice in each group. Rats in each group were subcutaneously injected with pure Caco-2 cells, Caco-2 cells combined with TAM, and Caco-2 cells combined with TAM overexpressing miR-373. After 4 weeks of cell inoculation, immunofluorescence staining was used to detect F4/80⁺CD206⁺cells level in tumor tissue; Real-time quantitative PCR and Western blot were used to detect miR-373, JAK2, STAT6, Arg1, Ym1, Fizz1, IL-10 mRNA and protein levels in tumor tissues. Results TAM tended to M2 polarization. After overexpression of miR-373, miR-373 level in TAM was increased, while Arg1, Ym1, Fizz1, IL-10, JAK2, STAT6 mRNA and protein levels were decreased, proliferation, migration, invasion ability of Caco-2 cells were decreased; Overexpression of JAK2 could partially reverse the effect of overexpression of miR-373 on the M2 polarization of TAM and proliferation, migration, invasion ability of Caco-2 cells. TAM could promote tumor growth; Overexpression of miR-373 could inhibit tumor growth and inhibit M2 polarization of TAM. Conclusion miR-373 could inhibit M2 polarization of TAM in rectal cancer, and miR-373 might inhibit proliferation and metastasis of rectal cancer cells by regulating the JAK2/STAT6 pathway.
MicroRNAs/metabolism* ; Humans ; STAT6 Transcription Factor/genetics* ; Signal Transduction/genetics* ; Animals ; Janus Kinase 2/genetics* ; Mice ; Tumor-Associated Macrophages/metabolism* ; Rectal Neoplasms/pathology* ; Caco-2 Cells ; Mice, Nude ; THP-1 Cells ; Mice, Inbred BALB C ; Cell Polarity ; Male

Objective Through integrative bioinformatics analysis of multi-source transcriptomic data, potential biomarkers to asthma epithelial cells were identified. The expression of these candidate target was subsequently validated in lung tissues and epithelial cells from asthma models. Methods The gene expression profile data of epithelial cells from three asthma patient cohorts and corresponding healthy controls were integrated from the Gene Expression Omnibus (GEO) database. Differential expression analysis and gene co-expression network analysis were performed to identify key genes and biological pathways associated with asthma. The key genes were validated in lung tissues and epithelial cells in asthma animal models. Results Differential gene expression analysis revealed 1121 upregulated and 1484 downregulated genes in epithelial cells from asthma patients compared with healthy controls. The biological pathway enrichment analysis revealed that the upregulated genes were mainly involved in glycosylation processes, whereas the downregulated genes were mainly associated with immune cell differentiation process. The gene co-expression network analysis revealed that module 9, enriched in glycosylation-related pathways, was significantly positively correlated with asthma, whereas module 17, associated with insulin and other signaling pathways, showed a significant negative correlation with asthma. We identified the genes of polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5), pyrroline-5-carboxylate reductase 1 (PYCR1), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as key genes within module 9, all of which were significantly upregulated in asthma. Finally, we validated that the expression levels of GALNT5, PYCR1, and CEACAM5 were significantly upregulated in epithelial cells from asthmatic lung tissue. Additionally, using a rat asthma model, we further confirmed that the protein levels of these three genes were significantly upregulated in lung tissues of the model group. Conclusion Through data integration and experimental validation, this study identified key genes and biological pathways closely associated with asthma pathogenesis. These findings provide a novel theoretical basis and potential targets for the diagnosis and treatment of asthma.
Asthma/metabolism* ; Humans ; Epithelial Cells/metabolism* ; Animals ; Biomarkers/metabolism* ; Gene Expression Profiling ; Transcriptome ; Gene Regulatory Networks ; Rats ; Computational Biology

Objective The study aims to investigate the immunological functions of the nucleocapsid (N) protein of the novel coronavirus Omicron (BA.1, BA.2) and evaluate the differences among different N proteins of mutant strains in immunogenicity. Methods By aligning sequences, the mutation sites of the Omicron (BA.1, BA.2) N protein relative to prototype strain of the novel coronavirus (Wuhan-Hu-1) were determined. The pET-28a-N-Wuhan-Hu-1 plasmid was used as template to construct pET-28a-BA.1/BA.2-N through single point mutation or homologous recombination. The three kinds of N protein were expressed in prokaryotic system, purified through Ni-NTA affinity chromatography, and then immunized into mice. The titer and reactivity of the polyclonal antibody, as well as the expression level of IL-1β and IFN-γ in mouse spleen cells, were detected using indirect ELISA and Western blot assay. Results The constructed prokaryotic expression plasmids were successfully used to express the Wuhan-Hu-1 N, BA.1 N, and BA.2 N proteins in E.coli BL21(DE3) at 37 DegreesCelsius for 4 hours. The indirect ELISA test showed that the titers of polyclonal antibody prepared by three N proteins were all 1:51 200. All three N proteins can increase the expression of IFN-γ and IL-1β cytokines, but the effect of Omicron N protein in activing two cytokines was more obvious than that of Wuhan-Hu-1 N protein. Conclusion The study obtained three new coronavirus N proteins and polyclonal antibodies, and confirmed that mutations in the amino acid sites of the N protein can affect its immunogenicity. This provides a basis for developing rapid diagnostic methods targeting N protein of different novel coronavirus variants.
Animals ; Mice ; SARS-CoV-2/genetics* ; Coronavirus Nucleocapsid Proteins/immunology* ; Nucleocapsid Proteins/isolation & purification* ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Mice, Inbred BALB C ; Interferon-gamma/metabolism* ; Interleukin-1beta/metabolism* ; Female ; Escherichia coli/metabolism* ; Mutation ; Humans

Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

Objective:To investigate the changes in brain functional network and structural-functional network coupling in children with drug-resistant epilepsy (DRE), and to analyze their correlation with cognitive function, disease duration, and age of onset.Methods:This study was a cross-sectional study. Clinical and imaging data of 19 children with DRE who received consultation and treatment at the Affiliated Hospital of Zunyi Medical University from August 2021 to August 2023 (DRE group) were prospectively included. Another 27 age-and sex-matched healthy children were collected as the healthy control group. All subjects had 3D-T 1WI, T 2 fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) scans and Wechsler Intelligence Scale assessments. Independent sample t-test and Mann-Whitney U test were used to analyze the global and local topological attributes, as well as the structural-functional coupling (SFC) values at the whole brain and modular levels in two groups. Correlations between abnormal resting state brain functional network indicators and the Wechsler Intelligence Scale score [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ)], disease duration and age of onset was evaluated using a Spearman or Pearson correlation analysis. Results:Compared to the healthy control group, DRE group exhibited decreased VCI, PRI, WMI, PSI, FSIQ and the differences were all statistically significant (all P<0.05). Both brain functional networks had small world attributes. There was a statistically significant difference in the area under the curve of sparsity of degree centrality (DC) in the left pallidum between the DRE group and healthy control group (2.998±0.942, 4.992±1.945, t=-4.07, FDR corrected P<0.05). Compared with the control group, the DRE group had decreased SFC within the limbic network (LN) ( P<0.05), increased SFC within the sensorimotor (SMN) ( P<0.05), decreased SFC between the default mode network-LN ( P<0.05), and increased SFC between the SMN-attentional network (AN) ( P<0.05). There was no statistically significant difference in SFC at the whole brain level between the two groups. Correlation analysis indicated that DC in left pallidum in DRE group negatively correlated with the PSI ( r=-0.537, P=0.018), and SFC between the SMN and AN demonstrated a negative correlation with age of onset ( r=-0.537, P=0.018). Conclusion:The altered DC in left pallidum may be related to cognitive impairment in children with DRE, providing biomarker information for the study of neural mechanisms in children with DRE.

Objective:To analyze the epidemic characteristics of human brucellosis in Tangshan City, Hebei Province from 2016 to 2024, and to establish a prediction model for forecasting incidence of human brucellosis in Tangshan City from 2025 to 2028, so that to provide evidence for prevention and control strategies.Methods:The incidence data of human brucellosis in Tangshan City from 2016 to 2024 were collected. Brucella strains isolated from blood cultures of patients with acute brucellosis were identified.The onset time and demographic distributions of brucellosis were analyzed using descriptive epidemiological methods. Chi-square test was used for statistical analysis. Python software was used to establish a seasonal autoregressive integrated moving average model (SARIMA model) and predict the incidence of brucellosis in Tangshan City from 2025 to 2028. Results:From 2016 to 2024, a total of 2 446 cases of human brucellosis in Tangshan City were reported, with the highest incidence in 2016 (378 cases) and the lowest in 2022 (277 cases).Seasonal variation was observed, with 54.87%(1 342/2 446) occurring in spring and summer (March to July). The incidence rate of male was 5.28/100 000, which was significantly higher than that of female (1.94/100 000) ( χ2=554.96, P<0.001). The cases spanned all age groups, with the highest incidence among those aged 50 to 59 (30.25%(740/2 446)). Farmers engaged in cattle/sheep breeding accounting for 85.73% (2 097/2 446) of cases. A total of 236 blood samples were collected from patients with acute brucellosis, and 12 Brucella strains were isolated and identified as sheep type Ⅲ Brucella. The optimal model constructed was SARIMA (1, 0, 0) (1, 0, 1) 12, which was used to predict the incidence of human brucellosis in Tangshan City from 2025 to 2028. The results showed that the overall incidence was relatively stable, retaining the characteristic single annual peak. Conclusions:Human brucellosis in Tangshan City peaks in spring/summer and predominantly affects cattle/sheep farmers. The SARIMA (1, 0, 0) (1, 0, 1) 12 model effectively fits the epidemiological data of human brucellosis in Tangshan City well and enables reliable future trend predictions, supporting scientific and effective prevention and control work.

Objective:To analyze the epidemic characteristics of human brucellosis in Tangshan City, Hebei Province from 2016 to 2024, and to establish a prediction model for forecasting incidence of human brucellosis in Tangshan City from 2025 to 2028, so that to provide evidence for prevention and control strategies.Methods:The incidence data of human brucellosis in Tangshan City from 2016 to 2024 were collected. Brucella strains isolated from blood cultures of patients with acute brucellosis were identified.The onset time and demographic distributions of brucellosis were analyzed using descriptive epidemiological methods. Chi-square test was used for statistical analysis. Python software was used to establish a seasonal autoregressive integrated moving average model (SARIMA model) and predict the incidence of brucellosis in Tangshan City from 2025 to 2028. Results:From 2016 to 2024, a total of 2 446 cases of human brucellosis in Tangshan City were reported, with the highest incidence in 2016 (378 cases) and the lowest in 2022 (277 cases).Seasonal variation was observed, with 54.87%(1 342/2 446) occurring in spring and summer (March to July). The incidence rate of male was 5.28/100 000, which was significantly higher than that of female (1.94/100 000) ( χ2=554.96, P<0.001). The cases spanned all age groups, with the highest incidence among those aged 50 to 59 (30.25%(740/2 446)). Farmers engaged in cattle/sheep breeding accounting for 85.73% (2 097/2 446) of cases. A total of 236 blood samples were collected from patients with acute brucellosis, and 12 Brucella strains were isolated and identified as sheep type Ⅲ Brucella. The optimal model constructed was SARIMA (1, 0, 0) (1, 0, 1) 12, which was used to predict the incidence of human brucellosis in Tangshan City from 2025 to 2028. The results showed that the overall incidence was relatively stable, retaining the characteristic single annual peak. Conclusions:Human brucellosis in Tangshan City peaks in spring/summer and predominantly affects cattle/sheep farmers. The SARIMA (1, 0, 0) (1, 0, 1) 12 model effectively fits the epidemiological data of human brucellosis in Tangshan City well and enables reliable future trend predictions, supporting scientific and effective prevention and control work.

Objective:To investigate the changes in brain functional network and structural-functional network coupling in children with drug-resistant epilepsy (DRE), and to analyze their correlation with cognitive function, disease duration, and age of onset.Methods:This study was a cross-sectional study. Clinical and imaging data of 19 children with DRE who received consultation and treatment at the Affiliated Hospital of Zunyi Medical University from August 2021 to August 2023 (DRE group) were prospectively included. Another 27 age-and sex-matched healthy children were collected as the healthy control group. All subjects had 3D-T 1WI, T 2 fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) scans and Wechsler Intelligence Scale assessments. Independent sample t-test and Mann-Whitney U test were used to analyze the global and local topological attributes, as well as the structural-functional coupling (SFC) values at the whole brain and modular levels in two groups. Correlations between abnormal resting state brain functional network indicators and the Wechsler Intelligence Scale score [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ)], disease duration and age of onset was evaluated using a Spearman or Pearson correlation analysis. Results:Compared to the healthy control group, DRE group exhibited decreased VCI, PRI, WMI, PSI, FSIQ and the differences were all statistically significant (all P<0.05). Both brain functional networks had small world attributes. There was a statistically significant difference in the area under the curve of sparsity of degree centrality (DC) in the left pallidum between the DRE group and healthy control group (2.998±0.942, 4.992±1.945, t=-4.07, FDR corrected P<0.05). Compared with the control group, the DRE group had decreased SFC within the limbic network (LN) ( P<0.05), increased SFC within the sensorimotor (SMN) ( P<0.05), decreased SFC between the default mode network-LN ( P<0.05), and increased SFC between the SMN-attentional network (AN) ( P<0.05). There was no statistically significant difference in SFC at the whole brain level between the two groups. Correlation analysis indicated that DC in left pallidum in DRE group negatively correlated with the PSI ( r=-0.537, P=0.018), and SFC between the SMN and AN demonstrated a negative correlation with age of onset ( r=-0.537, P=0.018). Conclusion:The altered DC in left pallidum may be related to cognitive impairment in children with DRE, providing biomarker information for the study of neural mechanisms in children with DRE.