In order to explore the relationship between ubiquitin proteasome system(UPS)and au-tophagy after macrophage was infected with Brucella.On the one hand,the levels of LC3 Ⅱ、P62 and 20S proteasomes in cell supernatant and peritoneal fluid were determined respectively after RAW264.7 cells were infected and BALB/c mice were intraperitoneal inoculated with Brucella suis(B.suis).The results displayed that UPS was activated firstly,followed by autophagy after B.suis infection.On the other hand,we prepared the UPS-inhibited-cells and ALP-inhibited-cells by lacta-cystin and 3-methy ladenine(3-MA),and then the cells were infected by B.suis and the levels of LC3 Ⅱ、P62 与 20S proteasomes in cell supernatant were determined.The results showed that the ALP function was significantly improved when the effect of M

OBJECTIVE To investigate the characteristics of influenza A and influenza B viruses infections in the children aged between 0 and 14 years old after COVID-19 was downgraded to category B management of infectious diseases.METHODS From Jan.2023 to Feb.2024,a total of 2349 children aged between 0 and 14 years old who were treated in Beijing Hospital of Traditional Chinese Medicine,Capital Medical University due to influenza-like symptoms of infection and received nucleic acid testing for influenza A and influenza B viruses were recruited as the research subjects.The gender and age of the children as well as the seasons were observed by chi-square test.RESULTS Totally 2349 children were included in the study,and the total positive rate of influenza was 49.85％(1171/2349);the positive rate of influenza A virus was 36.36％(854/2349),the positive rate of influenza B virus was 13.92％(327/2349),and the positive rate of the mixed infections of influenza A virus and influenza B virus was 0.43％(10/2349).The positive rate of influenza A of the girls was the highest(44.17％)(x2=8.980,P=0.011)among the children aged less than 5 years old;the positive rate of influenza B of the boys was the highest(17.19％)(x2=8.378,P=0.015)among the children aged between 5 and 10 years old.There was significant difference in the positive rate of influenza A virus among the seasons in 2023 to 2024(x2=268.12,P＜0.001);the prevalence rate was 60.93％in spring,44.40％in autumn,22.01％in winter.There was significant difference in the positive rate of influenza B virus among the seasons in 2023 to 2024(x2=373.16,P＜0.001),and the preva-lence rate was 25.44％in winter.CONCLUSIONS The influenza viruses are prevalent in spring,autumn and winter from 2023 to 2024,and the influenza A is dominant.The positive rate of influenza viruses shows an upward trend among the children aged between 0 and 14 years old after the COVID-19 is downgraded to category B management of infectious diseases,with the peak of prevalence lagging behind.

This study aims to evaluate the preventive effect of the exogenous protein chIFN-γ-chCD154 against Salmonella typhimurium(S.typhimurium)infection in White Leghorn chick-ens,and the potential mechanism.In this study,Escherichia coli was used to express the proteins chIFN-γ,chCD154 and chIFN-γ-chCD154.Before S.typhimurium infection,the White Leghorn chickens were pre-immunized via drinking water for three consecutive days,and infected with S.typhimurium by gavage.The results from Western blot,quantitative real-time PCR(qRT-PCR)analysis and histopathology analysis showed that compared to chIFN-γ and chCD154,chIFN-γ-chCD154 pre-treatment could synergistically increase the survival rate of infected chickens,reduce the bacterial load in the liver and cecum,and attenuate the pathological damage of liver and cecum.Moreover,chIFN-γ-chCD154 significantly decreased the mRNA expression of Toll-like receptor-4(TLR-4)and myeloid differentiation primary response gene 88(MyD88)in the cecum,and then inhibited the mRNA expression of NF-κB and pro-inflammatory cytokines(TNF-α and IL-6),and maintained the integrity of the intestinal tight junction proteins(zo-1,claudin-1,occlu-din).Compared with single protein pretreatment,chIFN-γ-chCD154 pretreatment significantly up-regulated the mRNA expression of the genes related to the vitamin D(VD)pathway(cyp27b1,VD receptor VDR,antimicrobial peptide AvBD7 and cathelicidin-b1)in S.typhimurium-infected peripheral blood mononuclear cells(PBMCs).The results of colony counting showed that the num-ber of S.typhimurium in the chIFN-γ-chCD154 group were the lowest.Also,chIFN-γ-chCD154 could up-regulate the relative abundance of beneficial bacteria such as Blautia,Ruminococcus,En-terococcus and Faecalibacterium,while down-regulate the relative abundance of harmful bacteria such as Staphylococcaceae in the cecum and improve the intestinal dysbiosis.In conclusion,chIFN-γ-chCD154 could activate the VD-antimicrobial peptide pathway and inhibit the TLR-4/MyD88/NF-κB inflammatory signaling pathway in S.typhimurium-infected chickens,which significantly improve the intestinal barrier function,reduce the inflammatory damage of liver and cecum,im-prove the structure of cecum microbial,promote the health of intestinal tract,and provide theoreti-cal basis for the development of chIFN-γ-chCD154 as a safe and effective alternative antibiotic.

This study aims to evaluate the preventive effect of the exogenous protein chIFN-γ-chCD154 against Salmonella typhimurium(S.typhimurium)infection in White Leghorn chick-ens,and the potential mechanism.In this study,Escherichia coli was used to express the proteins chIFN-γ,chCD154 and chIFN-γ-chCD154.Before S.typhimurium infection,the White Leghorn chickens were pre-immunized via drinking water for three consecutive days,and infected with S.typhimurium by gavage.The results from Western blot,quantitative real-time PCR(qRT-PCR)analysis and histopathology analysis showed that compared to chIFN-γ and chCD154,chIFN-γ-chCD154 pre-treatment could synergistically increase the survival rate of infected chickens,reduce the bacterial load in the liver and cecum,and attenuate the pathological damage of liver and cecum.Moreover,chIFN-γ-chCD154 significantly decreased the mRNA expression of Toll-like receptor-4(TLR-4)and myeloid differentiation primary response gene 88(MyD88)in the cecum,and then inhibited the mRNA expression of NF-κB and pro-inflammatory cytokines(TNF-α and IL-6),and maintained the integrity of the intestinal tight junction proteins(zo-1,claudin-1,occlu-din).Compared with single protein pretreatment,chIFN-γ-chCD154 pretreatment significantly up-regulated the mRNA expression of the genes related to the vitamin D(VD)pathway(cyp27b1,VD receptor VDR,antimicrobial peptide AvBD7 and cathelicidin-b1)in S.typhimurium-infected peripheral blood mononuclear cells(PBMCs).The results of colony counting showed that the num-ber of S.typhimurium in the chIFN-γ-chCD154 group were the lowest.Also,chIFN-γ-chCD154 could up-regulate the relative abundance of beneficial bacteria such as Blautia,Ruminococcus,En-terococcus and Faecalibacterium,while down-regulate the relative abundance of harmful bacteria such as Staphylococcaceae in the cecum and improve the intestinal dysbiosis.In conclusion,chIFN-γ-chCD154 could activate the VD-antimicrobial peptide pathway and inhibit the TLR-4/MyD88/NF-κB inflammatory signaling pathway in S.typhimurium-infected chickens,which significantly improve the intestinal barrier function,reduce the inflammatory damage of liver and cecum,im-prove the structure of cecum microbial,promote the health of intestinal tract,and provide theoreti-cal basis for the development of chIFN-γ-chCD154 as a safe and effective alternative antibiotic.

This study aims to investigate the mechanisms underlying the effects of the combined ac-tion of high-fat diet-induced obesity and the aflatoxin B1(AFB1)on hepatic oxidative stress and inflammatory responses.Thirty-six rats of similar weight and 4 weeks old were randomly divided into 4 groups,with 9 rats in each group:the blank control group(basal diet),the AFB1 group(0.4 mg/kg AFB1+basal diet),the HFD group(high-fat diet),and the HFD+AFB1 group(high-fat diet+0.4 mg/kg AFB1).Histological changes and lipid deposition were observed via hematox-ylin-eosin(HE)staining and Oil Red O staining.Levels of oxidative stress and inflammation-relat-ed factors were measured using commercial assay kits.The relative protein expression levels of factors involved in the Nrf2-Keap1 signaling pathway were assessed by Western blot analysis.The HE staining results showed that in the AFB1 group,the liver cells exhibited widespread watery de-generation,with shrunk and ruptured nuclei,inflammatory cells infiltration,and increased fibrosis.In the HFD group,liver cell fatty degeneration was observed,with cytoplasmic lipid droplet infil-tration.In the portal area,liver fibrosis was seen,with liver cell necrosis and inflammatory cell in-filtration in the fibrotic area,accompanied by lipofuscous granules.When HFD was applied to the AFB1 group,the abnormal state of liver interstitial and interstitial spaces was further aggravated,and a large number of lipid droplets appeared.The Oil Red O staining results showed that there were large numbers of dark red lipid droplets in the liver tissue of the HFD group,which were fused in strands.In the AFB1 group,lipid droplets could also be observed in the liver tissue of rats,but the number and degree were significantly less than those in the HFD group.The number and degree of red lipid droplets in the liver tissue of rats in the HFD+AFB1 group were higher than those in the AFB1 group and the HFD group.HFD exacerbated AFB1-induced oxidative stress by elevating ROS,MDA levels,and decreasing the expression of antioxidant stress factors such as CAT,SOD,Nrf2,HO-1,NQO1,and GCLC.Furthermore,the combined effect of HFD and AFB1 further significantly increased the levels of pro-inflammatory cytokines IL-2,IL-6,TNF-α,and IL-1β in the body.In summary,HFD treatment significantly exacerbated liver oxidative stress and in-flammatory responses in rats exposed to AFB1 through the Nrf2-keap1 signaling pathway.

This study aims to investigate the mechanisms underlying the effects of the combined ac-tion of high-fat diet-induced obesity and the aflatoxin B1(AFB1)on hepatic oxidative stress and inflammatory responses.Thirty-six rats of similar weight and 4 weeks old were randomly divided into 4 groups,with 9 rats in each group:the blank control group(basal diet),the AFB1 group(0.4 mg/kg AFB1+basal diet),the HFD group(high-fat diet),and the HFD+AFB1 group(high-fat diet+0.4 mg/kg AFB1).Histological changes and lipid deposition were observed via hematox-ylin-eosin(HE)staining and Oil Red O staining.Levels of oxidative stress and inflammation-relat-ed factors were measured using commercial assay kits.The relative protein expression levels of factors involved in the Nrf2-Keap1 signaling pathway were assessed by Western blot analysis.The HE staining results showed that in the AFB1 group,the liver cells exhibited widespread watery de-generation,with shrunk and ruptured nuclei,inflammatory cells infiltration,and increased fibrosis.In the HFD group,liver cell fatty degeneration was observed,with cytoplasmic lipid droplet infil-tration.In the portal area,liver fibrosis was seen,with liver cell necrosis and inflammatory cell in-filtration in the fibrotic area,accompanied by lipofuscous granules.When HFD was applied to the AFB1 group,the abnormal state of liver interstitial and interstitial spaces was further aggravated,and a large number of lipid droplets appeared.The Oil Red O staining results showed that there were large numbers of dark red lipid droplets in the liver tissue of the HFD group,which were fused in strands.In the AFB1 group,lipid droplets could also be observed in the liver tissue of rats,but the number and degree were significantly less than those in the HFD group.The number and degree of red lipid droplets in the liver tissue of rats in the HFD+AFB1 group were higher than those in the AFB1 group and the HFD group.HFD exacerbated AFB1-induced oxidative stress by elevating ROS,MDA levels,and decreasing the expression of antioxidant stress factors such as CAT,SOD,Nrf2,HO-1,NQO1,and GCLC.Furthermore,the combined effect of HFD and AFB1 further significantly increased the levels of pro-inflammatory cytokines IL-2,IL-6,TNF-α,and IL-1β in the body.In summary,HFD treatment significantly exacerbated liver oxidative stress and in-flammatory responses in rats exposed to AFB1 through the Nrf2-keap1 signaling pathway.

Organoids,as a three-dimensional structural model that has been rapidly developed and widely concerned in recent years,enable the key functions and microenvironment of internal organs to be simulated in the real world,and closely reflect the physiological and pathological characteristics of the natural occurrence and metastasis of tumors,providing a new platform for disease modeling,drug research and precision medicine.This paper briefly summarizes the limitations and development prospects of organoid models,analyzes the current construction and development of organoid models of lung cancer and its applicability compared with traditional models under the holistic concept of traditional Chinese medicine and the basic theory of syndrome differentiation and treatment,and discusses the application of organoid technology in the basic research of lung cancer treatment.The advantages in screening anti-tumor Chinese medicine and drug resistance research and precision medicine provide new ideas for realizing innovative breakthroughs in traditional Chinese medicine research combined with modern science and technology.

Objective:To analyze the association between inflammation-related dietary patterns and the risk for cognitive impairment in older adults aged ≥65 years in longevity areas in China by using reduced rank regression (RRR) analysis.Methods:This study used cross-sectional data from the 2021 Healthy Aging and Biomarkers Cohort Study, including the information about study participants' demographic characteristics, lifestyles, daily life activities, and disease histories. Dietary intake was obtained by using a simplified food frequency questionnaire. Cognitive impairment was evaluated based on the Mini-Mental State Examination Scale combined with years of education. Fasting venous blood samples were collected to detect inflammatory markers, especially high-sensitivity C-reactive protein (hs-CRP) and the platelet-to-lymphocyte ratio (PLR). RRR analysis was used to obtain inflammation-related dietary patterns using hs-CRP and PLR as response variables. Multivariate logistic regression model was used to analyze the association between dietary pattern score and the risk for cognitive impairment. Restricted cubic spline was used to explore the dose response relationship, and mediation analysis was used to quantify the mediating effects of hs-CRP and PLR.Results:Two dietary patterns were identified with RRR. The primary pattern was characterized by higher intakes of flour, red meat, and dairy products, and lower intake of fresh vegetables, explaining 6.84% of the variance in food intake and 0.50% of the variance in inflammatory markers. Compared with the T1 group, the T3 group had significantly higher risk for cognitive impairment ( OR=1.242, 95% CI: 1.034-1.491). Each one standard deviation increase in the dietary pattern score was associated with an 8.7% increase in the risk for cognitive impairment ( OR=1.087, 95% CI: 1.008-1.172), with a significant linear trend (overall-model P<0.001, non-linear P=0.295). Mediation analysis indicated that hs-CRP mediated 6.2% of the association between the dietary pattern and the risk for cognitive impairment. Conclusion:The inflammation- related dietary pattern characterized by higher consumption of flour, red meat, and dairy products and lower consumption of fresh vegetables is associated with an increased risk for cognitive impairment in older adults, and hs-CRP partially mediates this association.

Objective:To analyze the spatiotemporal correlation between the surveillance data of influenza in students reported by medical institutions and school absenteeism due to illness, and evaluate the application of Bayesian Structural Time Series model (BSTS) in the prediction of school influenza epidemic.Methods:A total of 13 schools in Dapeng new district of Shenzhen were selected. The incidence data of influenza in schools in Shenzhen from January 1, 2015 to December 31, 2019 were collected from China Disease Control and Prevention Information System and the illness related school absentence data during this period were collected from Shenzhen Student Health Surveillance System, and the spatiotemporal correlation between the data from two systems was analyzed and compared. BSTS was used to make long-term predictions of the monthly incidence of influenza in students in 2019 and short-term predictions of the weekly incidence of influenza in week 1-8 and week 45-52 of 2019 by using the data from two systems.Results:There was a temporal correlation between the data from China Disease Control and Prevention Information System and the data from Shenzhen Student Health Surveillance System ( r=0.93, P<0.001), and the lag of the former one was 1 day ( r=0.73, P<0.001). Influenza outbreaks were randomly distributed in different schools in Shenzhen, and there was no spatial correlation. The root mean square error ( RMSE) and mean absolute error ( MAE) were 0.35 and 0.28, respectively, in the long-term prediction, and the RMSE was 0.33 and 0.34, and the MAE was 0.26 and 0.28, respectively, in the short-term predictions of week 1-8 and week 45-52 of 2019, respectively, showing good prediction accuracy and fitting effect. Conclusion:By analyzing the data from China Disease Control and Prevention Information System and Shenzhen Student Health Surveillance System with BSTS, the dynamics of the school influenza epidemic can be accurately predicted, and effective technical support can be provided for the early warning and prevention and control of influenza epidemic.

Objective:To understand the changes in the prevelance smoking in people aged ≥15 years in Baoji, and provide evidence for the improvement of tobacco control strategies.Methods:Data were from the sampling survey of chronic diseases and their risk factors conducted in Baoji at an interval of five years from 2013 to 2023. The survey used multi-stage cluster random sampling method to select local people aged ≥15 years, and the information about their tobacco use were collected by face-to-face interview. Descriptive epidemiological methods were used to analyze the prevalence of smoking, and χ2 test was used to analyze the change trend. Results:The smoking rate in people aged ≥15 years in Baoji decreased from 2013 to 2023, and the standardized smoking rate decreased by 13.6% in 2023 compared with 2013. The standardized smoking cessation rate increased by 13.4% in 2018 compared with 2013, and the standardized smoking cessation rate decreased by 7.3% in 2023 compared with 2018. The standardized passive smoking rate decreased by 15.1% in 2018 compared with 2013, and the standardized passive smoking rate increased by 8.8% in 2023 compared with 2018. The average daily smoking amount increased by 3.7 cigarettes in 2018 compared with 2013, and the average daily smoking amount decreased by 3.9 cigarettes in 2023 compared with 2018.Conclusion:Progress has been made in tobacco control in Baoji, but problems still exist in tobacco control, to which close attention needs to be paid.