Objective The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains is exacerbating the global burden of tuberculosis (TB), highlighting the urgent need for new treatment strategies for TB. Methods The recombinant adenovirus vaccine expressing cyclic di-adenosine monophosphate (c-di-AMP) phosphodiesterase B (CnpB) (rAd-CnpB), was administered to normal mice via mucosal immunization, either alone or in combination with drug therapy, to treat Mtb respiratory infections in mice.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of antibodies in serum and bronchoalveolar lavage fluid (BALF). Real-time quantitative PCR was performed to assess the transcription levels of cytokines interferon γ(IFN-γ) and interleukin 10(IL-10) in mouse lungs. Flow cytometry was used to determine the proportions of CD4⁺ and CD8⁺ T cell subsets in the lungs and spleens. ELISA was employed to measure the levels of cytokines IFN-γ, IL-2, IL-10, inflammatory factors IL-6, and tumor necrosis factor α (TNF-α) secreted by spleen cells following antigen stimulation. The bacteria loads in the lungs and spleens of Mtb-infected mice were enumerated by plate counting methods. Resluts Intranasal immunization with rAd-CnpB induced high titers of IgG in mouse serum and the production of IgG and IgA in BALF, along with alterations in T lymphocyte subsets in the lungs and spleens. Administration of rAd-CnpB, either alone or in combination with drugs, to Mtb-infected mice significantly increased serum IgG levels as well as IgA and IgG levels in BALF. rAd-CnpB immunization promoted the secretion of CnpB-specific cytokines and inflammatory factors by splenocytes in Mtb-infected mice. However, rAd-CnpB immunotherapy, either alone or combined with drugs, did not significantly affect the bacterial loads in the lungs and spleens of mice with Mtb respiratory infections. Conclusion Mucosal immunization with rAd-CnpB induced significant mucosal, humoral and cellular immune responses in mice, and significantly enhanced CnpB-specific cellular immune responses in Mtb-infected mice.
Animals ; Adenoviridae/immunology* ; Mycobacterium tuberculosis/genetics* ; Mice ; Female ; Phosphoric Diester Hydrolases/genetics* ; Tuberculosis Vaccines/administration & dosage* ; Tuberculosis/prevention & control* ; Mice, Inbred BALB C ; Cytokines ; Lung/microbiology* ; Immunization ; Bronchoalveolar Lavage Fluid/immunology* ; Immunity, Mucosal

BACKGROUND: Recent studies have provided compelling evidence that exposure to brominated flame retardants (BFRs) can adversely affect human health. We aim to explore the potential impact of BFRs on adiposity and central obesity. METHODS: Data from the National Health and Nutrition Examination Surveys (NHANES) cycles conducted between 2009 and 2014 was used to study the connections between variables. After filtering, we analyzed a sample of 4,110 adults aged 20 years and above. Our goal was to examine the potential association between BFRs and consequences and investigate the part played by oxidative stress and inflammatory markers as intermediaries. To achieve this, we used advanced statistical methods such as weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and the Bayesian kernel machine regression (BKMR). RESULTS: The findings showed that among the examined chemicals, exposure to PBDE85 (weight: 41%), PBDE100 (24%), and PBB153 (23%) may be the dominant contributors to general obesity risk. Upon controlling for all variables that could impact the results, it was found that the QGC outcomes indicated a positive correlation between exposure to mixtures of brominated flame retardants and the occurrence of abdominal obesity (OR = 1.187, 95% CI: 1.056-1.334, p = 0.004). Significant contributions were made by PBDE85 (52%), PBB153 (27%), and PBDE100 (21%). Mediation analysis shows that lymphatic cells (LC) and albumin (ALB) partially mediate the link between brominated flame retardants and obesity. The results of BKMR are generally consistent with those of WQS and QGC. CONCLUSION At a population level, our research has revealed a noteworthy correlation between BFRs and obesity. However, further investigation is required through prospective cohort studies and in-depth mechanistic exploratory studies.
Humans ; Flame Retardants/adverse effects* ; Oxidative Stress/drug effects* ; Adult ; Male ; Female ; Middle Aged ; Inflammation/epidemiology* ; Obesity/chemically induced* ; Biomarkers/blood* ; Nutrition Surveys ; Mediation Analysis ; Young Adult ; United States/epidemiology* ; Environmental Exposure/adverse effects* ; Aged ; Environmental Pollutants/adverse effects* ; Halogenated Diphenyl Ethers/adverse effects*

Objective:To investigate the role of dynamic changes in liver stiffness measurement (LSM) in predicting liver-related end-point events (LREs) occurrence in patients with chronic hepatitis B (CHB) with liver fibrosis during long-term antiviral therapy.Methods:Data were collected from CHB patients whose liver biopsy results showed Metavir fibrosis stage F2～F4 or clinically diagnosed cirrhosis. Entecavir antiviral therapy was mainly administered. Follow-up was conducted once every six months. Clinical data such as demographic information, blood routine tests, liver biochemical parameters, HBV virological and serological test results, and LSM were collected. Dynamic changes in LSM were categorized into four types based on LSM levels before treatment (0y) and following two years of antiviral therapy (2y) : (1) LSM 0y < 10 kPa and LSM 2y < 10 kPa, i.e., LSM persisted < 10 kPa; (2) LSM 0y < 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM increased to ≥ 10 kPa; (3) LSM 0y ≥ 10 kPa and LSM 2y < 10 kPa, i.e., LSM decreased to < 10 kPa; (4) LSM 0y ≥ 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM persisted ≥ 10 kPa. The predictive role of the dynamic changes of LSM in the occurrence of LREs was analyzed. The Wilcoxon rank-sum test was used for quantitative data. Fisher's exact test was used for categorical data. Multivariate analysis was performed using the Cox proportional hazards regression model. Survival curves were plotted and compared using the Kaplan-Meier. Results:A total of 713 CHB cases with liver fibrosis were included, among whom 512 had cirrhosis. The cumulative incidence of LREs following two years of antiviral therapy was low in patients with LSM 0y < 10 kPa during follow-up (all patients: LSM persisted < 10 kPa 1.6% vs. LSM increased to ≥ 10 kPa 0%; cirrhosis subgroup: LSM persisted < 10 kPa 0% vs. LSM increased to ≥ 10 kPa 0%). The 5-year cumulative incidence of LREs following two years of antiviral treatment was significantly higher in patients with LSM0y ≥ 10 kPa than in those with LSM persisting ≥ 10 kPa and those with LSM decreasing to < 10 kPa during follow-up (all patients: LSM persisted ≥ 10 kPa 12.4% vs. LSM decreased to < 10 kPa 3.6%; cirrhosis subgroup: LSM persisted ≥ 10 kPa 12.6% vs. LSM decreased to < 10 kPa 4.3%). Patients with LSM persisting at ≥ 10 kPa had a significantly increased risk of LREs following two years of antiviral treatment compared with those whose LSM decreased to <10 kPa during follow-up after adjusting for age, gender, baseline body mass index, platelet count, and alanine aminotransferase (all patients, aHR=2.96, 95% CI: 1.41～6.24, P=0.005; cirrhosis subgroup, aHR=2.74, 95% CI:1.26～5.95, P=0.011). Conclusions:LSM<10 kPa before antiviral treatment had a lower risk of liver-related endpoint events following two years of treatment among CHB patients with liver fibrosis. LSM ≥10 kPa before antiviral treatment and LSM persisted ≥10 kPa two years following treatment had a significantly higher occurrence risk of liver-related endpoints than LSM<10 kPa following treatment among CHB patients with liver fibrosis.

Objective:To investigate the interventional effect of Rhizoma Corydalis on mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS),as well as the potential mechanism of Rhizoma Corydalis in the treatment of UC based on metabolomics and inflammation biomarkers.Methods:A mouse model of UC was established,and then the mice were divided into model group,high-dose group(1.517 g/kg crude drug),middle-dose group(0.986 g/kg crude drug),low-dose group(0.455 g/kg crude drug),and positive drug group(5-aminosalicylic acid at a dose of 718.8 mg/kg),while the mice without modeling were selected as normal group(0.9%NaCl by gavage).The mice in each group were administered for 7 consecutive days,and phenotypic parameters were dynamically moni-tored,such as body weight change,disease activity index(DAI),mean daily food intake,and daily water intake.The mice were sacri-ficed after 7 days to collect serum and colon tissue samples;ELISA was used to measure the serum levels of the proinflammatory fac-tors interleukin-6(IL-6),interleukin-17A(IL-17A),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α),and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was used to perform the non-targeted metabolomics analysis and compare the differences in se-rum metabolite profiles between groups.The mice were selected for modeling and validation with the same method,and glutathione(GSH)was selected as the positive drug.Colon length and mucosal damage were assessed,and quantitative real-time PCR was used to measure the relative mRNA expression levels of the key genes in the glutathione synthesis pathway(γ-glutamylcysteine synthetase[γ-GCS]and oxidative stress regulators yap1p and skn7)and mito-chondrial GSH transporter protein(Slc25a39)in colonic tissue.Results:Rhizoma Corydalis significantly improved weight loss,DAI,and colon length in a dose-dependent manner in the model animals,and there were reductions in the serum levels of IL-6,CRP,and TNF-α,while it had no significant effect on IL-17A.The metabolomics analysis revealed 21 potential biomarkers associated with amino acid and lipid metabolism,which were significantly regulated by Rhizoma Corydalis.In the verification experiment,both Rhi-zoma Corydalis and GSH exerted a significant protective effect against colonic mucosal damage without affecting colon length.Rhizoma Corydalis upregulated the expression of genes associated with glutathione synthesis,especially γ-GCS,suggesting that Rhizoma Co-rydalis could enhance intestinal antioxidant defenses.Conclusion:Rhizoma Corydalis has a therapeutic potential in a mouse model of DSS-induced UC and can alleviate symptoms,reduce the serum levels of inflammatory markers,and regulate metabolic pathways,and upregulation of the genes associated with glutathione synthesis suggests that the drug can enhance intestinal antioxidant defenses.

Objective To establish,based on new diagnostic criteria for osteoradionecrosis of the jaws(ORNJ),an animal model with a controllable bone defect range and early and mild ORNJ characteristics.Methods A method involving single high-dose irradiation with an electron linear accelerator was applied.According to the irradiation dose,the animals were divided into a group(control group);b group(12 Gy group);and c group(14 Gy group).Six rabbits were randomly assigned to each group,b and c groups were uniformly selected for further radiotherapy of the right mandibular area.After 1 week,all animals were prepared with a standard bone defect at the right mandibular angle.After 4 weeks,the animals were euthanized,and general observations were conducted.CBCT scans and HU values of mandibular specimens,HE staining histological observations,Trap staining histology,and osteoclast counts were compared.And the statistical analysis were carried out.Results 4 weeks after the bone defect was created,the soft tissue in the surgical area of b and c groups showed mild swelling,purple skin,and erosion and ulceration of the oral mucosa,with c group showing the most significant changes.CBCT examination showed that the cortical bone of the irradiated areas in b and c groups was rough,while that of c group had poor continuity.No significant changes were observed in the extent of the bone defect in any group,b and c groups had significantly decreased HU values compared with a group.HE staining and histological observation suggested that the bone continuity of b and c groups had deteriorated;there was a large amount of fibrotic tissue proliferation,an increase in blank bone pits without cells,and an infiltration of inflammatory cells.Trap staining revealed a significant increase in osteoclasts in c group compared with a group.Conclusion By using an electron linear accelerator,a single dose of 14 Gy irradiation was applied to the mandibular angle area to create bone defects with consistent specifications in rabbits.After 4 weeks,an animal model that met the early diagnostic criteria of ORNJ and had controllable consistency in the range and degree of bone defects was established.

Objective To establish,based on new diagnostic criteria for osteoradionecrosis of the jaws(ORNJ),an animal model with a controllable bone defect range and early and mild ORNJ characteristics.Methods A method involving single high-dose irradiation with an electron linear accelerator was applied.According to the irradiation dose,the animals were divided into a group(control group);b group(12 Gy group);and c group(14 Gy group).Six rabbits were randomly assigned to each group,b and c groups were uniformly selected for further radiotherapy of the right mandibular area.After 1 week,all animals were prepared with a standard bone defect at the right mandibular angle.After 4 weeks,the animals were euthanized,and general observations were conducted.CBCT scans and HU values of mandibular specimens,HE staining histological observations,Trap staining histology,and osteoclast counts were compared.And the statistical analysis were carried out.Results 4 weeks after the bone defect was created,the soft tissue in the surgical area of b and c groups showed mild swelling,purple skin,and erosion and ulceration of the oral mucosa,with c group showing the most significant changes.CBCT examination showed that the cortical bone of the irradiated areas in b and c groups was rough,while that of c group had poor continuity.No significant changes were observed in the extent of the bone defect in any group,b and c groups had significantly decreased HU values compared with a group.HE staining and histological observation suggested that the bone continuity of b and c groups had deteriorated;there was a large amount of fibrotic tissue proliferation,an increase in blank bone pits without cells,and an infiltration of inflammatory cells.Trap staining revealed a significant increase in osteoclasts in c group compared with a group.Conclusion By using an electron linear accelerator,a single dose of 14 Gy irradiation was applied to the mandibular angle area to create bone defects with consistent specifications in rabbits.After 4 weeks,an animal model that met the early diagnostic criteria of ORNJ and had controllable consistency in the range and degree of bone defects was established.

Objective:To investigate the role of dynamic changes in liver stiffness measurement (LSM) in predicting liver-related end-point events (LREs) occurrence in patients with chronic hepatitis B (CHB) with liver fibrosis during long-term antiviral therapy.Methods:Data were collected from CHB patients whose liver biopsy results showed Metavir fibrosis stage F2～F4 or clinically diagnosed cirrhosis. Entecavir antiviral therapy was mainly administered. Follow-up was conducted once every six months. Clinical data such as demographic information, blood routine tests, liver biochemical parameters, HBV virological and serological test results, and LSM were collected. Dynamic changes in LSM were categorized into four types based on LSM levels before treatment (0y) and following two years of antiviral therapy (2y) : (1) LSM 0y < 10 kPa and LSM 2y < 10 kPa, i.e., LSM persisted < 10 kPa; (2) LSM 0y < 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM increased to ≥ 10 kPa; (3) LSM 0y ≥ 10 kPa and LSM 2y < 10 kPa, i.e., LSM decreased to < 10 kPa; (4) LSM 0y ≥ 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM persisted ≥ 10 kPa. The predictive role of the dynamic changes of LSM in the occurrence of LREs was analyzed. The Wilcoxon rank-sum test was used for quantitative data. Fisher's exact test was used for categorical data. Multivariate analysis was performed using the Cox proportional hazards regression model. Survival curves were plotted and compared using the Kaplan-Meier. Results:A total of 713 CHB cases with liver fibrosis were included, among whom 512 had cirrhosis. The cumulative incidence of LREs following two years of antiviral therapy was low in patients with LSM 0y < 10 kPa during follow-up (all patients: LSM persisted < 10 kPa 1.6% vs. LSM increased to ≥ 10 kPa 0%; cirrhosis subgroup: LSM persisted < 10 kPa 0% vs. LSM increased to ≥ 10 kPa 0%). The 5-year cumulative incidence of LREs following two years of antiviral treatment was significantly higher in patients with LSM0y ≥ 10 kPa than in those with LSM persisting ≥ 10 kPa and those with LSM decreasing to < 10 kPa during follow-up (all patients: LSM persisted ≥ 10 kPa 12.4% vs. LSM decreased to < 10 kPa 3.6%; cirrhosis subgroup: LSM persisted ≥ 10 kPa 12.6% vs. LSM decreased to < 10 kPa 4.3%). Patients with LSM persisting at ≥ 10 kPa had a significantly increased risk of LREs following two years of antiviral treatment compared with those whose LSM decreased to <10 kPa during follow-up after adjusting for age, gender, baseline body mass index, platelet count, and alanine aminotransferase (all patients, aHR=2.96, 95% CI: 1.41～6.24, P=0.005; cirrhosis subgroup, aHR=2.74, 95% CI:1.26～5.95, P=0.011). Conclusions:LSM<10 kPa before antiviral treatment had a lower risk of liver-related endpoint events following two years of treatment among CHB patients with liver fibrosis. LSM ≥10 kPa before antiviral treatment and LSM persisted ≥10 kPa two years following treatment had a significantly higher occurrence risk of liver-related endpoints than LSM<10 kPa following treatment among CHB patients with liver fibrosis.

Objective:To explore the role and the intervention effect of emodin in intestinal neuropathy in rats with severe acute pancreatitis (SAP) through the nucleotide binding oligomerization domain like receptor protein 3/cysteine containing aspartic acid protease-1 (NLRP3/Caspase-1) pathway.Methods:Forty male healthy SD rats aged 6-8 weeks with a weight of approximately 200g were randomly divided into control group, SAP model group, emodin treatment (EMO) group, and NLRP3 knockdown group. SAP were induced by retrograde injection of sodium deoxycholate into the pancreatic duct of rats and serum amylase of which were detected. The effective NLRP3 knockdown sequence was screened for NLRP3 knockdown animal experiments. Fluorescence quantitative polymerase chain reaction was used to detect the expression of NLRP3, Caspase-1, gasdermin-D (GSDMD), interleukin (IL)-1β, IL-18 and tumor necrosis factor-α(TNF-α) in the small intestine of each group. Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein (GFAP) in the small intestine of each group.Results:The amylase levels of the control group, SAP group, EMO group, and NLRP3 knockdown group were (277.73±24.92) U/L, (1018.57±282.89) U/L, (625.43±134.40) U/L, and (391.01±27.63) U/L, respectively. The SAP and EMO groups were significantly higher than the control group ( P<0.001), while the EMO and NLRP3 knockdown groups were significantly lower than the SAP group (all P<0.001). Compared with control group, the expression levels of NLRP3, Caspase-1, IL-1β, IL-18, TNF-α and GSDMD in SAP group were increased, with statistical significance (all P<0.001). Compared with SAP group, the NLRP3 knockdown group showed the expressionlevels of the above 6 genes were all decreased, and EMO group showed decreased gene expressing levels of NLRP3, IL-1β, IL-18 and TNF-α, with statistical significance (all P<0.05). The relative expression of GFAP in small intestine of control group, SAP group, EMO group and NLRP3 knockdown group were (1.00±0), (1.66±0.11), (1.13±0.02) and (1.13±0.02), respectively. Among them, the expression of GFAP in SAP group was increased compared with the control group; The expression of GFAP in EMO group and NLRP3 knockdown group was lower than that in model group, and the differences were statistically significant (all P<0.05). Conclusions:Emodin and knocking down NLRP3 can both promote the repair of SAP small intestine injury through the NLRP3/Caspase-1 signaling pathway, and thus play a protective role in the intestine.

Objective To understand the epidemiological characteristics of scrub typhus disease and to provide a scientific basis for the prevention and control of scrub typhus disease. Methods Descriptive epidemiological methods were used to analyze the population and regional distribution of scrub typhus. Seasonal characteristics were analyzed using concentration method and circular distribution method, and incidence trend was analyzed using joinpoint regression model. Results The annual incidence rate of scrub typhus was 0.95/100 000 from 2010 to 2022. The incidence rate of male was 0.77/100 000, lower than that of female 1.12/100 000 (χ²=18.89, P<0.05). The incidence rate of the 60-74 years old group was 3.38/100,000, and the total number of cases in the age group 45-74 years was 416 (74.95%). Occupational distribution was mainly among farmers, with 448 cases (80.72%). The top three regions with the highest number of reported cases (in order: Donghai County, Ganyu District, and Guannan County) reported a total of 416 cases, accounting for 74.95%. Concentration ratio was M=0.9408, and the incidence of scrub typhus disease was strictly seasonal. Circular distribution results showed a^-=-62.3728, S=20.8960. The circular distribution results indicated that the peak day was October 19th, and the peak period was between October 7 to December 19. The average annual percentage change (AAPC) of the incidence rate from 2010 to 2022 was 13.70%, 95% CI (-8.62%~41.48%), and the incidence rate showed an upward trend (t=1.15, P=0.249). Conclusion The incidence of scrub typhus disease is strictly seasonal, and the incidence rate over the years shows an upward trend. It is necessary to strengthen monitoring and take various intervention measures to reduce the risk of scrub typhus disease.

AIM:To investigate the protective effect of decylubiquinone(DUb)against medium-wave ultravio-let(UVB)-induced photodamage in HaCaT cells and its molecular mechanism.METHODS:The photodamage model was established by irradiating HaCaT cells with UVB.The experiment was divided into 6 groups:control group,UVB model group(30 mJ/cm2),UVB+low-,medium-and high-concentration(2.5,5 and 10 μmol/L)DUb groups,and DUb(10 μmol/L)group.Cell viability was detected using the CCK-8 assay.The morphological changes of the HaCaT cells were observed under a light microscope.The production of reactive oxygen species(ROS)content in the HaCaT cells was analyzed by fluorescence probe of DCFH-DA,and the superoxide dismutase(SOD)activity,intracellular glutathione(GSH)and malondialdehyde(MDA)levels were detected using biochemical reagents.The apoptosis rate was detected through flow cytometry.The protein expression levels of Bax、Bcl-2、caspase-3 and p53 were detected by Western blot.RESULTS:Compared with the control group,the cell viability of UVB model group was significantly decreased(P＜0.01),and obvious morphological changes,ROS and MDA were significantly increased(P＜0.01),GSH and SOD were significantly decreased(P＜0.01),the apoptosis rate was increased(P＜0.01).DUb pretreatment significantly increased the viability of UVB-induced photodamage HaCaT cells(P＜0.01),decreased intracellular ROS and MDA production(P＜0.05,P＜0.01),increased GSH content and SOD activity(P＜0.05,P＜0.01),and reduced apoptosis(P＜0.01).Addi-tionally,the protein expression levels of Bax,caspase-3 and p53 in medium-and high-dose DUb groups were significantly decreased(P＜0.01),while the anti-apoptotic protein Bcl-2 was significantly increased(P＜0.01).CONCLUSION:Dec-ylubiquinone can alleviate UVB-induced photodamage to HaCaT cells,reduce apoptosis and enhance the antioxidant ca-pacity of cells,and protect HaCaT cells against UVB radiation.