AIM To explore the effects of Dahuang Lingxian Recipe on Th1/Th2 cell immune imbalance in a rat model of cholestatic liver fibrosis(CLF).METHODS 20 SD rats were randomly divided into the normal group,the model group,the ursodeoxycholic acid group(0.063 g/kg)and the Dahuang Lingxian Recipe group(4.8 g/kg),with 5 rats in each group.Except for those of the normal group,the rats of all other groups had open surgery of common bile duct ligation,followed by the gavage of corresponding drug two days later,and the procurement of the samples after gavage in the third week.The rats had their degree of liver fibrosis observed by HE and Masson stainings;their levels of serum total bile acid(TBA),alkaline phosphatase(AKP),γ-glutamyltransferase(γ-GT),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin(TBil)measured by the kit;their hepatic percentage of TGF-β1,p-Smad2 and p-Smad3 positive cells detected by immunofluorescence and immunohistochemical staining;their.hepatic expressions of TGF-β1,Smad4,NF-κB p65,Collagen Ⅰ and Collagen Ⅲ protein and mRNA detected by Western blot and RT-qPCR;their levels of helper T cell 1(Th1)and helper T cell 2(Th2)in peripheral blood detected by flow cytometry,and their ratio of Th1/Th2 calculated as well.RESULTS Compared with the model group,the groups intervened with either ursodeoxycholic acid or Dahuang Lingxian Recipe displayed well-ordered liver cells,hepatic lobules and hepatic cords;a small amount of fatty degeneration;significantly reduced connective hyperplasia of hepatic fibers;significantly narrowed fibrous cords;a small amount of blue fibrous septa;greatly improved pathological injuries including inflammatory infiltration of central vein and portal area;decreased levels of serum TBA,TBil,AKP,γ-GT,ALT and AST(P＜0.05);decreased hepatic expressions of TGF-β1,p-Smad2 and p-Smad3(P＜0.05);decreased hepatic expressions of TGF-β1,Smad4,NF-κB p65,Collagen Ⅰ and Collagen Ⅲ protein and mRNA(P＜0.05);and increased counts of Th1 cells in peripheral blood,decreased counts of Th2 cells,resultsing increased Th1/Th2 ratio(P＜0.05).And an even better effect was observed in the Dahuang Lingxian Recipe group.CONCLUSION Dahuang Lingxian Recipe can reduce or reverse CLF by inhibiting hepatic stellate cell activation through maintaining Th1/Th2 cell immune balance via the NF-κB/TGF-β1 signaling pathway.

Objective To explore the influencing factors of different types of small intestinal bacterial overgrowth(SIBO).Methods A total of 539 patients who were hospitalized in the Department of Gastroenterology,the Sixth Medical Center of PLA General Hospital from June 2021 to December 2021 and who underwent methane-hydrogen breath test were retrospectively selected.Based on breath test results,patients were divided into SIBO-negative group(n=300)and SIBO-positive group(n=239).The clinical data were compared between two groups.According to the specific values of breath test results,SIBO-positive patients were further divided into hydrogen-producing bacterial overgrowth(hydrogen-positive,n=103),intestinal methanogen overgrowth(methanogen-positive,n=80),and simultaneous methanogen and hydrogen-producing bacterial overgrowth(double positive,n=56)groups.Multivariate logistic regression analysis was employed to identify influencing factors of different SIBO types.Additionally,SIBO-positive patients were categorized by age into<45 years(n=23),45-60 years(n=82),60-75 years(n=124),and≥75 years(n=10)to compare SIBO positivity rates across age groups.Results The patients in SIBO-positive and double positive groups were older and had a lower body mass index(BMI)than those in SIBO-negative group,with statistically significant differences(P<0.05).Compared with the patients in SIBO-negative group,those in hydrogen-positive group showed a higher proportion of history of coronary heart disease,those in methanogen-positive group were older,and higher proportion of statin use,with statistically significant differences(P<0.05).Multivariate logistic regression analysis revealed that,among different SIBO types,a history of coronary heart disease served as an independent risk factor for hydrogen-producing bacterial overgrowth(OR=2.728,95%CI 1.271-5.857,P=0.010).For methanogen overgrowth,increasing age was identified as an independent risk factor(OR=1.040,95%CI 1.009-1.063,P=0.010),while the application of statin played the role of an independent protective factor(OR=0.420,95%CI 0.236-0.754,P=0.003).As for the simultaneous overgrowth of methane-producing and hydrogen-producing bacteria,increased BMI was found to be an independent protective factor(OR=0.870,95%CI 0.786-0.964,P=0.008).In SIBO-positive group,it was found that for patients aged<45 years,both the methane-positive rate and the double-positive rate were significantly lower than the hydrogen positivity rate(P<0.05).Moreover,among patients aged 45-60 years,the double-positive rate was significantly lower than the hydrogen positivity rate(P<0.01).When it comes to the hydrogen-positive rate,it was significantly lower for patients aged 45-60 and 60-75 years compared with that of patients aged<45 years(P<0.05).In contrast,the methane-positive rate and the double-positive rate were significantly higher for patients aged 45-60 and 60-75 years than those of patients aged<45 years(P<0.01).Conclusion A history of coronary heart disease and increasing age are independent risk factors for intestinal hydrogen-producing bacterial overgrowth and methanogen overgrowth,respectively.The application of statins and increased BMI are independent protective factors for intestinal methanogen simultaneous overgrowth of methanogen and hydrogen-producing bacteria,respectively.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.

Objective:To investigate the effects of TP53 genetic status(wild-type/mutated/null)on the drug resistance of decitabine(DAC)in myelodysplastic syndromes(MDS)and identify key resistance-associated genes.Methods:Two myeloid cell lines with distinct TP53 status(M-07e:wild-type;SKM-1:mutated;)were treated with gradient DAC concentrations(0-10 μmol/L)for 0-72 h.Cell viability was detected by CCK-8 assay.RNA-Seq transcriptomics,and methylation profiling were integrated to analyze differentially expressed genes.Results:Decitabine(DAC)treatment induced time-and dose-dependent inhibition of cell viability in CCK-8 assays,with SKM-1 cells exhibiting the highest resistance(IC50=5 μmol/L vs M-07e=0.5 μmol/L,P＜0.01).Transcriptomic analysis revealed 662 upregulated and 452 downregulated genes in DAC-treated M-07e cells,while SKM-1 cells showed 515 upregulated and 73 downregulated genes.By proteomic profiling,117 upregulated and 136 downregulated proteins were identified in M-07e cells,while 91 upregulated and 46 downregulated proteins were identified in SKM-1 cells following DAC exposure.Through integrated analysis of upregulated genes and proteins expression profiles,181 candidate genes were screened out,while methylation studies identified 884 hypomethylated genes with high-sensitivity loci and CpG density.Notably,31 genes overlapped between these datasets,and functional annotation indicated these drug-resistance-associated genes are primarily involved in positive regulation of cell differentiation,negative regulation of binding processes,and negative regulation of cellular component organization.Conclusion:TP53 mutations drive DAC resistance via epigenetic reprogramming.Targeting these genes may improve outcomes in TP53-mutated MDS.

Objective:To investigate the effects of TP53 genetic status(wild-type/mutated/null)on the drug resistance of decitabine(DAC)in myelodysplastic syndromes(MDS)and identify key resistance-associated genes.Methods:Two myeloid cell lines with distinct TP53 status(M-07e:wild-type;SKM-1:mutated;)were treated with gradient DAC concentrations(0-10 μmol/L)for 0-72 h.Cell viability was detected by CCK-8 assay.RNA-Seq transcriptomics,and methylation profiling were integrated to analyze differentially expressed genes.Results:Decitabine(DAC)treatment induced time-and dose-dependent inhibition of cell viability in CCK-8 assays,with SKM-1 cells exhibiting the highest resistance(IC50=5 μmol/L vs M-07e=0.5 μmol/L,P＜0.01).Transcriptomic analysis revealed 662 upregulated and 452 downregulated genes in DAC-treated M-07e cells,while SKM-1 cells showed 515 upregulated and 73 downregulated genes.By proteomic profiling,117 upregulated and 136 downregulated proteins were identified in M-07e cells,while 91 upregulated and 46 downregulated proteins were identified in SKM-1 cells following DAC exposure.Through integrated analysis of upregulated genes and proteins expression profiles,181 candidate genes were screened out,while methylation studies identified 884 hypomethylated genes with high-sensitivity loci and CpG density.Notably,31 genes overlapped between these datasets,and functional annotation indicated these drug-resistance-associated genes are primarily involved in positive regulation of cell differentiation,negative regulation of binding processes,and negative regulation of cellular component organization.Conclusion:TP53 mutations drive DAC resistance via epigenetic reprogramming.Targeting these genes may improve outcomes in TP53-mutated MDS.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional