This study aims to investigate the antipyretic effects and mechanisms of ethanol extracts from Arisaematis Rhizoma fermented with bile from different sources on a rat model of fever induced by a dry-yeast suspension. The rat model of fever was established by subcutaneous injection of 20% dry-yeast suspension into the rat back. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) in the serum, as well as prostaglandin E_2(PGE_2) and cyclic adenosine monophosphate(cAMP) in the hypothalamus, were determined by ELISA. Metabolomics analysis was then performed on serum and hypothalamus samples based on UPLC-Q-TOF MS to explore the potential biomarkers and metabolic pathways. The results showed that the body temperatures of rats significantly rose 4 h after modeling. After oral administration of high-dose ethanol extracts of Arisaematis Rhizoma fermented with bovine bile(NCH) and porcine bile(ZCH), the body temperatures of rats declined(P<0.05), and the NCH group showed better antipyretic effect than the ZCH group. Additionally, compared with the model group, the NCH and ZCH groups showed lowered levels of IL-1β, IL-6, TNF-α, PGE_2, and cAMP(P<0.01). The results of serum and hypothalamus metabolomics analysis indicated that both NCH and ZCH exerted antipyretic effects by regulating phenylalanine metabolism, sphingolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Collectively, both NCH and ZCH can play an obvious antipyretic role in the rat model of dry yeast-induced fever, and the underlying mechanism might be closely associated with inhibiting inflammation and regulating metabolic disorders. Moreover, NCH demonstrates better antipyretic effect.
Animals ; Rats ; Male ; Fermentation ; Rats, Sprague-Dawley ; Rhizome/metabolism* ; Drugs, Chinese Herbal/chemistry* ; Bile/chemistry* ; Antipyretics/chemistry* ; Fever/metabolism* ; Cattle ; Swine ; Tumor Necrosis Factor-alpha/metabolism* ; Ethanol/chemistry* ; Interleukin-6/blood* ; Interleukin-1beta/blood*

The chemical constituents of the petroleum ether extract derived from the 90% ethanol extract of Elephantopus scaber were investigated. By silica gel column chromatography, C_(18), MCI column chromatography and semi-preparative high performance liquid chromatography, ten compounds were isolated. Their structures were identified as 3β-hydroxy-6β,7β-epoxytaraxeran-14-ene(1), 3β-hydroxyolean-12-en-28-oic acid(2), D-friedoolean-14-ene-3β,7α-diol(3), 3β-hydroxy-11α-methoxyolean-12-ene(4), 3β-hydroxyolean-11,13(18)-diene(5), 11α-hydroxy-β-amyrin(6), betulinic acid(7), 3β-hydroxy-30-norlupan-20-one(8), 6-acetonylchelerythrine(9), and 4',5'-dehydrodiodictyonema A(10) by analysis of the 1D NMR, 2D NMR, MS, and IR spectral data. Among them, compound 1 was a new triterpene and other compounds except compounds 2 and 7 were isolated from this plant for the first time.
Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Molecular Structure ; Asteraceae/chemistry* ; Chromatography, High Pressure Liquid ; Magnetic Resonance Spectroscopy

Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Metabolomics ; Hyperlipidemias/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/pharmacology* ; Liver/metabolism* ; Humans ; Alanine Transaminase/metabolism* ; Triglycerides/metabolism* ; Aspartate Aminotransferases/metabolism*

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

OBJECTIVES: To explore the mechanism of Lacticaseibacillus paracasei E6 for improving vinorelbine-induced immunosuppression in zebrafish. METHODS: The intestinal colonization of L. paracasei E6 labeled by fluorescein isothiocyanate (FITC) in zebrafish was observed under fluorescence microscope. In a zebrafish model of vinorelbine-induced immunosuppression, the immunomodulatory activity of L. paracasei E6 was assessed by analyzing macrophage and neutrophil counts in the caudal hematopoietic tissue (CHT), the number of T-lymphocyte, and the expressions of interleukin-12 (IL-12) and interferon-γ (IFN-γ). The contents of short-chain fatty acids (SCFAs) in L. paracasei E6 fermentation supernatant and the metabolites of L. paracasei E6 in zebrafish were detected by LC-MS/MS-based targeted metabolomics. The immunomodulatory effects of the SCFAs including sodium acetate, sodium propionate and sodium butyrate were evaluated in the zebrafish model of immunosuppression. RESULTS: After inoculation, green fluorescence of FITC-labeled L. paracasei E6 was clearly observed in the intestinal ball, midgut and posterior gut regions of zebrafish. In the immunocompromised zebrafish model, L. paracasei E6 significantly alleviated the reduction of macrophage and neutrophil counts in the CHT, increased the fluorescence intensity of T-lymphocytes, and promoted the expressions of IL-12 and IFN-γ. Compared with MRS medium, L. paracasei E6 fermentation supernatant showed significantly higher levels of acetic acid, propionic acid and butyric acid, which were also detected in immunocompromised zebrafish following treatment with L. paracasei E6. Treatment of the zebrafish model with sodium acetate and sodium propionate significantly increased macrophage and neutrophil counts in the CHT and effectively inhibited vinorelbine-induced reduction of thymus T cells. CONCLUSIONS L. paracasei E6 can improve vinorelbine-induced immunosuppression in zebrafish through its SCFA metabolites acetic acid and propionic acid.
Animals ; Zebrafish/immunology* ; Acetic Acid/metabolism* ; Propionates/metabolism* ; Fatty Acids, Volatile/metabolism*

OBJECTIVES: To investigate the efficacy of Lactobacillus plantarum ZG03 (L. plantarum ZG03) for ameliorating oxidative stress in zebrafish. METHODS: We evaluated the growth pattern of L. plantarum ZG03, observed its morphology using field emission scanning electron microscopy, and assessed its safety and potential efficacy with whole-genome sequencing for genetic analysis. FITC-labeled ZG03 was used to observe its intestinal colonization in zebrafish. In a zebrafish model of 2% glucose-induced oxidative stress, the effect of ZG03 was evaluated by assessing the changes in neutrophils in the caudal hematopoietic tissue (CHT), superoxide dismutase (SOD) activity, reactive oxygen species (ROS) levels, and malondialdehyde (MDA) content. Liquid chromatography-mass spectrometry-based targeted metabolomics was used for analyzing short-chain fatty acids (SCFAs) in the zebrafish, and the antioxidant effects of the key metabolites (acetate, propionate, and caproate) were tested. RESULTS: On MRS agar, L. plantarum ZG03 formed circular, smooth, moist, and milky-white colonies with a rod-shaped cell morphology. Genomic analysis revealed abundant sugar metabolism gene clusters. After inoculation of FITC-labeled L. plantarum ZG03 in zebrafish, green fluorescence was clearly observed in the intestinal bulb, mid-intestine, and hind intestine. In zebrafish with glucose-induced oxidative stress, L. plantarum ZG03 significantly reduced ROS levels and the number of neutrophils in the CHT with increased SOD activity. L.plantarum ZG03 significantly increased the content of SCFAs including acetic acid, propionic acid, and caproic acid in zebrafish metabolites. In addition, sodium acetate, sodium propionate, and sodium caproate in the SCFAs significantly increased SOD activity in the zebrafish models. CONCLUSIONS L. plantarum ZG03 ameliorates oxidative stress in a glucose-induced zebrafish model through its metabolites, particularly the SCFAs including acetic acid, propionic acid and caproic acid.
Animals ; Zebrafish/metabolism* ; Oxidative Stress ; Lactobacillus plantarum/metabolism* ; Fatty Acids, Volatile/metabolism* ; Probiotics ; Reactive Oxygen Species/metabolism* ; Superoxide Dismutase/metabolism*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To analyze the classification characteristics of rheumatoid arthritis(RA)-related antibodies and to investigate the factors influencing the development of RA-related interstitial pulmonary diseases(RA-ILD)in RA patients using latent class analysis(LCA).Methods A retrospective analysis of 712 RA patients treated at the Department of Rheumatology and Immunology of the Second Hospital of Shanxi Medical University from December 2019 to October 2022 was conducted.According to whether patients had RA-ILD or not,they were divided into simple RA group(n=523)and RA-ILD group(n=189).Then,the differences in general data,clinical features,medication use and laboratory indicators were compared between the two groups.Based on the differences in RA-related antibody indicators,712 patients were divided into 3 latent categories using LCA:high-risk group(n=364),medium-risk group(n=205),and low-risk group(n=143).One-way analysis of variance was employed to compare clinical characteristics of the 3 groups,and the prevalence of RA-ILD was calculated.Multivariate logistic regression analysis was utilized to identify independent affect factors of RA-ILD.Results Significant differences in gender,age,and smoking history were observed between simple RA group and RA-ILD group(P<0.05).The high,medium and low risk groups exhibited significant differences in gender,age,prednisone(PRED)and methotrexate(MTX)medication history,Red blood cell count(RBC),interleukin-2(IL-2),IL-4,IL-10,IL-17,TNF-α,interferon-γ(INF-γ),serum globulins,and white blood albumins(P<0.05).The high-risk group had a higher proportion of males,RBC,IL-2,IL-4,IL-10,IL-17,TNF-α,INF-γ,and serum globulin levels,and a lower proportion of MTX medication compared with medium-and low-risk groups(P<0.05 or P<0.01).The medium-risk group had a higher proportion of MTX administration than that in high-and low-risk groups(P<0.05 or P<0.01).The low-risk group had a higher proportion of females and older age than those in other two groups(P<0.05 or P<0.01).The prevalence of RA-ILD was 30.5%,23.9%and 20.3%in the three groups,respectively.Multivariate logistic regression analysis indicated that male(OR=2.920,95%CI 1.722-4.952),age(OR=1.055,95%CI 1.035-1.074),IL-17(OR=1.013,95%CI 1.003-1.023),TNF-α(OR=1.050,95%CI 1.017-1.083),INF-γ(OR=0.962,95%CI 0.932-0.993),Serum albumin(OR=0.919,95%CI 0.869-0.971)and high risk antibody indicators(OR=1.725,95%CI 1.084-2.745)were independent predictors for RA-ILD.Conclusions RA patients exhibit distinct categories of antibody indicators,with a higher prevalence in high-risk patients with RA-ILD.RA-ILD is more likely to occur in male,elderly patients with abnormal liver function and high-risk antibody indictors.More attention should be paid to these patients and individualized interventions should be developed and implemented in a timely manner to improve the quality of patient survival.

Objective To investigate the effect and mechanism of hypoxia inducible factor-1 α/aquaporin-4(HIF-1α/AQP4)pathway in high altitude cerebral edema(HACE)after blood-brain barrier injury in rats.Methods Adult male SD rats(n=40)were randomly divided into two groups:control group(Ctrl,n=20)and high altitude cerebral edema group(HACE,n=20).The rats in the control group were reared in Xining(altitude 2261 m)for 4 days,and the rats in HACE group were reared in low-pressure simulation chamber(altitude 5000 m)for 4 days.Brain water content was measured by the method of dry and wet weight.The intracranial structure,morphology and signal changes of small animals were observed through T2 weighted image of 7.0 T MRI.The morphological changes of neurons and the apoptosis of nerve cells in the CA1 region of hippocampal tissue were observed by the staining of Nissl and TUNEL.Immunohistochemical staining was performed to observe the extravasation of immunoglobulin G(IgG).The expressions of HIF-1α,AQP4,matrix metalloproteinase-9(MMP-9),claudin-5,occludin and zonula occludens-1(ZO-1)in the tissue of hippocampal were detected by the method of Western blotting and immunofluorescent staining.Results The brain water content increased significantly in the HACE group(P＜0.05).The neurons in CA1 region of hippocampal tissue were atrophic and deformed,the arrangement of neurons was disordered in the HACE group.The number of neurons decreased significantly,the apoptosis of nerve cells increased significantly,and the IgG exudates obviously in the CA1 region of hippocampal tissue in the HACE group.The expressions of HIF-1α,AQP4 and MMP-9 proteins increased significantly,while claudin-5,occludin and ZO-1 proteins decreased significantly in the CA1 region of hippocampal tissue,which detected by the method of Western blotting and immunofluorescent staining(P＜0.05).Conclusion Acute high-altitude hypoxia can induce to blood-brain barrier disruption through the HIF-1α/AQP4 pathway,resulting in high-altitude cerebral edema.

Objective To investigate the mediating role of medical coping strategies in the relationship between perceived social support and resilience among patients with occupational pneumoconiosis (hereinafter referred to as pneumoconiosis). Methods A total of 240 pneumoconiosis patients were selected as the study subjects using the convenience sampling method. The Perceived Social Support Scale, the 10-item Connor-Davidson Resilience Scale and Medical Coping Strategies Questionnaire were used to evaluate their perceived social support, resilience and medical coping strategies. AMOS 26.0 software was used to construct the structural equation model. Results The average scores of perceived social support and resilience were (56.6±0.9) and (20.9±7.5), respectively. The scores for the dimensions of confrontation, avoidance and resignation of medical coping strategies were (20.2±3.6), (11.2±3.1) and (18.1±2.9), respectively. The score of resilience was positively correlated with the score of perceived social support, avoidance dimension and confrontation dimension of medical coping strategies (r=0.260, 0.176, 0.174, all P<0.01). It was negatively correlated with resignation coping (r=-0.292, P<0.01). The results of mediating effect test showed that the total effect of perceived social support on resilience was 0.252 [95% confidence interval (CI) was 0.056-0.448], which mainly affected the resilience by affecting the resignation coping (95%CI: -0.458 to -0.104), with the indirect effect value of 0.120, accounting for 47.6% of the total effect. Conclusion The resilience of pneumoconiosis patients is moderately low. Resignation coping in medical coping strategies plays a mediating role between perceived social support and resilience in pneumoconiosis patients.