OBJECTIVE To compare the anti-hepatitis mechanisms of Abrus pulchellus subsp. cantoniensis （Hance） Verdc. （AC） and Abrus pulchellus subsp. mollis（Hance） Verdc. （AM）. METHODS SD rats were randomly divided into blank group， AC- treated group， and AM-treated group， with each group consisting of 10 rats. The rats’ orbital venous blood was collected at 5， 15， 30 minutes， and 1， 1.5， 2， 4， 6， 8， 12 hours after gavage administration of 24 g/kg of the corresponding drug （calculated by crude drug） or water， respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology was utilized to identify the prototype components present in the serum. The network pharmacology method was adopted to predict the anti-hepatitis active components， key targets， and signaling pathways of AC and AM. Additionally， molecular docking technology was utilized to verify the binding activity of the core active components with key targets. RESULTS A total of 35 prototype components migrating to the blood of AC and AM were identified in the serum of administered rats， among which 24 were common components. The active components in AC， such as acetylanguidine， physcion， soyasaponin A3 and soyasaponin Ⅰ， as well as those in AM， including vicenin 3， acetylanguidine，soyasaponin Ⅰ and schaftoside， all acted on key targets such as steroid receptor coactivator， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha， epidermal growth factor receptor （EGFR）， and protein kinase B1（Akt1）. These components modulated pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the phosphoinositide 3-kinase （PI3K） -Akt pathway， thereby exerting anti-hepatitis effects. Furthermore， the binding energies between these active components and their key targets were all less than －5 kJ/mol. CONCLUSIONS There are differences in the active components of AC and AM against hepatitis， but their mechanisms of action are similar. Both may exert their anti-hepatitis effects through pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the PI3K-Akt pathway.

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

Bovine neosporosis,a significant disease affecting the livestock industry,is caused by the protozoan parasite Neospora caninum(N.caninum).The current absence of efficacious vaccines and therapeutics necessitates the exploration of novel interventions.Cordycepin,a bioactive nucleo-side derived from Cordyceps militaris,has garnered attention for its diverse pharmacological properties.This study endeavors to elucidate the inhibitory effects of cordycepin on N.caninum in-fection.The cytotoxicity of cordycepin to bovine macrophages was assessed using the CCK-8 assay to ascertain a non-toxic concentration range.The impact of cordycepin on the N.caninum burden within bovine macrophages was evaluated using qPCR analysis and immunofluorescence assays.Additionally,the modulation of cytokine,interferon,and defensin expression induced by N.cani-num in the presence of cordycepin was examined through qRT-PCR analysis.The results showed that cordycepin exhibited negligible cytotoxicity to bovine macrophages at concentrations ranging from 2.812 5 to 180.000 0 μmol/L,compared to the control group.At concentrations of 5.625 0,11.250 0,and 22.500 0 μmol/L,cordycepin significantly reduced the intracellular N.caninum loads and diminished the intensity of intracellular parasite fluorescence.While N.caninum infection downregulated the expression of pro-inflammatory cytokines such as TNF-α,IL-1β,and IL-6,cordycepin treatment robustly induced their expression.Furthermore,although cordycepin treatment reduced the expression levels of IFN-α,IFN-β,and IFN-γ that were upregulated by N.caninum infection,it maintained substantial expression levels.In conclusion,cordycepin demon-strates a promising resistance against N.caninum infection,suggesting its potential as a therapeu-tic agent for the treatment of bovine neosporosis.

Ménière's disease(MD)and vestibular migraine(VM)are two common episodic vertigo disor-ders.Patients with VM often exhibit auditory and vestibular symptoms similar to those of MD.Patients with MD are also prone to migraine features such as headache,photophobia,and a positive family history of migraine.There-fore,differentiating MD from VM is challenging,especially in the early stages of the disease.Although the two dis-eases overlap in many ways,some core features in terms of demographic characteristics,clinical symptoms,and la-boratory tests can be used to identify them.However,a highly specific test or biological marker to distinguish the two is not available.Physicians may combine various features such as symptoms,signs,and tests to differentiate MD and VM.

Bovine neosporosis,a significant disease affecting the livestock industry,is caused by the protozoan parasite Neospora caninum(N.caninum).The current absence of efficacious vaccines and therapeutics necessitates the exploration of novel interventions.Cordycepin,a bioactive nucleo-side derived from Cordyceps militaris,has garnered attention for its diverse pharmacological properties.This study endeavors to elucidate the inhibitory effects of cordycepin on N.caninum in-fection.The cytotoxicity of cordycepin to bovine macrophages was assessed using the CCK-8 assay to ascertain a non-toxic concentration range.The impact of cordycepin on the N.caninum burden within bovine macrophages was evaluated using qPCR analysis and immunofluorescence assays.Additionally,the modulation of cytokine,interferon,and defensin expression induced by N.cani-num in the presence of cordycepin was examined through qRT-PCR analysis.The results showed that cordycepin exhibited negligible cytotoxicity to bovine macrophages at concentrations ranging from 2.812 5 to 180.000 0 μmol/L,compared to the control group.At concentrations of 5.625 0,11.250 0,and 22.500 0 μmol/L,cordycepin significantly reduced the intracellular N.caninum loads and diminished the intensity of intracellular parasite fluorescence.While N.caninum infection downregulated the expression of pro-inflammatory cytokines such as TNF-α,IL-1β,and IL-6,cordycepin treatment robustly induced their expression.Furthermore,although cordycepin treatment reduced the expression levels of IFN-α,IFN-β,and IFN-γ that were upregulated by N.caninum infection,it maintained substantial expression levels.In conclusion,cordycepin demon-strates a promising resistance against N.caninum infection,suggesting its potential as a therapeu-tic agent for the treatment of bovine neosporosis.

Ménière's disease(MD)and vestibular migraine(VM)are two common episodic vertigo disor-ders.Patients with VM often exhibit auditory and vestibular symptoms similar to those of MD.Patients with MD are also prone to migraine features such as headache,photophobia,and a positive family history of migraine.There-fore,differentiating MD from VM is challenging,especially in the early stages of the disease.Although the two dis-eases overlap in many ways,some core features in terms of demographic characteristics,clinical symptoms,and la-boratory tests can be used to identify them.However,a highly specific test or biological marker to distinguish the two is not available.Physicians may combine various features such as symptoms,signs,and tests to differentiate MD and VM.

Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to β-glucuronidase (Gus) converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing. The anti-mucositis effect of DDIE is gut microbiota-dependent. Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria, particularly Enterococcus faecalis (E. faecalis). DDIE counters CPT11-induced augmentation of E. faecalis, leading to decreased intestinal Gus and SN38 levels. The Partial Least Squares Path Model (PLS-PM) algorithm initially links E. faecalis to dysregulated epithelial renovation. This is further validated in a 3D intestinal organoid model, in which both SN38 and E. faecalis hinder the formation and differentiation of organoids. Interestingly, colonization of E. faecalis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation. Our study unveils a microbiota-driven, epithelial reconstruction-mediated action of DDIE against mucositis, proposing the 'Gus bacteria-host-irinotecan axis' as a promising target for mitigating CPT11 chemotoxicity.

Objective To investigate the effect and mechanism of Congrong Shujing Granules on promoting microglial polarization and inhibiting neuroinflammation through the nucleotide-binding oligomeric domain-like receptor protein 3(NLRP3)/Caspase-1 signaling pathway.Methods Twenty Sprague-Dawley rats were assigned to the blank serum and Congrong Shujing Granules containing serum groups using random number table method,with 10 rats in each group.Rats in the Congrong Shujing Granules containing serum group received intragastric administration of Congrong Shujing Granules(2.57 g/kg)and the rats in the blank serum group received intragastric administration of physiological saline of equal volume.Blank serum and Congrong Shujing Granules containing serum were prepared separately.Mouse microglia cells BV-2 were cultured in vitro,and the optimal concentration of 1-methyl-4-phenylpyridine(MPP+)and optimal volume fraction of Congrong Shujing Granules containing serum were selected by the CCK-8 assay and immunofluorescence staining.And the NLRP3 inhibitor MCC950 was used as a postive control.Cells were divided into the blank serum group(10%blank serum),model group(10%blank serum+500 μmol/L MPP+),Congrong Shujing Granules containing serum group(10%Congrong Shujing Granules containing serum+500 μmol/L MPP+),and MCC950 group(10%blank serum+10 μmol/L MCC950+500 μmol/L MPP+),and intervened separately.After 14 h of intervention,morphological changes in BV-2 cells were observed.The contents of interleukin(IL)-1β,tumor necrosis factor-α(TNF-α),IL-6,and IL-4 were detected by an enzyme-linked immunosorbent assay.The mRNA expressions of differentiation cluster 86(CD86),inducible nitric oxide synthase(iNOS),CD206,and arginase 1(Arg1)were detected by real-time fluorescence PCR.The expressions of CD86,Arg1,Ionized calcium binding adaptor molecule 1(Iba1),and NLRP3 were detected by immunofluorescence staining.The expression of iNOS,Arg1,TNF-α,IL-6,IL-4,NLRP3,pro-cysteinyl aspartate specific proteinase 1(pro-Caspase-1),and Caspase-1 proteins was detected by Western blotting.Results Iba1 activation and expression increased under the MPP+(12 h,500 μmol/L)intervention(P<0.05),and cell viability was not affected.There was no statistically significant effect on cell viability after treatment with 10%Congrong Shujing Granules containing serum alone or in combination with MPP+(P>0.05).Compared to the blank serum group,BV-2 cells in the model group showed multiple branches and protruded in the shape of an amoeba.The contents of IL-1β,TNF-α,and IL-6 increased,while the contents of IL-4 decreased.The mRNA expressions of CD86 and iNOS increased,while mRNA expressions of CD206 and Arg1 decreased.The mean fluorescence intensity of CD86,Iba1,and NLRP3 increased,while the mean fluorescence intensity of Arg1 decreased.The protein expressions of iNOS,TNF-α,IL-6,NLRP3,pro-Caspase-1,and Caspase-1 increased,while the protein expressions of Arg1,IL-4 decreased,P<0.05.Compared to the model group,the Congrong Shujing Granules containing serum group and MCC950 group showed a decrease in the branch of cell protrusions,reduced cell activation,decreased levels of IL-1β,TNF-α,and IL-6,increased levels of IL-4,decreased expression of CD86 and iNOS mRNA,increased expression of CD206 mRNA,the decreased mean fluorescence intensity of CD86,Iba1,and NLRP3,the increased mean fluorescence intensity of Arg1,decreased expression of iNOS,TNF-α,IL-6,NLRP3,pro-Caspase-1,and Caspase-1 proteins,and increased expression of Arg1 and IL-4 proteins,P<0.05.Conclusion Congrong Shujing Granules containing serum may alleviate the MPP+-induced neuroinflammatory response by inhibiting the NLRP3/Caspase-1 signaling pathway to regulate M1/M2 phenotype polarization of microglia.

Objective:To evaluate the effect of different interventions in post-percutaneous coronary intervention (PCI) patients with kinesiophobia using network Meta-analysis.Methods:Computerized search of randomized controlled trials and quasi-experiment related to kinesiophobia interventions for post-PCI patients in WanFang database, China National Knowledge Infrastructure, China Biology Medicine, VIP database, Web of Science, PubMed, Cochrane Library and Embase was conducted with a time frame of searching from the establishment of the library to August 3, 2023. Literature screening, data extraction and literature quality evaluation were carried out independently by two researchers. Network Meta-analysis was performed using Stata 17.0 software.Results:A total of 13 literatures were included, including 9 randomized controlled trials and 4 quasi-experiments.Network Meta-analysis showed that cognitive behavioral therapy ( SMD = -4.08, 95% CI -6.49 --1.67), cognitive behavioral therapy combined with cardiac rehabilitation ( SMD = - 3.02, 95% CI -5.43 -- 0.61), dual heart medical intervention ( SMD = - 2.48, 95% , - 4.87 - - 0.09) can reduce the level of exercise fear in patients after PCI, and the difference were statistically significant compared with routine nursing (all P< 0.05). Ranked probability plots showed that the effects of the nine interventions in reducing kinesiophobia in post-PCI patients were cognitive behavioral therapy, cognitive behavioral therapy combined with cardiac rehabilitation, adaptive leadership theory-based intervention, dual heart medical intervention, COX health behavior interaction model, health education based on the behavioral change wheel, graded exposure therapy, mindfulness intervention, and high-intensity interval training in descending order of effectiveness. Conclusions:Cognitive behavioral therapy was the most effective intervention for kinesiophobia in post-PCI patients, but more high-quality randomized controlled trials are needed to further verify this conclusion.

Objective:To understand the current state of ethical competence levels of nurses and analyse the factors that influence them, in order to inform the development of targeted training programmes.Methods:This study adopted a cross-sectional survey method and used convenience sampling to select 825 clinical nurses from Tianjin Chest Hospital as the survey objects from July to August, 2023, and a questionnaire survey was conducted using the General Information Questionnaire, the Ethical Competence Scale, Ethical Competence Support Scale, and Ethical Safety Scale.Results:A total of 818 valid questionnaires were retracted. Among the 818 nurses, 48 were males and 770 were females, the age was (33.19 ± 7.40) years. The total score of nurses ′ Ethical Competence, Ethical Competence Support and Ethical Safety were (118.08 ± 19.96), (215.07 ± 32.02), (48.93 ± 7.55) points, all of which were at a high level. The total score of nurses ′ ethical competence were positively correlated with ethical competence support and ethical safety ( r=0.856, 0.830, both P<0.01); multivariate linear regression analysis showed that the department, the level of ethical competence support, and the level of ethical safety were the influencing factors of the level of ethical competence ( t=5.19, 12.35, 3.88, all P<0.01). Conclusions:Nurses ′ ethical competence, ethical competence support, and ethical safety were at a high level, and the department, the level of ethical competence support, and the level of ethical safety were the factors influencing the level of ethical competence. Nursing managers can provide more ethical education and address ethical issues in multiprofessional discussions, strengthen organizational and personal support for nurses ′ ethical competence, improve nurses ′ ethical safety, and help them implement good ethical care.