Primary biliary cholangitis （PBC） is an autoimmune liver disease characterized by intrahepatic cholestasis， while fatigue is a common symptom of PBC that significantly affects the quality of life of patients. The pathogenesis of fatigue is complex and may be associated with the factors such as cholestasis-induced inflammation， gut microbiota dysbiosis， brain structural and functional abnormalities， and mitochondrial dysfunction. At present， first-line therapies and liver transplantation have a limited effect in alleviating fatigue， and there is still a lack of standardized comprehensive assessment system. Emerging drugs and non-pharmaceutical interventions， including lifestyle modifications， have shown potential application prospects. This article systematically reviews the research advances in the clinical manifestations， pathogenesis， clinical assessment， and intervention of fatigue in PBC patients， in order to provide a reference for optimizing treatment strategies and promoting the research and development of new therapies.

Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

Background: Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression. Results: The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity. Conclusions Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.

Background/Aims: Distal mean nocturnal baseline impedance (MNBI) measuring via pH-impedance may be valuable in diagnosing patients with suspected laryngopharyngeal reflux (LPR). However, its wide adoption is hindered by cost and invasiveness. This study investigates whether baseline impedance measured during high-resolution impedance manometry (HRIM-BI) can predict pathological MNBI. Methods: A cross-sectional study in Taiwan included 74 subjects suspected of LPR, who underwent HRIM (MMS) and pH-impedance testing (Diversatek), after stopping proton pump inhibitors for more than 7 days. Subjects with grade C or D esophagitis or Barrett’s esophagus were excluded. The cohort was divided into 2 groups: those with concomitant typical reflux symptoms (CTRS, n = 28) and those with isolated LPR symptoms (ILPRS, n = 46). HRIM-BI measurements focused on both distal and proximal esophagi. Pathological MNBI was identified as values below 2065 Ω, measured 3 cm above the lower esophageal sphincter. Results: In all subjects, distal HRIM-BI values correlated weakly with distal MNBI(r = 0.34-0.39, P < 0.005). However, in patients with ILPRS, distal HRIM-BI corelated moderately with distal MNBI(r = 0.43-0.48, P < 0.005). The areas under the receiver operating characteristic curve was 0.78 (P = 0.001) with a sensitivity of 0.83 and a specificity of 0.68. No correlation exists between distal HRIM-BI and distal MNBI in patients with CTRS, and between proximal HRIM-BI and proximal MNBI in both groups. Conclusions Distal HRIM-BI from HRIM may potentially predict pathological MNBI in patients with ILPRS, but not in those with CTRS. Future outcome studies linked to the metric are warranted.

This study investigated the regulatory effects of carvacrol on lipopolysaccharide(LPS)-induced inflammatory response and endoplasmic reticulum(ER)stress in bovine mammary epithe-lial cells using in vitro cell culture techniques.Western blot analysis revealed significantly elevated expression levels of NF-κB pathway-related proteins and ER stress marker proteins in mastitis samples compared to healthy mammary tissues(P＜0.05).Cells were divided into a blank control group and carvacrol(CAV)treatment groups with varying concentrations(50,100,250,500,750,1 000 μmol/L).After 24 hours of culture,cell proliferation was assessed using the CCK-8 assay.An inflammatory model was established by stimulating MAC-T cells(a bovine mammary epithelial cell line)with LPS(10 mg/L)for 12 h,followed by measurement of the transcriptional levels of inflammatory-related genes(IL-6,IL-1β,and TNFα).MAC-T cells were pretreated with low,medi-um,and high doses of CAV for 12 h before LPS stimulation.Molecular docking analysis was per-formed to examine the interaction between CAV and GRP78,a key ER stress protein.Real-time quantitative PCR(qPCR)was used to analyze the mRNA expression levels of inflammatory cyto-kines(IL-6,IL-1β,TNFα),while Western blot was employed to assess the expression levels of NF-κB pathway proteins(p-IκB,p-NF-κB p65)and ER stress-related proteins(p-PERK,p-IRE1α,ATF6,GRP78,CHOP).The results from Western blot and qPCR demonstrated that CAV alleviated LPS-induced inflammatory response and cellular damage by inhibiting the NF-κB signa-ling pathway and ER stress.

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.

Aim To investigate the pharmacological mechanism of Ebselenin(Ebselen,EbSe)in the treat-ment of Escherichia coli(E.coli)infection,which had no significant inhibitory effect on Gram-negative bacte-ria,based on previous studies.Methods After EbSe intervention in E.coli infected Raw264.7 cells,the via-bility of Raw264.7 cells was determined by CCK-8 method,the morphology and structure of Raw264.7 cells were observed by electron microscope,and the in-tracellular bacterial load of Raw264.7 cells was calcu-lated by coated plate method.Polarization status of peritoneal macrophages,Raw264.7 intracellular NO and ROS content and intracellular HO-1 expression in Raw264.7 and E.coli acutely infected mice after E.co-li infection by flow cytometry.qPCR was used to detect the expression of related mRNAs in Raw264.7 cells.qPCR was used to detect the intracellular GSH content in Raw264.7 cells by spectrophotometric assay,and the state of cytoskeletal proteins was observed by immuno-fluorescence.Western blot assay was performed to de-tect the intracellular Txnrd1 expression level.Results Microtiter method,CCK-8,and electron microscopy observations showed that EbSe had no effect on the growth of E.coli and Raw264.7 cells in vitro.The re-sults of smear plate counting showed that EbSe reduced the intracellular bacterial load of Raw264.7 in the in-fected group.Flow cytometry results showed that EbSe upregulated the number of M2-type macrophages.The EbSe-treated infected group had reduced intracellular NO and ROS levels and increased GSH levels.The qPCR results showed that the expression of IL-6,IL-1β,and iNOS was decreased,and the expression of HO-1,Txnrd1,and Glut1 was increased in DHB4-in-fected Raw264.7 cells after EbSe treatment.Cytoskel-etal staining showed that the morphology of the EbSe-treated infected cells was similar to that of oxPAPC-in-duced cells.Western blot results showed the expres-sion of Txnrd1 protein in EbSe-treated infected cells in-creased.Conclusion EbSe exerts anti-E.coli acute infection effect by regulating macrophage polarization and inhibiting macrophage excessive inflammatory state.

To clarify the current situation of ketosis in dairy cattle on large-scale pastures in China and provide new insights,a questionnaire survey was conducted to analyze the incidence,preven-tion,treatment methods,and associated costs of ketosis in 79 large-scale pastures.The results showed that the average incidence of ketosis in dairy cows was 3.97％,with a cure rate of 92.40％.The order of importance of methods for preventing and controlling ketosis was as follows:feed for-mulation optimization＞blood ketone monitoring＞negative energy balance monitoring＞feed in-take monitoring＞milk yield monitoring.The most important treatment methods are intravenous glucose＞propylene glycol butyl phosphate＞vitamins＞choline.The most important diagnostic methods are blood ketone testing＞milk ketone testing＞negative energy balance testing＞clinical symptoms＞blood glucose testing.Economic analysis revealed that treatment costs were lower on larger farms and higher milk yields farms.Continuous optimization of feeding management,preven-tion,and control measures should be implemented on large-scale farms in China to reduce the oc-currence of ketosis in dairy cows.Additionally,more effective diagnostic and treatment methods should be employed to improve the cure rate and overall farm income.

In recent years,the intensification of dairy farming has significantly improved production efficiency but has also led to a rise in the incidence of metabolic diseases.Conditions such as keto-sis,fatty liver,and hypocalcemia pose serious threats to dairy cattle health and productivity.These diseases not only profoundly affect individual physiological function but also impose considerable economic pressures and challenges on farm management.As research advances,exosomes have e-merged as a novel intercellular signaling molecule,showing unique potential in regulating dairy cattle's nutritional metabolism.Studies suggest that exosomes hold promise as biomarkers for dis-ease and can even serve as carriers for disease detection and prevention.Acting as a crucial mediator of intercellular communication,exosomes play an important role in modulating the metabolic processes of dairy cattle.This review aims to systematically explore the role of exosomes in bovine nutritional metabolism and to provide new perspectives and theoretical support for their potential as tools for diagnosing,treating,and preventing metabolic diseases in dairy cattle,thus advancing research and practice in this field.

Objective:To establish a high-performance liquid chromatography method for the determination of related substances in panamivir injection.Methods:The Waters Xbridge Peptide BEH C18(250 mm×4.6 mm,3.5 μm).Phosphate buffer-acetonitrile was used as mobile phase,gradient elution,flow rate 0.8 mL·min-1,column temperature 35℃,detection wavelength 210 nm.Results:Peramivir could be effectively separated from all known impurities,with a limit of quantification of 5.29-18.02 ng and a limit of detection of 1.59-5.41 ng,with a good linear relationship(r＞0.999 0)in the range of 200%of the limit of quantification to the limit concen-tration,and the average recovery rate of each impurity was 99.6%-106.8%(n=12).The results of three batches of peramivir injection samples showed that the known impurities and other largest single impurities were less than 0.2%,and the total impurities were less than 1.0%.Conclusion:Verified by analytical methodology,the method is convenient,fast,specific,sensitive,and accurate,and can be used for the determination of peramivir injection-related substances.