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.

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.

Executive function(EF) is an advanced cognitive function of the central nervous system, and is closely related to an individual's capacity for daily living and adaptation. Patients with attention deficit hyperactivity disorder (ADHD) typically exhibit significant executive dysfunction. While most existing studies on the executive function of individuals with ADHD are cross-sectional, and little is known about the longitudinal maturation process of related brain structures and functional connectivity patterns. The findings indicate that ADHD patients exhibit differential developmental trajectories in brain structural and functional connectivity compared with typically developing group.Furthermore, there is a lifespan association between abnormal brain network development and ADHD symptoms. This article aims to elucidate the characteristics of executive function deficits in ADHD patients across different developmental stages, examining their relationship with the nervous system’s development from a development perspective.

To investigate the effect of VD3 on the concentration of Ca2+in neutrophils of subclinical hypocalcemia dairy cows and the autophagy of LC3,peripheral blood of dairy cows was collected and neutrophils were isolated and extracted.Western blot was used to detect the abundance of LC3 autophagy pathway-related proteins(LC3-Ⅱ,P62,ATG5)in cells.The intracellular Ca2+concen-tration of neutrophils was detected by flow cytometry.The LC3 autophagosome was detected by la-ser confocal technology.By adding VD3 to affect intracellular Ca2+concentration levels,the effects of vitamin D3 on calcium absorption and LC3 autophagy function were investigated.Western blot result showed that the protein abundances of LC3 and ATG5 in neutrophils of subclinical hypocal-cemia dairy cows decreased,while the protein abundance of p62 increased,indicating that the auto-phagy function of LC3 in subclinical hypocalcemia dairy cows was weakened.After VD3 treatment,the flow cytometry results showed that VD3 promoted the increase of Ca2+concentration levels in neutrophils.The Western blot results showed that the LC3 autophagy function of neutrophils from healthy cows and subclinical hypocalcemia cows was enhanced under the action of VD3,indicating that VD3 promoted the concentration of Ca2+in neutrophils and then affected the LC3 autophagy function.

Congenital long QT syndrome (LQTS) is a life-threatening ion channelopathy caused by mutations in genes encoding specific ion channels, which can result in malignant arrhythmia of the torsades de pointes type. LQTS type 4 represents less than 1% of inherited LQTS cases, in contrast to the 90% attributable to types 1-3, it is specifically caused by loss-of-function mutations in the membrane-binding domain of ANK2. Here, a novel ANK2 variant ( ANK2c 2245 A>C, resulting in p.Lys749Gln) associated with LQTS type 4 and Wolff-Parkinson-White syndrome was identified in a previously healthy 61-year-old male patient who suffered paroxysmal palpitations and pre-syncope due to recurrent torsades de pointes.

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.

To investigate the effect of capsaicin(CAP)on the replication of bovine viral diarrhea vi-rus(BVDV).Bovine nasal turbinate osteoblasts(BT)infected with BVDV served as the research model,and viral gene and protein levels were evaluated using RT-qPCR and Western blot.Moreo-ver,molecular docking,molecular dynamics simulation,and oil red O staining were applied to ana-lyze the mechanism by which CAP inhibits BVDV replication.The results revealed no significant effect of CAP at 6.25,12.5,25,and 50 mg/L on the viability of BT cells.CAP was found to signifi-cantly inhibit BVDV 5′UTR RNA and E2 protein levels,according to the antiviral effect study.Molecular docking and molecular dynamics simulations indicated that CAP could bind with high affinity to the active site of PI3K.Additional mechanistic studies indicated that CAP significantly reduced the activation of the PI3K/AKT signaling pathway triggered by BVDV.Furthermore,CAP notably decreased the mRNA levels of FASN,SREBP-1,and ACC-1,which are crucial fatty acid synthesis enzymes in the downstream PI3K/AKT signaling pathway,as well as the levels of lipid droplets.Interestingly,the addition of exogenous oleic acid greatly diminished the antiviral effec-tiveness of CAP and significantly lowered the mRNA levels of IFN-α and IFN-β.The results reveal for the first time that CAP can inhibit BVDV replication,establishing a foundation for its preven-tion and the development of feed additives.

Objective To explore the risk factors of"difficult pelvis"in laparoscopic middle and low rectal cancer surgery,and to construct and validate a nomogram prediction model.Methods 143 patients with middle and low rectal cancer who underwent laparoscopic radical resection in our hospital from May 2020 to May 2022 were selected as the training set,and 129 patients treated from June 2022 to June 2024 were selected as the validation set,analyzed its clinical data,and used multi-factor logistic regression analysis to explore the factors affecting the"difficult pelvis"in laparoscopic middle and low rectal cancer surgery.Based on these risk factors,a nomogram prediction model was constructed and verified.Results Multivariate logistic regression analysis showed that age,pubic symphysis height,and pelvic depth were independent risk factors for difficult pelvis in patients undergoing laparoscopic surgery for low-lying colon cancer,while the diameter between ischial spines,AB line,A angle,and B angle were independent protective factors for difficult pelvis.Based on The nomogram prediction model was constructed from the above factors.The receiver operating characteristic curve results showed that the areas under the curve of the training set and validation set were 0.870 and 0.843 respectively,and the sensitivity and specificity of the validation set were respectively 81.23％、80.06％,the prediction performance was good.Conclusion The prediction model for"difficult pelvis"in laparoscopic middle and low rectal cancer surgery constructed in this study has good prediction performance.

To explore the impacts of TGR5 on liver lipid metabolism and bile acid synthesis in dairy cows with fatty liver.Liver tissues of healthy cows and cows with fatty liver were collected through puncture technique.The protein and mRNA expressions of lipid synthesis-related factors ACC1,FAS,SREBF1,lipid oxidation factor CPT1A,and bile acid synthesis-related factors CYP8B1,CYP7B1,CYP27A1 were detected by Western blot and fluorescent quantitative PCR.Moreover,the mRNA levels of CYP7B1 were determined.Primary hepatocytes of 1-day-old calves were extracted and cultured in vitro,and four treatment groups were established,namely Control,NEFA,INT-777,and the INT-777+NEFA group.The concentration of NEFA group was 1.2 mmol/L,the con-centration of INT-777 group was 1 μmol/L,and the concentration of INT-777+NEFA group was 1.2 mmol/L NEFA and 1 μmol/L INT-777 simultaneously.After 12 h of stimulation,cells were collected,and the protein and mRNA levels of ACC1,FAS,SREBF1,CPT1A,CYP8B1,CYP7A1,CYP27A1,and the mRNA levels of CYP7B1 were detected by Western blot and fluorescent quanti-tative PCR.The content of lipid droplets and TG in the cells were detected by flow cytometry and kit.The results demonstrated that compared with healthy cows,the protein and mRNA expressions of ACC1,FAS,SREBF1,CYP8B1,and CYP7A1 in the liver tissues of fatty liver cows were upreg-ulated,while the protein and mRNA levels of CPT1 A,CYP27A1,TGR5,and the mRNA levels of CYP7B1 were downregulated.In vitro experiments revealed that compared with the Control group,the protein and mRNA levels of ACC1,FAS,SREBF1,CYP8B1,and CYP7A1 in the NEFA group were upregulated,and the protein and mRNA levels of CPT1A,CYP27A1,and TGR5,as well as the mRNA level of CYP7B1,were downregulated.Compared with the NEFA group,the protein and mRNA levels of ACC1,FAS,SREBF1,CYP8B1,CYP7A1 were downregulated in the INT-777+NEFA group,while the protein and mRNA levels of CPT1A CYP27A1,and TGR5 as well as the mRNA level of CYP7B1,were upregulated.The results of flow cytometry and the kit indicated that the lipid droplets and TG content in the NEFA group were upregulated compared with the Control group,while the lipid droplets and TG content in the INT-777+NEFA group were downregulated compared with the NEFA group.The above results suggested that the addition of TGR5 agonist promoted the expression of TGR5 and ameliorated the abnormal lipid metabolism and bile acid synthesis in the liver of dairy cows with fatty liver.

To explore the impacts of TGR5 on liver lipid metabolism and bile acid synthesis in dairy cows with fatty liver.Liver tissues of healthy cows and cows with fatty liver were collected through puncture technique.The protein and mRNA expressions of lipid synthesis-related factors ACC1,FAS,SREBF1,lipid oxidation factor CPT1A,and bile acid synthesis-related factors CYP8B1,CYP7B1,CYP27A1 were detected by Western blot and fluorescent quantitative PCR.Moreover,the mRNA levels of CYP7B1 were determined.Primary hepatocytes of 1-day-old calves were extracted and cultured in vitro,and four treatment groups were established,namely Control,NEFA,INT-777,and the INT-777+NEFA group.The concentration of NEFA group was 1.2 mmol/L,the con-centration of INT-777 group was 1 μmol/L,and the concentration of INT-777+NEFA group was 1.2 mmol/L NEFA and 1 μmol/L INT-777 simultaneously.After 12 h of stimulation,cells were collected,and the protein and mRNA levels of ACC1,FAS,SREBF1,CPT1A,CYP8B1,CYP7A1,CYP27A1,and the mRNA levels of CYP7B1 were detected by Western blot and fluorescent quanti-tative PCR.The content of lipid droplets and TG in the cells were detected by flow cytometry and kit.The results demonstrated that compared with healthy cows,the protein and mRNA expressions of ACC1,FAS,SREBF1,CYP8B1,and CYP7A1 in the liver tissues of fatty liver cows were upreg-ulated,while the protein and mRNA levels of CPT1 A,CYP27A1,TGR5,and the mRNA levels of CYP7B1 were downregulated.In vitro experiments revealed that compared with the Control group,the protein and mRNA levels of ACC1,FAS,SREBF1,CYP8B1,and CYP7A1 in the NEFA group were upregulated,and the protein and mRNA levels of CPT1A,CYP27A1,and TGR5,as well as the mRNA level of CYP7B1,were downregulated.Compared with the NEFA group,the protein and mRNA levels of ACC1,FAS,SREBF1,CYP8B1,CYP7A1 were downregulated in the INT-777+NEFA group,while the protein and mRNA levels of CPT1A CYP27A1,and TGR5 as well as the mRNA level of CYP7B1,were upregulated.The results of flow cytometry and the kit indicated that the lipid droplets and TG content in the NEFA group were upregulated compared with the Control group,while the lipid droplets and TG content in the INT-777+NEFA group were downregulated compared with the NEFA group.The above results suggested that the addition of TGR5 agonist promoted the expression of TGR5 and ameliorated the abnormal lipid metabolism and bile acid synthesis in the liver of dairy cows with fatty liver.