ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis （UC） by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E₂ related factor 2/solute carrier family 7 member/glutathione peroxidase 4 （Nrf2/SLC7A11/GPX4） signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group， a model group， high- and low-dose Xiezhuo Jiedu prescription groups （26.64 and 13.32 g·kg^-1， respectively）， a ferroptosis inhibitor group （Ferrostatin-1， 0.005 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid （TNBS）-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition， disease activity index （DAI） score， colon length， and mucosal injury index （CDMI） score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin （HE） staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin， Claudin-1， mucin 2 （MUC2）， and E-cadherin in intestinal tissue were detected by immunofluorescence （IF）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in each group， and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species （ROS）， ferrous ions （Fe²⁺）， glutathione （GSH）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE）， diamine oxidase （DAO）， and D-lactate （D-LA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was applied to detect the mRNA expression levels of Nrf2， SLC7A11， GPX4， Occludin， Claudin-1， MUC2， and E-cadherin in each group， and Western blot was adopted to detect the protein expression levels of Nrf2， p-Nrf2， SLC7A11， and GPX4 in each group. ResultsCompared with the normal group， rats in the model group exhibited listlessness， sluggish response， and mucopurulent and bloody stools. The model group also showed significantly increased DAI score， colon length， CDMI score， and expression levels of TNF-α， IL-6， ROS， Fe²⁺， MDA， 4-HNE， DAO， and D-LA （P<0.01）. In addition， it presented significantly decreased IF values of Occludin， Claudin-1， MUC2， and E-cadherin and mRNA and protein expression levels of IL-10， GSH， Nrf2， p-Nrf2， SLC7A11， and GPX4 （P<0.01）. There were different degrees of improvement in each administration group after treatment， and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group （P<0.01）. ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway， thereby exhibiting efficacy in the treatment of UC.

ObjectiveTo investigate the effects of paeoniflorin （PF） on neuroinflammation and cognitive impairment in the rat model of Alzheimer's disease （AD） and to clarify whether its mechanism is associated with regulation of the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsGlycosides related to AD-associated neuroinflammation were screened through bibliometric analysis， and the potential targets of PF were predicted through network pharmacology and molecular docking. A rat model of AD was established by intraperitoneal injection of D-galactose （100 mg·kg^-1·d^-1）. Rats were assigned into a control group， a model group， a PF （200 mg·kg^-1） group， and a donepezil （0.5 mg·kg^-1·d^-1） group， and drugs were administered by gavage for 21 days. The learning and memory abilities were evaluated by the Morris water maze （MWM）. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe hippocampal neuronal morphology. The mRNA levels of inflammatory factors were determined by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of molecules in the JAK2/STAT3 signaling pathway were determined by Western blot. ResultsCompared with the control group， the model group showed prolonged escape latency and decreased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， accompanied by increased expression of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as elevated ratios of phosphorylated （p）-JAK2/JAK2 and p-STAT3/STAT3 （P<0.01）. Compared with the model group， the PF group and donepezil group exhibited shortened escape latency and increased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， decreased expression levels of IL-1β and TNF-α， upregulated mRNA levels of interleukin-4 （IL-4） and interleukin-10 （IL-10）， and reduced ratios of p-JAK2/JAK2 and p-STAT3/STAT3 （P<0.05， P<0.01）. ConclusionPaeoniflorin can alleviate cognitive impairment and neuroinflammation in the rat model of AD by inhibiting the JAK2/STAT3 signaling pathway.

Post-translational modification of protein is a key mechanism for regulating cancer development and immune re-sponses,and has become an important target for cancer diagnosis and treatment.Among them,lactylation modification provides a new perspective for the precise prevention and control of tumors by affecting metabolism and epigenetics.Lactylation modification precisely regulates the functions of histone and non-histone,affecting tumor cell characteristics,microenvironment acidification,and immune cell functions,becoming a key hub connecting metabolic reprogramming and malignant phenotypes.This article reviews the regulatory roles of lactylation modification in tumor development,immune escape,clinical translation,and explores the potential of targeted inhi-bition of lactylation modification and its related pathways,as well as the inhibition of key enzyme activity.

Objective:To investigate the clinical, cytopathological characteristics, and differential diagnosis of metastatic clear cell renal cell carcinomas (CCRCC).Methods:Nine cases of metastatic CCRCC cytologically diagnosed in the Department of Pathology, the First Affiliated Hospital of Air Force Medical University from July 2021 to December 2024 were collected. The HE staining, May-Grunewald-Giemsa staining, liquid-based slides, cell block preparation, and immunocytochemistry of EnVision two-step staining were performed. The clinical and cytopathological features, treatments and follow-up data were analyzed in combination with literature review.Results:Among the 9 cases of metastatic CCRCC, there were 7 males and 2 females. The age range was 43-78 years, and the average age was 63.6 (57.5, 72.5) years. The metastatic sites were lymph node in 3 cases (2 cases of mediastinal lymph nodes and 1 case of left cervical lymph node), bone in 3 cases (pubis, thoracic vertebrae and femur, respectively), thyroid in 2 cases, and adrenal gland, lung and pancreas in 1 case, respectively. Two of the 9 cases had two metastatic sites (case 8 had metastases of lung and mediastinal lymph nodes; case 9 had metastases of thyroid and cervical lymph nodes). The median time from the diagnosis to metastasis was 9.4 years (range 1.1 to 13.8 years). The tumor cells were arranged in papillary, acinar, sheet, cluster or single scattered pattern. Most cases had uniform nuclei with mild atypia and inconspicuous nucleoli, while some cases had variable nuclei with prominent nucleoli. The cytoplasm of the tumor cells was abundant. Some cases showed clear cytoplasm with small vacuoles, while some of them showed eosinophilic and granular cytoplasm. Immunocytochemically, the tumor cells were positive for CKpan(AE1/AE3,6/6), PAX8 (9/9), CAⅨ (9/9), CD10 (9/9), and vimiten (8/8). Patients were treated primarily with targeted therapy and/or immunotherapy and curettage and radiation therapy for bone lesions. The follow-up time ranged from 1.0 month to 41.5 months (median, 20 months), and all patients survived at the end of follow-up.Conclusions:The cytology of metastatic CCRCC often shows uniform cell size, abundant and clear cytoplasm, low nuclear/cytoplasmic ratio, and mild nuclear atypia. Its cytological diagnosis is challenging because it occurs in various sites and needs to be differentiated from primary tumors of these sites. Emphasis should be placed on the morphological recognition of CCRCC, and immunocytochemical staining should be used to improve diagnosis. When necessary, molecular testing can be employed for diagnosis. Meanwhile, the medical history should be carefully inquired by pathologists to avoid missed diagnosis and misdiagnosis.

Post-translational modification of protein is a key mechanism for regulating cancer development and immune re-sponses,and has become an important target for cancer diagnosis and treatment.Among them,lactylation modification provides a new perspective for the precise prevention and control of tumors by affecting metabolism and epigenetics.Lactylation modification precisely regulates the functions of histone and non-histone,affecting tumor cell characteristics,microenvironment acidification,and immune cell functions,becoming a key hub connecting metabolic reprogramming and malignant phenotypes.This article reviews the regulatory roles of lactylation modification in tumor development,immune escape,clinical translation,and explores the potential of targeted inhi-bition of lactylation modification and its related pathways,as well as the inhibition of key enzyme activity.

Objective This study aims to develop a guideline for assessing and maintaining intrinsic capacity in older adults,offer recommendations to professionals regarding these assessments,and encourage the implementation of evidence-based clinical practices across various settings,including communities,hospitals,nursing homes,and other geriatric care environments.Methods An evidence-based approach guided the collection of questions through a lit-erature review.Preliminary recommendations were developed through a systematic search of domestic and interna-tional guideline networks,professional association websites,and comprehensive databases.Subsequently,the recom-mendations were revised,and the consensus was achieved through a round of expert consensus meetings and 3 rounds of expert correspondence,culminating in the formation of the guidelines.Results The developed guideline encompasses 2 aspects and 5 dimensions of assessment and maintenance,comprising a total of 28 questions and 39 recommendations.Specifically,6 questions and 9 recommendations were formulated for the cognitive dimension,5 questions and 7 recommendations for the locomotion dimension,6 questions and 7 recommendations for the vitality dimension,6 questions and 9 recommendations for the psychological dimension,and 5 questions and 7 recommenda-tions for the sensory dimension.Among these,34 are classified as strong recommendations,while 5 are categorized as weak recommendations.Conclusion The guideline offers scientifically robust,acceptable,and comprehensible rec-ommendations that equip the professionals with a foundation for decision-making aiming at preserving the intrinsic capacity of older adults.

Objective:To investigate the clinical, cytopathological characteristics, and differential diagnosis of metastatic clear cell renal cell carcinomas (CCRCC).Methods:Nine cases of metastatic CCRCC cytologically diagnosed in the Department of Pathology, the First Affiliated Hospital of Air Force Medical University from July 2021 to December 2024 were collected. The HE staining, May-Grunewald-Giemsa staining, liquid-based slides, cell block preparation, and immunocytochemistry of EnVision two-step staining were performed. The clinical and cytopathological features, treatments and follow-up data were analyzed in combination with literature review.Results:Among the 9 cases of metastatic CCRCC, there were 7 males and 2 females. The age range was 43-78 years, and the average age was 63.6 (57.5, 72.5) years. The metastatic sites were lymph node in 3 cases (2 cases of mediastinal lymph nodes and 1 case of left cervical lymph node), bone in 3 cases (pubis, thoracic vertebrae and femur, respectively), thyroid in 2 cases, and adrenal gland, lung and pancreas in 1 case, respectively. Two of the 9 cases had two metastatic sites (case 8 had metastases of lung and mediastinal lymph nodes; case 9 had metastases of thyroid and cervical lymph nodes). The median time from the diagnosis to metastasis was 9.4 years (range 1.1 to 13.8 years). The tumor cells were arranged in papillary, acinar, sheet, cluster or single scattered pattern. Most cases had uniform nuclei with mild atypia and inconspicuous nucleoli, while some cases had variable nuclei with prominent nucleoli. The cytoplasm of the tumor cells was abundant. Some cases showed clear cytoplasm with small vacuoles, while some of them showed eosinophilic and granular cytoplasm. Immunocytochemically, the tumor cells were positive for CKpan(AE1/AE3,6/6), PAX8 (9/9), CAⅨ (9/9), CD10 (9/9), and vimiten (8/8). Patients were treated primarily with targeted therapy and/or immunotherapy and curettage and radiation therapy for bone lesions. The follow-up time ranged from 1.0 month to 41.5 months (median, 20 months), and all patients survived at the end of follow-up.Conclusions:The cytology of metastatic CCRCC often shows uniform cell size, abundant and clear cytoplasm, low nuclear/cytoplasmic ratio, and mild nuclear atypia. Its cytological diagnosis is challenging because it occurs in various sites and needs to be differentiated from primary tumors of these sites. Emphasis should be placed on the morphological recognition of CCRCC, and immunocytochemical staining should be used to improve diagnosis. When necessary, molecular testing can be employed for diagnosis. Meanwhile, the medical history should be carefully inquired by pathologists to avoid missed diagnosis and misdiagnosis.

OBJECTIVE To study the mechanism of Xinnao shutong capsule alleviating cerebral ischemia reperfusion injury(CIRI)in rats by regulating the ferroptosis pathway.METHODS SD rats were randomly divided into sham operation group,model group,Xinnao shutong low-dose,high-dose group(220,440 mg/kg),Ginkgo biloba leaves extract group(positive control,150 mg/kg).Each group of rats was orally administered with the corresponding medication/normal saline for 7 consecutive days.Transient occlusion of the middle cerebral artery was adopted to induce the CIRI model;the samples were taken 24 h after the operation;the cerebral infarction area of rats was detected,and the cerebral infarction rate was calculated.The pathological changes of brain tissues were observed,and the levels of lipid peroxide(LPO),malondialdehyde(MDA)and glutathione(GSH)in cerebral tissue were detected;mRNA and protein expressions of nuclear factor-erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1)and glutathione peroxidase 4(GPX4)were all detected in cerebral tissue of rats.RESULTS Compared with model group,the cerebral infarction rate,the content of total iron in cerebral tissue and serum level of LPO(except for Ginkgo biloba leaves extract group and Xinnao shutong low-dose group)were all decreased significantly in G.biloba leaves extract group and Xinnao shutong groups(P＜0.05 or P＜0.01);the serum level of GSH,the protein and mRNA expressions of Nrf2,HO-1 and GPX4 were all increased significantly(P＜0.05 or P＜0.01).The pathological damage to brain tissue was reduced,the number of nerve cells increased,the edema was alleviated,and the nuclear membrane was flattened.CONCLUSIONS Xinnao shutong capsule can inhibit ferroptosis and reduce CIRI,the mechanism of which may be associated with the activation of the Nrf2/HO-1/GPX4 signaling pathway.

Objective:To assess the levels of circRNA and N6-methyladenosine(m6A)methylation in hippocampal tissue of Alzheimer's disease(AD)mice and wild-type(WT)mice, and to explore the potential role of circRNA m6A methylation modification in the pathogenesis of Alzheimer's disease.Methods:Differentially expressed circular RNAs(circRNAs)in the hippocampal tissue of APPswe/PS1dE9(APP/PS1)double-transgenic Alzheimer's disease(AD)model mice and matched wild type mice were identified using RNA high-throughput sequencing(RNA-seq).Subsequently, Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted on the source genes of these circRNAs.Validation of the RNA-seq results was performed using real-time quantitative PCR(qRT-PCR).Furthermore, the SRAMP website was utilized to predict potential m6A modification sites on the differentially expressed circRNAs.Finally, circRNAs with high confidence were validated and analyzed through methylated RNA immunoprecipitation-quantitative PCR(MeRIP-qPCR).Results:In comparison to the control group, 21 circRNAs exhibited differential expression in the APP/PS1 group, with 15 being up-regulated and 6 down-regulated.GO analysis revealed that the source genes of these differentially expressed circRNAs were primarily associated with synapse structure and function, while KEGG analysis indicated their involvement in the Hippo signaling pathway and Lipid metabolism.qRT-PCR results confirmed that the expression patterns of the differentially expressed circRNAs were consistent with the RNA-seq findings.Specifically, the expression of mmu-Bai3_0007 in the APP/PS1 group was significantly lower than that in the control group(0.033±0.002 vs.1.006±0.136, t=12.38, P<0.01), and the m6A methylation level of mmu-Bai3_0007 was also notably reduced in the APP/PS1 group compared to the control group(0.144±0.018 vs.0.431±0.087, t=5.62, P<0.01). Conclusions:The m6A methylation modification of Bai3circRNA could play a role in Alzheimer's disease by regulating the expression of Bai3 circRNA.

Objective:To investigate the potential mechanism of cellular senescence-related mitochondrial autophagy genes in diabetic retinopathy (DR).Methods:The DR gene datasets GSE53257 and GSE60436 from the GEO database and screened the differentially expressed genes (DEG) were downloaded. Cellular senescence-related genes and mitochondrial autophagy-related genes from the GeneCards database, and the intersection of the two to obtain the DR-related differentially expressed genes (CSRMRDEG) were collected. The obtained CSRMRDEG was subjected to Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis, protein-protein interaction network (PPI) analysis, and hub gene identification using Maximal Clique Centrality (MCC), Degree, Maximum Neighborhood Component (MNC)、Edge Percolated Component (EPC) and Closeness algorithms. Gene Set Enrichment Analysis (GSEA) was conducted to obtain the enriched pathways of DEG, and ssGSEA immune infiltration analysis was performed to screen the correlation between immune cells and DR. The diagnostic efficacy of hub genes for DR was evaluated by drawing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Meanwhile, the Wilcoxon rank sum test was used to compare the differences in the infiltration level of immune cells between the DR Group and the control group.Results:23 DR-related CSRMRDEG were obtained. GO analysis showed that they were mainly enriched in the pathways of dicarboxylic acid, biosynthetic process of folate-containing compounds, tetrahydrofolate conversion, mitochondrial matrix, mitochondrial endomembrane, structural components of ribosomes, and glutamate transmembrane transporter protein activity. The results of KEGG pathway enrichment analysis showed that CSRMRDEG was highly enriched in pathways such as the folate carbon pool, biosynthesis of cofactors, and pyruvate metabolism. The PPI analysis results show that there are 16 related CSRMRDEG. Five algorithms (MCC, Degree, MNC, EPC, Closeness) obtained the nine Hub genes. The results of ROC curve analysis showed that the AUC of the expression levels of 9 hub genes for diagnosing DR ranged from 0.7-0.9. The ssGSEA results showed that there were statistically significant differences in Wilcoxon of central memory CD4 + T cells, macrophages, natural killer cells, and helper T cell 1 between the DR group and the control group ( Z=-2.85, -2.23, -2.10, -2.52; P<0.05). Conclusion:Mitochondrial autophagy genes related to cellular senescence are potential diagnostic targets for DR.