Metabolic associated fatty liver disease （MAFLD） is a chronic liver disease with a rapidly increasing incidence rate worldwide， and its complex pathogenesis is closely associated with O-linked β-N-acetylglucosamine （O-GlcNAc） modification. As a dynamic and reversible post-translational modification of proteins， O-GlcNAc modification is mainly regulated by O-GlcNAc transferase and O-GlcNAcase. O-GlcNAc modification can drive hepatic steatosis， exacerbate insulin resistance， and impair mitochondrial function， thereby leading to the aggravation of metabolic disorders， promoting inflammation response， and driving the progression of MAFLD to metabolic associated steatohepatitis and hepatic fibrosis. This article systematically reviews the latest research advances in the role of O-GlcNAc modification in the development and progression of MAFLD， in order to provide theoretical support and research direction for a deeper understanding of the pathological mechanism of MAFLD and the development of effective therapeutic strategies.

Objective: To explore the muscle mass index (MMI) among adolescents in Xinjiangs agricultural and pastoral areas and its association with cardiovascular risk factors, providing references and basis for the prevention and intervention of cardiovascular diseases among adolescents in these regions. Methods: From March to July 2023, a total of 1 842 students aged 13-18 years from four middle schools in Yili agricultural and pastoral areas of Xinjiang were selected using cluster random sampling. Measurements of muscle mass, physical indicators, questionnaires, and blood samples were conducted and analyzed. Statistical analyses were performed using oneway analysis of variance, Kruskal-Wallis H test, Mann-Whitney U test, and Logistic regression analysis. Results: There were significant differences in weight，body mass index (BMI)，waist circumference，muscle mass，systolic blood pressure，diastolic blood pressure，total cholesterol，highdensity lipoprotein cholesterol and fasting blood glucose among adolescents with severe, insufficient, good, and sufficient MMI in Xinjiangs agricultural and pastoral areas(F=326.78，634.76，261.67，134.56，80.14，16.78，5.84，21.67，3.42，P<0.01). Logistic regression analysis showed that, after adjusting age and BMI, the risk of cardiovascular risk factors aggregation in adolescents with good (OR=0.55-0.62) and adequate (OR=0.52-0.57) MMI were lower than that in adolescents with insufficient MMI (P<0.05). After gender stratification, the risk of cardiovascular risk factors aggregation in adolescents with good MMI for boys (OR=0.48-0.62) and with good MMI for girls (OR=0.61) were also lower than that in adolescents with insufficient MMI (P<0.05). Conclusions MMI in adolescents from agricultural and pastoral areas of Xinjiang are positively correlated with cardiovascular health. Future efforts should focus on muscle strength training for adolescents in these areas, as improving MMI can play a positive role in promoting cardiovascular health in adolescents.

Preeclampsia is a placenta-originated disorder closely associated with impaired placental development and immune imbalance at the maternal-fetal interface. As a critical process in the regulation of cellular homeostasis, autophagy plays a pivotal role in trophoblast syncytialization, invasion, and immune tolerance at the maternal-fetal interface. Moderate autophagy enhances trophoblast function and promotes spiral artery remodeling, whereas insufficient or excessive autophagy correlates with placental pathological features of preeclampsia, including impaired syncytialization, protein aggregate accumulation, and immune dysregulation. Although trophoblast-specific autophagy deficiencies in animal models can manifest preeclampsia-like phenotypes, clinical studies reveal tissue-specific variability in autophagy-related protein expression, which may be attributable to placental regional heterogeneity, disease subtypes, and sampling timepoints. Future investigations integrating multi-stage clinical cohorts, multicellular models, and genetically modified animals are warranted to elucidate the dynamic role of autophagy in preeclampsia pathogenesis and establish its causal relationship with disease progression, thereby providing a basis for targeted therapeutic strategies.

Preeclampsia is a placenta-originated disorder closely associated with impaired placental development and immune imbalance at the maternal-fetal interface. As a critical process in the regulation of cellular homeostasis, autophagy plays a pivotal role in trophoblast syncytialization, invasion, and immune tolerance at the maternal-fetal interface. Moderate autophagy enhances trophoblast function and promotes spiral artery remodeling, whereas insufficient or excessive autophagy correlates with placental pathological features of preeclampsia, including impaired syncytialization, protein aggregate accumulation, and immune dysregulation. Although trophoblast-specific autophagy deficiencies in animal models can manifest preeclampsia-like phenotypes, clinical studies reveal tissue-specific variability in autophagy-related protein expression, which may be attributable to placental regional heterogeneity, disease subtypes, and sampling timepoints. Future investigations integrating multi-stage clinical cohorts, multicellular models, and genetically modified animals are warranted to elucidate the dynamic role of autophagy in preeclampsia pathogenesis and establish its causal relationship with disease progression, thereby providing a basis for targeted therapeutic strategies.

Diffuse large B-cell lymphoma(DLBCL)is a highly heterogeneous disease.Although standard first-line regimens can cure＞50%of patients,approximately one-third of them develop relapsed/refractory DLBCL(r/r DLBCL).Consequently,immunotherapy targeting molecular abnormalities has become pivotal for managing r/r DLBCL.The results of this review show that with advances in understanding DLBCL pathogenesis and the tumor immune microenvironment,antibody-based therapies have evolved rapidly,progressing from monoclonal antibodies(e.g.,rituximab,tafasitamab)to bispecific antibodies(e.g.,odronextamab,glofitamab,epcoritamab)and antibody-drug conjugate(e.g.,polatuzumab vedotin,loncastuximab tesirine).These engineered agents enhance immune cytotoxicity and tumor-specific targeting,providing novel therapeutic options for r/r DLBCL patients.

Etiological research is necessary for understanding the occurrence and epidemiological patterns of diseases, and is also a prerequisite for the diagnosis, prevention and treatment of clinical diseases. Mendelian randomization(MR), a method of research that combines genetics and epidemiology, has the advantage of exploring the causal relationship between exposure and disease genetically as well as avoiding confounding factors and reverse causation. Thus, it has been extensively utilized in the etiological study of diseases. This paper reviews the implementation of MR in the research of ocular diseases and provides ideas and approaches for the investigation of related mechanisms as well as the development of intervention strategies.

OBJECTIVES: To investigate the expression of cartilage acidic protein 1 (CRTAC1) in gastric cancer (GC) and its effect on biological behaviors and immune cell infiltration of GC. METHODS: Transcriptomic, GO and KEGG analyses were conducted to investigate the association of CRTAC1 expression with prognosis of GC patients and its involvement in cell function and signaling pathways. ESTIMATE algorithm was used to analyze the effect of CRTAC1 expression on the tumor microenvironment and the tumor mutation load. In two GC cell clines (HGC-27 and MKN-74), CCK8, EdU and clone formation assays, flow cytometry, and Hoechst staining were used to examine the effects of CRTAC1 knockdown on cell proliferation, cell cycle changes and apoptosis. Wound healing assay, Transwell assay, and Western blotting were performed to analyze the effect of CRTAC1 knockdown on GC cell migration and the underlying mechanism. RESULTS: Bioinformatics analysis showed significantly higher expression of CRTAC1 in GC tissues than in adjacent tissues (P<0.05). Age and tumor stage were both prognostic risk factors in GC patients with high CRTAC1 expression (P<0.001). Analysis using ESTIMATE algorithm showed that CRTAC1 expression increased immune cell infiltration and decreased tumor mutational load in GC (P<0.001). In HGC-27 and MKN-74 cells, CRTAC1 knockdown significantly inhibited cell proliferation and migration and promoted cell apoptosis. Western blotting demonstrated that CRTAC1 knockdown significantly increased E-cadherin expression and reduced the expression levels of vimentin, p-PI3K, AKT2, p-AKT and p-mTOR in GC cells. CONCLUSIONS High expression of CRTAC1 in GC tissues affects immunotherapeutic efficacy and prognosis of the patients, possibly by promoting epithelial-mesenchymal transition via modulating tumor mutational load, tumor microenvironment, and the PI3K/AKT signaling pathway.
Stomach Neoplasms/metabolism* ; Humans ; Cell Proliferation ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction ; Cell Movement ; Cell Line, Tumor ; Prognosis ; Apoptosis ; Tumor Microenvironment ; Female ; Male ; Epithelial-Mesenchymal Transition/genetics*

Pyroptosis, a form of cell death associated with inflammation, is known to be involved in diabetic nephropathy (DN), and discoid domain receptor 1 (DDR1), an inflammatory regulatory protein, is reported to be associated with diabetes.However, the mechanism underlying DDR1 regulation and pyroptosis in DN remains unknown. We aimed to investigate the effect of DDR1 on renal tubular epithelial cell pyroptosis and the mechanism underlying DN. In this study, we used high glucose (HG)-treated HK-2 cells and rats with a single intraperitoneal injection of streptozotocin as DN models. Subsequently, the expression of pyroptosis-related proteins (cleaved caspase-1, GSDMD-N, Interleukin-1β [IL-1β], and interleukin-18 [IL-18]), DDR1, phosphorylated NF-κB (p-NF-κB), and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes were determined through Western blotting. IL-1β and IL-18 levels were determined using ELISA. The rate of pyroptosis was assessed by propidium iodide (PI) staining. The results revealed upregulated expression of pyroptosisrelated proteins and increased concentration of IL-1β and IL-18, accompanied by DDR1, p-NF-κB, and NLRP3 upregulation in DN rat kidney tissues and HG-treated HK-2 cells. Moreover, DDR1 knockdown in the background of HG treatment resulted in inhibited expression of pyroptosis-related proteins and attenuation of IL-1β and IL-18 production and PI-positive cell frequency via the NF-κB/NLRP3 pathway in HK-2 cells. However, NLRP3 overexpression reversed the effect of DDR1 knockdown on pyroptosis. In conclusion, we demonstrated that DDR1 may be associated with pyroptosis, and DDR1 knockdown inhibited HG-induced renal tubular epithelial cell pyroptosis. The NF-κB/NLRP3 pathway is probably involved in the underlying mechanism of these findings.

OBJECTIVE: To screen potential traditional Chinese medicine and their active monomer ingredients for treatment of diabetic nephropathy (DN) through the mechanism of caspase-1-mediated pyroptosis. METHODS: Using the Chinese Medicine System Pharmacology Analysis Platform (TCMSP), we screened traditional Chinese drugs and their active monomer components targeting caspase-1, and searched for the potential gene targets of the monomer components using GeneCards database. Cytoscape was used to construct the monomer compound-gene target network. Gene ontology (GO) functional enrichment analysis and Kyoto Gene and Gene Encyclopedia (KEGG) pathway enrichment analysis were used to predict the molecular mechanism of the screened traditional Chinese medicine and monomers. In SD rat models of diabetic mellitus (DM), we tested the therapeutic effect of ginsenoside Rh2 (daily dose of 20 mg/kg for 12 weeks) by examining renal pathology with HE staining and detecting the expressions of pyroptosis marker proteins caspase-1, GSDMD, IL-1β and IL-18 in the renal tissues using Western blotting, the serum levels of IL-1β and IL-18 and activities of cathepsin B and cathepsin L. RESULTS: Ginsenoside Rh2 could effectively dock with caspase-1 molecule. Fourteen targets were identified in ginsenoside Rh2 target network. GO function enrichment analysis revealed 27 GO terms associated with molecular function (4 terms), cell component (10 terms) and biological process (13 terms). KEGG pathyway enrichment analysis identified 4 signaling pathways involving lysosomes, glycosaminoglycan degradation, galactose metabolism, and sphingolipid metabolism pathways. In the animal experiment, treatment with ginsenoside Rh2 significantly alleviated renal pathologies and down-regulated the expressions of pyroptosis marker proteins (cleaved caspase-1, GSDMD-N, IL-1β and IL-18) ( < 0.05 or 0.01), lowered serum levels of IL-1β and IL-18 ( < 0.01), and enhanced the activities of cathepsin B and cathepsin L in the serum of the diabetic rats. CONCLUSIONS Ginsenoside Rh2 may inhibit caspase-1-mediated pyroptosis through the lysosome pathway to improve kidney damages in rat models of DN.

Objective To assess the protective effect of rabbit serum paraoxonase-1 (PON-1) on renal injury induced by dichlorvos in rats.Methods Totally 30 healthy S-D rats were randomly divided into 5 groups:control group (group A,n =6),exposure group (group B,n =6),PON-1 pretreatment group (group C,n =6),traditional atropine,pralidoxime treatment group (group D,n =6) and combination therapy group (group E,n =6).The rats of group A were given normal saline in equal volume of dichlorvos injected into abdominal cavity to make a false model of dichlorvos poisoning.In rats of groups B,C,D and E,9 mg/kg dichlorvos was administered.In rats of groups C and E,PON-1 4 500 units/kg was injected into vein of the tails half an hour before dichlorvos administration.After dichlorvos exposure,rats in group D and E were treated with 45 mg/kg iodoprofen and 10 mg/kg atropine by intraperitoneal injection.The activity of blood urea nitrogen (BUN) was assayed with urease.Serum creatinine (Cr) were measured by picric acid colorimetry.Serum Cys-C,KIM-1 and NAG in urine were determined by ELISA.Ultrastructural changes in renal tissues of rats were examined by light microscopy.The differences in laboratory findings between groups were compared.Results The creatinine level in group B was significantly higher than that in other groups (P ＜0.05).The levels of Cys-C,KIM-1 and NAG in group B and group D were significantly higher than those in group A (P ＜ 0.01).But there were no significant differences in above biomarkers among group C,group E and group A.There were no significant differences in above biomarkers between group B and group D.In group B,inflammatory cells infiltrated extensively in renal tissues and,the renal cells were congested and edematous,the lumen was obliterated and the border of the brush disappeared.The tubular structures were not clearly distinct found in group B,but edema and inflammatory cell infiltration with lesser degree were found in group D than those in dichlorvos exposure groups.The clearly distinct structure of the tube without completely occluded lumen in group D,and the most serious lesions were found in distal convoluted tubules.In group C,and group E,there were only mild congestion and edema without significant cell degeneration and necrosis.In group A,the structure of renal tubular epithelium was clearly distinct with brush-shaped margin,and without tubular or necrotic cell debris in the lumen.Conclusion The rabbit serum PON-1 can protect the renal tissue of rats after dichlorvos exposure.