[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT⁺-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT⁺-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
Ameloblastoma/metabolism* ; Humans ; B7-H1 Antigen/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Signal Transduction ; Cell Proliferation ; Up-Regulation ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Telomerase/metabolism* ; Jaw Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Animals ; Cell Line, Tumor ; Female ; Male

This article reports a case of membranous nephropathy in an adolescent accompanied by monoclonal IgG1-κ deposition. The 16-year-old female patient was hospitalized for experiencing proteinuria and hematuria for more than 20 days. The patient had a history of mycoplasma infection and acute kidney injury, and renal pathology revealed glomerular membrane lesions accompanied by crescent formation. Electron microscopy showed electron dense deposits in the subepithelial and mesangial regions, and immunofluorescence demonstrated monotypic IgG1-κ deposits in the glomerulus. Bone marrow examination did not find any abnormal plasma cells, nor were there significant abnormalities in serum or urine free light chain κ/λ ratio. The diagnosis was proliferative glomerulonephritis characterized by membranous lesions with monoclonal IgG1-κ deposits. This disease is rare in children and adolescents, and currently there is limited understanding of its mechanism, with limited clinical treatment experience. This article aims to provide clinical insights through case analysis and literature review.

Objective To analyze differences in the intestinal microbiota and transcriptomics between N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)gastric cancer rats and normal rats and to analyze the correlation between the two,so as to provide a reference for related studies using MNNG gastric cancer rats as a model.Methods A total of 12 Wistar rats were randomly divided into normal(NM)and gastric cancer(GC)groups.The GC group was given a concentration of 20 mg/mL of MNNG by gavage with a dose of 100 g/mL once a day,and the NM group was given the same amount of normal saline by gavage.Samples were collected for testing after 16 weeks of continuous intervention.The gastric tissues were collected and stained by HE staining to observe morphological changes in the gastric mucosa of the two groups,and the expression levels of differential genes were detected by transcriptome sequencing.The cecal contents were collected for 16S rRNA sequencing.Results(1)Visual observation and HE results showed that the volume of gastric mucosa in the NM group was normal,the surface was glossy,the gastric wall was elastic,the direction of the mucosal folds was regular,there were no hyperplasia or hemorrhagic spots.In the GC group,the volume of gastric mucosa was reduced,the gastric wall was thinned,elasticity was poor,the direction of the folds was disordered and irregular,and there was a bulge accompanied by yellow-black keratotic hyperplasia.In the NM group,the squamous epithelial layer,submucosa,and muscular layer of the gastric mucosa were clear,with no hyperplasia and keratinization.In the GC group,the gastric mucosa had disorganized layers and cell polarity,with different cell morphologies;the squamous epithelial layer was destroyed,and squamous epithelial cells were hyperplasic,keratinized,and had invaded the muscular layer by proliferation.The modeling was considered successful.(2)The results of intestinal microbiota sequencing showed that the abundance of Akkermansia and Lactobacillus in MNNG gastric cancer rats decreased significantly,and the abundance of the rumen coccaceae Prevonella,and Blauter increased significantly.(3)The three key pathways obtained by transcriptomic sequencing and KEGG pathway enrichment analysis were amebiasis,systemic lupus erythematosus,and the PI3K-Akt signaling pathway,and five genes differentially enriched in these three pathways were those for MCPT8I2,IGH-6,IGHG1,ACTN2,and VEGF-D.(4)Combined analysis of intestinal microbiota and transcriptomics showed that_UCG-005,Prevonella_UCG-003 and Brautella were positively correlated with amebiasis,systemic lupus erythematosus,and the PI3K-Akt signaling pathway.Conclusions The abundance of intestinal microbiota in gastric cancer rats formed by MNNG gavage is different from that of normal rats.The genes for MCPT8I2,IGH-6,IGHG1,ACTN2 and VEGF-D may be up-regulated in gastric cancer induced by MNNG gavage.Combined analysis of intestinal microbiota and differential genes suggested that the mechanism of MNNG carcinogenesis may be mainly related to the destruction of gastric mucosa and the inflammatory response.

Objective To analyze differences in the intestinal microbiota and transcriptomics between N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)gastric cancer rats and normal rats and to analyze the correlation between the two,so as to provide a reference for related studies using MNNG gastric cancer rats as a model.Methods A total of 12 Wistar rats were randomly divided into normal(NM)and gastric cancer(GC)groups.The GC group was given a concentration of 20 mg/mL of MNNG by gavage with a dose of 100 g/mL once a day,and the NM group was given the same amount of normal saline by gavage.Samples were collected for testing after 16 weeks of continuous intervention.The gastric tissues were collected and stained by HE staining to observe morphological changes in the gastric mucosa of the two groups,and the expression levels of differential genes were detected by transcriptome sequencing.The cecal contents were collected for 16S rRNA sequencing.Results(1)Visual observation and HE results showed that the volume of gastric mucosa in the NM group was normal,the surface was glossy,the gastric wall was elastic,the direction of the mucosal folds was regular,there were no hyperplasia or hemorrhagic spots.In the GC group,the volume of gastric mucosa was reduced,the gastric wall was thinned,elasticity was poor,the direction of the folds was disordered and irregular,and there was a bulge accompanied by yellow-black keratotic hyperplasia.In the NM group,the squamous epithelial layer,submucosa,and muscular layer of the gastric mucosa were clear,with no hyperplasia and keratinization.In the GC group,the gastric mucosa had disorganized layers and cell polarity,with different cell morphologies;the squamous epithelial layer was destroyed,and squamous epithelial cells were hyperplasic,keratinized,and had invaded the muscular layer by proliferation.The modeling was considered successful.(2)The results of intestinal microbiota sequencing showed that the abundance of Akkermansia and Lactobacillus in MNNG gastric cancer rats decreased significantly,and the abundance of the rumen coccaceae Prevonella,and Blauter increased significantly.(3)The three key pathways obtained by transcriptomic sequencing and KEGG pathway enrichment analysis were amebiasis,systemic lupus erythematosus,and the PI3K-Akt signaling pathway,and five genes differentially enriched in these three pathways were those for MCPT8I2,IGH-6,IGHG1,ACTN2,and VEGF-D.(4)Combined analysis of intestinal microbiota and transcriptomics showed that_UCG-005,Prevonella_UCG-003 and Brautella were positively correlated with amebiasis,systemic lupus erythematosus,and the PI3K-Akt signaling pathway.Conclusions The abundance of intestinal microbiota in gastric cancer rats formed by MNNG gavage is different from that of normal rats.The genes for MCPT8I2,IGH-6,IGHG1,ACTN2 and VEGF-D may be up-regulated in gastric cancer induced by MNNG gavage.Combined analysis of intestinal microbiota and differential genes suggested that the mechanism of MNNG carcinogenesis may be mainly related to the destruction of gastric mucosa and the inflammatory response.

This article reports a case of membranous nephropathy in an adolescent accompanied by monoclonal IgG1-κ deposition. The 16-year-old female patient was hospitalized for experiencing proteinuria and hematuria for more than 20 days. The patient had a history of mycoplasma infection and acute kidney injury, and renal pathology revealed glomerular membrane lesions accompanied by crescent formation. Electron microscopy showed electron dense deposits in the subepithelial and mesangial regions, and immunofluorescence demonstrated monotypic IgG1-κ deposits in the glomerulus. Bone marrow examination did not find any abnormal plasma cells, nor were there significant abnormalities in serum or urine free light chain κ/λ ratio. The diagnosis was proliferative glomerulonephritis characterized by membranous lesions with monoclonal IgG1-κ deposits. This disease is rare in children and adolescents, and currently there is limited understanding of its mechanism, with limited clinical treatment experience. This article aims to provide clinical insights through case analysis and literature review.

Objective:To explore the correlation between subclavian artery stenosis disease (SASD) classification and posterior circulation ischemia.Methods:A retrospective study was performed; the clinical data, and Doppler vascular ultrasound and vascular imaging results of 81 SASD patients, admitted to Cerebrovascular Stenosis Diagnosis and Treatment Center, Second Affiliated Hospital of Qiqihar Medical College and Department of Neurology, Rocket Force Specialty Medical Center from May 2018 to August 2023, were collected. SASD was categorized into 2 types (single type and concurrent type) based on the presence or absence of other posterior circulation artery (basilar artery, vertebral artery, or subclavian artery distal segment) stenosis/occlusion, and into 3 groups (non-posterior circulation ischemia group, posterior circulation transient ischemic attack group and posterior circulation cerebral infarction group) based on the presence or absence of posterior circulation ischemia. Blood stealing pathways in different SASD classifications were analyzed, and correlation of SASD classification with posterior circulation ischemia was discussed.Results:Single-type SASD was noted in 44 patients (54.3%), mainly initiating blood stealing through the vertebral artery to the vertebral artery and then to the subclavian artery ( n=26); concurrent-type SASD was noted in 37 patients (45.7%), mainly initiating blood stealing through the occipital artery to the costocervical trunk and then to the subclavian artery ( n=10). Sixty-five patients (80.2%) were into the non-posterior circulation ischemia group, 4 (4.9%) into the posterior circulation transient ischemic attack group and 12 (14.8%) into the posterior circulation cerebral infarction group. Among the 44 patients with single-type SASD, 39 did not have posterior circulation ischemia, and 3 had posterior circulation cerebral infarction. Among the 37 patients with concurrent-type SASD, 26 did not have posterior circulation ischemia, and 9 had posterior circulation cerebral infarction. Conclusion:Initiation of blood stealing in SASD patients is related to SASD classification, and concurrent-type SASD patients trend to have posterior circulation ischemia.

Objective:To investigate the effects of different doses of rosuvastatin on blood lipid levels and 1-year outcomes in patients undergoing coronary artery bypass grafting.Methods:A total of 106 patients who underwent coronary artery bypass grafting at the Affiliated Hospital of Jining Medical University from February 2020 to February 2022 were prospectively selected and randomly divided into two groups using a random number table. The high-dose group (53 cases) was treated with 20 mg/d rosuvastatin, while the low-dose group (53 cases) was treated with 10 mg/d rosuvastatin. The two groups were compared after treatment in terms of the clinical efficacy, blood lipid levels [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], cardiac function indicators [left ventricular end diastolic diameter (LVDD), left atrial diameter (LAD), left ventricular ejection fraction (LVEF), one-year follow-up [recurrence, readmission, death, major adverse cardiovascular events (MACE)], and adverse reactions (liver injury, elevated creatine kinase, gastrointestinal reactions, rash).Results:The total effective rate of the high-dose group was 94.34%(50/53) higher than that of the low-dose group, which was 77.36%(41/53) ( P<0.05); After treatment, the levels of TC, TG, and LDL-C in both groups decreased, while the level of HDL-C increased (all P<0.05), and the levels of TC, TG, and LDL-C in the high-dose group were lower than those in the low-dose group, while the level of HDL-C was higher than that in the low-dose group (all P<0.05); After treatment, LVDD and LAD in both groups decreased, while LVEF increased (all P<0.05), and LVDD and LAD in the high-dose group were lower than those in the low-dose group, while LVEF was higher than that in the low-dose group (all P<0.05); After a one-year follow-up, the recurrence rate of the high-dose group was 7.55%(4/53), and the readmission rate was 5.66% (3/53), both lower than those of the low-dose group [26.42%(14/53), 20.75%(11/53)] (all P<0.05). There was no statistically significant difference in case fatality rate, MACE, and incidence of adverse reactions between the two groups (all P>0.05). Conclusions:The use of high-dose rosuvastatin in patients undergoing coronary artery bypass grafting can effectively reduce blood lipid levels, improve cardiac function, and has high safety. It is worthy of clinical application.

Background::Despite the adverse effects of ambient fine particulate matter (PM 2.5) on type 2 diabetes and the beneficial role of physical activity (PA), the influence of PM 2.5 on the relationship between PA and type 2 diabetes remains unclear. Methods::In this prospective study with 71,689 participants, PA was assessed by a questionnaire and was categorized into quartiles for volume and three groups for intensity. Long-term PM 2.5 exposure was calculated using 1-km resolution satellite-based PM 2.5 estimates. PM 2.5 exposure and PA's effect on type 2 diabetes were assessed by cohort-stratified Cox proportional hazards models, individually and in combination. Results::In 488,166 person-years of follow-up, 5487 incident type 2 diabetes cases were observed. The association between PA and type 2 diabetes was modified by PM 2.5. Compared with the lowest quartile of PA volume, the highest quartile was associated with reduced type 2 diabetes risk in low PM 2.5 stratification (≤65.02 μg/m 3) other than in high PM 2.5 stratification (>65.02 μg/m 3), with the hazard ratio (HR) of 0.75 (95% confidence interval [CI]: 0.66-0.85) and 1.10 (95% CI: 0.99-1.22), respectively. Similar results were observed for PA intensity. High PM 2.5 exposure combined with the highest PA levels increased the risk of type 2 diabetes the most (HR= 1.79, 95% CI: 1.59-2.01 for PA volume; HR = 1.82, 95% CI: 1.64-2.02 for PA intensity). Conclusion::PA could reduce type 2 diabetes risk in low-pollution areas, but high PM 2.5 exposure may weaken or even reverse the protective effects of PA. Safety and health benefits of PA should be thoroughly assessed for long-term polluted residents.

Objective To explore the differential expression genes(DEGs)and related signaling pathways of the Qi deficiency and blood stasis(QDBS)and Yin deficiency and blood stasis(YDBS)syndromes in ischemic stroke(IS)at the molecular level,elucidating the potential mechanisms and biological basis of blood stasis syndrome in IS.Methods The mRNA expression profile dataset GSE100235 of the two syndromes of IS rats was downloaded from the GEO database,and the limma package of R language was used to screen DEGs.Subsequently,GO and KEGG analyses were performed using the DAVID database.The miRDB and miRWalk databases were used to predict the miRNAs of DEGs,and aa miRNA-mRNA regulatory network was constructed.A protein-protein interaction network was built using the STRING database,and the cytoHubba plug-in was utilized to identify the core target genes.The rat model of QDBS in IS was established by exhaustive swimming training combined with modified Longa's thread embolism,and the rat model of YDBS in IS was established by hydrocortisone injection and thread embolism.RT-qPCR was employed to validate the expression levels of core target genes in rat brain tissues of the two groups.Results A total of 47 DEGs were identified.These genes were mainly involved in biological processes such as neuronal apoptosis,inflammatory response,and adaptive immune response,as well as pathways related to lipid metabolism,atherosclerosis,and C-type lectin receptor signaling.The miRNA-mRNA interaction network consisted of 64 nodes and 55 edges.Five core target genes were obtained,including Ccl2,Selp,Timp1,Ccr1l1,and Fpr1.Conclusion There are significantly differentially expressed genes in QDBS and YDBS syndrome of IS rats.These genes are involved in a variety of biological processes and pathways,and are most closely related to lipid metabolism and atherosclerosis signaling pathways.