Primary malignant melanoma of the esophagus successfully treated with camrelizumab:A case report and literature review

An 83-year-old Chinese woman presented with a 3-month history of dysphagia.She also had a history of hypertension,type 2 diabetes,fundus hemorrhage,and cataract but no history of cutaneous,ocular,or other-site melanomas.Upper gastrointestinal tract angiography revealed gastritis and duodenal diverticulum;thus,an endoscopic review was recommended.Enhanced computed tomography of the chest and upper abdomen revealed the following:(1)Esophageal space-occupying lesions and mediastinal lymph node enlargement(considering the high possibility of esophageal cancer,further endoscopy was recommended)and(2)A small amount of right pleural effusion,with no significant lymph node infiltration or distant metastasis.Esophagoscopy identified a bulge mass blocking the esophagus from 23 to 30 cm from the incisors.The upper mass had a spherical clustering,while the lower mass significantly festered.Pathological biopsy samples were obtained from the esophagus 23 and 28 cm from the incisors.Tissue biopsy showed proliferation of large round tumor cells and melanocytes.Immunohistochemistry showed positive findings for HMB45 and MelanA;partially positive findings for S100,CK7,CK5/6,CAM5.2,LCA,P63,and TTF-1;and negative findings for Syn.The Ki-67 positivity index was approximately 60%.Based on these findings,the patient was diagnosed with malignant esophageal melanoma with enlarged mediastinal lymph nodes.She was then treated with five cycles of camrelizumab therapy combined with chemotherapy from October 18,2019,to May 5,2020.Gastroscopy review following two courses of combination therapy revealed that the esophagus was 23-25 cm away from the incisors,and there were two continuous uplifted and beaded masses that had a smooth and black surface,with each of them having a length and diameter of approximately 1 cm.Melanosis of the mucosa around the lumen was observed at 40 cm from the incisors to the cardia;the dentate margin was clear;and the cardia had no stenosis.The patient then received five courses of combination therapy and became consistently stable after partial remission.No severe adverse events related to the immunotherapy were recorded.Camrelizumab may be a viable treatment option for patients with PMME.Additional evidence from future clinical trials and research is necessary to fully validate our findings.

Effect of Xinglou Chengqi Decoction on the blood brain barrier permeability, nerve damage and neurotrophy in rats with cerebral hemorrhage

Objective: To study the effect of Xinglou Chengqi Decoction on the blood brain barrier permeability, nerve damage and neurotrophy in rats with cerebral hemorrhage. Methods:Adult male SD rats were chosen as the experimental animals and randomly divided into control group, model group and intervention group, model group were made into cerebral hemorrhage models, and intervention group were made into cerebral hemorrhage models and given intragastric administration of Xinglou Chengqi Decoction for intervention. After 14 d of intervention, the blood brain barrier permeability, the expression of apoptosis genes as well as the contents of oxidative products, inflammatory products and nerve cytokines in brain tissues were determined. Results: The blood brain barrier permeability parameter EB level in brain tissue of model group was significantly higher than that of control group, and Bax, FasL, Fas and Caspase-3 mRNA expression as well as MDA, AOPP, TNF-α, HMGB1 and MCP-1 contents in brain tissue were significantly higher than those of control group whereas BDNF, NTF, VEGF and IGF-1 contents were significantly lower than those of control group;the blood brain barrier permeability parameter EB level in brain tissue of intervention group was significantly lower than that of model group, and Bax, FasL, Fas and Caspase-3 mRNA expression as well as MDA, AOPP, TNF-α, HMGB1 and MCP-1 contents in brain tissue were significantly lower than those of model group whereas BDNF, NTF, VEGF and IGF-1 contents were significantly higher than those of model group. Conclusion: Xinglou Chengqi Decoction intervention can reduce the blood brain barrier permeability, relieve the nerve damage and improve the neurotrophy in rat model with cerebral hemorrhage.

Correlation of the changes of blood brain barrier permeability with the activation of apoptosis, inflammatory response and stress response in rats with cerebral hemorrhage

Objective:To study the correlation of the changes of blood brain barrier permeability with the activation of apoptosis, inflammatory response and stress response in rats with cerebral hemorrhage.Methods: SD rats were chosen as experimental animals and divided into the cerebral hemorrhage group and the control group. 24 h after molding, formamide soaking method was referred to determine the levels of blood brain barrier permeability parameters as well as the contents of apoptosis molecules, inflammatory response molecules and oxidative stress molecules in brain tissues around the hematoma.Results: Blood brain barrier permeability parameter EB level in brain tissues around hematoma of cerebral hemorrhage group was significantly higher than that of control group, and DKK1, PAR-1, Bax, Cyt-C, NF-κB, ICAM1, VCAM1, TNF-α, MMP9, NOX4 and MDA contents were higher than those of control group, andβ-catenin, Bcl-2, Mn-SOD, GSH and T-AOC contents were lower than those of control group;Pearson correlation analysis showed that EB level in brain tissues around hematoma of cerebral hemorrhage group was positively correlated with DKK1, PAR-1, Bax, Cyt-C, NF-κB, ICAM1, VCAM1, TNF-α, MMP9, NOX4 and MDA contents, and negatively correlated withβ-catenin, Bcl-2, Mn-SOD, GSH and T-AOC contents. Conclusion:The increase of blood brain barrier permeability in rats with cerebral hemorrhage is related to the excessive activation of apoptosis, inflammatory response and stress response.

EZH2 is a biomarker associated with lung cancer diagnosis and immune infiltrates without prognostic specificity: a study based on the cancer genome atlas data

Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressive complex 2(PRC2).Dysregulation of EZH2 causes alteration of gene expression and functions,thereby promoting cancer development.Recent studies suggest that EZH2 has a potential prognostic role in patients with nonsmall cell lung cancer(NSCLC).However,the prognostic value of EZH2 expression levels in NSCLC is controversial.In this study,we evaluated the prognostic value in lung cancer(LC-LUAD/LUSC)based on data from The Cancer Genome Atlas(TCGA)database.Kruskal-Wallis test,Wilcoxon signed-rank test,and logistic regression were used to evaluate the relationship between EZH2 expression and clinicopathological features.Cox regression and the Kaplan-Meier method were adopted to evaluate prognosis-related factors.Gene set enrichment analysis(GSEA)was performed to identify the key pathways related to EZH2.The correlations between EZH2 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis(ssGSEA).EZH2 was found to be up regulated with amplification in tumor tissues in multiple LC cohorts.High EZH2 expression was associated with poorer overall survival(OS).GSEA suggested that EZH2 regulates innate immune system,ECM affiliated,matrisome,surfactant metabolism.Notably,ssGSEA indicated that EZH2 expression was positively correlated with infiltrating levels of Th2 cells and significantly negatively correlated with mast cell infiltration level.These results suggest that EZH2 is associated with LC immune infiltration and significantly over-expressed in lung cancer,and its diagnostic value is better than prognosis,which lays a foundation for further study of the immunomodulatory role of EZH2 in LC.

Functions and mechanisms of protein lysine butyrylation(Kbu):Therapeutic implications in human diseases

Post-translational modifications(PTM)are covalent modifications of proteins or peptides caused by proteolytic cleavage or the attachment of moieties to one or more amino acids.PTMs play essential roles in biological function and regulation and have been linked with several diseases.Modifications of protein acylation(Kac),a type of PTM,are known to induce epigenetic regulatory processes that promote various diseases.Thus,an increasing number of studies focusing on acylation modifications are being undertaken.Butyrylation(Kbu)is a new acylation process found in animals and plants.Kbu has been recently linked to the onset and progression of several diseases,such as cancer,cardiovascular diseases,diabetes,and vascular dementia.Moreover,the mode of action of certain drugs used in the treatment of lymphoma and colon cancer is based on the regulation of butyrylation levels,suggesting that butyrylation may play a therapeutic role in these diseases.In addition,butyrylation is also commonly involved in rice gene expression and thus plays an important role in the growth,development,and metabolism of rice.The tools and analytical methods that could be utilized for the prediction and detection of lysine butyrylation have also been investigated.This study reviews the potential role of histone Kbu,as well as the mechanisms underlying this process.It also summarizes various enzymes and analytical methods associated with Kbu,with the goal of providing new insights into the role of Kbu in gene regulation and diseases.