Objective To evaluate the changes of CD4+ CD25+ regulatory cells (Treg) in peripheral blood and the serum levels of transforming growth factor beta-1 (TGF-β1)in elderly patients with hepatocellular carcinoma. Methods The ratios of Treg in the peripheral blood of patients aged over 80 years from 22 hepatocellular carcinoma,26 metastatic liver cancer,20 healthy controls,were determined by flow cytometry.Meanwhile,the serum levels of TGF-β1 were detected by ELISA.Results The ratio of Treg to total CD; T cells in the peripheral blood [(9.71±3.23)％ vs.(5.81±1.18)％,P＜0.01]and the serum levels of TGF-β1 [(78.10±29.41)ng/L vs.(7.78± 3.54) ng/L,P＜0.01]of elderly patients with hepatocellular carcinoma were significantly higher than those in the healthy controls.Meanwhile,the ratio of Treg to total CD[ T cells in the peripheral blood [(9.71±3.23)％ vs.(7.36±2.07) ％,P＜0.05]and the serum levels of TGF-β1[(78.10± 29.41 )ng/L vs.(19.33± 10.90) ng/L,P＜ 0.01 ]in the patients with hepatocellular carcinoma was increased as compared with those in metastatic liver cancer (P＜0.05 or P＜0.01).The correlation indicated that the ratio of Treg to total CD4+ T cells in the peripheral blood were positively related with TGF-β1 levels and tumor clinical stage(r=0.698 and 0.782,P＜ 0.01 ),but negatively with Karnofsky performance status score(KPS) (r=-0.643,P＜0.01). Conclusions The ratio of Treg to total CD4+ T cells in the peripheral blood from elderly hepatocellular carcinoma is increased and correlated with TGF-βl level,tumor clinical stage and KPS.It might helpful to determine the prognosis of elderly hepatocellular carcinoma by detecting the ratio of Treg to total CD4+ T cells in the peripheral blood.

LR11, also known as SorLA or SORL1, is a type-I membrane protein from which a large extracellular part, soluble LR11 (sLR11), is released by proteolytic shedding on cleavage with a disintegrin and metalloproteinase 17 (ADAM17). A shedding mechanism is presumed to have a key role in the functions of LR11, but the evidence for this has not yet been demonstrated. Tetraspanin CD9 has been recently shown to regulate the ADAM17-mediated shedding of tumor necrosis factor-alpha and intercellular adhesion molecule-1 on the cell surface. Here, we investigated the role of CD9 on the shedding of LR11 in leukocytes. LR11 was not expressed in THP-1 monocytes, but it was expressed and released in phorbol 12-myristate 13-acetate (PMA)-induced THP-1 macrophages (PMA/THP-1). Confocal microscopy showed colocalization of LR11 and CD9 proteins on the cell surface of PMA/THP-1. Ectopic neo-expression of CD9 in CCRF-SB cells, which are LR11-positive and CD9-negative, reduced the amount of sLR11 released from the cells. In contrast, incubation of LR11-transfected THP-1 cells with neutralizing anti-CD9 monoclonal antibodies increased the amount of sLR11 released from the cells. Likewise, the PMA-stimulated release of sLR11 increased in THP-1 cells transfected with CD9-targeted shRNAs, which was negated by treatment with the metalloproteinase inhibitor GM6001. These results suggest that the tetraspanin CD9 modulates the ADAM17-mediated shedding of LR11 in various leukemia cell lines and that the association between LR11 and CD9 on the cell surface has an important role in the ADAM17-mediated shedding mechanism.
ADAM Proteins/*metabolism ; Antigens, CD9/genetics/*metabolism ; Cell Line, Tumor ; Humans ; LDL-Receptor Related Proteins/genetics/*metabolism ; Leukocytes/*metabolism ; Macrophages/metabolism ; Membrane Transport Proteins/genetics/*metabolism ; Proteolysis

Objective:To evaluate the development and application of gastrointestinal endoscopy technology in Beijing-Tianjin-Hebei (BTH) region from 2016 to 2020, and the impact of the corona virus disease 2019 (COVID-19) epidemic on gastrointestinal endoscopy screening and lesion detection rate of medical institutions.Methods:Data of gastroscopy and colonoscopy cases from 26 cooperative institutions in BTH Region Gastrointestinal Endoscopy Medical Association from January 2016 to December 2020 were collected by questionnaire. The number of gastrointestinal endoscopy, the detection of main lesions (including upper gastrointestinal malignant tumors, early gastric cancer and colon cancer), and the number of endoscopic treatment were retrospectively analyzed by year.Results:From 2016 to 2019, the number of gastroscopy and colonoscopy showed a yearly increasing trend with an annual growth rate of over 10%. Compared with 2019, the number of gastroscopy and colonoscopy decreased by 10.86% and 8.29%, respectively, in 2020 due to the impact of the epidemic. The annual detection rates of upper gastrointestinal malignant tumors, early gastric cancer and colon cancer were on a rise, from 7.22%, 1.49% and 8.98% in 2016 to 9.87%, 2.71% and 12.04% in 2020, respectively. The number of gastroscopic mucosal resection, submucosal dissection and colonoscopic endoscopic submucosal dissection increased yearly, from 2 132, 300 and 217 cases in 2016 to 5 466, 872 and 560 cases in 2020, respectively.Conclusion:The Medical Association has promoted the expansion of endoscopic screening and the application of endoscopic treatment techniques, resulting in a continuous increase in the endoscopy detection rate and early cancer diagnosis rate in the BTH region. The sharp decrease of gastrointestinal endoscopy procedures and the increase in the lesion detection rate in 2020 reflect the impact of epidemic COVID-19 on detection of gastrointestinal cancers.