CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling.

BACKGROUND: CD137 is a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis, has not been studied. METHODS: Foxp3+ and CD8+ T cells in GCs were investigated using immunohistochemistry (IHC). CD137 expression in GCs was detected using flow cytometry, IHC and immunofluorescence (IF). Peripheral blood mononuclear cells (PBMCs) and CD8+ T cells isolated from peripheral blood were stimulated with a CD137 agonist in vitro. CD8+ T cell proliferation and p65 expression was examined using flow cytometry. P65 nuclear translocation was analyzed using IF. IL-10, TGF-ß, IFN-γ, perforin and granzyme B were detected using real-time quantitative PCR (real-time PCR). PBMCs and primary GC cells were cocultured and stimulated with a CD137 agonist in vitro. Apoptosis of primary GC cells was detected using flow cytometry. RESULTS: Our data demonstrated that GC tumors showed characteristics of an immunosuppressive microenvironment. CD137 was predominantly expressed in CD8+ T cells in GCs and had a positive correlation with tumor cell differentiation. The CD137 agonist promoted CD8+ T cell proliferation and increased the secretion of IFN-γ, perforin and granzyme B, which induced primary GC cell apoptosis. Mechanistically, this study found that the CD137 agonist induced NF-κB nuclear translocation in CD8+ T cells. CONCLUSION: Our results demonstrated that a CD137 agonist induced primary GC cell apoptosis by enhancing CD8+ T cells via activation of NF-κB signaling.

Polyethylene glycol and divalent salt-induced DNA reentrant condensation revealed by single molecule measurements.

In this study, we investigated the DNA condensation induced by polyethylene glycol (PEG) with different molecular weights (PEG 600 and PEG 6000) in the presence of NaCl or MgCl2 by using magnetic tweezers (MT) and atomic force microscopy (AFM). The MT measurements show that with increasing NaCl concentration, the critical condensation force in the PEG 600-DNA or PEG 6000-DNA system increased approximately linearly. PEG 6000 solution has a larger critical force than PEG 600 solution at a given NaCl concentration. In comparison, a parabolic trend of the critical condensation force was observed with increasing MgCl2 concentration, indicating that DNA undergoes a reentrant condensation. The AFM results show that the morphologies of the compacted DNA-PEG complexes depended on the salt concentration and were consistent with the MT results.

Evaluation of Autofluorescence in Identifying Parathyroid Glands by Measuring Parathyroid Hormone in Fine-Needle Biopsy Washings.

Background: Near-infrared autofluorescence imaging has potentially great value for assisting endocrine surgeons in identifying parathyroid glands and may dramatically change the surgical strategy of endocrine surgeons in thyroid surgery. This study is designed to objectively evaluate the role of near-infrared autofluorescence imaging in identifying parathyroid glands during thyroid surgery by measuring intraoperative parathyroid hormone in fine-needle aspiration biopsy washings. Methods: This study was conducted at a tertiary referral teaching hospital in China from February 2020 to June 2020. Patients undergoing total thyroidectomy with or without neck lymph node dissection were consecutively included. The surgeon used near-infrared autofluorescence imaging to identify parathyroid glands during thyroid surgery and confirmed suspicious parathyroid tissues by measuring their intraoperative parathyroid hormone. Nanocarbon was injected into the thyroid gland if the thyroid autofluorescence intensity was too strong. The sensitivity and accuracy of near-infrared autofluorescence imaging and vision for identifying parathyroid glands, and the difference in autofluorescence intensity in various tissues were the main outcomes. Results: Overall, 238 patients completed the trial. Based on the pathological and aIOPTH results, the sensitivity of near-infrared autofluorescence imaging for detecting parathyroid glands (568 of 596 parathyroid glands; 95.30%)was significantly higher than that of vision (517 of 596 parathyroid glands; 86.74%, P<.001). The accuracy of near-infrared autofluorescence imaging (764 of 841 tissues; 90.84%) was significantly higher than that of vision (567 of 841 tissues; 67.42%, P<.001) when the evaluations of certain tissues were inconsistent. There was a significant difference between the autofluorescence intensity of the parathyroid glands and that of the lymph nodes (74.19 ± 17.82 vs 33.97 ± 10.64, P<.001). Conclusion: The use of near-infrared autofluorescence imaging, along with intraoperative parathyroid hormone and nanocarbon for the identification of parathyroid glands in thyroid surgery may increase the number of confirmed parathyroid glands. Using near-infrared autofluorescence imaging can effectively distinguish lymph nodes and parathyroid glands during lymph node dissection.

Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery.

BACKGROUND: The long-term pulmonary function and related physiological characteristics of COVID-19 survivors have not been studied in depth, thus many aspects are not understood. METHODS: COVID-19 survivors were recruited for high resolution computed tomography (HRCT) of the thorax, lung function and serum levels of SARS-CoV-2 IgG antibody tests 3 months after discharge. The relationship between the clinical characteristics and the pulmonary function or CT scores were investigated. FINDINGS: Fifty-five recovered patients participated in this study. SARS-CoV-2 infection related symptoms were detected in 35 of them and different degrees of radiological abnormalities were detected in 39 patients. Urea nitrogen concentration at admission was associated with the presence of CT abnormalities (P = 0.046, OR 7.149, 95% CI 1.038 to 49.216). Lung function abnormalities were detected in 14 patients and the measurement of D-dimer levels at admission may be useful for prediction of impaired diffusion defect (P = 0.031, OR 1.066, 95% CI 1.006 to 1.129). Of all the subjects, 47 of 55 patients tested positive for SARS-CoV-2 IgG in serum, among which the generation of Immunoglobulin G (IgG) antibody in female patients was stronger than male patients in infection rehabilitation phase. INTERPRETATION: Radiological and physiological abnormalities were still found in a considerable proportion of COVID-19 survivors without critical cases 3 months after discharge. Higher level of D-dimer on admission could effectively predict impaired DLCO after 3 months discharge. It is necessary to follow up the COVID-19 patients to appropriately manage any persistent or emerging long-term sequelae. FUNDING: Key Scientific Research Projects of Henan Higher Education Institutions.