Objective:Liver cancer is a deadly malignancy associated with high mortality and morbidity.Less than 20%of patients with advanced liver cancer respond to a single anti-PD-1 treatment.The high heterogeneity of neutroph...Objective:Liver cancer is a deadly malignancy associated with high mortality and morbidity.Less than 20%of patients with advanced liver cancer respond to a single anti-PD-1 treatment.The high heterogeneity of neutrophils in the tumor immune microenvironment in liver cancer may contribute to resistance to immune checkpoint blockade(ICB).However,the underlying mechanism remains largely unknown.Methods:We established an orthotopic liver cancer model by using transposable elements to integrate the oncogenes Myc and KrasG12Dinto the genome in liver cells from conditional Trp53 null/null mice(pTMK/Trp53^(-/-)).Flow cytometry and immunohistochemistry were used to assess the changes in immune cells in the tumor microenvironment.An ex vivo coculture assay was performed to test the inhibitory effects of tumor-associated neutrophils(TANs)on CD8^(+)T cells.The roles of neutrophils,T cells,and NK cells were validated through antibody-mediated depletion.The efficacy of the combination of neutrophil depletion and ICB was evaluated.Results:Orthotropic pTMK/Trp53^(-/-)mouse liver tumors displayed a moderate response to anti-Ly6G treatment but not PD-1 blockade.Depletion of neutrophils increased the infiltration of CD8^(+)T cells and decreased the number of exhausted T cells in the tumor microenvironment.Furthermore,depletion of either CD8^(+)T or NK cells abrogated the antitumor efficacy of anti-Ly6G treatment.Moreover,the combination of anti-Ly6G with anti-PD-L1 enhanced the infiltration of cytotoxic CD8^(+)T cells and thereafter resulted in a significantly greater decrease in tumor burden.Conclusions:Our data suggest that TANs may contribute to the resistance of liver cancer to ICB,and combining TAN depletion with T cell immunotherapy synergistically increases antitumor efficacy.展开更多
AIM: To explore the effect of saturated hydrogen saline on blue light-induced retinal damage in rats. METHODS: The retinal damage of rats was induced by blue light exposure for 6 hours and examined 8 hours, 16 hours a...AIM: To explore the effect of saturated hydrogen saline on blue light-induced retinal damage in rats. METHODS: The retinal damage of rats was induced by blue light exposure for 6 hours and examined 8 hours, 16 hours and 24 hours after the exposure. One hundred female Sprague-Dawley rats were randomly divided into four groups. Group 1 included 30 rats received light exposure without any other treatment. Group 2 included 30 rats received light exposure with intraperitoneal injection of normal saline. Group 3 included 30 rats received light exposure with intraperitoneal injection of saturated hydrogen saline. And Group 4 included the other 10 rats which did not receive any treatment. The amount of intraperitoneal injection of saturated hydrogen saline and normal saline was calculated in the ratio of 1ml/100g of rat weight. Specimens were collected and processed by H-E staining, ultrastructure observation, biochemical measurement. Morphological changes were observed by light microscope and transmission electron microscope (TEM) and the retinal outer nuclear layer (ONL) thickness was measured by IPP 6.0, while the malondialdehyde (MDA) was measured by colorimetric determination at 532nm. RESULTS: Although the structure of retina in Group 1 and Group 2 was injured heavily, the injury in Group 3 was mild. The differences between Group 1 and Group 2 were not significant. Compared with the rats in Group 1 and Group 2, the ones in Group 3 had more clearly demarcated retina structure and more ordered cells by light microscope and TEM observation. The ONL thicknesses (400 times) of four groups at each time point except between Group 1 and Group 2 were significantly different (P<0.05). The thicknesses of the ONL in Group 1 at three time points were 30.41 +/- 4.04 mu m, 26.11 +/- 2.82 mu m and 20.63 +/- 1.06 mu m, in Group 2 were 31.62 +/- 4.54 mu m, 25.08 +/- 3.63 mu m and 19.07 +/- 3.86 mu m, in Group 3 were 29.75 +/- 3.62 mu m, 28.83 +/- 1.97 mu m and 27.61 +/- 1.83 mu m. In Group 4 the mean of the thickness was 37.35 +/- 1.37 mu m. As time went by, the damage grew more severely. At 24h point, the differences were most significant. Compared with Group 4, the thickness was 46.23% thinner in Group 1, 50.29% thinner in Group 2 and 28.04% thinner in Group 3. The stack structures of membranous disc in Group 3 were injured slightly, but in Group 1 and Group 2 the damage was more obvious by TEM. Compared with Group 4 at each time point, the content of MDA in Group 1 was higher (P<0.05). The content of MDA in Group 3 was significantly lower than those of Group 1 ( P<0.05) and Group 2 (P<0.05). Between the Group 1 and Group 2, the MDA concentration at each time point was no significant difference (P>0.05). CONCLUSION: Saturated hydrogen saline could protect the retina from light-induced damage by attenuating oxidative stress.展开更多
Extensive lesions involving the posterior quadrant of the cerebral hemisphere （temporal, parietal, and occipital lobes） induce intractable epilepsy. These patients are potential candidates for surgical treatmenttu. ...Extensive lesions involving the posterior quadrant of the cerebral hemisphere （temporal, parietal, and occipital lobes） induce intractable epilepsy. These patients are potential candidates for surgical treatmenttu. Maintenance of isolated nerve tissue activity after surgery plays a crucial role in the neuroprotective effects of neurosurgery treatment. Disconnection surgery of the posterior quadrant is used to completely isolate nerve fibers, while blood supply at the isolated lobes is maintained. Subsequently, cavities caused by cystic or necrotic nerve tissues should be reduced as much as possible,展开更多
基金jointly supported by the National Natural Science Foundation of China(Grant Nos.81972735,82030079,and 81972656)Beijing Natural Science Foundation(Grant No.7212108)+2 种基金Michigan Medicine and PKU-HSC JI(Grant No.BMU2020JI005)Baidu Foundation(Grant No.2020BD015)Ying Shi Foundation。
文摘Objective:Liver cancer is a deadly malignancy associated with high mortality and morbidity.Less than 20%of patients with advanced liver cancer respond to a single anti-PD-1 treatment.The high heterogeneity of neutrophils in the tumor immune microenvironment in liver cancer may contribute to resistance to immune checkpoint blockade(ICB).However,the underlying mechanism remains largely unknown.Methods:We established an orthotopic liver cancer model by using transposable elements to integrate the oncogenes Myc and KrasG12Dinto the genome in liver cells from conditional Trp53 null/null mice(pTMK/Trp53^(-/-)).Flow cytometry and immunohistochemistry were used to assess the changes in immune cells in the tumor microenvironment.An ex vivo coculture assay was performed to test the inhibitory effects of tumor-associated neutrophils(TANs)on CD8^(+)T cells.The roles of neutrophils,T cells,and NK cells were validated through antibody-mediated depletion.The efficacy of the combination of neutrophil depletion and ICB was evaluated.Results:Orthotropic pTMK/Trp53^(-/-)mouse liver tumors displayed a moderate response to anti-Ly6G treatment but not PD-1 blockade.Depletion of neutrophils increased the infiltration of CD8^(+)T cells and decreased the number of exhausted T cells in the tumor microenvironment.Furthermore,depletion of either CD8^(+)T or NK cells abrogated the antitumor efficacy of anti-Ly6G treatment.Moreover,the combination of anti-Ly6G with anti-PD-L1 enhanced the infiltration of cytotoxic CD8^(+)T cells and thereafter resulted in a significantly greater decrease in tumor burden.Conclusions:Our data suggest that TANs may contribute to the resistance of liver cancer to ICB,and combining TAN depletion with T cell immunotherapy synergistically increases antitumor efficacy.
文摘AIM: To explore the effect of saturated hydrogen saline on blue light-induced retinal damage in rats. METHODS: The retinal damage of rats was induced by blue light exposure for 6 hours and examined 8 hours, 16 hours and 24 hours after the exposure. One hundred female Sprague-Dawley rats were randomly divided into four groups. Group 1 included 30 rats received light exposure without any other treatment. Group 2 included 30 rats received light exposure with intraperitoneal injection of normal saline. Group 3 included 30 rats received light exposure with intraperitoneal injection of saturated hydrogen saline. And Group 4 included the other 10 rats which did not receive any treatment. The amount of intraperitoneal injection of saturated hydrogen saline and normal saline was calculated in the ratio of 1ml/100g of rat weight. Specimens were collected and processed by H-E staining, ultrastructure observation, biochemical measurement. Morphological changes were observed by light microscope and transmission electron microscope (TEM) and the retinal outer nuclear layer (ONL) thickness was measured by IPP 6.0, while the malondialdehyde (MDA) was measured by colorimetric determination at 532nm. RESULTS: Although the structure of retina in Group 1 and Group 2 was injured heavily, the injury in Group 3 was mild. The differences between Group 1 and Group 2 were not significant. Compared with the rats in Group 1 and Group 2, the ones in Group 3 had more clearly demarcated retina structure and more ordered cells by light microscope and TEM observation. The ONL thicknesses (400 times) of four groups at each time point except between Group 1 and Group 2 were significantly different (P<0.05). The thicknesses of the ONL in Group 1 at three time points were 30.41 +/- 4.04 mu m, 26.11 +/- 2.82 mu m and 20.63 +/- 1.06 mu m, in Group 2 were 31.62 +/- 4.54 mu m, 25.08 +/- 3.63 mu m and 19.07 +/- 3.86 mu m, in Group 3 were 29.75 +/- 3.62 mu m, 28.83 +/- 1.97 mu m and 27.61 +/- 1.83 mu m. In Group 4 the mean of the thickness was 37.35 +/- 1.37 mu m. As time went by, the damage grew more severely. At 24h point, the differences were most significant. Compared with Group 4, the thickness was 46.23% thinner in Group 1, 50.29% thinner in Group 2 and 28.04% thinner in Group 3. The stack structures of membranous disc in Group 3 were injured slightly, but in Group 1 and Group 2 the damage was more obvious by TEM. Compared with Group 4 at each time point, the content of MDA in Group 1 was higher (P<0.05). The content of MDA in Group 3 was significantly lower than those of Group 1 ( P<0.05) and Group 2 (P<0.05). Between the Group 1 and Group 2, the MDA concentration at each time point was no significant difference (P>0.05). CONCLUSION: Saturated hydrogen saline could protect the retina from light-induced damage by attenuating oxidative stress.
基金The Science Fund of Health Bureau of Tianjin,No.2013KZ046
文摘Extensive lesions involving the posterior quadrant of the cerebral hemisphere （temporal, parietal, and occipital lobes） induce intractable epilepsy. These patients are potential candidates for surgical treatmenttu. Maintenance of isolated nerve tissue activity after surgery plays a crucial role in the neuroprotective effects of neurosurgery treatment. Disconnection surgery of the posterior quadrant is used to completely isolate nerve fibers, while blood supply at the isolated lobes is maintained. Subsequently, cavities caused by cystic or necrotic nerve tissues should be reduced as much as possible,
