Fas-ligand-mediated paracrine T cell regulation by the receptor NKG2D in tumor immunity

Tumor-associated ligands of the activating NKG2D receptor can effectively stimulate T cell responses at early but not late stages of tumor growth. In late-stage human tumor settings, we observed MIC-driven proliferation of NKG2D(+)CD4(+) T cells that produced the cytokine Fas ligand (FasL) as a result of NKG2D costimulation but were themselves protected from Fas-mediated growth arrest. In contrast, FasL suppressed proliferation of T cells in vitro that did not receive NKG2D costimulation. Similar observations with normal peripheral blood NKG2D(+)CD8(+) T cells demonstrated unrecognized NKG2D-mediated immune functions, whereby FasL release promotes tumor cell death and NKG2D costimulation prolongs T cell survival. These effects, beneficial in conditions of limited NKG2D ligand expression, may be counterweighed when massive expression and shedding of MIC occurs, such as in some late-stage tumors, that causes sustained NKG2D costimulation and population expansion of immunosuppressive T cells.     

A one-year follow-up study on dynamic changes of leukocyte subsets and virus-specific antibodies of patients with COVID-19 in Sichuan,China

Background: SARS-CoV-2 infection causes immune response and produces protective antibodies, and these changes may persist after patients discharged from hospital.Methods: This study conducted a one-year follow-up study on patients with COVID-19 to observe the dynamic changes of circulating leukocyte subsets and virus-specific antibodies.Results: A total of 66 patients with COVID-19 and 213 healthy patients with inactivated SARS-CoV-2 vaccination were included. The virus-specific total antibody, IgG and IgM antibody of patients after one year of recovery were higher than those of healthy vaccinated participants (94.13 vs 4.65, 2.67 vs 0.44, 0.09 vs 0.06, respectively) (P < 0.001). Neutrophil count (OR = 1.73, 95% CI: 1.10-2.70, P = 0.016) and neutrophil-to-lymphocyte ratio (OR = 1.59, 95% CI: 1.05-2.41, P = 0.030) at discharge were the influencing factors for the positivity of virus-specific IgG antibody in patients after one year of recovery. The counts of CD4+ and CD8+ T, B and NK cells increased with the time of recovery, and remained basically stable from 9 to 12 months after discharge. After 12 months, the positivity of IgG antibody was 85.3% and IgM was 11.8%, while the virus-specific antibody changed dynamically in patients within one year after discharge.Conclusions: The SARS-CoV-2 specific antibody of recovered patients showed dynamic fluctuation after discharge, while the leukocyte subsets gradually increased and basically stabilized after 9 months.     

前视超声内镜治疗食管-胃底静脉曲张的初步研究

目的 探讨前视超声内镜在食管-胃底静脉曲张（EGV）诊疗中的优势。方法 选取2019年5月－2021年5月郑州大学第一附属医院消化内科收治的EGV患者40例,行前视超声内镜引导下治疗的为观察组（n = 19）,普通内镜下治疗的为对照组（n = 21）。术后随访3～6个月,比较两组患者组织胶使用情况、术后并发症、治疗效果和再出血情况等。结果 观察组组织胶注射次数及用量均较对照组少,两组患者比较,差异有统计学意义（P < 0.05）。术后均无严重并发症发生,两组患者并发症总发生率比较,差异无统计学意义（P > 0.05）。术后72 h～3个月,观察组总出血率为10.52%,与对照组的19.05%比较,差异无统计学意义（P > 0.05）。术后1个月所有患者复查胃镜,观察组中治疗效果显著、一般和无效的占比分别为63.16%、31.58%和5.26%,与对照组的33.33%、38.10%和28.57%比较,差异有统计学意义（P < 0.05）。结论 前视超声内镜引导下治疗EGV,较普通内镜可减少组织胶用量,提高治疗效果。     

Comparison of differences in development potentials between frozen-thawed D5 and D6 blastocysts and their relationship with pregnancy outcomes

Purpose

Whether there are differences in the pregnancy outcomes of blastocysts cryopreserved during different developmental stages remains under debate because the results among studies are inconsistent. We analyzed blastocyst quality and pregnancy outcomes by considering blastocyst euploidy and investigated the differences in the development potential between blastocysts of different developmental stages (frozen-thawed day 5 [D5] and day 6 [D6] cycles) and their relationship with clinical pregnancy outcomes.

Methods

In total, 1374 D5 and 255 D6 frozen-thawed blastocyst transfer cycles were retrospectively analyzed. Additionally, the chromosome euploidy and clinical pregnancy rates of 237 blastocysts from 50 pre-implantation genetic diagnosis (PGS) cycles were statistically analyzed. The corresponding euploidy rate and pregnancy outcomes of the D5 and D6 blastocyst transfers were also compared.

Results

The clinical pregnancy rate (47.2 vs 40.0 %; P?=?0.04) and implantation rate (34.2 vs 28.8 %; P?=?0.03) of the D5 blastocysts were higher than were those of the D6 blastocysts. However, the clinical pregnancy rate (52.4 vs 52.6 %; P?=?0.97) and implantation rate (38.9 vs 35.6 %; P?=?0.39) of the high-quality D5 blastocysts did not significantly differ from those of the high-quality D6 blastocysts. Analysis of blastocyst euploidy in 237 blastocysts examined in 50 PGS cycles showed that the euploidy rates of the D5 and D6 blastocysts were both 48.1 % (P?=?0.99). The clinical pregnancy rate of the D5 blastocysts (48.5 vs 17.6 %; P?=?0.03) was higher than that of the D6 blastocysts. The euploidy rates (55.2 vs 55.3 %; P?=?0.99) and clinical pregnancy rates (60.0 vs 42.9 %; P?=?0.77) of the high-quality D5 and D6 blastocysts did not differ. The euploidy rate (55.3 vs 41.5 %, P?=?0.03) and clinical pregnancy rate (54.5 vs 25.0 %, P?=?0.03) of the high-quality blastocysts were higher than were those of the poor-quality blastocysts.

Conclusions

The euploidy rates between the D5 and D6 blastocysts did not differ. High-quality D6 blastocysts in frozen-thawed cycles had similar developmental potential and pregnancy outcomes compared to those of high-quality D5 blastocysts. The quality of the blastocysts was an important factor that affected the pregnancy outcomes of the frozen-thawed cycles.

     

Feeding with powdered diet after weaning increases visuospatial ability in association with increases in the expression of N-methyl-D-aspartate receptors in the hippocampus of female rats

We determined whether feeding with powdered diet improved the visuospatial ability in female rats by checking the expression of N-methyl-D-aspartate receptor (NMDAR) subunit 1 (NR1) mRNA in the hippocampus. In rats fed standard pelleted diet, males performed better than females in a radial 8-arm maze task as we reported previously. We found that the expression of NR1 mRNA, which may be the key mediator in visuospatial ability in the hippocampus, was also higher in males than in females. However, in rats fed powdered diet, no sex difference was seen in the radial 8-arm maze task and the expression of NR1 mRNA in the hippocampus, since feeding with powdered diet improved the visuospatial ability with increases in the expression of NR1 mRNA in the hippocampus in females. We suggest that the sex difference in visuospatial ability is at least in part due to feeding conditions.     

Mutational analysis of the yeast multidrug resistance ABC transporter Pdr5p with altered drug specificity

Multidrug resistance ABC transporter Pdr5p of Saccharomyces cerevisiae is particularly important due to its ability to export a wide range of unrelated substrates. To clarify its function, we generated Pdr5p mutants by random mutagenesis and screened for mutants with altered drug specificity in vivo by using 5 drug compounds. Nine point mutations that caused significant changes in drug specificity distributed throughout the length of Pdr5p, namely, in the extracellular, transmembrane or cytoplasmic regions of the transporter. We then investigated their effects upon drug resistance, using 36 chemically related or distinct substrates. From this study, overall geometry of the Pdr5p was suggested to contribute in acquiring the enormous range of drug specificity. Based on their ability to inhibit the growth of the mutant strains, the 36 tested drugs were classified into: drugs to which the mutants responded differently (Group 1), drugs to which all the mutants showed sensitivity (Group 2), and drugs to which all the mutants exhibited resistance (Group 3). The ability of the compounds to be partitioned to the plasma membrane seemed an important factor for recognition by Pdr5p.