The roles of prostaglandin E2 and D2 in lipopolysaccharide-mediated changes in sleep

When living organisms become sick as a result of a bacterial infection, a suite of brain-mediated responses occur, including fever, anorexia and sleepiness. Systemic administration of lipopolysaccharide (LPS), a common constituent of bacterial cell walls, increases body temperature and non-rapid eye movement (NREM) sleep in animals and induces the production of pro-inflammatory prostaglandins (PGs). PGE₂ is the principal mediator of fever, and both PGE₂ and PGD₂ regulate sleep–wake behavior. The extent to which PGE₂ and PGD₂ are involved in the effect of LPS on NREM sleep remains to be clarified. Therefore, we examined LPS-induced changes in body temperature and NREM sleep in mice with nervous system-specific knockouts (KO) for the PGE₂ receptors type EP₃ or EP₄, in mice with total body KO of microsomal PGE synthase-1 or the PGD₂ receptor type DP, and in mice treated with the cyclooxygenase (COX) inhibitor meloxicam. We observed that LPS-induced NREM sleep was slightly attenuated in mice lacking EP₄ receptors in the nervous system, but was not affected in any of the other KO mice or in mice pretreated with the COX inhibitor. These results suggest that the effect of LPS on NREM sleep is partially dependent on PGs and is likely mediated mainly by other pro-inflammatory substances. In addition, our data show that the main effect of LPS on body temperature is hypothermia in the absence of nervous system EP₃ receptors or in the presence of a COX inhibitor.     

Association of weight-adjusted-waist index with incident hypertension: The Rural Chinese Cohort Study

AimsTo explore the association between WWI and the incidence of HTN in the Rural Chinese Cohort Study.Methods and ResultsWe examined data for 10,338 non-hypertensive participants (39.49% men) aged ≥ 18 years from the Rural Chinese Cohort Study who completed a baseline examination during 2007–2008 and follow-up during 2013–2014. WWI was calculated as waist circumference (cm) divided by the square root of weight (kg). Multiple logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the probability of HTN across four WWI categories. Restricted cubic splines analysis was used to model the dose–response association of WWI and HTN. A total of 2078 participants had HTN during a median follow-up of 6 years. After adjusting for potential confounders, as compared with the lowest WWI category (<9.94 cm/√kg), with WWI 9.94 to 10.42, 10.42 to 10.91 and ≥ 10.91 cm/√kg, the ORs (95% CIs) for HTN were 1.12 (0.93–1.35), 1.40 (1.17–1.69) and 1.50 (1.24–1.82), respectively. Results of the sensitivity analyses were robust. The ORs were generally consistent on subgroup analysis by sex, smoking status, systolic blood pressure and diastolic blood pressure. Multiple logistic regression models with restricted cubic splines showed a non-linear positive association between WWI and HTN (P_nonlinearity < 0.001).ConclusionThe highest WWI category was significantly associated with increased risk of HTN. Our findings may facilitate the development and promotion of obesity prevention strategies aimed at reducing the risk of HTN and provide evidence for healthcare policy in rural China.     

健康成年人接种两剂新型冠状病毒灭活疫苗后序贯加强免疫重组新型冠状病毒疫苗(CHO细胞)的免疫原性和安全性研究

目的 评价在接种两剂已上市新冠病毒灭活疫苗的人群中序贯加强免疫重组新型冠状病毒疫苗(CHO细胞)后的免疫原性和安全性,为制定新型冠状病毒疫苗的加强免疫策略提供科学依据。 方法 采用开放性试验设计,筛选入组360例已接种两剂新冠病毒灭活疫苗3～4个月、6～8个月、11～13个月的18周岁及以上研究对象并接种1剂重组新型冠状病毒疫苗(CHO细胞)。采集所有研究对象研究用疫苗接种前、接种后14 d血样,用于体液免疫检测,收集研究用疫苗接种后1个月内的所有不良事件。 结果 本研究入组360例研究对象,按研究对象加强免疫与基础免疫间隔时间分3组(A组91～120 d,B组181～240 d,C组331～390 d),各组120例,无研究对象脱落。三组年龄均值分别为38.13、40.22和45.73岁,各组间年龄差异有统计学意义(F=13.516,P＜0.001),A、B组差异无统计学意义(P=0.168),C组和A、B组间差异均有统计学意义(P＜0.001)。三组 IgG GMC(几何平均浓度)免疫前分别为4.81、4.23、2.12 AU/ml,差异有统计学意义(F=10.054,P＜0.001),C组和A、B组间差异均有统计学意义(P＜0.001),A、B组间差异无统计学意义(P=0.520);三组免疫后 IgG GMC 分别为106.69、124.05、80.04 AU/ml,差异无统计学意义(F=2.028,P=0.133)。三组 IgG 抗体阳转率分别为84.17%、87.50%、79.17%,差异无统计学意义(χ²=3.081,P=0.214)。免疫前血清针对Delta变异株和原型株不同组别的中和抗体滴度比较,三组原型株中和抗体GMT(几何平均滴度)为1∶2.18、1∶2.18、1∶2.19,差异无统计学意义(F=0.011,P=0.990);三组Delta变异株中和抗体GMT为1∶2.09、1∶2.17、1∶2.16,差异无统计学意义(F=0.378,P=0.686)。免疫后血清三组原型株中和抗体 GMT为1∶31.09、1∶34.90、1∶21.98,差异无统计学意义(F=2.262,P=0.106);三组Delta变异株中和抗体GMT为1∶61.46、1∶77.44、1∶43.71,差异无统计学意义(F=2.105,P=0.123)。序贯加强免疫后血清对新型冠状病毒Delta变异株和原型株的中和抗体阳转率分别达到82.78%、83.33%。三组 SARS-CoV-2原型株中和抗体阳转率分别为86.67%、87.50%、75.83%,差异有统计学意义(χ²=7.320,P=0.026),其中C组低于A组和B组;三组 SARS-CoV-2 Delta变异株中和抗体阳转率分别为87.50%、84.17%、76.67%,差异无统计学意义(χ²=5.183,P=0.075)。发生不良事件人数为124人,不良事件总体发生率为34.44%。各组发生率分别为35.83%、40.83%和26.67%,差异无统计学意义(χ²=5.487,P=0.064),所有研究对象出现的不良事件以接种部位不良事件为主,主要表现为疫苗接种部位疼痛(23.89%);全身不良事件主要表现为疲劳/乏力(6.94%),未发生与疫苗接种有关的SAEs。结论 接种两剂新型冠状病毒灭活疫苗后序贯加强免疫重组新型冠状病毒疫苗(CHO细胞)具有良好的免疫原性和安全性。较长间隔期的免疫前IgG和免疫后原型株中和抗体阳转率较低,不同间隔期的免疫后IgG 、Delta变异株和原型株中和抗体水平比较差异均无统计学意义,建议基础免疫后6~8个月为最佳的接种间隔。