目的识别HIV阳性和阴性衰弱者衰弱类型并探索其分布和流行病学特征差异,以便为HIV阳性衰弱者采取的干预提供依据。方法选取2017年2月―2020年1月台州市“HIV与衰老相关疾病前瞻性队列研究”(the comparative HIV and aging research in ...目的识别HIV阳性和阴性衰弱者衰弱类型并探索其分布和流行病学特征差异,以便为HIV阳性衰弱者采取的干预提供依据。方法选取2017年2月―2020年1月台州市“HIV与衰老相关疾病前瞻性队列研究”(the comparative HIV and aging research in Taizhou cohort,CHART)基线数据中符合Fried衰弱表型标准的HIV阳性和阴性衰弱者,对五项衰弱问题进行潜类别聚类分析。结果83例HIV阳性衰弱者和101例阴性衰弱者被聚成三类(第一类:低体力活动、疲惫和握力差为特点的无力状,即无力组;第二类:以低步速为突出特点的五项功能差,即低步速组;第三类:体重减少和轻度无力状,即消瘦组)。HIV阳性衰弱者在低步速组中占比较高,为54.2%,阴性衰弱者在无力组中占比较高,为35.6%。HIV阳性衰弱者低步速组现在吸烟比例高于消瘦组(χ^(2)=10.889,P=0.004),无力组现在吸烟比例高于消瘦组(χ^(2)=7.909,P=0.019),消瘦组偏瘦比例高于无力组(χ^(2)=9.309,P=0.009)。阴性衰弱者无力组≥60岁比例高于消瘦组(χ^(2)=10.502,P=0.001),睡眠障碍患病率低于消瘦组(χ^(2)=6.541,P=0.011);低步速组≥60岁比例高于消瘦组(χ^(2)=6.232,P=0.013)。结论HIV阳性和阴性衰弱者衰弱类型构成不同,HIV阳性衰弱者表现为以低步速为突出特点的五项功能差。应结合其特征进行干预。展开更多
Background Treatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmon...Background Treatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmonary inflammation and lung injury during acute endotoxemia. Methods Thirty-two male Sprague-Dawley rats were randomly assigned to four groups： vehicle ＋ saline group, melatonin ＋ saline group, vehicle ＋ lipopolysaccharide group, melatonin ＋ lipopolysaccharide group. The rats were treated with melatonin （10 mg/kg, intraperitoneal injection （i.p.）） or vehicle （1% ethanol saline）, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, intravenous injection）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Blood gas analysis was carried out. Optical microscopy was performed to examine pathological changes in lungs and lung injury score was assessed. Wet/dry ratios （W/D）, myeloperoxidase activity, malondialdehyde concentrations and tumor necrosis factor-alpha （TNF-α） and interleukin-10 （IL-10） levels in lungs were measured. The pulmonary expression of nuclear factor-kappa B （NF-κB） p65 was evaluated by Western blotting. Results PaO2 in the vehicle ＋ lipopolysaccharide group decreased compared with that in the vehicle ＋ saline group. This decrease was significantly reduced in the melatonin ＋ lipopolysaccharide group. The lung tissues from the saline ＋ lipopolysaccharide group were significantly damaged, which were less pronounced in the melatonin ＋ lipopolysaccharide group. The W/D ratio increased significantly in the vehicle ＋ lipopolysaccharide group （6.1±0.18） as compared with that in the vehicle ＋ saline group （3.61±0.3） （P 〈0.01）, which was significantly reduced in the melatonin ＋ lipopolysaccharide group （4.8±0.25） （P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the vehicle ＋ lipopolysaccharide group compared with that in the vehicle ＋ saline group, which was reduced in the melatonin ＋ lipopolysaccharide group. The TNF-a level of pulmonary tissue increased significantly in the vehicle ＋ lipopolysaccharide group （（8.7±0.91） pg/mg protein） compared with that in the vehicle ＋ saline group （（4.3±0.62） pg/mg protein, P 〈0.01）. However, the increase of TNF-a level of pulmonary tissue was significantly reduced in the melatonin ＋ lipopolysaccharide group （（5.9±0.56） pg/mg protein, P 〈0.01）. Pulmonary IL-10 levels were elevated markedly in the vehicle ＋ lipopolysaccharide group in contrast to that in the vehicle ＋ saline group, whereas the elevation was augmented in the melatonin ＋ lipopolysaccharide group. The nuclear localization of p65 increased markedly in the vehicle ＋ lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the melatonin ＋ lipopolysaccharide group. Conclusion Melatonin reduces acute lung injury in endotoxemic rats by attenuating pulmonary inflammation and inhibiting NF-κB activation.展开更多
Background Valproic acid （VPA） improves early survival and organ function in a highly lethal poly-trauma and hemorrhagic shock model or other severe insults. We assessed whether VPA could improve organ function in a...Background Valproic acid （VPA） improves early survival and organ function in a highly lethal poly-trauma and hemorrhagic shock model or other severe insults. We assessed whether VPA could improve organ function in a rat model of septic shock and illustrated the possible mechanisms. Methods Forty Sprague-Dawley rats were randomly assigned to four groups （n=-10）： control group, VPA group, LPS group, and LPS＋VPA group. Lipopolysaccharide （LPS） （10 mg/kg） was injected intravenously to replicate the experimental model of septic shock. Rats were treated with VPA （300 mg/kg, i.v.） or saline. Six hours after LPS injection, blood was sampled for gas analysis, measurement of serum alanine aminotransferase, aspartate aminotransferase, urine nitrogen, creatinine and tumor necrosis factor-alpha. Lung, liver and kidney were collected for histopathological assessment. In addition, myeloperoxidase activity and tumor necrosis factor-α in pulmonary tissue were measured. Acetylation of histone H3 in lung was also evaluated by Western blotting. Results LPS resulted in a significant decrease in PaO2, which was increased by VPA administration followed LPS injection. In addition, LPS also induced an increase in the serum levels of alanine aminotransferase, aspartate aminotransferase, urine nitrogen, creatinine, and tumor necrosis factor-alpha. However, these increases were attenuated in the LPS＋VPA group. The lungs, liver and kidneys from the LPS group were significantly damaged compared with the control group. However, the damage was attenuated in the LPS＋VPA group. Myeloperoxidase activity and tumor necrosis factor-alpha levels in pulmonary tissue increased significantly in the LPS group compared with the control group. These increases were significantly inhibited in the LPS＋VPA group. Acetylation of histone H3 in lung tissue in the LPS group was inhibited compared with the control. However, the level of acetylation of histone H3 in the LPS＋VPA group was markedly elevated in contrast to the LPS group. Conclusions Treatment with VPA can attenuate multiple organ damage caused by LPS induced septic shock. Our data also suggest that the beneficial effects are in part due to the decrease in inflammatory cytokines and restoration of normal acetylation homeostasis.展开更多
Background Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung inju...Background Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung injury during acute endotoxaemia.Methods A total of 32 male Sprague-Dawley rats were randomly assigned to four groups： saline group, erythropoietin＋saline group, saline＋lipopolysaccharide group and erythropoietin＋lipopolysaccharide group. Rats were treated with erythropoietin （3000 U/kg, i.p.） or saline, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, i.v.）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Wet/dry （W/D） ratios, myeloperoxidase activity, malondialdehyde concentrations and tumour necrosis factor-alpha （TNF-α） as well as interleukin 1 beta （IL-1β） levels in lungs were measured. The pulmonary expression of nuclear factor kappaB （NF-κB） p65 was evaluated by Western blotting. Differences between the different groups were analysed by one-way analysis of variance （ANOVA）.Results The lung tissues from the saline＋lipopolysaccharide group were significantly damaged, which were less pronounced in the erythropoietin＋lipopolysaccharide group. The W/D ratio increased significantly in the saline＋lipopolysaccharide group （5.75±0.22） as compared with the saline group （3.85±0.20） （P 〈0.01）, which was significantly reduced in the erythropoietin＋lipopolysaccharide group （4.50±0.35） （P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the saline＋lipopolysaccharide group compared with the saline group, which was reduced in the erythropoietin ＋ lipopolysaccharide group. The TNF-α level of pulmonary tissue increased significantly in the saline＋lipopolysaccharide group （（9.80±0.82） pg/mg protein） compared with the saline group （（4.20=L-0.42） pg/mg protein, P 〈0.01）. However, the increase of TNF-α level of pulmonary tissue was significantly reduced in the erythropoietin＋lipopolysaccharide group （（6.50±0.66） pg/mg protein, P 〈0.01）. Similarly, pulmonary IL-1β levels were elevated markedly in the saline＋lipopolysaccharide group in contrast to the saline group, whereas the elevation was much less in the erythropoietin＋lipopolysaccharide group. The nuclear localization of p65 increased markedly in the saline＋lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the erythropoietin＋lipopolysacchadde group.Conclusion Erythropoietin attenuates pulmonary inflammation and suppresses TNF-α and IL-1β overproduction during acute endotoxaemia, which is partially mediated by inhibition of NF-KB.展开更多
文摘目的识别HIV阳性和阴性衰弱者衰弱类型并探索其分布和流行病学特征差异,以便为HIV阳性衰弱者采取的干预提供依据。方法选取2017年2月―2020年1月台州市“HIV与衰老相关疾病前瞻性队列研究”(the comparative HIV and aging research in Taizhou cohort,CHART)基线数据中符合Fried衰弱表型标准的HIV阳性和阴性衰弱者,对五项衰弱问题进行潜类别聚类分析。结果83例HIV阳性衰弱者和101例阴性衰弱者被聚成三类(第一类:低体力活动、疲惫和握力差为特点的无力状,即无力组;第二类:以低步速为突出特点的五项功能差,即低步速组;第三类:体重减少和轻度无力状,即消瘦组)。HIV阳性衰弱者在低步速组中占比较高,为54.2%,阴性衰弱者在无力组中占比较高,为35.6%。HIV阳性衰弱者低步速组现在吸烟比例高于消瘦组(χ^(2)=10.889,P=0.004),无力组现在吸烟比例高于消瘦组(χ^(2)=7.909,P=0.019),消瘦组偏瘦比例高于无力组(χ^(2)=9.309,P=0.009)。阴性衰弱者无力组≥60岁比例高于消瘦组(χ^(2)=10.502,P=0.001),睡眠障碍患病率低于消瘦组(χ^(2)=6.541,P=0.011);低步速组≥60岁比例高于消瘦组(χ^(2)=6.232,P=0.013)。结论HIV阳性和阴性衰弱者衰弱类型构成不同,HIV阳性衰弱者表现为以低步速为突出特点的五项功能差。应结合其特征进行干预。
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 30571787）.
文摘Background Treatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmonary inflammation and lung injury during acute endotoxemia. Methods Thirty-two male Sprague-Dawley rats were randomly assigned to four groups： vehicle ＋ saline group, melatonin ＋ saline group, vehicle ＋ lipopolysaccharide group, melatonin ＋ lipopolysaccharide group. The rats were treated with melatonin （10 mg/kg, intraperitoneal injection （i.p.）） or vehicle （1% ethanol saline）, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, intravenous injection）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Blood gas analysis was carried out. Optical microscopy was performed to examine pathological changes in lungs and lung injury score was assessed. Wet/dry ratios （W/D）, myeloperoxidase activity, malondialdehyde concentrations and tumor necrosis factor-alpha （TNF-α） and interleukin-10 （IL-10） levels in lungs were measured. The pulmonary expression of nuclear factor-kappa B （NF-κB） p65 was evaluated by Western blotting. Results PaO2 in the vehicle ＋ lipopolysaccharide group decreased compared with that in the vehicle ＋ saline group. This decrease was significantly reduced in the melatonin ＋ lipopolysaccharide group. The lung tissues from the saline ＋ lipopolysaccharide group were significantly damaged, which were less pronounced in the melatonin ＋ lipopolysaccharide group. The W/D ratio increased significantly in the vehicle ＋ lipopolysaccharide group （6.1±0.18） as compared with that in the vehicle ＋ saline group （3.61±0.3） （P 〈0.01）, which was significantly reduced in the melatonin ＋ lipopolysaccharide group （4.8±0.25） （P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the vehicle ＋ lipopolysaccharide group compared with that in the vehicle ＋ saline group, which was reduced in the melatonin ＋ lipopolysaccharide group. The TNF-a level of pulmonary tissue increased significantly in the vehicle ＋ lipopolysaccharide group （（8.7±0.91） pg/mg protein） compared with that in the vehicle ＋ saline group （（4.3±0.62） pg/mg protein, P 〈0.01）. However, the increase of TNF-a level of pulmonary tissue was significantly reduced in the melatonin ＋ lipopolysaccharide group （（5.9±0.56） pg/mg protein, P 〈0.01）. Pulmonary IL-10 levels were elevated markedly in the vehicle ＋ lipopolysaccharide group in contrast to that in the vehicle ＋ saline group, whereas the elevation was augmented in the melatonin ＋ lipopolysaccharide group. The nuclear localization of p65 increased markedly in the vehicle ＋ lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the melatonin ＋ lipopolysaccharide group. Conclusion Melatonin reduces acute lung injury in endotoxemic rats by attenuating pulmonary inflammation and inhibiting NF-κB activation.
基金This work was Supported by a grant from the National Natural Science Foundation of China （No. 30930089）.
文摘Background Valproic acid （VPA） improves early survival and organ function in a highly lethal poly-trauma and hemorrhagic shock model or other severe insults. We assessed whether VPA could improve organ function in a rat model of septic shock and illustrated the possible mechanisms. Methods Forty Sprague-Dawley rats were randomly assigned to four groups （n=-10）： control group, VPA group, LPS group, and LPS＋VPA group. Lipopolysaccharide （LPS） （10 mg/kg） was injected intravenously to replicate the experimental model of septic shock. Rats were treated with VPA （300 mg/kg, i.v.） or saline. Six hours after LPS injection, blood was sampled for gas analysis, measurement of serum alanine aminotransferase, aspartate aminotransferase, urine nitrogen, creatinine and tumor necrosis factor-alpha. Lung, liver and kidney were collected for histopathological assessment. In addition, myeloperoxidase activity and tumor necrosis factor-α in pulmonary tissue were measured. Acetylation of histone H3 in lung was also evaluated by Western blotting. Results LPS resulted in a significant decrease in PaO2, which was increased by VPA administration followed LPS injection. In addition, LPS also induced an increase in the serum levels of alanine aminotransferase, aspartate aminotransferase, urine nitrogen, creatinine, and tumor necrosis factor-alpha. However, these increases were attenuated in the LPS＋VPA group. The lungs, liver and kidneys from the LPS group were significantly damaged compared with the control group. However, the damage was attenuated in the LPS＋VPA group. Myeloperoxidase activity and tumor necrosis factor-alpha levels in pulmonary tissue increased significantly in the LPS group compared with the control group. These increases were significantly inhibited in the LPS＋VPA group. Acetylation of histone H3 in lung tissue in the LPS group was inhibited compared with the control. However, the level of acetylation of histone H3 in the LPS＋VPA group was markedly elevated in contrast to the LPS group. Conclusions Treatment with VPA can attenuate multiple organ damage caused by LPS induced septic shock. Our data also suggest that the beneficial effects are in part due to the decrease in inflammatory cytokines and restoration of normal acetylation homeostasis.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 30571787）.
文摘Background Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung injury during acute endotoxaemia.Methods A total of 32 male Sprague-Dawley rats were randomly assigned to four groups： saline group, erythropoietin＋saline group, saline＋lipopolysaccharide group and erythropoietin＋lipopolysaccharide group. Rats were treated with erythropoietin （3000 U/kg, i.p.） or saline, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, i.v.）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Wet/dry （W/D） ratios, myeloperoxidase activity, malondialdehyde concentrations and tumour necrosis factor-alpha （TNF-α） as well as interleukin 1 beta （IL-1β） levels in lungs were measured. The pulmonary expression of nuclear factor kappaB （NF-κB） p65 was evaluated by Western blotting. Differences between the different groups were analysed by one-way analysis of variance （ANOVA）.Results The lung tissues from the saline＋lipopolysaccharide group were significantly damaged, which were less pronounced in the erythropoietin＋lipopolysaccharide group. The W/D ratio increased significantly in the saline＋lipopolysaccharide group （5.75±0.22） as compared with the saline group （3.85±0.20） （P 〈0.01）, which was significantly reduced in the erythropoietin＋lipopolysaccharide group （4.50±0.35） （P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the saline＋lipopolysaccharide group compared with the saline group, which was reduced in the erythropoietin ＋ lipopolysaccharide group. The TNF-α level of pulmonary tissue increased significantly in the saline＋lipopolysaccharide group （（9.80±0.82） pg/mg protein） compared with the saline group （（4.20=L-0.42） pg/mg protein, P 〈0.01）. However, the increase of TNF-α level of pulmonary tissue was significantly reduced in the erythropoietin＋lipopolysaccharide group （（6.50±0.66） pg/mg protein, P 〈0.01）. Similarly, pulmonary IL-1β levels were elevated markedly in the saline＋lipopolysaccharide group in contrast to the saline group, whereas the elevation was much less in the erythropoietin＋lipopolysaccharide group. The nuclear localization of p65 increased markedly in the saline＋lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the erythropoietin＋lipopolysacchadde group.Conclusion Erythropoietin attenuates pulmonary inflammation and suppresses TNF-α and IL-1β overproduction during acute endotoxaemia, which is partially mediated by inhibition of NF-KB.
