Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring.However,the precise epigenetic mechanisms governing these intergenerational effects,pa...Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring.However,the precise epigenetic mechanisms governing these intergenerational effects,particularly during the early stages of offspring development,remain poorly understood.In this study,female C57BL/6J mice were randomly assigned to either a high-fat diet or normal chow diet throughout gestation and lactation.Methylated DNA immunoprecipitation(MeDIP)coupled with microarray analysis was employed to identify differentially methylated genes in the livers of offspring at weaning age.We found that maternal high-fat diet feeding predisposes offspring to obesity and impaired glucose metabolism as early as the weaning period.DNA methylation profile analysis unveiled a significant enrichment of differentially methylated genes within the natural killer(NK)cell-mediated cytotoxicity pathway.MeDIP-PCR validated reduced methylation levels of specific genes within this pathway,including tumour necrosis factorα(TNF-α),phosphoinositide 3-kinase(PI3K),and SHC adaptor protein 1(SHC1).Consistently,the expressions of TNF-α,PI3K,and SHC1 were significantly upregulated,accompanied by elevated serum TNF-αand interleukin-6(IL-6)levels in offspring from dams fed with high-fat diet.Moreover,we assessed the expressions of genes associated with NK cell activities,uncovering a notable rise in hepatic granzyme B levels and a trend towards increased CD107a expression in offspring from dams fed a high-fat diet.In addition,methylation levels of TNF-α,PI3K,and SHC1 promoters were inversely correlated with glucose response during glucose tolerance testing.In conclusion,our findings underscore the critical role of the NK cell-mediated cytotoxicity signaling pathway in mediating DNA methylation patterns,thereby contributing to the programming effects of maternal high-fat diet consumption on offspring glucose metabolism as early as the weaning period.展开更多
BACKGROUND: Because the continuity and integrity of the trachea are likely damaged to some extent after tracheostomy, the implementation of sequential ventilation has certain difficulties, and sequential invasive-noni...BACKGROUND: Because the continuity and integrity of the trachea are likely damaged to some extent after tracheostomy, the implementation of sequential ventilation has certain difficulties, and sequential invasive-noninvasive ventilation on patients after tracheostomy is less common in practice. The present study aimed to investigate the feasibility of invasive-noninvasive sequential weaning strategy in patients after tracheostomy.METHODS: Fifty patients including 24 patients with withdrawal of mechanical ventilation(conventional group) and 26 patients with sequential invasive-noninvasive weaning by directly plugging of tracheostomy(sequential group) were analyzed retrospectively after appearance of pulmonary infection control(PIC) window. The analysis of arterial blood gases, ventilator-associated pneumonia(VAP) incidence, the total duration of mechanical ventilation, the success rate of weaning and total cost of hospitalization were compared between the two groups.RESULTS: Arterial blood gas analysis showed that the sequential weaning group was better than the conventional weaning group 1 and 24 hours after invasive ventilation. The VAP incidence was lowered, the duration of mechanical ventilation shortened, the success rate of weaning increased, and the total cost of hospitalization decreased.CONCLUSION: Sequential invasive-noninvasive ventilator weaning is feasible in patients after tracheostomy.展开更多
BACKGROUND:Early withdrawal of invasive mechanical ventilation(IMV) followed by noninvasive MV(NIMV) is a new strategy for changing modes of treatment in patients with acute exacerbations of chronic obstructive pulmon...BACKGROUND:Early withdrawal of invasive mechanical ventilation(IMV) followed by noninvasive MV(NIMV) is a new strategy for changing modes of treatment in patients with acute exacerbations of chronic obstructive pulmonary disease(AECOPD) with acute respiratory failure(ARF).Using pulmonary infection control window(PIC window) as the switch point for transferring from invasive to noninvasive MV,the time for early extubation can be more accurately judged,and therapy efficacy can be improved.This study aimed to prospectively investigate the clinical effectiveness of fiberoptic bronchscopy(FOB) in patients with AECOPD during sequential weaning of invasive-noninvasive MV.METHODS:Since July 2006 to January 2011,106 AECOPD patients with ARF were treated with comprehensive medication and IMV after hospitalization.Patients were randomly divided into two groups according to whether fiberoptic bronchoscope is used(group A,n=54) or not(group B,n=52) during sequential weaning from invasive to noninvasive MV.In group A,for sputum suction and bronchoalveolar lavage(BAL),a fiberoptic bronchoscope was put into the airway from the outside of an endotracheal tube,which was accompanied with uninterrupted use of a ventilator.After achieving PIC window,patients of both groups changed to NIMV mode,and weaned from ventilation.The following listed indices were used to compare between the groups after treatment:1) the occurrence time of PIC,the duration of MV,the length of ICU stay,the success rate of weaning from MV for the first time,the rate of reventilatJon and the occurrence rate of ventilator-associated pneumonia(VAP);2) the convenience and safety of FOB manipulation.The results were compared using Student's f test and the Chi-square test.RESULTS:The occurrence time of PIC was(5.01 ±1.49) d,(5.87±1.87) d in groups A and B,respectively(P<0.05);the duration of MV was(6.98±1.84) d,(8.69±2.41) d in groups A and B,respectively(P<0.01);the length of ICU stay was(9.25±1.84) d,(11.10±2.63) d in groups A and B,respectively(P<0.01);the success rate of weaning for the first time was 96.30%,76.92%in groups A and B,respectively(P<0.01);the rate of reventilation was 5.56%,19.23%in groups A and B,respectively(P<0.05);and the occurrence rate of VAP was 3.70%,23.07%in groups A and B,respectively(P<0.01).Moreover,it was easy and safe to manipulate FOB,and no side effect was observed.CONCLUSIONS:The application of FOB in patients with AECOPD during sequential weaning of invasive-noninvasive MV is effective in ICU.It can decrease the duration of MV and the length of ICU stay,increase the success rate from weaning MV for the first time,reduce the rate of reventilation and the occurrence rate of VAP.In addition,such a method is convenient and safe in patients of this kind.展开更多
The experiment was conducted to study the effects and possible mechanism of GLP-2 on proliferation,metabolism and apoptosis of cultured enterocytes from a 28-d weaned piglet injured by exposure to β-conglycinin.A cel...The experiment was conducted to study the effects and possible mechanism of GLP-2 on proliferation,metabolism and apoptosis of cultured enterocytes from a 28-d weaned piglet injured by exposure to β-conglycinin.A cell damage model was established to investigate cell proliferation, metabolism and apoptosis by exposing primary cell cultures of intestinal epithelial cells(IEC) to 1.2 and 2.4 mg/mL β-conglycinin.A 2×3 factorial experiment was then used to study the effect of different GLP-2 concentrations of(1×10<sup>-9</sup>,1×10<sup>-8</sup> and 1×10<sup>-7</sup>mol/L),in combination with the two concentrations ofβ-conglycinin.Cells exposed to the allergenβ-conglycinin had decreased(P【0.05) MTT OD;decreased (P【0.01) protein retention and total protein content of cells;increased(P【0.01) LDH and caspase-3 activities and decreased(P【0.05) Na<sup>+</sup>,K<sup>+</sup>-ATPase activity.When GLP-2 was used in combination withβ-conglycinin,MTT OD,protein retention,total protein content and Na<sup>+</sup>,K<sup>+</sup>-ATPase activity significantly increased(P【0.05);LDH activity gradually decreased(P【0.05 or P【0.01) and Caspase-3 activity significantly decreased(P【0.01) with increasing concentrations of GLP-2.The results indicated thatβ-conglycinin had adverse effects on proliferation and integrity of IEC in vitro.GLP-2 relieved or prevented the adverse effects ofβ-conglycinin on proliferation and integrity of IEC by regulating Na<sup>+</sup>,K<sup>+</sup>- ATPase and Caspase-3 activities,and consequently affecting cell metabolism.展开更多
in this paper, 4N-HCLAIA method was adopted to conduct digestive tests in young female and male Dongtian F1 red deer (Cervus elaphus) of rearing seperatefy in growth period and mixed raising in weaning period in Harbi...in this paper, 4N-HCLAIA method was adopted to conduct digestive tests in young female and male Dongtian F1 red deer (Cervus elaphus) of rearing seperatefy in growth period and mixed raising in weaning period in Harbin Specialty Research Institute. Results indicated that digestive rate of crude protein and crude fiber were 95.35% and 73.68% respectively when rational protein content was 26.8% in growth period. Digestive rate was not significantly different between female and male(P>0.05)i During weaning period, When rational crude protein content is 22.06%, digestive rate of crude protein and crude fiber were 93.05% and 63.96%, respectively. The tests suggest that higher rational protein can be effective in accelerating groWth of young Dongtian F1 red deer during growth period and weaning period(before 10 months old).展开更多
为探究色氨酸对断奶仔猪生长性能的影响,本次试验对相关方面的研究进行了Meta分析。通过计算机检索中国知网、维普、万方、Web of science、scopus、Pubmed、EBSCO、Embase、Cochrance数据库,收集了色氨酸对仔猪影响的试验研究,按照纳...为探究色氨酸对断奶仔猪生长性能的影响,本次试验对相关方面的研究进行了Meta分析。通过计算机检索中国知网、维普、万方、Web of science、scopus、Pubmed、EBSCO、Embase、Cochrance数据库,收集了色氨酸对仔猪影响的试验研究,按照纳入标准和排除标准筛选文献和提取数据。总计收集了871篇文献,筛选排除后纳入近20年文献共11篇,通过Review Manager 5.3软件进行Meta分析,使用随机效应模型计算日增重、采食量和血清尿素氮的标准化均数差(SMD)及95%置信区间(CI),使用固定效应模型计算肝脏增重的标准化均数差(SMD)及95%置信区间(CI),通过亚组分析和敏感性分析解释异质性来源,利用漏斗图评估发表偏倚。结果表明:饲料中添加色氨酸极显著提高了断奶仔猪的平均日增重(P<0.01)和平均日采食量(P<0.01);饲料中添加色氨酸极显著降低了断奶仔猪血清尿素氮浓度(P<0.01);饲料中添加色氨酸提高了断奶仔猪肝脏增重(P=0.21)。亚组分析显示,色氨酸浓度≥0.25%能极显著提高断奶仔猪平均日增重(P=0.004,SMD=40.10,95%CI:13.12~67.08)、平均日采食量(P<0.01,SMD=39.46,95%CI:19.63~59.29);断奶日龄≥28 d能极显著提高断奶仔猪平均日增重(P=0.001,SMD=25.27,95%CI:9.90~40.63)。综上所述,在饲料中添加色氨酸能够很好的提高断奶仔猪的平均日增重、平均日采食量和肝脏增重,降低仔猪血清尿素氮浓度。当断奶日龄≥28 d时,平均日增重效果更好;当色氨酸浓度≥0.25%时,对断奶仔猪平均日增重及平均日采食量的提高更为显著。展开更多
目的系统评价机械通气脱机失败风险预测模型。方法计算机检索PubMed、Embase、Web of Science、Cochrane Library、CBM、CNKI、万方、维普数据库中有关机械通气脱机失败的风险预测模型,检索时限为建库至2025年2月。由2名研究员独立筛选...目的系统评价机械通气脱机失败风险预测模型。方法计算机检索PubMed、Embase、Web of Science、Cochrane Library、CBM、CNKI、万方、维普数据库中有关机械通气脱机失败的风险预测模型,检索时限为建库至2025年2月。由2名研究员独立筛选文献和提取资料,采用PROBAST偏倚风险评估工具对纳入文献进行偏倚风险和适用性评价。结果共纳入21篇文献,包含44个机械通气脱机失败风险预测模型。预测因子数量在3~21个之间,最常见的预测因子为机械通气时间、年龄、急性生理与慢性健康评分系统(acute physiology and chronic health evaluation,APACHEⅡ评分)。纳入模型AUC范围为0.689~0.926。模型总体预测性能较好,但整体偏倚风险高。结论目前机械通气脱机失败风险预测模型整体预测性能较好,但由于多数研究未进行外部验证且结局指标的定义存在差异,因此模型的临床适用性有待进一步验证。展开更多
基金sponsored by National Natural Science Foundation of China(81800703)Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20231088)+8 种基金Beijing Nova Program(Z201100006820117 and 20220484181)Beijing Municipal Natural Science Foundation(7184252)the Fundamental Research Funds for the Central Universitiesthe Fundamental Research Funds for the Central Universities(BMU2021MX013)Peking University Clinical Scientist Training Program(BMU2023PYJH022)Peking University Medicine Seed Fund for Interdisciplinary ResearchChina Endocrine and Metabolism Young Scientific Talent Research Project(2022-N-02-01)China Diabetes Young Scientific Talent Research ProjectBethune-Merck Diabetes Research Fund of Bethune Charitable Foundation。
文摘Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring.However,the precise epigenetic mechanisms governing these intergenerational effects,particularly during the early stages of offspring development,remain poorly understood.In this study,female C57BL/6J mice were randomly assigned to either a high-fat diet or normal chow diet throughout gestation and lactation.Methylated DNA immunoprecipitation(MeDIP)coupled with microarray analysis was employed to identify differentially methylated genes in the livers of offspring at weaning age.We found that maternal high-fat diet feeding predisposes offspring to obesity and impaired glucose metabolism as early as the weaning period.DNA methylation profile analysis unveiled a significant enrichment of differentially methylated genes within the natural killer(NK)cell-mediated cytotoxicity pathway.MeDIP-PCR validated reduced methylation levels of specific genes within this pathway,including tumour necrosis factorα(TNF-α),phosphoinositide 3-kinase(PI3K),and SHC adaptor protein 1(SHC1).Consistently,the expressions of TNF-α,PI3K,and SHC1 were significantly upregulated,accompanied by elevated serum TNF-αand interleukin-6(IL-6)levels in offspring from dams fed with high-fat diet.Moreover,we assessed the expressions of genes associated with NK cell activities,uncovering a notable rise in hepatic granzyme B levels and a trend towards increased CD107a expression in offspring from dams fed a high-fat diet.In addition,methylation levels of TNF-α,PI3K,and SHC1 promoters were inversely correlated with glucose response during glucose tolerance testing.In conclusion,our findings underscore the critical role of the NK cell-mediated cytotoxicity signaling pathway in mediating DNA methylation patterns,thereby contributing to the programming effects of maternal high-fat diet consumption on offspring glucose metabolism as early as the weaning period.
基金supported by the fund for clinical research project(2015xkj086)
文摘BACKGROUND: Because the continuity and integrity of the trachea are likely damaged to some extent after tracheostomy, the implementation of sequential ventilation has certain difficulties, and sequential invasive-noninvasive ventilation on patients after tracheostomy is less common in practice. The present study aimed to investigate the feasibility of invasive-noninvasive sequential weaning strategy in patients after tracheostomy.METHODS: Fifty patients including 24 patients with withdrawal of mechanical ventilation(conventional group) and 26 patients with sequential invasive-noninvasive weaning by directly plugging of tracheostomy(sequential group) were analyzed retrospectively after appearance of pulmonary infection control(PIC) window. The analysis of arterial blood gases, ventilator-associated pneumonia(VAP) incidence, the total duration of mechanical ventilation, the success rate of weaning and total cost of hospitalization were compared between the two groups.RESULTS: Arterial blood gas analysis showed that the sequential weaning group was better than the conventional weaning group 1 and 24 hours after invasive ventilation. The VAP incidence was lowered, the duration of mechanical ventilation shortened, the success rate of weaning increased, and the total cost of hospitalization decreased.CONCLUSION: Sequential invasive-noninvasive ventilator weaning is feasible in patients after tracheostomy.
文摘BACKGROUND:Early withdrawal of invasive mechanical ventilation(IMV) followed by noninvasive MV(NIMV) is a new strategy for changing modes of treatment in patients with acute exacerbations of chronic obstructive pulmonary disease(AECOPD) with acute respiratory failure(ARF).Using pulmonary infection control window(PIC window) as the switch point for transferring from invasive to noninvasive MV,the time for early extubation can be more accurately judged,and therapy efficacy can be improved.This study aimed to prospectively investigate the clinical effectiveness of fiberoptic bronchscopy(FOB) in patients with AECOPD during sequential weaning of invasive-noninvasive MV.METHODS:Since July 2006 to January 2011,106 AECOPD patients with ARF were treated with comprehensive medication and IMV after hospitalization.Patients were randomly divided into two groups according to whether fiberoptic bronchoscope is used(group A,n=54) or not(group B,n=52) during sequential weaning from invasive to noninvasive MV.In group A,for sputum suction and bronchoalveolar lavage(BAL),a fiberoptic bronchoscope was put into the airway from the outside of an endotracheal tube,which was accompanied with uninterrupted use of a ventilator.After achieving PIC window,patients of both groups changed to NIMV mode,and weaned from ventilation.The following listed indices were used to compare between the groups after treatment:1) the occurrence time of PIC,the duration of MV,the length of ICU stay,the success rate of weaning from MV for the first time,the rate of reventilatJon and the occurrence rate of ventilator-associated pneumonia(VAP);2) the convenience and safety of FOB manipulation.The results were compared using Student's f test and the Chi-square test.RESULTS:The occurrence time of PIC was(5.01 ±1.49) d,(5.87±1.87) d in groups A and B,respectively(P<0.05);the duration of MV was(6.98±1.84) d,(8.69±2.41) d in groups A and B,respectively(P<0.01);the length of ICU stay was(9.25±1.84) d,(11.10±2.63) d in groups A and B,respectively(P<0.01);the success rate of weaning for the first time was 96.30%,76.92%in groups A and B,respectively(P<0.01);the rate of reventilation was 5.56%,19.23%in groups A and B,respectively(P<0.05);and the occurrence rate of VAP was 3.70%,23.07%in groups A and B,respectively(P<0.01).Moreover,it was easy and safe to manipulate FOB,and no side effect was observed.CONCLUSIONS:The application of FOB in patients with AECOPD during sequential weaning of invasive-noninvasive MV is effective in ICU.It can decrease the duration of MV and the length of ICU stay,increase the success rate from weaning MV for the first time,reduce the rate of reventilation and the occurrence rate of VAP.In addition,such a method is convenient and safe in patients of this kind.
基金supported by Program for Changjiang Scholars and Innovative Reseach Team in University (IRTO 555)Applied Basic Research(045Y029-031) of Sichuan Province,People's Republic of China
文摘The experiment was conducted to study the effects and possible mechanism of GLP-2 on proliferation,metabolism and apoptosis of cultured enterocytes from a 28-d weaned piglet injured by exposure to β-conglycinin.A cell damage model was established to investigate cell proliferation, metabolism and apoptosis by exposing primary cell cultures of intestinal epithelial cells(IEC) to 1.2 and 2.4 mg/mL β-conglycinin.A 2×3 factorial experiment was then used to study the effect of different GLP-2 concentrations of(1×10<sup>-9</sup>,1×10<sup>-8</sup> and 1×10<sup>-7</sup>mol/L),in combination with the two concentrations ofβ-conglycinin.Cells exposed to the allergenβ-conglycinin had decreased(P【0.05) MTT OD;decreased (P【0.01) protein retention and total protein content of cells;increased(P【0.01) LDH and caspase-3 activities and decreased(P【0.05) Na<sup>+</sup>,K<sup>+</sup>-ATPase activity.When GLP-2 was used in combination withβ-conglycinin,MTT OD,protein retention,total protein content and Na<sup>+</sup>,K<sup>+</sup>-ATPase activity significantly increased(P【0.05);LDH activity gradually decreased(P【0.05 or P【0.01) and Caspase-3 activity significantly decreased(P【0.01) with increasing concentrations of GLP-2.The results indicated thatβ-conglycinin had adverse effects on proliferation and integrity of IEC in vitro.GLP-2 relieved or prevented the adverse effects ofβ-conglycinin on proliferation and integrity of IEC by regulating Na<sup>+</sup>,K<sup>+</sup>- ATPase and Caspase-3 activities,and consequently affecting cell metabolism.
文摘in this paper, 4N-HCLAIA method was adopted to conduct digestive tests in young female and male Dongtian F1 red deer (Cervus elaphus) of rearing seperatefy in growth period and mixed raising in weaning period in Harbin Specialty Research Institute. Results indicated that digestive rate of crude protein and crude fiber were 95.35% and 73.68% respectively when rational protein content was 26.8% in growth period. Digestive rate was not significantly different between female and male(P>0.05)i During weaning period, When rational crude protein content is 22.06%, digestive rate of crude protein and crude fiber were 93.05% and 63.96%, respectively. The tests suggest that higher rational protein can be effective in accelerating groWth of young Dongtian F1 red deer during growth period and weaning period(before 10 months old).
文摘目的系统评价机械通气脱机失败风险预测模型。方法计算机检索PubMed、Embase、Web of Science、Cochrane Library、CBM、CNKI、万方、维普数据库中有关机械通气脱机失败的风险预测模型,检索时限为建库至2025年2月。由2名研究员独立筛选文献和提取资料,采用PROBAST偏倚风险评估工具对纳入文献进行偏倚风险和适用性评价。结果共纳入21篇文献,包含44个机械通气脱机失败风险预测模型。预测因子数量在3~21个之间,最常见的预测因子为机械通气时间、年龄、急性生理与慢性健康评分系统(acute physiology and chronic health evaluation,APACHEⅡ评分)。纳入模型AUC范围为0.689~0.926。模型总体预测性能较好,但整体偏倚风险高。结论目前机械通气脱机失败风险预测模型整体预测性能较好,但由于多数研究未进行外部验证且结局指标的定义存在差异,因此模型的临床适用性有待进一步验证。
