目的探究孕妇孕期血清样本中血清十八碳一不饱和脂肪酸硬脂酰鞘氨醇(serum stearoyl sphingosine,C18∶1-Cer)和1-硬脂酰基-sn-甘油-3-磷酸胆碱(lysophosphatidyl choline,LPC18∶0)水平在预测孕妇患妊娠期糖尿病(gestational diabetes ...目的探究孕妇孕期血清样本中血清十八碳一不饱和脂肪酸硬脂酰鞘氨醇(serum stearoyl sphingosine,C18∶1-Cer)和1-硬脂酰基-sn-甘油-3-磷酸胆碱(lysophosphatidyl choline,LPC18∶0)水平在预测孕妇患妊娠期糖尿病(gestational diabetes mellitus,GDM)方面的价值。方法回顾性分析126例孕妇的临床资料和实验室指标,根据GDM诊断结果,将研究对象分为GDM组(n=66)和对照组(n=60)。采用质谱法检测研究对象孕早期和孕中期血清C18∶1-Cer和LPC18∶0水平,通过Logistic回归分析筛选出GDM的危险因素,采用受试者工作特征(receiver operating characteristic,ROC)曲线评估C18∶1-Cer,LPC188∶0和两者联合对GDM的预测价值。结果与对照组相比,GDM组血清C18∶1-Cer和LPC18∶0水平在孕早期(18.92±2.77ng/ml vs 23.47±4.18ng/ml,41.32±17.55ng/ml vs 88.08±16.02ng/ml)和孕中期(23.14±4.10ng/ml vs 18.76±4.05ng/ml,84.60±14.53ng/ml vs 40.50±17.79ng/ml)均显著升高,差异具有统计学意义(t=7.127,15.637;-5.984,2.174,均P<0.05)。C18∶1-Cer与空腹血糖(fasting plasma glucose,FPG)、空腹胰岛素(fasting plasma insulin,FPI)、胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)、糖化血红蛋白(glycated hemoglobin,HbA1c)和三酰甘油(triglyceride,TG)呈正相关(r=0.458,0.209,0.317,0.223,0.219,均P<0.05)。LPC18∶0与FPG,FPI,HOMA-IR,HbA1c,总胆固醇(total cholesterol,TC)和TG呈正相关(r=0.715,0.426,0.580,0.465,0.232,0.372,均P<0.05)。Logistic回归分析结果显示,C18∶1-Cer[OR(95%CI):1.522(1.136~.039),P<0.05]和LPC18∶0[OR(95%CI):1.198(1.102~1.302),P<0.001]是GDM的独立危险因素。ROC曲线分析结果显示,血清C18∶1-Cer,LPC18∶0和两指标联合的曲线下面积(area under the curve,AUC)分别为0.819,0.971和0.986,两者联合检测的预测效能优于单独检测。结论妊娠早期血清中的C18∶1-Cer和LPC18∶0与GDM的发生密切相关,C18∶1-Cer联合LPC18∶0对GDM早期诊断有一定的预测价值。展开更多
Background C16:0 and cis-9 C18:1 may have different effects on animal growth and health due to unique metabolism in vivo.This study was investigated to explore the different effects of altering the ratio of C16:0 and ...Background C16:0 and cis-9 C18:1 may have different effects on animal growth and health due to unique metabolism in vivo.This study was investigated to explore the different effects of altering the ratio of C16:0 and cis-9 C18:1 in fat supplements on growth performance,lipid metabolism,intestinal barrier,cecal microbiota,and inflammation in fattening bulls.Thirty finishing Angus bulls(626±69 kg,21±0.5 months)were divided into 3 treatments according to the randomized block design:(1)control diet without additional fat(CON),(2)CON+2.5%palmitic acid calcium salt(PA,90%C16:0),and(3)CON+2.5%mixed fatty acid calcium salt(MA,60%C16:0+30%cis-9 C18:1).The experiment lasted for 104 d,after which all the bulls were slaughtered and sampled for analysis.Results MA tended to reduce 0–52 d dry matter intake compared to PA(DMI,P=0.052).Compared with CON and MA,PA significantly increased 0–52 d average daily gain(ADG,P=0.027).PA tended to improve the 0–52 d feed conversion rate compared with CON(FCR,P=0.088).Both PA and MA had no significant effect on 52–104 days of DMI,ADG and FCR(P>0.05).PA tended to improve plasma triglycerides compared with MA(P=0.077),significantly increased plasma cholesterol(P=0.002)and tended to improve subcutaneous adipose weight(P=0.066)when compared with CON and MA.Both PA and MA increased visceral adipose weight compared with CON(P=0.021).Only PA increased the colonization of Rikenellaceae,Ruminococcus and Proteobacteria in the cecum,and MA increased Akkermansia abundance(P<0.05).Compared with CON,both PA and MA down-regulated the m RNA expression of Claudin-1 in the jejunum(P<0.001),increased plasma diamine oxidase(DAO,P<0.001)and lipopolysaccharide(LPS,P=0.045).Compared with CON and MA,PA down-regulated the ZO-1 in the jejunum(P<0.001)and increased plasma LPS-binding protein(LBP,P<0.001).Compared with CON,only PA down-regulated the Occludin in the jejunum(P=0.013).Compared with CON,PA and MA significantly up-regulated the expression of TLR-4 and NF-κB in the visceral adipose(P<0.001)and increased plasma IL-6(P<0.001).Compared with CON,only PA up-regulated the TNF-αin the visceral adipose(P=0.01).Compared with CON and MA,PA up-regulated IL-6 in the visceral adipose(P<0.001),increased plasma TNF-α(P<0.001),and reduced the Ig G content in plasma(P=0.035).Compared with CON,PA and MA increased C16:0 in subcutaneous fat and longissimus dorsi muscle(P<0.05),while more C16:0 was also deposited by extension and desaturation into C18:0 and cis-9 C18:1.However,neither PA nor MA affected the content of cis-9 C18:1 in longissimus dorsi muscle compared with CON(P>0.05).Conclusions MA containing 30%cis-9 C18:1 reduced the risk of high C16:0 dietary fat induced subcutaneous fat obesity,adipose tissue and systemic low-grade inflammation by accelerating fatty acid oxidative utilization,improving colonization of Akkermansia,reducing intestinal barrier damage,and down-regulating NF-κB activation.展开更多
BACKGROUND Endoscopic submucosal dissection(ESD)and surgical resection are the standard of care for cT1N0M0 esophageal cancer(EC),whereas definitive chemoradiotherapy(d-CRT)is a treatment option.Nevertheless,the compa...BACKGROUND Endoscopic submucosal dissection(ESD)and surgical resection are the standard of care for cT1N0M0 esophageal cancer(EC),whereas definitive chemoradiotherapy(d-CRT)is a treatment option.Nevertheless,the comparative efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC remain unclear.AIM To compare the efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC.METHODS We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th,2022.We analyzed demographic,medical recorded,histopathologic characteristics,imaging and endoscopic,and follow-up data.The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments.Inverse probability of treatment weighting(IPTW)was used to minimize potential confounding factors.RESULTS We retrospectively analyzed patients who underwent ESD(n=99)or surgery(n=220)or d-CRT(n=16)at the Sun Yat-sen University Cancer Center from 2017 to 2019.The median follow-up time for the ESD group,the surgery group,and the d-CRT group was 42.0 mo(95%CI:35.0-60.2),45.0 mo(95%CI:34.0-61.75)and 32.5 mo(95%CI:28.3-40.0),respectively.After adjusting for background factors using IPTW,the highest 3-year overall survival(OS)rate and 3-year recurrence-free survival(RFS)rate were observed in the ESD group(3-year OS:99.7% and 94.7% and 79.1%;and 3-year RFS:98.3%,87.4% and 79.1%,in the ESD,surgical,and d-CRT groups,respectively).There was no difference of severe complications occurring between the three groups(P≥0.05).Multivariate analysis showed that treatment method,histology and depth of infiltration were independently associated with OS and RFS.CONCLUSION For cT1N0M0 EC,ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery,with a similar rate of severe complications occurring.展开更多
Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucia...Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.展开更多
文摘目的探究孕妇孕期血清样本中血清十八碳一不饱和脂肪酸硬脂酰鞘氨醇(serum stearoyl sphingosine,C18∶1-Cer)和1-硬脂酰基-sn-甘油-3-磷酸胆碱(lysophosphatidyl choline,LPC18∶0)水平在预测孕妇患妊娠期糖尿病(gestational diabetes mellitus,GDM)方面的价值。方法回顾性分析126例孕妇的临床资料和实验室指标,根据GDM诊断结果,将研究对象分为GDM组(n=66)和对照组(n=60)。采用质谱法检测研究对象孕早期和孕中期血清C18∶1-Cer和LPC18∶0水平,通过Logistic回归分析筛选出GDM的危险因素,采用受试者工作特征(receiver operating characteristic,ROC)曲线评估C18∶1-Cer,LPC188∶0和两者联合对GDM的预测价值。结果与对照组相比,GDM组血清C18∶1-Cer和LPC18∶0水平在孕早期(18.92±2.77ng/ml vs 23.47±4.18ng/ml,41.32±17.55ng/ml vs 88.08±16.02ng/ml)和孕中期(23.14±4.10ng/ml vs 18.76±4.05ng/ml,84.60±14.53ng/ml vs 40.50±17.79ng/ml)均显著升高,差异具有统计学意义(t=7.127,15.637;-5.984,2.174,均P<0.05)。C18∶1-Cer与空腹血糖(fasting plasma glucose,FPG)、空腹胰岛素(fasting plasma insulin,FPI)、胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)、糖化血红蛋白(glycated hemoglobin,HbA1c)和三酰甘油(triglyceride,TG)呈正相关(r=0.458,0.209,0.317,0.223,0.219,均P<0.05)。LPC18∶0与FPG,FPI,HOMA-IR,HbA1c,总胆固醇(total cholesterol,TC)和TG呈正相关(r=0.715,0.426,0.580,0.465,0.232,0.372,均P<0.05)。Logistic回归分析结果显示,C18∶1-Cer[OR(95%CI):1.522(1.136~.039),P<0.05]和LPC18∶0[OR(95%CI):1.198(1.102~1.302),P<0.001]是GDM的独立危险因素。ROC曲线分析结果显示,血清C18∶1-Cer,LPC18∶0和两指标联合的曲线下面积(area under the curve,AUC)分别为0.819,0.971和0.986,两者联合检测的预测效能优于单独检测。结论妊娠早期血清中的C18∶1-Cer和LPC18∶0与GDM的发生密切相关,C18∶1-Cer联合LPC18∶0对GDM早期诊断有一定的预测价值。
基金financially supported by the earmarked fund for CARS36,the Natural Science Foundation of Heilongjiang Province(YQ2023C011)the National Key Research and Development Program of China(2023YFD2000701)the Key Research and Development Program of Heilongjiang Province(GZ20230028)。
文摘Background C16:0 and cis-9 C18:1 may have different effects on animal growth and health due to unique metabolism in vivo.This study was investigated to explore the different effects of altering the ratio of C16:0 and cis-9 C18:1 in fat supplements on growth performance,lipid metabolism,intestinal barrier,cecal microbiota,and inflammation in fattening bulls.Thirty finishing Angus bulls(626±69 kg,21±0.5 months)were divided into 3 treatments according to the randomized block design:(1)control diet without additional fat(CON),(2)CON+2.5%palmitic acid calcium salt(PA,90%C16:0),and(3)CON+2.5%mixed fatty acid calcium salt(MA,60%C16:0+30%cis-9 C18:1).The experiment lasted for 104 d,after which all the bulls were slaughtered and sampled for analysis.Results MA tended to reduce 0–52 d dry matter intake compared to PA(DMI,P=0.052).Compared with CON and MA,PA significantly increased 0–52 d average daily gain(ADG,P=0.027).PA tended to improve the 0–52 d feed conversion rate compared with CON(FCR,P=0.088).Both PA and MA had no significant effect on 52–104 days of DMI,ADG and FCR(P>0.05).PA tended to improve plasma triglycerides compared with MA(P=0.077),significantly increased plasma cholesterol(P=0.002)and tended to improve subcutaneous adipose weight(P=0.066)when compared with CON and MA.Both PA and MA increased visceral adipose weight compared with CON(P=0.021).Only PA increased the colonization of Rikenellaceae,Ruminococcus and Proteobacteria in the cecum,and MA increased Akkermansia abundance(P<0.05).Compared with CON,both PA and MA down-regulated the m RNA expression of Claudin-1 in the jejunum(P<0.001),increased plasma diamine oxidase(DAO,P<0.001)and lipopolysaccharide(LPS,P=0.045).Compared with CON and MA,PA down-regulated the ZO-1 in the jejunum(P<0.001)and increased plasma LPS-binding protein(LBP,P<0.001).Compared with CON,only PA down-regulated the Occludin in the jejunum(P=0.013).Compared with CON,PA and MA significantly up-regulated the expression of TLR-4 and NF-κB in the visceral adipose(P<0.001)and increased plasma IL-6(P<0.001).Compared with CON,only PA up-regulated the TNF-αin the visceral adipose(P=0.01).Compared with CON and MA,PA up-regulated IL-6 in the visceral adipose(P<0.001),increased plasma TNF-α(P<0.001),and reduced the Ig G content in plasma(P=0.035).Compared with CON,PA and MA increased C16:0 in subcutaneous fat and longissimus dorsi muscle(P<0.05),while more C16:0 was also deposited by extension and desaturation into C18:0 and cis-9 C18:1.However,neither PA nor MA affected the content of cis-9 C18:1 in longissimus dorsi muscle compared with CON(P>0.05).Conclusions MA containing 30%cis-9 C18:1 reduced the risk of high C16:0 dietary fat induced subcutaneous fat obesity,adipose tissue and systemic low-grade inflammation by accelerating fatty acid oxidative utilization,improving colonization of Akkermansia,reducing intestinal barrier damage,and down-regulating NF-κB activation.
基金Supported by the Guangdong Esophageal Cancer Institute Science and Technology Program,No.M202013Guangdong Medical Research Foundation,No.A2021369.
文摘BACKGROUND Endoscopic submucosal dissection(ESD)and surgical resection are the standard of care for cT1N0M0 esophageal cancer(EC),whereas definitive chemoradiotherapy(d-CRT)is a treatment option.Nevertheless,the comparative efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC remain unclear.AIM To compare the efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC.METHODS We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th,2022.We analyzed demographic,medical recorded,histopathologic characteristics,imaging and endoscopic,and follow-up data.The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments.Inverse probability of treatment weighting(IPTW)was used to minimize potential confounding factors.RESULTS We retrospectively analyzed patients who underwent ESD(n=99)or surgery(n=220)or d-CRT(n=16)at the Sun Yat-sen University Cancer Center from 2017 to 2019.The median follow-up time for the ESD group,the surgery group,and the d-CRT group was 42.0 mo(95%CI:35.0-60.2),45.0 mo(95%CI:34.0-61.75)and 32.5 mo(95%CI:28.3-40.0),respectively.After adjusting for background factors using IPTW,the highest 3-year overall survival(OS)rate and 3-year recurrence-free survival(RFS)rate were observed in the ESD group(3-year OS:99.7% and 94.7% and 79.1%;and 3-year RFS:98.3%,87.4% and 79.1%,in the ESD,surgical,and d-CRT groups,respectively).There was no difference of severe complications occurring between the three groups(P≥0.05).Multivariate analysis showed that treatment method,histology and depth of infiltration were independently associated with OS and RFS.CONCLUSION For cT1N0M0 EC,ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery,with a similar rate of severe complications occurring.
基金supported by the National Natural Science Foundation of China(Youth Program),No.81901282(to XC)the National Natural Science Foundation of China,Nos.81401416(to PX),81870992(to PX),81870856(to XC and MZ)+3 种基金Guangdong Basic and Applied Basic Research Foundation the Science Foundation,No.2019A1515011189(to XC)Central Government Guiding Local Science and Technology Development Projects,No.ZYYD2022C17(to PX)Key Project of Guangzhou Health Commission,No.2019-ZD-09(to PX)Science and Technology Planning Project of Guangzhou,Nos.202102020029(to XC),202102010010(to PX)。
文摘Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.
