目的通过18氟-氟脱氧葡萄糖(18F-FDG)小动物正电子发射计算机体层摄影术(micro PET)成像技术来研究激活小鼠棕色脂肪(BAT)细胞的不同方法,并研究这些激活方法在肥胖及糖尿病模型小鼠减体质量及降糖作用的潜在价值。方法对正常小鼠(23只...目的通过18氟-氟脱氧葡萄糖(18F-FDG)小动物正电子发射计算机体层摄影术(micro PET)成像技术来研究激活小鼠棕色脂肪(BAT)细胞的不同方法,并研究这些激活方法在肥胖及糖尿病模型小鼠减体质量及降糖作用的潜在价值。方法对正常小鼠(23只)给予温度刺激(冷刺激6只,冷刺激后热刺激6只)及交感神经系统相关药物(去甲肾上腺素3只,冷刺激后普萘洛尔3只)干预,对照组5只不行任何干预,行18F-FDG micro PET成像,计算BAT与肝脏18F-FDG的摄取比值(BAT/L)。在肥胖模型小鼠(14只)研究中,通过高脂饮食8周建立肥胖模型小鼠后,随机分成BRL37344干预组(6只)及肥胖对照组(8只)。肥胖BRL37344干预组通过腹腔给药每只2.5 mg/kg,每周3次共2周,肥胖对照组给以相同频率的0.9%氯化钠溶液。糖尿病模型小鼠(12只)研究中,高脂饮食8周后给予连续3 d腹腔注射链脲佐菌素160 mg/kg建立糖尿病模型小鼠(血糖大于11.1 mmol/L者),随机分成BRL37344干预组(6只)及糖尿病对照组(6只),各组给药方法同肥胖模型小鼠。模型小鼠在建模前后、完成干预后行18F-FDG micro PET成像,计算BAT/L,并测定肥胖模型小鼠的体质量变化、肥胖模型及糖尿病模型小鼠尾静脉血糖、总胆固醇、低密度脂蛋白水平,分析这些指标与BAT/L的相关性。结果正常小鼠mirco PET显像分析中,冷刺激和去甲肾上腺素刺激下BAT/L(5.70±0.75及5.77±0.50)显著高于正常对照小鼠BAT/L(3.63±0.79;P<0.05及P<0.01)。冷刺激后行热刺激、普萘洛尔小鼠的BAT/L(3.04±1.10及0.73±0.16)显著低于仅行冷刺激干预小鼠的BAT/L(5.70±0.75;P<0.01)。肥胖模型小鼠micro PET显像分析中,肥胖小鼠BAT/L较正常对照组显著降低(3.15±1.67 vs 5.33±1.48;P<0.05),肥胖模型BRL37344干预组BAT/L明显高于肥胖对照组(6.64±1.97 vs 4.20±1.13;P<0.05)。糖尿病模型小鼠BAT/L显著低于正常对照组(1.97±0.68 vs 5.33±1.48;P<0.05),糖尿病模型BRL37344干预组BAT/L显著高于糖尿病模型对照组(5.25±1.51 vs 2.32±1.01;P<0.01)。血生物化学分析中,肥胖模型小鼠及糖尿病模型小鼠BRL37344干预组血糖分别显著低于肥胖对照组(6.88±0.57 vs 8.47±1.54;P<0.05)及糖尿病模型对照组(8.84±2.86 vs 19.99±9.44;P<0.05)。肥胖及糖尿病模型小鼠BRL37344干预组血糖水平与其micro PET显像BAT/L均存在显著负相关性(r=-0.71,P=0.003及r=-0.74,P=0.010)。肥胖模型小鼠体质量分析中,肥胖模型小鼠BRL37344干预组体质量显著低于肥胖对照组[(52.52±4.22)g vs(59.09±6.89)g;P=0.001]。结论小鼠BAT细胞受温度刺激及交感神经系统相关药物调控,并可通过18F-FDG micro PET成像方法动态监测。肥胖模型与糖尿病模型小鼠BAT细胞活性降低,但仍具有被β3肾上腺素受体激动剂激活的潜能,且激活BAT细胞可产生降糖及减质量作用。激活BAT细胞可能是一种潜在的治疗肥胖及糖尿病的手段。展开更多
Objective In recent years,many studies have reported that air pollution is a risk factor for type 2 diabetes mellitus(T2DM).The aim of this systematic review and meta・analysis is to summarize the evidence about the as...Objective In recent years,many studies have reported that air pollution is a risk factor for type 2 diabetes mellitus(T2DM).The aim of this systematic review and meta・analysis is to summarize the evidence about the association between exposure to air pollution andT2DM in developing countries.Methods The databases,including PubMed,EMBASE and Web of Science,were systematically searched for studies published up to 31 March 2022.Studies about the association between air pollution andT2DM prevalence or incidence in developing countries were included.The odds ratio(OR)was used as effect estimate.We synthesized the included studies in the meta-analysis.Results We included 8 cross-sectional studies and 8 cohort studies,all conducted in developing countries.Meta-analysis of 8 studies on PM_(2.5)(particulate matter ≤2.5 μm in diameter)showed that T2DM prevalence was significantly associated with PM_(2.5)exposure(OR=1.12;95%CI:1.07,1.17;P<0.001).The association between air pollutants andT2DM incidence was not estimated due to the limited relevant studies.Conclusions The exposure to PM_(2.5)would be positively associated with an increased prevalence of T2DM in developing countries.Some effective measures should be taken to reduce air pollutant exposure in people who are vulnerable to diabetes.展开更多
Objective BAG3-related myopathy is a rare condition so far reported in twenty patients worldwide.The purpose of this study was to draw attention to this rare disease and to the fact that BAG3-related myopathy should b...Objective BAG3-related myopathy is a rare condition so far reported in twenty patients worldwide.The purpose of this study was to draw attention to this rare disease and to the fact that BAG3-related myopathy should be considered as a rare differential diagnosis of hypercapnia.Methods We report a sporadic case of a 14-year-old Chinese girl with a de novo p.Pro209 Leu mutation in BAG3 and reviewed the literatures for reported cases related to this mutation.Results We described a 14-year-old Chinese girl who presented with gradually appearing symptoms of hypercapnia that required assisted ventilation.The muscle biopsy and the blood whole-exome sequencing results confirmed the diagnosis of myofibrillar myopathy with a de novo p.Pro209 Leu mutation in BAG3.Totally twentyone patients from twenty families with a confirmed diagnosis of BAG3-related myopathy were reported to date,including this patient and literature review.The male to female ratio was 11:10 and most showed initial symptoms in the first decade of life.Most patients presented toe/clumsy walking or running as the onset symptom,followed by muscle weakness or atrophy.Creatine kinase levels were elevated in fourteen patients and were normal in three.Eighteen patients developed respiratory insufficiency during the disease course and thirteen(one could not tolerate non-invasive assisted ventilation)required non-invasive assisted ventilation for treatment.Except for one not reported,heart involvement was found in seventeen patients during the disease course and seven underwent heart transplantation.Z-disk streaming and aggregation could be observed in most of the patients’muscle histology.In the long-term follow-up,five patients died of cardiac or respiratory failure.Conclusion BAG3-associated myopathy is a rare type of myofibrillar myopathy.It should be considered as a rare differential diagnosis of hypercapnia.展开更多
文摘目的通过18氟-氟脱氧葡萄糖(18F-FDG)小动物正电子发射计算机体层摄影术(micro PET)成像技术来研究激活小鼠棕色脂肪(BAT)细胞的不同方法,并研究这些激活方法在肥胖及糖尿病模型小鼠减体质量及降糖作用的潜在价值。方法对正常小鼠(23只)给予温度刺激(冷刺激6只,冷刺激后热刺激6只)及交感神经系统相关药物(去甲肾上腺素3只,冷刺激后普萘洛尔3只)干预,对照组5只不行任何干预,行18F-FDG micro PET成像,计算BAT与肝脏18F-FDG的摄取比值(BAT/L)。在肥胖模型小鼠(14只)研究中,通过高脂饮食8周建立肥胖模型小鼠后,随机分成BRL37344干预组(6只)及肥胖对照组(8只)。肥胖BRL37344干预组通过腹腔给药每只2.5 mg/kg,每周3次共2周,肥胖对照组给以相同频率的0.9%氯化钠溶液。糖尿病模型小鼠(12只)研究中,高脂饮食8周后给予连续3 d腹腔注射链脲佐菌素160 mg/kg建立糖尿病模型小鼠(血糖大于11.1 mmol/L者),随机分成BRL37344干预组(6只)及糖尿病对照组(6只),各组给药方法同肥胖模型小鼠。模型小鼠在建模前后、完成干预后行18F-FDG micro PET成像,计算BAT/L,并测定肥胖模型小鼠的体质量变化、肥胖模型及糖尿病模型小鼠尾静脉血糖、总胆固醇、低密度脂蛋白水平,分析这些指标与BAT/L的相关性。结果正常小鼠mirco PET显像分析中,冷刺激和去甲肾上腺素刺激下BAT/L(5.70±0.75及5.77±0.50)显著高于正常对照小鼠BAT/L(3.63±0.79;P<0.05及P<0.01)。冷刺激后行热刺激、普萘洛尔小鼠的BAT/L(3.04±1.10及0.73±0.16)显著低于仅行冷刺激干预小鼠的BAT/L(5.70±0.75;P<0.01)。肥胖模型小鼠micro PET显像分析中,肥胖小鼠BAT/L较正常对照组显著降低(3.15±1.67 vs 5.33±1.48;P<0.05),肥胖模型BRL37344干预组BAT/L明显高于肥胖对照组(6.64±1.97 vs 4.20±1.13;P<0.05)。糖尿病模型小鼠BAT/L显著低于正常对照组(1.97±0.68 vs 5.33±1.48;P<0.05),糖尿病模型BRL37344干预组BAT/L显著高于糖尿病模型对照组(5.25±1.51 vs 2.32±1.01;P<0.01)。血生物化学分析中,肥胖模型小鼠及糖尿病模型小鼠BRL37344干预组血糖分别显著低于肥胖对照组(6.88±0.57 vs 8.47±1.54;P<0.05)及糖尿病模型对照组(8.84±2.86 vs 19.99±9.44;P<0.05)。肥胖及糖尿病模型小鼠BRL37344干预组血糖水平与其micro PET显像BAT/L均存在显著负相关性(r=-0.71,P=0.003及r=-0.74,P=0.010)。肥胖模型小鼠体质量分析中,肥胖模型小鼠BRL37344干预组体质量显著低于肥胖对照组[(52.52±4.22)g vs(59.09±6.89)g;P=0.001]。结论小鼠BAT细胞受温度刺激及交感神经系统相关药物调控,并可通过18F-FDG micro PET成像方法动态监测。肥胖模型与糖尿病模型小鼠BAT细胞活性降低,但仍具有被β3肾上腺素受体激动剂激活的潜能,且激活BAT细胞可产生降糖及减质量作用。激活BAT细胞可能是一种潜在的治疗肥胖及糖尿病的手段。
文摘Objective In recent years,many studies have reported that air pollution is a risk factor for type 2 diabetes mellitus(T2DM).The aim of this systematic review and meta・analysis is to summarize the evidence about the association between exposure to air pollution andT2DM in developing countries.Methods The databases,including PubMed,EMBASE and Web of Science,were systematically searched for studies published up to 31 March 2022.Studies about the association between air pollution andT2DM prevalence or incidence in developing countries were included.The odds ratio(OR)was used as effect estimate.We synthesized the included studies in the meta-analysis.Results We included 8 cross-sectional studies and 8 cohort studies,all conducted in developing countries.Meta-analysis of 8 studies on PM_(2.5)(particulate matter ≤2.5 μm in diameter)showed that T2DM prevalence was significantly associated with PM_(2.5)exposure(OR=1.12;95%CI:1.07,1.17;P<0.001).The association between air pollutants andT2DM incidence was not estimated due to the limited relevant studies.Conclusions The exposure to PM_(2.5)would be positively associated with an increased prevalence of T2DM in developing countries.Some effective measures should be taken to reduce air pollutant exposure in people who are vulnerable to diabetes.
基金supported by the Youth Program of National Natural Science Foundation of China(Grant No.82003309)the National Key Research and Development Program of China(Grant 2020YFB1313700)。
文摘Objective BAG3-related myopathy is a rare condition so far reported in twenty patients worldwide.The purpose of this study was to draw attention to this rare disease and to the fact that BAG3-related myopathy should be considered as a rare differential diagnosis of hypercapnia.Methods We report a sporadic case of a 14-year-old Chinese girl with a de novo p.Pro209 Leu mutation in BAG3 and reviewed the literatures for reported cases related to this mutation.Results We described a 14-year-old Chinese girl who presented with gradually appearing symptoms of hypercapnia that required assisted ventilation.The muscle biopsy and the blood whole-exome sequencing results confirmed the diagnosis of myofibrillar myopathy with a de novo p.Pro209 Leu mutation in BAG3.Totally twentyone patients from twenty families with a confirmed diagnosis of BAG3-related myopathy were reported to date,including this patient and literature review.The male to female ratio was 11:10 and most showed initial symptoms in the first decade of life.Most patients presented toe/clumsy walking or running as the onset symptom,followed by muscle weakness or atrophy.Creatine kinase levels were elevated in fourteen patients and were normal in three.Eighteen patients developed respiratory insufficiency during the disease course and thirteen(one could not tolerate non-invasive assisted ventilation)required non-invasive assisted ventilation for treatment.Except for one not reported,heart involvement was found in seventeen patients during the disease course and seven underwent heart transplantation.Z-disk streaming and aggregation could be observed in most of the patients’muscle histology.In the long-term follow-up,five patients died of cardiac or respiratory failure.Conclusion BAG3-associated myopathy is a rare type of myofibrillar myopathy.It should be considered as a rare differential diagnosis of hypercapnia.