原发性肺黏膜相关淋巴组织淋巴瘤侵犯心脏1例报道

原发性肺黏膜相关淋巴组织（mucosa-associated lymphoid tissue,MALT）淋巴瘤是一种罕见疾病。胸片或CT有可能将MALT淋巴瘤与其他肺部疾病相混淆,从而导致误诊或延误治疗,本例患者因为难以诊断而延误5年余。患者因胸痛就诊时发现右侧大量胸腔积液,当时给予抗结核治疗,但肺部病变仍缓慢进展,同时左肺也出现病变,纵膈内淋巴结融合,病变累及心脏,出现心包积液。在复旦大学附属中山医院经超声支气管镜行支气管、淋巴结及心房肿物穿刺病理检查,确诊为MALT淋巴瘤。     

短期低碳水化合物饮食对不同性别肥胖患者人体成分的影响

目的探讨短期低碳水化合物饮食对男女肥胖患者人体成分的影响。方法选择76例(26例男性、50例女性)单纯性肥胖患者,在专业营养(医)师的指导下采取短期低碳水化合物饮食干预1个月,比较干预前后不同性别的单纯性肥胖患者体重、体脂肪、内脏脂肪、去脂体重、基础代谢等人体成分的变化,以此来研究短期低碳水化合物饮食对不同性别肥胖患者的适用性。结果 (1)干预后无论男女,BW、BMI、BFM、PBF、VFA、WHR、AC等肥胖相关指标均显著下降,差异具有统计学意义(P0.05);(2)干预后女性去脂体重以及骨骼肌重量、身体细胞量、蛋白质重量、无机盐、身体水分含量等瘦体重组成成分下降,基础代谢下降,差异有统计学意义(P0.05);男性相关指标差异无统计学意义(P0.05)。结论短期低碳水化合物饮食减重法能够有效降低肥胖患者的体脂肪及体重,无论男女,但是该方法会降低女性患者的瘦体重(骨骼肌重量、身体细胞量、蛋白质重量、无机盐、身体水分含量等),需要增加抗阻力运动提高瘦体重。     

体位固定方式和BMI对胸部肿瘤放疗摆位误差的影响

目的探讨胸部肿瘤患者接受放疗时,体位固定方式和身体质量指数(Body Mass Index,BMI)对摆位误差的影响。方法回顾性分析接受调强放疗的132例胸部肿瘤患者的临床资料。根据放疗时患者双手摆放位置的不同分为A、B两组,A组患者(82例)双手十指交叉置于专用臂托上,B组患者(50例)双手置于身体两侧。根据患者的BMI分为1组(偏瘦)、2组(正常)和3组(超重)。首次治疗前行CBCT扫描,使用自动骨性配准结合手动微调,计算出x、y和z轴方向的摆位误差。比较不同体位固定方式和不同BMI的摆位差异。结果B组患者x方向摆位误差小于A组(P<0.05);B3组患者x方向摆位误差小于A3组(P<0.05)。在y和z方向上,A组和B组之间的差异均无统计学意义(P>0.05)。结论胸部肿瘤患者放疗时,患者双手摆放位置对摆位误差有影响,采用双手体侧位固定方式引起的摆位误差较小。患者BMI越大,摆位误差差异越明显,超重患者更宜选用双手体侧位固定方式。     

内源性大麻素及其代谢酶与孤独症谱系障碍严重程度的相关性

目的探讨内源性大麻素(endocannabinoid,eCB)及其代谢酶与孤独症谱系障碍(autism spectrum disorder,ASD)的关联,为ASD的病因及发病机制研究提供理论依据。方法采用病例对照的研究方法,收集2017年6月至2018年12月在哈尔滨医科大学儿童发育行为研究中心就诊和在省孤独症定点康复机构接受康复训练的58名ASD儿童作为ASD组。按照性别、年龄1∶1匹配的原则,在黑龙江省抽取58名正常发育儿童作为对照组。采集两组儿童空腹静脉血,采用液相色谱-质谱联用技术(LC-MS/MS)和实时荧光定量PCR(RT-qPCR)检测其外周血中内源性大麻素花生四烯酸乙醇胺(AEA)、花生四烯酸甘油(2-AG)、十六酰胺乙醇(PEA)、油酰乙醇胺(OEA)及其代谢酶花生四烯酸磷脂酰乙醇胺特异性磷脂酶D(NAPE-PLD)、酰胺水解酶(FAAH)、单酰基甘油脂酶(MAGL)和二酰基甘油脂酶(DAGL)的mRNA表达水平,采用Pearson相关分析eCB与ASD儿童症状严重程度之间的相关性。结果ASD儿童的AEA、OEA和PEA的水平[(10.10±2.60)nmol/L,(24.30±5.60)nmol/L,(15.92±2.28)nmol/L]均低于对照组儿童[(13.46±3.04)nmol/L,(27.85±6.89)nmol/L,(17.87±2.67)nmol/L,t=-6.612,-3.089,-4.579,均P<0.01];ASD儿童FAAH和DAGL mRNA的表达水平显著高于对照组,且差异有统计学意义(t=2.423,3.840,P<0.05),而NAPE-PLD和MAGL mRNA水平在两组间差异无统计学意义(t=0.024,0.885,均P>0.05);ASD组PEA水平与儿童孤独症行为量表(ABC)总分呈负相关(r=-0.288,P<0.05)。结论ASD儿童体内的eCB及其代谢酶可能存在代谢异常,且eCB水平与ASD的严重程度存在关联性。     

Metabolic profiling of four synthetic stimulants,including the novel indanyl-cathinone 5-PPDi,after human hepatocyte incubation

Synthetic cathinones are new psychoactive substances that represent a health risk worldwide.For most of the 130 reported compounds,information about toxicology and/or metabolism is not available,which hampers their detection(and subsequent medical treatment)in intoxication cases.The principles of forensic analytical chemistry and the use of powerful analytical techniques are indispensable for stab-lishing the most appropriate biomarkers for these substances.Human metabolic fate of synthetic cathinones can be assessed by the analysis of urine and blood obtained from authentic consumers;however,this type of samples is limited and difficult to access.In this work,the metabolic behaviour of three synthetic cathinones(4-CEC,4-CPrC and 5-PPDi)and one amphetamine(3-FEA)has been evalu-ated by incubation with pooled human hepatocytes and metabolite identification has been performed by high-resolution mass spectrometry.This in vitro approach has previously shown its feasibility for obtaining excretory human metabolites.4-CEC and 3-FEA were not metabolised,and for 4-CPrC only two minor metabolites were obtained.On the contrary,for the recently reported 5-PPDi,twelve phase I metabolites were elucidated.Up to our knowledge,this is the first metabolic study of an indanyl-cathinone.Data reported in this paper will allow the detection of these synthetic stimulants in intoxi-cation cases,and will facilitate future research on the metabolic behaviour of other indanyl-based cathinones.     

中国汉族2型糖尿病人群体质量指数与血脂谱在糖尿病肾脏病中的交互作用

目的：探讨中国汉族2型糖尿病人群体质量指数（BMI）与血脂谱在糖尿病肾脏病（DKD）中的交互作用。方法：收集住院2型糖尿病患者647例,包括283例DKD患者以及364例非DKD的患者。采用二分类logistic回归分析血脂谱与DKD的相关性以及BMI与血脂谱的交互作用。结果：TG（OR=1.446,95%CI：1.076～1.942,P=0.014）、nonHDL-C（OR=1.961,95%CI：1.011～3.804,P=0.046）、nonHDL-C/HDL-C（OR=1.804,95%CI：1.134～2.869,P=0.013）、TC/HDL-C（OR=2.293,95%CI：1.234～4.260,P=0.009）、TG/HDL-C（OR=1.345,95%CI：1.057～1.712,P=0.016）均与DKD显著相关（OR针对各指标的自然对数计算）。BMI与TG、nonHDL-C/HDL-C、TC/HDL-C、TG/HDL-C之间的交互作用具有显著统计学意义（P值分别为0.036、0.035、0.034、0.016）。结论：中国汉族人群血浆TG、nonHDL-C、nonHDL-C/HDL-C、TC/HDL-C、TG/HDL-C均与DKD独立相关。BMI与TG、nonHDL-C/HDL-C、TC/HDL-C、TG/HDL-C之间存在交互作用。     

Genetic activation of pyruvate dehydrogenase alters oxidative substrate selection to induce skeletal muscle insulin resistance

The pyruvate dehydrogenase complex (PDH) has been hypothesized to link lipid exposure to skeletal muscle insulin resistance through a glucose-fatty acid cycle in which increased fatty acid oxidation increases acetyl-CoA concentrations, thereby inactivating PDH and decreasing glucose oxidation. However, whether fatty acids induce insulin resistance by decreasing PDH flux remains unknown. To genetically examine this hypothesis we assessed relative rates of pyruvate dehydrogenase flux/mitochondrial oxidative flux and insulin-stimulated rates of muscle glucose metabolism in awake mice lacking pyruvate dehydrogenase kinase 2 and 4 [double knockout (DKO)], which results in constitutively activated PDH. Surprisingly, increased glucose oxidation in DKO muscle was accompanied by reduced insulin-stimulated muscle glucose uptake. Preferential myocellular glucose utilization in DKO mice decreased fatty acid oxidation, resulting in increased reesterification of acyl-CoAs into diacylglycerol and triacylglycerol, with subsequent activation of PKC-θ and inhibition of insulin signaling in muscle. In contrast, other putative mediators of muscle insulin resistance, including muscle acylcarnitines, ceramides, reactive oxygen species production, and oxidative stress markers, were not increased. These findings demonstrate that modulation of oxidative substrate selection to increase muscle glucose utilization surprisingly results in muscle insulin resistance, offering genetic evidence against the glucose-fatty acid cycle hypothesis of muscle insulin resistance.Lipid-induced muscle insulin resistance plays a major role in the pathogenesis of type 2 diabetes (T2D), but the cellular mechanisms remain unknown (1, 2). More than 50 y ago Randle et al. (3) postulated the glucose-fatty acid cycle to explain the impairment of insulin-stimulated glucose disposal by fatty acids in muscle. In this model, fat oxidation increases mitochondrial acetyl-CoA/CoA and NADH/NAD⁺ ratios. Acetyl-CoA and NADH allosterically inhibit pyruvate dehydrogenase complex (PDH), the mitochondrial enzyme that links glycolysis to the TCA cycle by converting pyruvate to acetyl-CoA. Additionally, fatty acid-derived acetyl-CoA produces citrate, which inhibits phosphofructokinase. This in turn increases glucose-6-phosphate (G6P), a potent allosteric inhibitor of hexokinase. By these mechanisms, increased fatty acid oxidation was hypothesized to reduce glycolytic flux and prevent further muscle glucose uptake. However, in vivo studies of human skeletal muscle metabolism have challenged the Randle hypothesis. Five hours of a lipid infusion, combined with heparin to activate lipoprotein lipase, raised plasma fatty acids and induced muscle insulin resistance in healthy individuals, yet intramyocellular G6P and glucose concentrations were reduced compared with control glycerol infusion studies, implicating defects in insulin-stimulated glucose transport activity (4, 5). An alternative hypothesis to explain the muscle insulin resistance associated with lipid exposure posits that accumulation of bioactive lipid intermediates initiates signaling cascades that impair insulin action. Lipid species implicated include diacylglycerols (DAGs) (6–10), ceramides (11, 12), and long-chain acyl-CoAs (13). DAG activation of PKC-θ in skeletal muscle has been shown to impair canonical insulin signaling at the level of insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation through increased IRS-1 serine phosphorylation at the 1101 position (2, 6, 7, 14).More recently, incomplete fat oxidation and subsequent accumulation of mitochondrially derived acylcarnitines has been proposed to contribute to lipid-induced muscle insulin resistance (15–17). According to this model, insulin resistance stems from increased fat oxidation, leading to increased conversion of acyl-CoA to medium- and long-chain acylcarnitines, which may mediate insulin resistance via unknown mechanisms. In contrast, short-chain acylcarnitines have been suggested to promote metabolic flexibility. The shortest acylcarnitine, acetylcarnitine, is synthesized from acetyl-CoA and carnitine by carnitine acetyltransferase (CrAT), a mitochondrial matrix enzyme, and is responsible for buffering the mitochondrial acetyl-CoA pool and mitigating acetyl-CoA inhibition of PDH (18). Consistent with the notion that CrAT regulates substrate selection by modulating PDH flux, mice with muscle-specific deletion of CrAT exhibited reduced PDH activity during the fed-to-fasted transition, resulting in glucose intolerance and metabolic inflexibility, a term coined by Kelley and Mandarino (19) to explain the impairment in the ability to adjust fuel oxidation to fuel availability.Although these studies emphasize the importance of PDH in the promotion of metabolic inflexibility, the role of PDH and mitochondrial oxidative substrate selection in the regulation of basal and insulin-stimulated muscle glucose metabolism has not been directly assessed in vivo. To examine this question, we sought to determine whether modulation of oxidative substrate selection in a genetic mouse model with constitutively active PDH activity would affect insulin sensitivity in skeletal muscle.     

Investigation of the molecular reactivity of bioactive oxiranylmethyloxy anthraquinones

The design of a multitarget and multifunctional small molecule containing two functional groups reacting through different mechanisms represents an attractive goal for the medicinal chemist. The preparation of two bifunctional oxiranylmethyloxy anthraquinones, previously investigated as anticancer agents, is described here. These compounds combine a planar, DNA‐intercalating and pro‐oxidant anthraquinone scaffold and the alkylating epoxide functions which can covalently react with the nucleic acid. Their multilevel molecular reactivity was studied through a combination of analytical techniques: The DNA‐binding properties were investigated using a mass spectrometry‐based binding assay and by nuclear magnetic resonance, highlighting the formation of a covalent adduct with a nucleobase. Moreover, the contribution of the pro‐oxidant redox cycling was evaluated.