Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes

BACKGROUND Cognitive dysfunction is the main manifestation of central neuropathy.Although cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking DM to cognitive dysfunction.Hyperglycemia is closely related to neurological abnormalities,while often disregarded in clinical practice.Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM(T2DM).AIM To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c(HbA1c)levels.METHODS A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital.The participants were divided into four groups according to their HbA1c levels using the interquartile method,namely Q1(<7.875%),Q2(7.875%-9.050%),Q3(9.050%-11.200%)and Q4(≥11.200%).Clinical data were collected and measured,including age,height,weight,neck/waist/hip circumferences,blood pressure,comorbidities,duration of DM,and biochemical indicators.Meanwhile,neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy.RESULTS The HbA1c level was significantly associated with urinary microalbumin(mALB),triglyceride,low-density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),and beta cell function(HOMA-β),N-acetylaspartate/creatine(NAA/Cr),and NAA/choline(NAA/Cho).Spearman correlation analysis showed that mALB,LDL-C,HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c(P<0.05),whereas HOMA-βwas negatively correlated with the HbA1c level(P<0.05).Ordered multiple logistic regression analysis showed that NAA/Cho[Odds ratio(OR):1.608,95%confidence interval(95%CI):1.004-2.578,P<0.05],LDL-C(OR:1.627,95%CI:1.119-2.370,P<0.05),and HOMA-IR(OR:1.107,95%CI:1.031-1.188,P<0.01)were independent predictors of poor glycemic control.CONCLUSION The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control,which may be the basis for the changes in cognitive function in diabetic patients.

1∶2 INTERNAL RESONANCE OF COUPLED DYNAMIC SYSTEM WITH QUADRATIC AND CUBIC NONLINEARITIES

The 1:2 internal resonance of coupled dynamic system with quadratic and cubic nonlinearities is studied. The normal forms of this system in 1 :2 internal resonance were derived by using the direct method of normal form. In the normal,forms, quadratic and cubic nonlinearities were remained. Based on a new convenient transformation technique, the 4-dimension bifurcation equations were reduced to 3-dimension. A bifurcation equation with one-dimension was obtained. Then the bifurcation behaviors of a universal unfolding were studied by using the singularity theory. The method of this paper can be applied to analyze the bifurcation behavior in strong internal resonance on 4-dimension center manifolds.

一种改进型1-3-2压电复合材料的研究

高质量的压电换能器需要具备较高的机电耦合系数和灵敏度。该文在传统型1-3-2压电复合材料的基础上提出了一种改进型1-3-2压电材料,提高了压电换能器的机电耦合系数和换能器的接收灵敏度。通过有限元仿真分析了不同间距对改进型1-3-2压电材料敏感元件的谐振频率、反谐振频率及机电耦合系数的影响,并与传统1-3-2型压电复合材料进行了对比。结果表明,与传统型1-3-2压电复合材料相比,在相同间距条件下,改进型压电材料的机电耦合系数约大0.03。制做的3种不同间距改进型压电材料表明,间距为1 mm的改进型压电材料的机电耦合系数较大,约为0.68。

SAE1与SAE2蛋白相互作用肽抑制剂的多种体外筛选体系的构建与评价

目的·构建用于发现小泛素样修饰蛋白(small ubiquitin-like modifier,SUMO)的活化酶亚基1(SUMO-activating enzyme subunit 1,SAE1)与亚基2(SUMO-activating enzyme subunit 2,SAE2)相互作用的肽抑制剂的多种体外筛选体系,并对不同筛选体系的优势与不足进行评价。方法·将编码SAE1和SAE2的目的基因分别插入pET-28a载体以构造原核蛋白表达质粒,在大肠埃希菌中表达并纯化人源SAE1和SAE2蛋白;利用纯化的蛋白先后构建等温滴定量热检测(isothermal titration calorimetry,ITC)实验、荧光偏振(fluorescence polarization,FP)实验、表面等离子共振(surface plasmon resonance,SPR)实验和基于SAE酶活的荧光实验等多种筛选体系。尝试利用不同的筛选体系检测候选多肽的抑制活性,基于检测结果,从灵敏度、稳定性、检测通量和检测成本等维度评价各筛选体系的优缺点与适用性。结果·经ITC测得SAE1和SAE2蛋白在体外相互作用的解离常数(K_(d))为0.96μmol/L,并将活性最好的多肽PEPT7改造为FP实验的示踪剂(tracer),但同SAE2的亲和力无法满足FP的要求;SPR测得SAE1和SAE2相互作用的K_(d)值为1.13μmol/L,与ITC数据接近;基于SAE酶活的荧光实验筛选得到抑制活性最强的多肽HP1B[半数抑制浓度(half-maximalinh ibitory concentration,IC_(50))达15.72μmol/L],SPR进一步确定其同SAE1的亲和力为34.4μmol/L。结论·尝试构建并比较了多种常见的蛋白-蛋白相互作用(protein-protein interaction,PPI)抑制剂的筛选体系。其中,ITC的检测通量低,且难以准确评估结合热不显著的低亲和力多肽;FP体系的可行性高度依赖于示踪剂同靶点蛋白之间的强亲和力,同样无法用于低亲和力多肽的筛选与优化;SPR检测的灵敏度高,但检测成本较高;酶活实验兼具高灵敏度、稳健性、高通量和可接受的检测成本,是最适宜的筛选方法。

Resonant interactions among two-dimensional nonlinear localized waves and lump molecules for the(2+1)-dimensional elliptic Toda equation

The(2+1)-dimensional elliptic Toda equation is a high-dimensional generalization of the Toda lattice and a semidiscrete Kadomtsev–Petviashvili I equation.This paper focuses on investigating the resonant interactions between two breathers,a breather/lump and line solitons as well as lump molecules for the(2+1)-dimensional elliptic Toda equation.Based on the N-soliton solution,we obtain the hybrid solutions consisting of line solitons,breathers and lumps.Through the asymptotic analysis of these hybrid solutions,we derive the phase shifts of the breather,lump and line solitons before and after the interaction between a breather/lump and line solitons.By making the phase shifts infinite,we obtain the resonant solution of two breathers and the resonant solutions of a breather/lump and line solitons.Through the asymptotic analysis of these resonant solutions,we demonstrate that the resonant interactions exhibit the fusion,fission,time-localized breather and rogue lump phenomena.Utilizing the velocity resonance method,we obtain lump–soliton,lump–breather,lump–soliton–breather and lump–breather–breather molecules.The above works have not been reported in the(2+1)-dimensional discrete nonlinear wave equations.

Codimension two bifurcation and chaos of a vibro-impact forming machine associated with 1：2 resonance case

A vibro-impact forming machine with double masses is considered. The components of the vibrating system collide with each other. Such models play an important role in the studies of dynamics of mechanical systems with impacting components. The Poincaré section associated with the state of the impact-forming system, just immediately after the impact, is chosen, and the period n single-impact motion and its disturbed map are derived analytically. A center manifold theorem technique is applied to reduce the Poincaré map to a two-dimensional map, and the normal form map associated with codimension two bifurcation of 1：2 resonance is obtained, Unfolding of the normal form map is analyzed. Dynamical behavior of the impact-forming system, near the point of codimension two bifurcation, is investigated by using qualitative analyses and numerical simulation. Near the point of codimension two bifurcation there exists not only Neimark-Sacker bifurcation associated with period one single-impact motion, but also Neimark-Sacker bifurcation of period two double-impact motion. Transition of different forms of fixed points of single-impact periodic orbits, near the bifurcation point, is demonstrated, and different routes from periodic impact motions to chaos are also discussed.

Research on 1:2 subharmonic resonance and bifurcation of nonlinear rotor-seal system

The 1：2 subharmonic resonance of the labyrinth seals-rotor system is inves- tigated, where the low-frequency vibration of steam turbines can be caused by the gas exciting force. The empirical parameters of gas exciting force of the Muszynska model are obtained by using the results of computational fluid dynamics （CFD）. Based on the multiple scale method, the 1：2 subharmonic resonance response of the dynamic system is gained by truncating the system with three orders. The transition sets and the local bifurcations diagrams of the dynamics system are presented by employing the singular theory analysis. Meanwhile, the existence conditions of subharmonic resonance non-zero solutions of the dynamic system are obtained, which provides a new theoretical basis in recognizing and protecting the rotor from the subharmonic resonant failure in the turbine machinery.

GPCR/endocytosis/ERK signaling/S2R is involved in the regulation of the internalization,mitochondria-targeting and-activating properties of human salivary histatin 1

Human salivary histatin 1(Hst1)exhibits a series of cell-activating properties,such as promoting cell spreading,migration,and metabolic activity.We recently have shown that fluorescently labeled Hst1(F-Hst1)targets and activates mitochondria,presenting an important molecular mechanism.However,its regulating signaling pathways remain to be elucidated.We investigated the influence of specific inhibitors of G protein-coupled receptors(GPCR),endocytosis pathways,extracellular signal-regulated kinases1/2(ERK1/2)signaling,p38 signaling,mitochondrial respiration and Na+/K+-ATPase activity on the uptake,mitochondria-targeting and-activating properties of F-Hst1.We performed a si RNA knockdown(KD)to assess the effect of Sigma-2 receptor(S2R)/Transmembrane Protein 97(TMEM97)—a recently identified target protein of Hst1.We also adopted live cell imaging to monitor the whole intracellular trafficking process of F-Hst1.Our results showed that the inhibition of cellular respiration hindered the internalization of F-Hst1.The inhibitors of GPCR,ERK1/2,phagocytosis,and clathrin-mediated endocytosis(CME)as well as siRNA KD of S2R/TMEM97 significantly reduced the uptake,which was accompanied by the nullification of the promoting effect of F-Hst1 on cell metabolic activity.Only the inhibitor of CME and KD of S2R/TMEM97 significantly compromised the mitochondria-targeting of Hst1.We further showed the intracellular trafficking and targeting process of F-Hst1,in which early endosome plays an important role.Overall,phagocytosis,CME,GPCR,ERK signaling,and S2R/TMEM97 are involved in the internalization of Hst1,while only CME and S2R/TMEM97 are critical for its subcellular targeting.The inhibition of either internalization or mitochondria-targeting of Hst1 could significantly compromise its mitochondria-activating property.

The application of C1-C2 pedicle screw internal fixation on the upper cervical diseases of children

Objective To report five cases of puerile (【9 years) atlantoaxial instability which underwent C1-C2 pedicle screw internal fixation by posterior approach,and to introduce the surgical technique and the key point

基于T_(1)-T_(2)^(*)弛豫相关的聚氨酯橡胶相态结构和动力学特征

磁共振技术具有非破坏性、对高分子链运动敏感等特点,是一种能够在分子水平上表征高分子系统相态结构和动力学特征的常用技术.本文利用T_(1)-T_(2)^(*)弛豫相关研究了聚氨酯橡胶的相态结构和分子动力学特征,并用高斯衰减和指数衰减模型分析了聚氨酯橡胶的T_(1)-T_(2)^(*)数据.聚氨酯橡胶的T_(1)-T_(2)^(*)谱显示了三种类型的信号:晶体氢组分的T2*最短,过渡相氢组分具有中等的T_(2)^(*),非晶体氢组分的T_(2)^(*)最长;但这三种氢组分表现出相近的T1,且T1随着聚氨酯橡胶硬度的增加或温度的降低而逐渐降低.三种氢组分的磁共振信号强度随聚氨酯橡胶的硬度和温度的变化而变化.随着聚氨酯橡胶硬度的增加,晶体氢组分含量增加,非晶体氢组分和过渡相氢组分的含量降低;随着温度的增加,晶体氢组分含量减少,过渡相氢组分含量保持不变,而非晶体氢组分含量增加.另外,聚氨酯橡胶的硬软比随温度的升高而降低.这些结果表明T_(1)-T_(2)^(*)弛豫相关可用于聚氨酯橡胶的相态结构和动力学评价.

司美格鲁肽对2型糖尿病合并超重及肥胖患者的胰腺和肝脏脂肪含量以及胰岛β细胞功能的影响

目的探讨司美格鲁肽对2型糖尿病(T2DM)合并超重及肥胖患者的血糖控制、胰腺和肝脏脂肪含量以及胰岛β细胞功能的影响。方法采用单中心、前瞻性、临床病例对照试验的方法,选取2021年10月至2022年10月在金华市中心医院诊断为T2DM合并超重(BMI 25~<28 kg/m^(2))及肥胖(BMI≥28 kg/m^(2))的86例患者为研究对象,均接受稳定剂量的二甲双胍单药或联合口服用药至少3个月,糖化血红蛋白(HbA1C)为6.5%~8.0%。采用随机数字表法将患者分为对照组和观察组,各43例。对照组继续原方案口服降糖,观察组在原方案的基础上联合司美格鲁肽(起始剂量0.25 mg,4周后增加至0.5 mg并稳定,1次/周,皮下注射)。两组均干预24周。比较两组患者血糖(FPG、餐后2 h血糖和HbA1C)、血脂(TC、TG、LDL-C、HDL-C)、BMI、腰围、胰岛细胞功能[空腹胰岛素(FINS)、胰岛β细胞功能指数(HOMA-β)和胰岛素抵抗指数(HOMA-IR)]。通过非对称回波的最小二乘估算法迭代水脂分离序列测量胰头、胰体和胰尾的胰腺脂肪分数(PFF),计算平均PFF并进行组间比较;测量肝脏右上、右下和左叶的肝脏脂肪分数(HFF),计算平均HFF并进行组间比较。结果对照组39例和观察组40例随访至研究结束。治疗后观察组患者FPG、餐后2 h血糖、HbA1C、BMI、FINS、HOMA-IR、平均PFF和平均HFF均低于对照组,而HOMA-β高于对照组,差异均有统计学意义(均P<0.01)。结论司美格鲁肽应用方便,对T2DM合并超重及肥胖患者能够在常规降糖药的基础上进一步改善胰岛素和胰岛β细胞功能,降低血糖水平、胰腺和肝脏脂肪含量,同时可产生额外的减重获益。

MOLECULES AND NEW INTERACTIONAL STRUCTURES FOR A(2+1)-DIMENSIONAL GENERALIZED KONOPELCHENKO-DUBROVSKY-KAUP-KUPERSHMIDT EQUATION

Soliton molecules(SMs)of the(2+1)-dimensional generalized KonopelchenkoDubrovsky-Kaup-Kupershmidt(gKDKK)equation are found by utilizing a velocity resonance ansatz to N-soliton solutions,which can transform to asymmetric solitons upon assigning appropriate values to some parameters.Furthermore,a double-peaked lump solution can be constructed with breather degeneration approach.By applying a mixed technique of a resonance ansatz and conjugate complexes of partial parameters to multisoliton solutions,various kinds of interactional structures are constructed;There include the soliton molecule(SM),the breather molecule(BM)and the soliton-breather molecule(SBM).Graphical investigation and theoretical analysis show that the interactions composed of SM,BM and SBM are inelastic.

1-3-2压电复合材料机电理论分析和频率仿真

该文研究了1-3-2压电复合材料的厚度振动谐振频率与尺寸的关系。应用压电学和弹性动力学理论建立了机电等效图,对1-3-2压电复合材料的厚度振动模态进行了机电理论分析,并对其谐振频率进行了计算。利用有限元仿真软件分析了在厚度振动模态下,1-3-2压电复合材料谐振频率、反谐振频率与尺寸变化的关系。结果表明,纵向尺寸比变大时,频率曲线呈下降趋势;横向尺寸比变大时,频率曲线呈上升趋势;横纵尺寸比变大时,频率曲线呈缓慢下降趋势;基底厚度变大时,频率曲线呈先减小后增大趋势。4种情况中,纵向尺寸比对于整体的谐振和反谐振频率影响最显著。

Drug-induced sarcoidosis-like reaction three months after BNT162b2 mRNA COVID-19 vaccination:A case report and review of literature

BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.

具有平方、立方非线性项的耦合动力学系统1∶2内共振分岔

对一类具有平方、立方非线性项的耦合动力学系统 1∶2内共振情形进行了研究· 首先 ,用直接方法求出该系统 1∶2内共振时的NormalForm ,该系统的NormalForm中 ,不仅含有平方非线性项 ,同时还含有立方非线性项· 通过采用适当的变量变换 ,将 4维分岔方程约化成 3维 ,进而得到单变量 4次分岔方程· 最后用奇异性理论 ,研究了一类普适开折的分岔特性· 该方法可用于 4维中心流形上流的强内共振时的分岔行为分析·

2-乙酰基-1-甲基吡咯激发态结构动力学及溶剂效应的共振拉曼光谱和密度泛函理论计算

获取了覆盖紫外光谱中A带和B带吸收的共7个不同激发波长的共振拉曼光谱,并结合密度泛函理论方法研究了2-乙酰基-1-甲基吡咯(2-Ac-NMP)的A带和B带电子激发和Franck-Condon区域结构动力学.在TD-B3LYP/6-311++G(d,p)计算水平上,A带和B带吸收的跃迁主体为π→π*.A带和B带共振拉曼光谱分别指认为13个振动模式和8个振动模式的基频、泛频和组合频,其中C O伸缩振动(ν8)、C3—C4—C5不对称伸缩振动+C2—C6伸缩振动(ν14)及环上CH面内摇摆(ν18)对拉曼光谱强度贡献最大,表明2-Ac-NMP的Sπ激发态结构动力学主要沿反应坐标展开.考察了溶剂对共振拉曼光谱强度模式的影响,结果表明,在同一溶剂中,随激发波长由长变短,C O伸缩振动模(ν8)的强度呈现出由强变弱再变强的现象.这种变化规律与Franck-Condon区域Sn/Sπ态混合或势能面交叉相关,并受溶剂的有效调控.

基于1,8-萘酰亚胺与罗丹明B间荧光共振能量转移的高选择性Hg^(2+)比率荧光探针

以罗丹明B与1,8-萘二甲酰亚胺反应合成了1个高选择性Hg^(2+)比率荧光探针(RN).在甲醇/乙腈/4-羟基哌嗪乙磺酸缓冲溶液(p H=7.2,体积比8∶1∶1)中,RN对Hg^(2+)具有比色和比率荧光双重响应.加入Hg^(2+)后,RN的紫外-可见光谱在约556 nm处产生强吸收,溶液由浅绿色变为橙色,其它金属离子对RN的紫外-可见光谱几乎无影响.无Hg^(2+)存在时,RN的荧光光谱在540 nm处出现萘二甲酰亚胺荧光团的特征峰;加入Hg^(2+)后,540 nm处的发射带逐渐消失,同时在580 nm附近产生强荧光,荧光颜色从绿色变为橙色.这归因于从萘酰亚胺到开环罗丹明B的荧光共振能量转移(FRET),探针RN对Hg^(2+)的比率荧光响应具有高选择性,不受其它共存金属离子的干扰.

4-氨基-5-[2-(4-氯苯氧甲基)苯并咪唑-1-亚甲基]-1,2,4-三唑-3-硫酮的核磁共振研究

在无水乙醇和KOH存在下,将2-(4-氯苯氧甲基)-1-苯并咪唑乙酰肼(1)与CS2反应,合成出了中间体酰肼二硫代甲酸钾盐。此中间体再与过量的水合肼反应,经环化得到一种新化合物4-氨基-5-[2-(4-氯苯氧甲基)苯并咪唑-1-亚甲基]-1,2,4-三唑-3-硫酮。采用元素分析、IR及NMR技术确定了新化合物的结构,并利用2D NMR技术对其两种异构体(硫酮和硫醇)的1H和13C NMR谱带进行了全归属,给出了相应的偶合常数J值以及异构体所占的比例。实验表明,新化合物在DMSO中存在硫酮和硫醇两种异构体的互变,并且硫酮占主导,含量为81.9%,而硫醇的含量仅为18.1%。

非线性转子-密封系统1∶2亚谐共振分岔研究

研究了转子-密封系统在气流激振力作用下的低频振动———1∶2亚谐共振现象.利用流体计算动力学(CFD)方法对转子-密封系统进行了流场模拟计算,辨识出适用于气流流场的Muszyns-ka模型参数,并建立了转子-密封系统动力学方程.采用多尺度方法将系统进行3次截断,并得到系统响应.采用奇异性理论研究了系统的1∶2亚谐共振,进一步得到系统亚谐共振的分岔方程和转迁集,根据转迁集给出了在不同奇异性参数空间内的分岔图.同时,由分岔方程得到了亚谐共振非零解存在的条件.其分析结果对抑制转子-密封系统的亚谐振动有重要的工程意义.

简谐横向荷载作用下弹性地基上不可伸长梁的1/2次亚谐共振响应分析

基于已建立的弹性地基上不可伸长梁的非线性动力学模型,本文针对简谐横向荷载作用下梁的1/2次亚谐共振响应进行研究。利用弹性地基梁的非线性运动方程和多尺度方法,求得梁1/2次亚谐共振响应的二次近似解。进而,运用幅频响应曲线对梁的亚谐共振响应进行研究,并分析了边界条件、地基模型、Winkler参数等对梁非线性共振响应的影响。结果表明:三参数地基模型中弹性层的引入对其支承梁的亚谐共振响应影响显著;临界激励幅值决定了弹性地基梁1/2次亚谐共振响应非平凡解的存在性;梁端约束条件在一定程上改变了Winkler参数对梁非线性动力响应的作用效应。