针灸治疗血管性痴呆的临床观察

30例患者经过 2个月的针灸治疗 ,其中显效 9例 ,有效 1 8例 ,无效 3例 ,有效率 90 %。针灸治疗前后 HDS测试及血浆 TXA2 、6-keto-PGF1α含量测定自身比较 ,差异均有显著意义 ( P<0 .0 1 )。说明针灸能改善血管性痴呆 ( VD)患者的智能 ,且能调整患者血浆 TXB2 和 PGI2 的平衡     

新型冠状病毒肺炎暴发流行中心疫区急腹症诊治经验

目的分析新型冠状病毒肺炎(COVID-19)疫情下在中心疫区开展急腹症诊治的临床效果,总结临床经验。方法回顾性分析2020年1月24日至2020年2月29日华中科技大学同济医学院附属同济医院急诊收治和院内会诊的急腹症病人的临床处置和预后,随访结束时间为2020年3月8日。结果2020年1月24日至2020年2月29日已处置腹痛为主要表现的急腹症病人19例,其中,合并COVID-19病人(确诊及疑似病例)5例。19例病人中,有急诊手术指征并行急诊手术处置的9例,恢复顺利者7例,死亡2例,其中确诊COVID-19病人行急诊手术处置1例,死亡1例;行保守治疗并密切观察病情变化者10例(包括4例COVID-19病人),均恢复良好;随访至今未见密切接触上述COVID-19病人的医护人员出现感染表现。结论COVID-19疫情期间在中心疫区诊治急腹症病人时无论其是否是COVID-19病人都做到仔细检查,严格把握手术指征,术中熟练操作,术后密切监护及观察,同时做好医护人员个人防护。     

Large Area,Highly Transparent,and Mechanically Stable Adhesive Films with Tunable Refractive Indices

Optical bonding with both excellent mechanical and optical properties is highly desirable for many advanced optical device applications. This paper presents a facile method for fabricating large‐area, highly transparent, and mechanically stable adhesive films with a tunable refractive index (RI) by the layer‐by‐layer (LbL) assembly of cationic branched poly(ethylenimine) (PEI) and an anionic blend of poly(acrylic acid) (PAA) and poly(4‐styrenesulfonic acid) (PSS). Scanning electron microscopy and atomic force microscopy studies indicate that the resulting (PEI/PAA–PSS)*n adhesive films with n PEI/PAA–PSS deposition layers are smooth and homogeneous. A satisfactory bonding strength is demonstrated for both two‐sided and one‐sided bonding methods, which provide a bonding strength greater than 5.71 ± 0.71 MPa. A linearly tunable RI from 1.5410 to 1.5792 is achieved with a transparency greater than 94% in the visible region. Moreover, the preparation and debonding of adhesive films can be conducted in water, which is convenient and environmentally friendly.     

MRI联合MR扩散加权成像在直肠癌T分期中的应用

目的 探讨MRI联合MR扩散加权成像(DWI)在直肠癌T分期中的应用价值.方法 选取我科2014年7月至2017年6月收治的39例直肠癌患者为研究对象,进行M RI平扫及增强联合DWI检查.结果 在39例病例中,35例M RI平扫及增强联合DWI检查获得准确的T分期诊断,符合率为89.74％,高于MRI平扫及增强检查诊断的准确率79.48％.其中以T4分期的的诊断符合率、特异度、敏感度、阳性预测值、阴性预测值最大.M RI联合DWI组与病理结果对T分期的诊断具有较高的一致性.结论 M RI联合DWI对直肠癌术前T分期具有诊断价值,可为治疗方案的制定提供参考.     

Distribution of ancestral chromosomal segments in admixed genomes and its implications for inferring population history and admixture mapping

The ancestral chromosomal segments in admixed genomes are of significant importance for both population history inference and admixture mapping, because they essentially provide the basic information for tracking genetic events. However, the distributions of the lengths of ancestral chromosomal segments (LACS) under some admixture models remain poorly understood. Here we introduced a theoretical framework on the distribution of LACS in two representative admixture models, that is, hybrid isolation (HI) model and gradual admixture (GA) model. Although the distribution of LACS in the GA model differs from that in the HI model, we demonstrated that the mean LACS in the HI model is approximately half of that in the GA model if both admixture proportion and admixture time in the two models are identical. We showed that the theoretical framework greatly facilitated the inference and understanding of population admixture history by analyzing African-American and Mexican empirical data. In addition, we found the peak of association signatures in the HI model was much narrower and sharper than that in the GA model, indicating that the identification of putative causal allele in the HI model is more efficient than that in the GA model. Thus admixture mapping with case-only data would be a reasonable and economical choice in the HI model due to the weak background noise. However, according to our previous studies, many populations are likely to be gradually admixed and have pretty high background linkage disequilibrium. Therefore, we suggest using a case-control approach rather than a case-only approach to conduct admixture mapping to retain the statistics power in recently admixed populations.     

Copy number variations and genetic admixtures in three Xinjiang ethnic minority groups

Xinjiang is geographically located in central Asia, and it has played an important historical role in connecting eastern Eurasian (EEA) and western Eurasian (WEA) people. However, human population genomic studies in this region have been largely underrepresented, especially with respect to studies of copy number variations (CNVs). Here we constructed the first CNV map of the three major ethnic minority groups, the Uyghur, Kazakh and Kirgiz, using Affymetrix Genome-Wide Human SNP Array 6.0. We systematically compared the properties of CNVs we identified in the three groups with the data from representatives of EEA and WEA. The analyses indicated a typical genetic admixture pattern in all three groups with ancestries from both EEA and WEA. We also identified several CNV regions showing significant deviation of allele frequency from the expected genome-wide distribution, which might be associated with population-specific phenotypes. Our study provides the first genome-wide perspective on the CNVs of three major Xinjiang ethnic minority groups and has implications for both evolutionary and medical studies.     

Energy landscape views for interplays among folding,binding, and allostery of calmodulin domains

Ligand binding modulates the energy landscape of proteins, thus altering their folding and allosteric conformational dynamics. To investigate such interplay, calmodulin has been a model protein. Despite much attention, fully resolved mechanisms of calmodulin folding/binding have not been elucidated. Here, by constructing a computational model that can integrate folding, binding, and allosteric motions, we studied in-depth folding of isolated calmodulin domains coupled with binding of two calcium ions and associated allosteric conformational changes. First, mechanically pulled simulations revealed coexistence of three distinct conformational states: the unfolded, the closed, and the open states, which is in accord with and augments structural understanding of recent single-molecule experiments. Second, near the denaturation temperature, we found the same three conformational states as well as three distinct binding states: zero, one, and two calcium ion bound states, leading to as many as nine states. Third, in terms of the nine-state representation, we found multiroute folding/binding pathways and shifts in their probabilities with the calcium concentration. At a lower calcium concentration, “combined spontaneous folding and induced fit” occurs, whereas at a higher concentration, “binding-induced folding” dominates. Even without calcium binding, we observed that the folding pathway of calmodulin domains can be modulated by the presence of metastable states. Finally, full-length calmodulin also exhibited an intriguing coupling between two domains when applying tension.Protein folding and conformational dynamics have often been characterized by the energy landscape of proteins (1–5). The energy landscape is dependent on the molecular physiochemistry and thus is modulated by many factors, such as chemical modification and ligand binding. Ligand binding, in turn, is dependent on the conformation of proteins. Thus, folding, binding, and allosteric conformational dynamics are mutually correlated. Despite their obvious correlation in concept, it has been very challenging to characterize how they are indeed coupled for any single proteins. Here, we address, in depth, how these three types of dynamics, folding, binding, and allosteric conformational dynamics, are coupled from the energy landscape perspective for a specific protein, calmodulin (CaM).CaM is a ubiquitous calcium-binding messenger protein involved in signal transduction (6) and, more importantly here, has been a model protein to investigate folding, binding, and allostery. Full-length CaM has two nearly symmetric globular domains connected by a flexible central helix (7, 8). Each domain is composed of paired EF hands containing two Ca²⁺-binding sites (Fig. 1A). Upon binding to Ca²⁺, each CaM domain undergoes substantial conformational change from a closed state to an open state, exposing a hydrophobic patch that can bind with target proteins and regulate downstream processes (9). CaM has been frequently used as a model in studying the folding of multidomain proteins (10, 11), allosteric transitions (12–14), slow conformational dynamics around physiological temperatures (15–18), metal ion binding (19, 20), and correlation between inherent flexibility and protein functions (21, 22). For example, using structure-based coarse-grained (CG) simulations, Chen and Hummer elucidated the coexistence of an unfolded state, a closed state, and an open state around physiological temperatures for the C-terminal domain of CaM (CaM-C) without Ca²⁺ binding (15), which reconciles some seemingly contradictory experimental observations on the slow conformational dynamics of CaM.Open in a separate windowFig. 1.(A) Three-dimensional structure of calmodulin domain at closed [Protein Data Bank (PDB) code: 1cfd] and open states (PDB code:1cll). Calcium ions are represented by yellow spheres. (B) Schematic of coupling among folding, calcium binding, and allosteric motions for the CaM domain. Due to the conformational transitions between open and closed states, in addition to the direct folding pathway (red solid arrow), folding to the most stable state may involve an alternative pathway via a metastable state (green arrow plus blue arrow). The calcium binding can modulate the relative stability of the conformational states and therefore the population of folding pathways. O, C, and U represent open, closed, and unfolded states, respectively.More recently, Rief and coworkers studied the Ca²⁺-dependent folding of CaM based on a new generation technique of single-molecule force spectroscopy, which can probe the reversible folding/unfolding transitions with near equilibrium conditions (10, 23, 24). Their results revealed that at high Ca²⁺ concentrations, the folding pathway of the CaM domain proceeds via a transition state capable of binding Ca²⁺ ions, demonstrating the coupling between Ca²⁺ binding and CaM folding. All these computational and experimental works provided unprecedented understanding of many aspects of the folding and allosteric transitions of CaM. However, a full picture of the coupling among folding, Ca²⁺ binding, and allosteric motions, as schematically shown in Fig. 1B, is still lacking. Particularly, two fundamental issues arising from the allostery and Ca²⁺-binding characteristics of CaM remain elusive: (i) How does the allosteric feature of the energy landscape contribute to the folding complexity? And (ii) how can the folding mechanism of CaM be modulated by Ca²⁺ binding?Motivated by previous computational and experimental studies (15, 23), in this work we investigated the folding coupled with Ca²⁺ binding and allosteric motions of the isolated CaM domains as well as the full-length CaM. To do so, we first integrated computational tools developed for folding, ligand binding, and allosteric motions together. The proposed CG protein model was used for the subsequent series of molecular dynamics (MD) simulations. First, corresponding to Rief’s experiments, we performed MD simulations of isolated CaM domains with pretensions, which gave consistent results with the experiments and, in addition, provided the direct structural assignment on the experimentally observed states. Second, at a higher temperature, without pretension we performed reversible folding/unfolding simulations for a wide range of Ca²⁺ concentrations. The conformational and ligand-binding energy landscape revealed as many as nine distinctive states. Then, we analyzed the binding-coupled folding reactions in terms of the nine states, finding multiple routes and their modulation by Ca²⁺ concentrations. Interestingly, as the Ca²⁺ concentration increases, the CaM domain folding mechanism switches from “combined spontaneous folding and induced fit” to “binding-induced folding,” which accords with the scenario deduced from single-molecule force spectroscopy experiments. Finally, the effects of tension on the conformational fluctuations of the full-length CaM are discussed.     

Refined-JinQi-JiangTang tablet ameliorates hypertension through activation of FGF21/FGFR1 axis in fructose-fed rats

Journal of Natural Medicines - The aim of this study was to investigate the therapeutic effect of JQ-R on metabolic hypertension and its correlation with Fibroblast growth factor 21/Fibroblast...     

Propofol induces neuronal apoptosis in infant rat brain under hypoxic conditions

Propofol is currently one of the most widely used intravenous anesthetic. In the present study, we investigated the effects of propofol on neuropathogenesis in newborn rats under hypoxic conditions. Seven-day old SD rats were assigned into one of the six treatments: propofol+50% oxygen (propofol-oxygen, PO), propofol+room air (propofol-air, PA), propofol+18% oxygen (propofol-hypoxia, PH), control group: lipid emulsion solvent+50% oxygen (CO), lipid emulsion solvent+room air (CA), lipid emulsion solvent+18% oxygen (CH). The rats assigned to anesthesia or control groups received intraperitoneally (ip) propofol 50 mg/kg or identical volume of lipid emulsion solvent (5.0 ml/kg) for seven days. SaO(2) (%) and respiratory rate (RR) were monitored throughout the procedures. The rats were decapitated 24h after 7 days exposure. TUNEL staining, Nissl staining, ultrastructural changes and the expression of caspase-3 in the brain tissues were assessed. We found propofol-induced attenuation of respiration could produce lower oxygen concentrations in the blood (hypoxia) under air or mild hypoxia conditions. Interestingly, in the presence of oxygen completely rescued hypoxia to normal levels, suggesting that propofol-induced respiratory depression led to hypoxia only under air or mild hypoxic conditions (propofol/hypoxia). In addition, propofol indirectly induced apoptosis through hypoxia resulting from respiratory depression under air or hypoxic conditions, which was determined by elevated expression of caspase-3, increased TUNEL-positive cells, ultrastructural changes of neuronal cell death and loss of Nissl staining neuronal in infant SD rat brains. However, in propofol-oxygen group and all control groups, no significant apoptosis were observed. These findings indicated that propofol per se or hypoxia per se did not directly induce significant apoptosis. However, propofol-induced attenuation of respiration could produce lower oxygen concentrations in the blood under air or mild hypoxia conditions and thereby result in neuronal degeneration. So, it is important to supply with supplementary oxygen during propofol anesthesia.