乙肝肝硬化肝胆湿热及肝肾阴虚证物质基础研究＊

目的 运用代谢组学技术分析乙肝肝硬化患者肝肾阴虚及肝胆湿热两种典型证候（同病异证）的血清差异代谢产物及其代谢通路,探寻虚、实两种典型证候的内在物质基础,以期从代谢水平上为中医证候分类提供客观依据。方法 对符合纳入标准的111例不同证候的乙肝肝硬化患者（肝胆湿热证40例,肝肾阴虚证41例,隐证(无证可辨）者30例）中医症状及体征进行描述性分析,发现两种不同证型的临床信息分布规律及证候特征;采用气相色谱-飞行时间质谱联用（GC-TOF/MS）技术对乙肝肝硬化患者,以及与之相匹配的60例健康人的血清样本进行检测,经非监督的主成分分析（Principal Components Analysis,PCA）、有监督的偏最小二乘判别分析（Partial Least Square Discriminant Analysis,PLS-DA）及监督的正交偏最小二乘法（Orthogonal Partial Least SquareDiscriminant Analysis,OPLS-DA）分析,找出与乙肝肝硬化疾病本身及其两种典型证候相关的差异性物质;运用MetaboAnalyst 3.0数据库,寻找并解析肝胆湿热及肝肾阴虚虚实两种证候间差异性物质的相关代谢通路。结果 （1）肝胆湿热证中出现频率较高（50%以上）的症状为小便色黄,口干,口苦,口臭或有异味等。肝肾阴虚证中出现频率较高的症状为口干、腰酸、乏力、腿软等。两证共见症/征为口干、尿黄、易怒、舌红。（2）各组间丙氨酸氨基转移酶（Alanine Aminotransferase,ALT）数值无统计学差异（P > 0.05）;与健康组比较,隐证组中白蛋白（Albumin,ALB）,肝胆湿热证中总胆红素（Total Bilirubin,TBil）、直接胆红素（Direct Bilirubin,DBil）、谷草转氨酶（Aspartate Transaminase,AST）、碱性磷酸酶（Alkaline Phosphatase,ALP）、谷氨酰转肽酶（Gamma-Glutamyl Transpeptidase,GGT）、总胆汁酸（Total Biliary Acid,TBA）及ALB,肝肾阴虚证TBil、ALP、GGT、TBA、ALB值差异均有统计学意义（P < 0.05）;与隐证比较,肝胆湿热证TBil、DBil、AST、ALP、TBA、ALB,肝肾阴虚证TBA、ALB差异有统计学意义（P < 0.05）;肝胆湿热证与肝肾阴虚证相比,TBil、DBil差异有统计学意义（P < 0.05）。（3）代谢组学检测及代谢通路分析,发现各组之间代谢谱均有良好的区分,并获得各组间的差异性物质。发现肝胆湿热及肝肾阴虚两典型证的共同物质10个,去除疾病（隐证）的信息,则得到两证共同物质6个,涉及的代谢通路为甘氨酸、丝氨酸及苏氨酸代谢和苯丙氨酸代谢;同时,分别获得两证各自特异性的代谢物质各8个,分别涉及亚油酸代谢和甘氨酸、苏氨酸及丝氨酸代谢。结论 运用代谢组学技术,发现肝胆湿热及肝肾阴虚不同证之间既存在病的共同物质（同病）,也存在证的差异物质（异证）,从而在代谢层面上为中医证候分类的科学性提供科学依据。     

Blast Resistance of 240 mm Building Wall Coated with Polyurea Elastomer

Enhancing the blast resistance of building walls is a research hotspot in the field of anti-terrorism and explosion protection. In this study, numerical simulation and experimental verification were combined to analyze the failure phenomenon of brick masonry wall and sprayed polyurea-reinforced brick wall under contact explosion and determine the failure response parameters of the wall. The failure limit, mode, and mechanism of a 240 mm wall without reinforcement and strengthened with polyurea elastomer under different strength loads were investigated. Under contact explosion, the increase in the size of the blasting pit of the 240 mm wall gradually slowed down after the dose was increased to higher than 0.5 kg. Thereafter, the energy of the explosive load was released by splashing wall fragments as well as by deflecting and movement of the wall. The results show that the 240 mm walls sprayed with polyurea elastomer had outstanding anti-explosion performance because it wraps the damaged area and fragments of masonry wall inside the polyurea layer. When the thickness of the polyurea layer increases to 8 mm, the damaged area of the masonry wall decreases by 55.6% compared with that without reinforcement. The numerical simulation results were in good agreement with the experimental results.     

Multiple occult intracranial diseases diverted diagnosis of glioma in a patient

Dizziness is an atypical symptom of the nervous system. Many neurological disorders can manifest as dizziness. When patients have multiple neurological disorders, the most obvious diagnosis is often considered, and diseases that are potentially more deadly are overlooked. Here, we report the case of a man aged in his early 50s with dizziness who was found to have four neurological disorders. A series of treatments failed to resolve the condition. A review of this case highlights that when a patient’s symptoms are not typical, a comprehensive examination and evaluation is required to determine the etiology, and imaging may reveal further minor problems.     

Autologous blood injection intracoronary artery for treating slow‐flow and no‐reflow in acute coronary syndrome related to primary pci

Slow‐flow and no‐reflow phenomenon are taken to sudden loss of coronary artery flow, typically after stenting or angioplasty in primary PCI. Otherwise conventional therapy, we report a technique, which autologous blood into intracoronary to supply oxygen and break process thrombosis results in successfully management no‐reflow in primary PCI in ACS.     

恩格列净通过抑制细胞焦亡改善糖尿病小鼠肾脏损伤

目的:研究恩格列净(empagliflozin)对db/db小鼠肾脏损伤的保护作用及其潜在作用机制。方法:db/db小鼠随机分为糖尿病肾病组(db/db组)和恩格列净治疗组(Empa组,恩格列净10 mg·kg -1·d -1灌胃),C57BL/6J小鼠作为正常对照组。干预3个月,检测血清生化、...     

除痹汤治疗强直性脊柱炎的临床观察

目的:观察除痹汤治疗强直性脊柱炎的临床效果.方法:将72例患者随机分为治疗组36例,服用除痹汤;对照组36例,服用双氯灭痛,对治疗前后的症状、体征、相关的实验室检查进行比较.结果:治疗组在改善临床症状、体征及阻止骨质破坏方面治疗组明显优于对照组,并可明显改善血清ESR、CRP、LgA等实验室指标.结论:除痹汤在治疗强直性脊柱炎上有良好的临床效果,并且减少或缓解强直性脊柱炎骨质的损害.     

Gold nanoclusters as prospective carriers and detectors of pramipexole

Pramipexole (PPX) is known in the treatment of Parkinson''s disease and restless legs syndrome. We carried out a theoretical investigation on pramipexole–Au cluster interactions for the applications of drug delivery and detection. Three Au_N clusters with sizes N = 6, 8 and 20 were used as reactant models to simulate the metallic nanostructured surfaces. Quantum chemical computations were performed in both gas phase and aqueous environments using density functional theory (DFT) with the PBE functional and the cc-pVDZ-PP/cc-pVTZ basis set. The PPX drug is mainly adsorbed on gold clusters via its nitrogen atom of the thiazole ring with binding energies of ca. −22 to −28 kcal mol⁻¹ in vacuum and ca. −18 to −24 kcal mol⁻¹ in aqueous solution. In addition to such Au–N covalent bonding, the metal–drug interactions are further stabilized by electrostatic effects, namely hydrogen-bond NH⋯Au contributions. Surface-enhanced Raman scattering (SERS) of PPX adsorbed on the Au surfaces and its desorption process were also examined. In comparison to Au₈, both Au₆ and Au₂₀ clusters undergo a shorter recovery time and a larger change of energy gap, being possibly conducive to electrical conversion, thus signaling for detection of the drug. A chemical enhancement mechanism for SERS procedure was again established in view of the formation of nonconventional hydrogen interactions Au⋯H–N. The binding of PPX to a gold cluster is expected to be reversible and triggered by the presence of cysteine residues in protein matrices or lower-shifted alteration of environment pH. These findings would encourage either further theoretical probes to reach more accurate views on the efficiency of pramipexole–Au interactions, or experimental attempts to build appropriate gold nanostructures for practical trials, harnessing their potentiality for applications.

Gold clusters as prospective carriers and detectors of pramipexole.     

Bandgap adjustment assisted preparation of >18% CsyFA1−yPbIxBr3−x-based perovskite solar cells using a hybrid spraying process

The preparation of Cs_yFA_1−yPbI_xBr_3−x-based perovskite by ultrasonic spraying has valuable application in the preparation of tandem solar cells on textured substrates due to its excellent stability and the advantages of large-area uniform preparation from the spraying technology. However, the bandgap of perovskite prepared by spraying method is difficult to adjust, and perovskites with a wide bandgap have the issue of phase instability. Here, we improved the crystallinity of the perovskite by simply controlling the post-annealing temperature. The results show that perovskite film prepared by hybrid spray method has the best crystallinity and device performance at a post-annealing temperature of 170 °C. On this basis, the bandgap of perovskite was changed from 1.53 eV to 1.76 eV by controlling the ratio of the organic halogen precursor solution. When the bandgap is 1.57 eV, a perovskite solar cell with an efficiency of 18.31% is obtained.

High-efficiency perovskite solar cells with good grain morphology and adjustable band gap were prepared by ultrasonic spray.     

Proton solvent-controllable synthesis of manganese oxalate anode material for lithium-ion batteries

Manganese oxalates with different structures and morphologies were prepared by the precipitation method in a mixture of dimethyl sulfoxide (DMSO) and proton solvents. The proton solvents play a key role in determining the structures and morphologies of manganese oxalate. Monoclinic MnC₂O₄·2H₂O microrods are prepared in H₂O-DMSO, while MnC₂O₄·H₂O nanorods and nanosheets with low crystallinity are synthesized in ethylene glycol-DMSO and ethanol-DMSO, respectively. The corresponding dehydrated products are mesoporous MnC₂O₄ microrods, nanorods, and nanosheets, respectively. When used as anode material for Li-ion batteries, mesoporous MnC₂O₄ microrods, nanorods, and nanosheets deliver a capacity of 800, 838, and 548 mA h g⁻¹ after 120 cycles at 8C, respectively. Even when charged/discharged at 20C, mesoporous MnC₂O₄ nanorods still provide a reversible capacity of 647 mA h g⁻¹ after 600 cycles, exhibiting better rater performance and cycling stability. The electrochemical performance is greatly influenced by the synergistic effect of surface area, morphology, and size. Therefore, the mesoporous MnC₂O₄ nanorods are a promising anode material for Li-ion batteries due to their good cycle stability and rate performance.

Manganese oxalates with different structures and morphologies were prepared by the precipitation method in a mixture of dimethyl sulfoxide (DMSO) and proton solvents.     

Characterization and application of natural and recombinant butelase-1 to improve industrial enzymes by end-to-end circularization

Butelase-1, an asparaginyl endopeptidase or legumain, is the prototypical and fastest known Asn/Asp-specific peptide ligase. It is highly useful for engineering and macrocyclization of peptides and proteins. However, certain biochemical properties and applications of naturally occurring and recombinant butelase-1 remain unexplored. Here we report methods to increase the yield of natural and bacterial expressed recombinant butelase-1 and how they can be used to improve the stability and activity of two important industrial enzymes, lipase and phytase, by end-to-end circularization. First, the yield of natural butelase-1 was increased 3-fold to 15 mg kg⁻¹ by determining its highest distribution which is found in young tissues, such as shoots. The yield of recombinantly-produced soluble butelase-1 was improved by promoting cytoplasmic disulfide folding, codon changes, and truncation of the N-terminal pro-domain. Natural and recombinant butelase-1 displayed similar ligase activity, physical stability, and salt tolerance. Furthermore, the processing and glycosylation sites of natural and recombinant butelase-1 were determined by proteomic analysis. Storage conditions for both forms of butelase-1, frozen or lyophilized, were also optimized. Cyclization of lipase and phytase mediated by either soluble or immobilized butelase-1 was highly efficient and simple, and resulted in increased thermal stability and enhanced enzymatic activity. Overall, improved production of butelase-1 can be exploited to improve the biocatalytic efficacy of lipase and phytase by end-to-end cyclization. In turn, ligase-improved enzymes could be a general and environmentally friendly strategy for producing more stable and efficient industrial enzymes.

Butelase-1, an asparaginyl endopeptidase or legumain, is the prototypical and fastest known Asn/Asp-specific peptide ligase that could be used for improving other enzymes by catalyzing simple and efficient end-to-end circularization.