基于国际认证标准的医疗耗材供应链安全能力建设

目的 以符合目前世界公认最高的国际医疗机构相关认证标准为目标,建立模型加强医疗耗材供应链安全能力,保护患者和员工免受污染、伪劣和用途改变产品的危害。 方法 根据供应链安全模型,医疗耗材供应链管理的设计上采取了相应的措施 结果 提高了医疗耗材供应链安全能力,降低风险,符合在医院物流方面的更高品质要求 结论 将供应链安全模型运用于医疗耗材供应链管理中,能有效加强医疗耗材供应链安全能力。     

Fibrinogen alpha amyloidosis: insights from proteomics

ABSTRACT

Introduction: Systemic amyloidosis is a diverse group of diseases that, although rare, pose a serious health issue and can lead to organ failure and death. Amyloid typing is essential in determining the causative protein and initiating proper treatment. Mass spectrometry-based proteomics is currently the most sensitive and accurate means of typing amyloid.

Areas covered: Amyloidosis can be systemic or localized, acquired or hereditary, and can affect any organ or tissue. Diagnosis requires biopsy, histological analysis, and typing of the causative protein to determine treatment. The kidneys are the most commonly affected organ in systemic disease. Fibrinogen alpha chain amyloidosis (AFib) is the most prevalent form of hereditary renal amyloidosis. Select mutations in the fibrinogen Aα (FGA) gene lead to AFib.

Expert commentary: Mass spectrometry is currently the most specific and sensitive method for amyloid typing. Identification of the mutated fibrinogen alpha chain can be difficult in the case of ‘private’ frameshift mutations, which dramatically change the sequences of the expressed fibrinogen alpha chain. A combination of expert pathologist review, mass spectrometry, and gene sequencing can allow for confident diagnosis and determination of the fibrinogen alpha chain mutated sequence.     

我国医药分开政策目的及其策略分析

目的 进一步明确医药分开政策目的及策略。方法 采用文献回顾性研究法,对医药利益链条及其形成原因,以及解决策略进行系统性地总结和分析。结果 现有研究一是认为医疗服务提供方拥有垄断地位造成利益链条存在,因而提出消除垄断;二是认为扭曲的“白色”或不良的“灰色”激励机制造成利益链条存在,因而提出完善“白色”或消除“灰色”激励机制的综合策略。结论 医药利益链条产生更深层次的原因是,非营利性的公立医疗机构不合理地追求经济利益,医生采用不合理方式追求部分合理经济利益。因此,医药分开目的应是让公立医疗机构真正成为非营利机构,使医生依靠技术获得合理的经济回报,让公立医疗机构、医生、政府、患者、药品企业及流通商间激励相容。建议采用外部补偿和内部薪酬制度为重点的综合改革策略,形成各利益相关方激励相容的良好局面,自然消除公立医疗机构、医生与药品销售间利益链条。     

Properties of Oligonucleotides Containing the Transition Bases P and K

Abstract

The properties of the degenerate nucleosides dP and dK, in templates and primers were determined. dP was copied as either pyrimidine, dK as either purine. In primers, an equimolar mixture of the two nucleosides functioned as a universal base equivalent in both sequencing and the polymerase chain reactions. Cloning of DNA containing dP or dK produced transition mutations in vivo.     

A three dimensional visualisation approach to protein heavy-atom structure reconstruction

Background

A commonly recurring problem in structural protein studies, is the determination of all heavy atom positions from the knowledge of the central α-carbon coordinates.

Results

We employ advances in virtual reality to address the problem. The outcome is a 3D visualisation based technique where all the heavy backbone and side chain atoms are treated on equal footing, in terms of the C_α coordinates. Each heavy atom is visualised on the surfaces of a different two-sphere, that is centered at another heavy backbone and side chain atoms. In particular, the rotamers are visible as clusters, that display a clear and strong dependence on the underlying backbone secondary structure.

Conclusions

We demonstrate that there is a clear interdependence between rotameric states and secondary structure. Our method easily detects those atoms in a crystallographic protein structure which are either outliers or have been likely misplaced, possibly due to radiation damage. Our approach forms a basis for the development of a new generation, visualization based side chain construction, validation and refinement tools. The heavy atom positions are identified in a manner which accounts for the secondary structure environment, leading to improved accuracy.

     

Synthesis and Evaluation of Acyclic Nucleotide Analogs

Abstract

Acyclic nucleotide analogs derived from antiviral 9-(2-phosphonylmethoxyethyl)adenine by modification at the side chain or by alternation of the heterocyclic base were synthesized and investigated for their antiviral activity.     

Thermodynamic Melting Studies on Oligonucleotide-Peptide Conjugates

Abstract

A small library of oligonucleotide-peptide conjugates has been prepared and studied to explore the influence of the various peptide side chain (cationic, anionic or hydrophobic) on the hybridation properties of the DNA.     

How origin,packaging and seasonality determine the environmental impact of apples,magnified by food waste and losses

Purpose

Using apple consumption in Belgium as a case study, this study examines the environmental impacts associated with Belgian (BE) and New Zealand (NZ) apples, how impacts evolve throughout the year and how packaging affects this impact. Additionally, impacts associated with food losses and food waste along the chain are assessed. The study aims to delineate the most important factors in determining environmental impacts associated with apple.

Methods

The environmental impacts are calculated using the ILCD (International Reference Life Cycle Data System) approach. The functional unit is 1 kg of apples purchased by a consumer in the supermarket. Primary data was collected through players along the chain. Various scenarios are analysed for both the BE and NZ apples, based on the moment of purchase and packaging method. Food loss and waste impacts are assessed by splitting the impacts along the chain into three categories: apples lost along the supply chain, apples purchased and eaten by the consumer and apples purchased and wasted by the consumer.

Results and discussion

For all impact categories assessed, NZ apples come at a higher environmental cost than BE ones due to overseas transport. For both BE and NZ apples, minimum impacts are found for bulk apples at the beginning of the season, whereas maximum values are found for pre-packed apples at the end of the season. For BE apples, the choice of packaging method highly affects the impact, while it is negligible relative to shipping impacts for NZ apples. Altering secondary packaging materials of BE apples allows for impact reductions up to 50%. In the case of climate change, food waste and losses contribute up to 25% or 15% for BE or NZ apples, respectively, as all lost food travels in vain through the food chain and needs to be disposed of.

Conclusions

The study shows the importance of origin and packaging, whereas the moment of purchase hardly affects the environmental impact of apples. From a supply chain perspective, there is room for improvement as altering the use of secondary packaging greatly reduces impacts along the chain. The study further highlights how impacts are magnified by food waste and losses.

     

Synthesis of Nucleotide Lipophilic Prodrugs Containing Two Inhibitors Targeted Against Different Phases of the HIV Replication Cycle

Abstract

We describe the preparation of nucleoside acyl 5′-di or 5′-triphosphates, containing a nucleoside analog moiety and 13-oxa-myristic acid as lipophilic chain. At physiological pH these products liberated exclusively the corresponding nucleotides.     

Synthesis and Biological Activities of New Carbaacyclonucleosides and 1′-Oxaacyclonucleosides Related to Clitocine

Abstract

We describe the synthesis of two series of acyclonucleosides: carbaacyclonucleosides and 1′-oxaacyclonucleosides which possess the same aglycone as clitocine 3 which is a natural nucleoside exhibiting interesting biological properties. These compounds have been obtained by condensation of 4-aminobutanol or 3-silyloxypropoxyamine with 4,6-dichloro-5-nitropyrimidine. Structural modifications have been made on the heterocyclic base and the side chain to enhance their potential activity.     

Rosmarinic acid and its esters inhibit membrane cholesterol domain formation through an antioxidant mechanism based,in nonlinear fashion,on alkyl chain length

BackgroundUnder conditions of oxidative stress, cholesterol aggregates into discrete membrane bilayer domains that precipitate the formation of extracellular crystals, a feature of advanced atheroma in cardiovascular disease. Therapeutic interventions using membrane-directed antioxidants, such as polyphenolic esters, may reduce cholesterol domains and crystal formation. In this study, the effects of rosmarinic acid (RC0) and rosmarinic esters, with alkyl chain lengths ranging from 4 to 16?carbons (RC4-RC16), on membrane lipid oxidation and cholesterol domain formation were investigated.MethodsModel membranes were prepared with 1,2-dilinoleoyl-sn-glycero-3-phosphocholine and cholesterol at different cholesterol-to-phospholipid mole ratios (0.3:1, 0.9:1, and 1.2:1), in the absence or presence of each molecule and exposed to 72 h of oxidation. Changes in lipid hydroperoxide (LOOH) and cholesterol domain formation were measured using iodometric and small angle x-ray diffraction approaches, respectively.ResultsRosmarinic acid and its esters had differential effects on LOOH formation based on alkyl chain length. RC8 exhibited the greatest antioxidant effect, reducing LOOH levels by 82%, and inhibited cholesterol domain formation. By contrast, RC0 and RC16 failed to inhibit either LOOH formation or cholesterol domain formation.ConclusionThese data indicate that the membrane antioxidant and cholesterol domain inhibition activities of rosmarinic acid esters are dependent, nonlinearly, on alkyl chain length. The mechanism for this effect is attributed to the influence of alkyl chain length on the optimal depth of the polyphenols into the lipid bilayer for trapping free radicals.General significanceThese findings provide insight into novel atheroprotective benefits of polyphenol esters that are dependent on their membrane location.     

Synthesis and Biological Activity of Methyl 3-Demethyl-Abscisate and Its Related Analogs

To elucidate the role of the methyl substituent on the side chain of abscisic acid (ABA), we synthesized (2Z,4E)-3-demethyl-α-ionylideneacetic acid (4) and its related analogs, methyl (2Z)-3-demethyl-β-ionylideneacetate 1′,2′-epoxide (9) and methyl (2Z) and (2E)-3-demethyl-abscisate (12) and (13). The biological assay of these compounds suggested that the 3-methyl group on the side chain of ABA was indispensable to biological activity.     

哈氏弧菌脂酰-ACP合成酶的体外功能

【目的】系统鉴定哈氏弧菌脂酰-ACP合成酶(Acyl-ACP synthetase,Aas S)以不同链长游离脂肪酸和非脂肪链羧酸作为底物的体外催化反应。【方法】利用非变性蛋白质凝胶电泳和紫外分光光度计法从定性和定量两个方面分析了Aas S的体外催化功能与活性。【结果】Aas S能够催化不同链长直链的自由脂肪酸合成脂酰-ACP,其中以C6–C12作为底物时活性最高;以羟基脂肪酸作为底物的情况下,Aas S催化C8–C14的羟基脂肪酸有较高的活性。非脂肪链羧酸类作为底物的反应中,20种蛋白质氨基酸、苯甲酸和水杨酸均可以作为Aas S的底物,合成相应的脂酰-ACP。【结论】本研究系统地证明了哈氏弧菌脂酰-ACP合成酶(Aas S)对不同底物的不同催化活性,为生物体内氨基酸代谢和菌黄素合成代谢的研究提供了可行性的分析依据。     

Solid Phase Non Isotopic Labelling of Oligodeoxynucleotides Using 5′- Protected Aminoalkyl Phosphoramidites: Application to the Specific Detection of Human Papilloma Virus Dna

Abstract

Phosphoramidites of thymidine or 2′-deoxyinosine, modified in 5′ by the addition of an aminoalkylcarbamate function, were prepared. The derivatized nucleotides can be used in automatic DNA synthesis to tag any oligodeoxynucleotide chain and provide a convenient reactive group for labelling with non radioactive reporters. As an example of application, we show the specific detection of Human Papilloma Virus DNA using a biotin-labelled 29-mer oligodeoxynucleotide entirely prepared on solid support.     

Synthesis of Long Chain Oxodicarboxylic Esters from Ethyl 3-Oxoglutarate

The mono-anion of the magnesium chelate prepared from ethyl 3-oxogiutarate (1) and magnesium ethoxide was alkylated with a haloester to give a monoalkylated derivative of 1. A second alkylation with a different haloester in the presence of sodium ethoxide followed by decarboxylative hydrolysis and esterification gave an unsymmetrical long chain oxodicarboxylic ester, such as ethyl 5-oxoheptadecanedioate (4b), methyl 6-methyl-8-oxopentadecane-dioate (4c), ethyl 6-methyl-4-oxopentadecanedioate (4d) or ethyl 2-methyl-4-oxopentade-canedioate (4e). Moreover, ethyl 8-oxopentadecanedioate (4a) was obtained by the alkylation of 1 with ethyl 6-bromohexanoate in the presence of sodium ethoxide alone as a catalyst. These esters are presumably suitable for cyclization to macrocyclic ketones.     

Sex determination of bovine embryos using the polymerase chain reaction

Abstract

One or two cell biopsies were obtained from 6‐7 days old bovine embryos. The sex of the embryos was determined with two different bovine Y‐chromosome‐specific primer pairs by using the polymerase chain reaction. These results were confirmed by karyotyping as well as in situ hybridization with an independent bovine Y‐chromosome‐specific sequence. The polymerase chain reaction was found to be a quick and accurate method of sex diagnosis of bovine preimplantation embryos.     

灌喂植物乳杆菌和干酪乳杆菌增加仔猪肠道菌群多样性及短链脂肪酸生成

【目的】研究断奶前给仔猪饲喂植物乳杆菌和干酪乳杆菌对断奶前、后肠道菌群组成、数量和短链脂肪酸(SCFA)浓度的影响,分析仔猪生长性能与肠道形态、微生物菌群及SCFAs的相关性,探讨测试菌株缓解仔猪断奶应激的可能机制。【方法】选取15窝7 d龄杜长大仔猪,随机分为3组,分别灌喂2 mL去离子水(对照组)、0.5×10~9 CFU/mL植物乳杆菌(LP组)或干酪乳杆菌(LC组)的菌液,每组以窝为单位5个重复,于21 d(断奶)、24 d和35 d屠宰,采集回肠和结肠食糜,分析菌群组成和数量的变化,测定SCFAs浓度。【结果】测试菌株均能显著提高断奶2周后回肠、结肠菌群多样性(P0.05),促进乳酸杆菌和双歧杆菌增殖;显著促进断奶前回肠和结肠中乙酸、丙酸、丁酸和总SCFA生成,促进断奶后乙酸和总SCFA产生;相关分析显示,测试菌株组仔猪腹泻率下降与SCFAs浓度上升、回肠绒毛高度增加和总菌数量上升显著相关,日增重提高与结肠乙酸和TSCFA浓度增加显著相关。【结论】测试菌株促进乳酸杆菌、双歧杆菌等有益菌增殖,增加肠道菌群多样性,促进肠道SCFAs生成。     

Studies on Reactions of Nucleoside H-Phosphonates with Bifunctional Reagents. Part VI. Reaction with Diols

Abstract

Reactions of nucleoside H-phosphonates with various diols using different types of condensing agents have been studied. Depending on the coupling procedure and the length of a polymethylene chain of the diol, acyclic H-phosphonate diesters or cyclic phosphite triesters were formed. The course of oxidation with iodine to produce cyclic nucleoside alkyl phosphotriesters or hydroxyalkyl nucleoside phosphodiesters can be controlled by the amount of water present in the reaction medium.     

Development of Human-Like scFv-Fc Neutralizing Botulinum Neurotoxin E

BackgroundBotulinum neurotoxins (BoNTs) are considered to be the most toxic substances known on earth and are responsible for human botulism, a life-threatening disease characterized by flaccid muscle paralysis that occurs naturally by food-poisoning or colonization of the gastrointestinal tract by BoNT-producing clostridia. BoNTs have been classified as category A agent by the Centers of Disease Control and Prevention (CDC) and are listed among the six agents with the highest risk to be used as bioweapons. Neutralizing antibodies are required for the development of effective anti-botulism therapies to deal with the potential risk of exposure.ResultsIn this study, a macaque (Macaca fascicularis) was immunized with recombinant light chain of BoNT/E3 and an immune phage display library was constructed. After a multi-step panning, several antibody fragments (scFv, single chain fragment variable) with nanomolar affinities were isolated, that inhibited the endopeptidase activity of pure BoNT/E3 in vitro by targeting its light chain. Furthermore, three scFv were confirmed to neutralize BoNT/E3 induced paralysis in an ex vivo mouse phrenic nerve-hemidiaphragm assay. The most effective neutralization (20LD₅₀/mL, BoNT/E3) was observed with scFv ELC18, with a minimum neutralizing concentration at 0.3 nM. Furthermore, ELC18 was highly effective in vivo when administered as an scFv-Fc construct. Complete protection of 1LD₅₀ BoNT/E3 was observed with 1.6 ng/dose in the mouse flaccid paralysis assay.ConclusionThese scFv-Fcs antibodies are the first recombinant antibodies neutralizing BoNT/E by targeting its light chain. The human-like nature of the isolated antibodies is predicting a good tolerance for further clinical development.