Functionaleation of Nucleoside Analogs: Regiospecific Conversion of 4″-Hydroxyl Groups to Thioesters and Deoxygenation of 3′-Hydroxyl Groups

Abstract

Nucleoside analogs 3a-e were conveniently functionalized by regiospecifically converting 4″-hydroxyl groups to thioesters 4a-e (>90% yield) and reducing 3-hydroxyl groups to give building blocks 2a-e in 85–90% yields.     

超声引导下微波消融在甲状腺良性结节中的价值分析

目的:分析超声引导下微波消融治疗甲状腺良性结节中的价值。方法:选取我院接受治疗的140例甲状腺良性结节患者,根据治疗方法分成两组,微波消融组接受超声引导下微波消融治疗,药物治疗组接受甲状腺激素药物治疗。对比分析两组患者甲状腺结节体积和数量、甲状腺功能变化,并比较两组副反应发生率。结果:微波消融组治疗后结节体积低于药物治疗组,而体积缩小率高于药物治疗组,组间差异存在统计学意义(P0.05)。治疗后,患者血清学T3、T4、TSH改善明显,其中微波消融组改善最显著,组间差异存在显著性(P0.05)。结论:超声引导下微波消融能够减小甲状腺良性结节数目和体积,促进甲状腺功能逐步恢复,建议临床推广。     

Comparative study of observed actions,motor imagery and control therapeutic exercise on the conditioned pain modulation in the cervical spine: a randomized controlled trial

Abstract

Aim: The aim of this study was to compare the effects of cervical exercise, motor imagery (MI) and action observation (AO) of cervical exercise actions on conditioned pain modulation and pressure pain thresholds. The second objective was to assess the effects of these interventions on cervical motor activity (ranges of motion and muscle endurance), attention, and the ability to generate motor images.

Study design: Single-blinded randomized controlled trial.

Materials and methods: Fifty-four healthy subjects were randomly assigned to each group. Response conditioned pain modulation, pressure pain threshold, were the main variables. The secondary outcome measures included, cervical range of motion, Neck flexor endurance test, mental movement representation associated and psychosocial variables.

Results: All groups showed significant differences in time factor for all evaluated variables (p?<?.01) except pressure pain threshold over the tibial region. The post hoc analysis revealed significant within-group differences in the AE and AO groups in conditioned pain modulation (p?<?.05), with medium effect size in time [AE (d –0.61); AO (d –0.74)].

Conclusion: The results showed that within-group changes in conditioned pain modulation, cervical muscle endurance, and attention where founded only in the AE and AO groups. Variations in pain thresholds at pressure in the trapezium area were also obtained in the three groups. Changes in the ranges of flexion-extension and rotation movement were presented exclusively in the exercise group, and in the capacity to generate motor images only in the AO group. However, there was no difference in the pressure pain threshold over the tibial region.     

Design,synthesis, spectral analysis and in vitro microbiological evaluation of 2-phenyl-3-(4,6-diarylpyrimidin-2-yl)thiazolidin-4-ones

A series of novel 2-phenyl-3-(4,6-diarylpyrimidin-2-yl)thiazolidin-4-ones 23-33 were synthesized, and studied for their in vitro antibacterial and antifungal activities against clinically isolated strains. Generally compounds possessing electron donating groups showed good antibacterial activity. Compound 31, which contain both electron withdrawing chloro and electron donating methyl groups showed potent activity against all the tested Gram positive and Gram negative bacterial strains whereas compounds 32 and 33 which contain electron donating methoxy functional group at the para position of the phenyl ring attached to pyrimidine ring showed promising activity against S.aureus, S.typhii and E.coli. Compounds 32 and 33, both containing electron withdrawing groups (-Cl, -F) showed excellent activities against all the tested A. flavus, Mucor, Rhizopus and M.gypsuem fungal strains. while against Mucor, compound 27 which contains an electron donating methyl group at the para position of the phenyl ring attached to pyrimidine ring showed promising activity. Also compound 31, which contains both electron withdrawing chloro and electron donating methyl groups showed potent activity against A. flavus and Rhizopus.     

猪小肠微生物对不同蛋白源的体外发酵特性比较

【目的】采用体外发酵技术比较小肠微生物对不同蛋白源的发酵规律。【方法】以成年猪的十二指肠、空肠和回肠内容物为接种物,以豆粕、菜粕或鱼粉水解物上清液为氮源底物,于发酵的0、4、8、12 h分别测定发酵液p H、微生物蛋白、氨氮和挥发性脂肪酸含量,同时提取细菌DNA并进行定量分析。【结果】添加含氮底物的空肠组和回肠组氨氮浓度和菌体蛋白浓度均相对增加,尤其是酶解菜粕组菌体蛋白合成量较高;十二指肠组菌体蛋白浓度以及氨氮含量不断减少。各发酵组乳酸和挥发酸快速积累,4–8 h积累量最大;8 h后空肠组和回肠组乳酸和挥发酸含量相对稳定,而十二指肠组后期丙酸含量增加约2 mmol/L,并伴随着乳酸含量的相对减少。同时,各组中总细菌、拟杆菌门、厚壁菌门和乳酸杆菌数量相对增加,且略高于无氮组,但不同蛋白源组间无显著差异。【结论】在体外培养条件下,空肠和回肠微生物具有相似的发酵规律,均能快速利用培养液中的含氮物质合成菌体蛋白;十二指肠微生物具有较强的产挥发酸能力,能够转化乳酸并大量产生丁酸和丙酸,这有利于宿主营养功能和肠道健康。     

Synthesis of Three New Carbocyclic Analogues of 3′-Deoxy Purine Ribonucleosides

Abstract

The 1-hydroxymethyl-3-cyclopentene (4) was converted, after epoxidation, to two new exocyclic amino carbocyclic nucleosides (1, 2), and a new cyclopentane nucleoside analogue (3), with potential biological activities. The regioselectivity of the epoxidation (4), which is the key step, is governed by steric control using aryl and silyl hydroxyl protecting groups.     

Synthesis of Protected 3′,5′-Di-2′-Deoxythymidine-(α-hydroxy-2-nitrobenzyl)-phosphonate Diesters as Dimer Building Blocks for Oligonucleotides

Abstract

The synthesis of 3′-succinyl-CPG bound 3′,5′-di-2′-deoxythymidyl-(α-hydroxy-2-nitrobenzyl)-phosphonate diester 1 and the 3′-phosphoamidite derivative 2 is descibed. The hydroxyl-groups of the backbone modification were protected with trialkylsilyl groups: TES and TBS. Compounds 1, 2 are suitable blocks for oligonucleotide synthesis.     

病种质量管理方式探讨 ——以剖宫产为例

目的 以剖宫产为例研究病种管理方式,探讨病种纳入标准。方法 采用统计学分析法,对不同指征剖宫产按照住院天数、住院费用进行分组,并对其住院费用的影响因素进行分析。结果 5组不同指征剖宫产数据根据住院费用指标可分为3组,按照住院天数指标分类则可归纳为2组,并且经分析发现,影响不同指征剖宫产术住院总费用的因素主要为药费、住院天数。结论 可以依据医疗资源消耗的相似性制定病种纳入标准,扩大病种质量控制体系范围;此外,通过控制关键影响因素来加强病种质量管理,降低患者医疗费用。     

A facile synthesis of d-ribo-C20-phytosphingosine and its C2 epimer from d-ribose

A facile synthetic route to d-ribo-C₂₀-phytosphingosine 31 and its C2 epimer 32 is described. The Overman rearrangement of allylic trichloroacetimidates derived from the known ribose derivative 7 has been used as the key step. The subsequent functional group interconversions in rearranged products 14 and 15 followed by Wittig olefination, Pd/C-mediated reduction and the removal of protecting groups successfully constructed the final molecules.     

血液净化治疗肾综合征出血热合并急性肾功能衰竭的疗效分析

目的:探讨血液净化治疗肾综合征出血热合并急性肾功能衰竭的疗效。方法:选取了60例肾综合征出血热合并急性肾功能衰竭患者,按住院单双号分为两组,观察组(31例)采用血液透析治疗,对照组(29例)采用连续性静脉-静脉血液滤过法治疗,观察并记录两组患者肾功能相关指标、血清离子、血常规相关指标及治疗期间不良反应情况,评估血液净化治疗肾综合征出血热合并急性肾功能衰竭的疗效。结果:治疗前两组K~+、HCO_3~-、血尿素氮(BUN)、血清肌酐(Cr)等指标无统计学差异(P0.05),治疗后两组K~+、BUN、Cr等指标均明显降低,且观察组上述指标低于对照组(P0.05);治疗后两组HCO_3~-水平升高,且观察组高于对照组(P0.05),治疗前,两组血红蛋白(Hb),红细胞压积(Hct),血小板(PLT)无统计学差异(P0.05),治疗后两组Hb,Hct,PLT均升高(P0.05),但组间比较没有统计学差异(P0.05),随访1年期间,观察组患者6个月和12个月生存率明显高于对照组(P0.05)。治疗期间,两组不良反应率无统计学差异(P0.05)。结论:血液透析对肾综合征出血热合急性肾功能衰竭具有较好的治疗效果,能调节体内电解质平衡,改善肾功能,提高生存率,改善血液状态的效果与连续性静脉-静脉血液滤过法相当。     

Effectiveness of using an unskilled model in action observation combined with motor imagery training for early motor learning in elderly people: a preliminary study

Abstract

Aim of the study: To investigate a more available model for the early phase of motor learning after action observation combined with motor imagery training in elderly people. To address the purpose, we focused on a slow, unskilled model demonstrating an occasional error.

Materials and methods: A total of 36 elderly people participated in the current study and were assigned to either the unskilled or skilled model observation groups (n?=?12, respectively), or the control group (n?=?12). The participants in the observation groups observed the assigned a video clip of an unskilled or skilled model demonstrating a ball rotation task. During the observation, the participants were instructed to imagine themselves as the person in the video clip. The participants in the control group read a scientific paper during the equivalent period of action observation and motor imagery. We measured ball rotation performance (the time required for five rotations, the number of ball drops) in pre- and post-intervention (observation combined with motor imagery training for intervention groups or reading for control group).

Results: Ball rotation performance (ball rotation speed) significantly improved in the unskilled model observation group compared to the other two groups.

Conclusions: Intervention for action observation using unskilled model combined with motor imagery was effective for improving motor performance during the early phase of motor learning.     

Markers of oxidative/nitrative damage of plasma proteins correlated with EDSS and BDI scores in patients with secondary progressive multiple sclerosis

Objectives: The objective of the present study was to evaluate oxidative/nitrative stress in the plasma of 50 patients suffering from the secondary progressive course of multiple sclerosis (MS), and to verify its correlation with physical and mental disability as assessed by the Expanded Disability Status Scale (EDSS), and the Beck Depression Inventory (BDI).

Methods: Oxidative and nitrative damage to proteins was determined by the level of carbonyl groups and 3-nitrotyrosine using ELISA test. Based on the reaction with Ellman’s reagent, we estimated the concentration of oxidized thiol groups. Additionally, we measured the level of lipid peroxidation.

Results: In plasma drawn from MS patients, we observed a significantly higher level of 3-NT (92%; P?P?P?P?Conclusion: Our results indicate that impaired red-ox balance can significantly promote neurodegeneration in secondary progressive MS.     

Studies on the Chemistry of 5-Acetoxy-6-(Acetoxymethyl)-Uridines: Synthesis of a New type of 5′-Cyclonucleoside1

Abstract

The 5-acetoxy-6-(acetoxymethy1)-uridine derivative 18 is converted in aqueous sodium hydroxide solution into the imidazole cyclonucleoside 22. Compound 22, in which an oxygen bridge links the sugar and base methano groups, represents a new type of 5′-cyclonucleoside.     

Solution Phase Synthesis of Dithymidine Phosphorothioate by a Phosphotriester Method Using New S-Protecting Groups

Abstract

ABSTRACT

A phosphotriester method for the synthesis of dithymidine phosphorothioates with eight S-protecting groups has been investigated. Three of the S-protecting groups possesed catalytic activity, however side reactions occurred under deprotection. The best S-protecting group was 4-chloro-2-nitrobenzyl which could be removed with a minimum of side reactions (0.3 %). The coupling reagent PyFNOP (11) gave protected dithymidine phosphorothioate in 96% yield after 15 min coupling.     

二级及以上医疗机构公共卫生职能承担现况调查

目的 了解我国二级及以上医疗机构公共卫生职能的承担情况。方法 对4个省进行实地调研,对180家二级及以上医院进行问卷调查。结果 上报医疗机构对15项公共卫生职能的承担数为0.78,发文组与设置组承担数更高。各项公共卫生工作在医疗机构的开展情况不尽相同。院内公共卫生职能管理分散。结论 建议在二级及以上医院内部单独设置公共卫生科（处）,统筹全院公卫工作,并对各级各类医疗机构的公卫职责进行重新划分。     

Effects of BMP-2 compound with fibrin on osteoporotic vertebral fracture healing in rats

Objectives:To investigate the effects of bone morphogenetic protein-2 (BMP-2) compound with fibrin on osteoporotic vertebral fracture healing in rats.Methods:For the present study 160 Specific-Pathogen Free 32-week-old female Sprague-Dawley rats were used. 120 rats were randomly divided in three groups (experimental, model and sham operation group- n=40 per group) and were ovariectomized to establish the osteoporosis model. 40 rats served as a control group without treatment. The expression of BMP-2 in the fracture zone at the 4^th, 6^th, 8^th, and 12^th weeks was detected by qRT-PCR. The expression of BALP and CTX-I in serum at the 12^th week was detected by Elisa.Results:At week 8, the morphology of the sham operation group was the same and the fracture healing occurred more slowly than in the other groups. At week 12, the expression of BMP-2 in the model group was significantly higher than that in the other three groups (p<0.05). At week 12, the maximum load, maximum strain, and elastic modulus of model group were significantly lower than those of the other three groups.Conclusions:BMP-2 compound with fibrin can enhance the timing and quality of bone fracture healing in rats.     

Randomised controlled trial of effect of feedback on general practitioners' prescribing in Australia

ObjectiveTo evaluate the effect on general practitioners’ prescribing of feedback on their levels of prescribing. DesignRandomised controlled trial.SettingGeneral practice in rural Australia.Participants2440 full time recognised general practitioners practising in non-urban areas.InterventionTwo sets of graphical displays (6 months apart) of their prescribing rates for 2 years, relative to those of their peers, were posted to participants. Data were provided for five main drug groups and were accompanied by educational newsletters. The control group received no information on their prescribing.ResultsThe intervention and control groups had similar baseline characteristics (age, sex, patient mix, practices). Median prescribing rates for the two groups were almost identical before and after the interventions. Any changes in prescribing observed in the intervention group were also seen in the control group. There was no evidence that feedback reduced the variability in prescribing nor did it differentially affect the very high or very low prescribers. ConclusionsThe form of feedback evaluated here—mailed, unsolicited, centralised, government sponsored, and based on aggregate data—had no impact on the prescribing levels of general practitioners.

Key messages

• Feedback of prescribing data to general practitioners is widely practised by government agencies
• The belief is that this will lead to reduced variability and lower rates of prescribing of key drugs, but this has not been tested in randomised trials
• In a large randomised trial Australian general practitioners received feedback comprising simple graphical displays of their prescribing data for five key groups of drugs
• This had no impact on the level or variability of subsequent prescribing rates
• Unsolicited, centralised, government sponsored feedback based on aggregate data had no impact on the prescribing levels of general practitioners

     

Cross sectional study of primary care groups in London: association of measures of socioeconomic and health status with hospital admission rates

ObjectivesTo calculate socioeconomic and health status measures for the primary care groups in London and to examine the association between these measures and hospital admission rates.DesignCross sectional study.Setting66 primary care groups in London, total list size 8.0 million people.ResultsStandardised hospital admission ratios varied from 74 to 116 for total admissions and from 50 to 124 for emergency admissions. Directly standardised admission rates for asthma varied from 152 to 801 per 100 000 (mean 364) and for diabetes from 235 to 1034 per 100 000 (mean 538). There were large differences in the mortality, socioeconomic, and general practice characteristics of the primary care groups. Hospital admission rates were significantly correlated with many of the measures of chronic illness and deprivation. The strongest correlations were with disability living allowance (R=0.64 for total admissions and R=0.62 for emergency admissions, P<0.0001). Practice characteristics were less strongly associated with hospital admission rates.ConclusionsIt is feasible to produce a range of socioeconomic, health status, and practice measures for primary care groups for use in needs assessment and in planning and monitoring health services. These measures show that primary care groups have highly variable patient and practice characteristics and that hospital admission rates are associated with chronic illness and deprivation. These variations will need to be taken into account when assessing performance.     

Molecular dynamics simulation of self-assembled nanocubes in methanol

Molecular dynamics simulations were performed for the hexameric nanocubes of methylated (1₆) and demethylated (2₆) gear-shaped amphiphiles in pure methanol to reveal the difference in structural fluctuation between 1₆ and 2₆. Within our simulation time of 2.0 ns, the cubic structure of 1₆ in methanol is maintained, whereas that of 2₆ is collapsed. We found that the triple π-stacking moieties consisting of the three 3-pyridyl groups in 2₆ are more fluctuated than those in 1₆. This suggests that methyl groups serve to reduce structural fluctuation for nanocubes. We also found that the existence of the solvent molecules near the nanocube is an important factor for the collapse of the 2₆ structure.     

甲氨蝶呤治疗急性淋巴细胞白血病的疗效及对患者BAFF、APRIL的影响

目的:探讨甲氨蝶呤治疗急性淋巴细胞白血病的疗效及对患者B淋巴细胞刺激因子(BAFF)、增殖诱导配体(APRIL)的影响。方法:选择2016年8月至2018年9月我院收治的急性淋巴细胞白血病患者50例进行研究,以随机数表法分为观察组(n=26)和对照组(n=24)。对照组给予化疗治疗,观察组采用甲氨蝶呤治疗。比较两组患者的临床疗效、BAFF、APRIL、CD4~+、CD8~+、CD4~+/CD8~+水平变化情况及不良反应发生情况。结果:治疗后,观察组总有效率84.62%显著高于对照58.33%,差异显著(P0.05);治疗前,两组BAFF、APRIL水平无显著差异(P0.05);治疗后,两组BAFF、APRIL水平均显著下降,且观察组低于对照组(P0.05);治疗前,两组T淋巴细胞亚群水平无显著差异(P0.05);治疗后,两组T淋巴细胞亚群水平均显著改善,且观察组CD4~+、CD4~+/CD8~+高于对照组,CD8~+低于对照组(P0.05);两组患者不良反应发生情况均无统计学意义(P0.05)。结论:在急性淋巴细胞白血病患者中应用甲氨蝶呤效果显著,可有效改善患者BAFF、APRIL水平。