基于近红外光谱技术对山茱萸炮制程度的质量评价

目的 采用近红外光谱技术建立山茱萸饮片中5-羟甲基糠醛含量的快速无损检测方法,并用于快速判别山茱萸饮片的炮制程度。方法 以54个样本作为校正集,运用偏最小二乘法建立定量校正模型并进行优化。以9个样本作为验证集,进行含量预测。结果 校正模型决定系数为0.925 6,相对分析误差为5.06,交叉验证均方根误差为0.022 0,外部验证均方差为0.019 3,光谱预测值与真值之间的相关性较好。结论 该法可直接用于中药山茱萸中5-羟甲基糠醛含量的快速预测,为快速判断山茱萸炮制程度提供可能。该方法具有操作简便、快速无损、准确可靠等优点。     

Catalytic N-methyl amidation of carboxylic acids under cooperative conditions

Amide is a fundamental group that is present in molecular structures of all domains of organic chemistry and the construction of this motif with high atom economy is the focus of the current research. Specifically, N-methyl amides are valuable building blocks in natural products and pharmaceutical science. Due to the volatile nature of methyl amine, the generation of N-methyl amides using simple acids with high atom economy is rare. Herein, we disclose an atom economic protocol to prepare this valuable motif under DABCO/Fe₃O₄ cooperative catalysis. This protocol is operationally simple and compatible with a range of aliphatic and (hetero)aromatic acids with very good yields (60–99%). Moreover, the Fe₃O₄ can be easily recovered and high efficiency is maintained for up to ten cycles.

The generation of N-methyl amides using simple acids with high atom economy is rare owning to the volatile nature of methyl amine. Herein, an atom economic protocol was disclosed to prepare this valuable motif under DABCO/Fe₃O₄ cooperative catalysis.

Amide is a fundamental group that is present in molecular structures of all domains of organic chemistry.¹ It is widely distributed in natural products, synthetic drugs and functional polymers, and is also the key chemical connection in proteins.² It has been shown that amide bond formation alone accounts for 65% of all preliminary screening reactions in the pharmaceutical industry.³ This means the generation of amide bonds with high atom efficiency is of high practical importance. And not surprisingly, ‘amide formation avoiding poor atom economy reagents’ was voted as the top challenge for organic chemistry by the ACS Green Chemistry Institute in 2007.³From synthetic point of view, the ideal way to produce amide bonds would be the direct coupling of readily available carboxylic acids and amines, but this process is thermodynamically unfavourable due to the formation of the corresponding carboxylate-ammonium salt,⁴ therefore, stoichiometric amount of coupling reagents, such as DCC, DIC, EDCI, HATU, HBTU, HCTU, SOCl₂, BOP, acid chloride etc, are generally required to sidestep thermal conditions for amide bond formation.⁵ These reagents are highly successful, but the process generally suffers from poor atom economy and side products removal issue especially in the large-scale applications.⁵ To overcome these drawbacks, “nonclassical” amide bonds formation routes were investigated.⁶ In these processes, the catalyst takes the role of a coupling reagent in generating an active ester suitable for amidation in a waste-free manner. However, these processes have not been applied in the preparation of N-methyl amides, probably because the methyl amine was delivered in its hydrochloride salt, alcoholic or aqueous form due to its volatile nature.On a different note, N-methyl amides are extensively presented in numerous natural products and pharmaceutical molecules, as shown in Fig. 1,⁷ and the methylation of amides is a promising way to improve the pharmacological property of molecules.⁸ However, the synthesis of N-methyl amides compounds relies heavily on non-catalytic approaches.^5,9 Catalytic approaches were also investigated by Hisaeda,¹⁰ Kundu,¹¹ Li,¹² Guo,¹³ Yu,¹⁴ Maruoka,¹⁵ Wang,¹⁶ Chen,¹⁷ Lamaty¹⁸ and their co-workers starting from nitriles, primiary amides, aldoximes, aldehydes, lignin, carbamoylsilane and alcohols. Until recently, Thakur,¹⁹ Marce,²⁰ Sadeghzadeh²¹ and their co-workers developed elegant N-methyl amidation approach starting from carboxylic acids under nano-MgO, diatomite Earth@IL/ZrCl₄ and Mg(NO₃)₂·6H₂O catalysis respectively, while limitations like poor substrate scope or sophisticated tailored catalyst still persist. Mindful of all the above issues, developing an N-methyl amidation process of simple carboxylic acids, which is still of great challenge in synthesis, and establishing a broad (hetero)aryl scope with high atom economy from commercial available reagents and catalysts were critical considerations in this study. Moreover, the significance of N-methyl amides combined with our interests in the development of green synthetic approaches motivated us to explore the direct coupling of the carboxylic acids and isothiocyanates. To the best of our knowledge, this is the first successful work using isothiocyanatomethane to prepare N-methyl amides.Open in a separate windowFig. 1Marketed drugs bearing N-methyl amide group.Our initial investigation begins with phenylacetic acid and isothiocyanatomethane as model substrate for condition optimization. Using acetonitrile as solvent, only trace amount of product was detected under catalyst free or p-toluenesulfonic acid (PTSA) catalysis conditions (

Triple Therapy-Based on Tegoprazan,a New Potassium-Competitive Acid Blocker,for First-Line Treatment of Helicobacter pylori Infection: A Randomized,Double-Blind,Phase III,Clinical Trial

Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03317223","term_id":"NCT03317223"}}NCT03317223).     

Acute abdomen caused by torsion of the omentum: A pediatric case report

Rationale:Torsion of the omentum and infarction are rare and unusual disorders that often present as acute abdominal pain in the population. The diagnosis of omental torsion is based on clinical and imaging examinations.Patient concerns:A 7-year-old girl presented with acute right lower quadrant abdominal pain, with symptoms resembling acute appendicitis.Diagnosis:The patient was diagnosed with omental torsion based on imaging and laparoscopy.Interventions:Laparoscopic exploration was performed.Outcomes:The patient was discharged seven days after satisfactory postoperative recovery.Lessons:Omental torsion should be included in the differential diagnosis of acute abdominal pain, particularly in patients with free hemorrhagic fluid in the abdominal cavity and pelvis.     

临床辅助决策平台构建

阐述基于云服务的临床辅助决策平台构建,包括建设目标、总体架构、知识转化工程、主要应用功能、云服务和云运维,介绍实践效果,指出该平台有助于扩大优质医疗资源服务范围,提升同质化服务水平等。     

冻干重组葡激酶对正常人凝血、纤溶系统影响的研究

目的　探讨冻干重组葡激酶 (r Sak)对正常人出、凝血及纤溶系统的影响 ,为进一步临床应用提供翔实的依据。方法　健康志愿者 2 0例静脉注射不同剂量r Sak(1、2 5、5、10、15mg) ,观察临床出血情况以及动态监测用药前后BT、BPC、APTT、PT、TT、Fg、D D、PL∶A、α2 PI∶A。结果　 2 0例中 4例有轻微出血 ,以皮肤粘膜为主 ,可自行止血 ,无 1例伴内脏出血。其中 3例牙龈渗血 ,2例穿刺部位出血。 4例有D D轻微异常 ,其余以上指标皆无变化。实验显示本药为高度选择性溶栓药 ,对正常人出凝血相无改变。结论　在本试验剂量范围内 ,该药是相对安全的 ,可很好耐受 ,但用于临床的最佳剂量有待进一步临床验证     

间歇性外斜视眼位控制力评分综述

在间歇性外斜视患者的管理中,眼位控制力至关重要,它是评价手术时机的重要参考指标及监测和判断病情发展严重程度的必要指标之一。因此,眼位控制能力的量化成为间歇性外斜视评估中的重要环节。本文旨在对间歇性外斜视患者眼位控制力评估方法做一综述,帮助临床医生对间歇性外斜视患者制定合理的治疗方案。