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1.
感染性发热归属于中医学火热证范畴,火热证的病机大多为阳气怫郁、阻遏于内,这种因郁而作的发热,称为火郁证。运用五辨(辨病、辨症、辨证、辨人、辨机)思维辨识火郁证,对火郁证的发病特点及规律进行概括,可把握火郁证的内在发病机制,有助于全面而深刻地理解感染性发热。  相似文献   
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Primary pleomorphic malignant fibrous histiocytoma of the heart is rare. The present study was performed to study the clinical and pathological features of the disease. We describe two rare cases of primary cardiac malignant fibrous histiocytoma and review the published individual data of the patients. Both patients complained of dyspnea, and underwent palliative tumor resection. However, they died several months after surgery. A thorough literature review with clinical presentations, diagnostic features, treatment, and outcomes was done. We have for the first time analyzed the factors related to the survival of malignant fibrous histiocytoma. It is usually difficult to make an appropriate preoperative diagnosis. Despite complete surgical resection and aggressive chemotherapy and radiotherapy, the prognosis is still poor.  相似文献   
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Journal of Natural Medicines - The article Search of anti-allodynic compounds from Plantaginis Semen, a crude drug ingredient of Kampo formula “Goshajinkigan”.  相似文献   
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An efficient and highly diastereoselective synthesis of 2-substituted benzo[b]azepin-5-ol via stereocontrolled addition of Grignard reagents to oxa-bridged benzazepines has been developed. The reaction proceeds efficiently starting from versatile skeletons with mild reaction conditions as well as simple operation. Furthermore, 2-substituted benzazepinones could been obtained by simple Dess–Martin oxidation in excellent yields.

An efficient and highly diastereoselective synthesis of 2-substituted benzo[b]azepin-5-ol via stereocontrolled addition of Grignard reagents to oxa-bridged benzazepines has been developed.

Benzofused azepines, a unique family of seven-member aza-heterocycles, are widely found in numerous bioactive molecules, natural products and pharmaceuticals.1–4 This is due to their chemotherapeutic properties, and exhibiting interesting biological activities,5–9 for instance, competitive vasopressin receptor antagonist (tolvaptan),10–12 antidepressants (mianserin),13 zilpaterol (beef improvement agent),14 ACE inhibitor (benazepril)15 (Fig. 1).Open in a separate windowFig. 1Selected examples containing a benzazepine skeleton.Consequently, tremendous efforts have recently been dedicated to developing new methodologies to construct the benzazepine derivatives. Typically, the benzazepine skeletons could be assembled by expansion of smaller rings, rearrangements,16,17 Dieckmann cyclization,18,19 transition-metal-catalyzed coupling, ring closure metathesis,15,20,21 and others.22–25 Nevertheless, most of these protocols are limited to highly engineered starting materials, expensive catalysts and hazardous handling, obviously expeditious strategies for the diverse construction of benzazepine backbones from readily available starting materials, remains highly attractive and challenging.Diversity-oriented synthesis (DOS), defined as a powerful synthetic strategy to the libraries of diverse highly valuable molecules from one parent compound,26,27 is therefore well-suited for the timely design and execution of parallel (library) synthesis.28 In recent years, our group focused on the development of a more facile and efficient diversity-oriented synthesis strategy for the generation of this class of 7-membered heterocyclic compounds.29–31 This newly introduced ene-type cyclization reaction was used to prepare a series of bridged aromatic fused azepines,29 as a versatile building block, which could be transformed into structurally different ring systems through selective ring opening of the cyclic acetals (Scheme 1A).30,31Open in a separate windowScheme 1Our previous work (A) and this work (B).As an extension of our ongoing work toward the synthesis of the azepine skeleton, we suggested a new reaction model could be achieved if the suitable nucleophile could be carefully designed. Recently, a couple of efficient approaches to access nitrogen-containing heterocycles has been developed through the nucleophilic addition of cyclic N,O-acetal with Grignard reagents.32–35 Inspired by their excellent studies and to showcase the utility of cyclic N,O-acetal building blocks for the preparation of functionalized azepines, we present a facile approach to a stereoselective synthesis of 2,5-substituted benzazepine derivatives from oxa-bridged benzazepines by Grignard addition. This strategy is complementary to our recently published cascade reaction to prepare the benzazepinone scaffold. Herein, the details of this study is disclosed.Our investigations commenced by exploring nucleophilic addition of 1a, which was readily prepared in two steps via substitution reaction and subsequent ene-type reaction (see the ESI). We started our screening with 1-allyl-2,3,4,5-tetrahydro-1H-2,5-epoxybenzo[b]azepine (1a) as a model substrate for the optimization of the reaction conditions (36,37 We were gratified to find that Grignard reagents could indeed be added with high selectivity (
EntrySolventAdditiveTimeYieldb (%) dr (syn/anti)c
1dTHF10 h0
2dDioxane10 h0
3Et2O30 min922a, 24/76
41,2-Dichloroethane10 min902a, 68/32
5CHCl310 min952a, 66/34
6CH2Cl210 min962a, 69/31
7CH2Cl2MgBr2 (1.2 equiv.)10 min902a, 70/30
8CH2Cl210 min972b, 91/9
9CH2Cl210 min882c, 100/0
Open in a separate windowaReaction conditions: 1a (1 mmol), MeMgBr in 10 mL of solvent at 0 °C under air.bIsolated yield after column chromatography.cDetermined by 1H NMR and X-ray crystallographic analysis.dThe reaction was conducted at 0 °C for 1 h, then at 25 °C for 9 h.However, there was no significant improvement in the diastereoselectivity was observed after the addition of magnesium bromide36 (Fig. 2). From the diffraction pattern, it could be clearly seen that the hydroxyl group and the methyl group are on the same side. The stereochemistry in the rest of the series could be unambiguously assigned by comparison of their NMR spectra with those of syn-2m.Nucleophilic addition with Grignard reagents on cyclic N,O-acetalsa
Entry N,O-AcetalsR1R2R3Time2Yield (%) syn/antib
11aMeHAllyl10 min2a9669/31
21aEtHAllyl10 min2b9791/9
31a i-PrHAllyl7 h2c88100/0
41aCyHAllyl18 h2d83100/0
51aAllylHAllyl10 min2e980/100
61aPhHAllyl10 min2f98100/0
71bMeMeAllyl10 min2g9188/12
81bAllylMeAllyl10 min2h900/100
91cMeClAllyl10 min2i9267/33
101cAllylClAllyl10 min2j910/100
111dMeHMe10 min2k9268/32
121d i-PrHMe5 min2l91100/0
131eMeHH1 h2m8091/9
141eAllylHH10 min2n8175/25
Open in a separate windowaUnless indicated otherwise, the reaction was carried out on 1.0 mmol scale in DCM (10 mL).bDiastereoisomeric ratios were determined by 1H NMR analysis of the mixture, see the ESI for details.Open in a separate windowFig. 2X-ray crystallographic structure of syn-2m.In general, the improved diastereoselectivities were observed with increasing steric bulk of the Grignard reagents, the syn-adduct was the major product in all cases (38–43 Even phenylmagnesium bromide could be added to 1a and provided the adduct in 98% yield and a single syn-adduct (37 7-Substituented substrates (1b, 1c) were also tolerated by this process, as well as Me at the nitrogen atom of the substrate (1d) (Fig. 3 (transition state A).36,44,45 However, this diastereoselectivity for Grignard addition to the N-unsubstituted cyclic N,O-acetal 1a may be attributed to a highly ordered transition state resulting from significant chelation of the alkoxy substituent and imino nitrogen to at least one magnesium cation as shown Fig. 3 (transition state B).46,47Open in a separate windowFig. 3Proposed transition states accounting for the diastereoselectivity.To give the intrinsic versatility of 2-substituted benzo[b]azepin-5-ol and as a complement to our recently published cascade reaction to prepare the benzazepinone scaffold, treatment of the above compounds 2 with Dess–Martin in CH2Cl2 gave the 2-substituted benzazepinones 3 in good to excellent yields ( EntryR1R2R3Time (min)3Yield (%)1HAllylMe303a852HAllylEt303b833HAllyl i-Pr153c864HAllylCy153d805HAllylAllyl153e756HAllylPh153f887MeAllylMe203g888MeAllylAllyl453h769ClAllylMe603i8410ClAllylAllyl603j7811HHMe203k38Open in a separate windowaUnless indicated otherwise, the reaction was carried out on 0.5 mmol scale in DCM (5 mL).The synthetic versatility of 2-substituted benzazepinones has also been explored. The fused tricyclic compound 4 (ref. 48) could also be readily synthesized from 3e. Treatment of 3e with Grubbs II catalyst led to 4 in 95% yield [eqn (1)].1In conclusion, we have demonstrated that the cyclic N,O-acetals were successfully applied to the diastereoselective addition of various Grignard reagents with encouraging levels of stereoselection. In the formation of 2,5-substituted 1-benzazepine derivatives, the reaction proceeds through a ring-opening/nucleophilic addition pathway. These benzo[b]azepin-5-ols then undergo simple Dess–Martin oxidation to afford the 2-substituted benzazepinones in excellent yields. In respect to the easy availability of the starting materials, simple manipulation, mild conditions and high diastereoselectivity, this reaction will be synthetically useful in organic chemistry.  相似文献   
7.
Antibiotic prophylaxis in craniotomy: a review     
Weiming Liu  Ming Ni  Yuewei Zhang  Rob J. M. Groen 《Neurosurgical review》2014,37(3):407-414
The effectiveness of antibiotic prophylaxis (AP) in craniotomies has been clarified through the accumulation of evidence and increased antibiotic knowledge. This paper focuses on the use of AP in craniotomies during different historical periods and collects highly relevant evidence on this issue. This review surveys different AP guidelines and explains why cefazolin was selected by most guidelines. Recent prominent topics, including strategies to update and implement guidelines and antibiotic efficacy in postoperative meningitis and surveillance and decolonization therapies for methicillin-resistant Staphylococcus aureus, are discussed.  相似文献   
8.
Chromopeptide A,a highly cytotoxic depsipeptide from the marine sediment-derived bacterium Chromobacterium sp. HS-13-94     
Zhenfang Zhou  Xin Wang  Hui Zhang  Jingya Sun  Linghui Zheng  Hongchun Liu  Jidong Wang  Aijun Shen  Meiyu Geng  Yuewei Guo 《药学学报(英文版)》2015,5(1):62-66
A bicyclic depsipeptide, chromopeptide A (1), was isolated from a deep-sea-derived bacterium Chromobacterium sp. HS-13-94. Its structure was determined by extensive spectroscopic analysis and by comparison with a related known compound. The absolute configuration of chromopeptide A was established by X-ray diffraction analysis employing graphite monochromated Mo Kα radiation (λ=0.71073 Å) with small Flack parameter 0.03. Chromopeptide A suppressed the proliferation of HL-60, K-562, and Ramos cells with average IC50 values of 7.7, 7.0, and 16.5 nmol/L, respectively.KEY WORDS: Chromopeptide A, Bacterium, Depsipeptide, Absolute configuration, Marine-derived, Sediments, Cytotoxicity, Chromobacterium sp.  相似文献   
9.
CXCR2-modified CAR-T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma     
Guangna Liu  Wei Rui  Hongli Zheng  Daosheng Huang  Fei Yu  Yuewei Zhang  Jiahong Dong  Xueqiang Zhao  Xin Lin 《European journal of immunology》2020,50(5):712-724
Unlike hematological malignancies, solid tumors have proved to be less susceptible to chimeric antigen receptor (CAR)-T cell therapy, which is partially caused by reduced accumulation of therapeutic T cells in tumor site. Since efficient trafficking is the precondition and pivotal step for infused CAR-T cells to exhibit their anti-tumor function, strategies are highly needed to improve the trafficking ability of CAR-T cells for solid tumor treatment. Here, based on natural lymphocyte chemotaxis theory and characteristics of solid tumor microenvironments, we explored the possibility of enhancing CAR-T cell trafficking by using chemokine receptors. Our study found that compared with other chemokines, several CXCR2 ligands showed relatively high expression level in human hepatocellular carcinoma tumor tissues and cell lines. However, both human peripheral T cells and hepatocellular carcinoma tumor infiltrating T cells lacked expression of CXCR2. CXCR2-expressing CAR-T cells exhibited identical cytotoxicity but displayed significantly increased migration ability in vitro. In a xenograft tumor model, we found that expressing CXCR2 in CAR-T cells could significantly accelerate in vivo trafficking and tumor-specific accumulation, and improve anti-tumor effect of these cells.  相似文献   
10.
RAL-STAINER自动染色仪对抗酸染色的性能评估     
徐阳颺  李志夫  赵越薇  李富升  娄加陶 《国际检验医学杂志》2020,(1):53-55,64
目的 评估RAL-STAINER自动染色仪对抗酸染色的性能。方法 收集标本,分别进行手工抗酸染色和仪器抗酸染色,评价自动染色仪的染色效果的合格率与手工染色的染色结果的一致率、仪器染色的重复性、与室间质评预期结果的符合率、交叉污染和工作性能等。结果 RAL-STAINER自动染色仪对各类标本抗酸染色背景基本无杂质,细菌和细胞色泽鲜明、结构清楚,染色效果的合格率为100%。自动染色仪与手工抗酸染色一致率为100%。仪器染色的重复性为100%。使用自动染色仪,两次室间质评结果均100%符合预期。自动染色仪批量染色时,无交叉污染。自动染色仪操作简便、通量高、染色效果稳定、生物安全性好。结论RAL-STAINER自动染色仪对抗酸染色的性能较好。  相似文献   
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