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101.
魏茜 《中华实用中西医杂志》2005,18(22):1690-1690
在医学法律纠纷中,由于心理因素造成的纠纷并不少见。例如在康复科,截瘫患者康复治疗的期望值与实际效果的差距,可能会成为医疗纠纷的背景因素,而有效的沟通则是化解矛盾、减少纠纷的重要手段之一。护士作为患者和医生的第一接触人,掌握良好的沟通技巧是基础。我康复科在3年里共收治截瘫患者10例。在患者的法律意识日渐增强的情况下,我们针对其主观愿望和客观实际,探讨与截瘫患者沟通的技巧,以取得良好效果,现报告如下。 相似文献
102.
Nicholas Thatcher Wendi Qian Peter I Clark Penelope Hopwood Robert J Sambrook Robert Owens Richard J Stephens David J Girling 《Journal of clinical oncology》2005,23(33):8371-8379
PURPOSE: Ifosfamide, carboplatin, etoposide, and vincristine, alone and in combination, are highly active against small-cell lung cancer (SCLC). This trial was designed to investigate whether survival could be improved by a regimen of all four drugs (ICE-V) compared with standard chemotherapy in patients with SCLC and good performance status, and to assess the patients' quality of life (QL). PATIENTS AND METHODS: Patients were randomly assigned to receive six cycles of either ICE-V at 4-week intervals without dose reduction or standard chemotherapy administered according to local practice. The recommended standard control regimens were cyclophosphamide, doxorubicin, and etoposide; and cisplatin and etoposide. RESULTS: A total of 402 patients were randomly assigned, and 350 (87%) patients have died. Overall survival was longer in the ICE-V group (hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P = .0049), median survival was 15.6 months in the ICE-V group and 11.6 months in the control group, and 2-year survival rates were 20% and 11%, respectively. There was no evidence that the relative survival benefit for ICE-V was less in extensive-stage than in limited-stage patients. An increased rate of septicemia was reported in the ICE-V group (15% v 7% in the control group), but this did not result in an increase in reported treatment-related deaths (four patients [2%] in both groups). The findings on QL were broadly similar in both groups, with some benefit in favor of ICE-V. CONCLUSION: Compared with standard chemotherapy, the ICE-V regimen improves overall survival without QL penalties, despite an increased but manageable level of toxicity. 相似文献
103.
Calpastatin participates in the regulation of cell migration in BAP1-deficient uveal melanoma cells 下载免费PDF全文
AIM: To detect how BRCA-associated protein 1 (BAP1) regulates cell migration in uveal melanoma (UM) cells.
METHODS: Wound healing and transwell assays were performed to detect UM cell migration abilities. Protein chip, immunoprecipitations and surface plasmon resonance analyses were applied to identify BAP1 protein partners. Western blot and calpain activity assays were used to test the expression and function of calpastatin (CAST).
RESULTS: CAST protein was confirmed as a new BAP1 protein partner, and loss of BAP1 reduced the expression and function of CAST in UM cells. The overexpression of CAST rescued the cell migration phenotype caused by BAP1 loss.
CONCLUSION: BAP1 interacts with CAST in UM cells, and CAST and its subsequent calpain pathway may mediate BAP1-related cell migration regulation. 相似文献
104.
认知是指人脑为获取和应用知识,将外界信息转化成内在心理活动的复杂过程。自
1998年Schmahmann和Sherman提出“小脑认知-情感综合征”起,小脑认知功能的研究越来越受到关注。
本文通过回顾国内外相关研究,从小脑的解剖与认知功能、小脑的神经网络机制以及交叉性小脑神经
机能联系不能 3 个角度探讨了小脑在认知神经网络中的作用及机制,旨在提高对小脑参与认知功能的
认识。 相似文献
105.
Liposarcoma is a rare malignant tumor type and surgical resection is the gold standard treatment. The present study reported on the case of a 51-year-old woman who presented with a mass in the left upper abdomen. Computed tomography revealed a 32-cm giant retroperitoneal liposarcoma. Complete tumor resection was performed without the removal of other organs. Postoperative pathological examination indicated retroperitoneal well-differentiated liposarcoma and immunohistochemistry revealed S-100(−), MDM2(+), vimentin(+), CDK4(+), p16(+) and STAT6(+) results. The patient recovered well after the surgery. Complete tumor resection during the first surgery is key to cure liposarcoma. The present case report will be helpful for clinical oncologists to fully understand giant retroperitoneal liposarcoma and treat it accordingly. 相似文献
106.
目的:研究低氧刺激慢性鼻窦炎伴鼻息肉(CRSwNP)与正常鼻黏膜上皮细胞炎性因子的变化与异同,探讨其在CRSwNP发病机制中的作用。方法:选择2015年6月至2018年1月在吉林大学中日联谊医院就诊的68例CRSwNP患者,其中男性36例,女性32例,年龄(45.2±12.5)岁(
xˉ±s,下同),患者的... 相似文献
107.
Lilan Jin Lu Deng Mark Bartlett Yiping Ren Jihong Lu Qian Chen Yixiao Pan Hai Wang Xiaokui Guo Chang Liu 《Nutrients》2022,14(10)
Air pollutants of PM2.5 can alter the composition of gut microbiota and lead to inflammation in the lung and gastrointestinal tract. The aim of this study was to evaluate the protective effect of a novel herbal extract blend, FC, composed of Lonicera japonica extract, Momordica grosvenori extract, and broccoli seed extract, on PM2.5-induced inflammation in the respiratory and intestinal tract. A549 cells and THP-1 cells, as well as C57BL/6 mice, were stimulated with PM2.5 to establish in vitro and in vivo exposure models. The models were treated with or without FC. The expression of inflammatory cytokines and tight junction proteins were studied. Proteomic analysis was performed to elucidate mechanisms. Mouse feces were collected for gut microbiota analysis. FC was shown to modulate the upregulation of pro-inflammatory cytokines mRNA expression in A549 and THP-1 cells and downregulated tight junction proteins mRNA expression in A549 cells due to PM2.5 stimulation. In animal models, the decreased expression of the anti-inflammatory factor il-10, tight junction protein ZO-1, and the elevated expression of COX-2 induced by PM2.5 were improved by FC intervention, which may be associated with zo-1 and cox-2 signaling pathways. In addition, FC was shown to improve the gut microbiota by increasing the abundance of beneficial bacteria. 相似文献
108.
Muchen Zhang Jiahui Qian Xinyan Xu Temoor Ahmed Yong Yang Chenqi Yan Mohsen Mohamed Elsharkawy Mohamed M. Hassan Jamal A. Alorabi Jianping Chen Bin Li 《Viruses》2022,14(5)
Phage therapy is a promising biocontrol management on plant diseases caused by bacterial pathogens due to its specificity, efficiency and environmental friendliness. The emergence of natural phage-resistant bacteria hinders the application of phage therapy. Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of the devastating bacterial leaf blight disease of rice. Here, we obtained a spontaneous mutant C2R of an Xoo strain C2 showing strong resistance to the lytic phage X2. Analysis of the C2R genome found that the CDS2289 gene encoding glycosyltransferase acquired a frameshift mutation at the 180th nucleotide site, which also leads to a premature stop mutation at the 142nd amino acid. This mutation confers the inhibition of phage adsorption through the changes in lipopolysaccharide production and structure and bacterial surface morphology. Interestingly, glycosyltransferase-deficient C2R and an insertional mutant k2289 also showed reduced virulence, suggesting the trade-off costs of phage resistance. In summary, this study highlights the role of glycosyltransferase in interactions among pathogenic bacteria, phages and plant hosts, which provide insights into balanced coevolution from environmental perspectives. 相似文献
109.
Xiaoran Chang Qian Lin Qun Zhang Junying Hu Gulbahar Tursun Yingrui Deng Chunguang Guo Xinping Wang 《Viruses》2022,14(5)
Here, we report the characterization of 13 novel caprine/ovine enterovirus strains isolated from different regions in China during 2016–2021. Immunoperoxidase monolayer assay showed that these viral strains shared strong cross-reaction with the previously reported caprine enterovirus CEV-JL14. Alignment analysis of the complete nucleotide sequences revealed 79.2%–87.8% and 75.0%–76.7% sequence identity of these novel caprine enterovirus strains to CEV-JL14 and TB4-OEV, respectively. Phylogenetic analyses clustered these novel strains to EV-G based on the amino acid sequences of P1 and 2C+3CD. Moreover, phylogenetic analysis of these caprine enterovirus strains identified three new EV-G types using VP1 sequences. These results demonstrate the genetic variations and the evolution of caprine enterovirus. 相似文献
110.
Ling Zhang Qian Chen Linlin Li Jian Jiang Hao Sun Li Li Ting Liu Lin Zhang Chun Li 《RSC advances》2022,12(23):14912
A series of cinchona alkaloid-based NNP ligands, including a new one, have been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various aromatic and heteroaromatic ketones were smoothly reacted, yielding valuable chiral alcohols with extremely high 99.9% ee. Moreover, a proposed reaction mechanism was discussed and verified by NMR.A series of cinchona alkaloid-based NNP ligands including a new one has been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various ketones were smoothly reacted with up to 99.9% ee.Since the well-known failure of using racemic thalidomide, attention has been paid to the manufacture of optically pure compounds as effective components in pharmaceuticals and agrochemicals. Asymmetric hydrogenation of ketones, especially heteroaromatic ketones, has emerged as a popular facile route to approach enantiopure secondary alcohols as essential intermediates for the construction of biologically active molecules.1–4 Knowles et al.5 pioneered the production of enantioenriched chiral compounds in 1968, and Noyori and co-workers6–8 laid the cornerstone of asymmetric hydrogenation in 1990s. Subsequently, numerous catalytic systems have been developed. Ru-BICP-chiral diamine-KOH was developed and proved to be effective for asymmetric hydrogenation of aromatic ketones by Xumu Zhang.9 Cheng-yi Chen reported asymmetric hydrogenation of ketone using trans-RuCl2[(R)-xylbinap][(R)-daipen] and afforded secondary alcohol in 92–99% ee.10 Mark J. Burk and Antonio Zanotti-Gerosa disclosed Phanephos-ruthenium-diamine complexes catalyzing the asymmetric hydrogenation of aromatic and heteroaromatic ketones with high activity and excellent enantioselectivity.11 Qi-Lin Zhou et al. designed and synthesized chiral spiro diphosphines as a new chiral scaffold applied in the asymmetric hydrogenation of simple ketones with extremely high activity and up to 99.5% ee.12–15 Similarly, Kitamura and co-workers have developed a set of tridentate binan-Py-PPh2 ligands for the asymmetric hydrogenation of ketones affording excellent results.16 Recently, chiral diphosphines and tridentate ligands based on ferrocene have been developed for the asymmetric hydrogenation of carbonyl compound with a remarkable degree of success.17–21 Despite many ligands for asymmetric hydrogenation of ketones have been reported, expensive reagent and multistep complicated reactions were employed to synthesize most of them.22–24 In light of increasing industrial demand, easily obtained, cheap and practical chiral ligands are still highly desirable. In addition to chiral ligands, the selection of metals was essential for asymmetric hydrogenation.25–27 Although Mn,28–30 Fe,31–34 Co,35–37 Ni38,39 and Cu40,41 metals were proved to be effective for asymmetric hydrogenation in recent years, Rh,42–44 Ir45,46 and especially Ru remained the most preferred metals. Ruthenium47–51 was chosen owing to its superior performances in terms of low price, selectivity and activity. Takeshi Ohkuma,52 Hanmin Huang53,54 and Johannes G. de Vries55 all successfully used ruthenium catalysts for asymmetric hydrogenation of ketones. Admittedly, there is a continuing interest in the development of cheaper, simpler and more efficient catalysts for the asymmetric hydrogenation of ketones under mild conditions to access corresponding secondary alcohols. Recently, we developed new NNP chiral ligands derived from cinchona alkaloid for the asymmetric hydrogenation of various ketones in extremely excellent results using a iridium catalytic system.56 Prompted by these encouraging results, we were interested in exploring a ruthenium-catalyzed asymmetric hydrogenation of ketones with NNP chiral ligands derived from cinchona alkaloid. Here, we showed that changing from iridium to ruthenium, with the same simple synthetic ligands, delivered a catalyst catalyzed asymmetric hydrogenation of ketones to give the industrially important chiral alcohols with up to 99.9% ee. Although the catalytic activity of ruthenium catalyst was not as high as that of the iridium catalyst, the enantioselectivity could be maintained, and even showed higher enantioselectivity in the hydrogenation of some substrates.Chiral tridentate ligand NNP (L1–L10) were synthesized and characterized as reported in our previous publication. With tridentate ligands in hand, we began to evaluate the catalytic performance in benzylidene-bis(tricyclohexylphosphine) dichlororuthenium-catalyzed asymmetric hydrogenation of acetophenone employed as a standard substrate (Fig. 2). MeOH was found to be a better one as the conversion and enantioselectivity were 99.9% and 98.2%, respectively. Bases screening showed that Ba(OH)2 was superior to the others, giving >99.9% conversion and 98.8% ee in the present catalytic system (Fig. 1). Ligand screening revealed that the configuration of chiral centers of cinchona alkaloids of the ligand markedly affected the catalytic performance. NNP ligands derived from cinchonine and quinidine appeared to benefit both the reaction rate and enantioselectivity, while those derived from cinchonidine and quinine had the opposite effect. Further, different NNP ligands that bearing different substituents on the phenyl rings were evaluated. Similar to our previous research, ligands with electron-withdonating substituents showed better catalytic performance than those with electron-withdrawing substituents. However, it was noted that the more electron-withdonating substituents furnished lower activity but same enantioselectivity. The optimal ligand L5 derived from quinidine with one methoxy group on benzene ring provided the corresponding chiral alcohol with 99.9% conversion and 98.8% ee. Considering that L3 derived from cinchonine had similar catalytic performance to L4 derived from quinidine, new ligand L10 similar to L5 with one methoxy group on benzene ring was synthesized and applied to the asymmetric hydrogenation of template substrate. 99.6% conversion and 97.6% ee was obtained. Hence, L5 was employed as better ligand in subsequent experiments.Open in a separate windowFig. 1The effect of different bases for the asymmetric hydrogenation of acetophenone (substrate/Ru/L5 = 500/1/2, ketones: 0.429 mol L−1, base: 0.15 mol L−1, MeOH: 2 mL, 30 °C, 6 MPa, 2 h.).Open in a separate windowFig. 2The effect of different solvents for the asymmetric hydrogenation of acetophenone. (substrate/Ru/L5 = 1000/1/2, ketones: 0.858 mol L−1, Ba(OH)2: 0.15 mol L−1, solvent: 2 mL, 30 °C, 6 MPa, 2 h.).The effect of different ligand for the asymmetric hydrogenation of acetophenonea
Open in a separate windowaSubstrate/Ru/L = 2000/1/2, ketones: 1.715 mol L−1, Ba(OH)2: 0.15 mol L−1, MeOH: 2 mL, 30 °C, 6 MPa, 2 h.In order to evaluate the general applicability of this method, we have surveyed the substrate scope. As can be discerned from the data in Fig. 3, most of aryl alkyl ketones P1–P21 were hydrogenated with very high enantioselectivities (97.1–99.9% ee). Under the conditions employed, the electron effect and steric hindrance seemed to have no significant impact on the enantioselectivities of asymmetric hydrogenation. However, the activities were slightly affected by steric hindrance, especially ortho-substituted group. Significantly, Ru/L5 showed high enantioselectivity 98.2% in the hydrogenation of [3,5-bis(trifluoromethyl)phenyl]ethanone and its corresponding enantiopure alcohol P21 was key chiral intermediates for the NK-1 receptor antagonist aprepitant.57,58 Additionally, chiral heteroaromatic alcohols containing nitrogen, oxygen or sulfur in the heterocyclic ring were considerable organic synthetic intermediate in pharmaceuticals and organic synthesis.59–61 Nevertheless, due to the coordination ability of the heteroaromatic moiety, the asymmetric hydrogenation of heteroaromatic ketones has been less investigated. Surprisingly, the protocol was found to be very effective for asymmetric hydrogenation of various heteroaromatic ketones P22–P35. The substrates were all well reduced smoothly to afford the corresponding chiral alcohol with 97.1–99.9% ee. Notably, meta- and para-acetyl pyridines, generally as a challenging hydrogenation substrates62–64 owe to stronger coordination ability, were also hydrogenated with up to 97.2% ee (P33 and P34). Gratifyingly, 97.4 ee was obtained when acetonaphthone employed (P36). Benzo-fused seven-membered cyclic ketone proceeded well to afford the corresponding chiral alcohols with 99.6% ee (P37). To further explore substrate scope, we checked the effectiveness of method for asymmetric hydrogenation of unsaturated ketones. Although, both substrates were hydrogenated with high yield, only medium enantioselectivity 73.8 and 78.3% ee were given, respectively.Open in a separate windowFig. 3Asymmetric hydrogenation of ketones catalyzed by Ru/L5. (Substrate/Ru/L5 = 200/1/2, ketones: 0.171 mol L−1, Ba(OH)2: 0.15 mol L−1, MeOH: 2 mL, 30 °C, 6 MPa, 2 h, isolated yield, ee was determined by GC or HPLC on chiral stationary phase (see the ESI†); asubstrate/Ru/L5 = 2000/1/2; bsubstrate/Ru/L5 = 100/1/2, 25 °C; csubstrate/Ru/L5 = 50/1/2, 25 °C, 24 h; dsubstrate/Ru/L5 = 25 °C; esubstrate/Ru/L5 = 50/1/2, 4 h; fEtOH).To understand the mechanism of the reaction, NMR was introduced to investigated active species. Single peak at δ = 19.91 ppm belonging to phenyl vinyl group of the complex disappeared in the 1H NMR spectrum when the complex was mixed with the ligand (Fig. S1, ESI†). In the meantime, 31P NMR spectrum of the mixture exhibited new singlet at δ = 55.71 ppm (s) with the signal of complex disappearing (Fig. S2, ESI†). These maybe indicated the formation of ruthenium complex A. Subsequently, a new weak signal was generated in the 31P NMR spectrum with the introduction of hydrogen and base (Fig. S3, ESI†). These may indicate the formation of ruthenium hydride complexes. Meanwhile, the 1H NMR spectrum exhibited several weak signals below 0 ppm (Fig. S4, ESI†). These data also verified the formation of ruthenium hydride complexes. Reference to relevant literature,65–67 the proposed catalytic cycle for the asymmetric hydrogenation of ketones with the ruthenium complex was shown in Scheme 1. First, the ruthenium complex reacted with ligands to form complex A. In the presence of base and hydrogen, the complex A lost two chlorine atoms to transform into dihydride complex B. Then, a hydridic Ru–H and a protic N–H unit were transferred from dihydride B to the carbonyl group of the ketones through the transition state TS to produce chiral alcohol. And the ruthenium complex lost two hydrogen atoms to form complex C. Finally, dihydride B was regenerated in hydrogen atmosphere. Compared with the reported iridium catalytic system with the same chiral ligands, the hydrogenation activity of the ruthenium catalytic system decreased significantly although maintained high enantioselectivity. The result indicates that the selection of metals was as important as chiral ligands for asymmetric hydrogenation.Open in a separate windowScheme 1Proposed mechanism for the asymmetric hydrogenation. 相似文献
Entry | Ligands | Con./% | ee/% | Config |
---|---|---|---|---|
1 | L1 | 47.5 | 78.2 | R |
2 | L2 | 56.1 | 77.8 | R |
3 | L3 | >99 | 94.0 | S |
4 | L4 | 80.8 | 97.0 | S |
5 | L5 | >99 | 98.8 | S |
6 | L6 | 54.2 | 98.0 | S |
7 | L7 | 2.1 | 84.2 | S |
8 | L8 | 91.1 | 98.0 | S |
9 | L9 | 36.5 | 92.8 | S |
10 | L10 | >99 | 97.6 | S |