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11.
Seunga Woo Yong-Gyun Kim Baegeun Lim Jiin Oh Yeonji Lee Hyeri Gwon Keepyung Nahm 《RSC advances》2018,8(4):2157
Chiral phase transfer catalysts of dimeric cinchona ammonium salts linked with a benzophenone bridge showed high enantioselectivity in the α-alkylation of a glycinate ester under mild industry-applicable conditions: 0.5 mol% PTC and near equivalents of alkyl halide. A dual function of the dimeric quinuclidiniums was proposed for the high efficiency.Novel cinchona-alkaloid derived dimeric phase transfer catalysts (PTC) with benzophenone linkers and their α-alkylation of glycinate esters has been presented.Since cinchona alkaloids were transformed to asymmetric quaternary quinuclidinium salts with benzyl halides and were used as a phase-transfer catalyst (PTC) (1) by Dolling1 and O''Donnell,2 cinchona alkaloids have been widely utilized as chiral templates for phase-transfer catalysis.3 (Scheme 1) These organic PTCs can be easily prepared from natural and low cost chiral cinchona alkaloids in a few synthetic steps and they are stable and facile under normal reaction conditions in water. Later N-9-anthracenylmethyl quinuclidinium salt PTC (2) was introduced and showed high enantioselectivity for the alkylation of the protected glycine tert-butyl ester.4 Quinuclidinium PTCs with each pseudo-enantiomeric cinchona alkaloids, such as (−)-cinchonidine and (+)-cinchonine, show enantiomeric selectivity each other, and have been successfully applied in various asymmetric organic synthesis including α-alkyl glycine derivatives synthesis.3Open in a separate windowScheme 1Representative cinchona-derived PTCs.Enantioselectivity in the alkylation of glycine esters has been probed by several experimental trials. Crystallographic study of the p-nitrophenoxide salt of PTC 2 showed that N-anthracenylmethy moiety of 2 is located in staggered position between the Cc and the Cd,4a which provides more hindered spaces around the Cb–Cc–Cd face (F4) around the ammonium.5 The Ca–Cb–Cd face (F2) is blocked by O-allyl group and the Ca–Cc–Cd face (F3) are covered by bicyclic ring, but the Ca–Cb–Cc face (F1) is less hindered. Therefore, anionic glycinate derivatives could approach toward the F1. Enolates of glycine esters would form tight ionic complexes with the ammonium nitrogen on the F1 face of PTC 2, and the alkylation with alkyl halides could follow along the direction of less hindered side of the si/re-face of the enolates.4aNOE correlations study of PTC 2 with borohydride ion6 indicated the borohydride occupies the F1 face of PTC 2. Computational simulation7 also described the stable transition states where an enolate locates on the F1 face.Dimeric cinchona-derived PTCs linked by either benzene or naphthalene ligand have been introduced by Park et al.8a–c Among ortho, meta and para-connected PTCs, the meta-disubstituted phenyl PTC 3a or 2,7-disubstituted naphthyl PTC 3b showed highly improved catalytic effects compared to monomeric PTC 2, such as lower dosage of catalyst (1–5 mol%) and high enantioselectivity. Role of additional quinuclidinium was thought to be a steric blocker which could increase the stereoselectivity of the enolate complex on the F1 face.Other dimeric cinchona alkaloid PTCs were also developed with various linkers, such as 9,10-dimethylanthracenyl,9 biphenyl, alkenyl,10 macrocyclic amine and calixarene,11 and their enantioselectivities were equal or lower than those of monomeric PTCs. Some dimeric PTCs were converted to ionic polymers by replacing bromides to a disufonate anion without loss of reactivity and enantioselectivity.12Alkylation of tert-butyl glycinate ester was performed with 1–10 mol% of PTC 1–3 and excess 5 equivalents of alkyl halide at 0 to −78 °C. These catalytic conditions are still to be improved for practical application; low mol% of PTC, near equimolar amount of alkyl halides and ambient temperature. Hence we investigated dimeric PTCs with various linkers for facile catalytic condition. Here we introduce new dimeric cinchona PTCs with a benzophenone linker and their application in asymmetric alkylation of glycine derivatives.Monomeric PTC 4p, N-(4-benzoylbenzyl)-O(9)-allylcinchonidium bromide, which has a benzoyl benzyl at N(1), was synthesized from 4-bromomethyl-benzophenone and (−)-cinchonidine. (Scheme 2) Dimeric cinchona-based quarternay ammonium salts (PTC 5–6) were synthesized from meta/para-di(bromomethyl) benzophenone13 and two equivalent cinchona alkaloids. Coupling reaction of the di(bromomethyl)benzophenone and (−)-cinchonidine or (+)-cinchonine in EtOH/DMF/CHCl3 (5 : 6 : 2)8 for 5 h at 100 °C and the O(9)-allylation with allyl bromide gave the dimeric quarternary salts, bis(4-(O(9)-allyl-cinchonidium-N-methyl)phenyl) methanone dibromide (5) and bis(4-(O(9)-allyl-cinchonium-N-methyl)phenyl) methanone dibromide (6), respectively, in good yields.‡Open in a separate windowScheme 2Monomeric and dimeric cinchona-PTC with a benzophenone bridge.Enantioselective PTC 4–6 system was applied in the alkylation of N-(diphenylmethylene)glycine tert-butyl ester (7) to the α-alkylated glycinate (8) under the condition of 0.5–1.0 mol% catalysts and 1.2 equivalent alkyl halides. We also explored the variation of enantioselectivity depending on the various positions of dimeric cinchonidium at benzophenone; 5pp, 5mp and 5mm.Monomeric PTC 4p showed enantioselectivity of 87% ee (S) at 25 °C (2 Geometric difference between PTC 1 and 4p is the extra p-benzoyl substituent on N-benzyl. Apparently the p-benzoyl moiety gives no big enhancement in enantioselectivity of 4p.Catalytic phase-transfer benzylation of 7 with monomeric and dimeric cinchona-based catalysts (4–6)a
Open in a separate windowaBenzylation of 7 (0.1 mmol) was carried out with 1.2 equivalents of benzyl bromide and 50% aqueous KOH (0.25 mL) in toluene/chloroform (7 : 3, 0.75 mL) under nitrogen atmosphere, unless otherwise stated.bYields of isolated product.cEnantiopurity of 8 was determined by HPLC analysis using a column with a chiral stationary phase (DAICEL Chiralcel OD) with hexane/isopropanol as the solvent.dThe absolute configuration was determined by comparison of the HPLC retention time with that of an authentic sample, which was synthesized independently by reported procedures.2,4,8e5.0 equivalents of benzyl bromide.fWith the same conditions expect the increased amount of 7 (1.0 mmol).When the dimeric PTC of bis(4-(O(9)-allyl-cinchonidium-N-methyl)phenyl)methanone dibromide (5pp) was applied in the benzylation, it showed big improvement of both enatioselectivity and catalytic condition.§ PTC 5pp (1.0 mol%) showed enantioselectivity of 97% ee (S) with 1.2 equivalents of benzyl bromide at 20 °C. (entry 2) At lower reaction temperature (0 °C: entry 3), its enantioselectivity increased to 98% ee. When 0.5 mol% of 5pp was applied at 0 and –20 °C, the product showed 98% and 99% ee. (entries 4 and 6) And with 0.25 mol% of 5pp, the enantioselectivity went down to 97% ee. Therefore, the practical catalytic condition for the benzylation with 5pp would be 0.5 mol% of PTC and 1.2 equivalents of benzyl bromide at 0 °C.The isomeric PTC 5mp and 5mm showed lower % ee; 5mp showed 89% ee (S) in benzylation (entry 8) and 5mm showed 71% ee (entry 9). These enatioselectivity values are similar or lower than that of the monomeric 4p. There was no enhanced catalytic effect by two cinchonidiums at meta/para and meta/meta position of 5mp and 5mm.Enantioselectivity of PTC 5 was varied in the order of 5pp > 5mp > 5mm depending on the position at benzophenone ring, which is different from those observed at PTC 3a (meta > para > ortho position).8 To deduce the enantioselectivity of PTC 5pp, one may consider a distance factor between dimeric cinchonidiums. The distance between two benzyl positions of the bridge benzophenone of PTC 5pp was calculated to be ∼10.4 Å at B3LYP/6-31G(d) level (see, ESI†), which is longer than those of PTC 3a and 3b (∼5.1 Å and ∼7.5 Å, respectively). And those of PTC 5pm and 5mm were 8.7 Å and 8.3 Å, respectively. The distance between two quarternary ammoniums could not be correlated with the enantioselectivity, and it would not be a main controlling factor for enantioselectivity.At the transition state for α-alkylation of glyciante 7 with benzyl bromide, there will be SN2-type bond formation/cleavage between the enolate carbon and the benzyl carbon and bromide, which occurs on the F1 face of the PTC.7b (Fig. 1) It is expected that the anionic oxygen of the enolate from 7 will form an ionic complex with the PTC ammonium at the transition state, and as the benzyl bromide approaches to the enolate of 7 in SN2 pattern, the leaving bromide will be attracted also by the ammonium.14 An estimated distance between enolate and the leaving bromide will be ∼5.0 Å.Open in a separate windowFig. 1Proposed TSs for benzylation of an enolate of gylcinate with PTC 1 and 5pp.At the monomeric PTC 1/2, both the enolate and bromide will be attracted by the same quinuclidinium. On the other hand, dimeric PTC 5 is expected to anchor the enolate of gylcinate 7 on one ammonium and attract the leaving bromide with another ammonium in a distance (Br–N(+)) of ∼5.0 Å at TS. (Fig. 1) Two phenyl rings of the benzophenone bridge of PTC 5 are not laid on a plane but twisted around the carbonyl (τ = 50°)15 and these two twisted cinchonidiums of PTC 5pp would provide a stabilized transition structure for the benzylation within ∼10 Å distance by dual functions of two quinuclidiniums. However, more crowded TSs will be formed in 5mp and 5mm because of the short ammonium distance, therefore their TSs will resemble to that of monomeric PTC 4p.Dimeric PTC of bis(4-(O(9)-allyl-cinchonium-N-methyl)phenyl) methanone dibromide (6pp) derived from (+)-cinchonine is a pseudo enantiomer of PTC 5pp. PTC 6pp showed also high enantioselectivity of 94% ee (R) in the benzylation at room temperature. (entry 10) Its selectivity increased to 95–98% ee at lower temperature (entries 11 and 12).The alkylation with selected alkyl halides with 0.5 mol% of PTC 5pp were summarized in 16 (entry 9) PTC 5pp has been proved to be an advanced phase transfer catalyst for the synthesis of various α-amino acids under mild catalytic conditions.Catalytic phase-transfer alkylation of 7 with dimeric cinchona-based catalyst 5ppa
Open in a separate windowaAlkylation of 7 (0.1 mmol) was carried out with 0.5 mol% of 5pp, 1.2 equivalents of R-X and 50% aqueous KOH (0.25 mL) in toluene/chloroform (7 : 3, 0.75 mL) at 0 °C under nitrogen atmosphere, unless otherwise noted.bYields of isolated product.cEnantiopurity of 8 was determined by HPLC analysis using a column with a chiral stationary phase (DAICEL Chiralcel OD) with hexane/isopropanol as the solvent. The absolute configuration was determined by comparison of the HPLC retention time with that of an authentic sample, which was synthesized independently by reported procedures.2,4,8dR–I (5.0 eq.) and CsOH·H2O (5.0 eq.) was uses as base.eWith 1.0 mol% of the catalyst.f N-Benzoyl derivative.α,α-Dialkylation of aldimine Schiff base of amino acid17 was examined with 5pp. Aldimine Schiff base of d,l-alanine ethyl ester 9, benzyl bromide (1.2 eq.) and CsOH·H2O (5 eq.) with PTC 5pp (1.0 mol%) in toluene/CHCl3 (7 : 3) at −10 °C for 4 hour, then the acid work-up gave ethyl 2-amino-2-methyl-3-phenylpropionate 10 in 94% yield, which was benzoylated to N-benzoyl α,α-dialkylated product 11 and analysed with chiral HPLC (92% ee (S)).In conclusion, we have provided the novel dimeric cinchona-based PTCs with a benzophenone bridge. The p,p′-linked PTC 5pp and 6pp showed high enantioselectivity (93–99% ee) in the alkylation of a glycine ester under mild catalytic conditions of 0.5 mol% PTC and near stoichiometric alkyl halide (1.2 equivalents) at 0–20 °C. Dialkylation under similar conditions gave high % ee with the aldimine Schiff base of alanine. Their efficiency and enantioselectivity were explained by dual functions dimeric cinchonidiums; one as an alkylating site and another as a receptor for a leaving anion. Novel PTCs 5pp and 6pp would be applied in the synthesis of natural and non-natural chiral α-amino acids and their derivatives. Applications to other asymmetric phase-transfer catalytic reactions with 5pp are under investigation. 相似文献
Entry | PTC | mol% | Temp (°C) | Time (h) | Yieldb (%) | % eec (config)d |
---|---|---|---|---|---|---|
1e | 4p | 5.0 | 20 | 1.5 | 89 | 87 (S) |
2 | 5pp | 1.0 | 20 | 2 | 92 | 97 (S) |
3 | 5pp | 1.0 | 0 | 3 | 95 | 98 (S) |
4 | 5pp | 0.5 | 0 | 4 | 95 | 98 (S) |
5 | 5pp | 0.25 | 0 | 8 | 94 | 97 (S) |
6 | 5pp | 0.5 | −20 | 6 | 95 | 99 (S) |
7f | 5pp | 0.5 | 0 | 6 | 95 | 98 (S) |
8 | 5mp | 2.0 | 20 | 1.5 | 89 | 89 (S) |
9 | 5mm | 2.0 | 20 | 1.5 | 84 | 71 (S) |
10 | 6pp | 0.5 | 20 | 3 | 90 | 94 (R) |
11 | 6pp | 0.5 | 0 | 6 | 92 | 95 (R) |
12 | 6pp | 0.5 | −20 | 8 | 93 | 98 (R) |
Entry | R–X | Time (h) | Yieldb (%) | % ee (config)c |
---|---|---|---|---|
1 | PhCH2–Br | 4 | 95 | 98 (S) |
2 | 11 | 89 | 97 (S) | |
3 | 12 | 86 | 97 (S) | |
4 | 3 | 88 | 93 (S) | |
5 | 9 | 69 | 95 (S) | |
6 | 9 | 93 | 94 (S) | |
7d | CH3CH2I | 6 | 92 | 95 (S) |
8d,e | CH3I | 4 | 64 | 93 (S) |
9 | 5 | 51 | 85f (S) |
12.
Joseph G. Ibrahim Ming‐Hui Chen Yeongjin Gwon Fang Chen 《Statistics in medicine》2015,34(28):3724-3749
The power prior has been widely used in many applications covering a large number of disciplines. The power prior is intended to be an informative prior constructed from historical data. It has been used in clinical trials, genetics, health care, psychology, environmental health, engineering, economics, and business. It has also been applied for a wide variety of models and settings, both in the experimental design and analysis contexts. In this review article, we give an A‐to‐Z exposition of the power prior and its applications to date. We review its theoretical properties, variations in its formulation, statistical contexts for which it has been used, applications, and its advantages over other informative priors. We review models for which it has been used, including generalized linear models, survival models, and random effects models. Statistical areas where the power prior has been used include model selection, experimental design, hierarchical modeling, and conjugate priors. Frequentist properties of power priors in posterior inference are established, and a simulation study is conducted to further examine the empirical performance of the posterior estimates with power priors. Real data analyses are given illustrating the power prior as well as the use of the power prior in the Bayesian design of clinical trials. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
13.
Ga Yeon Lee Joo-Yong Hahn Soo-Youn Lee Hee-Jin Kim Jun Hyung Kim Sang-Yup Lee Young Bin Song Seung-Hyuk Choi Jin-Ho Choi Hyeon-Cheol Gwon 《Yonsei medical journal》2013,54(1):34-40
Purpose
Whether addition of cilostazol is superior to increasing dose of clopidogrel in patients with hyporesponsiveness to chronic clopidogrel therapy is unknown.Materials and Methods
We studied 73 patients with hyporesponsiveness to clopidogrel on standard dual antiplatelet therapy for more than 2 weeks. Clopidogrel hyporesponsiveness was defined as percent inhibition of P2Y12 reaction units (PRU) <30% on VerifyNow P2Y12 assay. Patients were randomly assigned to increased dose of clopidogrel (aspirin 100 mg+clopidogrel 150 mg daily: group A, n=38) or to receiving additional cilostazol (aspirin 100 mg+clopidogrel 75 mg+cilostazol 100 mg bid daily: group B, n=35).Results
Baseline percent inhibition of PRU and PRU was similar between 2 groups (13.0±10.2% versus 11.8±9.7%, p=0.61, and 286.3±54.7 versus 295.7±53.7, p=0.44, respectively). At follow-up, percent inhibition of PRU was higher and PRU was lower significantly in group B than in group A (38.5±17.9% versus 28.3±16.6%, p=0.02, and 207.3±68.2 versus 241.3±76.7, p=0.050, respectively). Among those still showing hyporesponsiveness to clopidogrel at follow-up (21 patients in group A, 10 patients in group B), 12 patients completed further crossover study. Compared to the baseline, magnitude of change in percent inhibition of PRU and PRU showed an improved tendency after the crossover (from 2.7±8.7% to 15.8±18.4%, p=0.08, and from -18.6±58.0 to -61.9±84.3, p=0.08).Conclusion
Adjunctive cilostazol improved clopidogrel responsiveness better than the higher maintenance dose of clopidogrel in hyporesponsive patients with chronic clopidogrel therapy. 相似文献14.
Mi-Jeong Kim Doo Soo Jeon Hyeon-Cheol Gwon Soo-Joong Kim Kiyuk Chang Hyo-Soo Kim Seung-Jea Tahk The KOREAN MUSTANG Investigators 《Journal of Korean medical science》2013,28(6):848-854
Compared with ST elevation myocardial infarction (STEMI), long-term outcomes are known to be worse in patients with unstable angina/non-STEMI (UA/NSTEMI), which might be related to the worse health status of patients with UA/STEMI. In patients with UA/NSTEMI and STEMI underwent percutaneous coronary intervention (PCI), angina-specific and general health-related quality-of-life (HRQOL) was investigated at baseline and at 30 days after PCI. Patients with UA/NSTEMI were older and had higher frequencies in female, diabetes and hypertension. After PCI, both angina-specific and general HRQOL scores were improved, but improvement was much more frequent in angina-related HRQOL of patients with UA/NSTEMI than those with STEMI (44.2% vs 36.8%, P < 0.001). Improvement was less common in general HRQOL. At 30-days after PCI, angina-specific HRQOL of the patients with UA/NSTEMI was comparable to those with STEMI (56.1 ± 18.6 vs 56.6 ± 18.7, P = 0.521), but general HRQOL was significantly lower (0.86 ± 0.21 vs 0.89 ± 0.17, P = 0.001) after adjusting baseline characteristics (P < 0.001). In conclusion, the general health status of those with UA/NSTEMI was not good even after optimal PCI. In addition to angina-specific therapy, comprehensive supportive care would be needed to improve the general health status of acute coronary syndrome survivors. 相似文献
15.
Bochud PY Bibert S Kutalik Z Patin E Guergnon J Nalpas B Goossens N Kuske L Müllhaupt B Gerlach T Heim MH Moradpour D Cerny A Malinverni R Regenass S Dollenmaier G Hirsch H Martinetti G Gorgiewski M Bourlière M Poynard T Theodorou I Abel L Pol S Dufour JF Negro F;Swiss Hepatitis C Cohort Study Group;ANRS HC EP Genoscan Study Group 《Hepatology (Baltimore, Md.)》2012,55(2):384-394
Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma. CONCLUSION: In chronic hepatitis C, IL28B variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes. 相似文献
16.
Boursier J de Ledinghen V Zarski JP Fouchard-Hubert I Gallois Y Oberti F Calès P;multicentric groups from SNIFF VINDIAG ANRS/HC/EP FIBROSTAR studies 《Hepatology (Baltimore, Md.)》2012,55(1):58-67
The sequential algorithm for fibrosis evaluation (SAFE) and the Bordeaux algorithm (BA), which cross-check FibroTest with the aspartate aminotransferase-to-platelet ratio index (APRI) or FibroScan, are very accurate but provide only a binary diagnosis of significant fibrosis (SAFE or BA for Metavir F ≥ 2) or cirrhosis (SAFE or BA for F4). Therefore, in clinical practice, physicians have to apply the algorithm for F ≥ 2, and then, when needed, the algorithm for F4 ("successive algorithms"). We aimed to evaluate successive SAFE, successive BA, and a new, noninvasive, detailed classification of fibrosis. The study included 1785 patients with chronic hepatitis C, liver biopsy, blood fibrosis tests, and FibroScan (the latter in 729 patients). The most accurate synchronous combination of FibroScan with a blood test (FibroMeter) provided a new detailed (six classes) classification (FM+FS). Successive SAFE had a significantly (P < 10(-3) ) lower diagnostic accuracy (87.3%) than individual SAFE for F ≥ 2 (94.6%) or SAFE for F4 (89.5%), and required significantly more biopsies (70.8% versus 64.0% or 6.4%, respectively, P < 10(-3) ). Similarly, successive BA had significantly (P ≤ 10(-3) ) lower diagnostic accuracy (84.7%) than individual BA for F ≥ 2 (88.3%) or BA for F4 (94.2%), and required significantly more biopsies (49.8% versus 34.6% or 24.6%, respectively, P < 10(-3) ). The diagnostic accuracy of the FM+FS classification (86.7%) was not significantly different from those of successive SAFE or BA. However, this new classification required no biopsy. CONCLUSION: SAFE and BA for significant fibrosis or cirrhosis are very accurate. However, their successive use induces a significant decrease in diagnostic accuracy and a significant increase in required liver biopsy. A new fibrosis classification that synchronously combines two fibrosis tests was as accurate as successive SAFE or BA, while providing an entirely noninvasive (0% liver biopsy) and more precise (six versus two or three fibrosis classes) fibrosis diagnosis. 相似文献
17.
Ji Eun Lee Subin Park Min Park Myung Hun Kim Chun Gwon Park Seung Ho Lee Sung Yoon Choi Byung Hwi Kim Hyo Jin Park Ji-Ho Park Chan Yeong Heo Young Bin Choy 《Acta biomaterialia》2013,9(9):8318-8327
Surgical suture is a strand of biocompatible material designed for wound closure, and therefore can be a medical device potentially suitable for local drug delivery to treat pain at the surgical site. However, the preparation methods previously introduced for drug-delivery sutures adversely influenced the mechanical strength of the suture itself – strength that is essential for successful wound closure. Thus, it is not easy to control drug delivery with sutures, and the drug-delivery surgical sutures available for clinical use are now limited to anti-infection roles. Here, we demonstrate a surgical suture enabled to provide controlled delivery of a pain-relief drug and, more importantly, we demonstrate how it can be fabricated to maintain the mechanical strength of the suture itself. For this purpose, we separately prepare a drug-delivery sheet composed of a biocompatible polymer and a pain-relief drug, which is then physically assembled with a type of surgical suture that is already in clinical use. In this way, the drug release profiles can be tailored for the period of therapeutic need by modifying only the drug-loaded polymer sheet without adversely influencing the mechanical strength of the suture. The drug-delivery sutures in this work can effectively relieve the pain at the surgical site in a sustained manner during the period of wound healing, while showing biocompatibility and mechanical properties comparable to those of the original surgical suture in clinical use. 相似文献
18.
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20.
Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen 总被引:2,自引:0,他引:2
Kluin-Nelemans HC; Beverstock GC; Mollevanger P; Wessels HW; Hoogendoorn E; Willemze R; Falkenburg JH 《Blood》1994,84(9):3134-3141
Using the CD40 system, in vitro proliferation of hairy cell leukemia (HCL) was examined in 43 patients. In this culture system, cells were stimulated by interleukin-4 (IL-4) and anti-CD40 monoclonal antibodies (MoAbs) that were added in soluble form or were cross-linked via their Fc part using Fc gamma RII-transfected mouse fibroblast cells. Proliferation was induced and confirmed by 3H-thymidine incorporation in 14 cases and by the presence of metaphases in 42 cases. 3H-thymidine incorporation showed a heterogeneous pattern: cross-linking of anti- CD40 gave the highest proliferation in 8 cases; in 11 cases, stimulation with anti-CD40 MoAbs alone, without cross-linking also resulted in proliferation; the addition of IL-4 further enhanced 3H- thymidine incorporation in 5 cases, but suppressed this phenomenon in 5 other cases. The CD40 system proved to be very effective in obtaining cytogenetic data. With a success rate of 42 of 43 patients tested, we found clonal abnormalities in 8 cases (19%) and nonclonal abnormalities with involvement of one or two abnormal metaphases in another 7 cases. The chromosomes most frequently involved in the abnormal karyotypes, both structurally and numerically, were chromosomes 5, 7, and 14. By fluorescence-activated cell-sorting analysis of the cultured cells, and by immunophenotypic analysis of metaphase spreads, T-cell growth could be excluded and the HCL-lineage confirmed. Stimulation via the CD40 antigen is an excellent tool for growing hairy cell leukemia cells. 相似文献