Chemical compositions and antimicrobial activities of four different Anatolian propolis samples

Propolis means a gum that is gathered by bees from various plants. It is known for its biological properties, having antibacterial, antifungal and healing properties. The aims of this study were to evaluate the antimicrobial activity of four different Anatolian propolis samples on different groups of microorganisms including some oral pathogens and comparison between their chemical compositions. Ethanol extracts of propolis (EEP) were prepared from four different Anatolian propolis samples and examined whether EEP inhibit the growth of the test microorganisms or not. For the antimicrobial activity assays, minimum inhibitory concentrations (MIC) were determined by using macrodilution method. The MIC values of the most effective propolis (TB) were 2 microg/ml for Streptococcus sobrinus and Enterococcus faecalis, 4 microg/ml for Micrococcus luteus, Candida albicans and C. krusei, 8 microg/ml for Streptococcus mutans, Staphylococcus aureus, Staphylococcus epidermidis and Enterobacter aerogenes, 16 microg/ml for Escherichia coli and C. tropicalis and 32 microg/ml for Salmonella typhimurium and Pseudomonas aeruginosa. The chemical compositions of EEP's were determined by high-temperature high-resolution gas chromatography coupled to mass spectrometry. The main compounds of four Anatolian propolis samples were flavonoids such as pinocembrin, pinostropin, isalpinin, pinobanksin, quercetin, naringenin, galangine and chrysin. Although propolis samples were collected from different regions of Anatolia all showed significant antimicrobial activity against the Gram positive bacteria and yeasts. Propolis can prevent dental caries since it demonstrated significant antimicrobial activity against the microorganisms such as Streptococcus mutans, Streptococcus sobrinus and C. albicans, which involves in oral diseases.     

Trichophyton species susceptibility to green and red propolis from Brazil

Aims:  The in vitro antifungal activity of Brazilian green and red propolis was tested against different species of Trichophyton .
Methods and Results:  The antifungal activity of the Brazilian aqueous and alcoholic extracts of the green propolis and the alcoholic extract of red propolis was observed against Trichophyton rubrum , Trichophyton tonsurans and Trichophyton mentagrohytes samples, using as controls itraconazole and terbinafine. The minimal inhibitory concentration was determined following the microdilution method indicated by the 'Clinical and Laboratory Standards Institute'. The minimal fungicide concentration was determined by the absence of growth in liquid sabouraud culture medium. The data obtained showed that the green propolis alcoholic extract's antifungal activity was from 64 to 1024 μg ml⁻¹, whereas the red propolis alcoholic extract was from 8 to 1024 μg ml⁻¹.
Conclusions:  The antifungal activity of the red propolis alcoholic extract was more efficient than the green propolis alcoholic extract for all three species studied. The T. rubrum samples were shown to be more sensitive to the antifungal activity of the alcoholic extracts of the propolis.
Significance and Impact of the Study:  The antifungal potential of the alcoholic extracts of green and red propolis demonstrated suggest an applicable potential as an alternative treatment for dermatophytosis caused by these species.     

Antifungal activity of propolis extract against yeasts isolated from onychomycosis lesions

The aim of this study was to determine the in vitro activity of propolis extract against 67 yeasts isolated from onychomycosis in patients attending at the Teaching and Research Laboratory of Clinical Analysis of the State University of Maringá. The method used was an adaptation made from the protocol approved by the National Committee for Clinical Laboratory Standards. The yeasts tested were: Candida parapsilosis 35%, C. tropicalis 23%, C. albicans 13%, and other species 29%. The propolis extract showed excellent performance regarding its antifungal activity: the concentration capable of inhibiting the all of the yeasts was 5 x 10(-2) mg/ml of flavonoids and 2 x 10(-2) mg/ml of flavonoids stimulated their cellular death. Trichosporon sp. were the most sensitive species, showing MIC50 and MIC90 of 1.25 x 10(-2) mg/ml of flavonoids, and C. tropicalis was the most resistant, with CFM50 of 5 x 10(-2) mg/ml of flavonoids and MFC90 of 10 x 10(-2) mg/ml. In view of the fact that propolis is a natural, low cost, nontoxic product with proven antifungal activity, it should be considered as another option in the onychomycosis treatment.     

Potential application of Northern Argentine propolis to control some phytopathogenic bacteria

The antimicrobial activity of samples of Northern Argentine propolis (Tucumán, Santiago del Estero and Chaco) against phytopathogenic bacteria was assessed and the most active samples were identified. Minimal inhibitory concentration (MIC) values were determined by agar macrodilution and broth microdilution assays. Strong antibacterial activity was detected against Erwinia carotovora spp carotovora CECT 225, Pseudomonas syringae pvar tomato CECT 126, Pseudomonas corrugata CECT 124 and Xanthomonas campestris pvar vesicatoria CECT 792. The most active propolis extract (Tucumán, T1) was selected to bioguide isolation and identified for antimicrobial compound (2',4'-dihydroxychalcone). The antibacterial chalcone was more active than the propolis ethanolic extract (MIC values of 0.5-1 μg ml(-1) and 9.5-15 μg ml(-1), respectively). Phytotoxicity assays were realized and the propolis extracts did not retard germination of lettuce seeds or the growth of onion roots. Propolis solutions applied as sprays on tomato fruits infected with P. syringae reduced the severity of disease. Application of the Argentine propolis extracts diluted with water may be promising for the management of post harvest diseases of fruits.     

Antimicrobial effects of Piper guineense 'Uziza' and Phyllantus amarus 'Ebe-benizo' on Candida albicans and Streptococcus faecalis

Two pathogens were employed, Streptococcus faecalis and Candida albicans for the study of the antimicrobial effects of Piper guineense and Phyllantus amarus using agar-well diffusion and disc-diffusion methods. Phytochemical screening of ethanol, cold and hot water extracts detected the presence of tannins, saponins, flavonoids, terpenoids and phlobatannins. Antimicrobial effect of the plant extracts showed that the organic solvent and aqueous solvents of P. amarus were inhibitory to S. faecalis while the extracts of Phyllantus amarus were not inhibitory to Candida albicans. Agar-well determined Minimum Inhibitory Concentration (MIC) values ranged between 3.125 mg/ml and 6.25 mg/ml while the disc diffusion determined MIC values ranged between 6.25 mg/ml and 25.0 mg/ml. The agar-well determined MIC values for the ethanolic P. amarus extracts (3.12 mg/ml) were lower than the corresponding disc-diffusion MIC determined values (6.25 mg/ml-25.00 mg/ml). Bacteriocidal and bacteriostatic effect varied with, solvent type of extract, concentration of the plant extract and the method of the test adopted. The active components of the plant have no antifungal effect on the tested yeast (Candida albicans). These findings are discussed in relation to plant chemicals as a means of disease control and also to the problem of microbial resistance to synthetic drugs.     

Preparation of Water and Ethanolic Extracts of Propolis and Evaluation of the Preparations

Propolis was extracted using water and various concentrations of ethanol as solvents. The extracts were investigated by measurement of absorption spectrum with a UV spectrophotometer, reversed phase-high pressure thin-layer chromatography and reversed phase-HPLC. Maximum absorption of all extracts was 290 nm, resembling flavonoid compounds, and the 80% ethanolic extract showed highest absorption at 290 nm. The most isosakuranetin, quercetin, and kaempferol were extracted from mixtures of propolis and 60% ethanol, while 70% ethanol extracted the most pinocembrin and sakuranetin, but 80% ethanol extracted more kaempferide, acacetin, and isorhamnetin from propolis. The 60 to 80% ethanolic extracts of propolis strongly inhibited microbial growth and 70 and 80% ethanolic extracts had the greatest antioxidant activity and 80% ethanolic extract strongly inhibited hyaluronidase activity.     

In vitro antifungal activity of anidulafungin

Anidulafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses. The antifungal spectrum of anidulafungin reaches the most common pathogenic fungi. Anidulafungin is especially active against the genera Candida and Aspergillus. Its antifungal mechanism is based on the inhibition of the beta-1,3-D-glucan synthesis, an essential molecule for the cell wall architecture, with different consequences for Candida and Aspergillus, being anidulafungin fungicide for the former and fungistatic for the latter. This review describes the in vitro antifungal spectrum of anidulafungin based in the scientific and medical literature of recent years. We can underline that most than 99% of Candida isolates are susceptible to < or = 2 microg/ml of anidulafungin. MIC are very low (< or =0.125 microg/ml) for most clinical isolates of the species Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei while Candida parapsilosis and Candida guilliermondii isolates are susceptible to anidulafungin concentrations < or = 2 microg/ml. An excellent activity of anidulafungin has been also described against Aspergillus, Pneumocystis and other fungi. However, its activity is very low against Cryptococcus and the Zygomycetes. The excellent activity of anidulafungin has made this antifungal a first line therapeutic indication for candidemia and invasive candidiasis in non-neutropenic patients.     

<Emphasis Type="Italic">In vitro</Emphasis> antifungal activity of propolis samples of Czech and Slovak origin

Propolis has been used in traditional folk medicine for ages owing to a number of biological effects. Four propolis samples of Czech and one of Slovak origin were extracted using Soxhlet apparatus and analysed by thin-layer chromatography. Raw propolis samples and their extracts were tested by microdilution broth method to determine minimal inhibitory concentration (MIC) in eight strains of human pathogenic fungi. Raw propolis samples showed a lower in vitro antifungal activity than their extracts. In general, the petroleum ether extracts exhibited the highest in vitro antifungal activity (MIC range of 16–64 μg/ml). The content of flavonoids in the samples varied according to region. The highest amount of flavonoids was found in sample A that originated from Broumov (4%). The most susceptible to the propolis extracts were Trichophyton mentagrophytes and Candida albicans. The propolis samples of Czech and Slovak origin and their extracts showed a considerable in vitro antifungal effect which was associated especially with nonpolar petroleum ether and toluene extracts. There was only a partial correlation between flavonoids content and in vitro antifungal activity.     

Anti-saprolegnia potency of some plant extracts against Saprolegnia diclina,the causative agent of saprolengiasis

Saprolegnosis of fresh water fishes caused by Saprolegnia diclina often results in serious economic losses to fish hatcheries. Despite the proven efficiency of malachite green as a potential fungicide in prevention and control of fish saprolegnosis, there is a strong debate about its safety aspects in use since it was documented to be responsible for many carcinogenic and teratogenic attributes. Bioactivity of four ethanolic plant extracts were assessed to attain a natural alternative to the traditional fungicide currently used in saprolegnosis control. Ethanolic extracts of Punica granatum and Thymus vulgaris exhibited a potential efficacy in suppressing mycelial growth of S. diclina at concentration of 0.5 mg/ml while extracts of Nigella sativa and Zingiber officinales were not effective respectively. The extract of pomegranate showed the highest antifungal potency with minimum inhibitory concentration (MIC) of 200 ppm while thyme extract was less effective and recorded MIC of 400 ppm against S. diclina. The acute fish toxicity of the plant extracts indicated the low toxicity of P. granatum and T. vulgaris extracts as no fish mortalities were detected at aquaria containing 200, 400 and 800 ppm of plant extracts respectively. Considering the low toxicity of these plant extracts, it may be concluded that 200 and 400 ppm of pomegranate and thyme extracts which suppressed the mycelial growth of the S. diclina could be safely used for saprolegniasis control.Both of pomegranate and thyme extracts which proved to possess a potential antifungal activity can be considered as a natural alternative fungicides to control saprolegniasis avoiding carcinogenic malachite green application.     

Cassia alata and the preclinical search for therapeutic agents for the treatment of opportunistic infections in AIDS patients.

In our search for therapeutic agents from natural sources with potential for the treatment of opportunistic infections in patients afflicted with acquired immunodeficiency syndrome (AIDS), we investigated antibacterial and antifungal activities of water extracts of Cassia alata (C. alata). The extracts are traditionally used in Ivory Coast, West Africa to treat bacterial infections caused by Escherichia coli (E. coli), and fungal infections caused by Candida albicans (C. albicans) and dermatophytes. Our working hypothesis was that the extract contains active ingredient(s) which can be isolated, identified and developed into useful antibacterial/antifungal agents for the treatment of opportunistic infections in patients with AIDS. We used the broth dilution and agar dilution methods. Specifically, we focused on E. coli and C. albicans and the effectiveness of the extracts was evaluated relative to those of standard antibacterial agent chloramphenicol and antifungal agent amphotericin B. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the water extract of C. alata against E. coli were 1.6 mg/ml and 60 mg/ml, respectively; corresponding data for chloramphenicol were 2 micrograms/ml and 10 micrograms/ml. Similarly, the MIC and minimum fungicidal concentration (MFC) for the extract against C. albicans were 0.39 mg/ml and 60 mg/ml in contrast to 0.58 micrograms/ml and 0.98 micrograms/ml for amphotericin B. From the dose-response curve plots, the extract had an IC50 of 31 mg/ml for E. coli and 28 mg/ml for C. albicans. The data suggest that C. alata extracts contain agent(s) which have therapeutic potential and might be useful if isolated and developed for the treatment of opportunistic infections of AIDS patients.     

Cassia alata and the preclinical search for therapeutic agents for the treatment of opportunistic infections in AIDS patients.

In our search for therapeutic agents from natural sources with potential for the treatment of opportunistic infections in patients afflicted with acquired immunodeficiency syndrome (AIDS), we investigated antibacterial and antifungal activities of water extracts of Cassia alata (C. alata). The extracts are traditionally used in Ivory Coast, West Africa to treat bacterial infections caused by Escherichia coli (E. coli), and fungal infections caused by Candida albicans (C. albicans) and dermatophytes. Our working hypothesis was that the extract contains active ingredient(s) which can be isolated, identified and developed into useful antimicrobial/antifungal agents for the treatment of opportunistic infections in patients with AIDS. We used the broth dilution and agar dilution methods. Specifically, we focused on E. coli and C. albicans and the effectiveness of the extracts was evaluated relative to those of standard antibacterial agent chloramphenicol and antifungal agent amphotericin B. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the water extract of C. alata against E. coli were 1.6 mg/ml and 60 mg/ml respectively; corresponding data for chloramphenicol were 2 ug/ml. Similarly, the MIC and minimum fungicidal concentration (MFC) for the extract against C. albicans were 0.39 mg/ml and 60 mg/ml in contrast to 0.58 ug/ml and 0.98 ug/ml for amphotericin B. From the dose-response curve plots, the extract had an IC50 of 31 mg/ml for E. coli and 28 mg/ml for C. albicans. The data suggest that C. alata extracts contain agent(s) which have therapeutic potential and might be useful if isolated and developed for the treatment of opportunistic infections of AIDS patients.     

Adesmia aegiceras: antimicrobial activity and chemical study.

The antimicrobial activity of the ethanolic extract of Adesmia aegiceras was studied by the agar-well diffusion method. Antibacterial activity against Micrococcus luteus and eight pathogenic bacterial strains as well as antifungal activity against Candida albicans, was detected. Bacterial and fungal strains exhibited similar concentration-response curves (EC50 and Rmax values) and similar MIC. The MBC/MIC was about 8. These data would indicate the potential usefulness of the A. aegiceras extract as a microbiostatic, antiseptic or disinfectant agent. Furthermore, chemical study of the bioactive alcoholic extract was performed, which revealed quercetin, isorhamnetin-3-rutinoside, isovitexin, pinitol and chlorogenic acid as its main components.     

伊犁黑蜂蜂胶对不同生长状态白假丝酵母菌抑菌作用的体外研究

目的探究伊犁黑蜂蜂胶对白假丝酵母菌游离状态及其生物膜状态的影响。方法采用NCCLS M27-A2酵母微量稀释法结合平板法测定蜂胶对游离状态下白假丝酵母菌的最小抑菌浓度(MIC)和最低杀菌浓度(MBC);玻片法在体外构建白假丝酵母菌生物膜模型,采用MTT法检测蜂胶对白假丝酵母菌生物膜状态下的最低生物膜清除浓度(MBEC)及抑制作用;激光共聚焦显微镜(CLSM)观察不同浓度蜂胶醇提取物对同一时间白假丝酵母菌生物膜的抑菌效果,并进行红蓝荧光染色定量分析。结果伊犁黑蜂蜂胶对浮游白假丝酵母菌的MIC为4mg/mL,MBC为8mg/mL;伊犁黑蜂蜂胶对生物膜状态下白假丝酵母菌的MBEC为16mg/mL,随着药物浓度的增加抑菌性逐渐增大,差异具有统计学意义(P0.05);CLSM观察,伊犁黑蜂蜂胶作用于白假丝酵母菌生物膜后可使生物膜内活菌比例降低,生物膜活性减弱,生物膜内实验菌死亡率随蜂胶浓度增加呈上升趋势,与阴性对照组比较差异有统计学意义(P0.05)。结论伊犁黑蜂蜂胶在体外对不同状态下的白假丝酵母菌均起到了明显的抑制作用。     

Comparison of Protective Effect of Aqueous and Ethanolic Extracts of Propolis against Gastric Ulceration in Rats

This study focused on the protective effects of different types of propolis extracts on gastric mucosa in indomethacin-induced rats. The animals were divided into nine groups: control, negative control (ulcer), positive control (omeprazole), and experimental groups, which were summarized by 200, 400, and 600 mg/kg, bw for aqueous-based and ethanol, respectively. According to the histopathological evaluation, more than others, the doses of 200 and 400 mg/kg of aqueous-based propolis extracts had different degrees of positive effects on the gastric mucosa. Generally, the biochemical analyses of the gastric tissue showed a correlation with microscopic evaluations. According to the phenolic profile analysis, while pinocembrin (684.34±1.70 μg/ml) and chrysin (540.54±9.06 μg/ml) were the most abundant phenolics in the ethanolic extract, ferulic acid (53.77±0.07 μg/ml) and p-coumaric acid (52.61±0.42 μg/ml) dominated the aqueous-based extract. Also, the total phenolic content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity of the ethanolic extract showed almost nine-fold superiority compared to the aqueous-based extracts. Based on data from preclinical data, it was decided that the best doses for the main goal of the study were 200 mg and 400 mg/kg, bw for aqueous-based propolis extract.     

Actividad antifúngica in vitro de la micafungina

BackgroundMicafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses with a wide antifungal spectrum for the most common pathogenic fungi. Micafungin is especially active against the genera Candida and Aspergillus. Its antifungal mechanism is based on the inhibition of the β-1,3- D-glucan synthesis, an essential molecule for the cell wall architecture, with different con sequences for Candida and Aspergillus, being micafungin fungicide for the former and fungistatic for the latter.AimTo describe the in vitro antifungal spectrum of micafungin based in the scientific and medical lite rature of recent years.MethodsWe have done a bibliographic retrieval using the scientific terms, “micafungin”, “activity”, “Candida”, “Aspergillus”, “fungi”, “mycos*”, “susceptibility”, in PubMed/Medline from the National Library of Medicine de EE.UU. from 2005 to 2009.ResultsWe can underline that most than 99% of Candida isolates are susceptible to ≤ 2 μg/ml of micafungin. MIC are very low (≤ 0.125 μg/ml) for most clinical isolates of the species Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei while Candida parapsilosis and Candida guilliermondii isolates are susceptible to anidulafungin concentrations ≤ 2 μg/ml. The activity of micafungin is excellent against those medical important species of Aspergillus. However, its activity is very low against Cryptococcus and the Zygomycetes.ConclusionsThe excellent activity of micafungin has made this antifungal a first line therapeutic indication for candidemia and invasive candidiasis in non-neutropenic patients.     

Synthesis and antimycotic activity of N-azolyl-2,4-dihydroxythiobenzamides

N-pyrazole and N-1,2,4-triazole derivatives of 2,4-dihydroxythiobenzamide prepared from sulfinyl-bis-(2,4-dihydroxythiobenzoyl) and commercially available azole amines were tested for their antimycotic activity. The chemical structure of compounds was confirmed by IR, 1H NMR, MS and elemental analysis. The MIC values against the reference strain Candida albicans ATCC 10231, azole-resistant clinical isolates of Candida albicans and non-Candida albicans species were determined for their potential activity in vitro. The compounds exhibited comparable or higher activity than itraconazole and fluconazole tested under the same experimental conditions. Pyrazoline derivatives showed higher activity than other analogues. The strongest fungistatic activity for N-(2,3-dimethyl-1-phenyl-1,2-dihydro-5-oxo-5H-pyrazol-4-yl)-2,4-dihydroxythiobenzamide was found with MIC values significantly lower than those for the studied drugs.     

中药提取物对酵母菌抗真菌活性研究

目的探讨6味中药2种方法提取成分对酵母菌的抑菌和杀菌作用。方法采用药基琼脂稀释法,测定6味中药水提和醇提成分对白念珠菌和糠秕马拉色菌的MIC和MFC。结果对白念珠菌：水提黄连、醇提黄柏、醇提土槿皮MIC范围分别为0．625—1．25mg／mL、0．625～1．25mg/mL、0．313—0．625mg／mL;均值均为0．625mg／mL;对糠秕马拉色菌：水提和醇提黄连MIC范围分别为0．625～1．25mg／mL和1．25mg／mL,均值均为1．25mg／mL。对白念珠菌：醇提土槿皮MFC范围0．625～2．5mg/mL,均值0．625rag／mL。结论水提黄连、醇提黄柏和土槿皮对白念珠菌有较强抑菌作用,其中醇提土槿皮有较强杀菌作用。水提和醇提黄连对糠秕马拉色菌有较强抑菌作用。     

In vitro antibacterial activity of Psidium guajava Linn. leaf extract on clinical isolates of multidrug resistant Staphylococcus aureus

In the present study, antibacterial activity of aqueous and organic extracts of Psidium guajava leaves was evaluated against multidrug resistant (MDR) clinical isolates of Staphylococcus aureus strains collected from hospitals in northern (Malabar region) Kerala. The strains which exhibited resistance against all the antibiotics tested was selected for antibacterial assays. Minimum inhibitory concentration (MIC) for methanolic and aqueous extracts was found to be 625 ug/ml and 7.5 mg/ml, respectively. Minimum bactericidal concentration (MBC) recorded for methanolic and aqueous extracts was 1.25 and 12.5 mg/ml, respectively. Methanolic extract at minimum bactericidal concentration inhibited the growth of MDR strain by 80%. Time-kill assay revealed that methanolic extract (4 mg/ml) killed MDR bacteria within 10 hr. Total polypeptide profiling of bacterial cultures by SDS-PAGE indicated a high degree of protein degradative activity of the extract. Finally, a human RBC based haemolytic assay showed absence of haemolysis even at concentrations higher than that of MBC, advocating thereby its safety in therapeutic use.     

N-Phenyl and N-phenylalkyl-maleimides acting against Candida spp.: time-to-kill, stability, interaction with maleamic acids

N-Phenyl and N-phenylalkyl maleimides (alkyl chain=(CH(2))n; n=0-4) and their respective open derivatives (maleamic acids) were evaluated against Candida spp. with the microbroth dilution method following the guidelines of CLSI (formely NCCLS). MIC values of maleimides without pre-incubation and submitted to different pre-incubation times into the growth media, time-to-kill studies as well as a time-dependent UV-spectroscopy study of the maleimides in water, led to determine that maleimides display antifungal activities with their intact maleimide ring, being in addition their activities not dependent on the length of the alkyl chain. They are not only fungistatic but fungicidal with very low MICs and MFCs, displaying strong fungicide activities not only against standardized but also clinical isolates of Candida albicans and non-albicans Candida spp.     

Comparison of In Vitro and Vivo Efficacy of Caspofungin Against Candida parapsilosis, C. orthopsilosis, C. metapsilosis and C. albicans

Caspofungin activity was determined in vitro and in vivo against three Candida orthopsilosis, three C. metapsilosis, two C. parapsilosis sensu stricto and two C. albicans isolates. MIC values and killing activity were determined in RPMI-1640 plus 50?% human serum. Neutropenic (cyclophosphamide-treated) mice were infected intravenously. Five-day intraperitoneal treatment with caspofungin was started after 24?h postinfection. Kidney burden was analyzed using the Kruskal-Wallis test with Dunn's post-test. In killing studies, caspofungin was fungistatic and fungicidal against C. albicans at ≥0.25 and ≥2?μg/ml concentrations, respectively. Caspofungin was fungistatic at ≥8-16, ≥2-8 and at ≥2-8?μg/ml against C. parapsilosis, C. orthopsilosis and C. metapsilosis, respectively. In the murine model, C. albicans was inhibited by 1, 2 and 5 mg/kg of caspofungin (P?相似文献