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Traditional therapies for alopecia areata, especially moderate to severe alopecia areata and special types of alopecia areata, remain unsatisfactory. Compared with traditional therapies, small-molecule targeted drugs and biological agents have advantages of a more rapid onset of action and more marked efficacy, however, some patients may experience adverse reactions such as infections during treatment or relapses after drug withdrawal. Thus, their efficacy and safety still need to be further evaluated. This review summarizes research progress in small-molecule targeted drugs and biological agents in the treatment of alopecia areata.
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Objective To explore the recyclability and safety of Celect retrievable filter placement in the prevention of pulmonary embolism in patients with deep venous thrombosis(DVT).Methods The data of 120 DVT patients with Celect retrievable filter were collected from the Second Hospital of Shanxi Medical University from August 2015 to March 2017 and analyzed retrospectively. The Celect filter was placed in the inferior vena cava(IVC)at the inferior margin of the renal vein for 1 to 2 cm by puncturing the contralateral femoral vein or right internal jugular vein.The filter retrieve risk was assessed within 8 weeks after being implanted. The filters would be recovered through the right jugular vein when meeting the recovery standard, and the retrieve methods included conventional method, removing the guide wire into a loop trap method and guiding wire into a loop combined with balloon assisted method.The perforation of the vena cava was observed and the tilt angle of the filter was measured.The success rate of Celect filter retrieve was evaluated by the Kaplan-Meier method. Results Celect filters were successfully implanted in 120 patients with DVT.The IVC filters were implanted through femoral vein in 111 patients and 2 cases via right internal jugular vein.No complications,asymptomatic pulmonary embolism and related death was found in all patients.Twenty four patients did not reach the standard of filter retrieve,and were follow-uped.Ninety six cases were treated with Celect retrievable filter,among which,93 cases were successfully recovered with the filter indwelling time ranging from 7 to 144 days and the median being 50 days.The failure of the filter retrieve occurred in 3 cases because of the serious tilt of the filter or the encapsulation of filter by inferior vena cava thrombus.Perforation of vena cava with no clinical symptoms occurred in 21 cases.Filter tilt was found in 35 cases,among which,15 cases had inclined angle>15 degrees or the recovery hook closed to the IVC wall.Thirteen cases with filter tip or recovery hook attached to the wall were successfully removed by using the guide wire into a loop or trap guide wire into a loop combined with balloon assisted method instead of routine removal method.The retrieve rate was 100% when the retention time of Celect filter in the body was within 106 days. Conclusion Celect retrievable filter can be implanted in DVT patients with long retrieve time window and high retrieve rate,but the filter inclination rate and vena cava perforation rate are high.
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Objective To explore main technical points and clinical efficacy of individualized stepwise multiple embolization treatment for refractory hemoptysis. Methods To retrospectively analyze materials of 103 patients treated by individualized stepwise multiple embolization. According to disease categories, individualized stepwise multiple embolization treatment with polyvinyl alcohol and loaded sodium alginate microspheres as basic embolization agent were performed, after the type, number, abnormal branches, pulmonary circulation and systematic pulmonary shunt of targeted vessels were confirmed through radiography. To judge short(less than 3 months), medium(3 to 6 months) and long term(more than 6 months) efficacy, resolution of hemoptysis after operation were assessed. To evaluate efficacy of individualized stepwise multiple embolization treatment for refractory hemoptysis, Kaplan-Meier survival curves were used. According to the features of target vessels to supply blood, patients were classified into with SPS and without SPS. By using Log-Rank test, the effective rates of one-year were compared between them. Results Out of 103 patients, 215 target vessels were demonstrated, among which individualized stepwise multiple embolization was for 196 target vessels, peripheral embolization for 8 vessels, and main trunk embolization in 11 patients. The visits after operation were made to 103 patients after 6 to 50 months, with the medium of 21 months. Hemoptysis was instantly resolved in 97.1%(100/103). The effective rates were 94.5%,93.2%, 89.7%,88.9%,85.2%and 76.6%for one, three, six months and one, two and three years after operation. In 103 patients, patients with SPS were 22 and without SPS were 81. One-year effective rates with and without SPS were (69.50 ± 0.11)% and (98.30 ± 0.03)% , respectively (χ2=11.662,P<0.01). Conclusion Individualized stepwise multiple embolization treatment shows excellent short-term and mid-long term efficacy in the treatment of refractory hemoptysis.
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to common antifungal drugs.
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Objective To establish an animal model of dermatophytosis and to evaluate antifungal efficacy on dermatophytosis with this model. Methods Animal models of dermatophytosis were established by inoculating dermatophyte suspension onto abraded skin on the back of guinea pigs. Thirty- eight healthy guinea pigs were randomly and equally divided into 2 groups, namely, Trichophyton mentagrophytes group (infected with T. mentagrophytes), and Microsporum canis group (infected with M. canis), and each group was classified into three subgroups, i.e., itraconazole group treated with oral itraconazole of 4 mg per kilogram body weight per day from day 0 to day 14 after infection, terbinafine group treated with oral terbinafine of 5 mg per kilogram body weight per day from day 0 to day 14 after infection, and untreated group receiving no therapy. The therapeutic effect was evaluated according to skin lesion score and fungal examination results on day 8, 11 and 14 after infection. Results Obvious lesions were observed and fungal examination was positive in untreated, infected pigs on day 8 after infection. In T. mentagrophytes-infecyted pigs, the skin lesion score on day 8, 11, 14 was 9, 1 and 0 in itraconazole group, 8, 5, and 1 in terbinafine group, 48, 52, 40 in untreated group, respectively, and there was significant difference between treated and untreated groups on the three time points (all P<0.01); the mycological cure rates on the above time points were 66.7%, 83.3%, 83.3%, in itraconazole-treated pigs, 83.3%, 83.3%, 83.3%, in terbinafine-treated pigs, 0, 0, 0 in untreated pigs, respectively, with no significant difference between itraconazole and terbinafine group (all P>0.05) but statistical difference between untreated and treated groups (all P<0.01) on all time points. Meanwhile, in M. canis-infected pigs, the skin lesion score on day 8, 11, 14 reached 3, 0, 0 in itraconazole group, 9, 2, 0 in terbinafine group, 46, 47, 39 in untreated group, respectively, and mycological cure rates 83.3%, 83.3%, 83.3% in itraconazole group, 83.3%, 83.3%, 83.3% in terbinafine group, 0, 0, 0 in untreated group, respectively; significant difference was noticed in the two parameters between the treated and untreated groups (all P<0.01) but not between the two treated groups (all P>0.05). Conclusion Itraconazol and terbinafine exhibit similar excellent antifungal activity in routine model of T. mentagrophytes-and M. canis-dermatophytosis.
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Objective To construct a mutant strain of Aspergillus fumigatus with the mutant pbs2 gene, and to investigate the effect of the mutant gene on the morphology of A. fumigatus, the variation of os-motic pressure and the sensitivity of oxidative stress. Methods S. cerevisiae pbs2 gene homologs was identi-fied in A. fumigatus genome database. A PCR fragment, composed of the 5' flanking sequence(approximate-ly 1 kb) ofpbs20RF and its 3' flanking sequence (approximately 1 kb), was subcloned into a vector pDHt/SK with Xho Ⅰ/Xba Ⅰ enzyme to produce a recombinant plasmid PA. The selected marker pryG amplified from pLAX223 was cloned into PA with BamH Ⅰ/Pst Ⅰ enzyme to produce plasmid PB. PB was transformed into Agrobacterium tumefac/ens and named plasmid At pbs2. Then At pbs2 was transformed into A. fumigatus strain AF293.1 (pyrG) via ATMT to produce the transformants △pbs2. To observe the growth rate and the phenotype on the MM containing different oxidative stress and osmotic pressure between the △pbs2 and the wild type. Results There were no visible difference between △pbs2 and AF293 on the radial growth rate and morphology. △pbs2 mutant was not only more sensitive to osmotic pressure produced by sodium chloride and glycerol but also sensitive to oxidative stress produced by hydrogen peroxide than the wild type. Conclu-sion The pbs2 gene plays a role in osmotic pressure and oxidative stress signal tmnsductions in A. fumiga-tus but only involved in oxidative stress induced by hydrogen peroxide specifically. However, pbs2 gene has a minor effect on growth and morphology in A. fumigatus.
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AIM: To access the difference of the efficacy between terbinafine and itraconazole in the treatment of dermatophyte onychomycosis. METHODS: The Medline, Science Direct On Site (SDOS), and Springer database were searched in detail on the data of the mycological cure rates of the two antifungal agents for treatment of dermaphyte onychomycosis occourring in patients aged from 18 a to 60 a with the published double blind randomized clinical trials and then pooled. The odds ratio (OR) and its 95 % confidence interval (CI) were calculated. RESULTS: Six treatises of double blind randomized clinical trials were selected for this analysis according to the screening criteria. The mycological cure rate of continuous terbinafine 250 mg per day was higher than that of either therapeutic effect of itraconazole pulse 400 mg per day (OR = 5.01, 95 % CI (3.42 - 7.33)) or continuous itraconazole 200 mg per day (OR = 2.58, 95 % CI (1.91 - 3.49)) . CONCLUSION: Terbinafine is more effective than itraconazole in the treatment of dermatophyte onychomycosis.
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Objective:To investigate the efficiency of Agrobacterium tumefaciensmediated transfor-mation of Aspergillus fumigatus by using pyrG as a recessive selectable marker.Methods: FAP1 and SHO1 genes target sequences,composed of a selectable marker pyrG and the flanking sequences of the FAP1 and the SHO1 genes,were cloned into a binary plasmid pDHt/sk,respectively.The produced plasmids were transformed into A.tumefaciens.The A.tumefaciens and uracil auxotroph A.fumigatus were cocultured in induction medium without uricil and uridine at 24 ℃ for 48 h.To inhibit growth of A.tumefaciens and to select transformants,the cultures were transferred to 37 ℃ and incubated for another 48 h.Results: In this study,A.tumefaciens-medidated transformation of A.fumigatus produced high homologous recombination rates,which was 44%(7 of 16) for FAP1 and 35%(7 of 20) for SHO1.Conclusion: Our study showed that A.tumefaciens-medidated transformation by using pyrG as a recessive selectable marker is an efficient tool for target gene deletion of A.fumigatus.
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Objective:To construct the sho1 gene mutant of Aspergillus fumigatus,and to investigate the function of sho1 in adaptation to environmental changes.Methods:Saccharomyces cerivisiae sho1 gene homolog was identified by tblastn searches in A.fumigatus genome database.A PCR fragment,composed of the 5' flanking sequence(approximately 1 kb) of sho1,sho1 ORF,and its 3' flanking sequence(approximately 1 kb),was subcloned into a vector pDHt/SK2 with ApaⅠ/Xba Ⅰ enzyme to produce a recombinant plasmid PA.The selected marker pyrG cut from pLAX223 with Nco Ⅰ/Pst Ⅰ was cloned into PA,and PB was produced.The plasmid PB was transformed into competent Agrobacterium tumefaciens EHA105 by using the freeze/thaw method.The strain of A.tumefaciens was designated as At sho1.Then sho1 was produced via ATMT.The radial growth was observed and compared between sho1 and wild type(wt) on MM,CM and BHI medium,and the sensitivity of sho1 and wt to amphotericin B,itraconazole,voriconazole,and caspofungin investigated.Results:Radial growth had visible difference between sho1 and wt on MM,CM and BHI medium.sho1 mutant was sensitive to high osmotic pressure but not to low osmotic pressure.The susceptibility to antifungal drugs was similar between the sho1 and wt.Conclusion:Slow growth of the sho1 mutant has nothing to do with the different medium.The sho1 gene plays a role in response to osmotic pressure in A.fumigatus,but sho1 has a minor role in the susceptibility to the antifungal drugs despite the slow growth.
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Objective To compare 2 approaches with different culture media which induce hyphal form of Candida albicans.Methods Induction of hyphal form was conducted for 16 C.albicans strains with either RPMI 1640 medium or DMEM medium,at 37 ℃ for 24 h,respectively.The hyphal and yeast forms were counted separately and the ratio of hyphal form to total cells was calculated.Results The ratio of hyphal form to total cells was higher in RPMI 1640 medium than that in DMEM medium at the same incubation time for the majority of strains.The ratio was above 99% for all strains after 7-day incubation with 12 times of passages in RPMI 1640 medium at 37 ℃.Moreover the ratio of hyphal form was significantly higher for fluconazole-susceptible strains than that for fluconazole dose-dependent susceptible and resistant strains in incubation with DMEM medium at 37 ℃.Conclusion Incubation with RPMI 1640 medium at 37 ℃ for 7 days seems a favorable condition to induce hyphal form of C.albicans.
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Objectives To compare the difference of ERG11 partial promoter sequence(-440 ～ -1)between yeast-form and hypha-form of Candida albicans, and the relation between the mutation of ERG11 promoter and the susceptibility of C. albicans to fluconazole. Methods Yeast-form and hypha-form of C. albicans genome DNA were extracted from 4 substrains C. albicans, which were isolated from a single HIV-sero-positive patient. Partial ERG11 promoters of yeast-form and hypha-form of these 4 substrains were amplified by polymerase chain reaction (PCR) and the PCR products were sequenced. Results There was no sequence difference between the yeast-form and the hypha-form of C. albicans in this region. Heterogeneities at position -365, -353, -328, -310, -308, -299, -295, -293, -292, 290, -289 and a single base deletion (-284 delT) were found on one allele of ERG11 promoter region of fluconazole-susceptible substrains. No heterogeneities were observed in dose-dependent fluconazole-susceptible and fluconazole-resistant substrains. Conclusions There is no difference of ERG11 partial promoter sequence between the yeast-form and the hypha-form C. albicans. The mutation of ERG11 promoter may be associated with the resistance of C. albicans to fluconazole.
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Objective To prepare stable silybin oral microemulsion. Methods The formulation of the silybin oral microemulsion was optimized by the combination of surface tension measure, pseudo-ternary phase diagram drawing and orthogonal design. Results Microemulsion type was identified. Average particle diameter was measured. Distribution of silybin in microemulsion was measured by ultracentrifugation. The centrifugalization and influencing factors experiment of microemulsion were carried out,which could keep homogeneous and stable for three months on the storage condition of room temperature. Meanwhile,the influence of high-temperature and illumination was a little. Conclusion Stable oral microemulsion silybin can be prepared in this formulation, with fine-looking and desirable stability which is better for the further studies.
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To summarize the application of proteomics to modernization research of Chinese materia medica (CMM) and offer the reference for modernization of CMM and new medicine preparation exploitation. Based on the references and our project group studies in proteomic of drug biosynthesis pathway and metabolization;the main content,technology strategies and important application of the proteomics were introduced significantly;and the further development of protemics was analyzed. The proteomics will become one of absolutely necessary tackles in the modernization research of CMM.
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A new strain of Streptomyces regensis was isolated from soil to produce a novel antibiotic AGPM possessing a strong antitumor activity In order to study on the metabolic path of the novel antibiotic AGPM, the protein patterns from the strain of Streptomyces regensis at different culture period were analyzed by using two eimensional polyacrylamide gel electrophoresis Comparing with sample from growth phase, seventeen new protein spots were found in that from antibiotic production phase The results demonstrated that the special proteins might be related with the antibiotic AGPM biosynthesis from Streptomyces regensis