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The threat of fungal diseases is increasingly rigorous. The clinically invasive fungal infections remain a main cause of morbidity and mortality in certain high-risk groups, especially in critical patients or immunocompromised patients. In drug therapy, the problems of off-target toxicity and antifungal drug resistance are still challenging. With the wide application of biomaterials and nanotechnology, more nanomedicine studies have been carried out on antifungal drugs, such as the amphotericin B liposome which greatly reduced the renal toxicity of drugs has been successfully marketed. For the unique physical and chemical properties, the nano-drug delivery system possessed great potential in improving the bioavailability, reducing the side effects of drugs, increasing the stability of drugs, and achieving cells or tissue-specificity through the modification. This review summarized the applications and limitations of antifungal drugs. Some nanomedicines were summarized in discussion oriented around the antifungal therapy, including liposomes, niosomes, lipid nanoparticles, polymer nanoparticles, microemulsion, dendrimers, inorganic nanocarriers. Nanotechnology and nano-drug delivery system provide promising strategies for the research and development of new formulations that can improve antifungal activity and possibly overcome antifungal drug resistance.
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Systemic lupus erythematosus (SLE) is a complex autoimmune syndrome characterized by various co-existing autoantibodies (autoAbs) in patients' blood. However, the full spectrum of autoAbs in SLE has not been comprehensively elucidated. In this study, a commercial platform bearing 9400 antigens (ProtoArray) was used to identify autoAbs that were significantly elevated in the sera of SLE patients. By comparing the autoAb profiles of SLE patients with those of healthy controls, we identified 437 IgG and 1213 IgM autoAbs that the expression levels were significantly increased in SLE (P < 0.05). Use of the ProtoArray platform uncovered over 300 novel autoAbs targeting a broad range of nuclear, cytoplasmic, and membrane antigens. Molecular interaction network analysis revealed that the antigens targeted by the autoAbs were most significantly enriched in cell death, cell cycle, and DNA repair pathways. A group of autoAbs associated with cell apoptosis and DNA repair function, including those targeting APEX1, AURKA, POLB, AGO1, HMGB1, IFIT5, MAPKAPK3, PADI4, RGS3, SRP19, UBE2S, and VRK1, were further validated by ELISA and Western blot in a larger cohort. In addition, the levels of autoAbs against APEX1, HMGB1, VRK1, AURKA, PADI4, and SRP19 were positively correlated with the level of anti-dsDNA in SLE patients. Comprehensive autoAb screening has identified novel autoAbs, which may shed light on potential pathogenic pathways leading to lupus.
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OBJECTIVE@#To analyze the expression profile of serum cytokines in patients with systemic sclerosis (SSc) and explore its possible regulatory mechanisms.@*METHODS@#Serum and DNA of peripheral blood mononuclear cells were collected from 30 SSc patients and 80 normal controls (NCs). According to the presence or absence of interstitial lung disease (ILD) in SSc, the patients were divided into SSc with ILD group and SSc without ILD group. According to the degree of skin involvement, the patients were divided into diffuse systemic scleroderma (dcSSc) group and limited systemic scleroderma (lcSSc) group. According to the presence of anti-topoisomerase-1 antibody (anti-Scl-70 antibody) in the serum of patients with SSc, they were divided into SSc Scl-70 (+) group and SSc Scl-70 (-) group. 27 cytokines in serum were detected by Luminex MAGPIX detection system and Bio-Plex Pro Human Cytokine 27-plex Assay kit: interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12P70, IL-13, IL-15, IL-17, basic fiber growth factor (BASIC FGF), eotaxin, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), interferon-gamma induced protein 10(IP-10), monocyte chemotactic protein 1(MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein 1β(MIP-1β), platelet-derived growth factor BB (PDGF-BB), regulated on activation in normal T-cell expressed and secreted (RANTES), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor(VEGF). Methylation sites were detected by Illumina 450K methylation chip.@*RESULTS@#Compared with NCs group, the expression of 12 cytokines (BASIC FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1β, IL-1ra, IL-6, IP-10, MCP-1, TNF-α and RANTES) in the SSc group significantly increased (P<0.05), IL-5 was decreased expression in the SSc group (P<0.05), there was no significant difference in the expressions of the other 14 cytokines. Compared with lcSSc group, 9 cytokines (eotaxin, IL-5, MCP-1, IL-2, RANTES, IL17A, IL-8, MIP-1β and PDGF-BB) increased in dcSSc group, but there was no significant difference. Compared with SSc without ILD group, IL-15 increased in SSC with ILD group [18.2 (172.97) ng/L vs. 2.03(0.05) ng/L, P<0.05]. Compared with SSc Scl-70 (-) group, the expression of IP-10 decreased in SSc Scl-70 (+) group [1 030 (2 196.6) ng/L vs. 1 878 (2 964) ng/L, P<0.05]. The correlation analysis of serum cytokines with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) showed that IL-6 was positively correlated with ESR (r =0.04, P= 0.017), MCP-1 (r=0.49, P=0.043) and MIP-1β (r=0.41, P=0.007) positively correlated with CRP. By analyzing the changes of methylation sites of cytokines, it was found that cg17744604 in IL-10 TSS1500 region, cg06111286 in IL-12P70 TSS200 region, cg07935264 in IL-1β TSS200 region, cg01467417 in IL-1ra TSS1500 region, cg03989987 in IL-1ra 5'UTR region and cg21099624 in VEGF TSS200 region were all hypomethylated.@*CONCLUSION@#There were different cytokines expression profiles in the serum of SSc patients, and the altered cytokines were correlected with the degree of skin damage and pulmonary fibrosis. Many cytokines were regulated by methylation.
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Humans , Cytokines , Leukocytes, Mononuclear , Scleroderma, Systemic , Tumor Necrosis Factor-alpha , Vascular Endothelial Growth Factor AABSTRACT
<p><b>OBJECTIVE</b>To explore the pathomorphological change of the atlanto-occipital segment of vertebral artery (V3 part) related with cervical vertigo.</p><p><b>METHODS</b>From June 1999 to November 2011, the pathomorphological change of the atlanto-occipital segment of vertebral artery were observed in 1680 patients with cervical vertigo using 3D-CTA technology. The clinical data of these patients were analyzed. There were 783 males and 897 females, aged from 22 to 70 years old with an average of 52.8 years old. Doppler examination showed vertebral basilar artery flow velocity to speed up or slow down.</p><p><b>RESULTS</b>The blood vessel of 3360 branches were detected in 1680 patients and 2778 branches were detected out vascular anomaly. And 829 branches were in V1 segment, 421 were in V2, 328 were in V3, 1190 were in V4. The pathomorphological changes in the atlanto-occipital segment (V3) of vertebral artery included angiospasm, congenital absence, abnormal exit, localized stenosis.</p><p><b>CONCLUSION</b>There are 4 kinds of pathomorphological changes in the atlanto-occipital segment of vertebral artery related with cervical vertigo. The 3D-CTA result can be used to judge prognosis and adopt reasonable treatment for the patients.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Atlanto-Occipital Joint , Cervical Vertebrae , Tomography, X-Ray Computed , Vertebral Artery , Diagnostic Imaging , Pathology , Vertigo , PathologyABSTRACT
Stable isotope labeling by amino acids in cell culture (SILAC) is an in vivo metabolic labeling technique based on the abundance ratio of mass spectrometry. Combined with different methods of proteins affinity enrichment, SILAC can obtain sensitive, accurate and quantitative information of proteins. This article reviewed the history, rationale, characteristics and application of SILAC, with special focus on its role in studying protein interactions with small molecules, quantitative proteomics and post-translational modification of proteins.
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Objective To observe the expression of immune substances secreted by peripheral bloodγδT cells after stimulated by early secreted antigenic target-6(ESAT-6),and explore its mechanism of signaling pathway.Methods Peripheral blood mononucle-ar cells(PBMC)were collected from health human blood with the ficoll density gradient centrifugation method,and theγδT cells were separated from the PBMC with flow cytometry;the inhibitor of TLR-4 signaling pathway(E5564)was used to cocultured withγδT cells to inhibit the function of TLR-4,and the change of TLR-4 was analyzed by the methods of PCR and Western blot.ESAT-6 were used to stimulate theγδT cells,and the control group without any stimulating factor was established,then the expression levels of IL-17,TNF-α,IFN-γwere determined by ELISA method after 0、1、3、6、9 and 12 days.Results The results of PCR and Western blot showed that ESAT-6 could increase the expression of TLR-4(P<0.01);The results of ELISA showed that ESAT-6 could enhance the expression of IL-17,TNF-αand IFN-γ(P<0.01),and the inhibitor of TLR-4(E5564)could decrease the expres-sion of IL-17,INF-α,IFN-γ(P<0.01).Conclusion ESAT-6 can induceγδT cells to produce more IL-17,TNF-α,IFN-γ,and the mechanism of which maybe concerned with TLR-4 signaling pathway.
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<p><b>OBJECTIVE</b>To study the clinical efficacy of the frog shape four-step pulling method for the treatment of sacroiliac joint subluxation, and to explore the rationality of the method.</p><p><b>METHODS</b>Among 92 patients diagnosed as sacroiliac joint subluxation, 19 patients were male and 73 patients were female,ranging in age from 14 to 61 years, with an average of 38.7 years. The course of disease ranged from 1 month to 96 months,with an average of 18.4 months. All the patients were treated with the frog shape four-step pulling method. The therapeutic effects were observed.</p><p><b>RESULTS</b>The treatment times ranged from 1 to 10 (averaged 4.3 times). According to evaluation standard of sacroiliac joint subluxation, 71 patients got an excellent result, 19 good, 1 fair and 1 bad.</p><p><b>CONCLUSION</b>The frog shape four-step pulling method had many advantages such as simplicity of operation, targeted, high rate of success, not easy rebound and less pain for patients and so on.</p>
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Adolescent , Adult , Female , Humans , Male , Middle Aged , Joint Dislocations , Therapeutics , Manipulation, Orthopedic , Methods , Sacroiliac Joint , Wounds and InjuriesABSTRACT
<p><b>OBJECTIVE</b>To discuss the influence of manipulation on cervical vertigo arteria vertebralis morphology and blood flow speed.</p><p><b>METHODS</b>Forty-five patients with cervical vertigo included 27 males and 18 females with an average age of 41.6 years old ranging from 25 to 60. The course of disease was from 2 weeks to 5 years. TCD were applied to test arteria vertebralis blood flow speed and 3D-CTA applied to inspect arteria vertebralis morphology as the observation targets. According to the morphology change different stage localization, the 3-step manipulation were adopt to observe the arteria vertebralis blood flow speed and the morphology influence.</p><p><b>RESULTS</b>After cervical manipulation, the scoring of vertigo symptoms were improved remarkable (P<0.001); Among the patients of blood flow speed reduced and the patients of blood flow speed increased, the Vm before treament compared with after treament, there were statistical difference (P<0.01). The arteria vertebralis morphology partial patient had changed.</p><p><b>CONCLUSION</b>The cervical manipulation exceptionally has the bidirectional control action to arteria vertebralis morphology change and blood flow speed in the cervical vertigo, and can cause the partial blood tubular-shaped condition to have the reversal changed.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Acupuncture Points , Blood Flow Velocity , Brain , Pathology , Cerebrovascular Circulation , Physiology , Cervical Vertebrae , Exercise Therapy , Head Movements , Manipulation, Spinal , Methods , Risk Factors , Vertebral Artery , Pathology , Vertigo , Diagnosis , PathologyABSTRACT
<p><b>OBJECTIVE</b>To explore an effective method for treating Gentamicin-induced deafness and the mechanism.</p><p><b>METHODS</b>Guinea pigs were randomly divided into 5 groups: normal control group (group A), model group (group B), Ligustrazine group (group C), acupuncture group (group D) and Ligustrazine plus acupuncture group (group E). The group C, D and E were treated respectively by simple Ligustrazine, simple acupuncture at "Tinggong" (SI 19), "Yifeng" (TE 17), and "Waiguan" (TE 5), and Ligustrazine plus acupuncture. Ten days later, the auditory brainstem response (ABR) thresholds for the wave III , apoptosis and expressions of Bcl-2 and Bax proteins in the organ of Corti of the guinea pig were detected.</p><p><b>RESULTS</b>In the group E, the ABR threshold was significantly lower than that in the group C (P<0.05), and apoptotic cells, the expression of Bax protein and the ratio of Bax/Bcl-2 were lower than those in the group C and D in the organ of Corti, and Bcl-2 protein expression was increased.</p><p><b>CONCLUSION</b>Acupuncture at "Tinggong" (SI 19), "Yifeng" (TE 17), and "Waiguan" (TE 5) has a certain target-synergistic action on Ligustrazine and can increase therapeutic effect of Ligustrazine on Gentamicin-induced deafness, which are possible related with the inhibition of apoptosis, down-regulation of Bax expression and up-regulation of Bcl-2 expression.</p>
Subject(s)
Animals , Female , Male , Acupuncture Therapy , Anti-Bacterial Agents , Toxicity , Deafness , Therapeutics , Evoked Potentials, Auditory, Brain Stem , Gentamicins , Toxicity , Guinea Pigs , Pyrazines , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To describe the epidemiology of neural tube defects (NTDs) in high- and low-prevalence areas of China.</p><p><b>METHODS</b>Birth defects surveillance data, collected from 1992 through 1994 was analyzed. These data were collected as part of the Sino-American cooperative project on NTDs prevention. We classified NTDs as anencephaly, encephalocele, high-level and low-level spina bifida (SB) according to location of the lesion (high vs low) and whether the defect was isolated or occurred in association with other birth defects. Rates were compared in the high-prevalence (North) region and the low-prevalence (South) region, after adjusted for classification, urban and rural, season and sex, and calculated the adjusted rate of NTDs.</p><p><b>RESULTS</b>Among seven hundred and eighty-four NTDs cases in 326 874 recorded births (include in livebirth, stillbirth and fetal death with a gestational age of at least 20 weeks), the overall NTDs prevalence in the North was 5.57/1,000 births, and in the South was 0.88/1 000. There were also significant differences in the prevalence of anencephaly, encephalocele, high-level and low-level SB between North (0.97, 0.49, 2.75 and 1.11/1,000 birth) and South (0.36, 0.15, 0.21 and 0.14/1,000 birth) (P < 0.01), with adjusted prevalences in the North 3 - 7 times higher than those in the South. There were significant difference between urban (2.04) and rural areas (6.57/1,000 birth) in the North (P < 0.01), urban (0.52) and rural areas (0.95/1,000 birth) in the South (P < 0.05). Adjusted prevalence rates in the rural were 3 - 4 times higher than those of urban in the North and 1.6 - 1.9 times higher than in the South; The seasonal rate of high-level SB increased between September and November in the North (3.44/1,000 birth), while the seasonal rate of anencephaly decreased between September and November (0.18/1,000 birth) in the South. However there were no seasonal changes in other classified NTDs both in the South and North.</p><p><b>CONCLUSIONS</b>The birth prevalence of NTDs in the North of China was the highest in the world. There were significant differences between the North and the South, urban and rural. There was seasonal change in high-level SB in the North, which was in accordance to the phenotype of NTDs. It was suggested that there might exist etiological heterogeneity among anecephalus, low- and high-level SB.</p>
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Female , Humans , Male , China , Epidemiology , Incidence , Neural Tube Defects , Epidemiology , SeasonsABSTRACT
This paper deals with research and manufacture processes of the 8 millimeter wave therapeu- tic apparatus,the application to the clinical treatment for gastric and duodenal ulcer.