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Protein-protein interactions (PPI) are involved in a variety of biological processes, including cell-to-cell interactions, metabolism and development control. The misregulation, post-translational modification and interference of PPI are related to a variety of human diseases, making the regulation of these interactions a very attractive field of drug discovery. In recent years, the interaction between MDM2 and p53 has become a research hotspot, which plays an important role in the treatment of tumors. But unfortunately there are no such inhibitors approved all over the world. In this view, recent advances of MDM2-p53 inhibitors were briefly described and its inhibitors with potential therapeutic activities in clinical studies were introduced.
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@#【Objective】To prepare rapamycin（RAPA）sustained-release film and to evaluate its dissolution.【Methods】RAPA sustained- release film was created by using polymer polyactioglyconic acid （PLGA），copolymer of polyactic acid（PLA）and polyglycolic acid（PGA）. Drug content of the sustained-release film was determined using specificity test，recovery，relative standard deviation（RSD）and stability test. Then，the dissolution of the sustained- release film was analyzed.【Results】The concentration of RAPA had a linear relationship with peak area，which ranged between 0.408 μg/mL and 40.8 μg/mL through the standard curve. The specificity test of the drug content determination indicated the excipient of the film and the solution with 0.3% sodium dodecyl sulfate（SDS）did not affect in determining the RAPA content. The recovery and RSD were excellent through drug content determination in blank films，which had three different levels of RAPA concentrations. The mean RAPA content of the sustained-release films was（112.6±10.1）μg（RSD 8.99%）through the drug content determination of the films，and the stability of RAPA with 0.3% SDS was good within 15 days. In addition，dissolution test of the sustained- release film indicated that the amount of drug release reached a high level and sustained up to 15 days.【Conclusion】 The RAPA sustained-release film with certain behavioral characteristic parameters had a stable drug content and favorable sustained-release property，and it may have certain application potential in anti-proliferation after glaucoma filtering surgery.
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Objective To identify the risk factors of hematoma growth in young patients with intracerebral hemorrhage (1CH). Methods A total of 502 patients with spontaneous intracerebral hemorrhage from the cohort of cerebral small vessel disease of Peking Union Medic&l College Hospital were retrospectively recruited from May 2016 to August 2018. Comparison between cerebral hemorrhage with hematoma growth and non-growth wrre peffamed in the young (76cases,
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OBJECTIVE@#To illustrate the molecular mechanisms underlying the therapeutic effects of electroacupuncture (EA) on knee osteoarthritis (OA).@*METHODS@#Twenty-seven six-month-old New Zealand white rabbits were allocated into three groups in accordance with a random number table: normal group (no surgery-induced OA; without treatment), model group (surgery-induced OA; without treatment) and EA group [surgery-induced OA; received treatment with EA at acupoints Dubi (ST 35) and Neixiyan (EX-LE 5), 30 min twice a day]. After eight consecutive weeks of treatment, the histopathological alterations in cartilage were observed using optical microscopy and transmission electron microscopy, cartilage degeneration was evaluated by modified Mankin's score principles, the synovial fluid concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-3 (MMP-3) were evaluated by enzyme-linked immunosorbent assay, and the protein expression levels of IL-1β, IL-6, TNF-α, MMP-3, IκB kinase-β (IKK-β), nuclear factor of α light polypeptide gene enhancer in B-cells inhibitor α (IκB-α) and nuclear factor-κB (NF-κB) p65 were quantified by Western blot analysis.@*RESULTS@#EA treatment significantly improved cartilage structure arrangement and reduced cellular degeneration. The IL-1β, IL-6, TNF-α and MMP-3 of synovial fluid in the EA-treated group were significantly decreased compared with the model group (all P<0.01). Compared with the model group, the IL-1β, IL-6, TNF-α, MMP-3, IKK-β and NF-κB p65 protein expressions in cartilage of EA-treated group were significantly decreased (all P<0.01), whereas IκB-α expression was significantly up-regulated (P<0.01).@*CONCLUSION@#EA treatment may delay cartilage degeneration by down-regulating inflammatory factors through NF-κB signaling pathway, which may, in part, explain its clinical efficacy in the treatment of knee OA.
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<p><b>OBJECTIVE</b>To explore the safety testing evaluation index of breast-feeding by hepatitis B-positive mothers.</p><p><b>METHODS</b>HBV DNA from serum and breast milk of 252 hepatitis B-positive mothers were detected with the real-time quantitative PCR.</p><p><b>RESULTS</b>The total positive rate of HBV DNA in serum had no difference with that in breast milk in hepatitis B-positive mothers (P > 0.05). The positive rate of HBV DNA in serum and breast milk of positive HBeAg were significantly higher than that of hepatitis B-positive mothers with negative HBeAg (P < 0.01).</p><p><b>CONCLUSION</b>To detecte HBeAg and HBV DNA in serum and breast milk have important significance for guiding of breast feeding of hepatitis B-positive mothers.</p>
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Adult , Female , Humans , Pregnancy , Breast Feeding , DNA, Viral , Hepatitis B , Virology , Hepatitis B e Antigens , Milk, Human , Virology , Pregnancy Complications, Infectious , VirologyABSTRACT
Objective To investigate the effect and mechanisms of recipient-derived immature dendritic cells(imDC) transfected with IKK2dn and loaded with donor antigen on renal allografts survival in the rats.Methods DC were cultured from recipient rats'(Lewis) bone marrow,transfected with IKK2dn and loaded with donor antigen.The expression of CD86 and MHC Ⅱ was detected,and the ability of DC stimulating lymphocyte proliferation in vitro was measured.Male Brown Norwav rats and Lewis rats were used as donors and recipients respectively.Four groups were set up(DC group,empty transfection group,transfection group and control group),receiving 1×10~7 DC,Adv-0-DC,Adv-IKK2dn-DC loaded with BN antigen,and equal volume of normal saline,respectivelv 7 davs before transplantation.In the third party donor-group,Wistar rats as donors were treated the same as DC;group before transplantation.After transplantation,the T lymphocyte proliferation in reciPients was measured and the expression of serum IL-2 and IFN-γ was detected.The survival time of recipients and the acute reiection were observed.Pathological changes were examined tO identify the grade of rejection.Results DC assessment in vivo revealed that the transfected DC could still express CD86 and MHC Ⅱ in a low level as compared with those not transfected with IKK2dn. After DC were loaded with donor's antigen,the expression of CD86 and MHC Ⅱ was up-regulated.After DC were transfected with IKK2dn before loaded with donor's antigen, the expression of CD86 and MHC Ⅱ had no significant change. When DC were loaded with donor's antigen, its allostimulatory activity of T lymphocyte proliferation was enhanced (P<0. 05). When DC were transfected with IKK2dn before loaded with donor's antigen, its allostimulatory activity of T lymphocyte proliferation was not enhanced. Compared with control groups, IKK2dn-transfected DC pulsed with BN splenocyte lysate markedly prolonged the survival of renal allografts (26. 8±1.76d, P<0.01), and elicited markedly lower proliferative responses and reduced IL-2 and IFN-γ production. The pathological grade of rejection was low in the transfection group. Conclusion Recipient-derived imDC transfected with IKK2dn and loaded with donor splenocyte lysate could prolong the renal allograft survival in rats probably by down-regulating the expression of DC costimulatory molecules and inhibiting the T_H 1 cytokine production.
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<p><b>OBJECTIVE</b>To assess the efficacy, safety, procedural success and long-term clinical outcome in patients underwent percutaneous carotid stenting with distal device.</p><p><b>METHODS</b>Percutaneous carotid stents with distal device were implanted to 58 patients with 59 significant (> 75%) carotid artery stenosis (49 men, mean age 68 years) between January 2000 to December 2005. Forty-five out of 58 patients were symptomatic, 35 had coronary artery diseases and 10 had previous strokes.</p><p><b>RESULTS</b>Sixty one carotid stenting were implanted to 59 lesions in 58 patients. Stents with filter devices were successfully implanted in 57 out of 58 (98%) patients. Angioplasty success rate was 100%. Aspirin (300 mg/d) and Clopidogrel (75 mg x 2/d) were administered 3 days prior operation and clopidogrel was discontinued 30 days post stenting and aspirin was continued at dose of 100 mg/d. The percentage of stenotic carotid artery reduced from 85.3% to 6.2% after stenting and the diameter increased from 1.3 +/- 0.9 mm to 5.2 +/- 1.1 mm. Two minor strokes (3.4%) occurred during operation and at 14 days post stenting. All patients were discharged from the hospital after an average of 2.5 days hospitalization. At 14 +/- 2 months follow up, all patients survived and there were 2 asymptomatic restenosis (50% and 70% and the latter underwent successful balloon angioplasty), 2 myocardial infarctions (1 non-Q wave and 1 Q wave myocardial infarction, all underwent successful emergent PCI) and 2 minor strokes occurred at 6 and 8 months post stenting.</p><p><b>CONCLUSION</b>Carotid stenting with distal device appears to be safe and effective in treating patients with carotid artery stenosis.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Angioplasty, Balloon , Blood Vessel Prosthesis Implantation , Methods , Carotid Stenosis , Therapeutics , Follow-Up Studies , Stents , StrokeABSTRACT
<p><b>OBJECTIVE</b>To establish the optimized preparation procedure and study the method to determine the content for soybean isoflavone(SIF) Dropping Pills.</p><p><b>METHOD</b>The preparation conditions, such as the proportion between SIF and PEGs, the temperature of mixture of SIF and PEGs, dropping distance, etc., were studied with Uniform Design and One-way ANOVA. SIF was identified by TLC and the content of SIF was determined by UV spectrometry at 262 nm detection wavelength.</p><p><b>RESULT</b>Three batches of the prepared products meet the standards of the Chinese pharmacopoeia on dropping pills. SIF can be identified by TLC. Using UV spectrometry, the linear range of SIF was 0. 407 2 to 4. 072 g x mL(-1) and the correlation coefficient was 0. 999 8. In high, middle and low concentration, average recovery were 96. 54%, 97.27% and 97.21%, respectively (RSD were 1.3%, 0.78% and 0.71%).</p><p><b>CONCLUSION</b>The preparation procedure is feasible, simple and suitable, the method established in this paper can be adopted for the quality control of SIF dropping pills, and the determination method is simple, relatively fast and accurate.</p>