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ObjectiveTo observe the clinical efficacy of Jiawei Xiaochaihutang combined with microwave ablation （MWA） in the treatment of primary hepatocellular carcinoma （HCC） and its influence on tumor microenvironment. MethodA total of 128 patients were randomly divided into control group （64 cases： 2 cases of dropout，2 cases of elimination，and 60 cases of completion） and observation group （64 cases： 3 cases of dropout，2 cases of elimination，and 59 cases of completion）. Both groups were given comprehensive treatment after MWA surgery. Patients in control group took Biejiajian Wan orally （3 g/time，3 times/d）， and those in observation group took Jiawei Xiaochaihutang （1 dose/d）. The treatment lasted for 3 consecutive months. The size of solid tumor before and after treatment was evaluated to record the progression-free survival （PFS）. The alpha-fetoprotein-L13 （AFP-L3），des-γ-carboxy prothrombin （DCP），Golgi protein 73 （GP73），tumor necrosis factor-α （TNF-α），transforming growth factor-β （TGF-β），vascular endothelial growth factor （VEGF） and matrix metalloproteinase-2 （MMP-2） levels，as well as performance status （PS），liver function and syndrome of liver depression and Qi stagnation scores were also detected before and after treatment. In addition， the incidence of side effects of grade Ⅲ and above was compared. ResultThe total effective rate of solid tumor in observation group was 91.53% （54/59），higher than that （76.67%， 46/60） in control group（χ2=4.895，P<0.05）. The PFS in observation group was （7.16±0.95） months， longer than that （6.24±0.89 months） in control group （P<0.01）. The effective rate of traditional Chinese medicine （TCM） syndrome in observation and control groups were 88.14% （52/59）and 70.00% （42/60）， respectively （χ2=5.897，P<0.05）. The observation group （57.63%，34/59） had higher marked effective rate of TCM syndrome than control group （31.67%，19/60） （χ2=8.116，P<0.01）. The AFP-13，DCP，GP73，TNF-α，TGF-β，VEGF and MMP-2 levels and the PS，liver function and syndrome of liver depression and Qi stagnation scores in observation group were lower than those in control group （both P<0.01）. The cumulative incidence of side effects of grade Ⅲ and above in observation and control groups was 16.95% and 33.33%， respectively（χ2=4.261，P<0.05）. ConclusionConsolidation treatment of HCC after MWA surgery with Jiawei Xiaochaihutang relieved symptoms and side effects，improved PS and liver function，regulated tumor microenvironment，inhibited tumor markers and prolonged survival time. The clinical effect was better than that of Biejia decoction pill， and thus it was worthy of clinical use.
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@#【Objective】 To explore the effects and the possible mechanism of RNA targeting membrane-bound prostaglandin E2 synthase l（mPGES- 1）on proliferation，apoptosis and drug resistance of leukemia cell line K562/A.【Methods】RNA interference was used to inhibit the expression of mPGES-1 of K562/A cells. Four groups were set up as follows：untreated group（K562/A），negative control group after interference（K562/A-NC），group after interference（K562/ A-KD），and group after interference with exogenous PGE2（K562/A-KD+PGE2）.Cell viability was assessed by CCK-8 assay. Cell apoptosis was analyzed by flow cytometry. Concentration of PGE2 was detected by ELISA. Proteins expression was detected by western blot.【Results】The expression of mPGES- 1 in K562/A cells was significantly down- regulated and the synthesis of PGE2 decreased（P < 0.000 1）after RNA interference. After RNA interference，the proliferation of K562/A cells was inhibited and apoptosis increased，and the sensitivity to chemotherapy drugs was enhanced（P < 0.05）. Meanwhile，the expression of β-catenin and MDR1 was decreased（P < 0.01）. Exogenous PGE2 could reverse the effect of RNA interference on proliferation ，apoptosis and drug sensitivity in K562/A cells（P < 0.05），and up-regulate the expression of β-catenin and MDR1（P < 0.01）. XAV939，an inhibitor of β-catenin，could down-regulate the expression of β- catenin and MDR1 in an dose- dependent pattern in K562/A cells（P < 0.05）.【Conclusions】RNA interference of mPGES- 1 could inhibit proliferation，induce apoptosis and reverse drug resistance in K562/A cells. The mechanism was related to reducing the synthesis of PGE2 and thus down- regulating the expression of β- catenin and MDR1. Wnt/β- catenin signal pathway may participate in the regulation of MDR1 by mPGES-1/PGE2.
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This study using traditional Chinese medicine inheritance support software(TCMISS) to analyze the prescription rules of Tibetan medicine containing Terminalia chebula in the Encyclopedia of Chinese Medicine-Tibetan Medicine, Tibetan Medicine Composition Preparation of Modern Research and Clinical Application and Common Interpretation of Tibetan Medicine and so on. TCMISS(V2.5) was used to build a prescription database of Tibetan medicine containing T. chebula.The software statistical statement module, association rules and improved mutual information method and other data mining technologies were adopted to analyze the common herbs, combination rules and core combination of prescriptions containing T. chebula.Total 502 prescriptions containing T. chebula were analyzed and 14 common herbal combinations were summarized, whose ingredients mostly had the functions of clearing heat and detoxicating, promoting blood circulation and stopping pain, warming the middle-jiao and promoting the circulation of Qi. Prescriptions containing T. chebula were commonly used to treat 640 kinds of diseases, there are 22 kinds with high frequency(≥12) in which the representative "Tripa" disease, antiquated febrile symptoms, food poisoning had the highest frequency.T. chebula had different therapeutic effects through different compatibility.The complex composing and medication regularities of Tibetan medicine containing T. chebula have been clarified by TCMISS. That will provide reference for the clinical application of T. chebula and the new development.
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MicroRNA (miRNA) is newly discovered,a class of small non-coding RNA which plays critical roles in the regulation of gene expression at the posttranscriptional level by either degrading or blocking translation of messenger RNA targets.Growing evidence that some miRNAs have crucial roles in controlling and modulating immunity,while dysregulation of miRNAs can lead to autoimmunity,and miRNA-146 seems to be a popular topic discussed much.Thyroid associated ophthalmopathy (TAO) is an organ specificity autoimmune disease which is closely associated with Graves disease.Although many clinical and experimental investigations have been done,the precise aetiology and pathogenesis of TAO remain largely unclear.Here we review the roles of miRNA-146 regulation in immune functions and in the development of autoimmunity and autoimmune disease,and outlook for the roles of miRNA-146 in the pathogenesis of TAO.
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Sperm membrane fluidity is one of the causes of male infertility, and it is thought to be related with temperature, reactive oxygen species, oxygen free radicals, anti-sperm antibodies, stilbestrol, and fenvalerate. A deeper insight into the influencing factors of sperm membrane fluidity is of vital importance for in vitro sperm preservation, revival of frozen-thawed sperm, in vitro fertilization and management of male infertility.
Subject(s)
Humans , Male , Infertility, Male , Membrane Fluidity , Semen Preservation , Sperm Motility , Sperm-Ovum Interactions , Spermatozoa , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of Hedgehog-Gli1 signaling pathway on proliferation, apoptosis and activation of hepatic stellate cells (HSCs) in vitro.</p><p><b>METHODS</b>The expression of Shh, Smo, Ptc and Gli-1 in HSC-T6 cells was analyzed by RT-PCR. HSC-T6 cells were incubated with various concentration of cyclopamine (0, 50, 100, 150, 200, 250 mumol/L) for 24 hours, cell viability was checked by MTT colorimetric assay, cell cycle was analyzed by flow cytometry, apoptosis was assayed by agarose electrophoresis of DNA and PI-Annexin V fluorescent staining, and the mRNA levels of Gli-1, TGF beta 1, PDGF and Bcl-2 were quantified by real-time RT-PCR.</p><p><b>RESULTS</b>RT-PCR indicated that the components of the Hedgehog-Gli1 signaling pathway were expressed in HSC-T6 cells. MTT assay indicated that cyclopamine inhibited cell viability in a concentration dependant manner (F = 636.81, P less than 0.01). Flow cytometry indicated that cells were piled up at G0/G1 phase in cyclopamine treated cells (65.08%+/-1.50%) as compared to control cells (55.41%+/-2.54%, t = -8.05, P less than 0.01). Cyclopamine treatment resulted in apoptosis as indicated by DNA fragmentation and PI-Annexin V staining. The mRNA levels of Gli-1, TGF beta 1, PDGF and Bcl-2 in cyclopamine treated cells were significantly lower than that in control cells (P less than 0.01).</p><p><b>CONCLUSION</b>Cyclopamine may inhibit the Hedgehog-Gli1 signaling, and hence repress proliferation and promote apoptosis in hepatic stellate cells.</p>