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Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnerability of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.
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Hyperuricemic nephropathy （HN）， a secondary renal damage common in clinical practice， is characterized by early concealing and continuous progression. The understanding of HN in traditional Chinese medicine （TCM） is from a macroscopic perspective. According to the TCM theory， HN is caused by the combination of external pathogens and internal injuries， with the main pathogenesis being root deficiency combined with superficial excess and deficiency-excess in complexity. In western medicine， the understanding of HN is from the microscopic perspective， which holds that the occurrence of HN is the result of inflammation， oxidative stress， renin-angiotensin-aldosterone system （RAAS） activation， and metabolic abnormalities. The TCM syndromes of HN include internal dampness and heat， obstruction in dampness and turbidity， deficiency of spleen and kidney， and deficiency of kidney yin. Accordingly， the prescriptions should clear heat and dampness， remove dampness and turbidity， tonify spleen and kidney， and nourish kidney yin， respectively. In addition to TCM prescriptions， single herbal medicines and their extracts， Chinese patent medicines， and external applications of Chinese medicines have played a significant role in the treatment of HN， promoting the application of TCM in the treatment of HN. Moreover， the integrated traditional Chinese and western medicine has also played a role in the treatment of HN， enriching the treatment schemes of HN. Different from common kidney diseases such as acute and chronic glomerulonephritis and nephrotic syndrome， HN with particularity should be carefully differentiated in clinical practice. This article systematically summarizes the research progress in the treatment of traditional Chinese medicine and integrated traditional Chinese and western medicine on hyperuricemic nephropathy with TCM and integrated traditional Chinese and western medicine， aiming to enrich the system and theory of HN treatment and further guide the clinical practice.
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Objective:To analyze the characteristics of sleep disorders in patients with Parkinson disease (PD) and to explore the relationship between respiratory events and rapid eye movement sleep with hypotonia.Methods:Thirty-nine PD patients compared with 75 controls matched with gender, age and body mass index(BMI) were collected in the Dalian Municipal Central Hospital from January 1, 2019 to September 31, 2019. Both groups underwent polysomnography monitoring. The characteristics of sleep disorders were analyzed and discussed.Results:Apnea and hypopnea index (AHI) during total sleep, AHI during non-rapid eye movement(NREM) sleep, AHI during rapid eye movement (REM) sleep, obstructive apnea index, mixed apnea index, central apnea index, total apnea index, hypopnea index, the time with pulse oximetry <90% and oxygen desaturation index in the PD group were lower than those in the control group: 3.70(0.80, 20.00) /h vs. 17.30(7.30, 28.20)/h, 2.30(0.70, 13.90)/h vs. 15.20(4.90, 27.50)/h, 2.30(0.00, 29.80)/h vs. 16.90(5.70, 39.50)/h, 0.30(0.00, 5.10)/h vs. 3.10(0.50, 7.80)/h, 0.00(0.00, 0.20)/h vs. 0.20(0.00, 0.60)/h, 0.00(0.00, 0.30)/h vs. 0.30(0.00, 0.80)/h, 0.70(0.00, 6.00)/h vs. 3.90(0.80, 10.70)/h, 1.70(0.50, 8.90)/h vs. 8.70(2.70, 14.90)/h, 0.00(0.00, 0.40)min vs. 0.20(0.00, 1.70)min, 4.10(1.10, 18.40)% vs. 16.50(9.30, 30.80)%, and the differences were statistically significant ( P<0.05). The mean pulse oximetry and minimum pulse oximetry in the PD group were higher than those in the control group: 96.00(95.00, 97.00)% vs. 95.00(94.00, 96.00)%, 89.00(82.00, 91.00)% vs. 85.00(81.00, 89.00)%, and the differences were statistically significant ( P<0.05). PD group was divided into PD with RSWA group (PD + RSWA) and PD without RSWA group (PD-RSWA) according to whether there was atonia or not. AHI during REM sleep in the PD+RSWA group was lower than that in the PD-RSWA group: 0.00(0.00, 5.40)/h vs. 5.75(0.52, 34.57)/h, and the difference was statistically significant ( P<0.05). Conclusions:PD has a protective effect on nocturnal respiratory events, which may be due to the increased muscle tone of upper airway.
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@# Objective To systematically evaluate the expression of programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma and its relationship with prognosis. Methods The literature from PubMed, EMbase, The Cochrane Library, Web of Science, CNKI and Wanfang data from inception to February 22, 2020 was searched by computer. Data were extracted and the quality of literature was evaluated using RevMan 5.3 software for meta-analysis. Egger's and Begg's tests were used to evaluate publication bias, and Stata 15.1 software was used for sensitivity analysis. Results A total of 16 articles were included, and there were 3 378 patients with esophageal squamous cell carcinoma. The methodological index for nonrandomized studies (MINORS) scores were all 12 points and above. The meta-analysis results showed that the positive expression rates of PD-1 and PD-L1 in tumor cells were 37.8% (190/504) and 41.7% (1 407/3 378), respectively. The positive expression of PD-L1 in tumor immune infiltrating cells was 41.7% (412/987). The overall survival (OS) of the tumor cell with high PD-L1 expression was lower than that with low PD-LI expression (HR=1.30, 95%CI 1.01-1.69, P=0.04). The OS of the tumor immune infiltrating cell with high PD-L1 expression was significantly higher than that with low PD-LI expression (HR=0.65, 95%CI 0.53-0.80, P<0.000 1). Conclusion PD-L1 has a high expression rate in esophageal squamous cell carcinoma and is an important factor for the prognosis of esophageal squamous cell carcinoma.
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OBJECTIVE@#To investigate the expression of LINC01106 in colorectal cancer and its role in regulating the proliferation and apoptosis of colorectal cancer cells.@*METHODS@#We analyzed the data of LINC01106 expression levels in tumor tissues and normal tissues of patients with colorectal cancer in TCGA database and explored the association of LINC01106 expression level with the prognosis of the patients. Colorectal cancer SW480 cell lines with LINC01106 knockdown or overexpression were established, and their proliferation and apoptosis relative to the parental cells were evaluated using CCK-8 assay and flow cytometry, respectively. The expressions of p-STAT3, STAT3, and Bcl-2 in the cells were detected by immunoblotting. Nude mouse models bearing xenografts of SW480 cells with LINC01106 knockdown or na?ve SW480 cells were established to observe the effect of LINC01106 knockdown on the growth of SW480 cells .@*RESULTS@#Analysis of the data from TCGA database showed that the expression level of LINC01106 was significantly higher in colorectal cancer tissues than in normal tissues, and LINC01106 expression level was significantly related to the prognosis of the patients ( < 0.05). Knockdown of LINC01106 significantly inhibited the proliferation and promoted apoptosis of SW480 cells ( < 0.05), while LINC01106 overexpression significantly promoted proliferation of the cells. LINC01106 knockdown in SW-480 cells obviously lowered the expressions of p- STAT3 and Bcl-2 and suppressed the growth of the xenograft in nude mice.@*CONCLUSIONS@#LINC01106 is significantly up-regulated in colorectal cancer tissue and is related to the prognosis of the patients. LINC01106 can regulate the proliferation and apoptosis of SW480 cells through STAT3/Bcl-2 signaling and may serve as a potential marker for the diagnosis and prognostic evaluation of colorectal cancer.
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[Objective] To explore the clinical features,genetic characters in family amyotrophic lateral sclerosis (ALS10)patients.[Methods] TARDBP gene mutations in Chinese Han family patients with ALS10 diagnosed by the First Affiliated Hospital of Sun Yat-sen University in 2013 was screened by high-throughput sequencing.[Results] There were 5 patients in three generations in this family.The initial symptoms in all affected members were distal limb muscle weakness and dystrophy at their 50 age.With a rapid progression of symptoms about 8 to 18 months.A homozygous missense mutation (c.892G＞A) were detected in TARDBP gene exon 6 of the propositus,as well as the other three family members without any clinical symptoms.[Conclusion] ALS10 is a faster progressive and shorter survival time FALS.Since there was no effective treatment in ALS10,hereditary consultation and prenatal diagnosis play an important role in disease prevention and hereditary.
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Organoselenium compounds are bioactive substances with extensive physiological activities .As a representa-tive compound ,ebselen could be used as mimics of glutathione peroxidase ,and in the treatment of many diseases ,such as car-diovascular and cerebrovascular diseases ,inflammation and noise-induced hearing loss .the research progress in physiological activities and synthetic methods of ebselen were reviewed in this paper .
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Objective To study the difference ofLeonurus japonicus germplasm resources and provide good materials for breeding.Methods Totally 20 wildLeonurus japonicus germplasm resources from different places of China were collected. Experiment was conducted in homogeneous garden in Quzhou City of Zhejiang Province. Phenological phase, cold endurance and habitat adaptability were observed; the plant height, fresh weight and dry weight in early flowering were measured; the contents of stachydrine hydrochloride and leonurine hydrochloride were determined in early flowering and out-of-season cultivation.Results Considering the habitat adaptability, dry plant weight in early flowering, the contents of stachydrine hydrochloride and leonurine hydrochloride separately in early flowering and out-of-season cultivation, it was believed that the germplasms from Linbao County, Sheqi County in Henan Province and Guidong County in Hunan Province were better, in which Linbao germplasm was the best: the dry plant weight was 30.6 g, the content of stachydrine hydrochloride and leonurine hydrochloride were 1.31% and 0.19% respectively in early flowering, and were 3.44% and 0.37% respectively under anti-season cultivation, and it can be well adapted in Zhejiang Province.Conclusion The germplasm ofLeonurus japonicas from Lingbao can be the best materials for breeding.
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Objective To observe the clinical efficacy of acupuncture in treating male idiopathic oligoasthenozoospermia. Method A hundred patients with oligoasthenozoospermia were recruited and randomized into a treatment group and a control group, 50 cases in each group. The treatment group was intervened by acupuncture, while the control group was by placebo acupuncture at non-meridian points. The clinical efficacies and changes of the relevant parameters of sperms after treatment were observed. Result The clinical efficacy of the treatment group was significantly better than that of the control group (P0.05); after intervention, the improvements of the relevant parameters of sperms in the treatment group were more significant than that in the control group (P<0.05). Conclusion Acupuncture can effectively improve the sperm density, sperm motility, and sperm viability, and enhance the recovery rate in treating infertility, and it’s easy-to-operate, without significant adverse reactions, safe, and reliable.
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<p><b>OBJECTIVE</b>To investigate the effect of chloroquine in reversing multidrug resistance (MDR) of HNE1/DDP cell line and explore the mechanism.</p><p><b>METHODS</b>MTT assay was used to detect the cell viability of HNE1 and HNE1/DDP after exposure to different concentrations of DDP (2, 4, 8, 16 and 32 µmol/L) and different concentrations of chloroquine (5, 10, 20, 40, and 80 µmol/L). q-PCR was used to assess the expression of MDR1 mRNA and Western blotting was employed to detect P-glycoprotein (P-gp) expression in HNE1 and HNE1/DDP cells exposed to 5 and 10 µmol/L chloroquine. The cell apoptosis rate of HNE1 and HNE1/DDP cells exposed to 10 and 20 µmol<L chloroquine was determined by PI assay.</p><p><b>RESULTS</b>Chloroquine exposure caused dose-dependent suppression of the proliferation in both HNE1 and HNE1<DDP cells, and significantly reversed multidrug resistance in HNE1<DDP cells. The expressions of MDR1 mRNA and P-gp protein were significantly lowered in the cells treated with chloroquine.</p><p><b>CONCLUSION</b>Chloroquine can reverse multidrug resistance in HNE1<DDP cells possibly through down-regulation of MDR1 and inhibition of P-gp protein.</p>
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Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Metabolism , Antineoplastic Agents , Pharmacology , Apoptosis , Cell Line, Tumor , Chloroquine , Pharmacology , Down-Regulation , Drug Resistance, Multiple , Drug Resistance, NeoplasmABSTRACT
Objective To study different test positions on vestibular evoked myogenic potentials (VEMPs) in youth ,and to find a suitable position and provide a guidance for clinical practice .Methods Thirty normal young vol-unteers were tested by vestibular evoked myogenic potentials ,using three different positions :supine with the head held straight up(SHU),supine with the head held up and turned away from the test ear(SHT),sitting with the head turned away from the test(SIT) ,the derivation rate ,latency and amplitude were analyzed .Results The deri-vation rate of SHU ,SHT and SIT were 100% ,100% and 63 .3% ,respectively .The derivation rate ,p13 ,n23 la-tency and p13 n23 inter-latency between SHU and SIT ,and between SHT and SIT had statistical differences (P0 .05) .The amplitude was significantly different among the three positions (P 0 .05) .Conclusion The derivation rate of SHT was 100% with maximum amplitude .SHT is the most recommended position for clinical test in youth .The derivation rate of SHU was 100% ,and no statistical significant difference were found in p13 ,n23 latency and p13n23 inter-la-tency between SHU and SHT (P>0 .05) .SHU can be used in clinical test .SIT is not recommended for using in clinical test .Gender does not affect VEM Ps test .
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<p><b>OBJECTIVE</b>To study tissue culture and plant regeneration of Withania somnifera.</p><p><b>METHOD</b>Leaves of W. somnifera were used for explants, effects of different plant growth substances on callus and shoot induction were studied, different medium and plant growth substances for rooting induction was optimized.</p><p><b>RESULT AND CONCLUSION</b>The best plant growth substances combination for callus induction was MS + 1.0 mg x L(-1) 2,4-D + 0.1 mg x L(-1) KT. The optimal medium for germination was MS + 1.0 mg x L(-1) 6-BA + 0.1 mg x L(-1) NAA. The best medium and plant growth substances combination for rooting induction was 1/2MS + 0.5 mg x L(-1) NAA, transplant survival rate of plantlet reached 92% in humus soil-pearlite (1:1).</p>
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Culture Media , Pharmacology , Plant Growth Regulators , Pharmacology , Regeneration , Tissue Culture Techniques , WithaniaABSTRACT
Objective To enhance clinicians' intention to the importance of early diagnosis,early therapy and follow-up of type Ⅱ citrullinemia.Methods The clinical data of one adult-onset type Ⅱ citrullinemia pedigree were collected. The gene mutation type of SLC25A13 of proband and her daughter were determined by PCR and direct gene sequencing.Results The patient was a 27 years-old female,who complained of repeated dizziness, vomiting for more than 2 years and recurrent attacks of altered consciousness for about one and a half year.An abdominal ultrasonogram,liver magnetic resonance imaging and liver histology obtained by needle biopsy all determined the liver pathological changes of liver cirrhosis.Electroencephalogram showed sharp waves. The plasma amino acid showed a marked elevation of blood citrulline.Laboratory findings revealed a highly increased concentration of plasma ammonia during every episode. Mutation analysis of the SLC25A13 gene identified a homozygote of 851del4 in the patient,and heterozygote of 851del4 in her daughter. Conclusions For adults,unexplained dizziness,vomiting,but liver function still in the compensation,especially accompanied by neuropsychologic symptoms are highly suggestive of adult-onset type Ⅱ citrullinemia.SLC25A13 gene analysis contributes to the diagnosis of this disease,avoids invasive investigations and early confirmation of this disease means long-term dietary advice,genetic counseling,medical surveillance and early preparation for liver transplantation if is necessary.
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<p><b>OBJECTIVE</b>To establish integration processing method for pretreating and vinegar producing Corydalis yanhusuo.</p><p><b>METHOD</b>Different processing methods were contrasted with the traditional processing technology, and contents of corydalis B, water extract and ethanol extract in samples of different processing products were determined.</p><p><b>RESULT</b>The content of corydalis B were best in the samples of vacuumizing C. yanhusuo chips scaked in rice vinegar for twice or soaked in rice vinegar after chip drying. The water extract was highest in the samples of chip soaked in rice vinegar after drying, followed with chip vacuumizing twice, and there were no remarkable difference between the other samples and the traditional process. The difference of ethanol extract was not remarkable in all the samples.</p><p><b>CONCLUSION</b>The study provide the feasibility of C. yanhusuo producing and concocting integration processing.</p>
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Acetic Acid , Chemistry , Berberine Alkaloids , Metabolism , Corydalis , Chemistry , Metabolism , Freeze Drying , Methods , Plant Extracts , Metabolism , Plants, Medicinal , Chemistry , Rhizome , Chemistry , Metabolism , Solid Phase Extraction , Methods , Water , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To establish the transformation system of mulberry, and test its ability of quercetin biosynthesis.</p><p><b>METHOD</b>Hairy roots of mulberry were obtained through infecting etiolated seedlings with Agrobacterium tumefaciens strain C58C1. The culture condition of hairy roots was optimized. The transformation of T-DNA was examined by PCR assay and quercetin content was determined by HPLC.</p><p><b>RESULT</b>When infecting stem cutting of etiolated seedlings via C58C1 strain, the optimal transformation conditions were as follows: 10 minutes' infection, two-days pre-culture and co-culture, additional hydroxylacetosyringone (As) 100 mg x L(-1). The PCR examination result showed that rolB and rolC genes could be inserted into the hairy roots of mulberry. Hairy roots appeared in 10 days after infecting, the frequency of stems explants was up to 92% after 30 days culturing. After 50 days culturing in 1/2MS + 0.05 mg x L(-1) IBA liquid medium, the content of quercetin increased by 8. 5-fold.</p><p><b>CONCLUSION</b>Hairy root culture system of Moraceae plants was established successfully for the first time. In addition, it also provides a foundation for further industrial production of active compounds such as quercetin.</p>
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Agrobacterium tumefaciens , Genetics , Metabolism , Cells, Cultured , DNA, Bacterial , Genetics , Gene Targeting , Methods , Genetic Vectors , Genetics , Metabolism , Morus , Genetics , Metabolism , Microbiology , Quercetin , Transformation, GeneticABSTRACT
<p><b>OBJECTIVE</b>To explore the variety of the genetic polymorphism of eight Prunella germplasm resources by AFLP analysis.</p><p><b>METHOD</b>The amplified fragment length polymorphism (AFLP) tags were applied to screen out 32 selective amplification primer pairs, the amplified bands as original matrix were analyzed with NTSYS-PC software for the similarity between the Prunella germplasm and the construction of genetic phylogenetic tree.</p><p><b>RESULT</b>SDS extraction of genomic Prunella DNA showed a good quality, could meet the requirements of AFLP analysis. From 32 selective amplification primer pairs, 10 pairs with strong polymorphism, better band and higher resolution were used for the construction of the AFLP Prunella fingerprint, all eight Prunella germplasms were separated, they were divided into 3 categories.</p><p><b>CONCLUSION</b>Prunella germplasm resources are rich in genetic diversity, certain morphological characteristics and differences are associate with genotype.</p>