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This paper aimed to investigate the active components and mechanism of Taohong Siwu Decoction in the treatment of primary dysmenorrhea(PD) based on network pharmacology and molecular docking technology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to search the chemical compositions and targets of six herbs in Taohong Siwu Decoction. The targets for PD treatment were selected through the databases of DrugBank, OMIM, TTD and CTD, and gene annotation of the targets was conducted with UniProt database. Cytoscape 3.7.2 was then used to construct the drug-compound-target network. The protein-protein interaction(PPI) network was constructed based on STRING, and the core targets of Taohong Siwu Decoction in the treatment of PD were selected according to the topological parameters. David database was used for GO enrichment analysis and KOBAS 3.0 was used for KEGG enrichment analysis. The molecular docking technology was used to connect the components with higher medium values in the network with core targets. The results showed that the network contained 36 compounds such as quercetin, kaempferol, luteolin, myricanone and ferulic acid, and 99 targets such as PTGS2, PTGS2, PGR and PPARG. Totally 102 GO terms were obtained by GO functional enrichment analysis(P<0.01), and 228 signal pathways were obtained by KEGG pathway enrichment(P<0.05), mainly involving inflammatory factors, hormone regulation, central analgesia, amino acid metabolism and spasmolysis. The results of molecular docking showed that the main active components can spontaneously bind to the targets. This study preliminarily revealed the mechanism of Taohong Siwu Decoction for treatment of primary dysmenorrheal through multi-components, multi-targets and multi-pathways, providing theoretical references for further researches on mechanism of Taohong Siwu Decoction.
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Female , Humans , Drugs, Chinese Herbal , Dysmenorrhea/drug therapy , Molecular Docking Simulation , TechnologyABSTRACT
Verticillin A is a diketopiperazine compound which was previously isolated from Amanita flavorubescens Alk (containing parasitic fungi Hypomyces hyalines (Schw.) Tul.). Here, we initially found, by wound healing assay and Transwell assay in vitro, that verticillin A possesses an inhibitory effect against the migration and invasion of the human colon cancer cell. Subsequently, c-mesenchymal-epithelial transition factor (c-Met) was identified as a molecular target of verticillin A by screening key genes related to cell migration. Verticillin A-mediated c-Met suppression is at the transcriptional level. Further study demonstrated that verticillin A suppressed c-MET phosphorylation and decreased c-MET protein level. In addition, verticillin A inhibited the phosphorylation of c-MET downstream molecules including rat sarcoma (Ras)-associated factor (Raf), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT). Overexpression of Erk partially reversed the verticillin A-mediated anti-metastasis action in the human colon cancer cell. More importantly, verticillin A also inhibited cancer cell metastasis in vivo. Thus, verticillin A can significantly inhibit the migration and invasion of colon cancer cells by targeting c-Met and inhibiting Ras/Raf/mitogen-activated extracellular signal-regulated kinase (MEK)/ERK signaling pathways. Therefore, we determined that verticillin A is a natural compound that can be further developed as an anti-metastatic drug in human cancers.
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Objective At present, there are few reports about the relationship between Chemerin and the occurrence and development of breast cancer. The aim of this study is to investigate Chemerin expression in breast cancer mice and its effect on proliferation and migration of breast cancer cells. Methods 30 Balb/c mice were randomly divided into two groups (Normal mice 15, Tumor-bearing mice 15). The 4T1 breast cancer cells were inoculated to construct breast cancer mice model. The expressions of Chemerin in peripheral blood and breast cancer tissue were detected by ELISA and Western blot, respectively. The relationship between Chemerin expression and breast cancer was analyzed. Breast cancer cells MCF-7 and MDA-MB-231 were treated with different concentrations of recombinant Chemerin protein and Chemerin neutralizing antibody. Three groups were set up in the experiment, including control group (1640 or DMEM culture medium, no cells), recombinant Chemerin protein group (100 μg/L, no dilution by serum-free medium) and Chemerin neutralizing antibody group (100 μg/L, no dilution by serum-free medium). The effects of Chemerin on cell proliferation and migration were detected by MTT assay and wound healing assay respectively. Results The expressions of Chemerin in peripheral blood and mammary gland of tumor bearing mice were significantly higher than that in normal mice (both P<0.05). The scratch mobility and MTT absorbance (OD) values of breast cancer cells treated with recombinant chemerin protein increased significantly with the increase of protein concentration (P<0.05).However, they significantly decreased after cells treated with chemerin neutralizing antibody (P<0.05). Conclusion Chemerin could promote the proliferation and migration of breast cancer cells in a concentration-dependent manner, thereby promotinge the occurrence and development of breast cancer.
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BACKGROUND@#Approximately 70% patients with acute myocardial infarction (AMI) presented without ST-segment elevation on electrocardiogram. Patients with non-ST segment elevation myocardial infarction (NSTEMI) often presented with atypical symptoms, which may be related to pre-hospital delay and increased risk of mortality. However, up to date few studies reported detailed symptomatology of NSTEMI, particularly among Asian patients. The objective of this study was to describe and compare symptoms and presenting characteristics of NSTEMI vs. STEMI patients.@*METHODS@#We enrolled 21,994 patients diagnosed with AMI from China Acute Myocardial Infarction (CAMI) Registry between January 2013 and September 2014. Patients were divided into 2 groups according to ST-segment elevation: ST-segment elevation (STEMI) group and NSTEMI group. We extracted data on patients' characteristics and detailed symptomatology and compared these variables between two groups.@*RESULTS@#Compared with patients with STEMI (N = 16,315), those with NSTEMI (N = 5679) were older, more often females and more often have comorbidities. Patients with NSTEMI were less likely to present with persistent chest pain (54.3% vs. 71.4%), diaphoresis (48.6% vs. 70.0%), radiation pain (26.4% vs. 33.8%), and more likely to have chest distress (42.4% vs. 38.3%) than STEMI patients (all P < 0.0001). Patients with NSTEMI were also had longer time to hospital. In multivariable analysis, NSTEMI was independent predictor of presentation without chest pain (odds ratio: 1.974, 95% confidence interval: 1.849-2.107).@*CONCLUSIONS@#Patients with NSTEMI were more likely to present with chest distress and pre-hospital patient delay compared with patients with STEMI. It is necessary for both clinicians and patients to learn more about atypical symptoms of NSTEMI in order to rapidly recognize myocardial infarction.@*TRIAL REGISTRATION@#www.clinicaltrials.gov (No. NCT01874691).
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Aged , Female , Humans , Male , Middle Aged , Arrhythmias, Cardiac , Pathology , China , Electrocardiography , Methods , Hospital Mortality , Myocardial Infarction , Pathology , Odds Ratio , Registries , Risk Factors , ST Elevation Myocardial Infarction , PathologyABSTRACT
BACKGROUND@#The pathogenesis of multiple sclerosis (MS) is mediated primarily by T cells, but most studies of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have focused on CD4 T cells. The aims of the current study were to determine the pathological interrelationship between CD4 and CD8 autoreactive T cells in MS/EAE.@*METHODS@#Female C57BL/6 mice (n = 20) were induced by myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. At 14 days after immunization, T cells were isolated from the spleen and purified as CD4 and CD8 T cells by using CD4 and CD8 isolation kits, and then the purity was determined by flow cytometric analysis. These cells were stimulated by MOG35-55 peptide and applied to proliferation assays. The interferon-gamma (IFN-γ) and interleukin (IL)-4 secretion of supernatant of cultured CD4 and CD8 T cells were measured by enzyme-linked immunosorbent assays (ELISA). For adoptive transfer, recipient mice were injected with MOG35-55-specific CD8 or CD4 T cells. EAE clinical course was measured by EAE score at 0-5 scale and spinal cord was examined by staining with hematoxylin and eosin and Luxol fast blue staining.@*RESULTS@#CD8CD3 and CD4CD3 cells were 86% and 94% pure of total CD3 cells after CD8/CD4 bead enrichment, respectively. These cells were stimulated by MOG35-55 peptide and applied to proliferation assays. Although the CD8 T cells had a generally lower response to MOG35-55 than CD4 T cells, the response of CD8 T cells was not always dependent on CD4. CD8 T cell secreted less IFN-γ and IL-4 compared with CD4 T cells. EAE was induced in wildtype B6 naïve mice by adoptive transfer of MOG35-55-specific T cells from B6 active-induced EAE (aEAE) mice. A similar EAE score and slight inflammation and demyelination were found in naive B6 mice after transferring of CD8 T cells from immunized B6 mice compared with transfer of CD4 T cells.@*CONCLUSION@#Our data suggest that CD8 autoreactive T cells in EAE have a lower encephalitogenic function but are unique and independent on pathogenic of EAE rather than their CD4 counterparts.
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Objective To evaluate the diagnostic value of interferon-γ release assay of blood and pleural effusion for tuberculous pleurisy.Methods Fifty-six adult patients with suspected tuberculous pleurisy were enrolled in our study.The blood and pleural effusion interferon-γ release assay were measured by T-SPOT.TB test in 38 pleural tuberculosis patients and 18 nontuberculous pleurisy controls.The diagnostic sensitivity,specificity,predictive value of T-SPOT.TB in pleural effusion mononuclear cells (PE-MC) and peripheral mononuclear cells (PBMC) were analyzed.Results The sensitivities and specificities,positive predictive values and negative predictive values,respectively,of the PE-MC and PBMC for diagnosing were as follows:86.5％(95％ confidence interval[CI] 71.2％-95.5％) and 100％(95％CI 90.5％-100％);52.9％(95％CI 27.8％-77.0％) and 35.3％(95％CI 14.2％-61.7％);80.0％(95％CI 64.4％-90.9％) and 77.1％(95％CI 62.7％-88.0％);64.3％(95％CI 35.1％-87.2％) and 100％(95％CI 54.1％-100％).By ROC curve analysis,a cut-off value of 47SFC/2.5 × 105 cells in PE-MC showed a sensitivity of 89.2％ and a specificity of 88.2％.Conclusion T-SPOT.TB in PE-MC could be an accurate diagnostic method for tuberculous pleurisy in TB endemic settings.Moreover,47SFC/2.5 × 105 cells might be the optimal cut-off value for diagnosing tuberculous pleurisy.
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Objective The purpose of this study was to investigate the correlation between single nucleotide polymorphisms (SNP) of Toll-like receptor 9 (TLR9) and tuberculosis in the Chinese Tibetan population . Methods A total of 613 active tubercu-losis patients and 603 healthy controls were enrolled in this case -control study.Two SNPs in TLR9 (rs187084 and rs5743836) were genotyped using the multiplex ligation detection reaction technique .The association of the SNPs with the susceptibility of TB was inves -tigated using logistic regression analysis . Results There was no statistically significant difference in the allele distribution of rs 187084 G/A between the TB patients and the healthy controls (P=0.668) or correlation between the genotype of rs 187084 and the genetic suscepti-bility of TB ( P >0.05).Dominant, recessive and additive models showed no association of this SNP with TB , either (P >0.05). Conclusion The rs187084 polymorphism of TLR9 is not correlated with the genetic susceptibility of tuberculosis in the Chinese Tibetan population.
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Objective To analysis of consistency of results in evaluating urine dry chemical method and nephelometry in the detection of urine albumin(UAlb) and urine dry chemical method and enzymatic method in the detection of urinary creatinine (Cr) and albumin-to-creatinine ratio(ACR).Methods In 157 urine samples collected firstly in the morning,urine microalbumin was determined by the urine dry chemistry method and nephelometry,and urine creatinine was determined by the urine dry chemistry method and the enzyme method respectively.The kappa was applied to evaluating the consistency.Results The results of UAlb showed that the kappa was 0.837 9 (95％CI:0.718 1～0.957 7),the results of urine creatinine showed that the kappa was 0.769 7 (95％CI:0.665 2～0.874 2),and the results of albumin-to creatinine ratio showed that the kappa was 0.756 6 (95％CI:0.628 6～0.884 6).Conclusion The results of urine Alb,urinary creatininc and ACR by urine dry chemistry method and urine albumin by nephelometry,and urine Cr by enzymatic method and ACR had high consistency.Urine dry chemical method can be used for screening of early renal disease and for screening in CKD grading,screening for early screening or for long-term maintenance.
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AIM:To investigate the therapeutic effects of a novel fluid resuscitation protocol (early fluid resuscitation plus 2％ hydrogen inhalation) on acute kidney injury during septic shock induced by lipopolysaccharide (LPS) in rats.METHODS:Male Wistar rats were randomly divided into 4 groups (15 rats per group):control group,septic shock group,septic shock with early fluid resuscitation group (fluid group) and septic shock with early fluid resuscitation plus 2％ hydrogen inhalation group (fluid + H2 group).The rats were ventilated,and a 2％ hydrogen mixture was used in fluid + H2 group.LPS (10 mg/kg) was administered to establish the septic shock model in rats and fluid resuscitation was performed in fluid group and fluid + H2 group.RESULTS:Fluid resuscitation with 2％ hydrogen inhalation decreased the levels of serum creatinine,blood urea nitrogen and neutrophil gelatinase-associated lipocalin.It also reduced oxidative stress injury and decreased renal tumor necrosis factor-α and interleukin-6 levels compared with fluid resuscitation alone.CONCLUSION:Early fluid resuscitation plus 2％ hydrogen inhalation provided more protection against acute kidney injury during septic shock.
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Objective:To evaluate the safety and efficacy of ultrasound guidance for percutaneous balloon pulmonary valvuloplasty (PBPV) in comparison with conventional X-ray guidance.Methods:Our research included in 2 groups:Ultrasound group,n=102 patients with PBPV under ultrasound guidance in our hospital from 2013-03 to 2016-08 and X-ray group,n=280 patients with PBPV under traditional X-ray guidance in our hospital at the same period of time.Post-operative effect was evaluated by echocardiography and compared between 2 groups.Results:The patients' age,body weight,pulmonary artery diameter,immediate post-operative pulmonary transvalvular pressure gradient (PTPG),the in-hospital time and cost were similar between 2 groups,P＞0.05.The success rate of operation in Ultrasound group and X-ray group was 99.0％ vs 100％,P=0.267.In the ultrasound group,1 patient was converted to a conventional surgery due to right ventricular outflow tract muscle spasm after dilation.The operation time in X-ray group was longer than Ultrasound group,(38.9±9.2) min vs (34.6±10.0) min,P＜0.001.The X-ray exposure time was (3.9±1.2) min in X-ray group.The mean follow-up time was (25.5±13.2) months and PTPG in Ultrasound group and X-ray group were (16.2±4.3) mmHg and (15.3±4.5) mmHg,P=0.120.No serious complications as death,peripheral vascular injury,cardiac perforation and pericardial effusion occurred in either group.Conclusion:PBPV under complete ultrasound guidance may not only avoid radiation and contrast agent,but also keep the safety and efficacy of minimally invasive conventional percutaneous interventional treatment.
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AIM:To investigate the therapeutic effects of a novel fluid resuscitation protocol (early fluid resuscitation plus 2％ hydrogen inhalation) on acute kidney injury during septic shock induced by lipopolysaccharide (LPS) in rats.METHODS:Male Wistar rats were randomly divided into 4 groups (15 rats per group):control group,septic shock group,septic shock with early fluid resuscitation group (fluid group) and septic shock with early fluid resuscitation plus 2％ hydrogen inhalation group (fluid + H2 group).The rats were ventilated,and a 2％ hydrogen mixture was used in fluid + H2 group.LPS (10 mg/kg) was administered to establish the septic shock model in rats and fluid resuscitation was performed in fluid group and fluid + H2 group.RESULTS:Fluid resuscitation with 2％ hydrogen inhalation decreased the levels of serum creatinine,blood urea nitrogen and neutrophil gelatinase-associated lipocalin.It also reduced oxidative stress injury and decreased renal tumor necrosis factor-α and interleukin-6 levels compared with fluid resuscitation alone.CONCLUSION:Early fluid resuscitation plus 2％ hydrogen inhalation provided more protection against acute kidney injury during septic shock.
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Objective:To evaluate the safety and efficacy of ultrasound guidance for percutaneous balloon pulmonary valvuloplasty (PBPV) in comparison with conventional X-ray guidance.Methods:Our research included in 2 groups:Ultrasound group,n=102 patients with PBPV under ultrasound guidance in our hospital from 2013-03 to 2016-08 and X-ray group,n=280 patients with PBPV under traditional X-ray guidance in our hospital at the same period of time.Post-operative effect was evaluated by echocardiography and compared between 2 groups.Results:The patients' age,body weight,pulmonary artery diameter,immediate post-operative pulmonary transvalvular pressure gradient (PTPG),the in-hospital time and cost were similar between 2 groups,P＞0.05.The success rate of operation in Ultrasound group and X-ray group was 99.0％ vs 100％,P=0.267.In the ultrasound group,1 patient was converted to a conventional surgery due to right ventricular outflow tract muscle spasm after dilation.The operation time in X-ray group was longer than Ultrasound group,(38.9±9.2) min vs (34.6±10.0) min,P＜0.001.The X-ray exposure time was (3.9±1.2) min in X-ray group.The mean follow-up time was (25.5±13.2) months and PTPG in Ultrasound group and X-ray group were (16.2±4.3) mmHg and (15.3±4.5) mmHg,P=0.120.No serious complications as death,peripheral vascular injury,cardiac perforation and pericardial effusion occurred in either group.Conclusion:PBPV under complete ultrasound guidance may not only avoid radiation and contrast agent,but also keep the safety and efficacy of minimally invasive conventional percutaneous interventional treatment.
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<p><b>OBJECTIVE</b>The aim of the present study is to investigate the effect of low temperature vernalization on metabolism change of carbon and nitrogen of Isatis indigotica.</p><p><b>METHOD</b>The Yunnan and Beijing I. indigotica seedlings with six leaves were vernalized at 4 degrees C for 25 days, and the metabolism indicators of carbon and nitrogen were measured.</p><p><b>RESULT</b>There appeared a dramatic increase in the soluble sugar content, reducing sugar content and soluble protein content in response to the low temperature, after termination of vernalization it reached the maximum, however, starch and total nitrogen concentration decreased significantly, after termination of vernalization it reached the minimum.</p><p><b>CONCLUSION</b>The high C/N value can promote the low temperature vernalization of I. indigotica.</p>
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Carbon , Metabolism , Cold Temperature , Isatis , Metabolism , Nitrogen , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To identify mutations and variants in CASQ2 gene in 27 CPVT patients/family members.</p><p><b>METHODS</b>Mutational analysis was performed with direct DNA sequence analysis. The frequency of an identified CASQ2 variant was determined using the Taqman genotyping assay.</p><p><b>RESULTS</b>A novel heterozygous mutation, F189L, in CASQ2 gene was identified in one family with CPVT. This mutation occurred at the evolutionarily, highly conserved phenylalanine residue at codon 189, and was not present in 1400 control individuals. No other disease-causing mutations were identified in the CASQ2 gene.</p><p><b>CONCLUSION</b>A novel mutation of F189L in the CASQ2 gene was identified.</p>