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Objective:To explore the targets and relevant signaling pathways of Suoquanwan in the treatment of enuresis using network pharmacology，and animal expriments are applied to further define its mechanism of action. Method:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） database was used to screen out active chemical components of Suoquanwan，varieties of systematic biological databases were integrated to construct the "active component-disease-target" network relationship，and the common protein protein interaction network（PPI） network genes were functionally enriched. Quantitative real time polymerase chain reaction（Real-time PCR） and Western blot were used to verify the effect of Suoquanwan on AVPR2 and DRD2 gene. Result:A total of 32 active ingredients were screened from Suoquanwan. These active ingredients were interacted with 131 potential targets relating to Enuresis，which contained 14 core target genes，namely arginine vasopressin receptor 2 （AVPR2）， neurotrophic receptor tyrosine kinase 1（NTRK1）， dopamine receptor D2（DRD2）， opioid receptor mu 1（OPRM1）， 5-hydroxytryptamine receptor 1A（HTR1A）， 5-hydroxytryptamine receptor 1B（HTR1B），solute carrier family 6 member 4（SLC6A4），Adrenoceptor Alpha 2A（ADRA2A）， prostaglandin-endoperoxide synthase 2（PTGS2）， cholinergic receptor muscarinic 2（CHRM2）， solute carrier family 6 member 3 （SLC6A3）， 5-hydroxytryptamine receptor 6（HTR6）， solute carrier family 6 member 2（SLC6A2）， cytochrome P450 family 2 subfamily C member 19（CYP2C19）. Gene enrichments mainly involved to G protein-coupled receptor signaling pathway，regulation of trans-synaptic signaling，regulation of neurotransmitter transport and neuroactive ligand-receptor interaction. Real-time PCR and Western blot results showed that Suoquanwan could enhance the expression of AVPR2 in rat kidney，and weaken the expression of DRD2 in rat adrenal. Conclusion:The main chemical constituents in Suoquanwan may alleviate enuresis by regulating AVPR2 and DRD2 and then participating in the G protein-coupled receptor signaling pathway，regulation of trans-synaptic signaling，regulation of neurotransmitter transport and other biological processes.
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As known,simultaneous determination of various chemical indicators is one of the future trends in quality control of traditional Chinese medicines because of the extremely complex chemical compositions. This project is to screen the quality markers that can accurately control the quality of the Bufonis Venenum by exploring the intrinsic correlation of components. In this study,venom of Bufo bufo gargarizans from 17 different sources were used as research samples,and the contents of 7 bufogenin were determined by HPLC-DAD. Then,the data obtained were analyzed by Spearman correlation analysis and principal component analysis( PCA). In addition,a stepwise regression analysis was used to establish a predictive model for the contents of the seven bufogenin components( independent variable) and the total contents of the bufogenin( dependent variable). The results indicated that there is a significant positive correlation between the contents of telocinobufagin and cinobufotalin,and there is a significant positive correlation between the contents of bufalin,cinobufagin and resibufogenin. In contrast,the contents of telocinobufagin and cinobufotalin are negatively correlated with the contents of bufalin,cinobufagin and resibufogenin. However,the correlation between gamabufotalin and bufotalin and other components are not obvious. Furthermore,further study found that there is a correlation between the sum of the contents of bufalin,cinobufagin and telocinobufagin and the total contents of the bufogenin. In fact,the application of bufalin,cinobufagin and telocinobufagin as the quality control indicators of the Bufonis Venenum can better reflect the quality characteristics of the Bufonis Venenum compared with the previous quality control indicators. The conclusions will provide a reference for the revision of the quality standards of the Bufonis Venenum.
Subject(s)
Animals , Amphibian Venoms , Chemistry , Bufanolides , Bufo bufo , Chromatography, High Pressure Liquid , Medicine, Chinese Traditional , Quality ControlABSTRACT
PURPOSE: Although the interferon α (IFNα) signaling and the paired-like homeodomain transcription factor 2 (PITX2) have both been implicated in the progression of breast cancer (BCa), it remains obscure whether these two pathways act in a coordinated manner. We therefore aimed to elucidate the expression and function of PITX2 during the pathogenesis of endocrine resistance in BCa. MATERIALS AND METHODS: PITX2 expression was assessed in BCa tissues using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry and in experimentally induced letrozole-resistant BCa cells using RT-qPCR and immunoblotting. Effects of PITX2 deregulation on BCa progression was determined by assessing MTT, apoptosis and xenograft model. Finally, using multiple assays, the transcriptional regulation of interferon-inducible transmembrane protein 1 (IFITM1) by PITX2 was studied at both molecular and functional levels. RESULTS: PITX2 expression was induced in letrozole-resistant BCa tissues and cells, and PITX2 induction by IFNα signaling powerfully protected BCa cells against letrozole insult and potentiated letrozole-resistance. Mechanistically, PITX2 enhanced IFNα-induced AKT activation by transactivating the transcription of IFITM1, thus rendering BCa cells unresponsive to letrozoleelicited cell death. Additionally, ablation of IFITM1 expression using siRNA substantially abolished IFNα-elicited AKT phosphorylation, even in the presence of PITX2 overexpression, thus sensitizing BCa cells to letrozole treatment. CONCLUSION: These results demonstrate that constitutive upregulation of PITX2/IFITM1 cascade is an intrinsic adaptive mechanism during the pathogenesis of letrozole-resistance, and modulation of PITX2/IFITM1 level using different genetic and pharmacological means would thus have a novel therapeutic potential against letrozole resistance in BCa.
Subject(s)
Apoptosis , Breast Neoplasms , Breast , Cell Death , Heterografts , Immunoblotting , Immunohistochemistry , Interferons , Phosphorylation , Polymerase Chain Reaction , Reverse Transcription , RNA, Small Interfering , Transcription Factors , Transcriptional Activation , Up-RegulationABSTRACT
Objective To observe the effect of Shenmai injection combined with enteral nutrition (EN) on immune function in patients with severe cardiac insufficiency. Methods Fifty-seven patients with severe cardiac insufficiency admitted to the Department of Critical Care Medicine of Taizhou Hospital of Zhejiang Province from June 2015 to June 2018 were divided into an EN group (31 cases) and an EN group combined with Shenmai injection group (26 cases). The EN group was given EN on the basis of routine western medicine treatment, while in the EN combined with Shenmai injection group was treated additionally by intravenous drip of Shenmai injection 100 mL/d on the basis of above EN group treatment. The efficacies of the two groups were evaluated after consecutive 7-day treatment in the two groups. The changes in levels of subsets of T-lymphocytes (CD3+, CD4+, CD8+, CD4+/CD8+) and immunosuppressive cells CD14+ monocyte human leukocyte antigen DR (HLA-DR) were observed before and after treatment. Results After treatment, the levels of T-cell subsets CD3+, CD4+, CD4+/CD8+ and CD14+ monocytes HLA-DR in the peripheral blood of the two groups were significantly higher than those before treatment [CD3+: EN group was 0.539±0.126 vs. 0.379±0.093,Shenmai injection group was 0.652±0.185 vs. 0.393±0.091; CD4+: EN group was 0.402±0.121 vs. 0.275±0.066,Shenmai injection group was 0.524±0.168 vs. 0.281±0.077; CD4+/CD8+:EN group was 1.83±0.70 vs. 1.11±0.70,Shenmai injection group was 2.81±0.91 vs. 1.19±0.58; CD14+HLA-DR:EN group was (43.3±7.1)% vs. (35.4±5.7)%,Shenmai injection group was (54.9±6.2)% vs. (36.1±8.3)%]; After treatment, CD8+ in EN group decreased (0.223±0.052 vs. 0.253±0.081), while CD8+ in shenmai injection group increased (0.288±0.051 vs. 0.259±0.078), and the increase degrees of the above-mentioned indexes in EN combined with Shenmai injection group were more obvious than those in the EN group after treatment [CD3+: 0.652±0.185 vs. 0.539±0.126, CD4+: 0.524±0.168 vs. 0.402±0.121, CD8+: 0.288±0.051 vs. 0.223±0.052, CD4+/CD8+: 2.81±0.91 vs. 1.83±0.70, CD14+HLA-DR: (54.9±6.2)%, (43.3±7.1)%, all P < 0.05]. Conclusion The combined use of Shenmai injection and early EN can improve the immune function of T-lymphocytes in patients with severe cardiac insufficiency. The mechanism may be related to the enhancement of the activation of T lymphocytes and promotion of the CD14+ monocytes increase and immune function.
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BACKGROUND: Unicompartment knee arthroplasty (UKA) is gradually applied in the treatment of knee osteoarthritis, and the management of perioperative blood loss is a hot spot in clinical research. It is very important to control perioperative blood loss and changes in hemoglobin level for postoperative rapid recovery. OBJECTIVE: To investigate the changes in the blood-related indexes during the management of perioperative blood loss in UKA, so as to provide technical reference and data reference for clinical application. METHODS: Clinical data 70 patients undergoing UKA at the Department of Bone and Joint of Guangdong Provincial Hospital of Chinese Medicine from January to December 2015 were analyzed retrospectively, and received the management of perioperative blood loss. The operation time, intraoperative blood loss, postoperative drainage volume, total blood loss and rate of blood transfusion were recorded; the preoperative hemoglobin, albumin, coagulation indexes, D-dimer, erythrocyte sedimentation rate and C-reactive protein were investigated. The effect of operation on the postoperative blood loss and drainage volume was analyzed. RESULTS AND CONCLUSION: (1) The operation time was (89.36±19.89) minutes, intraoperative blood loss was (39.71±23.64) mL, postoperative drainage volume was (56.21±34.21) mL, and rate of autologous blood transfusion was 0. (2) The operation time exerted no effect on the intraoperative blood loss (P=0.685 7), but affected on the postoperative drainage volume (P=0.021 6). (3) The total postoperative blood loss was little, and the blood loss did not differ significantly at 3 hours, 1, 3 and 7 days postoperatively (P > 0.05). (4) There was a slight decline in hemoglobin on days 1-3 after surgery, and then returned slowly; the erythrocyte sedimentation rate and C-reactive protein increased rapidly within 1 day after surgery and declined within 1-3 days; the D-dimer rapidly increased on day 1 after surgery, then rapidly decreased on days 1-3, and then slowly increased on days 3-7; the plasma total protein and albumin were stable and fluctuated in the normal range within 1-3 days. (5) These results suggest that the UKA had short operation time, few total blood loss and slight fluctuation, and the blood-related indexes exhibit different fluctuations. Moreover, the preoperative management of blood loss can reduce the total blood loss and rate of blood transfusion..
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Objective To investigate the value of mean platelet volume(MPV)combined with red blood cell distribution width(RDW)in prognosis of severe acute pancreatitis(SAP). Methods 65 SAP patients from January 1,2013 to December 31,2016 were included in the study and were divided into pospital death group(n=7) and survival group(n = 58). The basic clinical data of two groups were compared,the risk factors for hospital death and the prognostic value of MPV and RDW were analyzed. Results Compared with the survival group,the APACHEⅡ score,RDW,PLT,MPV,PDW were statistically different(P < 0.05). Logistic regression analysis was used to show APACHEⅡ score(OR = 1.793,95% CI: 1.212 ~ 2.654),PLT(OR = 0.982,95% CI: 0.967 ~0.997),MPV(OR=2.964,95% CI: 1.341~6.549),PDW(OR=1.470,95% CI: 1.019~2.122),RDW(OR=3.274,95% CI: 1.271 ~ 8.429)(P < 0.05). ROC curve analysis showed that the area under the curve of APA-CHEII score was 0.861(95% CI: 0.743 ~ 0.979,P = 0.001),MPV was 0.828(95% CI: 0.689 ~ 0.967,P =0.003,RDW was 0.849(95% CI: 0.749 ~ 0.949,P = 0.001),MPV+RDW was 0.914(95% CI: 0.832 ~ 0.997, P = 0.000). Conclusion The APACHEⅡ score,PLT,MPV,PDW,RDW are all the independent risk factors for hospital death with SAP. MPV combined with RDW has an important reference value for the prognosis of SAP patients.
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BACKGROUND: Periprosthetic infection after total knee arthroplasty (TKA) has become the most serious complication. However, there is still a lack of clinical study on the distribution of pathogenic bacteria. Therefore, understanding the distribution characteristics of the main pathogenic bacteria is critical for preventing and treating OBJECTIVE: To analyze the bacteriological characteristics in the patients with periprosthetic joint infection following TKA, so as to provide reference for early prevention and treatment. METHODS: CNKI, VIP, WanFang and PubMed databases were retrieved for the literature concerning periprosthetic infection following TKA published before 2016. The incidence of periprosthetic joint infection after TKA was statistically analyzed. RESULTS AND CONCLUSION: (1) 103 articles were included, involving 1 399 patients. (2) The main pathogenic bacteria were Staphylococcus aureus,coagulase negative Staphylococcus aureus,Staphylococcus epidermidis,Escherichia coli, Streptococcus and Enterococcus.There is no significant difference in the distribution of bacteria at home and abroad. Treatment strategies are divided into conservative and surgical treatments. (3) The key for successfully preventing and treating periprosthetic infection after TKA lies in the multiple disciplinary team collaboration, understanding the distribution of bacteria, early diagnosis and active preventive measurements, as well as rational treatment strategies.
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Several previous studies have reported the role variant of ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms in the risk of glioma, but the results of these studies are inconsistent. Therefore, we aimed to conduct a meta-analysis to investigate the role of ERCC1 rs3212986 and ERCC2 rs13181 on the risk of glioma. A comprehensive research was conducted through the databases of Pubmed, EMBASE and the China National Knowledge Infrastructure [CNKI] platforms until June 1, 2014, including 14 eligible case-control studies. Our meta-analysis found that ERCC1 rs3212986 AA genotype was significantly associated with increased risk of glioma compared with CC genotype, and the pooled OR [95%CI] was 1.29[1.07-1.55]. By subgroup analysis, ERCC1 rs3212986 AA genotype was found to be significantly correlated with increased glioma risk in Chinese population [OR=1.37, 95%CI=1.07, 1.55], Similarly, we found that ERCC2 rs13181 GT and TT genotypes were significantly associated with increased risk of glioma in Chinese population, with ORs [95%CI] of 1.47[1.17-1.85] and 1.50[1.02-2.22]. But ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms had no significant association with glioma risk in Caucasian populations. By begg's funnel plot, we found that no publication bias was existed in this meta-analysis. Our meta-analysis suggested that ERCC1 rs3212986 and ERCC2 rs13181 polymorphism play an important risk factor for brain tumor development in Chinese population, but no association in Caucasian populations
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Humans , DNA-Binding Proteins , Endonucleases , Xeroderma Pigmentosum Group D Protein , Polymorphism, Genetic , RiskABSTRACT
OBJECTIVES@#To investigate the effect of microRNA (miR-184) on regulating the genesis, development and proliferation of glioma cells.@*METHODS@#Lipidosome was used to transfect miR-184 mimic and inhibitor to glioma cell line, and the cell proliferation ability changes were determined by MTT and plate cloning experiment after the transfection. WB test was used to measure the levels of cyclinD1, p27 and FOXO3. Meanwhile, QPCR was used to detect miR-184 expression in glioma cell line, glioma tissues and adjacent tissues. Luciferase experiment was used to test 3'UTR gene targeting regulation of miR-184 and FOXO3.@*RESULTS@#QPCR results showed a significant lower miR-184 expression level in glioma cell line and glioma tissues than that in juxtacancerous tissue. MTT and plate cloning experiments have shown that after over-expressing of miR-184, the cell proliferation capacity of glioma U87 and T98G was significantly increased, which was significantly inhibited after the inhibition of miR-184. WB results showed a lower expression level of p27 in U87 and T98G cells, and a higher expression level of cyclinD1 after over-expressing of miR-184 was observed. However, a lower expression level of cyclinD1 and a higher expression level of p27 after the inhibition of miR-184. The luciferase activity was inhibited after the over-expressing of miR-184.@*CONCLUSIONS@#MiR-184 can affect the proliferation abilities of glioma cells and regulate the cell cycle related protein. It plays an important role in the occurrence and development of gliomas.
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<p><b>OBJECTIVE</b>To investigate the expression of placenta-derived RASSF1A gene in maternal plasma during first and second trimesters, and to explore its value for the prediction of pre-eclampsia.</p><p><b>METHODS</b>For 325 pregnant women of the first trimester, free DNA of plasma samples was extracted at 7-12, 13-18, and 19-24 gestational weeks, respectively. Methylation-sensitive restriction enzyme digestion followed by fluorescence quantitative PCR (MSRE+ PCR) was employed for analyzing the concentrations of hypermethylated RASSF1A gene. Blood pressure, proteinuria and clinical feature were monitored at the same time. Those who had subsequently developed pre-eclampsia were selected as the pre-eclamptic group, 30 normal pregnant women were selected as the control group. Hypermethylated RASSF1A gene in maternal plasma was retrospectively analyzed. The relationship between clinical classification, type of pre-eclampsia and concentrations of the gene were further analyzed.</p><p><b>RESULTS</b>Twenty-six out of the 325 pregnant women developed pre-eclampsia as their only complication. At 13-18 gestational weeks, the mean concentrations of fetus-specific RASSF1A sequences were 141.62 copies/mL in maternal plasma of pre-eclamptic pregnancies, which was significantly greater than that of the controls (98.90 copies/mL). Fetus-derived RASSF1A levels were 2.03 fold higher in pre-eclamptic subjects than controls at 19-24 gestational weeks. There was a significant difference in the level of hypermethylated RASSF1A gene between the mild and severe pre-clamptic subjects at 13-24 gestational weeks (P< 0.05). The concentrations of the sequences were significantly higher in early-onset severe pre-eclampsia than late-onset severe pre-eclampsia at 19-24 gestational weeks (P< 0.05).</p><p><b>CONCLUSION</b>Altered expression of hypermethylated RASSF1A gene may be detected in maternal plasma during second trimester, which has important significance for early prediction of pre-eclampsia.</p>
Subject(s)
Female , Humans , Pregnancy , Gestational Age , Placenta , Metabolism , Pre-Eclampsia , Blood , Diagnosis , Genetics , Metabolism , Predictive Value of Tests , Pregnancy Trimester, Second , Prenatal Diagnosis , Methods , Tumor Suppressor Proteins , Blood , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To confirm the relations between the expression of cyclin E, p16ink4, ki67 and HPV16/18 infection using cervical exfoliated cells, and evaluate the usefulness of cyclin E, p16ink4 and ki67 as biomarkers for screening of cervical carcinomas.</p><p><b>METHODS</b>The expression of cyclin E, p16ink4 oncoproteins and ki67 proliferative activity was evaluated immunohistochemically in 78 cervical exfoliated epithelial specimens. Human papillomavirus type16 and 18 (HPV16/18) infection was assessed by polymerase chain reaction (PCR) using type specific primers.</p><p><b>RESULTS</b>Cyclin E, p16ink4 and ki67 were all overexpressed in cervical preneoplasia and neoplasia cells, compared with little expressed in ASCUS (P less than 0.005). Overexpression of cyclin E was observed in CIN, (P less than 0.01), p16ink4 and ki67 overexpressed in invasive carcinoma(100 percent and 90.9 percent respectively). The degree of p16ink4 and ki67 expression correlated well with the degree of cervical neoplasia (P less than 0.005). HPV16 infection was assessed at all stages of cervical neoplasia samples, and a significant relationship with the degree of cervical epithelial lession was observed at the same time. The expression level of p16ink4 and ki67 seemed to be more closely associated with HPV16 infection than cyclin E did (rs=1.0 vs rs=0.4). HPV18 was found positive in only 1 case in CIN1 and in 4 cases in CIN2-3. Therefore no significance was found on statistical analysis (P less than 0.005).</p><p><b>CONCLUSION</b>Cyclin E, p16ink4 and ki67 should be regarded as useful biomarkers of HPV-related cervical neoplasias, and be used for screening patients at high risk for developing cervical carcinomas. Moreover, cyclin E might be a significant cytologic marker for the primary screening of cervical carcinomas.</p>