Objective To investigate the expression level of serine/threonine phosphoprotein phosphatase 4C(PPP4C)in gastric cancer,and analyze its relationship with prognosis and the underlying regulatory mechanism.Methods The clinical data of 104 gastric cancer patients admitted to the First Affiliated Hospital of Bengbu Medical College between January 2012 and August 2016 were collected.Immunohistochemical staining was employed to determine the expression levels of PPP4C and Ki-67 in the gastric cancer tissue.The gastric cancer cell lines BGC823 and HGC27 were cultured and transfected with the vector for PPP4C knockdown,the vector for PPP4C overexpression,and the lentiviral vector(control),respectively.The effects of PPP4C on the cell cycle and proliferation were analyzed and the possible regulatory mechanisms were explored.Results PPP4C was highly expressed in gastric cancer(P<0.001),and its expression promoted malignant progression of the tumor(all P<0.01).Univariate and Cox multivariate analysis clarified that high expression of PPP4C was an independent risk factor affecting the 5-year survival rate of gastric cancer patients(P=0.003).Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that PPP4C may be involved in the cell cycle.The correlation analysis showed that the expression of PPP4C was positively correlated with that of Ki-67 in gastric cancer(P<0.001).The up-regulation of PPP4C expression increased the proportion of tumor cells in the S phase,alleviated the G2/M phase arrest,and promoted the proliferation of gastric cancer cells and the expression of cyclin D1 and cyclin-dependent kinase 6(CDK6)(all P<0.05).The down-regulation of PPP4C decreased the proportion of gastric cancer cells in the S phase,promoted G2/M phase arrest,and inhibited cell proliferation and the expression of cyclin D1,CDK6,and p53(all P<0.05).p53 inhibitors promoted the proliferation of BGC823 and HGC27 cells in the PPP4C knockdown group(P<0.001,P<0.001),while p53 activators inhibited the proliferation of BGC823 and HGC27 cells in the PPP4C overexpression group(P<0.001,P=0.002).Conclusions PPP4C is highly expressed in gastric cancer and affects the prognosis of the patients.It may increase the proportion of gastric cancer cells in the S phase and alleviate the G2/M phase arrest by inhibiting p53 signaling,thereby promoting cell proliferation.
Humans ; Stomach Neoplasms/genetics* ; Cyclin D1/metabolism* ; Tumor Suppressor Protein p53 ; Phosphoproteins/metabolism* ; Ki-67 Antigen ; Cell Line, Tumor ; Prognosis ; Cell Proliferation ; Phosphoprotein Phosphatases/metabolism* ; Threonine ; Serine

Objective To analyze the expression of m6A methyltransferase like 3(METTL3)gene in pan-tumor and its effect on tumor microenvironment.Methods The Cancer Genome Atlas(TCGA)database was used to analyze the gene sequencing and clinical data of patients with various tumors.The expressions of METTL3 gene in various tumors and its correlations with prognosis and tumor microenvironment were analyzed.Results METTL3 gene expression was upregulated in most malignancies,but only was associated with poor PFS of patients with hepatocellular carcinoma and prostate cancer(P＜0.05).The expression of METTL3 gene was associated with the infiltration levels of many inmmunet cells in hepatocellular carcinoma and prostate cancer,as well as the expression levels of inhibitory immune checkpoint genes(P＜0.05).Conclusions METTL3 gene overexpression could affect the prognosis of hepatocellular carcinoma and prostate cancer,which maybe associated with immune invasion and inhibitory immune checkpoints increased.

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.

Colla Corii Asini(Ejiao)is an important Chinese medicine used in China for thousands of years, and is well known for its famous tonic properties. The herbalogical study was detailed carried out based on the naming, habitat, harvesting, processing, medicinal properties and clinical efficacy. The results showed that the name of Ejiao could be traced back to Shennong's Materia Medica, and various names of Lvpi Jiao, Penfu Jiao and Fuzhi Jiao were recorded in other ancient books. In the many intervening centuries, the main materials of Ejiao had been replaced from cow leather before Tang Dynasty to donkey skin in the middle to late Tang Dynasty. This phenomenon could be probably caused by complicated social factors of various periods and different efficacy of Ejiao made by all kinds of raw materials. Ejiao was merely processed with the simple methods before Tang Dynasty, which subsequently improved avariety of methods to enhance the supplementation action. Most importantly, Ejiao has a wide clinic application along with the development of processing theories and methods, which can be found in various Classics, especially in imperial medical case record in Qing Dynasty.
Animals ; Cattle ; China ; Drugs, Chinese Herbal ; Female ; Gelatin ; Materia Medica ; Medicine, Chinese Traditional

OBJECTIVE: To investigate the risk factors for brain injury in preterm infants by a multicenter epidemiological investigation of brain injury in hospitalized preterm infants in Anhui, China. METHODS: Preterm infants who were hospitalized in the department of neonatology in 9 hospitals of Anhui Neonatal Collaboration Network between January 2016 and January 2017 were enrolled as subjects. The data of maternal pregnancy and clinical data of preterm infants were collected, and the logistic regression model was used to analyze the risk factors for brain injury in preterm infants. RESULTS: A total of 3 378 preterm infants were enrolled. Of the 3 378 preterm infants, 798 (23.56%) had periventricular-intraventricular hemorrhage (PVH-IVH), and 88 (2.60%) had periventricular leukomalacia (PVL). Intrauterine distress, anemia, hypoglycemia and necrotizing enterocolitis (NEC) were risk factors for PVH-IVH (OR=1.310, 1.591, 1.835, and 3.310 respectively; P<0.05), while a higher gestational age was a protective factor against PVH-IVH (OR=0.671, P<0.05). PVH-IVH, NEC and mechanical ventilation were risk factors for PVL (OR=4.017, 3.018, and 2.166 respectively; P<0.05), and female sex and use of pulmonary surfactant were protective factors against PVL (OR=0.514 and 0.418 respectively; P<0.05). CONCLUSIONS Asphyxia/anoxia, infection/inflammation, mechanical ventilation, anemia and hypoglycemia may increase the risk of brain injury in preterm infants.
Brain Injuries ; Cerebral Hemorrhage ; China ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Leukomalacia, Periventricular

OBJECTIVETo develop a rapid, highly sensitive, and quantitative method for the detection of NT-proBNP levels based on a near-infrared point-of-care diagnostic (POCT) device with wide scope.

METHODSThe lateral flow assay (LFA) strip of NT-proBNP was first prepared to achieve rapid detection. Then, the antibody pairs for NT-proBNP were screened and labeled with the near-infrared fluorescent dye Dylight-800. The capture antibody was fixed on a nitrocellulose membrane by a scribing device. Serial dilutions of serum samples were prepared using NT-proBNP-free serum series. The prepared test strips, combined with a near-infrared POCT device, were validated by known concentrations of clinical samples. The POCT device gave the output of the ratio of the intensity of the fluorescence signal of the detection line to that of the quality control line. The relationship between the ratio value and the concentration of the specimen was plotted as a work curve. The results of 62 clinical specimens obtained from our method were compared in parallel with those obtained from the Roche E411 kit.

RESULTSBased on the log-log plot, the new method demonstrated that there was a good linear relationship between the ratio value and NT-proBNP concentrations ranging from 20 pg/mL to 10 ng/mL. The results of the 62 clinical specimens measured by our method showed a good linear correlation with those measured by the Roche E411 kit.

CONCLUSIONThe new LFA detection method of NT-proBNP levels based on the near-infrared POCT device was rapid and highly sensitive with wide scope and was thus suitable for rapid and early clinical diagnosis of cardiac impairment.

Antibodies ; Biomarkers ; Heart Diseases ; diagnosis ; Humans ; Immunoassay ; methods ; Infrared Rays ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Point-of-Care Testing ; Reagent Strips ; Sensitivity and Specificity

Objective To investigate the association between the genetic variant of miRNA-1 target gene COG6 rs9548934 C→T and the risk of premature coronary artery disease (pCAD).Methods This study included 226 pACD patients and 275 gender and age matched pCAD-free controls hospitalized in our hospital,diagnosis was made based on coronary angiography ( CAG ) results.The genotypes of miRNA-1 target gene COG6 rs9548934 C→T were detected by PCR-RFLP.Results Compared with the wide genotype CC,subjects with the variant genotypes CT of rs9548934 C→T was associated with a 45％ lower risk of pACD (adjusted OR =0.55,95％ CI =0.36 -0.82,P =0.003),and the subjects with CT/TT genotypes were also associated with a significantly lower risk of pACD ( adjusted OR =0.64,95％ CI =0.44 - 0.92,P=0.015).Using the median serum TG level (1.20 mmol/L) in control group as the cutoff value,subjects with higher serum TG levels were associated with increased risk of pACD after adjustment for age,gender and BMI ( adjusted OR =2.32,95％ CI =1.57 - 3.41,P ＜ 0.001 ).In addition,subjects with higher HDL-C levels were associated with significantly lower risk of pACD ( adjusted OR =0.48,95％ CI =0.31 -0.75,P =0.001 ).Stratified analyses showed that the risk reduction for pCAD in CT/TT genotypes carriers was more significant in the female subjects ( adjusted OR =0.54,95％ CI =0.30 - 0.97,P=0.040),and in subjects with lower TG,TC,HDL-C and LDL-C levels (adjusted OR =0.62,95％ CI =0.39 - 0.98,P =0.040; adjusted OR =0.55,95 ％ CI =0.35 - 0.85,P =0.008; adjusted OR =0.43,95％CI=0.22-0.87,P=0.018; adjusted OR=0.49,95％CI=0.32-0.75,P=0.001,respectively).Conclusion The polymorphism of miRNA-1 target gene COG6 rs9548934C→T is associated with lower risk of pCAD,especially in female subjects and subjects with lower serum lipid levels.

BACKGROUNDSuperparamagnetic iron oxide (SPIO) particles have shown much promise as a means to visualize labeled cells using molecular magnetic resonance imaging (MRI). Micrometer-sized superparamagnetic iron oxide (MPIO) particles and nanometer-sized ultrasmall superparamagnetic iron oxide (USPIO) are two kinds of SPIO widely used for monitoring stem cells migration. Here we compare the efficiency of two kinds of SPIO during the use of stem cells to treat acute myocardial infarction (AMI).

METHODSAn AMI model in swine was created by 60 minutes of balloon occlusion of the left anterior descending coronary artery. Two kinds of SPIO particles were used to track after intracoronary delivered 10(7) magnetically labeled mesenchymal stem cells (MR-MSCs). The distribution and migration of the MR-MSCs were assessed with the use of 3.0T MR scanner and then the results were confirmed by histological examination.

RESULTSMR-MSCs appeared as a local hypointense signal on T₂*-weighted MRI and there was a gradual loss of the signal intensity after intracoronary transplantation. All of the hypointense signals in the USPIO-labeled group were found on T₂*-weighted MRI, contrast to noise ratio (CNR) decreased in the MPIO-labeled group (16.07 ± 5.85 vs. 10.96 ± 1.34) and USPIO-labeled group (11.72 ± 1.27 vs. 10.03 ± 0.96) from 4 to 8 weeks after transplantation. However, the hypointense signals were not detected in MPIO-labeled group in two animals. MRI and the results were verified by histological examination.

CONCLUSIONSWe demonstrated that two kinds of SPIO particles in vitro have similar labeling efficiency and viability. USPIO is more suitable for labeling stem cells when they are transplanted via a coronary route.

Animals ; Cell Survival ; Contrast Media ; Ferric Compounds ; Magnetic Resonance Imaging ; methods ; Male ; Myocardial Infarction ; diagnosis ; pathology ; Stem Cells ; cytology ; Swine

BACKGROUNDMesenchymal stem cells (MSCs) transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs (MR-MSCs) and monitor the restorative effects of MR-MSCs with magnetic resonance (MR) imaging.

METHODSAcute myocardial infarction (AMI) was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat (SPSS version 12.01).

RESULTSA total of 26 swine were divided into four groups (sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7). MSCs, MR-MSCs (10(7) cells) or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction (LVEF) was slightly increased in the AMI group ((41.87+/-2.45)% vs (39.04+/-2.80)%, P>0.05), but significantly improved in the MR-MSCs group ((56.85+/-1.29)% vs (40.67+/-2.00)%, P<0.05) and unlabeled group ((55.38+/-1.07)% vs (41.78+/-2.08)%, P<0.05) at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group.

CONCLUSIONTransplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2-month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.

Animals ; Blotting, Western ; Cell Survival ; Disease Models, Animal ; Magnetic Resonance Imaging ; Magnetics ; Mesenchymal Stem Cell Transplantation ; Myocardial Infarction ; physiopathology ; therapy ; Swine ; Ventricular Function, Left

Objective To evaluate the therapeutic effects of magnetically labeled mononuclear stem cells (MR-MNC) and mesenchymal stem cells (MR-MSC) transplantation in a swine acute myocardial infarction (AMI) model by MR imaging.Methods AMI model was established in swines by balloon occlusion of the left anterior descending coronary artery,107 autologous MR-MSC (n=7),MR-MNC (n=6) or PBS(n=6) were delivered via intracoronary infusion within 1 week after AMI [(4.8±1.3) days].Changes of infarct size and cardiac function were assessed with the use of 3.0T MR scanner before AMI,at 1 and 8 weeks post AMI.Results Magnetically labeled stem cells could be identified in the region of AMI by cardiac MR imaging.Eight weeks post transplantation,infarct size was significantly reduced in MR-MSC transplantation group(8.5%±0.5% vs.24.7%±3.1%,P＜0.05) and in MR-MNC transplantation (12.3%±1.5% vs.26.1%±1.5%,P＜0.05) while infaret size remained unchanged in PBS group (P＞0.05) compared to values at 1 week post AMI,left yentricular ejection fraction (LVEF) was also significantly higher in MR-MSC transplantation group (56.9%±1.3% vs.40.7%±2.0%,P＜0.05) and MR-MNC transplantation group (52.8%±1.4% vs.41.9%±3.3%,P＜0.06) compared to LVEF at 1 week post AML LVEF increase was more significant in swines received MR-MSC transplantation than MRMNC transplantation(16.2%±1.2% vs.10.9%±3.0%,P＜0.05).Prussian blue staining identified stem cells in corresponding myocardial regions with as by MRI.Western blot analysis demonstrated that cardiac expressions of myosin heavy chain (MHC) in MR-MSC group (100.3±5.5) and in MR-MNCs group (95.5±4.2) were significantly higher than that in PBS group (75.7±5.7,P＜0.05),myocardial troponin T (cTNT) expression in MR-MSC group (124.0±5.8) and MR-MNC group (118.4±4.4) were also significantly higher than in PBS group (93.3±3.9,P＜0.05) while MMP2/TIMP1 ratios in MR-MSC group (0.6±0.1) and MR-MNC group (0.6±0.1) were significandy lower than that in PBS group (4.2±0.2,P＜0.05).Conclusions Magnetically labeled MR-MSC and MR-MNC homed to heart post myocardial infarction and reduced infarct size,improved cardiac function.MR-MSC is superior to MR-MNC on improving cardiac function.