Objective By screening key genes and related pathways for hepatic fibrosis treatment through bioinformatics analysis,the differentially expressed genes of hepatic fibrosis patients were mined to predict potential therapeutic targets for liver fibrosis.Methods Gene expression profiles GSE197112 were obtained from GEO database.Differentially expressed genes were screened by Limma.DAVID online database was used to conduct GO enrichment analysis and KEGG signaling pathway enrichment analysis of differentially expressed genes.The protein-protein interaction(PPI)network diagram of differentially expressed genes were obtained from STRING database and visualize by Cytoscape software.At the same time,the plug-in CytoHubba in Cytoscape software was used to screen the target genes of hepatic fibrosis.Results A total of 399 differentially expressed genes were screened(P<0.01,∣log2FC∣>1.5),including 300 down-regulated genes and 99 up-regulated genes.These genes were mainly involved in GO biological processes such as mitosis checkpoint,DNA replication,chromosome segregation,cell division,apoptosis,adaptive immune response and so on,and mainly regulated the intestinal immune network for IgA production,progesterone-mediated oocyte maturation,human T-cell leukemia virus 1 infection,cell cycle,antigen processing and presentation,p53 signaling pathway,cancer transcription disorder,cell adhesion molecules and so on.Five target genes were screened by Cytoscape software:TTK,KIF2C,ASPM,DLGAP5,PBK.Conclusion In this study,399 differentially expressed genes and 5 target genes in hepatic fibrosis were screened by bioinformatics methods,which play key roles in the biological processes related to hepatic fibrosis,and provide a new direction for the pharmacological treatment of liver fibrosis.

italic>Acanthopanax senticosus is one of the genuine regional herb in Northeast China. In this study, we identified the germplasm resources of commercial A. senticosus samples based on atpI and atpB_rbcL according to the previous chloroplast genome sequencing results, and determinated the content of syringin by HPLC to evaluated the quality of commercial samples. A total of 80 A. senticosus samples were collected from 47 cities in 24 provinces. DNA was extracted to amplify the products of atpI and atpB_rbcL by PCR. The results showed that 7 haplotypes (H2, H5, H8, H10, H12, H14, H23) were formed by the combined analysis of the two gene fragments. H2 from Yichun in Heilongjiang, Shangzhi in Harbin, Suihua in Heilongjiang, Fushun in Liaoning, Benxi in Liaoning, Changbai in Jilin and Jingyu in Jilin were the dominant genotype, representing 58.75% of the total samples. H14 and H23 were the unique haplotypes of the producing area. It is speculated that the commercial A. senticosus samples with haplotypes of H14 and H23 are from Raohe, Shuangyashan, Heilongjiang and Mingshui, Suihua, Heilongjiang, respectively. HPLC analysis indicated that the content of syringin in 73.96% of the samples met the Pharmacopoeia standards. There was a significant difference in the content of syringin among the samples, ranging from 0.003 7% to 0.524 5%, with a difference of 0.520 8%, indicating that the quality of the samples in the market of A. senticosus was uneven. However, there were no significant differences in the contents of syringin in the commercial A. senticosus among different haplotypes. The content of syringin in the haplotype H23 in the market sample is relatively high, so it may be a germplasm with better quality. This study researched the germplasm resources and medicinal materials quality of commercial A. senticosus samples and will help guide the commercial circulation, reasonable medication of A. senticosus, and the screening of excellent germplasm.

Objective To investigate the levels of serum Vitamin D(VD) from preconception to pregnancy in Jiading district of Shanghai, and explore the risk factors of VD concentration deficiency in the second and third trimester of pregnancy. Methods A total of 94 women who planned to have antenatal care and delivery in Maternal and Child Health Hospital of Jiading district of Shanghai from September 2016 to December 2018 were recruited as the study participants. Chemiluminescent immunoassay (CLIA) was used to examine the concentration of women’s serum VD from preconception to pregnancy. A total of 282 serum samples were detected. Results The prevalence of VD deficiency among 94 women from preconception to pregnancy were 40.4%,57.4% and 48.9% respectively. Results of the mixed linear model showed that women who had dyed or permed hair within the past 1 year had significantly lower serum VD levels during pregnancy (P<0.05), and women who often drank milk and ate deep-sea fish during pregnancy had higher VD levels during pregnancy (P<0.05). Conclusions VD deficiency was common among women in Jiading district of Shanghai, and it should be emphasized to supplement VD before and during pregnancy.

BACKGROUNDMatrix metalloproteinase (MMP)-2 plays an important role in the remodeling of left ventricles (LVs) and right ventricles (RVs). We investigated the differences of MMP-2 expression between LV and RV in response to nandrolone decanoate (ND), swimming training (ST), and combined ND and ST (NS) in mice, based on their structural, functional, and biochemical characteristics.

METHODSTotally 28 male C57B1 mice (6 weeks old; 20-23 g) were divided into four groups, including the control (n = 7), ND (n = 6), ST (n = 8), and NS (n = 7) groups. After respective treatments for 8 weeks, echocardiographic examination was used to assess the cardiac structure and function. Van Gieson stain was used to examine the fibrosis of LV and RV in response to different treatments, and Western blotting analysis was performed to explore different MMP-2 expressions between LV and RV in response to ND and/or ST. Analysis of variance was used for comparing the four groups.

RESULTSAt 8 weeks, right ventricular dimension/body weight in the ND group was larger than the other three groups (F = 7.12, P < 0.05) according to the echocardiographic examination. Fibrosis induced by ND administration was increased more in RV (2.59%) than that in LV (2.21%). MMP-2 expression of the ND group in RV was significantly greater than the control and NS groups in RV and the corresponding ND group in LV.

CONCLUSIONThe experimental data support the hypothesis that ND administration induces greater MMP-2 expression increase in RV compared to LV, leading to consequent RV dilation.

BACKGROUNDThis study aimed to evaluate the effects of standard rescue procedure (SRP) in improving severe trauma treatments in China.

METHODSThis study was conducted in 12 hospitals located in geographically and industrially different cities in China. A standard procedure on severe trauma rescue was established as a general rule for staff training and patient treatment. A regional network (system) efficiently integrating prehospital rescue, emergency room treatments, and hospital specialist treatments was built under the rule for information sharing and improving severe trauma treatments. Treatment outcomes were compared between before and 1 year after the implementation of the SRP.

RESULTSThe outcomes of a total of 74,615 and 12,051 trauma cases were collected from 12 hospitals before and after the implementation of the SRP. Implementation of the SRP led to efficient cooperation and information sharing of different treatment services. The emergency response time, prehospital transit time, emergency rescue time, consultation call time, and mortality rate of patients were 24.24 ± 4.32 min, 45.69 ± 3.89 min, 6.38 ± 1.05 min, 17.53 ± 0.72 min, and 33.82% ± 3.87% (n = 441), respectively, before the implementation of the standardization and significantly reduced to 10.11 ± 3.21 min, 22.39 ± 4.32 min, 3.26 ± 0.89 min, 3.45 ± 0.45 min, and 20.49% ± 3.11%, separately (n = 495, P < 0.05) after that.

CONCLUSIONSStaff training and SRP can significantly improve the efficiency of severe trauma treatments in China.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; Emergency Medical Services ; standards ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Wounds and Injuries ; Young Adult

Objective To explore the establishment of a rat model of acute radiation-induced liver injury and sig-nificance of the dynamic changes of TGF-β1 expression.Methods Forty healthy 6-week old male SD rats were randomly divided into model group (n=30) and control group (n=10).The right liver of rats in the model group was given a single dose of 25 Gy 6 MV X-ray irradiation.Histopathological examination using HE staining and transmission electron microsco-py were conducted to observe the liver pathological changes in rats at 3, 5, and 10 days after irradiation, serum TGF-β1 was detected, and relevant indicators of liver function ( ALT, AST, ALP) were determined.Statistical analysis was per-formed using SPSS 17.0 software.Results At 3, 5 and 10 days after irradiation, early pathological changes in the liver cells were observed by electron microscopy, the expression of TGF-β1 was gradually increased with the time prolongation, and significant differences were found between the model group and the control group at different time points (P<0.05). The light microscopic observation of liver tissues did not show significant differences between the control group and model group.The liver ALT, AST, ALP at different time points did not show significant differences between the two groups ( P>0.05).Conclusion Electron microscopy can be used to evaluate the early changes of radiation-induced liver injury, pri-or to the alterations visible by routine light microscopy.TGF-β1 can be used to predict the degree of radiation-induced liver injury, and may be used as a sensitive serum cytokine in predicting the degree of radiation-induced acute liver injury.

Objective To analyze the clinical characteristics of dengue fever (DF) in Guangzhou Higher Education Mega Center (HEMC) in the year of 2014. Methods A retrospective analysis was carried out in the clinical data of 487 cases of DF patients. Results The incidence of DF accounted for 27.18% ( 527/1939) of the total emergeney fever cases. In 487 DF cases with detailed data, 261 were male, and 226 were female; 312 were young aged, 88 were middle aged, and 87 were old aged. For the systemic symptoms, fever accounted for 87.5%, headache 48.3%, and muscular soreness 47.6%. Cough ( 16.6%) , pharynx pain ( 16.8%) and running nose ( 10.9%) were common in respiratory symptoms; poor appetite ( 14.4%) and nausea ( 10.3%) were common in gastrointestinal symptoms. The abnormal laboratory parameters were mainly shown as WBC count ( 48.25%) and PLT count ( 41.68%) , following by creatine kinase ( CK, 39.49%) , aspartate aminotransferase ( AST, 34.12%) , and lactate dehydrogenase ( LDH, 31.96%) . Less cases had abnormal renal function. The distribution of Chinese medical syndrome types was shown as damp-heat blockage (65.7%), syndrome involving Weifen and Qifen simultaneously (23.6%), and Qi-yin deficiency (10.7%). Conclusion In the year of 2014, DF in Guangzhou HEMC occurred mainly among the youth people, the incidence of male DF was similar to that of the female DF, and DF cases usually have the primary symptoms of fever, aversion to cold, headache and muscular soreness. Bleeding is seldom seen in the DF patients, a few cases are complicated with the damage in the blood, liver and myocardium, and most of them have good prognosis.

Retinoid X receptor α (RXRα) and its N-terminally truncated version tRXRα play important roles in tumorigenesis, while some RXRα ligands possess potent anti-cancer activities by targeting and modulating the tumorigenic effects of RXRα and tRXRα. Here we describe NSC-640358 (N-6), a thiazolyl-pyrazole derived compound, acts as a selective RXRα ligand to promote TNFα-mediated apoptosis of cancer cell. N-6 binds to RXRα and inhibits the transactivation of RXRα homodimer and RXRα/TR3 heterodimer. Using mutational analysis and computational study, we determine that Arg316 in RXRα, essential for 9-cis-retinoic acid binding and activating RXRα transactivation, is not required for antagonist effects of N-6, whereas Trp305 and Phe313 are crucial for N-6 binding to RXRα by forming extra π-π stacking interactions with N-6, indicating a distinct RXRα binding mode of N-6. N-6 inhibits TR3-stimulated transactivation of Gal4-DBD-RXRα-LBD by binding to the ligand binding pocket of RXRα-LBD, suggesting a strategy to regulate TR3 activity indirectly by using small molecules to target its interacting partner RXRα. For its physiological activities, we show that N-6 strongly inhibits tumor necrosis factor α (TNFα)-induced AKT activation and stimulates TNFα-mediated apoptosis in cancer cells in an RXRα/tRXRα dependent manner. The inhibition of TNFα-induced tRXRα/p85α complex formation by N-6 implies that N-6 targets tRXRα to inhibit TNFα-induced AKT activation and to induce cancer cell apoptosis. Together, our data illustrate a new RXRα ligand with a unique RXRα binding mode and the abilities to regulate TR3 activity indirectly and to induce TNFα-mediated cancer cell apoptosis by targeting RXRα/tRXRα.
Apoptosis ; drug effects ; Cell Line, Tumor ; Enzyme Activation ; drug effects ; Humans ; Ligands ; Molecular Docking Simulation ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; genetics ; metabolism ; Oximes ; metabolism ; pharmacology ; Protein Conformation ; Proto-Oncogene Proteins c-akt ; metabolism ; Pyrazoles ; metabolism ; pharmacology ; Retinoid X Receptor alpha ; chemistry ; genetics ; metabolism ; Thiazoles ; metabolism ; pharmacology ; Transcription, Genetic ; drug effects ; Transcriptional Activation ; drug effects ; Tumor Necrosis Factor-alpha ; metabolism

With defined culture protocol, human embryonic stem cells (hESCs) are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for cardiac disease therapies. In this study, we successfully generated a highly pure population of human cardiomyocytes (hCMs) (>95% cTnT(+)) from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA methylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene functions and disease mechanisms. Moreover, we show that cardiac-structural genes and cardiac-transcription factors have distinct epigenetic mechanisms to regulate their gene expression, providing a better understanding of how the epigenetic machinery coordinates to regulate gene expression in different cell types.
Cell Differentiation ; Cell Line ; DNA Methylation ; Embryonic Stem Cells ; cytology ; metabolism ; Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Myocytes, Cardiac ; cytology ; metabolism ; Transcription, Genetic