Objective: To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha ( PPP2R3A) and hexokinase 1 ( HK1) in glycolysis of hepatocellular carcinoma (HCC). Methods: In HepG2 and Huh7 cells, PPP2R3A expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The PPP2R3A-related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of PPP2R3A and HK1. Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by PPP2R3A. Results: RNA sequencing data revealed that PPP2R3A siRNA significantly downregulated the expression of HK1. PPP2R3A gene overexpression promotes, while gene silencing suppresses, the level of HK1 and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. HK1 inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by PPP2R3A overexpression in liver cancer cells. Conclusion Our findings showed the correlation of PPP2R3A and HK1 in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of PPP2R3A in cancer.
Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glycolysis ; Hexokinase/metabolism* ; Humans ; Liver Neoplasms/pathology* ; Protein Phosphatase 2/metabolism* ; RNA, Small Interfering/metabolism*

BACKGROUND: Either good biocompatibility and biological activity of active biological materials or the potential of multidirectional differentiation of neural stem cells has great application prospect and value. OBJECTIVE: To investigate the effect of neurotrophic factor 3-chitosan active biomaterial scaffolds on the differentiation of neural stem cells and the expression of key proteins of the neurotrophic factor 3 signal pathway in vitro. METHODS: The neural stem cells were extracted and purified, and then divided into pure culture medium group, soluble neurotrophic factor 3 group, pure chitosan group, and neurotrophic factor 3-chitosan group for differentiation induction. The expression of TrkC, Akt / p-Akt and Erk/p-Erk in the neurotrophic factor 3 signaling pathway was detected by western blot after 6 hours of induction. After 7 days of induction, differentiation of neural stem cells was observed by immunocytochemistry of MAP2, MBP, and GFAP. After 14 days of induction, formation of neural network induced by neurotrophic factor 3-chitosan active biomaterials was observed by immunocytochemistry of MAP2, Synapsin-1, and PSD95. RESULTS AND CONCLUSION: The neurotrophic factor 3-chitosan group induced a high proportion of neural stem cells differentiated into neurons, with a ratio of 73.8%, which was significantly higher than that in the other three groups. Meanwhile, the proportion of cells differentiated into glial cells waslower than that in the other three groups. The expression of key proteins TrkC, p-Akt and p-Erk in the neurotrophic factor 3-chitosan group was higher than that in the other three groups. Meanwhile, neurotrophic factor 3-chitosan could induce the in vitro differentiation of neural stem cells to form neural network.

Based on the introduction to the clinical phenotype extraction technique,the paper conducts systematic review on the extraction of clinical phenotype from Electronic Medical Records (EMR) of diabetes by taking advantages of the clinical decision support technique,natural language processing technique and machine learning method,and indicates that the deep learning method can be used to extract clinical phenotype from the EMR data more effectively and accurately,help clinical researchers better conduct clinical tests,and improve the medical care level.

Objective To evaluate the safety of pirfenidone in treatment of idiopathic pulmonary fibrosis( IPF). Methods PubMed,the Cochrane library,EMbase,CNKI,and WanFang database were searched using the keywords pirfenidone,idiopathic pulmonary fibrosis,and IPF from January 1999 to January 2015. Randomized controlled trials( RCTs)of pirfenidone in treatment of IPF were selected. The patients in the trial group were given pirfenidone alone while the patients in the control group were given oral placebo. The primary end point event of the outcome was the incidence of pirfenidone′s adverse events. The Meta-analysis was performed using RevMan 5. 2. Results A total of 4 articles including 5 RCTs were enrolled. There were 945 patients in the trial group and 766 patients in the control group. The incidents of many kinds of adverse events in the trial group were markedly higher than those in the control group, including gastrointestinal discomfort[12. 6%(101/804)vs. 5. 2%(40/766),RR = 2. 31,95% CI:63-3. 29,P< 0. 01],nausea[34. 6%(241/695)vs. 15. 0%(99/659),RR = 2. 373,95% CI:1. 92-2. 92,P< 0. 01]and vomiting[13. 3%(83/623)vs. 6. 3%(39/624),RR= 2. 13,95% CI:1. 48-3. 06,P< 0. 01],diarrhea[25. 8%(161/623)vs. 20. 4%(127/624),RR= 1. 27,95% CI:1. 03-1. 56,P=0. 02],anorexia[15. 2%(122/804)vs. 4. 7%(36/766),RR= 3. 10,95% CI:2. 16-4. 46,P<0. 01],abnormal liver function[6. 0%(49/804)vs. 1. 7%(13/766),RR= 2. 48,95% CI:1. 46-4. 23,P<0. 01],rash[30. 4%(189/623)vs. 10. 3%(64/624),RR= 2. 95,95% CI:2. 27-3. 83,P<0. 01],photosensitivity reaction[24. 7%(129/526)vs. 6. 1%(30/489),RR= 5. 54,95%CI:1. 78-17. 30,P<0. 01],insomnia[10. 4%(65/623)vs. 6. 6%(41/624),RR=1. 59,95% CI:1. 09-2. 31,P= 0. 02],dizziness[16. 4%(120/732)vs. 9. 8%(72/731),RR=1. 67,95% CI:1. 27-2. 19,P<0. 01],fatigue[25. 6%(178/695)vs. 16. 3%(108/659),RR = 1. 60,95% CI:1. 29-1. 98,P< 0. 01],and weight loss[10. 1%(63/623)vs. 5. 4%(34/624),RR= 1. 85,95% CI:1. 24-2. 77,P = 0. 03]. However,there was no statistically significant difference in treatment-related serious events[26. 5%(165/623)vs. 26. 4%(165/624),RR = 1. 00,95% CI:0. 83-1. 20,P = 0. 94]. Compared with the control group,there was a statistical significance in the rate of drug withdrawal in the trial group[14. 6%( 117/804 ) vs. 9. 0%( 69/766 ),RR = 1. 62,95% CI:1. 22-2. 15,P <0. 01 ). Conclusion The common adverse events of pirfenidone are gastrointestinal,skin,and neurological system damage and fatigue and loss of weight. The adverse events are mild and mostly recoverable without obvious sequelae. The pirfenidone is safe and well-tolerated.

Objective To evaluate the safety of pirfenidone in treatment of idiopathic pulmonary fibrosis( IPF). Methods PubMed,the Cochrane library,EMbase,CNKI,and WanFang database were searched using the keywords pirfenidone,idiopathic pulmonary fibrosis,and IPF from January 1999 to January 2015. Randomized controlled trials( RCTs)of pirfenidone in treatment of IPF were selected. The patients in the trial group were given pirfenidone alone while the patients in the control group were given oral placebo. The primary end point event of the outcome was the incidence of pirfenidone′s adverse events. The Meta-analysis was performed using RevMan 5. 2. Results A total of 4 articles including 5 RCTs were enrolled. There were 945 patients in the trial group and 766 patients in the control group. The incidents of many kinds of adverse events in the trial group were markedly higher than those in the control group, including gastrointestinal discomfort[12. 6%(101/804)vs. 5. 2%(40/766),RR = 2. 31,95% CI:63-3. 29,P< 0. 01],nausea[34. 6%(241/695)vs. 15. 0%(99/659),RR = 2. 373,95% CI:1. 92-2. 92,P< 0. 01]and vomiting[13. 3%(83/623)vs. 6. 3%(39/624),RR= 2. 13,95% CI:1. 48-3. 06,P< 0. 01],diarrhea[25. 8%(161/623)vs. 20. 4%(127/624),RR= 1. 27,95% CI:1. 03-1. 56,P=0. 02],anorexia[15. 2%(122/804)vs. 4. 7%(36/766),RR= 3. 10,95% CI:2. 16-4. 46,P<0. 01],abnormal liver function[6. 0%(49/804)vs. 1. 7%(13/766),RR= 2. 48,95% CI:1. 46-4. 23,P<0. 01],rash[30. 4%(189/623)vs. 10. 3%(64/624),RR= 2. 95,95% CI:2. 27-3. 83,P<0. 01],photosensitivity reaction[24. 7%(129/526)vs. 6. 1%(30/489),RR= 5. 54,95%CI:1. 78-17. 30,P<0. 01],insomnia[10. 4%(65/623)vs. 6. 6%(41/624),RR=1. 59,95% CI:1. 09-2. 31,P= 0. 02],dizziness[16. 4%(120/732)vs. 9. 8%(72/731),RR=1. 67,95% CI:1. 27-2. 19,P<0. 01],fatigue[25. 6%(178/695)vs. 16. 3%(108/659),RR = 1. 60,95% CI:1. 29-1. 98,P< 0. 01],and weight loss[10. 1%(63/623)vs. 5. 4%(34/624),RR= 1. 85,95% CI:1. 24-2. 77,P = 0. 03]. However,there was no statistically significant difference in treatment-related serious events[26. 5%(165/623)vs. 26. 4%(165/624),RR = 1. 00,95% CI:0. 83-1. 20,P = 0. 94]. Compared with the control group,there was a statistical significance in the rate of drug withdrawal in the trial group[14. 6%( 117/804 ) vs. 9. 0%( 69/766 ),RR = 1. 62,95% CI:1. 22-2. 15,P <0. 01 ). Conclusion The common adverse events of pirfenidone are gastrointestinal,skin,and neurological system damage and fatigue and loss of weight. The adverse events are mild and mostly recoverable without obvious sequelae. The pirfenidone is safe and well-tolerated.