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ObjectiveTo investigate the expression and role of response gene to complement 32 （RGC32） in liver regeneration after partial hepatectomy （PH）. MethodsA total of 42 male C57BL/6 mice， aged 10 weeks， were randomly divided into control group， postoperative day 1 group （1－d group）， postoperative day 2 group （2－d group）， postoperative day 4 group （4－d group）， postoperative day 6 group （6－d group）， postoperative day 8 group （8－d group）， and postoperative day 10 group （10－d group）， with 6 mice in each group. In the control group， the complete liver of the mice was resected for weighing and photography as the normal control group （sham group）； further， the left and middle lobes of the liver were resected for weighing and photography as the surgical control group （0－day group）； the sham group and the 0－day group shared the same group of mice. After successful modeling by PH， the mice were sacrificed on days 1， 2， 4， 6， 8， and 10 after surgery， and the liver was collected to measure the change in size. HE staining and oil red O staining were used to evaluate liver histomorphological changes； serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured to evaluate the changes in liver function； immunohistochemical staining was used to measure the expression of proliferating cell nuclear antigen （PCNA） and Ki67 and analyze the change in cell proliferation during liver regeneration； quantitatie real－time PCR and immunohistochemical staining were uused to measure the expression and subcellular distribution of RGC32 during liver regeneration； EdU cell proliferation assay was used to analyze the effect of RGC32 overexpression or knocknout on hepatocyte proliferation in L02 cells. For continuous data， comparison between multiple groups was made by analysis of variance， and further pairwise comparisons were conducted using the LSD－t test. The independent samples t－test was used for comparison of continuous data between two groups. A Pearson correlation analysis was performed. ResultsThe liver gradually enlarged after PH， and the liver/body weight ratio rose to the peak from days 0 to 6， with significant differences between different time points （all P<0.05）， while there was no significant change in liver size from days 6 to 10. The number of liver lipid droplets significantly increased after PH surgery and gradually decreased with liver regeneration， with a significant difference between the portal vein region and the central vein region （all P<0.05）. Compared with the sham group， the 1d group had significant increases in the serum levels of ALT and AST （all P<0.05）， which gradually returned to the levels of the sham group on day 6 and day 2 after surgery， respectively （P>0.05）. Immunohistochemical staining showed that there were rapid increases in the numbers of PCNA－ and Ki67－positive liver parenchymal cells after PH surgery， with the highest numbers of 86±5 and 89±5， respectively， on day 2， which then gradually decreased； however， there were gradual increases in the numbers of PCNA－ and Ki67－positive nonparenchymal cells， with the peak numbers of 34±5 and 25±3， respectively， on day 6， which then gradually decreased. The total expression of RGC32 increased to the highest level on day 2 after PH surgery and then gradually decreased， and the changing trend of RGC32 expression in cytoplasm was consistent with that of total RGC32 expression； however， the expression of RGC32 in nucleus decreased to the lowest level on day 2 after PH surgery and then increased gradually. The correlation analysis showed that the expression of RGC32 in nucleus was negatively correlated with the proliferation of liver parenchymal cells （R2=0.308 3， P=0.016 7）， and the expression of RGC32 in cytoplasm was positively correlated with the proliferation of liver parenchymal cells （R2=0.808 6， P<0.000 1）. Cell experiments showed that compared with the control group， the EdU－positive rate was reduced by 15.6% after RGC32 overexpression （P<0.01） and was increased by 19.2% after RGC32 knockdown （P<0.01）. ConclusionLiver parenchymal cells and nonparenchymal cells show asynchronous proliferation and participate in liver regeneration together. During liver regeneration after hepatectomy， there are differences in the expression of RGC32 between nucleus and cytoplasm， and RGC32 in nucleus may inhibit hepatocyte proliferation.
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Objective To analyze the epidemiological characteristics of hepatitis B in Guangzhou from 2006 to 2018. Methods The data were retrieved from the National Infectious Disease Surveillance Information Report Management System. Descriptive methods were used to analyze and summarize the results. Chi-square test was used for statistical analysis of classification data, and Joinpoint software was used to analyze the annual change percentage and trend. Results A total of 292 674 cases of hepatitis B were reported in Guangzhou from 2006 to 2018, and the annual average reported incidence was 182.2 per 100,000. Chronic hepatitis B was the main type, accounting for 89.9%. The incidence rate of males (241.6 / 105) was higher than that of females (117.9 / 105), with a ratio of 2.0:1. During the period from 2006-2018, the reported incidence of hepatitis B in Guangzhou first increased, reached the highest in 2008, and then decreased year by year. There was no significant difference in the number of HBV cases among different months. The average onset age of hepatitis B reported in Guangzhou was 39.3 years old, and the average onset age increased year by year from 2006 to 2018. Conclusion The incidence rate of hepatitis B in Guangzhou has decreased since 2008, but it was still higher than the national average incidence rate. The hepatitis B infection in Guangzhou remains a big issue. It is suggested to further strengthen the prevention and control of hepatitis B in adults by maintaining a national immunization program for children, thereby reducing the epidemiological level of hepatitis B in Guangzhou.
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Two simple and sensitive high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) methods were developed and validated for the determination of fenticonazole in human plasma after percutaneous and intravaginal administration. Mifepristone was used as an internal standard (IS), and simple protein precipitation by acetonitrile containing 2%acetic acid was utilized for extracting the analytes from the plasma samples. Chromatographic separation was performed on a Kinetex XB-C18 column. The quantitation was performed by a mass spectrometer equipped with an electrospray ionization source in multiple reactions monitoring (MRM) positive ion mode using precursor-to-product ion transitions of m/z 455.2–199.1 for fenticonazole and m/z 430.2–372.3 for mifepristone. The validated linear ranges of fenticonazole were 5–1000 pg/mL and 0.1–20 ng/mL in plasma for the methods A and B, respectively. For the two methods, the accuracy data ranged from 85% to 115%, the intra- and inter-batch precision data were less than 15%, the recovery data were more than 90%, and no matrix interference was observed. The methods A and B were successfully validated and applied to the pharmacokinetic studies of fenticonazole gel in Chinese healthy volunteers after percutaneous and intravaginal administration, respectively.
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Objective To investigate the application of leukoreduction filter in removal of leukocytes in platelet concentrate . Methods Platelet concentrate was prepared by using platelet‐rich plasma method .35 bags of the same type of prepared platelet concentrate were filtered by using leukoreduction filter .The changes of conventional indicators of platelet before and after filter were measured and recorded .The activating platelets indicators PAC‐1 and CD62p were detected by using flow cytometry .The platelet hypotonic shock was measured by biochemical analyzer .The platelet aggregation was measured by using platelet aggrega‐tion instrument .Results After platelet concentrate was filtered by using leukoreduction filter ,leukocyte removal rate was(98 .28 ± 0 .97)% ,platelet recovery rate was(86 .37 ± 2 .84)% .After filtration ,white blood cell count ,platelets ,red blood cells were reduced than before filtration(P 0 .05) .Before and after filtration ,the expression of platelet activation markers PAC‐1 and CD62p ,platelet aggregation and platelet hypotonic shock were not statistically different(P>0 .05) .Conclusion Platelet leukore‐duction filter could effectively filter leukocytes in platelet concentrate .It would not change the conventional indicators ,and not affect platelet activation ,aggregation and anti‐hypotonic shock capacity significantly .
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Though all the marketed drugs of dipeptidyl peptidase IV inhibitors are structurally different, their inherent correlation is worthy of further investigation. Herein we rapidly discovered a novel DPP-IV inhibitor 8g (IC50 = 4.9 nmol.L-1) which exhibits as good activity and selectivity as the market drugs through scaffold hopping and drug splicing strategies based on alogliptin and linagliptin. This study demonstrated that the employment of classic medicinal chemistry strategy to the marketed drugs with specific target is an efficient approach to discover novel bioactive molecules.
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This study is to explore new lead compounds by inhibition of Pin1 for anticancer therapy using temperature sensitive mutants. As Pin1 is conserved from yeast to human, we established a high-throughput screening method for Pin1 inhibitors, which employed yeast assay. This method led to the identification of one potent hits, 8-11. In vitro, 8-11 inhibited purified Pin1 enzyme activity with IC50 of (10.40 +/- 1.68) micromol x L(-1), induced G1 phase arrest and apoptosis, showed inhibitory effects on a series of cancer cell proliferation, reduced Cyclin D1 expression, was defined as reciprocally matched for protein-ligand complex in virtual docking analysis and reduced cell migration ability. In vivo, we could observe reduction of tumor volume after treatment with 8-11 in xenograft mice compared with vehicle DMSO treatment. Altogether, these results provide for the first time the involvement of 8-11 in the anticancer activity against Pin1.
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@# Intrathecal (I. T.)administration of K opioid dynorphin A (1-17) is used as a model of neurological dysfunction which lnvolved in spinal cord injury and secondary affection according to several previous reports. 5-amlno-2-phosphoveroleric acid (APV ), an NMDA receptor antagonist, can significantlly prevent the hindlimb paralysis in rats produced by I. T. dynorPhin A (1-17). To further investigate the mechanisms, we establis11 a nlodel of [3H]L,-Glu release in rats spinal slices influenced by dynorphin A (dynA ) (1-17). [3H]L-Glu release evoked by high [K+] (5Ommol/L,)is a Ca2+-dependent process. DynA (1-17) slgnificantly inhibited [3H]L,-Glu release at 1O-8mol/L,, but very significantly enhanced [3H]L-Glu release at 10-6 mol /L. The synthetic k agonist U50, 488H, which has no neurotoxic effect, inhibited [3H]L-Glu release at both high and low concentrations and did not have any enhancing effect. The results suggest that the analgesic effect of dynA (1-17) at physiological dosage may be rnediated by presynaptic K opioid receptor through the inhibition of Ca2+ influx and L-Glu release;but dynA (1-l7)enhanced L-Glu release through a non-opioid pathway and induced hindlimb paralysis at high neurotoxic dosage.
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AIM: To explore the relationship between proliferation, hypertrophy of vascular smooth muscle cells(VSMC) and platelet-derived growth factor-AA(PDGF-AA) and PDGFR-? expression in spontaneously hypertension rats(SHRs) and the role of tyrosine protein kinase (PTK) in it. METHODS: 1. The difference of PDGF-AA, PDGFR-? and PDGFR-? expressions in SHR/Wistar-kyoto rat(WKY)-VSMC was examined by Western blot. 2.The effect of PTK inhibitor (genistein) on proliferation and hypertrophy of SHR-VSMC induced by PDGF-AA was observed by Western blot and incorporation. RESULTS: 1.PDGF-AA and PDGFR-? expression markedly increased in SHR-VSMC compared with WKY-VSMC. There was no difference in PDGFR-? expression levels between SHR and WKY-VSMC. 2.Dose-dependent PDGF-AA-stimulated PCNA expression and incorporation were observed in SHR-VSMC. 3. Genistein inhibited PCNA expression and incorporation induced by PDGF-AA in a dose-dependent manner in SHR-VSMC. CONCLUSIONS: Spontaneous increasing expression of PDGF-AA and PDGFR-? in spontaneously hypertension rats(SHRs) may be one of the important factors in vascular reactivity and vascular modeling mediated through proliferation and hypertrophy in SHR-VSMC. Tyrosine protein kinase plays an important role in this process.