[Factors influencing bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt].

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.

Dual-channel compressed ultrafast photography for Z-pinch dynamic imaging.

The compressed ultrafast photography (CUP) can capture non-repetitive time-evolving events at 7 × 1013 fps, which is anticipated to find a diverse range of applications in physics, biomedical imaging, and materials science. The feasibility of diagnosing ultrafast phenomenon of Z-pinch by using the CUP has been analyzed in this article. Specifically, a dual-channel CUP design has been adopted for acquiring high quality reconstructed images and the strategies of identical masks, uncorrelated masks, and complementary masks have been compared. Furthermore, the image of the first channel was rotated by 90° to balance the spatial resolution between the sweep direction and the non-sweep direction. Both five synthetic videos and two simulated Z-pinch videos were chosen as the ground truth to validate this approach. The average peak signal to noise ratio of the reconstruction results is 50.55 dB for the self-emission visible light video and 32.53 dB for the laser shadowgraph video with unrelated masks (rotated channel 1). The simulation results show that the time-space-evolving process of plasma distribution can be well retold, and the phenomenon of plasma instability can be accurately diagnosed by the dual-channel CUP with unrelated masks (rotated channel 1). This study may promote the practical applications of the CUP in the field of accelerator physics.

[Research on the relationship between V444A mutation of ABCB11 gene and primary intrahepatic stone].

Objective: To investigate the relationship between V444A mutation of the ABCB11 gene and primary intrahepatic stone (PIS). Methods: A total of 164 patients (including 91 males and 73 females, with an average age of (46.0±13.0) years) with PIS and 164 healthy (including 99 males and 65 females, with an average age of (43.8±16.7) years) volunteers were enrolled in this case-control study between October 2017 and June 2019. TaqMan-MGB was used for detecting the V444A polymorphism site of the ABCB11 gene. All the genotypes and allele frequencies were calculated. Pearson chi-squared test was performed to detect the differences in allele and genotype distribution between the two groups. Logistic regression analysis was used to identify genotypes associated with PIS. Results: There was no significant difference in age and gender between the two groups(both P>0.05). The distributions of V444A allele and genotype accorded with Hardy-Weinberg equilibrium law (P=0.161), which indicated that the selected control group represented statistically acceptable sample. Two alleles of T and C, and three genotypes of TT, TC and CC were detected in the locus of V444A. The T and C allele frequencies in the PIS group and the control group were 28.4% vs 35.4%, and 71.6% vs 64.6%, respectively. The frequencies of the T and C alleles were not different between the two groups (P=0.054). The frequencies of TT, TC and CC genotypes in the two groups were 5.5%, 45.7%, 48.8%, and 14.6%, 41.5%, 43.9%, respectively, with significant difference between the two groups (P=0.023). Logistic regression analysis revealed the V444A polymorphism (TC heterozygous mutation) was associated with PIS. Conclusion: ABCB11 gene polymorphism at the site of V444A may be related to the susceptibility of PIS.

Effects of dietary rapeseed meal inclusion levels on growth performance, organ weight, and serum biochemical parameters in Cherry Valley ducks.

The aim of this study was to investigate the effects of the inclusion levels of different types of rapeseed meal (RSM) on performance, organ weight, and serum biochemical parameters in Cherry Valley ducks in the starter period and grower-finisher period. In Exp. 1, a total of 750 seven-day-old male ducklings were divided into 5 dietary treatments with 6 replicate pens of 25 birds per pen. The starter diets with the inclusion of 0, 5, 10, 15, or 20% of double-low RSM contained 0, 1.37, 2.15, 3.46, or 5.31 µmol glucosinolates (GLS)/g in the finished feed (from day 7 to 21). In Exp. 2, a total of 900 fifteen-day-old male ducklings were divided into 6 dietary treatments with 6 replicate pens of 25 birds per pen. The grower-finisher diets with the inclusion of 0, 5, 10, 15, 20, or 25% of Indian RSM contained 0, 7.67, 15.34, 24.66, 31.21, or 38.44 µmol GLS/g in the finished feed (from day 15 to 42). For ducklings in the starter period (Exp. 1), body weight gain and feed intake decreased linearly as the dietary double-low RSM inclusion level increased at day 7 to 14, while growth rate was not influenced by dietary double-low RSM inclusion levels at day 15 to 21 and day 7 to 21. For ducks in the grower-finisher period (Exp. 2), growth performance decreased linearly as the dietary RSM inclusion level increased from 5 to 20%. In addition, dietary RSM inclusion levels induced liver enlargement in ducklings at day 21 (5 to 20% double-low RSM with 1.37 to 5.31 µmol/g GLS) and thyroid enlargement accompanied by increased serum AST and ALP activities in ducks at day 42 (5 to 15% Indian RSM with 7.67 to 23.66 µmol/g GLS). Therefore, our results indicated that the upper limit of using RSM sources in feed formulation should consider the anti-nutritional factor of GLS content at different stages of duck growth.

MiR-143-3p regulates early cartilage differentiation of BMSCs and promotes cartilage damage repair through targeting BMPR2.

OBJECTIVE: The aim of this study was to explore the role of microRNA-143-3p (miR-143-3p) in cartilage injury, and to investigate the possible underlying mechanism. MATERIALS AND METHODS: A chondrogenic differentiation cell model was established in bone marrow mesenchymal stem cells (BMSCs). The mRNA expression levels of runt-related transcription factor 2 (RUNX2), miR-143-3p and bone morphogenetic protein 2 (BMPR2) in BMSCs were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) after 0 d, 5 d and 10 d, respectively. Mesenchymal stem cells (MSCs) were transfected with miR-143-3p mimics and its control in accordance with the liposome method. Alcian blue colorimetric assay was used to evaluate proteoglycan deposition of MSCs. Meanwhile, qRT-PCR and Western blot were performed to analyze the expression levels of ACAN and COL2A1. Luciferase reporter gene assay was applied to verify the binding status of miR-143-3p and BMPR2 3'UTR. Also, proteoglycan deposition and the expression of ACAN and COL2A1 were detected after simultaneous transfection of miR-143-3p mimics and BMPR2 overexpression plasmid. RESULTS: 0 d, 5 d and 10 d after inducing cartilage differentiation, the mRNA expression levels of RUNX2 and BMPR2 were markedly increased. However, the expression level of miR-143-3p was significantly decreased with the prolongation of induction period. After transfection with miR-143-3p mimics, the level of miR-143-3p in MSCs was remarkably increased. Alcian blue colorimetric assay and staining assay showed that the deposition of proteoglycans in the mimics group was significantly lower than that of the control group. Meanwhile, after overexpressing miR-143-3p, the levels of cartilage differentiation marker proteins including ACAN and COL2A1 were remarkably reduced. Luciferase report gene assay indicated that miR-143-3p could negatively regulate BMPR2 by binding to its 3'UTR. In addition, overexpression of BMPR2 could strikingly reverse the above effects of overexpressed miR-143-3p. CONCLUSIONS: During chondrogenic differentiation, the level of miR-143-3p was decreased. Moreover, miR-143-3p could regulate the differentiation process by targeting BMPR2 in BMSCs.

HIF-1α promotes inflammatory response of chronic obstructive pulmonary disease by activating EGFR/PI3K/AKT pathway.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is an incomplete, reversible disease with progressive inflammation obstruction in airways. This study aims to explore the regulatory mechanism of hypoxia-inducible factor-1α (HIF-1α) in inflammatory response and progression of COPD. PATIENTS AND METHODS: 71 bronchoalveolar lavage fluid (BALF) samples were collected, including 59 samples from COPD patients (COPD group) and 12 from patients with normal pulmonary function (control group). The mRNA and protein levels of HIF-1α and epidermal growth factor receptor (EGFR) in BALF were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. Serum levels of interleukin-13 (IL-13), IL-9, IL-1, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Hypoxia cell model was constructed by COCl2 induction in human embryonic lung cells. Expression levels of HIF-1α, EGFR and p-AKT in NCI-H1563 cells treated with 740Y-P, the phosphoinositide 3-kinase (PI3K) agonist were detected. Finally, we detected proliferation and apoptosis in NCI-H1563 cells with HIF-1α overexpression by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. RESULTS: The mRNA and protein levels of HIF-1α and EGFR were higher in COPD groups compared with those of control group. Serum levels of IL-13, IL-9, IL-1, and TNF-α in COPD patients were elevated. CoCl2 induction in NCI-H1563 cells led to upregulated levels of IL-13, IL-9, IL-1, and TNF-α. 740Y-P treatment remarkably activated EGFR/PI3K/AKT pathway. Overexpressed HIF-1α inhibited proliferation but induced apoptosis of NCI-H1563 cells. CONCLUSIONS: HIF-1α was overexpressed in COPD, which upregulated expressions of inflammatory factors via activating the EGFR/PI3K/AKT pathway. The activated EGFR/PI3K/AKT pathway induced by pulmonary inflammation further upregulated HIF-1α expression in a feedback loop, thus aggravating COPD pathological changes.

MMP-14 aggravates onset of severe preeclampsia by mediating soluble endoglin release.

OBJECTIVE: Gestational hypertension is a pregnancy complication that serious damages the maternal and child health. Early onset severe preeclampsia accounts for about 0.9% of the gestational hypertension disease. Conservative treatment is proposed in recent years to early onset severe preeclampsia through delay delivery. Therefore, it is particularly important to explore the pathogenesis of severe preeclampsia. Soluble endoglin (sEng) has been identified as a central factor to induce endothelium dysfunction of preeclampsia, while its specific mechanism is unclear. MATERIALS AND METHODS: Matrix metallopeptidase 14 (MMP-14) and endoglin expressions and tissue localization in the placenta of preeclampsia and premature were detected by Western blot and immunohistochemistry. Endoglin level, mean arterial blood pressure (MABP), and urinary protein/creatinine ratio were analyzed for correlation to investigate their relationship and the influence of endoglin on eclampsia severity. MMP specific or broad spectrum inhibitor combining MMP-14 siRNA were used in JAR cell line BeWo to explore the regulatory role of MMP-14 on endoglin. RESULTS: MMP-14, endoglin, and sEng expression levels significantly increased in the placenta of severe preeclampsia patients. MMP-14 and endoglin exhibited expression co-localization. Endoglin expression was positively correlated with the severity of eclampsia. MMP-14 directly mediated the release of sEng. CONCLUSIONS: MMP-14 aggravated the onset of severe preeclampsia by mediating sEng release. MMP-14 was proposed as the effective target for the treatment of severe preeclampsia. Blocking the interaction between MMP-14 and endothelial protein may be an important treatment method.

Effects of miRNA-143 and the non-coding RNA MALAT1 on the pathogenesis and metastasis of HeLa cells.

Cervical cancer is a common female malignancy of global dimensions. MicroRNAs (miRNAs) play crucial roles in the development, differentiation, proliferation, and apoptosis of tumors. The non-coding RNA MALAT1 participates in various physiological processes that are important for proper functioning of the body. Here, we analyzed the expression of miRNA-143 and MALAT1 in HeLa cells to evaluate their roles in the occurrence and metastasis of cervical cancer. HeLa cells were divided into five groups depending on the treatment conditions, namely, transfected with miRNA-143, MALAT1, miRNA-143 inhibitor and the MALAT1 inhibitor, and the untreated control. Reverse transcription-polymerase chain reaction was used to analyze the expression of miRNA-143 and MALAT1, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess proliferation, the trans-well assay to study cell invasion and migration, and western blot to analyze the levels of E-cadherin and vimentin. The proliferation of HeLa cells increased upon treatment with the miRNA-143 inhibitor and decreased when treated with the MALAT1 inhibitor, compared to the proliferation of the groups that were transfected with miRNA-143 and MALAT1, respectively (P < 0.05). Thus, miRNA-143 decreased cell invasion and migration potency, downregulated vimentin and upregulated E-cadherin expression, while MALAT1 had the opposite effects. In conclusion, the low expression of miRNA-143 and high expression of MALAT1 in cervical cancer cells could possibly potentiate cell invasion/migration and alter the levels of vimentin and E-cadherin.

Research on the role of GLP-2 in the central nervous system EPK signal transduction pathway of mice with vascular dementia.

OBJECTIVE: To investigate the role of Glucagon-like peptide-2 (GLP-2) in the central nervous system eukaryotic protein kinase (EPK) signal transduction pathway of mice with vascular dementia. MATERIALS AND METHODS: We take the 3-week-old mice raised in the laboratory as the object of study in this research and then divide them into four groups in random, including sham operation group, control group, GLP-2 group, and GLP-2+ERK (extracellular-signal-regulated kinase) inhibitor intervention group, with 30 in each group. The step-down test, water-maze test, electron microscopy observation, immunohistochemical method, and Western-blotting are adopted to investigate the role of GLP-2 in the central nervous system EPK signal transduction pathway of mice with vascular dementia. RESULTS: The step-down test, as well as the water-maze learning and memory test, shows that the mice injected with GLP-2 in the experiment group have their learning and memory ability improved significantly when compared with other three groups, which is greatly different from that of other three groups (p < 0.05); the electron microscopy observation shows that the injection of GLP can partially reverse the reduction of vesicles while ERK inhibitor removes the said protection; the immunohistochemical result and image analysis result show that the EPK expression quantity in GLP-2 group has no significant difference from that of other three groups (p > 0.05). However, the content of pi-EPK in the GLP-2 group is significantly higher than that in VD group and GLP-2+PD98095 group and is significantly different from them (p < 0.05), and such result is in line with the result of Western-blotting. CONCLUSIONS: GLP can influence the change in hippocampus cells extensions and finally influence their cognitive function by activating the EPK signal transduction pathway of hippocampal neuron in the central nervous system.

Circulating B7-H4 in serum predicts prognosis in patients with hepatocellular carcinoma.

B7-H4 is member of the B7 family that negatively regulates the immune response, which are important for fine-tuning of the tumor microenvironment. Dysregulation of B7-H4 expression has been associated with tumor progression. However, expression level of B7-H4 in hepatocellular carcinoma (HCC) tissues is still a controversial topic. In addition, whether serum B7-H4 expression of HCC patients has any clinical value is unknown. We compared serum levels of B7-H4 in patients with HCC and healthy controls by using the ELISA method. Association between serum B7-H4 expression level and clinical parameters of HCC was further investigated. Log-rank test and Kaplan-Meier method were employed to evaluate the overall survival rate of HCC patients. Univariate and multivariate analysis of prognostic factors were performed with the Cox regression model. Our results showed that HCC patients had significantly higher serum B7-H4 level as compared with healthy controls (P < 0.001). In addition, serum B7-H4 expression was correlated with HCC clinical parameters including serum AFP expression and TNM stage. HCC patients in the higher serum B7-H4 expression group had a poorer 5-year overall survival rate (P = 0.028). Moreover, serum B7-H4 expression was shown to be an independent prognostic factor for HCC (P = 0.034). The findings from this study suggest that serum B7-H4 is an independent prognostic indicator for HCC and may be a promising biomarker for early diagnosis as well as disease prognosis of HCC.

Dipole, quadrupole and octupole plasmon resonance modes in non-concentric nanocrescent/nanodisk structure: local field enhancement in the visible and near infrared regions.

By deviating the nanodisk from the center in the silver nanocrescent/nanodisk structure, we find that the dipole, quadrupole and octupole modes can all induce very high local electric field enhancement (LFE, more than 750) for the coupling of nanocrescent and crescent gap modes, which makes the resonant wavelengths of the non-concentric nanostructures change from the visible to near infrared regions. In addition, the LFE factor of the quadrupole mode is more than 1000, which is suitable for single molecular detection by local surface enhanced spectroscopy.

[Synthesis and cardiovascular activities of peptidyl dopamine derivatives].

Amino acids and small peptides with different steric configurations and lipophilicities were appended to dopamine. Eighteen compounds have been synthesized. The attachment of D-amino acids or N-methyl amino acids onto the dopamine molecule caused a marked decrease in cardiovascular activity by intravenous injection, while the introduction of lipophilic amino acids caused a marked increase in myocardial contractility and blood pressure in anesthetized dogs. The durations of action were also prolonged.