UBE2O reduces the effectiveness of interferon-α via degradation of IFIT3 in hepatocellular carcinoma.

Interferon (IFN) exerts its effects through interferon-stimulated genes (ISGs), but its efficacy is limited by interferon resistance, which can be caused by the ubiquitination of key proteins. UBE2O was initially identified as a promising therapeutic target based on data from the TCGA and iUUCD 2.0 databases. Through the inhibition of UBE2O, interferon α/ß signaling and overall interferon signaling were activated. Integrating data from proteomic, mass spectrometry, and survival analyses led to the identification of IFIT3, a mediator of interferon signaling, as a ubiquitination substrate of UBE2O. The results of in vitro and in vivo experiments demonstrated that the knockdown of UBE2O can enhance the efficacy of interferon-α by upregulating IFIT3 expression. K236 was identified as a ubiquitination site in IFIT3, and the results of rescue experiments confirmed that the effect of UBE2O on interferon-α sensitivity is dependent on IFIT3 activity. ATO treatment inhibited UBE2O and increased IFIT3 expression, thereby increasing the effectiveness of interferon-α. In conclusion, these findings suggest that UBE2O worsens the therapeutic effect of interferon-α by targeting IFIT3 for ubiquitination and degradation.

Association of SLC22A12 and SLC2A9 genetic polymorphisms with hypouricemia in Ningxia population / 基础医学与临床

Objective To study the relationship among rs505802 in SLC22A12,rs6855911,rs737267,rs12498742, rs7442295, rs734553, rs16890979 in SLC2A9 genetic polymorphisms and hypouricemia in Ningxia.Methods 6 056 subjects were collected by multistage,stratified random cluster sampling method in October and November in 2011 in Ningxia Hui autonomous region, 98 subjects with hypouricemia were selected.According to gender and age,84 controls were selected.Physical examination and laboratory biochemical index test were conducted for the study population.T test was used to compare general clinical data and biochemical indexs between two groups. SNPs were detected by Sequenom Mass ARRAY technology.By x2test,we compared the frequencies of the geno-type and allele in each group.Samples representativeness was confirmed through the Hardy-Weinberg inspection. Results The levels of TC, LDLC, and Cr in the patients were lower than those in the control group(P<0.05). There were significant differences in the distribution of A,G allele frequencies of SLC2A9 gene rs7442295 between two groups.The risk of hypouricemia in patients with A/A genotype was lower than that of A/G genotype(Pc<0.05),indicating that A>G mutation was associated with hypouricemia.Conclusions Polymorphisms of SLC2A9 gene rs7442295 are significantly correlated with hyporuricemia in Ningxia.

Discussion on Difference of Different Compatibility Ratios of Astragali Radix and Puerariae Lobatae Radix Based on Content Analysis / 中国中医药信息杂志

Objective To study the contents of puerarin in decoction with different compatibility ratios of Astragali Radix and Puerariae Lobatae Radix; To verify the rationality of compatibility ratios of Huangqi Gegen Decoction and Yu y e Decoction; To provide references for clinical medication. Methods Different compatibility ratios of Astragali Radix and Puerariae Lobatae Radix were set as 0:1, 1:1, 2:1, 3:1, 4:1, 1:2, 1:3, and 1:4. SinoChrom ODS-BP (4.6 mm × 250 mm, 5 μm) was used as the chromatographic column to detect the contents of puerarin;methanol-0.1% phosphoric acid (35:65) was used as the mobile phase with 0.5 mL/min flow rate; sample volume was 20 μL; the wavelength was 250 nm. Results The regression equation of puerarin was Y=66 449.269 1X-175 665.663 1 (r=0.999 6) in the range of 5 to 300 μg/mL, showing a good linear relationship. The repeatability, stability and recovery rate were fine as well. The contents of puerarin were (2.506 7±0.025 8)%, (2.526 7±0.071 2)%, (2.863 3± 0.086 4)%, (2.956 7±0.119 6)%, (2.835 0±0.078 7)%, (2.480 0±0.072 4)%, (2.530 0±0.064 8)%, and (2.183 3±0.128 9)% in different compatibility ratios of Astragali Radix and Puerariae Lobatae Radix with 0:1, 1:1, 2:1, 3:1, 4:1, 1:2, 1:3, and 1:4, respectively. Conclusion When the compatibility ratios of Astragali Radix and Puerariae Lobatae Radix are 2:1. 3:1, and 4:1, the contents of puerarin in decoction are the highest. This study verifies that the compatibility ratios of Astragali Radix and Puerariae Lobatae Radix in classical prescriptions are rational, which can be the optimal compatibility ratios in clinic.

The performance evaluation of four Lp-PLA2 activity assays / 中华检验医学杂志

Objective To evaluate the analytical performance of four lipoprotein associated phospholipase A2(Lp-PLA2)activity reagents on Beckman AU5800 automatic biochemical analyzer. Methods The remaining serum samples of 214 patients and 140 apparently healthy individuals were collected from March to July 2017 in Peking Union Medical College Hospital.These samples were used for method comparison and reference interval evaluation.According to the guidelines of EP15-A,EP6-A,EP-17 and EP7-P from Clinical and Laboratory Standards Institute(CLSI)standards,the precision, linearity, sensitivity and common interferences(e.g free bilirubin, conjunct bilirubin, hemoglobin and chyle)were assessed.According to EP9-A2,method comparisons of differents regents(Evermed,DiaSys,Hengxiao and Zhongyuan were labeled as A,B,C and D,respectively)were conducted and the differences were estimated at medical decision levels(328U/L,391U/L and 485U/L).Results The precision of four reagents were acceptable.The repeatability(CV%)of A to D were 0.5%-1.7%, 0.7%-3.0%, 0.9%-2.0% and 0.5%-3.3%,respectively.The reproducibility(CV%)were 0.7%-2.9%, 1.4%-3.2%, 1.3%-1.9%and 0.8%-4.1%,respectively.Both of those achievedlaboratory defined quality objective(<5%).The linearity of A to D were 44 -1 992 U/L,39 -1 798 U/L,13 -540 U/L and 75-1 717U/L,respectively.The regression coefficient R2 was between 0.997 and 1.000, and the correlation coefficient(r)was between 0.998 and 1.000.The interference of chyle were acceptable among these four reagents andmet the manufacturer′s requirementsor clinical needs.In a low level of Lp-PLA2,bilirubin had an obvious interferenceonreagent C;B and C were negatively affected when the hemoglobin was 4.5 g/L; and D was positively affected when the hemoglobin was 2.45 g/L.The regression coefficients R2 of A,C,D compared with B were between 0.978 and 0.995,and the correlation coefficients(r)were between 0.989 and 0.998. The expected differences at medical decision levels ranged from -240 U/L to 113 U/L.For A to D,the Lp-PLA2 activity results of 131(93.6%), 140(100%), 82(58.6%), and 128(91.4%)cases were analysed within the manufacturer′s claimed reference intervals.Conclusion The precision and linearity of the four Lp-PLA2 activity detection reagents used in automatic biochemical analyzer are good, but the anti-interference ability needs to be improved.

Ratio of Primary Bone Marrow Cells after Induction Chemothrapy for Two Weeks in the Patients with PhALL and Its Influence on Complete Remission and Overall Progrosis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the influence of bone marrow blasts ratio after induction chemotherapy for 2 weeks in patients with PhALL, and it's influence on complete remission (CR) and overall prognosis.</p><p><b>METHODS</b>A total of 172 patients with PhALL in our hospital from March 2012 to February 2016 were selected. The bone marrow blast ratio was analyzed by the receiver-operating characteristic curve (ROC) in patients after induction chemotherapy for 2 weeks, at same time its influence on CR and overall prognosis of PhALL patients was evaluated.</p><p><b>RESULTS</b>The cutoff value of CR was 0.075, its area under ROC was 0.763; the comparison of area under ROC with A=0.5 showed statistically significant difference, therefore 172 patients with PhALL were grouped according to bone marrow blast ratio after induction chemotherapy for 2 weeks: 104 cases (60.5%) with bone marrow blast ratio <0.075, 68 cases (39.5%) with bone marrow blast ratio ≥0.075. The PhALL patinets with bone marrow blast ratio <0.075 who achieved CR and finally achieved CR after induction chemotherapy for 4 weeks acconnted for 89 (85.6%) and 99(95.2%) respectively, which were significantly higher than those in PhALL patients with bone marrow blast ratio≥0.075, [29(42.6%) and 52 (76.5%)](P<0.05). In addition, the influencing factor clinically reducing the OS and DFS rate of patients and enhancing the ralapse rate of patients were mainly chemotherapy, the failure of induction chemotherapy (patients did not achieve CR after induction therapy for 4 weeks), the bone marrow blast ratio≥0.075 after induction treatment for 2 weeks, and CNSL at diagnosis and so on, while the enhaced WBC count at diagnosis was poor factor affecting the DFS rate of patients.</p><p><b>CONCLUSION</b>After induction chemotherapy for 2 weeks, the elevated bone marrow blast ratio in PhALL patients will be infavourable to CR, and the overall prognosis is poor.</p>

[Study on genetic-chemical relation of Pterocephali Herba based on DNA barcode and UFLC].

DNA barcoding technique in combination with UFLC analysis technology was used to evaluate the quality of Tibetan medicine Pterocephalus hookeri from species identification and chemical qualitative and other aspects. Hybrid identification was established by DNA barcoding; UFLC-PDA was adopted to analyse fingerprint of different parts of Pterocephali Herba, and SPSS and Grey relation software were used for data analysis. The result showed that DNA barcoding is an accurate and reliable method in origin identification of Pterocephalus hookeri. The compounds in overground is more than underground by analysis of the different part fingerprint by UFLC. The genetic gene may be involved in the secondary metabolites of iridoid glycosides. Pertinence between gene and chemical component, as a new model established, could be suited for quality evaluation and resources protection.

Study on genetic-chemical relation of Pterocephali Herba based on DNA barcode and UFLC / 中国中药杂志

DNA barcoding technique in combination with UFLC analysis technology was used to evaluate the quality of Tibetan medicine Pterocephalus hookeri from species identification and chemical qualitative and other aspects. Hybrid identification was established by DNA barcoding; UFLC-PDA was adopted to analyse fingerprint of different parts of Pterocephali Herba, and SPSS and Grey relation software were used for data analysis. The result showed that DNA barcoding is an accurate and reliable method in origin identification of Pterocephalus hookeri. The compounds in overground is more than underground by analysis of the different part fingerprint by UFLC. The genetic gene may be involved in the secondary metabolites of iridoid glycosides. Pertinence between gene and chemical component, as a new model established, could be suited for quality evaluation and resources protection.

FSI simulation of patient-specific aortic dissection and its bypass grafting / 医用生物力学

Objective To investigate the effects of different bypass grafting for treating DeBakey Ⅲ aortic dissection. Methods The patient-specific models of DeBakey Ⅲ aortic dissection based on CT images were reconstructed by using Mimics software, and two bridge models of bypassing between ascending aorta and abdominal aorta (AA), and between left subclavian artery and abdominal aorta (LA) were established by computer-aided method, respectively. Then numerical simulations were performed by using fluid-structure interaction (FSI) method to compare hemodynamic differences of these two models. Results After bypass surgery, the mass flow, mean and maximum velocities of the through lumen models were reduced to different degrees. Meanwhile, both the maximum blood pressures and displacements of the vessel walls of AA models were decreased, but those of LA models were increased. In contrast, all the above-mentioned hemodynamic parameters of the blind lumen models were decreased, especially for AA models. Conclusions The AA bypassing is a better treatment for DeBakey Ⅲ aortic dissection of through lumen and blind lumen. The therapeutic effects can be easily explained through simulation results, to ensure the scientific validity and clinical utility of bypassing.

Effect on aneurysmal pressure after stent intervention treatment for aneurysm accompanied by stenosis / 医用生物力学

Objective To investigate the effect on aneurysmal pressure after stent intervention treatment for aneurysm accompanied by stenosis. Methods Computational fluid dynamics (CFD) analyses were carried out to make comparative study on aneurysm models with and without stenosis. Three models (M1, M2, M3) were constructed to compare the pressure variations. M1 was the aneurysm model with no stenosis and no stent, M2 was forming from M1 model with a preaneurysm stenosis, and M3 was the M2 model with stent implantation at the place of the aneurysm. Results For comparison between M2 and M1, pressure increase in the aneurismal sac caused by a mild stenosis (50%) was about 1.399 9 kPa(10.3 mmHg) with the peak systole, and the average pressure increase in a cardiac cycle was about 0.572 kPa(4.3 mmHg). For comparison between M2 and M3, pressure increase in the aneurismal sac was about 1.037 kPa(7.8 mmHg) at peak systole in a cardiac cycle, and the average pressure increase in the aneurismal sac in a cardiac cycle was about 0.399 kPa(3 mmHg). Conclusions A mild stenosis could not result in the sharp pressure increase with stent intervention applied to the treatment of aneurysm accompanied by stenosis harbored on a tortuous intracranial artery. The geometry of the parent vessel and its aneurysmal/stenotic diseases do have influence on the pressure variation at the place of aneurysm.

[Preparation and characterization of anti-human IL-15 monoclonal antibody].

AIM: To prepare monoclonal antibody (mAb) against human interleukin-15 (hIL-15) and identify its characterization. METHODS: The GST-IL-15 was extracted from the gene-engineering bacteria E. coli and identified by SDS-PAGE. The gel strip containing GST-IL-15 was cut off to immunize BALB/c mice. The splenocytes of immunized mice were fused with Sp2/0 myeloma cells by a routine method and the hybridomas were selected in HAT medium. The hybridoma cells secreting specific antibody were detected by ELISA and cloned by limiting dilution. The stability of the obtained hybridoma cells and the specificity of anti-hIL-15 mAb the hybridoma cells secreted were identified. In addition, the New Zealand rabbits were immunized with the rhIL-15 inclusion body protein (rhIL-15IBP) to prepare the polyclonal antibody (pAb) against hIL-15. A sandwich ELISA was established with the anti-IL-15 mAb and pAb as coating and sandwich antibodies, respectively, to detect hIL-15. RESULTS: One hybridoma cell line which could stably secrete specific mAb was obtained. A sandwich ELISA for detecting rhIL-15 protein was established and its sensitivity was as low as 10 microg/L. CONCLUSION: The anti-hIL-15 mAb was prepared successfully. A sandwich ELISA for the detection of hIL-15 was established.