OBJECTIVE: To analyze the results of activated partial thromboplastin time (APTT) mixing test in coagulation factor Ⅷ inhibitor-positive hemophilia patients, so as to increase the value of APTT mixing test in the screen of factor Ⅷ inhibitor. METHODS: Eighty plasmas samples with different titers of coagulation factor Ⅷ inhibitors had been collected and diluted for routine immediate APTT mixing test and at 37 ℃ 2 hours incubation APTT mixing test. Fifteen samples were selected for immediate and normal temperature incubation for 15 min, 30min, 1 hour, 2 hours and 37 ℃ for 30 min, 1 hour, 2 hours APTT mixing test. RESULTS: The results of APTT mixing test were significantly correlated with the titers of coagulation factor Ⅷ inhibitors. The ROC curve result showed that the best diagnostic cut-off value for 2 hours incubation APTT mixing test at 37 ℃ to determine the presence or absence of coagulation factor Ⅷ inhibitors was 43.8 s (sensitivity and specificity was 85.90% and 100%, respectively), while the best diagnostic cut-off value for distinguishing high-titer and low-titer Ⅷ inhibitors was 52.4 s (sensitivity and specificity was 98.18% and 95.65%, respectively). The critical coagulation factor Ⅷ inhibitor titer that could not be corrected by immediate APTT was 5.14 BU/ml, while that could not be corrected by 37 ℃ 2 hours incubation APTT was 1.31 BU/ml. Paired samples t -test was performed on the APTT mixing test results at different times and temperatures, and the differences were statistically significant (P < 0.05). CONCLUSIONS The APTT mixing test can be used as a screening index for coagulation factor Ⅷ inhibitors. APTT mixing test result shows a significant time-temperature dependence with lower titers of coagulation factor Ⅷ inhibitor. Patients with hemophilia who cannot be corrected by immediate APTT mixing test should be alert to the possibility of high titer of coagulation factor Ⅷ.
Humans ; Factor VIII ; Hemophilia A/diagnosis* ; Blood Coagulation Tests/methods* ; Partial Thromboplastin Time ; Blood Coagulation Factors

During fluorescence-guided cancer surgery, ultra-pH sensitive (UPS) fluorescent nanoprobes has multiple advantages such as real-time imaging procedures, ultra-high imaging sensitivity as well as broad tumor detection specificity. UPS nanoprobes stay at "OFF" state at higher pH and turn into "ON" state at lower pH with emission of strong fluorescence. Moreover, the transition pH points (transition pH point, pH_t) can be precisely controlled by structural-based strategy. One of the previously-reported UPS nanoprobes showed good imaging effect. However, it is still not clear about the effect of pH_t on cancer imaging efficiency of UPS nanoprobes and to further identify the optimal UPS. In this study, we synthesized a series of UPS nanoprobes with pH_t at 4.5, 6.2, 6.6, 7.8 by adjusting the hydrophobic blocks of UPS polymers. Each nanoprobe showed excellent stability in "OFF" state by dynamic light scattering and uniform morphology observed by transmission electron microscopy. In vitro imaging characterized the ultra-pH sensitive fluorescence transition of each probe. In vivo imaging results identified two UPS nanoprobes (NP-6.2 and NP-6.6) with superior tumor imaging effect. All animal experiments in this study were approved by the Animal Ethics Committee of Peking University Health Science Center and were strictly followed by the welfare regulations of laboratory animals of Peking University Health Science Center. Therefore, this study has explored the effect of pH_t on the cancer imaging efficiency of UPS nanoprobes and provides a new idea for design of the other cancer microenvironment-responsive polymers.

Objective: This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B (AFB ) in rats. Methods: Forty Sprague Dawley rats were randomly divided into control, AFB , AFB + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB and AFB + PCB2 groups were intraperitoneally injected with AFB (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured. Results: AFB significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB . Conclusion Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB .
Aflatoxin B1 ; toxicity ; Animals ; Biflavonoids ; administration & dosage ; pharmacology ; Catechin ; administration & dosage ; pharmacology ; Chemical and Drug Induced Liver Injury ; drug therapy ; etiology ; Male ; Poisons ; toxicity ; Proanthocyanidins ; administration & dosage ; pharmacology ; Protective Agents ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

【Objective】To investigate the analgesic and degenerated regularity of paravertebral ozone injection in the discogenic pain model of SD rats ，and to reveal the mechanism of analgesic effect of ozone preliminarily.【Methods】 Male SD rats（n = 65）were randomly divided into control group（n = 15），model group（n = 25）and ozone group（n = 25）. The L5- 6 intervertebral discs of SD rats in model group and ozone group were punctured to establish discogenic pain models. Ozone was injected paravertebrally in ozone group rats on the 22nd day after modeling. The rats in control group were normal. A quantitative allodynia assessment technique and MRI were used to detect the 50% mechanical withdrawal threshold（50%MWT）and Pfirrmann grade of L5-6 intervertebral discs at different time intervals. The expression of tumor necrosis factor-α（TNF- α）and calcitonin gene-related peptide（CGRP）in left dorsal root ganglion and sciatic nerve were detected by western blot.【Results】The 50% MWT of both hind paws were different from each other in three groups at each time after the 22nd day after modeling（P < 0.05）. In the ozone group，the 50% MWT rose on the 22nd day after modeling（left 7.6±6.8，right 3.6±1.0，P < 0.05 vs pre-ozone injection），and reached the peak on the 24th day after modeling（left 10.6±8.2，right 7.9±6.7，P < 0.05 vs pre-ozone injection），and maintained this level until the 56th day after molding. In the ozone group，the L5-6 intervertebral disc degeneration was apparently visible compared with model group（P < 0.05）. The expression of TNF- α and CGRP in dorsal root ganglion and sciatic nerve were different from each other in three groups（model>ozone>control，P < 0.05）.【conclusions】Paravertebral ozone injection can alleviate the pain of discogenic pain model rats，but aggravates the degeneration of the lumbar disc. Paravertebral ozone injection can reduce the expression of TNF-α and CGRP in the sciatic nerve and dorsal root ganglia of discogenic pain model rats.

Background: Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective. Methods: A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively. Results: In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results. Conclusion Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

Background: Glioma is the most common primary malignant tumor in the central nervous system. Because of the resistance of glioma to chemoradiotherapy and its aggressive growth, the survival rate of patients with glioma has not improved. This study aimed to disclose the effect of retinol dehydrogenase 10 (RDH10) on the migration and invasion of glioma cells, and to explore the potential mechanism. Methods: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression levels of RDH10 in healthy glial cells and glioma cells. Human glioma cell strains, U87 and U251, were infected with negative control or RDH10-interfering lentiviruses. RT-PCR and Western blotting were performed to determine the knockdown efficiency. Scratch and transwell assays were used to assess cell migration and invasion after RDH10 knockdown. Finally, changes in transforming growth factor-β (TGF-β)/SMAD signaling pathway-related expression were examined by Western blotting. Differences between groups were analyzed by one-way analysis of variance. Results: RDH10 was highly expressed in glioma cells. Compared with the control group, RDH10 knockdown significantly reduced RDH10 messenger RNA and protein expression levels in U87 and U251 glioma cells (U87: 1.00 ± 0.08 vs. 0.22 ± 0.02, t= 16.55, P < 0.001; U251: 1.00 ± 0.17 vs. 0.39 ± 0.01, t= 6.30, P < 0.001). The scratch assay indicated that compared with the control group, RDH10 knockdown significantly inhibited the migration of glioma cells (U87: 1.00% ± 0.04% vs. 2.00% ± 0.25%, t= 6.08, P < 0.01; U251: 1.00% ± 0.11% vs. 2.48% ± 0.31%, t= 5.79, P < 0.01). Furthermore, RDH10 knockdown significantly inhibited the invasive capacity of glioma cells (U87: 97.30 ± 7.01 vs. 13.70 ± 0.58, t = 20.36, P < 0.001; U251: 96.20 ± 7.10 vs. 18.30 ± 2.08, t = 18.51, P < 0.001). Finally, Western blotting demonstrated that compared with the control group, downregulation of RDH10 significantly inhibited TGF-β expression, phosphorylated SMAD2, and phosphorylated SMAD3 (TGF-β: 1.00 ± 0.10 vs. 0.53 ± 0.06, t= 7.05, P < 0.01; phosphorylated SMAD2: 1.00 ± 0.20 vs. 0.42 ± 0.17, t= 4.01, P < 0.01; phosphorylated SMAD3: 1.00 ± 0.18 vs. 0.41 ± 0.12, t= 4.12, P < 0.01). Conclusion RDH10 knockdown might inhibit metastasis of glioma cells via the TGF-β/SMAD signaling pathway.

Background: Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B virus (HBV) carriers infected by mother-to-child transmission (MTCT). This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group. Methods: The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016. Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected. Results: Patients infected by MTCT were more likely to have e antigen positive (68.6% vs. 58.2%, χ² = -2.491, P = 0.012) than those with horizontal transmission. However, in patients with MTCT, levels of alkaline phosphatase (ALP) (P = 0.031), Fibroscan (P = 0.013), N-terminal propeptide of Type III procollagen (PIIINP) (P = 0.014), and Laminin (LN) (P = 0.006) were high, in contrast to the patients with horizontal transmission for whom the levels of albumin (ALB) (P = 0.041), matrix metalloproteinase-3 (MMP-3) (P = 0.001) were high. The 47.2% of patients with MTCT and 36.8% of those with horizontal transmission had significant liver fibrosis (P = 0.013). Following antiviral therapy for 78 weeks, 21.2% and 38.0% patients with MTCT and horizontal transmission acquired hepatitis B e antigen (HBeAg) clearance, respectively (P = 0.043), and the virological response rates were 54.7% and 74.1% in the MTCT and horizontal groups, respectively (P = 0.005). MTCT was a risk factor for HBeAg clearance and virological response. Conclusion: Adult patients with MTCT were more prone to severe liver diseases, and the therapeutic efficacy was relatively poor, which underlined the importance of earlier, long-term treatment and interrupting perinatal transmission. Trial Registration NCT01962155; https://clinicaltrials.gov.

BACKGROUND: MRI T1ρ and T2 mapping have been applied to study lumbar intervertebral disc degeneration in human and rhesus monkey, showing that they can be used for evaluating the early degeneration, but their application in New Zealand rabbit lumbar intervertebral disc degeneration is never reported.OBJECTIVE: To compare the relaxation time values of T1ρ and T2 mapping at different time points in a New Zealand rabbit model of ischemic lumbar intervertebral disc degeneration, and to compare the sensitivity for degeneration.METHODS: Fifteen New Zealand rabbits were randomly divided into three groups, and one of intervertebral discs at L4-5,L5-6 and L6-7 was designed for ischemic lumbar intervertebral disc degenerative model and the other two discs for controls. All the rabbits underwent T1ρ and T2 mapping preoperatively, 1, 3 or 6 months postoperatively to analyze the changes in the relaxation time at different time points.RESULTS AND CONCLUSION: (1) In the modeling group, the T2 mapping relaxation time of nucleus pulposus was (118.53±20.51) ms and (85.42±11.65) ms at 3 and 6 months after modeling, respectively, which showed significant difference when compared with preoperatively (146.21±16.93) ms (P < 0.05); but the time showed no significant difference compared with 1 month after modeling (P > 0.05). (2)T1ρ relaxation time of nucleus pulposus was (64.75±14.63) ms at 6 months after modeling, which showed significant difference when compared with preoperatively (87.88±8.87) ms (P < 0.05); but the time showed no significant difference compared with 1 and 3 months after modeling (P > 0.05). (3) In the control group, there was no significant difference in the T1ρ or T2 mapping relaxation time of nucleus pulposus before operation with 1, 3 or 6 months after operation (P > 0.05). The Pfirrmann grade of lumbar intervertebral disc was changed to Pfirrmann grades II-III at 6 months after modeling. (4) These results suggest that MR T1ρ and T2 mapping both are quantitative tools for evaluating the progress of ischemic lumbar intervertebral disc degeneration in New Zealand rabbits, especially the T2 mapping MRI may be more sensitive to early degenerative changes.

Case reports of indium-related lung disease in workers have raised public concern to the human toxicity of indium (In) and its compounds. However, studies evaluating the exposure or health of workers in In smelting plants are rare. Therefore, in this study, we focused on four In smelting plants, with the main objective of characterizing In in smelter plants in China and discussing the potential exposure biomarkers of In exposure. We recruited 494 subjectsat four In smelting plants in China. Personal air samples, first morning urine and spot blood samples were collected. In concentrations in samples were analyzed using inductively coupled plasma mass spectrometry. In concentrations in air samples did not exceed the permissible concentration-time weighed average, but the smelter workers had a higher internal exposure to In. Positive correlations were observed between the air In and urine In concentrations, and between the air In and blood In concentrations. This study provides basic data for the following In exposure and health risk assessment.
Adult ; Air Pollutants, Occupational ; blood ; urine ; Biomarkers ; blood ; urine ; China ; Environmental Monitoring ; Female ; Humans ; Indium ; blood ; urine ; Male ; Mass Spectrometry ; Metallurgy ; Middle Aged ; Occupational Exposure ; Young Adult