Changes of serum uric acid levels in patients with chronic hepatitis C after using direct antiviral agents therapy / 中华肝脏病杂志

Objective: To observe the changes of serum uric acid levels and clinical characteristic in patients with chronic hepatitis C combined with hyperuricemia after direct antiviral agents (DAA) therapy. Methods: A prospective cohort study was used to investigate the risk of hyperuricemia in patients with chronic hepatitis C who received DAA treatment to obtain sustained virological response. The changes and factors influencing serum uric acid levels after 12 weeks of DAA treatment were observed. Comparisons between groups were performed using χ (2) test or Fisher's exact test, analysis of variance, Student's t test, or the non-parametric Mann-Whitney U test. Serum uric acid (SUA) changes, liver and kidney function indexes before and after treatment were compared by repeated measurement and paired t-test. Uric acid reduction was defined as a decrease in SUA from baseline at 12 weeks after treatment. Rates of change in eGFR, aspartate aminotransferase/platelet ratio, alanine aminotransferase and controlled attenuation parameter were defined from baseline (baseline to 12 weeks after treatment). Binary logistic regression analysis was used to compare the risk factors and factors influencing high and low uric acid level. Results: 161 cases with chronic hepatitis C who received DAA treatment were included, of which 19.3% patients were hyperuricemic. eGFR < 60 ml/(min·1.73 m(2)) and body mass index were independent risk factors for hyperuricemia in patients with chronic hepatitis C (eGFR: OR = 0.123, P = 0.002; body mass index: OR = 1.220, P = 0.002). SUA levels was changed significantly before treatment, at the end of treatment and at 12 weeks after treatment (327.96 vs. 320.76 vs. 314.92, F = 3.272, P = 0.042). At 12 weeks after treatment, SUA, liver stiffness, alanine aminotransferase and control attenuation parameters were all significantly lower than baseline (P < 0.05). The rate of increase in eGFR from baseline and the rate of decrease in controlled attenuation parameter during treatment were the factors influencing SUA reduction (eGFR: OR = 5124, P = 0.000; controlled attenuation index: OR = 0.010, P = 0.039). Conclusion: In chronic hepatitis C, reduced eGFR and body mass index are the risk factors for the development of hyperuricemia and a significant reduction in serum uric acid levels after DAA treatment can eradicate the virus.

Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study / 中华血液学杂志

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

In vitro anti-platelet aggregation effects of fourteen fruits and vegetables

In the present study, the anti-platelet aggregation activity of 14 vegetables and fruits was tested in vitro. The aqueous, 90% ethanol and ethyl acetate extracts, as well as concentrated juices of 14 foods [fruits and vegetables] were prepared, and the anti-platelet aggregation activity of those extracts was analyzed on a platelet aggregation analyzer in vitro with adenosine 5'-diphosphate [ADP], bovine thrombin [THR] and arachidonic acid [AA] as aggregation inducers, respectively. Aspirin [ASP] was used as the positive control. A number of the tested foods had inhibitory effects in concentration-dependent manner on platelet aggregations induced by various agonists. Especially, some foods such as lemon, leek, garlic, scallion, ginger, tomato and grapefruit showed good anti-platelet aggregation effect similar or higher than that of positive control group i.e. aspirin [ASP]. The results of present study provide scientific reference for reasonable selection of daily dietary with supplementary curative effects or prevention of cardiovascular diseases [CVD]

Analysis of chemical components in Cordyceps by online gradient extraction-HPLC / 中国中药杂志

Online gradient extraction-high performance liquid chromatography( HPLC) method was developed for simultaneous determination of high and low polar components in Cordyceps. The sample powder of Cordyceps was uniformly mixed with diatomaceous earth,packed into extraction tank,and installed into the HPLC system. Online gradient extraction was conducted with mobile phase at 70 ℃. The separation was performed on Zorbax SB-AQ( 4. 6 mm×150 mm,5 μm) column with 0. 1% formic acid solution-methanol as the mobile phase for gradient elution at 1. 0 mL·min~(-1). The column temperature was 30 ℃,and detection wavelength was set at 260 nm. The results showed that the high and low polar components in Cordyceps could be simultaneously extracted and separated by the developed method. Meanwhile,six high polar compounds( uracil,uridine,thymine,inosine,guanosine and adenosine) and one low polar compound( ergosterol) were identified by comparison with the reference peaks. The established method is rapid,stable and environment friendly,which is helpful to improve the quality evaluation level for Cordyceps.

Effects of different drying conditions on protein in Cordyceps / 中国中药杂志

In this study,the protein in different Cordyceps samples,which include fresh sample( S1),22 ℃ drying sample( S2),37 ℃ drying sample( S3) and 60 ℃ drying sample( S4),were analyzed by sodium dodecylsupinate-polyacrylamide gel electrophoresis( SDS-PAGE) and two-dimensional electrophoresis( 2-DE). The total protein contents in Cordyceps samples were from 1. 655-4. 493 mg·g~(-1) and the protein contents in fresh sample was the highest. The results of SDS-PAGE showed that the mainly ranges of protein molecular weight of Cordyces samples were 10-100 kDa and the numbers of protein bands were 28 to 41,the fresh sample had the maximum number of protein bands. The 2-DE profiles were analyzed by PDQuest software. The resulted indicated that 488-876 protein spots were detected in different Cordyceps samples and the isoelectric point( pI) was distributed between 4. 5 and 6. 5,the protein molecular weight was distributed in 10-20 kDa and 25-100 kDa,the fresh sample had the maximum number of protein spots. Therefore,the drying process could decrease contents and species of protein in Cordyceps,and the different drying conditions had different effects on protein. These results provide a reference for improving the drying process of Cordyceps.

SDS-PAGE and 2-DE protein profiles of Ganoderma lucidum from different origins

Ganoderma lucidum [Chizhi in Chinese] is one of the most valuable and widely used medicinal fungi in traditional Chinese medicines [TCMs]. Most of previous studies were focused on the triterpenoids and polysaccharides of G. lucidum, whereas less attention had been paid on the protein, which is another bioactive compound in it. In the present study, protein maps of fourteen G. lucidum samples were comprehensively analyzed by sodium dodecyl sulfate - polyacrylamide gel electrophoresis [SDS-PAGE] and two-dimensional electrophoresis [2-DE]. The results indicated that there were significant differences in protein profiles of G. lucidum samples from different origins. Furthermore, previous reported bioactive proteins from the fruiting bodies of G. lucidum, were mainly distributed in 4 taxa [A, B, C and D] based on their molecular weights on the 2-DE maps. The proteins should be considered as marker for the quality control of G. lucidum, because the proteomic variation may affect on their pharmacological activities

Establishment of a neonatal mouse model of hypoxic-ischemic brain damage / 中国实验动物学报

Objective To improve the classic Vannucci method for establishing a model of hypoxic-ischemic brain damage in the neonatal mice. Methods Postnatal day 11 KM mice were randomly assigned into normal control group ( N group, n=20) and hypoxic-ischemic brain damage group (HIBD group, n=160). For the HIBD group, the left common carotid artery of mice was ligated and exposed to hypoxia according to different conditions in the groups C1-C8, then com-pared the mortality and the success rates of all groups. TTC staining and relative infarct volume was measured to select the most stable conditions of modeling. In all groups, the growth and development of mice were evaluated by body weight growth curve at different time points after modeling. Longa test, grip test and hanging test were porformed to assess the neu-romotor function. HE staining was used to detect cerebral neuronal pathological changes. Results Neonatal mouse models of hypoxic-ischemic brain damage were established by the left common carotid artery ligation and hypoxia for 45 min under conditions of 8% O2 and 35℃, which resulted a low mortality rate (8. 3%) and high success rate (47. 92%). Compared with the normal group, mice of the HIBD group grew slowly in body weight and showed severe motor dysfunction. The liga-tion side of cerebral artery showed infarction area which accounted for 7. 76 ± 0. 70% of the total brain. The cortex and hip-pocampus of ligated brain tissue showed neuron degeneration and necrosis. Conclusions The neonatal mouse model of hy-poxic-ischemic brain damage is successfully established by our modified method , i. e. to ligate the left common carotid ar-tery and to expose the mice to hypoxia at 8% O2 and 35℃ for 45 min. This model provides a liable and stable experimental animal model for research of neonatal hypoxic-ischemic brain damage.

Establishment of a neonatal mouse model of hypoxic-ischemic brain damage / 中国实验动物学报

Objective To improve the classic Vannucci method for establishing a model of hypoxic-ischemic brain damage in the neonatal mice. Methods Postnatal day 11 KM mice were randomly assigned into normal control group ( N group, n=20) and hypoxic-ischemic brain damage group (HIBD group, n=160). For the HIBD group, the left common carotid artery of mice was ligated and exposed to hypoxia according to different conditions in the groups C1-C8, then com-pared the mortality and the success rates of all groups. TTC staining and relative infarct volume was measured to select the most stable conditions of modeling. In all groups, the growth and development of mice were evaluated by body weight growth curve at different time points after modeling. Longa test, grip test and hanging test were porformed to assess the neu-romotor function. HE staining was used to detect cerebral neuronal pathological changes. Results Neonatal mouse models of hypoxic-ischemic brain damage were established by the left common carotid artery ligation and hypoxia for 45 min under conditions of 8% O2 and 35℃, which resulted a low mortality rate (8. 3%) and high success rate (47. 92%). Compared with the normal group, mice of the HIBD group grew slowly in body weight and showed severe motor dysfunction. The liga-tion side of cerebral artery showed infarction area which accounted for 7. 76 ± 0. 70% of the total brain. The cortex and hip-pocampus of ligated brain tissue showed neuron degeneration and necrosis. Conclusions The neonatal mouse model of hy-poxic-ischemic brain damage is successfully established by our modified method , i. e. to ligate the left common carotid ar-tery and to expose the mice to hypoxia at 8% O2 and 35℃ for 45 min. This model provides a liable and stable experimental animal model for research of neonatal hypoxic-ischemic brain damage.

Research progress of pharmacological activities and analytical methods for plant origin proteins / 中国中药杂志

As one of the important active components of traditional Chinese medicine (TCM), plant origin active proteins have many significant pharmacological functions. According to researches on the plant origin active proteins reported in recent years, pharmacological effects include anti-tumor, immune regulation, anti-oxidant, anti-pathogeny microorganism, anti-thrombus, as well as hypolipidemic and hypoglycemic activities of plant origin were reviewed, respectively. On the other hand, the analytical methods including chromatography, spectroscopy, electrophoresis and mass spectrometry for plant origin proteins analysis were also summarized. The main purpose of this paper is providing a reference for future development and application of plant active proteins.

Expression and clinical significance of miR-21 in diffuse large B cell lymphoma / 中国实验血液学杂志

This study was aimed to investigate the expression of microRNA-21 and its correlation with PTEN in diffuse large B cell lymphoma (DLBCL) paraffin-embedded tissues, and evaluate its potential relevance with clinical characteristics. The expression levels of miR-21 in 26 primary DLBCL and 10 normal lymph node tissue specimens were examined by real-time polymerase chain reaction. The expression of PTEN was detected by immunohistochemical staining. The results indicated that the expression of miR-21 was significantly higher in tumor tissues [6.586(1.10,38.22)] than that in normal tissues [0.791 (0.35,2.87)] (P < 0.05). Among 26 patients with DLBCL the expression of PTEN protein was positive in 6 patients (23%), and was negative in 20 patients (77%). In patients with DLBCL, the expression level of miR-21 was negatively correlated with the level of PTEN protein. The high expression of miR-21 was positively correlated with the level of serum LDH. The expression level of miR-21 in patients with Ann Arbor III-IV stage was obviously higher than that of patients with Ann Arbor I-II stage, but did not correlate with the subtype of patients in clinic (P > 0.05). It is concluded that the expression of miR-21 is high in DLBCL and its overexpression may be related with poor prognosis of DLCBL. These findings suggest that PTEN is possibly one of the targets of miR-21 in DLBCL.

Study on quality control of Houttuynia Cordata, a traditional Chinese medicine by fingerprint combined with quantitative analysis of multi-components by single marker / 中国中药杂志

To establish a new method of quality evaluation of Traditional Chinese medicine by fingerprint and quantitative analysis of multi-components by single marker method (QAMS). The quality evaluation method was established and validated with Houttuyniae Herba. Chlorogcnic acid was selected as markers of ingredients to establish HPLC fingerprint and internal reference standard to determine the contents of other 6 components (new chlorogcnic acid, cryptochlorogenic acid, rutin, hyperin, isoquercitrin, quercitrin) according to the relative correction factor. At the same time, the seven components were determined by external standard method. The accuracy and feasibility of QAMS was evaluated by comparison of the results between external standard method and QAMS. All tested samples contained the 12 common peaks , 7 of which was verified ,and there was no significant differences between the quantitative results of 7 ingredients of multi-components by single marker method and external standard method in 20 batches. The method of fingerprint combined with QAMS has been verified in Houttuyniae Herba and it is to be a new quality evaluation pattern for Traditional Chinese medicine.

Beneficial effects of liver X receptor agonist on adipose-derived mesenchymal stem cells transplantation in mice with myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of liver X receptor (LXR) agonist on adipose-derived mesenchymal stem cells (AD-MSCs) implantation into infarcted hearts of mice.</p><p><b>METHOD</b>AD-MSC(Fluc+) which stably expressed firefly luciferase (Fluc) were isolated from β-actin-Fluc transgenic mice and characterized by flow cytometry. Male FVB mice were randomly allocated into the following four groups (n = 10 each): (1) sham group; (2) MI + PBS group; (3) MI + AD-MSC(Fluc+) group; (4) MI + AD-MSC(Fluc+) + LXR agonist (T0901317) group. AD-MSC(Fluc+) or PBS were injected intramyocardial into peri-infarcted region of mice heart after permanent left anterior descending (LAD) artery ligation. Bioluminescence imaging (BLI) was performed for quantification of injected cells retention and survival. Cardiac function was evaluated by echocardiography.</p><p><b>RESULTS</b>The AD-MSC(Fluc+) were positive for CD44 and CD90 by flow cytometry. BLI evidenced the firefly luciferase expression of AD-MSC(Fluc+) which was positively correlated with cell numbers (r(2) = 0.98). The results of BLI in vivo revealed that LXR agonist could improve the survival of AD-MSC(Fluc+) at day 7, 14 and 21 after transplantation compared with AD-MSC(Fluc+) alone group. Cardiac function was further improved in combination therapy group compared with AD-MSC(Fluc+) alone group (P < 0.05).</p><p><b>CONCLUSIONS</b>LXR agonist T0901317 can improve the retention and survival of intramyocardial injected AD-MSC(Fluc+) post-MI, and the combination therapy of T0901317 and AD-MSC(Fluc+) has a synergetic effect on improving cardiac function in this model.</p>

DDP-sensitivity-related genes in 10 lung cancer cell lines / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To search for genes related to cisplatin (DDP) sensitivity in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines.</p><p><b>METHODS</b>The sensitivity of 4 SCLC lines and 6 NSCLC lines to DDP was evaluated by MTT assay. The expression of 1291 genes related to DDP-sensitivity in the 10 cell lines was measured by cDNA macroarray and the relationship between genes and DDP-sensitivity was analyzed.</p><p><b>RESULTS</b>20 genes were negatively related to DDP-sensitivity in the SCLC and NSCLC cell lines, including Metallothionein, Cathepsin B, TIMP1, TNF-R1, TGF beta-induced 68 000, Cathepsin L, Galectin-1, Annexin 11, PAI-1, IGFBP4, UPAR, Jagged, CD13, alpha 1 A-AR, EphA2 (Eck), APC, RhoC, Fibromodulin, GATA-6 and HSC 70, while only procoagula and MDM2 were positively related to DDP-sensitivity in the SCLC and NSCLC cell lines. 10 genes were negatively related to DDP-sensitivity in the SCLC cell lines, including VHL, MMP-7, Elongin A, GSK-3 beta, SLC, Galectin-3, integrin beta 5, moesin, IKK beta, and ETV 1, while only AT2 was positively related to DDP-sensitivity in the SCLC cell lines. 10 genes were negatively related to DDP-sensitivity in the NSCLC cell lines, including Clusterin, FG FR-2, Thrombospondin 1, HSP 32, Lactate dehydrogenase A, P300, Thymosin beta l0, CD81, C/EBP gamma, Rak, while only CaMKK and TPA were positively related to DDP-sensitivity in the NSCLC cell lines.</p><p><b>CONCLUSION</b>There were 45 genes related to DDP-sensitivity in 10 lung cancer cell lines. There were 22 co-expressed genes in both SCLC and NSCLC cell lines, and only 11 and 12 genes expressed in the SCLC and NSCLC cell lines, respectively.</p>

Vaccination of rhesus monkeys with recombinant antigen fragments and protection from hepatitis E virus infection / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe anti-HEV IgG response to vaccination of recombinant antigen fragments and evaluate its protection from Hepatitis E Virus infection in rhesus monkeys (Macaca mulatta).</p><p><b>METHODS</b>Twelve monkeys were divided into three groups and immunized respectively with three different recombinant antigens: namely Ag1 (carboxyl terminal 431 amino acids of ORF2), Ag2 (128aa fragment at the carboxyl terminal of ORF2), and Ag3 (full length ORF3 ligated with two ORF2 fragments encoded by 6743-7126nt and 6287-6404nt). The monkeys were challenged intravenously with fecal suspension from experimentally infected rhesus monkeys, and the other three monkeys served as the placebo group for challenge with HEV. The dynamic changes of the levels of ALT and anti-HEV IgG were examined. Pathological changes of liver tissue were observed by light microscope. Excretion of virus was detected by RT-nPCR.</p><p><b>RESULTS</b>Hepatic histopathology of two monkeys in the placebo group was consistent with acute viral hepatitis, and ALT was elevated 3-4 weeks after inoculated with virus, up to 10-20 times higher than normal level. The liver tissue of monkeys immunized with antigen kept normal, ALT in several monkeys elevated mildly, and anti-HEV IgG conversation occurred at 1-2 weeks after vaccination, with the titer reaching 1:12,800. The virus RNA could be detected by RT-nPCR from days 7 to 50 in monkeys of control group, and from days 7 to 21 in vaccinated monkeys after challenged with virus.</p><p><b>CONCLUSIONS</b>The recombinant antigens could induce the production of anti-HEV IgG, which protected rhesus monkeys from acute Hepatitis symptoms related to HEV infection.</p>

DNA Immunization of Hepatitis E Virus (HEV) / 中国病毒学

Two plasmid constructs, pcE2 and pcE3, containing 3' fragment of open reading frame 2 (ORF2,1163 bp) of hepatitis E virus (HEV) and full-length ORF3 (369 bp), were injected into bilateral tibialis of Swiss mice respectively，for three times (0, 2nd and 4th weeks) and observed the HEV IgG by ELISA. HEV IgG was induced after the injection of pcE2 or pcE3 or both, and the percentage of seraconversion was 100% after two weeks of the third injection. Compared with injection of either construct, the antibody titers were higher in the group with combined injection of two constructs.