Effect of Celastrol Based on IRAK4/ERK/p38 Signaling Pathway on Proliferation and Apoptosis of Multiple Myeloma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect. @*METHODS@#CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot. @*RESULTS@#Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05). @*CONCLUSION@#Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells.

Analysis of Serum Metabonomics in Patients with Multiple Myeloma Based on Liquid Chromatography-Mass Spectrometry / 中国实验血液学杂志

OBJECTIVE@#To observe the changes of serum metabolites in patients with multiple myeloma (MM) by metabonomics, and explore the potential biomarkers for diagnosis, prognosis, and progression of MM.@*METHODS@#Serum samples were collected from 26 patients with MM and 50 healthy controls. The data detected by liquid chromatography-mass spectrometry (LC-MS) was input into SIMCA-14.0 software for multivariate statistical analysis. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the changes of metabolites.@*RESULTS@#The metabolic change of uric acid and trans-vaccenic acid in serum samples of MM patients was 9.39 times and 2.77 times of these in healthy people, respectively, which were significantly higher than those of healthy people, and the difference was statistically significant(P<0.01).@*CONCLUSION@#Uric acid and trans-vaccenic acid are expected to be important metabolic indicators for the diagnosis, prognosis, and efficacy evaluation of MM, thus providing some clues for the pathogenesis of MM.

Chromosomal aberrations detection in chronic lymphocytic leukemia by conventional cytogenetics using DSP30 and IL-2 / 中华血液学杂志

Objective: To study the value of unmethylated cytosine guanine dinucleotide oligodeoxynucleotide (DSP30) and IL-2 in the conventional cytogenetic (CA) detection of the chromosomal aberrations in chronic lymphocytic leukemia (CLL) . Methods: Bone marrow or peripheral blood cells of CLL patients were cultured with DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Fluorescence in situ hybridization (FISH) was performed in 85 patients. CA results were compared with data obtained by FISH. Results: Among 89 CLL patients, the success rate of chromosome analysis was 94.38% (84/89) . Clonal aberrations were detected in 51 patients (51/84, 60.71%) . Of them, 27 (27/51, 52.94%) were complex karyotype. Among 85 CLL patients tested by FISH, chromosomal abnormalities were detected in 74 (74/85, 87.06%) patients, of which 2 (2/74) patients were complex karyotypes, accounting for 2.70%. Of the 85 CLL patients examined by FISH, 50 had abnormal karyotype analysis, 30 had normal karyotype, 5 failed to have chromosome analysis. Among them, 25 cases showed clonal aberrations by FISH assay but normal by CA, and 4 cases were normal by FISH but displayed aberrations in chromosome analysis, and totally 78 (91.76%) cases with abnormality detected by the combination of the two methods. The frequency of 13q- abnormality detected by FISH was significantly higher than that by CA analysis (69.41%vs 16.67%, P<0.001) , while the frequency of 11q-,+12 and 17p- detected by two methods showed no significant difference (P>0.05) . The detection rate of complex abnormalities in conventional karyotype analysis was higher than that in FISH (50.98%vs 2.70%) . In addition, 11 low-risk and 9 intermediate-risk patients according to FISH results showed complex karyotype by cytogenetics, and were classified into high-risk cytogenetic subgroup. Conclusion: DSP30 and IL-2 are effective in improving the detection rate of CA in CLL patients (60.71%) and CA is more effective to detect complex karyotype. However, FISH had a higher overall abnormality detection rate (87.06%) than CA, especially for 13q-. The combination of CA and FISH not only enhanced the detection rate of clonal aberrations to 91.76%, but also provided more precise prognosis stratification for CLL patients, thus to provide more information for clinical implication.

Efficacy of tazarotene 0.05%/betamethasone dipropionate 0.05% cream in the treatment of mild to moderate psoriasis vulgaris: a multicenter clinical observational study / 中华皮肤科杂志

Objective:To preliminarily evaluate clinical efficacy and safety of tazarotene 0.05%/betamethasone dipropionate 0.05% cream in the treatment of psoriasis vulgaris.Methods:A multicenter, randomized, double-blinded, single-dummy, parallel-controlled clinical trial was conducted. Subjects with mild to moderate psoriasis vulgaris were randomized into 4 groups at a ratio of 2∶1∶1∶1, including tazarotene 0.05%/betamethasone dipropionate 0.05% cream (Taz/Bp) group, betamethasone dipropionate 0.05% cream (Bp) group, tazarotene 0.05% gel (Taz) group and cream vehicle control (Plb) group. The treatment lasted 4 weeks. After 1, 2 and 4 weeks of treatment, efficacy and safety of drugs were evaluated in the above groups. Two-way analysis of variance model with main effects was used to compare continuous indices, least significant difference t-test was used for multiple comparisons, and chi-square test or Fisher′s exact test for comparisons of categorical data. Results:A total of 300 subjects were enrolled from 7 research centers, including 120 in the Taz/Bp group, 60 in the Bp group, 60 in the Taz group and 60 in the Plb group. After 4 weeks of treatment, proportions of patients achieving a 75% reduction in PASI (PASI75) were 35.83%, 20.00%, 18.33% and 6.67% in the Taz/Bp, Bp, Taz and Plb groups respectively, and there was a significant difference among the 4 groups ( P < 0.05) ; the proportion of patients achieving PASI75 was significantly higher in the Taz/Bp group than in the Plb group (α = 0.05, P < 0.05) and Taz group (α = 0.025, P < 0.025) , but there was no significant difference between the Taz/Bp group and Bp group (α = 0.016 7, P > 0.016 7) ; the proportions of patients achieving PASI90 were 25.00%, 8.33%, 5.00% and 1.67% in the Taz/Bp, Bp, Taz and Plb groups respectively, which significantly differed among the 4 groups ( P < 0.05) , and the Taz/Bp group showed a significantly increased proportion of patients achieving PASI90 compared with the Plb group ( P < 0.05) , Taz group ( P < 0.025) and Bp group ( P < 0.016 7) . All the tested drugs were well tolerated in the 4 groups. Adverse drug reactions occurred in 15 (12.50%) , 5 (8.33%) , 19 (31.67%) and 9 (15.00%) patients in the Taz/Bp, Bp, Taz and Plb groups respectively. The incidence rate of adverse drug reactions significantly differed among the 4 groups ( P = 0.004) , and was significantly lower in the Taz/Bp group than in the Taz group ( P < 0.05) , but insignificantly different between the Taz/Bp group and Bp or Plb group (both P > 0.05) . Conclusion:Tazarotene 0.05%/betamethasone dipropionate 0.05% cream is effective and safe for the treatment of psoriasis vulgaris.

Efficacy of tazarotene/betamethasone dipropionate cream at different concentration ratios in the treatment of psoriasis vulgaris: a clinical observation / 中华皮肤科杂志

Objective:To evaluate the efficacy and safety of tazarotene/betamethasone dipropionate cream at different concentration ratios in the treatment of psoriasis vulgaris, and to determine the optimal drug concentration ratio for clinical use.Methods:A multicenter, randomized, double-blinded, multi-dose controlled study was conducted. From December 2008 to April 2009, a total of 180 patients with psoriasis vulgaris were enrolled from 7 research centers, such as Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College. These patients were randomly and equally divided into 5 groups: treatment groups 1, 2, 3, 4 treated with tazarotene/betamethasone dipropionate cream at concentration ratios of 0.025%/0.025%, 0.05%/0.025%, 0.025%/0.05% and 0.05%/0.05% respectively once a day, and control group treated with the cream vehicle once a day. The treatment lasted 4 weeks. Efficacy and safety were evaluated after 1, 2 and 4 weeks of treatment. One-way analysis of variance and least significant difference (LSD)- t test were used to compare measurement data among several groups, chi-square test and Fisher′s exact test to compare categorical data among groups, and Cochran-Mantel-Haenszel (CMH) test to compare psoriasis area severity index (PASI) response rates between groups. Results:After 4 weeks of treatment, 11 patients (30.56%) , 12 (33.33%) , 12 (33.33%) , 19 (52.78%) and 2 (5.56%) in the treatment groups 1, 2, 3, 4 and control group respectively achieved a 75% reduction in PASI (PASI75) , and the proportions of patients achieving PASI75 were significantly higher in the treatment groups than in the control group (all P < 0.012 7) . Additionally, the proportions of patients achieving PASI90 were also significantly higher in the treatment groups 1, 2 and 4 than in the control group (all P < 0.012 7) . After 4 weeks of treatment, the rates of reduction in PASI scores were 59.52% ± 26.79%, 57.19% ± 31.98%, 56.85% ± 30.46% and 68.21% ± 37.20% in treatment groups 1, 2, 3, and 4 respectively, which were all significantly higher than the rate of reduction in the control group (20.07% ± 28.55%; LSD- t = 5.36, 5.05, 5.00, 6.55, all P < 0.001) . The treatment group 4 showed marked comprehensive efficacy. All the tested drugs were well tolerated in the patients, and adverse reactions occurred in 11 (30.56%) , 8 (22.22%) , 2 (5.56%) , 4 (11.11%) and 2 (5.56%) cases in the treatment groups 1, 2, 3, 4 and control group respectively. The incidence rate of adverse reactions was significantly higher in the treatment group 1 than in the control group ( P = 0.012) , and there was no significant difference among the treatment groups 2, 3, 4 and control group (all P > 0.05) . Conclusion:The tazarotene 0.05%/betamethasone dipropionate 0.05% cream can be recommended for subsequent clinical trials in psoriasis vulgaris.

Influencing factors for first cases of varicella aggregation outbreaks in primary school in Pudong New Area of Shanghai / 上海预防医学

Objective To investigate influencing factors of the first cases of varicella outbreaks in primary school in Pudong New Area of Shanghai and to provide scientific evidence for effective prevention and control measures against it. Methods The first 80 cases of varicella outbreaks in primary school in Pudong New Area were included for the case-control study.Immunization history, outing activities and information of out-of-school training were gathered.Univariate and multivariate conditional logistic regression analysis were adopted for data analysis. Results Multivariate analysis revealed that varicella vaccination period(OR=0.08, 95%CI:0.01-0.44)was the protective factor for the first case in a varicella outbreak, while weekly frequency of visits to large commercial/supermarkets (OR=4.79, 95%CI:1.86-12.34)and weekly attendance at out-of-school training(OR=1.84, 95%CI:1.01-3.35)were risk factors of the disease. Conclusion It is important to promote the current varicella vaccine immunization strategy, to strengthen the disinfection and health education of large commercial/supermarkets and to strengthen infectious disease management, disease prevention guidance and supervision in out-of-school training institutions.

Public health service assessment: enlightenments from worldwide experience / 中华医院管理杂志

An assessment is a key to public health management. This article reviewed the experiences and researches of assessment on public-health system, as well as public health service quality of medical institutions in America, the United Kingdom and Australia among other countries. On such basis, suggestions were provided on assessments of public health service in China, in order to help the government to improve its indicator evaluation system.

Public health service delivered by public hospitals in China: function analysis and policy advices / 中华医院管理杂志

Hospitals, especially public hospitals, are an important part of the public health service system. To clarify public health functions of secondary and tertiary public hospitals in China and provide evidences for related health policy decisions, this article introduced the public health services of hospitals in the United States, Britain, Australia and Canada, and then analyzed public health functions of secondary and tertiary public hospitals in China through literature review and case study. The authors summed up eight kinds of public health service functions, and put forward policy advices to promote the performance of public health functions of public hospitals in China.

Public health service assessment: enlightenments from worldwide experience / 中华医院管理杂志

An assessment is a key to public health management. This article reviewed the experiences and researches of assessment on public-health system, as well as public health service quality of medical institutions in America, the United Kingdom and Australia among other countries. On such basis, suggestions were provided on assessments of public health service in China, in order to help the government to improve its indicator evaluation system.

Public health service delivered by public hospitals in China: function analysis and policy advices / 中华医院管理杂志

Hospitals, especially public hospitals, are an important part of the public health service system. To clarify public health functions of secondary and tertiary public hospitals in China and provide evidences for related health policy decisions, this article introduced the public health services of hospitals in the United States, Britain, Australia and Canada, and then analyzed public health functions of secondary and tertiary public hospitals in China through literature review and case study. The authors summed up eight kinds of public health service functions, and put forward policy advices to promote the performance of public health functions of public hospitals in China.

Association of TLR1 gene polymorphisms with pulmonary candida infection and candida colonization in Guizhou Han patients with chronic obstructive pulmonary disease / 医学研究生学报

Objective Studies are rarely reported on the correlation of the Toll-like receptor (TLR) gene polymorphisms with fungal infection in the Chinese Han population. This study aims to explore the association between TLR gene polymorphisms and pulmonary candida infection (PCI) and candida colonization (CC) in patients with chronic obstructive pulmonary disease (COPD) in the Guizhou Han population. Methods Using the polymerase chain reaction-direct sequencing (PCR-SBT) method, we genotyped six single nucleotide polymorphisms (SNP) of the TLR1, TLR2 and TLR4 genes in 344 Guizhou Han patients with COPD, including 80 cases complicated by PCI (the PCI group), 103 cases complicated by CC (the CC group), and 161 negative controls. We analyzed the correlation of the SNPs with PCI and CC in the COPD patients in different genetic models with the SNPstats online software, measured the levels of IL-6, IL-8, IL-1β and TNF-α proteins in the plasma of the patients by ELISA, and assessed the functional consequences of these polymorphisms. Results The polymorphisms of rs5743611, rs5743708, rs4986790 and rs4986791 were found in none of the patients. The genotype frequency of rs4833095 was significantly different between the PCI and control groups in the codominant, dominant and overdominant models (P < 0.05), with the dominant model as the best genetic pattern. No statistically significant difference was observed either in the rs4833095 genotype frequency between the CC and control groups (P > 0.05) or in the rs5743618 genotype frequency between any two groups (P > 0.05). In the PCI group, the T allele of the rs4833095 polymorphism significantly decreased the levels of IL-6, IL-8 and IL-1β in the plasma (P < 0.05), and that of TNF-α as well, though with no statistically significant difference (P > 0.05). Conclusion The rs4833095 polymorphism of the TLR1 gene is associated with PCI in COPD patients. The T allele of rs4833095 may affect the function of TLR1, decrease the levels of IL-6, IL-8 and IL-1β proteins in the plasma. Neither rs4833095 nor rs5743618 gene polymorphism is correlated with the susceptibility to candida colonization.

Propensity-matched comparison of laparoscopic and open radical cystectomy for female patients with bladder cancer / 北京大学学报(医学版)

OBJECTIVE@#To compare the perioperative and oncologic outcomes of female patients receiving laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC).@*METHODS@#Retrospective review of 91 consecutive female patients with urothelial carcinoma of bladder undergoing radical cystectomy at a single academic institution from 2006 to 2017. Those female patients received open radical cystectomy were matched to the patients who underwent laparoscopic radical cystectomy by using propensity score matching in 1 ∶1 ratio. The matching factors included age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, pathologic stage and pathologic nodal stage. The perioperation and oncology characteristics were compared, and Kaplan-Meier method was used to analyze the overall survival (OS), cancer specific survival (CSS) and progression-free survival (PFS) estimates. Finally, we did a sensitive analysis by using multivariable COX regression of all the patients, adjusting for the matching factors.@*RESULTS@#There were 65 ORC and 26 LRC patients identified in this cohort with urothelial carcinoma of bladder, the median follow-up time was 38 months (interquartile range 18-69). The age (P<0.001) and ASA scores (P=0.018) were less for LRC before being matched. There were 22 LRC and 22 ORC patients matching successfully. Before being matched, the estimate blood loss (P=0.005), transfusion rate (P<0.001) and total complications rate (P=0.015) were less for LRC, and the lymph nodes yield was greater for LRC, but there were no differences in OS (P=0.698), CSS (P=0.942) and PFS (P=0.837) between the two groups. After being matched, the estimate blood loss (P=0.009), transfusion rate (P=0.001) and total complications rate (P=0.040) were less for LRC, but there was no difference in the lymph nodes yield. Besides, there were no statistic differences in OS (P=0.432), CSS (P=0.429) and PFS (P=0.284) between the two groups. In addition, in multivariable COX regression analysis, surgical approaches (LRC/ORC) were not found to be a predictor of OS (HR 1.134, 95%CI 0.335-3.835, P=0.839), CSS (HR 1.051, 95%CI 0.234-4.719, P=0.949) and PFS (HR 0.538, 95%CI 0.138-2.095, P=0.371) of the female patients with urothelial carcinoma of bladder.@*CONCLUSION@#It is advantageous for laparoscopic radical cystectomy in terms of estimating blood loss, transfusion rate and complication rate. But there was no evidence that laparoscopic radical cystectomy for female patients with bladder cancer had a better oncologic prognosis than open radical cystectomy from this study.

An experimental study of CD4 targeted chimeric antigen receptor modified T cell with anti-lymphoma activity / 中华血液学杂志

Objective: To study the specific killing effect of CD4 membrane protein targeted chimeric antigen receptor modified T (CAR-T) cell. Methods: The second generation CD4 targeted chimeric antigen receptor containing 4-1BB costimulation domain was insert into lentiviral vector through recombinant DNA technology. Lentivirus was prepared and packaged by 293T cells with four plasmids. Beads activated T cells were transduced with lentivirus and the transduction efficiency was checked with Protein L and flow cytometry. T cell subsets and IFN-γ concentrations were detected with probe-tagged antibody and cytometric bead assay. Results: ①The transduction efficiency of activated T cells with prepared lentivirus were 50.0%-70.0%. A subset of CD8+ T cell acquired dim expression of CD4 membrane protein after activation. CD4+T cell and CD8+CD4dim T cell were gradually killed by CD4 targeted CAR-T post lentivirus transduction. ②The kill efficacy of CD4 targeted CAR-T cell and control T cell toward KARPAS 299 T cell at an E∶T ratio of 8∶1 for 24 h was (96.9±2.1)% and (11.2±3.1)%, CAR-T cell has a higher killing efficacy than control T cell (t=7.137, P=0.028). The IFN-γ concentrations in culture supernatant of CAR-T cell with K562-CD4 cell, CAR-T cell with K562 cell and CAR-T cell alone were (15 648±2 168), (1 978±354) and (1 785±268) pg/ml, CAR-T cell cocultured with K562-CD4 cell produced more IFN-γ than the other two controls (P<0.01). Conclusions: CD4 targeted CAR-T has an immunophenotype of CD8+CD4-T cell. CD4 targeted CAR-T cell has killing efficacy toward normal CD4+T cell and CD4+T lymphoma cell. CD4 targeted CAR-T cell also has a killing efficacy toward CD4dim target cell.

Influence of nifedipine combined metoprolol on blood pressure and heart rate in hypertensive patients with coronary heart disease / 心血管康复医学杂志

Objective:To study influence of nifedipine combined metoprolol sustained release tablets on blood pressure and heart rate in hypertensive patients with coronary heart disease (CHD).Methods:A total of 120 hypertensive patients with CHD were selected,randomly and equally divided into nifedipine group (n＝60,received nifedipine monotherapy) and combined treatment group (n＝60,received nifedipine combined metoprolol ),both groups were treated for 12 weeks.Blood pressure,heart rate and indexes of heart rate variability (HRV) were measured and compared between two groups.Results:Compared with before treatment,after treatment,there were significant reductions in 24h mean heart rate (24h HR AV) and mean arterial pressure (MAP),P＝0.001 both,and significant rise in standard deviation of normal to normal RR intervals calculated over the 24h period (SDNN),standard devia-tion of normal to normal RR intervals in all 5min segments of the entire recording (SDANN),root-mean square of differences between successive normal to normal intervals (rMSSD) and adjacent normal RR interval difference ＞50ms stroke accounted for a percentage of 24h total RR interval (PNN50) in two groups,P＜ 0.05 or ＜ 0.01.Compared with nifedipine group after treatment,there were significant reductions in 24hmHR [ (69.24 ± 10.67) beats/min vs.(64.08 ± 8.94) beats/min] and MAP [ (98.06 ± 5.18) mmHg vs.(92.64 ± 4.43) mmHg,P＜0.01 all],and significant rise in SDNN [ (113.89 ± 20.93) ms vs.(124.57 ± 25.34) ms,P＜0.05],SDANN [ (108.31 ± 20.26) ms vs.(119.29 ± 19.37) ms,P＝0.001],rMSSD [ (29.67 ± 11.92) ms vs.(36.23 ± 12.34) ms,P＝0.001] and PNN50 [ (11.25 ± 4.03)% vs.(15.37 ± 4.82)%,P＝0.001] in combined treatment group.There was no significant difference in total effective rate between two groups,P＝ 0.272.Conclusion:Nifedipine combined Metoprolol sustained release tablets possesses significant therapeutic effect on hypertensive patients with CHD.It can effectively control heart rate and blood pressure,and contribute to improving HRV and prognosis,which is worth extending.

Q fever vaccines / 中国人兽共患病学报

Q fever is a worldwide zoonosis and vaccination is the best measure to against its prevalence.Coxiella burnetii (Cb) is an obligate intracellular pathogen responsible for Q fever.Inactivated phase I Cb (Whole cell vaccine,WCV) can provide 100％ protection against Q fever,but its side effect of vaccination is strong.Phase I Cb is treated with chloroform-methanol or trichloroacetic acid and the chloroform-methanol residual (CMR) or the trichloroacetic acid extract (TCA) is used to substitute for WCV.Both CMR and TCA vaccine retain the protective efficient of WCV and significantly reduce the side effects.However,both CMR and TCA vaccine are required to isolate and purify Cb from chick embryos where Cb grows in a biosafety laboratory with the complex procedures.In recent 10 years,the scientists have investigated from protective antigens to CD4+ and CD8+ T cell epitopes of Cb,expecting that the genes encoding the T cell epitopes express highly and induce an efficient protection against Q fever in bodies.

Preliminary validation of high throughput screening methods for hepatotocity and genotoxicity in humanized HepaRG cells / 药物评价研究

Objective To detect the hepatotoxicity biomarkers using normal human hepatocyte (HepaRG) and high-content screening,and to combine the micronucleus test and single cell gel electrophoresis to estalish a rapid screening platform for in vitro cytotoxitity and genotoxicity.Methods The effects of rhubarb anthraquinones (AQs) on the reactive oxygen species (ROS),intracellular Ca2+ concentration and mitochondrial membrane potential (MMP) in HepaRG cells were studied using appropriate fluorescent probes Hoechst33342、DCFH-DA、Fluo4-AM、Mito Tracker Red CMX Ros and high-content screening methods,and the potential genotoxiciy triggered by AQs were analyzed using the high-content based cytokinesis block micronucleus test and high throughput comet assay.Results The intracellular ROS level of HepaRG cells was significantly elevated by a 24 h treatment with Emodin (25.0 μg/mL),aloe-emodin (25.0 μg/mL) or chrysophanol (50.0 μg/mL),which are dose-concentration dependent (P ＜ 0.05 and 0.01);the intracellular Ca2+ increased and mitochondrial damage were observed with the treatment of aloe-emodin (25.0 μg/mL) and rhein (50.0 μg/mL,P ＜ 0.05 and 0.01).Comparing to control group,Emodin (25.0 μg/mL) induced an increased micronucleus rate (1.59％ ± 0.68 ％,P ＜ 0.01) and significantly higher percentage tail DNA and Olive tail moment (respectively 10.155％ ± 2.17％ and 0.510 ± 0.06,P ＜ 0.05 and 0.01) after 24 h;while the chrysophanol increased the micronucleus rate to 1.29％ ± 0.54％ (P ＜ 0.01) after 72 h.Conelnsion The results on the cytotoxicities and genotoxicities of AQs are consistent with the literatures.In this study,a rapid screening model for both hepatotoxicity and genotoxicity was successfully established,which will help with the early screening during the drug development stage.

A simple microfluidic technology for assaying platelet adhesion and aggregation under physiological flow / 军事医学

Objective To develop a simple microfluidic chip technology for analyzing platelet adhesion and aggregation under the condition of physiological flow .Methods The basic structure of the proposed microfluidic chip was a straight microchannel , where a sample pool and an outlet were located on each side respectively .The fluid dynamic behavior ,of the fluid in the microchannel was analyzed by theoretical calculation and finite element numerical analysis software ANSYS . The microchannel was first coated with type Ⅰ collagen protein.Then,blood flowed through the microchannel at 200 s-1 venous physiological shear rate and 1000 s-1 arterial physiological shear rate respectively .The behavior of the fluorescence labeled platelet adhesion and aggregation was recorded by fluorescence microscopy .Results Theoretical calculation and finite element numerical analysis showed that the microchannel with a width of 700 μm and a height of 70 μm ( aspect ration 10:1 ) had a uniform fluidic shear rate distribution .Compared with those at the 200 s-1 shear rate, the initial adhesion time, aggregation rate and the maximum surface cover rate of the platelet were significantly reduced at the 1000 s-1 shear rate ( P<0.05 ) .At the 1000 s-1 shear rate, tirofiban, an anticoagulant drug , significantly reduced the platelet aggregation in a concentration-dependent manner and the IC 50 was 23.8 nmol/L.Conclusion The technology developed in this paper can dynamically assay platelet adhesion and aggregation under the condition of physiological flow . The proposed microfluidic methods have the advantage of simple implementation and low sample cousumpation , and can be used for point-of-care detection of human platelet function , assay of the efficacy of anticoagulant drugs and for inspection of the thrombin behaviors of small animal models .

A simple microfluidic technology for assaying platelet adhesion and aggregation under physiological flow / 军事医学

Objective To develop a simple microfluidic chip technology for analyzing platelet adhesion and aggregation under the condition of physiological flow .Methods The basic structure of the proposed microfluidic chip was a straight microchannel , where a sample pool and an outlet were located on each side respectively .The fluid dynamic behavior ,of the fluid in the microchannel was analyzed by theoretical calculation and finite element numerical analysis software ANSYS . The microchannel was first coated with type Ⅰ collagen protein.Then,blood flowed through the microchannel at 200 s-1 venous physiological shear rate and 1000 s-1 arterial physiological shear rate respectively .The behavior of the fluorescence labeled platelet adhesion and aggregation was recorded by fluorescence microscopy .Results Theoretical calculation and finite element numerical analysis showed that the microchannel with a width of 700 μm and a height of 70 μm ( aspect ration 10:1 ) had a uniform fluidic shear rate distribution .Compared with those at the 200 s-1 shear rate, the initial adhesion time, aggregation rate and the maximum surface cover rate of the platelet were significantly reduced at the 1000 s-1 shear rate ( P<0.05 ) .At the 1000 s-1 shear rate, tirofiban, an anticoagulant drug , significantly reduced the platelet aggregation in a concentration-dependent manner and the IC 50 was 23.8 nmol/L.Conclusion The technology developed in this paper can dynamically assay platelet adhesion and aggregation under the condition of physiological flow . The proposed microfluidic methods have the advantage of simple implementation and low sample cousumpation , and can be used for point-of-care detection of human platelet function , assay of the efficacy of anticoagulant drugs and for inspection of the thrombin behaviors of small animal models .

Role and significance of PANP in laparoscopic surgery for low rectal cancer / 中国现代普通外科进展

Objective:To investigate the clinical significance of preserving autonomic nerve (PANP) in patients with low rectal cancer.Methods:The clinical data of 68 cases of patients with low rectal cancer who underwent laparoscopic surgery in our hospital from March 2014 to January 2016 were retrospectively analyzed.According to the surgical methods,the patients were divided into PANP group and non PANP group.Two groups of patients with postoperative micturition function,sexual function and quality of life were observed,compared with the two groups of patients with postoperative satisfaction differences.Results:In retention of PANP group of patients with postoperative ultrasonic residual urine volume was lower than that in non retention in PANP group were less and recovery of automatic micturition time is short retention in PANP group,IPSS score was lower than that in non low retention in PANP group,the difference is statistically significant(P＜0.05);The female and male patients with retention of PANP group were better than those of non retention PANP group,and the difference was statistically significant (P＜0.05);There was no significant difference in quality of life between the two groups before surgery.After surgery,the quality of life of the two groups was lower than before treatment,and the decrease of PANP group was more obvious than that of the non retention group (P＜0.05).Conclusions:The autonomic nerve preservation in the operation of low rectal cancer has a good protective effect on the urinary function and sexual function,and can obviously improve the quality of life of patients after operation.

Roles of modifications of chromatin and histone in osteogenesis / 中国组织工程研究

BACKGROUND: Osteogenesis is a key part in bone tissue engineering. The modifications of chromatin and histone are paid much more attention during the process of osteogenesis. Methylation and acetylation are important styles of modifications, which are highlighted in the field of bone tissue engineering.OBJECTIVE: To summarize the effect of methylation and acetylation in osteogenesis and their mechanisms in modifications of chromatin and histone, especially in bone.METHODS: A computer-based online search was conducted in PubMed databases using the keywords of "osteogenesis,methylation, acetylation, epigenetics" from January 2007 to May 2016. The language was limited to English. The artides were screened based on inclusion and exclusion criteria, and then summarized in aspects of DNA methylation and its biological regulation, DNA methylation in bone, histone post-translational modifications, biological regulation of histone methylation and acetylation as well as histone modifications in bone.RESULTS AND CONCLUSION: A total of 102 articles were collected and 42 articles were included finally. These results show that methylation and acetylation are important styles of modifications of chromatin and histone, both playing important roles in osteogenesis. Modifications of osteogenic chromatin and histone are characterized as dynamization and specificity. The DNA methylation is beneficial to gene silence. The histone acetylation helps gene expression in osteogenesis, both playing important roles in information transduction and epigenetic information.