Objective To investigate the effects of immune system and immuno-related miRNAs expression in low-dose benzene and its homologue mixed-exposed workers in a short time. Methods A total of 40 workers were recruited from a petrochemical factory ,and their blood samples were collected before and after work to detect the levels of IgA,IgG,IgM,IFN-γ,IL-1β,IL-2,IL-8,TNF-αin serum and miRNA-146a,-155 expression in the peripheral blood mononuclear cell. In the meanwhile ,we measured the individual benzene and its homologue exposure level of recruited workers. Results According to the concentration of benzene ,the subjects were divided into benzene-exposed group(20 workers)and control group(20 workers). And toluene exposure level in benzene-exposed group was significantly higher than that in control group(P<0.05). Significant decrease of IgG was found in benzene-exposed workers after one work shift,compared with control group(P<0.05). Moreover,the interaction between benzene and toluene was significant correlated with the decrease of IL-1β and TNF-α(P < 0.05). Additionally,the interaction between miRNA-155 and miRNA-146a was significant correlated with the decrease of TNF-α(P<0.05). Conclusions:Occupational exposure to low-dose benzene and toluene in a short time could decrease immune function. And there may be an effect of miRNAs in the regulation of cytokine.

AIM: To investigate alteration of inward re ctifier potassium current (I K1) in atrial myocytes and mRNA expression of gene Kir2.1 encoding I K1 in atrial myocardial tissue in patients with chronic atrial fibrillation (AF) compared to that with sinus rhythm (SR).METHODS: Single myocytes were isolated by enzymatic dissociation with the chunk method an d the ionic current was recorded using whole cell patch clamp technique. The sem i-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of Kir2.1 in atrial myocardial tissue, and the g ene GAPDH was used as an internal control.RESULTS: (1) The I K1 density was increased in AF group at hyperpolarizing pot entials, at -120 mV the current densities was (-5.71?0.65) pA/pF in AF group (n=28 cells from 7 patients) and (-4.26?1.22) pA/pF in SR group (n=35 cells from 9 patients) (P0.05).CONCLUSIONS: The increase in I K1 at hyperpolarizing potentials may be related to th e atrial electrophysiological remodeling in chronic human AF. The increased I K1 density in atrial myocytes in AF group without alteration of Kir2.1 mRNA expression in atrial tissue suggests that I K1 may be mediated at post-transcriptional levels.

Objective There are few researches for the serum betatrophin level and diabetic nephropathy (DN) recently.The aim of this study was to investigate the change of serum betatrophin level and the correlation of serum betatrophin and urinary albumin-to-creatintine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM).Methods A total of 150 Chinese subjects from Mar 2013 to Jul 2016 were enrolled in the study, including 90 patients with type 2 diabetes and 60 healthy controls.According to the level of UACR, the diabetic patients were divided into two groups:normal UACR group (UACR<30 mg/g, n=60) and abnormal UACR group(UACR>30 mg/g, n=30).Serum betatrophin was measured by enzyme linked immunosorbent assay (ELISA).UACR was measured by turbidimetric inhibition immune assay.Blood glucose blood lipid were measured simultaneously.Results The serum betatrophin level was significantly higher in abnormal UACR group than that in normal UACR group[677.37±59.02 vs 486.13±41.22 pg/mL, P<0.05];Serum betatrophin level in T2DM patients was positively correlated with age (r=0.246), waist hip ratio (WHR) (r=0.240), fasting blood glucose (FPG) (r=0.234), 2 hour plasma glucose (2hPG) (r=0.363), glycosylated hemoglobin (HbA1c) (r=0.346), fasting insulin (FINS) (r=0.249), insulin resistance index (HOMA-IR) (r=0.309), blood urea nitrogen (BUN) (r=0.223), creatinine (CREA) (r=0.277) and UACR (r=0.244) (P<0.05),and negatively correlated with glomerular filtration rate (GFR) (r=0.308) (P<0.01).Serum betatrophin level in normal UACR group was positively correlated with age, HbA1c and UACR (P<0.05);Serum betatrophin level in abnormal UACR group was positively correlated with WHR (r=0.504), 2hPG (r=0.600), HbA1c (r=0.449), HOMA-IR (r=0.395) (P<0.05).The WHR, HbA1c, HOMA-IR and GFR were the influential factors of the serum betatrophin level.Conclusion The level of serum betatrophin was significantly increased in T2DM patients with albuminuria, which suggests that the betatrophin might play an important role in the pathogenesis of DN.

Objective To study the changes of amplitude of low-frequency fluctuation (ALFF) in blood oxygenation level dependent functional MRI (BOLD-fMPI) in non-lesional epilepsy (NLE),and discuss its underlying neurophysiological mechanism. Methods The BOLD-fMRI data of 16 patients with NLE and 15 normal volunteers were analyzed by ALFF. The amplitude of the blood oxygenation level dependent activation of the resting state brain was investigated. The brain structures showing increased and decreased ALFF in NLE patients were demonstrated by comparing to normal subjects with 2-sample t-test with threshold of P＜0.05. Results As compared with those in normal subjects,the regions showing increased ALFF in NLE patients were distributed in the right temporal lobe (Montreal Neurological Institute [MNI] coordinates:x=15,y=90,z=21),medial frontal lobe (MNI coordinates:0,24,-24),ventral anterior cingulated (MNI coordinates:-12,30,27) and right cerebellar hemisphere (MNI coordinates:-51,-57,-4); while the regions showing decreased ALFF covered the areas of the left cerebellar hemisphere (MNI coordinates:-48,-15,39),posterior cingulum gyrus (MNI coordinates:60,-21,33) and precuneus (MNI coordinates:-6,-54,66). Conclusion NLE patients show abnormal brain functional organization in resting state; the increased ALFF is considered to be the facilitation such as epileptic activity generation and propagation,while the decreased ALFF might be considered as the functional inhibition in these regions.

OBJECTIVEThe aim of the study was to evaluate the anti-HBs persistence and the long term preventive efficacy after vaccination 23 years with plasma-derived hepatitis B vaccine.

METHODSThe study consisted of 261 children who were 5 - 9 years aged, from two primary schools in two townships of Xi'an. 126 children were randomly selected as vaccine group, and 135 children in control group. These children were followed up again in 2009. Excluding self-inoculation, the vaccine and control groups were 81 and 75, who was used to ask to recall details of their experience for vaccination and liver-related illnesses during past twelve years. Individuals who had anti-HBs titers less 10 mIU/ml, HBsAg, anti-HBc and HBV-DNA all were negative, were given a booster dose vaccine and retest for anti-HBs titer after one month.

RESULTSAfter eliminated the interference of an early booster dose and vaccination outside the study, the positive rate of anti-HBs was 48.1% (39/81) in the vaccine group at year 23, higher than 34.7% (26/75) in control group. At year 23 after primary vaccination, 84.0% (21/25) individuals in the vaccine group whose anti-HBs and anti-HBc both are negative showed a stronger anamnestic response after received a booster dose, while 7.5% (3/40) in the control group. At year 23 after primary vaccination, none clinical case of hepatitis B was found among 194 individuals. However, anti-HBc positive rate in the vaccine group was 16.0% (13/81), while the rate in the control group was 30.7% (23/75) (χ(2) = 4.687, P < 0.05).

CONCLUSIONAt 23 years after implemented a full course of plasma-derived hepatitis B vaccine, the recipients of vaccine were maintained anti-HBs at a high level or strong immunological memory.

Child ; Child, Preschool ; Follow-Up Studies ; Hepatitis B ; immunology ; prevention & control ; Hepatitis B Antibodies ; blood ; Hepatitis B Vaccines ; immunology ; Humans ; Immunization, Secondary ; Immunologic Memory ; immunology ; Plasma ; immunology

OBJECTIVEThe present study was to evaluate the audiological characteristics of infants with normal auditory brainstem response thresholds in click and abnormal transiently evoked otoacoustic emissions. Relationships between test results of distortion product otoacoustic emissions (DPOAE) and other hearing testing methods were also evaluated.

METHODSThe participants consisted of eighty-nine infants, with a total of 123 ears. All participants' TEOAE screening results were abnormal but diagnostic click ABR results were normal. The participants were classified into the following groups based on the test results from distortion product otoacoustic emissions: group A (normal all-frequency), group B (abnormal low-frequency), group C (abnormal high-frequency), and group D (abnormal all-frequency).

RESULTSObtained from these groups were compared to results of other hearing tests including the latency of ABR wave I, 40 Hz auditory event related potential (40 Hz AERP), 226 Hz and 1000 Hz tympanometry, and acoustic reflex. Results In six hearing tests in the 123 ears, seven ears (5.7%) were normal, while 116 ears (94.3%) were abnormal. No significantly differences were detected between boys (93.9%) and girls (95.1%), as well as between left (93.1%) and right ears (95.4%). The proportion of abnormal test results ranked as follows: 59 ears in group D (48.0%), 34 ears in group B (27.6%), 20 ears in group A (16.3%), and 10 ears in group C (8.2%). The highest abnormal rates in groups A, B and D were acoustic reflex, which were 40.0% for group A, 55.9% for group B and 66.1% for group D respectively. The highest abnormal rate in group C was the latency of ABR wave I (50.0%). Distribution of low-frequency hearing loss in each group was mainly mild. However, one ear in group B was moderate hearing loss, six ears in group D were moderate hearing loss, and one ear in group D was severe hearing loss.

CONCLUSIONSThe present study showed that, of which infants with normal thresholds of ABR failed the hearing screening, comprehensively audiology assessment is needed. And of which infants with normal DPOAE in full frequency or abnormal in high frequency region or low frequency region need to be followed up.

Auditory Threshold ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Tests ; methods ; Humans ; Infant ; Infant, Newborn ; Male ; Neonatal Screening ; methods ; Otoacoustic Emissions, Spontaneous ; Reflex, Acoustic

OBJECTIVESTo explore the effects of E-selectin, ICAM-1 and their ligands on the adhesive metastasis of hepatocellular carcinoma (HCC), and to select possible anti-adhesion drugs for hepatocellular carcinoma metastasis.

METHODS78 HCC patients were analyzed with the correlation of clinical features to the expression levels of E-selectin, sLeX, sLeA and CD44v6 in the tumor tissue. The adhesion between HepG2 and endothelial cell lines was examined by solid phase adhesion assay in vitro. Two kinds of drugs were accessed for their anti-adhesion ability.

RESULTSThe positive rate of E-selectin in vascular endothelia cells adjacent to cancer nest is 70.51%, and which of sLeX, sLeA, CD44v6 within tumor cells is 64.10%, 69.23%, 62.90% respectively. The patients' life span is closely related with the positive expression of sLeX, sLeA, CD44v6 (P = 0.008, 0.001, 0.022). The positive expression of E-selectin, sLeX and sLeA is significantly correlated to portal vein tumor thrombus (PVTT), preoperative extrahepatic metastasis, and satellite foci, but not to the size of tumor and AFP. The level of CD44v6 expression is significantly correlated to patient's survival time. The expression levels of E-selectin and ICAM-1 are remarkably higher after ED25 and ECV304 cell lines be activated. Meanwhile the adhesive ability of HepG2 to endothelial cell is mediated. Dexamethasone, tanshinone IIA are able to block this adhesion at low concentration.

CONCLUSIONThe expression levels of E-selectin, sLeX, sLeA and CD44v6 are closely correlated with clinical features. E-selectin, ICAM-1 and their ligands are important molecules of hepatocellular carcinoma and endothelial cells to tumor adhesive metastasis. Dexamethasone, tanshinone II A can be hopefully used as anti-adhesion drugs.

Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Adhesion ; E-Selectin ; metabolism ; Endothelium ; metabolism ; Female ; Hep G2 Cells ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Ligands ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Young Adult

BACKGROUND: Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy. METHODS: In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1. RESULTS: The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein. CONCLUSION Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.
Adaptor Proteins, Signal Transducing ; Adult ; Arteriosclerosis Obliterans/genetics* ; Autophagy ; GRB2 Adaptor Protein ; Humans ; Phosphoproteins/metabolism* ; Phosphorylation ; Protein Binding ; Signal Transduction

Objective To evaluate the immunogenicity and safety of a split-virion influenza vac-cine after its manufacturing process was improved. Methods The immunological non-inferiority of trial to control vaccines was evaluated in 240 subjects aged 3-<18 years. Another 360 subjects aged 18-<60 years were randomly divided into three groups that were respectively given three consecutive lots of trail vaccine to assess the consistency of immunogenicity. Results There were 4. 17% of the subjects aged 3-<18 years showed adverse reactions following immunization with trail vaccine and it was not significantly different from that of the control group (P>0. 05). No significant difference in seroconversion rate, geometric mean titer (GMT) of haemagglutination inhibition antibodies(HIAb) or protection rate was found between trial and control groups (P>0. 05). No significant difference in seroconversion rate or HIAb GMT was found among the three lots (P>0. 05). Conclusion The trial influenza vaccine has good safety, immunogenicity and lot-to-lot consistency after the manufacturing process was improved.

The present study was aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet) in vitro and in vivo. The inhibitory effects of adriamycin (ADM) used alone or in combination with BrTet or Tet on the proliferation of K562 and K562/A02 cells were evaluated by MTT assay. The ADM accumulation and the protein levels of P-glycoprotein (P-gp) were detected by flow cytometry. The mRNA levels of P-gp were determined by RT-PCR. The in vivo effect of BrTet and Tet was investigated by using nude mice grafted with sensitive human leukemia cell line K562 and MDR cell line K562/A02. The results showed that BrTet at 0.25, 0.5 and 1 micromol/L reversed the resistance to ADM in MDR K562/A02 cells in a dose-dependent manner. Flow cytometry suggested that BrTet significantly increased the intracellular accumulation of ADM in K562/A02 cells in a dose-dependent manner. BrTet also inhibited the overexpression of P-gp in K562/A02 cells, and down-regulated mdr1 expression. In nude mice bearing K562 xenografts on the left flank and K562/A02 xenografts on the right flank, intraperitoneal injection of 10 mg/kg BrTet significantly enhanced the antitumor activity of ADM against K562/A02 xenografts with inhibitory rates of 26.1%, while ADM alone inhibited the growth of K562/A02 xenografts only by 5.8%. No enhancement effect by BrTet was seen in K562 xenografts. It is concluded that BrTet shows significant MDR reversal activity in vitro and in vivo. Its activity may be related to the inhibition of P-gp overexpression and the increase intracellular accumulation of anticancer drugs. BrTet may be a promising-MDR modulator for eventual assessment in the clinic.
ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Benzylisoquinolines ; pharmacology ; Drug Resistance, Multiple ; drug effects ; genetics ; Drug Resistance, Neoplasm ; drug effects ; genetics ; Female ; Humans ; K562 Cells ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays