Rare and common coding variants in lipid metabolism-related genes and their association with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is a complex disease that is influenced by environmental and genetic factors. In this study, we aimed to investigate the relationship between coding variants in lipid metabolism-related genes and CAD in a Chinese Han population. METHODS: A total of 252 individuals were recruited for this study, including 120 CAD patients and 132 healthy control individuals. Rare and common coding variants in 12 lipid metabolism-related genes (ANGPTL3, ANGPTL4, APOA1, APOA5, APOC1, APOC3, CETP, LDLR, LIPC, LPL, PCSK9 and SCARB1) were detected via next-generation sequencing (NGS)-based targeted sequencing. Associations between common variants and CAD were evaluated by Fisher's exact test. A gene-based association test of rare variants was performed by the sequence kernel association test-optimal (SKAT-O test). RESULTS: We found 51 rare variants and 17 common variants in this study. One common missense variant, LIPC rs6083, was significantly associated with CAD after Bonferroni correction (OR = 0.47, 95% CI = 0.29-0.76, p = 1.9 × 10- 3). Thirty-three nonsynonymous rare variants were identified, including two novel variants located in the ANGPTL4 (p.Gly47Glu) and SCARB1 (p.Leu233Phe) genes. We did not find a significant association between rare variants and CAD via gene-based analysis via the SKAT-O test. CONCLUSIONS: Targeted sequencing is a powerful tool for identifying rare and common variants in CAD. The common missense variant LIPC rs6083 confers protection against CAD. The clinical relevance of rare variants in CAD aetiology needs to be investigated in larger sample sizes in the future.

Association of lipid metabolism-related gene promoter methylation with risk of coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is a complex disease that is influenced by environmental and genetic factors. Lipid levels are regarded as a major risk factor for CAD, and epigenetic mechanisms might be involved in the regulation of CAD development. This study was designed to investigate the association between the DNA methylation status of 8 lipid metabolism-related genes and the risk of CAD in the Chinese Han population. METHODS: A total of 260 individuals were sampled in this study, including 120 CAD cases and 140 normal healthy controls. DNA methylation status was tested via targeted bisulfite sequencing. RESULTS: The results indicated a significant association between hypomethylation of the APOC3, CETP and APOC1 gene promoters and the risk of CAD. Individuals with higher methylation levels of the APOA5 and LIPC gene promoters had increased risks for CAD. In addition, ANGPTL4 methylation level was significantly associated with CAD in males but not females. There were no significant differences in the methylation levels of the APOB and PCSK9 gene promoters between CAD patients and controls. CONCLUSIONS: The methylation status of the APOC3, APOA5, LIPC, CETP and APOC1 gene promoters may be associated with the development of CAD.

Recombinant Bifidobacterium longum Carrying Endostatin Protein Alleviates Dextran Sodium Sulfate-Induced Colitis and Colon Cancer in Rats.

Bifidobacterium has been widely administrated orally as probiotics to prevent pathogen colonization and modulate the gut microbiome balance. Endostatin is an endogenous inhibitor of angiogenesis and has been shown to inhibit tumor growth, invasion, and metastasis. At present, the combination of endostatin and chemotherapeutic drugs has been regarded as a promising antitumor treatment strategy. In this study, we selected a safe strain of Bifidobacterium longum as a delivery system to transport endostatin to the gastrointestinal tract and explored their combined effect on inflammatory bowel disease (IBD) and colitis-associated cancer. The results indicated that B. longum-Endo relieved dextran sulfate sodium-induced body weight loss, diarrhea, colon shortening, and epithelium damage. Long-term oral administration of B. longum-Endo significantly decreased tumor formation rate, tumor number, and tumor size. Moreover, the effect of B. longum-Endo on gut microbiota dysbiosis was also confirmed by 16S rRNA sequencing analysis. The levels of potentially beneficial bacteria, such as Lactobacillus, Bifidobacterium, Allobaculum, and Parabateroides, were increased in the B. longum-Endo group compared to the model and B. longum groups. Meanwhile, levels of potentially pathogenic bacteria including Desulfovibrio, Helicobacter, and Enterorhabdus were decreased. Taken together, these results suggested that oral administration of recombinant B. longum-Endo strain may be a promising therapeutic strategy for IBD and colitis-associated cancer.

Therapeutic efficacy of Bifidobacterium longum-mediated human granulocyte colony-stimulating factor and/or endostatin combined with cyclophosphamide in mouse-transplanted tumors.

Granulocyte colony-stimulating factor (GCSF) is frequently used as an adjunctive agent in tumor chemotherapy. Bifidobacterium longums (B. longum) attracted researchers' interests due to its enhancement of immunity and selective location in solid tumors. B. longum-pBV22210-endostatin (Endo) was proved to have a definite inhibitive effect on tumor growth in our previous study. In the present study, we evaluated the effects of B. longum-pBV22210-GCSF and/or B. longum-pBV22210-Endo combined with cyclophosphamide (CTX) on H22 and S180 tumor-bearing mice. Based on our previous work, the plasmid pBV22210-GCSF was constructed and transformed by electroporation into B. longum. The B. longum-pBV22210-GCSF and/or B. longum-pBV22210-Endo combined with CTX were applied to treat H22 and S180 tumor-bearing mice. A leukocyte count was carried out and the tumor inhibition rate was calculated after treatment. In our study, CTX combined with B. longum-pBV22210-GCSF significantly raised the leukocyte level of tumor-bearing mice, while combined with B. longum-pBV22210-GCSF alone or B. longum-pBV22210-Endo alone combinations with CTX inhibited tumor growth by over 65%. The results showed that B. longum-pBV22210-GCSF had an effective antagonistic effect on bone marrow inhibited by CTX and could inhibit tumor growth when it was combined with B. longum-pBV22210-Endo and CTX. Our results provide an enhanced understanding of B. longum and GCSF as well as their potential as an adjunctive approach in cancer gene therapy.

Bioactivity, pharmacokinetics, and immunogenicity assays in preclinical and clinical trials for recombinant human endostatin.

AIM: To determine the in vitro and in vivo bioactivity of recombinant human endostatin (rhEndostatin) and to analyze its pharmacokinetics and immunogenicity in rhesus monkeys and patients. METHODS: The physical chemical characteristics of rhEndostatin were detected according to Pharmacopoeia of the People's Republic of China (2005 edition, part III). Its in vitro and in vivo bioactivities were assayed via proliferation-inhibition on human umbilical vein endothelial cells and their inhibitory effect on tumor-bearing mice models. Serum concentrations of rhEndostatin in monkeys and patients were determined by an enzyme immunoassay method. RESULTS: The corresponding specific in vitro activities of rhEndostatin obtained from the cell counting method, 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and lactate dehydrogenase assay, respectively, were 6.4 x 10(7), 6.7 x 10(7), and 3.8 x 10(8) U/mg, and the in vivo antitumoral potency was 4.04 x 10(7) U/mg. In rhesus monkeys, there were no gender differences in all pharmacokinetic parameters. Serum anti-rhEndostatin immunoglobulin (Ig)G antibodies were generated quickly after intravenous (iv) administration and decreased rapidly when therapy was stopped. In phase I clinical trials, linearity in the pharmacokinetics of rhEndostatin was indicated by dose-proportionate increases in the area under the curve and the maximum serum concentration. Serum rhEndostatin reached a steady-state level after 7 d of successive administration with the average concentration at a steady state of 272.44+/-91.98 ng/mL. Neither IgG nor IgM antibodies against rhEndostatin were observed in patients. CONCLUSION: RhEndostatin exhibited a definite proliferation- inhibition effect on HUVEC, and significant antitumoral activity in mice. The immunoreactivity of rhesus monkeys to rhEndostatin is common, and rhEndostatin showed no immunogenicity in patients in this trial. The results provide a basis for further clinical trials.

Protective role of nano-selenium-enriched Bifidobacterium longum in delaying the onset of streptozotocin-induced diabetes.

Bifidobacterium longum (B. longum) could accumulate Selenium (Se) and nano-Se in the form of Se-B. longum and Nano-Se-B. longum, respectively. In this study, the effect of Nano-Se-B. longum in diabetic mice was evaluated. Physiological and metabolic parameters such as blood glucose, body weight, serum insulin level, intraperitoneal glucose tolerance test (IPGTT), food intake, water consumption and urine output were evaluated. The expression of insulin signalling pathway-related proteins was evaluated by western blotting. Haematoxylin and eosin (H&E) was used for histological examination of the liver, pancreas and kidney sections. Creatinine levels in serum (SCr) and blood urea nitrogen (BUN) were measured. Nano-Se-B. longum was the best in terms of delaying the onset of diabetes. Nano-Se-B. longum decreased blood glucose and body weight compared with those noted for the model group. IPGTT, food intake, water consumption and urine output significantly increased and serum insulin levels significantly decreased in the model group compared with those in all the Nano-Se-B. longum-treated mice. Histological results showed that the Nano-Se-B. longum-treated mice were better than the model group mice in terms of pathological changes. The expression of insulin signalling pathway-related proteins was upregulated in the Nano-Se-B. longum-treated groups. A significant increase in SCr and BUN levels was noted in the model group. This study for the first time reported the dose-dependent preventive effect of Nano-Se-B. longum on the onset of diabetes and renal damage. The mechanism may be related to changes in insulin signalling.

A quantitative method for measuring the antitumor potency of recombinant human endostatin in vivo.

Recombinant human endostatin (rhEndostatin) has been shown to inhibit tumor growth, but the variable antitumor activity of different rhEndostatin preparations has necessitated the development of an accurate, reproducible in vivo bioassay for evaluating the rhEndostatin activity. To assess the in vivo antitumor efficacy of rhEndostatin, H22 tumor-bearing mice received three doses of rhEndostatin and the potency of rhEndostatin preparations in inhibiting tumor growth was determined by ED(50)-potency assay and validated by dose-response parallel-line assay. There was a consistent and highly reproducible linear regression relationship between rhEndostatin dosage and tumor growth inhibition rate. The ED(50) values were determined from dose-response regression lines for seven rhEndostatin preparations with high reproducibility. On the basis of the current study, the potency of rhEndostatin preparations was assigned a value of 6.09 x 10(5) U/ampoule and a 95% confidence limit of 5.96 x 10(5)-6.22 x 10(5). We consider that this procedure can be served as a potential candidate pharmacopoeial method for potency measurement of different rhEndostatin preparations.

Syphilis incidence among men who have sex with men in China: results from a meta-analysis.

The recent upsurge of syphilis infections among men who have sex with men (MSM) is one of the major challenges facing China. However, the overall burden is still not clear. This study aims to summarize the incidence of syphilis among MSM in China by using meta-analysis. We comprehensively searched PubMed-MEDLINE, China National Knowledge Infrastructure and Chinese Wanfang databases. Articles published between December 2009 and March 2015 that met the inclusion criteria were considerably involved in this meta-analysis. Two reviewers performed a quality assessment of the studies and extracted data for estimating the overall syphilis incidence. STATA 12.0 was used to summarize the overall incidence of syphilis. In all, 14 studies from 13 papers were included in this study. Follow-up duration of these studies ranged from six to 36 months, while drop-out rates ranged from 11.9% to 83.6%. The individual incidence rates of the included studies varied from 3.1/100 person-years (95% CI, 0.8-5.3/100 person-years) to 38.5/100 person-years (95% CI, 28.9-48.1/100 person-years), with a pooled incidence of 9.6/100 person-years (95% CI, 7.0-12.2/100 person-years). The subgroup meta-analysis revealed that incidence estimates were 38.5/100 person-years (95% CI, 28.9-48.1/100 person-years), 12.1/100 person-years (95% CI, 7.0-17.2/100 person-years), 11.2/100 person-years (95% CI, 0.7-23.1/100 person-years), 8.9/100 person-years (95% CI, 6.5-11.2/100 person-years), 5.7/100 person-years (95% CI, 3.4-8.0/100 person-years) and 3.1/100 person-years (95% CI, 0.8-5.3/100 person-years) in Northeast, North, Southwest, East, South and Northwest China, respectively. Syphilis incidence among Chinese MSM is high, and this may increase the spread of other sexually transmitted infections, including human immunodeficiency virus. It is essential to integrate syphilis control programs with HIV control programs. This can be achieved by establishing public health response systems to monitor and control the epidemic of syphilis and HIV together in China.

Bifidobacterium longum as an oral delivery system of endostatin for gene therapy on solid liver cancer.

To overcome difficulties that hampered widespread application of a specific delivery system in cancer gene therapy and to inhibit the growth of solid liver cancer, we utilized a strain of Bifidobacterium longum as a delivery system to transport an endostatin gene that can inhibit growth of tumor. The B. longum strain with the endostatin gene (B. longum-En) was taken orally by tumor-bearing nude mice through drencher preparation. The results showed that B. longum-En could strongly inhibit the growth of solid liver tumor in nude mice and prolong the survival time of tumor-bearing nude mice. Furthermore, tumor growth was inhibited more efficiently when the B. longum-En treatment included selenium. Enriching the B. longum-En treatment with selenium improves the activity of NK and T cells and stimulates the activity of IL-2 and TNF-alpha in BALB/c mice. These results suggest that B. longum may be a highly specific and efficient vector for transporting anticancer genes in cancer gene therapy.

RNA interference remarkably suppresses bcl-2 gene expression in cancer cells in vitro and in vivo.

Bcl-2 is an anti-apoptotic protein. If the level of Bcl-2 protein can be reduced sufficiently in tumors using RNA interference (RNAi) to target the gene message, the apoptosis of tumor cells may be promoted. In this study, we synthesized 19 nucleotides (nts) small interference RNA (siRNA) constructs suppressing bcl-2 gene expression in human tumor cells (HeLaB2 and BGC-823 cell lines) in vitro. The bcl-2 gene expression levels were significantly reduced when these siRNA were transfected into experimental two tumor cells for 72 hours. The apoptosis process was also examined in the tumor cells. Here we synthesized siRNA from a DNA template under the control of the RNA polymerase III promoter in transfected tumor cells. Using this DNA vector-based approach, we found that the siRNA efficiently and specifically inhibited the synthesis of protein encoded by the bcl-2 gene in HeLaB2 and BGC-823 tumor cells. Tumor growth was inhibited by 66.5% with 2mg/kg pSilencer 3.1H1-bcl-2 in mouse liver tumor-bearing BALB/c mice. This approach may prove to be a valuable clinical technique for the analysis of specific gene functions and gene therapy of malignant tumors that utilize the bcl-2 gene via RNA interference.

The methods for determining the purity and in vitro or in vivo activity of recombinant human endostatin.

In order to establish the methods of high-performance liquid chromatography (HPLC) for determining the purity of recombinant human endostatin (rhEndostatin) and in vitro or in vivo activity of rhEndostatin, two columns were firstly used in HPLC analysis for determining the purity of rhEndostatin, including Waters Symmetry 300C4 (4.6 mm x 250 mm, 5 microm) and the Superdex75 HR 10/30. Cell lines, bovine capillary endothelial cells (BCEs) or human umbilical vein endothelial cells (HUVECs) expression human vascular endothelial growth factor (hVEGF) were used in method MTT or LDH as substrate, respectively. The bioactivity in vivo was assayed by the anti-tumor proliferation rate in H22 liver tumor-bearing mice. The results showed that the retention time of rhEndostatin sample was stable at 19.066 min or 11.506 min in reverse phase HPLC (RP-HPLC) or gel filtering HPLC (GF-HPLC). The stableness, repeat and recovery rates were over 99% in both methods and there was no statistical difference between these two methods (p > 0.05). In nonserum culture medium, rhEndostatin can sensitively and stably inhibit the proliferation of the HUVEC cells that were transfected with plasmid encoding hVEGF. LDH substrate methods is the most sensitive and stable method. The anti-tumor activity in H22 tumor-bearing mice was also highly repeatable and had an inhibition rate over 50% at 20 mg kg(-1) weight. As a conclusion, the RP-HPLC and GF-HPLC set up in this paper are highly repeatable, accurate and sensitive for detecting the purity of rhEndostatin. The bioactivity of rhEndostatin can be measured through detection the proliferation-inhibition on HUVECs transfectants with hVEGF in vitro or on H22 liver tumor in vivo.

Bifidobacterium adolescentis as a delivery system of endostatin for cancer gene therapy: selective inhibitor of angiogenesis and hypoxic tumor growth.

In order to overcome difficulties that hampered widespread application of antiangiogenesis in cancer therapy, a highly specific delivery system may be engaged in vivo to deliver and express antiangiogenic genes. We selected a strain of Bifidobacterium adolescentis (B. adolescentis) as the delivery system to transport endostatin gene to solid tumors. B. adolescentis with endostatin gene were injected into tumor-bearing mice through the tail vein. After the mice were sacrificed, the tumor and some normal tissues of the mice were examined. B. adolescentis were only found in the tumors and no bacilli were found in other normal tissues. Also, a strong inhibition of angiogenesis had been shown to inhibit local tumor growth in the administrated group. These results suggested that B. adolescentis only germinated and proliferated in solid tumors and might be a highly specific and efficient vector for transporting anticancer genes into target tumor in cancer gene therapy.

Potent inhibition of angiogenesis and liver tumor growth by administration of an aerosol containing a transferrin-liposome-endostatin complex.

AIM: To obtain an efficient delivery system for transporting endostatin gene to mouse liver tumor xenografts by administration of aerosol. METHODS: Recombinant plasmid pcDNA3.0/endostatin containing human endostatin gene together with signal peptide from alkaline phosphatase were transferred into human umbilical vein endothelial cell (HUVEC) by transferrin(TF)-liposome-endostatin complex. Western blot was used to detect the expression of human endostatin in transfected HUVEC cells and its medium. After the tumor-bearing mice were administrated with TF-liposome-endostatin complex, the lung tissue was analyzed by immunohistochemical method for expression of endostatin and the tumors were treated with CD-31 antibody to detect the density of microvessels in tumor tissues. The inhibition of tumor growth was estimated by the weight of tumors from groups treated with different doses of TF-liposome-endostatin complex. DNA fragmentation assay was used to detect the apoptosis of the cells from primary liver tumor. RESULTS: Western blot analysis and immunohistochemical method confirmed the expression of endostatin protein in vitro and in vivo. After the tumor sections were treated with CD-31 antibody, the positive reaction cells appeared brown while the negative cells were colorless. The positively stained area of the TF-liposome-endostatin treated group was significantly smaller (P<0.01, 645.8+/-55.2 microm(2)) than that of the control group (1 325.4+/-198.5 microm(2)). The data showed a significant inhibition of angiogenesis. After administration of TF-liposome-endostatin, comparing with the control group administrated with TF-liposome-pcDNA3.0, liver tumor growth in the mice treated with 50, 250 and 500 mg DNA/kg was inhibited by 36.6 %, 40.8 %, and 72.8 %, respectively (P<0.01). And a typical DNA fragmentation of apoptosis was found in the cells from tumor tissues of the mice treated with TF-liposome-endostatin but none in the control group. CONCLUSION: Endostatin gene could be efficiently transported into the mice with TF-liposome-DNA delivery system by administration of aerosol. TF-liposome-mediated endostatin gene therapy strongly inhibited angiogenesis and the growth of mouse xenograft liver tumors. It also could promote the development of apoptosis of tumors without direct influence on tumor cells.

Anti-tumor effect of human endostatin mediated by retroviral gene transfer in nude mice.

OBJECTIVE: To explore the inhibitory effect of human endostatin gene mediated by retroviral vector on the growth of human liver carcinoma. METHODS: A recombinant retroviral plasmid containing human endostatin gene and signal peptide was engineered and transferred into PA317 cells to produce retrovirus. Human liver carcinoma cells (SMMC7721) were infected with the above retrovirus to build a stable endostatin-transfected liver carcinoma cell line (SMMC-endo). The control liver carcinoma cell line (SMMC-pLncx) was developed in a similar way except that the plasmid was replaced by an empty retroviral vector. Immunohistochemistry and Western blot were used to test the expression and secretion of human endostatin. The biological activity of the expressed human endostatin was assessed by endothelial cell proliferation assay. The growth rates of SMMC-endo and control SMMC-pLncx cells in vivo and in vitro were also observed. RESULTS: The expression and secretion of human endostatin by endostatin-transfected SMMC-endo cells were confirmed by immunohistochemistry and Western blot. Compared with the control group, concentrated supernatant of SMMC-endo cells remarkably inhibited the proliferation of human umbilical vein endothelial cells by 48%, significantly higher than the inhibition by the control (10.2%; P < 0.01). The endostatin-transfected SMMC-endo cells had similar in vitro growth rates to SMMC-pLncx cells. The in vivo experiment showed that the growth rate of SMMC-endo cells was slowed. Only in 3 out of 5 mice were tumors formed and flank tumors of SMMC-endo cells were 94.5% smaller than those of control cells 22 days after inoculation into nude mice (P < 0.001). CONCLUSIONS: Gene transfer of human endostatin mediated by retroviral vector is an effective form of cancer therapy.

[Mechanism of intimal hyperplasia of venous grafts after coronary artery bypass grafting, an experimental study].

OBJECTIVE: To study the mechanism of intimal hyperplasia after coronary artery bypass grafting (CABG) and to find an effective way for preventing intimal hyperplasia. METHODS: Twenty-four male New Zealand rabbits were randomly divided into two groups of 12 rabbits: operation group and sham-operation (control) group. The external jugular vein was harvested and anastomosed end-to-side to the ipsilateral carotid artery in operation group or grafted in situ in the control group. Six rabbits in each group were killed and their grafted veins were taken 2 weeks and 4 weeks after operation respectively. The mRNA expressions of transforming growth factor beta (TGF-beta), collagen I, collagen III, and angiotension 1 receptor (AT1R) were measured by RT-PCR and electrophoresis. RESULTS: The intimal hyperplasia was much more remarkable in the operation group than in the control group either 2 weeks or 4 weeks after operation. The mRNA expressions of TGF-beta, AT1R, collagen I, and collagen III were significantly higher in the operation group than in the control group, especially 2 weeks after (P < 0.01). Four weeks after the operation, the expressions of TGF-beta, AT1R, collagen I and collagen III were 4.05 +/- 0.49 vs 2.05 +/- 0.26, 18.23 +/- 1.32 vs 4.61 +/- 0.53, 80 +/- 0.17 vs 0.90 +/- 0.18, and 7.05 +/- 0.68 vs 2.80 +/- 0.17 respectively (all P < 0.05). CONCLUSION: TGF-beta and AT1R may have an important role in the intimal hyperplasia of venous graft in CABG. Continuous arterial pressure may be the main factor of increased expression of TGF-beta and AT1R that cause the enormous synthesis and deposit of collagen.

[Inhibitory effect of endostatin mediated by retroviral gene transfer on human liver carcinoma SMMC7721 in vivo].

OBJECTIVE: To explore the effect of human endostatin expressed by host cells on the growth of human liver carcinoma in vivo. METHODS: Human endostain gene was transferred into SMMC7721 cells by retroviral pLncx to build endostatin-transfected cell line. PCR, immunohistochemistry and Western blot analysis were applied to examine the transfection, expression and secretion of endostatin. Endothelial cell proliferation assay was used to determine the biological activity of expressed endostatin. The in vivo and in vitro growth rates of the endostatin-transfected and control SMMC7721 cells were also observed. RESULTS: PCR proved that the genome of endostatin-transfected SMMC7721 cells contained a 550 bp specific fragment of endostatin. The expression and secretion of human endostatin from endostatin-transfected SMMC7721 cells were confirmed by immunohistochemistry and Western blot analysis. Endostatin expressed by host cells could inhibit the proliferation of human umbilical vein endothelial cells by 48% (P < 0.01). In vitro proliferation assay showed that endostatin-transfected SMMC7721 cells had no change in proliferation rate compared to control SMMC7721 cells. In comparison with control group, however, tumor growth rate in vivo from endostatin-transfected SMMC7721 cells was inhibited greatly by 94.5%, 22 days after inoculation into nude mice (P < 0.01). CONCLUSION: Human endostatin mediated by retroviral gene transfer can inhibit greatly the growth of human liver carcinoma SMMC7721 in vivo.

[Application of RNA interference technique in the research of mammalian cells and human disease].

RNA interference provides a new approach for elucidation of gene function. It holds the advantages of quickness, convenience, high effect and high specificity. In spite of these, the application of RNA interference technique in studying the mammalian cells and human disease is still in the beginning. In this paper, a review of the development of RNA interference in mammalian cells and human disease is presented.

[The effect of HJ-1 NO--HFJV respirator on treating pulmonary edema caused by seawater drowning].

The study was to observe the therapeutic effect of HJ-1 NO--HFJV respirator on treating pulmonary edema caused by seawater drowning. Seawater was infused into the rabbit's lung to establish the animal model of pulmonary edema caused by seawater drowning(PE-SWD). Then the animals were divided into three groups: simple PE-SWD model as control group, treat group(animal model treated with HFJV respirator and four medicines) and HFJV respiratior plus NO group. Pao2, Sao2 and pH were measured by the blood-gas analyzer. The survival time and seawater drowing-respiratiory distress syndrom(SW-RDS) were observed. The results showed that Pao2, Sao2 in NO group were remarkably higher than that of PE-SWD control group, and the survival time was longer than that of medicine treated group and the incidence of SW-RDS decreased to zero. We assume that HJ-1 NO-HFJV respirator is efficient on treating pulmonary edema.

Preparation of selenium-enriched Bifidobacterium longum and its effect on tumor growth and immune function of tumor-bearing mice.

In this study, we demonstrated selenium (Se) accumulation in Bifidobacterium longum strain (B. longum) and evaluated the effect of Se-enriched B. longum (Se-B. longum) on tumor growth and immune function in tumor-bearing mice. Analysis using high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) revealed that more than 99% of Se in Se-B. longum was organic, the main component of which was selenomethionine (SeMet). In the in vivo experiments, tumor-bearing mice (n=8) were orally administrated with different doses of Se-B. longum alone or combined with cyclophosphamide (CTX). The results showed that the middle and high dose of Se-B. longum significantly inhibited tumor growth. When Se-B. longum and CTX were combined, the antitumor effect was significantly enhanced and the survival time of tumor-bearing mice (n=12) was prolonged. Furthermore, compared with CTX alone, the combination of Se-B. longum and CTX stimulated the activity of natural killer (NK) cells and T lymphocytes, increasing the levels of interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α), and the leukocyte count of H22 tumor-bearing mice (n=12).

UGT1A1*6 polymorphisms are correlated with irinotecan-induced toxicity: a system review and meta-analysis in Asians.

PURPOSE: Previous studies confirmed that genotyping uridine diphosphate glucuronosyltransferase (UGT) 1A1*28 polymorphisms could predict the side effects in cancer patients using irinotecan (IRI) and then reduce IRI-induced toxicity by preventative treatment or decrease in dose. However, the association between UGT1A1*6 polymorphisms and IRI-induced severe toxicity in Asian patients is still unclear. The aim of this study was to evaluate the association between UGT1A1*6 polymorphisms and IRI-induced severe neutropenia as well as diarrhea in Asian patients. METHODS: We searched all papers on PubMed and Embase from February 1998 to August 2013. Then we assessed the methodologies quality, extracted data and made statistics analysis using STATA software. To uncover the sources of heterogeneity, subgroup meta-analysis was conducted according to the dosage of IRI. RESULTS: Eleven papers were included according to the inclusion and exclusion criteria after searching Pubmed and Embase. Overall, an increased risk of severe toxicity in Asian patients with UGT1A1*6 polymorphisms was found. Patients with heterozygous variant of UGT1A1*6 showed an increased risk [odds ratio (OR) = 1.98, 95 % confidence intervals (CI) 1.45-2.71, P < 0.001], and homozygous mutation showed an even higher risk (OR = 4.44, 95 % CI 2.42-8.14, P < 0.001) for severe neutropenia. For severe diarrhea, heterozygous variant of UGT1A1*6 showed no significant risk, while the homozygous variant performed a notable risk (OR = 3.51, 95 % CI 1.41-8.73, P = 0.007). Subgroup meta-analysis indicated that for patients harboring either heterozygous or homozygous variant, low dose of IRI also presented comparably increased risk in suffering severe neutropenia. CONCLUSION: In this meta-analysis, UGT1A1*6 polymorphisms were revealed as potential biomarkers, predicting IRI-induced severe toxicity in patients from Asia, and increased incidences of severe neutropenia could occur in both high/medium and low doses of IRI.