NOS3 895G>T and CBR3 730G>A Are Associated with Recurrence Risk in Non-Muscle-Invasive Bladder Cancer with Intravesical Instillations of THP.

OBJECTIVES: To analyze the correlation between pharmacogenomic biomarkers and the efficacy of pirarubicin (THP, also named 4'-O-tetrahydropyranyl-adriamycin) and to explore potential associations of individual genetic backgrounds with the clinical outcomes of non-muscle-invasive bladder cancer (NMIBC) patients. METHODS: Between July 2003 and June 2011, a total of 91 patients were treated with transurethral resection (TUR) of the bladder tumor and were histopathologically confirmed to have NMIBC. Patients received an immediate instillation and maintenance therapy with THP. All patients underwent follow-up for recurrence. We genotyped 13 single nucleotide polymorphisms (SNPs) from blood and saliva DNA samples of all patients. RESULTS: The associations of patients' genotypes with tumor recurrence risks were analyzed by survival analysis. A total of 16 (17.6%) of the 91 patients with NMIBC had tumor recurrences with a median follow-up of 17 months (range, 2-83 months). We confirmed the effect of the European Organization for Research and Treatment of Cancer (EORTC) risk score for predicting tumor recurrence (p = 0.002, log-rank test). We adjusted for the EORTC score and found that 2 SNPs, NOS3 895G>T (rs1799983) (p = 0.02, HR = 4.32, 95% CI, 1.30-14.39, GT+TT vs. GG) and CBR3 730G>A (rs1056892) (p = 0.04, HR = 2.57, 95% CI, 1.07-6.18, GA+AA vs. GG), were significantly associated with a higher recurrence risk after TUR and instillations of THP in NMIBC patients. CONCLUSIONS: Our results suggest that NOS3 895G>T and CBR3 730G>A are genetic markers that can be used to predict tumor recurrence in NMIBC patients receiving intravesical instillations of THP. The effects of those 2 SNPs are independent of the EORTC scores. Further studies with larger sample sizes and longer follow-ups are needed to confirm our results.

A PEG-CMC-THB-PRTM hydrogel with antibacterial and hemostatic properties for promoting wound healing.

The introduction of antibacterial and hemostatic hydrogels with good mechanical properties that display desirable impacts on wound healing process is still an unmet essential for clinical wound dressings. Herein, a multifunctional hydrogel PEG-CMC-THB-PRTM was fabricated via a one-pot method combining carboxymethyl chitosan (CMC), 2,3,4-trihydroxybenzaldehyde (THB), protamine (PRTM) and 4-arm polyethylene glycol aldehyde (PEG). The hydrogel was formed by the dynamic Schiff base reaction between amino groups of carboxymethyl chitosan and aldehyde groups of 4-arm polyethylene glycol aldehyde and exhibited excellent mechanical properties. The developed hydrogel also showed outstanding effects on anti-bacteria and hemostasis through the release of PRTM. Moreover, the hydrogel could promote extracellular matrix formation and wound closure in vivo, thereby accelerating the healing of skin wound. These results suggested that the multifunctional PEG-CMC-THB-PRTM hydrogel is a promising candidate for the clinical treatment of full-thickness wounds.

Seroepidemiology of human enterovirus71 and coxsackievirusA16 in Jiangsu province, China.

BACKGROUND: The major etiology of hand, foot and mouth disease (HFMD) is infection with human enterovirus A (HEV-A). Among subtypes of HEV-A, coxsackievirusA16 (CoxA16) and enterovirus 71 (EV71) are major causes for recurrent HFMD among infants and children in Jiangsu Province, mainland China. Here, we analyzed maternal antibodies between prenatal women and their neonates, to determine age-specific seroprevalence of human EV71 and CoxA16 infections in infants and children aged 0 to 15 years. The results may facilitate the development of immunization against HFMD. METHODS: This study used cross-section of 40 pairs of pregnant women and neonates and 800 subjects aged 1 month to 15 years old. Micro-dose cytopathogenic effects measured neutralizing antibodies against EV71 and CoxA16. Chi-square test compared seroprevalence rates between age groups and McNemar test, paired-Samples t-test and independent-samples t-test analyzed differences of geometric mean titers. RESULTS: A strong correlation between titers of neutralizing antibody against EV71 and CoxA16 in prenatal women and neonates was observed (rEV71 = 0.67, rCoxA16 = 0.56, respectively, p < 0.05). Seroprevalence rates of anti-EV71 antibody gradually decreased with age between 0 to 6 months old, remained low between 7 to 11 months (5.0-10.0%), and increased between 1 and 4 years (22.5-87.5%). Age-specific seroprevalence rates of anti-EV71 antibody stabilized in >80% of children between 5 to 15 years of age. However, seroprevalence rates of anti-CoxA16 antibody were very low (0.0-13.0%) between 0 to 6 months of age, gradually increased between 7 months to 4 years (15.0-70.0%), and stabilized at 54.0% (108/200) between 5 to 15 years. Seroprevalence rates against EV71 and CoxA16 were low under 1 year (0.0-10.0%), and showed an age dependent increase with high seroprevalence (52.5-62.5%) between 4 and 10 years of age. CONCLUSIONS: Concomitant infection of EV71 and CoxA16 was common in Jiangsu Province. Therefore, development of bivalent vaccine against both EV71 and CoxA16 is critical. The optimal schedule for vaccination may be 4 to11 months of age.

Prompting immunostimulatory activity of curdlan with grafting methoxypolyethylene glycol.

The immunostimulatory activity of polysaccharides can improve human immunity, but their activity is low and prompting the activity is a great challenge. Curdlan, is a linear beta-1,3-glucan and has the potential to induce immune responses. However, owing to its tight triple helix structure and insolubility in water, its immunostimulatory activity is weakened. The keyway to promote its immunostimulatory activity is to relax its tight triple helix structure. In this work, methoxypolyethylene glycol (mPEG) was grafted onto curdlan (curdlan-g-mPEG) to unwind its triple helix structure. With its grafting mPEG, the water solubility of curdlan was enhanced. Moreover, with curdlan-g-mPEG treatment, macrophages secreted more tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 and exhibited favorable phagocytosis of bacteria (Staphylococcus aureus and Pseudomonas aeruginosa). These results reveal that curdlan-g-mPEG as an immunostimulant has potential applications in immunology and antibiotics.

Reprogramming microbial populations using a programmed lysis system to improve chemical production.

Microbial populations are a promising model for achieving microbial cooperation to produce valuable chemicals. However, regulating the phenotypic structure of microbial populations remains challenging. In this study, a programmed lysis system (PLS) is developed to reprogram microbial cooperation to enhance chemical production. First, a colicin M -based lysis unit is constructed to lyse Escherichia coli. Then, a programmed switch, based on proteases, is designed to regulate the effective lysis unit time. Next, a PLS is constructed for chemical production by combining the lysis unit with a programmed switch. As a result, poly (lactate-co-3-hydroxybutyrate) production is switched from PLH synthesis to PLH release, and the content of free PLH is increased by 283%. Furthermore, butyrate production with E. coli consortia is switched from E. coli BUT003 to E. coli BUT004, thereby increasing butyrate production to 41.61 g/L. These results indicate the applicability of engineered microbial populations for improving the metabolic division of labor to increase the efficiency of microbial cell factories.

Cellulose membrane modified with LED209 as an antibacterial and anti-adhesion material.

Bacterial adhesion infection caused by medical materials in clinical application has become a serious threat, and it urgently needs new strategies to deal with these clinical challenges. In this work, LED209, a highly selective histidine sensor kinase inhibitor of Gram-negative bacteria, was covalently attached on cellulose membrane (CM) via click reaction. The data of contact angle measurements, ATR-FTIR and X-ray photoelectron spectroscopy confirmed the successful synthesis of LED-CM. In addition, the results of antibacterial activity of the membranes shown that LED-CM exhibited excellent anti-adhesion ability to Enterohemorrhagic Escherichia coli (EHEC), and significantly reduced the formation of bacterial biofilm. Importantly, LED-CM was able to repress the expression of virulence genes in EHEC. Furthermore, LED209-functionalized cellulose membrane indicated no cytotoxicity to mammalian cells. Hence, our present work demonstrated that CM modified with LED209 possessed markedly anti-adhesion activity against EHEC, which offered a potent antimicrobial material for combating bacterial infections.

Light-powered Escherichia coli cell division for chemical production.

Cell division can perturb the metabolic performance of industrial microbes. The C period of cell division starts from the initiation to the termination of DNA replication, whereas the D period is the bacterial division process. Here, we first shorten the C and D periods of E. coli by controlling the expression of the ribonucleotide reductase NrdAB and division proteins FtsZA through blue light and near-infrared light activation, respectively. It increases the specific surface area to 3.7 µm-1 and acetoin titer to 67.2 g·L-1. Next, we prolong the C and D periods of E. coli by regulating the expression of the ribonucleotide reductase NrdA and division protein inhibitor SulA through blue light activation-repression and near-infrared (NIR) light activation, respectively. It improves the cell volume to 52.6 µm3 and poly(lactate-co-3-hydroxybutyrate) titer to 14.31 g·L-1. Thus, the optogenetic-based cell division regulation strategy can improve the efficiency of microbial cell factories.

Postpartum practices of puerperal women and their influencing factors in three regions of Hubei, China.

BACKGROUND: 'Sitting month' is a Chinese tradition for women's postpartum custom. The present study aims to explore the postpartum dietary and health practices of puerperal women and identify their influential factors in three selected regions of Hubei, China. METHODS: A cross-sectional retrospective study was conducted in the selected urban, suburban and rural areas in the province of Hubei from 1 March to 30 May 2003. A total of 2100 women who had given birth to full-term singleton infants in the past two years were selected as the participants. Data regarding postpartum practices and potentially related factors were collected through questionnaire by trained investigators. RESULTS: During the puerperium, 18% of the participants never ate vegetables, 78.8% never ate fruit and 75.7% never drank milk. Behaviour taboos such as no bathing, no hair washing or teeth brushing were still popular among the participants. About half of the women didn't get out of the bed two days after giving birth. The average time they stayed in bed during this period was 18.0 h. One third of them didn't have any outdoor activities in that time periods. The educational background of both women and their spouses, location of their residence, family income, postnatal visit, nutrition and health care educational courses were found to be the influencing factors of women's postpartum practices. CONCLUSION: Traditional postpartum dietary and health behaviours were still popular among women in Hubei. Identifying the factors associated with traditional postpartum practices is critical to develop better targeting health education programs. Updated Information regarding postpartum dietary and health practices should be disseminated to women.