Objective To analyze the immunogenomic characteristics of antibody repertoire in re-sponse to influenza vaccine in order to provide a theoretical basis for further development of antibody. Meth-ods Based on a time-series immunoglobulin heavy chain ( IGH) repertoire sequencing dataset, we analyzed the immunogenomic characteristics of antibody repertoire in response to trivalent influenza vaccine ( TIV ) from three aspects which included the features in complementarity-determining region 3 ( CDR3 ) , antibody mutation and VDJ usage. Results The frequency of antibody mutation increased significantly upon vaccina-tion. Analysis of the CDR3 region indicated that polar and aromatic amino acids had a higher preference. The length of CDR3 region in naive B cells followed a normal distribution, while specific CDR3 sequences with 15 to 18 amino acids in length occupied a dominant position after vaccination. In addition, the VDJ us-age altered obviously and IGHV3-7-derived antibody had a significant response to the vaccine. Response in-tensity reached the peak on day 7 and gradually weakened over time. Conclusion Antibody repertoire evolves dynamically to express specific antibody upon vaccination and the characteristics of immune responses at sequence level could be used to evaluate their effectiveness.

BACKGROUND: Tumor necrosis factor-α (TNF-α) is one of important cytokines to promote the maturation of dendritic cells. Blockage of TNF-α action by binding with soluble tumor necrosis factor receptor 1 (sTNFR1) may arrest dendritic cells in an immature state and induce stable, long-term tolerance. OBJECTIVE: To construct the lentiviral vectors carrying sTNFR1 gene and investigate sTNFR1 expression in immature dendritic cells. METHODS: Total RNA of human peripheral blood mononuclear cells was taken as a template. The sTNFR1 gene fragment was amplified by RT-PCR, subcloned to the lentiviral vectors pXZ208, and ligated to the enhanced green fluorescent protein (eGFP) reporter gene to establish lentiviral vector, called pXZ9-sTNFR1. DNA sequencing was performed for lentiviral vector identification. Lentivirus was prepared by transfection of 293 FT cells with pXZ9-sTNFR1. Viral titer was determined by eGFP expression. C57BL/6 mouse bone marrow-derived dendritic cells were in vitro cultured with low-dose granulocyte-macrophage colony stimulating factors and interleukin 4. On day 5 of culture, immature dendritic cells were transfected with pXZ9-sTNFR1 recombinant lentiviral supernatant, sTNFR1 transcription was detected by RT-PCR, sTNFR1 protein expression by Western blot analysis. Following sTNFR1 gene modification and lipopolysaccharide stimulation, the phenotype characteristics of dendritic cells were observed. RESULTS AND CONCLUSION: Recombinant plasmid pXZ9-sTNFR1 was successfully constructed. Twenty-four hours after 293 FT cell transfection, eGFP expression was observed and viral titer was over 10<'6> U/L. RT-PCR demonstrated that pXZ9-sTNFRl-transfected immature dendritic cells showed sTNFR1 positive expression. Western blot analysis revealed that sTNFR1 protein appeared in the immature dendritic cells and supernatant following 293 FT cell transfection. On day 5 of culture, dendritic cells expressed low level of class Ⅱ major histocompatibility complex (MHC Ⅱ), as well as CD40, CD86, CD80, molecules. However, following lipopolysaccharide stimulation, dendritic cells expressed high level of MHC Ⅱ, as well as CD40, CD80, and CD86, molecules, exhibiting the phenotype characteristics of mature dendritic cells. But after sTNFR modification, the expression level of MHC Ⅱ, as well as CD40, CD80, and CD86, molecules was not altered obviously. Lentiviral vectors carrying sTNFR1 gene and eGFP reporter gene were successfully constructed, and recombinant lentiviral plasmids with high titer were acquired. Following high efficacy of lentiviral gene transfection, immature dendritic cells stably express sTNFR1 mRNA and protein, which prevents immature dendritic cells from activation by exogenous lipopolysaccharide and maintains the immature state.

Drugs sharing similar therapeutic function may not bind to the same group of targets. However, their targets may be involved in similar pathway profiles which are associated with certain pathological process. In this study, pathway fingerprint was introduced to indicate the profile of significant pathways being influenced by the targets of drugs. Then drug-drug network was further constructed based on significant similarity of pathway fingerprints. In this way, the functions of a drug may be hinted by the enriched therapeutic functions of its neighboring drugs. In the test of 911 FDA approved drugs with more than one known target, 471 drugs could be connected into networks. 760 significant associations of drug-therapeutic function were generated, among which around 60% of them were supported by scientific literatures or ATC codes of drug functional classification. Therefore, pathway fingerprints may be useful to further study on the potential function of known drugs, or the unknown function of new drugs.
Drug Interactions ; Metabolic Networks and Pathways ; Pharmaceutical Preparations ; metabolism

Objective To evaluate the effect of ditching for drain on the control of the breed of Oncomelania hupensis snails in beaches of Dongting Lake. Methods From November,2009 to November,2012,an O. hupensis snail infested beach of the Yueyang jail and an O. hupensis snail infested beach of Junshan District were selected as research fields in the eastern Dongting Lake area,and the former,as the intervention field,was performed with the ditching for drain by excavators and the latter,as the control field,was not. Results Before the project implemented,the average soil moisture contents on the beaches in dry seasons of the two fields were both about 35.56%. After the project implemented,in the intervention field,the average soil mois?ture content was 26.53%which was significantly lower than that(35.56%)in the control field(F=6.53,P<0.05). The under?ground water levels in different heights in the intervention field were lower than those in the control field (χ2 = 33.33,P <0.05). Before the project implemented,the natural death rates of the snails were 0.98%and 0.89%in the two research fields re?spectively(P>0.05),and after the project implemented(in 2012),no adult and young snails were found in the interventional field,but in the control field,the average densities of living snails and young snails were 29.37 snails/0.1 m2 and 213±108.45 snails/0.1 m2 respectively. Conclusion The intervention of ditching for drain can decrease the soil moisture contents quickly and change the ecological condition,therefore,can control the breed of O. hupensis snails in the beaches of Dongting Lake.

OBJECTIVETo explore the feasibility and safety of Bishop-Koop stoma procedure in the treatment of neonates with refractory congenital intestinal atresia.

METHODSClinical and follow-up data of 25 neonates with refractory congenital intestinal atresia undergoing Bishop-Koop stoma procedure in our center from January 2011 to December 2014 were retrospectively analyzed. Of 25 neonates, 13 (52%) were male, 12(48%) were female, the birth weight was 1600-3800 g (mean 2920 g), the age of admission was 10 hours to 20 days, and the age of operation was 1-58 d (mean 7 d). Diameter ratio of proximal atresia intestine to distal atresia intestine was all greater than 4. Eleven cases(44%) were high jejunal atresia, 3 cases(12%) type III( b, 7 cases(28%) type IIII(, 14 cases(56%) were identified as complex meconium peritonitis, and 3 cases (12%) received reoperation.

RESULTSAll the cases completed their Bishop-Koop stoma operations successfully with median operative time of 3 (1.2-4.5) hours and median intra-operative blood loss of 3.5(1-18) ml. The postoperative complication rate was 20%(5/25), including 3 cases of cholestasis, 1 case of ileus, and 1 case of neonatal necrotizing enterocolitis with septicemia who died 6 days after operation resulting in the mortality of 4%. Besides, 1 case gave up treatment because of economic reason. For the rest 23 neonates, the median first feeding time was 11 days and mean time was 11(5 to 20) days; the median time of postoperative total parenteral nutrition (TPN) was 15 days and mean time was 21 (5 to 68) days; the median hospital stay was 33 days and mean hospital stay was 25(12 to 81) days, respectively. Two-stage stoma closure operations were performed in all the 23 cases afterwards and no postoperative associated complications were found. When discharge after Bishop-Koop stoma operations, Z score of body weight was normal in 3 cases(13.0%) and lower than normal in 20 cases(87.0%), while in hospitalization for stoma closure, Z score of body weight was normal in 19 cases(82.6%) and lower than normal in 4 cases (17.4%). Of 23 cases, serum albumin level was normal in 9 cases(39.1%) before operation, in 3 cases (13.0%) when discharge and in 22 cases(95.7%) in hospitalization for stoma closure.

CONCLUSIONBishop-Koop stoma procedure is safe and feasible in the treatment of neonates with refractory congenital intestinal atresia, and can obviously improve the nutritional status.

Female ; Humans ; Ileus ; Infant, Newborn ; Intestinal Atresia ; surgery ; Length of Stay ; Male ; Parenteral Nutrition, Total ; Postoperative Complications ; Reoperation ; Retrospective Studies ; Surgical Stomas

Developmental exposure to bisphenol A (BPA), an endocrine-disrupting contaminant, impairs cognitive function in both animals and humans. However, whether BPA affects the development of primary sensory systems, which are the first to mature in the cortex, remains largely unclear. Using the rat as a model, we aimed to record the physiological and structural changes in the primary auditory cortex (A1) following lactational BPA exposure and their possible effects on behavioral outcomes. We found that BPA-exposed rats showed significant behavioral impairments when performing a sound temporal rate discrimination test. A significant alteration in spectral and temporal processing was also recorded in their A1, manifested as degraded frequency selectivity and diminished stimulus rate-following by neurons. These post-exposure effects were accompanied by changes in the density and maturity of dendritic spines in A1. Our findings demonstrated developmental impacts of BPA on auditory cortical processing and auditory-related discrimination, particularly in the temporal domain. Thus, the health implications for humans associated with early exposure to endocrine disruptors such as BPA merit more careful examination.
Humans ; Rats ; Animals ; Benzhydryl Compounds/toxicity* ; Phenols/toxicity* ; Auditory Perception/physiology* ; Neurons/physiology*