A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating Clostridium butyricum spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded. Following oral administration, CBS germinated into Clostridium butyricum (CB) and colonized in the colon. Combined with colonic specifically β-glucosidase responsive degrading of CS, dual colon-specific release of liposomes was achieved. And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold. Simultaneously, the released liposomes penetrated deep tumor tissue via the permeation enhancement effect of CS to kill localized intratumoral bacteria. Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB, the intratumoral pathogenic bacteria were eliminated fundamentally, blocking their recruitment to immunosuppressive cells. Furtherly, synchronized with lipopolysaccharide (LPS) released from MTZ-induced dead Fusobacterium nucleatum and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells, they jointly enhanced tumor infiltration of CD8⁺ T cells and reactivated robust antitumor immunity.

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4⁺ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8⁺ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.

Objective To investigate the correlation of family environment and family functioning with life quality for children with asthma.Methods Totally 120 asthma children were selected and divided into mild asthma group (n =71)and moderate asthma group (n =49);and 120 healthy children were selected as healthy group at the same time.3 groups were given the Chinese version of family environment scale(FES-CV),family assessment device(FAD)and children′s subjective living quality (ISLQ).The scores of FES-CV,FAD,ISLQ of 3 groups were compared,and the correlation of FES-CV,FAD with ISLQ were analyzed.Results Besides the factor score of achievement orientation,the other factors scores of FES-CV and FAD were significantly different among the three groups(P <0.05).Compared with moderate asthma group,the scores of emotional expression, culture,entertainment in mild asthma group and healthy group were higher,and the scores of contradiction and controlled were lower (P <0.05).Compared with mild asthma group,the scores of culture in healthy group were higher,and the scores of contradiction were lower (P <0.05).FAD of mild asthma group and healthy group were lower than those of moderate asthma group (P <0.01).Factors of FAD of healthy group were lower than those of mild asthma group (P <0.05).There were significant differences on the scores of family life experience,self-awareness,depression,anxiety,body experience,cognitive component,emotional elements and total points of 3 groups (P <0.05).The scores of self-awareness,depression in mild asthma group were lower than that of healthy group;the scores of family life experience,self-awareness,depression,cognitive component and total points of moderate asthma group were lower than those of healthy group (P <0.05).ISLQ was negatively correlated with contradiction,controlling of FES-CV (r =-0.605,-0.445;P <0.05);and was positively correlated with intimacy,emotional expression,independence,culture,entertaining,moral religion, organization (r =0.345-0.628,P <0.05 ). ISLQ was negatively correlated with problem solving, communication,roles labor,emotional reactions,emotional involvement,behavior control and total score of FAD (r =-0.651--0.526,P <0.05).Conclusions Family environment and family functioning have closely relationship with the quality of life for children with asthma.

Objective To investigate the effects of hyperbaric oxygen combined with function training on motor function in children with cerebral palsy. Methods From December 2012 to December 2013 during the treatment,72 cases chil-dren with cerebral palsy were selected as the object of study confirmed in our hospital, two groups of children were given intensive training of motor function (Bobath method), Hyperbaric oxygen therapy, 1 time a day, continuous treatment for 10 d, intermittent 20 d was 1 course of treatment, continuous treatment after the 3 curative effect observation. And the observation group was combined with hyperbaric oxygen treatment, the change of GMF score before and after treatment were compared between the two groups after treatment. Results The total effective rate of observation group patients after the treatment was 94.4%, significantly higher than the control group (66.7%), the difference was significant (χ2=11.238, P<0.05) between two groups. Before treatment, GMF scores of two groups were not different significantly (P>0.05). After treatment, GMF scores of two groups decreased significantly (t=2.421, 2.235, P<0.05), and the GMF scores of observation group after treatment were sig nificantly lower than the control group, the difference was signifi-cant (t=2.387, P<0.05). Conclusion Training of hyperbaric oxygen combined with function training on motor function of relatively simple and the effect of the children is better than intensive training, two methods combined can obviously improved the movement function of children with cerebral palsy so as to further improve the effect of treatment of chil-dren with cerebral palsy, is worthy of extensive promotion and application.

OBJECTIVETo investigate the changes in methylation levels of the promoters of the tumor suppressor gene Wilms' tumor gene on the X-chromosome (WTX) and its possible role in gastric cancer.

METHODSWTX promoter methylation levels were detected in 20 pairs of specimens of gastric cancer and matched normal tissues and in 3 gastric cancer cell lines (MGC803, SCG7901, and BGC823) using the Sequenom MassARRAY quantitative analysis system. The gastric cancer cell line BGC823 was treated with 5-aza-2'-deoxycytidine (5-aza-dC) for demethylation and the changes in the level of WTX promoter methylation were investigated.

RESULTSWTX promoter methylation levels were very low and showed no significant differences among normal gastric tissues, gastric cancer tissues and the 3 gastric cancer cell lines. In BGC823 cells, treatment with 5-aza-dC did not obviously affect the promoter methylation levels of WTX.

CONCLUSIONHigh methylation levels of WTX promoters are rare in gastric cancer.

Cell Line, Tumor ; Chromosomes, Human, X ; DNA Methylation ; Genes, Wilms Tumor ; Humans ; Promoter Regions, Genetic ; Stomach Neoplasms ; genetics ; metabolism