Objective To investigate the effect of Helicobacter pylori (Hp) infection on macrophage migration inhibitory factor (MIF) protein expression and explore the role of Hp and MIF in the development of chronic gastritis and gastric ulcer. Methods The biopsy tissues of gastric mucosa were collected under gastroscope, and Hp was detected by 14C breath test and Warthin-starry method. We recruited 25 healthy people with normal gastric mucosa, 40 patients pathologically confirmed Hp-positive with chronic superficial gastritis, 40 with atrophic gastritis and 40 with gastric ulcer. MIF protein expression was examined by immunohistochemical SP staining method, then Hp eradication was performed on Hp-infected chronic superficial gastritis, atrophic gastritis and gastric ulcer for 2 weeks. Hp and MIF were re-examined 4 weeks after drug withdrawal, and difference in MIF expression was compared between Hp-infected patients and Hp-eradicated patients. Results The expression of MIF was low in normal gastric mucosa without Hp infection (2/25, 8%), but significantly higher in Hp-infected gastric mucosa with chronic superficial gastritis (12/40, 30%), atrophic gastritis (26/40, 65%) and gastric ulcer (19/40, 47.5%); there was a significant difference between normal gastric mucosa without Hp infection and that of comHp-infected patients (57/120 vs. 2/25; χ~2=13.376, P<0.01). MIF expression increased with the severity of inflammation in chronic gastritis, and there was a significant difference between superficial gastritis and atrophic gastritis (12/40 vs. 26/40; χ~2=9.825, P<0.01). The expression of MIF was noticeably decreased after Hp eradication compared with before(57/120 vs. 23/103; χ~2=15.264, P<0.01); however, there was no significant change in those patients whose Hp was still positive. Conclusion The expression of MIF on gastric mucosa is associated with the development of chronic gastritis and gastritis ulcer caused by Hp infection. Eradication of Hp could cut down the abnormally high MIF expression in gastric mucosa and slow down the formation and development of gastric carcinoma.

[Summary] The genotypes of rs6832151 in the 4p14 were genotyped by Taqman probe technique on FluidigmEPl platform in 617 patients with Graves′disease( GD) and 4 915 health control subjects. The result showed thatRs6832151 Gin4p14wasstronglyassociatedwithGD(OR=1.39,P<0.01),withstatisticalsignificancefor three genetic models according to the locus genotyping ( additive model,dominant model,and recessive model,all P<0.01). There was no statistically significant difference in the sizes of goiter between the genotype subgroups(P>0. 05). The result suggests that rs6832151 G in 4p14 is the susceptibility genes of Graves′ disease in Bengbu population, and is related to the high risk of GD.

Objective To identify the association of thyroid stimulating hormone receptor ( TSHR ) gene intron 1 susceptible loci and 4p14 susceptible locus rs6832151 polymorphisms with Graves’ disease ( GD) in Han Chinese population in Bengbu, Anhui, China. The gene-gene interaction among TSHR intron 1 susceptible loci and 4p14 susceptible locus rs6832151 was also investigated. Methods The genotypes of the single-nucleotide polymorphisms ( SNPs) were analyzed by Taqman probe technique on Fluidigm EP1 platform in 611 patients with GD and 555 control subjects, and linkage analysis, correlation analysis, haplotype analysis, and epistasis analysis with them were performed. Results Six SNPs in two candidate genes(rs12101261, rs4903964,rs179247, rs2284722 and rs17111394 in TSHR, rs6832151 in 4p14) were associated with GD (all P<0. 05). The frequency distributions of haplotypes of SNPs in TSHR intron 1 ( AGTA, GGCG, AATA, and CC) were significantly different between GD and control groups(all P<0. 01). There existed the interactions between rs179247 and rs12101261 in TSHR(P=0. 001) and among rs179247(TSHR),rs4903964(TSHR) and rs6832151(4p14) (P=0. 001). Conclusions rs683215 in 14p14 and rs12101261, rs4903964, rs179247, rs2284722 and rs17111394 in TSHR intron 1 were susceptible loci of GD in the Chinese Han population from Bengbu. The haplotypes in TSHR intron 1 were associated with GD. There exists the interaction between the SNPs in TSHR and 4p14,which may change the risk of GD.

Objective To investigate the prevalence of DUOX2 mutations in Chinese patients with congenital hypothyroidism (CH) and to discuss the inheritance pattern of DUOX2 gene.Methods Blood samples were collected from 91 CH children and their genomic DNA was extracted from peripheral blood leukocytes.All exons and exon-intron boundaries of DUOX2 were analyzed by target next-generation sequencing and family trios was established to study the inheritance pattern of DUOX2 gene.Results Fifty-four out of 91 children with CH carried DUOX2 mutation, with a prevalence of 59.34%.Of the 54 CH children, 36 carried DUOX2 biallelic mutations.In all 12 family trios with probands carrying biallelic DUOX2 mutations, the parents carried heterozygous DUOX2 mutations while still showing normal thyroid function, suggesting that CH caused by DUOX2 mutations is inherited in an autosomal recessive manner.Conclusion DUOX2 gene is one of the most frequently mutated genes in Chinese CH patients and its inheritance pattern is an autosomal recessive one.

Objective To investigate the effects of the genetic polymorphisms in osteoporosis-related genes and the gene-gene interaction on bone mineral density (BMD) and osteoporotic fractures.Methods Thirty-nine single nucleotide polymorphism (SNP) sites in 23 genes that related to bone mineral density ( BMD ) and osteoporotic fractures were scanned in 683 Shanghai Han postmenopausal women.TaqMan SNP Genotyping Assay or Sequenom Mass ARRAY System were applied for genotyping analysis.The relation of these SNP sites with BMD and osteoporotic fractures were analyzed.Results Altogether,12 SNPs in 9 candidate genes ( rs7524102 and rs6696981 in ZBTB40 gene,rs9479055 in ESR1 gene,rs6993813,rs6469804,and rs11995824 in OPG gene,rs3736228 in LRP5 gene,rs1107748 in SOST gene,rs87938 in CTNNB1 gene,rs1366594 in MEF2C gene,rs7117858 in SOX6 gene,and rs10048146 in FOXL1 gene) were associated with BMD at lumbar spine(L1-L4) or total hip.In addition,rs11898505 in SPTBN1 gene was related to osteoporotic fractures ( OR 0.522,95％ CI 0.326-0.838,P =0.007 ).Gene-gene interaction involving rs1038304 in ESR1 gene,rs1366594 in MEF2C gene,and rs10048146 in FOXL1 gene was associated with osteoporotic fractures ( P =0.010 7 ).Conclusions ( 1 ) SNPs in gene ZBTB40,ESR1,OPG,LRP5,SOST,CTNNB1,MEF2C,SOX6,FOXL1,and SPTBN1 are associated with BMD of lumbar spine or total hip,as well as osteoporotic fractures.(2) Gene-gene interaction involving rs1038304,rs1366594,and rs10048146may contribute to the risk of osteoporotic fractures.

Objective: To explore the status of sugar sweetened beverages(SSBs) and its associated factors among primary and middle school students in Shenzhen, providing reference for nutrition and health education. Methods: A random number table and convenience sampling method was used to select 40 135 primary and middle school students aged 6-18 years in Shenzhen. Data was collected to investigate their SSBs knowledge and associated factors. Results: The proportion of SSBs knowledge score less than 60 points, between 60-79 points and 80-100 points were 5.6%, 41.9% and 52.4%. Multivariate analysis showed that age(4-6 grade, junior middle and high school), gender(female), parents education(high school or vocational schools, colleges and universities as bachelors, masters or doctors), students pay attention to the ingredient list (seldom, none), parental dissuasion or reward behavior (only forced dissuasion, giving no dissuasion, occasional reward, no reward), and the storing beverages at home (seldom, none) were associated with total SSBs knowledge score and milk containing beverage knowledge score ( β =-0.79，-1.19，-1.74，0.58， 1.20 ，1.81，2.98，3.13，2.70，4.85，6.34,6.41，-0.99，-0.78，-1.81，-2.40，5.85，6.26，0.61，1.92， P <0.05). Age(4-6 grade, junior middle and high school), gender(female), father s education background(with colleges and universities as bachelor, masters or doctors), mother s education background(high schools or vocational schools, colleges and universities as bachelors, masters or doctors), parents dissuation behaviors(giving no dissuation), parents rewarding behavior(seldom, none), storing beverages at home(seldom, none) were associated with the total SSBs knowledge score and milk containing beverage knowledge score( β =-0.68， -0.92 ，-0.49，0.26，0.51，1.05，1.09，0.90，1.93，2.62，2.55，-0.68，0.93，1.13，0.21，0.92， P <0.05). Conclusion Primary and middle school students have moderate to high level of SSBs knowledge. It is necessary for students and their parents to learn more SSBs related nutrition healthy knowledge, and to reduce home availability of SSBs.

OBJECTIVE: To investigate the protective effect of edaravone and danshensu conjugate (IM-009) on focal cerebral ischemia-reperfusion injury in rats and its underlying mechanisms.
 METHODS: Rats were randomly assigned into 6 groups, including a sham group, a model group, an edaravone-treated group, a danshensu-treated group, a low dose of IM-009-treated group and a high dose of IM-009-treated group. The focal cerebral ischemia-reperfusion model was established by intraluminal filament. After the drug treatment, the infarct volume and extent of brain edema were measured. The levels of MDA and SOD were determined by the corresponding assay kit. The scavenging effect of IM-009 on hydroxyl radical and superoxide anion was also measured in a cell free system.
 RESULTS: 1) In comparison with the model group, the infarct volume and water content in rat brain after IM-009 treatment were significantly reduced. The protective effect of IM-009 at higher dose was much stronger than that of edaravone or danshensu (all P<0.05). 2) IM-009 significantly reduced the levels of MDA and increased the activity of SOD (all P<0.05). 3) IM-009 demonstrated strong activities in scavenging .OH and .O(2)(-) (all P<0.05).
 CONCLUSION IM-009 is able to protect rats from ischemia-reperfusion injury. The protective effect of IM-009 could be due to its radical-scavenging action.
Animals ; Antipyrine ; analogs & derivatives ; pharmacology ; Brain Edema ; Brain Ischemia ; drug therapy ; Cerebral Infarction ; drug therapy ; Edaravone ; Lactates ; pharmacology ; Malondialdehyde ; metabolism ; Rats ; Reperfusion Injury ; drug therapy ; Superoxide Dismutase ; metabolism

Objective:Clinical and genetic analysis were conducted in 2 patients with hypophosphatasia(HPP) and their families to explore the pathogenic mechanism of HPP.Methods:The genomic DNA was extracted from peripheral blood of two patients with HPP and their family members. Sanger sequencing and pedigree verification were performed on the pathogenic variants identified using whole-exome sequencing. Then the function of the mutation sites was analyzed with bioinformatics software.Results:Proband 1 presented with developmental retardation, pectus funnel and premature loss of deciduous tooth, of which the serum alkaline phosphatase level was slightly lower than the bound of the normal range. Two complex heterozygous missense variants c. 1120G>A and c. 1334C>G of ALPL gene were detected in the proband 1 which were inherited from his parents respectively, showing an autosomal recessive inheritance. Both the variants were predicted to inflict deleterious effects on ALPL gene function by multiple bioinformatics program, and were classified as likely pathogenetic variants according to American College of Medical Genetics and Genomics(ACMG) guidelines. Proband 2 showed three missing permanent teeth and the significantly lower level of serum alkaline phosphatase than normal range. A heterozygous variant c. 1190-3C>G of ALPL gene was detected in proband 2 whose pattern of inheritance was unknown. The clinical significance of this variant was unknown according to ACMG standards and guidelines. All of these variants were considered as novel since none of them has been reported. Along with the above combined results, proband 1 and 2 were diagnosed as childhood HPP and Odontohypophosphatasia, respectively.Conclusion:This study reinforced the relationship between HPP and variants in ALPL gene. Two variants, c. 1120G>A and c. 1334C>G, were located in the homodimer interface and crown domain of tissue-nonspecific alkaline phosphatase(TNSALP), respectively, while c. 1190-3C>G were located in the splice sites, which might result in low TNSALP activity.

Background Long-term excessive consuming sugar-sweetened beverages have a negative impact on health. In order to decrease the consumption of sugar-sweetened beverages and create a healthy food environment, the Health Commission of Shenzhen Municipality pioneered to enforce health warning labels presented in commercial locations vending sugar-sweetened beverages based on relevant provisions of the Health Regulations of Shenzhen Special Economic Zone，but its effect has not yet been evaluated. Objective To evaluate the impact of presenting health warning labels in commercial locations vending sugar-sweetened beverages in Shenzhen. Methods A multi-stage stratified sampling method was used to randomly select one street in each of the 10 districts (excluding the Shenzhen Shantou Special Cooperation Zone) of Shenzhen followed by a convenience sampling to select sampling sites to conduct an undercover investigation on the presentation of health warning labels for sugar-sweetened beverages in six different types of venues (n=232) such as shopping malls, ordinary supermarkets/convenience stores, self-service vending machines, catering service places, medical institutions, and venues serving minors' education and activities. At the same time, 238 site managers, 1002 adult consumers, and 7396 child and adolescent consumers were interviewed. Results Among 213 commercial locations vending sugar-sweetened beverages, the rate of health warning label installation was 26.3%, with the highest installation rate in shopping malls (55.0%). Among site managers, 47.8% were aware that commercial locations were required to install health warning labels, and 50.0% were aware of the standards for setting up health warning labels. The higher the awareness of relevant regulations, the higher the rate of installation of health warning labels. More than half of site managers (55.3%) believed that after installing health warning labels, the sales of sugar-sweetened beverages and sugar-sweetened beverages in large-volume packages had decreased compared to the same period in previous years. Most of the interviewed consumers indicated that if they saw the health warning labels for sugar-sweetened beverages, they would buy less, give up purchasing, or choose low-sugar or sugar-free beverages, and also discourage their family members or friends from drinking such beverages. Compared with participants without awareness of the health warning labels, both adult and child and adolescent consumers with awareness of the health warning labels believed that the installation is beneficial to their good eating habits and reported a higher proportion of discouraging family members or friends from drinking such beverages, with a lower frequency of consuming sugar-sweetened beverages. Conclusion Health warning labels for sugar-sweetened beverages have a significant effect on promoting behavior changes, and both site managers and citizens have a high level of support for them. However, in view of the low voluntary compliance rate of commercial locations and the installation rate of health warning labels, the publicity and enforcement of the Health Regulations of Shenzhen Special Economic Zone should be enhanced.