There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.

Objective To investigate the serological and molecular characteristics of twenty blood samples carrying ABO?AW.37 allele and to analyze ABO allelic enhancement.Methods The ABO phenotype of the twenty samples was de-termined by serological methods and the genotype of 1-7 ABO exons was analyzed by Sanger sequencing.Results Sequen-cing analysis showed that all twenty samples contained a c.940A>G(p.Lys314Glu)mutation of A allele,which was defined as ABO?AW.37.When ABO?AW.37 and B alleles were inherited simultaneously in 9 cases,in forward typing anti-A anti-bodies all agglutinated and the serological phenotype was Aw B.Among the 11 cases with ABO?AW.37 and O alleles inherited simultaneously,there was no agglutination of anti-A in forward typing.For absorption and elution tests,5 cases were weakly positive and the serological phenotype was Ael,while 6 cases were negative for absorption and elution tests and the serologi-cal phenotype was O type.Conclusion Allelic enhancement occured when both ABO?AW.37 allele and B allele were in-herited simultaneously.When ABO? AW.37 was inherited simultaneously with O allele,the serological phenotype was Aelor O type and attention should be paid to blood type identification.

OBJECTIVE: To explore the genetic basis for a fetus featuring infantile polycystic kidney disease (IPKD). METHODS: Following elective abortion, fetal tissue and peripheral blood samples of its parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out to detect potential variants correlated with the phenotype. RESULTS: The fetus was found to harbor a heterozygous c.1370C>T (p.P457L) variant of the HNF1B gene, which was unreported previously. The same variant was not detected in either parent. CONCLUSION The heterozygous c.1370C>T (p.P457L) variant of the HNF1B gene probably underlay the IPKD in this fetus. Above finding has enabled genetic counseling and prenatal diagnosis for the family.
Female ; Fetus ; Hepatocyte Nuclear Factor 1-beta/genetics* ; Humans ; Mutation ; Phenotype ; Polycystic Kidney, Autosomal Recessive ; Pregnancy ; Prenatal Diagnosis ; Whole Exome Sequencing

OBJECTIVE: To explore the molecular reasons of weak expression of B antigen on the red cell. METHODS: Serological test for blood group was carried out, including red cell and plasma grouping, and anti-A1 and anti-H testing, and confirming weak A or B antigens by adsorption and elution. Exons 1-7 were sequenced directly, and one of them was cloned and sequenced. RESULTS: All of the 23 samples showed the weak B antigen by serological method. The alleles of the subgroups were identified by DNA sequencing, including 2 Bel subgroup, 4 B3 subgroup, 14 Bw subgroup, 2 CisAB subgroup and a novel allele. The novel allele showed a nucleotide substitution 662G>A in the exon 7, and the sequence was submitted to Blood Group Antigen Gene Mutation Database, and the novel allele was named Bel10. CONCLUSION Nucleotide substitution in exon results in blood subgroup, which showed that the antigens were weakened, and Bw phenotype was the most frequently subgroup.
ABO Blood-Group System/genetics* ; Alleles ; Exons ; Genotype ; Humans ; Nucleotides ; Phenotype

Objective:To investigate whether the presence of complement factor H( CFH) gene polymorphisms is associated with unexplained mild visual loss (UMVL) in type 2 diabetes mellitus patients. Methods:A case control study was adopted.The participants included two groups from a previous population-based epidemiology study on type 2 diabetes mellitus patients in the Beixinjing community, Shanghai: UMVL was defined by a best corrected visual acuity(BCVA)<20/25 and≥20/63 in both eyes, with no eye diseases causing visual impairment, such as corneal diseases, cataract, age-related macular degeneration, glaucoma, optic nerve atrophy, diabetic retinopathy, etc.Genomic DNA was isolated from the peripheral venous blood of all the participants and then loaded onto Fluidigm Digital Arrays.Four CFH gene single nucleotide polymorphisms (SNPs)(rs800292, rs1061170, rs529825, rs1410996, rs203674) were assessed with the SPSS 13.0 and HAPLoVIEW 4.0 software to test the statistical association of CFH polymorphisms with UMVL.The study protocol was approved by the Ethics Committee of Shanghai General Hospital, Shanghai Jiaotong University(No.2013KY023). All the procedures were conducted according to the tenets of the Declaration of Helsinki.Written informed consent was obtained from each subject prior to entering the study cohort. Results:Total of 135 residents with UMVL and 133 with normal vision(BCVA≥20/25 in both eyes) were enrolled.The UMVL group matched the control group in terms of gender, age, onset age, and duration of diabetes mellitus, hemoglobin A1c levels, and body mass index(all at P>0.05). The four SNPs(rs800292, rs1061170, rs529825, rs1410996) except rs203674 tested in the UMVL and control groups were qualified by the Hardy-Weinberg equilibrium ( P>0.05). There were no differences in SNPs and genotypes between the two groups in the four loci of the CFH gene.The P value of allele frequencies of rs529825, rs800292, rs1410996 and rs1061170 were 0.79, 0.25, 0.69 and 0.77, respectively, and the P value of genotype frequencies were 0.61, 0.69, 0.87 and 0.43, respectively. Conclusions:There is no correlation between CFH gene polymorphism and UMVL in type 2 diabetic patients.

OBJECTIVE: To retrospectively analyze non-invasive prenatal screening (NIPS) data from two centers. METHODS: The NIPS results of 10 840 samples were analyzed, including 21/18/13 trisomies (T21/T18/T13), sex chromosome and other autosomal aneuploidies, and copy number variants (CNVs). The maternal age, gestational week, body mass index and concentration of free fetal DNA (cffDNA) were also analyzed. RESULTS: The average gestational age of the 10 840 pregnant women was (32.34±5.04) year old, and the average gestational week for NIPS was (17.60±3.55) week. The overall false positive rate for T21/T18/T13 was 0.11%, sensitivity was 100%, specificity was 99.89%, and positive predictive value was 81.5%. The positive predictive values for sex chromosome and other autosomal aneuploidies and CNVs were 56.67%, 11.76% and 83.33%, respectively. The incidence of T21/T18 in the elder women (35 years or elder) was 2.12 times(P<0.01) and 1.81 times (P> 0.05) that of young women. cffDNA was in proportion to gestational week (r = 0.207) and in inverse proportion to body mass index (r = -0.177). It has increased slowly before 15 weeks of gestation and thereafter at a rate of 0.5% per week after the 16th week. CONCLUSION The performance of NIPS in this study is by large close to the reported in the literature, and the results can provide a reference for further study.

BACKGROUND: Lung cancer is the most common cancer worldwide with the highest morbidity and mortality, in which the non-small cell lung cancer accounts for 80% of all cases. The expression of (HOX transcript antisense RNA) HOTAIR were abnormal in a variety of tumor tissues and is involved in the regulation of the occurrence and development of lung cancer. The purpose of this study is to investigate the effect and mechanism of down-regulation of HOTAIR on gefitinib resistance of lung adenocarcinoma HCC827 cells by targeting PTEN. METHODS: The HOTAIR downstream target gene was predicted by bioinformatics database. The small interfering RNAs (siRNA) which is corresponding to HOTAIR was transfected using Lipofectamine™ 2000. Quantitative real-time PCR (RT-qPCR) and Western blot were used to detect the expression of HOTAIR, PTEN, PI3K and AKT in HCC827 and HCC827GR cells. MTT assay was used to detect the changes in drug resistance of HCC827GR cells. Flow cytometry analysis were used to test the cell proliferation and the rate of apoptosis. RESULTS: The expression of HOTAIR increased in HCC827GR and the serum of NSCLC patients with gefitinib resistance (P<0.05). Transfection of HOTAIR siRNA decreased the expression of HOTAIR (P<0.05), and increased the expressions of PTEN (P<0.05), while the expression of PI3K and AKT were decreased (P<0.05). Compared with the blank control group, down-regulation of HOTAIR increased the sensitivity of HCC827GR cells to gefitinib. The cell proliferation ability was decreased and the apoptosis was promoted apparently (P<0.05). CONCLUSIONS Down-regulation of HOTAIR can suppress the cell growth and promote the apoptosis, and it can reverse the resistance of HCC827GR cells to gefitinib. Its potential mechanism may be related with the targeting of PTEN/PI3K/AKT pathway.

Objective: To investigate the clinical relevance of mannose-binding lectin 2 (MBL2) gene polymorphism with traumatic sepsis in Hainan Province. Methods: A retrospective case control study was conducted to analyze the clinical data of 112 severe trauma patients admitted to the First Affiliated Hospital of Hainan Medical College and Haikou People's Hospital from June 2017 to June 2018. There were 73 males and 39 females, aged 17-83 years [(41.8±8.9)years]. There were 48 patients in the sepsis group and 64 patients in the non-sepsis group. Multiplex single nucleotide extension polymorphism (SNaPshot) typing technique was used to detect the MBL2 gene polymorphism. The correlation between different genotypes and the risk of sepsis was analyzed. ELISA method was used to detect the level of MBL2 in plasma of each group. Results: Among the three polymorphic loci of MBL2 gene (rs5030737, rs1800450 and rs1800451), the mutation frequency of rs1800450 was 27.7%, while the mutation frequency of rs5030737 and of rs1800451 was 0. The genotype distribution in two groups was in accordance with Hardy-Weinberg equilibrium. The frequency of GA genotype in sepsis group was significantly higher than that in non-sepsis group (P<0.05). A allele frequency in sepsis group was also much higher than that in non-sepsis group (P<0.05). Patients with GA genotype had increased risk of traumatic sepsis when compared to GG genotype(OR=3.442, 95%CI 1.447-8.187). Allele A increased the prevalence of sepsis significantly as well when compared to allele G(OR=2.799, 95%CI 1.270-6.170). The MBL2 level in serum in sepsis patients with genotype GG and GA was significantly lower than that in non-sepsis group (P<0.05). In sepsis group, the MBL2 serum level of patients with genotype GA was obviously lower than that in patients with genotype GG (P<0.05). Conclusion MBL2 rs1800450G/A polymorphism is closely related to the occurrence of sepsis in Hainan province, and may be related to the decrease of serum MBL2 level in patients with mutant type.

OBJECTIVE:To provide reference for rational selection of antibiotics against non-fermentative Gram-negative bacilli in clinic. METHODS:Etiological data of clinical isolated Pseudomonas aeruginosa(PA),Acinetobacter baumanii(AB) and Stenotrophomonas maltophilia(SM)were collected from the Affiliated Hospital of Qingdao University(called"our hospital"for short)during Jan. 2004-Dec. 2016. Drug resistance of them to commonly used antibiotics was analyzed retrospectively. RESULTS:Totally 15 587 strains of PA,7 446 strains of AB and 2 950 strains of SM were detected. Resistance rates of PA to commonly used antibiotics fluctuated but were in a decreasing tendency. Except for imipenem,resistance rates of PA to commonly used antibiotics decreased significantly,and resistance rates of PA to amikacin and gentamicin decreased to 4.60% and 7.48%, respectively. Resistance rates of AB to most commonly used antibiotics were more than 40%,but it was sensitive to tigecycline (drug resistance of 0-4.03%). Resistance rates of SM to cefoperazone sodium and sulbactam sodium increased from 3.03% in 2004 to 39.01% in 2016,but it was sensitive to sulfamethoxazole,minocycline and levofloxacin. CONCLUSIONS:Non-fermentative Gram- negative bacilli detected in our hospital are mainly PA. Resistance rate of PA to most of the antibiotics is declining;drug resistance of AB is severe;resistance rates of SM to cefoperazone sodium and sulbactam sodium show increasing tendency.Above 3 non-fermentative Gram-negative bacilli are sensitive to amikacin,tegocycline and minocycline. Clinical selection should be based on the results of drug sensitivity test.

Objective To investigate the association between serum total testosterone (TT ) levels and type 2 diabetes(T2DM )and any gender differences in elderly patients. Methods Based on the Aging Health database built from 2008 to 2012 ,935 elderly individuals over 60 years old with a mean age of 65.8 years receiving physical examinations were included.According to the 1999 WHO criteria for diabetes ,participants were assigned into four groups :a T2DM group(n＝298) ,an impaired fasting glucose(IFG)group(n＝26) ,an impaired glucose tolerance(IGT)group(n＝121) ,and a normal glucose regulation(NGR)group(n ＝ 490).We measured serum TT by ELISA and analyzed the distribution patterns in the groups.Furthermore ,we examined the gender-specific correlation of TT with T2DM and homeostasis model assessment of insulin resistance (HOMA-IR). Results The prevalence of T2DM in the participants was 31.9%(298/935).One-way ANOVA analysis showed that the TT level was higher in the NGR group than in the T2DM and IGT groups (PANOVA＝ 0.001) . Logistic regression analysis indicated a significant protective association between TT and T 2DM in the elderly.Every one unit of increase in the SD of the TT level was accompanied by a 23% reduction in the risk for T2DM (P＝ 0.001).Further gender-stratification analysis suggested that the protective role of TT against T2DM only existed in males (OR＝ 0.55 ,95% CI :0.44-0.68 ;P＜ 0.001).After adjustment for age ,blood pressure ,blood lipids ,and waist circumference ,the protective role of TT against T2DM in males still remained (OR ＝ 0.68 ,95% CI :0.53-0.86 ;P ＝ 0.002 ).Pearson correlation analysis also indicated a significant negative correlation between TT and HOMA-IR in older males(P＝0.002).As for older females ,no significant correlation of TT with T2DM and HOMA-IR was found. Conclusions The serum TT level might be an independent protective factor for T 2DM in older males ,as evidenced by its correlation with improved insulin resistance status ,which is not present in older females.