OBJECTIVE To explore the potential mechanism of the effect of Xuebijing injection （XBJ） on neurological function and survival of rats after cardiac arrest （CA）/cardiopulmonary resuscitation （CPR） based on the S-nitrosoglutathione reductase （GSNOR）/S-nitrosoglutathione （GSNO） pathway. METHODS The CA/CPR rat model was established by ventricular fibrillation. Using a sham operation group as control， high-throughput sequencing was employed to analyze and mine the differentially expressed genes （DEGs）. Enzyme-linked immunosorbent assay was used to determine the contents of GSNOR and GSNO in the hippocampus； the active components of XBJ were screened and subjected to molecular docking analysis with GSNOR. The rats successfully modeled using the same method were divided into model group （n＝30）， inhibitor （GSNOR inhibitor） group （n＝30）， XBJ group （n＝30） and XBJ+inhibitor group （n＝30）， and a sham operation group （n＝30） was set up. Neurological function was evaluated and survival status was recorded at 3 hours， 24 hours and 3 days after the first 89） drug intervention. The contents of GSNOR and GSNO in the hippocampus of rats were determined in each group at the 0191） above time points， and the relationship of the contents of GSNOR and GSNO with modified neurologic severity scale （mNSS） score was analyzed. RESULTS GSNOR coding gene was differentially expressed between the model group and the sham operation group. Compared with the sham operation group， GSNOR content increased significantly in the hippocampus of rats in model group， while GSNO content decreased significantly （P＜0.05）. The active components of XBJ， such as 4- methylenemiltirone and salviolone， could be bound to GSNOR protein， with the binding energy lower than －6 kcal/mol， mainly connected by hydrogen bonds. Animal experiments revealed that mNSS score and GSNOR levels in the hippocampus of rats in the model group were significantly higher than those in the sham operation group （P＜0.05）， while GSNO levels and survival rate were significantly lower than those in the sham operation group （P＜0.05）. The above indexes of rats were improved significantly in administration groups， the mNSS score in the XBJ group was significantly lower than that in the inhibitor group， the content changes of GSNOR and GSNO in the inhibitor group were more obvious than those in the XBJ group， and the various indicators in the XBJ+inhibitor group were significantly better than the XBJ group and the inhibitor group （P＜0.05）. GSNOR content was positively correlated with the mNSS score， and GSNO content was negatively correlated with the mNSS score （P＜0.05）. CONCLUSIONS XBJ can improve the neurological function of rats and enhance their survival rates after CA/CPR， the mechanism of which may be associated with the down-regulation of GSNOR and the up-regulation of GSNO.

In the earliest days,the idea that surviving a single infection often resulted in lifelong immunity to the infecting pathogen was recorded and then led to the discovery of vaccination.We have now confirmed that such protection is primarily based on the generation of immunological memory in antibody response.With the wide implementation of more and more vaccines around the world,it is well documented that different vaccines have different potential regarding to the duration of antibody response.In clinical observations,live-attenuated vaccines often elicit long-term immunity but are also accompanied with risks in safety that are hard to avoid.In order to develop novel vaccines with both excellent potential in eliciting antibody memory and low safety risk,it is critical to further investigate the mechanism of antibody memory in the perspective of immunology.Antibody memory is mediated by certain long-lived B cells:long-lived plasma cell can secret antibody to maintain serum antibody titer while memory B cell contributes to the rapid immune response during the secondary encounter of pathogens.Cellular and molecular processes that drive the production of long-lived plasma cells and memory B cells are subjects of intensive research and have important implications for global health.Several factors in the vaccine would indeed affect and regulate these processes,including the antigen valency,vaccine kinetics and the signal integration of both antigen and danger molecules.Many studies have focused on strategies to manipulate these factors to improve or develop new vaccines.Here,we will summarize our current knowledge on how the component in vaccines will affect their potential in generating and sustaining antibody memory,and also point out the challenges we face in the route of developing a"perfect"vaccine.

OBJECTIVE: To assess the association of 7 single nucleotide polymorphisms (SNPs) including rs13278062 (TNFRSF10A), rs3750846 (ARMS2-HTRA1), rs429358 (APOE), rs5817082 (CEPT), rs2043085 (LIPC), rs1626340 (TGFBR1), and rs8135665 (SLC16A8) identified through genome-wide association study (GWAS) with age-related macular degeneration (AMD) among ethnic Han Chinese from Sichuan, China. METHODS: A cohort of 576 AMD patients and 572 healthy controls were enrolled in a case-control study. The SNPs were genotyped by a Mass array MALDI-TOF System. On the premise that the genotype distribution of each SNP locus in both groups satisfied Hardy-Weinberg equilibrium, the genetic pattern was analyzed and the scores of allele and genotype frequencies ware compared. RESULTS: There was a significant association between TNFRSF10A rs13278062 and AMD under the heterozygous model (P = 0.000, OR = 1.529, 95%CI = 1.196-1.954) and the dominant model (P = 0.002, OR = 1.459, 95%CI = 1.154-1.865), suggesting that subjects carrying rs13278062GT and rs13278062TT + GT are more likely to develop the AMD, whereas no significant difference was observed for rs13278062 under other models. No association was detected with the other six SNPs and AMD under various genetic models. CONCLUSION This case-control association study has indicated that TNFRSF10A rs13278062 is associated with AMD under the heterozygous and dominant models, suggesting that the TNFRSF10A variant may be involved in the development of AMD among ethnic Han Chinese population.
Case-Control Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; High-Temperature Requirement A Serine Peptidase 1/genetics* ; Humans ; Macular Degeneration/genetics* ; Polymorphism, Single Nucleotide

Objective: To explore the relationship among grit, self-identity and self-esteem and the mediating role of self-identity between grit and self-esteemin middle school students, so as to provide evidence for the study of grit of middle school students. Methods: In March 2019,1 476 middle school students were selected from two ordinary middle schools in a county of Fujian Province. 12-Ttem Grit-scale, Selt-identity Scale and Selt-esteem Scale were used to conduct the questionnaire survey. Results: Relevant analysis showed that perseverance of efforts, consistency of interests were positively correlated with self-identity (r=0.40, 0.31,P<0.01) and self-esteem (r=0.46, 0.18, P<0.01). Self-identity and self-esteem were positively correlated (r=0.67,P<0.01).The results of the mediation test showed that self-identity partially mediates the relationship between perseverance of efforts and self-esteem,mediation effect accounted for 50.38% of the total effect.Self-identity fullymediatesthe relationshipbetween consistency of interests and self-esteem. Conclusion The self-identity of middle school students partially mediates the relationship between perseverance of efforts and self-esteem, and completely mediates the relationship between consistency of interests and self-esteem.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integra-tion of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation,and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, hap-lotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Objective: To evaluate the value of methylation detection of plasma Septin9 gene in the diagnosis of colorectal cancer (CRC) and verify its performance. Methods: The plasma samples from 32 CRC patients before colonoscopy and 10 healthy controls during October 2016 and May 2017 were collected, and the methylation levels of Septin9 gene in these samples were detected by the detection kit of plasma Septin9 gene methylation. The coincidence rate, detection limit and precision of the kit in the diagnosis of CRC were evaluated, and its diagnostic value was compared with that of carcinoembryonic antigen (CEA) and facal immunochemical tests (FIT). Results: The positive and negative coincidence rates of the plasma Septin9 gene methylation kit in the detection of CRC were 100%. The reference materials assigned the detection limit were positive, and the coefficient of variation (CV) of precision was less than 5%, which met the basic performance requirements. The sensitivity, specificity, positive predictive value and negative predictive value of the kit in the diagnosis of CRC were 62.50%, 90.00%, 95.20% and 42.90%, respectively. The detection rate of CRC by the kit was 62.50%, significantly higher than those of FIT (28.13%) and CEA (28.13%) (all P＜0.05). The area under the ROC curve (AUC ROC ) of the kit in the diagnosis of CRC was 0.762, and the detection rate of stage Ⅰ CRC by the kit was 50.00%. Conclusion The performance of the plasma Septin9 gene methylation kit meets the anticipated clinical requirements, which may be used as a serological marker for the assistant diagnosis of CRC.

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

Objective To investigate the changes of postprandial serum insulin and C-peptide concentration of type 2diabetes mellitus (T2DM) patients with different fasting blood glucose concentrations, and to study the islet function of them.Methods There were 492T2DM patients from January 2016to June 2017in our hospital were selected and divided into three groups according to different fasting plasma glucose (FPG) levels:group A, 7.0mmol/L≤FPG＜11.1mmol/L;group B, 11.1mmol/L≤FPG＜14.0mmol/L;group C, FPG≥14.0mmol/L.Meanwhile, 50healthy examinees were collected as the control group.A standard 75g OGTT were performed in 492T2DM patients and 50healthy controls, and 2mL of venous blood of them were collected at 0.5, 1.0, 2.0and 3.0h.The concentration of insulin and C-peptide at each point was measured by chemiluminescence method, and then compared with the control group.Results The concentration of insulin and C-peptide in T2DM patients were slightly higher than those in the control group, but there was no statistical significance (P＞0.05).The serum insulin and C-peptide post-meal in the A, B and C groups and control group increased, but the 1.0hpostprandial blood glucose of control group increased to a peak, and gradually returned to normal at 3.0h;the 2.0hpostprandial blood glucose of A, B and C groups increased to a peak, and decreased at 3.0h, but did not return to normal level.The concentrations of insulin and C-peptide in the A, B and C groups at 0.5, 1.0, and 2.0hpost-meal were significantly lower than those in the control group (P＜0.05).Conclusion The function of isletβcells in T2DM patients decreases with the increase of blood glucose.The determination of insulin and C-peptide can provide a scientific evidence for judging the severity of disease and guiding treatment.

Objective To screen the pathogenic locus and gene in a primary open angle glaucoma(POAG),and to provide a basis for molecular genetic study of POAG.Methods A POAG pedigree with 35 members was diagnosed in Sichuan peoples' Hospital from January to August 2005.The disease history and clinical data were collected.Genome-wide scan was performed for the families.Specific software was used to calculate the LOD value,which based on the allele (haploid) typing result with two-point method to definite the positive loci by the largest LOD value.Results The POAG family had 35 members of 4 generations.18 patients were diagnosed as juvenile open angle glaucoma from visual disc shape abnormality and loss of typical visual field.All of the patients in this family suffered various degrees of binocular vision loss and vision loss in childhood,with poorly visual function.The LOD values of 3 short tandom repeat (STR) markers on chromosome 2 were greater than 3.0,they were D2S2369 (LOD value 4.0033),D2S2332 (LOD value 3.8402) and D2S337 (LOD value 4.7520).There was a genetic linkage near the three genetic markers in the family.The primary glaucoma positive locus was a in chromosome p15 to chromosome p16.2,and the genetic distance was about 9 Mb,locating in between the markers D2S2369 and D2S2397.Conclusions GLCIH is a pathogenic locus for this POAG pedigree,which supplies an evidence for elucidating the pathogenesis of POAG.

OBJECTIVETo detect potential mutations of fibrillin-1 (FBN1) gene in a child with Marfan syndrome (MFS) and explore its molecular pathogenesis.

METHODSThe 66 exons of the FBN1 gene were analyzed by direct sequencing. SIFT and PolyPhen-2 were used to predict the structural and functional changes at the protein level.

RESULTSA novel heterozygous mutation c.3998 G>A (p.Cys1333Tyr) was found in exon 32 in the child. The same mutation was not found among his unaffected family members and 683 healthy controls. Multiple sequence alignment showed that this novel mutation was located in a highly conserved region of the FBN1 protein across various species and may induce structural change to a functional domain.

CONCLUSIONThe novel c.3998G>A (p.Cys1333Tyr) mutation of the FBN1 gene probably predisposed the MFS in the child. Above finding has enriched the spectrum of FBN1 mutations.