Objective:To explore the effect of chronic intermittent hypoxia(CIH)on learning and memory dysfunc-tion in rats,as well as the expression of high mobility group box-1(HMGB1)and nuclear transcription factor-KB(NF-κB)in the hippocampus region.Methods:The CIH rat model was established,and forty SD rats were randomly divid-ed into four groups:normoxia group,hypoxia for 4 weeks group(CIH4 group),hypoxia for 8 weeks group(CIH8 group),and hypoxia for 12 weeks group(CIH12 group).Morris water maze was used to assess the learning memory ability of rats,and immunohistochemistry and ELISA were used to detect the expression of HMGB1 and NF-κB in the hippocampus of rats.Results:Compared with the normoxia group,the CIH12 and CIH8 groups had longer escape la-tency,the number of crossing the platform and the residence time in the quadrant of the platform were significantly shortened,but there was no significant difference in the CIH4 group.Additionally,there was no significant expression of HMGB1 and NF-κB in the hippocampal region of the normoxia group,but little expression was observed in CIH4 group,and significantly expressed in CIH8 group and CIH12 group,and the expression of CIH12 group was significantly higher than that of CIH8 group.Conclusion:CIH can lead to a decline in learning and memory function in rats,and the longer time of intermittent hypoxia led to the more significant effect on their learning and memory function.In addi-tion,CIH also leads to increased expression levels of HMGB1 and NF-κB in the hippocampus region,and the expres-sion increased more significantly after hypoxia for 12 weeks,comparing to hypoxia for 8 weeks.

Objective:To analyze the incidence and risk factors of acute kidney injury in children with biliary atresia after liver transplantation.Methods:The retrospective case-control study was conducted.The clinical data of 115 children with biliary atresia who received liver transplantation for the first time in Beijing Friendship Hospital Affiliated to Capital Medical University from December 2018 to November 2020 were collected.The patients were divided into AKI group ( n=39) and non-AKI group ( n=76) according to the diagnostic criteria of the Kidney Disease Improving Global Outcomes(KDIGO). The differences of clinical indicators between the two groups were compared, and multivariate logistic regression analysis was performed for statistically significant variables ( P<0.05) to further determine the independent risk factors for AKI after liver transplantation. The measurement data of normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for comparison between groups.Measurement data with non-normal distribution were represented by M( Q1, Q3), and Mann-Whitney U test was used for comparison between groups.Count data were expressed as cases and percentage, and comparisons between groups were made using Chi-square test or Fisher′s exact test. Results:The incidence of AKI in biliary atresia patients after liver transplantation was 33.9%. Univariate analysis showed that there were statistically significant differences in age ( OR=0.721, 95% CI: 0.553-0.938, P=0.014), preoperative infection ( OR=3.307, 95% CI: 1.294-8.468, P=0.013), PELD score ( OR=1.065, 95% CI: 1.031-1.101, P<0.001), serum creatinine numerical value ( OR=0.745, 95% CI: 0.657-0.858, P<0.001), intraoperative red blood cell transfusion ( OR=1.034, 95% CI: 1.028-1.051, P<0.001) and intraoperative plasma transfusion ( OR=1.055, 95% CI: 1.025-1.086, P=0.002) between the AKI group and the non-AKI group ( P< 0.05). Multivariate logistic regression analysis was performed on the selected indicators by univariate analysis, and the results showed that preoperative infection ( OR=3.763, 95% CI: 1.185-11.945, P=0.025) and low serum creatinine ( OR=0.685, 95% CI: 0.570-0.823, P<0.001), intraoperative red blood cell transfusion ( OR=1.033, 95% CI: 1.015-1.056, P=0.028) was independently associated with postoperative AKI ( P<0.05). The inpatient treatment time in ICU and in hospital between the two groups were statistically significant ( P<0.05). Conclusions:Preoperative infection, low creatinine numerical value and intraoperative red blood cell transfusion are independent risk factors for postoperative AKI in children with biliary atresia. AKI may prolong the time in ICU and in hospital.

Objective:To understand the vancomycin dose, therapeutic drug monitoring(TDM) situation and therapeutic effect of children after liver transplantation.Methods:A retrospective analysis of the data of 98 children who received intravenous vancomycin treatment after liver transplantation were conducted in the Department of Critical Care Medicine of Beijing Friendship Hospital from January 2017 to June 2019, including demographic data, vancomycin dose, serum trough concentration, drug-related adverse reactions and clinical outcome data.Results:A total of 98 children received intravenous vancomycin treatment and at least one steady-state TDM blood sample was collected.Among them, 53 cases (54.1%) were male, and the median age was 9 months(5 months to 14 years old). The median first daily dose of vancomycin treatment was 50(30-60)mg/(kg·d), and the median duration of treatment was 14(3-54)days.Only 27.5%(27/98)of the children′s initial trough concentration reached the target concentration (10-20 mg/L), while 26 cases(26.5%) did not reach the target after adjusting the treatment.Six children(6.1%)had renal toxicity caused by vancomycin, and two children had skin rash.The effective treatment rate accounted for 51.7%(15/29). The initial trough concentrations of vancomycin in the effective and ineffective groups were(5.92±3.82)mg/L and(10.43±5.37)mg/L, respectively.The difference was statistically significant ( P=0.041). Conclusion:The rate of intravenous vancomycin in children after liver transplantation is low, and the dose needs to be adjusted individually.

Objective To study the relationship between uridine diphosphate glucuronic acid (UGT1A1) gene polymorphism and unexplained neonatal unconjugated hyperbilirubinemia in Jinhua.Method Full-term infants with unidentified non-binding hyperbilirubinemia were selected as hyperbilirubinemia group from January 2016 to December 2017 in the obstetrics or neonatal intensive care unit of Jinhua Central Hospital,healthy full-term neonates and those with physiological jaundice admitted during the same period were selected as control group.Whole blood DNA was extracted and UGT1A1 was sequenced and then annotated with human gene mutation database.The distribution and frequency of UGT1A1 genotype were analyzed.The correlation between different genotypes and unexplained unconjugated hyperbilirubinemia in neonates was also studied.Result Two hundred and forty cases were enrolled in the hyperbilirubinemia group,and 216 cases were enrolled in the control group.Four single nucleotide variation (SNV) sites associated with the disease were found on UGT1A1,which were c.211G＞A (Gly71Arg),c.686C＞A (Pro229Gln),c.1091C＞T (Pro364Leu) and c.1456T＞G (Tyr486Asp),accounting for 83.9％(141/168),1.8％(3/168),8.9％(15/168) and 5.4％(9/168) in the experimental group respectively.The genotype frequency and allele frequency analysis showed that the distribution of the two SNV sites of c.211G＞A and c.1456T＞G were statistically different between the experimental group and the control group (P＜0.05),whereas there was no statistical difference of the other two SNV sites of c.686C＞A and c.1091C＞T between the two groups.Binary Logistic regression analysis showed that c.211G＞A and c.1456T＞G were related to the occurrence of unexplained hyperbilirubinemia,The OR values (95％CI) were 5.412 (3.567～ 8.212) and 8.377 (1.052～66.670) respectively,but no correlation was found of the other two polymorphic loci.At the different genotypes of c.211G＞A locus,the levels of total bilirubin and non-binding bilirubin in infants with homozygous mutant (AA) were higher than those in infants with heterozygous mutant (GA) and wild type (GG),which was statistically significant (P＜0.05).Conclusion The most common mutation site of the UGT1A1 gene in Jinhua is c.211G＞A.The mutations of c.211G＞A and c.1456T＞G are risk factors forunconjugated hyperbilirubinemia in neonates.Of the different genotypes of c.211G＞A locus,the serum bilirubin level of homozygous mutant group was significantly higher than heterozygous mutant group and wild type group.

OBJECTIVE: To analyze the clinical characteristics and genetic basis of a child affected with Glass syndrome. METHODS: Clinical manifestations and auxiliary examination results of the child were analyzed. Potential mutation was detected with next generation sequencing and validated by Sanger sequencing. RESULTS: The child has featured growth and mental retardation, delayed speech, cleft palate, crowding of teeth, and downslanting palpebral fissures. DNA sequencing revealed a de novo heterozygous missense mutation c.1166G>A (p.R389H) in exon 8 of the SATB2 gene in the child. CONCLUSION The heterozygous mutation c.1166G>A (p.R389H) of the SATB2 gene probably account for the Glass syndrome in the patient.
Abnormalities, Multiple ; genetics ; Child ; Chromosome Deletion ; Chromosomes, Human, Pair 2 ; Humans ; Intellectual Disability ; genetics ; Matrix Attachment Region Binding Proteins ; genetics ; Mutation ; Transcription Factors ; genetics

Objective To study the effect of enhancer of rudimentary homolog (ERH) gene on migration and invasion in human bladder cancer T24 and 5637 cells.Methods After knocking out the ERH gene of human bladder cancer T24 and 5637 cells,Wound healing assay,Transwell cell migration assay and Transwell cell invasion assay were used to verify the migration and invasion function.Cell migration related protein was detected by Western blot.Nude mouse tail vein transfer assay was used to study the metastasis ability of bladder cancer cells in vivo.Results (1) The Wound healing assay showed that there were significant differences in the migration cell counts of human bladder cancer 5637 and T24 (P ＜ 0.05).(2) There were significant differences in migration and invasion cell counts of Transwell assay (P ＜0.05).(3) Western blot showed that the expression of E-Cadherin in human bladder cancer 5637 cells and T24 cells was significantly increased (P ＜ 0.05) after knocking out ERH gene,while the expression of Fibronectin,Twist,Vimentin and Snail2 protein were significantly decreased (P ＜ 0.05).(4) Nude mouse tail vein transfer assay showed that lung metastases were significantly reduced in the ERH knockout group compared with the normal ERH group.Conclusions Both in vitro and in vivo experiments suggest that ERH knockout affects the migration and invasion of human bladder cancer T24 and 5637 cells.

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Bio-sciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree gen-ome is 1.12 Gb, with 28,422 predicted genes and over 73％ repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites;17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effectsbetween transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.

Objective:To evaluate the association of microsatellite status with clinicopathological features of colorectal cancer patients after surgery.Methods:In total,572 colorectal cancer cases with clear pathological diagnosis and clinicopathological features from the Department of Pathology,Nanjing Drum Tower Hospital from June 2014 to June 2017 were included in the study.Microsatellite status and RAS mutations were detected by polymerase chain reaction.Ki67,EGFR,MGMT,and Lgr5 were detected by immunohistochemis-try.Clinicopathological features were analyzed based on the microsatellite states.Results:In this study,we found MSI-H in 7.0% of all patients,whereas 93.0% cases showed MSS/MSI-L.Compared with MSS and MSI-L colorectal cancer cases,MSI-H colorectal cancer cases showed the following characteristics:1)more likely located in the right colon,2)comparable incidences at different ages,3)ear-ly cancer stage(Ⅰ/Ⅱ)(P=0.003),4)a lower proportion of lymph node metastasis(P=0.023),5)a lower proportion of cancerous nod-ules(P=0.005),6)a lower mutation rate of KRAS(P=0.004),and no mutation of NRAS.There was no significant difference in the posi-tive rates of MGMT,EGFR,Lgr5,and Ki67 between the two groups.Conclusions:Compared with MSS/MSI-L patients,MSI-H patients have specific clinicopathological features.A lower mutation rate of KRAS/NRAS and higher methylation rate of MGMT were also found in MSI-H patients.Our results provide a basis for individual diagnosis and treatment in colorectal cancer.

Objective: To evaluate the clinical performance of HPV genotyping with cytology for detecting cervical precancer among women attending co-testing. Methods: A total of 2 883 females who participated in cervical cancer screening program were recruited from Erdos in 2016. All the participants were tested by cytology and HPV genotyping. In 2017, women with abnormal cytology results or HPV positive were followed up. Pathological cervical intraepithelial neoplasia (CIN) 2+ was the study end-point. Clinical performance indexes were calculated, including sensitivity, specificity, positive predictive value, negative predictive value, referral rate and missed cases. Results: INNO-LiPA resulted in a detection rate of 18.87%(544/2 883) for the 14-type high risk HPV. HPV16 was the most common infectious genotype (4.06%), followed by HPV52 (3.61%), HPV51 (2.50%), HPV58 (1.98%), and HPV18 (1.56%). With more HPV genotypes added into the group, sensitivity increased and the specificity decreased. Addition of HPV16, 58, 33, 39, 52, 18, 31 for detection lead to the maximun value of area under the curve (AUC)=0.913 (95%CI: 0.882-0.944). Compared with traditional screening method by cytology, cotesting decreased the number of missed diagnosis. Meanwhile, the fifth method (co-testing: triage of women with HPV16/18+ , cytological minor abnormalities and HPV58, 33, 39, 52, 31+ or cytological high grade abnormalities) did not increase referral rate (8.99% vs. 8.71%, P=0.525), with five cases of missed diagnosis (sensitivity of 92.1% and specificity of 93.2%). Conclusions Co-testing with triage of women with HPV16/18+ , cytological minor abnormalities and HPV58, 33, 39, 52, 31+ or cytological high grade abnormalities would provide better clinical performance. In co-testing, triage of HPV16/18 was used in women with normal cytology; triage of HPV58, 33, 39, 52 and 31 was used in women with low-grade abnormal cytology; referral colposcopy was used in women with high-grade abnormal cytology, which would provide better clinical performance.

OBJECTIVE: To investigate the effect of G protein-coupled receptor 17 (GPR17) on hypoxia injury in retinal ganglion cells . METHODS: CoCl (400 μmol/L) was used to induce hypoxic injury in RGC-5 cells. The expression of GPR17 and the effect of GPR17 ligands were investigated, and the role of GPR17 in hypoxia injury was further studied by transfection of RGC-5 cells with GPR17 small interfering RNA (siRNA). The cell viability was determined by MTT and the cell apoptosis rate was detected by flow cytometry analysis. The expression of GPR17 mRNA was determined with RT-PCR. RESULTS: mRNA expressions of GPR17 in RGC-5 cells with and without CoCl treatment were 0.36±0.05 and 0.26±0.08(<0.01). Compared with hypoxia without any treatment, pretreatment with GPR17 agonists (LTD, UDP, UDP-G) significantly reduced cell viability (the survival rates of cells decreased by 29.6%, 31.8% and 33.9%, all <0.01), while the effect of GPR17 antagonist (cangrelor) was the opposite (the survival rates of cells increased by 33.2%, <0.01). Transfection with GPR17 SiRNA inhibited hypoxia-induced up-expression of GPR17 mRNA (<0.01)and reduced cell apoptosis[rates of cell apoptosis were(39.73±2.06)%,(42.50±3.64)% and (24.98±2.16)% for blank control, NC siRNA and GPR17 siRNA groups, <0.01]. CONCLUSIONS GPR17 may mediate hypoxia injury in RGC-5 cells, while the knockdown of GPR17 can reduce the hypoxia injury.
Apoptosis ; Cell Hypoxia ; genetics ; Cell Line ; Cell Survival ; Cobalt ; Gene Expression Regulation ; drug effects ; Gene Knockdown Techniques ; Humans ; Hypoxia ; chemically induced ; genetics ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Retinal Ganglion Cells ; drug effects