[Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers].

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.

[Predictive value of left ventricular ejection fraction reserve assessed by SPECT G-MPI for major adverse cardiovascular event in patients with coronary artery disease].

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.

[Risk factors of anxiety during anesthesia induction in children undergoing eye and ear-nose-throat surgery].

Objective: To explore the risk factors of anxiety during anesthesia induction in children undergoing eye and ear-nose-throat (ENT) surgeries. Methods: The clinical data of 930 children who underwent eye and ENT surgeries in the Eye & ENT Hospital of Fudan University from January to December 2019 were collected. The outcome variable was the degree of anxiety during anesthesia induction. Demographic information about the children and their family members, anxiety scores and the usage of preoperative sedative drugs were collected as the exposure factors. The risk factors of anxiety during anesthesia induction were determined by logistic regression analysis. Results: A total of 930 children were included in the study, of which 56(6.0%) cases developed anxiety during the induction period. Univariate logistic regression analysis showed that age (OR=0.72, 95%CI:0.61-0.86, P<0.001), anxiety grading of children by medical evaluation method (mild as the reference, moderate OR=5.42, 95%CI:2.92-10.07, P<0.001; severe OR=7.53, 95%CI: 2.54-22.29, P<0.001), Modified Yale Preoperative Anxiety Scale (mYPAS) score at arrival in the preoperative waiting room (OR=1.05, 95%CI:1.02-1.07, P<0.001) and sedation score (OR=0.48, 95%CI: 0.30-0.76, P<0.001) were risk factors for the development of anxiety during the induction period. Multivariate logistic regression analysis revealed that anxiety grading of children by medical evaluation method was a risk factor for affecting anxiety in the induction period (mild as the reference, moderate OR=4.08, 95%CI:1.81-9.18, P<0.01; severe OR=4.95, 95%CI:1.26-19.44, P=0.022). Conclusion: Anxiety grading of children by medical evaluation method is an essential risk factor for predicting anxiety during induction period.

[An epigenetic clock model for assessing the human biological age of healthy aging].

Objective: To construct an epigenetic clock model for assessing and calibrating human biological age. Methods: Convenience sampling was used to select 186 subjects from the longevity cohort of Guangxi Zhuang Antonornous Region from July 1 to November 30, 2019, and 124 subjects from the physical examination population of the Seventh Medical Center of the PLA General Hospital from October 1 to December 31, 2020. Self-designed questionnaire was applied to collect demographic characteristics and family history of disease. Physical examination was applied to determine heart rate and blood pressure. Fasting peripheral venous blood was drawn for determination of fasting plasma glucose, plasma total cholesterol, triglyceride, plasma high-density lipoprotein cholesterol, plasma low-density lipoprotein cholesterol and telomere length. Methylation levels of EDARADD cg09809672, IPO8 cg19722847, NHLRC1 cg22736354, P2RX6 cg05442902 and SCGN cg06493994 were detected by targeted methylation site sequencing. A total of 54 subjects with unqualified quality control of DNA methylation and telomere length were excluded, and 256 subjects' data were finally analyzed. Trend test was used for the change of methylation level among different ages groups, multiple linear regression method was used to build prediction models of biological age. Kendal rank correlation analysis was used to evaluate the correlation of age gap (Gregorian calendar age minus biological age) with telomere length. Independent sample t-test was used to compare the health-related indicators between subjects with different age gap within different age groups. Results: The M(Q1, Q3)of age of subjects were 67 (51, 91) years old, including 166 females (64.84%). With increase of age, the methylation levels of gene loci were decreased (EDARADD cg09809672, IPO8 cg19722847 and P2RX6 cg05442902) and increased (NHLRC1 cg22736354 and SCGN cg06493994) (all P values<0.05). The established biological age prediction model was as follows: Y=-53.121×EDARADD cg09809672-137.564×IPO8 cg19722847+141.040×NHLRC1 cg22736354-67.893×P2RX6 cg05442902+149.547×SCGNcg06493994+4.592×sex+64.185 (R2=0.86, P<0.001), where Y was the biological age, and the items in the equation were methylation level, sex (male =1, female =2) and intercept in sequence. The Kendall rank correlation coefficient between age gap and telomere length was 0.731 (P<0.001). Compared with the subjects whose age gaP<0, the subjects with age gaP≥0 had higher systolic blood pressure in adolescence [(88.50±8.89) and (109.83±9.48) mmHg, respectively, 1 mmHg=0.133 kPa]; lower TC [(5.48±0.23) and (3.98±0.54) mmol/L, respectively, ] and TG [(3.51±0.32) and (3.41±0.20) mmol/L] in young adults; lower fasting blood glucose in middle age [(6.17±0.67) and (5.37±0.79) mmol/L, respectively, ] and higher diastolic blood pressure in nonagenarian age [(76.99±6.78) and (83.97±9.36) mmHg, respectively, ] (all P values<0.05). Conclusion: The constructed epigenetic clock model can be used to evaluate and calibrate human biological age.

[A case-control study on the relationship between DNA methylation and occupational noise hearing loss].

Objective: To explore the relationship between DNA methylation and occupational noise-induced hearing loss. Methods: A case-control study was conducted. People with hearing loss induced by occupational noise were recruited as the case group and those with normal hearing but still exposed to occupational noise were recruited as the control group. A total of 60 participants were included, of which 30 participants were in the case group and 30 in the control group. The methylation level was detected by 850k genome-wide DNA methylation chip technology. The significance of differential methylated position (DMP) was tested by R-packet 'Champ'. The differential methylated region (DMR) was analyzed by using Champ's Bumphunter algorithm. Cluster profiler was used to analyze the gene list for GO and KEGG pathway enrichment. Results: There was significant difference between two groups in binaural high-frequency average hearing threshold (P<0.05), but there was no significant difference in age, smoking, drinking, hypertension, physical exercise and cumulative noise exposure. The results of DMP and DMR analysis showed that 713875 sites were detected in the case group and the control group, and 439 methylation sites with significant difference, accounting for 0.06%; 650 regions were detected, and 72 methylation regions with significant differences, accounting for 11.08%. Compared with the control group, the results of GO enrichment analysis showed that the case group had statistically significant differences in four pathways: axogenesis of projection neurons in the central nervous system, neuronal development in the central nervous system, axogenesis of neurons in the central nervous system and neuronal differentiation in the central nervous system. KEGG enrichment analysis showed that there were significant differences in sphingolipid metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis pathway between the case group and the control group. Conclusion: The occurrence of occupational noise-induced hearing loss may be related to the regulation of gene expression related to axogenesis of projection neurons in the central nervous system, development of neurons in the central nervous system, axogenesis of neurons in the central nervous system, differentiation of neurons in the central nervous system, sphingolipid metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis and gene methylation related to metabolism.

Application of ultrasound-based radiomics technology in fetal-lung-texture analysis in pregnancies complicated by gestational diabetes and/or pre-eclampsia.

OBJECTIVES: To analyze and compare, using ultrasound-based radiomics technology, fetal-lung texture in pregnancies affected by gestational diabetes mellitus (GDM) and/or pre-eclampsia (PE) and in normal pregnancies, overall and at different gestational ages. METHODS: In this retrospective study, 430 high-throughput features per fetal-lung image were extracted from 548 fetal-lung ultrasound images (obtained at the level of the four-chamber view of the heart) in 548 pregnant women who delivered between July 2018 and August 2019 at the Obstetrics and Gynecology Hospital of Fudan University. Images had been obtained during ultrasound examinations between 28 and 41 weeks of gestation. The data were divided randomly into training set (80% of fetal-lung images) and independent test set (20% of images), and 20% of the images in the training set were then selected as the validation set. A standard machine-learning model based on ultrasound-based radiomics technology was created using features of fetal-lung texture extracted from the images, and a regression model was used to evaluate the relationship between lung-texture features, GDM and/or PE and gestational age. RESULTS: Of the 548 pregnancies included, 108 were affected by GDM alone, 71 by PE alone and 25 by both GDM and PE, and 344 were normal. The overall performance of the GDM and PE prediction model was superior to that of the gestational-age prediction model, with an area under the receiver-operating-characteristics curve of 0.95-0.99, sensitivity of 78.8-97.1% in the validation set and 74.5-91.3% in the independent test set, specificity of 79.8-94.3% in the validation set and 75.7-88.4% in the independent test set and accuracy of 81.0-95.3% in the validation set and 80.6-86.4% in the independent test set. CONCLUSIONS: Using ultrasound-based radiomics technology, fetal lungs from pregnancies grouped according to whether they were affected by GDM and/or PE could be distinguished from each other and from fetal lungs of normal pregnancies, and lungs from pregnancies at different gestational ages could be distinguished. These findings support further research to explore the use of this non-invasive technology to predict neonatal respiratory complications in women with PE, GDM or their combination. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Spatial and temporal organization of jejunal microbiota in goats during animal development process.

AIMS: This research aimed to investigate the temporal bacterial colonization relating to non-rumination, transition and rumination phases, together with the spatial organization of microbial community in the jejunal mucosa and digesta of goats. METHODS AND RESULTS: This study explored the colonization programme of the jejunal microbiota by employing 16S rRNA amplicon sequencing. The colonization pattern of jejunal bacterial community exhibited an age- and gut region-dependent progression during animal development process. Approximately 268 bacterial signatures contributed to the discrimination between gut regions, with Lactobacillus, Ruminococcus, Eubacterium and Clostridium_sensu_stricto were enriched in the jejunal digesta, and Bacteroides and unclassified bacteria were enriched in the jejunal mucosa. Intriguingly, a shift from Lactobacillus to Butyrivibrio, Eubacterium and Ruminococcus after d 20 was observed for jejunal digesta. In mucosa, Bifidobacterium, Corynebacterium, Faecalibacterium and Roseburia increased with age (P < 0·05) while Arcobacter, Bacteroides and Porphyromonas peaked at d 10. CONCLUSIONS: The jejunal bacterial community was settled after solid starter provision, which may mark the potential boundary of a timeframe for intervention in goats. The spatial heterogeneity highlighted the complicacy of ecological niches during manipulation of gut microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study extended the understanding of microbial programming and niche specific in the jejunum among different life stages and the basal cognition of persistent enhancement of nutrient utilization and decline of enteric diseases in ruminants.

Double-cone ignition scheme for inertial confinement fusion.

While major progress has been made in the research of inertial confinement fusion, significant challenges remain in the pursuit of ignition. To tackle the challenges, we propose a double-cone ignition (DCI) scheme, in which two head-on gold cones are used to confine deuterium-tritium (DT) shells imploded by high-power laser pulses. The scheme is composed of four progressive controllable processes: quasi-isentropic compression, acceleration, head-on collision and fast heating of the compressed fuel. The quasi-isentropic compression is performed inside two head-on cones. At the later stage of the compression, the DT shells in the cones are accelerated to forward velocities of hundreds of km s-1. The head-on collision of the compressed and accelerated fuels from the cone tips transfer the forward kinetic energy to the thermal energy of the colliding fuel with an increased density. The preheated high-density fuel can keep its status for a period of approximately 200 ps. Within this period, MeV electrons generated by ps heating laser pulses, guided by a ns laser-produced strong magnetic field further heat the fuel efficiently. Our simulations show that the implosion inside the head-on cones can greatly mitigate the energy requirement for compression; the collision can preheat the compressed fuel of approximately 300 g cm-3 to a temperature above keV. The fuel can then reach an ignition temperature of greater than 5 keV with magnetically assisted heating of MeV electrons generated by the heating laser pulses. Experimental campaigns to demonstrate the scheme have already begun. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 1)'.

Quantification of late gadolinium enhancement cardiovascular MRI in patients with coronary artery chronic total occlusion.

AIM: To determine the most accurate and reproducible semi-automated greyscale thresholding technique for quantifying late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMRI), by using positron-emission tomography (PET) as the reference standard in patients with coronary artery chronic total occlusion (CTO). MATERIALS AND METHODS: LGE in CMRI, single-photon-emission computed tomography (SPECT), and PET were performed within 1 week in each of 63 patients with known CTO. The presence and quantity of LGE were determined with greyscale thresholds of 2, 4, 5, 6, and 8 standard deviations (SDs) above the mean signal intensity for normal remote myocardium and full width at half maximum (FWHM). The infarcted myocardium was delineated by PET. RESULTS: Sixty-three patients and 1,008 segments were analysed. Based on patient analysis, with PET as the reference standard, the 5 SD method yielded the strongest correlation (r=0.85, p<0.0001) compared with the 2 SDs (r=0.42), 4 SDs (r=0.73), 6 SDs (r=0.81), 8 SDs (r=0.71), and FWHM (r=0.69; p<0.001 for all comparisons). The 5 SDs threshold quantification showed high interobserver and intra-observer agreement (intraclass correlation coefficient [ICC]=0.90, p<0.0001; ICC=0.93, p<0.0001, respectively). CONCLUSIONS: Semi-automated LGE CMRI greyscale thresholding with 5 SDs above the mean signal intensity for normal remote myocardium yields the strongest correlation to the extent of LGE identified using PET and is highly reproducible in patients with CTO.

[Associations of impaired glucose metabolism with chronic peridontitis in pre-diabetes patients].

OBJECTIVE: To investigate the associations of impaired glucose metabolism and insulin resistance with chronic periodontitis in pre-diabetes patients. METHODS: A cross-sectional analysis was conducted and we included a total of 171 pre-diabetes patients aged 30-65 years, free of diabetes. pre-diabetes was defined as impaired fasting glucose (IFG) [fasting glucose (FG): 6.1-7.0 mmol/L] and/or impaired glucose tolerance (IGT) [oral glucose tolerance test (OGTT): 7.8-11.0 mmol/L]. Chronic periodontitis was defined according to Centers for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) definition and the patients were divided into mild, moderate, and severe chronic periodontitis groups [mild: at least two interproximal sites with clinical attachment loss (CAL) ≥3 mm and at least two interproxima sites with probing depth (PD) ≥4 mm or 1 site with PD≥5 mm; moderate: at least two interproximal sites with CAL ≥4 mm and at least two interproxima sites with at least two interproximal sites with PD ≥5 mm; severe: at least two interproximal sites with CAL ≥6 mm and at least one interproxima site with at least two interproximal sites with PD≥5 mm]. A periodontal examination indexes [plaque index (PLI), PD, CAL, and bleeding on probing (BOP)] and glucose metabolism indexes [FG, OGTT, hemoglobinA1c (HbA1c), fasting insulin and homeostasis model assessments of insulin resistance (HOMA-IR)] were measured. The association of glucose metabolism and chronic periodontitis was investigated by multivariable logistic regression analysis. RESULTS: FG in the moderate and severe chronic periodontitis groups was significantly higher compared with mild chronic periodontitis group, HOMA-IR in the moderate and severe chronic periodontitis groups was significantly higher compared with mild chronic periodontitis group, OGTT in the severe chronic periodntitis group was significantly higher compared with mild chronic peridontitis group and moderate chronic periodontitis groups, and there was no significant difference between moderate and mild chronic periodontitis groups. For the insulin and HbA1c, there was no significant difference among mild, moderate and severe chronic periodontitis groups. After multivariable adjustment of age, gender, smoking status, hypertension and body mass index, IFG (OR=1.39, 95%CI: 1.01-1.98) and HOMA-IR (OR=1.36, 95%CI: 1.04-1.76) were associated with moderate periodontitis; IFG (OR=1.64, 95%CI: 1.17-2.40), IGT (OR=1.65, 95%CI: 1.21-2.26), and HOMA-IR (OR=1.72, 95%CI: 1.23-2.41) were significantly associated with severe periodontitis. CONCLUSION: Our data provided evidences that impaired glucose metabolism were associated with chronic periodontitis among pre-diabetes patients.

[Cloning and expression analysis of CpPMM gene in Codonopsis pilosula].

GDP-mannose is an important precursor for the synthesis of Codonopsis pilosula polysaccharides and involved in the synthesis of sugar chains. Phosphomannomutase(PMM)catalyzes the conversion of mannose-6-phosphate(Man-6-P)to mannose-1-phosphate(Man-1-P)to synthesize GDP-mannose. In this study, specific primers were designed based on the PMM gene sequence information in transcriptome data, and the full length of the C. pilosula PMM gene was cloned and named CpPMM. The correlation between the CpPMM gene expression and C. pilosula polysaccharide synthesis was analyzed by a series of bioinformatics analysis, prokaryotic expression and qRT-PCR. The results show that the CpPMM gene contains a 741 bp open reading frame(ORF), encoding 246 amino acids, which is highly similar to the PMM of other species and highly homologous to the Helianthus annuus from the Asteraceae family. It was predicted to be a hydrophilic non-transmembrane protein without signal peptide, which was predicted to be located in the cytoplasm with multiple phosphorylation sites. Combined with predictive analysis of conserved domains, this protein belongs to the HAD(haloacid dehalogenase)superfamily; prokaryotic expression studies show that the size of the CpPMM fusion protein is about 29 kDa, which is consistent with the relative molecular mass predicted. The target protein is an inclusion body and is partially soluble. The qRT-PCR results showed that the CpPMM gene exerted spatiotemporal expression patterns, and the expression level in fruiting period was significantly higher than that in the other three periods such as the flowering period. Along with the growth period of C. pilosula, the polysaccharide content of C. pilosula showed a gradual increase trend, reaching the highest during the harvest time. And there are significant differences in the polysaccharide content of C. pilosula in each period. In this study, the CpPMM gene was cloned from the root of C. pilosula, at the same time, the prokaryotic expression system was constructed. In addition, its gene expression level is highly correlated with the polysaccharide content of C. pilosula. It lays the foundation for further studying the function of CpPMM gene and the analysis of biosynthetic pathways of polysaccharides in medicinal plants.

[Association between GPX1 gene polymorphisms and noise-induced hearing loss].

Objective: To identify association between genetic polymorphism in the Glutathione peroxidase 1 gene (GPX1) and noise-induced hearing loss (NIHL) . Methods: A nested case control study was conducted based on a cohort of noise-exposed subjects. 392 cases were selected from the steel factory in Henan Province, 392 matched control subjects for each case were designated on the basis of the matched criterion including same gender, age (±5years) and duration of exposure to noise (±2years) . Two single nucleotide polymorphisms (SNPs) of GPX1 were genotyped by SNPscanTM multiplex SNP genotyping kit. Hardy-Weinberg equilibrium (HWE) tests were performed using Pearson's χ(2) for each SNP among control group, effects of genotypes of GPX1 on NIHL were analyzed by logistic regression. Results: All two SNPs were in HWE. After adjustment for covariates including smoking status, rs1987628 polymorphism was statistically significantly associated with the NIHL risk under codominant and Dominant inheritance models; In the subjects carrying rs1987628 GA genotype had a higher NIHL risk than those carrying the GG genotype, the adjusted OR value was 1.803 (95%CI 1.215-2.676, P=0.003) . And meanwhile, rs1987628 GA+AA genotype had a higher NIHL risk than those carrying the GG genotype, the adjusted OR value was 1.762 (95%CI 1.197-2.593, P=0.004) . Conclusion: It was suggested that genetic polymorphism in the GPX1 gene might be the genetic susceptible factor for NIHL.

[Association between PON2 gene polymorphisms and susceptibility to noise-induced hearing loss].

Objective: To investigate the relationship between SNP and noise-induced hearing loss (NIHL) susceptibility in occupational noise exposure population in China. Methods: From 6297 for a certain steel works in contact with noise, contact length of 3 years or more and workplace noise exposure intensity of 80 dB (A) , ears or high frequency (3 000, 4 000, 6 000 Hz) average of hearing acuity 40 dB (HL) , or high frequency loss in both ears, on the basis of single whisper frequency (500, 1, 000, 2 000 Hz) average threshold of 26 dB (HL) or object as case group. A case-control study was designed with 1:1 matching. Subjects with the same gender, the same type of work, age ±5 years old, and working age ±2 years after noise exposure were selected as the control group. Subjects with any whisper frequency (500, 1, 000, 2, 000 Hz) whose hearing threshold in any frequency band was ≤25 dB (A) and whose average high-frequency hearing threshold in pure tone hearing test was <35 dB (A) were selected as the control group. Four sites of PON2 gene were genotyped by medium-and high-throughput SNP genotyping. Univariate logistic regression was used to analyze the relationship between single SNP polymorphism and NIHL. Results: A total of 286 case-control pairs were included. Smoking was statistically significant difference between cases and controls (P<0.001) . Conclusion: No statistical difference has been found between single SNP polymorphism and NIHL. At the level of greater than 92 dB of high noise exposure, rs7785846 (CT+TT) genotype is a risk factor for occupational noise deafness, and its OR is 2.74 (95%CI: 1.09-6.89) compared with wild homozygous type (CC) . Conclusion. The rs7785846 (CT+TT) genotype carriers of PON2 gene are more susceptible to hearing impairment when exposed to high noise intensity.

[Relationship research among CDH23 gene and the risk of noise-induced hearing loss].

Objective: To explore the relationship among CDH23 gene variation and the risk of noise-induced hearing loss (NIHL) . Methods: The nested case-control study was performed and this study followed a cohort of 6297 noise-exposed workers in a steel factory of Henan province in China from January 1, 2006 to December 31, 2015. In July 2019, subjects whose average hearing threshold were more than 40 dB in high frequency were defined as the case group, and subjects whose average hearing threshold were less than 35 dB in high frequency and less than 25 dB in speech frequency were defined as the control group. A nested case-control study which included 572 subjects was carried out, in which subjects consisted of 286 cases and 286 controls. 18 single nucleotide polymorphisms (SNPs) in CDH23 were selected and genotyped, then we analyzed the association among SNPs in CDH23, haplotypes in CDH23 and NIHL risk. Logistic regression was performed to analyze the main effects of SNPs and the interactions between CNE and SNPs adjusting cumulative noise exposure (CNE) , smoking, drinking, physical exercise and hypertension. Moreover, the association between haplotypes in CDH23 and NIHL risk were also analyzed. We ananlyzed the relationship amongst different SNP groups and NIHL risk using the generalized multifactor dimensionality reduction (GMDR) method. Results: The results suggested that significant associations were observed for rs3802711, rs3752751, rs3752752, rs11592462, rs10762480, rs3747867 for NIHL overall and/or various CNE strata by adjusting CNE, smoking, drinking, physical exercise and blood pressure. For rs3802711, workers exposure to noise carrying the AA/GA genotype of rs3802711 increased risk of NIHL than those carrying GG genotype (OR=3.121; 95%CI:1.054-9.239, P=0.035) in overall; In the stratified analysis of CNE (>97 dB (A) ·year at rs3802711 locus, workers exposure to noise carrying GA genotype (OR=2.056; 95%CI:1.226~3.448, P=0.006) and GA+AA/GA genotype (OR=2.221; 95%CI:1.340~3.681, P=0.002) increased NIHL risk. For rs11592462, workers exposure to noise carrying the GG genotype of rs11592462 increased risk of NIHL than those carrying CC genotype in overall (OR=3.951; 95%CI:1.104-14.137, P=0.04) ; workers exposure to noise carrying the GG genotype of rs11592462 increased risk of NIHL than those carrying CG+CC genotype in overall (OR=4.06; 95%CI:1.145-14.391, P=0.03) . After adjusting CNE, smoking, drinking, physical exercise and blood pressure, the haplotypes of CDH23 rs1227049, rs10999947, rs3752752, rs3752751, rs10762480, rs3802711, rs11592462, rs10466026, rs4747194, rs4747195 were not associated with the risk of NIHL. GMDR analysis showed no association between SNP combination and NIHL risk after adjusting CNE, smoking, drinking, physical exercise and blood pressure. Conclusion: Gene polymorphisms in CDH23 might associate significantly with the risk of NIHL.

[Association between GSTP1 gene polymorphisms and susceptibility to noise-induced hearing loss].

Objective: To investigate the association between the single nucleotide polymorphisms (SNPS) at rs1695 and rs6591256 in glutathione S-transferase P1 (GSTP1) gene and susceptibility to noise-induced hearing loss in Chinese Han workers exposed to noise. Methods: Using the 1: 1 nested case-control study and taking 6297 workers exposed to noise in a steel plant in Henan province as the cohort study population in July 2019, we screened those who have been exposed to noise for ≥3 years and whose binaural high frequency (3000, 4000, 6000 Hz) average hearing threshold is ≥40 dB (A) into the case group. The control group was selected according to the matching criteria of the same sex, same type of work, and the age difference was not more than 5 years old, and the working age difference was not more than 2 years. 276 subjects were selected into the case group and the control group respectively. The medium and high throughout single nucleotide polymorphism typing technology (SNPscanTM technology) was used to detect the polymorphism of three nucleotide sites of GSR gene, and conditional logistic regression was used to analyze the relationship between single nucleotide polymorphism (SNP) and NIHL, and the relationship between different polymorphic sites and the risk of NIHL after adjusting covariates. After stratification with different cumulative noise exposure (CNE) , Conditional logistic regression analysis was used to analysis the risk of NIHL at different loci. Results: The mean and standard deviation of age of the selected subjects was (40.28±8.00) , the mean and standard deviation of noise-exposed working years was (18.7±8.92) years. The range of noise exposure levels and comulative noise exposure were 80.05-93.35dB (A) and 86.83-107.92 dB (A) ·year, respectively. Compared with the control group, there were no statistically significant differences in age, noise-exposured working years, intensity of noise exposure, CNE, gender, drinking, hypertension prevalence and noise exposure level in the hearing loss group (P>0.05) , while there were statistically difference in smoking, binaural high-frequency average hearing threshold and binaural speech frequency (P<0.05) . After adjusting for smoking, drinking, hypertension and other factors, in the co-dominant model, compared with GGgenotype, the risk of NIHL was higher in rs1002149 GT genotype and rs2251780 GA genotype (OR=1.558, 95%CI: 1.028-2.361; OR=1.550, 95%CI: 1.020-2.355, P<0.05) ; compared with TT/GT genotype, the rs1002149 TT genotype has a higher risk of developing NIHL (OR=1.494, 95%CI: 1.002-2.228, P<0.05) , while rs3779647 genotype had no relationship with the risk of NIHL (P>0.05) . In the equivalent sound level (L(Aeq)) of noise >85 dB (A) stratification, compared with GG genotype, carrying rs1002149 GT genotype and rs2251780 GT genotype has higher risk of nihl (OR=1.801, 95%CI: 1.093-2.967; OR=1.720, 95%CI: 1.050-2.817, P<0.05) . Haplotype analysis of two sites, rs1002149 and rs2251780, was not found to be related to NIIHL susceptibility. Conclusion: The allele G of rs1695 and rs6591256 may be risk factors of NIHL.

AID and TET2 co-operation modulates FANCA expression by active demethylation in diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is traced to a mature B malignance carrying abnormal activation-induced cytidine deaminase (AID) expression. AID activity initially focuses on deamination of cytidine to uracil to generate somatic hypermutation and class-switch recombination of the immunoglobulin (Ig), but recently it has been implicated in DNA demethylation of genes required for B cell development and proliferation in the germinal centre (GC). However, whether AID activity on mutation or demethylation of genes involves oncogenesis of DLBCL has not been well characterized. Our data demonstrate that the proto-oncogene Fanconi anaemia complementation group A (FANCA) is highly expressed in DLBCL patients and cell lines, respectively. AID recruits demethylation enzyme ten eleven translocation family member (TET2) to bind the FANCA promoter. As a result, FANCA is demethylated and its expression increases in DLBCL. On the basis of our findings, we have developed a new therapeutic strategy to significantly inhibit DLBCL cell growth by combination of the proteasome inhibitor bortezomib with AID and TET2 depletion. These findings support a novel mechanism that AID has a crucial role in active demethylation for oncogene activation in DLBCL.

Evaluating consumptive and nonconsumptive predator effects on prey density using field time-series data.

Determining the degree to which predation affects prey abundance in natural communities constitutes a key goal of ecological research. Predators can affect prey through both consumptive effects (CEs) and nonconsumptive effects (NCEs), although the contributions of each mechanism to the density of prey populations remain largely hypothetical in most systems. Common statistical methods applied to time-series data cannot elucidate the mechanisms responsible for hypothesized predator effects on prey density (e.g., differentiate CEs from NCEs), nor can they provide parameters for predictive models. State-space models (SSMs) applied to time-series data offer a way to meet these goals. Here, we employ SSMs to assess effects of an invasive predatory zooplankter, Bythotrephes longimanus, on an important prey species, Daphnia mendotae, in Lake Michigan. We fit mechanistic models in an SSM framework to seasonal time series (1994-2012) using a recently developed, maximum-likelihood-based optimization method, iterated filtering, which can overcome challenges in ecological data (e.g., nonlinearities, measurement error, and irregular sampling intervals). Our results indicate that B. longimanus strongly influences D. mendotae dynamics, with mean annual peak densities of B. longimanus observed in Lake Michigan estimated to cause a 61% reduction in D. mendotae population growth rate and a 59% reduction in peak biomass density. Further, the observed B. longimanus effect is most consistent with an NCE via reduced birth rates. The SSM approach also provided estimates for key biological parameters (e.g., demographic rates) and the contribution of dynamic stochasticity and measurement error. Our study therefore provides evidence derived directly from survey data that the invasive zooplankter B. longimanus is affecting zooplankton demographics and offer parameter estimates needed to inform predictive models that explore the effect of B. longimanus under different scenarios, such as climate change.

[Occlusal changes before and after orthodontic treatment in patients with aggressive periodontitis].

OBJECTIVE: To evaluate the efficacy of occlusal improvement in the labial fixed orthodontic treatment in aggressive periodontitis patients and to explore the relationship between occlusal improvement and inflammation control. METHODS: Twenty-two aggressive periodontitis patients who underwent combined periodontal-orthodontic treatment were included in this study. The patient's photos were matched to the dental models and digital three dimentional models were acquired using 3Shape R700 laser scanner. The occlusal force distribution maps were generated in the OrthoAnalyzer software. The newly established occlusal force distribution score (OFDS) and proximal contact score (PCS) were used to evaluate the occlusal distribution changes before and after labial fixed orthodontic treatment for assessing the effectiveness of orthodontic treatment. The multi-level linear regression analysis was used to explore the relationship between the probing depth changes and OFDS or PCS changes to screen out the favorable orthodontic strategy for inflammation control, which would provide clinical strategy for combined periodontal-orthodontic treatment in aggressive periodontitis patients. RESULTS: At the patient level, OFDS was improved significantly after orthodontic treatment compared with the score before orthodontic treatment (84.5±20.9 vs.105.3±22.6, P <0.001) and PCS was improved significantly after orthodontic treatment compared with the score before orthodontic treatment (68.9±9.1 vs. 83.7±6.3, P <0.001).At the tooth level, the OFDS was significantly increased in the maxillary anterior teeth (P <0.001) while the PCS of the anterior teeth in both maxillary and mandible arches were significantly increased significantly (P <0.01). No significant changes were found in other tooth positions. The multilevel linear regression model showed that no significant correlation was found between age and gender and probing depth decrease (P >0.05). The baseline probing depth,OFDS improvements and PCS improvements (P <0.001) were positively correlated with probing depth decrease. CONCLUSION: This study showed that the distribution of occlusal force was more reasonable and the proximal contacts were more ideal in aggressive periodontitis patients. Orthodontic treatment was effective in improving occlusal force distribution by the above two ways. Especially, the OFDS and PCS improvements were both positively correlated with probing depth decrease, indicating that in the combined periodontal-orthodontic treatment for aggressive periodontitis patients, occlusal force distribution and proximal contact should be improved in order to facilitate periodontal improvement.

[Effect of orthodontic tooth movement on keratinized gingival width].

OBJECTIVE: The relationship between the orthodontic tooth movement and the change of keratinized gingival width was analyzed by measuring the keratinized gingival width and position of the teeth before and after 28 orthodontic treatments. METHODS: The photos were matched to the model and the width of the keratinized gingival was obtained by measuring the length of the crown, and the keratinized gingiva. The pre- and post-treatment models were overlapped on rapidform 2006 and the change of tooth position before and after orthodontic movement could be accurately measured, and the relationship between tooth intrusion and extrusion, retraction and forward movement, torque variation and keratinized gingival width was statistically investigated. RESULTS: Analysis of the correlation between data before and after treatments for 213 teeth in 28 patients revealed a strong correlation between changes in tooth torque angle and changes in keratinized gingiva width (r=-0.47, P<0.001). In the multi-level linear regression analysis, the correlation between them was verified (regression coefficient<0, P<0.001), and there was no significant correlation between the intrusion and retraction of the teeth and the change of the width of keratinized gingiva (P>0.05). Regression coefficient was negatively relative to the reference incisor between the teeth for the canines and premolars (canine regression coefficient=-0.35, premolar regression coefficient=-0.38, P<0.05). Therefore, the study found that there was a strong negative correlation between the changes in tooth torque angle and width of keratinized gingival (r=-0.41, P<0.001), that is, an increase in positive torque led to the reduction of width of keratinized gingiva, and on the contrary the increase of negative torque would cause the width of keratinized gingiva increase. There was no significant correlation between the intrusion and extrusion of the teeth for the width of keratinized gingiva. The sensitivity of different teeth for the width of keratinized gingiva differed, with incisor compared with canines and premolars that were more prone to keratinized gingiva width changes. CONCLUSION: Tooth movement during orthodontics affected the width of the keratinized gingiva width, and the increase in positive torque was more likely to cause a reduction in the width of keratinized gingiva. There was no significant correlation between the intrusion and retraction of the teeth and the change in the width of keratinized gingiva. Incisors were more prone to changes in the width of keratinized gingiva relative to the cuspids and premolars during tooth movement. In the orthodontic process, it is possible to predict the effect of changes in the position of the teeth on the keratinized gingiva width, and attention shoud be to the changes in the keratinized gingiva width.

[Tooth loss and multivariable analysis after 5-year non-surgical periodontal treatment on molars with furcation involvement].

OBJECTIVE: To evaluate the tooth loss status of mandibular molars with furcation involvements after 5-year non-surgical periodontal treatment, and to analyze the factors that affected the tooth loss. METHODS: A retrospective analysis was conducted in 79 patients with chronic periodontitis, who had received non-surgical periodontal treatment and 5 years of periodontal maintenance treatment in Department of Periodontology, Peking University School and Hospital of Stomatology from 1988 to 2012. Their clinical indexes, including probing depth (PD), bleeding index (BI), furcation index (FI) and tooth mobility were both evaluated before treatment and at the last time of the maintenance treatment. Bone resorption at furcation area was measured at the first visit by periapical radiographs taken by professional doctors of medical imaging. The status of tooth loss after 5-year non-surgical periodontal treatment on mandibular molars with furcation involvement, and the factors that affected the tooth loss were analyzed. RESULTS: (1) Non-surgical treatment was significantly effective on the changes of PD in the patients of chronic periodontitis with furcation involvement, while the presence of furcation involvement could affect the improvement of PD here. (2) PD at the furcation area, tooth mobility, vertical bone resorption, and bone resorption area were all significant risk factors of mandibular molar missing (P<0.001), and the same with FI=3 and FI=4 (P=0.017, P=0.007), while age (P=0.703), gender (P=0.243) and smoking history (P=0.895) were not related to the tooth loss in this study. (3) The risk of tooth loss in mandibular molars with FI≥3 were significantly higher than those with FI≤2, and the survival rate of the former was less than 50%. CONCLUSION: The loss of mandibular molars with furcation involvement was related to the furcation involvement, meanwhile the degree of furcation involvement and bone resorption can significantly increase the risk of tooth loss.