A small proton charge radius from an electron-proton scattering experiment.

Elastic electron-proton scattering (e-p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, rp. In 2010, a new method using muonic hydrogen atoms1 found a substantial discrepancy compared with previous results2, which became known as the 'proton radius puzzle'. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen3,4. Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e-p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e-p experiments and enabled measurements at very small forward-scattering angles. Our result, rp = 0.831 ± 0.007stat ± 0.012syst femtometres, is smaller than the most recent high-precision e-p measurement5 and 2.7 standard deviations smaller than the average of all e-p experimental results6. The smaller rp we have now measured supports the value found by two previous muonic hydrogen experiments1,7. In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant8-one of the most accurately evaluated fundamental constants in physics.

A novel bivalent anti-c-MET/PD-1 bispecific antibody exhibits potent cytotoxicity against c-MET/PD-L1-positive colorectal cancer.

Previously, we generated a novel bispecific antibody (BsAb) simultaneously targeting both c-MET and PD-1 (PDCD1), which can bridge T cells and c-MET positive tumor cells. However, the specific mechanisms and antitumor activities of the BsAb against c-MET/PD-L1 (CD274) positive colorectal cancer (CRC) is not completely understood. In this study, in addition to the tumor intrinsic mechanism investigation with molecular biology assay in vitro, a humanized mouse model was used to evaluate antitumor activity of the BsAb in vivo. The BsAb could inhibit c-MET/PD-L1+ CRC cell migration and show strong antitumor activity against HCT116 tumors in mice, potentially by inducing the degradation of c-MET protein in a dose and time-dependent manner. The BsAb could suppress the phosphorylation of c-MET downstream proteins GRB2-associated-binding protein 1 (Gab1) and focal adhesion kinase (FAK). Considering the tumor extrinsic mechanism, the BsAb may promote phagocytosis of macrophage. Furthermore, the level of plasma exosomal-c-MET/PD-L1 is able to distinguish CRC patients from healthy controls. In summary, the BsAb exhibited potent anti-tumor activities by two distinguished mechanisms: inhibition of c-MET signal transduction and promotion of macrophage-mediated phagocytosis. Our BsAb may provide a novel therapeutic agent for patients with c-MET/PD-L1+ CRC, and the status of exosomal-c-MET/PD-L1 can serve as a biomarker to predict responsiveness to treatment of our BsAb.

[Knockdown of ACC1 promotes migration of esophageal cancer cell].

Objective: To investigate the effect of acetyl-CoA carboxylase 1 (ACC1) knockdown on the migration of esophageal squamous cell carcinoma (ESCC) KYSE-450 cell and underlying mechanism. Methods: Lentiviral transfection was conducted to establish sh-NC control cell and ACC1 knocking down cell (sh-ACC1). Human siRNA HSP27 and control were transfected by Lipo2000 to get si-HSP27 and si-NC. The selective acetyltransferase P300/CBP inhibitor C646 was used to inhibit histone acetylation and DMSO was used as vehicle control. Transwell assay was performed to detect cell migration. The expression of HSP27 mRNA was examined by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and the expressions of ACC1, H3K9ac, HSP27 and epithelial-mesenchymal transition-related proteins E-cadherin and Vimentin were detected by western blot. Results: The expression level of ACC1 in sh-NC group was higher than that in sh-ACC1 group (P<0.01). The number of cell migration in sh-NC group was (159.00±24.38), lower than (361.80±26.81) in sh-ACC1 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC group were statistically significant compared with sh-AAC1 group (P<0.05). The migrated cell number in sh-NC+ si-NC group was (189.20±16.02), lower than (371.60±38.40) in sh-ACC1+ si-NC group (P<0.01). The migrated cell number in sh-NC+ si-NC group was higher than that in sh-NC+ si-HSP27 group (152.40±24.30, P<0.01), and the migrated cell number in sh-ACC1+ si-NC group was higher than that in sh-ACC1+ si-HSP27 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC+ si-NC group were significantly different from those in sh-ACC1+ si-NC and sh-NC+ si-HSP27 groups (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-ACC1+ si-NC group were significantly different from those in sh-ACC1+ si-HSP27 group (P<0.01). After 24 h treatment with C646 at 20 µmmo/L, the migrated cell number in sh-NC+ DMSO group was (190.80±11.95), lower than (395.80±17.10) in sh-ACC1+ DMSO group (P<0.01). The migrated cell number in sh-NC+ DMSO group was lower than that in sh-NC+ C646 group (256.20±23.32, P<0.01). The migrated cell number in sh-ACC1+ DMSO group was higher than that in sh-ACC1+ C646 group (87.80±11.23, P<0.01). The protein expressions of H3K9ac, HSP27, E-cadherin and Vimentin in sh-NC+ DMSO group were significantly different from those in sh-ACC1+ DMSO group and sh-NC+ C646 group (P<0.01). The protein expression levels of H3K9ac, HSP27, E-cadherin and Vimentin in sh-ACC1+ DMSO group were significantly different from those in sh-ACC1+ C646 group (P<0.01). Conclusion: Knockdown of ACC1 promotes the migration of KYSE-450 cell by up-regulating HSP27 and increasing histone acetylation.

[Follow-up analysis of sex hormone levels and prognosis in women after hematopoietic stem cell transplantation].

Objective: To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT. Methods: Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results: The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions: The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

Measurement of the Nucleon F_{2}

The ratio of the nucleon F_{2} structure functions, F_{2}^{n}/F_{2}^{p}, is determined by the MARATHON experiment from measurements of deep inelastic scattering of electrons from ^{3}H and ^{3}He nuclei. The experiment was performed in the Hall A Facility of Jefferson Lab using two high-resolution spectrometers for electron detection, and a cryogenic target system which included a low-activity tritium cell. The data analysis used a novel technique exploiting the mirror symmetry of the two nuclei, which essentially eliminates many theoretical uncertainties in the extraction of the ratio. The results, which cover the Bjorken scaling variable range 0.19

Three genetic-environmental networks for human personality.

Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are jointly organized and develop in an integrated manner. In three large independent genome-wide association studies from Finland, Germany, and Korea, we used a data-driven machine learning method to uncover joint phenotypic networks of temperament and character and also the genetic networks with which they are associated. We found three clusters of similar numbers of people with distinct combinations of temperament and character profiles. Their associated genetic and environmental networks were largely disjoint, and differentially related to distinct forms of learning and memory. Of the 972 genes that mapped to the three phenotypic networks, 72% were unique to a single network. The findings in the Finnish discovery sample were blindly and independently replicated in samples of Germans and Koreans. We conclude that temperament and character are integrated within three disjoint networks that regulate healthy longevity and dissociable systems of learning and memory by nearly disjoint sets of genetic and environmental influences.

What is an appropriate caesarean delivery rate for China: a multicentre survey.

OBJECTIVE: To assess the current status of caesarean delivery (CD) in China, propose reference CD rates for China overall, and by regions, investigate the main indications for CDs and identify possible areas for safe reduction. DESIGN: A multicentre cross-sectional study. SETTING: A total of 94 hospitals across 23 provinces in China. POPULATION: A total of 73 977 randomly selected deliveries. METHODS: We used a modified Robson classification to characterise CDs in subgroups and by regions, and the World Health Organization (WHO) C-Model to calculate reference CD rates. MAIN OUTCOME MEASURES: CD rates in China. RESULTS: In 2015-2016, the overall CD rate in China was 38.9% (95% CI 38.6-39.3%). Considering the obstetric characteristics of the population, the multivariable model-based reference CD rate was estimated at 28.5% (95% CI 28.3-28.8%). Accordingly, an absolute reduction of 10.4% (or 26.7% relative reduction) may be considered. The CD rate varied substantially by region. Previous CD was the most common indication in all regions, accounting for 38.2% of all CDs, followed by maternal request (9.8%), labour dystocia (8.3%), fetal distress (7.7%) and malpresentation (7.6%). Overall, 12.7% of women had prelabour CDs, contributing to 32.8% of the total CDs. CONCLUSIONS: Nearly 39% of births were delivered by caesarean in China but a reduction of this rate by a quarter may be considered attainable. Repeat CD contributed more than one-third of the total CDs. Given the large variation in maternal characteristics, region-specific or even hospital-specific reference CD rates are needed for precision management of CD. TWEETABLE ABSTRACT: The caesarean rate in 2015-2016 in China was 38.9%, whereas the reference rate was 28.5%.

The influence of CYP2R1 polymorphisms and gene-obesity interaction with hypertension risk in a Chinese rural population.

BACKGROUND AND AIMS: Several studies have reported that variants in CYP2R1 have been linked with an increased risk of hypertension. However, the interaction between CYP2R1 variants and environmental factors on the susceptibility of hypertension remained unclear. Therefore, this study evaluated the influence of CYP2R1 polymorphisms on hypertension susceptibility, and explored the interaction effect of CYP2R1 variations and obesity on the disease. METHODS AND RESULTS: We included 766 incident hypertension cases matched with non-hypertension controls in a 1:1 ratio by sex, age (within 3 years). Two loci in CYP2R1 gene (rs10766197 and rs12794714) were genotyped by TaqMan probe assays. The concentration of 25-hydroxyvitamin-D was determined by human enzyme-linked immunosorbent assay (ELISA) kits. The associations of CYP2R1 polymorphisms and risks of vitamin D deficiency (VDD) were analyzed by logistic regression. Multifactor dimensionality reduction (MDR) was used to analyze the gene-environment interaction. Multiple logistic regression was used to examine the effect of CYP2R1 gene variations, and the interaction between CYP2R1 variation and obesity on hypertension susceptibility. The results showed that rs10766197 (GG vs. AA) and rs12794714 (GG vs. AA) polymorphisms were both associated with an increased risk of VDD (OR = 1.49, 95% confidence interval (CI) = 1.08-2.05 and OR = 1.63, 95% CI = 1.19-2.25, respectively), after adjustment for potential risk factors. We also found that rs12794714 polymorphism was significantly associated with elevated risk of hypertension under the dominant model (OR = 1.26, 95% CI = 1.01-1.56). In addition, the interactions between rs12794714 with both general obesity (OR = 3.93, 95% CI = 2.72-5.68) and central obesity (OR = 3.22, 95% CI = 2.29-4.52) have significant effects on hypertension susceptibility. CONCLUSIONS: The study provided further evidence that CYP2R1 variation was associated with a higher risk of hypertension in Chinese rural population. The interaction between CYP2R1 rs12794714 and obesity may increase the risk of hypertension.

Risk factors for progression of Urolith Associated with Obstructive Urosepsis to severe sepsis or septic shock.

INTRODUCTION: To analyze the risk factors for progression of urolith associated with obstructive urosepsis to severe sepsis or septic shock, we had done the retrospective cross-sectional study, which would facilitate the early identification of high-risk patients. MATERIALS AND METHODS: Datas were retrospectively reviewed from 160 patients, suffering from obstructive urosepsis associated with urolith between December 2013 and December 2019. There were 49 patients complicating by severe sepsis (severe sepsis group), 12 patients complicating by septic shock (septic shock group), and 99 patients without progressing to severe sepsis or septic shock (sepsis group). The data covered age, gender, BMI (body mass index), time interval from ED (emergency department) to admission, WBC count (white blood cell count), NLR (neutrophil/lymphocyte ratio), HGB (hemoglobin), etc. Datas were analyzed by univariate analyses and multivariate logistic regression analysis. The corresponding nomogram prediction model was drawn according to the regression coefficients. RESULTS: Univariate analysis showed that the differences of age, the time interval from ED to admission, history of diabetes mellitus, history of CKI (chronic kidney disease), NLR, HGB, platelet count, TBil (total bilirubin), SCr (serum creatinine), ALB (albumin), PT (prothrombin time), APTT (activated partial thromboplastin time), INR (international normalized ratio), PCT (procalcitonin), and positive rate of pathogens in blood culture were statistically significant (P < 0.05). Multivariatelogistic regression analysis showed that age, SCr, and history of CKI were independent risk factors for progression to severe sepsis, or septic shock (P < 0.05). CONCLUSIONS: Aged ≥ 65 years, SCr ≥ 248 mol/L, and history of CKI were independent risk factors for progression of urolith associated with obstructive urosepsis to severe sepsis or septic shock. We need to pay more attention to these aspects, when coming across the patients with urolithic sepsis.

Real-world efficacy and safety of dupilumab in Chinese patients with atopic dermatitis: a single-centre, prospective, open-label study.

BACKGROUND: Dupilumab, an antibody against interleukin-4 receptor α, has demonstrated elegant efficacy and safety profiles in patients with moderate-to-severe atopic dermatitis (AD). However, the efficacy of dupilumab varies among AD patients, and compared with the Caucasian population, the data of dupilumab for Asian people, especially Chinese AD patients, is very limited. OBJECTIVE: To investigate the efficacy and safety of dupilumab for AD in a real-world Chinese single-centre prospective cohort. METHODS: We enrolled 138 moderate-to-severe AD patients receiving dupilumab treatment at Huashan Hospital, Shanghai, China in this 16-week, single-centre, prospective, open-label study. The patients were evaluated at baseline, 2, 4, 8 and 16 weeks after first dupilumab administration for multiple physician- and patient-reported outcome measures. Blood eosinophil counts and total serum IgE were measured. RESULTS: There were early and sustained improvement in all the efficacy measures evaluated after dupilumab administration. 64.5% AD patients achieved an improvement of ≥75% in the Eczema Area and Severity Index from baseline, and 60.9% patients achieved the Investigator's Global Assessment 0/1 (or a reduction of ≥2 points from baseline) at week 16. The trunk demonstrated the most significantly decreased efficacy score [median decreased 96.24% (interquartile range, 89.04 to 100%)] compared with other body sites. Female (adjusted OR: 2.12, 95% confidence interval: 0.79-5.74) and body mass index (BMI) <24 (3.03; 1.19-7.68) were identified as potential predictive factors of good response; while age >60 (0.57; 0.10-3.28) predicted poor response. Adverse events were reported by 34.1% patients, and facial erythema (13%) and ocular symptoms (10.9%) were the most common. CONCLUSIONS: Dupilumab demonstrated favourable efficacy and well-tolerated safety in Chinese AD patients in real-world practice.

Genetic and phenotypic characteristics of Clostridium (Clostridioides) difficile from canine, bovine, and pediatric populations.

OBJECTIVES: Carriage of Clostridioides difficile by different species of animals has led to speculation that animals could represent a reservoir of this pathogen for human infections. The objective of this study was to compare C. difficile isolates from humans, dogs, and cattle from a restricted geographic area. METHODS: C. difficile isolates from 36 dogs and 15 dairy calves underwent whole genome sequencing, and phenotypic assays assessing growth and virulence were performed. Genomes of animal-derived isolates were compared to 29 genomes of isolates from a pediatric population as well as 44 reference genomes. RESULTS: Growth rates and relative cytotoxicity of isolates were significantly higher and lower, respectively, in bovine-derived isolates compared to pediatric- and canine-derived isolates. Analysis of core genes showed clustering by host species, though in a few cases, human strains co-clustered with canine or bovine strains, suggesting possible interspecies transmission. Geographic differences (e.g., farm, litter) were small compared to differences between species. In an analysis of accessory genes, the total number of genes in each genome varied between host species, with 6.7% of functional orthologs differentially present/absent between host species and bovine-derived strains having the lowest number of genes. Canine-derived isolates were most likely to be non-toxigenic and more likely to carry phages. A targeted study of episomes identified in local pediatric strains showed sharing of a methicillin-resistance plasmid with dogs, and historic sharing of a wide range of episomes across hosts. Bovine-derived isolates harbored the widest variety of antibiotic-resistance genes, followed by canine CONCLUSIONS: While C. difficile isolates mostly clustered by host species, occasional co-clustering of canine and pediatric-derived isolates suggests the possibility of interspecies transmission. The presence of a pool of resistance genes in animal-derived isolates with the potential to appear in humans given sufficient pressure from antibiotic use warrants concern.

[Differential diagnosis model of benign and malignant breast BI-RADS category 4 nodules based on serum SP70 and conventional laboratory indicators].

Objective: To develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS (Breast Imaging Reporting and Data System) category 4 nodules based on serum tumor specific protein 70 (SP70) and conventional laboratory indicators and validate its predictive efficacy. Methods: A case-control study design was used to retrospectively analyze the data of 429 female patients diagnosed with BI-RADS category 4 breast nodules by breast color doppler flow imaging at the First Affiliated Hospital of Nanjing Medical University from January 2021 to April 2022 with an age range of 16 to 91 years and a median age of 50 years, and the patients were divided into a training cohort (314 patients) and a validation cohort (115 patients) according to the inclusion time successively. Using postoperative pathological findings as the"gold standard", univariate and multivariate logistic regression analyses were used to identify the predictor variables used for the model. The nomogram, receiver operating characteristic (ROC) curves and calibration curves were drawn for the prediction model, and the discrimination and calibration of the model were evaluated using the consistency index (C-index) and calibration plots. Results: The postoperative pathological results showed that 286 (66.7%) were malignant nodules and 143 (33.3%) were benign nodules of 429 breast BI-RADS category 4 nodules. The serum SP70 (OR=1.227,95%CI: 1.033-1.458,P=0.020), NLR (OR=1.545,95%CI: 1.047-2.280,P=0.028), LDL-C (OR=2.215, 95%CI: 1.354-3.622, P=0.002), GLU (OR=2.050,95%CI:1.222-3.438,P=0.007), PT (OR=1.383,95%CI: 1.046-1.828,P=0.023), nodule diameter (OR=1.042, 95%CI: 1.008-1.076, P=0.015) and age (OR=1.062,95%CI: 1.011-1.116,P=0.016) were independent risk factors which could be used to distinguish benign and malignant breast BI-RADS category 4 nodules (P<0.05). The nomogram was plotted by the above seven independent variables, and the concordance index (C-index) for the training cohort and validation cohort were 0.842 (95%CI:0.786-0.898) and 0.787 (95%CI:0.687-0.886), respectively. The sensitivity and specificity of using this model to identify benign and malignant breast BI-RADS category 4 nodules in the training and validation cohort were 83.5%, 72.5% and 79.2%, 73.6%, respectively. The calibration curves showed good agreement between the predicted and actual values in the nomogram. Conclusions: This study combined serum SP70, conventional laboratory indicators and breast color doppler flow imaging to develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS category 4 nodules. The model may have good predictive efficacy and may provide a basis for clinical treatment options, which is beneficial for guiding breast cancer screening and prevention.

Donor-specific phenotypic variation in hiPSC cardiomyocyte-derived exosomes impacts endothelial cell function.

Exosomes are an important mechanism of cell-cell interaction in the cardiovascular system, both in maintaining homeostasis and in stress response. Interindividual differences that alter content in exosomes may play a role in cardiovascular disease pathology. To study the effect of interindividual cardiomyocyte (CM) variation, we characterized exosomal content in phenotypically diverse human induced pluripotent stem cell-derived CMs (hiPSC-CMs). Cell lines were generated from six participants in the HyperGEN cohort: three with left ventricular hypertrophy (LVH) and three with normal left ventricular mass (LVM). Sequence analysis of the intracellular and exosomal RNA populations showed distinct expression pattern differences between hiPSC-CM lines derived from individuals with LVH and those with normal LVM. Functional analysis of hiPSC-endothelial cells (hiPSC-ECs) treated with exosomes from both hiPSC-CM groups showed significant variation in response, including differences in tube formation, migration, and proliferation. Overall, treatment of hiPSC-ECs with exosomes resulted in significant expression changes associated with angiogenesis and endothelial cell vasculogenesis. However, the hiPSC-ECs treated with exosomes from the LVH-affected donors exhibited significantly increased proliferation but decreased tube formation and migration, suggesting angiogenic dysregulation.NEW & NOTEWORTHY The intracellular RNA and the miRNA content in exosomes are significantly different in hiPSC-CMs derived from LVH-affected individuals compared with those from unaffected individuals. Treatment of endothelial cells with these exosomes functionally affects cellular phenotypes in a donor-specific manner. These findings provide novel insight into underlying mechanisms of hypertrophic cell signaling between different cell types. With a growing interest in stem cells and exosomes for cardiovascular therapeutic use, this also provides information important for regenerative medicine.

New biomarker for lung cancer - focus on circSETD3.

In order to explore the mechanism of gefitinib-acquired resistance in lung cancer, a new biomarker has been developed for early clinical diagnosis and intervention; human NSCLC (Non-Small Cell Lung Cancer) cell lines H292 (denoted as H292S) and PC9 (denoted as PC9S) were used to establish gefitinib-resistant NSCLC cell lines H292 and PC9 models. CCK-8 (Cell Counting Kit-8) method was used to test the drug resistance of the cells. circRNAs (circular RNAs) that were differentially expressed before and after resistance were screened by RNA sequencing technology. The effects of circSETD3 overexpression and interference on the sensitivity of gefitinib was observed to analyze the nuclear localization of circSETD3 and verify the interaction between circSETD3-miR-520h-ABCG2. The results showed that the most significant change in differential expression of human NSCLC cell lines before and after drug resistance was hsa_circ_0000567, that is, circSETD3, which is mainly present in the cytoplasm. In H292S and PC9S, compared with the negative control group, the cell proliferation ability of the overexpression group was significantly increased, and the apoptosis ability was significantly decreased. In H292R and PC9R, compared with the negative control group, the proliferation ability of the interference group was significantly decreased, and the apoptosis ability was significantly increased. Overexpression of circSETD3 to H292S and PC9S, the expression of ABCG2 increased significantly. Also, the expression of ABCG2 decreased significantly after transfection with miR-520h mimics. H292R and PC9R interfered with circSETD3, the expression of ABCG2 decreased significantly. Moreover, the expression of ABCG2 increased significantly after transfection with miR-520h inhibitor. In conclusion, circSETD3 can be used as a novel biomarker for lung cancer. It relieves miR-520h degradation of the transporter ABCG2 by down-regulating the miR-520h expression, causing gefitinib to be pumped out of the cell.

[Effects of protein disulfide isomerase on hyperglycemia and hypoxia/reoxygenation injury in H9c2 cardiomyocytes].

Objective: To explore the effect of protein disulfide isomerase (PDI) in diabetic ischemic heart disease. Methods: We established an in vitro model of high glucose and hypoxia/reoxygenation in H9c2 rat myocardial cells. Cultured cells were divided into four groups: Control, high glucose (HG), hypoxia/reoxygenation (H/R) and HG+H/R. Changes in PDI expression mediated by PDI adenovirus(Ad-PDI) infection and siRNA(PDI-siRNA) transfection in myocardial cells were observed by inverted fluorescence microscopy. We also measured lactate dehydrogenase(LDH) activity and malondialdehyde(MDA) and high molecular weight(HMW)-APN concentrations. PDI, APN, cleaved caspase-3, and glucose regulated protein 78 (Grp78) protein expression were detected. Results: PDI expression was significantly decreased in the HG, H/R and HG+H/R groups compared to the Control group; however, LDH activity[(179.7±10.4) U/L、(218.4±18.4) U/L、(328.2±5.3) U/L vs (91.0±11.0) U/L], MDA concentration[(7.0±0.4) µmol/L、(10.0±1.0) µmol/L、(11.7±1.0) µmol/L vs (4.2±1.8) µmol/L], cleaved caspase-3, and Grp78 expression were increased. Interestingly, APN and HMW-APN expression were decreased [(2.01±0.21) µg/L、(1.64±0.27) µg/L、(1.20±0.14) µg/L vs (2.62±0.12) µg/L, all P<0.05]. Over expression of PDI attenuated high glucose and hypoxia/reoxygenation induced apoptosis and oxidative stress in H9c2 cardiomyocytes(all P<0.05), and simultaneously increased APN and HMW-APN expression [(2.86±0.03) µg/L vs (3.03±0.10) µg/L、(2.06±0.05) µg/L vs (2.31±0.06) µg/L、(1.83±0.07) µg/L vs (1.96±0.11) µg/L、(1.20±0.06) µg/L vs (1.39±0.09) µg/L]. PDI-siRNA transfection increased LDH activity, MDA concentration, and cleaved caspase-3 and Grp78 expression, and decreased APN and HMW-APN expression [(0.75±0.09) µg/L vs (0.59±0.09) µg/L、(0.62±0.04) µg/L vs (0.53±0.05) µg/L、(0.55±0.14) µg/L vs (0.51±0.12) µg/L、(0.48±0.12) µg/L vs (0.35±0.08) µg/L] in response to different treatments in cultured H9c2 cardiomyocytes (all P<0.05). Conclusion: PDI may regulate the expression of APN and HMW-APN, and play an important role in the function of diabetic ischemia-reperfusion cardiomyocytes.

[Expressions of MPV, P-LCR and NLR in patients with novel coronavirus disease 2019].

To provide new ideas for clinical diagnosis and treatment of coronavirus disease 2019 (COVID-19), this study explore the expression level and prognostic value of platelet parameters in mild, moderate and severe COVID-19. This is a retrospective analysis. From January to May 2020, a total of 69 patients who were diagnosed with COVID-19 in the Third Central Hospital and the Jinnan Hospital (both situated in Tianjin) were enrolled in the disease group. According to the severity, these patients were divided into mild group (15 cases), moderate group (46 cases), and severe group (8 cases). In the same period, 70 non-infected patients were enrolled in control group. The level of white blood cell count (WBC), absolute neutrophil count (NEU#), absolute lymphocyte count (LY#), neutrophil-lymphocyte ratio (NLR), red blood cell count (RBC), hemoglobin (Hb), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large contrast ratio (P-LCR) before and after treatment were analyzed. Binary logistic regression analysis is used to establish a mathematical model of the relationship between these indexes and the outcome of severe COVID-19 patients. The receiver operating characteristic(ROC) curve is used to further explore the prognosis value of MPV, P-LCR, NLR separately and jointly in COVID-19 patients. Compare to the control group, WBC and NE# increase (Z=-5.63, P<0.01;Z=-9.19,P<0.01) and LY# decrease (Z=-9.34, P<0.01) in the severe group; NLR increase with the aggravation of the disease, there is significant difference between groups (Z=17.61, P<0.01); PLT, PDW, MPV and P-LCR decrease with the aggravation of the disease, there is significant difference between groups (Z=9.47, P<0.01; Z=11.41, P<0.01; Z =16.76, P<0.01; Z=13.97, P<0.01). Binary logistic regression analysis shows MPV, P-LCR and NLR have predictive value for severe COVID-19 patients. There is a negative correlation between MPV, P-LCR and severe COVID-19 patients (OR=1.004, P=0.034; OR=1.097, P=0.046). There is a positive correlation between NLR and severe COVID-19 patients (OR=1.052, P=0.016). MPV and P-LCR of patients with good prognosis after treatment were significantly higher than those before treatment (Z=-6.47, P<0.01; Z=-5.36, P<0.01). NLR was significantly lower than that before treatment (Z=-8.13, P<0.01). MPV and P-LCR in poor prognosis group were significantly lower than those before treatment (Z=-9.46, P<0.01; Z=-6.81, P<0.01). NLR was significantly higher than that before treatment (Z=-3.24, P<0.01). There were significant differences between good and poor prognosis groups before and after treatment in MPV, P-LCR and NLR (P<0.01). Combination of these three indexes, ROC shows the AUC is 0.931, the sensitivity is 91.5%, the specificity is 94.1%, the positive predictive value is 88.9%, and the negative predictive value is 87.4%, which is better than any of these indexes separately. Changes in these parameters are closely related to clinical stage of COVID-19 patients. MPV, P-LCR and NLR are of great value in the prediction and prognosis of severe COVID-19 patients.

[Comparison and application of postprandial and fasting blood lipid levels in 839 physical examinees in Beijing].

Objective: To investigate the feasibility of application of non-fasting dyslipidemia cutoff values in community population. Methods: Self-control study was used. 839 physical examinees (292 males and 547 females) were recruited in clinical laboratory of Guang'an men Hospital from January to October 2018. The median (interquartile range) of age was 60 (54, 66) years. Blood samples were collected before and at 4 h after a standard breakfast. Comparison of fasting and postprandial lipoprotein levels was performed using Paired-Samples T Test or Two-Related-Samples Wilcoxon. The changes of 4-hour postprandial blood lipid levels and the percentages of postprandial dyslipidemia according to different stratification of fasting dyslipidemia were performed using one-way ANOVA and χ2 test, respectively. Results: Compared with fasting, 4-hour postprandial total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) decreased slightly, postprandial triglyceride (TG) increased by 0.72 mmol/L, and postprandial remnant-like lipoprotein cholesterol (RLP-C) increased by 0.27 mmol/L (t or Z values = 10.26,22.94,24.22,4.71,16.61,26.92,-23.58,-19.35, P<0.05, respectively). According to the non-fasting dyslipidemia cut-off values recommended by the European consensus, there were 10%, 16.6%, 10.1%, 12.3%, 30% and 34.9% of the population in the appropriate levels of fasting TC, LDL-C, HDL-C, non-HDL-C, TG and RLP-C distributed in elevated levels of postprandial, respectively. The changes of 4-hour postprandial TC, LDL-C, non-HDL-C and HDL-C increased with the elevation of fasting level (F=9.50,6.18,8.07,3.86,P<0.01), and the maximum changes of TC≤3.5%, LDL-C≤6.8%, non-HDL-C≤2.9%, HDL-C≤6.3%; the change of 4-hour postprandial TG increased slightly first and then decreased significantly (51.3% vs. 57.9% vs. 39.2%, F=19.05, P<0.01); the change of 4-hour postprandial RLP-C decreased (50.8% vs. 33.2%, F=10.40, P<0.01). The cut-off values of 4-hour postprandial dyslipidemia were TC ≥5.1 mmol/L, LDL-C ≥3.2 mmol/L, HDL-C ≤0.9 mmol/L, non-HDL-C ≥4.0 mmol/L and RLP-C ≥1.0 mmol/L. The cut-off values of borderline elevated and elevated TG levels were ≥2.2 mmol/L and ≥3.4 mmol/L, respectively. Conclusions: The cut-off values of postprandial dyslipidemia including TC, LDL-C, HDL-C, non-HDL-C and RLP-C were preliminarily established in community population, which could be applied to the routine lipid profile evaluation in the physical examination population. And it might be needed that postprandial TG was managed hierarchically according to different cut-off values.

[Effect of early-life antibiotic exposure on allergic symptoms in children aged 6-11 months and 18-23 months based a birth cohort study].

Objective: To analyze the associations between prenatal and 1-year-old exposure to antibiotics and allergic symptoms in children aged 6-11 months and 18-23 months. Methods: In this study, a prospective birth cohort study was adopted. A total of 2 122 pregnant women were enrolled in Maternal and Child Health Care Center of Ma'anshan from June 2015 to June 2016, and they were followed up from the beginning of pregnancy to children's 24 months of age. Excluding 564 pairs of mothers and children who were lost to follow-up or with incomplete information on the use of antibiotics and children's allergic symptoms, a total of 1 558 pairs of mothers and children were included in the analysis of this study. The parents and children's general demographic information, early-life antibiotic exposure and other data were collected, the information about allergic symptoms in children aged 6-11 months and 18-23 months were investigated by reference to the "International Study of Asthma and Allergies in Childhood (ISAAC)". The univariate and multivariate binary unconditional logistic regression model was used to was used to estimate associations between the effects of early-life antibiotic exposure on allergic symptoms in 2-year-old children. Results: The antibiotic usage rate of pregnant women during pregnancy was 3.4% (53), and the antibiotic usage rates of children between 0 to 2 months, 3 to 5 months, and 6 to 11 months were separately 15.2%(237), 15.5%(242) and 17.3%(269). The total prevalence of allergic diseases in children aged 6 to 11 months was 24.1% (375 children), and the total prevalence of allergic diseases in children aged 18 to 23 months was 22.0% (342 children). After adjust parental (maternal) education level, family monthly income per capita, parental (maternal) allergy history, parental (maternal) age at pregnancy, mother's Body Mass Index (BMI) before pregnancy, exposure to second-hand smoke during pregnancy, delivery method, child gender, birth weight, preterm birth, the use of antibiotics when children were 3-5 months old (RR=1.61,95%CI:1.19-2.17) and 6-11 months old (RR=1.43,95%CI:1.06-1.93) were the risk factors for allergic symptoms at 6-11 months of age; and the use of antibiotics when children were 0-2 months old (RR=1.41, 95%CI: 1.03-1.95), 3-5 months old (RR=1.54, 95%CI: 1.12-2.11) and 6-11 months old (RR=1.58, 95%CI: 1.17-2.14) were the risk factors for allergic symptoms at 18-23 months of age. Conclusion: Children's exposure to antibiotics within 1 year of age was a risk factor for allergic symptoms in children aged 6-11 months and 18-23 months, children should avoid unnecessary antibiotic use in infancy.

Probing Few-Body Nuclear Dynamics via

We report the first measurement of the (e,e^{'}p) three-body breakup reaction cross sections in helium-3 (^{3}He) and tritium (^{3}H) at large momentum transfer [⟨Q^{2}⟩≈1.9 (GeV/c)^{2}] and x_{B}>1 kinematics, where the cross section should be sensitive to quasielastic (QE) scattering from single nucleons. The data cover missing momenta 40≤p_{miss}≤500 MeV/c that, in the QE limit with no rescattering, equals the initial momentum of the probed nucleon. The measured cross sections are compared with state-of-the-art ab initio calculations. Overall good agreement, within ±20%, is observed between data and calculations for the full p_{miss} range for ^{3}H and for 100≤p_{miss}≤350 MeV/c for ^{3}He. Including the effects of rescattering of the outgoing nucleon improves agreement with the data at p_{miss}>250 MeV/c and suggests contributions from charge-exchange (SCX) rescattering. The isoscalar sum of ^{3}He plus ^{3}H, which is largely insensitive to SCX, is described by calculations to within the accuracy of the data over the entire p_{miss} range. This validates current models of the ground state of the three-nucleon system up to very high initial nucleon momenta of 500 MeV/c.

Copy number variation in HOXB7 and HOXB8 involves in the formation of beard trait in chickens.

The derived feathering phenotype beard in domestic birds is an ideal resource to investigate the genetic mechanisms controlling feather development and differentiation. In the present study, we performed a GWAS and QTL linkage analysis on the trait of beard in Beijing fatty chicken. One major QTL (1.2-1.9 Mb) was identified that could explain 34% of the phenotypic variation. The copy number variation that was copied from the region (GGA27:3 578 409-3 592 890 bp) containing homebox B7 (HOXB7) and homebox B8 (HOXB8) was validated to be only exhibited in the genome of bearded chickens. Protein-protein interaction analysis indicated that HOXB7 and HOXB8 proteins could highly interact with the HOXB family members, including HOXB4, HOXB5 and HOXB6, whose genomic locations near HOXB7 and HOXB8 suggested that they may regulate their family members to involve in the formation of the beard trait in chickens. Overall, our work provides basic data for understanding the mechanisms regulating beard development and differentiation.