Assistive diagnostic technology for congenital heart disease based on fusion features and deep learning.

Introduction: Congenital heart disease (CHD) is a cardiovascular disorder caused by structural defects in the heart. Early screening holds significant importance for the effective treatment of this condition. Heart sound analysis is commonly employed to assist in the diagnosis of CHD. However, there is currently a lack of an efficient automated model for heart sound classification, which could potentially replace the manual process of auscultation. Methods: This study introduces an innovative and efficient screening and classification model, combining a locally concatenated fusion approach with a convolutional neural network based on coordinate attention (LCACNN). In this model, Mel-frequency spectral coefficients (MFSC) and envelope features are locally fused and employed as input to the LCACNN network. This model automatically analyzes feature map energy information, eliminating the need for denoising processes. Discussion: The proposed classification model in this study demonstrates a robust capability for identifying congenital heart disease, potentially substituting manual auscultation to facilitate the detection of patients in remote areas. Results: This study introduces an innovative and efficient screening and classification model, combining a locally concatenated fusion approach with a convolutional neural network based on coordinate attention (LCACNN). In this model, Mel-frequency spectral coefficients (MFSC) and envelope features are locally fused and employed as input to the LCACNN network. This model automatically analyzes feature map energy information, eliminating the need for denoising processes. To assess the performance of the classification model, comparative ablation experiments were conducted, achieving classification accuracies of 91.78% and 94.79% on the PhysioNet and HS databases, respectively. These results significantly outperformed alternative classification models.

Advances in the relationship between ferroptosis and epithelial-mesenchymal transition in cancer.

Epithelial-mesenchymal transition (EMT) is a cellular reprogramming process that converts epithelial cells into mesenchymal-like cells with migratory and invasive capabilities. The initiation and regulation of EMT is closely linked to a range of transcription factors, cell adhesion molecules and signaling pathways, which play a key role in cancer metastasis and drug resistance. The regulation of ferroptosis is intricately linked to various cell death pathways, intracellular iron homeostasis, and the protein network governing iron supply and storage. The ability of ferroptosis to disrupt cancer cells and overcome drug resistance lies in its control of intracellular iron ion levels. EMT process can promote the accumulation of iron ions, providing conditions for ferroptosis. Conversely, ferroptosis may impact the regulatory network of EMT by modulating transcription factors, signaling pathways, and cell adhesion molecules. Thus, ferroptosis related genes and signaling pathways and oxidative homeostasis play important roles in the regulation of EMT. In this paper, we review the role of ferroptosis related genes and their signaling pathways in regulating cancer EMT to better understand the crosstalk mechanism between ferroptosis and EMT, aiming to provide better therapeutic strategies for eradicating cancer cells and overcoming drug resistance.

Analysis of Zinc and Stromal Immunity in Disuse Osteoporosis: Mendelian Randomization and Transcriptomic Analysis.

OBJECTIVE: Disuse osteoporosis is known to be primarily caused by a lack of exercise. However, the causal relationships between zinc and immunity and disuse osteoporosis remain unknown. This study investigated these relationships and their potential mechanisms. METHODS: This study was an integrative study combining genome-wide association studies and transcriptomics. Two-sample Mendelian randomization analysis (MR) was used to analyze the causal relationships between exposures (zinc, immunity, physical activity) and the outcome (osteoporosis) with the aid of single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Four models, MR-Egger, inverse variance weighted, weighted median and MR-Pleiotrophy RESidual Sum and Outlier (MRPRESSO), were used to calculate odds ratio values. Sensitivity and heterogeneity analyses were also performed using MRPRESSO and MR-Egger methods. The mRNA transcriptomic analysis was subsequently conducted. Zinc metabolism scores were acquired through single-sample Gene Set Enrichment Analysis algorithms. Stromal scores were obtained using the R Package "estimate" algorithms. Important Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathways were also derived through gene set variation analysis. Cytoscape software helped construct the transcription factor (TF)-mRNA-microRNA (miRNA) network. Virtual screening and molecular docking were performed. Polymerase chain reaction validation was also carried out in vivo. RESULTS: Causal relationships were demonstrated between zinc and exercise (95% confidence interval [CI] = 1.30-2.95, p = 0.001), exercise and immunity (95% CI = 0.36-0.80, p = 0.002), exercise and osteoporosis (95% CI = 0.97-0.99, p = 0.0007), and immunity disorder and osteoporosis (95% CI = 1.30-2.03, p = 0.00002). One hundred and seventy-nine mRNAs in important modules were screened. Combining the differential expressional genes (DEGs) and the Boruta selection, six DEGs were screened (AHNAK, CSF2, ADAMTS12, SRA1, RUNX2, and SLC39A14). TF HOXC10 and miRNA hsa-miR-204 were predicted. Then, the TF-mRNA-miRNA network was successfully constructed. RUNX2 and SLC39A14 were identified as hub mRNAs in the TF-mRNA-miRNA network. Eventually, the novel small drug C6O4NH5 was designed according to the pharmacophore structure of SLC39A14. The docking energy for the novel drug was -5.83 kcal/mol. SLC39A14 and RUNX2 were downregulated (of statistical significance p-value < 0.05) in our animal experiment. CONCLUSION: This study revealed that zinc had a protective causal relationship with disuse osteoporosis by promoting exercise and immunity. SLC39A14 and RUNX2 mRNA participated in this zinc-related mechanism.

APOA2: New Target for Molecular Hydrogen Therapy in Sepsis-Related Lung Injury Based on Proteomic and Genomic Analysis.

Target biomarkers for H2 at both the protein and genome levels are still unclear. In this study, quantitative proteomics acquired from a mouse model were first analyzed. At the same time, functional pathway analysis helped identify functional pathways at the protein level. Then, bioinformatics on mRNA sequencing data were conducted between sepsis and normal mouse models. Differential expressional genes with the closest relationship to disease status and development were identified through module correlation analysis. Then, common biomarkers in proteomics and transcriptomics were extracted as target biomarkers. Through analyzing expression quantitative trait locus (eQTL) and genome-wide association studies (GWAS), colocalization analysis on Apoa2 and sepsis phenotype was conducted by summary-data-based Mendelian randomization (SMR). Then, two-sample and drug-target, syndrome Mendelian randomization (MR) analyses were all conducted using the Twosample R package. For protein level, protein quantitative trait loci (pQTLs) of the target biomarker were also included in MR. Animal experiments helped validate these results. As a result, Apoa2 protein or mRNA was identified as a target biomarker for H2 with a protective, causal relationship with sepsis. HDL and type 2 diabetes were proven to possess causal relationships with sepsis. The agitation and inhibition of Apoa2 were indicated to influence sepsis and related syndromes. In conclusion, we first proposed Apoa2 as a target for H2 treatment.

Preoperative prediction of sonic hedgehog and group 4 molecular subtypes of pediatric medulloblastoma based on radiomics of multiparametric MRI combined with clinical parameters.

Purpose: To construct a machine learning model based on radiomics of multiparametric magnetic resonance imaging (MRI) combined with clinical parameters for predicting Sonic Hedgehog (SHH) and Group 4 (G4) molecular subtypes of pediatric medulloblastoma (MB). Methods: The preoperative MRI images and clinical data of 95 patients with MB were retrospectively analyzed, including 47 cases of SHH subtype and 48 cases of G4 subtype. Radiomic features were extracted from T1-weighted imaging (T1), contrast-enhanced T1 weighted imaging (T1c), T2-weighted imaging (T2), T2 fluid-attenuated inversion recovery imaging (T2FLAIR), and apparent diffusion coefficient (ADC) maps, using variance thresholding, SelectKBest, and Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithms. The optimal features were filtered using LASSO regression, and a logistic regression (LR) algorithm was used to build a machine learning model. The receiver operator characteristic (ROC) curve was plotted to evaluate the prediction accuracy, and verified by its calibration, decision and nomogram. The Delong test was used to compare the differences between different models. Results: A total of 17 optimal features, with non-redundancy and high correlation, were selected from 7,045 radiomics features, and used to build an LR model. The model showed a classification accuracy with an under the curve (AUC) of 0.960 (95% CI: 0.871-1.000) in the training cohort and 0.751 (95% CI: 0.587-0.915) in the testing cohort, respectively. The location of the tumor, pathological type, and hydrocephalus status of the two subtypes of patients differed significantly (p < 0.05). When combining radiomics features and clinical parameters to construct the combined prediction model, the AUC improved to 0.965 (95% CI: 0.898-1.000) in the training cohort and 0.849 (95% CI: 0.695-1.000) in the testing cohort, respectively. There was a significant difference in the prediction accuracy, as measured by AUC, between the testing cohorts of the two prediction models, which was confirmed by Delong's test (p = 0.0144). Decision curves and nomogram further validate that the combined model can achieve net benefits in clinical work. Conclusion: The combined prediction model, constructed based on radiomics of multiparametric MRI and clinical parameters can potentially provide a non-invasive clinical approach to predict SHH and G4 molecular subtypes of MB preoperatively.

[Heart sound classification based on improved mel frequency cepstrum coefficient and integrated decision network method].

Heart sound analysis is significant for early diagnosis of congenital heart disease. A novel method of heart sound classification was proposed in this paper, in which the traditional mel frequency cepstral coefficient (MFCC) method was improved by using the Fisher discriminant half raised-sine function (F-HRSF) and an integrated decision network was used as classifier. It does not rely on segmentation of the cardiac cycle. Firstly, the heart sound signals were framed and windowed. Then, the features of heart sounds were extracted by using improved MFCC, in which the F-HRSF was used to weight sub-band components of MFCC according to the Fisher discriminant ratio of each sub-band component and the raised half sine function. Three classification networks, convolutional neural network (CNN), long and short-term memory network (LSTM), and gated recurrent unit (GRU) were combined as integrated decision network. Finally, the two-category classification results were obtained through the majority voting algorithm. An accuracy of 92.15%, sensitivity of 91.43%, specificity of 92.83%, corrected accuracy of 92.01%, and F score of 92.13% were achieved using the novel signal processing techniques. It shows that the algorithm has great potential in early diagnosis of congenital heart disease.

The value of cardiac magnetic resonance imaging in endocardial fibroelastosis.

Introduction: Endocardial fibroelastosis (EFE), an uncommon congenital heart disorder often occurring in infants, has a poor prognosis. It is of great significance to perform early diagnosis and accurately analyze cardiac function to enable further clinical treatment and prognosis decisions. This study aimed to explore the findings of cardiac magnetic resonance (CMR) in patients with EFE, including morphological changes and cardiac function analyses. Additionally, we compared the difference in the evaluation of the cardiac function between CMR and echocardiography (Echo). Methods: Eleven patients with EFE (nine females and two males, aged between 0.3 and 1.9 years), treated in our hospital, were analyzed retrospectively. Left ventricular posterior wall thickness (LVPW), anterior wall thickness (LVAW), fractional shortening (FS), ejection fraction (EF), end-systolic diameter (ESD), end-diastolic diameter (EDD), end-systolic volume (ESV), and end-diastolic volume (EDV) were assessed using both Echo and CMR. The Original Ross classification and the New York Heart Association functional classification were used to grade the patients' cardiac function. The correlations between clinical cardiac function classification and MRI- and Echo-derived imaging data were determined. Results: All patients showed a thickened endocardium and left ventricle globular dilatation on CMR. We observed significant systolic dysfunction and whole or segmental abnormal ventricular movement. Compared with those measured by Echo, the EF, FS, and EDV values were significantly lower when measured using CMR. Compared with Echo measurements, the ESV, ESD, LVAW, and LVPW values were significantly higher when measured using CMR. CMR-measured EF and FS correlated better with the clinical cardiac functional score than those derived from Echo (EF, r = 0.646 > 0.224; FS, r = 0.627 > 0.245, respectively). Conclusion: In patients with EFE, the characteristic morphological changes of the heart could be displayed accurately using CMR. The parameters measured by CMR were more accurate than those of Echo and correlated well with clinical cardiac function scores, mainly because it does not make invalid geometrical assumptions.

Expression pattern and clinical value of Key RNA methylation modification regulators in ischemic stroke.

Ischemic stroke (IS) is one of the major causes of death and disability worldwide, and effective diagnosis and treatment methods are lacking. RNA methylation, a common epigenetic modification, plays an important role in disease progression. However, little is known about the role of RNA methylation modification in the regulation of IS. The aim of this study was to investigate RNA methylation modification patterns and immune infiltration characteristics in IS through bioinformatics analysis. We downloaded gene expression profiles of control and IS model rat brain tissues from the Gene Expression Omnibus database. IS profiles were divided into two subtypes based on RNA methylation regulators, and functional enrichment analyses were conducted to determine the differentially expressed genes (DEGs) between the subtypes. Weighted gene co-expression network analysis was used to explore co-expression modules and genes based on DEGs. The IS clinical diagnosis model was successfully constructed and four IS characteristic genes (GFAP, GPNMB, FKBP9, and CHMP5) were identified, which were significantly upregulated in IS samples. Characteristic genes were verified by receiver operating characteristic curve and real-time quantitative PCR analyses. The correlation between characteristic genes and infiltrating immune cells was determined by correlation analysis. Furthermore, GPNMB was screened using the protein-protein interaction network, and its regulatory network and the potential therapeutic drug chloroquine were predicted. Our finding describes the expression pattern and clinical value of key RNA methylation modification regulators in IS and novel diagnostic and therapeutic targets of IS from a new perspective.

Analysis of Adverse Effects of COVID-19 Vaccines Experienced by Healthcare Workers at Guizhou Provincial Staff Hospital, China.

Objective: A retrospective survey was conducted of adverse events following immunization (AEFI) experienced by health care workers (HCWs) in a relatively remote ethnic region in southwest China (Guizhou Province) who received COVID-19 vaccines. Methods: From 18 January 2021 to 21 January 2022, all HCWs of Guizhou Provincial Staff Hospital, China, who received at least one dose of inactivated COVID-19 vaccine (Vero cell), recombinant novel coronavirus vaccine (CHO cell), or one dose of adenovirus type-5 (Ad5) vectored COVID-19 vaccine were asked to complete a self-report questionnaire to provide information on any adverse events that may have occurred in the first 3 days after injection. The frequency of AEFI corresponding to the three types of vaccines were compared and the potential risks of AEFI due to the three different vaccines were predicted by multivariate logistic regression analysis. Results: Of the 904 HCWs who completed the survey, the rates of AEFI were 10.1% (80/794) due to Vero cell, 16.3% (13/80) due to CHO cell, and 46.67% (14/30) due to Ad5 vectored vaccines, and the rates were significantly different (χ2 = 38.7, p < 001) between the three vaccines. Multivariate logistic regression models predict that (1) compared to the Ad 5 vectored group, the risk of AEFI occurrence in the Vero cell group was reduced by about 85.9% (OR = 0.141, 95% CI: 0.065−0.306, p < 0.001) and in the CHO cell group by about 72.1% (OR = 0.279, 95% CI: 0.107−0.723, p = 0.009), (2) the odds for women experiencing AEFI were about 2.1 (OR = 2.093, 95% CI: 1.171−3.742, p = 0.013) times as high as those of men, and (3) the risk of AEFI for HCWs with a Bachelor's degree or above was about 2.2 (OR = 2.237, 95% CI: 1.434−3.489, p = 0.001) times higher than in HCWs who do not have a Bachelor's degree. Conclusions: 1. The inactivated COVID-19 vaccine (Vero cell), recombinant novel coronavirus vaccine (CHO cell), and adenovirus type-5 (Ad5) vectored COVID-19 vaccine made in China are safe and relatively broad-spectrum. 2. The prevalence of AEFI is more common in women healthcare workers. 3. The risk of AEFI was higher in those with a Bachelor's degree or above and may be related to the psychological and social effects triggered by the global COVID-19 pandemic.

Exploring the Association between Glutathione Metabolism and Ferroptosis in Osteoblasts with Disuse Osteoporosis and the Key Genes Connecting them.

Disused osteoporosis is a kind of osteoporosis, a common age-related disease. Neurological disorders are major risk factors for osteoporosis. Though there are many studies on disuse osteoporosis, the genetic mechanisms for the association between glutathione metabolism and ferroptosis in osteoblasts with disuse osteoporosis are still unclear. The purpose of this study is to explore the key genes and other related mechanism of ferroptosis and glutathione metabolism in osteoblast differentiation and disuse osteoporosis. By weighted gene coexpression network analysis (WGCNA), the process of osteoblast differentiation-related genes was studied in GSE30393. And the related functional pathways were found through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. By combining GSE1367 and GSE100933 together, key genes which were separately bound up with glutathione metabolism and ferroptosis were located. The correlation of these key genes was analyzed by the Pearson correlation coefficient. GSTM1 targeted agonist glutathione (GSH) selected by connectivity map (CMap) analysis was used to interfere with the molding disused osteoporosis process in MC3T3-E1 cells. RT-PCR and intracellular reactive oxygen species (ROS) were performed. Two important pathways, glutathione metabolism and ferroptosis pathways, were found. GSTM1 and TFRC were thought as key genes in disuse osteoporosis osteoblasts with the two mechanisms. The two genes have a strong negative correlation. Our experiment results showed that the expression of TFRC was consistent with the negative correlation with the activation process of GSTM1. The strong relationship between the two genes was proved. Glutathione metabolism and ferroptosis are important in the normal differentiation of osteoblasts and the process of disuse osteoporosis. GSTM1 and TFRC were the key genes. The two genes interact with each other, which can be seen as a bridge between the two pathways. The two genes participate in the process of reducing ROS in disuse osteoporosis osteoblasts.

Comparison of the clinical and patient-reported outcomes between medial stabilized and posterior stabilized total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Total knee arthroplasty (TKA) is effective in relieving pain and improving function in patients with end-stage knee osteoarthritis. Both medial stabilized total knee arthroplasty (MS-TKA) and posterior stabilized total knee arthroplasty (PS-TKA) can achieve satisfactory clinical results, but comparisons between MS-TKA and PS-TKA have yielded contradictory conclusions. This systematic review and meta-analysis were performed to investigate the differences in clinical and patient-reported outcomes (PROMs) between MS-TKA and PS-TKA. METHODS: In December 2020, systematic searches of the following databases were undertaken: Pubmed, Embase, Cochrane Library, Clinical Trials.gov. Studies with PROMs comparing MS-TKA to PS-TKA were included. Meta-analysis was conducted for range of motion (ROM), Knee Society Score (KSS), Knee Society Functional Score (KFS), Forgotten Joint Score (FJS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Oxford Knee Score (OKS). RESULTS: There were 17 studies included in this review, 13 studies used for quantitative analysis, and 4 studies used for qualitative synthesis. Meta-analysis concluded that the WOMAC mean difference (MD) for MS-TKA was 1.55 higher than for PS-TKA (MD = -1.55; 95 %CI = -2.45 to -0.64, P = 0.0008); however, this difference was less than the minimum clinically important difference (MCID) value of 15. Assessment using the OKS determined that the MD for PS-TKA was 0.58 higher than for MS-TKA (MD = 0.58; 95 %CI = 0.25 to 0.91, P = 0.0006); again, this MD was less than the MCID value of 5. There were no significant differences between MS-TKA and PS-TKA when assessed by ROM (P = 0.23), KSS (P = 0.13), KFS (P = 0.61), or FJS (P = 0.22). CONCLUSION: Derived from numerous sources, utilizing a multitude of validated functional and patient-reported outcome assessment tools, there was no clinically evident advantage of MS-TKA compared to PS-TKA. REGISTRATION: The registration number on PROSPERO is CRD42021228555.

Au@MnSe2 Core-Shell Nanoagent Enabling Immediate Generation of Hydroxyl Radicals and Simultaneous Glutathione Deletion Free of Pre-Reaction for Chemodynamic-Photothermo-Photocatalytic Therapy with Significant Immune Response.

As a typical tumor microenvironment-responsive therapy, chemodynamic therapy (CDT), producing hydroxyl radicals (• OH) to eliminate tumor cells, has demonstrated great promise. Nevertheless, there are still major challenges: • OH generated from endogenous H2 O2 is usually insufficient; the CDT effect is strongly dependent on the pre-reaction with glutathione. Addressing the challenges, Au@MnSe2 core-shell nanoagent for synergetic chemodynamic-photothermo-photocatalytic therapy combined with tetramodal imaging, including magnetic resonance imaging, computed tomography, photoacoustic, and infrared thermal imaging is reported. Distinct from the reported glutathione-depleting agents, Mn2+ in MnSe2 allows immediate generation of • OH, independent of pre-reaction. Meanwhile, Mn3+ consumes glutathione by its conversion to Mn2+ . The Au-MnSe2 combination promotes photothermal conversion and photocatalytic reaction, resulting in largely enhanced • OH generation from endogenous H2 O2 and significant hyperthermia. Meanwhile, immune response is effectively activated: the intratumoral expression of programmed cell death-1 and proinflammatory cytokines increase to 4-7 folds; the cytotoxic and helper T lymphocytes cells in the tumor area increase to more than 2.5-folds; an evident, temporary systemic immunostimulatory effect is demonstrated. High tumor inhibition rate (≈97.3%) and greatly prolonged survival are obtained. This highly-integrated design coordinating three different therapies with four different imaging modals provide new possibilities for high-performance theranostic nanoagents.

Reductions in crop yields across China from elevated ozone.

Exposure of crops to high concentrations of ozone can cause substantial reductions in yield that pose a serious threat to global food security. Here we provide comprehensive estimates of yield losses for key crops across China between 2014 and 2017 attributed to ozone using a number of new approaches. We use an air quality model at 5 km resolution and crop-specific dose-response functions developed for both concentration- and flux-based metrics. We bias correct modelled ozone concentrations and metrics using observations from more than 1000 locations. We find that on a 4-year average basis, production losses of key crops are 34-91 million metric tonnes (Mt/yr), dependent on the approach used, with highest losses in Henan province. At a national level, loss of winter wheat production derived using a China-specific dose-response function increased by 82% from 2014 to 2017, with large interannual variations in the North China Plain and in eastern China. Winter wheat losses estimated using flux-based functions, which require robust simulation of stomatal conductance and underlying vegetation physiology, are significantly lower, at 30 Mt/yr. We show that the definition of the growing season may have a greater impact on estimated losses than small biases in ozone surface concentrations. Although uncertainties remain, our findings demonstrate that increasing ozone concentrations have substantial adverse impacts on crop yields and threaten food security in China. It is important to control ozone concentrations to mitigate these negative impacts.

Identification of key genes in osteosarcoma - before and after CDK7 treatment.

BACKGROUND: Osteosarcoma is one of the most common bone tumors, with a high degree of malignancy and a poor prognosis. Recent studies have shown that THZ2, a cyclin-dependent kinase 7 inhibitor, can exhibit strong antibone tumor effects in vivo and in vitro by inhibiting transcriptional activity. In this study, by screening the differentially expressed genes (DEGs) of osteosarcoma cells before and after THZ2 treatment, it provides new possible targets for the future targeted therapy of osteosarcoma. METHODS: Download the gene expression profile of GSE134603 from the Gene Expression Omnibus database, and use the R software package "limma Geoquery" to screen DEGs. DAVID database was used for gene ontology analysis of DEGs. Use search tool for the retrieval of interacting genes online database and Cytoscape software to construct protein-protein interaction network. Use the "MCODE" plugin in Cytoscape to analyze key molecular complexes (module) of DEGs, and use the "Cluego" plugin to perform Kyoto Encyclopedia of Genes and Genomes enrichment analysis on module genes. The Hub gene is selected from the genes in DEGs that coexist in the top 30 Degree and the Kyoto Encyclopedia of Genes and Genomes pathway. RESULTS: A total of 1033 DEGs were screened, including 800 up-regulated genes and 233 down-regulated genes. Gene ontology analysis showed that cell component is the main enrichment area of DEGs, mainly in the nucleus, cytoplasm, and nucleoplasm. In addition, in molecular function analysis, DEGs are mainly enriched in the process of protein binding. In biological process analysis, changes in DEGs can also be observed in transcription and regulation using DNA as a template. Twenty-nine module genes are enriched in the Ribosome biogenesis in eukaryotes pathway. Finally, 4 key genes are drawn: essential for mitotic growth 1, U3 SnoRNP protein 3 homolog, U3 small nucleolar RNA-associated protein 15 homolog, and WD repeat domain 3. CONCLUSION: This study found that the 4 genes essential for mitotic growth 1, U3 SnoRNP protein 3 homolog, U3 small nucleolar RNA-associated protein 15 homolog, WD repeat domain 3, and the ribosome biogenesis in eukaryotes pathway play a very important role in the occurrence and development of osteosarcoma, and can become a new target for molecular targeted therapy of osteosarcoma in the future.

Development of 1-2 years Offspring Born to Mothers with Polycystic Ovary Syndrome.

OBJECTIVE: To evaluate the body mass index and neurologic development of 1-2 years offspring born to mothers with polycystic ovary syndrome. STUDY DESIGN: A case-control study. PLACE AND DURATION OF STUDY: Dongyang Women and Children's Hospital, Zhejiang Province, China, between June 2018 and January 2019. METHODOLOGY: A total of 145 children were included in the final analysis, including 16 daughters of mothers with PCOS, 13 sons of mothers with PCOS, 55 daughters of mothers without PCOS and 61 sons of mothers without PCOS. Developmental assessments for each child were conducted, including anthropometric measurements and ability developments using the Denver developmental screening test. RESULTS: The body mass index of children was significantly lower in polycystic ovary syndrome group than control group (p=0.022). Children of mothers with polycystic ovary syndrome and control group had no significant differences in the outcomes of the Denver developmental screening test (all p >0.05). CONCLUSION: Maternal polycystic ovary syndrome may affect body mass index of offspring aged 1-2 years and had no negative effects on neurologic development. However, this conclusion may be limited due to the small sample size. Key Words: Neurologic development, Polycystic ovary syndrome, Offspring, Denver development screening test, Body mass index.

Alterations of brain metrics in fetuses of women with polycystic ovary syndrome : a retrospective study based on fetal magnetic resonance imaging.

BACKGROUND: Maternal polycystic ovary syndrome (PCOS) has potential detrimental effects on the neurodevelopment of offspring. This study aimed to evaluate the brain metrics in fetuses of women with PCOS based on fetal magnetic resonance imaging (MRI). METHODS: This retrospective study included 60 pregnant women with PCOS (PCOS group) and 120 pregnant non-PCOS women (control group). Fetal MRI was performed followed an ultrasound and for numerous clinical indications including known or suspected fetal pathology, history of fetal abnormality in previous pregnancy or in a family member. Fetal brain biometry and apparent diffusion coefficient (ADC) value were analysed. RESULTS: After adjusting for potential confounders, fetuses in the PCOS group showed the following characteristics compared to fetuses in the control group: (1) smaller cerebral fronto-occipital diameter (FOD), vermian height (VH) and anteroposterior diameter of the pons (APDP) (evident before 32 weeks; P = 0.042, P = 0.002 and P = 0.016, respectively); (2) larger left and right biparietal index (evident before 32 weeks; P = 0.048 and P = 0.025, respectively); (3) smaller left lateral ventricle (LV) (evident after 32 weeks; P = 0.005); (4) larger anteroposterior diameter of the vermis (APDV) and hippocampal infolding angle (HIA) (evident after 32 weeks; P = 0.003 and P < 0.001, respectively); (5) higher ADC value in frontal white matter (FWM) and in basal ganglia (BG) (evident before and after 32 weeks; all P < 0.05). CONCLUSIONS: There exist a different pattern of brain metrics in PCOS offspring in utero.

Calcyclin (S100A6) Attenuates Inflammatory Response and Mediates Apoptosis of Chondrocytes in Osteoarthritis via the PI3K/AKT Pathway.

OBJECTIVE: To clarify the regulatory effect of Calcyclin (S100A6) on chondrocytes apoptosis and its relationship with progression of osteoarthritis in an effort to explore potential therapeutic targets for osteoarthritis. METHOD: Immunofluorescence assay was produced to identify the rat chondrocyte sample and western blots assay was detected the expression changes of S100A6 between control group and osteoarthritis model which induced by interleukin-1ß. Adenovirus were transfected into the chondrocytes in vitro, in order to regulate the S100A6 expression. The influence of S100A6 on inflammatory reaction of osteoarthritis was detected by RT-PCR. Also, Caspase-3 activity assay and TUNEL assay were performed to evaluate the apoptosis changes. In addition, RT-PCR and western blots were performed to verify that S100A6 mediated the PI3K/AKT signaling pathway. Through the usage of pathway regulator, we detected S100A6 produced the effect by mediating the PI3K/AKT pathway. RESULTS: We determined the expression of S100A6 decreased in osteoarthritis model, the relative expression level in osteoarthritis model was about 0.5 fold compared with control group. Through adenovirus transfection we revealed that the inflammatory factors of osteoarthritis (interleukin-6 and matrix metalloproteinase-13) showed a negative correlation with the S100A6 expression. The relative expression level of interleukin-6 and matrix metalloproteinase-13 were 1.534 and 1.259 when S100A6 was up-regulated and the values were up to 2.445 and 2.074, respectively, when S100A6 was down-regulated. Also, the data verified the apoptosis could be reduced when the S100A6 was up-regulated and be activated when the S100A6 was down-regulated, the Caspase-3 activity was 16.512 U/µg and 24.45 U/µg respectively. Similar results were shown in TUNEL assay, the apoptosis index was 4.46% and 31.44%, respectively. Additionally, the results of polymerase chain reaction and western blots both demonstrated that the expression level of PI3K and AKT were increased when S100A6 was up-regulated, conversely the expression level of those two signal modules were reduced if the S100A6 was down-regulated. More importantly, the apoptosis triggered by S100A6 can be offset by the PI3K/AKT pathway inhibitor and activator (LY294002 and IGF-1), the values of Caspase-3 activity and apoptosis index became close to the untreated osteoarthritis group. The experimental results in this study were statistically significant. CONCLUSION: We investigated that Calcyclin (S100A6) relieved the inflammation and mediated the chondrocyte apoptosis through PI3K/AKT pathway and we confirmed that S100A6 might be an attractive therapeutic target.

Health impacts of long-term ozone exposure in China over 2013-2017.

Increasing ozone concentrations are becoming a severe problem for air pollution in China and have an adverse impact on human health. Here we evaluate premature deaths attributable to long-term exposure to ambient ozone in China between 2013 and 2017 with an air quality model at 5 km resolution and the latest estimates of the relative risk to health. We use a modified inverse distance weighting method to bias-correct the key model-simulated ozone metrics. We find that on a 5-year average basis there are 186,000 (95% Confidence Interval: 129,000-237,000) respiratory deaths and 125,000 (42,000-204,000) cardiovascular deaths attributable to ozone exposure. Sichuan exhibits the largest per capita respiratory mortality (0.31‰) among all provinces. We find that there are 73,000 (51,000-93,000) premature respiratory deaths in urban areas, accounting for 39% of total deaths. Between 2013 and 2017 the population-weighted annual average maximum daily 8-h average ozone (AMDA8) and premature respiratory deaths increased by 14% and 31%, respectively, at a national level. Changes in precursor emissions explain most of these increases, with differences in meteorology accounting for 21% and 16% respectively. Interannual variations in population-weighted ozone and premature respiratory deaths at a provincial level are much larger than those at a national level, particularly in northern, central and eastern China. These findings emphasize that ozone should be an important focus of future air quality policies in China, and tighter controls of precursor emissions are urgently needed.

Normobaric hyperoxia plays a protective role against renal ischemia-reperfusion injury by activating the Nrf2/HO-1 signaling pathway.

Following renal ischemia-reperfusion injury (RIRI), because of the decrease in oxygen supply to the kidney, a large amount of oxygen-free radicals is generated, and in severe cases, tissue cells will undergo apoptosis or even die. Normobaric hyperoxia (NBHO) is a very common clinical adjuvant treatment. It restores the oxygen supply after renal ischemia and combats oxidative stress in tissues, thus playing a protective role. In this study, our aim is to elucidate the protective mechanism of NBHO inhalation in a rat RIRI model. We performed a surgical excision of the left kidney of the rat and established a right kidney solitary kidney model. Later, the right renal pedicle of the rat was clamped using a non-invasive vascular clamp for 45 min. After the vascular clamp was released and reperfused for 24 h, the rat was placed in a closed oxygen chamber. It was subjected to inhalation of high-concentration oxygen (50%-55%), 2 h daily, for 7 days.RIRI induces postoperative weight loss, impaired renal function, increased oxygen free radicals, reduced antioxidant substances, increased histopathological damage, and increased levels of apoptosis. These effects were significantly improved after treatment with NBHO. At the same time, NBHO significantly increased the expression levels of Nrf2 and HO-1 in the tissues after RIRI. To verify whether HO-1 induced by Nrf2 is involved in the resistance to oxidative stress, after the rat RIRI and before inhaling NBHO, we intraperitoneally injected HO-1 specific inhibitor zinc protoporphyrin (ZnPP) (45 µmol/Kg). However, we found that ZnPP reversed the protective effect of NBHO on RIRI in rats. Combining all the results, we have demonstrated the protective effect of NBHO on RIRI, which can be at least partially attributed to the activation of the Nrf2/HO-1 antioxidative stress pathway.