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Objective To investigate the application value of combining the Demirjian’s method with machine learning algorithms for dental age estimation in northern Chinese Han children and adolescents. Methods Oral panoramic images of 10 256 Han individuals aged 5 to 24 years in northern China were collected. The development of eight permanent teeth in the left mandibular was classified into different stages using the Demirjian’s method. Various machine learning algorithms, including support vector regression （SVR）, gradient boosting regression （GBR）, linear regression （LR）, random forest regression （RFR）, and decision tree regression （DTR） were employed. Age estimation models were constructed based on total, female, and male samples respectively using these algorithms. The fitting performance of different machine learning algorithms in these three groups was evaluated. Results SVR demonstrated superior estimation efficiency among all machine learning models in both total and female samples, while GBR showed the best performance in male samples. The mean absolute error （MAE） of the optimal age estimation model was 1.246 3, 1.281 8 and 1.153 8 years in the total, female and male samples, respectively. The optimal age estimation model exhibited varying levels of accuracy across different age ranges, which provided relatively accurate age estimations in individuals under 18 years old. Conclusion The machine learning model developed in this study exhibits good age estimation efficiency in northern Chinese Han children and adolescents. However, its performance is not ideal when applied to adult population. To improve the accuracy in age estimation, the other variables can be considered.

Abstract Meandering flow can be formed during the advance of natural rivers by the scouring of river banks. However, this phenomenon is not common in artificial cement channels. This study used experimental scouring terrain data for a numerical simulation to study the meandering flow pattern formed between double alternating deflectors in a straight channel. The numerical results showed that the path of the accelerated flow generated by the upstream deflector was changed by installing a downstream deflector while the flow rate remained unchanged. Thus, a meandering flow formed, and a stable, narrow, high-speed zone formed in the downstream area. The accelerated flow between the two deflectors hit the channel bank soon after its direction changed. Then, a strong downward flow formed in this area, which may have produced an elliptical scour hole. A large-scale vortex structure was formed in the elliptical scour hole, which was influenced by the horseshoe vortex system before the downstream deflector.

Abstract KRAS is one of the leading mutations reported in colon cancer. However, there are few studies on the application of KRAS related signature in predicting prognosis and drug sensitivity of colon cancer patient. We identified KRAS related differentially expressed genes (DEGs) using The Cancer Genome Atlas (TCGA) database. A signature closely related to overall survival was recognized with Kaplan–Meier survival analysis and univariate cox regression analysis. Then we validated this signature with overall expression score (OE score) algorithm using both scRNA-seq and bulk RNA-seq data. Based on this signature, we performed LASSO cox regression to establish a prognostic model, and corresponding scores were calculated. Differences in genomic alteration, immune microenvironment, drug sensitivity between high- and low-KRD score groups were investigated. A KRAS related signature composed of 80 DEGs in colon cancer were recognized, among which 19 genes were selected to construct a prognostic model. This KRAS related signature was significantly correlated with worse prognosis. Furthermore, patients who scored lower in the prognostic model presented a higher likelihood of responding to chemotherapy, targeted therapy and immunotherapy. Furthermore, among the 19 selected genes in the model, SPINK4 was identified as an independent prognostic biomarker. Further validation in vitro indicated the knockdown of SPINK4 promoted the proliferation and migration of SW48 cells. In conclusion, a novel KRAS related signature was identified and validated based on clinical and genomic information from TCGA and GEO databases. The signature was proved to regulate genomic alteration, immune microenvironment and drug sensitivity in colon cancer, and thus might serve as a predictor for individual prognosis and treatment.

AbstractBackground The value of plasma Platelet-Derived Growth Factor (PDGF) as a biomarker in predicting major adverse cardiovascular events (MACEs) in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear.Methods A total of 242 patients with NSTEMI were enrolled in this observational cohort study. The correlation between PDGF and MACEs was evaluated during a five-year follow-up. Kaplan–Meier survival analysis with Cox proportional-hazards regression was used to identify predictive values of PDGF.Results The mean follow-up of NSTEMI patients was 1334 days. It was found that as the PDGF level increased, a significant uptrend in the incidence of MACEs and all-cause death, including the MACEs of 30 days, 180 days, 1 year, 5 years and the death of 1 year and 5 years (All Log-rank p 65 years, GRACE score ≥140 and platelet count (PLT) >200 × 109/L.Conclusion PDGF levels can predict short-term and long-term MACEs in NSTEMI patients after discharge, especially for patients with older age, higher GRACE score and baseline PLT > 200 × 109/L.Key messagesPDGF is a risk factor for short- and long-term MACEs in patients with STEMI.PDGF has a better prognostic value in patients with older age and PLT > 200 × 109/L.Baseline plasma PDGF levels were positively correlated with GRACE score.

Objectives The personalised treatment demands of patients with psoriasis did not get significant attention during the pandemic lockdown. This study aimed to investigate the treatment demands of patients with psoriasis with different severities, stratified by COVID-19 pandemic conditions.Design Cross-sectional study design.Setting Multicentre study based on a national psoriasis registry in China.Participants A total of 22 425 adult patients with psoriasis were enrolled between August 2020 and September 2021.Primary and secondary outcome measures The primary outcomes were patient demands for quick healing of skin lesions and improving mental health, which were collected by questionnaires. Multivariable logistic models were used to examine the impact of disease severity, as measured by Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Investigator’s Global Assessment (IGA), on treatment demands, as stratified by COVID-19 pandemic conditions (lockdown vs non-lockdown).Results Increasing PASI score significantly increased patient demands for rapid healing of skin lesions and improving mental health during non-lockdown periods. The magnitude of both associations further increased during the COVID-19 lockdown from an OR of 1.45 (95% CI 1.27 to 1.65) to 2.19 (95% CI 1.57 to 3.05) and 2.21 (95% CI 2.03 to 2.40) to 2.82 (95% CI 2.24 to 3.55), respectively. The skin lesion healing demand was more triggered by the overall irritation level (measured by IGA, OR 1.64, 95% CI 1.35 to 1.99 during non-lockdown periods vs OR 2.70, 95% CI 1.63 to 4.49 during lockdowns), while the mental health improving demand was more triggered by lesion coverage (measured by BSA, OR 2.01, 95% CI 1.85 to 2.19 vs OR 3.27, 95% CI 2.57 to 4.15).Conclusions Psoriasis aggravation significantly increased patients’ treatment demands, especially during lockdowns. The used psoriasis severity measures highlighted patients’ treatment demands differently. This suggests more accessible and personalised healthcare for patients with psoriasis should be available during future pandemics.

The Chinese government's environmental conservation efforts require the active participation of all society. This study investigated how internal and external efficacy influence pro-environmental behavior with environmental willingness as a mediator. This study employed a structural equation model to analyze the data from 1499 survey questionnaires. The analysis revealed that both internal and external efficacy can enhance individuals' pro-environmental behavior in the private and public spheres. External efficacy has a stronger impact on environmental willingness and public sphere environmental behavior, while internal efficacy more significantly influences private sphere environmental behavior. Additionally, environmental willingness only mediates efficacy and public sphere environmental behavior. The innovation of this study is the examination of internal and external efficacy from the perspective of different sources and the comparison of their differential impacts on pro-environmental behavior. Relevant policies should effectively enhance residents' internal and external efficacy to comprehensively improve their level of pro-environmental behavior.

Involving in the immune response after cerebral infarction, astrocytes could secrete large amounts of pro- and anti-inflammatory factors. The aim of this study is to investigate the effect of Wnt3a intervention on the inflammatory response of oxygen-glucose deprivation (OGD) followed by reoxygenation (OGD/R) astrocyte model, and to provide a new target for immunoprotective treatment of cerebral infarction. We constructed the OGD/R rat astrocyte model, the astrocytes were treated by different concentrations of glucose (25, 50, 100 mM) intervened with/without Wnt3a (25 µg/ml). Microscope was used to observe the cell survival in rat astrocytes. The relative expression of inflammatory factors (TNF-a, IL-6, HIF-a) in rat astrocytes was detected by qRT-PCR. The expression of inflammatory factors such as TNF-a, IL-6 and HIF-a in rat astrocytes was increased after OGD/R treatment. The Wnt3a intervention promoted cell survival and decreased the expression of inflammatory factors in rat astrocytes induced by OGD/R. There is a neuroprotective effect that Wnt3a intervention could reduce inflammatory response in the OGD/R rat astrocyte model.

Abstract Background Interleukin-17A (IL-17A), a proinflammatory cytokine primarily secreted by Th17 cells, γδT cells and natural killer T (NKT) cells, performs essential roles in the microenvironment of certain inflammation-related tumours by regulating cancer growth and tumour elimination proved in previous literature. In this study, the mechanism of IL-17A that induces mitochondrial dysfunction promoted pyroptosis has been explored in colorectal cancer cells. Method The records of 78 patients diagnosed with CRC were reviewed via the public database to evaluate clinicopathological parameters and prognosis associations of IL-17A expression. The colorectal cancer cells were treated with IL-17A, and the morphological characteristics of those cells were indicated by scanning electron microscope and transmission electron microscope. After IL-17A treatment, mitochondrial dysfunction was tested by mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). The expression of pyroptosis associated proteins including cleaved caspase-4, cleaved gasdermin-D (GSDMD), IL-1β, receptor activator of nuclear NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck like protein containing a card (ASC), and factor-kappa B was measured through western blotting. Results Positive IL-17A protein expression was observed in CRC compared to the non-tumour tissue. IL-17A expression indicates a better differentiation, earlier stage, and better overall survival in CRC. IL-17A treatment could induce mitochondrial dysfunction and stimulate intracellular reactive oxygen species (ROS) production. Furthermore, IL-17A could promote pyroptosis of colorectal cancer cells and significantly increase the secretion of inflammatory factors. Nevertheless, the pyroptosis induced by IL-17A could be inhibited through the pre-treatment with Mito-TEMPO (a mitochondria-targeted superoxide dismutase mimetic with superoxide and alkyl radical scavenging properties) or Z-LEVD-FMK (caspase-4 inhibitor, fluoromethylketone). Additionally, after being treated with IL-17A, an increasing number of CD8 + T cells showed in mouse-derived allograft colon cancer models. Conclusion IL-17A, as a cytokine mainly secreted by γδT cells in the colorectal tumour immune microenvironment, can regulate the tumour microenvironment in multiple ways. IL-17A could induce mitochondrial dysfunction and pyroptosis through the ROS/NLRP3/caspase-4/GSDMD pathway, and promote intracellular ROS accumulation. In addition, IL-17A can promote the secretion of inflammatory factors such as IL-1β、IL-18 and immune antigens, and recruit CD8 + T cells to infiltrate tumours. Graphical Abstract

AbstractBackground Bile acids play crucial roles in various metabolisms, as well as Lactobacillus in the intestine. But studies on their roles in acute coronary syndrome (ACS) are still insufficient. The aim of this study was to investigate their role and potential association with the severity of coronary lesions and the prognosis of ACS.Methods Three hundred and sixty ACS patients were selected. Detection of gut Lactobacillus levels was done through 16S rDNA sequence analysis. Evaluation of the extent of lesions was done using the SYNTAX (SS) score. Mediation analysis was used to assess the relationship between serum total bile acid (TBA), Lactobacillus, atherosclerotic lesions and prognosis of ACS.Results Logistic regressive analysis disclosed that serum TBA and Lactobacillus were independent predictors of coronary lesions (high vs. low SS: serum TBA adjusted odds ratio (aOR) = 0.8, 95% confidence interval (CI): 0.6–0.9, p

Abstract Background Hepatocellular carcinoma (HCC) is one of the most malignant tumors to threaten human life, and the survival rate remains low due to delayed diagnosis. Meanwhile, lncRNAs have great potential for application in tumor prognosis, therefore relevant research in hepatocellular carcinoma is indispensable. Methods Based on the EZH2 expression, the differentially expressed lncRNAs DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified in hepatocellular carcinoma by using the TCGA database. Bioinformatics technology was utilized to determine the effect of key genes in HCC progression. The methylation and immune infiltration analyses were performed to explore the underlying function of hub genes. Finally, cellular function experiments were performed to investigate the association between identified genes and biological phenotypes in HCC. Results lncRNA-AC079061.1, hsa-miR-765, and VIPR1 were identified as independent factors that affect the prognosis of hepatocellular carcinoma. The immune infiltration analyses revealed that lncRNA-AC079061.1 can alter the immune microenvironment and thus inhibit the development of HCC by regulating the expression of an immune-related gene (VIPR1). Methylation analyses demonstrated that VIPR1 expression is negatively related to the methylation level in HCC. Experimental results suggested that lncRNA-AC079061.1 and VIPR1 were frequently downregulated in HCC cells, while hsa-miR-765 was significantly upregulated. Moreover, the lncRNA-AC079061.1/VIPR1 axis suppressed the proliferation and invasion of HCC cells. Conclusion The present study identified the lncRNA-AC079061.1/VIPR1 axis as a novel biomarker that inhibited the proliferation and invasion of hepatocellular carcinoma, affecting the ultimate disease outcome.

Four patients with localized plaque psoriasis had used various systemic drugs along with topical cream. However, their skin lesions recurred, and the disease was refractory. After 2 weeks of discontinuation of oral and external medication, they were given three consecutive irradiation treatments with intense pulsed light once every 2 weeks for a 6-week period. After treating for 6 weeks, the erythema colors of the patients were evidently darkened, the scales were evidently reduced, and the skin lesions were significantly thinner or even flattened. The treatment was satisfactory, without occurrence of severe adverse reactions.

Objective To investigate the association between red cell distribution width (RDW) and the RDW to platelet count ratio (RPR) and cardiovascular diseases (CVDs) and to further investigate whether the association involves population differences and dose–response relationships.Design Cross-sectional population-based study.Setting The National Health and Nutrition Examination Survey (1999–2020).Participants A total of 48 283 participants aged 20 years or older (CVD, n=4593; non-CVD, n=43 690) were included in this study.Primary and secondary outcome measures The primary outcome was the presence of CVD, while the secondary outcome was the presence of specific CVDs. Multivariable logistic regression analysis was performed to determine the relationship between RDW or the RPR and CVD. Subgroup analyses were performed to test the interactions between demographics variables and their associations with disease prevalence.Results A logistic regression model was fully adjusted for potential confounders; the ORs with 95% CIs for CVD across the second to fourth quartiles were 1.03 (0.91 to 1.18), 1.19 (1.04 to 1.37) and 1.49 (1.29 to 1.72) for RDW (p for trend

Abstract This study proposes the use of the voxel-based morphometry (VBM) technique to investigate structural alterations of the cerebral cortex in patients with strabismus and amblyopia (SA). Sixteen patients with SA and sixteen healthy controls (HCs) underwent magnetic resonance imaging. Original whole brain images were analyzed using the VBM method. Pearson correlation analysis was performed to evaluate the relationship between mean gray matter volume (GMV) and clinical manifestations. Receiver operating characteristic (ROC) curve analysis was applied to classify the mean GMV values of the SA group and HCs. Compared with the HCs, GMV values in the SA group showed a significant difference in the right superior temporal gyrus, posterior and anterior lobes of the cerebellum, bilateral parahippocampal gyrus, and left anterior cingulate cortex. The mean GMV value in the right superior temporal gyrus, posterior and anterior lobes of the cerebellum, and bilateral parahippocampal gyrus were negatively correlated with the angle of strabismus. The ROC curve analysis of each cerebral region confirmed the accuracy of the area under the curve. Patients with SA have reduced GMV values in some brain regions. These findings might help to reveal the potential pathogenesis of SA and its relationship with the atrophy of specific regions of the brain.

Abstract. In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

Summary: Background: Early detection of gastric cancer (GC) remains challenging. We aimed to examine urine proteomic signatures and identify protein biomarkers that predict the progression of gastric lesions and risk of GC. Methods: A case–control study was initially designed, covering subjects with GC and gastric lesions of different stages. Subjects were aged 40–69 years, without prior diagnosis of renal or urological diseases. We enrolled a total of 255 subjects, with 123 in the discovery stage from Linqu, China, a high-risk area for GC and 132 in the validation stage from Linqu and Beijing. A prospective study was further designed for a subset of 60 subjects with gastric lesions, which were followed for 297–857 days. Findings: We identified 43 differentially expressed urine proteins in subjects with GC vs. mild or advanced gastric lesions. Baseline urinary levels of ANXA11, CDC42, NAPA and SLC25A4 were further positively associated with risk of gastric lesion progression. Three of them, except for SLC25A4, also had higher expression in GC than non-GC tissues. Integrating these four proteins showed outstanding performance in predicting the progression of gastric lesions (AUC (95% CI): 0.92 (0.83–1.00)) and risk of GC (AUC (95% CI): 0.81 (0.73–0.89) and 0.84 (0.77–0.92) for GC vs. mild or advanced gastric lesions respectively). Interpretation: This study revealed distinct urine proteomic profiles and a panel of proteins that may predict the progression of gastric lesions and risk of GC. These biomarkers in a non-invasive approach may have translational significance for defining high-risk populations of GC and its early detection. Funding: Funders are listed in the Acknowledgement.

Abstract This study investigated neurologic changes in patients with dry eye (DE) by functional magnetic resonance imaging (fMRI) and to used regional homogeneity (ReHo) analysis to clarify the relationship between these changes and clinical features of DE. A total of 28 patients with DE and 28 matched healthy control (HC) subjects (10 males and 18 females in each group) were enrolled. fMRI scans were performed in both groups. We carried out ReHo analysis to assess differences in neural activity between the 2 groups, and receiver operating characteristic curve (ROC) analysis was performed to evaluate the performance of ReHo values of specific brain areas in distinguishing DE patients from HCs. The relationship between average ReHo values and clinical characteristics was assessed by correlation analysis. ReHo values of the middle frontal gyrus, inferior frontal gyrus, and superior frontal gyrus were significantly lower in DE patients compared to HCs. The ROC analysis showed that ReHo value had high accuracy in distinguishing between DE patients and HCs (P

Abstract. Purpose:. To explore the offset distribution of pupillary centres, the offset between the pupil centre and the coaxially sighted corneal light reflex (P-Dist) and their correlation in femtosecond laser combined with excimer laser in situ keratomileusis. Methods:. Randomly selected 194 patients (398 eyes) who underwent femtosecond-assisted laser in situ keratomileusis with preoperative use of WaveLight Allegro Topolyzer Corneal Topography (WaveLight Laser Technologies AG, Erlangen, Germany) to measure the pupil size and centre position. The P-Dist of the patients was recorded by the X and Y axis eyeball tracking adjustment program of the WaveLight Eagle Vision EX500 excimer laser system. Results:. The P-Dist was 0.214 ± 0.092 mm in the right eyes and 0.228 ± 0.105 mm in the left eyes (P = .041). Under scotopic conditions, the pupil centre of left eye X-axis was −0.046 ± 0.091 mm, the right eye was −0.152 ± 0.084 mm, with significant differences (P = .015), and the Y-axis direction showed no significant changes (P = .062). The white to white was positively correlated with changes of pupil diameter (scotopic pupil diameter-photopic pupil diameter) (r = 0.270, P

ABSTRACT BACKGROUND: For critically ill patients, physicians tend to administer sufficient or even excessive oxygen to maintain oxygen saturation at a high level. However, the credibility of the evidence for this practice is unclear. OBJECTIVE: To determine the effects of different oxygen therapy strategies on the outcomes of mechanically ventilated intensive care unit (ICU) patients. DESIGN AND SETTING: Systematic review of the literature and meta-analysis conducted at Jiangxi Provincial People’s Hospital, Affiliated to Nanchang University, Nanchang, China. METHODS: We systematically searched electronic databases such as PubMed and Embase for relevant articles and performed meta-analyses on the effects of different oxygen therapy strategies on the outcomes of mechanically ventilated ICU patients. RESULTS: A total of 1802 patients from five studies were included. There were equal numbers of patients in the conservative and liberal groups (n = 910 in each group). There was no significant difference between the conservative and liberal groups with regard to 28-day mortality (risk ratio, RR = 0.88; 95% confidence interval, CI = 0.59-1.32; P = 0.55; I2 = 63%). Ninety-day mortality, infection rates, ICU length of stay, mechanical ventilation-free days up to day 28 and vasopressor-free days up to day 28 were comparable between the two strategies. CONCLUSIONS: It is not necessary to use liberal oxygen therapy strategies to pursue a higher level of peripheral oxygen saturation for mechanically ventilated ICU patients. Conservative oxygen therapy was not associated with any statistically significant reduction in mortality.

Abstract Yellow leaf disease caused by sugarcane yellow leaf virus (SCYLV) is one of the most prevalent diseases worldwide. In this study, six near-complete genome sequences of SCYLV were determined to be 5775–5881 bp in length. Phylogenetic analysis revealed that the two SCYLV isolates from Réunion Island, France, and four from China were clustered into REU and CUB genotypes, respectively, based on 50 genomic sequences (this study = 6, GenBank = 44). Meanwhile, all 50 isolates were clustered into three phylogroups (G1–G3). Twelve significant recombinant events occurred in intra- and inter-phylogroups between geographical origins and host crops. Most recombinant hotspots were distributed in coat protein read-through protein (RTD), followed by ORF0 (P0) and ORF1 (P1). High genetic divergences of 12.4% for genomic sequences and 6.0–24.9% for individual genes were determined at nucleotide levels. The highest nucleotide diversity (π) was found in P0, followed by P1 and RdRP. In addition, purifying selection was a main factor restricting variability in SCYLV populations. Infrequent gene flow between Africa and the two subpopulations (Asia and America) were found, whereas frequent gene flow between Asia and America subpopulations was observed. Taken together, our findings facilitate understanding of genetic diversity and evolutionary dynamics of SCYLV.

Abstract In the present work, Ag@AgCl-reinforced cellulose composites with enhanced antibacterial and photocatalytic degradation properties were successfully synthesized via oil bath heating method. During the process, zinc chloride (ZnCl2) solution was used as both Cl− resource to form AgCl and the solvent to dissolve cellulose. The samples were synthesized with different temperatures, times, and concentrations of ZnCl2 solution. The morphology, microstructure and phase of the as-prepared samples were analyzed with X-ray powder diffraction (XRD), fourier transform infrared (FTIR) spectrometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HR-TEM), X-ray photoelectron spectroscopy (XPS), photocatalytic activity studies and inhibition zone experiments. Results showed that dye solution could be completely degraded by the materials in 1 h, and higher concentrations of ZnCl2 solution favored for larger inhibition zones (higher to 10.8 mm). This synthetic strategy displayed here offers more possibilities to high value-added applications of cellulose.

Abstract. Background:. Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM. Methods:. We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤ 168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM,

Abstract. Background:. Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression. Methods:. The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed. Results:. Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios+ Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA. Conclusion:. Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.

Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management. Methods: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280–473 days), and an independent case-control study from Beijing (n = 99). Findings: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78–0.99) vs. 0.56 (0.36–0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins. Interpretation: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention. Funding: The funders are listed in the Acknowledgement.

A 52-year-old woman presented with erythema, papules, pain, and itching on the buttocks and trunk that had persisted for 1 week. Twenty-two days before admission, the patient received three intramuscular injections of vitamin K1 in the gluteal muscles. Two weeks after the last intramuscular injection edematous hard erythema developed bilaterally on the gluteal muscles, accompanied by itching, pain, and a burning sensation. Afterward, the erythema and papules gradually spread to the trunk, with notable itching. Dermatological examination revealed a large area of well-defined edematous hard erythema, and blisters around the injection sites on both hips. The skin temperature was high, with mild tenderness. Dense distributions of edematous erythema and papules were observed on the trunk, some of which were fused into pieces. The patient received a diagnosis of a skin reaction induced by intramuscular injections of vitamin K1. Therefore, she was administered glycyrrhizin, calcium, vitamin C, antihistamines, topical polysulfonic mucopolysaccharide cream, and glucocorticoid cream, and the lesions subsided after 2 weeks.

Abstract. Background:. Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT. Methods:. From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups. Results:. After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P

Abstract. Background:. Macrophage accumulation in the vascular wall is a hallmark of atherosclerosis. Studies showed that shifting of oxidized lipids-induced inflammatory macrophages towards an anti-inflammatory phenotype by promoting oxidative metabolism attenuated atherosclerosis progression. Therefore, this study aimed to investigate whether metformin, which has ameliorated atherosclerosis in animal models and clinical trials, modulated oxidized low-density lipoprotein (Ox-LDL) induced inflammatory status in macrophages by regulating cellular oxidative metabolism. Methods:. Murine raw264.7 macrophages were incubated with Ox-LDL (50 μg/mL) in the presence or absence of metformin (15 μmol/L) for 24 h. Real-time polymerase chain reaction was used to quantify the transcription of classically activated (M1) pro-inflammatory and alternatively activated (M2) anti-inflammatory markers and mitochondrial DNA copy numbers. Cellular reactive oxygen species (ROS) production and mitochondrial membrane potential were detected by immunofluorescence. Cellular adenosine triphosphate (ATP) synthesis, glucose uptake, and lactic acid production were measured by commercial kit and normalized to cellular lysates. Western blotting analysis was performed to detect the expression of mitochondrial fusion/fission related proteins, enzymes mediating lipid metabolism and signaling pathway of glucose transport. Differences between groups were analyzed using one-way analysis of variance. Results:. Metformin improved Ox-LDL-impaired anti-inflammatory phenotype in raw264.7 macrophages as shown by up-regulated transcription of anti-inflammatory markers including interleukin 10 (0.76 ± 0.04 vs. 0.94 ± 0.01, P = 0.003) and Resistin-like molecule alpha (0.67 ± 0.08 vs. 1.78 ± 0.34, P = 0.030). Conversely, Ox-LDL-diminished phosphorylation of Akt was up-regulated by metformin treatment (0.47 ± 0.05 vs. 1.02 ± 0.08, P = 0.040), associated with an improvement of mitochondrial function, characterized by decreased ROS generation (2.50 ± 0.07 vs. 2.15 ± 0.04, P = 0.040), increased lipid oxidation, and elevated cellular ATP production (0.026 ± 0.001 vs. 0.035 ± 0.003, P = 0.020). Moreover, metformin-mediated Akt activation increased Akt substrate of 160 kDa (AS160) phosphorylation (0.51 ± 0.04 vs. 1.03 ± 0.03, P = 0.0041), promoted membrane translocation of glucose transporter 1, and increased glucose influx into the cells (4.78 ± 0.04 vs. 5.47 ± 0.01, P

Abstract Intimate partner violence (IPV) and HIV are highly prevalent worldwide among MSM. However, the association between IPV and HIV seroconversion is virtually unknown. This 12-month prospective cohort study was conducted among MSM in Shenyang, China to explore the causality between IPV and the incidence of HIV. Adjusted Hazard Ratios (aHRs) of HIV acquisition were derived from a multivariate time-dependent Cox model and applied to calculate population attributable fractions (PAFs). Among 476 HIV-negative MSM subjects, 89(18.7%) reported being victims of IPV in the past 3 months (P3M). IPV was significantly correlated with lower education, having more condomless anal intercourse (CAI) and being depressed (each P

Abstract High-carbon martensite steels (with C > 0.5 wt.%) are very hard but at the same time as brittle as glass in as-quenched or low-temperature-tempered state. Such extreme brittleness, originating from a twin microstructure, has rendered these steels almost useless in martensite state. Therefore, for more than a century it has been a common knowledge that high-carbon martensitic steels are intrinsically brittle and thus are not expected to find any application in harsh loading conditions. Here we report that these brittle steels can be transformed into super-strong ones exhibiting a combination of ultrahigh strength and significant toughness, through a simple grain-refinement treatment, which refines the grain size to ~4 μm. As a result, an ultra-high tensile strength of 2.4~2.6 GPa, a significant elongation of 4~10% and a good fracture toughness (K1C) of 23.5~29.6 MPa m1/2 were obtained in high-carbon martensitic steels with 0.61–0.65 wt.% C. These properties are comparable with those of “the king of super-high-strength steels”—maraging steels, but achieved at merely 1/30~1/50 of the price. The drastic enhancement in mechanical properties is found to arise from a transition from the conventional twin microstructure to a dislocation one by grain refinement. Our finding may provide a new route to manufacturing super-strong steels in a simple and economic way.

Abstract Based on our initial genome-wide association study (GWAS) on esophageal squamous cell carcinoma (ESCC) in Han Chinese, we conducted a follow-up study to examine the single nucleotide polymorphisms (SNPs) associated with family history (FH) of upper gastrointestinal cancer (UGI) cancer in cases with ESCC. We evaluated the association between SNPs and FH of UGI cancer among ESCC cases in a stage-1 case-only analysis of the National Cancer Institute (NCI, 541 cases with FH and 1399 without FH) and Henan GWAS (493 cases with FH and 869 without FH) data (discovery phase). The top SNPs (or their surrogates) from discovery were advanced to a stage-2 evaluation in additional Henan subjects (2801 cases with FH and 3136 without FH, replication phase). A total of 19 SNPs were associated with FH of UGI cancer in ESCC cases with P

There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs), but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs) are associated with susceptibility for mKCs. A genome-wide association study (GWAS) of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls) from Harvard cohorts (the Nurses' Health Study [NHS], NHS II, and the Health Professionals Follow-Up Study) and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1). We sought to replicate the most significant statistical associations (p-value≤ 5.5x10-6) in an independent cohort of 574 mKCs and 872 sKCs from the Rotterdam Study. In the discovery stage, 40 SNPs with suggestive associations (p-value ≤5.5x10-6) were identified, with eight independent SNPs tagging all 40 SNPs. The most significant SNP was located at chromosome 9 (rs7468390; p-value = 3.92x10-7). In stage-2, none of these SNPs replicated and only two of them were associated with mKCs in the same direction in the combined meta-analysis. We tested the associations for 19 previously reported basal cell carcinoma-related SNPs (candidate gene association analysis), and found that rs1805007 (MC1R locus) was significantly associated with risk of mKCs (p-value = 2.80x10-4). Although the suggestive SNPs with susceptibility for mKCs were not replicated, we found that previously identified BCC variants may also be associated with mKC, which the most significant association (rs1805007) located at the MC1R gene.