CD73 polymorphisms are associated with schizophrenia.

Ecto-5'-nucleotidase/CD73 enzyme plays a key role in the regulation of extracellular adenosine levels, thereby exerting influence on adenosine homeostasis. Emerging evidence suggests that perturbations in purines and ecto-5'-nucleotidase activity are associated with an augmented susceptibility to schizophrenia. However, the precise impact of genetic variations in CD73 on individuals with schizophrenia remains poorly understood. Here, our study demonstrated that rs3734442 allele and rs4431401 heterozygote were conferred a significant risk of schizophrenia disease (rs3734442: odds ratio, 0.556; 95% CI, 0.375 to 0.825; p = 0.004; rs4431401: odds ratio, 1.881, 95% CI, 1.117 to 3.166; p = 0.020). Comparing different genders, we observed a significant association between rs3734442 genotypes and male cases (rs3734442: odds ratio, 0.452; 95% CI, 0.257 to 0.796; p = 0.007). Likewise, there was a significant association between rs4431401 genotypes and male patients (rs4431401: odds ratio, 2.570; 95% CI, 1.196 to 5.522; p = 0.015). Based on family history and antipsychotics medication usage, our data reveals that the rs9444348 allele exhibits the most significant association with familial susceptibility to schizophrenia (odds ratio, 1.541; 95% CI, 1.009 to 2.353; p = 0.048 for A vs G). Moreover, individuals carrying variants of rs6922, rs2229523, and rs2065114 while being treated with clozapine demonstrate a higher frequency proportion compared to those receiving risperidone treatment (p = 0.035; p = 0.049; p = 0.027 respectively). Additionally, our results indicate that patients with GG genotype of rs9444348 had significantly higher likelihood of using clozapine instead of sulpiride (p = 0.048). Overall, our data strongly suggest that genetic variations in CD73 are significantly associated with schizophrenia risk and may serve as valuable resources for identifying therapeutic targets.

VDR promotes pancreatic cancer progression in vivo by activating CCL20-mediated M2 polarization of tumor associated macrophage.

BACKGROUND: Activation of VDR pathway was a promising anti-tumor therapy strategy. However, numerous clinical studies have demonstrated the effect of activating VDR is limited, which indicates that VDR plays a complex role in vivos. METHODS: We analyzed the TCGA database to examine the association between VDR expression and immune cell infiltration in pancreatic adenocarcinoma (PAAD). Western blot, ELISA, ChIP, and dual-luciferase reporter assays were performed to determine the mechanism of VDR regulating CCL20. Migration assay and immunofluorescence were used to investigate the role of CCL20 in M2 macrophage polarization and recruitment. We employed multiplexed immunohistochemical staining and mouse models to validate the correlation of VDR on macrophages infiltration in PAAD. Flow cytometry analysis of M2/M1 ratio in subcutaneous graft tumors. RESULTS: VDR is extensively expressed in PAAD, and patients with elevated VDR levels exhibited a significantly reduced overall survival. VDR expression in PAAD tissues was associated with increased M2 macrophages infiltration. PAAD cells overexpressing VDR promote macrophages polarization towards M2 phenotype and recruitment in vitro and vivo. Mechanistically, VDR binds to the CCL20 promoter and up-regulates its transcription. The effects of polarization and recruitment on macrophages can be rescued by blocking CCL20. Finally, the relationship between VDR and M2 macrophages infiltration was evaluated using clinical cohort and subcutaneous graft tumors. A positive correlation was demonstrated between VDR/CCL20/CD163 in PAAD tissues and mouse models. CONCLUSION: High expression of VDR in PAAD promotes M2 macrophage polarization and recruitment through the secretion of CCL20, which activates tumor progression. This finding suggests that the combination of anti-macrophage therapy may improve the efficacy of VDR activation therapy in PAAD.

Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.

Repeat corneal transplantation in Southern China: Indications, surgical technique, outcomes, and risk factors for repeat keratoplasty failure.

PURPOSE: To report the indications, surgical techniques, and outcomes of repeat keratoplasty and evaluate the risk factors for graft failure in the Chinese population. METHODS: The medical records of 216 patients (243 cases) who underwent at least two keratoplasties at a leading eye hospital in southern China between 2011 and 2020 were retrospectively reviewed. Indications and surgical procedures for repeat corneal transplantation were analyzed. Kaplan-Meier survival analysis was used to determine the graft survival rate after repeat keratoplasty. A multivariable survival model was used to assess the risk factors. RESULTS: Repeated keratoplasties increased continuously from 2011 to 2020 (P = 0.002). The most common primary indication was infectious keratitis (38.7%), and the most common reason for repeat keratoplasty was graft rejection (30.04%). Regraft techniques included penetrating keratoplasty (PK) in 165 cases (67.9%), deep lamellar keratoplasty (DALK) in 52 cases (21.40%), and endothelial keratoplasty (EK) in 26 cases (10.7%). Median survival was 5.3, 6.8, and 6.4 years for PK, DALK, and EK, respectively. The 5-year survival rate was 53.5%, 66.6%, and 69.8% for PK, DALK, and EK, respectively. The median LogMAR visual acuity was 1.4 for PK, 0.75 for DALK, and 1.2 for EK at the end of the follow-up. Multivariate analysis revealed that graft rejection is a risk factor for repeat keratoplasty failure (P = 0.002). CONCLUSIONS: DALK and EK may provide better outcomes than PK in treating graft failure. Preventing and treating postoperative graft rejection may be key to improving regraft survival. These findings will aid in the management of failed corneal grafts.

Characterizing the Efficacy and Safety of Chemotherapy Plus Everolimus in HER2-Negative Metastatic Breast Cancer Harboring Altered PI3K/AKT/mTOR.

BACKGROUND: The clinical outcomes of chemotherapy (CT) for the treatment of metastatic triple-negative (TN) and hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) have proven to be disappointing. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, a tumor-promoting signaling cascade frequently mutated in breast cancer (BC), has been implicated in chemoresistance. In this study, our objective is to investigate the efficacy and safety of combining everolimus with chemotherapy in mBC patients exhibiting mutations in the PI3K/AKT/mTOR pathway. METHODS: We conducted a retrospective analysis to characterize the efficacy, safety, and their association with clinical and molecular characteristics of metastatic lesions in 14 patients with HER2- mBC. These patients harbored at least one altered member of the PI3K/AKT/mTOR signaling pathway and were treated with a combination of a chemotherapy agent and the mTOR inhibitor everolimus (CT+EVE). RESULTS: The majority of patients belonged to the triple-negative (TN) subtype (9/14, 64.3%), having already undergone 2 lines of chemotherapy (CT) in the metastatic setting (11, 78.6%). These patients carried altered phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and were administered a vinorelbine-containing regimen (10, 71.4%). The objective response rate (ORR) was 42.9%, with a disease control rate of 92.9%. The median progression-free survival (PFS) and overall survival (OS) were 5.9 (95% confidence interval (CI): 4.9-13.6) months and 14.3 (95% CI: 8.5-not reached (NR)) months, respectively. Patients with fewer prior treatment lines tended to exhibit longer PFS. OS, PFS, and ORR were comparable between hormone receptor-positive (HR+) and triple-negative breast cancer (TNBC) patients, but numerical improvements were noted in patients with a single PI3K pathway alteration compared to those with more than one alteration. Genomic alterations that surfaced upon progression on CT+EVE included cyclin dependent kinase 4 (CDK4) and epidermal growth factor receptor (EGFR) amplification, as well as neurofibromin 1 (NF1) mutation, suggesting potential mechanisms of acquired resistance. An analysis of adverse events indicated manageable toxicities. CONCLUSIONS: The findings of this study suggest both activity and safety for the combination of chemotherapy and the mTOR inhibitor everolimus (CT+EVE) in patients with HER2- mBC who have alterations in the PI3K pathway, particularly those who have received fewer prior chemotherapy. However, it is crucial to note that large-scale, randomized control studies are warranted to more comprehensively characterize the efficacy and safety of this combination therapy.

N6-methyladenosine (m6A) sequencing reveals Heterodera glycines-induced dynamic methylation promoting soybean defense.

Unraveling the intricacies of soybean cyst nematode (Heterodera glycines) race 4 resistance and susceptibility in soybean breeding lines-11-452 (highly resistant) and Dongsheng1 (DS1, highly susceptible)-was the focal point of this study. Employing cutting-edge N6-methyladenosine (m6A)-seq and RNA-seq techniques, we delved into the impact of m6A modification on gene expression and plant defense responses. Through the evaluation of nematode development in both resistant and susceptible roots, a pivotal time point (3 days post inoculation) for m6A methylation sequencing was identified. Our sequencing data exhibited robust statistics, successful soybean genome mapping, and prevalent m6A peak distributions, primarily in 3'UTR (Untranslated region) and stop codon regions. Analysis of differentially expressed m6A peaks (DMPs) and expressed genes (DEGs) revealed distinctive patterns between resistant and susceptible genotypes. In the highly resistant line (11-452), key resistance and defense-associated genes displayed increased expression coupled with inhibited methylation, encompassing crucial players like R genes, receptor kinases, and transcription factors. Conversely, the highly susceptible DS1 line exhibited heightened expression correlated with decreased methylation in genes linked to susceptibility pathways, including Mildew Locus O (MLO)-like proteins and regulatory elements affecting defense mechanisms. Genome-wide assessments, GO/KEGG analyses, and DMP/DEG overlap emphasized the intricate interplay of m6A modifications, alternative splicing, microRNA and gene regulation in plant defense. Protein-protein interaction networks illuminated defense-pivotal genes, delineating divergent mechanisms in resistant and susceptible responses. This study sheds light on the dynamic correlation between methylation, splicing, and gene expression, providing profound insights into plant responses to nematode infection.

Identification of groundwater pollution sources and health risk assessment in the Fengshui mining area of Central Shandong, China.

The crux of groundwater protection lies in a profound understanding of the sources of pollutants and their impacts on human health. This study selected 47 groundwater samples from the Fengshui mining area in central Shandong Province, China, employing advanced hydrogeochemical techniques, positive matrix factorization (PMF), and Monte Carlo analysis methods, aimed at unveiling the characteristics, origins, and health risks of water pollutants. The results indicated that the majority of samples exhibited a slightly alkaline nature. Notably, the concentrations of fluoride (F-) and nitrate (NO3-) exceeded China's safety standards in 40.43% and 23.40% of the samples, respectively. Moreover, a water quality index (WQI) below 50 was observed in approximately 68.09% of the sites, suggesting that the water quality in these areas generally met acceptable levels. However, regions with higher WQI values were predominantly located in the northern and southern parts of the mining area. PMF analysis revealed that regional geological and industrial activities were the primary factors affecting water quality, followed by mining discharges, fundamental geological and agricultural processes, and leachate enrichment activities. The health risk assessment highlighted the heightened sensitivity of the youth demographic to fluoride, with a more pronounced non-carcinogenic risk compared to nitrate, affecting about 31.89% of the youth population. Hence, it is imperative for local authorities and relevant departments to take prompt actions to remediate groundwater contamination to minimize public health risks.

Enhanced SSD framework for detecting defects in cigarette appearance using variational Bayesian inference under limited sample conditions.

In high-speed cigarette manufacturing industries, occasional minor cosmetic cigarette defects and a scarcity of samples significantly hinder the rapid and accurate detection of defects. To tackle this challenge, we propose an enhanced single-shot multibox detector (SSD) model that uses variational Bayesian inference for improved detection of tiny defects given sporadic occurrences and limited samples. The enhanced SSD model incorporates a bounded intersection over union (BIoU) loss function to reduce sensitivity to minor deviations and uses exponential linear unit (ELU) and leaky rectified linear unit (ReLU) activation functions to mitigate vanishing gradients and neuron death in deep neural networks. Empirical results show that the enhanced SSD300 and SSD512 models increase the model's detection accuracy mean average precision (mAP) by up to 1.2% for small defects. Ablation studies further reveal that the model's mAP increases by 1.5%, which reduces the computational requirements by 5.92 GFLOPs. The model also shows improved inference in scenarios with limited samples, thus highlighting its effectiveness and applicability in high-speed, precision-oriented cigarette manufacturing industries.

An immune-related gene prognostic prediction risk model for neoadjuvant chemoradiotherapy in rectal cancer using artificial intelligence.

Background: This study aimed to establish and validate a prognostic model based on immune-related genes (IRGPM) for predicting disease-free survival (DFS) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy, and to elucidate the immune profiles associated with different prognostic outcomes. Methods: Transcriptomic and clinical data were sourced from the Gene Expression Omnibus (GEO) database and the West China Hospital database. We focused on genes from the RNA immune-oncology panel. The elastic net approach was employed to pinpoint immune-related genes significantly impacting DFS. We developed the IRGPM for rectal cancer using the random forest technique. Based on the IRGPM, we calculated prognostic risk scores to categorize patients into high-risk and low-risk groups. Comparative analysis of immune characteristics between these groups was conducted. Results: In this study, 407 LARC samples were analyzed. The elastic net identified a signature of 20 immune-related genes, forming the basis of the IRGPM. Kaplan-Meier survival analysis revealed a lower 5-year DFS in the high-risk group compared to the low-risk group. The receiver operating characteristic (ROC) curve affirmed the model's robust predictive capability. Validation of the model was performed in the GSE190826 cohort and our institution's cohort. Gene expression differences between high-risk and low-risk groups predominantly related to cytokine-cytokine receptor interactions. Notably, the low-risk group exhibited higher immune scores. Further analysis indicated a greater presence of activated B cells, activated CD8 T cells, central memory CD8 T cells, macrophages, T follicular helper cells, and type 2 helper cells in the low-risk group. Additionally, immune checkpoint analysis revealed elevated PDCD1 expression in the low-risk group. Conclusions: The IRGPM, developed through random forest and elastic net methodologies, demonstrates potential in distinguishing DFS among LARC patients receiving standard treatment. Notably, the low-risk group, as defined by the IRGPM, showed enhanced activation of adaptive immune responses within the tumor microenvironment.

Non-IG::MYC in diffuse large B-cell lymphoma confers variable genomic configurations and MYC transactivation potential.

MYC translocation occurs in 8-14% of diffuse large B-cell lymphoma (DLBCL), and may concur with BCL2 and/or BCL6 translocation, known as double-hit (DH) or triple-hit (TH). DLBCL-MYC/BCL2-DH/TH are largely germinal centre B-cell like subtype, but show variable clinical outcome, with IG::MYC fusion significantly associated with inferior survival. While DLBCL-MYC/BCL6-DH are variable in their cell-of-origin subtypes and clinical outcome. Intriguingly, only 40-50% of DLBCL with MYC translocation show high MYC protein expression (>70%). We studied 186 DLBCLs with MYC translocation including 32 MYC/BCL2/BCL6-TH, 75 MYC/BCL2-DH and 26 MYC/BCL6-DH. FISH revealed a MYC/BCL6 fusion in 59% of DLBCL-MYC/BCL2/BCL6-TH and 27% of DLBCL-MYC/BCL6-DH. Targeted NGS showed a similar mutation profile and LymphGen genetic subtype between DLBCL-MYC/BCL2/BCL6-TH and DLBCL-MYC/BCL2-DH, but variable LymphGen subtypes among DLBCL-MYC/BCL6-DH. MYC protein expression is uniformly high in DLBCL with IG::MYC, but variable in those with non-IG::MYC including MYC/BCL6-fusion. Translocation breakpoint analyses of 8 cases by TLC-based NGS showed no obvious genomic configuration that enables MYC transactivation in 3 of the 4 cases with non-IG::MYC, while a typical promoter substitution or IGH super enhancer juxtaposition in the remaining cases. The findings potentially explain variable MYC expression in DLBCL with MYC translocation, and also bear practical implications in its routine assessment.

Dual role of CD73 as a signaling molecule and adenosine-generating enzyme in colorectal cancer progression and immune evasion.

Metastasis and limited benefits of immune checkpoint blockade are two obstacles to the battle against colorectal cancer (CRC). CD73, encoded by the gene 5'-Nucleotidase Ecto (NT5E), is a major enzyme that generates extracellular adenosine. However, whether CD73 affects cancer progression and immune response in CRC remains unclear. Here, the clinical significance of CD73 was assessed in human CRC specimens using immunohistochemistry and bioinformatic analyses. We demonstrated that CD73 is elevated in CRC tissues, particularly in those with metastasis, and correlates with poor prognosis. Gain- and loss-of-function experiments demonstrate that tumor CD73 supports tumor progression and impairs the viability and effector functions of CD8+ T cells. Targeting CD73 on CRC cells reduces their malignant phenotypes and improves the anti-cancer response of CD8+ T cells in the tumor microenvironment (TME). Moreover, the combination of CD73 blockade and PD-1 inhibitors exhibited enhanced anti-cancer effects when compared to a single-agent treatment. Thus, CD73 may be a promising target in the treatment of CRC.

N-acetylcysteine alleviated tris(2-chloroisopropyl) phosphate-induced sperm motility decline and functional dysfunction in mice through reversing oxidative stress and DNA damage.

The decline in male fertility caused by environmental pollutants has attracted worldwide attention nowadays. Tris(2-chloroisopropyl) phosphate (TCPP) is a chlorine-containing organophosphorus flame retardant applied in many consumer products and has multiple side effects on health. However, whether TCPP impairs spermatogenesis remains unclear. In this study, we found that TCPP reduced the sperm motility and blastocyst formation, inhibited proliferation and induced apoptosis in mice testes and spermatocyte cell line GC-2. Moreover, TCPP induced imbalance of oxidant and anti-oxidant, DNA damage and mitochondrial dysfunction, thus induced abnormal spermatogenesis. In this process, p53 signaling pathway was activated and N-acetylcysteine treatment partially alleviated the side effects of TCPP, including decrease of sperm motility, activation of p53 signaling pathway and DNA damage. Finally, our study verified that TCPP elevated reactive oxygen species (ROS), decreased mitochondrial membrane potential and induced apoptosis in human semen samples. Overall, ROS mediated TCPP-induced germ cell proliferation inhibition and apoptosis, which finally led to the decline of sperm motility.

The effect of photobiomodulation on hearing loss: A systematic review.

OBJECTIVES: To assess outcomes associated with photobiomodulation therapy (PBMT) for hearing loss in human and animal studies. DESIGN: Systematic review and narrative synthesis in accordance with PRISMA guidelines. SETTING: Data bases searched: MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov and Web of Science. No limits were placed on language or year of publication. Review conducted in accordance with the PRISMA 2020 statement. PARTICIPANTS: All human and animal subjects treated with PBMT for hearing loss. MAIN OUTCOME MEASURES: Pre- and post-PBMT audio metric outcomes. RESULTS: Searches identified 122 abstracts and 49 full text articles. Of these, 17 studies met the inclusion criteria, reporting outcomes in 327 animals (11 studies), 30 humans (1 study), and 40 animal specimens (5 studies). PBMT parameters included 6 different wavelengths: 908 nm (1 study), 810 nm (1 study), 532 & 635 nm (1 study), 830 nm (3 studies), 808 nm (11 studies). The duration ranged from 4 to 60 minutes in a session, and the follow-up ranged from 5-28 days. Outcomes improved significantly when wavelengths within the range of 800-830 nm were used, and with greater duration of PBMT exposure. Included studies predominantly consisted of non-randomized controlled trials (10 studies). CONCLUSIONS: Hearing outcomes following PBMT appear to be superior to no PBMT for subjects with hearing loss, although higher level evidence is required to verify this. PBMT enables concentrated, focused delivery of light therapy to the inner ear through a non-invasive manner with minimal side effects. As a result of heterogeneity in reporting PBMT parameters and outcomes across the included studies, direct comparison is challenging.

Relapses in early-stage follicular lymphoma frequently develop via a divergent evolution from their clonally related precursor cells.

Follicular lymphoma (FL) develops through a stepwise acquisition of cooperative genetic changes with t(14;18)(q32;q21)/IGH::BCL2 occurring early at the pre-B stage of B-cell development. Patients with FL typically show an indolent clinical course, remitting and relapsing with the eventual development of resistance to treatments. Interestingly, the majority of transformed FL do not progress directly from FL but originate from their clonally related lymphoma precursor (CLP) cells. To examine whether such divergent tumour evolution also underpins the relapses in patients with early-stage FL, we investigated by targeted next-generation sequencing 13 cases (stage I = 9, stage II = 4), who showed complete remission (mean: 5 years; range: 1-11.5 years) following local radiotherapy but subsequently relapsed (≥2 in 5). A clonal relationship between the diagnostic FL and relapses was confirmed in 11 cases. In six cases, common and distinct variants were seen between the paired diagnostic and relapsed lymphomas, indicating their divergent evolution from a CLP. In two cases, different B-cell clones were involved in the diagnostic and relapsed lymphomas, including one case involving two different BCL2 translocations. In the remaining five cases, the relapsed lymphoma developed via a linear progression (n = 4) or a mixed evolutionary path (n = 1). These findings may bear important implications in the routine diagnosis and management of relapsed FL. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Classification of Acoustic Hearing Preservation After Cochlear Implantation Using Electrocochleography.

The objective to preserve residual hearing during cochlear implantation has recently led to the use of intracochlear electrocochleography (ECochG) as an intraoperative monitoring tool. Currently, a decrease in the amplitude of the difference between responses to alternating-polarity stimuli (DIF response), predominantly reflecting the hair cell response, is used for providing feedback. Including other ECochG response components, such as phase changes and harmonic distortions, could improve the accuracy of surgical feedback. The objectives of the present study were (1) to compare simultaneously recorded stepwise intracochlear and extracochlear ECochG responses to 500 Hz tone bursts, (2) to explore patterns in features extracted from the intracochlear ECochG recordings relating to hearing preservation or hearing loss, and (3) to design support vector machine (SVM) and random forest (RF) classifiers of acoustic hearing preservation that treat each subject as a sample and use all intracochlear ECochG recordings made during electrode array insertion for classification. Forty subjects undergoing cochlear implant (CI) surgery at the Oslo University Hospital, St. Thomas' Hearing Implant Centre, or the University Hospital of Zurich were prospectively enrolled. In this cohort, DIF response amplitude decreases did not relate to postoperative acoustic hearing preservation. Exploratory analysis of the feature set extracted from the ECochG responses and preoperative audiogram showed that the features were not discriminative between outcome classes. The SVM and RF classifiers that were trained on these features could not distinguish cases with hearing loss and hearing preservation. These findings suggest that hearing loss following CI surgery is not always reflected in intraoperative ECochG recordings.

Diagnostic value of circulating miRNA in the benign and malignant lung nodules: A systematic review and meta-analysis.

BACKGROUND: Lung cancer is the leading cause of death worldwide, and its diagnosis remains a significant challenge. Identifying effective methods to differentiate benign from malignant lung nodules is of paramount importance. This meta-analysis aimed to evaluate the clinical utility of circulating microRNAs (miRNAs) for the differential diagnosis of benign and malignant lung nodules. METHODS: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search was conducted across 4 electronic databases, without any temporal restrictions. The inclusion and exclusion criteria were strictly applied to assess the clinical applications of circulating miRNAs. A robust and transparent quality assessment was performed using the quality assessment of diagnostic accuracy studies-2 tool, and rigorous statistical analyses were conducted to synthesize the various diagnostic measures. RESULTS: In the meta-analysis of 11 studies, quality assessment of diagnostic accuracy studies-2 assessment revealed < 5% high-risk methodologies, ensuring robustness. Sensitivity and Specificity were consolidated at 0.83 (95% confidence interval [CI]: 0.72-0.90) and 0.81 (95% CI: 0.73-0.88), respectively. The positive likelihood ratio and negative likelihood ratio were 4.45 (95% CI: 3.03-6.54) and 0.21 (95% CI: 0.12-0.35), respectively. The diagnostic odds ratio was 21.31 (95% CI: 10.25-44.30) and area under the receiver operating characteristic curve was 0.89 (95% CI: 0.86-0.91). Subgroup analysis highlighted significant variations in diagnostic accuracy by ethnicity and miRNA source, with non-Asian populations and serum-based tests showing higher diagnostic accuracy. CONCLUSION: This meta-analysis demonstrated that circulating miRNAs hold substantial diagnostic value in distinguishing between benign and malignant lung nodules.

A single-institutional retrospective analysis of factors related to vaginal intraepithelial neoplasia.

BACKGROUND: To date, few studies on the factors related to vaginal intraepithelial neoplasia (VaIN) have been published. In this study, we aimed to analyze the features of VaIN and identify underlying risk factors. METHODS: Patients with VaIN or vaginitis histologically confirmed at the Industrial Street Branch of Chengdu Women's and Children's Central Hospital from July 2020 to December 2021 were included. We statistically analyzed their baseline clinical characteristics, human papillomavirus (HPV) infection status, cytology results, and pathology results. Categorical indicators were analyzed using the chi-square test or Fisher's exact test, as appropriate. Differences were considered to be statistically different with p < 0.05. RESULTS: A total of 62 patients with VaIN (mean age: 39.06 ± 11.66 years) and 32 with vaginitis (mean age: 41.13 ± 13.43 years) were included. Synchronous cervical intraepithelial neoplasia (CIN) was histologically identified in 46 (74.2%) patients with VaIN and 7 (21.9%) with vaginitis (p < 0.001). Low-grade squamous intraepithelial lesions (LSILs) and atypical squamous cells of undetermined significance (ASC-US) were the most frequent cytological abnormalities in both groups. Patients with VaIN only (62.5%) were more likely to be negative for intraepithelial lesion or malignancy than patients with synchronous CIN (32.6%; p = 0.036). No statistically significant difference in HPV infection was noted between patients with VaIN and those with vaginitis (p = 0.439). The most prevalent HPV genotype in patients with VaIN or vaginitis was HPV16, whereas both HPV58 and HPV16 were the most common in patients with concurrent CIN. CONCLUSIONS: Attention should be paid to HPV16- and HPV58-positive patients with cytological abnormalities such as ASC-US and LSILs (especially with synchronous CIN) to avoid misdiagnosis or underdiagnosis and to facilitate early interventions for VaIN.

Chronotype is associated with eating behaviors, physical activity and overweight in school-aged children.

BACKGROUND: A later chronotype has been found to be associated with unhealthy habits and diseases, such as an unhealthy diet and metabolic syndrome in adults. Little is known about the association between chronotype, eating habits, physical activity and obesity. Thus, this study aimed to explore the relationships between chronotype, eating behaviors, physical activity, and overweight in Chinese school-aged children. METHODS: Data from this study was based on 952 schoolchildren (10-12 y) from six primary schools that participated in China. Anthropometric measurements of height and body weight were performed. Information about sleeping habits, dietary behaviors, and other lifestyle behaviors was gathered using a self-administered questionnaire. Multiple linear regression analysis or multivariable logistic regression model was performed to assess the associations between chronotype, eating behaviors, physical activity, and overweight. RESULTS: Nearly 70% (69.9%) of the participants had a self-reported morning chronotype. Multiple linear regression analysis revealed chronotype score was positively associated with physical activities (all P values < 0.001) and sleep duration (all P values < 0.001) and negatively associated with BMI, meal time, eating jet lag and social jet lag (all P values < 0.001). Multivariable logistic regression analysis showed that compared to morning types, non-morning types individuals were more likely to be overweight (OR = 1.593, P value < 0.05), and had more frequent consumption of fast food (OR = 1.616, P value < 0.05), but less frequent consumption of milk (OR = 0.716, P value < 0.05), less time taking part in moderate (OR = 1.356, P value < 0.05) or muscle strengthening (OR = 1.393, 1.877, P value < 0.05) physical activity. CONCLUSIONS: This study indicates that early chronotype children are more active, have healthier dietary habits, get more sleep, have shorter social jet lag, and are less likely to be overweight than non-early chronotype children. Our findings suggest that later chronotype may be a potential indicator in the early detection of overweight, unhealthy eating, and physical inactivity behaviors. Chronotype has been found to have an important impact on individual's health. In the present study, we conducted a cross-sectional study to investigate the association between chronotype, eating behaviors, physical activity, and overweight in school-aged children. The findings showed that children with early chronotype is associated with more active, healthier dietary behaviors, longer sleep duration, short social jet lag, and a lower risk of overweight.

Centrifugal Microfluidic Synthesis of Nickel Sesquioxide Nanoparticles.

Nickel sesquioxide (Ni2O3) nanoparticles were synthesized using centrifugal microfluidics in the present study. The obtained nanoparticles were characterized using SEM to investigate their morphology and microstructure, and XRD was employed to analyze their purity. The nanoparticle size data were measured and analyzed using ImageJ (v1.8.0) software. The flow process and mixing procedure were monitored through computational fluid dynamics simulation. Among the synthesized Ni2O3 nanoparticles, those obtained at the rotation speed of 1000 rpm for 10 min with angular acceleration of 4.2 rad/s2 showed the best performance in terms of high purity, complete shape and microstructure, small diameter, and narrow diameter distribution. The experimental results demonstrate that the rotation speed of the microfluidic chip and reaction time contribute to a decrease in particle diameter and a narrower diameter distribution range. In contrast, an increase in acceleration of the rotation speed leads to an expanded nanoparticle size range and, thus, a wider distribution. These findings contribute to a comprehensive understanding of the effects exerted by various factors in centrifugal microfluidics and will provide new insights into nanoparticle synthesis using centrifugal microfluidic technology.