PESSA: A web tool for pathway enrichment score-based survival analysis in cancer.

The activation levels of biologically significant gene sets are emerging tumor molecular markers and play an irreplaceable role in the tumor research field; however, web-based tools for prognostic analyses using it as a tumor molecular marker remain scarce. We developed a web-based tool PESSA for survival analysis using gene set activation levels. All data analyses were implemented via R. Activation levels of The Molecular Signatures Database (MSigDB) gene sets were assessed using the single sample gene set enrichment analysis (ssGSEA) method based on data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), The European Genome-phenome Archive (EGA) and supplementary tables of articles. PESSA was used to perform median and optimal cut-off dichotomous grouping of ssGSEA scores for each dataset, relying on the survival and survminer packages for survival analysis and visualisation. PESSA is an open-access web tool for visualizing the results of tumor prognostic analyses using gene set activation levels. A total of 238 datasets from the GEO, TCGA, EGA, and supplementary tables of articles; covering 51 cancer types and 13 survival outcome types; and 13,434 tumor-related gene sets are obtained from MSigDB for pre-grouping. Users can obtain the results, including Kaplan-Meier analyses based on the median and optimal cut-off values and accompanying visualization plots and the Cox regression analyses of dichotomous and continuous variables, by selecting the gene set markers of interest. PESSA (https://smuonco.shinyapps.io/PESSA/ OR http://robinl-lab.com/PESSA) is a large-scale web-based tumor survival analysis tool covering a large amount of data that creatively uses predefined gene set activation levels as molecular markers of tumors.

Measuring Protein-Ligand Binding by Hyperpolarized Ultrafast NMR.

Protein-ligand interactions can be detected by observing changes in the transverse relaxation rates of the ligand upon binding. The ultrafast NMR technique, which correlates the chemical shift with the transverse relaxation rate, allows for the simultaneous acquisition of R2 for carbon spins at different positions. In combination with dissolution dynamic nuclear polarization (D-DNP), where the signal intensity is enhanced by thousands of times, the R2 values of several carbon signals from unlabeled benzylamine are observable within a single scan. The hyperpolarized ultrafast chemical shift-R2 correlated experiment separates chemical shift encoding from the readout phase in the NMR pulse sequence, which allows it to beat the fundamental limit on the spectral resolution otherwise imposed by the sampling theorem. Applications enabled by the ability to measure multiple relaxation rates in a single scan include the study of structural properties of protein-ligand interactions.

CAMOIP: a web server for comprehensive analysis on multi-omics of immunotherapy in pan-cancer.

Immune checkpoint inhibitors (ICIs) have completely changed the approach pertaining to tumor diagnostics and treatment. Similarly, immunotherapy has also provided much needed data about mutation, expression and prognosis, affording an unprecedented opportunity for discovering candidate drug targets and screening for immunotherapy-relevant biomarkers. Although existing web tools enable biologists to analyze the expression, mutation and prognostic data of tumors, they are currently unable to facilitate data mining and mechanism analyses specifically related to immunotherapy. Thus, we effectively developed our own web-based tool, called Comprehensive Analysis on Multi-Omics of Immunotherapy in Pan-cancer (CAMOIP), in which we are able to successfully screen various prognostic markers and analyze the mechanisms involved in biomarker expression and function, as well as immunotherapy. The analyses include information relevant to survival analysis, expression analysis, mutational landscape analysis, immune infiltration analysis, immunogenicity analysis and pathway enrichment analysis. This comprehensive analysis of biomarkers for immunotherapy can be carried out by a click of CAMOIP, and the software should greatly encourage the further development of immunotherapy. CAMOIP provides invaluable evidence that bridges the information between the data of cancer genomics based on immunotherapy, providing comprehensive information to users and assisting in making the value of current ICI-treated data available to all users. CAMOIP is available at https://www.camoip.net.

Immune checkpoint inhibitor plus chemotherapy as first-line treatment for non-small cell lung cancer with malignant pleural effusion: a retrospective multicenter study.

BACKGROUND: Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. METHODS: Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. RESULTS: Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403-0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420-1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). CONCLUSIONS: In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.

Widespread reductions in cortical thickness following ketamine abuse.

BACKGROUND: Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine. METHODS: We acquired structural brain images for patients with ketamine use disorder and drug-free healthy controls. We used FreeSurfer software to measure cortical thickness for 68 brain regions. We compared cortical thickness between the 2 groups using analysis of covariance with covariates of age, gender, educational level, smoking, drinking, and whole-brain mean cortical thickness. RESULTS: We included images from 95 patients with ketamine use disorder and 169 controls. Compared with healthy controls, patients with ketamine use disorder had widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed among ketamine users relative to comparison participants. Estimated total lifetime ketamine consumption was correlated with reductions in the right inferior parietal and the right rostral middle frontal cortical thickness. LIMITATIONS: We conducted a retrospective cross-sectional study, but longitudinal studies are needed to further validate decreased cortical thickness after nonmedical use of ketamine. CONCLUSION: This study provided evidence that, compared with healthy controls, chronic ketamine users have widespread reductions in cortical thickness. Our study underscores the importance of the long-term effects of ketamine on brain structure and serves as a reference for the antidepressant use of ketamine.

Risk factors for Pneumocystis jirovecii pneumonia after kidney transplantation: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Pneumocystis jirovecii pneumonia (PJP), an opportunistic infection, often leads to an increase in hospitalization time and mortality rates in kidney transplant (KT) recipients. However, the risk factors associated with PJP in KT recipients remain debatable. Therefore, we conducted this meta-analysis to identify risk factors for PJP, which could potentially help to reduce PJP incidence and improve outcome of KT recipients. METHODS: We systematically retrieved relevant studies in PubMed, EMBASE, and the Cochrane Library up to November 2023. Pooled odds ratios (ORs) or mean differences (MDs) and the corresponding 95% confidence intervals (CIs) were calculated to assess the impact of potential risk factors on the occurrence of PJP. RESULTS: 27 studies including 42383 KT recipients were included. In this meta-analysis, age at transplantation (MD = 3.48; 95% CI = .56-6.41; p = .02), cytomegalovirus (CMV) infection (OR = 4.00; 95% CI = 2.53-6.32; p = .001), BK viremia (OR = 3.38; 95% CI = 1.70-6.71; p = .001), acute rejection (OR = 3.66; 95% CI = 2.44-5.49; p = .001), ABO-incompatibility (OR = 2.51; 95% CI = 1.57-4.01; p = .001), estimated glomerular filtration rate (eGFR) (MD = -14.52; 95% CI = -25.37- (-3.67); p = .009), lymphocyte count (MD = -.54; 95% CI = -.92- (-.16); p = .006) and anti-PJP prophylaxis (OR = .53; 95% CI = .28-.98; p = .04) were significantly associated with PJP occurrence. CONCLUSION: Our findings suggest that transplantation age greater than 50 years old, CMV infection, BK viremia, acute rejection, ABO-incompatibility, decreased eGFR and lymphopenia were risk factors for PJP.

Extramedullary relapsed acute lymphoblastic leukemia presenting as asymptomatic acute kidney injury after hematopoietic stem cell transplantation.

Acute kidney injury (AKI) is a common complication in children with hematological malignancies. Although AKI due to infiltration of tumor cells in children is rare, it negatively impacts treatment outcomes and increases the risk of mortality. We introduce a case of a child with acute lymphoblastic leukemia (ALL) who experienced kidney relapse resulting in asymptomatic AKI after remission from treatment, to remind clinicians not to overlook the primary disease in clinical judgment. In cases of unexplained AKI, kidney biopsy should be performed when feasible to get an accurate diagnosis and scientific treatment. In brief, children with leukemia who have achieved remission after treatment still need regular monitoring of urine routine and kidney function.

The role of exosomal circular RNA ZNF292 in intermittent hypoxia-induced AC16 cardiomyocytes injury.

BACKGROUND: Exosomes are involved in cell-to-cell communication in numerous diseases including cardiovascular diseases, neurological diseases. Little attention has been dedicated to exosomal circular RNAs in obstructive sleep apnea (OSA)-related cardiovascular diseases. The aim of this study was to explore the role of exosomal circular RNA ZNF292 (circZNF292) on AC16 cells exposure to intermittent hypoxia (IH). METHODS: Exosome release inhibitor GW4869 was used to examine the effect of exosomes on IH-induced AC16 cells apoptosis. The expression of exosomal circZNF292 was detected by qRT-PCR in AC16 cells exposure to IH, and a luciferase reporter assay was conducted to confirm the connection between circZNF292 and miR-146a-5p. Exosomal circZNF292 was stably transfected with short hairpin RNAs (shRNAs) against circZNF292 and co-cultured with AC16 cells. The expression of miR-146a-5p and apoptosis-related protein was then measured to evaluate the effect of exosomal circZNF292. RESULTS: We found that IH contributed to the AC16 cells apoptosis, and the administration of GW4869 increased the apoptosis of cardiomyocytes when exposed to IH. The expression of exosomal circZNF292 decreased and miR-146a-5p increased significantly in AC16 cells exposed to IH compared to normoxic conditions. Bioinformatics analysis predicted a circZNF292/miR-146a-5p axis in IH-induced cardiomyocytes apoptosis. The dual-luciferase reporter system validated the direct interaction of circZNF292 and miR-146a-5p. Knockdown of circZNF292 increased the expressions of miR-146a-5p and accelerated the AC16 cardiomyocytes apoptosis. CONCLUSIONS: The findings of this study suggested a novel mechanism by which exosomes transmit intrinsic regulatory signals to the myocardium through the exosomal circZNF292/miR-146a-5p axis. This finding highlights the potential of targeting this pathway as a therapeutic approach for treating cardiovascular diseases associated with OSA.

Evolution and health risk of indicator microorganisms in landscape water replenished by reclaimed water.

As an important means to solve water shortage, reclaimed water has been widely used for landscape water supply. However, with the emergence of large-scale epidemic diseases such as SARS, avian influenza and COVID-19 in recent years, people are increasingly concerned about the public health safety of reclaimed water discharged into landscape water, especially the pathogenic microorganisms in it. In this study, the water quality and microorganisms of the Old Summer Palace, a landscape water body with reclaimed water as the only replenishment water source, were tracked through long-term dynamic monitoring. And the health risks of indicator microorganisms were analyzed using Quantitative Microbial Risk Assessment (QMRA). It was found that the concentration of indicator microorganisms Enterococcus (ENT), Escherichia coli (EC) and Fecal coliform (FC) generally showed an upward trend along the direction of water flow and increased by more than 0.6 log at the end of the flow. The concentrations of indicator microorganisms were higher in summer and autumn than those in spring. And there was a positive correlation between the concentration of indicator microorganisms and COD. Further research suggested that increased concentration of indicator microorganisms also led to increased health risks, which were more than 30% higher in other areas of the park than the water inlet area and required special attention. In addition, (water) surface operation exposure pathway had much higher health risks than other pathways and people in related occupations were advised to take precautions to reduce the risks.

A novel pathogenic variant c.262delA in PBX1 causing oligomeganephronia identified using whole-exome sequencing and a literature review.

Oligomeganephronia (OMN) is a rare congenital renal hypoplasia reported more often in children than in adults. The diagnosis of OMN relies on renal biopsy and exhibits a significant reduction in the number of glomeruli and pronounced glomerular hypertrophy. Here, we report the case of an 8-year-old boy with recurrent proteinuria and abnormal external ears. A renal biopsy revealed large and rare glomeruli. The histological findings confirmed the diagnosis of OMN. Whole-exome sequencing of the patient revealed a new pathogenic variant in PBX1 (hg19, NM_002585, c.262delA, p.Thr88Glnfs*3). The PBX1 gene encodes a transcription factor whose pathogenic variants can result in congenital renal and urinary system anomalies, with or without hearing loss, abnormal ears, and developmental retardation (CAKUTED). This is the first report to detect PBX1 pathogenic variants in children with OMN, a novel phenotype of human PBX1 pathogenic variants. We performed functional prediction analyses of deletions in the corresponding structural domains. We summarized 27 cases of PBX1 single pathogenic variants reported between 2003 and 2023 in terms of truncating and missense pathogenic variants, which can deepen our understanding of the PBX1 structural domain and expand our knowledge of the PBX1 genotype and phenotype.

Gender differences in alcohol abuse/dependence among medical undergraduates during the post-COVID­19 pandemic period (October 20, 2020-April 5, 2021) in China.

BACKGROUND: This study aimed to assess the prevalence and the gender-specific risk factors of alcohol abuse/dependence among medical undergraduates during the post-COVID­19 pandemic period in China. METHOD: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) was used to identify respondents with alcohol abuse/dependence. A questionnaire on basic demographics and mental distresses (learning burnout, depression symptoms, anxiety symptoms, excessive daytime sleepiness, and history of mental disorders) was used. The logistic regression model was used to explore the associations between the above characteristics and alcohol abuse/dependence. RESULTS: A total of 3,412 medical undergraduates were included in the analysis. Males showed a higher prevalence of alcohol abuse/dependence than females (16.6% vs 7.4%, p < 0.001). Alcohol abuse/dependence was associated with learning burnout (OR: 2.168, p < 0.001) and having a partner (OR: 1.788 p = 0.001) among female medical undergraduates. Among male medical undergraduates, excessive daytime sleepiness (OR: 1.788 p = 0.001) and older age (OR: 1.788, p = 0.001) were independently associated with alcohol abuse/dependence. CONCLUSION: Alcohol abuse/dependence was common among medical undergraduates during the post-COVID­19 pandemic period. Substantial gender differences in the prevalence and risk factors of alcohol abuse/dependence were found among medical undergraduates in this study, which highlighted the need for timely gender-specific screening and interventions. However, the cross-sectional design adopted in this study has limited the examination of causality, thus further longitudinal studies are warranted.

The role of PPARγ in intermittent hypoxia-related human umbilical vein endothelial cell injury.

PURPOSE: Patients with obstructive sleep apnoea (OSA) have a high incidence of vascular endothelial injury. The most important pathophysiological feature of OSA is chronic intermittent hypoxia (CIH). This study aimed to investigate the mechanisms of CIH-related vascular endothelial injury. METHODS: IH exposure was applied to human umbilical vein endothelial cells (HUVECs). After modeling, cell viability, the expression levels of peroxisome proliferator activated receptor γ (PPARγ), apoptosis-associated proteins and mitochondrial division fusion proteins, and the levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assessed via Cell Counting Kit-8 (CCK-8), western blotting, fluorescent microscope, and flow cytometry, respectively. Rosiglitazone (PPARγ agonist), tempo (the mitochondrial-specific antioxidant), and tempo combined with PPARγ interfering RNA were used to treat HUVECs, respectively. RESULTS: After IH exposure, cell viability and levels of MMP decreased, cell apoptosis and ROS levels increased, and the expression levels of PPARγ decreased. Both tempo and rosiglitazone pretreatment ameliorated cell apoptosis and improved cell viability. In addition, mitochondrial function became better after tempo pretreatment. PPARγ interference reversed the protective effects of tempo on IH-related mitochondrial function injury and cell injury. CONCLUSIONS: PPARγ regulated the apoptosis and cell viability of IH-treated HUVECs by altering mitochondrial function. This finding clarifies the mechanism of CIH-related vascular endothelial injury.

The role of ferroptosis and endoplasmic reticulum stress in intermittent hypoxia-induced myocardial injury.

PURPOSE: Obstructive sleep apnea (OSA) is related to increased risk of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by iron overload and plays critical roles in myocardial injury. This study aimed to investigate the role of ferroptosis in intermittent hypoxia (IH)-induced myocardial injury involving endoplasmic reticulum stress (ERS). METHODS: AC16 human cardiomyocytes were exposed to IH or normoxia conditions. Mice were randomly grouped as follows: normal control (NC), IH, ferrostatin-1 + IH (FIH), and N-acetylcysteine + IH (AIH). The mRNA levels of GPX4, xCT, FTH1, and FACL4 in AC16 cells were detected by qRT-PCR. The protein levels of GPX4, xCT, NOX4, ATF4, CHOP, Bcl-2, and Bax in myocardial tissue were detected by Western blot analysis. RESULTS: The mRNA expression levels of GPX4 and xCT in AC16 cells were significantly lower in IH group than that of NC group. In IH mice, myocardial tissues were injured accompanied by increased level of ferroptosis and ERS. Inhibition of ferroptosis and treatment of N-acetylcysteine reduced ERS and myocardial injury in mice exposed to IH. In addition, compared to ferrostatin-1, N-acetylcysteine exerted a greater effect in relieving IH-induced myocardial damage and ERS. CONCLUSIONS: Ferroptosis was involved in IH-related myocardial injury accompanied by the activation of ERS. Inhibition of ferroptosis and acetylcysteine treatment alleviated IH-related myocardial injury, which may be a potential target for therapeutic approaches to OSA-induced myocardial injury.

Nrf2 plays protective role during intermittent hypoxia-induced ferroptosis in rat liver (BRL-3A) cells.

PURPOSE: Ferroptosis is reported to be involved in the chronic intermittent hypoxia (CIH)-related liver damage in vivo. Nuclear factor E2-related factor 2 (Nrf2) has an essential role in the regulation of ferroptosis. This study tested the hypothesis that intermittent hypoxia (IH) could lead to hepatocyte ferroptosis in vitro and the function of Nrf2 in IH-induced hepatocyte ferroptosis. METHODS: BRL-3A cells (rat liver cells) were exposed to normoxia or IH. The protocol of IH consisted of 32 cycles of 60-min hypoxic exposure with 30-min reoxygenation phase (nadir of 1% oxygen to peak of 20% oxygen). Ferroptosis was evaluated by cell viability, iron concentration, lipid reactive oxygen species (ROS), protein content of ferritin heavy chain (FTH1), and glutathione peroxidase 4 (GPX4). Both ferrostatin-1 (a ferroptosis inhibitor) and Nrf2 interfering RNA were applied to treat BRL-3A cells, respectively. RESULTS: IH exposure induced ferroptosis in BRL-3A cells with decreased cell viability and increased total iron content and lipid ROS levels. The protein contents of GPX4 and FTH1 in IH group were markedly lower than that in normoxic control. Ferroptosis inhibitor ferrostatin-1 alleviated IH-induced ferroptosis in BRL-3A cells. IH treatment enhanced expression of Nrf2, and Nrf2 knockdown augmented IH-induced ferroptosis in BRL-3A cells. CONCLUSIONS: The results revealed that Nrf2 played a protective role during IH-induced ferroptosis in BRL-3A cells. The finding provides a therapeutic target for obstructive sleep apnea-related liver injury.

MiR-210-3p enhances intermittent hypoxia-induced tumor progression via inhibition of E2F3.

PURPOSE: Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which is related to tumorigenesis and progression. Although micro-ribonucleic acid-210-3p (miR-210-3p) is correlated with hypoxia-induced tumor development, its role in the relationship between IH and tumor function remains poorly understood. The present work focused on elucidating the molecular mechanism through which miR-210-3p drives tumor progression under IH. METHODS: MiR-210-3p levels were quantified within tumor samples from patients with lung adenocarcinoma who had or did not have OSA. Correlations between miR-210-3p and polysomnographic variables were analyzed. For in vitro experiments, miR-210-3p was inhibited or overexpressed via transfection under IH conditions. Cell viability, growth, invasion and migration assays were carried out. For in vivo modeling of IH using mouse xenografts, a miR-210-3p antagomir was intratumorally injected, tumor biological behaviors were evaluated, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry and western blot were carried out for detecting miR-210-3p and E2F transcription factor 3 (E2F3) expression. RESULTS: For patients with lung adenocarcinoma and OSA, high miR-210-3p levels showed positive relation to polysomnographic variables, such as oxygen desaturation index, apnea-hypopnea index, and proportion of total sleep time with oxygen saturation in arterial blood < 90%. IH enhanced tumor viability, proliferation, migration, and invasion, downregulated E2F3 expression, and increased miR-210-3-p levels. miR-210-3p overexpression induced similar changes. These changes were reversed by miR-210-3p inhibition in vitro or miR-210-3p antagomir through intratumoral injection in vivo. CONCLUSIONS: IH-induced tumor development is driven through miR-210-3p by E2F3 suppression. MiR-210-3p represents a potential therapeutic target among patients with concomitant cancer and OSA.

Estimation of the relationship between meteorological factors and measles using spatiotemporal Bayesian model in Shandong Province, China.

BACKGROUND: Measles-containing vaccine (MCV) has been effective in controlling the spread of measles. Some countries have declared measles elimination. But recently years, the number of cases worldwide has increased, posing a challenge to the global goal of measles eradication. This study estimated the relationship between meteorological factors and measles using spatiotemporal Bayesian model, aiming to provide scientific evidence for public health policy to eliminate measles. METHODS: Descriptive statistical analysis was performed on monthly data of measles and meteorological variables in 136 counties of Shandong Province from 2009 to 2017. Spatiotemporal Bayesian model was used to estimate the effects of meteorological factors on measles, and to evaluate measles risk areas at county level. Case population was divided into multiple subgroups according to gender, age and occupation. The effects of meteorological factors on measles in subgroups were compared. RESULTS: Specific meteorological conditions increased the risk of measles, including lower relative humidity, temperature, and atmospheric pressure; higher wind velocity, sunshine duration, and diurnal temperature variation. Taking lowest value (Q1) as reference, RR (95%CI) for higher temperatures (Q2-Q4) were 0.79 (0.69-0.91), 0.54 (0.44-0.65), and 0.48 (0.38-0.61), respectively; RR (95%CI) for higher relative humidity (Q2-Q4) were 0.76 (0.66-0.88), 0.56 (0.47-0.67), and 0.49 (0.38-0.63), respectively; RR (95%CI) for higher wind velocity (Q2-Q4) were 1.43 (1.25-1.64), 1.85 (1.57-2.18), 2.00 (1.59-2.52), respectively. 22 medium-to-high risk counties were identified, mainly in northwestern, southwestern and central Shandong Province. The trend was basically same in the effects of meteorological factors on measles in subgroups, but the magnitude of the effects was different. CONCLUSIONS: Meteorological factors have an important impact on measles. It is crucial to integrate these factors into public health policies for measles prevention and control in China.

The association between obstructive sleep apnea and lung nodule, carcinoembryonic antigen.

PURPOSE: The association between obstructive sleep apnea (OSA) and cancer risks gaining more and more attention. Data on the association between OSA and lung cancer risk are limited. This study is to investigate whether a link exists between low-dose computed tomography (LDCT) scanning of the chest findings, carcinoembryonic antigen (CEA) and OSA in patients suspected of OSA. METHODS: The cross-sectional study included patients aged 18 years or older who underwent continuous nocturnal polysomnography at our sleep center between February 2019 and November 2020. All subjects underwent chest LDCT and CEA. Patients with an apnea-hypopnea index (AHI) of ≥ 15/h were classified as clinically significant OSA group, whereas patients with an AHI < 15/h were classified as control group. RESULTS: A total of 277 patients were enrolled in the study. 176 patients were categorized into the OSA group, while 101 patients were categorized into the control group. There is no relationship between any OSA-related parameter and presence of lung nodule or presence of ≥ 6 mm lung nodule in the binary logistic regression analysis. OSA group demonstrated a significant higher value of CEA than control group. Stepwise multiple linear regression analysis showed that lowest O2 saturation (ß = - 0.256, p < 0.001), smoking status (ß = 0.156, p = 0.007) and age (ß = 0.153, p = 0.008) were independent predictors of elevated CEA. CONCLUSIONS: OSA was independently related to the elevated of serum CEA level, but not with presence of pulmonary nodule or ≥ 6 mm pulmonary nodule in LDCT. Further well-designed longitudinal studies with pathology available are needed to identify the association between OSA and risk of lung cancer.

Comparative Analysis of Transcriptome and Proteome Revealed the Common Metabolic Pathways Induced by Prevalent ESBL Plasmids in Escherichia coli.

Antibiotic resistance has emerged as one of the most significant threats to global public health. Plasmids, which are highly efficient self-replicating genetic vehicles, play a critical role in the dissemination of drug-resistant genes. Previous studies have mainly focused on drug-resistant genes only, often neglecting the complete functional role of multidrug-resistant (MDR) plasmids in bacteria. In this study, we conducted a comprehensive investigation of the transcriptomes and proteomes of Escherichia coli J53 transconjugants harboring six major MDR plasmids of different incompatibility (Inc) groups, which were clinically isolated from patients. The RNA-seq analysis revealed that MDR plasmids influenced the gene expression in the bacterial host, in particular, the genes related to metabolic pathways. A proteomic analysis demonstrated the plasmid-induced regulation of several metabolic pathways including anaerobic respiration and the utilization of various carbon sources such as serine, threonine, sialic acid, and galactarate. These findings suggested that MDR plasmids confer a growth advantage to bacterial hosts in the gut, leading to the expansion of plasmid-carrying bacteria over competitors without plasmids. Moreover, this study provided insights into the versatility of prevalent MDR plasmids in moderating the cellular gene network of bacteria, which could potentially be utilized in therapeutics development for bacteria carrying MDR plasmids.

Genetic testing enables a precision medicine approach for nephrolithiasis and nephrocalcinosis in pediatrics: a single-center cohort.

OBJECTIVE: Hereditary factors are the main cause of pediatric nephrolithiasis (NL)/nephrocalcinosis (NC). We summarized the genotype-phenotype correlation of hereditary NL/NC in our center, to evaluate the role of genetic testing in early diagnosis. METHODS: The clinical data of 32 NL/NC cases, which were suspected to have an inherited basis, were retrospectively analyzed from May 2017 to August 2020. The trio-whole exome sequencing was used as the main approach for genetic testing, variants were confirmed by Sanger sequencing, and pathogenicity analysis according to protein function was predicted with custom-developed software. RESULTS: Causative monogenic mutations were detected in 24 of 32 NL/NC patients, and copy number variation was detected in one patient. A summary of manifestations in patients with inherited diseases revealed a significant degree of growth retardation, increased urinary excretion of the low-molecular weight protein, hypercalciuria, electrolyte imbalances, and young age of onset to be common in heredity disease. In addition, some patients had abnormal renal function (3 ppm 25). The most frequent pathology identified was distal renal tubular acidosis (with inclusion of SLC4A1, ATP6V1B1, and ATP6VOA4 genes), followed by Dent disease (CLCN5 and OCRL1 genes), primary hyperoxaluria (PH) (AGXT and HOGA1 genes) and Kabuki syndrome (KMT2D gene), which was more likely to present as NC or recurrent stone and having a higher correlation with a specific biochemical phenotype and extrarenal phenotype. CONCLUSION: The etiology of NL/NC is heterogeneous. This study explored in depth the relationship between phenotype and genotype in 32 patients, and confirmed that genetic testing and clinical phenotype evaluation enable the precision medicine approach to treating patients.

Even sampling photonic-integrated interferometric array for synthetic aperture imaging.

To improve the effectiveness of spatial spectrum sampling for the photonic-integrated interferometric imaging, an array forming scheme is proposed with evenly distributed interferometric baselines, which is referred to as the even sampling photonic-integrated interferometric array (ESPIA). The subaperture array of ESPIA is configured as equi-spaced concentric rings. The subaperture beams are coupled and transmitted to the photonic integrated circuit through fiber optic channels and paired into baselines by the interferometric beam combination. The characteristics of ESPIA are analyzed with the discrete modulation transfer function (D-MTF) and multi-resolution mutual information (MR-MI). The simulation results show that it can realize the even sampling coverage of spatial spectrum effectively. With the same scale of synthetic aperture and subaperture array, it can also improve the capabilities of information acquisition for the interferometric array.