VP1 codon deoptimization and high-fidelity substitutions in 3D polymerase as potential vaccine strategies for eliciting immune responses against enterovirus A71.

Enterovirus A71 (EV-A71) can induce severe neurological complications and even fatal encephalitis in children, and it has caused several large outbreaks in Taiwan since 1998. We previously generated VP1 codon-deoptimized (VP1-CD) reverse genetics (rg) EV-A71 viruses (rgEV-A71s) that harbor a high-fidelity (HF) 3D polymerase. These VP1-CD-HF rgEV-A71s showed lower replication kinetics in vitro and decreased virulence in an Institute of Cancer Research (ICR) mouse model of EV-A71 infection, while still retaining their antigenicity in comparison to the wild-type virus. In this study, we aimed to further investigate the humoral and cellular immune responses elicited by VP1-CD-HF rgEV-A71s to assess the potential efficacy of these EV-A71 vaccine candidates. Following intraperitoneal (i.p.) injection of VP1-CD-HF rgEV-A71s in mice, we observed a robust induction of EV-A71-specific neutralizing IgG antibodies in the antisera after 21 days. Splenocytes isolated from VP1-CD-HF rgEV-A71s-immunized mice exhibited enhanced proliferative activities and cytokine production (IL-2, IFN-γ, IL-4, IL-6, and TNF-α) upon re-stimulation with VP1-CD-HF rgEV-A71, as compared to control mice treated with adjuvant only. Importantly, administration of antisera from VP1-CD-HF rgEV-A71s-immunized mice protected against lethal EV-A71 challenge in neonatal mice. These findings highlight that our generated VP1-CD-HF rgEV-A71 viruses are capable of inducing both cellular and humoral immune responses, supporting their potential as next-generation EV-A71 vaccines for combating EV-A71 infection.IMPORTANCEEV-A71 can cause severe neurological diseases and cause death in young children. Here, we report the development of synthetic rgEV-A71s with the combination of codon deoptimization and high-fidelity (HF) substitutions that generate genetically stable reverse genetics (rg) viruses as potential attenuated vaccine candidates. Our work provides insight into the development of low-virulence candidate vaccines through a series of viral genetic editing for maintaining antigenicity and genome stability and suggests a strategy for the development of an innovative next-generation vaccine against EV-A71.

Exceptionally Fast Separation of Xylene Isomers with Zeolitic Nanotube Array Membranes.

The separation of xylene isomers is of vital importance in chemical industry but remains challenging due to their similar structure and overlapping physiochemical properties. Membrane-based separations using the zeolite MFI, graphene oxide, and metal-organic frameworks have been intensively studied for this application, but the performance is limited by the well-known rule that the filtrate permeance scales inversely with the membrane thickness. We propose a novel membrane design that is capable of breaking this rule, based on an array of recently discovered zeolite nanotubes. Each zeolite nanotube possesses a 3.6-nm-wide central channel, connecting to dense, uniform 0.8-nm-wide holes on its wall that act as selective pores. Comprehensive molecular dynamics simulations show that this membrane exhibits permeance exceeding current state-of-the-art membranes by at least an order of magnitude while simultaneously maintaining an acceptable selectivity. In particular, a thicker membrane featuring longer zeolite nanotubes exhibits a higher permeance due to the presence of more selective pores. The proposed membrane design is expected to be broadly applied to other gas separations and even desalination as long as zeolitic nanotubes with customized pores are available.

USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

Myelin oligodendrocyte glycoprotein antibody and N-methyl-d-aspartate receptor antibody overlapping syndrome: insights from the recent case reports.

The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.

Viscosities of the Baryon-Rich Quark-Gluon Plasma from Beam Energy Scan Data.

This work presents the first Bayesian inference study of the (3+1)D dynamics of relativistic heavy-ion collisions and quark-gluon plasma viscosities using an event-by-event (3+1)D hydrodynamics+hadronic transport theoretical framework and data from the Relativistic Heavy Ion Collider Beam energy scan program. Robust constraints on initial state nuclear stopping and the baryon chemical potential-dependent shear viscosity of the produced quantum chromodynamic (QCD) matter are obtained. The specific bulk viscosity of the QCD matter is found to exhibit a preferred maximum around sqrt[s_{NN}]=19.6 GeV. This result allows for the alternative interpretation of a reduction (and/or increase) of the speed of sound relative to that of the employed lattice-QCD based equation of state for net baryon chemical potential µ_{B}∼0.2(0.4) GeV.

Proton Coulomb Blockade Effect Involving Covalent Oxygen-Hydrogen Bond Switching.

Instead of the canonical Grotthuss mechanism, we show that a knock-on proton transport process is preferred between organic functional groups (e.g., -COOH and -OH) and adjacent water molecules in biological proton channel and synthetic nanopores through comprehensive quantum and classical molecular dynamics simulations. The knock-on process is accomplished by the switching of covalent O─H bonds of the functional group under externally applied electric fields. The proton transport through the synthetic nanopore exhibits nonlinear current-voltage characteristics, suggesting an unprecedented proton Coulomb blockade effect. These findings not only enhance the understanding of proton transport in nanoconfined systems but also pave the way for the design of a variety of proton-based nanofluidic devices.

Peripheral Lymphocyte Changes Associate With the Progression of Necrotizing Enterocolitis in Infants.

INTRODUCTION: Immune factors are important antecedents in the pathophysiology of necrotizing enterocolitis (NEC). However, studies on the peripheral blood lymphocyte subsets changes in NEC patients among different Bell stages and in patients requiring surgery are scarce. METHODS: 34 infants with NEC and 33 age-matched controls were included. Peripheral blood was collected within 48 h after NEC diagnosis. Peripheral blood B and T lymphocytes subsets were detected by 12-color flow cytometry. Cell ratios were calculated, and their relationship to disease severity and their roles as indicators for surgery were assessed. RESULTS: NEC patients showed elevated percentages of unSwB cells (CD27+IgD+ unswitched memory/activated B cells)/B cells, SwB cells (CD27+IgD-switched memory B cells)/B cells, CD8+ T (CD3+CD8+ T cells)/T cells, Tem (CD45RA-CCR7-effector memory T cells)/CD4+ T cells, Tem/CD8+ T cells and decreased Bn (CD27-IgD+ naïve B cells)/B cells, CD4+T (CD3+CD4+ T cells)/T cells, CD45RA+ CCR7+ naïve T cells (CD45RA+CCR7+ naïve T cells)/CD8+T cells. Compared to NEC patients at BELL stage I + II, patients at BELL stage III showed increased percentages of SwB cells/B cells, antibody secreting cell (ASC, CD3-CD20-CD27high CD38high ASCs)/B cells and Tem/CD4+ T cells, and decreased percentages of CD45RA+CCR7+ naïve T cells/CD4+ T cells. The Receiver Operating Characteristic Curve analysis showed that the sensitivity of ASC/B cells ratio (0.52%) is 86.67% and the specificity of Tem/CD4+T ratio (5.22%) is 100%, indicating that NEC patients required surgery. CONCLUSIONS: The severity of NEC exhibits codirectional changes with the maturation of B and T lymphocytes, especially CD4+ T cells. The increased ASC/B and Tem/CD4+ T cells could serve as potential indicators for NEC patients requiring surgery.

Nontrivial effects of geometric and charge defects on one-dimensional confined water.

Water confined within nanochannels with specific functionalities serves as the foundation for a variety of emerging nanofluidic applications. However, the structure and dynamics of the confined liquid are susceptibly influenced by practically hard-to-avoid defects, yet knowledge of this fact remains largely unexplored. Here, using extensive molecular dynamics simulations, we elucidate the significant influence of geometric and charge defects on one-dimensional confined water. We show that the two types of defects can both reshape the water density distribution by constraining the translocation of water molecules along the circumferential direction. In addition to structural alterations, collective translocation and rotation of water slabs arise during transportation under external pressure. Below the temperature threshold marking the initiation of liquid-solid transition, the geometric defect retards water diffusion through a pinning effect, while the charge defect induces an anti-freezing effect. The latter is attributed to the electrostatic interaction between the charge defect and water molecules that hinders the formation of a stable hydrogen bond network by disrupting molecular dipole orientation. Consequently, this behavior results in a reduction in the number and lifetime of hydrogen bonds within the phase transition interval. The distinct roles of the two types of defects could be utilized to control the structure and dynamics of confined liquids that may result in distinct functionalities for nanofluidic applications.

"All in one" nanoprobe Au-TTF-1 for target FL/CT bioimaging, machine learning technology and imaging-guided photothermal therapy against lung adenocarcinoma.

The accurate preoperative diagnosis and tracking of lung adenocarcinoma is hindered by non-targeting and diffusion of dyes used for marking tumors. Hence, there is an urgent need to develop a practical nanoprobe for tracing lung adenocarcinoma precisely even treating them noninvasively. Herein, Gold nanoclusters (AuNCs) conjugate with thyroid transcription factor-1 (TTF-1) antibody, then multifunctional nanoprobe Au-TTF-1 is designed and synthesized, which underscores the paramount importance of advancing the machine learning diagnosis and bioimaging-guided treatment of lung adenocarcinoma. Bright fluorescence (FL) and strong CT signal of Au-TTF-1 set the stage for tracking. Furthermore, the high specificity of TTF-1 antibody facilitates selective targeting of lung adenocarcinoma cells as compared to common lung epithelial cells, so machine learning software Lung adenocarcinoma auxiliary detection system was designed, which combined with Au-TTF-1 to assist the intelligent recognition of lung adenocarcinoma jointly. Besides, Au-TTF-1 not only contributes to intuitive and targeted visualization, but also guides the following noninvasive photothermal treatment. The boundaries of tumor are light up by Au-TTF-1 for navigation, it penetrates into tumor and implements noninvasive photothermal treatment, resulting in ablating tumors in vivo locally. Above all, Au-TTF-1 serves as a key platform for target bio-imaging navigation, machine learning diagnosis and synergistic PTT as a single nanoprobe, which demonstrates attractive performance on lung adenocarcinoma.

Postnatal treatment and evolution patterns of giant fetal hepatic hemangioma: a case series of 29 patients.

OBJECTIVES: To explore the clinical characteristics, postnatal treatment and prognosis of giant fetal hepatic hemangioma (GFHH). METHOD: Retrospective analysis was performed on children with giant fetal hepatic hemangioma (maximum tumor diameter > 40 mm) diagnosed by prenatal ultrasound and MRI from December 2016 to December 2020. These patients were observed and treated at the Children's Hospital of Fudan University after birth. The clinical data were collected to analyze the clinical characteristics, treatment, and prognosis of GFHH using independent sample t tests or Fisher's exact tests. RESULTS: Twenty-nine patients who were detected by routine ultrasound in the second and third trimester of pregnancy with giant fetal hepatic hemangiomas were included. The first prenatal ultrasound diagnosis of gestational age was 34.0 ± 4.3 weeks, ranging from 22 to 39 weeks. Of the patients, 28 had focal GFHHs and 1 had multifocal GFHHs. Surgery was performed, and the diagnosis was confirmed histopathologically in two patients. There were 8 cases with echocardiography-based evidence of pulmonary hypertension, 11 cases had a cardiothoracic ratio > 0.6, and 4 cases had hepatic arteriovenous fistula (AVF). The median follow-up time was 37 months (range: 14-70 months). During the follow-up, 12 patients received medical treatment with propranolol as the first-line therapy. The treatment group had a higher ratio of cardiothoracic ratio > 0.6 (P = 0.022) and lower albumin levels (P = 0.018). Four (14.8%) lesions showed postnatal growth before involuting. Complete response was observed in 13 (13/29) patients, and partial response was observed in 16 (16/29) patients. CONCLUSIONS: Fetal giant hepatic hemangioma is mainly localized, and its clinical outcome conforms to RICH (rapidly involuting) and PICH (partially involuting), but some fetal giant hepatic hemangiomas will continue to grow after birth and then gradually decrease. For uncomplicated giant fetal hepatic hemangioma, postnatal follow-up is the main concern, while those with complications require aggressive medical treatment. Propranolol may have no effect on the volume change of GFHH.

Serum Metabolomic Signatures of Hirschsprung's Disease Based on GC-MS and LC-MS.

Hirschsprung's disease (HSCR) is a congenital digestive tract malformation characterized by the absence of intramural ganglion cells in the myenteric and submucosal plexuses along variable lengths of the gastrointestinal tract. Although the improvement of surgical methods has allowed great progress in the treatment of HSCR, its incidence and postoperative prognosis are still not ideal. The pathogenesis of HSCR remains unclear to date. In this study, metabolomic profiling of HSCR serum samples was performed by an integrated analysis of gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) as well as multivariate statistical analyses. Based on the random forest algorithm and receiver operator characteristic analysis, 21 biomarkers related to HSCR were optimized. Several amino acid metabolism pathways were identified as important disordered pathways of HSCR, among which tryptophan metabolism was crucial. To our knowledge, this is the first serum metabolomics study focusing on HSCR, and it provides a new perspective for explaining the mechanism of HSCR.

Phenotyping the late- and younger-onset neuronal surface antibody-mediated autoimmune encephalitis: a multicenter study.

Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay.

Multiscale Imaging of Nuclear Deformation at the Electron-Ion Collider.

We show within the color glass condensate framework that exclusive vector meson production at high energy is very sensitive to the geometric deformation of the target nucleus at multiple length scales. We show that different multipole deformation parameters affect different regions of transverse momentum transfer. These results have two important consequences: (1) Deformations of nuclear targets need to be taken into account when making predictions for and interpreting certain observables at the EIC. (2) Differential diffractive vector meson production has the potential to become a powerful tool, enabling the most direct measurements of nuclear structure at different length scales, ranging from large scale nuclear deformation at low transverse momentum transfer to fluctuations on nucleon- and subnucleon-size scales at higher transverse momentum transfer.

Evidence of Hexadecapole Deformation in Uranium-238 at the Relativistic Heavy Ion Collider.

State-of-the-art hydrodynamic simulations of the quark-gluon plasma are unable to reproduce the elliptic flow of particles observed at the BNL Relativistic Heavy Ion Collider (RHIC) in relativistic ^{238}U+^{238}U collisions when they rely on information obtained from low-energy experiments for the implementation of deformation in the colliding ^{238}U ions. We show that this is due to an inappropriate treatment of well-deformed nuclei in the modeling of the initial conditions of the quark-gluon plasma. Past studies have identified the deformation of the nuclear surface with that of the nuclear volume, though these are different concepts. In particular, a volume quadrupole moment can be generated by both a surface hexadecapole and a surface quadrupole moment. This feature was so far neglected in the modeling of heavy-ion collisions, and is particularly relevant for nuclei like ^{238}U, which is both quadrupole deformed and hexadecapole deformed. With rigorous input from Skyrme density functional calculations, we show that correcting for such effects in the implementation of nuclear deformations in hydrodynamic simulations restores agreement with BNL RHIC data. This brings consistency to the results of nuclear experiments across energy scales, and demonstrates the impact of the hexadecapole deformation of ^{238}U on high-energy collisions.

Factors associated with depression among healthcare workers during the COVID-19 pandemic: a systematic review and meta-analysis.

The COVID-19 pandemic has had a profound impact on the mental health of healthcare workers (HCWs). We aimed to identify the factors associated with depression among HCWs during the pandemic. We conducted literature search using eight electronic databases up to July 27 2022. Observational studies with more than 200 participants investigating correlates of depression in HCWs after COVID-19 outbreak were included. We used fixed- and random-effects models to pool odds ratios (ORs) across studies, and Cochran's chi-squared test and I 2 statistics to assess study heterogeneity. Publication bias was evaluated by funnel plots. Thirty-five studies involving 44,362 HCWs met the inclusion criteria. Female (OR=1.50, 95% CI [1.23,1.84]), single (OR=1.36, 95% CI [1.21,1.54]), nurse (OR=1.69, 95% CI [1.28,2.25]), history of mental diseases (OR=2.53, 95% CI [1.78,3.58]), frontline (OR=1.79, 95% CI [1.38,2.32]), health anxiety due to COVID-19 (OR=1.88, 95% CI [1.29,2.76]), working in isolation wards (OR=1.98, 95% CI [1.38,2.84]), and insufficient personal protective equipment (OR=1.49, 95% CI [1.33,1.67]) were associated with increased risk of depression. Instead, HCWs with a positive professional prospect (OR=0.34, 95% CI [0.24,0.49]) were less likely to be depressed. This meta-analysis provides up-to-date evidence on the factors linked to depression among HCWs during the COVID-19 pandemic. Given the persistent threats posed by COVID-19, early screening is crucial for the intervention and prevention of depression in HCWs.

The ABCD Study: Brain Heterogeneity in Intelligence During a Neurodevelopmental Transition Stage.

A complex curvilinear relationship exists between intelligence and age during the neurodevelopment of cortical thickness. To parse out a more fine-grained relationship between intelligence and cortical thickness and surface area, we used a large-scale data set focusing on a critical transition juncture in neurodevelopment in preadolescence. Cortical thickness was derived from T1-weighted structural magnetic resonance images of a large sample of 9- and 11-year-old children from the Adolescent Brain Cognitive Development study. The NIH Toolbox Cognition Battery composite scores, which included fluid, crystallized, and total scores, were used to assess intelligence. Using a double generalized linear model, we assessed the independent association between the mean and dispersion of cortical thickness/surface area and intelligence. Higher intelligence in preadolescents was associated with higher mean cortical thickness in orbitofrontal and primary sensory cortices but with lower thickness in the dorsolateral and medial prefrontal cortex and particularly in the rostral anterior cingulate. The rostral anterior cingulate findings were particularly evident across all subscales of intelligence. Higher intelligence was also associated with greater interindividual similarity in the rostral cingulate. Intelligence during this key transition juncture in preadolescence appears to reflect a dissociation between the cortical development of basic cognitive processes and higher-order executive and motivational processes.

Increased brain volume from higher cereal and lower coffee intake: shared genetic determinants and impacts on cognition and metabolism.

It is unclear how different diets may affect human brain development and if genetic and environmental factors play a part. We investigated diet effects in the UK Biobank data from 18,879 healthy adults and discovered anticorrelated brain-wide gray matter volume (GMV)-association patterns between coffee and cereal intake, coincidence with their anticorrelated genetic constructs. The Mendelian randomization approach further indicated a causal effect of higher coffee intake on reduced total GMV, which is likely through regulating the expression of genes responsible for synaptic development in the brain. The identified genetic factors may further affect people's lifestyle habits and body/blood fat levels through the mediation of cereal/coffee intake, and the brain-wide expression pattern of gene CPLX3, a dedicated marker of subplate neurons that regulate cortical development and plasticity, may underlie the shared GMV-association patterns among the coffee/cereal intake and cognitive functions. All the main findings were successfully replicated. Our findings thus revealed that high-cereal and low-coffee diets shared similar brain and genetic constructs, leading to long-term beneficial associations regarding cognitive, body mass index (BMI), and other metabolic measures. This study has important implications for public health, especially during the pandemic, given the poorer outcomes of COVID-19 patients with greater BMIs.

Myelin oligodendrocyte glycoprotein antibody-associated disease preceding primary central nervous system lymphoma: causality or coincidence?

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or eyes, in the absence of systemic diffusion. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly identified benign immune-mediated CNS inflammatory disorder with specific anti-MOG antibody seropositivity. These two seemingly unrelated nosological entities both have abundant clinical and radiological manifestations, and whether there is a potential link between them is unclear. CASE REPORT: We describe a 49-year-old man who presented progressive headache, dizziness, and unsteady gait with multifocal scattered T2 hyperintensities with contrast enhancement. The serum anti-MOG antibody test was positive, and a brain biopsy showed inflammatory infiltration. Initially, he was diagnosed with MOGAD and his condition improved after corticosteroid therapy. The patient relapsed with exacerbation of symptoms and neuroimaging showed new mass-forming lesions four months later. A second brain biopsy confirmed PCNSL. DISCUSSION: This is the first report of histologically confirmed successive MOGAD and PCNSL. Our case broadens the phenotypic spectrum of sentinel lesions in PCNSL. Though rare, PCNSL should be considered in patients diagnosed with benign CNS inflammatory disorder and responding well to steroid treatment when their clinical symptoms worsen and the imaging deteriorates. A timely biopsy is critical for accurate diagnosis and appropriate therapy.

The Diagnostic Accuracy of N-Terminal Pro-B-Type Natriuretic Peptide and Soluble ST2 for Heart Failure in Chronic Kidney Disease Patients: A Comparative Analysis.

BACKGROUND N-terminal proatrial natriuretic peptide (NT-proBNP) levels are often markedly elevated in patients with chronic kidney disease (CKD). Identifying novel biomarkers is an important step toward effective diagnosis. Interleukin-1 receptor-like 1 (IL1RL1) protein and human/Soluble suppression of tumorigenesis-2 (sST2) are promising biomarkers for heart failure (HF). This study aimed to assess the trend of NT-proBNP and sST2 in chronic kidney disease and their diagnostic value for HF. MATERIAL AND METHODS This study was carried out on 420 patients who were divided into a no heart failure group (N=182) and a heart failure group (N=238). Spearman correlation analysis was used to test the association of sST2 and NT-proBNP with renal function. The diagnostic value of each biomarker was assessed using receiver operating characteristic (ROC) curves according to 3 different forms: Total group (n=420), non-CKD group (n=217), and CKD group (n=203). RESULTS A striking correlation between eGFR and NT-proBNP (r=-0.525; P<0.001) seemed to be far stronger than that with sST2 (r=-0.147; P<0.05). The optimum cutoff points for sST2 and NT-proBNP to detect HF were 28.960 ng/mL and 1280 pg/mL, respectively, in total, 28.71 ng/mL and 481 pg/mL, respectively, in non-CKD patients, and 30.55 ng/mL and 3314 pg/mL, respectively, in CKD patients. The combined model of sST2 and NT-proBNP was superior to the model of sST2 or NT-proBNP alone, and the difference was statistically significant (P<0.05). CONCLUSIONS The diagnostic value of sST2 is less affected by decreased renal function. sST2 combined with NT-proBNP may improve the diagnostic accuracy of HF.

Prevention and management of esophageal stricture after esophageal ESD: 10 years of experience in a single medical center.

BACKGROUND/PURPOSE: Endoscopic submucosal dissection (ESD) is a minimally invasive endoscopic procedure to deal with local early esophageal neoplasm, although post-ESD esophageal stricture is a major delayed complication of esophageal ESD greatly influencing the patient's quality of life. This retrospective study was conducted to analyze the esophageal stricture after esophageal ESD while determining further treatment and outcome of stricture management. METHODS: From 2009 to 2021, we reviewed all patients who underwent ESD for esophageal squamous cell neoplasia in Kaohsiung Medical University Hospital. RESULTS: Totally, 133 patients with esophageal squamous cell neoplasm were enrolled. Among these 133 patients, 108 patients had lesions less than three-fourths in circumferential and 25 patients had lesions in excess of three-fourths circumferentially. Totally, 18 patients (13.5%) had symptomatic esophageal stricture and 17 patients (94.4%) had stricture existing over the upper or middle esophagus. The most important risk factor of esophageal stricture was the extent of resection of esophageal circumference, especially whole circumferential resection. Although oral steroid prevention medication was prescribed for high-risk patients with lesions more than three-fourth circumferential ESD, the stricture rate was still up to 40% (10/25). Endoscopic/luminal management with balloon dilation, radial incision and self-bougination achieved 83% (15/18) symptom remission. Three patients received surgical intervention with esophagectomy or jejunostomy. CONCLUSION: Esophageal stricture is frequently encountered in esophageal ESD. Aggressive preventative strategy is warranted for the high-risk group. Endoscopy/luminal management has high efficacy for post-ESD esophageal stricture.