Gut flora disequilibrium promotes the initiation of liver cancer by modulating tryptophan metabolism and up-regulating SREBP2.

The gut microbiota and liver cancer have a complex interaction. However, the role of gut microbiome in liver tumor initiation remains unknown. Herein, liver cancer was induced using hydrodynamic transfection of oncogenes to explore liver tumorigenesis in mice. Gut microbiota depletion promoted liver tumorigenesis but not progression. Elevated sterol regulatory element-binding protein 2 (SREBP2) was observed in mice with gut flora disequilibrium. Pharmacological inhibition of SREBP2 or Srebf2 RNA interference attenuated mouse liver cancer initiation under gut flora disequilibrium. Furthermore, gut microbiota depletion impaired gut tryptophan metabolism to activate aryl hydrocarbon receptor (AhR). AhR agonist Ficz inhibited SREBP2 posttranslationally and reversed the tumorigenesis in mice. And, AhR knockout mice recapitulated the accelerated liver tumorigenesis. Supplementation with Lactobacillus reuteri, which produces tryptophan metabolites, inhibited SREBP2 expression and tumorigenesis in mice with gut flora disequilibrium. Thus, gut flora disequilibrium promotes liver cancer initiation by modulating tryptophan metabolism and up-regulating SREBP2.

Impact of pretransplant T2DM on left ventricular deformation and myocardial perfusion in heart transplanted recipients: a 3.0 T cardiac magnetic resonance study.

BACKGROUND: Pretransplant type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular and all-cause mortality after heart transplant (HT), but the underlying causes of this association remain unclear. The purpose of this research was to examine the impact of T2DM on left ventricular (LV) myocardial deformation and myocardial perfusion following heart transplantation using cardiovascular magnetic resonance imaging. METHODS: We investigated thirty-one HT recipients with pretransplant T2DM [HT(DM+)], thirty-four HT recipients without pretransplant T2DM [HT(DM-)] and thirty-six controls. LV myocardial strains, including the global longitudinal, radial, and circumferential strain (GLS, GRS and GCS, respectively), were calculated and compared among groups, as were resting myocardial perfusion indices, which included time to peak myocardial signal intensity (TTM), maximum signal intensity (MaxSI), and Upslope. The relationships between LV strain parameters or perfusion indices and biochemical indicators were determined through Spearman's analysis. The impact of T2DM on LV strains in HT recipients was assessed using multivariable linear regression analyses with backward stepwise selection. RESULTS: In the HT(DM+) group, the LV GLS, GRS, and GCS exhibited significantly lower magnitudes than those in both the HT(DM-) and control groups. TTM was higher in the HT(DM+) group than in both the HT(DM-) and control groups, while no significant differences were observed among the groups regarding Upslope and MaxSI. There was a negative correlation between glycated hemoglobin and the magnitude of strains (longitudinal, r = - 0.399; radial, r = - 0.362; circumferential, r = - 0.389) (all P < 0.05), and a positive correlation with TTM (r = 0.485, P < 0.001). Regression analyses that included both pretransplant T2DM and perfusion indices revealed that pretransplant T2DM, rather than perfusion indices, was an independent determinant of LV strain (ß = longitudinal, - 0.508; radial, - 0.370; circumferential, - 0.371) (all P < 0.05). CONCLUSION: In heart transplant recipients, pretransplant T2DM has a detrimental effect on subclinical left ventricular systolic function and could potentially impact myocardial microcirculation following HT.

Development of a label-free photoelectrochemical immunosensor for novel astrovirus detection.

Since 2017, an infectious goose gout disease characterized by urate precipitation in viscera, mainly caused by novel goose astrovirus (GoAstV) infection, has emerged in the main goose-producing region of China. The current challenge in managing goose gout disease is largely due to the absence of a rapid and efficient detection method for the GoAstV pathogen. Notably, the potential application of immunosensors in detecting GoAstV has not yet been explored. Herein, a label-free PEC immunosensor was fabricated by using purchased TiO2 as the photoactive material and antibody against GoAstV P2 proteins as the specific recognition element. First, we successfully expressed the capsid spike domain P2 protein of ORF2 from GoAstV CHSH01 by using the pET prokaryotic expression system. Meanwhile, the polyclonal antibody against GoAstV capsid P2 protein was produced by purified protein. To our knowledge, this is the first establishment and preliminary application of the label-free photoelectrochemical immunosensor method in the detection of AstV. The PEC immunosensor had a linear range of 1.83 fg mL-1 to 3.02 ng mL-1, and the limit of detection (LOD) was as low as 0.61 fg mL-1. This immunosensor exhibited high sensitivity, great specificity, and good stability in detecting GoAstV P2 proteins. To evaluate the practical application of the immunosensor in real-world sample detection, allantoic fluid from goose embryos was collected as test samples. The results indicated that of the eight positive samples, one false negative result was detected, while both negative samples were accurately detected, suggesting that the constructed PEC immunosensor had good applicability and practical application value, providing a platform for the qualitative detection of GoAstV.

An End-Tidal Carbon Monoxide Nomogram for Term and Late-Preterm Chinese Newborns.

OBJECTIVE: To establish a reference nomogram for end-tidal CO corrected for ambient CO (ETCOc) levels in term and late-preterm Chinese newborns and then assess its efficacy to identify hemolytic hyperbilirubinemia. STUDY DESIGN: We conducted a prospective study by measuring concurrent ETCOc and total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) levels collected postnatally at 12, 24, 48, 72, 96, and 120 hours of age. ETCOc at the 25th, 50th, 75th, and 95th percentiles at each epoch were used to construct the reference nomogram. We then explored the ability of predischarge ETCOc and TSB/TcB metrics to predict the development of hyperbilirubinemia requiring phototherapy in early postnatal period and jaundice readmission in late postnatal period. RESULTS: Our nomogram, based on 990 measurements from 455 infants who were not nonhemolytic, displayed a steady line within 3 postnatal days, followed by a subsequent decline. From a cohort of infants with a serial ETCOc measurements (n = 130) and those readmitted (n = 21), we found that ETCOc and TSB/TcB ≥75th percentile can identify most hemolytic hyperbilirubinemia between 12 and 72 hours after birth with an area under the curve (AUC) of 0.741. An ETCOc ≥1.7 ppm alone between 96 and 120 hours after birth can identify most hemolytic hyperbilirubinemia with an AUC of 0.816. In addition, 90.5% of readmitted infants had an ETCOc ≥75th percentile. CONCLUSIONS: An ETCOc reference nomogram during the first 5 postnatal days in nonhemolytic term and late-preterm newborns can be used to identify hemolytic hyperbilirubinemia requiring phototherapy in the early postnatal period and readmission in the late postnatal period.

Intravoxel Incoherent Motion Diffusion-Weighted Imaging for Predicting and Monitoring the Response of Anti-Angiogenic Treatment in the Orthotopic Nude Mouse Model of Lung Adenocarcinoma.

BACKGROUND: The treatment efficacy of angiogenesis inhibitor could be underestimated at an early stage based on tumor volume changes. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can quantitatively assess tumors at the cellular level, but it is unclear whether it can provide useful information for assessing treatment response of anti-angiogenic treatment for lung adenocarcinoma. PURPOSE: To determine the use of IVIM-DWI for non-invasive monitoring of the early response to anti-angiogenic treatment in the orthotopic transplantation of lung adenocarcinoma model. STUDY TYPE: Prospective. POPULATION: Thirty-seven nude mice were randomized into two groups: treatment group (received bevacizumab + cisplatin, N = 20) and control group (received saline, N = 17). FIELD STRENGTH/SEQUENCE: Single-shot turbo spin-echo (TSE) IVIM-DWI, TSE T2-weighted imaging at 3.0 T. ASSESSMENT: Tumor volume, IVIM parameters (apparent diffusion coefficient [ADC], diffusivity [D], perfusion fraction [f], and pseudo-diffusion coefficient [D*]) were measured before and 2 hours, 3, 7, 10 and 14 days after treatment. Regions of interest were manually drawn along the inner edge of the tumor by two radiologists with 5 and 10-year experience in magnetic resonance imaging. Pathological examinations (hematoxylin and eosin stain, cluster of differentiation 34) were performed. STATISTICAL TESTS: Kolmogorov-Smirnov test, repeated-measure two-way analysis of variance test, Mann-Whitney U test, Pearson correlation analysis, receiver operating characteristic curve. P < 0.05 was considered statistically significant. RESULTS: The tumor volume of the two groups was significantly different only on day 14 (control group vs. treatment group, 43.15 ± 18.28 mm3 vs. 28.41 ± 1.71 mm3 ). ADC2h , ADC10d , D2h , D7d , D10d , and D14d were significantly higher, while f10d and f14d were significantly lower in the treatment group compared to those of the control group. Both the △ADC2h (r = -0.631) and △D2h (r = -0.700) showed moderate correlations with the relative tumor volume on day 14. DATA CONCLUSION: IVIM has the potential to predict and monitor the early response to anti-angiogenic treatment, earlier than size changes, for lung adenocarcinoma. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 4.

Evaluation of peripheral nerve acute crush injury in rabbits: comparison among diffusion kurtosis imaging, diffusion tensor imaging and electromyography.

OBJECTIVE: Diffusion kurtosis imaging (DKI) has been proven to provide additional value for assessing many central nervous system diseases compared with conventional diffusion tensor imaging (DTI); however, whether it has the same value in peripheral nerve injury is unclear. This study aimed to investigate the performance of DKI, DTI, and electromyography (EMG) in evaluating peripheral nerve crush injury (PNCI) in rabbits. MATERIALS AND METHODS: A total of 27 New Zealand white rabbits were selected to establish a PNCI model. Longitudinal DTI, DKI, and EMG were evaluated before surgery and 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks after surgery. At each time point, two rabbits were randomly selected for pathological examination. RESULTS: The results showed that fractional anisotropy (FA) derived from both DKI and DTI demonstrated a significant difference between injured and control nerves at all time points (all P < 0.005) mean kurtosis of the injured nerve was lower than that on the control side after 2-8 weeks (all P < 0.05). No statistically significant difference was found in radial kurtosis, axial kurtosis, and apparent diffusion coefficient at almost every time point. The difference in compound muscle action potential (CMAP) of the bilateral gastrocnemius at each time point was statistically significant (all P < 0.001). CONCLUSIONS: CMAP was a sensitive and reliable method to assess acute PNCI without being affected by perineural edema. DKI may not be superior to DTI in evaluating peripheral nerves, DTI with a shorter scanning time was preferred as an effective choice for evaluating acute peripheral nerve traumatic injury.

Effects of less invasive surfactant administration versus intubation-surfactant-extubation on bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome: a single-center, retrospective study from China.

BACKGROUND: This study evaluated the effects of less invasive surfactant administration (LISA) and intubation-surfactant-extubation (InSurE) on bronchopulmonary dysplasia (BPD) in preterm infants with respiratory distress syndrome (RDS). METHODS: Neonates with respiratory distress syndrome requiring surfactant, with gestational age < 32 weeks and birth weight < 1500 g admitted to our neonatal intensive care unit from January 2018 to December 2019, were retrospectively analyzed. LISA and InSurE were used independently. The incidence of BPD at 36 weeks postmenstrual age, pre-discharge mortality, and need for mechanical ventilation (MV) within 72 h of birth were compared between LISA and InSurE group. Secondary outcomes including necrotizing enterocolitis requiring surgery, retinopathy of prematurity ≥ stage 3, patent ductus arteriosus requiring medical therapy or surgery, and length of hospitalization were analyzed. RESULTS: Among the 148 included neonates, there were 46 and 102 infants in LISA group and InSurE group, respectively. There were no significant differences in BPD incidence, the severity of BPD at 36 weeks postmenstrual age, and the rate of MV within the first 72 h after birth between the two groups (P > 0.05, respectively). The incidences of necrotizing enterocolitis requiring surgery, retinopathy of prematurity ≥ stage 3, patent ductus arteriosus requiring medical therapy or surgery, and length of hospitalization did not differ significantly between the two groups (P > 0.05, respectively). CONCLUSIONS: For surfactant administration among preterm infants with respiratory distress syndrome, LISA did not decrease bronchopulmonary dysplasia and severity of BPD at 36 weeks postmenstrual age. The benefits of LISA would require further evaluations.

[Remote monitoring of neonatal jaundice in newborns with ABO hemolytic disease].

OBJECTIVE: To explore the feasibility of remote monitoring of neonatal jaundice in newborns with ABO hemolytic disease. METHODS: Forty six neonates of gestational age >35 weeks with ABO hemolytic disease admitted to Women's Hospital, Zhejiang University School of Medicine from January 20th, 2020 to February 29th, 2020 were enrolled in the study (study group). The newborns were followed up at home after discharge, the transcutaneous bilirubin (TCB) levels were measured by parents using the provided device and the results were sent to the doctor by smart phone using the installed APP. Fifty six newborns with ABO hemolytic disease admitted in 2018 who received conventional outpatient follow-up after discharge served as the control group. The demographic characteristics, total serum bilirubin (TSB) level during hospitalization, number of outpatient visit and rate of re-admission due to rebound hyperbilirubinemia were compared between the two groups. RESULTS: There were no significant differences between the two groups in gestational age, birth weight, delivery mode, gender, length of the first hospitalization, TSB level before phototherapy and before discharge, and the managements during the first hospitalization (all P>0.05). Compared with the control group, TSB level before readmission [(265±16) µmol/L vs. (295±15) µmol/L] and the number of outpatient visits (1.3±0.8 vs. 3.8±0.5) were significantly lower in the study group (all P<0.01), while the rate of readmission (17.4%vs. 12.5%) and the weight at the time of readmission[(3398±452) g vs. (3477±324) g] were not significantly different (all P>0.05). No cases of acute bilirubin encephalopathy occurred in both groups. CONCLUSIONS: The remote follow-up for neonatal jaundice at home can effectively reduce the number of outpatient visits without increasing the risk of readmission and severe neonatal hyperbilirubinemia for newborns with ABO hemolytic disease.

Differentiating between malignant and benign solid solitary pulmonary lesions: are intravoxel incoherent motion and diffusion kurtosis imaging superior to conventional diffusion-weighted imaging?

OBJECTIVE: To quantitatively compare the diagnostic values of various diffusion parameters obtained from mono- and biexponential diffusion-weighted imaging (DWI) models and diffusion kurtosis imaging (DKI) in differentiating between benign and malignant solitary pulmonary lesions (SPLs). METHODS: Multiple b-value DWIs and DKIs were performed in 89 patients with SPL by using a 3-T magnetic resonance (MR) imaging unit. The apparent diffusion coefficient (ADC) of various b-value sets, true diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), apparent diffusional kurtosis (Kapp), and kurtosis-corrected diffusion coefficient (Dapp) were calculated and compared between the malignant and benign groups using a Mann-Whitney U test. Receiver-operating characteristic analysis was performed for all parameters. RESULT: The ADC(0, 150) values of malignant tumors were lower than those of the benign group (p = 0.01). The ADC(0, 300), ADC(0, 500), ADC(0, 600), ADC(0, 800), ADC(0, 1000), ADCtotal, D, and Dapp of malignant tumors were significantly lower than those of benign lesions (all p < 0.001). D*, f, and Kapp showed no statistically significant differences between the two groups. ADCtotal showed the highest area under the curve (AUC = 0.862), followed by ADC(0, 800)(AUC = 0.844), ADC(0, 600)(AUC = 0.843), D(AUC = 0.834), ADC(0, 1000)(AUC = 0.834) and ADC(0, 500)(AUC = 0.824), Dapp(AUC = 0.796), and ADC(0, 300) (AUC = 0.773). However, the difference in diagnostic efficacy among these parameters was not statistically significant (p > 0.05). CONCLUSION: Intravoxel incoherent motion (IVIM) and DKI-derived parameters have similar performance compared with conventional ADC in differentiating SPLs. KEY POINTS: • Mono- and biexponential DWI and DKI are feasible for differentiating SPLs. • ADC (0, ≥500) has better performance than ADC (0, <500) in assessing SPLs. • IVIM and DKI have similar performance compared with conventional DWI in differentiating SPLs.

Fenofibrate treatment attenuated chronic endoplasmic reticulum stress in the liver of nonalcoholic fatty liver disease mice.

Fenofibrate is widely used in clinical practice, but its influence on chronic endoplasmic reticulum (ER) stress induced by feeding a high-calorie and high-cholesterol diet (HCD) has still not been studied. We thus investigated its effects on the liver of the nonalcoholic fatty liver disease (NAFLD) mouse model. Male C57BL/6 mice fed an HCD for 3 months were treated with fenofibrate (HCD + FF, 40 mg/kg, once daily) via gavage for 4 weeks. Insulin sensitivity, serum lipid and inflammatory cytokines were measured. Liver tissues were procured for histological examination as well as analysis of hepatic triglyceride levels, distribution of inflammatory cytokines and genes involved in ER stress. Our results showed that chronic feeding of an HCD successfully induced an NAFLD model accompanied by inflammatory activation, apoptosis and severe ER stress in the liver. Fenofibrate administration significantly improved symptoms of NAFLD and decreased apoptosis, expression of inflammatory cytokines and genes involved in ER stress, such as inositol-requiring enzyme 1α (IRE1α), X-box binding protein 1 (XBP1) and JNK phosphorylation. Thus, our study suggests that fenofibrate protected against inflammatory injury and apoptosis, maybe alleviating ER stress through the IRE1α-XBP1-JNK pathway in the liver of NAFLD mice.

A pilot study of less invasive surfactant administration in very preterm infants in a Chinese tertiary center.

BACKGROUND: Less invasive surfactant administration (LISA) to spontaneously breathing preterm infants has been reported to reduce the duration of mechanical ventilation and the incidence of bronchopulmonary dysplasia (BPD) in previous study. The objective of this study was to explore the feasibility and potential benefits of LISA in early preterm infants on nasal continuous positive airway pressure (nCPAP) compared to conventional endotracheal instillation. METHODS: All infants with respiratory distress born at 28-32 weeks' gestational age from January 2012 to December 2012 (n=90), who were eligible for exogenous pulmonary surfactant (PS) therapy were randomized to receive PS by intubation with an endotracheal tube (Intubation group, n=43), or by intubation using a catheter while on nCPAP (LISA group, n=47). Respiratory indices were recorded every 30 seconds during PS administration, and every 1 hour thereafter for the first day. The rate of mechanical ventilation (MV) in the first 72 hours, mean duration of both MV and nCPAP, mean duration of oxygen requirement and neonatal outcomes were recorded. RESULTS: PS was successfully administered in 43 (100%) out of 43 babies using the conventional approach and in 46 (97%) out of 47 babies using LISA. The duration of both MV and nCPAP was significantly shorter in LISA group, when compared with intubation group. However, there were no significant differences in both the rate of MV in the first 72 hours and mean duration of oxygen requirement. There were also no differences in the mortality or in the incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity and necrotizing enterocolitis, or in the duration of respiratory support. CONCLUSIONS: LISA in spontaneously breathing infants on nCPAP is an alternative therapy for PS delivery, avoiding intubation with an endotracheal tube. The method is feasible and potentially effective, and deserves further clinical trials. TRIAL REGISTRATION: Current Controlled Trials ChiCTR-ICR-15006001. Registered 20 February 2015.

Association between Ureaplasma colonization and bronchopulmonary dysplasia defined by different criteria in very low birth weight infants: A retrospective cohort study.

OBJECTIVE: To study the association between Ureaplasma colonization and bronchopulmonary dysplasia (BPD) with different definitions in very low birth weight (VLBW) infants. METHODS: A retrospective cohort study was performed with VLBW infants admitted from January 2019 to October 2021. Neonates with a positive respiratory tract Ureaplasma culture were included in the study group. Control group infants, matched for gestational age (±1 week), birth weight (±100 g), and birth year, had a negative respiratory tract Ureaplasma culture during the same period. The primary outcomes included the incidence and severity of BPD, defined by various criteria. RESULTS: The study included 302 neonates (151 in the study group and 151 in the control group). After adjusting for confounders, Ureaplasma colonization was not associated with BPD as defined by the National Institutes of Health (NIH) in 2001 (adjusted odds ratio [aOR]: 0.820, 95% confidence interval [CI]: 0.362-1.860, p = .635). However, it was associated with BPD as defined by the NIH in 2018 (aOR: 2.490, 95% CI: 1.128-5.497, p = .024) and the Neonatal Research Network (NRN) in 2019 (aOR: 2.352, 95% CI: 1.077-5.134, p = .032). Additionally, VLBW infants with Ureaplasma colonization had a higher risk of moderate-severe BPD according to the NIH 2001 (aOR: 2.352, 95% CI: 1.077-5.134, p = .032), NIH 2018 (aOR: 6.339, 95% CI: 1.686-23.836, p = .006), and NRN 2019 definitions (aOR: 3.542, 95% CI: 1.267-9.904, p = .016). CONCLUSIONS: Ureaplasma colonization is not associated with BPD by the NIH 2001 definition, but is associated with an increased incidence by the NIH 2018 or NRN 2019 definitions.

UNC13B regulates the sensitivity of Wilms' tumor cells to doxorubicin by modulating lysosomes.

Wilms' tumor is a malignant neoplasm where current medical advancements have significantly improved survival rates; however, challenges persist such as the resistance of the tumor to chemotherapy drugs like doxorubicin. This necessitates higher dosages, leading to decreased sensitivity. However, using high doses of doxorubicin can have late effects on the heart. Unc-13 homolog B (UNC13B) may be involved in the drug resistance in several tumors, yet its role in modulating drug sensitivity in Wilms' tumor remains unexplored. UNC13B levels were quantified using reverse transcription-qPCR and Western blotting. The half-maximal inhibitory concentration for doxorubicin, vincristine, and actinomycin-D was determined using CCK-8 assays. Cell cycle and apoptosis were analyzed using flow cytometry, and lysosomal changes were observed using Lyso-Tracker staining. The present study initially evaluated UNC13B expression levels in the Wilms' tumor 17.94 cell line. Additionally, through short hairpin RNA-mediated knockdown, changes in doxorubicin sensitivity in 17.94 Wilms' tumor cells were assessed. Concurrently, preliminary investigations into the role of UNC13B in regulating lysosomes was performed, revealing a significant positive association between UNC13B levels and lysosome formation in the 17.94 cell line. Lysosomes likely serve a role in the sensitivity of Wilms' tumor cell lines to drugs. Elevated UNC13B expression was observed in the 17.94 Wilms' tumor cell line compared to normal kidney cells. UNC13B knockdown also resulted in increased apoptosis levels upon doxorubicin treatment. Immunofluorescence revealed UNC13B localization within cellular vesicles, and its knockdown significantly decreased lysosome levels. Overall, the findings of the present study demonstrate that UNC13B regulates the sensitivity of the Wilms' tumor 17.94 cell line to doxorubicin by modulating lysosome formation within cells. The results suggest that UNC13B is likely an enriched target involved in lysosomal regulation in certain tumors, offering a new approach for optimizing chemotherapy in Wilms' tumor and other cancers with high UNC13B expression.

Identification of a Prognostic Model Based on NK Cell-Related Genes in Multiple Myeloma Using Single-Cell and Transcriptomic Data Analysis.

Background: Multiple myeloma (MM), an incurable plasma cell malignancy. The significance of the relationship between natural killer (NK) cell-related genes and clinical factors in MM remains unclear. Methods: Initially, we extracted NK cell-related genes from peripheral blood mononuclear cells (PBMC) of healthy donors and MM samples by employing single-cell transcriptome data analysis in TISCH2. Subsequently, we screened NK cell-related genes with prognostic significance through univariate Cox regression analysis and protein-protein interaction (PPI) network analysis. Following the initial analyses, we developed potential subtypes and prognostic models for MM using consensus clustering and lasso regression analysis. Additionally, we conducted a correlation analysis to explore the relationship between clinical features and risk scores. Finally, we constructed a weighted gene co-expression network analysis (WGCNA) and identified differentially expressed genes (DEGs) within the MM cohort. Results: We discovered that 153 NK cell-related genes were significantly associated with the prognosisof MM patients (P <0.05). Patients in NK cluster A exhibited poorer survival outcomes compared to those in cluster B. Furthermore, our NK cell-related genes risk model revealed that patients with a high risk score had significantly worse prognoses (P <0.05). Patients with a high risk score were more likely to exhibit adverse clinical markers. Additionally, the nomogram based on NK cell-related genes demonstrated strong prognostic performance. The enrichment analysis indicated that immune-related pathways were significantly correlated with both the NK subtypes and the NK cell-related genes risk model. Ultimately, through the combined use of WGCNA and DEGs analysis, and by employing Venn diagrams, we determined that ITM2C is an independent prognostic marker for MM patients. Conclusion: In this study, we developed a novel model based on NK cell-related genes to stratify the prognosis of MM patients. Notably, higher expression levels of ITM2C were associated with more favorable survival outcomes in these patients.

A clinically-recommended MR whole lung imaging protocol using free-breathing 3D isotropic zero echo time sequence.

Rationale and objectives: This study aimed to assess the feasibility and image quality of free-breathing 3D isotropic zero echo time (ZTE) whole-lung imaging and explore a clinically appropriate protocol for MR lung imaging. Materials and methods: The study was approved by the local ethics committee. A total of thirty healthy volunteers were enrolled in this study from October 2022 to May 2023. Free-breathing pulmonary 3D isotropic ZTE scans were implemented with various acquisition planes and the number of excitations (NEX). ZTE images were evaluated by two radiologists for the overall Image quality and visibility of intrapulmonary structures as well as the signal-to-noise ratio (SNR) of the lung parenchyma. ZTE images with different acquisition parameters were compared. For preliminary clinical visual assessment, three patients with interstitial lung disease underwent both ZTE imaging and computed tomography (CT). Results: The overall image quality of the lung in healthy subjects was good to excellent. The visibilities of pulmonary arteries and bronchus were up to the 7th and 5th generation, respectively. The display of lung fissures was poor. The overall image quality, the visibility of the pulmonary artery, and lung fissures in the axial acquisition were better than in the coronal acquisition (P = 0.011, 0.008, 0.010, respectively) but not statistically different from those in the sagittal acquisition (all P > 0.05). Conclusion: The free-breathing pulmonary ZTE is feasible and may serve as an alternative method in chest imaging. Either axial or sagittal ZTE image acquisition would be preferred in clinical practice.

Risk factors for readmission for hyperbilirubinemia in neonates with ABO hemolytic disease: a single-center retrospective cohort study.

OBJECTIVE: ABO hemolytic disease of the newborn (ABO-HDN) is a major risk factor for severe hyperbilirubinemia, a common readmission reason for newborns. In this study, we aimed to assess the risk factors for readmission associated with hyperbilirubinemia in neonates with ABO-HDN. METHODS: A retrospective cohort study was conducted including newborns with gestational age ≥35 weeks and ABO-HDN in 2018. Among 291 newborns, 36 were readmitted for hyperbilirubinemia and defined as the readmission group. The remaining 255 cases were used as a control group. We then performed between-group comparisons of clinical conditions associated with hyperbilirubinemia. Logistic regression was used to select risk predictors of readmission associated with hyperbilirubinemia due to ABO-HDN. RESULTS: Baseline characteristics were similar between both groups (p > .05, respectively). However, total serum bilirubin (TSB) before initiating phototherapy was significantly higher in the readmission group when compared with that in the control group at 0-24 h, 24-48 h, and 48-72 h (183.70 µmol/L [interquartile range (IQR) 161.18-196.48] vs. 150.35 µmol/L [IQR 131.73-175.38], p = .005; 229.90 µmol/L [IQR 212.45-284.30] vs. 212.50 µmol/L [IQR 197.85-230.28], p = .026; 268.10 µmol/L [IQR 257.70-279.05] vs. 249.50 µmol/L [IQR 236.80-268.70], p = .045, respectively). The age of initiation of phototherapy in the readmission group was significantly lower than that in control group (30.0 h [IQR 18.0-49.00] vs. 42.0 h [IQR 23.0-61.0], p = .012). The rate of rebound hyperbilirubinemia after the first phototherapy treatment was significantly higher in the readmission group compared to that in the control group (9 [25%] vs. 13 [5.1%], p = .000), and the rate of positive direct antiglobulin testing was significantly higher than that in control group (17 [47.2%] vs. 74 [29.0%], p = .027). Logistic regression analysis showed that the age of initiation of photography, TSB level before the first phototherapy, and rebound hyperbilirubinemia after first phototherapy were independent risk factors for readmission in newborns with hyperbilirubinemia associated with ABO-HDN. CONCLUSIONS: Earlier age of phototherapy initiation, higher TSB levels at the time of initiating phototherapy and rebound hyperbilirubinemia after the first phototherapy treatment may increase the risk of readmission for hyperbilirubinemia in neonates with ABO-HDN. These factors should be considered in discharge planning and follow-up for newborns with ABO-HDN associated hyperbilirubinemia.

Screening and Identification of Host Factors Interacting with the Virulence Factor P0 Encoded by Sugarcane Yellow Leaf Virus by Yeast Two-Hybrid Assay.

Sugarcane yellow leaf virus (SCYLV), a member of the genus Polerovirus in the family Luteoviridae, causes severe damage and represents a great threat to sugarcane cultivation and sugar industry development. In this study, inoculation of Nicotiana benthamiana plants with a potato virus X (PVX)-based vector carrying the SCYLV P0 gene induced typical mosaic, leaf rolling symptoms and was associated with a hypersensitive-like response (HLR) necrosis symptom, which is accompanied with a systemic burst of H2O2 and also leads to higher PVX viral genome accumulation levels. Our results demonstrate that SCYLV P0 is a pathogenicity determinant and plays important roles in disease development. To further explore its function in pathogenic processes, a yeast two-hybrid assay was performed to screen the putative P0-interacting host factors. The recombinant plasmid pGBKT7-P0 was constructed as a bait and transformed into the yeast strain Y2HGold. The ROC22 cultivar (an important parental resource of the main cultivar in China) cDNA prey library was constructed and screened by co-transformation with the P0 bait. We identified 28 potential interacting partners including those involved in the optical signal path, plant growth and development, transcriptional regulation, host defense response, and viral replication. To our knowledge, this is the first time we have reported the host proteins interacting with the P0 virulence factor encoded by sugarcane yellow leaf virus. This study not only provides valuable insights into elucidating the molecular mechanism of the pathogenicity of SCYLV, but also sheds light on revealing the probable new pathogenesis of Polerovirus in the future.

Sintilimab-induced Alopecia Universalis in a Patient With the Anti-tumor Effect of Complete Remission After Hepatectomy.

Immune checkpoint blockades have been widely used to treat various malignancies. Programmed cell death protein 1 (PD-1) inhibitor-induced alopecia areata, one of the immune-related adverse events, is rarely reported. We present a case of alopecia universalis during the treatment of Sintilimab, a monoclonal anti-PD-1 antibody, in a patient with hepatocellular carcinoma. A 65-year-old male was diagnosed with hepatocellular carcinoma in liver segment VI (S6) and chose to receive Sintilimab due to predicted insufficient residual liver volume for hepatectomy. He presented extensive hair loss in all the parts of the body 4 weeks after Sintilimab treatment. And without using any dermatologic drug, the alopecia areata gradually developed to be alopecia universalis after Sintilimab continuous treatment for 21 months. The pathological examination of skin revealed remarkable increased lymphocytes infiltration around the hair follicles, which contained predominantly CD8 positive T cells in the dermis. During single immunotherapy, the tumor marker of serum alpha-fetoprotein level soon decreased from 512.1 mg/L to a normal level within 3 months, accompanied with a remarkable tumor regression in liver S6 by magnetic resonance imaging scans. The patient received hepatectomy and pathological examination demonstrated the nodule was full of extensive necrosis. By combining immunotherapy and hepatectomy, the patient finally achieved a remarkable anti-tumor effect of complete remission. Immune checkpoint blockades-induced alopecia areata is a rare immune-related adverse event and accompanied with a good anti-tumor efficacy in our case. Regardless of alopecia treatment, PD-1 inhibitor treatment is recommended to be continued, especially when the immunotherapy is effective.

Association of tea and coffee consumption with the risk of all-cause and cause-specific mortality among individuals with metabolic syndrome: a prospective cohort study.

BACKGROUND: The relationship between tea and coffee consumption and mortality among patients with metabolic syndrome (MetS) remains barely explored. Herein, this study aimed to examine the association between tea and coffee consumption and the likelihood of all-cause and cause-specific mortality in patients with MetS. METHODS: A total of 118,872 participants with MetS at baseline from the UK Biobank cohort were included. Information on tea and coffee consumption was obtained during recruitment using a touchscreen questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were determined using Cox proportional hazards models. RESULTS: During a median follow-up of 13.87 years, 13,666 deaths were recorded, with 5913, 3362, and 994 deaths from cancer, cardiovascular diseases (CVD), and respiratory disease (RD), respectively. This research showed a significant inverse association between tea intake and the risk of all-cause and cancer mortality, the respective HRs (95% CI) for consuming tea 2 vs. 0 cup/day were 0.89 (0.84-0.95), and 0.91 (0.83-0.99), and tea intake ≥ 4 cups/day could reduce CVD mortality by 11% (HR 0.89; 95% CI 0.81-0.98). The U-shaped nonlinear association between coffee intake and all-cause/CVD mortality was examined (all p-nonlinear < 0.001). The HRs (95% CI) for coffee consumption 1 vs. 0 cup/day were 0.93 (0.89-0.98) and 0.89 (0.80-0.99), and for ≥ 4 vs. 0 cup/day were 1.05 (1.01-1.11) and 1.13 (1.03-1.25), respectively. Notably, the combined intake of tea and coffee presented a protective effect against all-cause mortality (HR < 1). CONCLUSIONS: The importance of daily tea and moderate coffee consumption in individuals with MetS to optimise health benefits are highlighted.