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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.
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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.
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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.
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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.
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Circulação Coronária , Diabetes Mellitus Tipo 2 , Transplante de Coração , Imagem de Perfusão do Miocárdio , Valor Preditivo dos Testes , Disfunção Ventricular Esquerda , Função Ventricular Esquerda , Humanos , Transplante de Coração/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Imagem de Perfusão do Miocárdio/métodos , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Resultado do Tratamento , Adulto , Imagem Cinética por Ressonância Magnética , Fatores de Risco , Idoso , Estudos de Casos e Controles , Fatores de Tempo , Fenômenos Biomecânicos , Biomarcadores/sangue , Contração MiocárdicaRESUMO
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.
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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.
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Técnicas Biossensoriais , Técnicas Eletroquímicas , Limite de Detecção , Titânio , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Animais , Imunoensaio/métodos , Titânio/química , Gansos , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/química , Avastrovirus/química , Avastrovirus/imunologia , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/química , Anticorpos Antivirais/imunologia , Processos FotoquímicosRESUMO
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.
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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.
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Luteoviridae , Fatores de Virulência , Técnicas do Sistema de Duplo-Híbrido , Peróxido de Hidrogênio , Luteoviridae/genéticaRESUMO
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.
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Eritroblastose Fetal , Hiperbilirrubinemia Neonatal , Feminino , Recém-Nascido , Humanos , Lactente , Estudos Retrospectivos , Readmissão do Paciente , Bilirrubina , Hiperbilirrubinemia/terapia , Eritroblastose Fetal/terapia , Fatores de Risco , Fototerapia , Hiperbilirrubinemia Neonatal/terapia , Sistema ABO de Grupos SanguíneosRESUMO
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.
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Alopecia em Áreas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Humanos , Idoso , Alopecia em Áreas/tratamento farmacológico , Alopecia em Áreas/patologia , Hepatectomia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
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.
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Displasia Broncopulmonar , Permeabilidade do Canal Arterial , Enterocolite Necrosante , Surfactantes Pulmonares , Síndrome do Desconforto Respiratório do Recém-Nascido , Retinopatia da Prematuridade , Lactente , Recém-Nascido , Humanos , Estudos Retrospectivos , Recém-Nascido Prematuro , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/terapia , Extubação , Enterocolite Necrosante/epidemiologia , Tensoativos/uso terapêutico , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Respiração Artificial , Intubação Intratraqueal , Recém-Nascido de muito Baixo PesoRESUMO
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.
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Disbiose , Microbioma Gastrointestinal , Neoplasias Hepáticas , Proteína de Ligação a Elemento Regulador de Esterol 2 , Animais , Camundongos , Carcinogênese , Neoplasias Hepáticas/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Triptofano/metabolismo , Disbiose/complicaçõesRESUMO
The existence of tumor heterogeneity is widely recognized; however, heterogeneity of the antitumor response in multiple tumor nodules in the same patient has not been reported. Sintilimab, a monoclonal antiprogrammed cell death receptor-1 (PD-1) antibody, was used to treat patients with unresectable hepatocellular carcinoma (HCC). In the present study, we report a case of therapeutic heterogeneity in relapsed HCC with lung metastases. A 57-year-old female patient was diagnosed with HCC and underwent radical hepatectomy. One and a half years later, imaging scans found multiple metastatic tumors in the lung, which were accompanied by an increased α-fetoprotein (AFP) level. The patient then started to receive sintilimab. In the first 6 months after sintilimab treatment, all the metastatic nodules regressed gradually and ultimately disappeared, except for one nodule, which remained stable in the following 3 months. Finally, the patient underwent pulmonary lobectomy to remove the remaining nodule. Thereafter, follow-up visits showed the AFP level decreased to normal and imaging scans showed no signs of recurrence, confirming that the patient exhibited a clinically complete response. Pathological assessments showed that in the primary tumor site, the tumor comprised moderately differentiated HCC with a few infiltrated cytotoxic T cells and negative PD-L1 expression. While in the metastatic site, the nodule was composed of poorly differentiated HCC with cytotoxic T-cell infiltration with few cells inside the tumor and expressed PD-L1 in some areas of the tumor. There were dynamic alterations of PD-L1 expression and cytotoxic T-cell infiltration in the primary and relapsed HCC lesions after anti-PD-1 treatment. This case presented the heterogeneities of both the tumor microenvironment and the following antitumor response among the metastatic nodules in the same patient and revealed the importance of comprehensive therapy in cancer treatment.
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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.
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Monóxido de Carbono , Hiperbilirrubinemia Neonatal , Humanos , Recém-Nascido , Monóxido de Carbono/análise , Bilirrubina , Nomogramas , Estudos Prospectivos , Hiperbilirrubinemia , Hemólise , China , Hiperbilirrubinemia Neonatal/diagnóstico , Triagem NeonatalRESUMO
The melatonin 1A receptor (MTNR1A) is a membrane receptor distributed across the mammalian gonadal axis-associated membrane. Melatonin (MT) can specifically bind with MTNR1A on the cell membrane and regulates mammalian reproductive activities. However, the role of MTNR1A in regulating the reproductive physiological activities of sheep in the Tibetan Plateau remains unclear. In this study, the MT content in Tibetan sheep blood during the estrous cycle was detected by ELISA. The distribution of MTNR1A in the hypothalamus-pituitary-gonadal axis (HPGA) was analyzed by immunohistochemistry and immunofluorescence. Western blot and qRT-PCR were used to detect dynamic changes of MTNR1A mRNA and protein expression, and the protein distributions in the HPGA. The results showed that the average secretion level of MT in Tibetan sheep blood was highest occurred during diestrus and the lowest during proestrus. Additionally, the secretion of MT at night was significantly higher than during the day. The immunopositive products of MTNR1A were primarily distributed around the glial cells in the dorsal hypothalamic nucleus region, chromophobe cells, and eosinophilic cytoplasm in the pituitary gland, follicular granular layer, follicular adventitia, tubal mucosa, cilia, endometrium, interstices, and glands in the uterus. The expression trends of MTNR1A mRNA and proteins in the HPGA during the estrous cycle were the same. The relative expression levels of MTNR1A mRNA and proteins in the hypothalamus and ovaries were the highest during proestrus and the lowest during metestrus; the highest during diestrus in the pituitary and oviducts; the highest during metestrus in the uterus. Collectively, the differences in the secretion of MT in Tibetan sheep blood and the expression of MTNR1A in HPGA suggest that they may be affected by steroid hormone secretion during the estrous cycle of Tibetan sheep, which has a potential impact on the regulation of animal estrous cycle.
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Melatonina , Animais , Ciclo Estral , Feminino , Hipotálamo/metabolismo , Mamíferos/metabolismo , Melatonina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Melatonina , Ovinos , TibetRESUMO
Aim: To identify infants with very low birth weight at risk of late respiratory diseases after discharge. Methods: This retrospective longitudinal study included 388 preterm infants with gestational age of < 32 weeks and birth weight of < 1,500 g and evaluated perinatal information, assessments performed while in the neonatal intensive care unit, and longitudinal follow-up via questionnaire until the corrected gestational age of 18-24 months. Results: The mean birth weight and gestational age were 1,191.2 ± 191.8 g and 29.1 ± 1.4 weeks, respectively. Sixty-four (16.5%) infants developed late respiratory diseases after discharge to the corrected gestational age of 18-24 months. Univariate analyses showed that gestational age, birth weight, respiratory support, oxygen use, bronchopulmonary dysplasia diagnosed at 36 weeks' postmenstrual age and length of hospital stay were associated with late respiratory diseases. After adjusting for covariates, respiratory support was significantly associated with serious respiratory morbidities to 18-24 months corrected gestational age. With each day of respiratory support, the odds of late respiratory diseases increased by 1.033-fold. Conclusion: Respiratory support was associated with increased odds of developing late respiratory diseases during early childhood, which may be an early predictor to late respiratory morbidities. Thus, it is imperative to identify a safe and effective strategy to prevent chronic dependency on respiratory support.
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Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating inflammatory bowel disease (IBD), and intraperitoneal delivery of MSCs have become a more effective route for IBD treatment. However, the underlying mechanisms are still poorly understood. Here, we found that intraperitoneally delivered MSCs significantly alleviated experimental colitis. Depletion of peritoneal B cells, but not macrophages, clearly impaired the therapeutic effects of MSCs. Intraperitoneally delivered MSCs improved IBD likely by boosting the IL-10-producing B cells in the peritoneal cavity, and a single intraperitoneal injection of MSCs could significantly prevent disease severity in a recurrent mouse colitis model, with lower proinflammation cytokines and high level of IL-10. The gene expression profile revealed that thrombospondin-1 (THBS1) was dramatically upregulated in MSCs after coculture with peritoneal lavage fluid from colitis mice. Knockout of THBS1 expression in MSCs abolished their therapeutic effects in colitis and the induction of IL-10-producing B cells. Mechanistically, THBS1 modulates the activation of transforming growth factor-ß (TGF-ß), which combines with TGF-ß receptors on B cells and contributes to IL-10 production. Blocking the interaction between THBS1 and latent TGF-ß or inhibiting TGF-ß receptors (TGF-ßR) significantly reversed the THBS1-mediated induction of IL-10-producing B cells and the therapeutic effects on colitis. Collectively, our study revealed that intraperitoneally delivered MSCs secreted THBS1 to boost IL-10+Bregs and control the progression and recurrence of colitis, providing new insight for the prevention and treatment of IBD.
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Linfócitos B Reguladores , Colite , Doenças Inflamatórias Intestinais , Células-Tronco Mesenquimais , Animais , Linfócitos B Reguladores/metabolismo , Colite/induzido quimicamente , Colite/metabolismo , Colite/terapia , Sulfato de Dextrana , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/terapia , Interleucina-10/genética , Interleucina-10/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Knockout , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
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.
Assuntos
Lesões por Esmagamento , Traumatismos dos Nervos Periféricos , Animais , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão/métodos , Eletromiografia , Traumatismos dos Nervos Periféricos/diagnóstico por imagem , Nervos Periféricos/diagnóstico por imagem , CoelhosRESUMO
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 â³ADC2h (r = -0.631) and â³D2h (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.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/tratamento farmacológico , Animais , Imagem de Difusão por Ressonância Magnética/métodos , Modelos Animais de Doenças , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Camundongos Nus , Movimento (Física) , Estudos ProspectivosRESUMO
Coix lacryma-jobi L. is a very important economic crop widely cultivated in Southeast Asia. Drought affects more than four million square kilometers every year, and is a significant factor limiting agricultural productivity. However, relatively little is known about how Coix lacryma-jobi L. responds to drought treatments. To obtain a detailed and comprehensive understanding of the mechanisms regulating the transcriptional responses of Coix lacryma-jobi L. to drought treatment, we employed high throughput short-read sequencing of cDNA prepared from polyadenylated RNA to explore global gene expression after a seven-day drought treatment. We generated a de novo assembled transcriptome comprising 65,480 unique sequences. Differential expression analysis based on RSEM-estimated transcript abundances identified 5,315 differentially expressed genes (DEGs) when comparing samples from plants following drought-treatment and from the appropriate controls. Among these, the transcripts for 3,460 genes were increased in abundance, whereas 1,855 were decreased. Real-time quantitative PCR for 5 transcripts confirmed the changes identified by RNA-Seq. The results provide a transcriptional overview of the changes in Coix lacryma-jobi L. in response to drought, and will be very useful for studying the function of associated genes and selection of molecular marker of Coix lacryma-jobi L in the future.