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.

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.

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.

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.

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.

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.

Case report: A case of heterogeneity of the antitumor response to immune checkpoint inhibitors in a patient with relapsed hepatocellular carcinoma.

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.

Identification of Premature Infants at High Risk of Late Respiratory Diseases: A Retrospective Cohort Study.

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.

Intraperitoneally Delivered Mesenchymal Stem Cells Alleviate Experimental Colitis Through THBS1-Mediated Induction of IL-10-Competent Regulatory B Cells.

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.

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.

Long-Term Outcomes of Bronchopulmonary Dysplasia Under Two Different Diagnostic Criteria: A Retrospective Cohort Study at a Chinese Tertiary Center.

Unlike other complications among very low birth weight infants (VLBW), the incidence of bronchopulmonary dysplasia (BPD) has not decreased substantially, partly because of the different definitions of BPD applied by different researchers. In this retrospective cohort study, we aimed to compare the 2018 revised definition and the 2001 consensus definition of BPD proposed by the National Institute of Child Health and Human Development (NICHD), as well as to identify which definition better predicts severe respiratory morbidities or death. We included 417 infants born at a gestational age <32 weeks and classified them as having BPD or without BPD based on the two definitions, with a final follow-up at 18-24 months. We performed between-group comparisons of death and respiratory outcomes. Statistical analyses were performed using descriptive statistics, comparative tests, and receiver operating characteristic curves. The mean ± standard deviation gestational age and birth weight of the 417 eligible infants were 29.1 ± 1.4 weeks and 1186.6 ± 197.8 g, respectively. Among the included infants, five and three infants died before and after 36 weeks of post-menstrual age (PMA), respectively, with 68 and 344 infants evaluated at discharge and 36 weeks' PMA, respectively. We diagnosed 163 (39.1%) and 70 (16.8%) infants with BPD according to the 2001 and 2018 NICHD definitions, respectively. The 2001 NICHD definition displayed a higher sensitivity (0.60 vs. 0.28), better negative predictive value (0.89 vs. 0.85), and larger area under the receiver operating characteristic curve (0.66 vs. 0.57), but a lower specificity (0.65 vs. 0.87) and worse positive predictive value (0.26 vs. 0.31), than the 2018 definition for serious respiratory morbidity or mortality at a corrected age of 18-24 months. Compared with the 2018 NICHD definition of BPD, the 2001 NICHD consensus definition may result in more cases of false-positive or unclassified severity. However, it may be a better indicator of severe respiratory morbidities or death during the first 18-24 months. Nevertheless, there is a need for future studies to assess the validity of the new diagnostic criteria.

Less invasive surfactant administration versus endotracheal surfactant instillation followed by limited peak pressure ventilation in preterm infants with respiratory distress syndrome in China: study protocol for a randomized controlled trial.

BACKGROUND: Less invasive surfactant administration (LISA) is a way of giving surfactant without endotracheal intubation and has shown to be promising in reducing the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. However, the mechanism underlying its beneficial effect and variations in the technique of administration may prevent its widespread use. This trial aims to evaluate the effects of two methods of surfactant administration, LISA or endotracheal surfactant administration followed by low peak pressure (LPPSA) ventilation, in preterm infants with respiratory distress syndrome (RDS). METHODS: The LISA Or Low Peak Pressure trial is to be conducted in 14 tertiary neonatal intensive care units in China. A total of 600 preterm infants born with gestational age between 250/7 and 316/7 weeks and with a primary diagnosis of RDS will be involved in the study. Infants will be randomized to the LISA or LPPSA group when surfactant therapy is indicated. Primary outcomes include mortality, severity of bronchopulmonary dysplasia at 36 weeks of postmenstrual age (PMA), and mechanical ventilation (MV) in the first 72 h of life. Secondary outcomes include the days of MV, duration of all sorts of non-invasive respiratory support, fraction of inspired oxygen, oxygen saturation before and after surfactant administration, and time required to perform the procedure for surfactant administration. The incidence of comorbidities, including retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), hemodynamically significant patent ductus arteriosus (hsPDA), pneumothorax, and massive pulmonary hemorrhage within 48 h of surfactant administration, and the failure rates of each technique will be determined. DISCUSSION: Data from recent systematic review and meta-analysis have suggested a possible improvement in outcomes of preterm infants with RDS by the LISA technique. However, robust evidence is lacking. Why LISA plays a potential role in reducing respiratory morbidity, mainly BPD in preterm infants, remains unclear. The possible explanations are the active and uninterrupted delivery of continuous positive airway pressure during the LISA procedure and the avoidance of complications caused by intubation and relatively high pressure/volume ventilation following surfactant administration. We hypothesized that LISA's effectiveness lies mainly in avoiding relatively high-pressure positive ventilation immediately following surfactant administration. Thus, this multicenter randomized controlled trial will focus on issues of endotracheal intubation and the pressure/volume used during conventional surfactant administration. The effectiveness, safety and comorbidities of preterm infants following LISA or LPPSA will be evaluated. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900020970. Registered on 23 January 2019.

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.

Epithelioid hemangioendothelioma of right innominate vein mimics a teratoma: A case report.

RATIONAL: Epithelioid hemangioendothelioma (EHE) is a rare neoplasm commonly known to arise from the soft tissue, lung, and liver. EHE arising from right innominate vein (RIV) has scarcely been reported in English literature. PATIENT CONCERNS: Herein, we present a rare case of EHE of RIV in a 51-year-old woman with right-lower chest pain for 4 days. Computed tomography of the chest revealed a spherical mass with calcification and fatty foci located in the anterior mediastinum, thus a presumptive diagnosis of teratoma was made. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Video-assisted thoracoscopic explorations and resection of mediastinal tumor were then performed. The pathological examination showed that the tumor was EHE. Postoperative radiotherapy was delivered to the patient. Pulmonary metastases were found by chest CT a year after surgery. LESSONS: A diagnosis of EHE might be considered, when a mediastinal tumor closely related to veins showing intratumoral calcification and obvious enhancement, despite the presence of a clear boundary and visible fat content.

Intravoxel incoherent motion diffusion-weighted MR imaging in assessing and characterizing solitary pulmonary lesions.

This study aimed to investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted MR imaging in assessing solitary pulmonary lesions (SPLs). Sixty-two patients with pathologically confirmed SPLs, including 51 and 11 cases of malignant and benign lesions, respectively, were assessed. Diffusion weighted imaging (DWI) with 13 b values was used to derive apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Our results showed that, there was an excellent inter-observer agreement on the measurements of D and ADC between observers (inter-class correlation coefficient, ICC = 0.902 and 0.884, respectively). Meanwhile, f and D* showed good and substantial reproducibility (ICC = 0.787 and 0.623, respectively). D and ADC of malignant lesions were significantly lower than those of benign lesions (both P ≤ 0.001), while similar values were obtained in both groups for D* and f (both P > 0.05). In receiver operating characteristic (ROC) analysis, D showed the highest area under curve (AUC) for distinguishing malignant from benign lesions, followed by ADC. Accompanying signs of SPLs have specific features on IVIM maps. In conclusion, IVIM provides functional information in characterizing SPLs which is helpful to differential diagnosis. D and ADC have a significantly higher diagnostic value than f and D*.

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.