Outcomes of children with clear cell sarcoma of kidney following NWTS strategies in Shanghai China (2003-2021).

BACKGROUND: Although clear cell sarcoma of kidney (CCSK) is rare, it is the second most common renal tumor in children after Wilms' tumor. NWTS and SIOP are two major groups which had made tremendous efforts on renal tumors, but the strategies are different, for NWTS follows the upfront surgery principle providing definite pathology and the SIOP follows the upfront chemotherapy principle, each has its own advantages. Here we aimed to evaluate the outcomes of CCSK in China following NWTS strategies to analyze the prognostic factors. METHODS: For this multicenter retrospective study, a total of 54 patients were enrolled from three children's hospitals, between April 2003 and December 2021. Treatment comprised upfront radical nephrectomy, followed by radiotherapy and intensive chemotherapy. Clinical records were regularly updated. Prognostic factors and survival rates were evaluated. RESULTS: The 54 enrolled patients had a median age of 37 months (range, 4 months to 11.4 years). The stage distribution was 16% stage I (n = 9), 30% stage II (n = 16), 39% stage III (n = 21), and 15% stage IV (n = 8). Among stage IV, metastasis sites included the lung (n = 6), bone (n = 1), and intra-orbital/cervical lymph node (n = 1). After a median follow-up of 5.6 years, the 5-year event-free survival (EFS) was 82.4±5.4%, and overall survival was 88.1±4.6%. The EFS was 100% for stage I, 93.8 ±6.1% for stage II, 71.1±10.0% for stage III, and 68.6±18.6% for stage IV. Univariate analysis revealed that staging (III/IV), tumor rupture, and inferior vena cava tumor thrombus were inferior prognostic factors. Multivariate analysis revealed that tumor rupture was independent poor prognostic factor (P = 0.01, HR 5.9). Among relapsed patients, relapse occurred a median of 11 months after diagnosis (range, 4-41 months), and 50% (4/8) achieved a second complete remission after multiple treatment. None of the six lung metastasis patients received lung RT, only one patient developed a relapse and was salvaged by RT after relapse. CONCLUSIONS: Tumor rupture was independent poor prognostic factor. Upfront surgery of NWTS strategies can make a definite pathology diagnosis, but how to reduce tumor rupture during surgery is important especially in developing countries. The outcomes of patients with stage I-III CCSK in China were comparable to findings in other developed countries. Better outcomes were achieved in stage IV CCSK by using an intensive chemotherapy regimen including carboplatin, which require further confirmation by AREN0321. Lung RT may be safely omitted in selected patients who achieve a compete radiographic response after 6 weeks of systemic treatment (including surgery). Treatment should be encouraged even in CCSK cases with metastasis and relapse.

The Joint Effects of Thunderstorms and Power Outages on Respiratory-Related Emergency Visits and Modifying and Mediating Factors of This Relationship.

BACKGROUND: While limited studies have evaluated the health impacts of thunderstorms and power outages (POs) separately, few have assessed their joint effects. We aimed to investigate the individual and joint effects of both thunderstorms and POs on respiratory diseases, to identify disparities by demographics, and to examine the modifications and mediations by meteorological factors and air pollution. METHODS: Distributed lag nonlinear models were used to examine exposures during three periods (i.e., days with both thunderstorms and POs, thunderstorms only, and POs only) in relation to emergency department visits for respiratory diseases (2005-2018) compared to controls (no thunderstorm/no PO) in New York State (NYS) while controlling for confounders. Interactions between thunderstorms and weather factors or air pollutants on health were assessed. The disparities by demographics and seasons and the mediative effects by particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) and relative humidity (RH) were also evaluated. RESULTS: Thunderstorms and POs were independently associated with total and six subtypes of respiratory diseases in NYS [highest risk ratio (RR) = 1.12; 95% confidence interval (CI): 1.08, 1.17], but the impact was stronger when they co-occurred (highest RR = 1.44; 95% CI: 1.22, 1.70), especially during grass weed, ragweed, and tree pollen seasons. The stronger thunderstorm/PO joint effects were observed on chronic obstructive pulmonary diseases, bronchitis, and asthma (lasted 0-10 d) and were higher among residents who lived in rural areas, were uninsured, were of Hispanic ethnicity, were 6-17 or over 65 years old, and during spring and summer. The number of comorbidities was significantly higher by 0.299-0.782/case. Extreme cold/heat, high RH, PM2.5, and ozone concentrations significantly modified the thunderstorm-health effect on both multiplicative and additive scales. Over 35% of the thunderstorm effects were mediated by PM2.5 and RH. CONCLUSION: Thunderstorms accompanied by POs showed the strongest respiratory effects. There were large disparities in thunderstorm-health associations by demographics. Meteorological factors and air pollution levels modified and mediated the thunderstorm-health effects. https://doi.org/10.1289/EHP13237.

Association of asthma and lung cancer risk: A pool of cohort studies and Mendelian randomization analysis.

BACKGROUND: Over the past 2 decades, population-based studies have shown an increased association between asthma and the risk of lung cancer. However, the causal links between these 2 conditions remain poorly understood. METHODS: We conducted a comprehensive search of various databases, including PubMed, Embase, Web of Science, and Cochrane Library, up until May 04, 2023. Only articles published in English were included in our study. We performed a meta-analysis using random-effects models to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI). Subgroup analyses were conducted based on study design, gender, and histologic types. We also conducted a 2-sample Mendelian randomization (MR) using the genome-wide association study pooled data (408,422 people) published by the UK Biobank to explore further the potential causal relationship between asthma and lung cancer. RESULTS: Our meta-analysis reviewed 24 population-based cohort studies involving 1072,502 patients, revealing that asthma is significantly associated with an increased risk of lung cancer (OR = 1.29, 95% CI 1.19-1.38) in all individuals. Subgroup analysis showed a significantly higher risk of lung cancer in females with asthma (OR = 1.23, 95% CI 1.01-1.49). We found no significant association between asthma and lung adenocarcinoma (LUAD) (OR = 0.76, 95% CI 0.54-1.05), lung squamous carcinomas (LUSC) (OR = 1.09, 95% CI 0.79-1.50), or small-cell lung cancer (SCLC) (OR = 1.00, 95% CI 0.68-1.49). Interestingly, our MR analysis supported an increasing causality between asthma and lung cancer (OR = 1.11, 95% CI 1.04-1.17, P = .0008), specifically in those who ever smoker (OR = 1.09, 95% CI 1.01-1.16, P = .0173) and LUSC pathological type (OR = 1.15, 95% CI 1.05-1.26, P = .0038). CONCLUSION: Through meta-analysis, our study confirms that patients with asthma have a higher risk of developing lung cancer. Our MR study further support an increasing causal relationship between asthma and the risk of lung cancer, particularly in smokers and LUSC. Future studies examining the link between asthma and the risk of developing lung cancer should consider the bias of controlled and uncontrolled asthma.

Diffuse infantile hepatic hemangioma successfully treated with propranolol orally: a case report and literature review.

Background: Infantile hepatic hemangioma (IHH) is a common vascular, fast-growing hepatic tumor that is usually accompanied by multiple cutaneous hemangiomas. Diffuse IHH (DIHH) is a rare type of IHH that exhibits many tumors with nearly complete hepatic parenchymal replacement. At present, there is no specific standardized treatment plan for DIHH. Herein, we present the case of a 2-month-old girl with DIHH and without cutaneous hemangioma who achieved complete remission after undergoing propranolol monotherapy. Case presentation: The infant with low birth weight was presented to the pediatric department with a 2-month history of persistent vomiting and feeding difficulty. Ultrasonography and abdominal magnetic resonance imaging revealed hepatomegaly and diffused intrahepatic lesions. A computed tomography-guided percutaneous liver biopsy was performed, and the pathological examination suggested the diagnosis was DIHH. The patient exhibited remarkably response to an increasing dose of oral propranolol, from 0.5 mg/kg to 2 mg/kg every day. The intrahepatic lesions were almost completely regressed after one year of treatment and no distinct adverse reaction was observed. Conclusion: DIHH can induce life-threatening complications that require prompt interventions. Propranolol monotherapy can be an effective and safe first-line treatment strategy for DIHH.

Persistent warm-eddy transport to Antarctic ice shelves driven by enhanced summer westerlies.

The offshore ocean heat supplied to the Antarctic continental shelves by warm eddies has the potential to greatly impact the melting rates of ice shelves and subsequent global sea level rise. While featured in modeling and some observational studies, the processes around how these warm eddies form and overcome the dynamic sub-surface barrier of the Antarctic Slope Front over the upper continental slope has not yet been clarified. Here we report on the detailed observations of persistent eddies carrying warm modified Circumpolar Deep Water (CDW) onto the continental shelf of Prydz Bay, East Antarctica, using subsurface mooring and hydrographic section data from 2013-2015. We show the warm-eddy transport is most active when the summer westerlies strengthen, which promotes the upwelling of CDW and initiates eddy formation and intrusions. Our study highlights the important role of warm eddies in the melting of Antarctica's ice shelves, both now and into the future.

Subarachnoid hemorrhage misdiagnosed as acute coronary syndrome leading to catastrophic neurologic injury: A case report.

BACKGROUND: Elevated levels of cardiac troponin and abnormal electrocardiogram changes are the primary basis for clinical diagnosis of acute coronary syndrome (ACS). Troponin levels in ACS patients can often be more than 50 times the upper reference limit. Some patients with subarachnoid hemorrhage (SAH) also show electrocardiogram abnormalities, myocardial damage, and elevated cardiac biomarkers. Unlike ACS patients, patients with SAH only have a slight increase in troponin, and the use of anticoagulants or antiplatelet drugs is prohibited. Because of the opposite treatment modalities, it is essential for clinicians to distinguish between SAH and ACS. CASE SUMMARY: A 56-year-old female patient was admitted to the emergency department at night with a sudden onset of severe back pain. The final diagnosis was intraspinal hematoma in the thoracic spine. We performed an emergency thoracic spinal canal hematoma evacuation procedure with the assistance of a microscope. Intraoperatively, diffuse hematoma formation was found in the T7-T10 spinal canal, and no obvious spinal vascular malformation changes were observed. Postoperative head and spinal magnetic resonance imaging (MRI) showed a small amount of SAH in the skull, no obvious abnormalities in the cervical and thoracic spinal canals, and no abnormal signals in the lumbar spinal canal. Thoracoabdominal aorta computed tomography angiography showed no vascular malformation. Postoperative motor system examination showed Medical Research Council Scale grade 1/5 strength in both lower extremities, and the patient experienced decreased sensation below the T12 rib margin and reported a Visual Analog Scale score of 3. CONCLUSION: Extremely elevated troponin levels (more than 50 times the normal range) are not unique to coronary artery disease. SAH can also result in extremely high troponin levels, and antiplatelet drugs are contraindicated in such cases. Emergency MRI can help in the early differential diagnosis, as a misdiagnosis of ACS can lead to catastrophic neurological damage in patients with spontaneous spinal SAH.

Analysis of the incidence, characteristics, and risk factors of complications during induction chemotherapy in children with high-risk neuroblastoma.

Patients with high-risk neuroblastoma (HR-NB) exhibit suboptimal 5-year survival rates, leading to a widespread international preference for high-intensity chemotherapeutic regimens in these children. We analyzed the incidence and risk factors for complications during induction chemotherapy in children with HR-NB and tried to assist clinicians in predicting such complications and optimizing therapeutic strategy. The clinical data of children with HR-NB admitted to our hospital from January 2007 to December 2019 were retrospectively analyzed. The incidence, characteristics, and risk factors of complications (infection, hemorrhage, and chemotherapy-related adverse reactions (CRAR)) requiring hospitalization during induction chemotherapy in these children were explored. (1) A total of 108 patients with HR-NB were included in the final analysis. The overall infection rate was 92.6% (100/108), with the highest incidence of 71.3% observed during the first cycle. FN, bacterial infection, as well as fungal infection were common infectious complications in children with HR-NB during induction chemotherapy. (2) The overall hemorrhage rate was 24.1% (26/108), with the highest incidence of 14.8% also observed in the first cycle. Among the children with hemorrhage, there were 72% with bone marrow involved, while 65.0% of them had a high vanillylmandelic acid (VMA) value. And children with hemorrhage also exhibited neuron-specific enolase (NSE) ≥ 200 µg/L in 88.5% of cases and lactic dehydrogenase (LDH) ≥ 1000U/L in 73.1% of cases. (3) The incidence of CRAR rate was 100%, and 99.1% (107/108) patients experienced myelosuppression. The incidence of myelosuppression peaked in the third cycle, reaching up to 85.2%. Most children suffered severe myelosuppression existed with bone marrow metastases (76.3%), abnormal VMA (67.5%), and LDH ≥ 1000 U/L (60%). (4) Non-myelosuppressive adverse effects were observed in 75.9% children (82/108), with the highest incidence occurring in the third cycle at 42.6%. (5) Patients who experienced three types of complications had a lower median survival time (MST) of 54.4 months, a 3-year event-free survival (EFS) rate of (44.2 ± 10.7)%, and a 3-year overall survival (OS) rate of (75.8 ± 8.6)%, in comparison to those with only one or two complications, who had a higher MST of 59.5 months, a 3-year EFS rate of (73.5 ± 5.2)% (X2 = 10.457, P = 0.001), and a 3-year OS rate of (84.8 ± 4.1)% (X2 = 10.511, P = 0.001). CONCLUSION: The presence of bone marrow involved and increased VMA were high-risk factors for infection, while NSE ≥ 200 µg/L and LDH ≥ 1000 U/L were high-risk factors for hemorrhage. For those children who had experienced severe myelosuppression, the presence of bone marrow metastases, increased VMA, and LDH ≥ 1000 U/L were their risk factors. The presence of bone involvement was a high-risk factor for children to have non-myelosuppressive adverse effects. Complications that arise during induction chemotherapy could negatively impact the children's prognosis and overall quality of life. WHAT IS KNOWN: • The high-risk neuroblastoma (HR-NB) had a worse prognosis; there was a general international preference for high-intensity chemotherapeutic regimens in the induction phase to these children. WHAT IS NEW: • We analyzed the incidence and risk factors of complications during induction chemotherapy in children with HR-NB and tried to help clinicians predict such complications and adopt optimized therapeutic strategy.

A multicenter prospective study on the management of hepatoblastoma in children: a report from the Chinese Children's Cancer Group.

BACKGROUND: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. METHODS: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan-Meier curve methods were used. RESULTS: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. CONCLUSIONS: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

Elevated serum uric acid is associated with the risk of advanced staging and vascular involvement in patients with hepatoblastoma: a 14-year retrospective study.

Background: Uric acid is the end product of the purine metabolism pathway, and has been linked to cancer risks and prognosis, but its relationship with hepatoblastoma (HB) remains unclear. This study aims to investigate the association between serum uric acid (SUA) and the advanced tumor staging and unfavorable extra-parenchymal tumor characteristics in patients with HB. Methods: This study enrolled pediatric patients from Xinhua Hospital between 2007 to 2021. A total of 101 participants with newly diagnosed HB were recruited in the study. PRETreatment EXTent of disease (PRETEXT)/PostTreatment Extent of disease (POSTTEXT) staging were evaluated at diagnosis and following neoadjuvant chemotherapy (NAC). Adjusted smoothing spline plots, subgroup analysis and multivariate logistic regression analysis were conducted to estimate the association of different levels of SUA with the advanced tumor staging and present annotation factors. Results: In accordance with SUA tertiles, those patients with higher pretreatment SUA levels showed increased percentages of PRETEXT group IV, vessel involvement and multifocality of tumors. After fully adjustment with the confounding factors, SUA was positively associated with advanced PRETEXT stage IV (OR: 1.72, 95%CI 1.15-2.57, p=0.0080), as well as vascular invasion (OR: 1.29, 95%CI 1.01-1.64, p=0.0396). Compared with the lowest SUA concentration tertile, the highest tertile were independently associated with vessel involvement of tumor in all of the adjusted models. Following NAC, SUA levels were significantly reduced in response to the downstaging of tumors. SUA remained positively associated with advanced POSTTEXT staging and vessel involvement in adjusted models. Patients with highest tertile of posttreatment SUA showed worse 5-year EFS and OS. Conclusion: Elevated SUA were associated with an increased occurrence of advanced PRETEXT/POSTTEXT staging and unfavorable vessel involvement at diagnosis and following NAC in patients with HB. High posttreatment SUA reflected poor tumor responses to NAC. This study linked SUA, a non-invasive laboratory test, with tumor staging and risk prediction for HB.

RT-PCR demonstrates superior sensitivity and specificity in detecting the five neuroblastoma genes compared to the flow cytometry method for measurable residual disease.

Background: Exploring sensitive prognostic methods for patients with relapsed or refractory neuroblastoma (NB) is critical. The five NB genes (NB5) share a common trait: they are highly expressed in NB. Previous studies have identified their expression levels as markers for guiding micrometastasis. This study aimed to explore whether an improved NB5 detection method is superior to flow cytometry for predicting NB metastasis, measurable residual disease (MRD), and prognosis, and whether this result could serve as an independent factor to influence progression-free survival (PFS). Methods: We utilized reverse transcriptase polymerase chain reaction (RT-PCR) to assess the expression of NB5 (CHGA, DCX, DDC, PHOX2B, and TH) in bone marrow (BM), peripheral blood (PB), or cerebrospinal fluid (CSF) samples collected from 71 patients. The correlation between gene expression changes and clinical characteristics, as well as survival rates, based on 113 detections were analyzed. The NB5 detection results' sensitivity and specificity in all 71 patients collected from six research centers with a median follow-up of 14 months were assessed. Results: PB specimens showed 100% concordance with the BM specimens in terms of positive results. Furthermore, the BM specimens exhibited an additional 45.455% (5/11) positive results compared to the 34.091% (30/88) of PB specimens. The BM specimens were positive for NB5 assay, which was significantly higher than the positive results of flow cytometric MRD (15/88, 17.045%). NB5 was mainly expressed in newly diagnosed patients (P=0.043) and positive patients with flow cytometric MRD (P<0.001) or BM morphology (P<0.001). Positive rates of droplet digital PCR (ddPCR) were consistent with those of quantitative RT-PCR (qRT-PCR) in BM (13/18, 72.222%). However, in PB, the positive rate of ddPCR (2/5, 40.000%) was higher than that of qRT-PCR. A total of 38 specimens (BM, PB, CSF) were detected as positive under qRT-PCR. Among the positive results, the analysis revealed a significant difference between the CHGA and TH in pairwise comparisons (P=0.005). PFS analysis showed that among MRD-negative patients, the survival time of the NB5-positive group was significantly lower than that of NB5-negative group (27.408±10.791 vs. 35.961±3.084 months; P=0.034), and in the Cox regression model, risk stratification based on NB5 expression level was an independent prognostic factor for relapsed or refractory disease [95% confidence interval (CI):1.020 to 9.099, hazard ratio (HR) =3.046, P=0.046]. Combining the follow-up results, we found that the sensitivity and specificity of NB5 detection were both 100%. Conclusions: In our study, the improved NB5 detection method showed significantly higher sensitivity in assessing tumor relapse or residual disease compared to flow cytometric MRD. Moreover, it provided a more accurate assessment of treatment efficacy and prognosis. These findings support NB5 detection as an effective method for further stratification and monitoring of patients with relapsed or refractory NB.

Single-cell profiling of peripheral neuroblastic tumors identifies an aggressive transitional state that bridges an adrenergic-mesenchymal trajectory.

Peripheral neuroblastic tumors (PNTs) represent a spectrum of neural-crest-derived tumors, including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Malignant cells in PNTs are theorized to interconvert between adrenergic/noradrenergic and mesenchymal/neural crest cell states. Here, single-cell RNA-sequencing analysis of 10 PNTs demonstrates extensive transcriptomic heterogeneity. Trajectory modeling suggests that malignant neuroblasts move between adrenergic and mesenchymal cell states via an intermediate state that we term "transitional." Transitional cells express programs linked to a sympathoadrenal development and aggressive tumor phenotypes such as rapid proliferation and tumor dissemination. Among primary bulk tumor patient cohorts, high expression of the transitional gene signature is predictive of poor prognosis compared with adrenergic and mesenchymal expression patterns. High transitional gene expression in neuroblastoma cell lines identifies a similar transitional H3K27-acetylation super-enhancer landscape. Collectively, our study supports the concept that PNTs have phenotypic plasticity and uncovers potential biomarkers and therapeutic targets.

A nomogram for predicting recurrence-free survival of intermediate and high-risk neuroblastoma.

This study aimed to confirm the independent risk factors for recurrence-free survival (RFS) in intermediate and high-risk neuroblastoma (NB) patients and set up an effective nomogram model for predicting the recurrence of NB. A total of 212 children with intermediate- and high-risk neuroblastoma, who had ever achieved complete remission (CR) or very good partial remission (VGPR) after standardized treatment in this hospital, were chosen as study objects. After retrospective analysis of the clinical data, Cox regression model was used to explore the factors related to the recurrence of neuroblastoma, to determine the variables to construct the Nomogram. The consistency index would predict the accuracy of this nomogram. RFS rate in 1-year, 3-year, 5-year, and 10-year was 0.811, 0.662, 0.639, and 0.604, respectively. Children with MYCN amplification had a higher neuron-specific enolase (NSE) value (P = 0.031) at the initial diagnosis than MYCN non-amplification. The univariate analysis predicted that increased vanillylmandelic acid (VMA) and NSE value and dehydrogenase (LDH) > 1000 U/L were important adverse factors for the recurrence of NB. Multivariate analysis demonstrated that age at diagnosis, tumor localization, MYCN state, histologic subtype, and tumor capsule were significantly associated with RFS (all P values < 0.05). Nomograms were established for predicting the recurrence of NB according to the Cox regression analysis. Internal verification by the Bootstrap method showed that the prediction of the nomogram's consistency index (C-index) was 0.824 (P = 0.023).   Conclusion: Age at diagnosis, tumor localization, MYCN state, histologic category, and tumor capsule were independent risk factors for the recurrence of NB. The nomogram model could accurately predict the recurrence of children with neuroblastoma. What is Known: • The prognoses of neuroblastoma (NB) could vary greatly due to the high heterogeneity, the 5-year survival rate of low-risk NB exceeded 90%, while the 5-year survival rate of children in the intermediate and high-risk groups was not satisfactory.. What is New: • Increased vanillylmandelic acid (VMA) and neuron-specific enolase (NSE) value, and lactate dehydrogenase (LDH)>1000U/L were important adverse factors for the recurrence of NB. • NSE value was more valuable for predicting NB recurrence.

BCL11A Facilitates Cell Proliferation and Metastasis in Neuroblastoma via Regulating the PI3K/Akt Signaling Pathway.

PURPOSE: The study aims to access the value of B-cell lymphoma/leukemia 11A (BCL11A) in the prognosis of patients with neuroblastoma (NB) and to explore its role and possible mechanism in NB. METHODS: Tumor specimens from 53 children with neuroblastoma were evaluated for the relationship between BCL11A expression level and prognosis of NB patients. Online datasets like SEQC and Asgharzadeh were analyzed to further check out the suppose.The role of BCL11A in the proliferation and migration of NB cells was studied by functional experiments such as CCK8, colony formation, flow cytometry, transwell and wound healing assay after knocking down BCL11A by small interfering RNA (siRNA) in vitro. The protein makers of the potential pathways were tested by western blot. RESULTS: High expression of BCL11A in NB patients was closely correlated with high-risk and poor prognosis. The proliferation and migration abilities of NB cell lines SK-N-BE(2) and IMR-32 were significantly impaired by silencing BCL11A. Downregulation of BCL11A expression level in NB cells inhibited the epithelial-mesenchymal transition (EMT) process and affected the PI3K/Akt signaling pathway. CONCLUSION: As a prognostic indicator of survival in NB patients, BCL11A might serve as a potential therapeutic target. BCL11A played a regulatory role in cell proliferation, invasion, and migration in NB, which may be through the PI3K/AKT signaling pathway and induce EMT.

The roles of 10-methacryloyloxydecyl dihydrogen phosphate and its calcium salt in preserving the adhesive-dentin hybrid layer.

OBJECTIVES: 10-Methacryloyloxydecyl dihydrogen phosphate (MDP) has been regarded as the most effective dentin-bonding monomer for more than 20 years. Although the dentin-bonding promoting effect of MDP has been well demonstrated, the mechanisms by which it benefits the stably of collagen within the adhesive-dentin hybrid layer are not currently fully understood. The objective of this study was to investigate the roles of MDP and its calcium salt in preserving the adhesive-dentin hybrid layer. METHODS: MDP-conditioned collagen was investigated by Fourier-transform infrared spectroscopy, Ultraviolet-visible spectroscopy, and molecular docking. The structural changes to the dentin surface upon acid-etching and MDP-conditioning were observed by SEM. X-ray diffraction and nuclear magnetic resonance were used to investigate the chemical interactions between MDP and HAp. The collagen-protecting effects of MDP and its Ca salt were investigated using in-situ zymography, rhMMP-9 colorimetric assay, hydroxyproline assay, and molecular docking. RESULTS: MDP forms a stable collagen-phosphate complex through hydrogen bonding with the collagen in dentin. Furthermore, it generates MDP-Ca salts that are deposited on the dentin collagen scaffold, protecting it from degradation. Moreover, both free MDP and the MDP-Ca salt inhibit matrix metallopeptidase and exogenous proteases, with the inhibitory effect of the calcium salt being significantly stronger than that of the free form. SIGNIFICANCE: MDP-based adhesives preserve the collagen within the hybrid layer by simultaneously improving collagen's resistance to exogenous enzymes and inhibiting MMP activity, both of which contribute to the longevity of dentin-resin bonding.

Role of 3-Methacryloxypropyltrimethoxysilane in Dentin Bonding.

In this study, we aimed to examine the effect of 3-methacryloxypropyltrimethoxysilane (MPS) on dentin collagen and the impact of MPS and 10-methacryloyloxydecyl dihydrogen phosphate (MDP) together and separately on resin-dentin bonding. Eight groups of primers were prepared: control group, MDP, MPS5, MPS5 + MDP, MPS10, MPS10 + MDP, MPS15, and MPS15 + MDP. The potential interaction between MPS and collagen was assessed by molecular dynamics, contact angle measurement, zeta potential measurement, and chemoanalytic characterization using X-ray photoelectron spectroscopy, Raman spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and ultraviolet-visible spectroscopy. Microtensile bond strength (µTBS) and nanoleakage were evaluated after 24 h or 12 months of water storage. In situ zymography was used to evaluate the enzyme activity at the bonded interface. According to chemoanalytic characterization and molecular dynamics, a weak interaction between MPS and collagen was observed. MPS enhanced the hydrophobicity and negative charge of the collagen surface (P < 0.05). Applying an MDP-containing primer increased µTBS (P > 0.05) and reduced fluorescence after 24 h of water storage. Water storage for 12 months decreased µTBS (P < 0.05) and increased nanoleakage for all groups. MPS conditioning did not change µTBS and nanoleakage after 24 h of water storage or aging. The MPS10 + MDP and MPS15 + MDP groups presented more silver nitrate and µTBS decrease than the MDP group (P < 0.05). These results indicated that MPS had a weak interaction with collagen that enhanced its surface negative charge and hydrophobicity without adversely affecting dentin bonding. However, compared to MDP alone, mixing MDP with MPS impaired their effectiveness and made the dentin bonding unstable.

Interactions of two phosphate ester monomers with hydroxyapatite and collagen fibers and their contributions to dentine bond performance.

OBJECTIVES: To evaluate the interactions of two phosphate ester monomers [10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) and dipentaerythritol penta-acrylate phosphate (PENTA)] with hydroxyapatite and collagen and understand their influence on dentine bonding. METHODS: Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, nuclear magnetic resonance, ultraviolet-visible, and molecular docking were applied for separately evaluating the interactions of two monomers with hydroxyapatite and collagen. Hydrophilicity tests and morphological observation were employed to characterize pretreated dentine. Microtensile bond strength (µTBS) and nanoleakage were investigated to evaluate the bonding performance. Hydroxyproline assay, in situ zymography, and matrix metalloproteinase-9 (MMP-9) activity assay were used to confirm the MMP inhibition. RESULTS: Chemoanalytic characterization confirmed the interactions of 10-MDP and PENTA with hydroxyapatite and collagen. The interactions of PENTA were weaker than 10-MDP. PENTA possessed better dentine tubule sealing after etching than 10-MDP. Dentine treated with PENTA was more hydrophilic than 10-MDP. 10-MDP and PENTA treating significantly increased the initial µTBS than the control group without primer conditioning. µTBS decreased significantly during aging, and the decrease was more severe in the PENTA group than 10-MDP. The 10-MDP and PENTA groups exhibited relatively less fluorescence than the control. The relative inhibition percentages of MMP-9 decreased in the order of 10-MDP-Ca salt, 10-MDP and PENTA. The 10-MDP, PENTA, and 10-MDP-Ca salt groups showed significantly lower hydroxyproline contents than the control. CONCLUSIONS: Although PENTA adsorbed on hydroxyapatite, it did not form a stable calcium salt. The interactions of 10-MDP with hydroxyapatite and collagen are different than those of PENTA. CLINICAL SIGNIFICANCE: The sealing of dentinal tubules by PENTA and the inhibition of MMP by 10-MDP and its calcium salts contribute to improving the dentine bonding durability.

Does Waldenstrom's macroglobulinemia also cause bone destruction? A rare case report.

Waldenstrom's macroglobulinemia (WM) is a rare type of malignant B-cell lymphoma. The main feature of WM is elevated serum monoclonal immunoglobulin M, similar to multiple myeloma (MM). Unlike in MM, the rarity of destructive bone lesions in WM has been repeatedly emphasized. We report a unique case of WM with a vertebral compression fracture as the first symptom. This case highlights that the presence or absence of bone destruction may not clearly distinguish between WM and MM. The possibility of WM should be considered in patients with vertebral fracture and destruction as the first presentation. Performing vertebral bone marrow aspiration biopsy during percutaneous vertebroplasty is a convenient and effective method to assist in the diagnosis of WM.

CTRL: Closed-Loop Transcription to an LDR via Minimaxing Rate Reduction.

This work proposes a new computational framework for learning a structured generative model for real-world datasets. In particular, we propose to learn a Closed-loop Transcriptionbetween a multi-class, multi-dimensional data distribution and a Linear discriminative representation (CTRL) in the feature space that consists of multiple independent multi-dimensional linear subspaces. In particular, we argue that the optimal encoding and decoding mappings sought can be formulated as a two-player minimax game between the encoder and decoderfor the learned representation. A natural utility function for this game is the so-called rate reduction, a simple information-theoretic measure for distances between mixtures of subspace-like Gaussians in the feature space. Our formulation draws inspiration from closed-loop error feedback from control systems and avoids expensive evaluating and minimizing of approximated distances between arbitrary distributions in either the data space or the feature space. To a large extent, this new formulation unifies the concepts and benefits of Auto-Encoding and GAN and naturally extends them to the settings of learning a both discriminative and generative representation for multi-class and multi-dimensional real-world data. Our extensive experiments on many benchmark imagery datasets demonstrate tremendous potential of this new closed-loop formulation: under fair comparison, visual quality of the learned decoder and classification performance of the encoder is competitive and arguably better than existing methods based on GAN, VAE, or a combination of both. Unlike existing generative models, the so-learned features of the multiple classes are structured instead of hidden: different classes are explicitly mapped onto corresponding independent principal subspaces in the feature space, and diverse visual attributes within each class are modeled by the independent principal components within each subspace.