Recurrent Cerebral Venous Sinus Thrombosis Occurred in an Acute Lymphoblastic Leukemia Child with Mutated Lipoprotein Lipase Gene during Asparaginase Therapy.

Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation.

METTL14 downregulation drives S100A4+ monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression.

Without intervention, a considerable proportion of patients with metabolism-associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism-associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1+Ccr2+ monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1+Ccr2+ Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1+Ccr2+ Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.

An energy-efficient solution to sludge drying and combustion process through Camellia oleifera shells amended foaming.

Foaming pretreatment has been proven effective in promoting sludge drying, however, the variation in sludge properties significantly influences the foaming efficiency. Inspired by foam stabilizer of solid particles, Camellia oleifera shells (COS) was screened out from various biomasses as an additive incorporated with the CaO for promoting the sludge foaming. For the introduction of COS, this study analyzed the drying behaviors of foamed sludge, quantified the surface cracks information, characterized the combustion performance, and evaluated the energy consumption. The results indicated that 46.72-50.10% of time could be saved in foaming the sludge to 0.70 g/mL by addition of 3.0 wt% COS. Compared with the original sludge (OS), the 0.70 g/mL foamed sludge saved 47.43% of time for sludge drying at 80 °C, and this value further increased to 53.14% with 3.0 wt% COS addition. Combining the multifractal spectra and drying kinetics analysis, the foaming promoted the formation of complex surface cracks in the warm-up period, while COS further improved the complexity of cracks in the constant rate period, and the shrinkage of isolated sludge blocks in the falling rate period, thus enhanced the moisture diffusion and heat transfer. Furthermore, the appropriate porous structure and additional volatile matters promoted the combustion performance. The 0.90 g/mL foamed sludge with COS presented the lowest activation energy of 180.362 kJ/mol in combustion. Overall, compared with OS, the 0.70 g/mL foamed sludge with COS saved 40.65% energy consumption during the foaming, drying and combustion processes, providing an energy-efficient solution for the sludge treatment and disposal.

Early Detection of Molecular Residual Disease and Risk Stratification for Children with Acute Myeloid Leukemia via Circulating Tumor DNA.

PURPOSE: Patient-tailored minimal residual disease (MRD) monitoring based on circulating tumor DNA (ctDNA) sequencing of leukemia-specific mutations enables early detection of relapse for pre-emptive treatment, but its utilization in pediatric acute myelogenous leukemia (AML) is scarce. Thus, we aim to examine the role of ctDNA as a prognostic biomarker in monitoring response to the treatment of pediatric AML. EXPERIMENTAL DESIGN: A prospective longitudinal study with 50 children with AML was launched, and sequential bone marrow (BM) and matched plasma samples were collected. The concordance of mutations by next-generation sequencing-based BM-DNA and ctDNA was evaluated. In addition, progression-free survival (PFS) and overall survival (OS) were estimated. RESULTS: In 195 sample pairs from 50 patients, the concordance of leukemia-specific mutations between ctDNA and BM-DNA was 92.8%. Patients with undetectable ctDNA were linked to improved OS and PFS versus detectable ctDNA in the last sampling (both P < 0.001). Patients who cleared their ctDNA post three cycles of treatment had similar PFS compared with persistently negative ctDNA (P = 0.728). In addition, patients with >3 log reduction but without clearance in ctDNA were associated with an improved PFS as were patients with ctDNA clearance (P = 0.564). CONCLUSIONS: Thus, ctDNA-based MRD monitoring appears to be a promising option to complement the overall assessment of pediatric patients with AML, wherein patients with continuous ctDNA negativity have the option for treatment de-escalation in subsequent therapy. Importantly, patients with >3 log reduction but without clearance in ctDNA may not require an aggressive treatment plan due to improved survival, but this needs further study to delineate.

[Detection of BCR-ABL Fusion Gene in Chronic Myeloid Leukemia by Novel Digital PCR].

OBJECTIVE: To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABLp190/210/230. METHODS: A new dPCR system for detecting BCR-ABLp190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared. RESULTS: Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal. CONCLUSIONS: This new dPCR detection system can be applied to the detection of BCR-ABLp190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.

Integration of Transcriptomic Features to Improve Prognosis Prediction of Pediatric Acute Myeloid Leukemia With KMT2A Rearrangement.

Lysine methyltransferase 2A-rearranged acute myeloid leukemia (KMT2A-r AML) is a special entity in the 2022 World Health Organization classification of myeloid neoplasms, characterized by high relapse rate and adverse outcomes. Current risk stratification was established on the treatment response and translocation partner of KMT2A. To study the transcriptomic feature and refine the current stratification of pediatric KMT2A-r AML, we analyzed clinical and RNA sequencing data of 351 patients. By implementing least absolute shrinkage and selection operator algorithm, we identified 7 genes (KIAA1522, SKAP2, EGFL7, GAB2, HEBP1, FAM174B, and STARD8) of which the expression levels were strongly associated with outcomes. We then developed a transcriptome-based score, dividing patients into 2 groups with distinct gene expression patterns and prognosis, which was further validated in an independent cohort and outperformed the LSC17 score. We also found cell cycle, oxidative phosphorylation, and metabolism pathways were upregulated in patients with inferior outcomes. By integrating clinical characteristics, we proposed a simple-to-use prognostic scoring system with excellent discriminability, which allowed us to distinguish allogeneic hematopoietic stem cell transplantation candidates more precisely. In conclusion, pediatric KMT2A-r AML is heterogenous on transcriptomic level and the newly proposed scoring system combining clinical characteristics and transcriptomic features can be instructive in clinical routines.

Pediatric acute myeloid leukemia and hyperleukocytosis with WBC count greater than 50 × 109/L.

BACKGROUND: Acute myeloid leukemia (AML) and hyperleukocytosis have an unfavorable prognosis, but the impact of hyperleukocytosis on the prognosis of pediatric AML remains uncertain. We investigated the clinical characteristics and prognosis of pediatric AML with hyperleukocytosis, defined as WBC ≥ 50 × 109/L. METHODS: A total of 132 patients with newly diagnosed childhood AML with hyperleukocytosis were consecutively enrolled at our center from September 2009 to August 2021 to investigate prognostic factors and clinical outcomes. RESULTS: Hyperleukocytosis occurred in 27.4% of AML patients. Pediatric patients with hyperleukocytosis had similar CR and OS rates to those without hyperleukocytosis, but had a lower EFS rate. In our study, rates of CR1, mortality, relapsed/refractory disease, and HSCT were comparable between AML patients with WBC counts of 50-100 × 109/L and ≥ 100 × 109/L. AML patients with a WBC count of 50-100 × 109/L had a similar 5-year OS rate to patients with a WBC count ≥ 100 × 109/L (74.6% vs. 75.4%, P = 0.921). Among all patients with hyperleukocytosis, the FAB M5 subtype was associated with significantly inferior survival, and the prognosis of CBF-AML was good. CONCLUSIONS: Pediatric AML patients with hyperleukocytosis have the similar prognosis regardless of whether their WBC count is 50-100 × 109/L or ≥ 100 × 109/L.

High risk of bloodstream infection of carbapenem-resistant enterobacteriaceae carriers in neutropenic children with hematological diseases.

BACKGROUND: Neutropenic children with hematological diseases were associated with higher morbidity of carbapenem-resistant enterobacteriaceae (CRE) blood-stream infection (BSI) or colonization. But it was still murky regarding clinical characteristics, antimicrobial susceptibility, and outcomes of CRE-BSI in these patients. We aimed to identify the potential risk factors for subsequent bacteremia and clinical outcome caused by CRE-BSI. METHODS: Between 2008 and 2020, 2,465 consecutive neutropenic children were enrolled. The incidence and characteristics of CRE-BSI were explored in CRE-colonizers versus non-colonizers. Survival analysis was performed and risk factors for CRE-BSI and 30-day mortality were evaluated. RESULTS: CRE-carriers were identified in 59/2465 (2.39%) neutropenic children and19/59 (32.2%) developed CRE-BSI, while 12/2406 (0.5%) of non-carriers developed CRE-BSI (P < 0.001). The 30-day survival probability was significantly lower in patients with CRE-BSI than in non-BSI (73.9% vs. 94.9%, P = 0.050). Moreover, the 30-day survival probability of patients with CRE-BSI was also poorer in CRE-carriers versus non-carriers (49.7% vs. 91.7%, P = 0.048). Tigecycline and amikacin exhibited satisfactory antimicrobial activity against all isolated strains. Fluoroquinolone sensitivity was lower in E. coli (26.3%) strains versus satisfactory susceptibility of E. cloacae and other CRE-strains (91.2%). CRE-BSI accompanying intestinal mucosal damage were independent risk factors for 30-day survival probability (both P < 0.05), while combined antibiotic therapy and longer duration of neutropenia were more prone to developed CRE-BSI (P < 0.05). CONCLUSION: CRE-colonizers were prone to subsequent BSI and CRE-BSI was regarded as an independent predictor predisposing to high mortality in neutropenic children. Moreover, individualized antimicrobial therapy should be adopted due to different features of patients with separate CRE strains.

Cancer cell-derived extracellular vesicles drive pre-metastatic niche formation of lymph node via IFNGR1/JAK1/STAT1-activated-PD-L1 expression on FRCs in head and neck cancer.

OBJECTIVE: The aim of this study is to evaluate the role of FRCs regulated by cancer cell-derived extracellular vesicles (CEVs) played in pre-metastatic niche (PMN) formation of lymph node (LN). MATERIALS AND METHODS: The FRCs in sixty fresh cervical LNs from 20 patients were evaluated by flow cytometric analysis. Cells in LN with or without metastasis were analyzed by single-cell RNA sequencing (scRNA-seq). CEVs were isolated from the culture supernatant of primarily cultured cancer cells and cocultured with FRCs. Mass Spectrometry was used to identify LN metastasis related protein in CEVs. The activation of IFNGR1/JAK1/STAT1-activated-PD-L1 pathway in FRCs was detected by western blotting. FRCs were co-cultured with CD8+ T lymphocytes to confirm the cytotoxicity assay of FRCs. RESULTS: The proportion of fibroblastic reticular cells (FRCs) was significantly higher in micro-metastatic LN in head and neck squamous cell carcinoma patients (HNSCC, p < 0.05) and scRNA-seq analysis further showed a high focus of extracellular vesicles-related pathway on FRCs in LN with metastasis (p < 0.05). Interferon gamma receptor 1 (IFNGR1) in CEVs can be engulfed by FRCs and promote PD-L1 expression on FRCs via JAK1-STAT1 pathway, resulting in an increased CD8+ T cell exhaustion. CONCLUSION: IFNGR1, originated from cancer cell-derived extracellular vesicles, promote PD-L1 expression on FRCs and subsequent CD8+ T cell exhaustion via JAK1-STAT1 activation, which facilitate pre-metastatic niche formation and tumor metastasis in sentinel lymph node in HNSCC.

Phenotypic and genotypic correlation evaluation of 148 pediatric patients with Fanconi anemia in a Chinese rare disease cohort.

BACKGROUND: Fanconi anemia (FA) is a rare autosomal recessive, X-linked or autosomal dominant disease. Few large-scale FA investigations of rare disease cohorts have been conducted in China. METHODS: We enrolled 148 patients diagnosed with FA according to evidence from the clinical phenotype, family history, and a set of laboratory tests. Next, the clinical manifestations and correlation between the genotype and phenotype of FA pediatric cases were investigated. RESULTS: The most common FA subtype in our cohort was FA-A (51.4 %), followed by FA-D2 and FA-P. Finger (26 %) and skin (25 %) deformities were the most common malformations. Based on family history, blood system diseases (51 %) had the highest incidence rate, followed by digestive system tumours. A set of new or prognosis-related mutation sites was identified. For example, c.2941 T > G was a new most common missense mutation site for FANCA. FANCP gene mutation sites were mainly concentrated in exons 12/14/15. The mutations of FANCI/FANCD2 were mainly located at the α helix and ß corners of the protein complex. FA-A/D1 patients with splicing or deletion mutations showed more severe disease than those with missense mutations. Chromosome 1/3/7/8 abnormalities were closely linked to the progression of FA to leukemia. CONCLUSION: Our study investigated the clinical features and genotype/phenotype correlation of 148 Chinese pediatric FA patients, providing new insight into FA.

Effects of initial particle sizes of Triarrhena lutarioriparia on processing performance, material properties, and heavy metal speciation in sewage sludge composting.

The purpose of this study was to investigate the effect of initial particle size (IPS) on the environmental parameters and heavy metal speciation during sludge composting. Three piles were conducted: fine material (FM, screen underflow), coarse material (CM, oversize product), and mixed material (MM, mix FM and CM in 1:1). Results showed that the temperature trends of the three piles in different layers were highly repeatable during the thermophilic period. With the decrease of IPS, the heating rate and the highest temperature of the pile increased, the thermophilic period was prolonged, and the highest temperature area in the pile shifted to a lower layer. It also promoted the organic matter degradation, compost maturation, and nitrogen fixation effect. Composting had a good effect on the passivation of heavy metals, especially Cd, Cu, and Pb. The passivation effect on Cd and Cu was FM > CM > MM, and on Pb was CM > FM > MM. Fourier transform infrared spectroscopy, excitation-emission matrix, and thermogravimetric thermal analysis indicated that FM had the highest content of aromatic structure and humic-like substance on D40. The redundancy analysis revealed that MM was beneficial to improve the internal uniformity during composting.

Metastatic parotid gland malignancy: A preliminary study in an eastern Chinese population.

OBJECTIVE: This study aimed to determine the incidence and clinicopathological patterns of metastatic carcinoma of the parotid gland. METHOD: Ninety patients with parotid gland metastases admitted to our hospital between January 2003 and December 2018 were included in this study. Clinical and pathological data were obtained from the medical records and follow-ups. Kaplan-Meier analysis was used to assess overall survival of patients. RESULTS: Among the 90 patients, parotid gland metastases originated from the head and neck in 86 (95.6%), from non-head and neck in 4 (4.4%), from the oral cavity in 30(33.3%), and from the eyelid in 21 (23.3%). Among the 85 cases with parotid gland lymph node metastasis, 45 (52.9%) were diagnosed with extra-lymph node metastasis. The capsule of the parotid lymph nodes was thinner than that of the cervical lymph nodes (P < 0.05). Hematogenous metastases to the parotid gland (only five cases) were rare, mainly from the non-head and neck malignancies. Patients with oral squamous cell carcinoma and meibomian adenocarcinoma with parotid metastatic disease had poorer overall survival (P < 0.05). CONCLUSION: Eastern China population analysis showed that parotid gland metastases usually arise from oral squamous cell carcinoma and eyelid, but rarely from cutaneous squamous cell carcinoma. Most cases metastasize to the parotid lymph nodes via the lymphatic system and are prone to extranodal extension with little or no facial nerve involvement. These findings have important implications for the treatment of metastatic parotid malignancies.

Sex differences in patients with COVID-19 after bariatric surgery: a multicenter cross-sectional study.

Objectives: This multicenter, cross-sectional study aimed to investigate whether sex differences persist among patients who have undergone bariatric surgery and tested positive for the coronavirus disease (COVID-19). Methods: We conducted a multicenter cross-sectional study via an online electronic questionnaire to collect data. Categorical data were presented as absolute and relative frequencies. Data for continuous variables were expressed as mean and standard deviation (SD) or median [interquartile range (IQR)]. We employed ordered logistic regression to assess whether females had higher odds of an increased self-reported duration of the most severe symptom compared to males. Using a modified Poisson regression model with robust standard errors to assess the differences in clinical characteristics among COVID-19 cases. Results: Statistical analysis revealed significant differences in the prevalence rates of various comorbidities. Among participants who reported their temperature during COVID-19 infection, more than half engaged in vitamin supplementation and regular exercise, while 4.2% remained asymptomatic. The probability of females experiencing a longer duration of severe symptoms increased compared to males [adjusted Odds Ratio (aOR) = 1.92, 95% confidence interval (CI) 1.73-2.12]. In the multivariate mixed-effects Poisson regression analysis, compared to males, females exhibited a lower prevalence rate of asymptomatic infection [adjusted prevalence ratio (aPR 0.40, 95% CI 0.28-0.58), lower prevalence of infection without therapeutic medication use (aPR 0.76, 95% CI 0.70-0.82), and lower prevalence of multiple infections (aPR 0.39, 95% CI 0.20-0.74)]. Conclusion: This cross-sectional study indicates the persistence of sex differences among patients with COVID-19 who have undergone bariatric surgery. Further research is needed to explore the underlying factors contributing to this disparity.

Targeting DNA damage response as a potential therapeutic strategy for head and neck squamous cell carcinoma.

Cells experience both endogenous and exogenous DNA damage daily. To maintain genome integrity and suppress tumorigenesis, individuals have evolutionarily acquired a series of repair functions, termed DNA damage response (DDR), to repair DNA damage and ensure the accurate transmission of genetic information. Defects in DNA damage repair pathways may lead to various diseases, including tumors. Accumulating evidence suggests that alterations in DDR-related genes, such as somatic or germline mutations, single nucleotide polymorphisms (SNPs), and promoter methylation, are closely related to the occurrence, development, and treatment of head and neck squamous cell carcinoma (HNSCC). Despite recent advances in surgery combined with radiotherapy, chemotherapy, or immunotherapy, there has been no substantial improvement in the survival rate of patients with HNSCC. Therefore, targeting DNA repair pathways may be a promising treatment for HNSCC. In this review, we summarized the sources of DNA damage and DNA damage repair pathways. Further, the role of DNA damage repair pathways in the development of HNSCC and the application of small molecule inhibitors targeting these pathways in the treatment of HNSCC were focused.

The successful combination of grapefruit juice and venetoclax in an unfit acute myeloid leukemia patient with adverse risk: A case report.

Venetoclax combined with hypomethylating agents such as azacitidine and decitabine is the standard regime for the elderly patient with acute myeloid leukemia (AML) unfit for intensive induction therapy. However, many patients struggle with finances and forgo treatments due to the high costs of venetoclax. In this study, we performed the regime with azacitidine, low-dose venetoclax, and grapefruit juice on an unfit AML patient with TP53 mutation. The peak venetoclax concentration (Cmax) and side effects on the patient were also monitored. The patient achieved complete remission with the venetoclax Cmax within the effective concentration range (1,000-3,000 ng/ml) and maintained durable remission until recently. Febrile neutropenia, thrombocytopenia, and pneumonia appeared during the first cycle and were recovered by stimulating agents and antibiotic treatment. This improvement combination approach by drug-food interaction may enlighten other similarly patients with AML, especially those in low-middle income countries.

Pediatric non-Down's syndrome acute megakaryoblastic leukemia patients in China: A single center's real-world analysis.

Non-Down's syndrome acute megakaryocytic leukemia (non-DS-AMKL) is a subtype of childhood acute myeloid leukemia (AML), whose prognosis, prognostic factors and treatment recommendations have not yet to be defined in children. We conducted a retrospective study with 65 newly diagnosed non-DS-AMKL children from August 2003 to June 2020 to investigate the clinical impact of factors and clinical outcome. Among all 65 patients, 47 of them were treated at our center who received three different regimens due to time point of admission (CAMS-another, CAMS-2009 and CAMS-2016 protocol), and the efficacy were compared. Patients with newly diagnosed non-DS-AMKL accounted for 7.4% of pediatric AML cases. The median age of the patients was 18 months at diagnosis, and over 90% of them were under three-years-old. The overall survival (OS) rates were 33.3% ± 1.7%, 66.7% ± 24.4% and 74.2% ± 4.0% for three groups (CAMS-another, CAMS-2009 and CAMS-2016 regimen), respectively. In CAMS-2016 group, the complete remission (CR) rate after induction was 67.7% (21/31), while the total CR rate after all phases of chemotherapy was 80.6% (25/31). The 2-year survival probability did not significantly improve in patients underwent HSCT when compared with non-HSCT group (75.0% ± 4.7% vs. 73.9% ± 4.6%, p=0.680). Those who had a "dry tap" during BM aspiration at admission had significantly worse OS than those without "dry tap" (33.3% ± 8.6% vs. 84.0% ± 3.6%, p=0.006). Moreover, the results also revealed that patients with CD34+ had significantly lower OS (50.0% ± 6.7% vs. 89.5% ± 3.5%, p=0.021), whereas patients with CD36+ had significantly higher OS than those who were negative (85.0% ± 4.0% vs. 54.5% ± 6.6%, p=0.048). In conclusion, intensive chemotherapy resulted in improved prognosis of non-DS-AMKL children and subclassification may base on "dry tap" and immunophenotypic. Although some progress has been made, outcomes of non-DS-AMKL children remain unsatisfactory, especially in HSCT group, when compared with other AML types.

Development and validation of a prognostic scoring model to risk stratify childhood acute myeloid leukaemia.

To create a personal prognostic model and modify the risk stratification of paediatric acute myeloid leukaemia, we downloaded the clinical data of 597 patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database as a training set and included 189 patients from our centre as a validation set. In the training set, age at diagnosis, -7/del(7q) or -5/del(5q), core binding factor fusion genes, FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)/nucleophosmin 1 (NPM1) status, Wilms tumour 1 (WT1) mutation, biallelic CCAAT enhancer binding protein alpha (CEBPA) mutation were strongly correlated with overall survival and included to construct the model. The prognostic model demonstrated excellent discriminative ability with the Harrell's concordance index of 0.68, 3- and 5-year area under the receiver operating characteristic curve of 0.71 and 0.72 respectively. The model was validated in the validation set and outperformed existing prognostic systems. Additionally, patients were stratified into three risk groups (low, intermediate and high risk) with significantly distinct prognosis, and the model successfully identified candidates for haematopoietic stem cell transplantation. The newly developed prognostic model showed robust ability and utility in survival prediction and risk stratification, which could be helpful in modifying treatment selection in clinical routine.

Droplet digital PCR for genetic mutations monitoring predicts relapse risk in pediatric acute myeloid leukemia.

Multiparameter flow cytometry (MFC)-based minimal residual disease has been a poor predictor of prognosis in children with acute myeloid leukemia (AML). This study aimed to evaluate the incremental value of serial monitoring by droplet digital PCR (ddPCR) in forecasting the outcome of AML. Twenty-four children with AML were enrolled and the relapse-free survival (RFS) rate was estimated using the Kaplan-Meier method. Survival estimates were compared using the log-rank test. Survival analysis showed that the RFS rate in the ddPCR ≥ 0.1% group was significantly lower than that in the < 0.1% group (35.7% ± 19.8% vs. 83.6% ± 10.8%, P = 0.003). Moreover, serial monitoring by ddPCR showed that some mutations remained positive in some patients even though other co-mutations were eliminated, and those patients were more prone to relapse, with a significantly poorer RFS compared to patients negative for mutation (22.0% ± 19.2% vs 83.3% ± 11.3%, P = 0.001). Consequently, ddPCR may assist in prognostic forecasting for pediatric AML.

HIF-1α induced NID1 expression promotes pulmonary metastases via the PI3K-AKT pathway in salivary gland adenoid cystic carcinoma.

BACKGROUND: This study aimed to investigate the potential role of nidogen 1 (NID1), a basement membrane component, in the growth and metastasis of salivary gland adenoid cystic carcinoma (SACC) and the underlying molecular mechanism. METHODS: High-throughput next-generation sequencing was used to compare the gene expression profiles of SACC with and without lung metastasis. Luciferase gene reporter assays were used to measure the NID1 promoter activity. BALB/c nude mice were used to establish a lung metastasis model of SACC to evaluate the prometastatic activity of NID1. ChIP and dual-luciferase reporter assays were performed to confirm the HIF-1α-binding site in the NID1 promoter. RESULTS: NID1 expression in SACC was significantly increased and associated with lung metastasis (P = 0.011). The elevated NID1 expression was a predictor of poor outcomes in patients with SACC (P < 0.05). Overexpression of NID1 promoted cancer cell migration and invasion through PI3K/AKT pathway activation and subsequent epithelial-mesenchymal transition (EMT), as indicated by the upregulation of N-cadherin and vimentin. Furthermore, in vivo live monitoring of a mouse model of lung cancer demonstrated the pro-metastatic role of NID1 in SACC cell lung metastasis. Hypoxia-inducible factor 1α (HIF-1α) upregulation via transfection of an HIF-1α-overexpressing plasmid enhanced HIF-1α binding to the NID1 promoter and the subsequent transcriptional activity and expression of NID1. CONCLUSION: HIF-1α-activated NID1 overexpression promotes SACC cell metastasis via PI3K/AKT pathway activation and EMT. Thus, NID1 could be a novel biomarker and therapeutic target for preventing metastasis and treating patients with SACC in future.