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.

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.

Clinical study on the pattern of lower-level lymphatic metastasis in primary tongue squamous cell carcinoma.

OBJECTIVES: To study and analyze the clinical patterns of lower-level lymph node (Ⅳ and Ⅴ) metastasis in primary tongue squamous cell carcinoma, and establish a reference for the decision-making of the lower-level neck dissection in tongue squamous cell carcinoma. METHODS: A total of 203 patients with primary tongue squamous cell carcinoma were recruited. These patients underwent simultaneous/secondary comprehensive neck (level Ⅰ-Ⅴ) dissection in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2015. Their clinicopathological and follow-up data were obtained and analyzed to reveal the prognosis and risk factors of primary tongue squamous cell carcinoma with lower-level lymph node metastasis. RESULTS: Among the 203 patients, the metastasis rates of levels Ⅳ and Ⅴ are 14.78% and 4.93%, respectively. Level Ⅳ metastasis is more prevalent in males than females (P=0.04); non-smokers are more likely to have level Ⅴ metastasis than smokers (P=0.046). Lymph node status in levels Ⅲ and Ⅳ are significantly associated with the risk of metastasis in level Ⅴ (P=0.001). Patients with extracapsular invasion in level Ⅲ have a significantly increased risk of metastasis in levels Ⅳ (P=0.014) and Ⅴ (P=0.026). The 5-year survival rate of patients with lower lymph node (Ⅳ/Ⅴ) metastasis is only 14.70%, which is an independent poor prognostic factor for patients with primary tongue squamous cell carcinoma (P<0.000 1). CONCLUSIONS: Most primary tongue squamous cell carcinoma metastases occur in levels Ⅰ-Ⅲ. However, the rate of lower-level lymph node metastasis is rather low. For the cN0 and cN+ patients with levels Ⅰ-Ⅱ lymph node metastases without extracapsular invasion, the strategy for level Ⅴ management may be observation rather than dissection.