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Abstract Background The humanized anti-disialoganglioside-2 monoclonal antibody naxitamab was approved in the USA in 2020 for the treatment of patients with relapsed/refractory high-risk neuroblastoma, limited to the bone or bone marrow, in combination with granulocyte-macrophage colony-stimulating factor. Treatment with naxitamab under expanded access was initiated by physicians from the Children’s Hospital of Fudan University, Shanghai, China, in August 2021. Objective We reviewed all suspected adverse reactions (ARs) reported to the Y-mAbs Argus Global Pharmacovigilance Safety Database for patients treated with naxitamab under expanded access in China from 1 August 2021 to 31 July 2022. Methods We assessed patient demographics and the safety profile of naxitamab over multiple treatment cycles. Results At the data cutoff, 41 patients with relapsed/refractory high-risk neuroblastoma had received a total of 150 treatment cycles (451 infusions) of naxitamab. The median number of cycles completed was three; 13 patients (32%) were receiving ongoing naxitamab treatment. The median patient age was 3 years (range 1–9 years) and 63% were female. Overall, ARs were reported in 89/150 cycles (59%); serious ARs were reported in 23/150 cycles (15%). The cumulative reporting rate (ARs/cycle) decreased after 3 versus 12 months of expanded access: all ARs (8.7–4.6), serious ARs (0.9–0.3), hypotension (1.4–1.0), flushing (0.7–0.5), cough (0.6–0.3), pain (0.5–0.2), and hypoxia (0.3–0.2). Conclusions During the first 12 months of expanded access treatment in China, 41 patients received naxitamab therapy with a cumulative 451 infusions administered. Over the course of this expanded access program, a reduction in the AR rate, including serious ARs, was observed as more patients were initiated and proceeded to later treatment cycles. While additional research is needed, the observed decrease in the AR rate may be attributed to clinicians’ increased knowledge of AR management and hands-on experience with naxitamab-treated patients.

Abstract Recent years, the tremendous number of distributed photovoltaic are integrated into low‐voltage distribution network, generating a significant amount of operational data. The centralized cloud data centre is unable to process the massive data precisely and promptly. Therefore, the operational status of distributed photovoltaic systems in low‐voltage distribution network becomes difficult to predict. However, edge computing in the distribution network enable local processing of data to improve the real‐time and reliability of the forecasting service. In this regard, this paper proposes a distributed photovoltaic short‐term power forecasting model based on lightweight AI algorithms. Firstly, based on the Pearson correlation coefficient method, an analysis is conducted on the historical operational data in the network to extract important meteorological features that are correlated with the photovoltaic power output. Secondly, a distributed photovoltaic power forecasting model for the distribution network is constructed based on the Xception and attention mechanism. Finally, the model is trained using pruning, which involves removing redundant parts of the model, resulting in a compact and efficient forecasting model. By conducting validation on real‐world datasets, the results demonstrate that the model presented in this article possesses a smaller size and higher forecasting accuracy compared to other state‐of‐the‐art forecasting models.

Hydraulic fracturing has become an important means for shale gas exploration. Understanding the evolution characteristics and influencing factors of pores and micro-fractures during the imbibition process in shale reservoirs is crucial for optimizing post-fracturing production enhancement measures. This study focuses on the black shale at the base of the first section of the first member of the Longmaxi Formation (Long 1-1 sub-member), the main production layer in the Dazu area, western Chongqing area of the Sichuan Basin. Argon ion polishing and field-emission scanning electron microscopy (FE-SEM) experiments were conducted at fixed sites to observe the evolution pattern of microscopic pores and fractures in shale reservoirs at various stages of water imbibition process. The findings revealed: (1) After water imbibition for 7 days, organic pores at the edges of organic matter exhibited varying degrees of reduction, while the internal pore shapes and sizes remained largely unchanged. (2) Intragranular dissolution pores and intergranular pores exhibited noticeable dissolution effects, resulting in mineral particle dissolution and detachment, which increased the leakage area for shale gas. (3) The water imbibition did not induce a significant amount of new micro-fractures. Instead, it extended existing micro-fractures, with the fracture width expanding by 5 to 10 times after imbibition for 14 days. (4) The surface porosity of the shale reservoir reached its peak value at day 7 of water imbibition. After 7 days, due to the continuous swelling of clay minerals, micro-fracture widths experienced varying degrees of reduction. (5) The intensity of pore and fracture expansion in shale reservoirs was primarily affected by mineral composition and pore permeability properties. Higher contents of unstable minerals and brittle minerals with larger particle sizes led to more pronounced pore expansion effects, which were conducive to post-fracturing shale gas seepage.

Abstract Prostate cancer is a malignant tumor of the male urological system with the highest incidence rate in the world, which seriously threatens the life and health of middle-aged and elderly men. The progression of prostate cancer involves the interaction between tumor cells and tumor microenvironment. Understanding the mechanisms of prostate cancer pathogenesis and disease progression is important to guide diagnosis and therapy. The emergence of single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (ST-seq) technologies has brought breakthroughs in the study of prostate cancer. It makes up for the defects of traditional techniques such as fluorescence-activated cell sorting that are difficult to elucidate cell-specific gene expression. This review summarized the heterogeneity and functional changes of prostate cancer and tumor microenvironment revealed by scRNA-seq and ST-seq, aims to provide a reference for the optimal diagnosis and treatment of prostate cancer.

Abstract Background Mechanical ventilation (MV) can cause diaphragmatic injury and ventilator induced diaphragmatic dysfunction (VIDD). Diaphragm ultrasonography (DU) is increasingly used to assess diaphragmatic anatomy, function and pathology of patients receiving MV in the pediatric intensive care unit (PICU). We report the poor contractile ability of diaphragm during ventilation of critically ill patients in our PICU and the association to prolonged length of MV and PICU stay. Methods Patients who received MV within 24 h of admission to the PICU, expected to undergo continuous MV for more than 48 h and succeeded to extubate were included in the study. DU monitoring was performed daily after the initiation of MV until extubation. Diaphragm thickening fraction (DTF) measured by DU was used as an indicator of diaphragmatic contractile activity. Patients with bilateral DTF = 0% during DU assessment were allocated into the severe VIDD group (n = 26) and the rest were into non-severe VIDD group (n = 29). The association of severe VIDD with individual length of MV, hospitalization and PICU stay were analyzed. Results With daily DU assessment, severe VIDD occurred on 2.9 ± 1.2 days after the initiation of MV, and lasted for 1.9 ± 1.7 days. Values of DTF of all patients recovered to > 10% before extubation. The severe VIDD group had a significantly longer duration (days) of MV [12.0 (8.0-19.3) vs. 5.0 (3.5–7.5), p

Abstract Background Metagenomic next-generation sequencing (mNGS) excels in diagnosis of infection pathogens. We aimed to evaluate the performance of mNGS for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-HIV infected children. Methods Totally 36 PJP children and 61 non-PJP children admitted to the pediatric intensive care unit from March 2018 to December 2021 were retrospectively enrolled. Clinical features of PJP children were summarized. 1,3-β-D glucan (BDG) test and bronchoalveolar lavage fluid (BALF) mNGS were used for evaluation of PJP diagnostic performance. Antimicrobial management modifications for PJP children after the mNGS results were also reviewed. Results Pneumocystis jirovecii was detected in all PJP children by mNGS (36/36), and the sensitivity of mNGS was 100% (95% confidence interval [CI]: 90.26–100%). The sensitivity of BDG was 57.58% (95% CI: 39.22–74.52%). Of the 26 (72.2%) PJP patients with mixed infection, twenty-four (66.7%) were detected by BALF-mNGS. Thirteen patients (36.1%) had their antimicrobial management adjusted according to the mNGS results. Thirty-six PJP children included 17 (47.2%) primary immunodeficiency and 19 (52.8%) secondary immunodeficiency, of whom 19 (52.8%) survived and 17 (47.2%) died. Compared to survival subgroup, non-survival subgroup had a higher rate of primary immunodeficiency (64.7% vs. 31.6%, P = 0.047), younger age (7 months vs. 39 months, P = 0.011), lower body weight (8.0 kg vs. 12.0 kg, P = 0.022), and lower T lymphocyte counts. Conclusions The mortality rate of PJP in immunosuppressed children without HIV infection is high and early diagnosis is challenging. BALF-mNGS could help identify PJP and guide clinical management.

Abstract To mitigate the decrease in mechanical performance of Sn58Bi/Cu solder joints resulting from electromigration-induced damage. The CeO2 nanoparticles were incorporated into Sn58Bi solder by a melt-casting method, and their effects on the microstructure and properties of Sn58Bi/Cu solder joints under electromigration were investigated. The study results demonstrate that the addition of 0.125 ~ 0.5 wt% CeO2 nanoparticles refines the eutectic microstructure of Sn58Bi solder alloy. At an addition amount of 0.5 wt%, the composite solder alloy exhibits the maximum tensile strength of 68.9 MPa, which is 37% higher than that of the base solder. CeO2 nanoparticle-reinforced Sn58Bi solder can achieve excellent solderbility with Cu substrates and the joints can significantly inhibit the growth of the anodic Bi-rich layer, which is responsible for electromigration. With the extension of current stressing time, Bi-rich and Sn-rich layer are respectively formed on the anode and cathode in the joints. The intermetallic compound (IMC) layer grows asymmetrically, transitioning from a fan-shaped morphology to a flattened structure at the anode and to a thickened mountain-like morphology at the cathode. Adding the CeO2 nanoparticles helps to mitigate the decrease in mechanical performance caused by electromigration damage during current application to some extent. Over the current stressing period of 288 ~ 480 h, the fracture position shifts from the anodic IMC/Bi-rich interface to the cathodic Sn-rich/IMC interface. The fracture mechanism transitions from a brittle fracture characterized by plate-like cleavage to a ductile–brittle mixed fracture with fine dimples and cleavage.

BackgroundPremature infants are at high risk for neonatal respiratory distress syndrome (RDS) and secondary infections. This study aims to investigate the association between immunoinflammatory markers—the systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and neutrophil-to-albumin ratio (NAR)—and the risk of developing RDS in premature infants.MethodsA total of 2164 premature infants were enrolled in this retrospective study. The clinical records of these neonates (respiratory tract infections, adverse pregnancy history, placental abnormalities, birth weight, Apgar scores, and immunoinflammatory indices) were collected. Comparisons were made between infants with and without RDS. Logistic regression analysis was used to evaluate the relationship between SII, SIRI, NAR and RDS.ResultsAmong the cohort, 962 infants developed RDS, while 1202 did not. The RDS group showed higher proportions of mothers with adverse pregnancy history, placental abnormalities, birth weight

Idiopathic pulmonary fibrosis (IPF) is a progressive and life-threatening respiratory disease characterized by worsening lung function due to excessive scarring. The objective of this study was to investigate the role of the long non-coding RNA ANRIL (antisense non-coding RNA in the INK4 locus) in the development of IPF. Our research revealed a significant increase in ANRIL expression in pulmonary fibrosis, consistent with prior studies indicating elevated ANRIL levels in fibrotic tissues. In vitro experiments demonstrated that elevated ANRIL expression promoted fibroblast activation, as evidenced by the upregulation of fibrosis-related markers. Mechanistically, we found that ANRIL interacts with let-7d-5p, a microRNA involved in gene regulation, acting as a sponge for let-7d-5p. Functional experiments confirmed a potential influence of let-7d-5p on fibroblast activation through direct interaction with ANRIL. Furthermore, our investigation identified TGFBR1 as a potential mediator of ANRIL’s fibrogenic effects. Silence of TGFBR1 mitigated the fibrotic phenotype induced by ANRIL overexpression. Collectively, these results suggest that ANRIL promotes fibroblast activation and fibrosis development, possibly through the let-7d-5p/TGFBR1 axis, indicating that ANRIL could be a potential therapeutic target for pulmonary fibrosis.

Preschool children have different thermal characteristic from adults, while research on their thermal comfort within kindergartens remains scarce. This study conducted a survey among 205 children aged 4–6 years and 25 teachers in China, yielding a total of 6441 records. Although the survey area with most indoor temperatures falling below the comfort zone, a significant portion of the survey sessions in class (52 %) reported hot dissatisfaction. Children reported more hot sensations than adults, with almost no cold sensations reported. The mean Thermal Sensation (MTS) of children remained above the neutral point across the surveyed temperature range. The analysis suggests that a primary cause of children's discomfort is over-clothing. The average level of the investigated children’s clothing insulation was 1.78 clo, which was 0.19 clo more than that of the adults in the same environment, equivalent to adding a vest and a T-shirt. Moreover, the children have limited initiative to adjust their clothing. The excessive clothing likely stems from parental overconcern for cold environment, which leading to preventative dressing. Among the surveyed children, those wearing less clothing exhibited better thermal comfort status, underscoring the unnecessity of excessive clothing.

Abstract Background This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development. Methods By using immunofluorescence and Western blot, we were able to locate EP receptors in the ureter. In vitro experiments assessed the impact of PGE2, receptor antagonists, and agonists on ureteral relaxation rate. We constructed a model of ureteral calculi with flowable resin and collected ureteral tissue from postoperative side of the ureter after obstruction surgery. Western blot analysis was used to determine the protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Additionally, PGE2 was added to smooth muscle cells to observe downstream cAMP and PKA changes. Results The expression of EP2 and EP4 proteins in ureteral smooth muscle was verified by Western blot analysis. According to immunofluorescence, EP2 was primarily found on the cell membrane, while EP4 was found in the nucleus. In vitro, PGE2 induced concentration-dependent ureteral relaxation. Maximum diastolic rate was 70.94 ± 4.57% at a concentration of 30µM. EP2 antagonists hindered this effect, while EP4 antagonists did not. Obstructed ureters exhibited elevated mPGES-1 and EP2 protein expression (P

Abstract Background Antimicrobial resistance (AMR) is a major threat to children’s health, particularly in respiratory infections. Accurate identification of pathogens and AMR is crucial for targeted antibiotic treatment. Metagenomic next-generation sequencing (mNGS) shows promise in directly detecting microorganisms and resistance genes in clinical samples. However, the accuracy of AMR prediction through mNGS testing needs further investigation for practical clinical decision-making. Methods We aimed to evaluate the performance of mNGS in predicting AMR for severe pneumonia in pediatric patients. We conducted a retrospective analysis at a tertiary hospital from May 2022 to May 2023. Simultaneous mNGS and culture were performed on bronchoalveolar lavage fluid samples obtained from pediatric patients with severe pneumonia. By comparing the results of mNGS detection of microorganisms and antibiotic resistance genes with those of culture, sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Results mNGS detected bacterial in 71.7% cases (86/120), significantly higher than culture (58/120, 48.3%). Compared to culture, mNGS demonstrated a sensitivity of 96.6% and a specificity of 51.6% in detecting pathogenic microorganisms. Phenotypic susceptibility testing (PST) of 19 antibiotics revealed significant variations in antibiotics resistance rates among different bacteria. Sensitivity prediction of mNGS for carbapenem resistance was higher than penicillins and cephalosporin (67.74% vs. 28.57%, 46.15%), while specificity showed no significant difference (85.71%, 75.00%, 75.00%). mNGS also showed a high sensitivity of 94.74% in predicting carbapenem resistance in Acinetobacter baumannii. Conclusions mNGS exhibits variable predictive performance among different pathogens and antibiotics, indicating its potential as a supplementary tool to conventional PST. However, mNGS currently cannot replace conventional PST.

Recent years, the tremendous number of distributed energy resources, electric vehicles are integrated into the Low-Voltage Distribution Network (LVDN), large amount of data are generated by edge devices in LVDN. The cloud data centers are unable to process these data timely and accurately, making it impossible to meet the demand for fine-grained control of LVDN. To solve the above problems, this paper proposes a flexible orchestration of lightweight artificial intelligence (AI) for edge computing in LVDN. Firstly, the application requirements of LVDN are analysed through feature extraction of its historical data, and a lightweight AI library is constructed to meet its requirements. Secondly, based on the multi-factor priority, a flexible orchestration model is established, to allow the lightweight AI embedded in the edge devices of the LVDN. Finally, the particle swarm optimization algorithm is used to provide the best solution. The simulation results show that the method proposed in this paper can support the deployment of AI at the edge. It can significantly improve the utilization of edge computing resources, and reduce the pressure of cloud computing and the time of application processes.

IntroductionOmega-3 polyunsaturated fatty acids (PUFAs) have been widely studied and used as nutritional supplements because of their anti-inflammatory effects. Previous studies have shown an association between polyunsaturated fatty acids such as omega-3 and omega-6 PUFAs with the development of malignant tumors. However, the relationships of omega-3 and omega-6 PUFAs with esophageal diseases have not been characterized.MethodsMendelian randomization (MR) is a statistical method for identifying instrumental variables (IVs) from genome-wide association study (GWAS) data, and is associated with little confounding by environmental or other disease-related factors. We used genome-wide association study (GWAS) data from previously published studies on circulating concentrations of omega-3, omega-6, docosahexaenoic acid (DHA) and linoleic acid (LA), as well as esophageal cancer and other esophageal diseases, which were downloaded from the IEU OpenGwas database (https://gwas.mrcieu.ac.uk/) and the GWAS Catalog database (https://www.ebi.ac.uk/). The inverse variance-weighted approach was used as the principal analysis, and the MR–Egger and weighted median methods were used alongside. A series of sensitivity analyses were used to ensure the robustness of the causality estimates.ResultsWe found that the circulating omega-3 PUFAs concentration was positively associated with esophageal cancer (p = 8 × 10−4), and circulating DHA concentration (the main component of omega-3 in food), was also positively associated with esophageal cancer (p = 2 × 10−2), but no significant association was found between circulating omega-6 PUFAs and esophageal cancer (p = 0.17), and circulating LA concentration (the main component of omega-6 in food), was also no significant associated with esophageal cancer (p = 0.32). We found no significant relationships of circulating omega-3 and omega-6 PUFAs concentration with four other esophageal diseases.ConclusionThis study indicates that higher levels of circulating omega-3 PUFAs and DHA concentrations may be a risk factor for the development of esophageal cancer. Conversely, an increased omega-6/omega-3 ratio may serve as a protective factor against esophageal cancer. These findings have significant implications for the clinical application of omega-3 PUFAs and the prevention and treatment of esophageal cancer.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017–2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Abstract Background Anaesthetic methods and drugs with rapid onset, rapid recovery and better postoperative analgesia are more suitable for rapid recovery in obstetric anaesthesia. We formulated the following hypothesis: a combination of mepivacaine and ropivacaine could provide a longer analgesic effect and have more advantages in terms of rapid-recovery indicators. Methods A total of 180 pregnant women scheduled to undergo elective caesarean sections were randomly assigned to three surgical groups, which received 2% mepivacaine (Group M), 2% mepivacaine + 0.75% ropivacaine (Group MR) (Volume 1:1) or 0.75% ropivacaine (Group R) through an epidural catheter. The situation of postoperative analgesia and other indicators of rapid recovery were recorded. Results One hundred and fifty patients were included in the final analysis. Their demographic data were similar. The visual analogue scale (VAS) scores of Group MR and Group R were lower than Group M at 1 and 2 h after surgery both at rest and with movement (P

Synthetic aperture radar (SAR), which can work normally under various meteorological conditions, has been widely researched and applied in marine vessel target monitoring and identification. Among the many research topics, due to the inconsistency of ship scale in SAR images, susceptibility to sea and land noise and clutter interference, resulting in a low detection rate of near-shore ship targets and inaccurate edge delineation of densely lined ships, a target detection algorithm based on deep convolutional neural network is proposed. The algorithm employs the channel-space grouping attention mechanism during feature extraction to enhance features by utilizing global positional and edge information associated with instances. The feature mobility fusion module is employed to merge features of various scales, bolster the interconnection among these features, and enhance multiscale ship target detection capabilities. The decoupled head is employed for ship target localization, while the angle-weighted intersection over union is used to mitigate regression errors. The experimental results show that the precision (P) achieved on HRSID and SSDD datasets reaches 94.81% and 99.01%, respectively, exceeding the control algorithm by more than 1.35% and 0.94%; the average precision (mAP) reaches 92.06% and 99.50%, respectively, exceeding the control algorithm by more than 2.32% and 2.51%; this indicates that the proposed algorithm has a good performance on SAR image ship detection and a strong generalization ability.

In the classification of motor imagery Electroencephalogram (MI-EEG) signals through deep learning models, challenges such as the insufficiency of feature extraction due to the limited receptive field of single-scale convolutions, and overfitting due to small training sets, can hinder the perception of global dependencies in EEG signals. In this paper, we introduce a network called EEG TBTSCTnet, which represents Three-Branch Temporal-Spatial Convolutional Transformer. This approach expands the size of the training set through Data Augmentation, and then combines local and global features for classification. Specifically, Data Augmentation aims to mitigate the overfitting issue, whereas the Three-Branch Temporal-Spatial Convolution module captures a broader range of multi-scale, low-level local information in EEG signals more effectively than conventional CNNs. The Transformer Encoder module is directly connected to extract global correlations within local temporal-spatial features, utilizing the multi-head attention mechanism to effectively enhance the network’s ability to represent relevant EEG signal features. Subsequently, a classifier module based on fully connected layers is used to predict the categories of EEG signals. Finally, extensive experiments were conducted on two public MI-EEG datasets to evaluate the proposed method. The study also allowed for an optimal selection of channels to balance accuracy and cost through weight visualization.

A Sn58Bi composite solder reinforced by Ni nanoparticles was prepared using a mechanical mixing technique, and the thermomigration microstructure and properties of the solder joints were studied. The findings indicate that incorporating an appropriate quantity of Ni nanoparticles can enhance the microstructure of the composite solder and mitigate the coarsening of Bi-phase segregation. At 0.75 weight percent Ni nanoparticle content, the composite solder’s tensile strength is 59.7 MPa and its elongation is 54.6%, both of which are noticeably greater than those of the base solder. When the thermal loading time is 576 h, the shear strength of the composite solder joint is 25.5 MPa, which is 30.1% higher than that of the base solder joint. This study reveals that the shear fracture path shifts from the boundary region between the solder seam and the IMC layer to the IMC layer itself. Concurrently, the fracture mode evolves from a mix of brittle–ductile fracture, characterized by quasi-cleavage, to a predominantly brittle fracture, marked by numerous “rock candy-like” cross-sectional features and secondary cracking. Adding Ni nanoparticles to the Sn58Bi composite solder/Cu solder junction can significantly extend its service life.

BackgroundJuvenile dermatomyositis (JDM) is a systemic autoimmune disease primarily involving the muscles and skin; it can also affect the central nervous system (CNS). The relevant literature provides limited information regarding the characteristics of JDM with CNS involvement.MethodWe reviewed patients with JDM who were hospitalized at our center between January 2016 and August 2023, with a focus on those with CNS involvement. The aim was to provide detailed case reports on these patients, and to summarize the relevant literature about the characteristics of similar cases.ResultsAmong 193 hospitalized patients with JDM, two (1.03%) had CNS involvement. Two patients, a 5.5-year-old girl and an 11-year-old boy, were admitted with severe proximal muscle weakness and seizures, and presented with active cutaneous vasculitis. Both were ultimately diagnosed with JDM, with CNS involvement. Both patients had confirmed presence of anti-NXP2 antibody through myositis-specific antibody analysis. Additionally, they all exhibited hyperferritinemia and thrombocytopenia. Salvage therapies like intravenous methylprednisolone (IVMP) pulse therapy and/or plasma exchange were administered successfully. At final follow-up, both patients had achieved complete clinical response and full neurological recovery. Our literature review identified nine similar case studies. CNS involvement usually occurred within the first 10 months of the disease course, and most of these patients had fatal outcomes, with a mortality rate of 66.6% (6/9). Including the two patients described herein, the median age for disease onset is 10.5 years (range 4–17 years), and the male: female ratio is 6:5. Seizures are the most common neurological symptom, accompanied by active cutaneous vasculitis. The brain biopsies showed two distinct pathological presentations: one was central nervous system vasculitis, and the other was cerebral macrophage activation syndrome.ConclusionsCNS involvement is a rare but life-threatening JDM complication. Herein, our cases and the literature indicate that it typically occurs within the first 10 months of the disease course and manifests as seizures, often accompanied by active cutaneous vasculitis, with fatal outcomes. Timely implementation of salvage therapies, like IVMP pulse therapy and plasma exchange, may significantly impact patient outcomes.

ObjectiveTo evaluate the incidence, outcome, and prognostic factors of prolonged mechanical ventilation (PMV) in children in Mainland China.MethodsA prospective study was conducted in 11 pediatric intensive care units (PICUs) from May 1, 2021, to April 30, 2022. All pediatric patients on mechanical ventilation meeting the criteria for PMV were included in the study.ResultsOut of 5,292 patients receiving mechanical ventilation, 278 children met the criteria for PMV (5.3%). After excluding case with incomplete data or lost to follow-up, the study included 250 patients. Among them, 115 were successfully weaned from mechanical ventilation, 90 died, and 45 were still on mechanical ventilation. The 6-month survival rate was 64%. The primary associated conditions of PMV were lower airway diseases (36%), central nervous system diseases (32%), and neuromuscular diseases (14%). The stepwise multiple logistic regression analysis indicated that the utilization of vasoactive agents and an elevated pediatric logistic organ dysfunction-2 (PELOD-2) score on the day of PMV diagnosis were significantly associated with an increased of PMV death. Specifically, the odds ratio (OR) for vasoactive agent use was 2.86; (95% CI: 0.15–0.84; P = 0.018), and for the PELOD-2 score, it was 1.37; 95% CI: 1.17–1.61; P

X-linked lymphoproliferative disease (XLP) is a rare genetic disorder characterized by immune dysregulation. The three most common clinical phenotypes are EBV-associated infectious mononucleosis (FIM), abnormal gammaglobulinemia, and lymphoma. We present a rare case of XLP1 with neurovasculitis, which is non-EBV-related and involves multiple systems, a condition rarely seen in children. The patient initially presented with an unsteady gait, which progressively evolved into language and consciousness disorders. Additionally, CT scans revealed multiple nodules in the lungs. Subsequent genetic testing and brain tissue biopsy confirmed the diagnosis: XLP1-related cerebral vasculitis and cerebral hemorrhage. Tragically, during the diagnostic process, the child experienced a sudden cerebral hemorrhage and herniation, ultimately resulting in fatality. This case offers a comprehensive insight into XLP1-related cerebral vasculitis and cerebral hemorrhage, underscoring the significance of early diagnosis and prompt treatment, while also imparting valuable clinical experience and lessons to the medical community.

Background: Serum prostate-specific antigen (PSA) is a primary metric for diagnosis and prognosis of prostate cancer (PCa). Exposure to heavy metals, such as lead, cadmium, mercury, and zinc can impact PSA levels in PCa patients. However, it is unclear whether this effect also occurs in men without PCa, which may lead to the overdiagnosis of PCa. Method: Data on a total of 5089 American men who had never been diagnosed with PCa were obtained from the National Health and Nutrition Examination Survey performed from 2003–2010. The relationship between serum PSA levels (dependent variable) and concentrations of lead (μmol/L), cadmium (nmol/L), and mercury (μmol/L) were investigated with dietary zinc intake being used as a potential modifier or covariate in a weighted linear regression model and a generalized additive model. A series of bootstrapping analyses were performed to evaluate sensitivity and specificity using these models. Results: Regression analyses suggested that, in general, lead, cadmium, or mercury did not show an association with PSA levels, which was consistent with the results of the bootstrapping analyses. However, in a subgroup of participants with a high level of dietary zinc intake (≥14.12 mg/day), a significant positive association between cadmium and serum PSA was identified (1.06, 95% CI, P = 0.0268, P for interaction=0.0249). Conclusions: With high-level zinc intake, serum PSA levels may rise in PCa-free men as the exposure to cadmium increases, leading to a potential risk of an overdiagnosis of PCa and unnecessary treatment. Therefore, environmental variables should be factored in the current diagnostic model for PCa that is solely based on PSA measurements. Different criteria for PSA screening are necessary based on geographical variables. Further investigations are needed to uncover the biological and biochemical relationship between zinc, cadmium, and serum PSA levels to more precisely diagnose PCa.

Objective The association between haemoglobin-to-red blood cell distribution width ratio (HRR) and all-cause mortality remains poorly understood. This study aimed to examine the influence of HRR at the time of admission mortality over 1 year and 30 days in patients with sepsis.Design This was a secondary analysis.Setting This study was conducted in intensive care units (ICUs).Participants Adult patients with sepsis were identified and included from an intensive care database based on eligibility criteria.Primary outcome and measure The primary outcome was the rate of death within 1 year. The secondary outcome was the death rate within 30 days.Results A total of 4233 patients with sepsis who met the inclusion criteria were analysed, excluding those ineligible. These participants were divided into quartiles based on their HRR at admission. The overall mortality rates at 1 year and 30 days were 42.9% and 25.5%, respectively. A significant inverse association was observed between HRR quartiles and all-cause mortality (p

BackgroundCardiovascular disease (CVD) and cancer are the first and second causes of death in over 130 countries across the world. They are also among the top three causes in almost 180 countries worldwide. Cardiovascular complications are often noticed in cancer patients, with nearly 20% exhibiting cardiovascular comorbidities. Physical exercise may be helpful for cancer survivors and people living with cancer (PLWC), as it prevents relapses, CVD, and cardiotoxicity. Therefore, it is beneficial to recommend exercise as part of cardio-oncology preventive care.ObjectiveWith the progress of deep learning algorithms and the improvement of big data processing techniques, artificial intelligence (AI) has gradually become popular in the fields of medicine and healthcare. In the context of the shortage of medical resources in China, it is of great significance to adopt AI and machine learning methods for prescription recommendations. This study aims to develop an interpretable machine learning-based intelligent system of exercise prescription for cardio-oncology preventive care, and this paper presents the study protocol.MethodsThis will be a retrospective machine learning modeling cohort study with interventional methods (i.e., exercise prescription). We will recruit PLWC participants at baseline (from 1 January 2025 to 31 December 2026) and follow up over several years (from 1 January 2027 to 31 December 2028). Specifically, participants will be eligible if they are (1) PLWC in Stage I or cancer survivors from Stage I; (2) aged between 18 and 55 years; (3) interested in physical exercise for rehabilitation; (4) willing to wear smart sensors/watches; (5) assessed by doctors as suitable for exercise interventions. At baseline, clinical exercise physiologist certificated by the joint training program (from 1 January 2023 to 31 December 2024) of American College of Sports Medicine and Chinese Association of Sports Medicine will recommend exercise prescription to each participant. During the follow-up, effective exercise prescription will be determined by assessing the CVD status of the participants.Expected outcomesThis study aims to develop not only an interpretable machine learning model to recommend exercise prescription but also an intelligent system of exercise prescription for precision cardio-oncology preventive care.EthicsThis study is approved by Human Experimental Ethics Inspection of Guangzhou Sport University.Clinical trial registrationhttp://www.chictr.org.cn, identifier ChiCTR2300077887.

This study firstly used sugarcane leaf polyphenols (SGLp) to modify zein to form covalent nanoparticles (SGLpZ) and used SGLpZ as an emulsifier to stabilize pickering emulsions (SZP) via ultrasonic method. The results showed that the addition of SGLp could alter the physicochemical properties of zein, including improving increasing the hydrophilicity of zein and the antioxidant properties of zein (three basic antioxidant activities test in vitro). SGLpZ could be able to form a dense film on the surface of the pickering emulsions which inhibited lipid oxidation as the concentration of SGLp increased at 4 ℃ for 20 days, thus stabilizing pickering emulsions (SZP). Further assessment of storage stability of pickering emulsions stabilized by SGLp was evaluated via measuring the free fatty acids (FFA) release in vitro gastrointestinal digestion. The results showed that the FFA release of SZP decreased from 20.61 ± 0.10% to 16.14 ± 0.69%. In addition, SGLp gave SZP a yellow color, which inspired that SZP could be used in the food industry to make yellow-colored functional foods. Finally, the safety of SZP initially assessed by in-vitro hemocompatibility and cytotoxicity (MTT) assays. In conclusion, our fingdings were beneficial for the further design and development of SGLp in food fields and enabled the development a new type in functional protein-plant polyphenols food pickering emulsions.

BackgroundDegradation of the endothelial glycocalyx is critical for sepsis-associated lung injury and pulmonary vascular permeability. We investigated whether sulodexide, a precursor for the synthesis of glycosaminoglycans, plays a biological role in glycocalyx remodeling and improves endothelial barrier dysfunction in sepsis.MethodsThe number of children with septic shock that were admitted to the PICU at Children’s Hospital of Fudan University who enrolled in the study was 28. On days one and three after enrollment, venous blood samples were collected, and heparan sulfate, and syndecan-1 (SDC1) were assayed in the plasma. We established a cell model of glycocalyx shedding by heparinase III and induced sepsis in a mouse model via lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP). Sulodexide was administrated to prevent endothelial glycocalyx damage. Endothelial barrier function and expression of endothelial-related proteins were determined using permeability, western blot and immunofluorescent staining. The survival rate, histopathology evaluation of lungs and wet-to-dry lung weight ratio were also evaluated.ResultsWe found that circulating SDC1 levels were persistently upregulated in the non-alive group on days 1 and 3 and were positively correlated with IL-6 levels. Receiver operating characteristic curve analysis showed that SDC1 could distinguish patients with mortality. We showed that SDC1-shedding caused endothelial permeability in the presence of heparinase III and sepsis conditions. Mechanistically, sulodexide (30 LSU/mL) administration markedly inhibited SDC1 shedding and prevented endothelial permeability with zonula occludens-1 (ZO-1) upregulation via NF-κB/ZO-1 pathway. In mice with LPS and CLP-induced sepsis, sulodexide (40 mg/kg) administration decreased the plasma levels of SDC1 and increased survival rate. Additionally, sulodexide alleviated lung injury and restored endothelial glycocalyx damage. ConlusionsIn conclusion, our data suggest that SDC1 predicts prognosis in children with septic shock and sulodexide may have therapeutic potential for the treatment of sepsis-associated endothelial dysfunction.

BackgroundMetagenomic next-generation sequencing (mNGS) is a powerful method for pathogen detection in various infections. In this study, we assessed the value of mNGS in the pathogen diagnosis and microbiome analysis of pneumonia in pediatric intensive care units (PICU) using bronchoalveolar lavage fluid (BALF) samples.MethodsA total of 104 pediatric patients with pneumonia who were admitted into PICU between June 2018 and February 2020 were retrospectively enrolled. Among them, 101 subjects who had intact clinical information were subject to parallel comparison of mNGS and conventional microbiological tests (CMTs) for pathogen detection. The performance was also evaluated and compared between BALF-mNGS and BALF-culture methods. Moreover, the diversity and structure of all 104 patients’ lung BALF microbiomes were explored using the mNGS data.ResultsCombining the findings of mNGS and CMTs, 94.06% (95/101) pneumonia cases showed evidence of causative pathogenic infections, including 79.21% (80/101) mixed and 14.85% (15/101) single infections. Regarding the pathogenesis of pneumonia in the PICU, the fungal detection rates were significantly higher in patients with immunodeficiency (55.56% vs. 25.30%, P =0.025) and comorbidities (40.30% vs. 11.76%, P=0.007). There were no significant differences in the α-diversity either between patients with CAP and HAP or between patients with and without immunodeficiency. Regarding the diagnostic performance, the detection rate of DNA-based BALF-mNGS was slightly higher than that of the BALF-culture although statistically insignificant (81.82% vs.77.92%, P=0.677) and was comparable to CMTs (81.82% vs. 89.61%, P=0.211). The overall sensitivity of DNA-based mNGS was 85.14% (95% confidence interval [CI]: 74.96%-92.34%). The detection rate of RNA-based BALF-mNGS was the same with CMTs (80.00% vs 80.00%, P>0.999) and higher than BALF-culture (80.00% vs 52.00%, P=0.045), with a sensitivity of 90.91% (95%CI: 70.84%-98.88%).ConclusionsmNGS is valuable in the etiological diagnosis of pneumonia, especially in fungal infections, and can reveal pulmonary microecological characteristics. For pneumonia patients in PICU, the mNGS should be implemented early and complementary to CMTs.

Major Histocompatibility Complex Class II (MHC II) deficiency is a rare primary immunodeficiency disorder (PID) with autosomal recessive inheritance pattern. The outcome is almost fatal owing to delayed diagnosis and lacking of effective therapy. Therefore, prompt diagnosis, timely and effective treatment are critical. Here, we report a 117-day-old boy with diarrhea, cough, cyanosis and tachypnea who was failed to be cured by empiric antimicrobial therapy initially and progressed to severe pneumonia and respiratory failure. The patient was admitted to the pediatric intensive care unit (PICU) immediately and underwent a series of tests. Blood examination revealed elevated levels of inflammatory markers and cytomegalovirus DNA. Imaging findings showed signs of severe infection of lungs. Finally, the diagnosis was obtained mainly through next-generation sequencing (NGS). We found out what pathogenic microorganism he was infected via repeated conventional detection methods and metagenomic next-generation sequencing (mNGS) of sputum and bronchoalveolar lavage fluid (BALF). And his whole exome sequencing (WES) examination suggested that CIITA gene was heterozygous mutation, a kind of MHC II deficiency diseases. After aggressive respiratory support and repeated adjustment of antimicrobial regimens, the patient was weaned from ventilator on the 56th day of admission and transferred to the immunology ward on the 60th day. The patient was successful discharged after hospitalizing for 91 days, taking antimicrobials orally to prevent infections post-discharge and waiting for stem cell transplantation. This case highlights the potential importance of NGS in providing better diagnostic testing for unexplained infection and illness. Furthermore, pathogens would be identified more accurately if conventional detection techniques were combined with mNGS.

The vision of reaching a carbon peak and achieving carbon neutrality is guiding the low-carbon transition of China’s socioeconomic system. Currently, a research gap remains in the existing literature in terms of studies that systematically identify opportunities to achieve carbon neutrality. To address this gap, this study comprehensively collates and investigates 1105 published research studies regarding carbon peaking and carbon neutrality. In doing so, the principles of development in this area are quantitively analyzed from a space–time perspective. At the same time, this study traces shifts and alterations in research hotspots. This systematic review summarizes the priorities and standpoints of key industries on carbon peaking and carbon neutrality. Furthermore, with an emphasis on five key management science topics, the scientific concerns and strategic demands for these two carbon emission-reduction goals are clarified. The paper ends with theoretical insights on and practical countermeasures for actions, priority tasks, and policy measures that will enable China to achieve a carbon-neutral future. This study provides a complete picture of the research status on carbon peaking and carbon neutrality, as well as the research directions worth investigating in this field, which are crucial to the formulation of carbon peak and carbon neutrality policies.

Abstract Background The purpose of this study was to characterize the pathophysiological changes of hydronephrosis caused by ureteral calculi obstruction in a new rabbit ureteral calculi model by implanting flowable resin. Methods Forty New Zealand rabbits were randomly divided into two groups: the calculi group and the sham control group. In the calculi group (n = 20), rabbits were operated at left lower abdomen and the left ureter was exposed. Then flowable resin (flowable restorative dental materials) was injected into the left ureter using a 0.45 mm diameter intravenous infusion needle. Then light-cured for 40 s by means of a dental curing light to form calculi. In the sham control group, normal saline was injected into the ureter. Rabbits underwent X-ray and routine blood and urine tests preoperatively, as well as X-ray, CT, dissection, HE staining and routine blood and urine tests on 1, 3, 5 and 7 days postoperatively. Stone formation was assessed by X-ray and unenhanced CT scan after surgery. The pathophysiological changes were evaluated through dissection, HE staining and routine blood and urine tests. Results Ureteral calculi models were successfully constructed in 17 rabbits. In calculi group, high-density shadows were observed in the left lower abdomen on postoperative day 1st, 3rd, 5th and 7th by X-ray and CT scan. Dissection found obstruction formation of the left ureters, dilatation of the renal pelvis and upper ureter during 7 days after surgery. The renal long-diameters of the left ureters increased only on the 1st postoperative day. HE staining found ureteral and kidney damage after surgery. In calculi group and sham group,the serum creatinine, urea nitrogen, white blood cells and urine red blood cells were raised at day 1 after surgery. However, the indicators returned to normal at day 3, 5, and 7. Conclusions This is a stable, less complicated operation and cost-effective ureteral calculi model by implanting flowable resin. And this novel model may allow us to further understand the pathophysiology changes caused by ureteral calculi obstruction.

Objective: This study focused on designing and subsequently screening novel phenanthroimidazole derivatives with activity as potential inhibitors of hepatocellular carcinoma. Methods: We synthesized a series of phenanthroimidazole derivatives and their molecular structures were characterized by ESI-MS and 1H NMR. The anti-tumor activity was evaluated using the MTT assay. The potential mechanism of anti-tumor activity based on DNA-damage-mediated apoptosis was analyzed by flow cytometry, immunofluorescence, and comet assay. Additionally, the anti-angiogenic activity was assessed by transgenic zebrafish. Furthermore, in vivo biodistribution of the compound was studied using a nude mice xenograft model. Results: The screening results for anti-tumor activity revealed that the compounds, especially 2, exhibited promising restrain activity against the growth of HepG2 cells with an IC50 value of 0.68 µM. Further studies showed that 2 can accumulate in the mitochondria of HepG2 cells, decreased the mitochondrial membrane potential, induce DNA damage and apoptosis of cells. Moreover, it was also discovered that 2 can inhibit the formation of neovascularization, which was confirmed by the decrease in ISV angiogenesis of zebrafish after being incubated with 2, as well as the decrease in the number and length of tubes formed in HUVECs cells. Besides, in vivo distribution and metabolism studies show that 2 is rapidly distributed in the whole body and accumulated in the tumor tissue of BALB/c mice. Conclusion: Taken together, this type of phenanthroimidazole derivatives, especially 2, will be developed to be potent inhibitors against the growth of HepG2 cells through anti-angiogenesis and apoptosis based on mitochondrial-dependent pathways in the near future.

Background Psoriasis is a chronic immune-mediated skin disease. Recent studies showed its pathogenesis involved circular RNA (circRNA). However, the role of circ_0060531 in psoriasis development and the behind mechanism remain to be explored. Methods Psoriasis cell model was constructed by treating keratinocytes (HaCaT cells) using interleukin 22 (IL-22). Expression of circ_0060531, microRNA-330-5p (miR-330-5p) and GRB2 associated binder 1 (GAB1) was determined by quantitative real-time polymerase chain reaction. The functional effects of circ_0060531 on IL-22-caused cell injury were investigated by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide, 5-Ethynyl-29-deoxyuridine, wound-healing and enzyme-linked immunosorbent assays. Protein expression was analysed by Western blot. The interactions among circ_0060531, miR-330-5p and GAB1 were identified by dual-luciferase reporter or RNA immunoprecipitation assay. Results Circ_0060531 and GAB1 expression were significantly increased, while miR-330-5p was decreased in psoriatic skin biopsies and IL-22-stimulated HaCaT cells in comparison with controls. In function, circ_0060531 knockdown assuaged IL-22-induced cell proliferation, cell migration and inflammation. Besides, circ_0060531 acted as a miR-330-5p sponge, and regulated the processes of IL-22-treated HaCaT cells by binding to the miRNA. Under the treatment of IL-22, miR-330-5p mediated HaCaT cell damage by targeting GAB1. Importantly, circ_0060531 modulated GAB1 production by interacting with miR-330-5p. Conclusion Circ_0060531 knockdown assuaged IL-22-induced keratinocyte dysfunction through miR-330-5p/GAB1 pathway, proving a novel target for the therapy of psoriasis.

BackgroundThe role of specific unsaturated fatty acids (FAs) in the development of overweight/obesity remains unclear in the general population. Here, we aimed to explore the associations of different types of unsaturated FAs with overweight/obesity risk among the Chinese population.MethodsEight thousand seven hundred forty-two subjects free of overweight/obesity at entry in the China Health and Nutrition Survey (CHNS) were followed up until 2015. Dietary unsaturated FAs were assessed by 3-day 24-h recalls with a weighing method in each wave. Cox regression models were used to obtain the hazard ratios (HRs) and 95% confidence intervals (CIs) for overweight/obesity risk associated with unsaturated FAs.ResultsDuring a median follow-up of 7 years, 2,753 subjects (1,350 males and 1,403 females) developed overweight/obesity. Consuming more monounsaturated FAs (MUFAs) was associated with a lower risk of overweight/obesity (highest vs. lowest quartile: HR 0.80, 95% CI 0.67–0.96; P-trend = 0.010). Similar inverse associations were observed for plant-MUFAs (HRQ4vsQ1 0.83, 95% CI: 0.73–0.94; P-trend = 0.003) and animal-MUFAs (HRQ4vsQ1 0.77, 95% CI: 0.64–0.94; P-trend = 0.004), total dietary oleic acid (OA) (HRQ4vsQ1 0.66, 95% CI: 0.55–0.79; P-trend

Lichtheimia ramosa (L. ramosa) is an opportunistic fungal pathogen of the order Mucorales that may result in a rare but serious mucormycosis infection. Mucormycosis could be angioinvasive, causing thrombosis and necrosis in the nose, brain, digestive tract, and respiratory tract. The infection is highly lethal, especially in immunocompromised hosts, and the incidence has been on the rise. However, due to its relatively low incidence in pediatric population and the challenges with diagnosis, the awareness and management experience for pediatric mucormycosis are extremely limited, which might lead to poor outcomes. In this study, we comprehensively reviewed the course of a fatal rhinocerebral mucormycosis case in a pediatric neuroblastoma patient receiving chemotherapy. Due to a lack of awareness of the infection, the standard care of amphotericin B treatment was delayed and not administered until the identification of L. ramosa by metagenomic next-generation sequencing (mNGS)-based pan-pathogen detection of the patient's peripheral blood sample. We also reviewed the literature on L. ramosa infection cases reported worldwide between 2010 and 2022, with an analysis of clinical manifestation, prognosis, and epidemiological data. Our study not only highlighted the clinical value of comprehensive mNGS in rapid pathogen detection but also raised awareness of recognizing lethal fungal infection early in immunocompromised hosts including pediatric cancer patients.

BackgroundOccupational burnout is a type of psychological syndrome. It can lead to serious mental and physical disorders if not treated in time. However, individuals tend to conceal their genuine feelings of occupational burnout because such disclosures may elicit bias from superiors. This study aims to explore a novel method for estimating occupational burnout by elucidating its links with social, lifestyle, and health status factors.MethodsIn this study 5,794 participants were included. Associations between occupational burnout and a set of features from a survey was analyzed using Chi-squared test and Wilcoxon rank sum test. Variables that are significantly related to occupational burnout were grouped into four categories: demographic, work-related, health status, and lifestyle. Then, from a network science perspective, we inferred the colleague’s social network of all participants based on these variables. In this inferred social network, an exponential random graph model (ERGM) was used to analyze how occupational burnout may affect the edge in the network.ResultsFor demographic variables, age (p

Abstract Background Community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen that leads to severe outcomes, especially in pediatric patients with multiple sites infection. Case presentation We report a case of multiple sites and life-threatening infection caused by CA-MRSA in a 6-year-old girl who manifested sepsis, myelitis, purulent arthritis, purulent meningitis, hydropericardium, pneumonia, and empyema. The girl exhibited good response to the combination therapy of linezolid and rifampicin after treatment failure of vancomycin with maximum dose due to its serum concentration unable to reach therapeutic goal. We performed pleural effusion and hydropericardium effusion drainage and treated left lower limb infection using interdisciplinary approaches. Conclusion This case highlights the need to be aware of CA-MRSA infection, which requires accurate diagnosis, identification of infected sites, appropriate antibiotic treatment, and surgical debridement.

BackgroundThe term “neuroblastoma (NB)” refers to a type of solid pediatric tumor that develops from undivided neuronal cells. According to the American Cancer Society report, between 700 and 800 children under the age of 14 are diagnosed with NB every year in the United States (U.S.). About 6% of all cases of pediatric cancer in the U.S. are caused by NB. NB is the most frequent malignancy in children younger than 1 year; however, it is rarely found in those over the age of 10 and above.ObjectiveTo accurately predict cancer-specific survival (CSS) in children with NB, this research developed and validated an all-encompassing prediction model.MethodsThe present retrospective study used the Surveillance, Epidemiology, and End Results (SEER) database to collect information on 1,448 individuals diagnosed with NB between 1998 and 2019. The pool of potentially eligible patients was randomly split into two groups, a training cohort (N = 1,013) and a validation cohort (N = 435). Using multivariate Cox stepwise regression, we were able to identify the components that independently predicted outcomes. The accuracy of this nomogram was measured employing the consistency index (C-index), area under the time-dependent receiver operating characteristic curve (AUC), calibration curve, and decision-curve analysis (DCA).ResultsIn this study, we found that age, primary location, tumor size, summary stage, chemotherapy, and surgery were all significant predictors of CSS outcomes and integrated them into our model accordingly. The C-index for the validation cohort was 0.812 (95% CI: 0.773–0.851), while for the training cohort it was 0.795 (95% CI: 0.767–0.823). The C-indexes and AUC values show that the nomogram is able to discriminate well enough. The calibration curves suggest that the nomogram is quite accurate. Also, the DCA curves demonstrated the prediction model's value.ConclusionA novel nomogram was developed and validated in this work to assess personalized CSS in NB patients, and it has been indicated that this model could be a useful tool for calculating NB patients’ survival on an individual basis and enhancing therapeutic decision-making.

BackgroundSevere pneumonia due to lower respiratory tract infections (LRTIs) is a significant cause of morbidity and mortality in children. Noninfectious respiratory syndromes resembling LRTIs can complicate the diagnosis and may also make targeted therapy difficult because of the difficulty of identifying LRTI pathogens. In the present study, a highly sensitive metagenomic next-generation sequencing (mNGS) approach was used to characterize the microbiome of bronchoalveolar lavage fluid (BALF) in children with severe lower pneumonia and identify pathogenic microorganisms that may cause severe pneumonia. The purpose of this study was to use mNGS to explore the potential microbiomes of children with severe pneumonia in a PICU.MethodsWe enrolled patients meeting diagnostic criteria for severe pneumonia admitted at PICU of the Children’s Hospital of Fudan University, China, from February 2018 to February 2020. In total, 126 BALF samples were collected, and mNGS was performed at the DNA and/or RNA level. The pathogenic microorganisms in BALF were identified and correlated with serological inflammatory indicators, lymphocyte subtypes, and clinical symptoms.ResultsmNGS of BALF identified potentially pathogenic bacteria in children with severe pneumonia in the PICU. An increased BALF bacterial diversity index was positively correlated with serum inflammatory indicators and lymphocyte subtypes. Children with severe pneumonia in the PICU had the potential for coinfection with viruses including Epstein–Barr virus, Cytomegalovirus, and Human betaherpesvirus 6B, the abundance of which was positively correlated with immunodeficiency and pneumonia severity, suggesting that the virus may be reactivated in children in the PICU. There was also the potential for coinfection with fungal pathogens including Pneumocystis jirovecii and Aspergillus fumigatus in children with severe pneumonia in the PICU, and an increase in potentially pathogenic eukaryotic diversity in BALF was positively associated with the occurrence of death and sepsis.ConclusionsmNGS can be used for clinical microbiological testing of BALF samples from children in the PICU. Bacterial combined with viral or fungal infections may be present in the BALF of patients with severe pneumonia in the PICU. Viral or fungal infections are associated with greater disease severity and death.

Sepsis is a critical condition affecting patients worldwide. Systemic inflammatory response syndrome in sepsis contributes to organ dysfunction and mortality. The oXiris is a recently developed continuous renal replacement therapy (CRRT) hemofilter indicated for the adsorption of cytokines from the bloodstream. In our study, in a septic child, CRRT with three filters, including the oXiris hemofilter, resulted in a downregulation of inflammatory biomarkers and a reduction of vasopressors. Herein, we described the first report of such usage in septic children.

Objective: To synthesize copper (II) porphyrin complexes and study their interactions with c-myc G-quadruplex DNA. Methods: The 5-p-hydroxyphenyl-10, 15, 20-tris (p-methoxyphenyl) copper (II) porphyrin complex [p-HTMOPPCu (II)] was synthesized by the conventional heating method. Ultraviolet (UV) titration, fluorescence titration, fluorescence resonance energy transfer (FRET) melting point and competitive assays were used to study the interactions between p-HTMOPPCu (II) and c-myc G-quadruplex DNA. Results: The UV absorption spectrum and fluorescence spectroscopy results indicated that the complex of p-HTMOPPCu (II) bound better with c-myc G-quadruplex DNA; the FRET melting point assay, and competitive melting point assay demonstrated that p-HTMOPPCu (II) could selectively bind and stabilize c-myc G-quadruplex DNA. Conclusion: p-HTMOPPCu (II) can bind and stabilize c-myc G-quadruplex DNA and will potentially be developed into a class of small molecule inhibitors targeting c-myc G-quadruplex DNA for clinical applications in the treatment of tumors.

Bleeding complications limits the use of effective antithrombotics therapeutics. Here, the authors developed next-generation direct thrombin inhibitors with low bleeding risks as safe peri-percutaneous coronary intervention anticoagulants when used in combination with antiplatelets.

BackgroundAngiostrongylus eosinophilic meningitis (AEM) is a rare yet emerging disease caused by Angiostrongylus cantonensis infection. Its atypical symptoms may delay the diagnosis and cause fatal outcomes, especially in the early stages of infection and among children.Case presentationHere we reported the use of metagenomic next-generation sequencing (mNGS) to facilitate the diagnosis and treatment of an 8-year-old boy with severe A. cantonensis infection. The mNGS tests consistently identified the infection of A. cantonensis prior to the detection by the immunologic method and confirmed it as AEM. Owing to the multidisciplinary team (MDT)-administrated treatments and close disease monitoring based on regular clinical tests and sequential mNGS tests, the patients eventually fully recovered from severe infectious conditions.ConclusionThis case demonstrated the advantages of mNGS for early diagnosis of AEM in pediatric patients, highlighting its application for pan-pathogen detection, as well as disease monitoring for severe A. cantonensis infection.

Background: The incidence and mortality of influenza in children had risen, but data are limited on children with severe influenza virus infection in China. Methods: We conducted a retrospective case–control study and collected the patients' clinical data. Clinical data including demography, clinical presentation, laboratory findings, radiologic findings, treatment and outcomes were collected. Children were clinically confirmed to have virus infection in Shanghai in three hospitals from June 2014 to June 2019. Results: During the study, 36,047 children were enrolled. Among them, 118 met the criteria for severe flu. Clinical symptoms such as fever, cough, gastrointestinal symptoms, coma and epilepsy were higher in the severe group. Complications such as pneumorrhagia, heart failure, septic shock, acute renal failure and influenza-associated encephalitis were higher in the severe influenza group than the death group. The laboratory findings including decreased hemoglobin, high alanine aminotransferase, high urea nitrogen and high lactate levels were risk factors for death in children with influenza. Conclusion: Influenza-associated encephalopathy (IAE), acute respiratory distress syndrome (ARDS) were the common clinical manifestations and complications for the severe influenza, and delayed use of oseltamivir was found to be associated with fatality.

Electromigration is one of the most important research issues affecting the reliability of solder joints. Current-induced Joule heating affects the electromigration behavior of solder joints. Solder joints with different cross-sectional areas were designed to obtain different Joule heating properties. The effects of the interfacial intermetallic compound (IMC) and mechanical properties of Sn58Bi/Cu solder joints were studied for different Joule heating properties. The results showed that as the cross-sectional area of the Sn58Bi/Cu solder joints increased, the Joule heating of the joint increased. The anode IMC thickness of the joint thickened and transformed into a planar shape. The Bi migrated to the anode region to form a Bi-rich layer and gradually increased in thickness. The cathode IMC thickness first increased, then decreased, and gradually dissolved. The Sn-rich layer formed near the solder side and gradually increased in thickness, with microcracks occurring when the cross-sectional area of the joint increased to 0.75 mm2. The joint shear fracture path moved from the soldering zone near the cathode IMC layer to the interfacial IMC layer. The fracture mechanism of the joint changed from a mixed brittle/tough fracture, dominated by deconstruction and secondary cracking, to a brittle fracture dominated by deconstruction. The joint shear strength was reduced by 60.9% compared to that in the absence of electromigration.

Objective To explore the association between dynamic changes in red blood cell distribution width to platelet count ratio (RPR) during hospitalisation and short-term mortality in patients with sepsis.Design A retrospective cohort study using propensity score matching.Setting Intensive care units (ICUs) of Beth Israel Deaconess Medical Center.Participants A total of 8731 adult patients with sepsis were included in the study. The patients were identified from the ICU of the Medical Information Mart for Intensive Care database. The observed group included patients who experienced an increase in RPR of more than 30% during the first week of ICU admission, whereas the control group included the rest.Main outcome and measure Using propensity score matching, a matched control group was created. The primary outcome was 28-day mortality, and the length of hospital stay and in-hospital mortality were the secondary outcomes.Results The difference was evident in 28-day mortality between the two groups (85.8% vs 74.5%, p

Abstract Machine translation of chemical nomenclature has considerable application prospect in chemical text data processing between languages. However, rule based machine translation tools have to face significant complication in rule sets building, especially in translation of chemical names between English and Chinese, which are the two most used languages of chemical nomenclature in the world. We applied two types of neural networks in the task of chemical nomenclature translation between English and Chinese, and made a comparison with an existing rule based machine translation tool. The result shows that deep learning based approaches have a great chance to precede rule based translation tools in machine translation of chemical nomenclature between English and Chinese.

Abstract Background Growing evidence demonstrated that dietary protein intake may be a risk factor for prostate cancer and elevate the level of prostate-specific antigen (PSA). However, proof for the correlation between dietary protein intake and PSA in American adults without prostate tumor history is limited. Our goal was to investigate the association of dietary protein intake with PSA using the National Health and Nutrition Examination Survey (NHANES) (2003–2010) database. Methods After the screening, 6403 participants were included in the study. The interested independent is the dietary protein intake, and the dependent variable is PSA levels, the covariates included demographic, dietary, biological data, and physical examination variables. A weighted linear model and a weighted linear regression model were used to examine the distribution of variables in the covariate differences between the different independent groups according to quartiles. Four models were used to survey the association between dietary protein intake and PSA. We also attempted to find a nonlinear relationship between dietary protein intake and PSA using the GAM model and the penalty spline method and further solved the nonlinear problem using weighted two-piecewise linear model. Results The weighted multivariate linear regression analysis demonstrated that dietary protein intake was not independently associated with PSA levels after adjusting potential confounders (β = 0.015, 95%CI:-0.024, 0.055). However, we found the non-linear relationship between dietary protein intake and PSA, whose point was 18.18 g (per 10 g change). The magnitude and confidence intervals for the left and right inflection points are − 0.03 (− 0.09, 0.02) and 0.22 (0.07, 0.36), respectively. On the right side of the inflection point, one gram of increment in protein intake was associated with increased PSA levels by 0.22 (log2 transformation: 0.22, 95%CI: 0.07, 0.36). Conclusions After adjusting for potential covariates, the non-linear correlation between dietary protein intake and PSA was observed. When dietary protein intake exceeded the threshold of 181.8 g, dietary protein intake was positively correlated with elevated PSA levels.