Idiopathic multicentric Castleman disease and connective tissue disorder successfully treated by siltuximab: a pediatric case report.

Background: Castleman disease (CD) is a rare lymphoproliferative disease. Idiopathic multicentric CD (iMCD), representing a distinct entity in CD, is partly attributed to autoimmune abnormalities and the hyperplastic process in iMCD involving the immune system. Consequently, iMCD presents a range of overlapping manifestations with connective tissue disorder (CTD), resulting in an inability to tell whether they coexist or imitate each other. Reports of CD combined with CTD are rare, more cases are needed to be summarized and analyzed to improve the efficiency of diagnosis and accelerate the development of novel treatments. Case Description: A male pediatric patient was diagnosed with CTD in October 2019 and had been receiving regular treatment with tocilizumab and glucocorticoid or methotrexate since April 2020. He was further diagnosed with iMCD of the hyaline vascular subtype according to biopsy-proven histopathological features and imaging-proven multiple involvement in August 2021. He received 4 doses of rituximab and then a combination of thalidomide and dexamethasone for about 1 year. His clinical symptoms were well controlled throughout the disease for a long period, but inflammatory markers were repeatedly elevated, which eventually turned normal after switching to siltuximab from July 2023, although a significant elevation of interleukin-6 occurred. Conclusions: We reported a pediatric case diagnosed as CTD and iMCD, whose inflammation finally be well controlled by siltuximab. Hopefully, our work will add insight into such rare situations and it is undoubtedly that the pathophysiological mechanism of CD and CTD coexistence and prediction models of treatment response remains to be explored to facilitate the clinical management and optimal treatment.

Characteristic substance analysis and rapid detection of bacteria spores in cooked meat products by surface enhanced Raman scattering based on Ag@AuNP array substrate.

BACKGROUND: Bacterial spores are the main potential hazard in medium- and high-temperature sterilized meat products, and their germination and subsequent reproduction and metabolism can lead to food spoilage. Moreover, the spores of some species pose a health and safety threat to consumers. The rapid detection, prevention, and control of bacterial spores has always been a scientific problem and a major challenge for the medium and high-temperature meat industry. Early and sensitive identification of spores in meat products is a decisive factor in contributing to consumer health and safety. RESULTS: In this study, we developed a novel and stable Ag@AuNP array substrate by using a two-step synthesis approach and a liquid-interface self-assembly method that can directly detect bacterial spores in actual meat product samples without the need for additional in vitro bacterial culture. The results indicate that the Ag@AuNP array substrate exhibits high reproducibility and Raman enhancement effects (1.35 × 105). The differentiation in the Surface enhanced Raman scattering (SERS) spectra of five bacterial spores primarily arises from proteins in the spore coat and inner membrane, peptidoglycan of cortex, and Ca2⁺-DPA within the spore core. The correct recognition rate of linear discriminant analysis for spores in the meat product matrix can reach 100 %. The average recovery accuracy of the SERS quantitative model was at around 101.77 %, and the limit of detection can reach below 10 CFU/mL. SIGNIFICANCE: It provides a promising technological strategy for the characteristic substance analysis and timely monitoring of spores in meat products.

Probiotic Bacillus as fermentation agents: Status, potential insights, and future perspectives.

Probiotic Bacillus strains can solve the problems of single flavor and long fermentation time of fermented products caused by the lack of certain functional genes and insufficient metabolism ability of fermenter strains (Lactobacillus and Bifidobacterium) at the present stage. There is a lack of systematic evaluation and review of probiotic Bacillus as food fermentation agents. In this paper, it is observed that probiotic Bacillus strains are involved to varying degrees in liquid-state, semi-solid state, and solid-state fermentation and are widely present in solid-state fermented foods. Probiotic Bacillus strains not only produce abundant proteases and lipases, but also effective antifungal lipopeptides and extracellular polymers, thus enhancing the flavor, nutritional value and safety of fermented foods. Bacillus with probiotic qualities is an underutilized group of probiotic food fermentation agents, which give a potential for the development of fermentation technology in the food business and the integration of ancient traditional fermentation techniques.

Single-cell RNA sequencing unveils tumor heterogeneity and immune microenvironment between subungual and plantar melanoma.

Acral melanoma (AM) is a subtype of melanoma with high prevalence in East Asians. AM is characterized by greater aggressiveness and lower survival rates. However, there are still fewer studies on immune mechanisms of AM especially subungual melanoma (SM) versus non-subungual melanoma (NSM). In order to explore tumor heterogeneity and immune microenvironment in different subtypes of AM, we applied single-cell RNA sequencing to 24,789 single cells isolated from the SM and plantar melanoma (PM) patients. Aspects of tumor heterogeneity, melanocytes from PM and SM had significant differences in gene expression, CNV and pathways in which tumor-associated such as NF-kb and Wnt were involved. Regarding the immune microenvironment, PM contained more fibroblasts and T/NK cells. The EPHA3-EFNA1 axis was expressed only in cancer-associated fibroblast (CAF) and melanocytes of PM, and the TIGIT-NECTIN2 axis was expressed in both AM subtypes of T/NK cells and melanocytes. Altogether, our study helps to elucidate the tumor heterogeneity in AM subpopulations and provides potential therapeutic targets for clinical research.

[A case of neonatal liver failure]. / 新生儿肝衰竭1例.

The patient was a male infant, born full-term, admitted to the hospital at 28 days of age due to jaundice for 20 days and abdominal distension for 15 days. The patient developed symptoms of jaundice, hepatosplenomegaly, massive ascites, and progressively worsening liver function leading to liver failure, severe coagulation disorders, and thrombocytopenia one week after birth. Various treatments were administered, including anti-infection therapy, fluid restriction, use of diuretics, use of hepatoprotective and choleretic agents, intermittent paracentesis, blood exchange, and intravenous immunoglobulin, albumin, and plasma transfusions. However, the patient's condition did not improve, and on the 24th day of hospitalization, the family decided to discontinue treatment and provide palliative care. Sequencing of the patient's liver tissue and parental blood samples using whole-exome sequencing did not identify any pathogenic variants that could explain the liver failure. However, postmortem liver tissue pathology suggested congenital hepatic fibrosis (CHF). Given the rarity of CHF causing neonatal liver failure, further studies on the prognosis and pathogenic genes of CHF cases are needed in the future. This article provides a comprehensive description of the differential diagnosis of neonatal liver failure and introduces a multidisciplinary diagnostic and therapeutic approach to neonatal liver failure.

Postnatal treatment and evolution patterns of giant fetal hepatic hemangioma: a case series of 29 patients.

OBJECTIVES: To explore the clinical characteristics, postnatal treatment and prognosis of giant fetal hepatic hemangioma (GFHH). METHOD: Retrospective analysis was performed on children with giant fetal hepatic hemangioma (maximum tumor diameter > 40 mm) diagnosed by prenatal ultrasound and MRI from December 2016 to December 2020. These patients were observed and treated at the Children's Hospital of Fudan University after birth. The clinical data were collected to analyze the clinical characteristics, treatment, and prognosis of GFHH using independent sample t tests or Fisher's exact tests. RESULTS: Twenty-nine patients who were detected by routine ultrasound in the second and third trimester of pregnancy with giant fetal hepatic hemangiomas were included. The first prenatal ultrasound diagnosis of gestational age was 34.0 ± 4.3 weeks, ranging from 22 to 39 weeks. Of the patients, 28 had focal GFHHs and 1 had multifocal GFHHs. Surgery was performed, and the diagnosis was confirmed histopathologically in two patients. There were 8 cases with echocardiography-based evidence of pulmonary hypertension, 11 cases had a cardiothoracic ratio > 0.6, and 4 cases had hepatic arteriovenous fistula (AVF). The median follow-up time was 37 months (range: 14-70 months). During the follow-up, 12 patients received medical treatment with propranolol as the first-line therapy. The treatment group had a higher ratio of cardiothoracic ratio > 0.6 (P = 0.022) and lower albumin levels (P = 0.018). Four (14.8%) lesions showed postnatal growth before involuting. Complete response was observed in 13 (13/29) patients, and partial response was observed in 16 (16/29) patients. CONCLUSIONS: Fetal giant hepatic hemangioma is mainly localized, and its clinical outcome conforms to RICH (rapidly involuting) and PICH (partially involuting), but some fetal giant hepatic hemangiomas will continue to grow after birth and then gradually decrease. For uncomplicated giant fetal hepatic hemangioma, postnatal follow-up is the main concern, while those with complications require aggressive medical treatment. Propranolol may have no effect on the volume change of GFHH.

Effect of aging on the release of di-(2-ethylhexyl) phthalate from biodegradable and petroleum-based microplastics into soil.

Due to microplastics (MPs) being widely distributed in soil, the use of advanced oxidation to remediate organic-contaminated soils may accelerate the aging of MPs in soil and impact the release of di-(2-ethylhexyl) phthalate (DEHP), a potential carcinogen used as a plasticizer in plastics, from MPs. In this study, persulfate oxidation (PO) and temperature treatment (TT) were used to treat biodegradable and petroleum-based MPs, including polylactic acid (PLA), polyvinyl chloride (PVC), and polystyrene (PS). The methods used for evaluating the characteristics changes of MP were X-ray diffraction (XRD) analysis and water contact angle measurement. The effects of aging on DEHP release from MPs were investigated via soil incubation. The results showed PO and TT led to increased surface roughness, oxygen-containing functional group content, and hydrophilicity of the MPs with prolonged aging, consequently accelerating the release of DEHP from the MPs. Interestingly, PLA aged faster than PVC and PS under similar conditions. After 30 days of PO treatment, DEHP release from PLA into the soil increased 0.789-fold, exceeding the increase from PVC (0.454-fold) and PS (0.287-fold). This suggests that aged PLA poses a higher ecological risk than aged PVC or PS. Furthermore, PO treatment resulted in the oxidation and degradation of DEHP on the MP surface. After 30 days of PO treatment, the DEHP content in PLA, PVC, and PS decreased by 19.1%, 25.8%, and 23.5%, respectively. Specifying the types of MPs studied and the environmental conditions would provide a more precise context for the results. These findings provide novel insights into the fate of biodegradable and petroleum-based MPs and the potential ecotoxicity arising from advanced oxidation remediation in contaminated soils.

Effect of lignin on the formation of polycyclic aromatic hydrocarbons in smoked and grilled meat products.

In order to explore the influence of wood types on formation of polycyclic aromatic hydrocarbons (PAHs) in traditional smoked and grilled meat products, the effect of lignin in woods on formation of PAHs was investigated in meat model systems. The results showed that PAHs formation was much dependent on the heating conditions. The addition of lignin led to significantly increased PAHs, which being connected with lignin structure. In comparison, the formation of PAHs was more facilitated by lignin with G structure than that with G/S structure. However, further study of adding lignin precursors demonstrated that lignin precursors with S structure were more favorable to the formation of PAHs than those with G structure. It was proposed that the relative content and activity of G/S structure of lignin in wood played a significant role in the formation of PAHs, which might provide theoretical reference for inhibition of PAHs fundamentally.

Development of fluorescent GO-AgNPs-Eu3+ nanoparticles based paper visual sensor for foodborne spores detection.

Foodborne spores are ubiquitous with extremely strong resistance, and pose a serious threat to food safety and human health. Therefore, rapid, sensitive, and selective detection of spores are crucial. In this study, a fluorescent probe was developed based on lanthanide ion (Eu3+)-labeled nano-silver-modified graphene oxide (GO-AgNPs-Eu3+) for the detection of 2,6-dipicolinic acid (DPA), a biomarker unique to spores, to allow quantitative spores detection. The GO-AgNPs-Eu3+ nano-fluorescent probe was loaded onto a polyvinylidene fluoride microfiltration membrane, and a smartphone-assisted portable GO-AgNPs-Eu3+ nanoparticles-based paper visual sensor was designed for rapid on-site quantitative and real-time online detection of spores. The results indicated that the developed probe achieved equilibrium binding with DPA within 5 min, and enhanced fluorescence emission through antenna effect. The fluorescence detection presented a good linear relationship in the DPA concentration range of 0-45 µM, with a DPA detection limit of 4.62 nM and spore detection limit of 104 cfu/mL. The developed sensor showed a change in fluorescence from blue to red with increasing DPA concentration, and this color change was quantitatively detected through smartphone RGB variations, with a detection limit of 13.1 µM for DPA and 6.3 cfu/mL for Bacillus subtilis spores. Subsequently, the sensitivity and selectivity of the developed sensor were verified using actual milk and water samples spiked with B. subtilis spores. The results of this study provided objective technological support for rapid detection of spores, which is important for reducing the occurrence of foodborne diseases and improving food safety.

Selective purification and rapid quantitative detection of spores using a "stepped" magnetic flow device.

A study on the inactivation and germination mechanism of spores is very important in the application of spores, as such high-purity spores are the basis of related research. However, spores and vegetative cells of bacteria often coexist, and it is difficult to separate them. In this study, a magnetic flow device for the purification of spores in the culture medium system was developed based on a "stepped" structure with a magnetic force that could absorb vegetative cells with magnetic nanoparticles. The operation process was as follows: first, vancomycin functionalized nanoparticles were used to prepare Van-Fe3O4 NPs, which were then combined with vegetative cells to form a magnetic conjugate. Subsequently, the magnetic conjugate (vegetative cells) flowed through the "stepped" magnetic flow device and was adsorbed. Meanwhile, the spores moved through the channel and were collected. The achieved purity of the collected spores was more than 95%. Further, the number of the obtained spores was quickly quantified using Raman spectroscopy. The entire purification and quantitative process can be completed within 30 min and the limit of detection was 5 CFU mL-1. This study showed outstanding spore purification ability and provided a new method for purification and rapid quantitative detection of spores.

Effect of Molecular Weight on the Structural and Emulsifying Characteristics of Bovine Bone Protein Hydrolysate.

The emulsifying capacity of bovine bone protein extracted using high-pressure hot water (HBBP) has been determined to be good. Nevertheless, given that HBBP is a blend of peptides with a broad range of molecular weights, the distinction in emulsifying capacity between polypeptide components with high and low molecular weights is unclear. Therefore, in this study, HBBP was separated into three molecular weight components of 10-30 kDa (HBBP 1), 5-10 kDa (HBBP 2), and <5 kDa (HBBP 3) via ultrafiltration, and the differences in their structures and emulsifying properties were investigated. The polypeptide with the highest molecular weight displayed the lowest endogenous fluorescence intensity, the least solubility in an aqueous solution, and the highest surface hydrophobicity index. Analysis using laser confocal Raman spectroscopy showed that with an increase in polypeptide molecular weight, the α-helix and ß-sheet contents in the secondary structure of the polypeptide molecule increased significantly. Particle size, rheological characteristics, and laser confocal microscopy were used to characterize the emulsion made from peptides of various molecular weights. High-molecular-weight peptides were able to provide a more robust spatial repulsion and thicker interfacial coating in the emulsion, which would make the emulsion more stable. The above results showed that the high-molecular-weight polypeptide in HBBP effectively improved the emulsion stability when forming an emulsion. This study increased the rate at which bovine bone was utilized and provided a theoretical foundation for the use of bovine bone protein as an emulsifier in the food sector.

Clinical features and treatment outcomes of Castleman disease in children: a retrospective cohort in China.

Castleman disease (CD) is a rare lymphoproliferative disorder of undetermined etiology. Unicentric CD (UCD) and multicentric CD (MCD) are two phenotypes of CD diagnosed by the histopathology of lymph nodes. We attempted to describe a pediatric CD cohort to optimize the management of this disease. We reviewed the medical records of pediatric patients diagnosed with CD between April, 2004, and October, 2022, at the Children's Hospital of Fudan University. Prognosis information was collected in January, 2023, by telephone inquiry. Twenty-two patients with UCD and 2 patients with MCD were identified, all with hyaline vascular (HV) type. The median ages at diagnosis were 10.75 years (IQR 8, 12.81) for UCD and 14.42 years (IQR 13.42, 15.42) for MCD. The most common lesion location of UCD was the neck (9/22, 40.91%) and abdomen (9/22, 40.91%). Systematic symptoms occurred on 10/22 (45.45%) patients with UCD and 1/2 (50%) patients with MCD, and abnormal laboratory indexes were detected in both. Resection and biopsy were performed on all patients. One out of two patients with MCD also received rituximab for upfront therapy. After a median of 4 years (IQR 1.5, 6) of follow-up time, the overall survival was 100% and the complete remission rate in UCD was 63%. There was no relapse or progression. CONCLUSIONS: Our series demonstrated that HV-UCD was the most common type in children. Resection and biopsy were used for both deterministic diagnoses and treatments. Despite the high possibility to develop systematic inflammation, children with CD showed promising outcomes. WHAT IS KNOWN: • Castleman disease is a rare lymphoproliferative disorder with limited cohort studies, especially in pediatrics. • The ubiquity of delayed confirmations and misdiagnoses points to a lack of knowledge about etiology and characteristics, which is a prerequisite for novel therapeutics. WHAT IS NEW: • We retrospectively reviewed and analyzed the clinical and pathological symptoms, laboratory and imaging features, and treatment outcomes of a Chinese pediatric cohort with Castleman disease. • Our work may improve the recognition and optimize the management of this rare disease in children.

[Congenital pulmonary alveolar proteinosis in a neonate]. / æ–°ç”Ÿå„¿å ˆå¤©æ€§è‚ºæ³¡è›‹ç™½æ²‰ç§¯ç—‡1例.

The male patient was referred to the hospital at 44 days old due to dyspnea after birth and inability to wean off oxygen. His brother died three days after birth due to respiratory failure. The main symptoms observed were respiratory failure, dyspnea, and hypoxemia. A chest CT scan revealed characteristic reduced opacity in both lungs with a "crazy-paving" appearance. The bronchoalveolar lavage fluid (BALF) showed periodic acid-Schiff positive proteinaceous deposits. Genetic testing indicated a compound heterozygous mutation in the ABCA3 gene. The diagnosis for the infant was congenital pulmonary alveolar proteinosis (PAP). Congenital PAP is a significant cause of challenging-to-treat respiratory failure in full-term infants. Therefore, congenital PAP should be considered in infants experiencing persistently difficult-to-treat dyspnea shortly after birth. Early utilization of chest CT scans, BALF pathological examination, and genetic testing may aid in early diagnosis.

Review of Energy Management Methods for Fuel Cell Vehicles: From the Perspective of Driving Cycle Information.

Energy management methods (EMMs) utilizing sensing, communication, and networking technologies appear to be one of the most promising directions for energy saving and environmental protection of fuel cell vehicles (FCVs). In real-world driving situations, EMMs based on driving cycle information are critical for FCVs and have been extensively studied. The collection and processing of driving cycle information is a fundamental and critical work that cannot be separated from sensors, global positioning system (GPS), vehicle-to-vehicle (V2V), vehicle-to-everything (V2X), intelligent transportation system (ITS) and some processing algorithms. However, no reviews have comprehensively summarized the EMMs for FCVs from the perspective of driving cycle information. Motivated by the literature gap, this paper provides a state-of-the-art understanding of EMMs for FCVs from the perspective of driving cycle information, including a detailed description for driving cycle information analysis, and a comprehensive summary of the latest EMMs for FCVs, with a focus on EMMs based on driving pattern recognition (DPR) and driving characteristic prediction (DCP). Based on the above analysis, an in-depth presentation of the highlights and prospects is provided for the realization of high-performance EMMs for FCVs in real-world driving situations. This paper aims at helping the relevant researchers develop suitable and efficient EMMs for FCVs using driving cycle information.

Irreversible electroporation combined with chemotherapy and PD-1/PD-L1 blockade enhanced antitumor immunity for locally advanced pancreatic cancer.

Background: Irreversible electroporation (IRE) is a novel local tumor ablation approach with the potential to stimulate an antitumor immune response. However, it is not effective in preventing distant metastasis in isolation. This study aimed to compare the potential of augmenting the antitumor immune response in patients with locally advanced pancreatic cancer (LAPC) who underwent IRE combined with chemotherapy and PD-1/PD-L1 blockade with those who underwent IRE combined with chemotherapy. Methods: A retrospective review was conducted on LAPC patients treated either with IRE in combination with chemotherapy and PD-1/PD-L1 blockade (group A) or with IRE with chemotherapy alone (group B) from July 2015 to June 2021. The primary outcomes were overall survival (OS) and progression-free survival (PFS), with immune responses and adverse events serving as secondary endpoints. Risk factors for OS and PFS were identified using univariate and multivariate analyses. Results: A total of 103 patients were included in the final analysis, comprising 25 in group A and 78 in group B. The median duration of follow-up was 18.2 months (3.0-38.6 months). Group A patients demonstrated improved survival compared to group B (median OS: 23.6 vs. 19.4 months, p = 0.001; median PFS: 18.2 vs. 14.7 months, p = 0.022). The data suggest a robust immune response in group A, while adverse events related to the treatment were similar in both groups. The multivariate analysis identified the combination of IRE, chemotherapy, and PD-1/PD-L1 blockade as an independent prognostic factor for OS and PFS. Conclusion: The addition of PD-1/PD-L1 blockade to the regimen of IRE combined with chemotherapy enhanced antitumor immunity and extended survival in LAPC patients.