Pediatric Acute Myeloid Leukemia: Unraveling Complexities in Intensive Chemotherapy and the Emergence of Superbugs - A Case Study.

Background: This case report underscores the intricate challenges in managing paediatric patients with acute myeloid leukaemia (AML) undergoing intensive chemotherapy, particularly when complicated by the emergence of multidrug-resistant pathogens such as Carbapenem-Resistant Pseudomonas aeruginosa (CRPA). Case Presentation: An 11-year-old male with AML presented with skin purpura and persistent cough. Clinical and laboratory assessments revealed a high-risk AML profile with genetic mutations, leading to the initiation of intensive chemotherapy per the C-HUANA-AML-2015 protocol. Despite successful disease remission after initial chemotherapy courses, the patient experienced unexpected complications. Notably, septic shock, bone marrow failure, and the emergence of CRPA were encountered during the clinical course. Septic shock occurred following Course B3 chemotherapy, marked by a fever unresponsive to initial antibiotic therapy. Despite negative blood cultures, meropenem and vancomycin were initiated, successfully normalizing temperature. Subsequent challenges included persistent bone marrow suppression, perianal dermatitis, and the identification of CRPA in stool cultures, leading to altered antibiotic therapy guided by minimum inhibitory concentration (MIC) considerations. Whole-genome sequencing (WGS) of the CRPA strain revealed a highly virulent clone (ST-970) with numerous resistance and virulence genes. Conclusion: This case report offers new insights into the complexities of pediatric AML management, with a focus on the emergence of CRPA. The discovery of a high-risk CRPA clone with detailed genomic data underscores the growing challenge of antimicrobial resistance in pediatric oncology. The persistent presence of CRPA and ongoing bone marrow failure highlight the difficulties in managing these complications. This case calls for a reassessment of treatment strategies and encourages further research to improve outcomes in pediatric AML, emphasizing the need for a multidisciplinary approach to address infectious complications and antimicrobial resistance.

Genetic landscape of ESBL producing international clone ST410 of Escherichia coli from pediatric infections in Shenzhen, China.

Background: The emergence of ESBLs producing cephalosporin-resistant Escherichia coli isolates poses a threat to public health. This study aims to decipher the genetic landscape and gain insights into ESBL-producing E. coli strains belonging to the high-risk clone ST410 from pediatric patients. Methods: 29 E. coli ST410 isolates were collected from young children and subjected to antimicrobial susceptibility testing, Whole-genome sequencing (WGS), serotype analysis, MLST, ESBL genes, virulence genes, and plasmid profiling. Results: Antimicrobial susceptibility testing demonstrated a high level of resistance to cephalosporins followed by aminoglycoside, sulfonamide, carbapenem and penicillin group of antibiotics. However, n=20/29 shows MDR phenotype. Phylogenetic group B2 (n=15) dominated, followed by group D (n=7), group A (n=4), and group B1 (n=3). Serotyping analysis identified O1:H7 (n=8), O2:H1 (n=6), O8:H4 (n=5), O16:H5 (n=4), and O25:H4 (n=3). Other serotypes identified included O6:H1, O15:H5, and O18:H7 (n=1 each). The most commonly detected ESBL genes were bla CTX-M, (n=26), followed by bla TEM (n=23), and bla SHV (n=18). Additionally, bla OXA-1 (n=10), bla OXA-48 (n=5), bla KPC-2 (n=3), bla KPC-3 (n=2), bla NDM-1 (n=4), bla NDM-5 (n=1), bla GES-1 (n=2), bla GES-5 (n=1), and bla CYM-1 (n=3). Notable virulence genes identified within the ST410 isolates included fimH (n=29), papC (n=24), hlyA (n=22), and cnf1 (n=18), among others. Diverse plasmids were observed including IncFIS, IncX4, IncFIA, IncCol, IncI2 and IncFIC with transmission frequency ranges from 1.3X10-2 to 2.7X10-3. Conclusion: The ST410 clone exhibited a complex resistance profile, diverse serotypes, the presence of specific resistance genes (ESBL genes), virulence gene repertoire, and diverse plasmids. The bla CTX-M was the most prevalent ESBL gene detected.

Hematopoietic stem cell transplantation activity in China 2022-2023. The proportions of peripheral blood for stem cell source continue to grow: a report from the Chinese Blood and Marrow Transplantation Registry Group.

Over past two years, a total of 39,918 hematopoietic stem cell transplantation (HSCT) cases were reported, with 18,194 and 21,714 transplants performed in 2022 and 2023, respectively. Autologous HSCT accounted for 6562 cases (31%) in 2022, while allogeneic HSCT comprised 12,632 cases (69%). In 2023, the number of allogeneic HSCTs exceeded 15,000, maintaining a 69% share. Participation in the 2022 and 2023 surveys included 193 and 212 transplantation teams, respectively, from 27 provinces, municipalities, or autonomous regions. The leading indication of HSCT was acute leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed phenotype acute leukemia, with a total of 17,421 cases. AML was the most common disease (10,339, 38%) for allogeneic HSCT, which was followed by ALL (5925 cases, 21%). Peripheral blood emerged as the primary source of stem cell grafts, utilized in 54% of matched sibling donor transplants and 77% of haploidentical donor transplants. The BuCy-based conditioning regimen was the most prevalent, used in 53% of allogeneic HSCT cases in the past two years. This survey offers a comprehensive overview of the current HSCT landscape and serves as a valuable resource for clinical practice.

TRIM8 as a predictor for prognosis in childhood acute lymphoblastic leukemia based on a signature of neutrophil extracellular traps.

Background: Neutrophil extracellular traps (NETs) can be attributed to the metastasis, occurrence, and immune evasion of cancer cells. We investigated the prognostic value of NET-related genes in childhood acute lymphoblastic leukemia (cALL) patients. Methods: Differential gene expression analysis was conducted on samples collected from public databases. Grouping them based on the expression level of NET-related genes, we assessed the correlation between immune cell types and the risk score for having a poor prognosis of cALL, with an evaluation of the sensitivity of drugs used in cALL. We further divided the groups, integrating survival data. Subsequently, methods including multivariable Cox algorithms, least absolute shrinkage and selection operator (LASSO), and univariable were utilized to create a risk model predicting prognosis. Experiments in cell lines and animals were performed to explore the functions of TRIM8, a gene selected by the model. To validate the role of TRIM8 in leukemia development, lentivirus-mediated overexpression or knockdown of TRIM8 was employed in mice with T-ALL and B-ALL. Results: Kaplan-Meier (KM) analysis underscored the importance of differentially expressed genes identified in the groups divided by genes participated in NETs, with enrichment analysis showing the mechanism. Correlation analysis revealed significant associations with B cells, NK cells, mast cells, T cells, plasma cells, dendritic cells, and monocytes. The IC50 values of drugs such as all-trans-retinoic acid (ATRA), axitinib, doxorubicin, methotrexate, sorafenib, and vinblastine were increased, while dasatinib exhibited a lower IC50. A total of 13 NET-related genes were selected in constructing the risk model. In the training, testing, and merged cohorts, KM analysis demonstrated significantly improved survival for low-risk cALL patients compared to high-risk cALL patients (p < 0.001). The area under the curve (AUC) indicated strong predictive performance. Experiments in Jurkat and SUP-B15 revealed that TRIM8 knockdown decreased the proliferation of leukemia cell lines. Further experiments demonstrated a more favorable prognosis in mice with TRIM8-knockdown leukemia cells. Results of cell lines and animals showed better outcomes in prognosis when TRIM8 was knocked down. Conclusion: We identified a novelty in a prognostic model that could aid in the development of personalized treatments for cALL patients. Furthermore, it revealed that the expression of TRIM8 is a contributing factor to the proliferation of leukemia cells and worsens the prognosis of cALL.

Genome-wide methylation and gene-expression analyses in thalassemia.

Thalassemia is the most common autosomal genetic disorder in humans. The pathogenesis of thalassemia is principally due to the deletion or mutation of globin genes that then leads to disorders in globin-chain synthesis, and its predominant clinical manifestations include chronic forms of hemolytic anemia. However, research on the epigenetics and underlying pathogenesis of thalassemia is in its nascency and not yet been systematically realized. In this study, we compared the results of RNA-seq and the whole-genome bisulfite sequencing (WGBS) on 22 peripheral blood samples from 14 thalassemic patients and eight healthy individuals revealed a genome-wide methylation landscape of differentially methylated regions (DMRs). And functional-enrichment analysis revealed the enriched biological pathways with respect to the differentially expressed genes (DEGs) and differentially methylated genes (DMGs) to include hematopoietic lineage, glucose metabolism, and ribosome. To further analyze the interaction between the transcriptome and methylome, we implemented a comprehensive analysis of overlaps between DEGs and DMGs, and observed that biological processes significantly enriched the immune-related genes (i.e., our hypermethylated and down-regulated gene group). Hypermethylated and hypomethylated regions of thalassemia-related genes exhibited different distribution patterns. We thus, further identified and validated thalassemia-associated DMGs and DEGs by multi-omics integrative analyses of DNA methylation and transcriptomics data, and provided a comprehensive genomic map of thalassemia that will facilitate the exploration of the epigenetics mechanisms and pathogenesis underlying thalassemia.

Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: A long-term follow-up pilot study.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre- and early-symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early-onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with post-symptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over nine years. The most common adverse events (AEs) within two months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with post-symptomatic juvenile MLD.

A Retrospective Cohort Study on Treponema pallidum Infection: Clinical Trends and Treatment Outcomes for Congenital Syphilis in Guangxi, China (2013-2023).

Background: Syphilis, a prevalent sexually transmitted infection, poses severe risks, especially during pregnancy. This study aimed to elucidate the trends and impacts of syphilis in Guangxi, China, focusing on prevalence, clinical manifestations, and treatment outcomes in pregnant women and newborns. The objectives included understanding the demographic characteristics of affected pregnant women, analysing the clinical manifestations in newborns, and assessing the effectiveness of the treatment protocol. Methods: Conducted in adherence to ethical guidelines, a retrospective cohort study from January 2013 to December 2023 included 54,048 pregnant women tested for T. pallidum. Diagnosis involved a comprehensive approach, utilizing tests like the Toluidine Red Unheated Serum Test (TRUST) and the Treponema pallidum Particle Agglutination (TPPA) assay. Infant diagnosis and clinical manifestations were evaluated through a decade-long follow-up. Treatment protocols, including Benzathine penicillin, were implemented. Statistical analyses were conducted using SAS version 9.4. Results: Among 54,048 pregnant women, 0.10% were syphilis positive, correlating with a rise in hospitalizations. Newborns exhibited varied clinical manifestations, with neonatal pneumonia and jaundice being prevalent. The treatment protocol, especially with Benzathine penicillin, achieved a remarkable 100% cure success rate. The study noted a significant reduction in mother-to-child transmission. Syphilis in mothers and babies was diagnosed at different clinical stages, including primary, secondary, latent, and tertiary. Conclusion: This study underscores the escalating impact of syphilis on pregnant women and newborns in Guangxi, China. The findings highlight the necessity for robust preventive measures, early diagnosis, and effective treatment strategies. The observed 100% cure success rate with Benzathine penicillin emphasizes the importance of strict treatment protocols in mitigating the adverse effects of congenital syphilis and reducing its transmission.

Case report: Clinical features of pediatric acute myeloid leukemia presenting with cardiac tamponade: a case series study and literature review.

Objective: This study aims to elucidate the clinical features observed in cases of pediatric acute myeloid leukemia (AML) initially presenting with cardiac tamponade and to share treatment experiences. Materials and methods: Five pediatric patients were initially diagnosed with AML accompanied by cardiac myeloid sarcoma (MS). The diagnosis was established by examining our hospital records and reviewing pertinent literature from 1990 to July 2023, accessible through MEDLINE/PubMed. We comprehensively assessed the clinical characteristics and treatment modalities employed for these patients. Result: Five pediatric patients presented with acute symptoms, including shortness of breath, malaise, cough, and fever, leading to their hospitalization. Physical examination revealed irritability, hypoxia, tachypnea, tachycardia, and hypotension. Initial detection utilized chest X-ray or echocardiogram, leading to subsequent diagnoses based on pericardial effusion and/or bone marrow examination. Two patients received chemotherapy at the time of initial diagnosis, one with cytarabine and etoposide, and the other with cytarabine and cladribine. Post-treatment, their bone marrow achieved remission, and over a 2.5-year follow-up, their cardiac function remained favorable. Unfortunately, the remaining three patients succumbed within two weeks after diagnosis, either due to receiving alternative drugs or without undergoing chemotherapy. Conclusion: This is the first and largest case series of pediatric AML patients with cardiac MS, manifesting initially with cardiac tamponade. It highlights the rarity and high mortality associated with this condition. The critical factors for reducing mortality include identifying clinical manifestations, conducting thorough physical examinations, performing echocardiography promptly, initiating early and timely pericardial drainage, and avoiding cardiotoxic chemotherapy medications.

Diffuse large B-cell lymphoma with central nervous system symptoms during the maintenance therapy of acute lymphoblastic leukemia: a case report and literature review.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) secondary to acute lymphoblastic leukemia (ALL) is a rare disease with poor prognosis, usually attributed to delayed diagnosis. To date, only four cases of ALL developing DLBCL have been reported, while none of them exhibiting central nervous system (CNS) symptoms. CASE DESCRIPTION: Here, we report an unusual case of a 15-year-old boy diagnosed with ALL and treated based on the SCCLG-ALL 2016 protocol. While he was receiving maintenance treatment, the patient developed dizziness and vomiting. An Epstein-Barr virus (EBV)-positive DLBCL with CNS involvement was diagnosed from inguinal lymph nodes biopsy, EBV DNA tests and head magnetic resonance imaging (MRI). Meanwhile, a dramatic decrease of immune cells and immunoglobulin was detected in the occurrence of DLBCL. He received therapy based on SCCCG-NHL-2017 protocol immediately after the diagnosis. CONCLUSIONS: We present the first retrospective report of four cases of non-Hodgkin lymphoma (NHL) secondary to ALL between 1990 and 2022. The pathogenesis of secondary DLBCL may be related to infection, immunodeficiency, genetic susceptibility, and treatment. Thus, the detection of EBV DNA during the full course of ALL therapy and genetic tests were needed in the occurrence of secondary DLBCL. Given to the rare rate and insufficient treatment experience, longer follow-up and enough sample size are needed.

Research advances on short-chain fatty acids in gastrointestinal acute graft-versus-host disease.

Gastrointestinal acute graft-versus-host disease (GI-aGVHD) is a severe early complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). It has been shown that the intestinal microbiota plays a critical role in this process. As metabolites of the intestinal microbiota, short-chain fatty acids (SCFAs) are vital for maintaining the host-microbiota symbiotic equilibrium. This article provides an overview of the protective effect of SCFAs in the gastrointestinal tract, emphasizes their association with GI-aGVHD, and explores relevant research progress in prevention and treatment research.

Research advances on short-chain fatty acids in gastrointestinal acute graft-versus-host disease Gastrointestinal acute graft-versus-host disease (GI-aGVHD) is a severe early complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). It has been shown that the intestinal microbiota plays a critical role in this process. As metabolites of the intestinal microbiota, short-chain fatty acids (SCFAs) are vital for maintaining the host-microbiota symbiotic equilibrium. This article provides an overview of the protective effect of SCFAs in the gastrointestinal tract, emphasizes their association with GI-aGVHD and explores relevant research progress in prevention and treatment research.

Diagnostic significance of cerebrospinal fluid flow cytometry in Chinese children with B lineage acute lymphoblastic leukemia.

BACKGROUND: Central nervous system leukemia (CNSL) is one of the major causes of the poor prognosis of childhood leukemia. We aimed to compare the sensitivity of cytomorphology (CM) and flow cytometry (FCM) in diagnosing CNSL, emphasizing the importance of FCM in the diagnosis process. METHODS: One-hundred-sixty-five children with newly diagnosed B-cell Acute Lymphoblastic Leukemia (B-cell ALL) were included in this study. Cerebrospinal fluid (CSF) samples were taken for routine CSF analysis, CM analysis, and FCM examination. Computed tomography scans and/or magnetic resonance imaging were performed at diagnosis. Patients with CNS2, CNS3, and traumatic lumbar puncture (TLP) at diagnosis received two additional courses of triple intrathecal injections during induction treatment. We compared the sensitivity of FCM and CM in the diagnosis of children with CNSL. RESULTS: One hundred and twenty-eight (77.58%) CSF samples were negative by either CM or FCM (CM-/FCM-), four (2.42%) were positive by both CM and FCM (CM+/FCM+), and thirty-three (20%) displayed a single positive finding by FCM (CM-/FCM+) (p = 0.044). By adding two intrathecal injections in the induction treatment, ten children with TLP+ had no CNS relapse, like those with TLP-. However, compared to CNS1 and TLP, the event-free survival (EFS) did not significantly improve in patients with CNS2 and CNS3. Moreover, CNSL status was associated with worse 3-year EFS (p < 0.05). CONCLUSIONS: We have validated that FCM is more accurate in stratifying the status of the CNS compared to CM analysis. However, to improve the EFS rate of childhood leukemia, it is necessary to combine CM examination, FCM, and cranial imaging for the early diagnosis of CNSL.

Surveillance and Outcomes of Pediatric Hematopoietic Stem Cell Transplantation Recipients During the Recent COVID-19 Outbreak in China.

Background: The COVID-19 pandemic presents challenges for healthcare systems globally, especially in vulnerable populations such as pediatric hematopoietic stem cell transplant (HSCT) recipients. This study examines the clinical characteristics and outcomes of COVID-19 infection in pediatric HSCT recipients within one year post-HSCT. Methods: Retrospective analysis was conducted on data from 247 pediatric patients. None of them had received SARS-CoV-2 vaccination or had prior infection. SARS-CoV-2 infection was confirmed using RT-PCR testing. COVID-19 disease severity was categorized according to established guidelines. Demographic, clinical, laboratory, imaging and treatment data were collected. Results: The median age of the cohort was 7±3.7 years, with thalassemia major as the predominant underlying disease. Allogeneic HSCT was performed in the majority of cases, with haploidentical donors being the most common source of grafts. Nearly half of the patients developed COVID-19, with significantly higher infection rates observed in recipients over 100 days compared to recipients within 100 days post-HSCT (40.1% vs 21.7%, p<0.05, Fisher's Exact test). Fever (n=107, 43.2%) and cough (n=88, 35.6%) were the most common symptoms. While most patients had mild disease and did not require specific anti-viral treatment, a significant proportion required hospitalization (n=34, 13.8%). Various treatments were employed hospitalized patients, including Paxlovid (n=19, 55.9%), methylprednisolone (n=7, 20.6%), IL-6 antibody (n=2, 5.9%), mesenchymal stem cells (n=3, 8.8%), and exosomes nebulization therapy (n=2, 5.9%). Despite multidisciplinary approaches, one patient died from severe respiratory failure. However, overall survival of all patients remained high (99.53%; CI 96.72-99.93%), indicating favorable outcomes in pediatric HSCT recipients with COVID-19. Conclusion: This study provides insights into clinical features, therapeutic measures, and outcomes of pediatric HSCT recipients following COVID-19 infection in a large HSCT center in China. These findings contribute to our understanding of COVID-19 in this population and inform strategies to mitigate the impact the pandemic's impact on their care.

Self-driven immune checkpoint blockade and spatiotemporal-sensitive immune response monitoring in acute myeloid leukemia using an all-in-one turn-on bionanoprobe.

Immune checkpoint (ICP) blockade (ICB) is one of the most promising immunotherapies for acute myeloid leukemia (AML). However, owing to their heterogeneity, AML cells may cause uncoordinated metabolic fluxes and heterogeneous immune responses, inducing the release of a spatiotemporally sensitive immune response marker. Timely and in situ detection of immune responses in ICB therapy is important for therapeutic strategy adjustment. Herein, we constructed an all-in-one nanoprobe for self-driving ICB and simultaneously detecting an immune response in the same AML cell in vivo, thus enabling accurate evaluation of heterogenetic immune responses in living AML mice without additional drug treatment or probe processes. The nature-inspire polydopamine (PDA) nanoparticles loaded with an ICP blocker were targeted to the leukocyte immunoglobulin like receptor B4 (a new ICP) of AML cells to induce the release of immune response marker granzyme B (GrB). The PDA nanoparticles were additionally paired with carbon-derived graphene quantum dots (GQDs) to construct a full-organic 'turn-on' bionanoprobe that can transfer fluorescence resonance energy for GrB detection. This multifunctional nanoprobe was validated for triggering ICB therapy and monitoring the changes of GrB levels in real-time both in vitro and in vivo. The organic nanoprobe showed excellent permeability and retention in tumor cells and high biocompatibility in vivo. This bionanoprobe orderly interacted with the upstream ICP molecules and downstream signal molecule GrB, thereby achieving in situ immune response signals within the therapeutic efficacy evaluation window.

Synthesis of Berberis aristate rhizome extract stabilized magnesium nanoparticles using green chemistry: rhizome characterization, in vitro antimicrobial and anti-inflammatory activity.

In the present study, magnesium nanoparticles (Mg NPs) were synthesized utilizing an aqueous extract of Berberis aristate rhizome and evaluated for antimicrobial and anti-inflammatory activity. Technofunctional properties of rhizome powder were evaluated and during thermal stability evaluation four stages of decomposition with a maximum delta Y value of 76.04 % was observed. Optimization of Mg NPs was carried out by employing eight different concentrations (C1-C8) and the C4 showed maximum absorbance at 330 nm confirming the NPs synthesis. The Mg NPs showed the particle size of 62 nm, zeta potential of -24.7 mV and hexagonal mprphology. Potential inhibition against S. aureus and E. coli (76.78 ± 0.05% and 74.62 ± 0.17%)and anti-inflammatory activity ranging from 42.43 ± 0.07-82.92 ± 0.04% was observed for Mg NPs. Therefore, green synthesis of Mg NPs is a promising approach for the development ofbiological active NPs to cure microbial infections.

Green extraction of Milletia pinnata oil for the development, and characterization of pectin crosslinked carboxymethyl cellulose/guar gum herbal nano hydrogel.

Milletia pinnata oil and Nardostachys jatamansi are rich sources of bioactive compounds and have been utilized to formulate various herbal formulations, however, due to certain environmental conditions, pure extract form is prone to degradation. Therefore, in this, study, a green hydrodistillation technology was used to extract M. pinnata oil and N. jatamansi root for the further application in development of pectin crosslinked carboxymethyl cellulose/guar-gum nano hydrogel. Both oil and extract revealed the presence of spirojatamol and hexadecanoic acid methyl ester. Varied concentrations (w/w) of cross-linker and gelling agent were used to formulate oil emulsion extract gel (OEEG1, OEG1, OEEG2, OEG2, OEEG3, OEG3, OEEG4, OEG4, OEEG5, OEG5), in which OEEG2 and OEG2 were found to be stable. The hydrogel displayed an average droplet size of 186.7 nm and a zeta potential of -20.5 mV. Endo and exothermic peaks and the key functional groups including hydroxyl, amide II, and amide III groups confirmed thermal stability and molecular structure. The smooth surface confirmed structural uniformity. Bactericidal activity against both Gram-positive (25.41 ± 0.09 mm) and Gram-negative (27.25 ± 0.01 mm) bacteria and anti-inflammatory activity (49.25%-83.47%) makes nanohydrogel a potential option for treating various infections caused by pathogenic microorganisms. In conclusion, the use of green hydrodistillation technology can be used to extract the bioactive compounds that can be used in formulation of biocompatible and hydrophobic nanohydrogels. Their ability to absorb target-specific drugs makes them a potential option for treating various infections caused by pathogenic microorganisms.

Trends in Antibiotic Resistance Patterns and Burden of Escherichia Coli Infections in Young Children: A Retrospective Cross-Sectional Study in Shenzhen, China from 2014-2018.

Purpose: The emergence of multi-drug resistant ESBL-producing E. coli poses a global health problem. In this study, we aimed to investigate the prevalence of E. coli infections and their antibiotic susceptibility profiles in paediatric clinical cases in Shenzhen, China from Jan 1, 2014, to Jan 30, 2019, while also determining temporal trends, identifying ESBL-producing strains, and recommending potential empirical antibiotic therapy options. Methods: We isolated a total of 4148 E. coli from different specimens from a single paediatric healthcare centre. Additionally, we obtained relevant demographic data from the hospital's electronic health records. Subsequently, we performed antimicrobial susceptibility testing for 8 classes of antibiotics and assessed ESBL production. Results: Out of the 4148 isolates, 2645 were from males. The highest burden of E. coli was observed in the age group of 0-1 years, which gradually declined over the five-year study period. Antimicrobial susceptibility results indicated that 82% of E. coli isolates were highly resistant to ampicillin, followed by 52.36% resistant to cefazolin and 47.46% resistant to trimethoprim/sulfamethoxazole. Notably, a high prevalence of ESBL production (49.54%) was observed among the E. coli isolates, with 60% of them displaying a multi-drug resistance phenotype. However, it is worth mentioning that a majority of the isolates remained susceptible to ertapenem and imipenem. Our findings also highlighted a decrease in E. coli infections in Shenzhen, primarily among hospitalized patients in the 0-1 year age group. However, this decline was accompanied by a considerably high rate of ESBL production and increasing resistance to multiple antibiotics. Conclusion: Our study underscores the urgent need for effective strategies to combat multi-drug resistant ESBL-producing E. coli Infections.

A Retrospective Analysis of the Therapeutic Outcomes of 117 Neuroblastoma Patients Treated at a Single Pediatric Oncology Center in China.

OBJECTIVE: Recent therapeutic advances have greatly enhanced the survival rates of patients with neuroblastoma (NB). However, the outcomes of neuroblastoma patients in China, particularly those with high-risk (HR) NB, remain limited. METHOD: We retrospectively analyzed the clinical data and outcomes of NB patients who were treated at a tertiary pediatric cancer facility in China between January 2013 and October 2021. RESULTS: A total of 117 NB patients were recruited. Patients with very low-risk (VLR), low-risk (LR), intermediate-risk (IR), and HR-NB patients made up 4%, 27%, 15%, and 54% of total patient population, respectively. Patients diagnosed between 2013 and 2018 were treated according to the protocol of Sun Yat-Sen University Cancer Center and those diagnosed between 2019 and 2021 were treated according to the COG ANBL0531 or ANBL0532 protocol with or without autologous stem cell transplantation (ASCT). The 5-year EFS and OS of all risk groups of patients were 67.29% and 77.90%, respectively. EFS and OS were significantly decreased in patients with higher risk classifications (EFS: VLR/LR vs IR vs HR: 97.22% vs 67.28% vs 51.83%; ***P = .001; OS: VLR/LR vs IR vs HR: 97.06% vs 94.12% vs 64.38%; *P = .046). In HR-NB patients treated according to the COG protocol between 2019 and 2021, the 3-year OS of patients who received tandem ASCT was significantly greater than those who did not receive ASCT (93.33% % vs 47.41%; *P = .046; log-rank test). EFS was not significantly different between patients with and without ASCT (72.16% vs 60.32%). CONCLUSION: Our findings show that patients with lower risk classification have a positive prognosis for survival. The prognosis of patients with HR-NB remains in need of improvement. ASCT may enhance OS in HR-NB patients; however, protocol adjustment may be necessary to increase EFS in these patients.

Genomic characterisation of multi-drug resistant Escherichia coli and Klebsiella pneumoniae co-harbouring mcr-1 and mcr-3 genes on a single plasmid from paediatric clinical cases.

OBJECTIVES: Emergence of the plasmid-born mobile colistin resistance (mcr) gene is a growing concern in healthcare. Therefore, this study aimed to genomically characterise multidrug-resistant Escherichia coli and Klebsiella pneumoniae co-harbouring the mcr-1 and mcr-3 genes in young children. METHODS: E. coli (n = 3) and K. pneumoniae (n = 2) were collected from abdominal secretions and blood, respectively. The isolates were screened using tryptone soy broth with 4 µL/mL polymyxin-B. Growing bacteria were identified using the VITEK-2 system, matrix-assisted laser desorption/ionisation time-of-flight, and 16s RNA sequencing, followed by antibiotic susceptibility testing. Metallo-ß-lactamase (MBL) and extended-spectrum ß-lactamase (ESBL) production was also detected. Afterwards, strains were subjected to molecular screening targeting mcr variants and ESBL/MBL-encoding genes. Conjugation, pulsed-field gel electrophoresis, Southern hybridisation, multilocus sequence typing, and phylogenic group detection were performed, along with plasmid-genome sequencing and bioinformatics analysis. RESULTS: E. coli isolates (EC-19-322, 323, and 331) and K. pneumoniae isolates (KP-19-225 and 226) harboured both mcr-1 and mcr-3 genes. These strains were also found to be resistant to more than three classes of antibiotics. The conjugation experiment revealed the presence of mcr-1 and mcr-3 on a single plasmid, and the transmission frequency was 10-2 to 10-3. Both strains were found to be able to produce ESBLs and MBL. E. coli EC-19-322 and 323 were identified as ST131(O25a:H41); SP-19-331, as ST1577 (O16:H30); and K. pneumoniae, as ST231 (K2). All E. coli strains belonged to phylogenetic group B2, and the results of pulsed-field gel electrophoresis supported the multilocus sequence typing findings. CONCLUSION: This study reported the co-occurrence of mcr-1 and mcr-3 genes on a single plasmid in pathogenic ESBL/MBL-producing E. coli and K. pneumoniae isolated from young children.

Resistance genomics and molecular epidemiology of high-risk clones of ESBL-producing Pseudomonas aeruginosa in young children.

Introduction: The emergence of multidrug-resistant Pseudomonas aeruginosa poses a global threat, but the distribution and resistance profiling are unclear, especially in young children. Infections due to P. aeruginosa are common, associated with high mortality, and increasingly ß-lactam drug resistant. Methods: We studied the molecular epidemiology and antibiotic resistance mechanisms in 294 clinicalisolates of P. aeruginosa from a pediatric hospital in China. Non-duplicate isolates were recovered from clinical cases and were identified using an API-20 kit followed by antimicrobial susceptibility testing using the VITEK®2 compact system (BioMerieux, France) and also by broth dilution method. In addition, a double-disc synergy test for the ESBL/E-test for MBL was performed. The presence of beta-lactamases, plasmid types, and sequence types was determined by PCR and sequencing. Results: Fifty-six percent (n = 164) of the isolates were resistant to piperacillin-tazobactam, followed by cefepime (40%; n = 117), ceftazidime (39%; n = 115), imipenem (36%; n = 106), meropenem (33%; n = 97), and ciprofloxacin (32%; n = 94). Forty-two percent (n = 126) of the isolates were positive for ESBL according to the double-disc synergy test. The blaCTX-M-15 cephalosporinase was observed in 32% (n = 40/126), while 26% (n = 33/126) werepositive for blaNDM-1 carbapenemase. Aminoglycoside resistance gene aac(3)IIIawas observed in 16% (n = 20/126), and glycylcyclines resistance gene tet(A) was observed in 12% (n = 15/126) of the isolates. A total of 23 sequence types were detected, including ST1963 (12%; n = 16), followed by ST381 (11%; n = 14), ST234 (10%; n = 13), ST145 (58%; n = 10), ST304 (57%; n = 9), ST663 (5%; n = 7), and a novel strain. In ESBL-producing P. aeruginosa, 12 different Incompatibility groups (Inc) were observed, the most common being IncFI, IncFIS, and IncA/C. The MOBP was the most common plasmid type, followed by MOBH, MOBF, and MOBQ. Discussion: Our data suggest that the spread of antibiotic resistance is likely due toclonal spread and dissemination of different clinical strains of P. aeruginosa harbouring different plasmids. This is a growing threat in hospitals particularly in young children which needs robust prevention strategies.

Tumor Microenvironment Mediated Spermidine-Metal-Immunopeptide Nanocomplex for Boosting Ferroptotic Immunotherapy of Lymphoma.

Immunotherapy as an alternative treatment strategy for B-cell lymphoma is undesirable because of tumor heterogeneity and immune surveillance. Spermidine (SPM), as a regulator of the tumor microenvironment (TME), can facilitate the release of damage-associated molecular patterns (DAMPs) from cancer cells, promote immune recognition, and thus alleviate immune surveillance in the TME. Hence, in this work, self-assembled spermidine-based metal-immunopeptide nanocomplexes (APP-Fe NCs; APP is anti-programmed death ligand-1 peptide) with pH-responsive release kinetics were prepared via the flash nanocomplexation (FNC) technique based on the noncovalent interaction between APP-SPM-dextran (DEX) and sodium tripolyphosphate (TPP) and coordination between Fe3+ and TPP. An in vitro study suggested that APP-Fe NCs effectively induce strong oxidative stress and mitochondrial dysfunction and subsequently lead to ferroptosis in cells by interfering with homeostasis in lymphoma cells. Further investigation on lymphoma mice models demonstrated that APP-Fe NCs effectively inhibited the growth and liver metastasis of lymphomas. Mechanistically, by triggering ferroptosis in tumor tissues, these spermidine-containing APP-Fe NCs efficiently facilitated the release of DAMPs and ultimately reshaped TME to enhance immunotherapy efficacy in lymphoma. Combined with its good histocompatibility and facile preparation technique, this pH-responsive APP-Fe NCs with regulation on TME may hold potential for cascade amplification on the combinative immunotherapy of lymphoma in the clinic.