Results From First-in-Human Phase I Dose-Escalation Study of a Novel Bicycle Toxin Conjugate Targeting EphA2 (BT5528) in Patients With Advanced Solid Tumors.

PURPOSE: BT5528 is a Bicycle Toxin Conjugate, a novel class of chemically synthesized molecules, comprising a bicyclic peptide targeting EphA2 tumor antigen, linked to a cytotoxin (monomethyl auristatin E [MMAE]). EphA2 is overexpressed in many solid tumors and contributes to oncogenesis, tumor-associated angiogenesis, and metastasis. MATERIALS AND METHODS: The primary objectives were to investigate the safety and tolerability of BT5528 and to define the maximum-tolerated dose, if observed, and recommended phase II dose (RP2D)/expansion dose. Dose escalation exploring once every week or once every 2 weeks administration of BT5528 employed a 3 + 3 dose-escalation design for the first two dose levels, followed by a Bayesian logistic regression model. Secondary and exploratory end points included preliminary efficacy and the pharmacokinetics of BT5528 and MMAE. RESULTS: Forty-five patients were enrolled and received BT5528 doses between 2.2 mg/m2 once every week to 10.0 mg/m2 once every 2 weeks within the dose-escalation stage of the study. The most frequent BT5528-related adverse events (AEs) were nausea (44.4%), diarrhea (35.6%), and fatigue (33.3%), and the most common grade ≥3 BT5528-related AE was neutropenia/neutrophil count decrease (22.2%). Dose level 6.5 mg/m2 once every 2 weeks was selected as a RP2D. At 6.5 mg/m2 once every 2 weeks, the overall response rate was 6.7%, and the disease control rate was 20.0%. BT5528 and MMAE pharmacokinetics are generally dose proportional. BT5528 has a short half-life (0.4-0.7 hours), and the half-life of MMAE is longer (35-47 hours). CONCLUSION: BT5528 was well tolerated and demonstrated favorable and preliminary antitumor activity. We believe these data provide preliminary validation of a Bicycle Toxin Conjugate approach to EphA2 tumor antigen. The study is ongoing and is evaluating BT5528 as monotherapy at a RP2D of 6.5 mg/m2 once every 2 weeks.

A turn-on anthraquinone-derived colorimetric and fluorometric dual-mode probe for highly selective Hg2+ determination and bioimaging in living organisms.

Mercury ion (Hg2+) is considered a harmful neurotoxin, and real-time monitoring of Hg2+ concentrations in environmental and biological samples is critical. Fluorescent probes are a rapidly emerging visualization tool owing to their simple design and good selectivity. Herein, a novel fluorescence (FL) probe 2-(4-((6-((quinolin-8-yloxy)methyl)pyridin-2-yl)methyl)piperazin-1-yl)anthracene-9,10-dione (QPPA) is designed using piperazine as a linker between the anthraquinone group, which serves as a fluorophore, and N4O as the Hg2+ ligand. The probe exhibits FL "turn-on" sensing of Hg2+ because the complex inhibits the photo-induced electron transfer (PET) process. Moreover, QPPA can overcome the invasion by other possible cations, resulting in a clear color change from orange to colorless with the addition Hg2+. The chelation of QPPA with Hg2+ in a 1:1 ratio. Subsequently, the theoretically determined binding sites of the ligand to Hg2+ are validated through 1H NMR titration. The in situQPPA-Hg2+ complex can be subjected to Hg2+ extraction following the introduction of S2- owing to its robust binding capacity. The exceptional limit of detection values for Hg2+ and S2- are obtained as 63.0 and 79.1 nM (S/N = 3), respectively. Moreover, QPPA can display bright red FL in the presence of Hg2+ in different biological specimens such as HeLa cells, zebrafish, onion root tip tissues, and water flea Daphnia carinata, further providing an effective strategy for environmental monitoring and bioimaging of Hg2+ in living organisms.

The Epidemiology of Pathogens in Community-Acquired Pneumonia Among Children in Southwest China Before, During and After COVID-19 Non-pharmaceutical Interventions: A Cross-Sectional Study.

OBJECTIVE: This study aimed to investigate the pathogen epidemiology of community-acquired pneumonia (CAP) among children in Southwest China before, during and after the COVID-19 non-pharmaceutical interventions (NPIs). METHODS: Pathogen data of hospitalised children with CAP, including multiple direct immunofluorescence test for seven viruses, bacterial culture and polymerase chain reaction (PCR) for Mycoplasma pneumoniae, were analysed across three phases: Phase I (pre-NPIs: 1 January 2019 to 31 December 2019), Phase II (NPI period: 1 January 2020 to 31 December 2020) and Phase III (post-NPIs: 1 January 2023 to 31 December 2023). RESULTS: A total of 7533 cases were enrolled, including 2444, 1642 and 3447 individuals in Phases I, II and III, respectively. M. pneumoniae predominated in Phases I and III (23.4% and 35.5%, respectively). In Phase II, respiratory syncytial virus (RSV) emerged as the primary pathogen (20.3%), whereas detection rates of influenza A virus (Flu A) and M. pneumoniae were at a low level (1.8% and 9.6%, respectively). In Phase III, both Flu A (15.8%) and M. pneumoniae epidemic rebounded, whereas RSV detection rate returned to Phase I level, and detection rates of Streptococcus pneumoniae and Haemophilus influenzae decreased significantly compared to those in Phase I. Detection rates of adenovirus and parainfluenza virus type 3 decreased phase by phase. Age-stratified analysis and monthly variations supported the above findings. Seasonal patterns of multiple pathogens were disrupted during Phases II and III. CONCLUSIONS: COVID-19 NPIs exhibited a distinct impact on CAP pathogen epidemic among children, with post-NPIs increases observed in M. pneumoniae and Flu A prevalence. Continuous pathogen monitoring is crucial for effective prevention and control of paediatric CAP.

Compressible Hollow Microlasers in Organoids for High-Throughput and Real-Time Mechanical Screening.

Mechanical stress within organoids is a pivotal indicator in disease modeling and pharmacokinetics, yet current tools lack the ability to rapidly and dynamically screen these mechanics. Here, we introduce biocompatible and compressible hollow microlasers that realize all-optical assessment of cellular stress within organoids. The laser spectroscopy yields identification of cellular deformation at the nanometer scale, corresponding to tens of pascals stress sensitivity. The compressibility enables the investigation of the isotropic component, which is the fundamental mechanics of multicellular models. By integrating with a microwell array, we demonstrate the high-throughput screening of mechanical cues in tumoroids, establishing a platform for mechano-responsive drug screening. Furthermore, we showcase the monitoring and mapping of dynamic contractile stress within human embryonic stem cell-derived cardiac organoids, revealing the internal mechanical inhomogeneity within a single organoid. This method eliminates time-consuming scanning and sample damage, providing insights into organoid mechanobiology.

Comprehensive cognition of yak (Bos grunniens) AIFM2 gene and its anti-ferroptosis role in bisphenol A-induced fetal fibroblast model.

Apoptosis-inducing factor mitochondrion-associated 2 (AIFM2) has been identified as a gene with anti-ferroptosis properties. To explore whether AIFM2 exerts anti-ferroptosis role in yaks (Bos grunniens), we cloned yak AIFM2 gene and analyzed its biological characteristics. The coding region of AIFM2 had 1122 bp and encoded 373 amino acids, which was conserved in mammals. Next, RT-qPCR results showed an extensive expression of AIMF2 in yak tissues. Furthermore, we isolated yak skin fibroblasts (YSFs) and established a bisphenol A (BPA)-induced ferroptosis model to further investigate the role of AIFM2. BPA elevated oxidative stress (reactive oxygen species, ROS) and lipid peroxidation (malondialdehyde, MDA and BODIPY), and reduced cell viability and antioxidant capacity (glutathione, GSH), with the severity depending on the dosage. Of note, a supplement of Ferrostatin-1 (Fer), an inhibitor of ferroptosis, restored the previously mentioned indicators. Subsequently, we constructed an AIFM2 overexpression vector and designed AIFM2 specific interfering siRNAs, which were transfected into YSFs. The results showed that overexpressing AIFM2 alleviated ferroptosis, characterizing by significant changes of cell viability, ROS, BODIPY, MDA and GSH. Meanwhile, interfering AIFM2 aggravated ferroptosis, demonstrating the critical anti-ferroptosis role of the yak AIFM2 gene. This study shed light on further exploring the molecular mechanism of AIFM2 in plateau adaptability.

Development and Validation of an ICU-Venous Thromboembolism Prediction Model Using Machine Learning Approaches: A Multicenter Study.

Purpose: The purpose of this study was to establish and validate machine learning-based models for predicting the risk of venous thromboembolism (VTE) in intensive care unit (ICU) patients. Patients and Methods: The clinical data of 1494 ICU patients who underwent Doppler ultrasonography or venography between December 2020 and March 2023 were extracted from three tertiary hospitals. The Boruta algorithm was used to screen the essential variables associated with VTE. Five machine learning algorithms were employed: Random Forest (RF), eXtreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), Gradient Boosting Decision Tree (GBDT), and Logistic Regression (LR). Hyperparameter optimization was conducted on the predictive model of the training dataset. The performance in the validation dataset was measured using indicators, including the area under curve (AUC) of the receiver operating characteristic (ROC) curve, specificity, and F1 score. Finally, the optimal model was interpreted using the SHapley Additive exPlanation (SHAP) package. Results: The incidence of VTE among the ICU patients in this study was 26.04%. We screened 19 crucial features for the risk prediction model development. Among the five models, the RF model performed best, with an AUC of 0.788 (95% CI: 0.738-0.838), an accuracy of 0.759 (95% CI: 0.709-0.809), a sensitivity of 0.633, and a Brier score of 0.166. Conclusion: A machine learning-based model for prediction of VTE in ICU patients were successfully developed, which could assist clinical medical staff in identifying high-risk populations for VTE in the early stages so that prevention measures can be implemented to reduce the burden on the ICU patients.

Nursing-sensitive Indicators for Quality Improvement for Patients with Traumatic Brain Injury.

Context: Traumatic brain injury (TBI) can result in lifelong cognitive, emotional, and motor impairments. The emergency department is the first stop for diagnosing and treating patients with acute TBI, and the quality of nursing care can greatly influence the prognosis and progression of a patient's condition. Currently, standardized evaluation tools are lacking in the world for assessment of the quality of nursing care. Objective: The study intended to construct a nursing-sensitive indicator system for TBI patients, based on the scientific method of evidence-based nursing and the Delphi method, to provide a quantitative tool for emergency-nursing personnel to manage the quality of care for those patients. Design: Based on the Joanna Briggs Institute's evidence-based healthcare model, the research team performed a literature search and consulted reference guidelines, conducted two rounds of consultations with experts. sensitive indicators for quality of care, and constructed the sensitive indicator system. The team then conducted a retrospective study. Setting: The study took place in the department of emergency surgery at Shanxi Norman Bethune Hospital in Taiyuan, Shanxi, China. Participants: Participants were 56 patients with TBI who had been admitted to the emergency department between January 2022 and December 2022 and 44 patients with TBI who had been admitted to the emergency department between January 2023 and December 2023. Interventions: The research team assigned: (1) the 56 patients in the first group to the control group, who received routine nursing care and (2) the 44 patients in the second group to the intervention group, who received treatment using the sensitive indicator system for the quality of emergency care for TBI patients as well as routine care. Outcome Measures: In the verification study, the research team compared the group's rescue effects and satisfaction with emergency care. Results: In the first and second rounds of inquiries to experts, the research team distributed 25 questionnaires each time, with 25 valid questionnaires collected both times. The response rate for both rounds of inquiries was 100%. The expert authority coefficients for the first and second rounds of inquiries are 0.844 and 0.878, respectively. The sensitive indicator system's final construction included three primary indicators, seven secondary indicators, and 17 tertiary indicators. The AUC for the sensitive indicators was 0.8355882. The indicator system's use found that the intervention group had a shorter time to diagnosis (P < .001), emergency-department stay (P < .001), and emergency-department-to-surgery time (P < .001) compared to the control group. The intervention group also has a higher success rate for the emergency treatment (P = .014) and a higher nursing satisfaction with nurse-patient communications (P = .003), first-aid operations (P < .001), nursing attitudes (P < .001), and emergency environment (P < .001) compared to the control group. Conclusions: The process of constructing quality-sensitive indicators for the nursing care of TBI patients was scientific. The constructed quality-sensitive indicator system for the care of patients with TBI covers key factors that influence the quality of care. It's highly practical and has the ability to transform certain indicators, which can better guide the management of quality of care for TBI.

A review on advancements in atmospheric microplastics research: The pivotal role of machine learning.

Microplastics (MPs), recognized as emerging pollutants, pose significant potential impacts on the environment and human health. The investigation into atmospheric MPs is nascent due to the absence of effective characterization methods, leaving their concentration, distribution, sources, and impacts on human health largely undefined with evidence still emerging. This review compiles the latest literature on the sources, distribution, environmental behaviors, and toxicological effects of atmospheric MPs. It delves into the methodologies for source identification, distribution patterns, and the contemporary approaches to assess the toxicological effects of atmospheric MPs. Significantly, this review emphasizes the role of Machine Learning (ML) and Artificial Intelligence (AI) technologies as novel and promising tools in enhancing the precision and depth of research into atmospheric MPs, including but not limited to the spatiotemporal dynamics, source apportionment, and potential health impacts of atmospheric MPs. The integration of these advanced technologies facilitates a more nuanced understanding of MPs' behavior and effects, marking a pivotal advancement in the field. This review aims to deliver an in-depth view of atmospheric MPs, enhancing knowledge and awareness of their environmental and human health impacts. It calls upon scholars to focus on the research of atmospheric MPs based on new technologies of ML and AI, improving the database as well as offering fresh perspectives on this critical issue.

Emission of Intermediate Volatile Organic Compounds from Animal Dung and Coal Combustion and Its Contribution to Secondary Organic Aerosol Formation in Qinghai-Tibet Plateau, China.

Intermediate volatility organic compounds (IVOCs) are important precursors to secondary organic aerosols (SOAs), but they are often neglected in studies concerning SOA formation. This study addresses the significant issue of IVOCs emissions in the Qinghai-Tibetan plateau (QTP), where solid fuels are extensively used under incomplete combustion conditions for residential heating and cooking. Our field measurement data revealed an emission factor of the total IVOCs (EFIVOCs) ranging from 1.56 ± 0.03 to 9.97 ± 3.22 g/kg from various combustion scenarios in QTP. The markedly higher EFIVOCs in QTP than in plain regions can be attributed to oxygen-deficient conditions. IVOCs were dominated by gaseous phase emissions, and the primary contributors of gaseous and particulate phase IVOCs are the unresolved complex mixture and alkanes, respectively. Total IVOCs emissions during the heating and nonheating seasons in QTP were estimated to be 31.7 ± 13.8 and 6.87 ± 0.45 Gg, respectively. The estimated SOA production resulting from combined emissions of IVOCs and VOCs is nearly five times higher than that derived from VOCs alone. Results from this study emphasized the pivotal role of IVOCs emissions in air pollution and provided a foundation for compiling emission inventories related to solid fuel combustion and developing pollution prevention strategies.

A potential antiviral role for CCR5+CD8+ T cells in children with hepatitis B.

While dysfunctional exhausted CD8+ T cells hamper viral control when children acquire hepatitis B virus (HBV) infection, it's crucial to recognize that CD8+ T cells have diverse phenotypes and functions. This study explored a subset of CD8+ T cells expressing C-C chemokine receptor type 5 (CCR5) in children with HBV infection. Thirty-six patients in the immune tolerant group, 33 patients in the immune active group, 55 patients in the combined response group, and 22 healthy control children were enrolled. The frequency, functional molecules, and effector functions of the CCR5+CD8+ T cell population in different groups were evaluated. The frequency of CCR5+CD8+ T cells correlated positively with the frequency of CCR5+CD4+ T cells and patient age, and it correlated negatively with alanine aminotransferase, aspartate transaminase, HBV DNA, hepatitis B surface antigen, and lactic dehydrogenase levels. CCR5+CD8+ T cells had higher levels of inhibitory and activated receptors and produced higher levels of IFN-γ, IL-2, and TNF-α than CCR5-CD8+ T cells. CCR5+CD8+ T cells were partially exhausted but possessed a stronger antiviral activity than CCR5-CD8+ T cells. The identification of this subset increases our understanding of CD8+ T cell functions and serves as a potential immunotherapeutic target for children with HBV infection.

Transcriptional regulation of TacL-mediated lipoteichoic acids biosynthesis by ComE during competence impacts pneumococcal transformation.

Competence development is essential for bacterial transformation since it enables bacteria to take up free DNA from the surrounding environment. The regulation of teichoic acid biosynthesis is tightly controlled during pneumococcal competence; however, the mechanism governing this regulation and its impact on transformation remains poorly understood. We demonstrated that a defect in lipoteichoic acid ligase (TacL)-mediated lipoteichoic acids (LTAs) biosynthesis was associated with impaired pneumococcal transformation. Using a fragment of tacL regulatory probe as bait in a DNA pulldown assay, we successfully identified several regulatory proteins, including ComE. Electrophoretic mobility shift assays revealed that phosphomimetic ComE, but not wild-type ComE, exhibited specific binding to the probe. DNase I footprinting assays revealed the specific binding sequences encompassing around 30 base pairs located 31 base pairs upstream from the start codon of tacL. Expression of tacL was found to be upregulated in the ΔcomE strain, and the addition of exogenous competence-stimulating peptide repressed the tacL transcription in the wild-type strain but not the ΔcomE mutant, indicating that ComE exerted a negative regulatory effect on the transcription of tacL. Mutation in the JH2 region of tacL upstream regulatory sequence led to increased LTAs abundance and displayed higher transformation efficiency. Collectively, our work identified the regulatory mechanisms that control LTAs biosynthesis during competence and thereby unveiled a repression mechanism underlying pneumococcal transformation.

The Timing and Dose Effect of Acupuncture on Pregnancy Outcomes for Infertile Women Undergoing In Vitro Fertilization and Embryo Transfer: A Systematic Review and Meta-Analysis.

Background: Women undergoing in vitro fertilization and embryo transfer (IVF-ET) often utilize acupuncture to enhance pregnancy outcomes. Yet, the optimal timing for acupuncture sessions and the relationship between dosage and effect remain uncertain. Objectives: To investigate the impact of the timing and dosage of acupuncture on pregnancy outcomes, drawing on existing research. Methods: A comprehensive search of eight databases was conducted from their inception to January 14th, 2023, without restrictions on language. Only randomized controlled trials comparing acupuncture with either sham acupuncture or no adjuvant treatment were selected for inclusion. This meta-analysis assessed the efficacy of acupuncture in IVF-ET, analyzing the influence of varied timing and dosage on pregnancy outcomes. Subgroup analyses were undertaken to address any heterogeneity across the studies. Results: A total of 38 RCTs involving 5,991 participants were analyzed. In infertile women undergoing IVF fresh cycles, acupuncture performed during controlled ovarian hyperstimulation (COH) significantly increased the clinical pregnancy rate (CPR) (relative risk [RR] = 1.33, 95% confidence interval [CI]: 1.07-1.65, p = 0.01), whereas acupuncture administered either before COH or on the day of ET did not demonstrate reproductive benefits. Regarding frozen cycles, acupuncture before freeze-thaw embryo transfer (FET) significantly enhanced the CPR (RR = 1.71, 95% CI: 1.36-2.16, p < 0.00001) and live birth rate (LBR) (RR = 2.40, 95% CI: 1.20-4.79, p = 0.01). Improvements in CPR were observed across all dosage groups, but only the high-dosage group showed a significant increase in LBR (RR = 1.75, 95% CI: 1.05-2.92, p = 0.03). Conclusions: Timing and dosage of acupuncture are crucial factors affecting pregnancy outcomes in IVF-ET. For women undergoing IVF fresh cycles, acupuncture during COH yielded more significant reproductive benefits. In addition, acupuncture before freeze-thaw embryo transfer (FET) was associated with improved pregnancy outcomes in frozen cycles. Furthermore, higher dosages of acupuncture were linked to more favorable outcomes.

Inhibition of Nogo-B reduces the progression of pancreatic cancer by regulation NF-κB/GLUT1 and SREBP1 pathways.

Pancreatic cancer (PC) is a lethal disease and associated with metabolism dysregulation. Nogo-B is related to multiple metabolic related diseases and types of cancers. However, the role of Nogo-B in PC remains unknown. In vitro, we showed that cell viability and migration was largely reduced in Nogo-B knockout or knockdown cells, while enhanced by Nogo-B overexpression. Consistently, orthotopic tumor and metastasis was reduced in global Nogo knockout mice. Furthermore, we indicated that glucose enhanced cell proliferation was associated to the elevation expression of Nogo-B and nuclear factor κB (NF-κB). While, NF-κB, glucose transporter type 1 (GLUT1) and sterol regulatory element-binding protein 1 (SREBP1) expression was reduced in Nogo-B deficiency cells. In addition, we showed that GLUT1 and SREBP1 was downstream target of NF-κB. Therefore, we demonstrated that Nogo deficiency inhibited PC progression is regulated by the NF-κB/GLUT1 and SREBP1 pathways, and suggested that Nogo-B may be a target for PC therapy.

Single-cell transcriptome reveals highly complement activated microglia cells in association with pediatric tuberculous meningitis.

Background: Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB) causing high mortality and disability. TBM arises due to immune dysregulation, but the underlying immune mechanisms are unclear. Methods: We performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells isolated from children (n=6) with TBM using 10 xGenomics platform. We used unsupervised clustering of cells and cluster visualization based on the gene expression profiles, and validated the protein and cytokines by ELISA analysis. Results: We revealed for the first time 33 monocyte populations across the CSF cells and PBMCs of children with TBM. Within these populations, we saw that CD4_C04 cells with Th17 and Th1 phenotypes and Macro_C01 cells with a microglia phenotype, were enriched in the CSF. Lineage tracking analysis of monocyte populations revealed myeloid cell populations, as well as subsets of CD4 and CD8 T-cell populations with distinct effector functions. Importantly, we discovered that complement-activated microglial Macro_C01 cells are associated with a neuroinflammatory response that leads to persistent meningitis. Consistently, we saw an increase in complement protein (C1Q), inflammatory markers (CRP) and inflammatory factor (TNF-α and IL-6) in CSF cells but not blood. Finally, we inferred that Macro_C01 cells recruit CD4_C04 cells through CXCL16/CXCR6. Discussion: We proposed that the microglial Macro_C01 subset activates complement and interacts with the CD4_C04 cell subset to amplify inflammatory signals, which could potentially contribute to augment inflammatory signals, resulting in hyperinflammation and an immune response elicited by Mtb-infected tissues.

Analysis of Risk Factors for Intraoperative Bleeding in the Surgical Treatment of Cesarean Scar Pregnancy and Development of Predictive Models.

Objective: The objective of this study was to investigate the risk factors associated with cesarean scar pregnancy (CSP) and to develop a model for predicting intraoperative bleeding risk. Methods: We retrospectively analyzed the clinical data of 208 patients with CSP who were admitted to the People's Hospital of Leshan between January 2018 and December 2022. Based on whether intraoperative bleeding was ≥ 200 mL, we categorized them into two groups for comparative analysis: the excessive bleeding group (n = 27) and the control group (n = 181). Identifying relevant factors, we constructed a prediction model and created a nomogram. Results: We observed that there were significant differences between the two groups in several parameters. These included the time of menstrual cessation (P = 0.002), maximum diameter of the gestational sac (P < 0.001), thickness of the myometrium at the uterine scar (P = 0.001), pre-treatment blood HCG levels (P = 0.016), and the grade of blood flow signals (P < 0.001). We consolidated the above data and constructed a clinical prediction model. The model exhibited favorable results in terms of predictive efficacy, discriminative ability (C-index = 0.894, specificity = 0.834, sensitivity = 0.852), calibration precision (mean absolute error = 0.018), and clinical decision-making utility, indicating its effectiveness. Conclusion: The clinical prediction model related to the risk of hemorrhage that we developed in this experiment can assist in the development of appropriate interventions and effectively improve patient prognosis.

Prevalence of Respiratory Viruses in Children With Acute Respiratory Infections in Shanghai, China, From 2013 to 2022.

BACKGROUND: A variety of viruses can cause acute respiratory infections (ARIs), resulting in a high disease burden worldwide. To explore the dominant viruses and their prevalence characteristics in children with ARIs, comprehensive surveillance was carried out in the Pudong New Area of Shanghai. METHODS: Between January 2013 and December 2022, the basic and clinical information, and respiratory tract specimens of 0-14 years old children with ARIs were collected in five sentinel hospitals in Shanghai Pudong. Each specimen was tested for eight respiratory viruses, and the positive rates of different age groups, case types (inpatient or outpatient) were analyzed. RESULTS: In our study, 30.67% (1294/4219) children with ARIs were positive for at least one virus. Influenza virus (IFV) was the most commonly detected respiratory virus (349/4219, 8.27%), followed by respiratory syncytial virus (RSV) (217/4219, 5.14%), para-influenza virus (PIV) (215/4219, 5.10%), and human coronavirus (HCoV, including 229E, OC43, NL63, and HKU1) (184/4219, 4.36%). IFV was the leading respiratory virus in outpatients aged 5-14 years (201/1673, 12.01%); RSV was the most prevalent respiratory virus in both inpatients (61/238, 25.63%) and outpatients (4/50, 8.00%) for ARI patients aged <6 months old. For PIV, HMPV, HCoV, and HRV, the risk of infection usually was higher among young children. Co-infection with more than two viruses was seen in 3.25% (137/4219). CONCLUSIONS: IFV and RSV played important roles in ARIs among children, but the risk populations were different. There are needs for targeted diagnosis and treatment and necessary immunization and non-pharmaceutical interventions.

Nitroaromatic compounds in six major Chinese cities: Influence of different formation mechanisms on light absorption properties.

Nitroaromatic compounds (NACs) are important nitrogen organics in aerosol with strong light-absorbing and chemically reactive properties. In this study, NACs in six Chinese megacities, including Harbin (HB), Beijing (BJ), Xi'an (XA), Wuhan (WH), Chengdu (CD), and Guangzhou (GZ), were investigated for understanding their sources, gas-particle partitioning, and impact on BrC absorption properties. The concentrations of ΣNACs in PM2.5 in the six cities ranged from 9.15 to 158.8 ng/m3 in winter and from 2.02 to 9.39 ng/m3 in summer. Nitro catechols (NCs), nitro phenols (NPs), and nitro salicylic acids (NSAs) are the main components in ΣNACs, with NCs being dominant in particulate phase and NPs being dominant in the gas phase. Correlation analysis between different pollutant species revealed that coal and biomass combustions were the major sources of NACs in the northern cities during wintertime, while secondary formation dominated NACs in the southern cities during summertime. The contribution of ΣNACs to brown carbon (BrC) light absorption ranged from 0.85 to 7.98 % during the wintertime and 2.07-6.44 % during the summertime. The mass absorption efficiency at 365 nm (MAE365) were highest for 4-nitrocatechol (4NC, 17.4-89.0 m2/g), 4-methyl-5-nitrocatechol (4M5NC, 15.0-76.9 m2/g), and 4-nitroguaiacol (4NG, 11.7-59.8 m2/g). The formation of NCs and NG through oxidation and nitration of catechol and guaiacol led to a significant increase in aerosol light absorption. In contrast, NPs and NSAs formed by the photonitration and photooxidation in liquid phase showed high polarity but low light absorption ability, and the proportions of (NPs + NSAs) in the light absorption of ΣNACs were lower than 15.3 % in the six megacities.

A multicenter clinical epidemiology of pediatric pneumococcal meningitis in China: results from the Chinese Pediatric Bacterial Meningitis Surveillance (CPBMS) 2019-2020.

Objective: To analyze the clinical epidemiological characteristics including clinical features, disease prognosis of pneumococcal meningitis (PM), and drug sensitivity of S. pneumoniae isolates in Chinese children. Methods: A retrospective analysis was performed on the clinical, laboratory microbiological data of 160 hospitalized children less than 15 years of age with PM from January 2019 to December 2020 in 33 tertiary hospitals in China. Results: A total of 160 PM patients were diagnosed, including 103 males and 57 females The onset age was 15 days to 15 years old, and the median age was 1 year and 3 months. There were 137 cases (85.6%) in the 3 months to <5 years age group, especially in the 3 months to <3 years age group (109 cases, 68.2%); S. pneumoniae was isolated from cerebrospinal fluid (CSF) culture in 95(35.6%), and 57(35.6%) in blood culture. The positive rates of S. pneumoniae detection by CSF metagenomic next-generation sequencing (mNGS)and antigen detection method were 40.2% (35/87) and 26.9% (21/78). Fifty-five cases (34.4%) had one or more predisposing factors of bacterial meningitis; and 113 cases (70.6%) had one or more extracranial infection diseases Fever (147, 91.9%) was the most common clinical symptom, followed by vomiting (61, 38.1%) and altered mental status (47,29.4%). Among 160 children with PM, the main intracranial imaging complications were subdural effusion and (or) empyema in 43 cases (26.9%), hydrocephalus in 24 cases (15.0%), cerebral abscess in 23 cases (14.4%), intracranial hemorrhage in 8 cases (5.0%), and other cerebrovascular diseases in 13 cases (8.1%) including encephalomalacia, cerebral infarction, and encephalatrophy. Subdural effusion and (or) empyema and hydrocephalus mainly occurred in children < 1 years old (90.7% (39/43) and 83.3% (20/24), respectively). 17 cases with PM (39.5%) had more than one intracranial imaging abnormality. S. pneumoniae isolates were completely sensitive to vancomycin (100.0%, 75/75), linezolid (100.0%,56/56), ertapenem (6/6); highly sensitive to levofloxacin (81.5%, 22/27), moxifloxacin (14/17), rifampicin (96.2%, 25/26), and chloramphenicol (91.3%, 21/23); moderately sensitive to cefotaxime (56.1%, 23/41), meropenem (51.1%, 23/45) and ceftriaxone (63.5, 33/52); less sensitive to penicillin (19.6%, 27/138) and clindamycin (1/19); completely resistant to erythromycin (100.0%, 31/31). The cure and improvement rate were 22.5% (36/160)and 66.3% (106/160), respectively. 18 cases (11.3%) had an adverse outcome, including 6 cases withdrawing treatment therapy, 5 cases unhealed, 5 cases died, and 2 recurrences. S. pneumoniae was completely susceptible to vancomycin (100.0%, 75/75), linezolid (100.0%, 56/56), and ertapenem (6/6); susceptible to cefotaxime, meropenem, and ceftriaxone in the order of 56.1% (23/41), 51.1% (23/45), and 63.5 (33/52); completely resistant to erythromycin (100.0%, 31/31). Conclusion: Pediatric PM is more common in children aged 3 months to < 3 years old. Intracranial complications mostly occur in children < 1 year of age with fever being the most common clinical manifestations and subdural effusion and (or) empyema and hydrocephalus being the most common complications, respectively. CSF non-culture methods can facilitate improving the detection rate of pathogenic bacteria. More than 10% of PM children had adverse outcomes. S. pneumoniae strains are susceptible to vancomycin, linezolid, ertapenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Genetic characterization of pediatric SARI-associated human adenoviruses in eight Chinese provinces during 2017-2021.

Human adenovirus (HAdV) is a significant viral pathogen causing severe acute respiratory infections (SARIs) in children. To improve the understanding of type distribution and viral genetic characterization of HAdV in severe cases, this study enrolled 3404 pediatric SARI cases from eight provinces of China spanning 2017-2021, resulting in the acquisition of 112 HAdV strains. HAdV-type identification, based on three target genes (penton base, hexon, and fiber), confirmed the diversity of HAdV types in SARI cases. Twelve types were identified, including species B (HAdV-3, 7, 55), species C (HAdV-1, 2, 6, 89, 108, P89H5F5, Px1/Ps3H1F1, Px1/Ps3H5F5), and E (HAdV-4). Among these, HAdV-3 exhibited the highest detection rate (44.6%), followed by HAdV-7 (19.6%), HAdV-1 (12.5%), and HAdV-108 (9.8%). All HAdV-3, 7, 55, 4 in this study belonged to dominant lineages circulating worldwide, and the sequences of the three genes demonstrated significant conservation and stability. Concerning HAdV-C, excluding the novel type Px1/Ps3H1F1 found in this study, the other seven types were detected both in China and abroad, with HAdV-1 and HAdV-108 considered the two main types of HAdV-C prevalent in China. Two recombinant strains, including P89H5F5 and Px1/Ps3H1F1, could cause SARI as a single pathogen, warranting close monitoring and investigation for potential public health implications. In conclusion, 5 years of SARI surveillance in China provided crucial insights into HAdV-associated respiratory infections among hospitalized pediatric patients.