Impact of COVID-19 Nonpharmaceutical Interventions on Respiratory Syncytial Virus Infections in Hospitalized Children.

BACKGROUND: Nonpharmaceutical interventions (NPIs) targeted at SARS-CoV-2 have remarkably affected the circulation of other respiratory pathogens, including respiratory syncytial virus (RSV). This study aimed to assess the changes in epidemiological and clinical characteristics of RSV infections in hospitalized children before and during the pandemic in Suzhou, China. METHODS: We prospectively enrolled children aged < 18 years who were hospitalized in Soochow University Affiliated Children's Hospital with acute lower respiratory infection (ALRIs) from January 2018 to July 2022. Changes in epidemiological and clinical characteristics of RSV infections were analyzed. RESULTS: Compared with the same period in 2018-2019, the difference in the overall positive rate of RSV was not statistically significant in 2020, while it increased significantly in 2021 (11.8% [662/5621] vs. 20.8% [356/1711], p < 0.001) and 2022 (9.0% [308/3406] vs. 18.9% [129/684], p < 0.001). Specifically, the positive rates declined considerably from October to December 2020 but sharply increased during the summer of 2021. Compared to prepandemic period, RSV infections were more frequently observed in older children during the pandemic. RSV-positive children exhibited milder clinical characteristics during the COVID-19 pandemic, including decreased proportion of patients with hospital stay ≥ 11 days (10.3% vs. 6.7%, p < 0.05), less requirement for oxygen therapy (13.7% vs. 6.9%, p < 0.001), and fewer cases of polypnea (12.2% vs. 9.7%, p < 0.05) and wheeze (50.1% vs. 42.9%, p < 0.001). CONCLUSIONS: The implementation of multilayered NPIs targeted at COVID-19 has affected the activity of RSV. Ongoing monitoring of RSV is warranted as the changing RSV epidemiology can provide valuable insights for future healthcare system planning.

Epidemiology and drug resistance analysis of bloodstream infections in an intensive care unit from a children's medical center in Eastern China for six consecutive years.

BACKGROUND: Children in the intensive care unit (ICU) who suffer from severe basic diseases and low immunity are usually in critical condition. It is crucial to assist clinicians in selecting the appropriate empirical antibiotic therapies for clinical infection control. METHODS: We retrospectively analyzed data from 281 children with bloodstream infection (BSI). Comparisons of basic data, pathogenic information, and drug resistance of the main bacteria were conducted. RESULTS: We detected 328 strains, including Gram-positive bacteria (223, 68%), mainly coagulase-negative Staphylococci (CoNS); Gram-negative bacteria (91, 27.7%); and fungi (14, 4.3%). The results of the binary logistic regression analysis showed that the main basic disease was an independent risk factor for death. Compared with Escherichia coli, Klebsiella pneumoniae exhibited a higher proportion of extended-spectrum ß-lactamases (ESBLs), and its resistance to some ß-lactamides and quinolones antibiotics were lower. Twenty-seven isolates of multidrug-resistant (MDR) bacteria were detected, of which carbapenem-resistant Acinetobacter baumannii (CRAB) accounted for the highest proportion (13, 48.2%). CONCLUSIONS: CoNS was the principal pathogen causing BSI in children in the ICU of children, and Escherichia coli was the most common Gram-negative pathogen. The main basic disease was an independent risk factor for death. It is necessary to continuously monitor patients with positive blood cultures, pay special attention to detected MDR bacteria, and strengthen the management of antibiotics and prevention and control of nosocomial infections.

Modeling the optimal seasonal monoclonal antibody administration strategy for respiratory syncytial virus (RSV) prevention based on age-season specific hospitalization rate of RSV in Suzhou, China, 2016-2022.

BACKGROUND: The approval of nirsevimab brings light to reducing the heavy disease burden caused by respiratory syncytial virus (RSV). Considering the seasonality of RSV, the timing of administrating monoclonal antibody (mAb) is critical to maximize health utility. This study aimed to model and seek the optimal seasonal mAb administration strategy for preventing RSV-associated hospitalization. METHODS: Age-season specific hospitalization rates for RSV-associated acute lower respiratory infection (RSV-ALRI) were estimated from a hospital-based birth cohort. Using these rates, we simulated and evaluated the effect of diverse mAb administration strategies on preventing RSV-ALRI hospitalization. Optimal strategies were selected based on their effectiveness and relative cost-effectiveness. RESULTS: Compared with the year-round strategy of administration mAb at birth for all children, 291 out of the 854 candidate strategies, featuring diverse administration timing and age thresholds, demonstrated a greater number of averted RSV-ALRI hospitalizations and a lower number needed to treat (NNT). The NNT represents the number of mAb doses needed to prevent one case of RSV-ALRI hospitalization. Among the 291 strategies, administration mAb to children born in July-January or August-January at birth and administrating to the remaining <12 months old children in September, exhibited the highest increase in averted RSV-ALRI hospitalizations than the year-round strategy, with a magnitude of 23 %, while also achieve an 18 % reduction in NNT. CONCLUSION: Administrating monoclonal antibodies to children born in July to January at birth, and administrating to the remaining <1-year-old children in September or October would be the optimal seasonal mAb administration strategy for children in Suzhou, China.

Are we ready to face the next wave of RSV surge after the COVID-19 Omicron pandemic in China?

Background: China had its first wave of COVID-19 in 2020 and second wave of COVID-19 Omicron in 2022. The number of RSV cases decreased sharply in 2020 and 2022. Investigation of the resurge of RSV infections after the first wave of COVID-19 will guide us to take preventive actions before the resurge of RSV infections after the second wave of COVID-19 Omicron. Methods: We analysed epidemiological and clinical data of 59934 patients with lower respiratory tract infections (LRTI) from a prospective long-term cohort surveillance programme in Suzhou, China, collected from February 2016 to January 2022. The annual incidence of RSV infection in children aged<16 years in 2020 and 2021 was compared with the pre-pandemic years 2016 to 2019. We also compared the clinical characteristics, and RSV-related ICU admissions between pre-pandemic years and 2021. Results: Among children with LRTI, the positive rate of RSV increased by 70.7% in 2021 compared to the average level in the pre-pandemic years. The RSV resurge in 2021 was most prominently in children aged 2-4 years (a significant rise compared with the expected value 149.1%; 95%CI, 67.7% to 378%, P<.01). The percentage of RSV-related ICU admissions decreased in 2021 (3.2% vs 6.7%, P<0.01). The death rate of RSV infections in 2021 was 0.2%, while that in pre-pandemic years was only 0.02%. RSV-associated death in immunocompetent children (complicated by necrotizing encephalitis) was firstly occurred in 2021. Conclusions: Our findings raise concerns for RSV control in Southeast China after the COVID-19 pandemic especially for children aged 2-4 years. Although ICU admissions were significantly reduced in this resurgence, we could not ignore the increase of RSV-associated death.

Study on Shrinkage in Alkali-Activated Slag-Fly Ash Cementitious Materials.

Traditional silicate cement materials produce a large amount of CO2 during production, making it urgent to seek alternatives. Alkali-activated slag cement is a good substitute, as its production process has low carbon emissions and energy consumption, and it can comprehensively utilize various types of industrial waste residue while possessing superior physical and chemical properties. However, the shrinkage of alkali-activated concrete can be larger than that of traditional silicate concrete. To address this issue, the present study utilized slag powder as the raw material, sodium silicate (water glass) as the alkaline activator, and incorporated fly ash and fine sand to study the dry shrinkage and autogenous shrinkage values of alkali cementitious material under different content. Furthermore, combined with the change trend of pore structure, the impact of their content on the drying shrinkage and autogenous shrinkage of alkali-activated slag cement was discussed. Based on the author's previous research, it was found that by sacrificing a certain mechanical strength, adding fly ash and fine sand can effectively reduce the drying shrinkage and autogenous shrinkage values of alkali-activated slag cement. The higher the content, the greater the strength loss of the material and the lower the shrinkage value. When the fly ash content was 60%, the drying shrinkage and autogenous shrinkage of the alkali-activated slag cement mortar specimens decreased by about 30% and 24%, respectively. When the fine sand content was 40%, the drying shrinkage and autogenous shrinkage of the alkali-activated slag cement mortar specimens decreased by about 14% and 4%, respectively.

Lymph nodes primary staging of colorectal cancer in 18F-FDG PET/MRI: a systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic efficacy of 18F-FDG PET/MRI for lymph node (LN) metastasis primary staging in patients with colorectal cancer (CRC). METHODS: This study was conducted and reported in accordance with the PRISMA-DTA statement. Electronic databases (PubMed, Embase, Cochrane Library) were searched for studies on 18F-FDG PET/MRI for diagnosing LN metastasis. The pooled sensitivity (SEN), specificity (SPE), and area under the curve (AUC) were applied to assess the diagnostic performance. Heterogeneity was identified and processed using meta-regression and sensitivity analysis. All data analyses were performed via STATA 15 and Meta-Disc 1.4 software. RESULTS: There were finally 7 studies included, involving a total of 184 patients. The Spearman rank correlation coefficient was 0.108 (P = 0.818), with no threshold-effect observed. The pooled SEN was 0.81 (95%CI 0.66-0.90) and the SPE was 0.89 (95% CI 0.73-0.96). In sub-groups, prospective groups demonstrated to have the highest SEN of 0.92 (95%CI 0.79-1.00). The studies conducted by Catalano et al. and Kang et al. were considered to be potential sources of heterogeneity. CONCLUSION: 18F-FDG PET/MRI has shown remarkable diagnostic performance in identification of LN metastases in newly diagnosed CRC patients. It would be of great application value for the primary staging of CRC lymph node metastases.

Epidemiological and clinical characteristics of human rhinovirus caused bronchiolitis in children in Southeast China.

BACKGROUND: Human rhinovirus (hRV) is a critical viral pathogen implicated in bronchiolitis in children. However, there is no study on hRV bronchiolitis in children from Southeast China. The aim of this study was to determine the incidence and clinical features of hRV bronchiolitis in Southeast China. METHODS: The study was carried out in Children's Hospital of Soochow University on children admitted with the diagnosis of bronchiolitis from January 2013 to December 2014. hRV was tested using reverse-transcription polymerase chain reaction. RESULTS: hRV was identified in 140 of 797 specimens (17.6%). hRV was detected with a highest rate in June and August. The hRV positive rate in patients younger than 6 months of age was significantly lower than that in other age groups (P<0.01). The most common radiological finding was hyperinflation (51.4%). Patients with hRV infection were older and more likely to have eczema than those with RSV. CONCLUSIONS: The hRV was an important viral pathogen associated with bronchiolitis in children with an epidemic peak in summer. Most of patients were between 6 to 24 months and with a high presence of eczema.

Cellulose-based superhydrophobic wrinkled paper and electrospinning film as green tribolayer for water wave energy harvesting.

Water waves are viable low-carbon and renewable sources of power that can be optionally combined with triboelectric nanogeneration (TENG). Herein, we report on the synthesis of a TENG device based on green wrinkled paper tribolayers (W-TENG) assembled in grids (G-TENG) with channels that enable contact-separation modes involving metal balls that roll in phase with the waves. The paper's wrinkle wavelength and amplitude were adjusted by using a crepe blade at a given angle with respect to a drying cylinder, as well as the speed and torque. Polar hierarchical superhydrophobic cellulose micro/nanostructures, proposed as positive tribolayers with enhanced contact area and triboelectric density. The negative (biodegradable) tribolayers were prepared by electrospinning aqueous suspensions of polyvinyl alcohol and poly (ethylene oxide) reinforced with cellulose nanofibers. The charge transfer by the W-TENG reached up to 40 nC in air and retained 27 nC under 85 % relative humidity, ~5 and 7 times higher than those measured in planar TENG counterparts. A G-TENG array charging time (100-µF capacitor) of ~188 s was measured when the voltage of the capacitor raised to ~1.5 V. Overall, we introduce a new, scalable TENG system that is demonstrated for its remarkable ability to harvest blue energy.

Insight into carbapenem resistance and virulence of Acinetobacter baumannii from a children's medical centre in eastern China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) appeared more frequently in children and caused a great threat to global public health. It is urgent to investigate the carbapenem resistance and virulence of CRAB for clinicians to choose appropriate antibiotics. A retrospective study of 77 nonduplicated CRAB isolates was conducted. The carbapenem resistance and virulence genes were characterized by polymerase chain reaction (PCR) and gel electrophoresis. In the present study, A. baumannii mainly came from the intensive care unit and was mostly isolated from sputum samples. The carbapenem resistant rate of A. baumannii in 2018-2020 increased significantly compared with that in 2016-2017. All isolates had carbapenem resistant genes. They were highly resistant to a variety of antibiotics but were relatively sensitive to fluoroquinolones and tetracyclines. blaVIM and blaOXA-23 were detected in all isolates, whereas blaOXA-51, blaIMP and blaNDM were present in 98.70%, 67.53% and 31.17% of isolates, respectively. Notably, 1 isolate A. baumannii was identified as multidrug-resistant A. baumannii (MDR-AB), and 76 other extensively drug-resistance (XDR) isolates were also detected. Virulence genes were present in 100% of all isolates, including genes in the iron acquisition system (basJ), secretion systems (ompA, plcD), quorum sensing system (abaI) and biofilm formation (csuA). adeH, pgaA, and ptk were present in 98.70%, 98.70% and 94.80% of isolates, respectively. CRAB, which is prevalent in east China, carries a large number of drug resistance and virulence genes. Fluoroquinolones and tetracyclines may be effective antibiotics for the treatment of CRAB infection in children. An in-depth understanding of the resistance and virulence of CRAB is conducive to timely guiding empirical drug use and controlling infection.

Hypoxia-Regulated Tumor-Derived Exosomes and Tumor Progression: A Focus on Immune Evasion.

Tumor cells express a high quantity of exosomes packaged with unique cargos under hypoxia, an important characteristic feature in solid tumors. These hypoxic tumor-derived exosomes are, crucially, involved in the interaction of cancer cells with their microenvironment, facilitating not only immune evasion, but increased cell growth and survival, enhanced angiogenesis, epithelial-mesenchymal transition (EMT), therapeutic resistance, autophagy, pre-metastasis, and metastasis. This paper explores the tumor microenvironment (TME) remodeling effects of hypoxic tumor-derived exosome towards facilitating the tumor progression process, particularly, the modulatory role of these factors on tumor cell immune evasion through suppression of immune cells, expression of surface recognition molecules, and secretion of antitumor soluble factor. Tumor-expressed exosomes educate immune effector cells, including macrophages, monocytes, T cells, natural killer (NK) cells, dendritic cells (DCs), γδ T lymphocytes, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mast cells, and B cells, within the hypoxic TME through the release of factors that regulate their recruitment, phenotype, and function. Thus, both hypoxia and tumor-derived exosomes modulate immune cells, growth factors, cytokines, receptor molecules, and other soluble factors, which, together, collaborate to form the immune-suppressive milieu of the tumor environment. Exploring the contribution of exosomal cargos, such as RNAs and proteins, as indispensable players in the cross-talk within the hypoxic tumor microenvironmental provides a potential target for antitumor immunity or subverting immune evasion and enhancing tumor therapies.

Use of perampanel in children with refractory epilepsy of genetic aetiology

OBJECTIVE: Pathogenic mutations in refractory childhood epilepsy are being increasingly discovered. In this study, we analysed the efficacy and tolerability of perampanel as treatment for genetically-related refractory childhood epilepsy. METHODS: This prospective study, conducted in China, included 50 patients with refractory epilepsy of genetic aetiology, who were treated with adjunctive perampanel therapy. Perampanel treatment was considered effective when the seizure frequency was reduced by >50%. Perampanel treatment was evaluated over at least nine months, from January 2020. RESULTS: A total of 184 paediatric patients with refractory epilepsy received addon perampanel therapy, and of these, 128 received treatment for ≥nine months and underwent genetic analysis. Fifty children were identified with pathogenic or likely pathogenic variants. A total of 24 different causative monogenic mutations were found, and the most common causative monogenic variants were observed in the SCN1A gene (n = 15). The mean maximal dose of perampanel was 3.4±1.2 mg/day in responders. The response rates to perampanel in children with genetically-related refractory epilepsy (n=50) were 68.0%, 58.0%, and 46.0% at three, six and nine months post-initiation, respectively. Adverse events were reported in 23 patients (46.0%) with genetic aetiology. Somnolence, ataxia, and irritability were the most common adverse events. The response rates to perampanel in children with pathogenic or likely pathogenic variants associated with Dravet syndrome, tuberous sclerosis, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, Rett syndrome, and dentatorubral-pallidoluysian atrophy were high. SIGNIFICANCE: A low maintenance dose of perampanel may be effective and well-tolerated as adjunctive treatment in children with refractory epilepsy of genetic aetiology.

Synthesis of Holmium-Oxide Nanoparticles for Near-Infrared Imaging and Dye-Photodegradation.

The development of multifunctional nanomaterials has received growing research interest, thanks to its ability to combine multiple properties for severing highly demanding purposes. In this work, holmium oxide nanoparticles are synthesized and characterized by various tools including XRD, XPS, and TEM. These nanoparticles are found to emit near-infrared fluorescence (800-1100 nm) under a 785 nm excitation source. Imaging of the animal tissues was demonstrated, and the maximum imaging depth was found to be 2.2 cm. The synthesized nanoparticles also show the capability of facilitating dye (fluorescein sodium salt and rhodamine 6G) degradation under white light irradiation. The synthesized holmium oxide nanoparticles are envisioned to be useful for near-infrared tissue imaging and dye-degradation.

Epidemiology and Drug Resistance of Neonatal Bloodstream Infection Pathogens in East China Children's Medical Center From 2016 to 2020.

Introduction: To analyze the pathogen distribution and drug resistance of newborns with bloodstream infection (BSI) to help clinicians choose the appropriate empirical antibiotic therapy for clinical infection control. Methods: A total of 707 neonatal BSI cases were retrospectively analyzed. The bacteria in blood culture-positive samples were cultured, identified, and analyzed for drug sensitivity by routine methods. Statistical software was used to compare and analyze the basic data, pathogenic information, and drug resistance of the main bacteria. Results: The 5-year average positive rate of neonatal blood culture was 2.50%. The number of specimens submitted for inspection in 2020 significantly decreased. The top five infectious pathogens with the highest proportion were coagulase-negative Staphylococcus (67.35%), of which Staphylococcus epidermidis had the highest proportion (31.26%), followed by Escherichia coli (12.87%), Klebsiella pneumoniae (9.05%), Streptococcus agalactiae (8.63%), and Staphylococcus aureus (3.25%). Gram-positive (G+) bacteria were dominant, accounting for 69.45%. The main G+ bacteria had a higher rate of resistance to erythromycin and penicillin G. The main Gram-negative (G-) bacteria had a high resistance rate to a variety of antibacterial drugs, especially cephalosporin antibiotics. The overall resistance of K. pneumoniae was higher than that of E. coli. The top two fungi detected were Candida parapsilosis and Candida albicans. C. parapsilosis did not appear to be resistant to antibiotics, while C. albicans was resistant to multiple antibiotics. The type of microbial infection had a statistically significant difference in the positive rate among the age at delivery and wards (p < 0.05). There were significant differences in the detection of fungi among these groups (p < 0.05). The positive rate of G+ bacteria in the term newborns was significantly higher than that in the preterm newborns (p < 0.05). Preterm newborns are more susceptible to pneumonia. Conclusion: G+ bacteria are the main pathogens of neonatal BSI. Preterm newborns are more likely to be infected with G- bacteria. E. coli and K. pneumoniae are the most common G- bacteria, and both have a high resistance rate to a variety of antibacterial drugs. According to the distribution characteristics and drug resistance, it is very important to select antibiotics reasonably.

Downregulation of ADAM17 in pediatric immune thrombocytopenia impairs proplatelet formation.

BACKGROUND: Immune thrombocytopenia (ITP) is the most common etiology of acquired thrombocytopenia diseases in children. ITP is characterized by the immune-mediated decreased formation and excessive destruction of platelets. The pathogenesis and management of pediatric ITP are distinct from adult ITP. A disintegrin and metalloproteinase 17 (ADAM17) mediates the shedding of platelet receptor glycoprotein Ib α (GPIb α) in extracellular domain, functioning in the platelet activation and clearance. Our study aims to probe the roles and mechanisms of ADAM17 in pediatric ITP. METHODS: The differently expressed ADAM17 in megakaryocytes was obtained from children with ITP through the next-generation RNA-Sequence. Hematoxylin-eosin and Giemsa staining were performed for cell morphology identification. Flow cytometry was applied to assess autoantibodies against platelets, subtypes of lymphocytes, the surface expression level of ADAM17 and polyploidization of megakaryocytes, as well as the full-length GP Ib α. RESULTS: ADAM17 was significantly downregulated in megakaryocytes and platelets in children with ITP. Higher values of PDW and positive autoantibodies presence were observed in children with ITP. Loss of ADAM17 in mice led to defects in proplatelet formation and significantly elevated expression of phosphorylated myosin light chain (p-MLC) in megakaryocytes. CONCLUSIONS: Our study indicated that the downregulation of ADAM17 might be an innate cause of inefficient platelet production in pediatric ITP.

Rotavirus Infection in Children <5 Years of Age in Suzhou, China, 2013-2019: Disease Burden, Genotype Distribution and Seasonality.

BACKGROUND: This study aimed to determine the disease burden and strain distribution of rotavirus in children with diarrhea <5 years old in Suzhou, China. METHODS: The study was conducted among children with diarrhea <5 years old at Suzhou University Affiliated Children's Hospital from 2013 to 2019. Rotavirus antigen was detected in clinical laboratory and then sent to Suzhou Centers for Disease Control and Prevention for further molecular analysis. Group A rotavirus (RVA) was detected through enzyme-linked immunosorbent assays, and G-genotype and P-genotype of RVA were tested using reverse transcription-polymerase chain reaction. RESULTS: Of a total of 198,130 children with diarrhea, 70,813 (35.7%) were positive for RVA; RVA-related diarrhea was detected in 7798 (20.7%, n = 7798/37,710) inpatients and 63,015 (39.3%, n = 63,015/160,420) outpatients. Most children (92.0%, n = 65,171/70,813) positive for RVA were found as children <3 years old. Children 12-35 months old were reported as the highest prevalence among all age groups. The seasonal peak of RVA was in the autumn and winter. Among all 673 RVA strains genotyped, the G9P[8] strain was reported to be persistently predominant in the pediatric population from 2013 to 2019. CONCLUSIONS: The burden of diarrhea disease due to rotavirus infection remains high in Suzhou.

Epidemiology and Drug Resistance of Pathogens Isolated from Cerebrospinal Fluids at a Children's Medical Center in Eastern China During 2006-2020.

OBJECTIVE: To investigate the epidemiology and drug resistance of pathogens isolated from cerebrospinal fluid samples at a children's medical center in eastern China and provide the basis for anti-infection treatments. METHODS: In all, 307 non-duplicated strains of pathogens were isolated from cerebrospinal fluid samples in the Children's Hospital of Soochow University from January 2006 to December 2020. Mass spectrometry was used for pathogen identification. The VITEK 2 Compact system and Kirby-Bauer method were applied to determine antimicrobial susceptibility. RESULTS: Among the 307 isolates, gram-positive bacteria, gram-negative bacteria and fungi accounted for 60.26%, 34.53%, and 5.21%, respectively. The most prevalent pathogens were Streptococcus pneumoniae (26.06%), Escherichia coli (20.20%) and Streptococcus agalactiae (17.26%). The number of isolates was highest in winter. The most prevalent gram-positive bacterium in children <6 months old was Streptococcus agalactiae, while Streptococcus pneumoniae was the most in children were >6 months old. The drug resistance of gram-positive bacteria, fungi and Haemophilus influenza were not high. In addition, 35 strains of gram-negative bacteria produced extended-spectrum ß-lactamases (ESBLs) and 6 strains were identified as multidrug-resistant (MDR) bacteria. These strains showed much higher resistance to the antibiotics than other strains. CONCLUSION: Cases of meningitis among children have increased in the past 15 years and MDR bacteria were also identified. The emergence of MDR bacteria is a cause for great concern and requires further investigation.

[Enhanced Autophagy Suppresses Proplatelet Formation in Pediatric Immune Thrombocytopenia].

OBJECTIVE: To investigate the effect of enhanced autophagy in megakaryocyte to proplatelet formation in children with immune thrombocytopenia(ITP). METHODS: Giemsa staining and immunofluorescence staining were used to observe megakaryocyte morphology and proplatelet formation, Western blot was used to determine the expression of cytoskeleton protein and autophagy related protein. Autophagr regulation drugs Rap or 3-MA was used to regulate autophagy of megakaryocytes. RESULTS: Some vacuole-like structures was found in ITP megakaryocytes of the children, the expression of LC3II/I (ITP 1.32±0.18； Ctrl 0.49±0.16，P<0.05) and Atg5-Atg12 (ITP 0.69±0.17； Ctrl 0.12±0.08，P<0.05) was significantly higher in ITP children as compared with those in control group. The immu- nofluorescence staining showed that the cytoskeleton arrangement in megakaryocytes of ITP children was abnormal, and the phosphorylation of myosin light chain was also increased(ITP 0.74±0.09, Ctrl 0.05±0.02，P<0.05). In vitro, inducer or inhibitor of autophagy could regulate the production of proplatelet and the expression of cell cycle related protein, including CyclinD1（Veh 1.08±0.12; Rap 0.46±0.04; Rap+3-MA 0.70±0.03）, CyclinD2（Veh 0.47±0.04; Rap 0.27±0.04; Rap+3-MA 0.41±0.03）, P21（Veh 0.15±0.01; Rap 0.04±0.01; Rap+3-MA 0.05±0.01）. CONCLUSION: Enhanced autophagy is the key factor of poor proplatelet formation in megakaryocytes of ITP children.

The Epidemiology, Virulence and Antimicrobial Resistance of Invasive Klebsiella pneumoniae at a Children's Medical Center in Eastern China.

OBJECTIVE: This study investigated the epidemiology, virulence and drug resistance of invasive Klebsiella pneumoniae (K. pneumoniae) isolates at a children's medical center in eastern China in order to obtain epidemiologic, virulence, and antimicrobial resistance data that can guide for the selection and development of anti-infection treatments. METHODS: A total of 94 invasive K. pneumoniae strains were isolated from children between January 2016 and December 2020 at the Children's Hospital of Soochow University. The strains were identified by mass spectrometry. The Kirby-Bauer method and VITEK 2 Compact system were used to analyze the antimicrobial susceptibility. Polymerase chain reaction (PCR) and sequencing was performed to detect the capsular serotypes, virulence-associated genes, ß-lactam antibiotic resistance genes and multilocus sequence typing. RESULTS: The PCR results showed that 87 strains (92.55%) of invasive K. pneumoniae were hypervirulent capsular serotypes, with K57 as the dominant capsular serotype (62.77%). All strains carried virulence-associated genes. Among them, 84 strains (89.36%) carried hypervirulence genes, with iroB (86.17%) being the predominant; meanwhile, other virulence genes, including wabG (100.00%), mrkD (98.94%), ycfM (96.81%), fimH (95.74%) and Uge (88.30%), were detected in most strains. All strains carried ß-lactam antibiotic resistance genes; the main extended-spectrum ß-lactamase gene was bla SHV-11 (86.17%) and the major AmpC cephalosporinase genes were bla FOX-1 (86.17%) and bla ACT-1 (70.21%). Carbapenemase genes were detected in only a few isolates. Notably, 12 invasive K. pneumoniae isolates were identified as carbapenem-resistant and hypervirulent K. pneumoniae (CR-HVKP), and 14 other multidrug resistance (MDR) isolates were also detected. CONCLUSION: The results of this study reveal the epidemiology, virulence and antimicrobial resistance of invasive K. pneumoniae in pediatric patients. Both CR-HVKP and MDR strains were identified, which should be of great concern to clinicians.

NEDD9 overexpression: Prognostic and guidance value in acute myeloid leukaemia.

It has been demonstrated that neural precursor cell expressed developmentally downregulated protein (NEDD) plays crucial roles in tumorigenesis and may serve as potential biomarkers in cancer diagnosis and prognosis. However, few studies systematically investigated the expression of NEDD family members in acute myeloid leukaemia (AML). We systemically determined the expression of NEDD family members in AML and determined their clinical significance. We identified that NEDD9 expression was the only member among NEDD family which was significantly increased in AML. NEDD9 overexpression was more frequently classified as FAB-M4/M5 (p = 0.008 and 0.013, respectively), hardly as FAB-M2/M3. Moreover, NEDD9 overexpression was significantly associated with complex karyotype and TP53 mutation. The significant association between NEDD9 overexpression and survival was also observed in whole-cohort AML and non-M3 AML patients. Notably, AML patients with NEDD9 overexpression may benefit from hematopoietic stem cell transplantation (HSCT), whereas those cases without NEDD9 overexpression did not. Finally, a total of 822 mRNAs and 31 microRNAs were found to be differentially expressed between two groups. Among the microRNAs, miR-381 was also identified as a microRNA that could direct target NEDD9. Taken together, our findings demonstrated that NEDD9 overexpression is associated with genetic abnormalities as well as prognosis and might act as a potential biomarker guiding the choice between HSCT and chemotherapy in patients with AML after achieving complete remission.

Effectiveness of 13-valent pneumococcal conjugate vaccine against community acquired pneumonia among children in China, an observational cohort study.

BACKGROUND: In China, 13-valent pneumococcal conjugate vaccine (PCV13) has been available since 2017, but only via the private market with low uptake rate. We assessed the direct effectiveness of PCV13 against community acquired pneumonia (CAP) associated with PCV13 serotype carriage (VT-CAP). METHODS: We conducted an observational cohort study of children born during 12-Dec-2016 to 30-Nov-2018 identified in the Suzhou Centers for Disease Control vaccine registry database, and who had at least one inpatient or outpatient record at the Suzhou University Affiliated Children's hospital (SCH) health-information-system (HIS) database. The vaccine registry cohort was followed through the HIS database through 30-Jun-2019 to identify hospitalized VT-CAP. Pneumococci were isolated from deep upper respiratory aspirates and serotyped with Quellung reactions. RESULTS: We included 139,127 children of whom 9024 (6.5%) received 1 + PCV13 doses (95.8% received 2 + doses). Within the total cohort, we identified 548 children hospitalized at SCH for VT-CAP, of whom 10 had received 2 + PCV13 doses. Adjusted for demographics, receipt of other childhood vaccines, and underlying medical conditions, the first visit vaccine effectiveness among children who had received 2 + PCV13 doses was 60.9% (95% CI: 25.8% to 79.4%) for VT-CAP and 17.9% (95% CI: 5.5% to 28.6%) for clinical CAP. Incidence rate reductions per 100,000 child-years of observation for all visits were 208 (95% CI: 118 to 298) for VT-CAP and 720 (95% CI: 304 to 1135) for clinical CAP. CONCLUSIONS: PCV13 was protective against hospitalized VT-CAP and clinical CAP with large associated incidence rate reductions among children living in Suzhou, China.