p53 suppresses the inflammatory response following respiratory syncytial virus infection by inhibiting TLR2.

-Respiratory syncytial virus (RSV) is a pivotal virus leading to acute lower respiratory tract infections in children under 5 years old. This study aimed to explore the correlation between p53 and Toll-like receptors (TLRs) post RSV infection. p53 levels exhibited a substantial decrease in nasopharyngeal aspirates (NPAs) from infants with RSV infection compared to control group. Manipulating p53 expression had no significant impact on RSV replication or interferon signaling pathway. Suppression of p53 expression led to heightened inflammation following RSV infection in A549 cells or airways of BALB/c mice. while stabilizing p53 expression using Nutlin-3a mitigated the inflammatory response in A549 cells. Additionally, Inhibiting p53 expression significantly increased Toll-like receptor 2 (TLR2) expression in RSV-infected epithelial cells and BALB/c mice. Furthermore, the TLR2 inhibitor, C29, effectively reduced inflammation mediated by p53 in A549 cells. Collectively, our results indicate that p53 modulates the inflammatory response after RSV infection through TLR2.

Genome and proteomic analysis of risk factors for fatal outcome in children with severe community-acquired pneumonia caused by human adenovirus 7.

INTRODUCTION: Human adenovirus 7 (HAdV-7) is an important viral pathogen of severe pneumonia in children and a serious threat to health. METHODS: A cohort of 45 pediatric patients diagnosed with HAdV-7-associated severe pneumonia and admitted to the Pediatric Intensive Care Unit at the Children's Hospital of Chongqing Medical University from May 2018 to January 2020 were included. Risk factors of death were analyzed by the Cox proportional risk mode with Clinical data, serum, and nasopharyngeal aspirate adenovirus load, Genome analysis, Olink proteomics, and cytokine profile between dead and surviving patients were also analyzed. RESULTS: A total of 45 children with a median age of 12.0 months (interquartile range [IQR]: 6.5, 22.0) were included (female 14), including 14 (31.1%) who died. High serum viral load was an independent risk factor for mortality (hazard ratio [HR] = 2.16, 95% confidence interval [CI], 1.04-4.49, p = 0.039). BTB and CNC homology 1 (BACH1), interleukin-5 (IL-5), and IL-9 levels were significantly correlated with serum viral load (p = 0.0400, 0.0499, and 0.0290; r = 0.4663, 0.3339, and -0.3700, respectively), with significant differences between the dead and survival groups (p = 0.021, 0.001, and 0.021). CONCLUSIONS: Severe cytokine storm-associated high serum viral load after HAdV-7 infection may be the main mechanism responsible for poor prognosis in children.

USP3 inhibition is Active Against Chemo-resistant Hepatocellular Carcinoma Anchorage-independent Growth via Suppressing Wnt/ß-catenin.

BACKGROUND: USPs are a family of enzymes that regulate protein degradation, and their dysregulation has been implicated in the development and progression of cancer. AIMS: This study aimed to determine whether ubiquitin-specific proteases 3 (USP3) could be a potential target for therapy in hepatocellular carcinoma (HCC), particularly in resistant HCC. This study systematically investigated the role of USP3 in HCC, with a focus on chemo-resistant HCC cells. METHODS: The level of USP3 from clinical samples was measured using an ELISA assay. Cell proliferation, apoptosis, migration, and anchorage-independent colony formation assays were performed. Transfection was performed to knock down USP3 expression and measure ß-catenin activity, and real-time PCR was used to measure levels of MYC and CYCLIN D1 genes. RESULTS: USP3 protein was upregulated in HCC tissues, but its upregulation was not associated with clinicopathology. USP3 knockdown had a similar inhibitory effect on growth in both sensitive and resistant HCC cells, did not affect migration, and induced apoptosis in sensitive but not resistant HCC cells. Furthermore, USP3 knockdown was more effective in suppressing anchorage-independent colony formation in chemoresistant HCC cells compared to their chemo-sensitive counterparts. Pearson correlation coefficient analysis revealed a strong positive correlation between USP3 and CTNNB1, and consistently, USP3 knockdown reduced the levels and activities of ß-catenin in HCC cells. Using a Wnt activator (lithium) in rescue studies significantly reversed the inhibitory effects of USP3 knockdown. CONCLUSION: The findings suggest that inhibiting USP3 is an effective strategy against cancer stem cells and chemo-resistant HCC cells.

Lipoprotein(a) as a Higher Residual Risk for Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus than without.

Purpose: Lipoprotein(a) (Lp[a]) is well-known as a residual risk factor for coronary artery disease (CAD). However, the different adverse effects of Lp(a) about CAD in patients with or without type 2 diabetes mellitus (T2DM) are unclear. This study aimed to investigate the Lp(a) thresholds for CAD diagnosis in T2DM and non-T2DM patients, and further compare the Lp(a) alarm values along with optimal low-density lipoprotein cholesterol (LDL-C) level. Methods: This retrospective study consecutively enrolled patients with suspected CAD who underwent coronary angiography in Guangdong Provincial People's Hospital between September 2014 and July 2015. A logistic regression model was established to explore the association of Lp(a) and CAD in patients. Restricted cubic splines were used to compare the threshold values of Lp(a) for CAD in patients with and without T2DM, and further in optimal LDL-C level situation. Results: There were 1522 patients enrolled finally. After multivariable adjustment, Lp(a) was an independent risk factor for CAD in patients with T2DM (odds ratio [OR]: 1.98, 95% CI]: 1.12-3.49, p = 0.019) and without T2DM (OR: 3.42, 95% CI: 2.36-4.95, p < 0.001). In the whole population, the Lp(a) threshold of CAD was 155, while 145 mg/L for T2DM and 162 mg/L for non-T2DM ones, respectively. In patients with LDL-C<1.8 mmol/l, the alarm value of Lp(a) was even lower in T2DM than non-T2DM patients (155 vs 174 mg/L). Conclusion: Lp(a) was a significant residual risk for CAD in patients whether with T2DM or not. And Lp(a) had a lower alarm value in T2DM patients, especially in optimal LDL-C level.

Preterm birth and detection of common respiratory pathogens among pediatric pneumonia.

Pneumonia complicated by preterm birth is related to adverse clinical sequelae from the neonatal period to childhood. Children with pneumonia during 2009-2021 were enrolled at the Children's Hospital of Chongqing Medical University. Altogether 20 respiratory pathogens were detected and compared. Among 8,206 children, 779 were in the preterm group with 246 of early-preterm and 533 of late preterm. The positive rates for all viral pathogens were comparable between the preterm group and the full-term group. For bacterial pathogens, higher positive rates for Escherichia coli and Klebsiella pneumoniae were observed in the preterm group. Severe pneumonia developed in 16.52% of all, which was higher in the preterm group than in the full-term group. A significantly higher rate of severe pneumonia was observed in the early-preterm group compared to the late-preterm group. Preterm birth has an impact on the detection of bacterial pathogens in children and is a risk factor for severe pneumonia.

A Web-Based Instrument for Infantile Atopic Dermatitis Identification (Electronic Version of the Modified Child Eczema Questionnaire): Development and Implementation.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory cutaneous disease that affects 30.48% of young children; thus, there is a need for epidemiological studies in community settings. Web-based questionnaires (WBQs) are more convenient, time-saving, and efficient than traditional surveys, but the reliability of identifying AD through WBQs and whether AD can be identified without the attendance of doctors, especially in community or similar settings, remains unknown. OBJECTIVE: This study aimed to develop and validate a web-based instrument for infantile AD identification (electronic version of the modified Child Eczema Questionnaire [eCEQ]) and to clarify the possibility of conducting WBQs to identify infantile AD without the attendance of doctors in a community-representative population. METHODS: This study was divided into 2 phases. Phase 1 investigated 205 children younger than 2 years to develop and validate the eCEQ by comparison with the diagnoses of dermatologists. Phase 2 recruited 1375 children younger than 2 years to implement the eCEQ and verify the obtained prevalence by comparison with the previously published prevalence. RESULTS: In phase 1, a total of 195 questionnaires were analyzed from children with a median age of 8.8 (IQR 4.5-15.0) months. The identification values of the eCEQ according to the appropriate rules were acceptable (logic rule: sensitivity 89.2%, specificity 91.5%, positive predictive value 97.1%, and negative predictive value 72.9%; statistic rule: sensitivity 90.5%, specificity 89.4%, positive predictive value 96.4%, and negative predictive value 75%). In phase 2, a total of 837 questionnaires were analyzed from children with a median age of 8.4 (IQR 5.2-14.6) months. The prevalence of infantile AD obtained by the eCEQ (logic rule) was 31.9% (267/837), which was close to the published prevalence (30.48%). Based on the results of phase 2, only 20.2% (54/267) of the participants identified by the eCEQ had previously received a diagnosis from doctors. Additionally, among the participants who were not diagnosed by doctors but were identified by the eCEQ, only 6.1% (13/213) were actually aware of the possible presence of AD. CONCLUSIONS: Infantile AD can be identified without the attendance of doctors by using the eCEQ, which can be easily applied to community-based epidemiological studies and provide acceptable identification reliability. In addition, the eCEQ can also be applied to the field of public health to improve the health awareness of the general population.

Defining RSV epidemic season in southwest China and assessing the relationship between birth month and RSV infection: A 10-year retrospective study from June 2009 to May 2019.

Respiratory syncytial virus (RSV) is one of the most common causes of lower respiratory tract infections (LRTI). However, only limited information is available regarding its seasonality and its relationship with birth month. A retrospective hospital-based study was carried out from June 2009 to May 2019 in Chongqing, southwest of China. LRTI cases under 5 years were enrolled in this study and PCR was used to detect 8 respiratory viruses. RSV seasonality was determined using "average annual percentage" (AAP) and "percent positivity" method. A total of 6991 cases were enrolled in this study, with an RSV positivity of 34.5%. From June 2009 to May 2019, we analyzed RSV epidemic season during 10 RSV epidemic years in Chongqing using two methods. The result of AAP method was similar to that of percent positivity method with a 30% threshold, which showed an epidemic season of roughly October to March in the subsequent year, with a small peak in June. On average, the RSV epidemic season in RSV-A dominant years typically started earlier (week 42 for RSV-A vs. week 46 for RSV-B), ended earlier (week 12 for RSV-A vs. week 14 for RSV-B), lasted longer (24 weeks for RSV-A vs. 22 weeks for RSV-B), and reached its peak earlier (week 2 for RSV-A vs. week 3 for RSV-B) than in RSV-B dominant years. The proportion of severe LRTI was higher in cases of single infection with RSV-A compared to those of single infection with RSV-B (26.3% vs. 22.3%, p = 0.024). Among infants under 1 year, those born in May and August through December were more likely to be infected with RSV. Infants born 1-2 months before the epidemic season were relatively more susceptible to RSV infection. In Chongqing, the RSV epidemic was seasonal and usually lasted from October to March of next year with a small peak in summer. Infants born 1-2 months before the epidemic season were relatively more susceptible to RSV infection and this population should be targeted while developing RSV immunization strategies.

Identification of functional pathways and potential genes associated with interferon signaling during human adenovirus type 7 infection by weighted gene coexpression network analysis.

Human adenovirus type 7 (HAdV-7) can cause severe pneumonia and complications in children. However, the mechanism of pathogenesis and the genes involved remain largely unknown. We collected HAdV-7-infected and mock-infected A549 cells at 24, 48, and 72 hours postinfection (hpi) for RNA sequencing (RNA-Seq) and identified potential genes and functional pathways associated with HAdV-7 infection using weighted gene coexpression network analysis (WGCNA). Based on bioinformatics analysis, 12 coexpression modules were constructed by WGCNA, with the blue, tan, and brown modules significantly positively correlated with adenovirus infection at 24, 48, and 72 hpi, respectively. Functional enrichment analysis indicated that the blue module was mainly enriched in DNA replication and viral processes, the tan module was largely enriched in metabolic pathways and regulation of superoxide radical removal, and the brown module was predominantly enriched in regulation of cell death. qPCR was used to determine transcript abundance of some identified hub genes, and the results were consistent with those from RNA-Seq. Comprehensively analyzing hub genes and differentially expressed genes in the GSE68004 dataset, we identified SOCS3, OASL, ISG15, and IFIT1 as potential candidate genes for use as biomarkers or drug targets in HAdV-7 infection. We propose a multi-target inhibition of the interferon signaling mechanism to explain the association of HAdV-7 infection with the severity of clinical consequences. This study has allowed us to construct a framework of coexpression gene modules in A549 cells infected with HAdV-7, thus providing a basis for identifying potential genes and pathways involved in adenovirus infection and for investigating the pathogenesis of adenovirus-associated diseases.

IL-17A plays a critical role in RSV infection in children and mice.

BACKGROUND: IL-17A is a pleiotropic cytokine and intimately associated with asthma, but its role in respiratory syncytial virus (RSV) infection is conflicting in the literature. METHODS: Children hospitalized in the respiratory department with RSV infection during RSV pandemic season of 2018-2020 were included. Nasopharyngeal aspirates were collected for pathogen and cytokines determination. In the murine model, RSV intranasal administrations were performed in wild-type and IL-17A-/- mice. Leukocytes and cytokines in bronchoalveolar lavage fluid (BALF), lung histopathology, and airway hyperresponsiveness (AHR) were measured. RORγt mRNA and IL-23R mRNA were semi-quantified by qPCR. RESULTS: IL-17A increased significantly in RSV-infected children and was positively associated with pneumonia severity. In the murine model, IL-17A significantly increased in BALF of mice with RSV infection. Airway inflammation, lung tissue damage and AHR were significantly alleviated in wild-type mice following IL-17A neutralization and in the IL-17A-/- mice. IL-17A decreased by removing CD4+ T cells but increased by depleting CD8+ T cells. IL-6, IL-21, RORγt mRNA and IL-23R mRNA dramatically increased in parallel with the rise of IL-17A. CONCLUSIONS: IL-17A contributes to the airway dysfunctions induced by RSV in children and murine. CD3+CD4+T cells are its major cellular sources and the IL-6/IL-21-IL-23R-RORγt signaling pathway might participate in its regulation.

Trans-epithelial migration is essential for neutrophil activation during RSV infection.

The recruitment of neutrophils to the infected airway occurs early following respiratory syncytial virus (RSV) infection, and high numbers of activated neutrophils in the airway and blood are associated with the development of severe disease. The aim of this study was to investigate whether trans-epithelial migration is sufficient and necessary for neutrophil activation during RSV infection. Here, we used flow cytometry and novel live-cell fluorescent microscopy to track neutrophil movement during trans-epithelial migration and measure the expression of key activation markers in a human model of RSV infection. We found that when migration occurred, neutrophil expression of CD11b, CD62L, CD64, NE, and MPO increased. However, the same increase did not occur on basolateral neutrophils when neutrophils were prevented from migrating, suggesting that activated neutrophils reverse migrate from the airway to the bloodstream side, as has been suggested by clinical observations. We then combined our findings with the temporal and spatial profiling and suggest 3 initial phases of neutrophil recruitment and behavior in the airways during RSV infection; (1) initial chemotaxis; (2) neutrophil activation and reverse migration; and (3) amplified chemotaxis and clustering, all of which occur within 20 min. This work and the novel outputs could be used to develop therapeutics and provide new insight into how neutrophil activation and a dysregulated neutrophil response to RSV mediates disease severity.

Age-related differences in IgE between childhood and adulthood allergic asthma: Analysis of NHANES 2005-2006.

Background: Asthma exhibits varying clinical features in children and adults. However, previous studies have mainly focused on the clinical significance of immunoglobulin E (IgE) in the diagnosis and treatment of asthma, disregarding the characteristics of IgE and its relevant factors. Objective: This study aimed to gain a better understanding of the differences in the characteristics of IgE between childhood and adulthood allergic asthma (AA). Methods: Patients with AA from the 2005 to 2006 National Health and Nutrition Examination Survey (NHANES) were divided into 3 groups based on their current age and onset age of AA: childhood AA (Group 1), childhood-onset adult AA (Group 2), and adulthood-onset AA (Group 3). Intragroup analysis and intergroup comparison were carried out, focusing on the characteristics and relevant factors of IgE, as well as the clinical relevance of total IgE (total IgE, tIgE) and allergen-specific IgE (allergen-specific IgE, sIgE). Results: A total of 424 patients were analyzed, including 187 with childhood AA, 132 with childhood-onset adult AA, and 105 with adulthood-onset AA. The concentration of tIgE was found to be higher in Group 1 (268.0, 118.0-686.0 kU/L) than in Group 2 (224.0, 78.0-494.0 kU/L) and Group 3 (165.0, 74.4-350.5 kU/L). The sensitization rates did not differ between Group 1 and Group 2 but were higher compared with Group 3, particularly for Alternaria-sIgE (50.3% and 46.2% vs 15.2%) and Aspergillus-sIgE (43.9% and 37.1% vs 16.2%). In Group 1, there was a negative correlation between pollen-sIgEs and indoor allergens, but this correlation was not commonly observed in Group 2 and Group 3. On the other hand, in Group 1, environmental chemicals such as phthalates, polyaromatic hydrocarbons, trihalomethanes, and phenols showed a positive correlation with IgE. However, a greater number of chemicals was observed in Group 2 and Group 3, including cotinine, metals, trihalomethanes, phthalates, phenols, and other volatile organic compounds (VOCs). Furthermore, in Group 1, IgE was positively correlated with asthma-related issues such as emergency visits, absenteeism, limited activities, and medication needs. These correlations were less common in Group 2 and Group 3, particularly in Group 3. Conclusions: There are notable differences in the characteristics and environmental factors of IgE among childhood AA, childhood-onset adult AA, and adulthood-onset AA. Additionally, IgE plays a more significant role in childhood AA due to its higher concentration, fewer relevant environmental chemicals and greater clinical relevance. This may partially explain the age-related features of asthma.

C-Fiber Degeneration Enhances Alveolar Macrophage-Mediated IFN-α/ß Response to Respiratory Syncytial Virus.

Stimulation of unmyelinated C fibers, the nociceptive sensory nerves, by noxious stimuli is able to initiate host responses. Host defensive responses against respiratory syncytial virus (RSV) infection rely on the induction of a robust alpha/beta interferon (IFN-α/ß) response, which acts to restrict viral production and promote antiviral immune responses. Alveolar macrophages (AMs) are the major source of IFN-α/ß upon RSV infection. Here, we found that C fibers are involved in host defense against RSV infection. Compared to the control mice post-RSV infection, degeneration and inhibition of C fibers by blockade of transient receptor potential vanilloid 1 (TRPV1) lowered viral replication and alleviated lung inflammation. Importantly, AMs were markedly elevated in C-fiber-degenerated (KCF) mice post-RSV infection, which was associated with higher IFN-α/ß secretion as measured in bronchoalveolar lavage fluid (BALF) samples. Degeneration of C fibers contributed to the production of vasoactive intestinal peptide (VIP), which modulated AM and IFN-α/ß levels to protect against RSV infection. Collectively, these findings revealed the key role of C fibers in regulating AM and IFN-α/ß responses against RSV infection via VIP, opening the possibility for new therapeutic strategies against RSV. IMPORTANCE Despite continuous advances in medicine, safe and effective drugs against RSV infection remain elusive. As such, host-RSV interactions and host-directed therapies require further research. Unmyelinated C fibers, the nociceptive sensory nerves, play an important role in regulating the host response to virus. In the present study, from the perspective of neuroimmune interactions, we clarified that C-fiber degeneration enhanced the AM-mediated IFN-α/ß response against RSV via VIP, providing potential therapeutic targets for the treatment of RSV infection.

Exploring Key Genes and Mechanisms in Respiratory Syncytial Virus-Infected BALB/c Mice via Multi-Organ Expression Profiles.

Respiratory syncytial virus (RSV) a leading cause of pediatric and adult morbidity and mortality worldwide. It can cause complications in multiple organs, thus increasing hospital stays and costs. However, RSV-based studies have primarily focused on effects in the lungs and blood, thereby potentially neglecting critical genes and pathways. Hence, studying RSV infection via a novel multi-organ approach is important. In this study, lung, intestine, brain, and spleen tissues from six BALB/c mice (6-8 weeks old; three in control group and three in RSV-infected group) were subjected to RNA sequencing. Differentially expressed genes (DEGs) in each organ were obtained and functional enrichment analysis was performed. We first used CIBERSORT to evaluate the immune-infiltration landscape. Subsequently, common DEGs (co-DEGs) among the four organs were analyzed to identify key genes and pathways. After quantitative reverse transcription-polymerase chain reaction, western blotting, and external validation analysis of key hub genes, their correlation with immune cells and potential functions were explored. We found that the host response to RSV infection varied among the four organs regarding gene expression profiles and immune cell infiltration. Analysis of the 16 co-DEGs indicated enrichment in the platelet and neutrophil degranulation pathways. Importantly, the key gene hemopexin (Hpx) was strongly correlated with the immune cell fraction in the lungs and may participate in the regulation of platelet activation and immune response.

Age-specific spectrum of etiological pathogens for viral diarrhea among children in twelve consecutive winter-spring seasons (2009-2021) in China.

Viral diarrhea is one of the leading causes of morbidity and mortality in children. This study was conducted to disclose the etiological cause and epidemiological features of viral diarrhea among children in China. From 2009 to 2021, active surveillance was performed on pediatric patients with acute diarrhea and tested for five enteric viruses. Positive detection was determined in 65.56% (3325/5072) patients and an age-specific infection pattern was observed. A significantly higher positive rate was observed in 12-23-month-old children for rotavirus (47.46%) and adenovirus (7.06%), while a significantly higher positive rate was observed for norovirus (37.62%) in 6-11-month-old patients, and for astrovirus (11.60%) and sapovirus (10.79%) in 24-47-month-old patients. A higher positive rate of rotavirus in girls and norovirus in boys was observed only among 6-11 months of patients. We also observed more norovirus among patients from rural areas in the 0-5- and 36-47-month groups and more rotavirus among those from rural areas in the 12-23-month group. Diarrhea severity was greater for rotavirus in the 6-23-month group and norovirus in the 6-11-month group. Coinfections were observed in 29.26% (973/3325) of positive patients, and were most frequently observed between rotavirus and others (89.31%). Our findings could help the prediction, prevention, and potential therapeutic approaches to viral diarrhea in children.

Respiratory tract infection of fatal severe human bocavirus 1 in a 13-month-old child: A case report and literature review.

Human bocavirus 1 (HBoV1) belongs to the family Parvoviridae and it is acknowledged that HBoV1 is a respiratory pathogen. We report the case of a 13-month-old boy who presented with a cough, shortness of breath, and wheezing, and who eventually died of severe pneumonia and acute respiratory distress syndrome (ARDS). Metagenomics next-generation sequencing (mNGS) showed that HBoV1 was the only detected pathogen. The nasopharyngeal aspirate viral load was 2.08 × 1010 copies/ml and the serum viral load was 2.37 × 105 copies/ml. The child was still oxygen deficient under mechanical ventilation. Chest imaging suggested diffuse lesions in both lungs, an injury caused by ARDS. In this case, the clinical symptoms and signs of the child, the high viral load, viremia, and the detection of mNGS in the tracheal aspirate all supported that HBoV1 could cause severe acute respiratory tract infection in children without other pathogen infections.

The Identification and Genetic Characterization of Parechovirus Infection Among Pediatric Patients With Wide Clinical Spectrum in Chongqing, China.

Human parechoviruses (HPeVs) are important causes of infection in children. However, without a comprehensive and persistent surveillance, the epidemiology and clinical features of HPeV infection remain ambiguous. We performed a hospital-based surveillance study among three groups of pediatric patients with acute respiratory infection (Group 1), acute diarrhea (Group 2), and hand, foot and mouth disease (Group 3) in Chongqing, China, from 2009 to 2015. Among 10,212 tested patients, 707 (6.92%) were positive for HPeV, with the positive rates differing significantly among three groups (Group 1, 3.43%; Group 2, 14.94%; Group 3, 3.55%; P < 0.001). The co-infection with other pathogens was detected in 75.2% (531/707) of HPeV-positive patients. Significant negative interaction between HPeV and Parainfluenza virus (PIV) (P = 0.046, OR = 0.59, 95% CI = 0.34-0.98) and positive interactions between HPeV and Enterovirus (EV) (P = 0.015, OR = 2.28, 95% CI = 1.23-4.73) were identified. Among 707 HPeV-positive patients, 592 (83.73%) were successfully sequenced, and 10 genotypes were identified, with HPeV1 (n = 396), HPeV4 (n = 86), and HPeV3 (n = 46) as the most frequently seen. The proportion of genotypes differed among three groups (P < 0.001), with HPeV1 and HPeV4 overrepresented in Group 2 and HPeV6 overrepresented in Group 3. The spatial patterns of HPeV genotypes disclosed more close clustering of the currently sequenced strains than those from other countries/regions, although they were indeed mixed. Three main genotypes (HPeV1, HPeV3, and HPeV4) had shown distinct seasonal peaks, highlighting a bi-annual cycle of all HpeV and two genotypes (HPeV 1 and HPeV 4) with peaks in odd-numbered years and with peaks in even-numbered years HPeV3. Significantly higher HPeV1 viral loads were associated with severe diarrhea in Group 2 (P = 0.044), while associated with HPeV single infection than HPeV-EV coinfection among HFMD patients (P = 0.001). It's concluded that HPeV infection was correlated with wide clinical spectrum in pediatric patients with a high variety of genotypes determined. Still no clinical significance can be confirmed, which warranted more molecular surveillance in the future.

Establishing a patient registry study database of dust mite allergic asthma in children: design, methodology and preliminary exploration.

BACKGROUND: Asthma is a heterogeneous disease with different phenotypes, endotypes and responses to treatment. Dust mite allergic asthma (DMAA) is the most common type in children. Compared with randomized control trials, a patient registry study (PRS) can reflect the real physical condition and clinical diagnosis more comprehensively. METHODS: Children who visited the asthma clinic of the Children's Hospital of Chongqing Medical University between August 2018 and August 2020, and met the inclusion criteria and also agreed to participate, were enrolled in the registry study. Clinical information, laboratory tests and peripheral blood samples were collected after informed consent was given by guardians. RESULTS: To date, 208 children have been enrolled in the patient registry database of DMAA. They are mainly male, with >50% having a history of allergic rhinitis, cesarean section, positive family history and passive smoking. Eosinophils and total immunoglobulin E levels were all significantly higher than normal. According to results for the childhood asthma control test (c-ACT) and ratio of forced expiratory volume in 1 s to predicted value after inhaled corticosteroid treatment, the uncontrolled group had higher hemoglobin (Hb) levels than the control group. The group exhibiting abnormal pulmonary function was older, and had longer disease duration, higher fractional exhaled nitric oxide and Hb than the group in which pulmonary function was restored. CONCLUSIONS: We have preliminarily established a registered study database of children with DMAA. By cluster analysis and using blood samples, we can further study the different pathophysiological mechanisms in order to provide more individualized and targeted treatments for all children.

Respiratory syncytial virus activates Rab5a to suppress IRF1-dependent IFN-λ production, subverting the antiviral defense of airway epithelial cells.

The limited antiviral options and lack of an effective vaccine against human respiratory syncytial virus (RSV) highlight the need for a novel antiviral therapy. One alternative is to identify and target the host factors required for viral infection. Here, using RNA interference to knock down Rab proteins, we provide multiple lines of evidence that Rab5a is required for RSV infection: (a) Rab5a is upregulated both in RSV-A2-infected A549 cells and RSV-A2-challenged BALB/c mice's airway epithelial cells at early infection phase; (b) shRNA-mediated knockdown of Rab5a is associated with reduced lung pathology in RSV A2 challenged mice; (c) Rab5a expression is correlated with disease severity of RSV infection of infants. Knockdown of Rab5a increases IFN-λ (lambda) production by mediating IRF1 nuclear translocation. Our results highlight a new role for Rab5a in RSV infection, such that its depletion inhibits RSV infection by stimulating the endogenous respiratory epithelial antiviral immunity, which suggests that Rab5a is a potential target for novel therapeutics against RSV infection.Importance This study highlights the important role of Rab5a in RSV infection, such that its depletion inhibits RSV infection by stimulating the endogenous respiratory epithelial antiviral immunity and attenuates inflammation of the airway, which suggests that Rab5a is a powerful potential target for novel therapeutics against RSV infection.