Identification of m6A-related lncRNAs LINC02471 and DOCK9-DT as potential biomarkers for thyroid cancer.

Thyroid cancer (THCA) is the most common endocrine malignancy worldwide and has been rising at the fastest rate in recent years. Long-stranded non-coding RNAs (lncRNAs) and N6-methyladenosine (m6A) have been associated with immunotherapy efficacy and cancer prognosis. However, how m6A-associated lncRNAs (mrlncRNAs) affect the prognosis of patients with thyroid cancer is unclear. Therefore, this study utilized The Cancer Genome Atlas (TCGA) database to provide thyroid cancer-related transcriptomic data and related clinical data. The R program was used to identify m6A-related lncRNAs, and a risk model consisting of two lncRNAs (LINC02471 and DOCK9-DT) was obtained using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Kaplan-Meier survival analysis and transient subject operating characteristics (ROC) were used for analysis. The results showed a substantial association between immune cell infiltration and risk scores. Independent analyses confirmed that the expression of LINC02471 and DOCK9-DT was significantly higher in thyroid cancer tissues than in normal tissues, suggesting that they may be useful biomarkers for thyroid cancer.

MCM10, a potential diagnostic, immunological, and prognostic biomarker in pan-cancer.

Microchromosome maintenance (MCM) proteins are a number of nuclear proteins with significant roles in the development of cancer by influencing the process of cellular DNA replication. Of the MCM protein family, MCM10 is a crucial member that maintains the stability and extension of DNA replication forks during DNA replication and is significantly overexpressed in a variety of cancer tissues, regulating the biological behaviour of cancer cells. But little is understood about MCM10's functional role and regulatory mechanisms in a range of malignancies. We investigate the impact of MCM10 in human cancers by analyzing data from databases like the Gene Expression Profiling Interaction Analysis (GEPIA2), Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA), among others. Possible relationships between MCM10 and clinical staging, diagnosis, prognosis, Mutation burden (TMB), microsatellite instability (MSI), immunological checkpoints, DNA methylation, and tumor stemness were identified. The findings demonstrated that MCM10 expression was elevated in the majority of cancer types and was connected to tumor dryness, immunocytic infiltration, immunological checkpoints, TMB and MSI. Functional enrichment analysis in multiple tumors also identified possible pathways of MCM10 involvement in tumorigenesis. We also discovered promising MCM10-targeting chemotherapeutic drugs. In conclusion, MCM10 may be a desirable pan-cancer biomarker and offer fresh perspectives on cancer therapy.

MicroRNAs in the Regulation of RIG-I-like Receptor Signaling Pathway: Possible Strategy for Viral Infection and Cancer.

The retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play a crucial role as pattern-recognition receptors within the innate immune system. These receptors, present in various cell and tissue types, serve as essential sensors for viral infections, enhancing the immune system's capacity to combat infections through the induction of type I interferons (IFN-I) and inflammatory cytokines. RLRs are involved in a variety of physiological and pathological processes, including viral infections, autoimmune disorders, and cancer. An increasing body of research has examined the possibility of RLRs or microRNAs as therapeutic targets for antiviral infections and malignancies, despite the fact that few studies have focused on the regulatory function of microRNAs on RLR signaling. Consequently, our main emphasis in this review is on elucidating the role of microRNAs in modulating the signaling pathways of RLRs in the context of cancer and viral infections. The aim is to establish a robust knowledge base that can serve as a basis for future comprehensive investigations into the interplay between microRNAs and RIG-I, while also facilitating the advancement of therapeutic drug development.

Factors associated with afebrile presentation and delayed defervescence of bacterial meningitis in children under 3 years of age: a multi-centre retrospective analysis.

BACKGROUND: This multi-center study aimed to identify factors affecting fever and delayed defervescence in bacterial meningitis (BM) patients under 3 years of age because of the variability of fever in this patient population. METHODS: Only BM patients under 3 years treated at 49 centers in China from November 2018 to end-April 2021 were included in the study. Univariate and multivariate logistic regression analyses were performed to determine factors associated with afebrile presentation and fever of delayed defervescence. RESULTS: A total of 863 BM patients under 3 years were included in the study. Coagulase negative staphylococcus was associated with afebrile presentation (OR = 1.176), while septicaemia and ear-nose-throat infections were associated with fever (P < 0.05). The patients with fever were assigned into early and delayed defervescence groups based on defervescence time (less than and more than or equal to one week). Furthermore, Streptococcus agalactiae meningitis (OR = 1.124), concomitant gastrointestinal infection (OR = 1.276), encephalomalacia (or = 1.339), and subdural effusion (OR = 1.454) were independently associated with delayed defervescence (all P < 0.05). CONCLUSIONS: The findings can aid in the efficient utilization of fever in auxiliary diagnosis and evaluating the condition of the disease.

Molecular mechanisms underlying the anticancer property of Dendrobium in various systems of the human body: A review.

Dendrobium, which belongs to the family of Orchidaceae, is a highly valuable traditional Chinese medicine commonly used in China. It exerts pharmacological activities such as antitumor and hypoglycemia effects, and its main components are alkaloids, polysaccharides, and terpenoids, among others. In recent years, research on the clinical application of Dendrobium in antitumor therapy has gained increasing attention. Accumulating evidence suggests that the active components of Dendrobium possess significant inhibitory effects on the viability of cancer cells as evident from in vivo and in vitro experiments, which indicates that Dendrobium exerts significant anticancer effect in treating and preventing cancer development, inhibiting the underlying potential molecular mechanisms, including suppression of cancer cell growth and proliferation, epithelial-mesenchymal transition (EMT), apoptosis induction, tumor angiogenesis, and reinforcement of cisplatin (DDP) -induced apoptosis. We herein present a review that summarizes the research progress of the application of Dendrobium in cancer therapy and its molecular mechanisms. This review describes the positive aspects of the active ingredients of Dendrobium in the treatment of cancers in various systems of the human body, their inhibitory effects on tumor survival and tumor microenvironment, and their potential mechanisms. Additionally, this review proposes future application prospects of Dendrobium in cancer therapy to promote further research and future extensive clinical applications of Dendrobium in cancer therapy.

The comparisons of procalcitonin and age between mild and severe Hand, foot, and mouth disease.

Background: Hand, foot, and mouth disease (HFMD) is an epidemic infectious disease in children, usually associated with fever, mouth lesions, and limb rashes. Although benign and self-limiting, it can be dangerous or even fatal in rare cases. Early identification of severe cases is crucial to ensure optimal care. Procalcitonin (PCT) is an early marker for predicting sepsis. Therefore, in this study, we aimed to investigate the significance of PCT levels, age, lymphocyte subsets, N-terminal pro-brain natriuretic peptide (BNP) in the early diagnosis of severe HFMD. Methods: Using strict inclusion and exclusion criteria, we retrospectively enrolled 183 children with HFMD between January 2020 and August 2021 and divided them into mild (76 cases) and severe (107 cases) groups according to their condition. Data on the patients' PCT levels, lymphocyte subsets, and clinical characteristics at admission were evaluated and compared using the Student's t-test and χ2 test. Results: We found that compared with mild disease forms, the severe disease forms were associated with higher blood PCT levels (P=0.001) and lower ages of onset (P<0.001). The percentages of lymphocyte subsets, including suppressor T cells (CD3+CD8+), T lymphocytes (CD3+), T helper cells (CD3+CD4+), natural killer cells (CD16+56+), and B lymphocytes (CD19+), were identical between the two disease forms in patients under 3 years of age. Conclusions: Age and blood PCT levels play a vital role in the early identification of severe HFMD.

Gut microecological regulation on bronchiolitis and asthma in children: A review.

INTRODUCTION: Asthma and bronchiolitis in children are considered common clinical problems associated with gut microbiota. However, the exact relationship between gut microbiota and the above-mentioned diseases remains unclear. Here, we discussed recent advances in understanding the potential mechanism underlying immune regulation of gut microbiota on asthma and bronchiolitis in children as well as the role of the gut-lung axis. METHODS: We retrieved and assessed all relevant original articles related to gut microbiota, airway inflammation-induced wheezing in children, and gut-lung axis studies from databases that have been published so far, including PubMed/MEDLINE, Scopus, Google Scholar, China National Knowledge Infrastructure (CNKI) and the Wanfang Database. RESULTS: The infant period is critical for the development of gut microbiota, which can be influenced by gestational age, delivery mode, antibiotic exposure and feeding mode. The gut microbiota in children with asthma and bronchiolitis is significantly distinct from those in healthy subjects. Gut microbiota dysbiosis is implicated in asthma and bronchiolitis in children. The presence of intestinal disturbances in lung diseases highlights the importance of the gut-lung axis. CONCLUSION: Gut microbiota dysbiosis potentially increases the risk of asthma and bronchiolitis in children. Moreover, a deeper understanding of the gut-lung axis with regard to the gut microbiota of children with respiratory diseases could contribute to clinical practice for pulmonary diseases.

UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats.

Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) promotes the maintenance of established patterns of DNA methylation in mammalian cells. Extensive methylation of connexin26 (COX26) during hearing impairment has been demonstrated. The present study aims to determine whether UHRF1 can induce the methylation of COX26 in cochlea damaged by intermittent hypoxia (IH). After the establishment of the cochlear injury model through IH treatment or isolation of the cochlea containing Corti's organ, pathological changes were observed via HE staining. Expressions of COX26 and UHRF1 were detected by quantitative reverse-transcription polymerase chain reaction and Western blot. The effect of COX26 methylation levels was analyzed by methylation-specific PCR (MSP). Phalloidin/immunofluorescence staining was used to observe structural changes. The binding relationship between UHRF1 and COX26 was verified by chromatin immunoprecipitation. IH caused cochlear damage, accompanied by increased methylation of COX26 and expression of UHRF1 in the cochlea of neonatal rats. CoCl2 treatment caused the loss of cochlear hair cells, downregulation and hypermethylation of COX26, abnormal upregulation of UHRF1, and disordered expressions of apoptosis-related proteins. UHRF1 in cochlear hair cells binds to COX26, and its knockdown upregulated COX26 level. Overexpressed COX26 partially alleviated the CoCl2-caused cell damage. UHRF1 induces COX26 methylation and aggravates the cochlear damage caused by IH.

Analysis of Serum Inflammatory Markers in Infants Under 6 Months of Age with Non-Syndromic Moderate and Severe Hearing Loss Associated with GJB2 Gene Mutations.

BACKGROUND The GJB2 gene is reported to be the main hereditary factor responsible for non-syndromic hearing impairment in infants. Several kinds of hearing loss have been linked to elevated inflammatory markers. This study aimed to evaluate serum levels of IL-2, IL-4, IL-6, IL-10, IL-17, alpha-TNF, and γ-IFN and the severity of hearing loss. MATERIAL AND METHODS Ninety newborns were divided into 3 groups: severe hearing impairment (31 infants), moderate hearing impairment (30 infants), and normal hearing (29 infants). Hearing screening was performed using otoacoustic emissions test. Mutations of the GJB2 gene were detected with Sanger sequencing. The patients had DNFB1 mutation. Seven blood inflammatory markers were tested using Cytometric Bead Array. We performed the t test to examine differences in expression of 7 inflammatory markers between sexes in the groups. The correlation between indicators within groups was studied using the Pearson correlation test. Correlation of different indicators among groups was studied using the Spearman correlation test. RESULTS When compared among the 3 groups (severe, moderate hearing impairment, and normal hearing group), we found that IL-10 had a positive correlation with the severity of GJB2-associated hearing loss, which was statistically significant (P<0.05). CONCLUSIONS This research aimed to assess the relationship of 7 serum inflammatory markers with GJB2-associated hearing loss in infants. Inflammatory marker IL-10 had a positive correlation with the severity of GJB2-associated infant hearing loss, and it might have the potential to become a future therapeutic target.

Human bocavirus-1 screening in infants with acute lower respiratory tract infection.

BACKGROUND: Recent studies have reported associations between, human bocavirus (HBoV), and respiratory tract diseases in children. However, there is limited information on the epidemiology of HBoV in infants. This prospective study investigated the prevalence and clinical characteristics of HBoV infection in infants with acute lower respiratory tract infection (ALRTI) in eastern China. METHODS: Nasopharyngeal aspirates and throat swab samples were collected from infants with ALRTI and age-matched healthy infants between January 2016 and December 2019. HBoV was identified by polymerase chain reaction. Laboratory data and clinical characteristics were analyzed. RESULTS: Of 2510 infants, 145 tested positive for HBoV. The highest prevalence of HBoV was detected during the winter. Co-infection was frequently observed during this period of high viral transmission. There were no HBoV-positive infants in the control group. Clinical signs and symptoms included cough, wheezing, fever, nasal discharge, vomiting, diarrhea, hypoxemia, and tachypnea. Co-infections included: Streptococcus pneumoniae, Staphylococcus aureus, Mycoplasma pneumoniae, Chlamydophila pneumoniae, respiratory syncytial virus, and adenovirus. CONCLUSIONS: HBoV was frequently detected in infants with ALRTI in China. The prevalence of HBoV was highest in winter. Co-infection was common, especially in infants requiring intensive care unit admission. Comprehensive clinical evaluation may facilitate optimal treatment.

The low contagiousness and new A958D mutation of SARS-CoV-2 in children: An observational cohort study.

AIMS: To explore the contagiousness and new SARS-CoV-2 mutations in pediatric COVID-19. METHODS: This cohort study enrolled all pediatric patients admitted to 8 hospitals in Zhejiang Province of China between 21 January and 29 February 2020, their family members and close-contact classmates. Epidemiological, demographic, clinical and laboratory data were collected. Bioinformatics was used to analyze the features of SARS-CoV-2. Individuals were divided into 3 groups by the first-generation case: Groups 1 (unclear), 2 (adult), and 3 (child). The secondary attack rate (SAR) and R0 were compared among the groups. RESULTS: The infection rate among 211 individuals was 64% (135/211). The SAR in Groups 2 and 3 was 71% (73/103) and 3% (1/30), respectively; the median R0 in Groups 2 and 3 was 2 (range: 1-8) and 0 (range: 0-1), respectively. Compared with adult cases, the SAR and R0 of pediatric cases were significantly lower (p<0.05). We obtained SARS-CoV-2 sequences from the same infant's throat and fecal samples at a two-month interval and found that the new spike protein A958D mutation detected in the stool improved thermostability theoretically. CONCLUSIONS: Children have lower ability to spread SARS-CoV-2. The new A958D mutation is a potential reason for its long residence in the intestine.

Epidemiological features and viral shedding in children with SARS-CoV-2 infection.

A pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. We conducted a retrospective, multicenter study, and followed-up with all children from the families with SARS-CoV-2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS-CoV-2 RNA with real-time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal-viral excretion times among groups with different antiviral regiments were compared with Kaplan-Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS-CoV-2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty-three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS-CoV-2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal-viral-excreting children. Children have lower susceptibility of SARS-CoV-2 infection, longer incubation, and fecal-viral excretion time. Positive results of fecal SARS-CoV-2 RNA detection were not used as indication for hospitalization or quarantine.

[Clinical effect of pidotimod oral liquid as adjuvant therapy for infectious mononucleosis].

OBJECTIVE: To study the clinical effect of pidotimod oral liquid as adjuvant therapy for infectious mononucleosis and its effect on T lymphocyte subsets. METHODS: A total of 76 children with infectious mononucleosis, who were admitted to the hospital between July 2016 and June 2017, were enrolled and randomly divided into two groups: conventional treatment and pidotimod treatment (n=38 each). The children in the conventional treatment group were given antiviral therapy with ganciclovir for injection and symptomatic treatment. Those in the pidotimod treatment group were given pidotimod oral liquid in addition to the treatment in the conventional treatment group. The course of treatment was two weeks for both groups. The two groups were compared in terms of the recovery of clinical indices and the changes in peripheral blood T lymphocyte subsets. RESULTS: Compared with the conventional treatment group, the pidotimod treatment group had significantly shorter fever clearance time, time to the disappearance of isthmopyra, time to the relief of lymph node enlargement, time to the relief of hepatosplenomegaly, and length of hospital stay (P<0.05). After treatment, the pidotimod treatment group had significant reductions in the percentages of CD3+ and CD8+ T cells and had significantly lower percentages of CD3+ and CD8+ T cells than the conventional treatment group (P<0.001). The pidotimod treatment group had significant increases in the percentage of CD4+ T cells and CD4+/CD8+ ratio after treatment, which was significantly higher than those in the conventional treatment group (P<0.001). The conventional treatment group had no significant changes in T lymphocyte subsets after treatment (P>0.05). CONCLUSIONS: Pidotimod oral liquid has a good clinical effect as the adjuvant therapy for infectious mononucleosis and can improve cellular immune function, so it holds promise for clinical application.

Association of T lymphocyte immune imbalance and IL-10 gene polymorphism with the risk of obstructive sleep apnea in children with obesity.

PURPOSE: The purpose of this study is to determine the role of T lymphocyte immune imbalance and interleukin (IL)-10 gene polymorphism in the development of obstructive sleep apnea (OSA) in obese children. METHODS: One hundred obese children at high-risk and low-risk for OSA based upon a sleep questionnaire were selected. Peripheral blood T lymphocyte subsets were measured by flow cytometry, and plasma IFN-γ, IL-4, and IL-10 cytokines were detected by ELISA. The relationships between OSA and the above variables were analyzed. IL-10 gene polymorphisms were analyzed by DNA sequencing. RESULTS: Ninety subjects completed all the tests. Forty-two patients were diagnosed as OSA by PSG. Compared with non-OSA children, the levels of CD4+ T cells, IFN-γ, and IL-4 were increased (P < 0.05) whereas the numbers of CD4+ CD25+ Treg and NKT cells and the levels of IL-10 were reduced (P < 0.05). Multiple linear regression analysis showed that IL-10 level was negatively associated with OAHI (OR 0.352, 95% CI 0.286-0.540; P < 0.05). In multivariate analysis, IL-10 also had a strong negative association with OSA after adjustment for confounding factors from models 1 to 3. Correlative analysis showed that IL-10 levels had a positive association with CD4+ CD25+ Treg (r = 0.628, P < 0.01). Furthermore, the IL-10/A-1082G gene polymorphism correlated with OSA. CONCLUSIONS: T lymphocyte immune imbalance was associated with OSA and IL-10 may play an important protective role in the pathogenesis of OSA in obese children.

[The correlational study of viral load of human bocavirus and clinical features in children with acute respiratory tract infection].

OBJECTIVE: To analyze the correlations between clinical features in paediatric patients with acute respiratory tract infection (ARTI) and viral load of human bocavirus. METHODS: A prospective study was conducted on 956 children < 5 years admitted with an acute respiratory tract infection from November 2009 to December 2010, and 251 healthy children conclused as control group in the corresponding period. Human bocavirus was investigated in nasopharyngeal aspirates (NPA) and throat swab by PCR, and viral load was detected by real-time polymerase chain reaction (RT-PCR) in HBoV positive sample. Clinical data were also prospectively recorded. RESULTS: A significant difference was found in HBoV positive rate between children with ARTI and control group at enrollment. There was a significant difference in HBoV viral load between children with upper respiratory tract infection and lower respiratory tract infection. HBoV viral load did not differ significantly between children with upper respiratory tract infection and control group. Among children with lower respiratory tract infection, no significant difference were detected between common and severe cases in HBoV viral load. HBoV viral load did not differ significantly whether the children were with or without co-infection. CONCLUSIONS: HBoV could be detected perennial and considered as a major pathogen associated with acute respiratory tract infection in children. However, HBoV may not be a independent factor in children with ARTI and the HBoV viral load was not associated with the severity of respiratory illness.

[Regulative mechanism of dexamethasone on Toll-like receptor 4 signal transduction of infant asthma rat].

OBJECTIVE: Eosinophilic airway inflammation is one of the basic characteristics of allergic asthma. Toll-like receptor is one of the most important innate immunity pattern recognition receptors. Glucocorticoids (GCS) are still the most effective treatment for asthma. However, few reports of studies on regulatory mechanism of GCS on the innate immunity system are available. The mechanism of effects of GCS on TLR4 is unclear. The present study aimed at understanding the effect of dexamethasone (DXM) on change of TLR4 and mechanism of regulatory effect of TLR4 on eosinophil (EOS) apoptosis. METHODS: Twenty-seven Sprague-Dawley (SD) rats (age 28 to 42 days, body weight 120 to 180 gram) were randomly divided into the control group, asthma group and DXM group with 9 in each. Asthma model rats were sensitized with the mixture of ovalbumin (OVA, 1 mg) and Al (OH)(3), 100 mg on day 1 and day 8, repeatedly exposed to aerosolized OVA after day 15, once a day for three days and continued for 30 minutes at every time. During the sensitization stage, 100 microg/ml DXM were prepared with DXM group for every other day, and the same doses DXM were prepared for every day on the stage of challenge. The histopathological changes of lung tissues were observed with light microscope (LM). EOS and other inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted; the concentrations of OVA-sIgE in serum were measured by using "sandwich" ELISA; The expressions of TLR4 mRNA were determined by in situ hybridization, the apoptosis of EOS was detected by TUNEL. RESULTS: (1) LM showed many inflammatory cells infiltration around the bronchi and blood vessels, bronchus mucus increased, airway epithelium damage and desquamation, and airway mucous plugs in asthma group, whereas DXM group showed significantly milder changes. (2) Inflammationary cells count in BALF of asthma group was significantly higher as compared to control group (P < 0.01); compared with asthma group, the total cell count, EOS absolute count and EOS% were all significantly decreased in DXM group [(2.14 +/- 0.10) x 10(9)/L, (4.78 +/- 1.23) x 10(7)/L, (2.17 +/- 0.25)%]. (3) Levels of OVA-sIgE in serum of asthma group [(83.40 +/- 6.80) microg/ml] were significantly higher than those of the control group [(14.38 +/- 4.25) microg/ml] (P < 0.01), while those of DXM group [(45.02 +/- 7.47) microg/ml] were significantly lower than asthma group (P < 0.0 1). (4) There were no significant differences in TLR4 mRNA detected by in situ hybridization between control group (24.71 +/- 0.85) and asthma group (25.81 +/- 3.56) (P > 0.05); but it significantly increased in DXM group (29.86 +/- 3.92) as compared to asthma group. (5) The percentages of apoptotic EOS in asthma group [(7.39 +/- 1.93)%] were significantly lower than those in control group [(9.06 +/- 1.52)%] (P < 0.01); and significantly higher in DXM group [(13.33 +/- 1.09)%] than in asthma group (P < 0.01). There were significantly positive correlations between TLR4 mRNA and the percentage of apoptotic EOS (r = 0.612, P < 0.01). CONCLUSION: DXM can decrease OVA-sIgE level, induce EOS apoptosis, which may correlate with the activation of TLR4 signal transduction.