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Human cytomegalovirus (HCMV) infection is ubiquitous and is often asymptomatic in healthy individuals, but it can cause great damage to newborns, AIDS patients, and other immune deficiency patients. In this study, we found that HCMV infection caused mitochondrial fusion, and expression of mitofusin 1 (MFN1), which is a protein associated with mitochondrial antiviral signaling protein (MAVS), positively regulates mitochondrial fusion and HCMV-induced IFN1 response.

Background: Respiratory tract infection (RTIs) is one of common diseases among the children. In recent years, the incidence of mycoplasma pneumoniae (M. pneumoniae) infection rate has been increasing, which cause respiratory tract infection. This study sought to analyze the epidemiological characteristics of M. pneumoniae hospitalized children with RTIs to provide a theoretical basis for clinical diagnosis and treatments in Chengdu, China. Methods: The data of 22,882 cases of children who had been hospitalized for RTIs were collected. M. pneumoniae immunoglobulin M (IgM) antibody was detected using the indirect immunofluorescence method and passive agglutination method. The demographic features of patients, clinical diagnoses and laboratory data were also analyzed. Results: A total of 4,213 children tested positive for M. pneumoniae. The total positive rate was 18.41% (18.30% for males and 22.72% for females). Female children had statistically significant higher positive rates than male children (chi2=198.078, P 0.05). There was negative correlation with PM2.5 (particulate matter in the air

Microbial translocation (MT) and altered gut microbiota have been described in acute leukemic patients and contribute to immune activation and inflammation. However, phage translocation has not been investigated in leukemia patients yet. We recruited 44 leukemic patients and 52 healthy adults and quantified the levels of 3 phages in peripheral blood, which were the most positive phages screened from fecal samples. The content of 16S rRNA in plasma was detected by qPCR to assess the intestinal mucosa of these patients. Spearman’s rank correlation was used to analyze the relationship between phage load and the relevant clinical data. We found the most prevalent phages in fecal samples were λ phage, Wphi phage, and P22 phage, and λ phage had the highest detection rate in plasma (68%). Phage content was affected by chemotherapy and course of disease and correlated with the levels of CRP (r = 0.43, p = 0.003), sCD14 (r = 0.37, p = 0.014), and sCD163 (r = 0.44, p = 0.003). Our data indicate that plasma phage load is a promising marker for gut barrier damage and that gut phage translocation correlates with monocyte/macrophage activation and systemic inflammatory response in leukemic patients.

Human Cytomegalovirus (HCMV) infection of monocytes results in the production of inflammatory cytokine interleukin-1β (IL-1β). The objective of the study was to explore the mechanism behind the activation of inflammation. HCMV infection activated the NLRP3 inflammasome and enhanced the secretion of IL-1β in THP-1 cells. Besides, HCMV infection caused mitochondrial dysfunction, including excessive ROS production, decreased mitochondrial membrane potential, and increased mitochondrial fusion. Importantly, the infection reduced the expression of TFAM protein and the release of mitochondrial DNA into the cytoplasm, which may contribute to the activation of NLRP3 inflammasome. Collectively, our finding suggests that HCMV infection may activate NLRP3 inflammasome by releasing mtDNA into the cytosol in human THP-1 cells and provides novel insights into the innate immune response against HCMV infection.

To investigate the value of high-sensitivity C-reactive protein (hs-CRP) in evaluating the myocardial damage and prognosis in children with mycoplasmal pneumonia.A total of 150 children with mycoplasmal pneumonia were selected. According to their serum creatine kinase isoenzyme (CK-MB) level, they were divided into 72 cases of the myocardial damage group and 78 cases of the non-myocardial damage group. Eighty healthy children undergoing physical examination were selected as the control group. The electrocardiography results and serum CK-MB and hs-CRP levels were compared among the subjects. The correlations among the above indexes were analyzed.The levels of hs-CRP and CK-MB in the myocardial damage group were significantly higher than those in the nonmyocardial damage group and control group, respectively (hs-CRP may be an important index for evaluating the myocardial damage and prognosis in children with mycoplasmal pneumonia. The combination of hs-CRP and CK-MB detection has obvious guiding significance for the monitoring and treatment of mycoplasmal pneumonia complicated by myocardial damage.

Human cytomegalovirus (HCMV) is an opportunistic prototypic beta-herpesvirus that can cause severe and even fatal diseases in immune-naive newborns and immunocompromised adults. Host-virus interactions occurring at the transcriptional and posttranscriptional levels are critical for establishing an HCMV latent or lytic infection, but the mechanisms remain poorly understood. Herein, we investigated the expression of circRNAs in human leukemia monocytes (THP-1 cells) latently infected with HCMV and explored the diagnostic value of circRNAs in children with HCMV infection. A total of 2,110 and 1,912 circRNAs were identified in mock-infected and HCMV latent-infected THP-1 cells, respectively. Of these, we identified 1,421 differently expressed circRNAs, of which 650 were upregulated and 771 were downregulated. The host genes corresponding to the differentially expressed circRNAs were mainly involved in the regulation of host cell secretion pathways, cell cycle, and cell apoptosis. The differentially expressed circRNAs had binding sites for microRNAs, suggesting an important role in the mechanism of HCMV latent infection. Furthermore, a clinical analysis showed that the expression levels of hsa_circ_0001445 and hsa_circ_0001206 were statistically significantly different in HCMV-infected patients vs. normal controls, suggesting that these circRNAs could potentially serve as biomarkers of HCMV-infection.

BACKGROUND: Respiratory tract infection (RTIs) is one of common diseases among the children. In recent years, the incidence of mycoplasma pneumoniae (M. pneumoniae) infection rate has been increasing, which cause respiratory tract infection. This study sought to analyze the epidemiological characteristics of M. pneumoniae hospitalized children with RTIs to provide a theoretical basis for clinical diagnosis and treatments in Chengdu, China. METHODS: The data of 22,882 cases of children who had been hospitalized for RTIs were collected. M. pneumoniae immunoglobulin M (IgM) antibody was detected using the indirect immunofluorescence method and passive agglutination method. The demographic features of patients, clinical diagnoses and laboratory data were also analyzed. RESULTS: A total of 4,213 children tested positive for M. pneumoniae. The total positive rate was 18.41% (18.30% for males and 22.72% for females). Female children had statistically significant higher positive rates than male children (χ(2)=198.078, P0.05). There was negative correlation with PM(2.5) (particulate matter in the air

Aim: The hospitalized children with Mycoplasma pneumonia (M. pneumonia) infection caused by respiratory tract infection in Chengdu were studied and analysis of the epidemiological characteristics was carried out to provide a theoretical basis for clinical diagnosis and treatment.Method: 22882 hospitalized children with respiratory tract infections between January 2014 and December 2020 were collected M. pneumonia IgM antibody was detected by indirect immunofluorescence method and passive agglutination method. Demographic characteristics, clinical diagnose and laboratory data of these children were analyzed.retrospectively.. Result : The 4213 specimens with M. pneumonia were tested positive, the total positive rate was18.41%(18.30% in male and 22.72% in female). Higher positive rates were found in female children,Look from the statistical analysis results, the consistency between the two sets of data is low（ｘ2=198.078、P＜0.01）. The results of different age patients with contrast different M. pneumonia infection degree were statistically significant（F=162.7532、P＜0.01）,there was higher M. pneumonia positive rate in Preschoolers and school-age children ,33.98% and 32.98%, respectively.The incidence rate of M. pneumonia in 2017 and 2019 was significantly higher than average （F=538.95, P＜0.01)The difference of incidence rate of M. pneumonia was not significant in different months in 2014, 2015 and 2020 (P>0.05). But the probability of M .pneumonia infection patients was much higher from April to May and September to October in2016,2017,2018 and 2019（P＜0.05）. There was no correlation about M. pneumonia infection with temperature and humidity( P＞0.05)，there was negative correlation with PM2.5（R=0.09362, P10.（R=0.1185, P of M. pneumonia infection between 2014 and 2019 (F=32.34,P>0.05).The Common respiratory diseases of M. pneumonia infection, bronchopneumonia accounts for the highest proportion,followed the exacerbation of asthma and severe pneumonia.There was significantly difference about constituent ratio of case of M. pneumonia infection between in 2020 and in other years (F=159.35,PThe Common respiratory diseases of M. pneumonia infection, bronchopneumonia accounts for the highest proportion,followed the acute bronchitis and exacerbation of asthma.Conclusion:The distribution and epidemiological trend of M. pneumonia in patients with respiratory tract infection showed the risk of inflammation was connected with the gender, age, year and month, no relationship with temperature and humidity in Chengdu,.Higher M. pneumonia positive rate was shown in the children with bronchial pneumonia and exacerbation of asthma.The prevention measures which controlled the COVID-19 disease had effectively controlled the infection rate of M. pneumonia.

Background The serum alanine aminotransferase (ALT) level is a critical parameter for evaluating liver injury in non‐alcoholic fatty liver disease (NAFLD). However, the currently accepted upper limits of normal (ULN) for serum ALT (ULN‐ALT) are debated, as they may be excessively high. Methods A total of 1638 children aged 6‐16 years, comprising 507 children with normal BMI (500 healthy children and 7 children with NAFLD), 199 overweight children, and 932 obese children, were included in the analysis. We re‐evaluated the ULN‐ALT in 500 healthy Chinese children using the 95th percentiles of serum ALT levels as revised ULN‐ALT. Fatty liver was identified by ultrasound examination. Results Significant positive correlations between serum ALT levels and body mass index (BMI) were detected in overweight boys (r = .399, P 50, 25‐50, and ≤25 U/L and were 81.6%, 67.9%, and 20.6% in obese girls with serum ALT levels of >40, 20‐40, and ≤20 U/L, respectively. Conclusion Serum ALT levels significantly correlated with abnormal BMI values in children, suggesting a rigorous BMI threshold is needed to establish the cutoffs for serum ULN‐ALT in children. Besides, the revised serum ULN‐ALT can uncover mild liver injury in obese children with NAFLD.

Epstein-Barr virus (EBV) is a widespread human virus that establishes latent infection, potentially leading to tumors, hematological disorders, and other severe diseases. EBV infections are associated with diverse symptoms and affect various organs; therefore, early diagnosis and treatment are crucial. B cell receptor (BCR) repertoires of B cell surface immunoglobulins have been widely studied for their association with various infectious diseases. However, the specific genetic changes that modulate the BCR repertoires after an EBV infection are still poorly understood. In this study, we employed high-throughput sequencing (HTS) to investigate the diversity of BCR repertoires in an EBV-transformed lymphoblastic cell line (LCL). Compared with the noninfected control B cell line, the LCL exhibited a decrease in overall BCR diversity but displayed an increase in the expansion of some dominant rearrangements such as IGHV4-31/IGHJ4, IGHV4-59/IGHJ4, IGHV5-51/IGHJ3, and IGHV3-74/IGHJ3. A higher frequency of occurrence of these rearrangement types was confirmed in patients with EBV infection. Interestingly, the IGHV3-74 rearrangement was only detected in EBV-infected children, suggesting that our experimental observations were not coincidental. In addition, we identified a highly dominant consensus motif, CAR(xRx)YGSG(xYx)FD, in complementarity-determining region 3 (CDR3) sequences of the heavy chain in the LCL. Our findings demonstrated the utility of HTS technology for studying the variations in signature motifs of the BCR repertoires after EBV infection. We propose that the analysis of BCR repertoire sequences represents a promising method for diagnosing early EBV infections and developing novel antibody- and vaccine-based therapies against such infections.

Human cytomegalovirus (HCMV) has been recognized as a cause of severe, sometimes life-threatening disease in congenitally infected newborns as well as in immunocompromised individuals. However, the molecular mechanisms of the host-virus interaction remain poorly understood. Here, we profiled the expression of mRNAs and long noncoding RNAs (lncRNAs) in THP-1 cells using the emerging RNA-seq to investigate the transcriptional changes during HCMV latent infection. At 4 days post HCMV infection, a total of 169,008,624 sequence reads and 180,616 transcripts were obtained, respectively. Of these transcripts, 1,354 noncoding genes and 12,952 protein-coding genes were observed in Refseq database. Differential gene expression analysis identified 2,153 differentially expressed genes (DEGs) between HCMV-infected and mock-infected THP-1 cells, including 1,098 up-regulated genes and 1,055 down-regulated genes. These regulated genes were involved in pathways of apoptosis, inflammatory response and cell cycle progression, all of which may be implicated in viral pathogenesis. In addition, 646 lncRNAs (208 known lncRNAs and 438 novel lncRNAs) were upregulated and 424 (140 known and 284 novel) were downregulated in infected THP-1 cells. These findings have provided a dynamic scenario of DE candidate genes and lncRNAs at the virus-host interface and clearly warrant further experimental investigation associated with HCMV infection., Highlights • Differential gene expression analysis identified 2,153 differentially expressed genes between HCMV-infected cells and mock-infected THP-1 cells. • These regulated genes were involved in pathways of apoptosis, inflammatory response and cell cycle progression, all of which may be implicated in viral pathogenesis. • lncRNAs may involved in regulation of HCMV latent infection.

BackgroundNephrotic syndrome is related to immune system dysfunction. Soluble human leukocyte antigen-G has been suggested to have an immunomodulatory role. Additionally, human leukocyte antigen-G expression may be influenced by the 14-base pair insertion/deletion polymorphism. However, this molecule has not been investigated in nephrotic syndrome.MethodsFifty-five children with nephrotic syndrome were enrolled: 24 primary nephrotic syndrome patients and 31 recurrent nephrotic syndrome patients. A group of 120 healthy subjects were included as reference controls. Additionally, 22 patients in nephrotic syndrome remission after treatments were also included. Both nephrotic syndrome patients and healthy subjects were genotyped for the 14-base pair insertion/deletion polymorphism. Plasma soluble human leukocyte antigen-G concentrations and serum immunoglobulin concentrations were determined.ResultsNephrotic syndrome patients showed significantly higher levels of both soluble human leukocyte antigen-G and immunoglobulin E compared to normal controls. Nephrotic syndrome patients presented a higher frequency of the −14-base pair allele than did normal controls. Soluble human leukocyte antigen-G concentrations in remission patients were dramatically lower compared to in nephrotic syndrome patients. Moreover, soluble human leukocyte antigen-G and immunoglobulin E were moderately correlated in nephrotic syndrome patients.ConclusionsThe present study demonstrated that plasma soluble human leukocyte antigen-G concentrations were significantly elevated and that a relationship between serum total immunoglobulin E in nephrotic syndrome patients and the human leukocyte antigen-G −14-base pair allele may be a risk factor for nephrotic syndrome. These findings suggest that soluble human leukocyte antigen-G may be used as a monitoring marker for nephrotic syndrome patients' condition.

Key Clinical Message To investigate an oncogenic mutation of SETBP1 in the evolution from acute myelomonocytic leukemia (M4) to secondary aCML. Clinical data and molecular studies were analyzed of paired aCML and 'normal'DNA from a case with M4. We identified a mutation in SETBP1 (encoding a p.Asp868Ala alteration). The analysis of paired sample indicated that SETBP1 mutation was acquired during leukemic evolution.

Although human autologous B cells represent a promising alternative to dendritic cells (DCs) for easy large-scale preparation, the naive human B cells are always poor at antigen presentation. The safe and effective usage record of human adenovirus type 7 (HAdV7) live vaccines makes it attractive as a promising vaccine vector candidate. To investigate whether HAdV7 vector could be used to induce the human B cells cross-presentation, in the present study, we constructed the E3-defective recombinant HAdV7 vector encoding green fluorescent protein (GFP) and carcinoembryonic antigen (CEA). We demonstrated that naive human B cells can efficiently be transduced, and that the MAPKs/NF-κB pathway can be activated by recombinant HAdV7. We proved that cytokine TNF-α, IL-6 and IL-10, surface molecule MHC class I and the CD86, antigen-processing machinery (APM) compounds ERp57, TAP-1, and TAP-2. were upregulated in HAdV7 transduced human B cells. We also found that CEA-specific IFNγ expression, degranulation, and in vitro and ex vivo cytotoxicities are induced in autologous CD8(+) T cells presensitized by HAd7CEA modified human B cells. Meanwhile, our evidences clearly show that Toll-like receptors 9 (TLR9) antagonist IRS 869 significantly eliminated most of the HAdV7 initiated B cell activation and CD8(+) T cells response, supporting the role and contribution of TLR9 signaling in HAdV7 induced human B cell cross-presentation. Besides a better understanding of the interactions between recombinant HAdV7 and human naive B cells, to our knowledge, the present study provides the first evidence to support the use of HAdV7-modified B cells as a vehicle for vaccines and immunotherapy.