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1.
Transl Pediatr ; 12(3): 396-404, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37035403

ABSTRACT

Background: Refractory mycoplasma pneumoniae pneumonia (RMPP) is a serious mycoplasma pneumoniae infection and is difficult to diagnose early. The levels of serum soluble B7-dendritic cell (sB7-DC) in children with mycoplasma pneumoniae pneumonia (MPP) were assessed to explore the clinical significance of sB7-DC levels in RMPP. Methods: A total of 65 patients with mycoplasma pneumoniae pneumonia (MPP) were enrolled in this study between January 2017 and December 2018. The patients were divided into the general mycoplasma pneumoniae pneumonia (GMPP) (n=30) and RMPP groups (n=35); the data of 20 normal children served as a control group (n=20). An enzyme-linked immunoassay kit was used to detect the expression of soluble B7-dendritic cell (sB7-DC) and other inflammatory factors. Binary logistic regression was performed to identify the independent predictors of RMPP. Receiver operating characteristic (ROC) curves were drawn to evaluate the value of each independent risk factor in the early diagnosis of RMPP. Results: The results showed that compared to the GMPP group, children in the RMPP group had a significantly longer hospital stay and had a significantly longer fever duration (P<0.05). The values of interferon-gamma (IFN-γ), interleukin 17 (IL-17), and sB7-DC in the RMPP group were significantly higher than those in the normal control and GMPP groups (all P<0.05). The results of the correlation analysis showed that sB7-DC was positively correlated with IFN-γ and IL-17 and these indicators could be used in combination to evaluate the severity of the disease. The binary logistic regression analysis identified IL-17 and sB7-DC as independent risk factors for RMPP (P<0.05). The ROC curve analysis showed that the cut-off values of IL-17 and sB7-DC were 309.6 pg/L and 1,109.7 pg/mL, respectively. The areas under the curve (AUCs) of IL-17 and sB7-DC were 0.741 and 0.794, respectively. The sensitivity of IL-17 to RMPP prediction was 83.3%, and the specificity was 62.9%. The sensitivity and specificity of sB7-DC to RMPP were 86.7% and 62.9%, indicating that sB7-DC had the highest predictive power for RMPP. Conclusions: The level of serum sB7-DC may play an important role in the early diagnosis of RMPP. Our research results provide a theoretical basis for the early diagnosis of RMPP.

2.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(12): 1351-1355, 2022 Dec 15.
Article in Chinese | MEDLINE | ID: mdl-36544418

ABSTRACT

OBJECTIVES: To investigate the epidemiological characteristics of respiratory Haemophilus influenzae (HI) infection in children in Suzhou, China and its association with climatic factors and air pollutants. METHODS: The data on air pollutants and climatic factors in Suzhou from January 2016 to December 2019 were collected. Respiratory secretions were collected from 7 940 children with acute respiratory infection who were hospitalized during this period, and bacterial culture results were analyzed for the detection of HI. A stepwise regression analysis was used to investigate the association of HI detection rate with air pollutants (PM2.5, PM10, NO2, SO2, CO, and O3) and climatic factors (monthly mean temperature, monthly mean humidity, monthly total rainfall, monthly total sunshine duration, and monthly mean wind speed). RESULTS: In 2016-2019, the 4-year overall detection rate of HI was 9.26% (735/7 940) among the children in Suzhou. The children aged <1 year and 1-<3 years had a significantly higher HI detection rate than those aged ≥3 years (P<0.01). The detection rate of HI in spring was significantly higher than that in the other three seasons, and the detection rate of HI in autumn was significantly lower than that in the other three seasons (P<0.001). The multiple linear regression analysis showed that PM10 and monthly mean wind speed were independent risk factors for the detection rate of HI: the detection rate of HI was increased by 0.86% for every 10 µg/m3 increase in the concentration of PM10 and was increased by 5.64% for every 1 m/s increase in monthly mean wind speed. Air pollutants and climatic factors had a lag effect on the detection rate of HI. CONCLUSIONS: HI is an important pathogen for acute respiratory infection in children in Suzhou and is prevalent in spring. PM10 and monthly mean wind speed are independent risk factors for the detection rate of HI.


Subject(s)
Air Pollutants , Air Pollution , Haemophilus Infections , Respiratory Tract Infections , Child , Humans , Air Pollutants/adverse effects , Air Pollutants/analysis , Seasons , China/epidemiology , Haemophilus Infections/etiology , Haemophilus Infections/chemically induced , Air Pollution/adverse effects , Air Pollution/analysis
3.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1867(12): 159221, 2022 12.
Article in English | MEDLINE | ID: mdl-35981705

ABSTRACT

Polo-like kinase 1 (PLK1) is a serine/threonine kinase involving lipid metabolism and cardiovascular disease. However, its role in atherogenesis has yet to be determined. The aim of this study was to observe the impact of PLK1 on macrophage lipid accumulation and atherosclerosis development and to explore the underlying mechanisms. We found a significant reduction of PLK1 expression in lipid-loaded macrophages and atherosclerosis model mice. Lentivirus-mediated overexpression of PLK1 promoted cholesterol efflux and inhibited lipid accumulation in THP-1 macrophage-derived foam cells. Mechanistic analysis revealed that PLK1 stimulated the phosphorylation of AMP-activated protein kinase (AMPK), leading to activation of the peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα) pathway and up-regulation of ATP binding cassette transporter A1 (ABCA1) and ABCG1 expression. Injection of lentiviral vector expressing PLK1 increased reverse cholesterol transport, improved plasma lipid profiles and decreased atherosclerotic lesion area in apoE-deficient mice fed a Western diet. PLK1 overexpression also facilitated AMPK and HSL phosphorylation and enhanced the expression of PPARγ, LXRα, ABCA1, ABCG1 and LPL in the aorta. In summary, these data suggest that PLK1 inhibits macrophage lipid accumulation and mitigates atherosclerosis by promoting ABCA1- and ABCG1-dependent cholesterol efflux via the AMPK/PPARγ/LXRα pathway.


Subject(s)
Atherosclerosis , Cell Cycle Proteins , Protein Serine-Threonine Kinases , Proto-Oncogene Proteins , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , ATP Binding Cassette Transporter 1/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics , Animals , Apolipoproteins E/metabolism , Atherosclerosis/metabolism , Cell Cycle Proteins/genetics , Cholesterol/metabolism , Liver X Receptors/genetics , Liver X Receptors/metabolism , Mice , PPAR gamma/genetics , PPAR gamma/metabolism , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins/genetics , Serine , Polo-Like Kinase 1
4.
Sci Rep ; 12(1): 5018, 2022 03 23.
Article in English | MEDLINE | ID: mdl-35322129

ABSTRACT

Wheezing diseases are one of the major chronic respiratory diseases in children. To explore the effects of meteorological and environmental factors on the prevalence of children wheezing diseases, clinical data of children hospitalized with wheezing diseases in Suzhou, China from 2013 to 2017 were collected. Meteorological and environmental factors from 2013 to 2017 were obtained from the local Meteorological Bureau and Environmental Protection Bureau. Relationships between wheezing diseases and meteorological and environmental factors were evaluated using Pearson's correlation and multivariate regression analysis. An autoregressive integrated moving average (ARIMA) model was used to estimate the effects of meteorological and environmental variables on children wheezing diseases. Children wheezing diseases were frequently presented in infants less than 12 months old (1897/2655, 58.28%), and the hospitalization rate was highest in winter (1024/3255, 31.46%). In pathogen-positive specimens, the top three pathogens were respiratory syncytial virus (21.35%), human rhinovirus (16.28%) and mycoplasma pneumoniae (10.47%). The seasonality of wheezing children number showed a distinctive winter peak. Children wheezing diseases were negatively correlated with average temperature (P < 0.001, r = - 0.598). The ARIMA (1,0,0)(0,0,0)12 model could be used to predict temperature changes associated wheezing diseases. Meteorological and environmental factors were associated with the number of hospitalized children with wheezing diseases and can be used as early warning indicators for the occurrence of wheezing diseases and prevalence of virus.


Subject(s)
Respiratory Sounds , Respiratory Syncytial Virus, Human , Child , Child, Hospitalized , China/epidemiology , Humans , Infant , Respiratory Sounds/etiology , Seasons
5.
Front Pharmacol ; 12: 690371, 2021.
Article in English | MEDLINE | ID: mdl-34950023

ABSTRACT

Atrial fibrosis is the basis for the occurrence and development of atrial fibrillation (AF) and is closely related to the Warburg effect, endoplasmic reticulum stress (ERS) and mitochondrion dysfunctions-induced cardiomyocyte apoptosis. Hydrogen sulfide (H2S) is a gaseous signalling molecule with cardioprotective, anti-myocardial fibrosis and improved energy metabolism effects. Nevertheless, the specific mechanism by which H2S improves the progression of atrial fibrosis to AF remains unclear. A case-control study of patients with and without AF was designed to assess changes in H2S, the Warburg effect, and ERS in AF. The results showed that AF can significantly reduce cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate thiotransferase (3-MST) expression and the H2S level, induce cystathionine-ß-synthase (CBS) expression; increase the Warburg effect, ERS and atrial fibrosis; and promote left atrial dysfunction. In addition, AngII-treated SD rats had an increased Warburg effect and ERS levels and enhanced atrial fibrosis progression to AF compared to wild-type SD rats, and these conditions were reversed by sodium hydrosulfide (NaHS), dichloroacetic acid (DCA) or 4-phenylbutyric acid (4-PBA) supplementation. Finally, low CSE levels in AngII-induced HL-1 cells were concentration- and time-dependent and associated with mitochondrial dysfunction, apoptosis, the Warburg effect and ERS, and these effects were reversed by NaHS, DCA or 4-PBA supplementation. Our research indicates that H2S can regulate the AngII-induced Warburg effect and ERS and might be a potential therapeutic drug to inhibit atrial fibrosis progression to AF.

6.
Langenbecks Arch Surg ; 406(2): 497-502, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33420833

ABSTRACT

PURPOSE: Esophagojejunostomy is a challenging step in laparoscopic gastrectomy. Although the overlap method is a safe and feasible approach for esophagojejunostomy, it has several technical limitations. We developed novel modifications for the overlap method to overcome these disadvantages. METHODS: Forty-eight consecutive gastric cancer patients underwent totally laparoscopic total gastrectomy or laparoscopic proximal gastrectomy with double-tract reconstruction at our institution from January 2019 to April 2020 using the overlap method with the following modifications. The esophagus was initially rotated by 90° counterclockwise, followed by transection of two-thirds of the esophageal diameter. The unstapled esophagus was then transected with a harmonic ultrasonic scalpel to enable esophagostomy at the posterior side of the esophagus. A side-to-side esophagojejunostomy was then formed at the posterior side of the esophagus using an endoscopic linear stapler through the right lower trocar. The common entry hole was closed via hand sewing method using V-Loc suture. This procedure was termed "esophagus two-step-cut overlap method." RESULTS: Only one patient suffered from esophagojejunal anastomotic leakage but subsequently recovered after conservative treatment. Patients did not experience anastomotic bleeding or stricture. CONCLUSION: Our modified overlap method provides satisfactory surgical outcomes and overcomes several technical limitations, such as entering the false lumen of the esophagus, unnecessary pollution caused by nasogastric tube, and unintended left crus stapling during anastomosis.


Subject(s)
Laparoscopy , Stomach Neoplasms , Anastomosis, Surgical , Esophagus/surgery , Gastrectomy/adverse effects , Humans , Jejunum/surgery , Stomach Neoplasms/surgery , Surgical Stapling/adverse effects
7.
Ann Transl Med ; 9(23): 1727, 2021 Dec.
Article in English | MEDLINE | ID: mdl-35071421

ABSTRACT

BACKGROUND: Programmed death-ligand 1 (PD-L1) is an important immune checkpoint inhibitor. Recent studies suggest that the PD-L1-mediated pathway may be a promising target in allergic asthma. However, the mechanism by which PD-L1 represses neutrophilic asthma (NA) remains unclear. In this study, we examined correlations between the expression of PD-L1 and the production of T helper cell type 1 (Th1), T helper cell type 2 (Th2), and T helper cell type 17 (Th17) cells in pediatric patients with NA and a mouse model. METHODS: The clinical samples of 26 children with asthma and 15 children with a bronchial foreign body were collected over a period of 12 months by the Children's Hospital of Soochow University. An experimental mouse model of asthma was established to study NA. An enzyme-linked immunoassay (ELISA) was used to assess soluble PD-L1 (sPD-L1) and cytokines [e.g., interleukin (IL)-4, IL-6, interferon gamma (IFN-γ), IL-17 and granulocyte-macrophage colony-stimulating factor (GM-CSF)] in bronchoalveolar lavage fluid (BALF). RESULTS: NA patients had significantly higher levels of sPD-L1, IL-6, IL-17, and GM-CSF in their BALF than non-NA and control patients (P<0.05). In a murine model of asthma, the positive rate and fluorescence intensity of PD-L1 in the NA group and the immunoglobulin G (IgG)-treated NA group were higher than in the PD-L1 antibody (Ab)-treated NA group and the phosphate-buffered saline (PBS) control group (P<0.05). In the plasma and the BALF of the NA group and the IgG-treatment NA group, the levels of IL-17, IL-4, tumor necrosis factor alpha (TNF-α), and granulocyte colony-stimulating were higher than those in the PBS control group (P<0.05). The histopathological examination of lung tissues from all mice groups showed that a large number of inflammatory cells were found around the airway in the NA group and the IgG-treatment group. CONCLUSIONS: PD-L1 may contribute to the Th17/IL-17 immune response, which is associated with neutrophilic inflammation and asthma. A PD-L1 blockade reduces pulmonary neutrophils and mucus production.

8.
Ann Transl Med ; 8(6): 386, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32355830

ABSTRACT

BACKGROUND: This study set out to evaluate the clinical significance and diagnostic effectiveness of serological tests and real-time polymerase chain reactions (RT-PCR) in children of different age groups and disease durations infected with Mycoplasma pneumoniae (MP). METHODS: Pediatric patients with lower respiratory tract infection (LRTI) confirmed by polymerase chain reaction (PCR) were enrolled and subjected to bronchoalveolar lavage fluid PCR (BALF-PCR) for MP infection. The diagnostic values of the serum immunoglobulin M (IgM) test, paired sera immunoglobulin G (IgG) test, RT PCR applied to nasopharyngeal aspirates (NPA-PCR), and combined IgM and NPA-PCR test were evaluated. RESULTS: When BALF PCR was used as the gold standard, the MP positivity rate of combined IgM and NPA PCR was 78.85%in children aged 3-5 years. The positivity rates of IgM, NPA PCR, and combined IgM and NPA PCR in children older than 5 years were 71.21%, 72.72%, and 84.85%, respectively. The detection rate of combined IgM and NPA PCR was consistent with BALF PCR (Kappa =0.727). The MP positivity rates of combined IgM and NPA PCR at 1-2 weeks was as high as 91.11%, and was consistent with the BALF PCR (Kappa =0.756). Moreover, the positivity rates of IgM or NPA PCR at 2-3 weeks were 63.16%, and were consistent with each other (Kappa =0.771). CONCLUSIONS: Combined IgM and NPA PCR is the optimal test to confirm MP infection among children aged 3-5 years in cases with a disease duration of less than2 weeks, and either NPA PCR or IgM is recommended for children older than 5 years with a disease duration of 2-3 weeks. KEYWORDS: Mycoplasma pneumoniae pneumonia (MPP); diagnosis; children; age; disease duration.

9.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(6): 505-510, 2019 Jun.
Article in Chinese | MEDLINE | ID: mdl-31208500

ABSTRACT

OBJECTIVE: To investigate the viral etiology and allergen distribution in infants and young children at high risk of asthma during a wheezing episode. METHODS: A total of 135 infants and young children at high risk of asthma were enrolled who were admitted due to asthmatic bronchitis or asthmatic bronchopneumonia between April 2016 and August 2017. Fluorescent probe PCR was used to measure influenza A (Flu A), respiratory syncytium virus (RSV), adenovirus (ADV), parainfluenza virus (PinF), human rhinovirus (HRV), human partial lung virus (hMPV) and human bocavirus (HBoV) in nasopharyngeal aspirates. ImmunoCAP was used to measure inhaled allergens, food allergens, and total IgE concentration. RESULTS: Among the 135 patients, the overall virus detection rate of nasopharyngeal aspirates was 49.6%, and HRV had the highest detection rate of 25.2%, followed by HBoV (9.6%), RSV (8.1%), PinF (5.9%), Flu-A (3.7%), ADV (1.5%) and hMPV (0.7%). The 1-3 years group had a significantly higher detection rate of HRV than the <1 year group (P<0.05). The positive rate of allergen screening was 59.3%, with 44% for inhaled allergens and 89% for food allergens. Among the inhaled allergens, dust mites had the highest positive rate of 77%, followed by mould (37%), pollen (26%) and animal dander (9%). Among the food allergens, egg white had a positive rate of 73% and milk had a positive rate of 68%. The <1 year group had a significantly higher positive rate of inhaled allergens than the 1-3 years group (P<0.05). The 1-3 years age group had a significantly higher level of T-IgE than the <1 year group (P<0.05). The positive virus group had a significantly higher positive rate of inhaled allergens than the non-virus group (P<0.05). The children with the second wheezing episode had significantly higher positive rates of inhaled allergens and food allergens and level of T-IgE than those with the first wheezing episode (P<0.05). The children with the second wheezing episode also had significantly higher positive rates of dust mites and mould than those with the first wheezing episode (P<0.05). CONCLUSIONS: Early HRV infection and inhaled allergen sensitization are closely associated with the development of wheezing in infants and young children at high risk of asthma.


Subject(s)
Asthma , Egg Hypersensitivity , Allergens , Animals , Child , Child, Preschool , Humans , Infant , Pyroglyphidae , Respiratory Sounds
10.
Ital J Pediatr ; 45(1): 61, 2019 May 14.
Article in English | MEDLINE | ID: mdl-31088519

ABSTRACT

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is one of the most common causes of community-acquired pneumonia in children. Recent studies demonstrated that the incidence of severe or fatal M. pneumoniae was gradually increasing, which may be related to the excessive inflammation. However, the exact pathogenesis of excessive inflammation in Mycoplasma pneumoniae pneumonia(MPP) is still unclear. This study aimed to reveal the role of miR-29c/B7-H3/Th17 axis in children with MPP. METHODS: Children hospitalized in Respiratory Department during Jan. 2014 to Dec. 2015 were enrolled. All children enrolled was confirmed with MP infection using real-time PCR and ELISA. Children were excluded if they were co-infected with other pathogens. A total of 52 children with MPP and 26 controls were enrolled. miR-29c expression in monocytes of children with MPP was determined by real-time PCR and soluble B7-H3 (sB7-H3) and IL-17 were determined by ELISA, and explore their clinical significance. miR-29c overexpression and silencing technology and luciferase reporter assay were performed to confirm whether B7-H3 is the direct target of miR-29c. The levels of transcription factor ROR-γt in CD4+ T cells and cytokine IL-17A in supernatant were detected after stimulated by different concentrations of B7-H3 fusion protein in vitro. RESULTS: Of all 52 children with MPP, the mean age of the children were 77 ± 33 months, and 23 cases were male accounting for 44.2%. Nineteen cases had pleural effusion accounting for 36.5%. Children with MPP had significantly lower level of miR-29c and higher level of sB7-H3 and IL-17 compared to controls (both P < 0.05). The level of miR-29c significantly increased during convalescent phase compared to that of acute phase while sB7-H3 and IL-17 significantly decreased during convalescent phase (both P < 0.05). There was a positive correlation between the level of sB7-H3 and IL-17 in children with MPP during acute-stage (r = 0.361,P = 0.009). Children with MPP combined with pleural effusion had significantly higher level of sB7-H3 compared to those without pleural effusion (9952.3 ± 3065.3 vs. 7449.7 ± 2231.5, pg/ml), and the levels of sB7-H3 was positively correlated with the number of days of fever. The level of miR-29c was negatively correlated with M. pneumoniae specific IgG, IgM level. High concentrations of B7-H3(15µg/ml) could enhance ROR-γt expression and increase IL-17A. Functional studies based on luciferase reporter assay and immunofluorescence staining suggested that B7-H3 is the direct target of miR-29c, and miR-29c silencing or overexpression could up- or down-regulate the expression of B7-H3 in THP-1 cells. CONCLUSIONS: The axis of miR-29c/B7-H3/Th17 plays a vital role in children with MPP through excessive inflammation. miR-29c and B7-H3 may be the new target for the prevention and treatment of MPP, and may be the novel and potential biomarkers for the assessment of prognosis.


Subject(s)
B7 Antigens/metabolism , Interleukin-17/metabolism , MicroRNAs/metabolism , Mycoplasma pneumoniae , Pneumonia, Mycoplasma/diagnosis , Pneumonia, Mycoplasma/metabolism , Case-Control Studies , Child, Preschool , Community-Acquired Infections , Female , Humans , Infant , Male , Pneumonia, Mycoplasma/etiology
11.
Medicine (Baltimore) ; 97(52): e13808, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30593171

ABSTRACT

This study aims to analyze and summarize the imaging features of spinal atypical teratoid/rhabdoid tumors (AT/RT) in children.Imaging features in 8 children with spinal AT/RT confirmed by surgical pathology were retrospectively analyzed. All patients had underwent total spine 3.0 T magnetic resonance imaging (MRI) and 64-slice spiral computed tomography (CT). Among these 8 patients, head MR non-enhanced and spinal enhanced scanning was applied to 5 patients, while CT examination was applied to 3 patients.All 8 patients were characterized by cauda equina syndrome. The lesions of 7 patients were in the thoracolumbar spinal junction, while the lesion of the remaining patient was in the lumbar spine. Furthermore, among these patients, the lesions of 5 patients were limited to the intraspinal canal (1 lesion in the epidural space, and 4 lesions in the subdural space), while the lesions of 3 patients invaded the paravertebra (2 lesions in the epidural space and 1 lesion in the subdural space). Three or more spinal segments were invaded by tumors in 7 patients, while sacral canal was affected in 5 patients. All 8 patients experienced bleeding in the tumors. Enhanced MRI revealed meningeal enhancement in 6 patients, and bilateral nerve root enhancement in 4 patients. The masses in 3 patients brought damages to the intervertebral foramen or sacral pore. The lesion of 1 patient was featured by skip growth. One patient had total spinal metastasis and 3 had hydrocephalus. The masses in 2 patients had a slightly low density when detected by CT, and enhanced scanning revealed a mild to moderate enhancement.Spinal AR/TR had the following characteristics: children were characterized by cauda equina syndrome; the mass that invaded the thoracolumbar spinal junction and the extramedullary space of multiple segments grew along the spinal longitudinal axis; bleeding mass was revealed in MRI imaging; meninges, nerve root, and sacral canal metastases occurred. The gold standard for the definite diagnosis of AT/RT is biopsy combined with immunohistochemistry.


Subject(s)
Magnetic Resonance Imaging , Rhabdoid Tumor/diagnostic imaging , Spinal Neoplasms/diagnostic imaging , Teratoma/diagnostic imaging , Tomography, X-Ray Computed , Cauda Equina Syndrome/diagnostic imaging , Cauda Equina Syndrome/etiology , Child, Preschool , Female , Humans , Male , Retrospective Studies , Rhabdoid Tumor/complications , Spinal Neoplasms/complications , Spine/diagnostic imaging , Teratoma/complications
12.
Acta Pharmacol Sin ; 39(10): 1645-1660, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29849127

ABSTRACT

Escin, a triterpene saponin isolated from horse chestnut seed, has been used to treat encephaledema, tissue swelling and chronic venous insufficiency. Recent studies show that escin induces cell cycle arrest, tumor proliferation inhibition and tumor cell apoptosis. But the relationship between escin-induced DNA damage and cell apoptosis in tumor cells remains unclear. In this study, we investigated whether and how escin-induced DNA damage contributed to escin-induced apoptosis in human colorectal cancer cells. Escin (5-80 µg/mL) dose-dependently inhibited the cell viability and colony formation in HCT116 and HCT8 cells. Escin treatment induced DNA damage, leading to p-ATM and γH2AX upregulation. Meanwhile, escin treatment increased the expression of p62, an adaptor protein, which played a crucial role in controlling cell survival and tumorigenesis, and had a protective effect against escin-induced DNA damage: knockdown of p62 apparently enhanced escin-induced DNA damage, whereas overexpression of p62 reduced escin-induced DNA damage. In addition, escin treatment induced concentration- and time-dependent apoptosis. Similarly, knockdown of p62 significantly increased escin-induced apoptosis in vitro and produced en escin-like antitumor effect in vivo. Overexpression of p62 decreased the rate of apoptosis. Further studies revealed that the functions of p62 in escin-induced DNA damage were associated with escin-induced apoptosis, and p62 knockdown combined with the ATM inhibitor KU55933 augmented escin-induced DNA damage and further increased escin-induced apoptosis. In conclusion, our results demonstrate that p62 regulates ATM/γH2AX pathway-mediated escin-induced DNA damage and apoptosis.


Subject(s)
Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Colorectal Neoplasms/drug therapy , DNA Damage/drug effects , Escin/therapeutic use , Sequestosome-1 Protein/metabolism , Animals , Antineoplastic Agents/pharmacology , Ataxia Telangiectasia Mutated Proteins/genetics , Ataxia Telangiectasia Mutated Proteins/metabolism , Autophagy/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Down-Regulation , Escin/pharmacology , Female , Histones/genetics , Histones/metabolism , Humans , Mice, Nude , Sequestosome-1 Protein/genetics , Signal Transduction/drug effects , Up-Regulation
13.
World J Gastroenterol ; 24(3): 387-396, 2018 Jan 21.
Article in English | MEDLINE | ID: mdl-29391761

ABSTRACT

AIM: To investigate the prevalence and clinical significance of autoimmune liver disease (ALD)-related autoantibodies in patients with biliary atresia (BA). METHODS: Sera of 124 BA patients and 140 age-matched non-BA controls were assayed for detection of the following autoantibodies: ALD profile and specific anti-nuclear antibodies (ANAs), by line-blot assay; ANA and anti-neutrophil cytoplasmic antibody (ANCA), by indirect immunofluorescence assay; specific ANCAs and anti-M2-3E, by enzyme linked immunosorbent assay. Associations of these autoantibodies with the clinical features of BA (i.e., cytomegalovirus infection, degree of liver fibrosis, and short-term prognosis of Kasai procedure) were evaluated by Spearman's correlation coefficient. RESULTS: The overall positive rate of serum autoantibodies in preoperative BA patients was 56.5%. ALD profile assay showed that the positive reaction to primary biliary cholangitis-related autoantibodies in BA patients was higher than that to autoimmune hepatitis-related autoantibodies. Among these autoantibodies, anti-BPO was detected more frequently in the BA patients than in the controls (14.8% vs 2.2%, P < 0.05). Accordingly, 32 (25.8%) of the 124 BA patients also showed a high positive reaction for anti-M2-3E. By comparison, the controls had a remarkably lower frequency of anti-M2-3E (P < 0.05), with 6/92 (8.6%) of patients with other liver diseases and 2/48 (4.2%) of healthy controls. The prevalence of ANA in BA patients was 11.3%, which was higher than that in disease controls (3.3%, P < 0.05), but the reactivity to specific ANAs was only 8.2%. The prevalence of ANCAs (ANCA or specific ANCAs) in BA patients was also remarkably higher than that in the healthy controls (37.9% vs 6.3%, P < 0.05), but showed no difference from that in patients with other cholestasis. ANCA positivity was closely associated with the occurrence of postoperative cholangitis (r = 0.61, P < 0.05), whereas none of the autoantibodies showed a correlation to cytomegalovirus infection or the stages of liver fibrosis. CONCLUSION: High prevalence of autoantibodies in the BA developmental process strongly reveals the autoimmune-mediated pathogenesis. Serological ANCA positivity may be a useful predictive biomarker of postoperative cholangitis.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/blood , Antibodies, Antinuclear/blood , Biliary Atresia/blood , Cholangitis, Sclerosing/blood , Hepatitis, Autoimmune/blood , Antibodies, Antineutrophil Cytoplasmic/immunology , Autoantigens/immunology , Biliary Atresia/immunology , Biliary Atresia/surgery , Biomarkers/blood , Cholangitis, Sclerosing/immunology , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Enzyme-Linked Immunosorbent Assay , Female , Fluorescent Antibody Technique, Indirect , Hepatitis, Autoimmune/immunology , Humans , Infant , Liver Cirrhosis/blood , Liver Cirrhosis/immunology , Male , Portoenterostomy, Hepatic/adverse effects , Portoenterostomy, Hepatic/methods , Postoperative Complications/blood , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Preoperative Period , Prognosis , Retrospective Studies
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(1): 34-38, 2017 Jan.
Article in Chinese | MEDLINE | ID: mdl-28100319

ABSTRACT

OBJECTIVE: To study the epidemiological characteristics of respiratory adenovirus (ADV) infections in children from the Suzhou area, China. METHODS: The clinical data of ADV-positive children out of 35 529 children with respiratory tract infections who were hospitalized in the Children's Hospital of Soochow University between January 2006 and December 2015 were retrospectively studied. RESULTS: Of the 35 529 children with respiratory tract infections, 440 (1.24%) were ADV-positive. There was no significant difference in the rate of ADV infections between boys and girls (1.18% vs 1.34%). The ADV infection rates of children at the age of <1 year old, 1-3 years old, 3-7 years old and 7-14 years old were 0.39% (71/18 002), 1.12% (103/9 191), 3.14% (201/6 398), and 3.35%( 65/1 938) respectively and the rate increased with age (P<0.01). The ADV infection rates in spring [1.85%(60/8 658)] and summer [2.20%(189/8 606)] were significantly higher than in autumn [0.30%(27/8 952)] and winter [0.69%(64/9 313)] (P<0.01). CONCLUSIONS: The ADV infection rate is increased with age in the children from the Suzhou area, but it is not associated with gender. ADV infections are more common in spring and summer.


Subject(s)
Adenoviridae Infections/epidemiology , Respiratory Tract Infections/epidemiology , Adolescent , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Male , Time Factors
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(11): 1094-1099, 2016 Nov.
Article in Chinese | MEDLINE | ID: mdl-27817772

ABSTRACT

OBJECTIVE: To investigate the detection rates, epidemical characteristics, and clinical features of human rhinovirus C (HRV-C) in hospitalized children with respiratory tract infections (RTIs) in Suzhou, China. METHODS: A total of 1 702 hospitalized children with RTIs from January to December, 2014 were enrolled, and 1 702 nasopharyngeal aspirate samples were collected from all children. RT-PCR was used to measure HRV mRNA, and quantitative real-time PCR combined with high-resolution melting curve was used to measure HRV-C. RESULTS: Of all children, 244 (14.34%) were detected to have HRV infection, among whom 69 (69/244, 28.3%) had HRV-C infection. The rate of mixed infection of HRV-C with other viruses and bacteria was 61% (42/69). HRV-C was detected in each month of the year, and the detection rate of HRV-C in autumn was significantly higher than that in spring, summer, and winter (P<0.05). The children aged 2-5 years had a significantly higher detection rate of HRV-C than those in the other age groups (P<0.05). Compared with HRV-A/B infection, HRV-C infection led to significantly higher proportions of patients with lobar pneumonia and acute exacerbation of asthma (P<0.05), as well as patients with increased neutrophil count and CRP level (P<0.05). There were no significant differences in sex distribution or other clinical manifestations (P>0.05). CONCLUSIONS: HRV-C infection accounts for about 1/3 of HRV infection, with a high incidence rate in autumn. The rate of mixed infection of HRV-C with other viruses and bacteria is high, and children aged 2-5 years have the highest detection rate of HRV-C. Children with HRV-C infection have similar clinical manifestations as those with HRV-A/B infection.


Subject(s)
Respiratory Tract Infections/virology , Rhinovirus/isolation & purification , Child , Child, Hospitalized , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Real-Time Polymerase Chain Reaction , Rhinovirus/classification , Seasons
16.
J Med Virol ; 88(2): 211-5, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26240959

ABSTRACT

To compare the presence of human bocavirus (HBoV) in nasopharyngeal aspirates (NPA) versus broncho-alveolar lavage fluids (BAL) in children with lower respiratory tract infections (LRTIs), as revealed by real-time PCR, in order to confirm the diagnostic validity of NPA samples. A retrospective 5-year study was performed from 2009 to 2014 in 1,194 patients under the age of 17 years (mean age of 3 years) that were diagnosed with LRTIs and from whom both NPA and BAL were obtained. Clinical and demographic data were recorded, and NPA and BAL samples were analyzed for HBoV-positivity by real-time PCR. Of the 1,194 patients enrolled, 65 (5.4%) patients had HBoV detected from NPA, and 61 (5.1%) had HBoV detected from BAL. For HBoV, there was a significant association between the NPA and BAL samples (P < 0.001), but the diagnostic validity was relatively low (kappa = 0.414). When real-time PCR-positivity for HBoV in BAL was used as a reference for diagnosis, NPA had a good specificity and better positive predictive validity in male patients or those younger than 3 years of age. NPA has a similar yield and a good specificity for diagnosis of LRTIs with HBoV compared to BAL. The best diagnostic validity for NPA was detected in male patients or those younger than 3 years old.


Subject(s)
Bodily Secretions/virology , Bronchoalveolar Lavage Fluid/virology , Human bocavirus/isolation & purification , Nasopharynx/virology , Parvoviridae Infections/diagnosis , Respiratory Tract Infections/diagnosis , Specimen Handling/methods , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Parvoviridae Infections/virology , Real-Time Polymerase Chain Reaction/methods , Respiratory Tract Infections/virology , Retrospective Studies
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 17(9): 937-41, 2015 Sep.
Article in Chinese | MEDLINE | ID: mdl-26412174

ABSTRACT

OBJECTIVE: To compare the detection rates of Mycoplasma pneumoniae (MP) from nasopharyngeal aspirates (NPA) and bronchoalveolar lavage fluid (BALF) in children with pneumonia. METHODS: A total of 164 hospitalized children with pneumonia were enrolled. NPA and BALF of these children were collected within 24 hours of admission, and MP-DNA was detected by fluorescence quantitative PCR. Venous blood samples of all these children were collected within 24 hours of admission and on days 7-10 of treatment, and serum MP-IgM was detected using ELISA. RESULTS: The positive rate of MP-DNA in NAP of the 164 cases was 51.8% , which was lower than 63.4% as the detection rate of MP-IgM in serum (P=0.044), and the two detection rates were moderately consistent with each other (Kappa=0.618, P<0.01). The positive rate of MP in BALF was 71.3%, which was not significantly different with that of MP-IgM in serum (P>0.05), and the detection rates were well consistent (Kappa=0.793, P<0.01). The detection rate of MP in NPA was lower than that in BALF (P<0.01), with moderate consistency between two of them (Kappa=0.529, P<0.01). The median MP copy number in BALF was significantly higher than that in NPA (P<0.01). The MP detection rates in NPA and BALF were significantly different among different courses of disease (P<0.05). As the course of disease extended, the MP detection rates in both NPA and BALF showed a declining trend; children with MP pneumonia of 1-2 weeks' duration and 2-4 weeks' duration had a higher MP-DNA detection rate in BALF than in NPA (P<0.05). CONCLUSIONS: MP-DNA in BALF has a high sensitivity, with a great significance for early diagnosis of MP pneumonia, while NPA MP-DNA tests may lead to a missed diagnosis.


Subject(s)
Bronchoalveolar Lavage Fluid/microbiology , DNA, Bacterial/analysis , Nasopharynx/microbiology , Pneumonia, Mycoplasma/diagnosis , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male
18.
World J Gastroenterol ; 21(19): 5893-900, 2015 May 21.
Article in English | MEDLINE | ID: mdl-26019453

ABSTRACT

AIM: To validate the value of aspartate aminotransferase to platelet ratio index (APRI) in assessment of liver fibrosis and prediction of postoperative prognosis of biliary atresia (BA) infants from Mainland China. METHODS: Medical records of 153 BA infants who were hospitalized from January 2010 to June 2013 were reviewed. The efficacy of APRI for diagnosis of liver fibrosis was assessed using the receiver operator characteristic (ROC) curve compared to the pathological Metavir fibrosis score of the liver wedge specimens of 91 BA infants. The prognostic value of preoperative APRI for jaundice persistence, liver injury, and occurrence of cholangitis within 6 mo after KP was studied based on the follow-up data of 48 BA infants. RESULTS: APRI was significantly correlated with Metavir scores (rs = 0.433; P < 0.05). The mean APRI value was 0.76 in no/mild fibrosis group (Metavir score F0-F1), 1.29 in significant fibrosis group (F2-F3), and 2.51 in cirrhosis group (F4) (P < 0.001). The area under the ROC curve (AUC) of APRI for diagnosing significant fibrosis and cirrhosis was 0.75 (P < 0.001) and 0.81 (P = 0.001), respectively. The APRI cut-off of 0.95 was 60.6% sensitive and 76.0% specific for significant fibrosis diagnosis, and a threshold of 1.66 was 70.6% sensitive and 82.7% specific for cirrhosis. The preoperative APRI in infants who maintained jaundice around 6 mo after KP was higher than that in those who did not (1.86 ± 2.13 vs 0.87 ± 0.48, P < 0.05). The AUC of APRI for prediction of postoperative jaundice occurrence was 0.67. A cut-off value of 0.60 showed a sensitivity of 66.7% and a specificity of 83.3% for the prediction of jaundice persistence. Preoperative APRI had no significant association with later liver injury or occurrence of cholangitis. CONCLUSION: Our study demonstrated that APRI could diagnose significant liver fibrosis, especially cirrhosis in BA infants, and the elevated preoperative APRI predicts jaundice persistence after KP.


Subject(s)
Aspartate Aminotransferases/blood , Biliary Atresia/diagnosis , Blood Platelets , Clinical Enzyme Tests , Liver Cirrhosis/diagnosis , Liver Function Tests , Area Under Curve , Biliary Atresia/blood , Biliary Atresia/enzymology , Biliary Atresia/pathology , Biliary Atresia/surgery , Biomarkers/blood , Biopsy , China , Female , Humans , Infant , Infant, Newborn , Liver Cirrhosis/blood , Liver Cirrhosis/enzymology , Liver Cirrhosis/pathology , Liver Cirrhosis/surgery , Male , Medical Records , Platelet Count , Portoenterostomy, Hepatic , Predictive Value of Tests , ROC Curve , Reproducibility of Results , Retrospective Studies , Severity of Illness Index , Time Factors , Treatment Outcome
19.
J Formos Med Assoc ; 113(7): 463-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24961189

ABSTRACT

BACKGROUND/PURPOSE: To investigate the prevalence of common viruses and Mycoplasma pneumoniae (MP) in hospitalized infants with acute bronchiolitis and study the relationship between bronchiolitis and meteorological conditions. METHODS: A 2-year prospective study was conducted on infants with a first episode of bronchiolitis admitted to Respiratory Department of Suzhou Children's Hospital. Demographic and clinical characteristics and meteorological conditions were obtained and analyzed. RESULTS: Pathogens were identified in 59.6% of 998 cases analyzed. The most frequent pathogen identified was respiratory syncytial virus (28.7%), followed by human bocavirus (11.6%), MP (9.0%), human parainfluenza virus-3 (7.8%), human metapneumovirus (6.6%), influenza A (3.5%), adenovirus (1.0%), and human parainfluenza virus-1 (0.3%). The clinical scores in children with MP or human metapneumovirus single infections, based on the assessment of severity of acute bronchiolitis, were significantly lower than in children with respiratory syncytial virus single infections. Respiratory syncytial virus had the strongest inverse correlation with mean temperature, followed by influenza A and human metapneumovirus. In addition, MP and human parainfluenza virus-3 showed positive correlations with mean temperature. CONCLUSION: Although respiratory syncytial virus was the most frequent pathogen in patients in whom bronchiolitis was diagnosed, other pathogens, including newly identified viruses and MP, also play important roles in infants with bronchiolitis. Different respiratory pathogens have different traits in response to certain meteorological conditions.


Subject(s)
Bronchiolitis/virology , Virus Diseases/complications , Virus Diseases/virology , Weather , Acute Disease , Adenoviridae , Child, Preschool , China , Cross-Sectional Studies , Hospitalization , Human bocavirus , Humans , Infant , Influenza A virus , Metapneumovirus , Mycoplasma pneumoniae , Parainfluenza Virus 1, Human , Parainfluenza Virus 3, Human , Prospective Studies , Respiratory Syncytial Viruses
20.
J Med Virol ; 86(12): 2154-62, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24782248

ABSTRACT

Lower respiratory tract infection is a major cause of morbidity and mortality in children. Human bocavirus (HBoV) is confirmed to have an association with pediatric lower respiratory tract infection. Seasonal and meteorological factors may play a key role in the epidemiology of HBoV. The purpose of this study was to ascertain the frequency, season, and clinical characteristics of hospitalized children with HBoV infection. In addition, an evaluation of the effects of meteorological factors on the incidence of HBoV in a subtropical area in China will be conducted. Children were <14 years in age and hospitalized for lower respiratory tract infection between January 1, 2009 and December 31, 2012 in the Respiratory Disease Department at the Children's Hospital affiliated to Soochow University. Multi-pathogens were detected in nasopharyngeal aspirate samples. The association between HBoV activity and regional meteorological conditions was analyzed. The average incidence of HBoV infection was 6.6% (502/7,626). Of the 502 HBoV positive children, the median age was 13 months (range 1-156 months). The HBoV infection rate was highest among the 7-12 months groups (12.9%, 163/1,267). Seasonal distribution of HBoV was noted during June to November, especially during the summer season (June to August). HBoV activity was associated with temperature and humidity although the lag effect between temperature and HBoV activity observed. HBoV is one of the most common viral pathogens in children with lower respiratory tract infection. HBoV infection occurs throughout the year with a peak during the summer. Temperature and humidity may affect the incidence of HBoV.


Subject(s)
Child, Hospitalized , Human bocavirus/isolation & purification , Parvoviridae Infections/epidemiology , Parvoviridae Infections/pathology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/pathology , Adolescent , Age Factors , Child , Child, Preschool , China/epidemiology , Climate , Coinfection/virology , Humans , Incidence , Infant , Male , Nasopharynx/virology , Parvoviridae Infections/virology , Respiratory Tract Infections/virology , Retrospective Studies , Seasons
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