Objectives To investigate the relationship between self-reported occupational noise exposure and levels of plasma inflammatory cytokines in asthmatic patients. Methods A total of 910 adult asthmatic patients were selected as the study subjects, and their occupational noise exposure history and other related information were collected. The peripheral blood samples were collected from the patients, and the expression levels of plasma soluble CD14 (sCD14), complement factor D (CFD), Eotaxin-11 (CCL11), and IL-9 were determined. The relationship between self-reported occupational noise exposure and the expression levels of the four inflammatory cytokines in patients’ plasma were analyzed using multiple linear regression models. The interactions between confounding factors and self-reported occupational noise exposure were further analyzed by interaction analysis. Results The plasma CCL11, sCD14 and CFD expressions in asthmatic patients with self-reported occupational noise exposure were significantly higher than those in patients without the exposure (P<0.05). After adjusting for confounding factors, compared with patients reporting no occupational noise exposure, the plasma CFD expression was increased by 0.17 (95% CI: 0.02, 0.31) natural logarithm units in patients with self-reported occupational noise exposure. During remission, the levels of plasma CCL11 and sCD14 in asthmatic patients with self-reported occupational noise exposure were increased by 0.27 (95% CI: 0.05, 0.49) and 0.22 (95% CI: 0.02, 0.41) natural logarithm units, respectively, when compared with patients without the exposure. Interaction analysis showed that self-reported occupational noise exposure had significant multiplicative interaction with smoking or pet ownership on plasma CCL11 or CFD expressions in asthmatic patients (all P<0.05). Conclusion Self-reported occupational noise exposure is significantly associated with increased expression levels of plasma CFD, CCL11, and sCD14 in adult asthmatic patients.

Objective:To explore the clinical characteristics of interleukin-6 (IL-6) and interleukin-8 (IL-8) in cerebrospinal fluid (CSF) of children with bacterial meningitis (BM) and provide reference for clinical diagnosis and treatment of BM.Methods:The clinical data of BM children hospitalized in Women and Children′s Medical Center Affiliated to Guangzhou Medical University from December 2019 to March 2022 were collected and retrospectively analyzed in this case series study.Cytokines in CSF of these children were detected at least twice during the treatment. t test, Mann-Whitney test or analysis of variance were carried out for statistical analysis. Results:There were 40 patients included in this study.The age of onset was 2(1, 8) months, ranging from 2 days to 8 years, and the length of time from onset to hospitalization was (15±17) days, ranging from 1 day to 69 days.The main symptoms at the onset were fever (40 cases, 100%), poor mental state (16 cases, 35.0%), convulsion (9 cases, 22.5%), and vomiting (9 cases, 22.5%).According to pathogens, the patients were divided into the Streptococcus agalactia group (GBS group, 9 cases), Streptococcus pneumoniae group (SP group, 9 cases), other bacteria group (9 cases), and unknown bacteria group (13 cases).The levels of cytokines in the CSF of BM children were increased, along with significantly elevated levels of IL-6 and IL-8 within 1 st week of BM, followed by the peak at 2 nd-3 rd weeks, and then levels of IL-6 and IL-8 presented an overall decreasing trend with the progression of BM.The level of IL-6 in CSF of 10 cases significantly decreased in the 4 th week of BM [within 2 weeks: 773.5(164.1, 1 781.2) ng/L vs. 4 th week: 10.8(2.2, 21.1) ng/L, P=0.005].Such statistical differences didn′t occur to the level of IL-8 [within 2 weeks 182.9(33.6, 657.7) ng/L vs. 4 th week: 92.9(22.6, 226.6) ng/L, P=0.303].After effective antibiotic therapy, 6 patients had elevated white blood cell count in CSF during the 4 th-20 th weeks, with or without repeating intermittent fever.Among them, 4 cases of GBS and 1 case of SP were negative for pathogens in CSF during the retest after treatment, and the levels of IL-6 and IL-8 [(149.1-4 218.6) ng/L and (124.2-1 890.3) ng/L, respectively] in CSF were elevated.Low-dose glucocorticoid was administered for anti-inflammatory treatment, with additional gamma globulin for 1 case and Ibuprofen instead for 1 case.Subsequently, the fever completely subsided.The white blood cell count in CSF decreased significantly ( P=0.024). Conclusions:The levels of IL-6 and IL-8 in CSF increase significantly in the acute phase of BM and generally decrease with the progression of BM.If they are still significantly elevated in the later course of BM, it should be noted that an intracranial hyperinflammatory response may occur, especially when the pathogenic bacteria are GBS or SP.

OBJECTIVE: To explore the genetic basis for a child featuring global developmental disorder with epilepsy. METHODS: A child who had presented at Guangzhou Women and Children's Medical Center in July 2022 was selected as the study subject. Clinical data was collected. Potential variant was detected by whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a three-year-old ethnic Zhuang Chinese girl, had presented with global developmental disorder and epilepsy, for which rehabilitation therapy was ineffective. Genetic testing revealed that she has harbored a homozygous c.821T>C (p.Leu274Pro) missense variant of the PIGW gene, for which both of her parents and sister were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of uncertain significance. CONCLUSION The homozygous c.821T>C (p.Leu274Pro) variant of the PIGW gene probably underlay the onset of disease in this child. Above finding has enriched the mutational spectrum of the PIGW gene.
Child, Preschool ; Female ; Humans ; Computational Biology ; Developmental Disabilities ; Epilepsy/genetics* ; Genetic Testing ; Homozygote

OBJECTIVE: To explore the genetic basis for a child with optic atrophy and global developmental delay. METHODS: A child who had presented at the Guangzhou Women and Children's Medical Center in January 2022 was selected as the study subject. Clinical data were collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a nine-month-old female, had manifested dysopia and global developmental delay. Genetic testing revealed that she has harbored a de novo c.425G>C (p.Arg142Pro) variant of the NR2F1 gene, which has been associated with Bosch-Boonstra-Schaaf syndrome. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+PM1+PM2_Supporting+PM5+PP3+PP4). CONCLUSION The c.425G>C (p.Arg142Pro) variant of the NR2F1 gene probably underlay the pathogenesis in this child. Above finding has enriched the genotypic and phenotypic spectrum of the NR2F1 gene.
Female ; Humans ; Infant ; Computational Biology ; COUP Transcription Factor I/genetics* ; Genetic Testing ; Genomics ; Genotype ; Optic Atrophy/genetics*

Objective:To understand the spectrum of pathogens and epidemic characteristics of respiratory infectious diseases in influenza virus-negative influenza-like cases in Yantai, and provide reference for disease prevention and control and clinical diagnosis and treatment.Methods:From March 2020 to February 2021, nasopharyngeal swab samples of 233 influenza virus-negative influenza like cases were collected in all sentinel hospitals monitored by Yantai National Influenza Network Laboratory, and 22 respiratory pathogens were detected by multiple fluorescence quantitative polymerase chain reaction to analyze epidemiological characteristics.Results:The total pathogen detection rate of 233 samples was 69.96% (163/233). A total of 17 respiratory pathogens were detected. The top three pathogens were human coronavirus (HCoV, 32.62%), rhinovirus/enterovirus (RhV/EV, 17.17%) and Legionella pneumophila (LP, 16.74%). The detection rates in different age groups were 80.28% (57/71) in the 0-15 years old group, 62.65% (52/83) in the 16-30 years old group, 68.18% (30/44) in the 31-45 years old group, 64.28% (9/14) in the 46-60 years old group, and 71.43% (15/21) in the >60 years old group. There was no significant difference among the groups. Respiratory pathogens were detected throughout the year, mainly in a single pathogen carrying mode (44.21%), and there was no significant difference in the physical examination rate of respiratory pathogens in different seasons. The seasonal prevalence of various pathogens was different, and the detection rate of HCoV 229E was the highest in spring (68.75%); the detection rate of rhinovirus/enterovirus was higher in autumn (26.98%) and winter (23.08%); the detection rate of LP was high in spring (19.05%) and summer (27.27%); the detection rate of human parainfluenza virus (HPIV) in spring (22.22%) was significantly higher than that in summer (3.64%). The number of HPIV and Bordetella pertussis (Bp) detected in the 0-15 year old group was the highest, and the detection rate was statistically significant among different age groups. Conclusions:The continuous monitoring of respiratory pathogens such as HCoV, RhV, EV, LP, HPIV should be strengthened to understand their epidemiologic characteristics and the standardization of pathogenicity, which provides data support and reference for epidemiological investigation of outbreaks that may be caused by other pathogens.

Objective:To investigate the effect and molecular mechanism of circular RNA-UBXN7 (circ_UBXN7) on the proliferation, migration and apoptosis of hepatocellular carcinoma cells.Methods:Circ_UBXN7 expression in the tissues and cells of hepatocellular cancer was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the relationship between circ_UBXN7 expression and clinicopathological features, including age, gender, tumor volume, pathological classification, staging, and lymph node metastasis was analyzed. The full-length sequence of circ_UBXN7 with lentivirus carrying lenti circ_UBXN7 and lenti circ_UBXN7 shRNA was constructed to transfect hepatocellular cell lines (HepG2 and Huh-7), respectively. CCK-8 experiments were performed to detect the ability of up- or down-regulation of circ_UBXN7 on the proliferation of HEPG2 and HUH-7 cells. Annexin V / PI experiment was used to detect the changes in apoptosis of HEPG2 and HUH-7 cells after up-regulation or down-regulation of circ_UBXN7 expression. JC-1 assay was used to detect the changes in mitochondrial potential energy of HEPG2 and HUH-7 cells after up-regulation or down-regulation of circ_UBXN7 expression. Transwell was used to detect the migration ability of HEPG2 and HUH-7 cells after up-regulation or down-regulation of circ_UBXN7 expression. Western blotting was used to detect the expressional change of TWIST, E-cadherin, N-cadherin and vimentin. Statistical analysis: The expression levels of circ_UBXN7 and clinicopathological features were measured by chi-square test. Two groups were compared by t-test and three groups and above were compared by single factor analysis of variance. LSD method was used for comparison between groups.Results:The expression of circ_UBXN7 in liver cancer tissues was significantly higher than adjacent tissues, and its expression level was significantly positively correlated with tumor volume, stage, and lymph node metastasis ( P < 0.05). Lenti-circ_UBXN7 had up-regulated the expression of circ_UBXN7 in HEPG2 and HUH-7 cells and promoted cell proliferation. Lenti-circ_UBXN7-shRNA had down-regulated the expression of circ_UBXN7 and induced apoptosis. Lenti-circ_UBXN7-shRNA had reduced the mitochondrial membrane potential of cells. Lenti-circ_UBXN7 had promoted cell migration, while lenti-circ_UBXN7-shRNA had inhibited cell migration. Lenti-circ_UBXN7 had induced increased expression of Twist, N-cadherin, and Vimentin proteins, and reduced the expression of E-cadherin protein. Lenti-circ_UBXN7-shRNA had opposite effects on the expression levels of each protein. Starbase V2.0 software showed that miR-203a and circ_UBXN7 had potential binding sites, and miR-203a and circ_UBXN7 expression levels were negatively correlated in HEP ??G2 and HUH-7 cells. Conclusion:circ_UBXN7 plays an important role in promoting the occurrence and development of liver cancer, and is expected to become a potential target for the treatment of liver cancer.

Objective Toinvestigatetheconsistencyofultrasoundand MSCTindiagnosing microvascularinvasion (MVI)in hepatocellularcarcinoma,andtocomparethediagnosticefficiencyofbothtwomethods.Methods TheultrasoundandMSCTdataof 82patientswithhepatocellularcarcinomawerecollected.Accordingtothepostoperativepathologicalresults,theconsistencyanddiagnostic efficiencyofultrasoundandMSCTindiagnosingMVIinhepatocellularcarcinomawerecompared.Results Accordingtothepostoperative pathologicalfindingsof82patients,30caseswerepositiveofMVI,while52caseswerenegative.ThepreoperativeMSCTandultrasound examinations had a strong consistency (Cohen’s Kappa＝0.829 ,P＜0.001 ).The sensitivity ,specificity and accuracy of preoperative ultrasoundinpredictingtheMVIinhepatocellularcarcinomawere76.67% (23/30),67.31% (35/52)and70.73% (58/82),respectively. Thesensitivity,specificityandaccuracyofpreoperativeMSCTinpredictinghepatocellularcarcinomaMVIwere83.33% (25/30),73.08%(38/52)and75.61% (63/82),respectively.Conclusion Preoperativeultrasoundand MSCThavegoodconsistencyandhighdiagnostic efficiencyindiagnosing MVIinhepatocellularcarcinoma.

To investigate the potential risk factors for hepatocellular carcinoma in primary biliary cholangitis (PBC) patients. Methods:The data of 670 PBC inpatients between January 2011 and December 2016 were collected from the database of The First Affiliated Hospital of Zhengzhou University. The potential risk factors were evaluated, and odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed by univariate (unadjusted OR) and multivariate [adjusted OR (AOR)] conditional Logistic regression. Results: In total, 35 PBC patients developed liver carcinoma (5.2%); of these, 4 patients (female) were excluded because of incomplete data for influencing factors and 6 (2 male; 4 female) were excluded as they were diagnosed with hepatocellular carcinoma (HCC) during or before PBC. Therefore, 25 patients were included in the case-control study. Male patients were more likely than female patients to show alcohol in-take, smoking, a family history of malignancy, and serious liver injury (all P<0.05), indicated by the increasing levels of alanine amino-transferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) (P<0.05). Conditional Logistic regression analysis revealed that body mass index (BMI) ≥25 kg/m2 (AOR=1.015, 95% CI: 1.001-1.257, P=0.032) and history of alcohol intake (AOR=10.014, 95% CI: 1.009-91.071, P=0.039) were significantly associated with increased odds of HCC development in PBC patients. Conclusions:The risk factors for PBC-associated liver carcinoma include BMI≥25 kg/m2 and history of alcohol intake. In addition to regular monitoring, PBC patients may benefit from alcohol abstinence and body weight control.

Objective: To investigate the clinical characteristics, treatment and prognosis of relapsed demyeli-nating disease (RDD) associated with myelin oligodendrocyte glycoprotein antibodies (MOG abs) children in southern China. Methods: Children with RDD associated with MOG abs at Department of Neurology in Guangzhou Women and Children′s Medical Center from January 2015 to December 2018 were retrospectively analyzed.The annualized relapse rates (ARRs) and expand disability status scale (EDSS) were used to assess the recurrence frequency and neurological dysfunction respectively. Results: Ten children were included with the age of (6.4±3.6) years old, and male to female ratio was 4∶6.(1)Clinical phenotype: all children had 24 episodes during follow-up, with acute disseminated encephalomyelitis (ADEM)(7/10 cases) and neuromyelitis optica spectrum disorders (NMOSD)(3/10 cases) on the first episode.Among 14 recurrent episodes, ADEM (9/14 times) was the most common, followed by optic neuritis(ON)(3/14 times)and brainstem encephalitis (2/14 times). By the final follow-up, the final diagnosis was multiphasic disseminated encephalomyelitis(MDEM)(6/10 cases), NMOSD(3/10 cases), ADEM-ON(1/10 case), respectively.(2)Laboratory examination: all the children had positive serum MOG abs in the acute stage.The serum MOG abs titer high group(≥1∶640)(6 cases)on the first episode complicated ON (3 cases) and long segment myelitis (3 cases) more common than those of low group(1∶320)(4 cases). (3)Imaging changes: 25 times of bain magnetic resonance imaging (MRI) were performed in the acute stage, MRI changes mostly involved the cortex and subcortical white matter.Four cases had abnormal spinal cord MRI.(4)Treatment and prognosis: intravenous methylprednone (IVMP) combined with intravenous immunoglobulin (IVIG) were administrated in acute stage.Rituximab (2/10 cases), mycophenolate mofetil (4/10 cases), IVIG (2/10 cases) monthly and low dose prednisone orally (2/10 cases) were given respectively in maintains stage.ARRs decreased from 1.4 to 0 and EDSS score improved significantly after these treatments above.Seven cases had residual neurological dysfunction with 3 cases of NMOSD, 3 cases of MDEM and 1 case of ADEM-ON, including motor dysfunction, learning disability and inattention, symptomatic epilepsy and visual impairment. Conclusions ADEM is the most common form of RDD associated with MOG abs in children.Those with high serum MOG abs titer on the first episode are prone to have ON or long segment myelitis.Immunomodification therapy is effective in the relapsed patients, residual neurological sequelae were related to the type of repeated demyelination.

Objective To investigate the role and mechanism of circular RNA-vimentin (circ-VIM) in the proliferation and apoptosis of colorectal cancer cells.Methods From December 2016 to December 2017, at Department of General Surgery of The First Affiliated Hospital of Zhengzhou University, the clinical data of 100 patients who underwent radical resection of colorectal cancer and were confirmed by pathological examination after operation were collected.The tumor tissues and corresponding paracancerous tissues (negative control) were also collected.The expression of circ-VIM in the colorectal cancer tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR).The proliferation of HCT-116 and HT29 colorectal cancer cells was detected by cell counting kit-8 assay.The ratio of apoptosis of HCT-116 and HT29 cells was measured by annexin Ⅴ/propidium iodide double staining assay.The mitochondrial membrane potential of HCT-116 and HT29 cells was examined by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) assay.The expression changes of protein kinase B and mammalian target of rapamycin were tested by Western blotting.The target miRNA of circ-VIM was predicted by miRDB software.T-test and chi-square test were performed for statistical analysis. Results The expression of circ-VIM in colorectal cancer tissues was 2.387 ±0.536, which was higher than that in corresponding paracancerous tissues (1.110 ±0.134), and the difference was statistically significant (t =23.096, P <0.01).And the expression levels of circ-VIM were significantly different in patients with different tumor size, TNM stage and lymph node metastasis (all P <0.05).The proliferation of HCT-116 cells and HT29 cells in lenti-circ-VIM group was 0.737 ±0.023 and 0.835 ±0.025, respectively, which were both higher than those in control group (0.449 ±0.020 and 0.531 ±0.019), and the differences were statistically significant (t =20.706 and-15.374, both P <0.01).The proliferation of HCT-116 cells and HT29 cells in lenti-circ-VIM-shRNA group was 0.236 ±0.027 and 0.243 ±0.019, which were lower than those in control group, and the differences were statistically significant (t =24.557 and -23.197, both P <0.01).The ratio of apoptosis of HCT-116 cells and HT29 cells in lenti-circ-VIM-shRNA group was (18.00 ±1.82)％ and (20.80 ±0.61)％, which was higher than those in control group ((6.64 ±2.01)％ and (7.35 ±1.36)％), and the differences were statistically significant (t =8.826 and 17.454, both P <0.01).The fluorescence intensity ratio of JC-1 aggregate and JC-1 monomer of HCT-116 cells and HT29 cells in lenti-circ-VIM-shRNA group was 2.21 ±0.12 and 1.40 ±0.11, which was lower than those in control group (14.54 ±1.00 and 9.24 ±1.18), and the differences were statistically significant (t =-19.558 and-15.685, both P <0.01), which indicated mitochondrial membrane potential decreased.After treated with lenti-circ-VIM-shRNA, the expression of phosphorylated protein kinase B, phosphorylated mammalian target of rapamycin, B-cell lymphoma-2 and mitochondrial cytochrome C at protein level were all down-regulated, however the expression of cytoplasmic cytochrome C, B-cell lymphoma-2 associated X protein and cleaved caspase-3 at protein level were all up-regulated.When the expression of circ-VIM was up-regulated, the expression of miRNA-147b, miRNA-4447 and miRNA-3656 was down-regulated.When the expression of circ-VIM was down-regulated, the expression of miRNA-147b, miRNA-4447 and miRNA-3656 was up-regulated.Conclusion The expression of circ-VIM in colorectal cancer is abnormally increased, which is involved in the proliferation and apoptosis of colorectal cancer cells.