Ceftriaxone-induced severe hemolytic anemia, renal calculi, and cholecystolithiasis in a 3-year-old child: a case report and literature review.

Ceftriaxone is widely used in pediatric outpatient care for its efficacy against respiratory and digestive system infections, yet its increasing association with severe immune hemolytic reactions requires heightened vigilance from pediatricians. This report details a rare and severe case of ceftriaxone-induced severe immune hemolytic anemia (IHA), hemolytic crisis, myocardial injury, liver injury, renal calculi, and cholecystolithiasis in a previously healthy 3-year-old child. The child, treated for bronchitis, experienced sudden pallor, limb stiffness, and altered consciousness following the fifth day of ceftriaxone infusion, with hemoglobin (Hb) levels precipitously dropping to 21 g/L. Immediate cessation of ceftriaxone and the administration of oxygen therapy, blood transfusion, intravenous immunoglobulin (IVIG), and corticosteroids led to a gradual recovery. Despite initial improvements, the patient's condition necessitated extensive hospital care due to complications including myocardial injury, liver injury, renal calculi, and cholecystolithiasis. After a 12-day hospital stay and a 3-month follow-up, the child showed complete normalization of Hb and liver function and resolution of calculi. In children, ceftriaxone infusion may trigger severe, potentially fatal, hemolytic reactions. Pediatricians must promptly recognize symptoms such as pallor, limb stiffness, and unresponsiveness, indicative of ceftriaxone-induced severe IHA, and immediately discontinue the drug. Effective management includes timely blood transfusion, respiratory support, IVIG administration, and corticosteroids when necessary, along with rigorous vital signs monitoring. Continued vigilance is imperative, even after cessation of ceftriaxone, to promptly address any residual adverse effects.

Genetically Predicted Milk Intake Increased Femoral Neck Bone Mineral Density in Women But Not in Men.

Background: Cow milk contains more calcium, magnesium, potassium, zinc, and phosphorus minerals. For a long time, people have believed that increasing milk intake is beneficial to increasing bone density. Many confounding factors can affect milk consumption, and thus the association described to date may not be causal. We explored the causal relationship between genetically predicted milk consumption and Bone Mineral Density (BMD) of the femoral neck and lumbar spine based on 53,236 individuals from 27 studies of European ancestry using the Mendelian randomization (MR) study. 32,961 individuals of European and East Asian ancestry were used for sensitivity analysis. Methods: A genetic instrument used for evaluating milk consumption is rs4988235, a locus located at 13,910 base pairs upstream of the LCT gene. A Mendelian randomization (MR) analysis was conducted to study the effect of selected single nucleotide polymorphisms (SNPs) and BMD. The summary-level data for BMD of the femoral neck and lumbar spine were obtained from two GWAS meta-analyses ['Data Release 2012' and 'Data Release 2015' in the GEnetic Factors for OSteoporosis Consortium (GEFOS)]. Results: we found that genetically predicted milk consumption was not associated with FN-BMD(OR 1.007; 95% CI 0.991-1.023; P = 0.385), LS-BMD(OR 1.003; 95% CI 0.983-1.024; P = 0.743) by performing a meta-analysis of several different cohort studies. High levels of genetically predicted milk intake were positively associated with increased FN-BMD in Women. The OR for each additional milk intake increasing allele was 1.032 (95%CI 1.005-1.059; P = 0.014). However, no causal relationship was found between milk consumption and FN-BMD in men (OR 0.996; 95% CI 0.964-1.029; P = 0.839). Genetically predicted milk consumption was not significantly associated with LS-BMD in women (OR 1.017; 95% CI 0.991-1.043; P = 0.198) and men (OR 1.011; 95% CI 0.978-1.045; P = 0.523). Conclusion: Our study found that women who consume more milk have a higher FN-BMD. When studying the effect of milk consumption on bone density in further studies, we need to pay more attention to women.

Intestinal Microbes-based Analysis of Immune Mechanism of Childhood Asthma.

This work was developed to explore the relationship between intestinal microflora composition and immune function changes in children with asthma and to provide theoretical references for clinical diagnosis and treatment. Forty-eight children with asthma who received standardized treatment in the outpatient department of pediatric respiratory asthma in Children's Hospital were selected as the research objects, which were rolled into 24 cases of S0 group (complete control) and 24 cases of S1 group (incomplete control group). In addition, ten healthy children with general data matching the research objects were selected as a blank control (D0 group). The intestinal microbial composition and immune function indexes of each group were detected. The results showed that there were differences in the intestinal microbes of the three groups of children with Bifidobacterium, Megasphaera, Oscillibacter, Bilophila, and f_Ruminococcaceae. Among them, the proportions of Bifidobacterium, Megasphaera, and f_Ruminococcaceae in the intestinal microbes of the children in the S1 group were notably less than those in the S0 and D0 groups. The proportion of these three bacterial genera in the S0 group was also considerably smaller than that in the D0 group (P<0.05). In addition, the CD3+ levels of children in the S1 group were notably lower than those in the S0 and D0 groups, while the CD4+ and CD4+/CD3+ were higher than the S0 and D0 groups (P<0.05). The differences between CD3+, CD4+, and CD4+/CD3+ in the S0 and D0 groups were not considerable (P<0.05). The proportions of Bifidobacterium, Megasphaera, f_Ruminococcaceae, and Parasutterella in children with intestinal microbes were significantly positively correlated with CD3+ levels (P<0.05), and significantly negatively correlated with CD4+ and CD4+/CD3+ levels (P<0.05). In short, children with different levels of asthma control had a certain degree of flora disorder and decreased immune function in the intestinal flora. The decrease in the relative abundance of Bifidobacterium, f_Ruminococcaceae of Firmicutes, and Parasutterella of Riken Bacteria, and the increase in the relative abundance of Oscillatoria meant the decline of the immune function of the children.

Relationship Between Plasma Vitamin C and COVID-19 Susceptibility and Severity: A Two-Sample Mendelian Randomization Study.

Background: Considering the antioxidant function of Vitamin C, also called ascorbic acid, it is widely used against viral infections such as coronavirus disease (COVID-19) based on in vitro, observational, and ecological studies. Many confounding factors that can affect Vitamin C levels. Thus, the association described to date may not be causal. To determine the causal relationship between genetically predicted plasma Vitamin C and COVID-19 susceptibility and severity, we performed two-sample Mendelian randomization (MR) based on large samples. Methods: The summary-level data for Vitamin C was obtained from a GWAS meta-analysis, which included 52,018 individuals from four studies of European ancestry. Data for COVID-19 HGI results were obtained from the meta-analysis of 35 GWASs with more than 1,000,000 subjects of European ancestry, including 32,494 cases with COVID-19 susceptibility and 1,316,207 controls, 9,986 cases with COVID-19 hospitalization and 1,877,672 controls, and 5,101 cases with COVID-19 severe disease and 1,383,241 controls. Mendelian randomization (MR) analysis was conducted to examine the effect of selected single nucleotide polymorphisms and COVID-19 susceptibility, hospitalization, disease severity. Several sensitivity analyses were performed with inverse-variance weighted (random-effect model), inverse variance weighted (fixed-effect model), weighted median, and maximum likelihood methods for estimating the causal effects. Results: In this MR study, genetic predisposition to the levels of plasma Vitamin C was not associated with COVID-19 susceptibility (OR: 0.99, 95% CI: 0.84-1.17, P = 0.91), hospitalization (OR: 1.10, 95% CI: 0.71-1.71, P = 0.67) and severity (OR: 0.83, 95% CI: 0.43-1.59, P = 0.58). The association was consistent in complementary analyses. No potential heterogeneities and directional pleiotropies were observed for the analysis results. Conclusion: According to our study, no correlation was observed between plasma Vitamin C levels and COVID-19 susceptibility and severity. Further studies in different ethnics are necessary to explore the potential role and mechanisms of circulating serum Vitamin C levels on COVID-19.

Perinatal Risk Factors Influencing Neonatal Hypoxic Ischemic Encephalopathy in Southern China: A Case-Control Study.

OBJECTIVE: In this study, our objective was to explore the relevant influencing factors of neonatal hypoxic-ischemic encephalopathy (HIE) in Southern China and provide scientific basis for improving the quality of life for neonates. STUDY DESIGN: A retrospective analysis of 306 cases with HIE neonates who were admitted during April 2015 to October 2017 was conducted. A total of 306 non-HIE patients admitted to the same hospital during the same period were also included as controls. The basic clinical characteristics were analyzed, and the risk factors for HIE were assessed by logistic regression analysis. RESULTS: Univariate analysis showed that the differences in medicals during pregnancy, placenta previa, fetal distress during labor, cesarean section, amniotic fluid contamination, abnormal labor stage, and Apgar showed significantly different in the case group and the control group (p < 0.05). The multivariate logistic regression analysis revealed that the placenta previa, medicals during pregnancy, fetal distress, abnormal labor stage, Apgar's score, amniotic fluid contamination, and cesarean section were independent risk factors for HIE. CONCLUSION: The placenta previa, medicals during pregnancy, fetal distress, and abnormal labor stage can increase the risk of HIE. Early detection, early diagnosis, and treatment might make great achievement in improving the life quality of HIE neonates.

Prevalence of herpes and respiratory viruses in induced sputum among hospitalized children with non typical bacterial community-acquired pneumonia.

OBJECTIVE: Few comprehensive studies have searched for viruses in infants and young children with community-acquired pneumonia (CAP) in China. The aim of this study was to investigate the roles of human herpes viruses (HHVs) and other respiratory viruses in CAP not caused by typical bacterial infection and to determine their prevalence and clinical significance. METHODS: Induced sputum (IS) samples were collected from 354 hospitalised patients (infants, n = 205; children, n = 149) with respiratory illness (CAP or non-CAP) admitted to Wenling Hospital of China. We tested for HHVs and respiratory viruses using PCR-based assays. The epidemiological profiles were also analysed. RESULTS: High rate of virus detection (more than 98%) and co-infection (more than 80%) were found among IS samples from 354 hospitalised infants and children with respiratory illness in this study. Of 273 CAP samples tested, CMV (91.6%), HHV-6 (50.9%), RSV (37.4%), EBV (35.5%), HBoV (28.2%), HHV-7 (18.3%) and rhinovirus (17.2%) were the most commonly detected viruses. Of 81 non- CAP samples tested, CMV (63%), RSV (49.4%), HHV-6 (42%), EBV (24.7%), HHV-7 (13.6%) and HBoV (8.6%) were the dominant viruses detected. The prevalence of several viral agents (rhinovirus, bocavirus, adenovirus and CMV) among IS samples of CAP were significantly higher than that of non-CAP control group. We also found the prevalence of RSV coinfection with HHVs was also higher among CAP group than that of non-CAP control. CONCLUSIONS: With sensitive molecular detection techniques and IS samples, high rates of viral identification were achieved in infants and young children with respiratory illness in a rural area of China. The clinical significance of rhinovirus, bocavirus, adenovirus and HHV (especially CMV) infections should receive greater attention in future treatment and prevention studies of CAP in infants and children.

[Expression of Rock2 and TGF-ß1 mRNA and glucocorticoid intervention in asthmatic rats].

OBJECTIVE: To study the roles of rhoassociated coiled coil forming protein kinase 2 (Rock2) and transforming growth factor-ß1 (TGF-ß1) mRNA in acute asthma and the effect of glucocorticoid intervention on the Rock2 and TGF-ß1 mRNA expression in rats. METHODS: Forty-eight male rats were randomly divided into 4 groups (n=12 each): asthma, control, dexamethasone treated (DXM) and budesonide treated (BUD). Rat model of asthma was prepared by the ovalbumin (OVA) challenge. The animals were sacrificed 24 hrs after the last challenge. The total cell number and differentiation cell number were counted in bronchoalveolar lavage fluid (BALF). The protein expression of Rock2 was ascertained by immunohistochemistry and the mRNA expression of TGF-ß1 was ascertained by hybridization in situ. RESULTS: The pathological changes in the BUD and the DXM groups were alleviated when compared with the asthma group. The total cell number and the percentage of eosinophil (EOS), polymorphonuclear leukocytes (PMN) and lymphocytes (Lym) in BALF in the asthma group were significantly higher than those in the control group (P<0.01). The percentage of macrophage (Mф) in the asthma group was significantly lower than that in the control group (P<0.01). The total cell number and the percentage of EOS and Lym in BALF in the DXM and the BUD groups decreased, while the percentage of Mф increased significantly compared with those in the asthma group (P<0.01). The Rock2 and TGF-ß1 mRNA expression in lung tissues in the asthma group increased significantly compared with those in the control, BUD and DXM groups, while there were no significant differences in the Rock2 expression and TGF-ß1 mRNA expression between the DXM or BUD group and the control group. CONCLUSIONS: The expression of Rock2 and TGF-ß1 mRNA in lung tissues is increased in rats with acute asthma. Glucocorticoids can significantly decrease the expression of Rock2 and TGF-ß1 in lung tissues, thus alleviates airway inflammation.

[Expression of recombinant VP2 gene in insect sf9 cells and screening of clinical specimens].

OBJECTIVE: To clone and express VP, gene from HBoV, and the expressed VP, protein was as the antigen in order to detect serum from children in Wenling area with lower respiratory tract infections. METHODS: The VP, gene was recombined with the genome of Baculovirus, which infected the insect cell. The fusion protein with HA tag was applied to confirm the specificity of expressed protein. Furthermore, the recombinant protein was observed using electron microscopy. The 176 serum from children in Wenling area with lower respiratory tract infections was screened using Western blot. RESULTS: The expressed VP2 protein was more than 60% in total proteins from insect cell, and MWt about 60 x 10(3). The virus-like particle (VLP) was observed using electron microscopy, and size about 20 nm. The 176 serum from children in wenling area with lower respiratory tract infections was screened using Western blot. The HBoV positive rate was 2.28% (4/176). CONCLUSION: The VP2 protein from human bocavirus was expressed in insect cell successfully. Through HA tag the VP2 protein was specific, and then the assay using SDS-PAGE with Western blot could detect and screen the antibody in serum from children with lower respiratory tract infections rapidly and accurately.

[Isolation and cell culture of human bocavirus (HBoV) by human bronchial epithelial cell lines].

OBJECTIVE: To investigate pave a way for studying pathogenicty of HBoV. METHODS: Isolation and cell culture of HBoV by human bronchial epithelial cell line, which was founded in our laboratory. The morphology of the virus were primarily studied with a transmission electron microscope. In addition, transcript mRNA was detected in human bronchial epithelial cells, which was passaged and infected within HBoV, using the reverse-transcription polymerase chain reaction (RT-PCR). The amplified products nucleotide sequence of HBoV were sequencing and sequence analysis. RESULTS: Cytopathic effect (CPE) was observed after the aseptic residue of filtration of 2 case sputum specimens with HBoV, which was inoculated to the human bronchial epithelial cell line. The virus particles were observed in the cytoplasm, which were hexagonal or spherical in shape and 18-26 nm in diameter,bulk was 20 nm. cDNA amplicon obtained 295 bp fragment results of electrophoresis bands as same as NS1 region of the conserved matrix gene of publish sequence of HboV. PCR products nucleotide sequence of HboV were compared with corresponding HboV GeneBank sequences. The comparison/alignment and construction of phylogenetic trees also point to an affiliation of the parvovirus to the species HBoV. CONCLUSION: Isolation and identification of HBoV could be done in the human bronchial epithelial cell, and we found some characterizing CPE in the human bronchial epithelial cell after HBoV infection. The above studies pave a way for studying pathogenicty of human bocavirus.

[Identification of KI polyomavirus in children with lower respiratory tract infections from Zhejiang region of China].

KI polyomavirus, which was firstly discovered in 2007, is a new human polyomavirus belonging to Polyomaviridae and containing circular double-strand genomic DNA. This study was based on identification assay of KI polyomavirus reported. Total 2293 clinical sputum specimens from children under 3-years-old were collected and screened from Wenzhou Medical College affiliated Wenling Hospital, Zhejiang Province. A KI polyomavirus was detected and identified, the positive rate was 0.04%. The sequences of PCR products was identical to that of the viral capsid protein (VP1) gene derived from KI polyomavirus. The results strongly suggested that the KI polyomavirus was found firstly in Chinese children with acute lower respiratory tract infections from Zhejiang region. This study provided new information for further investigation of etiopathogenisis and diagnosis in children with lower respiratory tract infections.

[Characterization of the cytopathic effect in human bronchial epithelial cell after Human Bocavirus Infection (HBoV)].

OBJECTIVE: In this study, human bronchial epithelial cells were inoculated with positive sputum specimens of HBoV. After four days' infection, cytopathic effects (CPE) were observed by inverted microscopy. These viruses all cause typical cell damages such as rounded and shrivelled, fusion and fallout. These damages got quick following increased future degenerations. The other assay result of CPE within the infected cells were observed by inverted microscopy, have typical "owl's eye" plaque and above 90 percent hemadsorption within the infected cells by erythrocytes for hemadsorption technique. The typical fluorescence lump of nucleus within the infected cells was found by indirect immunofluorescence technique. CONCLUSION: Isolation and identification of HBoV could be done in the human bronchial epithelial cell, and we found some characterizing CPE in the human bronchial epithelial cell after HBoV infection. The above studies pave a way for studying pathogenicity of human bocavirus.

[Discovery and identification of WU polyomavirus in children from Zhejing region].

WU polyomavirus, which was firstly discovered in 2007, is a new human polyomavirus belonging to Polyomaviridae and containing circular double-stranded genomic DNA. In this study, the 278 clinical sputum specimens from children under 5 years old were collected from Wenzhou Medical College affiliated Wenling First Hospital, Zhejiang Province. Based on identification assay of WU polyomavirus previously reported, a WU polyomavirus was identified from clinical samples successfully, the positive rate was 0.4%. The sequences of PCR products were identical to that of VP2 gene and large T antigen gene derived from WU polyomavirus reported. The above results strongly suggested that the WU polyomavirus isolated was firstly found in Chinese children with acute lower respiratory tract infections. This study provides a firm basis for further research of WU polyomavirus.

WU polyomavirus in children with acute lower respiratory tract infections, China.

BACKGROUND: WU polyomavirus (WUPyV), a new member of the genus of Polyomavirus in the family Polyomaviridae, has been found and associated with respiratory tract infections recently. However, its clinical role and pathogenicity has not been known. OBJECTIVES: To confirm that WU polyomavirus has been found in Chinese children. STUDY DESIGN: WU polyomavirus was detected and identified using PCR methods. A total of 278 specimens of nasopharyngeal aspirate were collected, and then PCR products were sequenced directly. RESULTS: One of 278 nasopharyngeal aspirates was positive for WUPyV in one child, and the positive rate was 0.4%. The results showed that the sequences of genome, LTAg and VP2 gene was identical to the reference sequences of WU polyomavirus prototype strains. CONCLUSIONS: We confirmed that WU polyomavirus had been found and identified in the respiratory secretions in China.

[Sequence analysis of the complete genome of bocavirus WLL-1].

Human bocavirus, which was firstly discovered in 2005, is a new human parvovirus associated with lower respiratory tract infection in children. In this study, a human bocavirus, named WLL-1 isolate, was identified in Wenlin County, Zhejiang Province. The genome of bocavirus WLL-1 has been sequenced and analyzed. Phylogenetic analyses showed that WLL-1 shares 99% homology with other bocaviruses recently reported, but also has some special variations.