Cadmium contributes to cardiac metabolic disruption by activating endothelial HIF1A-GLUT1 axis.

Cadmium (Cd) is an environmental risk factor of cardiovascular diseases. Researchers have found that Cd exposure causes energy metabolic disorders in the heart decades ago. However, the underlying molecular mechanisms are still elusive. In this study, male C57BL/6 J mice were exposed to cadmium chloride (CdCl2) through drinking water for 4 weeks. We found that exposure to CdCl2 increased glucose uptake and utilization, and disrupted normal metabolisms in the heart. In vitro studies showed that CdCl2 specifically increased endothelial glucose uptake without affecting cardiomyocytic glucose uptake and endothelial fatty acid uptake. The glucose transporter 1 (GLUT1) as well as its transcription factor HIF1A was significantly increased after CdCl2 treatment in endothelial cells. Further investigations found that CdCl2 treatment upregulated HIF1A expression by inhibiting its degradation through ubiquitin-proteasome pathway, thereby promoted its transcriptional activation of SLC2A1. Administration of HIF1A small molecule inhibitor echinomycin and A-485 reversed CdCl2-mediated increase of glucose uptake in endothelial cells. In accordance with this, intravenous injection of echinomycin effectively ameliorated CdCl2-mediated metabolic disruptions in the heart. Our study uncovered the molecular mechanisms of Cd in contributing cardiac metabolic disruption by inhibiting HIF1A degradation and increasing GLUT1 transcriptional expression. Inhibition of HIF1A could be a potential strategy to ameliorate Cd-mediated cardiac metabolic disorders and Cd-related cardiovascular diseases.

Symmetrical peripheral gangrene: potential mechanisms and therapeutic approaches in severe COVID-19.

Symmetrical peripheral gangrene is a rare condition that is characterized by ischemic damage and tissue death (gangrene) in the extremities. Recent reports have shed light on SPG in patients with severe COVID-19. This condition presents with symmetrical cyanosis of the extremities and common COVID-19 symptoms and what the most frightening is within a few days, cutaneous necrosis occurred and patients died. Skin biopsy results have shown the presence of microthrombi in small vessels. The formation of SPG in COVID-19 patients results from immunothrombosis, endothelial dysfunction, and procoagulant platelets, leading to a hypercoagulation state and microvascular thrombosis. Thrombotic microangiopathy, shock, disseminated intravascular coagulation, and anticoagulant depletion promote the development of SPG in COVID-19. At the early stage, SPG patients with COVID-19 exhibit similar clinical manifestations. TMA causes early damage to microvasculature in SPG, and the shock state further exacerbates the ischemic injury due to local hypo-perfusion. The disturbed procoagulant-anticoagulant balance caused by DIC and anticoagulant depletion, combined with the pre-ischemic state brought on by TMA and shock, leads to the rapid formation of extensive microthrombi in the late stage of COVID-19 associated SPG. This review will delve into the clinical features, possible mechanisms, and potential therapeutic managements for COVID-19 associated SPG.

Revealing mechanism of Methazolamide for treatment of ankylosing spondylitis based on network pharmacology and GSEA.

Methazolamide is a carbonic anhydrase (CA) inhibitor with satisfactory safety. Our previous studies have demonstrated the elevation of CA1 expression and the therapeutic effect of Methazolamide in Ankylosing spondylitis (AS). In this study, we explored the pathogenic role of CA1 and the pharmacological mechanism of Methazolamide in AS through Gene Set Enrichment Analysis (GSEA) and network pharmacology. Seven out of twelve CA1 related gene sets were enriched in AS group. CA1 was core enriched in above seven gene sets involving zinc ion binding, arylesterase activity and one carbon metabolic process. Functional analysis of the candidate target genes obtained from the intersection of AS associated genes and Methazolamide target genes indicated that Methazolamide exerts therapeutic effects on AS mainly through inflammatory pathways which regulate the production of tumor necrosis factor, IL-6 and nitric oxide. PTGS2, ESR1, GSK3ß, JAK2, NOS2 and CA1 were selected as therapeutic targets of Methazolamide in AS. Molecular docking and molecular dynamics simulations were performed successfully. In addition, we innovatively obtained the intersection of Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and GSEA results, and found that 18 GO terms and 5 KEGG terms were indicated in the pharmacological mechanism of Methazolamide in AS, involving bone mineralization, angiogenesis, inflammation, and chemokine signaling pathways. Nevertheless, validation for these mechanisms is needed in vivo/vitro experiments.

[Value of heparin-binding protein in the diagnosis of severe adenovirus pneumonia in children]. / è‚ç´ ç»“åˆè›‹ç™½å¯¹å„¿ç«¥é‡ç—‡è ºç— æ¯’è‚ºç‚Žçš„è¯Šæ–­ä»·å€¼.

OBJECTIVES: To study the value of serum heparin-binding protein (HBP) in the early diagnosis of severe adenovirus pneumonia in children. METHODS: A total of 80 children who were admitted to the Department of Pediatrics, Changsha Central Hospital Affiliated to University of South China, from February 2019 to August 2021 and were diagnosed with adenovirus pneumonia were enrolled as subjects. According to the diagnostic criteria for severe pneumonia, they were divided into two groups: severe adenovirus pneumonia (40 children) and non-severe adenovirus pneumonia (40 children). The two groups were compared in terms of the serum levels of inflammatory markers within 24 hours after admission, such as HBP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), white blood cell count, platelet count (PLT), and C-reactive protein. The receiver operating characteristic (ROC) curve was plotted to identify the value of these inflammatory markers in the early diagnosis of severe adenovirus pneumonia. RESULTS: Compared with the non-severe adenovirus pneumonia group, the severe adenovirus pneumonia group had a significantly higher serum level of HBP [(46±16) ng/mL vs (28±13) ng/mL, P<0.05], as well as significantly higher levels of TNF-α, IL-6, and PLT (P<0.05). HBP had an area under the ROC curve (AUC) of 0.804 in the early diagnosis of severe adenovirus pneumonia, with a sensitivity of 80.0% and a specificity of 70.0% at the optimal cut-off value of 31.76 ng/mL. The ROC curve analysis of HBP combined with other indicators for the early diagnosis of severe adenovirus pneumonia showed that HBP+TNF-α, HBP+PLT, HBP+IL-6, HBP+TNF-α+IL-6, and HBP+TNF-α+IL-6+PLT had an AUC of 0.866, 0.850, 0.863, 0.886, and 0.894, respectively. CONCLUSIONS: Serum HBP may be used as a biomarker for the early diagnosis of severe adenovirus pneumonia, and its combination with TNF-α, IL-6, and PLT can improve its diagnostic value.

Risk assessment and prediction model of renal damage in childhood immunoglobulin A vasculitis.

Objectives: To explore the risk factors for renal damage in childhood immunoglobulin A vasculitis (IgAV) within 6 months and construct a clinical model for individual risk prediction. Methods: We retrospectively analyzed the clinical data of 1,007 children in our hospital and 287 children in other hospitals who were diagnosed with IgAV. Approximately 70% of the cases in our hospital were randomly selected using statistical product service soltions (SPSS) software for modeling. The remaining 30% of the cases were selected for internal verification, and the other hospital's cases were reviewed for external verification. A clinical prediction model for renal damage in children with IgAV was constructed by analyzing the modeling data through single-factor and multiple-factor logistic regression analyses. Then, we assessed and verified the degree of discrimination, calibration and clinical usefulness of the model. Finally, the prediction model was rendered in the form of a nomogram. Results: Age, persistent cutaneous purpura, erythrocyte distribution width, complement C3, immunoglobulin G and triglycerides were independent influencing factors of renal damage in IgAV. Based on these factors, the area under the curve (AUC) for the prediction model was 0.772; the calibration curve did not significantly deviate from the ideal curve; and the clinical decision curve was higher than two extreme lines when the prediction probability was ~15-82%. When the internal and external verification datasets were applied to the prediction model, the AUC was 0.729 and 0.750, respectively, and the Z test was compared with the modeling AUC, P > 0.05. The calibration curves fluctuated around the ideal curve, and the clinical decision curve was higher than two extreme lines when the prediction probability was 25~84% and 14~73%, respectively. Conclusion: The prediction model has a good degree of discrimination, calibration and clinical usefulness. Either the internal or external verification has better clinical efficacy, indicating that the model has repeatability and portability. Clinical trial registration: www.chictr.org.cn, identifier ChiCTR2000033435.

Coexistence of nodal marginal zone B-cell lymphoma and multiple myeloma: A case report and literature review.

RATIONALE: Nodal marginal zone B-cell lymphoma (NMZL) is a relatively rare indolent lymphoma that is the least common subtype of marginal zone B-cell lymphoma. Furthermore, coexistence of lymphoma and multiple myeloma (MM) is rare. Here, we report a case of the coexistence of NMZL and MM. PATIENT CONCERNS: The patient was a 66-year-old man with pain in the left rib and lower left back. Enlarged lymph nodes were palpable in the cervical and inguinal regions, the biggest of which was 4.0 × 2.0 cm in size in the left groin. DIAGNOSIS: Pathological and immunohistochemical findings of the left inguinal lymph node revealed NMZL. The patient met the diagnostic criteria for symptomatic MM. Therefore, the patient was diagnosed with NMZL and lambda-type MM. INTERVENTION: We adopted a bortezomib, liposomal adriamycin, and dexamethasone (PAD) chemotherapy regimen mainly for MM. OUTCOMES: After 3 cycles of treatment, the patient achieved complete remission of myeloma. A 50% decrease in enlarged lymph node size was observed. LESSON: To our knowledge, this is the first case report of the simultaneous occurrence of NMZL and MM. Further studies are required to explain the association between these 2 tumors and improve treatment selection.

Revealing key lncRNAs in cytogenetically normal acute myeloid leukemia by reconstruction of the lncRNA-miRNA-mRNA network.

Cytogenetically normal acute myeloid leukemia (CN-AML) is a heterogeneous disease with different prognoses. Researches on prognostic biomarkers and therapy targets of CN-AML are still ongoing. Instead of protein-coding genes, more and more researches were focused on the non-coding RNAs especially long non-coding RNAs (lncRNAs) which may play an important role in the development of AML. Although a large number of lncRNAs have been found, our knowledge of their functions and pathological process is still in its infancy. The purpose of this research is to identify the key lncRNAs and explore their functions in CN-AML by reconstructing the lncRNA-miRNA-mRNA network based on the competitive endogenous RNA (ceRNA) theory. We reconstructed a global triple network based on the ceRNA theory using the data from National Center for Biotechnology Information Gene Expression Omnibus and published literature. According to the topological algorithm, we identified the key lncRNAs which had both the higher node degrees and the higher numbers of lncRNA-miRNA pairs and total pairs in the ceRNA network. Meanwhile, Gene Ontology (GO) and pathway analysis were performed using databases such as DAVID, KOBAS and Cytoscape plug-in ClueGO respectively. The lncRNA-miRNA-mRNA network was composed of 90 lncRNAs,33mRNAs,26 miRNAs and 259 edges in the lncRNA upregulated group, and 18 lncRNAs,11 mRNAs,6 miRNAs and 45 edges in the lncRNA downregulated group. The functional assay showed that 53 pathways and 108 GO terms were enriched. Three lncRNAs (XIST, TUG1, GABPB1-AS1) could possibly be selected as key lncRNAs which may play an important role in the development of CN-AML. Particularly, GABPB1-AS1 was highly expressed in CN-AML by both bioinformatic analysis and experimental verification in AML cell line (THP-1) with quantitative real-time polymerase chain reaction. In addition, GABPB1-AS1 was also negatively correlated with overall survival of AML patients. The lncRNA-miRNA-mRNA network revealed key lncRNAs and their functions in CN-AML. Particularly, lncRNA GABPB1-AS1 was firstly proposed in AML. We believe that GABPB1-AS1 is expected to become a candidate prognostic biomarker or a potential therapeutic target.

Detection of pulmonary tuberculosis in children using the Xpert MTB/RIF Ultra assay on sputum: a multicenter study.

Microbiological confirmation is rare in children with active tuberculosis; therefore, a more accurate test is needed to detect pulmonary tuberculosis in children. In this multicenter study, we evaluated the utility of the Xpert MTB/RIF Ultra (Ultra) on sputum, an assay recommended by the World Health Organization to test for childhood tuberculosis in high-burden settings. Children with symptoms suggestive of tuberculosis were enrolled at three hospitals in China and categorized as having active tuberculosis or nontuberculosis. The sensitivity and specificity of Ultra were 42.1% (48/114) and 99.0% (208/210), respectively. Using three MTB culture results as the reference, the sensitivity of Ultra in the subset of 38 children with culture-positive and 76 children with culture-negative was 68.4% (26/38) and 28.9% (22/76), respectively(p < 0.001). A single MTB culture combined with a single Ultra could detect 54 (54/114,47.4%) cases with active TB, while repeated MTB culture combined with a single Ultra detected 60 (60/114, 52.6%) cases with active TB(p = 0.427). Among 155 children (58 with TB and 97 with RTIs) simultaneously tested with the Ultra and Xpert MTB/RIF (Xpert), the sensitivity of the Xpert (24.1%, 14/58) was lower than that of the Ultra (41.4%, 24/58; p = 0.048). Eight children were found to have rifampin-resistant MTB strains. The Xpert MTB/RIF Ultra assay should be implemented to test for pulmonary tuberculosis in children to achieve higher confirmation rates.

Clinical Characteristics of Pediatric Cases of COVID-19 in Hunan, China: A Retrospective, Multi-Center Case Series.

Objective: Aimed to investigate the epidemiological characteristics, clinical features, treatment, and short-term prognosis of COVID-19 in children. Methods: Retrospective analysis was conducted in 48 children with COVID-19 admitted to 12 hospitals in eight cities in Hunan province, China, from January 26, 2020 to June 30, 2020. Results: Of the 48 cases, Familial clusters were confirmed for 46 children (96%). 16 (33%) were imported from other provinces. There were 11 (23%) asymptomatic cases. only 2 cases (4%) were severe. The most common symptom was fever (n = 20, 42%). Other symptoms included cough (n = 19, 40%), fatigue (n = 8, 17%), and diarrhea (n = 5, 10%). In the early stage, the total peripheral blood leukocytes count increased in 3(6%) cases and the lymphocytes count decreased in 5 (10%) cases. C-reactive protein and procalcitonin were elevated respectively in 3 (6%) cases and 2 (4%) cases. There were abnormal chest CT changes in 22 (46%) children, including 15 (68%) with patchy ground glass opacity, 5 (22%) with consolidation, and 2 (10%) with mixed shadowing. In addition to supportive treatment, antiviral therapy was received by 41 (85%) children, 11 (23%) patients were treated with antibiotics, and 2 (4%) were treated with methylprednisolone and intravenous immunoglobulin. Compared to 2 weeks follow-up, one child developed low fever and headache during the 4 weeks follow-up, 3 (6%) children had runny noses, one of them got mild cough, and 4 (12%) children had elevated white blood cells and lymphocytes. However, LDH and CK increased at 2 weeks and 4 weeks follow-up. 2 weeks follow-up identified normal chest radiographs in 33 (69%) pediatric patients. RT-PCR detection of SARS-CoV-2 was negative in all follow-up patients at 2 and 4 weeks follow-up. All 48 pediatric patients were visited by calling after 1 year of discharge. Conclusions: Most cases of COVID-19 in children in Hunan province were asymptomatic, mild, or moderate. Close family contact was the main route of infection. It appeared that the younger the patient, the less obvious their symptoms. Epidemiological history, nucleic acid test, and chest imaging were important tools for diagnosis in children.

Diagnostic and Prognostic Value of Plasma Factor V Activity and Parameters in Thrombin Generation for Disseminated Intravascular Coagulation in Patients with Hematological Malignancies.

In this study, we used plasma factor V activity and parameters of the thrombin generation test to discuss their diagnostic and prognostic value for disseminated intravascular coagulation (DIC) in patients with hematological malignancies. A total of 164 patients who were diagnosed with hematological malignancies in the Department of Hematology, Union Hospital, between Apr. 2014 and Dec. 2014 were enrolled in this study. There were 131 patients in the study group and 33 patients in the control group in terms of the laboratory results for DIC. The patients in the study group were divided into a DIC subgroup (n=59) and a non-DIC subgroup (n=72) based on the International Society of Thrombosis and Hemostasis (ISTH) Integral System, and they were divided into four subgroups [score ≤3 (n=35), score=4 (n=37), score=5 (n=47), and score ≥6 (n=12)] according to ISTH scores. Using 28-day mortality as the endpoint, the patients in the study group were divided into a survival subgroup (n=111) and a non-survival subgroup (n=20). The results showed that the plasma factor V activity was significantly weaker, and lag time and time to peak were significantly shorter in the study group than in the control group (P<0.01). The factor V activity, peak and endogenous thrombin potential (ETP) were significantly decreased in the DIC subgroup as compared with those in the non-DIC subgroup (P<0.01). Among factor V activity, lag time, peak, ETP, and ttPeak, only the factor V activity was significantly decreased in the non-survival subgroup compared with the survival subgroup (P<0.01). With the increase in ISTH score, the ETP and peak decreased gradually. The binary logistic regression analysis revealed that PLT, D-dimer, factor V activity and ETP had linear relationship with DIC diagnosed by ISTH Integral System. Using DIC diagnosed by ISTH Integral System as the endpoint, the area under curve (AUC) of factor V activity was found to be similar to that of blood platelet count (PLT) and prothrombin time (PT). In conclusion, factor V activity, ETP and peak had diagnostic value for DIC in patients with hematological malignancies, and only factor V activity had limited prognostic value.

IL-1α and IL-1ß promote NOD2-induced immune responses by enhancing MAPK signaling.

Both toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) induce a tightly regulated inflammatory response at risk of causing tissue damage, depending on the effectiveness of ensuing negative feedback regulatory mechanisms. Cross-regulation between TLRs, NLRs, and cytokine receptors has been observed. However, the cross-regulation between interleukin-1 (IL-1) receptors and NOD2 is not completely understood. In this study, we found that IL-1α/ß increased NOD2-induced inflammatory response in human monocytic THP1 cells, peripheral blood mononuclear cells (PBMCs), mouse macrophage RWA264.7 cells and spleen cells, and in an in vivo experiment. IL-1α/ß pre-treatment induced the production of CXC chemokines, including growth-regulated oncogene (GRO)-α, GRO-ß, and IL-8, and proinflammatory cytokines, including IL-1ß, IL-6, and TNFα, which are induced by the activation of NOD2, in a dose- and time-dependent manner. However, pre-treatment with the NOD2 ligand muramyl dipeptide (MDP) did not up-regulate the expression of cytokines induced by IL-1α/ß re-treatment. IL-1ß treatment increased the expression of A20, which is an important inhibitor of the innate immune response. However, the overexpression of A20 failed to inhibit MDP-induced cytokine production, suggesting that A20 had no effects on the NOD2-induced immune response. In addition, IL-1α/ß increased the expression of NOD2 and its downstream adaptor RIP2, and IL-1α/ß pre-treatment increased MDP-induced activation of mitogen-activated protein kinases (MAPKs), including ERK, JNK, and P38, which contributed to MDP-induced cytokine production. Based on these results, IL-1α/ß promote the NOD2-induced immune responses by enhancing MDP-induced activation of MAPK signaling pathways.

Retrospective Evaluation of New Chinese Diagnostic Scoring System for Disseminated Intravascular Coagulation.

OBJECTIVES: To retrospectively validate the new Chinese DIC scoring system (CDSS). METHODS: This study retrospectively collected the information of 619 patients (371 cases with non-hematologic malignancies, 248 cases with hematologic malignancies) who suspected of DIC in Wuhan Union Hospital during 2013-4 to 2014-6. We validated CDSS by comparing it with three leading scoring systems, from International Society on Thrombosis and Haemostasis (ISTH), Japanese Association for Acute Medicine (JAAM) and Japanese Ministry of Health and Welfare (JMHW), and evaluated its prognostic value by 28 days mortality, APACHE II and SOFA score. RESULTS: In non-hematologic malignancies, CDSS was more specific than JAAM (72.55% vs. 50.49%, p<0.05) and more sensitive than ISTH (77.07% vs. 62.03%, p<0.05). In hematologic malignancies, the area under the ROC curve of CDSS was larger than ISTH and JMHW (0.933 vs. 0.889, p<0.01 with ISTH, 0.944 vs. 0.845, p<0.01 with JMHW). In addition, the 28-day mortality rate, SOFA scores, APACHE II scores of DIC patients diagnosed by CDSS were significantly greater than non-DIC (P <0.05). CONCLUSIONS: We are the first group to propose CDSS. It emphasized the values of the clinical manifestations, the rapidly declining platelet count, APTT in the diagnosis of DIC and used D-dimer as the fibrin-related maker. DIC with hematological malignancies was treated as a special part. In this study we can see that CDSS displayed an acceptable property for the diagnosis of DIC with appropriate sensitivity and specificity, and also had a good prognostic value for DIC patients.

Role of plasma high mobility group box-1 in disseminated intravascular coagulation with leukemia.

INTRODUCTION: High mobility group box 1(HMGB1) is a DNA-binding protein which can act as a proinflammatory cytokine when released by necrotic cells, monocytes or macrophages. It also plays a role in the coagulation activation and several tumors including leukemia. The objective of this study was to investigate the role of HMGB1 in the diagnosis of DIC with leukemia. METHODS: 89 subjects with leukemia in Wuhan Union Hospital were prospectively recruited. Among them, 83 cases were suspected of DIC, while the other 6 were the negative controls. Their clinical data, laboratory tests and plasma samples were collected or measured respectively. Accordingly, we made scores for these subjects by the Japanese Ministry of Health and Welfare (JMHW) criteria. RESULTS: This study demonstrated that the plasma levels of HMGB1 were higher in the DIC group than non-DIC (115.16 ng/ml vs. 63.94 ng/ml, p=0.003). The similar results were achieved in infected or non-infected groups. And along with the increase of DIC scores, the levels of HMGB1 increased gradually (p=0.006). In addition, HMGB1 was an independent factor in the diagnosis of DIC with leukemia(p<0.05). The diagnostic sensitivity of HMGB1 was high (Se=90.32%), and there was a tendency of increased HMGB1 levels in the pre-DIC patients. Three of these six pre-DIC patients were diagnosed as DIC by the new revised scoring system which contained HMGB1. Finally, the HMGB1 levels were significantly higher in patients with organ failures (SOFA≥2) than those without (118.76 vs. 72.75, p=0.032). CONCLUSION: The increased plasma levels of HMGB1 were related tightly to the diagnosis and severity of DIC in leukemia patients. Furthermore, the diagnostic sensitivity of HMGB1 was high. So HMGB1 in plasma is a helpful molecular marker, and can be added in the scoring system for the early diagnosis of DIC with leukemia.

[Effects of neonatal recurrent seizures on glucocorticoid receptor expression in the rat brain].

OBJECTIVE: To investigate the effets of flurothyl-induced neonatal recurrent seizures on glucocorticoid receptor (GR) expression in the rat brain. METHODS: Forty-eight seven-day-old Sprague-Dawley rats were randomly divided into two groups: control and seizure. Seizures were induced by inhalant flurothyl daily for six consecutive days. Brains were sampled on postnatal days 13, 15 and 19. The expression of GR protein in the cerebral cortex was detected by Western blot and immunohistochemical method. RESULTS: The expression of GR in the cerebral cortical plasma protein was significantly lower in the seizure group than in the control group on postnatal day 15. The expression of GR protein in the cerebral cortical nuclear protein decreased significantly in the seizure group compared with that in the control group on postnatal days 15 and 19 (p<0.05). Compared to the control group, the accumulated optical density (AOD) of GR immunoreactivity (IR) decreased significantly in the parietal cortex on postnatal day 13 (p<0.05), the AOD of GR IR decreased significantly in the parietal cortex and the temporal cortex on postnatal day 15 (p<0.05), and the AOD of GR IR decreased significantly in the parietal cortex, temporal cortex and the frontal cortex in the seizure group on postnatal day 19 (p<0.05). CONCLUSIONS: Recurrent seizures in neonatal rats result in abnormal GR expression in the cerebral cortex which might play an important role in short-term brain injury induced by early recurrent seizures.

[Roles of IL-4, IL-5 and IgE in childhood cough variant asthma].

OBJECTIVE: To study the roles of IL-4, IL-5 and IgE in childhood cough variant asthma (CVA). METHODS: The IL-4 and IL-5 levels in peripheral blood mononuclear cell (PBMC) and the serum IgE levels were determined using ELISA in children with CVA in the acute stage (n=21) and in the convalesce stage (n=9). The samples from 30 children with acute bronchial asthma and from 30 healthy children were used as controls. RESULTS: The levels of PBMC IL-4 (91.57 +/- 12.19 ng/L) and IL-5 (13.28 +/- 0.31 ng/mL) in children with CVA in the acute stage were significantly higher than those in the convalesce stage (74.68 +/- 11.54 ng/L, 6.53 +/- 0.28 ng/mL) and also higher than those in the healthy controls (70.32 +/- 18.16 ng/L, 5.29 +/- 0.36 ng/mL) (P < 0.01). The levels of serum IgE in children with CVA in the acute stage (279.6 +/- 41.3 KU /L) were strikingly higher than those in the convalesce stage (153.8 +/- 37.5 KU/L) (P < 0.01). The levels of serum IgE in children with CVA either in the acute stage or in the convalesce stage were significantly higher than those in healthy controls (90.6 +/- 44.8 KU /L) (P < 0.01). There were no significant differences in the levels of IL-4, IL-5 and IgE between children with acute CVA and acute asthma. CONCLUSIONS: A combined determination of PBMC IL-4 and IL-5 and serum IgE may be valuable for the diagnosis and the outcome evaluation of CVA. IL-4 and IL-5 may play a role in the pathogenesis of CVA. It is speculated that CVA may have similar pathogenesis to bronchial asthma since acute CVA patients have similar IL-4, IL-5 and IgE levels to children with acute bronchial asthma.