This study aims to investigate the antipyretic effects and mechanisms of ethanol extracts from Arisaematis Rhizoma fermented with bile from different sources on a rat model of fever induced by a dry-yeast suspension. The rat model of fever was established by subcutaneous injection of 20% dry-yeast suspension into the rat back. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) in the serum, as well as prostaglandin E_2(PGE_2) and cyclic adenosine monophosphate(cAMP) in the hypothalamus, were determined by ELISA. Metabolomics analysis was then performed on serum and hypothalamus samples based on UPLC-Q-TOF MS to explore the potential biomarkers and metabolic pathways. The results showed that the body temperatures of rats significantly rose 4 h after modeling. After oral administration of high-dose ethanol extracts of Arisaematis Rhizoma fermented with bovine bile(NCH) and porcine bile(ZCH), the body temperatures of rats declined(P<0.05), and the NCH group showed better antipyretic effect than the ZCH group. Additionally, compared with the model group, the NCH and ZCH groups showed lowered levels of IL-1β, IL-6, TNF-α, PGE_2, and cAMP(P<0.01). The results of serum and hypothalamus metabolomics analysis indicated that both NCH and ZCH exerted antipyretic effects by regulating phenylalanine metabolism, sphingolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Collectively, both NCH and ZCH can play an obvious antipyretic role in the rat model of dry yeast-induced fever, and the underlying mechanism might be closely associated with inhibiting inflammation and regulating metabolic disorders. Moreover, NCH demonstrates better antipyretic effect.
Animals ; Rats ; Male ; Fermentation ; Rats, Sprague-Dawley ; Rhizome/metabolism* ; Drugs, Chinese Herbal/chemistry* ; Bile/chemistry* ; Antipyretics/chemistry* ; Fever/metabolism* ; Cattle ; Swine ; Tumor Necrosis Factor-alpha/metabolism* ; Ethanol/chemistry* ; Interleukin-6/blood* ; Interleukin-1beta/blood*

This study developed ferritin-based nanoparticles carrying the African swine fever virus (ASFV) p30 protein and evaluated their immunogenicity, aiming to provide an experimental basis for the research on nanoparticle vaccines against ASFV. Initially, the gene sequences encoding the p30 protein and SpyTag were fused and inserted into the pCold-I vector to create the pCold-p30 plasmid. The gene sequences encoding SpyCatcher and ferritin were fused and then inserted into the pET-28a(+) vector to produce the pET-F-np plasmid. Both plasmids were expressed in Escherichia coli upon induction. Subsequently, the affinity chromatography-purified p30 protein was conjugated with ferritin in vitro, and the p30-ferritin (F-p30) nanoparticles were purified by size-exclusion chromatography. The morphology and structural integrity of F-p30 nanoparticles were examined by a particle size analyzer and transmission electron microscopy. Mice were immunized with F-p30 nanoparticles, and the humoral and cellular immune responses were assessed. The results showed that F-p30 nanoparticles were successfully prepared, with the particle size of approximately 20 nm. F-p30 nanoparticles were efficiently internalized by bone marrow-derived dendritic cells (BMDCs) cells in vitro. Compared with the p30 protein alone, F-p30 nanoparticles induced elevated levels of specific antibodies and cytokines in mice and stimulated the proliferation of follicular helper T cell (T_FH) and germinal center B cell (GCB) in lymph nodes as well as CD4⁺ and CD8⁺ T cells in the spleen. In conclusion, we successfully prepared F-p30 nanoparticles which significantly enhanced the immunogenicity of p30 protein, giving insights into the development of vaccines against ASFV.
Animals ; Nanoparticles/chemistry* ; Mice ; African Swine Fever Virus/genetics* ; Ferritins/chemistry* ; Swine ; Viral Vaccines/genetics* ; African Swine Fever/immunology* ; Mice, Inbred BALB C ; Viral Proteins/genetics* ; Escherichia coli/metabolism* ; Dendritic Cells/immunology* ; Immunogenicity, Vaccine ; Antibodies, Viral/blood* ; Female ; Capsid Proteins/genetics*

Objective: To investigate the effect of oxidative stress caused by heat exposure on the blood pressure increase of treadmill rats and the intervention of antioxidants. Methods: In June 2021, Twenty-four healthy SD male rats were randomly divided into four groups: normal temperature feeding, normal temperature treadmill, high temperature treadmill and high temperature treadmill supplementation with vitamin C groups, 6 rats in each group. The rats run on the platform in normal temperature or heat exposure environment for 30 min in the morning and in the afternoon daily, 6 days per week. The daily vitamin C supplement dose of high temperature treadmill supplementation with vitamin C group was 10 mg/kg. BP recordings were done at the end of the week. The rat vascular lipofuscin (LF) was detected by ELISA, the rat serum nitric oxide (NO) was detected by nitrate reductase method, the serum malondialdehyde (MDA) was detected by thibabituric acid method, the serum glutathione peroxidase (GPx) and superoxide dismutase (SOD) were detected by chemiluminescence method, and the serum catalase (CAT) was detected by ammonium molybdate method. The total antioxidant capacity (T-AOC) of serum was measured by iron reduction/antioxidant capacity method, and the content of nuclear erythroid 2-related factor 2 (Nrf2) in vascular tissue was measured by Western blot. The intra-group mean was compared by repeated measurement analysis of variance, and the inter-group mean was compared by single-factor analysis of variance and post-event LSD-t test. Results: Compared with the previous time point, the systolic BP and diastolic BP of the high temperature treadmill group were significantly increased at 7, 14 and 21 d, and decreased at 28 d which were higher than the initial level (P<0.05), and the systolic BP and diastolic BP values at each experimental time point were significantly higher than those of normal temperature treadmill group (P<0.001). The changes of thickening of the artery wall, no smoothing of the endodermis and irregular arrangement of muscle cells in high temperature treadmill group were observed. Compared with the normal temperature treadmill group, the content of MDA in serum, and LF in vascular tissue were significantly increased, the activities of SOD, CAT, T-AOC, the content of NO in serum, and the expression of Nrf2 in vascular tissue were significantly decreased in high temperature treadmill group (P<0.05). Compared with the high temperature treadmill group, the systolic BP and diastolic BP values at 7, 14, 21 and 28 d, the content of serum MDA and LF in vascular tissue were significantly decreased, the activities of CAT and T-AOC, and the expression of Nrf2 in vascular tissue significantly increased (P<0.05), the histopathological changes of the artery wall improved in high temperature treadmill supplementation with vitamin C group. Conclusion: Heat exposure has effect on oxidative stress, which may be related to the increase of BP. Vitamin C as an anti-oxidative enhancer can prevent those negative effects, which could alleviate the pathological changes of vessel intima in heat-exposed rats. And the Nrf2 may be a regulated factor to vascular protection.
Male ; Animals ; Rats ; Ascorbic Acid ; Antioxidants/pharmacology* ; Blood Pressure ; Hot Temperature ; NF-E2-Related Factor 2 ; Oxidative Stress ; Fever

Objective: To analyze the clinical characteristics of children with multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 in China, and to improve the understanding of MIS-C among pediatricians. Methods: Case series study.Collect the clinical characteristics, auxiliary examinations, treatment decisions, and prognosis of 64 patients with MIS-C from 9 hospitals in China from December 2022 to June 2023. Results: Among the 64 MIS-C patients, 36 were boys and 28 were girls, with an onset age being 2.8 (0.3, 14.0) years. All patients suffered from fever, elevated inflammatory indicators, and multiple system involvement. Forty-three patients (67%) were involved in more than 3 systems simultaneously, including skin mucosa 60 cases (94%), blood system 52 cases (89%), circulatory system 54 cases (84%), digestive system 48 cases (75%), and nervous system 24 cases (37%). Common mucocutaneous lesions included rash 54 cases (84%) and conjunctival congestion and (or) lip flushing 45 cases (70%). Hematological abnormalities consisted of coagulation dysfunction 48 cases (75%), thrombocytopenia 9 cases (14%), and lymphopenia 8 cases (13%). Cardiovascular lesions mainly affected cardiac function, of which 11 patients (17%) were accompanied by hypotension or shock, and 7 patients (12%) had coronary artery dilatation.Thirty-six patients (56%) had gastrointestinal symptoms, 23 patients (36%) had neurological symptoms. Forty-five patients (70%) received the initial treatment of intravenous immunoglobulin in combination with glucocorticoids, 5 patients (8%) received the methylprednisolone pulse therapy and 2 patients (3%) treated with biological agents, 7 patients with coronary artery dilation all returned to normal within 6 months. Conclusions: MIS-C patients are mainly characterized by fever, high inflammatory response, and multiple organ damage. The preferred initial treatment is intravenous immunoglobulin combined with glucocorticoids. All patients have a good prognosis.
Male ; Child ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Blood Coagulation ; COVID-19 ; China/epidemiology* ; Connective Tissue Diseases ; Coronary Aneurysm ; Fever ; Systemic Inflammatory Response Syndrome/therapy*

OBJECTIVES: To study the clinical characteristics and prognosis of SARS-CoV-2 Omicron variant infection-associated acute necrotizing encephalopathy (ANE) in children . METHODS: A retrospective analysis was conducted on the medical data of 12 children with SARS-CoV-2 Omicron variant infection-associated ANE who were admitted to the Pediatric Intensive Care Unit, Qingdao Women and Children's Hospital from December 18 to 29, 2022. The children were divided into two groups based on outcomes: death group (7 cases) and survival group (5 cases). The clinical manifestations and auxiliary examination results were compared between the two groups. RESULTS: The median age of the 12 patients was 30 months, with a male-to-female ratio of 1:1. All patients presented with persistent high fever, with a median highest body temperature of 41℃. The median time from fever onset to seizure or consciousness disturbance was 18 hours. The death group had a higher proportion of neurogenic shock, coagulation dysfunction, as well as elevated lactate, D-dimer, interleukin-6, interleukin--8, and interleukin-10 levels compared to the survival group (P<0.05). CONCLUSIONS Children with SARS-CoV-2 Omicron variant infection-associated with ANE commonly present with persistent high fever, rapidly progressing disease, and have a high likelihood of developing consciousness disorders and multiorgan dysfunction within a short period. The occurrence of neurogenic shock, coagulation dysfunction, and significantly elevated cytokine levels suggests an increased risk of mortality.
Humans ; Female ; Child ; Male ; Infant ; SARS-CoV-2 ; Retrospective Studies ; COVID-19/complications* ; Brain Diseases/etiology* ; Prognosis ; Fever ; Blood Coagulation Disorders

To investigate the antipyretic effect of active components of Mahuang Decoction in febrile rats, and explore its correlation with pharmacokinetics at different time points. The feverished rat models were induced by dry yeast, and intragastrically administered with the effective components of Mahuang Decoction with different orthogonal compatibility ratios. At different time points after administration, body temperature was measured; blood was taken from orbital vena plexus, and the contents of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in rat serum were determined with the kits. Combined with the pharmacokinetic data of the seven effective components in Mahuang Decoction, PK-PD(pharmacokinetics-pharmacodynamics) data fitting was conducted by using the analysis method of non-atrioventricular model, and then the pharmacodynamic parameters were calculated to determine the optimal binding model. The results showed that the effective components of Mahuang Decoction inhibited the release of heat-causing factors IL-6, IL-1β and TNF-α, and reduced the increase of body temperature. There was a significant lag between drug effect and blood drug concentration, which was consistent with Sigmoid-E_(max) model. The model fitting value showed a good correlation with mea-sured data, which could be used to evaluate and predict the correlation between PK and PD in Mahuang Decoction, and further applied to the multiple-indicator and multiple-effect study of PK-PD in other compound traditional Chinese medicines.
Animals ; Antipyretics/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Ephedra sinica/chemistry* ; Fever/drug therapy* ; Interleukin-1beta/blood* ; Interleukin-6/blood* ; Medicine, Chinese Traditional ; Rats ; Tumor Necrosis Factor-alpha/blood*

BACKGROUND AND OBJECTIVES: Acute epiglottitis is a life-threatening condition that can result in airway obstruction. The present study reports clinical features, management and patient outcomes in an acute epiglottitis. SUBJECTS AND METHOD: Included in our retrospective study were 315 patients who were admitted with the diagnosis of acute epiglottitis between January 2006 and July to the department Otolaryngology-Head and Neck surgery, Hallym University Sacred Heart Hospital 2018. The diagnosis of acute epiglottitis was established by confirmation of inflamed epiglottis using laryngoscope or computed tomography. RESULTS: Among 315 patients, 89 cases (28%) and 83 cases (26%) were found in the fifth and fourth decades, respectively. The mean age of patients was 45.0±13.94 years. The male to female ratio was 1.33:1. A total of 75 patients (23.8%) had co-morbidities, with hypertension (13.6%) being the most common. Fever was relatively uncommon, whereas most patients complained of sore throat. Ceftriaxone was the most common empirical antibiotic regimen prescribed and the use of steroids did not affect the length of hospital stay. Nine patients required airway intervention, including eight who underwent endotracheal intubation and one emergency tracheostomy. In patients who need airway intervention, systolic blood pressure, body temperature, respiratory rate, heart rate, white blood cells and the proportion of dyspnea were significantly higher in comparison to the patients without airway intervention. CONCLUSION: Although acute epiglottitis often has nonspecific symptoms, it may lead to sudden dyspnea and unstable vital signs, so an in-depth understanding of this disease is needed.
Airway Obstruction ; Anti-Bacterial Agents ; Blood Pressure ; Body Temperature ; Ceftriaxone ; Clinical Study ; Diagnosis ; Dyspnea ; Emergencies ; Epiglottis ; Epiglottitis ; Female ; Fever ; Heart ; Heart Rate ; Humans ; Hypertension ; Intubation, Intratracheal ; Korea ; Laryngoscopes ; Length of Stay ; Leukocytes ; Male ; Methods ; Neck ; Pharyngitis ; Respiratory Rate ; Retrospective Studies ; Steroids ; Tracheostomy ; Vital Signs

PURPOSE: Kawasaki disease (KD) is a common, acute systemic vasculitis in children. Acute phase reactants (APRs) have been used to assist diagnosis, and to predict outcome in children with KD. However, it remains unknown on levels of APRs depending on duration of fever. We aimed to compare APR levels of children with KD who visited with < 5 days duration of fever and with ≥ 5 days. METHODS: Children (≤ 15 years) with complete KD who visited the emergency department were enrolled from March 2012 through February 2018. The children were divided into the early (fever < 5 days) and late (fever ≥ 5 days) presenters. The baseline characteristics, APR levels, such as platelet count, and outcomes were compared between the 2 groups. RESULTS: A total of 145 children with complete KD were enrolled. Median age was 27.0 (interquartile range [IQR], 12.0–46.5) months, and boys accounted for 60.0%. The early presenters (63 [43.4%]) had a younger age (17.0 [IQR, 7.0–45.0] vs. 32.5 [IQR, 14.0–48.0] months; P = 0.006), shorter duration of fever (3.0 [IQR, 2.0–4.0] vs. 6.0 [IQR, 5.0–7.0] days; P < 0.001), and a lower platelet count (336.7 ± 105.2 [× 10³/µL] vs. 381.6 ± 121.8 [× 10³/µL], P = 0.02) than the late presenters. The other APR levels, and frequency of resistance to intravenous immunoglobulin and coronary artery abnormalities showed no differences between the 2 groups. CONCLUSION: Children with KD who visited with < 5 days duration of fever had a lower platelet count compared to those with ≥ 5 days. No differences were found in the other APR levels and the outcomes. It may be necessary to consider the differences in APR levels depending on duration of fever when treating children with KD.
Acute-Phase Proteins ; Blood Platelets ; C-Reactive Protein ; Child ; Coronary Vessels ; Diagnosis ; Emergency Service, Hospital ; Fever ; Humans ; Immunoglobulins ; Leukocyte Count ; Mucocutaneous Lymph Node Syndrome ; Platelet Count ; Systemic Vasculitis

PURPOSE: The aim of this study was to evaluate the clinical significance of inflammatory biomarkers in acute infectious diarrhea among children. METHODS: Clinical parameters including fever, bacterial and viral etiology based on stool culture and multiplex polymerase chain reaction, and nine biomarkers including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and leukocytes in blood and calprotectin, lactoferrin, myeloperoxidase, polymorphonuclear elastase, leukocytes, and occult blood in feces were evaluated in children who were hospitalized due to acute diarrhea without underlying disease. RESULTS: A total of 62 patients were included. Among these patients, 33 had fever, 18 showed bacterial infections, and 40 patients were infected with 43 viruses. Of all the biomarkers, CRP was significantly correlated with fever (p<0.001). CRP, ESR, calprotectin, lactoferrin, myeloperoxidase, fecal leukocytes, and occult blood were significantly associated with infection with bacterial pathogens (p<0.001, p=0.04, p=0.03, p=0.003, p=0.02, p=0.03, p=0.002, respectively). The combination of CRP and fecal lactoferrin at their best cut-off values (13.7 mg/L and 22.8 µg/mL, respectively) yielded a sensitivity of 72.2%, and a specificity of 95.5% for bacterial etiology compared with their individual use. CONCLUSION: Blood CRP is a useful diagnostic marker for both fever and bacterial etiology in acute pediatric diarrhea. The combination of CRP and fecal lactoferrin yields better diagnostic capability for bacterial etiology than their use alone for acute diarrhea in children without underlying gastrointestinal disease.
Bacterial Infections ; Biomarkers ; Blood Sedimentation ; C-Reactive Protein ; Child ; Diarrhea ; Feces ; Fever ; Gastrointestinal Diseases ; Humans ; Lactoferrin ; Leukocyte L1 Antigen Complex ; Leukocytes ; Multiplex Polymerase Chain Reaction ; Occult Blood ; Pancreatic Elastase ; Peroxidase ; Sensitivity and Specificity

Postinfectious glomerulonephritis (PIGN) is most commonly caused by Streptococcus pyogenes in children, but PIGN associated with other pathogens has been described in the literature. A previously healthy 6-year-old boy was admitted with complaints of cough, fever, and right chest pain. The patient was diagnosed with pneumococcal bacteremia and influenza A virus infection and treated with antibiotics and antiviral agent. During hospitalization, generalized edema, hematuria, proteinuria, and increased blood pressure were observed; therefore, we started administering diuretics. The boy was discharged with gross hematuria, and even microscopic hematuria disappeared 14 weeks after discharge. We report a case of PIGN associated with bacteremic pneumococcal pneumonia and influenza A virus infection in children. A urine test and blood pressure measurement should be considered for the early detection of PIGN in children with pneumococcal or influenza A virus infection when they present with nephritic symptoms.
Anti-Bacterial Agents ; Bacteremia ; Blood Pressure ; Chest Pain ; Child ; Cough ; Diuretics ; Edema ; Fever ; Glomerulonephritis ; Hematuria ; Hospitalization ; Humans ; Influenza A virus ; Influenza, Human ; Male ; Pneumonia ; Pneumonia, Pneumococcal ; Proteinuria ; Streptococcus pneumoniae ; Streptococcus pyogenes