Nasal solitary chemosensory cells govern daily rhythm in mouse model of allergic rhinitis.

BACKGROUND: While the daily rhythm of allergic rhinitis (AR) has long been recognized, the molecular mechanism underlying this phenomenon remains enigmatic. OBJECTIVE: We aim to investigate the role of circadian clock in AR development and to clarify the mechanism by which the daily rhythm of AR is generated. METHODS: AR was induced in mice using the ovalbumin method. Toluidine blue staining, LC-MS/MS analysis, qPCR, and immunoblotting were performed with AR and control mice. RESULTS: Ovalbumin-induced AR is diurnally rhythmic and associated with clock gene disruption in nasal mucosa. In particular, Rev-erbα is generally down-regulated, and its rhythm retained but with a near 12-h phase shift. Furthermore, global knockout of the core clock gene Bmal1 or Rev-erbα increases the susceptibility of mice to AR and blunts AR rhythmicity. Importantly, nasal SCCs (solitary chemosensory cells) are rhythmically activated, and inhibition of the SCC pathway leads to attenuated AR and a loss of its rhythm. Moreover, rhythmic activation of SCCs is accounted for by diurnal expression of ChAT (an enzyme responsible for the synthesis of acetylcholine) and temporal generation of the neurotransmitter acetylcholine. Mechanistically, REV-ERBα trans-represses Chat through direct binding to a specific response element, generating a diurnal oscillation in this target gene. CONCLUSION: These findings identify SCCs, under the control of REV-ERBα, as a driver of AR rhythmicity, and suggest targeting SCCs as a new avenue for AR management.

Structural and in vivo-in vitro myocardial injury protection features of two novel polysaccharides from Allium macrostemon Bunge and Allium chinense G. Don.

This study aimed to investigate the structural characteristics, in vivo antiatherosclerosis activity, and in vitro myocardial injury protection effects of polysaccharides from Allium macrostemon Bunge and Allium chinense G. Don. Thus, crude polysaccharides of Allium macrostemon Bunge and Allium chinense G. Don significantly reduced serum lipid levels, improved cardiac myocyte morphology and arrangement, and relieved the development of myocardial fibrosis. Meanwhile, the lesion areas of the aorta and aortic valve had evident visual improvements. Furthermore, two main novel purified polysaccharides, namely, AMB-1 and ACGD-1, were isolated and characterized from crude Allium macrostemon Bunge and Allium chinense G. Don fractions, respectively. The purified polysaccharides mainly consisted of fructose and glucose and had molecular weights of 25.22 and 19.53 kDa, respectively. In addition, Fourier transform infrared spectroscopy, methylation, and nuclear magnetic resonance data revealed the primary structures of the AMB1 (or ACGD1) backbone with branched side chains. Scanning electron microscope analysis showed that the purified polysaccharides were both piled together in a lamellar or clastic form with a smooth surface along with linear or irregular bulges. Moreover, the purified polysaccharides both showed nontoxicity on H9c2 cells and effectively dropped hypoxia/reoxygenation-induced apoptosis by the BCL-2/BAX pathway. Overall, the characterization of the structural properties and in vivo and in vitro myocardial injury protection effects of Allium macrostemon Bunge and Allium chinense G. Don polysaccharides enriched our understanding of their nutritional and medicinal values. To the best of our knowledge, this is the first study on the structural characteristics and bioactivities of Allium chinense G. Don polysaccharides.

Abnormal Changes in IL-13 and IL-17A Serum Levels in Children with Adenovirus Pneumonia and their Diagnostic Value.

Background: Human adenovirus (HAdV) is an enveloped icosahedral DNA virus. HAdV infection can lead to immune system damage, resulting in decreased numbers and compromised function of T cells and B cells. It can also cause an imbalanced Th1/Th2 ratio and dysregulation of pro-inflammatory and anti-inflammatory cytokines. Objective: To investigate the serum levels of interleukin (IL)-13 and IL-17A in children with HAdV pneumonia. Methods: Pediatric patients diagnosed with HAdV pneumonia were divided into a non-severe group or a severe group based on the severity of their condition. Patients in the severe group were further classified into good and poor prognosis subgroups. We collected 2-2.5 mL of venous blood from each patient, which was then centrifuged. Using an ELISA detection kit, we determined the concentrations of IL-13 and IL-17A. Results: Patients with a severe condition exhibited significantly higher serum concentrations of IL-13 and IL-17A than the non-severe cases. Out of 50 severe cases, 32 had good prognoses, while 18 cases showed poor prognoses. Patients with poor prognoses showed significantly higher serum concentrations of IL-13 compared to those with good prognoses. Conclusion: Serum concentrations of IL-13 and IL-17A are potential diagnostic markers for pediatric patients with severe HAdV pneumonia. Additionally, they demonstrate good predictive value for a poor prognosis in severe pneumonia cases.

Deciphering the diurnal rhythm regulating mechanism of flavin-containing monooxygenase 3 in mouse liver.

Circadian genes play an important role in the field of drug metabolism. Flavin-containing monooxygenase 3 is a well-known phase I enzyme which participates in metabolism of many exogenous and endogenous substances, especially production of trimethylamine N-oxide. Here, we aimed to decipher diurnal rhythms of flavin-containing monooxygenase 3 expression and activity, and explore the regulation mechanism by clock genes. Our results showed that its mRNA and protein exhibited robust diurnal rhythms in mouse liver and cell lines. Consistently, significant alterations were observed for in vitro microsomal N-oxidation rates of procainamide, which kept in line with its protein expression at different time in wild-type and reverse erythroblastosis virus α knockout mice. Further, flavin-containing monooxygenase 3 was negatively regulated by E4 promoter-binding protein 4 in AML12 and Hepa1-6 cells, while it was positively influenced by reverse erythroblastosis virus α and brain and muscle ARNT-like protein-1. Moreover, luciferase reporter assays and electrophoretic mobility shift assays showed E4 promoter-binding protein 4 inhibited the transcription of flavin-containing monooxygenase 3 by binding to a D-box1 element (-1606/-1594 bp), while brain and muscle ARNT-like protein-1 positively activated the transcription via direct binding to three E-boxes (-863/-858 bp, -507/-498 bp, and -115/-104 bp) in this enzyme promoter. Taken together, this study would be helpful to reveal the mechanism of clock-controlled drug metabolism and facilitate the practice of chrono-therapeutics.

Perceptions, barriers, and challenges of oral care among nursing assistants in the intensive care unit: a qualitative study.

BACKGROUND: Although oral hygiene is closely related to various diseases, it is sub-optimal in the Intensive Care Unit (ICU). Oral care in the ICU is challenged by nursing workloads, low staffing, and higher acuity patients, there are few policies and written guidelines for oral care. Nurses often delegate oral care to nursing assistants (NAs) whose role is overlooked. This study is to explore the perspectives, obstacles, and challenges of NAs in the oral care of the ICU. METHODS: A qualitative study and semi-structured interviews were conducted with NAs in three ICU units, and Colaizzi's phenomenological method was used to analyze the records. RESULTS: Initially, 13 NAs met the inclusion criteria, and two did not participate in this study as they refused to be recorded. Finally, 11 ICU NAs were interviewed, with three receiving face-to-face interviews and eight receiving telephone interviews. Using Colaizzi's phenomenological method, two themes and eight subthemes emerged from the data, we examined the self-perception, barriers and challenges of NAs regarding oral care and identified the subthemes: (1) The target audience, frequency, and importance; (2) Role; (3) Evaluation; (4) Patient-related factors; (5) Oral care tools; (6) Psychology of NAs; (7) Lack of education and training; (8) Lack of team support. CONCLUSION: Nursing assistants whose roles are overlooked by the nursing team are important members of the ICU team. Though oral care is closely related to disease prevention, it is rarely considered an essential task. Major barriers to implementing oral care in the ICU environment and patients include the psychological quality of participants, non-standard education and training, and inadequate team support. The expectation is that medical personnel will prioritize oral hygiene and recognize the significance of NAs in nursing work. Furthermore, future ICU oral care should investigate suitable tools and mouthwashes, simplified and standardized processes, standardized training, and multidisciplinary team collaboration.

Mitochondrion-NLRP3 inflammasome activation in macrophages: A novel mechanism of the anti-inflammatory effect of Notopterygium in rheumatoid arthritis treatment.

OBJECTIVE: The mechanism by which Notopterygium (NE) regulates the nucleotide-binding, oligomerization domain (NOD)-like receptor family and pyrin domain-containing 3 (NLRP3) inflammasome to treat rheumatoid arthritis (RA) was investigated to reveal the scientific implications of NE in RA treatment. METHODS: Adjuvant arthritis (AA) rats were replicated. After NE intervention, the anti-inflammatory efficacy of NE in vivo was determined. The mechanism of NE in RA treatment was predicted by network pharmacology, and the key target for further experiments was found through the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG). The effect of NE on the NLRP3 inflammasome in AA rats was verified. Furthermore, with the induction of inflammation in RAW264.7 cells by lipopolysaccharide (LPS), several techniques, such as Griess assay, enzyme linked immunosorbent assays, electron microscopy, and fluorescence probe technology, were used to investigate the anti-inflammatory and related mechanisms of NE in RA treatment. RESULTS: NE could inhibit inflammation in AA rats. KEGG results showed that NLRP3 participated in the top three pathways of NE in RA treatment. Through Western blotting and immunofluorescence assays, this study demonstrated that NE can regulate NLRP3, pro-Caspase-1, Caspase-1, and CD11b in the ankle joint of AA rats. NE may significantly reduce the LPS-induced inflammatory response of RAW264.7 cells by alleviating mitochondrial damage, reducing the number of mitochondrial deoxyribonucleic Acid and mitochondrial reactive oxygen species, inhibiting NLRP3 inflammasome activation. CONCLUSION: The anti-inflammatory and antirheumatic effect of NE may involve regulating NLRP3 inflammasome activation through mitochondria. NLRP3 is probably the key target molecule of NE in the treatment of RA.

Effect of Antilogous Platelet-Rich Plasma on the Revascularization of Rabbit Prefabricated Flap.

BACKGROUND We aimed to investigate the effect of the local application of autologous platelet-rich plasma (PRP) on the angiogenesis of the rabbit prefabricated flap. MATERIAL AND METHODS Femoral arteriovenous bundle prefabricated flaps were constructed on both sides of the abdomen of 20 New Zealand white rabbits and were randomly divided into experimental sides and control sides, with 40 sides in total. Autologous PRP was injected around the prefabricated femoral vascular bundle on the experimental side, and the same amount of saline was injected on the control side. After 14 days, stage II surgery was performed to lift the island flap with the implanted femoral vascular bundle at the tip of the preconfigured flap marker line and suture it in situ. Twenty rabbits were divided equally into 4 groups: group A, 7 days after stage I surgery; group B, 14 days after stage I surgery; group C, 7 days after stage II surgery; and group D, 14 days after stage II surgery. The survival of neovascularization and the flaps in the 4 groups were compared by microscopic observation, histology, and immunohistochemistry. RESULTS The density of neovascularization was much higher on the experimental side than on the control side in the 4 groups, and statistically significantly increased with time (P<0.05). Seven days after stage II surgery, flap survival was better on the experimental side than on the control side. CONCLUSIONS PRP effectively promoted the revascularization of a prefabricated flap, and vascular density increased with time.

An isolated pulmonary nodule secondary to Streptococcus intermedius infection in an otherwise healthy 10-year-old boy: A case report and literature review.

Streptococcus intermedius, as a Gram-positive commensal bacterium, tends to cause various infections, such as brain and liver abscesses, endocarditis, and empyema, especially in immunocompromised patients. However, an isolated pulmonary nodule caused by S. intermedius in previously healthy individuals without traditional risk factors is rarely reported. Herein, we present a case of a 10-year-old immunocompetent boy referred to our department with a 5-day history of intermittent, left-sided chest pain. Chest X-ray and computed tomography revealed a left lung nodule. Although his blood, sputum, and bronchoalveolar lavage fluid cultures were negative, metagenomic next-generation sequencing (mNGS) showed only the presence of S. intermedius in ultrasonography-guided lung biopsy tissue and pleural fluid (416 and 110 reads, respectively). He was then successfully treated with appropriate intravenous antibiotics and avoided surgical intervention. To the best of our knowledge, this is the first report of S. intermedius-related pulmonary nodule confirmed by mNGS analysis in healthy children. For achieving proper diagnosis and treatment, infection with S. intermedius should be included in the differential diagnosis when coming across such a similar pulmonary nodule. mNGS, as a valuable supplement to conventional culture methods, is an essential diagnostic tool for identifying pathogens without typical characteristics.

Telehealth Education via WeChat Improves the Quality of Life of Parents of Children with Type-1 Diabetes Mellitus.

OBJECTIVE: The purpose of this study was to explore the effect of telehealth education and care guidance via WeChat (Tencent Ltd., Shenzhen, China; a popular smartphone-based social media application) on improving the quality of life of parents of children with type-1 diabetes mellitus. METHODS: A prospective randomized controlled study was conducted in our hospital from March 2019 to September 2020 to compare the quality of life of parents of children with type-1 diabetes mellitus in the intervention group and the control group. RESULTS: Six months after discharge, the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores of parents in the intervention group were significantly lower than those in the control group (p < 0.05). Compared with the SAS and SDS scores at discharge time, those scores of parents at 6 months after discharge time in intervention group were significantly lower (p < 0.05), while those scores of parents at 6 months after discharge time in control was similar (p > 0.05). Six months after discharge, the scores of the physiological field, psychological field, social relationship field, and environmental field in the intervention group were significantly higher than those of the control group according to the result of the World Health Organization Quality of Life Brief Scale (WHOQOL-BREF; p < 0.05). CONCLUSION: Using WeChat to provide telehealth education and home care guidance to the parents of children with type-1 diabetes mellitus can effectively relieve the anxiety and depression of the parents and improve their quality of life.

[The Association between the Level of Plasma D-dimer and Disease Severity and Prognosis of Mycoplasma pneumoniae Pneumonia in Children].

OBJECTIVE: To explore the association between the levels of plasma D-dimer and the disease severity and prognosis of Mycoplasma pneumoniae pneumonia (MPP) in children. METHODS: We retrospectively analyzed the clinical data of pediatric MPP patients who were admitted in our hospital between January 1, 2016 and December 31, 2018. According to the peak value of D-dimer, patients were divided into the normal group (D-dimer<0.55 mg/L) and the elevated group (D-dimer≥0.55 mg/L). Information regarding the demographics, clinical manifestations, auxiliary examinations and treatments of patients in the two groups was compared. RESULTS: Of the 231 MPP patients included in the study, 70 were in the normal group and 161 were in the elevated group. The age of patients in the D-dimer elevated group was significantly higher than that of the normal group ( P<0.01). Compared with the normal group, the elevated group had longer lengths of fever, hospital stay and antibiotic therapy, and more severe radiographic manifestations (all P<0.01). In addition, the incidence of extrapulmonary complications, refractory MPP and severe MPP in the elevated group were significantly higher than those in the normal group ( P<0.01). As for the laboratory data, we found that neutrophils, C-reactive protein, lactate dehydrogenase, interleukin-6, interleukin-10 and interferon-γ were significantly higher in the elevated group than those in the normal group ( P<0.05). After treatments, all patients showed improvement and were discharged, but the proportions of patients requiring glucocorticoids, bronchoscopy, thoracentesis were significantly higher in the elevated group than those in the normal group ( P<0.05). Follow-up findings showed that the absorption rate of lung lesions 4 weeks after admission was significantly higher, the time needed for lung lesions absorption was significantly shorter, and the incidence of pulmonary sequelae was significantly lower in the normal group than those in the elevated group (all P<0.05). Correlation analysis showed that D-dimer level was positively correlated with the severity of pneumonia ( r=0.272, P=0.000) and the incidence of pulmonary sequelae ( r=0.235, P=0.000). CONCLUSION: Pediatric patients of MPP who had elevated plasma D-dimer had clinical manifestations that were more severe, required longer duration of treatment and longer recovery time for lung lesions, and were more likely to have pulmonary sequelae.

Psychological intervention in children with transfusion-dependent ß-thalassaemia.

BACKGROUND AND OBJECTIVES: Transfusion-dependent ß-thalassaemia can lead to severe psychological issues in paediatric and adolescent patients. However, the psychological interventions for these patients are limited in clinical practice. We aimed to investigate the impact of a 3-month psychological intervention on the quality of life (QOL) of children with ß-thalassaemia (12-18 years old) who relied on blood transfusion in this study. MATERIALS AND METHODS: In the current randomized controlled trial, a total of 143 paediatric or adolescent patients (12-18 years old) with transfusion-dependent ß-thalassaemia were recruited. They were randomized into the control group (n = 71) who received standard physiological treatment and the intervention group (n = 72) who received a 3-month intervention in addition to standard physiological treatment. The effects of the interventions on the QOL and psychological outcomes of these participants were analysed. RESULTS: The 3-month intervention significantly improved the scores of PedsQoL 4.0 Generic Core Scales of paediatric patients with transfusion-dependent ß-thalassaemia. It also significantly improved the psychological status and alleviated the depression among children and adolescent patients by alleviating anhedonia, negative mood and negative self-esteem among them. CONCLUSION: Psychological intervention has positive effects on the treatment for children with transfusion-dependent ß-thalassaemia.

The Level of D-Dimer Is Positively Correlated With the Severity of Mycoplasma pneumoniae Pneumonia in Children.

Objective: Mycoplasma pneumoniae pneumonia (MPP) is an important disease in children. Studies have demonstrated that the levels of D-dimer are elevated in some children with MPP, especially those with thrombotic complications. However, the potential association between MPP and D-dimer remains unclear. In our study, we sought to explore the relationship between the levels of plasma D-dimer and clinical characteristics of MPP patients. Methods: Retrospective analysis was conducted on 356 patients who were hospitalized in our hospital for MPP between January 1, 2017, and December 31, 2019. According to the peak value of D-dimer, patients were divided into three groups: the normal group (D-dimer<0.55 mg/L), the mild-moderately elevated group (D-dimer 0.55-5.5 mg/L) and the severely elevated group (D-dimer >5.5 mg/L). The demographic and clinical information, radiological findings, laboratory data, and treatments of patients were compared among different groups. Results: 106 patients were in the normal group, 204 patients were in the mild-moderately elevated group, and 46 patients were in the severely elevated group. More severe clinical and radiographic manifestations, longer length of fever, hospital stay and antibiotic therapy duration, higher incidences of extra-pulmonary complications, refractory MPP (RMPP), severe MPP (SMPP) were found in the elevated group, when compared with the normal group (P<0.01). Meanwhile, we found that the percentage of neutrophil (N%) and CD8+ lymphocyte (CD8+%), C-reactive protein (CRP), lactate dehydrogenase (LDH), interleukin (IL)-6, IL-10, and interferon-gamma (IFN-γ) trended higher with increasing D-dimer, whereas the percentage of lymphocyte (L%) and prealbumin (PAB) trended lower (P<0.01). In addition, the proportions of patients requiring oxygen therapy, glucocorticoid, bronchoscopy, immunoglobulin use, thoracentesis, or ICU admission were significantly higher in the severely elevated group than those in the other two groups (P<0.01). Correlation analysis showed that N%, L%, CRP, LDH, IL-10, length of fever, length of stay, and length of antibiotic therapy had strong correlations with the level of D-dimer. Conclusions: MPP patients with higher levels of D-dimer had more severe clinical manifestations and needed longer duration of treatment, which might be closely related to the severity of lung inflammation after MP infection.

Cardiopulmonary bypass as a bridge for bronchial foreign body removal in a child with pulmonary artery sling: A case report.

RATIONALE: Successful removal of an airway foreign body (FB) in some intractable cases can be very challenging, because of tracheal anomalies, unstable respiratory status of the patients, and the location of FB. The use of cardiopulmonary bypass (CPB) support for the treatment of a FB is extremely rare. PATIENT CONCERNS: We present a case of a 39-month-old previously healthy girl who was admitted to our hospital for suspected FB aspiration (FBA). Initially, the attempt for removal of the FB by conventional bronchoscopy failed because of hypoxic intolerance. DIAGNOSES: Bronchoscopy revealed tracheal anomalies and subsequent computed tomography angiography demonstrated the presence of a pulmonary artery sling (PAS), which confirmed the diagnosis of PAS accompanied with FBA. INTERVENTIONS: With the assistance of CPB, multidisciplinary treatment involving the respiratory, cardiothoracic and anesthetic teams were involved and the bronchial FB was removed by flexible bronchoscopy successfully and then PAS was corrected by surgical intervention. OUTCOMES: The patient remained asymptomatic, without shortness of breath or wheezing during the 15 months follow-up. LESSONS: This case highlights that in a complicated case of FBA, bronchoscopy and computed tomography imaging are of great importance to achieve an accurate diagnosis, and a multidisciplinary treatment approach is essential for a satisfactory outcome. If the patient is unstable for bronchoscopy, CPB can be temporarily used in the stabilization of the patient to allow safe removal of the FB.

Gastrodin Inhibits Virus Infection by Promoting the Production of Type I Interferon.

Type I interferon (IFN-I) plays a critical role in the antiviral immune response. However, viruses have developed different strategies to suppress the production of IFN-I for its own escape and amplification. Therefore, promoting the production of IFN-I is an effective strategy against virus infection. Gastrodin (GTD), a phenolic glucoside extracted from Gastrodia elata Blume, has been reported to play a protective role in some central nervous system -related diseases and is beneficial for the recovery of diseases by inhibiting inflammation. However, the effect of GTD on virus infection is largely unknown. Here we found GTD treatment increased the survival rate of mice infected with vesicular stomatitis virus (VSV) or herpes simplex virus-1 (HSV-1). The production of IFN-I was increased in GTD-treated mice or macrophages compared to the control group, during virus infection. Furthermore, the activation of interferon regulatory factor 3 (IRF3) was promoted by GTD in macrophages upon VSV and HSV-1 infection. Our results demonstrated that GTD could inhibit the VSV and HSV-1 infection by promoting the production of IFN-I in macrophages and might provide an effective strategy against virus infection.

Cytokines as the good predictors of refractory Mycoplasma pneumoniae pneumonia in school-aged children.

Excessive immune response against pathogens may play an important role in refracory Mycoplasma pneumoniae pneumonia (RMPP). The aim of this study was to elucidate the associations between cytokines and the prediction of RMPP in school-aged patients. Retrospective analysis was performed on school-aged children with Mycoplasma pneumoniae pneumonia (MPP) hospitalized in our hospital between January 1, 2011 and December 31, 2015. The clinical charcteristics, including the cytokines in serum between the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group were compared and the predictive values of RMPP were explored. Of total 180 patients, 115 patients were in the GMPP group, 65 were in the RMPP group. We found the levels of cytokines, including nterleukin (IL)-6, IL-10, interferon gamma (IFN-γ) in RMPP group were significantly higher than those in GMPP group (P < 0.01). In ROC curve analysis, IL-10 and IFN-γ were useful for differentiating patients with RMPP from those with GMPP. Logistic regression analysis showed that the IL-10 ≥ 3.65 pg/ml and IFN-γ ≥ 29.05 pg/ml were significant predictors regarding to RMPP. Additionally, a positive correlation between serum IL-10 and IFN-γ concentrations was observed. CONCLUSIONS: IL-10 and IFN-γ could be used as the good predictors of RMPP in school-aged children.

A target analogue imprinted polymer for the recognition of antiplatelet active ingredients in Radix Salviae Miltiorrhizae by LC/MS/MS.

The purpose of this study was to prepare a propyl gallate (PrG) molecular imprinted polymer as a cartridge stuffing material to isolate antiplatelet active ingredients. A macroporous polymer was synthesized utilizing ethylene glycol dimethacrylate (EDMA) as the crosslinking agent, PrG as the template molecule and 4-vinylpyridine (4-Vpy) as the functional monomer. Subsequently, PrG was removed by washing with methanol-glacial acetic acid (9:1, v/v). The molecular imprinted polymer recognized an active ingredient, protocatechuic acid, from a crude extract of the Chinese herbal medicine, Radix Salviae Miltiorrhizae (Danshen), using an on-line column switching solid phase extraction process. Pharmacological experiments showed that protocatechuic acid inhibits arachidonic acid (10 mg/kg) induced aggregation of rat platelets in vivo. This study provides an example of an application of separation-analysis technique for screening potentially bioactive compounds.