Reference values for exhaled nitric oxide in healthy children aged 6-18 years in China: a cross-sectional, multicenter clinical study.

BACKGROUND: The reference values of eNO have certain differences among people of different countries and races. We aimed to obtain the reference value of eNO in healthy children and adolescents (6-18 years old) in China and to explore the associations between the reference values with ages, gender, heights, BMI, and regions. METHODS: We measured FeNO50 levels in 5949 healthy Chinese children and adolescents, FeNO200 and CaNO levels in 658 participants from 16 provinces of 7 administrative areas in China aged 6-18. All persons were studied after obtaining informed consent from children and their parents. RESULTS: The mean FeNO50 of 5949 Chinese children and adolescents aged 6-18 years was 14.1 ppb, with a 95% confidence interval of 1-38.1 ppb. The mean FeNO200 of 658 persons was 6.9 ppb with a 95% upper confidence interval of 15.0 ppb, and the mean CaNO was 3.0 ppb with a 95% upper confidence interval of 11.2 ppb. In the 6-11 age group, age and height were correlated with the logarithm of FeNO50 (P < 0.001, P < 0.05). There was no significant correlation between the logarithm of FeNO200 and gender, age, height and BMI (all P > 0.05). The logarithm of CaNO was correlated with gender (P < 0.05). In the 12-18 age group, gender, height, and region were correlated with the logarithm of FeNO50 (all P < 0.001). There was only a weak correlation between the logarithm of FeNO200 and height (P < 0.001). The logarithm of CaNO was negatively correlated with age (P < 0.05). CONCLUSIONS: Higher FeNO50, FeNO200 and CaNO values were found in healthy children and adolescents in China compared with foreign reports, and is affected by age, height, gender, and region. This study provides useful references for clinical application of eNO in children, especially Asian children.

Changes in coagulation markers in children with Mycoplasma pneumoniae pneumonia and their predictive value for Mycoplasma severity.

BACKGROUND: This study investigates the correlation between coagulation levels and the severity of Mycoplasma pneumoniae pneumonia (MPP) in children. In addition, the study analyses the predictive value of coagulation abnormalities in MPP combined with necrotising pneumonia (NP). METHODS: A total of 170 children with MPP who underwent treatment between June 2021 and February 2022 were selected for this study. The study population was divided into groups according to the severity of the disease to compare differences in the incidence of coagulation abnormalities between the groups. The participants were also divided into groups according to imaging manifestations to compare the differences in coagulation function among the different groups. All data information was processed for statistical analysis using SPSS Statistics 25.0 and GraphPad Prism 7.0 statistical analysis software. RESULTS: The incidence of coagulation abnormalities in the children in the severe MPP (SMPP) group was significantly higher than that in the normal MPP (NMPP) group (P < 0.05). The multi-factor logistic regression analysis revealed that the D-dimer level is an independent risk factor for the development of NP in SMPP (P < 0.05). The receiver operating characteristic curve analysis revealed statistically significant differences (P < 0.05) in D-dimer, fibrinogen degeneration products (FDP), neutrophils, lactate dehydrogenase and serum ferritin for predicting SMPP combined with NP. Bronchoscopic manifestations of coagulation indicators (D-dimer and FDP levels) were significantly higher in the mucus plug group than in the non-mucus plug group, while the activated partial thromboplastin time levels were lower in the former than in the latter (P < 0.05). CONCLUSION: The degree of elevated D-dimer and FDP levels was positively correlated with the severity of MPP, with elevated serum D-dimer levels (> 3.705 mg/L) serving as an independent predictor of MPP combined with NP in children.

Construction of carboxymethyl chitosan-based nanoparticles of hypoxia response for co-loading doxorubicin and tanshinone IIA.

As a first-line drug for breast cancer chemotherapy, the effectiveness of doxorubicin (DOX) is challenged by high doses and high toxicity. Studies showed the combination of Tanshinone IIA (TSIIA) and DOX could enhance the efficacy of DOX for cancer and reduce the toxic effects to normal tissues. Unfortunately, free drugs are easily metabolized in the systemic circulation, which are less prone to aggregation at the tumor site to exert anticancer efficacy. In present study, we prepared a carboxymethyl chitosan-based hypoxia-responsive nanoparticles loaded with DOX and TSIIA for the treatment of breast cancer. The results demonstrated that these hypoxia-responsive nanoparticles not only improved the delivery efficiency of the drugs but also enhanced the therapeutic efficacy of DOX. The average size of nanoparticles was about 200-220 nm, the optimal drug loading and encapsulation efficiency of TSIIA in DOX/TSIIA NPs were 9.06 % and 73.59 %, respectively. Hypoxia-responsive behavior were recorded in vitro, while the synergistic efficacy is significantly exhibited in vivo and the tumor inhibitory rate was 85.87 %. Notably, TUNEL assay and immunofluorescence staining verified that the combined nanoparticles exerted a synergistic anti-tumor effect by inhibiting tumor fibrosis, decreasing the expression of HIF-1α and inducing tumor cell apoptosis. Collectively, this carboxymethyl chitosan-based hypoxia-responsive nanoparticles could have promising application prospect for effective breast cancer therapy.

Nasal nitric oxide in healthy Chinese children aged 6-18 years.

Objectives: To obtain the normal values of fractional concentration of nasal nitric oxide in Chinese children aged 6-18 years, so as to provide reference for clinical diagnosis. Methods: 2,580 out of 3,200 children (1,359 males and 1,221 females), whom were included from 12 centers around China were taken tests, their height and weight were also recorded. Data were used to analyze the normal range and influencing factors of fractional concentration of nasal nitric oxide values. Measurements: Data was measured using the Nano Coulomb Breath Analyzer (Sunvou-CA2122, Wuxi, China), according to the American Thoracic Society/European Respiratory Society (ATS/ERS) recommendations. Main Results: We calculated the normal range and prediction equation of fractional concentration of nasal nitric oxide values in Chinese children aged 6-18 years. The mean FnNO values of Chinese aged 6-18 yrs was 454.5 ± 176.2 ppb, and 95% of them were in the range of 134.5-844.0 ppb. The prediction rule of FnNO values for Chinese children aged 6-11 yrs was: FnNO = 298.881 + 17.974 × age. And for children aged 12-18 yrs was: FnNO = 579.222-30.332 × (male = 0, female = 1)-5.503 × age. Conclusions: Sex and age were two significant predictors of FnNO values for Chinese children(aged 12-18 yrs). Hopefully this study can provide some reference value for clinical diagnosis in children.

Angle ß combined with FeNO and FEV1/FVC% for the detection of asthma in school-aged children.

OBJECTIVE: The diagnostic value of angle ß in school-aged children with asthma is unknown. We speculate that angle ß may reflect diversification of the forced expiratory flow (FEF) to some extent. The objective of this study was to assess the diagnostic accuracy of angle ß, FeNO, pulmonary function parameters and their combinations for asthma in school-aged children. METHODS: In total, 248 children participated in this study (140 children with asthma and 108 healthy children). The diagnostic performance of angle ß, FeNO and pulmonary function parameters was determined using receiver operating characteristic (ROC) curves. In the ROC analysis, we used the hold out cross-validation method to avoid overfitting. This study was performed in China and followed the Guidelines for the diagnosis and optimal management of asthma in children (China). RESULTS: 1) In the asthma group, the mean angle ß value was significantly smaller than that in the control group (P < 0.001), but the mean FeNO value was significantly higher than that in the control group (P < 0.001). 2) More acute exacerbation or greater severity corresponded to a smaller angle ß. 3) Among the single indices, the area under the ROC curve of angle ß was the largest (except for FEV1/FVC%). For combined indicators, after cross-verification, the combination of angle ß, FEV1/FVC% and FeNO showed the highest diagnostic accuracy. CONCLUSION: Angle ß combined with FeNO and FEV1/FVC% can improve the diagnostic accuracy for asthma in school-aged children.

Association of specific biotypes in patients with Parkinson disease and disease progression.

OBJECTIVE: To identify biotypes in patients with newly diagnosed Parkinson disease (PD) and to test whether these biotypes could explain interindividual differences in longitudinal progression. METHODS: In this longitudinal analysis, we use a data-driven approach clustering PD patients from the Parkinson's Progression Markers Initiative (n = 314, age 61.0 ± 9.5, years 34.1% female, 5 years of follow-up). Voxel-level neuroanatomic features were estimated with deformation-based morphometry (DBM) of T1-weighted MRI. Voxels with deformation values that were significantly correlated (p < 0.01) with clinical scores (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Parts I-III and total score, tremor score, and postural instability and gait difficulty score) at baseline were selected. Then, these neuroanatomic features were subjected to hierarchical cluster analysis. Changes in the longitudinal progression and neuroanatomic pattern were compared between different biotypes. RESULTS: Two neuroanatomic biotypes were identified: biotype 1 (n = 114) with subcortical brain volumes smaller than heathy controls and biotype 2 (n = 200) with subcortical brain volumes larger than heathy controls. Biotype 1 had more severe motor impairment, autonomic dysfunction, and much worse REM sleep behavior disorder than biotype 2 at baseline. Although disease durations at the initial visit and follow-up were similar between biotypes, patients with PD with smaller subcortical brain volume had poorer prognosis, with more rapid decline in several clinical domains and in dopamine functional neuroimaging over an average of 5 years. CONCLUSION: Robust neuroanatomic biotypes exist in PD with distinct clinical and neuroanatomic patterns. These biotypes can be detected at diagnosis and predict the course of longitudinal progression, which should benefit trial design and evaluation.

Curvilinearity of a Maximum Expiratory Flow-Volume Curve: A Useful Indicator for Assessing Airway Obstruction in Children With Asthma.

BACKGROUND: Lung function parameters are used as signs in the diagnosis and evaluation of asthma; however, their sensitivity and specificity are not ideal. We calculated and combined angle ß with lung function parameters to identify the ideal indicator. OBJECTIVE: We aimed to identify an ideal indicator for evaluating the severity of airway obstruction in children with asthma. METHODS: In total, 151 school-age children diagnosed with asthma were selected as the asthma group, and 106 healthy children were selected as the control group. The subjects were divided into the exacerbation group, chronic persistent group, and clinical remission group. Furthermore, the subjects were classified into mild and moderate groups or severe and critical groups. Angle ß was calculated in each group. A receiver operating characteristic curve analysis was performed to determine the cutoff values of angle ß and lung function parameters that together provided high sensitivity and specificity for airway obstruction evaluation in children with asthma. RESULTS: The mean value of angle ß in the asthma group was significantly smaller than that in the control group (178.18° and 196.72°, respectively, P < .001). More exacerbations or greater severity corresponded to smaller angle ß values (P < .001). The best cutoff value of angle ß was 189.43°, and the area under the receiver operating characteristic curve of angle ß was 0.877, which is greater than the area under the receiver operating characteristic curve of FEV1, forced expiratory flow (FEF) at 75% vital capacity (FEF25%), and FEF at 50% vital capacity (FEF50%), but smaller than the area under the receiver operating characteristic curve of FEF75% and FEV1/FVC%. Interestingly, combining these measures can enhance the sensitivity and specificity in assessing airway obstruction. CONCLUSIONS: Angle ß was a useful indicator for assessing airway obstruction. Furthermore, angle ß combined with FEV1, FEV1/FVC%, FEF25%, FEF50%, and FEF75% can enhance the sensitivity and specificity of airway obstruction evaluations.