Risk factors and prediction models for bronchiolitis obliterans after severe adenoviral pneumonia.

Severe adenoviral pneumonia (SAP) can cause post-infectious bronchiolitis obliterans (PIBO) in children. We aimed to investigate the relevant risk factors for PIBO and develop a predictive nomogram for PIBO in children with SAP. This prospective study analysed the clinical data of hospitalised children with SAP and categorised them into the PIBO and non-PIBO groups. Least absolute shrinkage and selection operator (LASSO) regressions were applied to variables that exhibited significant intergroup differences. Logistic regression was adopted to analyse the risk factors for PIBO. Additionally, a nomogram was constructed, and its effectiveness was assessed using calibration curves, C-index, and decision curve analysis. A total of 148 hospitalised children with SAP were collected in this study. Among them, 112 achieved favourable recovery, whereas 36 developed PIBO. Multivariable regression after variable selection via LASSO revealed that aged < 1 year (OR, 2.38, 95% CI, 0.82-6.77), admission to PICU (OR, 24.40, 95% CI, 7.16-105.00), long duration of fever (OR, 1.16, 95% CI, 1.04-1.31), and bilateral lung infection (OR, 8.78, 95% CI, 1.32-195.00) were major risk factors for PIBO. The nomogram model included the four risk factors: The C-index of the model was 0.85 (95% CI, 0.71-0.99), and the area under the curve was 0.85 (95% CI, 0.78-0.92). The model showed good calibration with the Hosmer-Lemeshow test (χ2 = 8.52, P = 0.38) and was useful in clinical settings with decision curve analysis. CONCLUSION: Age < 1 year, PICU admission, long fever duration, and bilateral lung infection are independent risk factors for PIBO in children with SAP. The nomogram model may aid clinicians in the early diagnosis and intervention of PIBO. WHAT IS KNOWN: • Adenoviruses are the most common pathogens associated with PIBO. • Wheezing, tachypnoea, hypoxemia, and mechanical ventilation are the risk factors for PIBO. WHAT IS NEW: • Age < 1 year, admission to PICU, long duration of fever days, and bilateral lung infection are independent risk factors for PIBO in children with SAP. • A prediction model presented as a nomogram may help clinicians in the early diagnosis and intervention of PIBO.

An Evaluation of the Coupling Coordination of Technological Innovation System in China's Marine Biopharmaceutical Industry.

The marine biopharmaceutical industry (MBI) has been considered as an important part of the blue economy. The high-quality development of this industry depends on the high-level coordinated development of technological innovation system (TIS). In the present study, the coupling mechanism of industrial innovation input subsystem and innovation output subsystem was analyzed for the first time. On this basis, the development level and coupling coordination level of TIS in China's MBI during 2008-2018 were empirically evaluated with the capacity coupling coordination model. Then, the obstacle factors were diagnosed and recognized with the obstacle model. The results showed that the innovation input index fluctuated at a low level in China's MBI. The innovation output index has basically maintained a growth trend, whereas the quality of development was not high. Although the coupling coordination level of TIS showed a positive change as mild disordered → primary coordinated → well-coordinated, the development type of innovation system has changed from the lagging output of innovation into the lagging input of innovation. Insufficient input of innovation factors remained the main obstacle to the improvement of coordination level. Based on the above analysis, suggestions were put forward from the perspectives of policy and fund guarantees to improve the coupling coordination level in China's MBI.

Effectiveness of Bacillus Calmette-Guérin vaccination against severe childhood tuberculosis in China: a case-based, multicenter retrospective study.

BACKGROUND: Evidence varies regarding the efficacy of Bacillus Calmette-Guérin (BCG) vaccine. Data on protection by BCG vaccination against severe tuberculosis (TB) among children in China remain unclear. METHODS: We conducted a case-based, multicenter retrospective study at three children's hospitals in China. Sociological factors affecting BCG vaccination and risk factors associated with disease types were analyzed using a multivariable model. RESULTS: A total 1701 children with active TB were enrolled. Children who were younger, female, residing in a rural area, living in the western regions, and with no BCG vaccination history were at higher risk of developing severe TB. Children with a BCG scar had significantly lower risk for severe TB (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.51-0.67). Children with no BCG scar but who were vaccinated at birth still had lower risk of severe TB types, such as tuberculous meningitis (OR 0.88, 95% CI 0.80-0.97) and miliary TB (OR 0.77, 95% CI 0.69-0.87). CONCLUSIONS: Neonatal BCG vaccination could be an effective means to control TB. In the absence of a new, more effective TB vaccine, our results lend support to continued use of the BCG vaccine in China.

Pseudomembranous laryngotracheobronchitis due to coinfection with human bocavirus 1 and Mycoplasma pneumoniae: a case report.

Pseudomembranous laryngotracheobronchitis is rarely reported yet potentially life-threatening infectious cause of airway obstruction in children. The causative organisms of this condition are often considered to promote bacterial superinfection following viral infection. We report a case of pseudomembranous laryngotracheobronchitis in a patient caused by human bocavirus 1 and Mycoplasma pneumoniae (M. pneumoniae). A 2-year-old child was admitted to our hospital presenting with cough, hoarseness, and labored breathing. Computed tomography of the chest revealed atelectasis of the right middle lobe of the lung with bronchostenosis and occlusion. Laryngeal edema, pseudomembrane formation and ulceration of the trachea were found during bronchoscopy. Chronic inflammation of the mucosa and local cellulose exudation with acute and chronic inflammatory cell infiltration were confirmed by hematoxylin-eosin staining. Human bocavirus 1 and M. pneumoniae were detected in the bronchoalveolar lavage fluid by next-generation sequencing. The patient tested positive for IgM antibodies against M. pneumoniae. Bronchoscopy was performed three times to clear the secretions in the airway, and azithromycin, ceftriaxone, methylprednisolone, budesonide inhalation, and ambroxol were administered as treatment. The patient's condition improved and she was discharged 21 days after admission. Clinicians should be aware of the potential involvement of human bocavirus 1 and M. pneumoniae in pseudomembranous laryngotracheobronchitis for accurate diagnosis and timely antibiotic administration, and to lower mortality and morbidity rates.

Case Report: Hemoptysis Caused by Pulmonary Tuberculosis Complicated With Bronchial Artery-Pulmonary Artery Fistula in Children.

Bronchial artery-pulmonary artery fistula secondary to pulmonary tuberculosis is an important cause of hemoptysis in adults, but it's relatively rare in children. Bronchial artery-pulmonary artery fistulas are mostly congenital in children and may have no clinical manifestations in the early stage. Congenital bronchial artery-pulmonary fistula with pulmonary tuberculosis can lead to hemoptysis. From 2016 to 2020, two children with pulmonary tuberculosis complicated with bronchial artery and pulmonary artery fistula were admitted and treated in our hospital. We reminded pediatricians to pay attention to a variety of etiology combined with the possibility of children's hemoptysis.

Effect of Dimethoate on the Activity of Hepatic CYP450 Based on Pharmacokinetics of Probe Drugs.

BACKGROUND: Dimethoate (DM), one of the most widely used systemic organophosphate insecticide, has been reported to exert toxic effects after long-time subchronic exposure. This study aims at investigating the toxic effect of DM on liver after repeated administration of low doses of DM in rats. METHODS: Twenty Sprague-Dawley rats were randomly divided into the control group (n = 10) and the DM group (n = 10). After 2 weeks' exposure to DM at low dosage (5 mg/kg), biochemical parameters of hepatic functions were measured, histology and CYP450 expressed in liver was detected. The activities of CYP1A2, CYP2C11, CYP2D1, and CYP3A2 were evaluated by the Cocktail method. RESULTS: The level of AChE (acetylcholinesterase) was significantly decreased, hepatic functions were damaged and the mRNA level of CYP2D1 was significantly increased in the DM group (p < 0.05). The pharmacokinetics of probe drug revealed AUC(0-t), AUC(0-∞), t1/2 and Cmax of metoprolol was shorten in the DM group (p < 0.05). However, there were no statistical differences in MRT, t1/2, CL and Tmax for phenacetin, tolbutamide and midazolam. CONCLUSIONS: A low dosage of DM could induce the activity of CYP2D1 in liver and increase the metabolism of metoprolol when exposed for 2 weeks.

Congenital tuberculosis detected by T-SPOT.TB assay in a male infant after in vitro fertilization and followed up with radiography.

Congenital tuberculosis (TB) is a rare disease with a high mortality rate, and is difficult to diagnose. Here we present a case of congenital TB detected by the T-SPOT.TB assay in a male infant after in vitro fertilization. He ultimately survived after anti-TB therapy despite a delayed diagnosis, and underwent radiological follow-up. The delay in diagnosis of congenital TB resulted in a severe lung lesion, as evidenced by prolonged oxygen dependence, predisposing to recurrent pneumonia. Radiological follow-up revealed uniform rim calcification of multiple enlarged lymph nodes in the mediastinum, and long-term consolidation in the bilateral lung, with slow radiographic regression of the lung lesion. To the best of our knowledge, this is the first report on using the T-SPOT.TB assay in the detection of congenital TB, and no case of congenital TB with such clinical features and image findings has been described in previous reports.

Selective etching of n-type silicon in pn junction structure in hydrofluoric acid and its application in silicon nanowire fabrication.

Boron is selectively implanted on the surface of an n-type silicon wafer to form a p-type area surrounded by an n-type area. The wafer is then put into a buffered oxide etch solution. It is found that the n-type area can be selectively etched without illumination, with an etching rate lower than 1 nm min(-1), while the p-type area can be selectively etched under illumination with a much higher etching rate. The possible mechanism of the etching phenomenon is discussed. A simple fabrication process of silicon nanowires is proposed according to the above phenomenon. In this process only traditional micro-electromechanical system technology is used. Dimensions of the fabricated nanowire can be controlled well. A 50 nm wide and 50 nm thick silicon nanowire has been formed using this method.

[The role of external signal regulated kinase and transforming growth factor beta(1) in asthma airway remodeling and regulation of glucocorticoids].

OBJECTIVE: To study role of external signal regulated kinase (ERK) and transforming growth factor beta(1) (TGF-beta1) in asthma airway remodeling and to explore the regulation of glucocorticoids on ERK, TGF-beta1, and airway remodeling. METHODS: Thirty SD rats were randomly divided into 3 equal groups: control group; asthma group, undergoing intra-peritoneal injection of ovalbumin (OVA) on days 1 and 8 and inhalation of OVA every other day for 8 weeks since day 15 to establish chronic asthma models; dexamethasone (DM) intervention group, undergoing intra-peritoneal injection of DM 30 min before every inhalation instigation; and control group, receiving normal saline instead of DM. 1 - 2 hours after the last instigation the left lungs were taken out. The total bronchial wall thickness (Wat) and smooth muscle thickness (Wam) were measured by image analysis system. Phosphorylated ERK (P-ERK) was detected by immunohistochemistry. 1 - 2 hours after the last instigation blood samples were collected from the femoral artery. The concentration of transforming growth factor (TGF)-beta1 in the serum was measured by sandwich ELISA. Rat airway epithelial cells were cultured, stimulated with platelet-derived growth factor-BB (PDGF-BB, 1, 10, 25, or 50 microg/L), U0126 (specific inhibitor of phosphorylation of ERK), or budesonide (BUD). Western blotting was used to detect the P-ERK level. The level of TGF-beta1 in the cell culture supernatant was detected by sandwich ELISA. RESULTS: The Wat and Wam of the asthma group was significantly higher than those of the control group (both P < 0.01), and the Wat and Wam of the DM group were both significantly lower than those of the asthma group (both P < 0.01). The mean optical density of P-ERK and concentration of TGF-beta1 in the serum of the asthma group were 31.1 +/- 2.2 and 28.1 +/- 7.4 microg/L respectively, both significantly higher than those of the control group (12.8 +/- 2.4 and 13.6 +/- 2.7 microg/L respectively, both P < 0.01), and the mean optical density of P-ERK and concentration of TGF-beta1 in the serum of the DM group were 18.7 +/- 3.1 and 15.0 +/- 3.2 microg/L respectively, both significantly lower than those asthma group (both P < 0.01). In the PDGF-BB (25 microg/L) stimulated cells marked phosphorylation of ERK occurred 15 min later, the level of P-ERK remained high up to 8 hour later, and the maximal activation occurred at the period of 2 h - 4 h later, 6.5 +/- 0.4 times that of the control value (P < 0.01). The phosphorylation levels of ERK depended on the concentration of PDGF-BB and the maximal level phosphorylation was detected with the concentration of PDGF-BB of 50 microg/L, which was 4.1 +/- 0.3 times that of the control value (P < 0.01). U0126 and BUD inhibited the phosphorylation of ERK in the cells stimulated by PDGF-BB of the concentration of 25 microg/L. there was no difference in the level of TGF-beta1 in the cell culture supernatant among different groups. CONCLUSION: Phosphorylation of ERK and TGF-beta1 have an important role in asthma airway remodeling; PDGF-BB does not induce normal rat airway epithelial cells to product or release TGF-beta1 by phosphorylation of ERK. Glucocorticoids can inhibit phosphorylation of ERK.

[Role of external signal regulated kinase signal transduction pathway in airway remodeling of rats with asthma and regulation by glucocorticoids].

OBJECTIVE: Airway remodeling in asthma makes treatment of asthma very difficult, and study of its pathogenesis becomes very important. The present study aimed to explore the role of external signal regulated kinase (ERK) signal transduction pathway in airway remodeling in rats asthma model and regulatory effects of glucocorticoids on ERK signal transduction pathway and airway remodeling. METHODS: Totally 80 male Sprague-Dawlay rats (6-8 weeks old, weighing about 120 g) were randomly divided into control groups (30 rats), asthma groups (30 rats) and treated groups [including a group intervened with dexamethasone (DM group) and budesonide (BUD group), each had 10 rats]. The rats were sensitized for inducing asthma by intraperitoneal injection of ovalbumin and Al (OH)(3) and were repeatedly exposed to aerosolized ovalbumin for 4, 8, or 12 weeks [respectively called 4, 8 or 12 wk asthma group (A4, A8 or A12 group), each had 10 rats]; and correspondingly control rats were intraperitoneally injected with 0.9% NaCl, then were repeatedly exposed to 0.9% NaCl for 4, 8, or 12 weeks [respectively called 4, 8 or 12 wk control group (C4, C8 or C12 group), each had 10 rats]; DM group rats were repeatedly exposed to aerosolized ovalbumin for 8 wk, and BUD group rats for 12 wk. Total bronchial wall thickness (Wat) and smooth muscle thickness (Wam) were measured by an image analysis system. Concentrations of PDGF-AB in serum were measured by sandwich ELISA. Phospho-ERK (P-ERK) and c-Fos were detected by immunohistochemical technique; lung tissue extracts were analyzed for phosphorylation of ERK by Western blotting. RESULTS: Wat and Wam in all asthma groups were significantly higher than those in corresponding control groups (P < 0.01, respectively), those of the treated groups were significantly lower than asthma groups (P < 0.01). The concentrations of PDGF-AB in serum of asthma groups [(228 +/- 18) pg/ml, (293 +/- 77) pg/ml, (225 +/- 66) pg/ml for A4, A8, A12 groups, respectively] were all significantly higher than those of the control groups [(160 +/- 14) pg/ml, (165 +/- 29) pg/ml and (164 +/- 27) pg/ml for C4, C8, C12 group, respectively] (P < 0.01 or P < 0.05); the value of DM group [(157 +/- 46) pg/ml] was significantly lower than that of the group A8 (P < 0.01), no significant difference was found when the values of BUD group [(208 +/- 40) pg/ml] was compared with that of A12 group (P > 0.05). Mean absorbance values (by immunohistochemistry) of P-ERK and c-Fos in asthma groups were significantly higher than those in corresponding control groups (P < 0.01, respectively), DM group had a significantly lower value than group A8 (P < 0.01), BUD group had a significantly lower value than group A12 (P < 0.01); absorbance (by Western blot) of P-ERK in A4, A8, A12 group was significantly higher than that in C4 and C8 group, the value of DM group was significantly lower than that of group A8 (P < 0.01), and that of BUD group (1.8 +/- 0.2) was significantly lower than that of group A12 (P < 0.01). CONCLUSION: Asthmatic rats have higher concentrations of PDGF-AB in serum and phosphorylation of ERK and c-Fos; glucocorticoids inhibit phosphorylation of ERK and c-Fos in asthmatic rats, and to some extent also inhibit Wat and Wam.

[Regulative mechanism of dexamethasone on Toll-like receptor 4 signal transduction of infant asthma rat].

OBJECTIVE: Eosinophilic airway inflammation is one of the basic characteristics of allergic asthma. Toll-like receptor is one of the most important innate immunity pattern recognition receptors. Glucocorticoids (GCS) are still the most effective treatment for asthma. However, few reports of studies on regulatory mechanism of GCS on the innate immunity system are available. The mechanism of effects of GCS on TLR4 is unclear. The present study aimed at understanding the effect of dexamethasone (DXM) on change of TLR4 and mechanism of regulatory effect of TLR4 on eosinophil (EOS) apoptosis. METHODS: Twenty-seven Sprague-Dawley (SD) rats (age 28 to 42 days, body weight 120 to 180 gram) were randomly divided into the control group, asthma group and DXM group with 9 in each. Asthma model rats were sensitized with the mixture of ovalbumin (OVA, 1 mg) and Al (OH)(3), 100 mg on day 1 and day 8, repeatedly exposed to aerosolized OVA after day 15, once a day for three days and continued for 30 minutes at every time. During the sensitization stage, 100 microg/ml DXM were prepared with DXM group for every other day, and the same doses DXM were prepared for every day on the stage of challenge. The histopathological changes of lung tissues were observed with light microscope (LM). EOS and other inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted; the concentrations of OVA-sIgE in serum were measured by using "sandwich" ELISA; The expressions of TLR4 mRNA were determined by in situ hybridization, the apoptosis of EOS was detected by TUNEL. RESULTS: (1) LM showed many inflammatory cells infiltration around the bronchi and blood vessels, bronchus mucus increased, airway epithelium damage and desquamation, and airway mucous plugs in asthma group, whereas DXM group showed significantly milder changes. (2) Inflammationary cells count in BALF of asthma group was significantly higher as compared to control group (P < 0.01); compared with asthma group, the total cell count, EOS absolute count and EOS% were all significantly decreased in DXM group [(2.14 +/- 0.10) x 10(9)/L, (4.78 +/- 1.23) x 10(7)/L, (2.17 +/- 0.25)%]. (3) Levels of OVA-sIgE in serum of asthma group [(83.40 +/- 6.80) microg/ml] were significantly higher than those of the control group [(14.38 +/- 4.25) microg/ml] (P < 0.01), while those of DXM group [(45.02 +/- 7.47) microg/ml] were significantly lower than asthma group (P < 0.0 1). (4) There were no significant differences in TLR4 mRNA detected by in situ hybridization between control group (24.71 +/- 0.85) and asthma group (25.81 +/- 3.56) (P > 0.05); but it significantly increased in DXM group (29.86 +/- 3.92) as compared to asthma group. (5) The percentages of apoptotic EOS in asthma group [(7.39 +/- 1.93)%] were significantly lower than those in control group [(9.06 +/- 1.52)%] (P < 0.01); and significantly higher in DXM group [(13.33 +/- 1.09)%] than in asthma group (P < 0.01). There were significantly positive correlations between TLR4 mRNA and the percentage of apoptotic EOS (r = 0.612, P < 0.01). CONCLUSION: DXM can decrease OVA-sIgE level, induce EOS apoptosis, which may correlate with the activation of TLR4 signal transduction.