Objective:To analyze the efficacy and safety of Minocycline for treating macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) in children aged 6-14 years, and to investigate the influencing factors of severe Mycoplasma pneumoniae pneumonia (SMPP). Methods:Retrospective cohort study.The clinical data of 247 children with MUMPP hospitalized in the Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University from August to December 2023 were analyzed.According to the medication 3 to 7 days after conventional macrolide treatment, the children were divided into an Azithromycin group (107 cases) and a Minocycline group (140 cases). Clinical indicators such as the length of hospital stay and chest radiograph absorption time were compared between the two groups.Multivariate Logistic regression analysis was performed on children with SMPP to explore the correlation of the incidence of severe cases with the initiation time of Minocycline, serum vitamin D, lactate dehydrogenase (LDH), C-reactive protein (CRP) levels.Results:In the Minocycline group, the median hospital stay was shortened by 1.0 d (4.0 d vs.5.0 d, P=0.008), the median time for cough improvement after hospitalization was reduced by 3.0 d (2.0 d vs.5.0 d, P<0.001), and the duration of coughing, time to normal body temperature, and the 1-2-week improvement rate of chest imaging [91.4%(128/140) vs.49.5%(53/107), P<0.001] were all significantly better, compared with those in the Azithromycin group.In addition, the Glucocorticoid use rate [35.7%(50/140) vs.49.5%(53/107), P=0.029] in the Minocycline group was significantly lower than that in the Azithromycin group.The incidence of drug-related adverse reactions was only 0.71%(1/140) in the Minocycline group.A longer duration of macrolide treatment before Minocycline administration [odds ratio ( OR)=1.386, 95% confidence interval ( CI): 1.038-1.850, P=0.027], lower serum vitamin D levels ( OR=0.841, 95% CI: 0.748-0.945, P=0.004), elevated LDH levels ( OR=1.023, 95% CI: 1.009-1.037, P=0.001), and elevated CRP levels ( OR=1.074, 95% CI: 1.035-1.114, P<0.001) were associated with SMPP.The area under the receiver operating characteristic curve of the combined model for predicting SMPP was 0.912 7. Conclusions:Minocycline shows better efficacy than Azithromycin in treating MUMPP children aged 6-14 years, with comparable safety.LDH and CRP levels are independent risk factors for SMPP, while the serum vitamin D level is a protective factor.Early initiation of Minocycline treatment can optimize the clinical outcome.

Objective:To analyze the efficacy and safety of Minocycline for treating macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) in children aged 6-14 years, and to investigate the influencing factors of severe Mycoplasma pneumoniae pneumonia (SMPP). Methods:Retrospective cohort study.The clinical data of 247 children with MUMPP hospitalized in the Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University from August to December 2023 were analyzed.According to the medication 3 to 7 days after conventional macrolide treatment, the children were divided into an Azithromycin group (107 cases) and a Minocycline group (140 cases). Clinical indicators such as the length of hospital stay and chest radiograph absorption time were compared between the two groups.Multivariate Logistic regression analysis was performed on children with SMPP to explore the correlation of the incidence of severe cases with the initiation time of Minocycline, serum vitamin D, lactate dehydrogenase (LDH), C-reactive protein (CRP) levels.Results:In the Minocycline group, the median hospital stay was shortened by 1.0 d (4.0 d vs.5.0 d, P=0.008), the median time for cough improvement after hospitalization was reduced by 3.0 d (2.0 d vs.5.0 d, P<0.001), and the duration of coughing, time to normal body temperature, and the 1-2-week improvement rate of chest imaging [91.4%(128/140) vs.49.5%(53/107), P<0.001] were all significantly better, compared with those in the Azithromycin group.In addition, the Glucocorticoid use rate [35.7%(50/140) vs.49.5%(53/107), P=0.029] in the Minocycline group was significantly lower than that in the Azithromycin group.The incidence of drug-related adverse reactions was only 0.71%(1/140) in the Minocycline group.A longer duration of macrolide treatment before Minocycline administration [odds ratio ( OR)=1.386, 95% confidence interval ( CI): 1.038-1.850, P=0.027], lower serum vitamin D levels ( OR=0.841, 95% CI: 0.748-0.945, P=0.004), elevated LDH levels ( OR=1.023, 95% CI: 1.009-1.037, P=0.001), and elevated CRP levels ( OR=1.074, 95% CI: 1.035-1.114, P<0.001) were associated with SMPP.The area under the receiver operating characteristic curve of the combined model for predicting SMPP was 0.912 7. Conclusions:Minocycline shows better efficacy than Azithromycin in treating MUMPP children aged 6-14 years, with comparable safety.LDH and CRP levels are independent risk factors for SMPP, while the serum vitamin D level is a protective factor.Early initiation of Minocycline treatment can optimize the clinical outcome.

In recent years, the discovery of Group 2 innate lymphoid cells(ILC2) has expanded the understanding of type 2 immunity and promoted the birth of the concept of type 2 inflammation.Type 2 inflammation is an inflammatory reaction mediated by both innate and adaptive immunity.It is mainly involved by ILC2 cells and T helper 2 cells and is characterized by upregulation of type 2 cytokines and IgE-mediated release of inflammatory mediators and barrier dysfunction.Due to the common intrinsic mechanism, several kinds of type 2 inflammatory diseases always coexist in the same person, and their prevalence rate and severity continue to rise among children and adolescents, placing a heavy burden on them and their families.This review summarizes the recent development in understanding the mechanism of type 2 immune response and the pathophysiological mechanism of type 2 inflammatory diseases, emphasize the importance of ILC2 and summarize some targeted biologics used in the treatment of related diseases, so as to have a more systematic, comprehensive and in-depth understanding of type 2 inflammation.

Objective : To investigate the protective effect of caffeine on oxidative stress injury induced by hyperoxia in neonatal SD rats with bronchopulmonary dysplasia ( BPD) and its related mechanism． Methods : Neonatal SD rats were randomly divided into air control group ( N group) ，caffeine air control group ( NC group) ，model group (H group) and caffeine intervention group ( HC group) ．The high oxygen induction method was used to establish the BPD model．Blood and lung tissue of six samples were collected from each group on day 3，7，14 and 21．Each group was divided into four subgroups according to four days of age．The 21-day panel of four groups measured their body weights．The upper lobe of the right lung was used to measure wet-dry weight ratio (W / D) of lung tissue in each group ; the lower lobe of the right lung was sliced after paraffin embedding and stained with hematoxylin-eosin ( HE) to observe morphological changes and calculate radial alveolar count (RAC) values ; the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood and lung tissues were determined to evaluate the imbalance of oxidative and antioxidant homeostasis in neonatal rats ; real-time fluorescence quantitative reverse transcrip- tion polymerase chain reaction ( RT-qPCR) was used to detect the relative expression level of nuclear factor-ery- throid 2-related factor 2 (Nrf2) mRNA in lung tissues. Results : ① H group showed a gradual decline in activity after 3 days and an increasing trend in body weight after 14 days. ② W / D value of H group reached its peak at day 14，and the trend of HC group was similar to that of H group. ③ The lung tissue structure of H group was irregular， RAC value of which decreased significantly after 7 days of peak，and the difference between H group and HC group was statistically significant (P＜0. 01) . ④ The MDA value of H group increased on day 7 and gradually decreased on day 14，while the SOD activity decreased obviously on day 7，and there were significant differences in MDA and SOD activity between H group and HC group at 14 days and 21 days (P＜0. 05) . ⑤ The expression of Nrf2 mRNA in H group was significantly enhanced at day 7 and stabilized at day 14，and there were statistically significant differences between H and HC groups at day 3，day 7 and day 14 (P ＜0. 05) . ⑥ The relative expression level of Nrf2 mRNA was positively correlated with MDA and negatively correlated with SOD． Conclusion Caffeine can regulate oxidative stress response through Nrf2 pathway and alleviate lung oxidative stress injury induced by hyperoxia in neonatal rats with BPD.

Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.

Hypoxemia is a common complication of pneumonia, asthma, and bronchopulmonary dysplasia in children.Rapid identification of hypoxemia is of great significance for the disposal and management of critical children.Pulse oximetry is recognized by the World Health Organization as the best way to monitor hypoxemia in children, and it can monitor pulse oxygen saturation noninvasively and continuously.Based on the related literature at home and abroad, combined with the clinical needs of pediatrics, the " Expert consensus on clinical application of pulse oximetry in children" is formulated to improve the understanding of pediatricians and nurses on the application in pediatric clinical practice, principle, operation techniques, and limitations of pulse oximetry.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

Objective: Construct a paraquat (PQ) cell fibrosis model in vitro, observe the effect of PQ on the expression of a disintegrin and metalloproteinase-17 (ADAM17) in A549 cells, and explore the role of ADAM17 in the pulmonary fibrosis induced by PQ poisoning. Methods: A549 cells are divided into normal control group, different concentration of PQ groups, CCK-8 is used to detect cell viability, screening concentration and time of PQ, cell morphology is observed under microscope; Enzyme-linked immunosorbent assay (ELISA) detectes fibrosis markers of collagen type I (Col I) and fibronectin (FN) expression. Establishment of cell model of fibrosis; distribution by immunocytochemical detection of ADAM17 in A549 cells, Reverse transcription-polymerase chain reaction and Western blot are used to detect the expression of ADAM17 mRNA and protein. Results: 1. With the increase of PQ concentration and the prolongation of the action time, the activity of A549 cells decreased (P< 0.05) , which is dose-dependent and time dependent. 2.The normal A549 cells fusion is paving stone growth and arranged more closely. After PQ induction, the cell arrangement was loose, the intercellular connection became loose, and some cells dissolved and died. 3.ELISA showed that with the increase of PQ concentration, the expression of Col I and FN increased (P<0.05) , and Col I and FN expression gradually increased with the prolongation of PQ time (P<0.05) , and the fibroblast model is successfully established. 4. Immunocytochemistry showes that ADAM17 is expressed in the cytoplasm of A549 cells. 5. RT-PCR and Western blot showed that the expression of ADAM17 mRNA and protein increased significantly with the increase of PQ concentration (P<0.05) , which is most obvious at PQ 200 μmol/L. With the prolonged action of PQ, the expression level of ADAM17 mRNA and protein also increased significantly (P<0.05) , and reached the peak in 24 h. Conclusion PQ can induce morphological changes of alveolar epithelial cells, cause cell damage, and successfully establish a cell fibrosis model, which has a dose and time dependence on the toxicity of A549 cells. ADAM17 is overexpressed in the A549 cells induced by PQ and may be involved in the process of pulmonary fibrosis induced by paraquat.

Apoptosis of dopaminergic neurons in the nigrostriatal projection plays a crucial role in the pathogenesis of Parkinson's disease (PD). Although the detailed mechanisms responsible for dopaminergic neuron loss are still under investigation, oxidative stress is identified as a major contributor for neuronal apoptosis. In the current study, we studied the effects of MPP(+), a substrate that mimics oxidative stress, on neuron-like PC12 cells and the underlying mechanisms. PC12 cells were cultured and treated by 100 μmol/L MPP(+) for 4, 8, 16, 24 and 48 h, respectively. For drug pretreatment, the PC12 cells were incubated with N-acetyl-l-cysteine (NAC, 5 mmol/L), an antioxidant, SP600125 (20 μmol/L) or PD98059 (100 μmol/L), two pharmacological inhibitors of JNK and ERK1/2, for 1 h before addition of MPP(+). Cell apoptosis was measured by flow cytometry. The mRNA expression of Cu(2+)/Zn(2+)-SOD, GSH-Px, Bcl-2 and Bax was detected by RT-PCR. The protein expression of p-ERK1/2 and p-JNK was determined by Western blotting. Our results showed that MPP(+) exposure could induce substantial PC12 cell apoptosis. The pretreatment of SP600125 or PD98059 could effectively reduce the apoptosis rate by reducing the ratio of Bax/Bcl-2 mRNA levels. MPP(+) exposure also induced high level of reactive oxygen species (ROS), marked by dramatic increase of Cu(2+)/Zn(2+)-SOD and GSH-Px mRNA levels. The elevated ROS was strongly associated with the activation of JNK and ERK1/2 signal pathways after MPP(+) exposure, since the pretreatment of NAC significantly reduced the upregulation of p-JNK and p-ERK1/2. Finally, the pretreatment of SP600125, but not PD98059, alleviated the increase of Cu(2+)/Zn(2+)-SOD and GSH-Px mRNAs induced by MPP(+), suggesting that the activation of the JNK signal pathway, but not the ERK1/2 signal pathway, could, in some degree, antagonize the generation of ROS induced by oxidative stress. In conclusion, our results suggest that JNK and ERK1/2 signal pathways, which are activated via ROS, play a crucial role in neuronal apoptosis induced by oxidative stress.
Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; PC12 Cells ; Piperidines ; pharmacology ; Pyrazoles ; pharmacology ; Rats ; Reactive Oxygen Species ; metabolism

Objective To explore the effects of 14-3-3 γ gene on dopaminergic neurons of PD rat model.Methods 6 hydroxydopamine (6-OHDA) was injected into the corpus striatum of 60 SD rats to establish PD model.A week later,Ad/14-3-3 γ was injected into the corpus striatum of 16 rats,while PBS and Ad-LacZ were injected into the corpus striatum of 16 and 28 rats,respectively,as control.X-gal dyeing was utilized to examine the LacZ reporter gene expression in the corpus striatum at 3 day,2 week and 6 week.Real-time PCR was utilized to test the expression level of 14-3-3 γmRNA at 2 weeks after Ad/14-3-3 γ injection.Immunohistochemistry technique was used to detect TH positive neurons and fibers in the corpus striatum and substantial nigra.Western blotting was performed to check the expression of 14-3-3 γ in the corpus striatum at 2 weeks and caspase-3 at 6 veeks after Ad/14-3-3 γ injection.High performance liquid chromatography (HPLC) method was used to examine the contents of DA and DOPAC in the corpus striatum.The rats underwent rotational ethological examination at 1,2 and 6 weeks after the second injection.Results The expression of β-gal,which showed the successful LacZ gene transfection,was found in the corpus striatum of LacZ groups.The 14-3-3 γ mRNA and protein expression in the corpus striatum were significantly higher in the Ad/14-3-3 γ group than in the other two groups.The TH-positive cell ratio of substania nigra to contralateral area in the lesion side was 0.44±0.17 and the optical density (OD) of TH-positive fibers was 0.62±0.14 in the Ad/14-3-3 γ group,both higher than those in PBS group (0.16±0.13 and 0.36±0.15) and LacZ group (0.15±0.09 and 0.30±0.11) (all P＜0.01).The contents of DA and DOPAC in the lesion sides of corpus striatum were increased in the Ad/14-3-3 γ group [(248± 116)ng/g and (752±177) ng/g] than in PBS group [(106±35) ng/g and (724±159) ng/g] and LacZ group [(136±49) ng/g and (765±163) ng/g] (P＜0.01).The DA and DOPAC ratios of the lesion side of corpus striatum to the contralateral side were 0.37±0.14 and 0.38±0.17 in the Ad/14-3-3 γgroup,higher than those in PBS group (0.15±0.08 and 0.13±0.10,respectively) and LacZ group (0.19±0.11 and 0.16±0.09 (all P＜0.01).The expression level of caspase-3 was decreased in Ad/14-3-3 γ group than in PBS and LacZ groups at 6 weeks after the second injection.The turns/min induced by apomorphine in Ad/14-3-3 γ group were 9.4 ± 2.5 at 1 week after the Ad/14-3-3 γinjection,and reduced to 4.6±2.2 at 6 weeks later.While in PBS and LacZ group,the turns were 14.5±4.9 and 13.8±3.5 at 1 week after the second injection,6 weeks later rised to 18.7±5.2 and 20.6± 6.7 respectively,significantly higher than those in Ad/14-3-3 γ group (all P＜0.01).Conclusions 14-3-3γ gene transfer has a protective effect on the dopaminergic neurons and it may be a promising candidate gene for curing PD.