Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To investigate the impact of abnormal patterns of 75 g oral glucose tolerance test (OGTT) in the second trimester on the risk of large for gestational age (LGA) newborn deliveries.Methods:General clinical data and OGTT results of 66 290 pregnant women who received regular prenatal care and delivered in Guangdong Maternal and Child Health Hospital from December 24, 2016 to July 26, 2022 were collected. According to the results of OGTT, the pregnant women were divided into 8 groups: normal blood glucose group (normal fasting blood glucose, 1-hour and 2-hour after oral glucose, 54 518 cases), gestational diabetes mellitus (GDM) 0 group (only abnormal fasting blood glucose, 1 430 cases), GDM 1 group (only abnormal blood glucose at 1-hour after oral glucose, 2 150 cases), GDM 2 group (only abnormal blood glucose at 2-hour after oral glucose, 3 736 cases), GDM 0+1 group (both fasting blood glucose and 1-hour after oral glucose were abnormal, 371 cases), GDM 0+2 group (both fasting blood glucose and 2-hour after oral glucose were abnormal, 280 cases), GDM 1+2 group (abnormal blood glucose at 1-hour and 2-hour after oral glucose, 2 981 cases) and GDM 0+1+2 group (abnormal fasting blood glucose, 1-hour and 2-hour after oral glucose, 824 cases). Multivariate logistic regression was used to analyze the effects of different abnormal OGTT patterns on LGA. In addition, the blood glucose measurements at the three time points of OGTT were combined and used as continuous variables in the receiver operating characteristic (ROC) curve to evaluate the predictive value of each blood glucose measurement mode for LGA and the area under the curve (AUC) was compared.Results:(1) Multivariate logistic regression analysis showed that the risks of LGA were significantly increased in GDM 0 group ( OR=1.76, 95% CI: 1.50-2.08; P<0.001), GDM 0+1 group ( OR=2.29, 95% CI: 1.72-3.04; P<0.001), and GDM 0+1+2 group ( OR=1.98, 95% CI: 1.61-2.43; P<0.001). (2) ROC curve analysis showed that fasting blood glucose, 1-hour after oral glucose, 2-hour after oral glucose, fasting+1-hour after oral glucose, fasting+2-hour after oral glucose, 1-hour+2-hour after oral glucose, and fasting+1-hour+2-hour after oral glucose had certain predictive value for LGA (all P<0.001). The AUC of fasting blood glucose measurement was higher than that of 2-hour blood glucose measurement in predicting LGA, and the difference was statistically significant ( P<0.05). There was no significant difference in the AUC between fasting blood glucose and other blood glucose measurement modes for predicting LGA (all P>0.05). Conclusions:In the abnormal OGTT patterns, pregnant women with abnormal fasting blood glucose, abnormal fasting+1-hour after oral glucose, and abnormal fasting+1-hour+2-hour after oral glucose have an increased risk of LGA. Fasting blood glucose measurement is of great significance for the prediction of LGA, and could be used as an optimal indicator to evaluate the risk of LGA in clinical practice.

Objective:To explore the diagnostic value of different machine learning models and optimal machine learning model combined with clinical data for diagnosing Hashimoto′s thyroiditis (HT).Methods:The thyroid gland images of 643 patients with 643 thyroid nodules who underwent preoperative ultrasound examination and had pathological results in the Second Affiliated Hospital of Xi′an Jiaotong University from December 2018 to March 2024 were retrospectively collected, and the images were divided into training set and test set according to a ratio of 7 to 3. Twenty ultrasound imaging omics models were constructed using pairwise combination of 5 feature screening components and 4 classifiers. The area under the curve (AUC) of each model in the test set was compared. Meanwhile, 3 basic network models were respectively used to construct deep learning models for diagnosing HT, and the diagnostic efficacies of the deep learning models and the ultrasound imaging omics models for HT were compared. The model with the greatest efficacy was selected as the optimal machine learning model. Further, the optimal machine learning model was combined with clinical data to construct a combined model. The ROC curves were plotted to compare the diagnostic efficacy of the optimal machine learning model and the combined model for HT.Results:In the comparison of the efficacies of ultrasound imaging omics models and deep learning models in diagnosing HT, the efficacy of stable feature screening-logistic regression (LR) model was the greatest, and the accuracy, sensitivity and specificity of using the LR model in diagnosing HT in the test set were 78%, 75%, 74%, respectively, with an AUC of 0.82(95% CI=0.76-0.88). After combining the LR model with clinical data, the accuracy, sensitivity, and specificity of the combined model in the test set were 87%, 74%, and 95%, respectively, with an AUC of 0.91(95% CI=0.87-0.95), which was strongly consistent with pathology (Kappa value=0.708, P<0.001). Conclusions:The optimal machine learning model (LR model) constructed in this study demonstrates a strong ability to diagnose HT and can accurately detect patients with atypical ultrasound manifestations of HT. The combination with clinical data can improve its diagnostic efficacy with higher accuracy and specificity.

Objective:To explore the diagnostic value of different machine learning models and optimal machine learning model combined with clinical data for diagnosing Hashimoto′s thyroiditis (HT).Methods:The thyroid gland images of 643 patients with 643 thyroid nodules who underwent preoperative ultrasound examination and had pathological results in the Second Affiliated Hospital of Xi′an Jiaotong University from December 2018 to March 2024 were retrospectively collected, and the images were divided into training set and test set according to a ratio of 7 to 3. Twenty ultrasound imaging omics models were constructed using pairwise combination of 5 feature screening components and 4 classifiers. The area under the curve (AUC) of each model in the test set was compared. Meanwhile, 3 basic network models were respectively used to construct deep learning models for diagnosing HT, and the diagnostic efficacies of the deep learning models and the ultrasound imaging omics models for HT were compared. The model with the greatest efficacy was selected as the optimal machine learning model. Further, the optimal machine learning model was combined with clinical data to construct a combined model. The ROC curves were plotted to compare the diagnostic efficacy of the optimal machine learning model and the combined model for HT.Results:In the comparison of the efficacies of ultrasound imaging omics models and deep learning models in diagnosing HT, the efficacy of stable feature screening-logistic regression (LR) model was the greatest, and the accuracy, sensitivity and specificity of using the LR model in diagnosing HT in the test set were 78%, 75%, 74%, respectively, with an AUC of 0.82(95% CI=0.76-0.88). After combining the LR model with clinical data, the accuracy, sensitivity, and specificity of the combined model in the test set were 87%, 74%, and 95%, respectively, with an AUC of 0.91(95% CI=0.87-0.95), which was strongly consistent with pathology (Kappa value=0.708, P<0.001). Conclusions:The optimal machine learning model (LR model) constructed in this study demonstrates a strong ability to diagnose HT and can accurately detect patients with atypical ultrasound manifestations of HT. The combination with clinical data can improve its diagnostic efficacy with higher accuracy and specificity.

Group A Streptococcus (GAS) is a very important pathogen, especially for children.On a global scale, GAS is an important cause of morbidity and mortality.But the burden of disease caused by GAS is still unknown in China and also has not obtained enough attention.For this purpose, the expert consensus is comprehensively described in diagnosis, treatment and prevention of GAS diseases in children, covering related aspects of pneumology, infectiology, immunology, microbiology, cardiology, nephrology, critical care medicine and preventive medicine.Accordingly, the consensus document was intended to improve management strategies of GAS disease in Chinese children.

Ergothioneine (ERG) is a natural antioxidant that has been widely used in the fields of food, medicine and cosmetics. Compared with traditional plant extraction and chemical synthesis approaches, microbial synthesis of ergothioneine has many advantages, such as the short production cycle and low cost, and thus has attracted intensive attention. In order to engineer an ergothioneine high-yielding Escherichia coli strain, the ergothioneine synthesis gene cluster egtABCDE from Mycobacterium smegmatis and egt1 from Schizosaccharomyces pombe were introduced into E. coli BL21(DE3) to generate a strain E1-A1 harboring the ergothioneine biosynthesis pathway. As a result, (95.58±3.2) mg/L ergothioneine was produced in flask cultures. To further increase ergothioneine yield, the relevant enzymes for biosynthesis of histidine, methionine, and cysteine, the three precursor amino acids of ergothioneine, were overexpressed. Individual overexpression of serA^T410STOP and thrA resulted in an ergothioneine titer of (134.83±4.22) mg/L and (130.26±3.34) mg/L, respectively, while co-overexpression of serA^T410STOP and thrA increased the production of ergothioneine to (144.97±5.40) mg/L. Eventually, by adopting a fed-batch fermentation strategy in 3 L fermenter, the optimized strain E1-A1-thrA-serA^* produced 548.75 mg/L and 710.53 mg/L ergothioneine in glucose inorganic salt medium and rich medium, respectively.
Culture Media ; Ergothioneine/metabolism* ; Escherichia coli/metabolism* ; Fermentation ; Histidine/metabolism* ; Metabolic Engineering

Objective:To explore the expressions of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) and clinicopathological characteristics in post-transplant lymphoproliferative disorder (PTLD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, with the aim of clarifying whether checkpoint inhibition of PD-1/PD-L1 inhibitors may serve as a therapy option.Methods:The clinical data of 13 cases of PTLD after allo-HSCT pathologically confirmed in Shenzhen Children′s Hospital from January 1, 2012 to December 30, 2019 were retrospectively analyzed.The detection was performed by immunohistochemical staining by MaxVision? method, Epstein-Barr virus(EBV) in situ hybridization and lymphoma gene rearrangement.The relationship between the expression of PD-1 and PD-L1 and the clinicopathological characteristics of PTLD were analyzed.Results:The expression of PD-1 was not correlated with gender, age, primary diseases, histopathological types, transplantation mode and the expression of EBV in situ hybridization (all P>0.05). The expression of PD-L1 was correlated with histopathological types ( P<0.05). Furthermore, the expression rate of PD-L1 on severe β-thalassemia was significantly higher than that of severe aplastic anemia [90.0%(9/10 cases) vs. 66.7%(2/3 cases)] and monomorphic PTLD was higher than that of polymorphic PTLD [100.0%(2/2 cases) vs. 83.3%(5/6 cases)]. Moreover, the positive PTLD in EBV was higher than the negative PTLD in EBV [90.9%(10/11 cases) vs. 50.0%(1/2 cases)]. The positive rates of PD-1 and PD-L1 in 13 cases with PTLD were 46.2%(6/13 cases) and 61.5%(8/13 cases) in tumor cells, 92.3% (12/13 cases) and 76.9% (10/13 cases) in microenvironmental cells, and 84.6%(11/13 cases) in EBV, respectively. Conclusions:PD-L1 has a higher positive rate in tumor cells with monomorphic PTLD; and routine staining for PD-1 and PD-L1 can be performed in all types of PTLD when standard immunotherapy and chemotherapy are ineffective.

In recent years, tumor immunotherapy has become a new hot spot in the field of cancer treatment. Besides the great success of immunological checkpoint inhibitors and cellular immunotherapy, small molecule immunotherapy has also attracted more and more attention. As a key signal transduction molecule involved in the innate immune response, stimulator of interferon genes plays an important role in defending against viral and intracellular bacterial infections, mediating type I IFN production and regulating the production of spontaneous anti-tumor immune responses in vivo. This paper briefly introduces the biological mechanism of STING signaling pathway and reviews the research progress of STING agonists based on the structural classification, so as to provide some reference for the design and discovery of STING agonist drugs.

Novel Coronavirus Pneumonia (NCP) is a class B infectious disease, which is prevented and controlled according to class A infectious diseases. Recently, children′s NCP cases have gradually increased, and children′s fever outpatient department has become the first strategic pass to stop the epidemic. Strengthening the management of the fever diagnosis process is very important for early detection of suspected children, early isolation, early treatment and prevention of cross-infection. This article proposes prevention and control strategies for fever diagnosis, optimizes processes, prevents cross-infection, health protection and disinfection of medical staff, based on the relevant diagnosis, treatment, prevention and control programs of the National Health and Health Commission and on the diagnosis and treatment experience of experts in various provinces and cities. The present guidance summarizes current strategies on pre-diagnosis; triage, diagnosis, treatment, and prevention of 2019-nCoV infection in common fever, suspected and confirmed children, which provide practical suggestions on strengthening the management processes of children′s fever in outpatient department during the novel coronavirus pneumonia epidemic period.