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 analyze the current status and quality of existing obstetrics and gynecology enhanced recovery after surgery(ERAS)guidelines/consensus,understand the evidence-based practices in this field,and provide a basis for clinical decision-making.Methods A systematic search of PubMed,CNKI,and other databases,as well as NGC,SIGN,and websites of anesthesia societies domestically and internationally was conducted to obtain relevant guidelines and consensus on ERAS for gynecological surgery.The search was conducted from inception to July 1,2023,and the AGREE Ⅱ and RIGHT tools were used to analyze the current status and quality of the included guidelines/consensus,as well as to conduct a summary of the recommendations.Results A total of 5 guidelines and 10 consensus statements were included.The publication years were from 2018 to 2023,originating from the United States,China,Canada,and the United Kingdom.In the 6 areas evaluated using AGREEⅡ,clarity(66.06％)scored highest,followed by scope and purpose(56.67％),involvement of stakeholders(42.02％),and editorial independence(37.64％)with scores above 30％.The scores for rigor of development(26.88％)and applicability(4.17％)were relatively low.The same items among different evaluators indicated good consistency.The results of the scores in each area were as follows:A-level 2,B-level 13,and no C-level.Two high-quality guidelines were selected.The average RIGHT reporting rate was 44.38％.Subgroup analysis showed that guidelines were higher than consensus statements in the areas of rigor of development and applicability(P＜0.05),and that using GRADE was higher than not using(P＜0.05).The areas of rigor of development and clarity were higher in foreign guidelines than domestic guidelines(P＜0.05),and using evidence grading tools was higher than not using(P＜0.05).The summary of the recommendations showed that the quality of the evidence supporting the recommendations was uneven,and some recommendations were not specific enough.Conclusion The quality of the 15 included ERAS guidelines/consensus in obstetrics and gynecology is uneven,and 2 of them can be used as high-quality guidelines for clinical reference.The quality of evidence-based guidelines in foreign countries is higher,and the use rate of GRADE in foreign guidelines is high,most of which can provide clear recommendation strength and evidence level.Chinese guidelines/consensus are of lower quality compared to overseas,and methodology and report quality need further improvement.Overall,it is still necessary to strengthen the formulation of methods and reporting standards,improve the quality of evidence,and refine specific recommendations.

Objective To investigate the application value of fractional exhaled nitric oxide (FeNO), alveolar nitric oxide (CaNO), and eosinophils (EOS) in the differential diagnosis of respiratory diseases in children aged 3 to 6 years in Lanzhou, Gansu Province. Methods A total of 360 children aged 3 to 6 years with confirmed asthma, allergic rhinitis, or lower respiratory tract infection were selected as research subjects. Spearman's rank correlation coefficient was used to evaluate the correlation between FeNO, CaNO and EOS. The diagnostic value of FeNO, CaNO, and EOS for the differential diagnosis of the three diseases was assessed through random forest models, receiver operating characteristic (ROC) curves, and multivariate Logistic regression analysis. Results The median valuesof FeNO and CaNO were higher in asthmatic children than in those with other diseases. The median value of EOS was the lowest in children with allergic rhinitis, and the median values of FeNO and CaNO were the lowest in children with lower respiratory tract infection. Correlation analysis showed a positive correlation between FeNO and CaNO (r=0.59, P < 0.05), a negative correlation between FeNO and EOS (r=-0.61, P < 0.05), and a negative correlation between CaNO and EOS (r=-0.63, P < 0.05). The random forest model indicated that FeNO had the highest importance in disease classification. ROC curve analysis revealed that FeNO, CaNO, and EOS had the highest diagnostic efficiency for lower respiratory tract infection among the three diseases (with areas under the curve of 0.86, 0.91, and 1.00, respectively). The area under the curve of the multivariate Logistic regression model for diagnosing asthma was 0.96, with a sensitivity of 0.902 and a specificity of 0.881. Conclusion FeNO, CaNO and EOS demonstrate good potential in the differential diagnosis of asthma, allergic rhinitis, and lower respiratory tract infection in children aged 3 to 6 years in Lanzhou. Furthermore, the multivariate Logistic regression model based on these three factors can effectively improve the diagnostic accuracy of asthma.

Purpose: Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis. Materials and Methods: RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis. Results: We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties. Conclusion Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

Sugar-sugar glycosyltransferases play important roles in constructing complex and bioactive saponins. Here, we characterized a series of UDP-glycosyltransferases responsible for biosynthesizing the branched sugar chain of bioactive steroidal saponins from a widely known medicinal plant Paris polyphylla var. yunnanensis. Among them, a 2'-O-rhamnosyltransferase and three 6'-O-glucosyltrasferases catalyzed a cascade of glycosylation to produce steroidal diglycosides and triglycosides, respectively. These UDP-glycosyltransferases showed astonishing substrate promiscuity, resulting in the generation of a panel of 24 terpenoid glycosides including 15 previously undescribed compounds. A mutant library containing 44 variants was constructed based on the identification of critical residues by molecular docking simulations and protein model alignments, and a mutant UGT91AH1^Y187A with increased catalytic efficiency was obtained. The steroidal saponins exhibited remarkable antifungal activity against four widespread strains of human pathogenic fungi attributed to ergosterol-dependent damage of fungal cell membranes, and 2'-O-rhamnosylation appeared to correlate with strong antifungal effects. The findings elucidated the biosynthetic machinery for their production of steroidal saponins and revealed their potential as new antifungal agents.

Multiple myeloma (MM) is still an incurable hematologic malignancy, which is eagerly to the discovery of novel therapeutic targets and methods. N-acetyltransferase 10 (NAT10) is the first reported regulator of mRNA acetylation that is activated in many cancers. However, the function of NAT10 in MM remains unclear. We found significant upregulation of NAT10 in MM patients compared to normal plasma cells, which was also highly correlated with MM poor outcome. Further enforced NAT10 expression promoted MM growth in vitro and in vivo, while knockdown of NAT10 reversed those effects. The correlation analysis of acetylated RNA immunoprecipitation sequencing (acRIP-seq) and ribosome profiling sequencing (Ribo-seq) combined with RIP-PCR tests identified centrosomal protein 170 (CEP170) as an important downstream target of NAT10. Interfering CEP170 expression in NAT10-OE cells attenuated the acceleration of cellular growth caused by elevated NAT10. Moreover, CEP170 overexpression promoted cellular proliferation and chromosomal instability (CIN) in MM. Intriguingly, remodelin, a selective NAT10 inhibitor, suppressed MM cellular growth, induced cellular apoptosis in vitro and prolonged the survival of 5TMM3VT mice in vivo. Collectively, our data indicate that NAT10 acetylates CEP1 70 mRNA to enhance CEP170 translation efficiency, which suggests that NAT10 may serve as a promising therapeutic target in MM.

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:To determine the risk factors, clinical characteristics and treatment prognosis, so as to provide reference for clinicians to diagnose, treat and prevent drug-induced liver injury (DILI).Methods:Data of 712 confirmed DILI cases were collected from the Second Affiliated Hospital of Kunming Medical University between 2013 to 2019. Among them, 498 cases were included in the study. All patients medical history, clinical manifestations and classification, laboratory parameters, disease severity, and mortality rate were collected. Statistical analysis was performed using t-test, Mann-Whitney U test/Pearson χ2 test/Fisher's exact test or Spearman's rank test. Results:Among the suspicious drugs causing DILI, single medication accounted for 89.56%, mainly including traditional Chinese medicine (56.43%), anti-tumor and immunomodulatory agents (8.03%), anti-infective drugs (4.42%), antipyretic and analgesic drugs (4.22%) %), etc., while combination medication accounted for 10.44%. The clinical classification was dominated with hepatocyte injury (63.05%), and there was a statistically significant difference in clinical classification among age groups ( P<0.001). Age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and total bile acid (TBA) had statistically significant difference among different suspicious drugs in DILI caused by different drug ( P<0.001, 0.003, 0.001, <0.001 and <0.001). Laboratory test results showed that there were statistically significant differences in ALT, AST, ALP, γ-glutamyltransferase (GGT), TBA, international normalized ratio (INR), and eosinophils ( P<0.001, <0.001, <0.001, 0.018, 0.003 and 0.019, respectively). Chronic hepatitis was more common in the 54 cases who completed histopathological examination of the liver biopsy. Fibrosis degree was higher in the Western medicine group than Chinese herbal medicine group ( P<0.05), and the difference was statistically significant ( P<0.05). 96.99% of DILI patients were cured or improved, and 3.01% of patients were uncured. Ordinal logistic regression analysis showed that GGT and INR were independent predictors of poor prognosis. Conclusions:Suspicious drugs for DILI are herbal/dietary supplements, anti-tumor and immunomodulatory, anti-infective, and antipyretic and analgesic. The most common clinical classification is hepatocyte injury. Most patients with DILI have a good prognosis after drug withdrawal and GGT and INR are independent predictors of poor prognosis.

Drug-induced liver injury (DILI) has a complex pathogenesis and obvious individual difference. Early diagnosis and treatment of DILI may achieve good prognosis, but due to a lack of specific clinical symptoms, most cases cannot be identified in the early stage. If no timely treatment is given, DILI may progress to irreversible liver failure with a high mortality rate, and there are no effective therapies for advanced DILI except liver transplantation. Therefore, early diagnosis and treatment are of great importance for patients with DILI. This article summarizes the recent research advances in DILI, including suspected drugs, risk factors, pathogenesis, pathological features, clinical types and manifestations, diagnostic criteria and evaluation, and network database, in order to provide a basis for early diagnosis, clinical typing, treatment guidance, and prognostic evaluation of DILI.