ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Children， as a special group， frequently experience of off-label drug use worldwide. Common reasons for off-label drug use in children include the lack of data on pediatric patients during the clinical trial stage of drug development， delayed updates to drug instructions， and the non-standard professional behavior of some doctors. Off-label drug use in children is a double-edged sword. It could save lives and provide a way to explore additional functions of drugs， while it may also lead to the phenomenon of hyper-indication abuse， increasing the risk of adverse drug events. Regulating off-label drug use in children can safeguard the best treatment rights and interests of children. It is recommended to encourage pharmaceutical enterprises to conduct research and development of pediatric new drugs， simplify the approval process for drug instructions amendments， accumulate evidence-based medical evidence for off-label drug use in children， standardize the process of off-label drug use in children in medical institutions， continuously improve the standardized diagnosis and treatment capabilities of pediatricians， and actively cooperate with the families of pediatric patients in diagnosis and treatment， so as to comprehensively safeguard the rights and interests of both doctors and patients.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor with unique characteristics, and its treatment regimens are primarily derived from those for small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In recent years, the incidence rate has been on the rise, and the prognosis are affected by the interaction of multiple factors such as individual, clinical stage and treatment mode, and the heterogeneity is significant. In the study of molecular subtypes, multiple subgroups were divided according to key gene mutations such as RB1 and TP53, and genomic subtypes were associated with survival, chemotherapy response, and efficacy of precision therapy. Targeted therapy excavates multiple targets, and the efficacy of drugs is different. Immunotherapy has made remarkable progress, and immune checkpoint inhibitors (ICIs) have been effective in all stages of chemotherapy alone or in combination with chemotherapy or radiation therapy, but there is a risk of hyperprogressive diseases, and accurate prognostic markers need to be explored urgently. This review reviews the latest research progress in the study of molecular subtypes and precision therapies such as targeted therapy and immunotherapy of pulmonary LCNEC, and points out that pulmonary LCNEC treatment will develop in the direction of precision and individualization in the future.
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Humans ; Lung Neoplasms/drug therapy* ; Carcinoma, Neuroendocrine/drug therapy* ; Precision Medicine ; Immunotherapy ; Carcinoma, Large Cell/drug therapy*

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 composition characteristics and biological functions of tumor cell subpopulations in glioblastoma(GBM)through multi-transcriptomics sequencing technology,and explore the hypoxia characteristics and spatial localization features of the mesenchymal-like(MES-like)tumor cell subpopulation in GBM and the influence on malignant biological behaviors.Methods Multi-transcriptomics sequencing data,including single-cell RNA sequencing(scRNA-seq)data(18 patients),bulk RNA sequencing(bulk RNA-seq)and spatial transcriptomics(ST)data of GBM,were employed to define cell subpopulations in GBM,and Gene Ontology(GO)and Gene Set Enrichment Analysis(GSEA)were utilized to analyze their functions.The proportions and locations of cell subpopulations in bulk RNA-seq data were evaluated with BayesPrism deconvolution.Immunofluorescence assay was conducted for verification on 12 paraffin samples of GBM from patients who visited the neurosurgical department of our hospital from 2015 to 2023 and met the pathological diagnostic criteria for GBM(10 males and 2 females,at an average age of 53.50 years and a median age of 54.50 years).pySCENIC was applied to predict specific transcription factors of tumor cell subpopulations.Results Tumor cells in GBM were highly heterogeneous,and could be mainly divided into 4 subpopulations:astrocyte-like(AC-like),neural progenitor-like(NPC-like),oligodendrocyte progenitor-like(OPC-like)and MES-like.Differential gene analysis found that the MES-like tumor cells highly expressed vascular endothelial growth factor A(VEGFA),adrenomedullin(ADM),N-myc downstream regulated 1(NDRG1),insulin like growth factor binding protein 5(IGFBP5),and A-kinase anchoring protein 12(AKAP12)(P<0.001).pySCENIC transcription factor prediction found that the high-active transcription factors of the MES-like tumor cells were AT-rich interaction domain 3A(ARID3A),FOS like 2,AP-1 transcription factor subunit(FOSL2),endothelial PAS domain protein 1(EPAS1),CCAAT enhancer binding protein delta(CEBPD),and CCAAT enhancer binding protein beta(CEBPB)(P<0.05).GO and GSEA enrichment analyses found that the MES-like tumor cells were enriched in hypoxia-related pathways,especially the pathway of cell responses to hypoxia levels(NES=2.437,P<0.001).BayesPrism deconvolution showed that the MES-like tumor cells mainly existed in PAN(Pseudopalisading cells around necrosis)and perinecrotic zone.Immunofluorescence assay confirmed CD44+(CD44 antigen)MES-like tumor cells were mainly located in hypoxia areas with highly expression of hypoxia inducible factor 1 subunit alpha(HIF1α)(P<0.01).Multivariate Cox regression analysis indicated that the MES-like tumor cells were significantly correlated with the adverse prognosis of GBM patients(HR=1.71,95%CI:1.38～2.11,P<0.001).Conclusion Tumor cells in GBM are of highly heterogeneity.They could be mainly divided into 4 subpopulations:AC-like,NPC-like,OPC-like and MES-like.MES-like tumor cells,mainly locating in PAN and perinecrotic zone,are characterized by hypoxia,which can promote the malignant progression of GBM.

OBJECTIVE To analyze the correlation between styloid process related parameters and symptoms in patients with styloid process syndrome.METHODS A retrospective study was conducted on the 3D reconstruction CT results of the styloid process in 68 patients diagnosed with styloid process syndrome who visited the Department of Otolaryngology Head and Neck Surgery,the Second Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2024.The relationship between parameters such as styloid process length,angle,distance from styloid process tip to pharynx,and specific symptoms in patients with styloid process syndrome was analyzed.RESULTS Among 68 patients with styloid process syndrome,44 had unilateral symptoms and 24 had bilateral symptoms.The length of the styloid process on the symptomatic side of patients with unilateral symptoms(3.86±0.16)cm was significantly longer than that on the asymptomatic side(2.98±0.17)cm(Z=-2.191,P=0.028);The length of the styloid process on the side with severe symptoms in patients with bilateral symptoms(3.98±0.37)cm was also significantly longer than that in patients with mild symptoms(3.37±0.15)cm(t=2.448,P=0.024).Patients with styloid process syndrome mainly present with pharyngalgia(64.71%,44/68).There were no significant differences in the length,inclination angle,anteversion angle,and distance between the styloid process tip and the pharynx among those with unilateral pharyngalgia(n=29),bilateral pharyngalgia(n=15),and non pharyngalgia(n=24)(P>0.05).However,among the 68 patients with styloid syndrome,12 had calcification of the styloid hyoid ligament,while 56 did not.The incidence of unilateral pharyngalgia was significantly higher in patients with calcification of the styloid hyoid ligament than in patients without calcification(66.7%vs.35.7%,χ2=3.909,P=0.048).CONCLUSION The severity of symptoms in patients with styloid process syndrome is related to the length of the styloid process,and those with calcification of the styloid hyoid ligament are more likely to experience pharyngalgia.

In recent years，the prevalence of asthma in children has been on the rise，affecting children's physical and mental health and placing a burden on families and society. As the in-depth study of asthma phenotypes and endotypes progresses，targeted therapy for asthma has become a new treatment strategy. Dupilumab，a drug targeting IL-4 and IL-13，is used treating patients with uncontrolled moderate-to-severe type 2 asthma. It has been approved for use in children aged 6-11 years with moderate-to-severe asthma in the United States and Europe，but there are fewer reports on the treatment of type 2 asthma in children in China. Therefore，this article aims to review the research progress of Dupilumab in the treatment of type 2 asthma in children，in order to provide reference for the clinical treatment of asthma in children.

"Clinical microbiology testing technology" is one of the core courses of medical laboratory science (MLS). Clinical microbiology testing enables quick and accurate identification of pathogens causing infectious diseases and provides guidance to the rational use of medications, thereby playing a key role in the diagnosis and treatment of infectious diseases. To address the evolving needs for intelligent testing and to nurture proficient microbiology technologists with self-learning abilities and advanced critical thinking skills, this course has undergone a series of reforms, focusing on content structure, method diversification, and the establishment of a skill-based assessment system. After three years of exploration and practice, an online-offline hybrid teaching mode aimed at improving students' thinking skills was developed. This teaching mode enhanced students' learning and logical thinking abilities and strengthened their professional training, serving as a reference for the reform of MLS courses.

Small cell lung cancer(SCLC)is a highly malignant neuroendocrine tumor,which is prone to metastasis and is associated with a very poor prognosis.SCLC was previously regarded as a homogeneous disease that lacked individualized treatment strategies.In recent years,molecular typing studies have revealed the high heterogeneity of SCLC.However,issues such as inconsistent typing standards,the dy-namic transformation of subtypes,and complex drug resistance mechanisms restrict the clinical translation of the results.This article sys-tematically expounds the research progress of SCLC molecular typing,summarizes its potential and challenges in driving precision treatment,and aims to provide ideas for the development of precise medical treatment plans and promote the clinical translation of the"typing-guided treatment"model for SCLC.

Objective To investigate the role of Glycoprotein non-metastatic melanoma protein B(GPNMB)in hypoxia-induced epithelial-mesenchymal transition(EMT)in human chorionic trophoblast HTR-8/SVneo cells.Methods HTR-8/SVneo cells were cultured in vitro to investigate the effect of hypoxia on GPNMB expression.The cells were transfected with either a GPNMB overexpression plasmid(pcDNA3.1-GPNMB),small interfering RNA targeting GPNMB(si-GPNMB-1/2),or their respective negative controls(pcDNA3.1-NC or si-NC),and were also treated with the autophagy agonist rapamycin(Rap).The experimental groups were categorized as follows:Normoxia,Hypoxia,Normoxia/Hypoxia+si-NC or si-GPNMB,Normoxia/Hypoxia+pcDNA3.1-NC or pcDNA3.1-GPNMB,Normoxia/Hypoxia+Rap,and Hypoxia+Rap+pcDNA3.1-NC or pcDNA3.1-GPNMB.GPNMB expression levels were evaluated using qRT-PCR,Western blotting,and immunofluorescence staining.The expression of autophagy-related proteins(LC3B Ⅱ/Ⅰ,p62)and epithelial-mesenchymal transition(EMT)markers(E-cadherin,N-cadherin)was analyzed by Western blotting.Cell migration and invasion capacities were assessed using wound healing and Transwell assays.Results Compared with the Normoxia group,the mRNA and protein levels of GPNMB were downregulated in the Hypoxia group.Additionally,the protein levels of p62 and N-cadherin were reduced,while LC3B Ⅱ/Ⅰ and E-cadherin expression levels were increased(P<0.05).Compared with the Hypoxia+si-NC group,the Hypoxia+si-GPNMB-2 group showed significantly decreased protein levels of p62 and N-cadherin,along with elevated levels of LC3B Ⅱ/Ⅰ and E-cadherin(P<0.05).Compared with the Hypoxia+pcDNA3.1-NC group,the Hypoxia+pcDNA3.1-GPNMB group exhibited opposite trends.Notably,compared with the Hypoxia group,the Hypoxia+Rap group showed increased LC3B Ⅱ/Ⅰ and E-cadherin levels,accompanied by reduced p62 and N-cadherin levels(P<0.05).However,compared with the Hypoxia+pcDNA3.1-GPNMB group,the Hypoxia+Rap+pcDNA3.1-GPNMB group attenuated the promoting effect of GPNMB overexpression on EMT in HTR-8/SVneo cells,as evidenced by decreased p62 and N-cadherin protein expression levels and increased LC3BⅡ/Ⅰ and E-cadherin protein expression levels(P<0.05).Conclusion In hypoxia-induced HTR-8/SVneo cells,GPNMB inhibits autophagy,promotes the epithelial-mesenchymal transition,and enhances cell migration and invasion.