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.

ObjectiveTo explore the relationship between self-assessed health and age-adjusted Charlson comorbidity index （AICC） in older adults， and to further analyze the differences in this relationship across gender groups. MethodsBased on the China health and retirement longitudinal study （CHARLS） database， this study selected data on basic characteristics， chronic disease status， depressive symptoms， and self-assessed health of older adults aged ≥60 years. Chi-square tests were used to perform a preliminary analysis of the association between these factors and AICC scores. A multifactorial ordered logistic regression model was constructed to assess the effects of each influencing factor on AICC， while multiple linear regression analysis was used to explore the linear relationship between self-rated health and AICC scores. Additionally. Stratified analysis by gender was performed to evaluate gender differences. ResultsA total of 10 911 participants were included， with a mean age of 67.40±5.94 years； 6 249 （57.3%） were male and 4 662（42.7%） were female. The distribution of AICC scores was categorized into low-risk， moderate-risk， higher-risk， and high-risk groups， accounting for 23.5%， 50.2%， 20.6%， and 5.7%， respectively. Multifactorial logistic regression analysis revealed that self-rated health was negatively associated with AICC in the total population and in the male geriatric group （OR=0.843， 95% CI： 0.776， 0.917， P=0.001）， （OR=0.886， 95% CI： 0.796 ， 0.987， P=0.028）， but did not reach statistical significance in the female geriatric group . Linear regression analysis further indicated a significant negative linear relationship between self-rated health and AICC （b=-0.485， 95% CI： -0.516，-0.455， P＜0.001）.This relationship was consistent in both male （b=-0.356， 95% CI： -0.406，-0.305， P＜0.001） and female （b=-0.373， 95% CI： -0.435，-0.310， P＜0.001） subgroups， with a stronger negative association in females. ConclusionSelf-rated health is significantly negatively associated with AICC， and attention should be given to self-rated health in the female geriatric population. Self-rated health can serve as an important tool for identifying elderly group at high risk of comorbidities providing a valuable basis for precise intervention.

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 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.

Objective To analyze the clinical features and magnetic resonance imaging(MRI)features of adult diffuse glioma,define the preoperative MRI enhancement grade(ET grade)of the disease,and explore the relationship of ET grade with isocitrate dehydrogenase(IDH)mutation and WHO grade.Methods The clinical data of 306 cases of adult diffuse glioma confirmed by surgery and pathology admitted in our hospital from January 2018 to December 2023 were collected and retrospectively analyzed.There were 169 cases of mutant IDH and 137 cases of wildtype IDH.The differences in gender,age,MRI signal uniformity,clear tumor margin,obvious edema,compression of adjacent ventricles and ET grade were analyzed between the 2 types of IDH patients.A logistic regression model was established to identify the independent influencing factors for IDH mutation,and the correlation of ET grade with IDH status and WHO grade was analyzed.Results There were significant differences in age,whether the MRI signal was uniform,whether the tumor margin was clear,whether the edema was obvious,the compression of the adjacent ventricle and the ET grade in patients with different IDH status.The independent variables were screened by Forward method and then included in the logistic regression model.ET grade,age and tumor margin were independent influencing factors of IDH mutation status and negatively correlated with IDH mutation.For every 1 year increase in age,the probability of mutant IDH in adult diffuse glioma was decreased by 0.93 times.The accuracy of the established regression model for predicting IDH status was 0.859,the sensitivity was 0.852,the specificity was 0.869,and the AUC value was 0.922(0.892～0.952).ET grade was significantly correlated with WHO grade.The most prominent proportion of glioma patients with WHO grade 2 was noET,that with WHO grade 3 was ET2,and that with WHO grade 4 was ET3.Conclusion For adult diffuse glioma,preoperative MRI ET grade is negatively correlated with IDH mutation status,and positively with WHO grade.ET grade is helpful for determination of of IDH mutation status and WHO grade.

Objective To evaluate the precision and effectiveness of ultrasound-guided visualization for nasojejunal tube placement with the"R(right reclining)-S(shoulder)-A(abdominal)"3-point positioning for critically ill patients.Methods A retrospective analysis was conducted on all critically ill patients who underwent nasojejunal tube placement in Department of Critical Medicine of a tertiary hospital in Chongqing from April 2022 to August 2023.According to the position of the catheter,they were divided into a control group and an observation group.The control group received ultrasound-guided nasojejunal tube insertion,while the observation group used the"R-S-A"3-point positioning (the patient were placed in a right lateral position,the nurse stood at the right shoulder of the patient,and the ultrasound operator stood on the right side of the abdomen in the operating direction)for ultrasound-guided nasojejunal tube insertion.And,the control group had no specific requirements for positioning during the procedure.After propensity matching,the time and success rate of catheter insertion and incidence of complications were compared between the 2 groups.Results The time of catheter insertion was significantly shorter (36.2±10.3 vs 42.3±8.3 min),and the success rate of insertion was obviously higher (95.2％ vs 66.7％)in the observation group when compared with the control group (P<0.05).The incidence of complication was 9.5％ in the observation group,and 28.6％ in the control group,but there was no statistical difference between the 2 groups.Conclusion Ultrasound-guided nasojejunal tube placement based on "R-S-A"3-point positioning has high precision and strong effectiveness in critically ill patients,which can shorten the time and improve the success rate of catheter insertion.

OBJECTIVE To investigate the application of endoscopic Draf Ⅱ-Ⅲ frontal sinus surgery in the treatment of recurrent frontal sinus infection and fistula formation after craniocerebral trauma.METHODS There were 8 cases of recurrent frontal sinus infection after craniocerebral trauma,the main manifestations were headache,recurrent frontal infection,discharge of pus,fistula formation.The average onset time was 43.25 months.The patients underwent DRAF Ⅱ-Ⅲ frontal sinus surgery under nasal endoscopy,including Draf Ⅱa 2,Draf Ⅱb 5,and Draf Ⅲ1,respectively.During the operation,the frontal sinus ostium was expanded.It was found that bone wax blocked the frontal sinus ostium in the frontal sinus.The bone wax was removed,and the frontal sinus drainage was smooth.No facial incision was made in all patients.RESULTS There were 8 patients with frontal infection who were cured after surgery.No cerebrospinal fluid rhinorrhea or intracranial infection occurred during or after operation.After discharge,the outpatient follow-up review was conducted in 1,3,6,and 12 months.It was found that the frontal sinus remained unobstructed.The frontal sinus did not become infected again,and the fistula gradually healed.CONCLUSION Draf Ⅱ-Ⅲ frontal sinus surgery under nasal endoscopy is an effective way to treat recurrent frontal sinus infection and fistula formation after craniocerebral trauma.

OBJECTIVE To analyze the narrow-band imaging(NBI)endoscopic characteristics of recurrent early glottic carcinoma patients after undergoing CO2 laser surgery with a suspend laryngoscopy.METHODS A retrospective study was conducted on patients with early-stage glottic carcinoma(Ⅰ-Ⅱ stage)who received CO2 laser surgery under supportive laryngoscopy at the Department of Otolaryngology Head and Neck Surgery,the Second Affiliated Hospital of Xi'an Jiao Tong University from January 2017 to December 2023.The medical history,treatment methods,laryngoscopy(including common white light endoscopy and NBI endoscopy),imaging examinations,and pathological results of patients with recurrent glottic carcinoma were collected at different time points including preoperation,postoperative 1 month,postoperative 3 months,and postoperative 6 months.The endoscopic characteristics of NBI in patients with recurrent glottic carcinoma were summarized.RESULTS First,among 18 patients with early-stage glottic cancer recurrence after CO2 laser,the diagnostic rate of NBI endoscopy for laryngeal cancer recurrence(88.89％,16/18)was significantly higher than that of common white light endoscopy(55.56％,10/18)(χ2=4.985,P=0.026).The intraepithelial papillary capillary loop(IPCL)was classified as a vertical vessel according to ELS in all relapsed patients.However,according to Ni classification,the IPCL of the 72.22％(13/18)were classified as type V,while the IPCL of 27.78％(5/18)showed suspicious abnormal neovascularization(punctate or dilated and curved).The proportion of patients with abnormal IPCL on the surgical surface at 1 month,3 months,and 6 months postoperatively was 0.00％,27.78％(5/18),and 61.11％(11/18),respectively,with statistically significant differences(χ2=16.164,P<0.001),which indicated that the longer the follow-up time for recurrent laryngeal cancer patients,the higher the proportion of patients with abnormal IPCL on the surface of the surgical area under NBI endoscopy.CONCLUSION For early glottic carcinoma after CO2 laser surgery with a suspend laryngoscopy,the appearance of suspicious new blood vessels with type Ⅴ IPCL and punctate or dilated curvature under NBI endoscopy may indicate early recurrence of laryngeal cancer.