ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Advances in targeted therapy and immunotherapy have significantly improved clinical outcomes for patients with advanced non-small cell lung cancer (NSCLC), reshaping treatment paradigms. However, most patients ultimately face drug resistance, with limited options for subsequent therapies and suboptimal treatment efficacy, presenting a prominent challenge in current clinical practice. Antibody-drug conjugates (ADCs), characterized by high efficacy and favorable safety profiles, have emerged as a promising therapeutic frontier in recent years. This systematic review provides a comprehensive overview of the latest advancements in ADCs-based therapies for lung cancer, alongside discussions of the prevailing challenges in this rapidly evolving domain.
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Humans ; Carcinoma, Non-Small-Cell Lung/immunology* ; Immunoconjugates/therapeutic use* ; Lung Neoplasms/immunology* ; Antineoplastic Agents/therapeutic use* ; Immunotherapy

Immunotherapy has changed the treatment landscape of advanced non-small cell lung cancer(NSCLC),showing great potential in the treatment of untreated and relapsed or refractory(R/R)patients.However,numerous issues that need further exploration remain with the wide application of immunotherapy.They include the exploration of biomarkers for efficacy prediction,the optimization of immunotherapy modalities,immune-related adverse effects,and the management of special populations.This review summarizes the progress of the research on immunotherapy for advanced NSCLC and discusses its challenges and future directions.

At present, immunotherapy combined with chemotherapy has become the first-line standard of treatment for extensive-stage small cell lung cancer (ES-SCLC). In recent years, immune checkpoint inhibitors (ICIs) have received extensive attention and research in the field of lung cancer. At the same time, there are many challenges and tests in this process, such as the exploration of biomarkers, the exploration of new targets and new models, and the management of special populations. This article reviews the research progress in the field of ES-SCLC immunotherapy, and looks forward to the future development trend and potential direction of this field.
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Humans ; Small Cell Lung Carcinoma/pathology* ; Immunotherapy/methods* ; Lung Neoplasms/pathology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoplasm Staging ; Animals

15q11-q13 Duplication syndrome is a rare genetic disease of the nervous system, characterized by developmental retardation, intellectual impairments, hypotonia, autism, epilepsy and so on. This article reports a 33-year-old male patient, with the clinical manifestation of early-onset intractable epilepsy and mental retardation. The high-throughout whole exome sequencing showed a 10.53 Mb repeat sequence in the 15q11.2-q13.3 region, further confirming the diagnosis of 15q11-q13 duplication syndrome. The literature reports of the pathogenic mechanism, classification, typical clinical manifestation, seizure features,accessory examination and therapy of the 15q11-q13 duplication syndrome are summarized and reviewed, so as to enhance the understanding of the disease, as well as to improve the diagnosis and treatment level of the clinicians.

Humans ; Asthma/drug therapy* ; Biological Therapy

With the in-depth research on pressure injury, pressure injury-related pain has gradually attracted attention, but its definition is not uniform yet, and there is a lack of targeted assessment tools. This research systematically searches the Chinese and English literature related to pressure injury-related pain published from 1995 to 2019, and uses Rodgers' evolutionary concept analysis method to systematically analyze the concept, and clarify its defining attributes, causes and consequences. This research also puts forward the attributes of pressure injury-related pain, clarifies related concepts such as chronic wound-related pain and wound-related pain, as well as the concept with typical cases, so as to provide a reference for the management of pressure-related pain.

Objective: To establish comprehensive laboratory reference intervals for Chinese children. Methods: This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex. Results: In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old. Conclusion This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.

OBJECTIVE: To observe the effect of flurbiprofen( FPA) combined with dexamethasone on preemptive analgesia for whole lung lavage in pneumoconiosis patients. METHODS: Ninety pneumoconiosis patients who underwent whole lung lavage under general analgesia were divided into three groups by random number table method: combine treatment group,FPA group and control group,30 cases in each group. Patients in combine treatment group were given 2 mg/kg body weight( bw) of flurbiprofen axetil injection and 10 mg of dexamethasone through intravenous injection before 2 hours of surgery. Patients in FPA group were given 2 mg/kg bw of FPA axetil injection intravenously. The control group was injected with 2 m L 0. 9% sodium chloride solution. Visual Analogue Scale( VAS) score,Bruggramann Comfort Scale( BCS) score,and adverse reaction of the three groups were recorded in 2,6,8,12 and 24 hours after operation. RESULTS: The postoperative VAS and BCS scores of combine treatment group at the 5 time points after operation were lower than that of control group and FPA group respectively( P < 0. 01). The VAS score between the 5 time points presented an decreasing tendency with the increase of time in the combine treatment group( P < 0. 05),and the BCS score presented an increasing tendency with the increase of time( P < 0. 05). The adverse reaction,such as nausea,vomiting dizziness and drowsiness,sore throat and skin itching in combine treatment group was lower than that of control group and FPA group 24 hours postoperatively( P < 0. 017). CONCLUSION: The therapy of FPA combined with dexamethasone on preemptive analgesia is a safe and effective method for reducing postoperative pain of whole lung lavage in pneumoconiosis patients.

Objective To evaluate the effects of propofol on the proliferation of hippocampal neurons in fetal rats in vitro.Methods Pregnant Sprague-Dawley rats at 16-18 days of gestation,were sacrificed and the fetal rats were taken out from the abdominal cavity.The hippocampal neurons of the fetal rats were isolated and seeded in culture plates.After being cultured for 9 days,the neurons were divided into 7 groups using a random number table(n =36 each):control group (C group),intralipid group (I group) and propofol 0.1,1.0,10.0,100.0,1 000.0 μmol/L groups (P1-5 groups).In group I,10％ intralipid was added to the culture media until the final concentration reached 100 μmol/L.In P1-5 groups,propofol was added to the culture media until the final concentration reached 0.1,1.0,10.0,100.0 and 1 000.0 μmol/L,respectively.The neurons were then incubated for 3 h.The proliferation of hippocampal neurons was determined by MTT assay at 12,24,36,48,60 and 72 h after the end of incubation with propofol.Results Compared with group C,the proliferation of hippocampal neurons was significantly decreased in P1-5 groups (P ＜ 0.05),while no significant change was found in group I (P ＞ 0.05).Compared with group P1,the proliferation of hippocampal neurons was significantly decreased in group P5 (P ＜ 0.05),while no significant change was found in P2-4 groups (P ＞ 0.05).Conclusion Propofol can decrease the proliferation of hippocampal neurons in fetal rats in vitro.