For patients with advanced non-small cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor (EGFR) mutations, guidelines prioritize the use of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), which offer higher objective response rate (ORR), longer progression-free survival (PFS), and better quality of life. However, due to the low proportion of elderly patients enrolled in clinical trials, the existing evidence is insufficient to fully guide clinical practice. This review examines the efficacy and safety differences of third-generation EGFR-TKIs as monotherapy or in combination in the elderly NSCLC by integrating subgroup analyses or pre-specified research objectives from prospective and retrospective studies. The results show that third-generation EGFR-TKIs have comparable efficacy in elderly patients to younger populations and are well-tolerated. Although combination therapies may extend survival time, the associated increased toxicity necessitates careful risk-benefit assessment.
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Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Lung Neoplasms/enzymology* ; ErbB Receptors/metabolism* ; Protein Kinase Inhibitors/adverse effects* ; Aged ; Antineoplastic Agents/adverse effects*

Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it's imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI^- towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
Schwann Cells/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Cancer-Associated Fibroblasts/metabolism* ; Animals ; Carcinoma, Squamous Cell/metabolism* ; Neoplasm Invasiveness/pathology* ; Male ; Female ; Mice ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Cell Line, Tumor ; Leukemia Inhibitory Factor/metabolism* ; Middle Aged

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed that aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3, and H3K27me3. In addition, it reinstated the expression levels of ZGA-related genes by reestablishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.
Animals ; Mice ; Histone-Lysine N-Methyltransferase/biosynthesis* ; Histones/genetics* ; Nuclear Transfer Techniques ; Female ; Gene Expression Regulation, Developmental ; Promoter Regions, Genetic ; Epigenesis, Genetic ; Embryo, Mammalian/metabolism*

Objective To analyze the current occupational health literacy (OHL) level and its influencing factors among manufacturing workers in Bao'an District, Shenzhen City. Methods The front-line workers of manufacturing enterprises from seven key industries in two streets of Bao'an District were selected as the research subjects using a stratified cluster random sampling method. The Occupational Health Literacy Questionnaire of National Key Populations was used to online investigate their OHL level. Multivariable logistic regression analysis was used to screen the influencing factors of OHL. Results A total of 633 front-line workers of manufacturing enterprises were surveyed, and 283 had OHL, with an overall OHL level of 44.7%. The levels of literacy across different dimensions, from high to low, were basic knowledge of occupational health protection (84.5%), legal knowledge of occupational health (41.5%), health behaviors and practices (41.2%), and basic skills for occupational health protection (22.0%). The results of the multivariable logistic regression analysis showed that younger age, higher educational level, and higher personal monthly income, were related to higher OHL level among the workers (all P<0.05). Conclusion The OHL level of manufacturing workers in Bao'an District, Shenzhen City still has room for improvement. Efforts should focus on workers with low education levels, low incomes, and older ages, with targeted training in theoretical knowledge to improve the practical application of basic skills for occupational health protection, to improve their OHL.

Objective:To observe the projections from tyrosine hydroxylase(TH)positive neurons in locus coerule-us(LC)to tachykinin-1(TAC1)neurons in paraventricular nucleus of the thalamus(PVT),and morphologically determine whether they are involved in transmission and modulation of nociceptive information.Methods:TAC1-ires-Cre mice were hybridized with Rosa26:CAG-LSL-tdTomato(Ai9)mice.And spared nerve injury(SNI)induced neu-ropathic pain model was established with TAC1-ires-Cre::Ai9 mice to observe the colocalization of TAC1 and Fos and the close appositions between TAC1/FOS double-labeled neurons and TH positive axonal terminals.The distribution of the TH positive neurons and FG retrogradely labeled neurons were observed in the LC after Fluorogold(FG)was injec-ted into the PVT.Finally,the coexistences of TH positive neurons and RV labeled neurons in the LC were observed after injection of RV-mediated retrograde tracing system.Results:TAC1 positive neurons were shown with red fluores-cence in TAC1-ires-Cre::Ai9 mice.TAC1/FOS double-labeled neurons were found in the PVT of the SNI model.Some TAC1/FOS double labeled neurons made close appositions with TH positive axonal terminals.FG retrogradely labeled neurons were observed in the LC after FG injected into the PVT,and some of the FG labeled neurons coexisted with TH positive neurons.Using RV retrograde transsynaptic tracing virus,the results showed that presynaptic neurons of TAC1 positive neurons in the PVT were found in the LC,and most of the presynaptic neurons were TH positive neu-rons.Conclusion:TH positive neurons in the LC project to TAC1 positive neurons of the PVT,forming LCTH+-PVTTAC1+neural circuit,which were activated by nociceptive information.It demonstrates that this pathway plays a role in pain transmission or regulation.

Environmental pollution is closely linked to the occurrence and development of cancer. Chemical carcinogens are the most important environmental factors causing cancer in humans. Among them, persistent organic pollutants (POPs) are characterized by their widespread distribution, persistence, and bioaccumulation. Research on the carcinogenic effects of POPs has received considerable attention in recent years. This article reviewed the internal exposure, association with cancer risk, and potential carcinogenic mechanisms of five typical classes of POPs in the environment, including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), per- and poly-fluoroalkyl substances (PFAS), brominated flame retardants (BFRs), and short-chain chlorinated paraffins (SCCPs). These five types of POPs have distinct carcinogenic mechanisms, including interfering with cell proliferation cycle, altering epigenetic inheritance, promoting oxidative stress, altering energy metabolism, and affecting immune function. The development of cancer is the result of interaction between intrinsic genetic factors and external environmental factors. In addition to focusing on how environmental POPs affect the genetic material of organisms, it is also important to consider their effects on the tumor microenvironment, including tumor immunity and angiogenesis. Understanding these effects is crucial for guiding future efforts in pollution control and precision medicine in cancer treatment.

Objective Coronary heart disease(CHD)is one of the major lethal diseases in the world at present.The detection of biomarkers is an important non-invasive method to evaluate the progression of CHD,which is of great significance for the diagnosis and secondary prevention of CHD.This study aims to screen diagnostic biomarkers in the pathogenesis of myocardial infarction,analyze cuprotosis-related genes in the development of this disease,and further predict the traditional Chinese medicine of regulating cuprotosis-related genes.Methods The GEO database was searched to obtain chip data of myocardial infarction,differentially expressed genes(DEGs)were analyzed.Then,DEGs enrichment analysis was performed,and key genes were screened based on least absolute shrinkage and selection operator(LASSO)and random forest(RF)methods.Diagnostic model was constructed and verified.After immune cell infiltration analysis was performed on differential genes,the results were further combined with weighted gene co-expression network analysis to obtain differentially expressed immune-related genes,which were intersected with cuproptosis genes to obtain cuproptosis immune-related Hub genes.The correlation between cuproptosis-related genes and diagnostic genes were analyzed.Gene set enrichment analysis(GSEA)was performed on cuproptosis-related genes to further predict the traditional Chinese medicines of regulating the genes related to cuproptosis.Results A total of 115 DEGs,which were mainly enriched in the biological processes and pathways related to lymphocyte-mediated immunity,mitochondrial respiratory chain complex Ⅳ,C-type lectin receptor signaling pathway,and chemokine signaling pathway,were obtained by differential analysis.Five diagnostic genes,SNORA20,SNORA19,H4C3,SNORD81,and COX7B,were screened out by machine learning methods.Immune infiltration analysis found dendritic cells,macrophages M2,monocytes,neutrophils,natural killer cells,CD4+T cells,CD8+T cells,and γδ T cells.It was indicated the above eight immune cells play a certain role in the pathogenesis of myocardial infarction in coronary heart disease.Weighted correlation network analysis(WGCNA)and immune infiltration analysis were used to obtain 358 key module genes,which were intersected with cuproptosis genes to obtain three cuproptosis and immune signature genes.The correlation analysis results of five diagnostic genes and Hub genes showed that there was a correlation between the expressions of SLC31A1 and SNORA20,LIAS and SNORA19,SNORD81,MTF1 and H4C3,SNORA20,SNORA19,SNORD81.GSEA analysis results indicated that LIAS and MTF1 had a significant effect on the NF-κB signaling pathway,NOD-like receptor signaling pathway and Toll-like receptor signaling pathway.The potential regulatory Chinese medicines are mainly blood-activating and stasis-eliminating,qi-promoting and analgesic drugs.Conclusion SNORA20,SNORA19,H4C3,SNORD81,COX7B have a certain diagnostic value for myocardial infarction in coronary heart disease.The prediction of genes related to cuproptosis and immune infiltration in the pathogenesis of myocardial infarction provides a certain reference for the study of the mechanism of traditional Chinese medicine intervention in myocardial infarction.

BACKGROUND:Studies have shown that both Panax notoginseng saponins and concentrated growth factor can promote fracture healing,but there are few studies addressing their combined effects on fracture healing.Panax notoginseng saponins may accelerate fracture healing by promoting the release of concentrated growth factor-related factors over a certain period of time. OBJECTIVE:To study the effect of Panax notoginseng saponins on concentrated growth factor release and fracture healing in rats. METHODS:Eighteen 8-week-old Sprague-Dawley rats were numbered and randomly divided into three groups:Panax notoginseng saponins group,model control group and blank group.Panax notoginseng saponins group was fed with Panax notoginseng saponins for 2 weeks.Model control group was given 2 mL of normal saline for 2 weeks and blank group was fed normally.Concentrated growth factor was obtained by the centrifugation method both from the Panax notoginseng saponins group and model control group.After 1 week of normal feeding,all animals underwent modeling for femoral fracture.The Panax notoginseng saponins group and the model control group were implanted with autologous concentrated growth factor,and then the release concentration of growth factors at different time points(1 hour,1,3,5,7,9 and 11 days)were measured by ELISA.Fracture healing was assessed based on postoperative X-ray and hematoxylin-eosin staining of bone tissues. RESULTS AND CONCLUSION:Compared with the model control group,the Panax notoginseng saponins group had higher release concentrations of vascular endothelial growth factor A and transforming growth factor β at 7,9,and 11 days,Platelet-derived growth factor BB at 5,9,and 11 days,and basic fibroblast growth factor at 1-11 days(P<0.01).X-ray examinations indicated that fracture healing in the Panax notoginseng saponins group was better than that in the model control group,and fracture healing in these two groups was better than that in the blank group at 2 months after surgery.Hematoxylin-eosin staining results found that the constituent osteocyte density in the Panax notoginseng saponins group was greater than that in the model control group,and the constituent osteocyte density in these two groups was better than that in the blank group.These findings indicate that Panax notoginseng saponins can increase the concentration of concentrated growth factor-related factors.After intervention with Panax notoginseng saponins,concentrated growth factors are more advantageous in promoting fracture healing in rats.

Objective To analyze the medication rule of Traditional Chinese Medicine(TCM)in treating diabetes nephropathy(DN)and to explore the interaction between core components and key targets.Methods Based on the ancient and modern medical case cloud platform,the medication rules of TCMs and the drug pairs with the highest frequency in treating DN were summarized.Then the network pharmacology approach was utilized to analyze the pharmacodynamic material basis and mechanisms of the highest frequency-drug pairs.The potential targets were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)databases.TTD,DISGENET,and GENECARD databases were used to obtain the related targets of DN and screen out the potential targets for DN.In order to clarify the relationships between the active ingredients,the core targets,and pathways,STRING and Cytoscape 3.7.1 software were used to construct the protein-protein interaction(PPI)network and core drugs-ingredients-targets-disease interaction network,DAVID database was screened for Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis of core targets.Sybyl 2.1 software and biofilm interference verify the combined capacity between the core ingredients and key targets.Results Among 183 prescriptions,Astragali Radix had the highest use frequency and average dose,43 times and 37 g,respectively,followed by Salviae miltiorrhizae Radix and Poria cocos.To find the core combined with the highest confidence in association analysis was astragalus,salvia miltiorrhiza,and tuckahoe.Correlation analysis indicates that the core combination with the highest confidence was Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos.Network pharmacologic showed 89 potential targets and 15 key signaling pathways for the treatment of DN by the drug pair.TNF signaling pathway,Nod-like receptor signaling pathway,and MAPK signaling pathway were disease-related pathways,and IL-6,TNF,and vascular endothelial growth factor A(VEGFA)were core targets.Isorhamnetin and quercetin of the drug pair had high binding ability with IL6,the scores were 8.2 and 7.4,respectively,and the dissociation constants(KD)were 5.6×10-5 mol·L-1 and 6.8×10-5 mol·L-1,respectively.Conclusion This study preliminarily finds the prescription rule of treating DN with Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos as the core drug pair,isorhamnetin,and quercetin are probably the main active compounds of this drug pair in DN treatment,which provides a basis for clinical treatment and drug discovery of DN.