With the publication of several phase Ⅱ and Ⅲ clinical studies, the multidisciplinary diagnostic and therapeutic strategies for early resectable non-small cell lung cancer (rNSCLC) are rapidly evolving. These studies have elucidated the significant effects of neoadjuvant and adjuvant therapies on improving the prognosis of rNSCLC patients, while also highlighting the urgent need to revise and refine corresponding treatment protocols and clinical pathways. In response, the International Association for the Study of Lung Cancer has assembled a diverse, multidisciplinary international expert panel to evaluate current clinical trials related to rNSCLC and to provide diagnostic, staging, and treatment recommendations for rNSCLC patients in accordance with the 8th edition of the AJCC-UICC staging system. The consensus recommendations titled "Neoadjuvant and adjuvant treatments for early stage resectable non-small cell lung cancer: Consensus recommendations from the International Associationfor the Study of Lung Cancer" outline 20 recommendations, 19 of which received over 85% agreement from the experts. The recommendations indicate that early rNSCLC patients should undergo evaluation by a multidisciplinary team and complete necessary imaging studies. For stage Ⅱ patients, consideration should be given to either adjuvant therapy following surgery or direct neoadjuvant/perioperative treatment, while stage Ⅲ patients are recommended to receive neoadjuvant chemoimmunotherapy followed by surgery. Postoperatively, adjuvant immunotherapy should be considered based on the expression levels of programmed cell death ligand 1, along with testing for other oncogenic driver mutations. For patients with epidermal growth factor receptor or anaplastic lymphoma kinase mutations sensitive to tyrosine kinase inhibitors, corresponding adjuvant targeted therapy is recommended. These recommendations aim to provide personalized and precise treatment strategies for early rNSCLC patients to enhance the efficacy of neoadjuvant and adjuvant therapies. This article provides an in-depth interpretation of these consensus recommendations.

BACKGROUND:Parkinson's disease has the main pathological changes in the midbrain,especially in the dense substantia nigra,leading to impaired motor and non-motor function in patients.At present,research is limited by cellular heterogeneity,and its pathogenesis still needs to be further elucidated.In recent years,single-cell RNA sequencing(scRNA-seq)has gradually been applied in neurodegenerative diseases,which is of great significance for understanding intercellular heterogeneity,disease development mechanisms,and treatment strategies. OBJECTIVE:To review the research progress of scRNA-seq technology applied to Parkinson's disease in recent years,providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson's disease. METHODS:The first author used a computer system to search for relevant literature in the CNKI,WanFang,PubMed,and Web of Science databases,with the Chinese search terms"single-cell RNA sequencing,Parkinson's disease,cell heterogeneity,cell subtypes,dopaminergic neurons,glial cells"and English search terms"single-cell RNA seq,Parkinson disease,heterogenicity,subtypes,dopaminergic neurons,glial cells."71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION:(1)scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations,revealing cellular mysteries at the molecular level.Compared with traditional sequencing techniques,scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome.(2)By using scRNA-seq,the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated,in order to better understand potential therapeutic molecular targets.(3)The use of scRNA-seq analysis has improved our understanding of the response of Parkinson's disease glial cells,enabling us to comprehensively map and characterize different cell type populations,identify specific glial cell subpopulations related to neurodegeneration,and draw valuable single cell maps as reference data for future research.(4)The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy,as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.

BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

BACKGROUND:Erythropoietin has anti-inflammatory,anti-apoptotic,and pro-bone defect repair effects.To date,fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury. OBJECTIVE:To explore the effect of erythropoietin on restorative dentin formation after pulp injury. METHODS:(1)Animal experiment:Thirty-two rats were randomly divided into control group(n=16)and experimental group(n=16).In the experimental group,collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury,and in the control group,collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury.The cavity was then closed with glass ionomer adhesive.After 2 and 4 weeks of treatment,the maxillary bones of the two groups were collected,and the expression of nestin in dentin was detected by immunohistochemistry,and the reparative dentin production was observed by hematoxylin-eosin staining.The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth.(2)Cell experiment:Human dental pulp cells,human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue,periodontal ligament,and gingival tissue.Real-time reverse transcription PCR(RT-PCR)was used to detect the mRNA expression of erythropoietin.Erythropoietin,dentin sialophosphoprotein,dentin matrix protein 1,and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation.After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation,the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR,and the formation of mineralized nodules was detected by alizarin red S staining,and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:(1)Animal experiment:Compared with the control group,the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment.The expression of erythropoietin was weakly positive in pulp,odontoblastic cell layer and periodontal membrane of the rat's first maxillary molar,and strongly positive in odontoblasts.(2)Cell experiment:The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells.The mRNA expressions of dentin sialophosphorin,dentin matrix protein 1,nestin,erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions.The mRNA expression of dentin sialophosphoprotein,dentin matrix protein 1,nestin,bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation,and the protein expression of bone morphogenetic protein 2 was also decreased.After exogenous erythropoietin intervention,the expression of the above indexes in human dental pulp cells increased.To conclude,erythropoietin can promote the formation of dentin to some extent.

Objective To discuss the main pathological types and imaging characteristics of pulmonary nodules that are highly suspected to be malignant in clinical practice but are pathologically confirmed to be benign. Methods A retrospective analysis was performed on the clinical data of patients with pulmonary nodules who were initially highly suspected of malignancy but were subsequently pathologically confirmed to be benign. These patients were treated at the First Affiliated Hospital of Xiamen University from December 2020 to April 2023. Based on the outcomes of preoperative discussions, the patients were categorized into a benign group and a suspicious malignancy group. The clinical data and imaging characteristics of both groups were compared. Results A total of 232 patients were included in the study, comprising 112 males and 120 females, with a mean age of (50.7±12.0) years. Among these, 127 patients were classified into the benign group, while 105 patients were categorized into the suspicious malignancy group. No statistically significant differences were observed between the two groups regarding age, gender, symptoms, smoking history, or tumor history (P>0.05). However, significant differences were noted in nodule density, CT values, margins, shapes, and malignant signs (P＜0.05). Further analysis revealed that in the suspicious malignancy group, solid nodules were predominantly characterized by collagen nodules and fibrous tissue hyperplasia (33.3%), followed by tuberculosis (20.4%) and fungal infections (18.5%). In contrast, non-solid nodules were primarily composed of collagen nodules and fibrous tissue hyperplasia (41.2%) and atypical adenomatous hyperplasia (17.7%). Conclusion Benign pulmonary nodules that are suspected to be malignant are pathologically characterized by the presence of collagen nodules, fibrous tissue hyperplasia, tuberculosis, atypical adenomatous hyperplasia, and fungal infections. Radiologically, these nodules typically present as non-solid lesions and may exhibit features suggestive of malignancy, including spiculation, lobulation, cavitation, and pleural retraction.

Sleep is an instinctive behavior alternating awakening state, sleep entails many active processes occurring at the cellular, circuit and organismal levels. The function of sleep is to restore cellular energy, enhance immunity, promote growth and development, consolidate learning and memory to ensure normal life activities. However, with the increasing of social pressure involved in work and life, the incidence of sleep disorders (SD) is increasing year by year. In the short term, sleep disorders lead to impaired memory and attention; in the longer term, it produces neurological dysfunction or even death. There are many ways to directly or indirectly contribute to sleep disorder and keep the hormones, including pharmacological alternative treatments, light therapy and stimulus control therapy. Exercise is also an effective and healthy therapeutic strategy for improving sleep. The intensities, time periods, and different types of exercise have different health benefits for sleep, which can be found through indicators such as sleep quality, sleep efficiency and total sleep time. So it is more and more important to analyze the mechanism and find effective regulation targets during sleep disorder through exercise. Dopamine (DA) is an important neurotransmitter in the nervous system, which not only participates in action initiation, movement regulation and emotion regulation, but also plays a key role in the steady-state remodeling of sleep-awakening state transition. Appreciable evidence shows that sleep disorder on humans and rodents evokes anomalies in the dopaminergic signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Experiments have shown that DA in different neural pathways plays different regulatory roles in sleep behavior, we found that increasing evidence from rodent studies revealed a role for ventral tegmental area DA neurons in regulating sleep-wake patterns. DA signal transduction and neurotransmitter release patterns have complex interactions with behavioral regulation. In addition, experiments have shown that exercise causes changes in DA homeostasis in the brain, which may regulate sleep through different mechanisms, including cAMP response element binding protein signal transduction, changes in the circadian rhythm of biological clock genes, and interactions with endogenous substances such as adenosine, which affect neuronal structure and play a neuroprotective role. This review aims to introduce the regulatory effects of exercise on sleep disorder, especially the regulatory mechanism of DA in this process. The analysis of intracerebral DA signals also requires support from neurophysiological and chemical techniques. Our laboratory has established and developed an in vivo brain neurochemical analysis platform, which provides support for future research on the regulation of sleep-wake cycles by movement. We hope it can provide theoretical reference for the formulation of exercise prescription for clinical sleep disorder and give some advice to the combined intervention of drugs and exercise.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Cholelithiasis is a common biliary system disease with a high incidence worldwide. Abnormal lipid metabolism has been shown to play a key role in the mechanism of gallstones. Therefore, recent research literature on the genes, proteins, and molecular substances involved in lipid metabolism during the pathogenesis of gallstones has been conducted. This study aimed to determine the role of lipid metabolism in the pathogenesis of gallstones and provide insights for future studies using previous research in genomics, metabolomics, transcriptomics, and other fields.

Objective To investigate the relationship between primary pulmonary mucinous adenocarcinoma (PPMA) mass type and pneumonia type and their difference in malignant degree, and to analyze the role of clinical manifestations and CT features in the diagnosis of this disease. Methods The clinical data of PPMA patients admitted in the First Affiliated Hospital of Xiamen University from May 2011 to March 2022 were retrospectively analyzed. According to CT features, they were divided into a mass type group and a pneumonia type group. The clinical manifestations, CT features and the degree of malignancy between the two groups were analyzed and compared. Results A total of 57 PPMA patients were enrolled. There were 17 males and 40 females, with an average age of (53.82±10.65) years, and 28 (49%) patients had reversed hato-like sign. There were 42 patients in the mass type group and 15 patients in the pneumonia type group. PPMA often occurs in both lower lungs, with clinical manifestations mainly of coughing and expectorating white mucoid sputum. There were statistical differences between the two groups in the maximum diameter of tumor (P<0.001), boundary condition (P<0.001) and pleural indentation sign (P=0.019). There was no statistical difference between the two groups in Ki-67 index (P>0.05). Conclusion There is no statistical difference in the degree of malignancy between the two types of PPMA. Considering their clinical manifestations and differences in imaging features, it is supported that the pneumonia type is just a progression of the mass type. CT can present various manifestations, among which the reversed hato-like sign is expected to become an important imaging feature. Combined with a high proportion of solid components, pleural indentation sign, and vacuole sign, reversed hato-like sign can play a significant role in the diagnosis of PPMA.

It is believed that diabetes complicated with coronary heart disease is closely related to the functional interplay of the heart， spleen， and kidneys. This paper proposed the concept of the heart-spleen-kidney as a unified system for understanding and treating the disease. At the early stage， spleen and kidney deficiency leads to the internal accumulation of phlegm， dampness， and turbid lipids， causing impaired blood circulation and vascular obstruction， so treatment should focus on tonify the kidneys and strengthening the spleen， activating blood circulation and resolving stasis， using the self-prescribed Tangxin Maiwen Formula （糖心脉温方）. As the disease progresses， further decline of spleen and kidney function results in inadequate nourishment of the heart， leading to blood stasis and the accumulation of phlegm， dampness， and turbid lipids， which may transform into pathogenic heat and toxins， causing heart damage， then treatment should emphasize on boosting qi and nourishing yin， clearing heat， activating blood and resolving toxins， using the self-prescribed Tangxin Maiqing Formula （糖心脉清方）. In advanced stages， three zang organs， the heart， spleen， and kidneys， become severely impaired， leading to mental activity fail to be nourished and abnormal cognitive functions， so treatment should focus on harmonizing the three zang organs simultaneously， using the self-prescribed Yunpi Tiaoxin Decoction （运脾调心汤）. This approach aims to provide a clinical framework for the diagnosis and treatment of diabetes with coronary heart disease.