BackgroundAnxiety disorder is a common mental disorder， with its prevalence showing a continuous upward trend， significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice， the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases， however， the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders， and to elucidate the associated biological pathways， in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus （pQTL） data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database， and the genome-wide association studies （GWAS） data of 50 486 patients with anxiety disorders and 330 460 healthy controls， the inverse-variance weighted （IVW） method was used as the main analysis method， supplemented by MR-Egger method， weighted median method， simple model method， and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test， MR-Egger intercept test， MR-PRESSO test， and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these， SPATA9 （OR=0.856， 95% CI： 0.784–0.934， P<0.01） and PDE5A （OR=0.911， 95% CI： 0.864–0.961， P<0.01） were identified as protective factors， while CRYGD （OR=1.209， 95% CI： 1.095–1.334， P<0.01）， BTN3A3 （OR=1.045， 95% CI： 1.018–1.073， P<0.01）， SERPINB13 （OR=1.102， 95% CI： 1.040–1.168， P<0.01）， ERBB4 （OR=1.283， 95% CI： 1.109–1.484， P<0.01）， LSAMP （OR=1.096， 95% CI： 1.037–1.158， P<0.01）， ICOSLG （OR=1.283， 95% CI： 1.104–1.490， P<0.01）， DNAJB11 （OR=1.172， 95% CI： 1.076–1.277， P<0.01）， and TREML1 （OR=1.115， 95% CI： 1.054–1.179， P<0.01） were identified as risk factors. The sensitivity analysis showed that the results were robust， with no heterogeneity （Cochran's Q test P>0.05） or pleiotropy （MR-Egger intercept test P>0.05）. Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction， lymphocyte proliferation， cell membrane structure and synaptic function， as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.

The prevention and treatment of chronic obstructive pulmonary disease （COPD） pose a major global challenge， with difficulties in effectively integrating holistic regulation and precise micro-intervention. The traditional Chinese medicine （TCM） theory of state-target pattern differentiation and treatment advocates the combination of state regulation and target intervention， offering a new paradigm for integrated TCM and Western medicine. This article systematically reviews the theoretical connotations of this theory and constructs a dynamic correspondence framework linking TCM pattern states， signaling pathways， and targeted interventions across different stages of COPD. At the acute exacerbation stage， the phlegm-heat obstructing the lung state is characterized by hyperactivation of the nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3） inflammation pathway， and formulas for clearing heat and resolving phlegm suppress the cytokine storm through multi-component synergy. At the stable stage， the lung-spleen Qi deficiency state is characterized by functional decompensation of the nuclear factor erythroid 2-related factor 2 （Nrf2）/Kelch-like ECH-associated protein 1 （Keap1） antioxidative stress pathway， and therapies for tonifying the lung and spleen repair the essence of Qi deficiency through antioxidative defense and energy metabolism. At the severe/very severe stable stage， the lung-kidney deficiency state is pathologically based on dysregulation of the transforming growth factor （TGF）-β/Wnt repair network and depletion of stem/progenitor cells， and therapies for tonifying the kidney and reinforcing Qi absorption achieve simultaneous regulation of deficiency and stasis by inhibiting aberrant fibrosis and guiding ordered regeneration. These three pathways are not isolated but exhibit dynamic shifts in dominance and cross-talk， constituting the molecular network basis of deficiency causing excess and intermingled deficiency and excess. Furthermore， this article points out the current shortcomings in quantitative evidence， objective syndrome standardization， and coverage of syndrome states， and proposes future directions including building multi-omics databases， conducting biomarker-stratified randomized controlled trials， and developing disease-pattern combined animal models， aiming to provide a theoretical perspective that integrates holism and micro-targeting for precision prevention and treatment of COPD.

The prevention and treatment of chronic obstructive pulmonary disease （COPD） pose a major global challenge， with difficulties in effectively integrating holistic regulation and precise micro-intervention. The traditional Chinese medicine （TCM） theory of state-target pattern differentiation and treatment advocates the combination of state regulation and target intervention， offering a new paradigm for integrated TCM and Western medicine. This article systematically reviews the theoretical connotations of this theory and constructs a dynamic correspondence framework linking TCM pattern states， signaling pathways， and targeted interventions across different stages of COPD. At the acute exacerbation stage， the phlegm-heat obstructing the lung state is characterized by hyperactivation of the nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3） inflammation pathway， and formulas for clearing heat and resolving phlegm suppress the cytokine storm through multi-component synergy. At the stable stage， the lung-spleen Qi deficiency state is characterized by functional decompensation of the nuclear factor erythroid 2-related factor 2 （Nrf2）/Kelch-like ECH-associated protein 1 （Keap1） antioxidative stress pathway， and therapies for tonifying the lung and spleen repair the essence of Qi deficiency through antioxidative defense and energy metabolism. At the severe/very severe stable stage， the lung-kidney deficiency state is pathologically based on dysregulation of the transforming growth factor （TGF）-β/Wnt repair network and depletion of stem/progenitor cells， and therapies for tonifying the kidney and reinforcing Qi absorption achieve simultaneous regulation of deficiency and stasis by inhibiting aberrant fibrosis and guiding ordered regeneration. These three pathways are not isolated but exhibit dynamic shifts in dominance and cross-talk， constituting the molecular network basis of deficiency causing excess and intermingled deficiency and excess. Furthermore， this article points out the current shortcomings in quantitative evidence， objective syndrome standardization， and coverage of syndrome states， and proposes future directions including building multi-omics databases， conducting biomarker-stratified randomized controlled trials， and developing disease-pattern combined animal models， aiming to provide a theoretical perspective that integrates holism and micro-targeting for precision prevention and treatment of COPD.

Objective·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells(hESCs)into neural progenitor cells(NPCs)using in vitro differentiation models and high-throughput multi-omics sequencing technologies.Methods·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method,and cells at both stages were collected.The cell phenotypes were identified by reverse transcription-quantitative real-time PCR(RT-qPCR)and immunofluorescence(IF)staining.Transcriptome sequencing(RNA-seq)was conducted to detect and analyze the differentially expressed genes(DEGs)between hESCs and NPCs.The assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)was employed to assess chromatin accessibility changes between hESCs and NPCs.Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors.Finally,an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction(PPI)network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro.Results·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers(NANOG and POU5F1)were high at the hESC stage but significantly decreased at the NPC stage,while early neural differentiation markers(PAX6,SOX1,and NES)were minimally expressed at the hESC stage but markedly upregulated at the NPC stage.RNA-seq analysis revealed that compared to the hESC stage,there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage.Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development.ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC,with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility.Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs.Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance,forebrain development,and neuron migration.After neural differentiation,the expression levels of CTNND2 and LHX2 genes increased,and the chromatin accessibility of related genomic regions also increased.PPI network analysis indentified candidate downstream genes including PRKACA,CDH2,and ERBB4.Conclusion·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs.In this process,the expression levels of genes related to axon guidance,forebrain development,and neuronal migration pathways increase and related chromatin accessibility is enhanced.

Objective To investigate the establishment and evaluation method of a rat model for cold asthma syndrome during the acute exacerbation phase of asthma.Methods Thirty-two rats were randomly allocated into four distinct groups:normal control group,asthma group,cold asthma group,and Shegan Mahuang Decoction group(SMD).While the normal control group was not subjected to any modeling procedures,the remaining groups were induced to develop asthma by a combination of intraperitoneal injections and atomized inhalation of ovalbumin sensitization solution.Furthermore,to emulate the traditional Chinese medicine syndrome of cold asthma,the cold asthma group and the SMD underwent an additional protocol involving"swimming,cold water consumption,and external cold stimulation."Commencing from the 14th day of the experiment,the SMD received daily gavage administration of Shegan Mahuang Decoction for a consecutive period of 14 days.The cold asthma rat model was comprehensively evaluated from both macroscopic and microscopic perspectives.Results ①Following model induction,both the asthma and cold asthma groups exhibited significant increases in asthmatic behavioral scores,sluggish weight gain,and airway hyperreactivity.Additionally,there was a notable rise in eosinophils(EOS)in the bronchoalveolar lavage fluid(BALF),decreased expression of aquaporin-5(AQP5)in lung tissue,and altered immune balances with reduced Th1/Th2 ratios and elevated Th17/Treg ratios in the spleen.Hemorheological changes included increased whole blood viscosity,relative high-shear,and low-shear indices,alongside a marked decline in erythrocyte aggregation index.The cold asthma group further displayed pronounced cold asthma symptoms,slower weight gain,and more significant increases in whole blood viscosity and low-shear relative index compared to the asthma group.②Administration of SMD alleviated asthmatic behaviors and traditional Chinese medicine syndrome manifestations in cold asthma rats,resulting in enhanced weight gain.SMD also mitigated airway hyperreactivity,reduced EOS percentage in BALF,and ameliorated lung tissue damage and inflammatory cell infiltration.The treatment increased AQP5 expression levels and rectified the immune imbalances of Th1/Th2 and Th17/Treg in cold asthma rats.Furthermore,SMD significantly lowered whole blood viscosity,relative high-shear,and low-shear indices in these rats.Conclusion The research effectively established a model for cold asthma syndrome in TCM through a method that integrates intraperitoneal injection,nebulized ovalbumin sensitization,and a triad of swimming,cold water intake,and external cold exposure.This model consistently displays the symptoms of cold asthma and corresponds with the microscopic pathological alterations seen in asthma,thereby validating the robustness of the model's creation process.

Objective:To investigate human factors underlying radiotherapy planning safety incidents and quantitatively explore their interrelationships.Methods:A total of 1 619 safety incidents recorded in the automated plan checking system developed by West China Hospital of Sichuan University were utilized. Human factors were identified and statistically analyzed using the Human Factors Analysis and Classification System (HFACS). A Bayesian network model was developed and combined with sensitivity analysis for quantitative assessment.Results:Key contributing factors included organizational processes (12.89%), inadequate supervision (11.85%), and personnel factors (13.50%). Utilizing the established HFACS Bayesian network hybrid model in conjunction with sensitivity analysis, it has been found that the most significant influences on skill‐based errors and decision errors were condition of operators and environmental factors, with corresponding indices of 0.96 and 0.76. Additionally, personnel factors had the greatest impact on routine, with an index of 3.51.Conclusions:Key contributing factors span all HFACS levels, with organizational processes, supervision, personnel, and condition of operators each playing a significant role. Upstream factors — such as organizational climate, environment factors, and personnel factors — strongly influence downstream risks. These offer actionable insights for developing targeted safety protocols.

Acupuncture and moxibustion have their unique advantages in treating tumors,but the theoretical framework of acupuncture and moxibustion intervention in tumors needs to be improved,and the academic system still needs to be sorted out.In this paper,we try to describe the commonalities between Chinese medical theories and modern medical technologies in order to consolidate the theoretical foundation of acupuncture intervention in tumor.Specifically:① Acupuncture regulates immune function and energy metabolism,which is a specific form of tonifying the spleen and stomach to support positive qi.② Tumors belong to the broad definition of"sores and ulcers"in traditional Chinese medicine,which is a special kind of chronic inflammation,and acupuncture intervenes in tumors by intervening in inflammatory reactions from ulcers.③ Tumor is a"dynamic pseudo-organ"with yin and yang attributes and"life attributes".Acupuncture and moxibustion can regulate various cells and factors in the tumor environment in a multi-targeted way,so as to make it tend to the state of yin and yang equilibrium.④ Acupuncture and moxibustion have unique advantages in the reduction of toxicity,enhancement of efficacy,tonicity,rejuvenation,treatment of complications,etc.,which complement the allopathic therapies of modern medicine,and can help to realize survival with tumors.

Geriatric oral health care encounters significant challenges with the increase in the proportion of older individuals. Age-related changes in the dentition, muscles, and joints result in a decline in objective masticatory function, subjective restoration requirements, and acceptability among the elderly population, with individual variations influenced by systemic health. Considering functional requirements, the adaptability of stomatognathic and systemic health conditions, health economics and other factors, the authors believe that it should not be limited to the conventional "one-to-one" strategy for replacing missing teeth in geriatric prosthodontics. There is an urgent need for a precise and adaptable restoration strategy that is more suitable for older individuals. The proposal of a new concept of functional tooth loss updates the minimal restoration standards for elderly patients and establishes the theory of age-friendly functional restoration. Based on the restoration strategy of functional tooth loss, this paper proposes a new concept termed "age-friendly functional restoration of the stomatognathic system", which integrates treatment considerations including endodontics, periodontology, mucosa, muscles, temporomandibular joint, and systemic health. Efforts should be made in four areas as follows. Firstly, the "assessment of accessible function" should be enhanced by considering the interrelationship between stomatognathic and systemic health. Secondly, the "evaluation of appropriate function" is supposed to be optimised in view of subjective needs and objective evaluation of the stomatognathic system. Moreover, the "formulation of treatment plans" needs to be accomplished with the aid of assistive technologies, such as artificial intelligence, to accurately exert appropriate functional restoration. Lastly, the "management and maintenance of health" is likely to be strengthened through follow-ups, propaganda and education, and preventive healthcare, so as to improve quality of life and ultimately achieve healthy ageing among older individuals.
Humans ; Tooth Loss/therapy* ; Aged ; Stomatognathic System ; Oral Health ; Dental Care for Aged ; Dental Restoration, Permanent/methods*

Objective·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells(hESCs)into neural progenitor cells(NPCs)using in vitro differentiation models and high-throughput multi-omics sequencing technologies.Methods·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method,and cells at both stages were collected.The cell phenotypes were identified by reverse transcription-quantitative real-time PCR(RT-qPCR)and immunofluorescence(IF)staining.Transcriptome sequencing(RNA-seq)was conducted to detect and analyze the differentially expressed genes(DEGs)between hESCs and NPCs.The assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)was employed to assess chromatin accessibility changes between hESCs and NPCs.Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors.Finally,an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction(PPI)network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro.Results·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers(NANOG and POU5F1)were high at the hESC stage but significantly decreased at the NPC stage,while early neural differentiation markers(PAX6,SOX1,and NES)were minimally expressed at the hESC stage but markedly upregulated at the NPC stage.RNA-seq analysis revealed that compared to the hESC stage,there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage.Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development.ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC,with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility.Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs.Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance,forebrain development,and neuron migration.After neural differentiation,the expression levels of CTNND2 and LHX2 genes increased,and the chromatin accessibility of related genomic regions also increased.PPI network analysis indentified candidate downstream genes including PRKACA,CDH2,and ERBB4.Conclusion·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs.In this process,the expression levels of genes related to axon guidance,forebrain development,and neuronal migration pathways increase and related chromatin accessibility is enhanced.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.