The α7 nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated ion channel characterized by high Ca²⁺ permeability, rapid activation, and rapid desensitization. It is widely expressed in the nervous system and various non-neuronal cell types. α7 nAChR is involved in regulating neuronal excitability, synaptic transmission and plasticity, cognitive function, and inflammatory responses. These properties have made α7 nAChR a potential therapeutic target for neuropsychiatric and inflammatory diseases. In recent years, advances in cryo-electron microscopy have provided structural insights into α7 nAChR gating, ligand recognition, allosteric modulation, and allosteric activation. The receptor mainly undergoes transitions among resting, open, and desensitized states. Recent structural studies have further revealed asymmetric conformational changes and multiple intermediate states during receptor activation and recovery from desensitization. Conformational rearrangements in the extracellular domain-transmembrane domain coupling region and the pore-forming M2 helices are closely associated with channel opening and desensitization. However, structural characterization of the α7 nAChR gating cycle still largely depends on pharmacological stabilization. Open-state structures have been resolved in the presence of PNU-120596 or GAT107, whereas a high-resolution structure of the open state induced by acetylcholine alone remains to be determined. These physiological roles underpin the involvement of α7 nAChR in multiple disease processes. In the hippocampus, α7 nAChR regulates local neuronal circuits, theta oscillations, synaptic transmission, and synaptic plasticity, thereby contributing to learning, memory, attention, and other cognitive processes. In macrophages, microglia, and other immune-related cells, α7 nAChR activation regulates inflammatory responses and oxidative stress. These effects involve several signaling pathways, including Janus kinase 2 (JAK2)/STAT3, phosphoinositide 3-kinase (PI3K)/AKT, and NF-κB signaling, as well as regulation of the NLRP3 inflammasome and IL-1β production. Such anti-inflammatory effects may also contribute to α7 nAChR-mediated neuroprotection. Although several compounds targeting α7 nAChR have entered clinical studies, no α7 nAChR-selective drug has been approved for clinical use. Limited clinical translation may be related to rapid receptor desensitization, inconsistent efficacy across clinical studies, insufficient or variable target engagement, patient heterogeneity, and clinical endpoint selection. TC-5619 showed promising effects on cognitive impairment and negative symptoms in an early exploratory study of schizophrenia, but these effects were not confirmed in a subsequent, larger phase II trial. Encenicline (EVP-6124) also showed cognitive improvement in early studies, whereas two global phase III trials in schizophrenia failed to meet their co-primary cognitive and functional endpoints. Pharmacological strategies targeting α7 nAChR have expanded from orthosteric agonists to positive allosteric modulators (PAMs) and allosteric agonist-positive allosteric modulators (ago-PAMs). Orthosteric agonists directly activate the receptor by binding to the orthosteric site, but their effects are limited by rapid receptor desensitization. Type I PAMs mainly enhance agonist-evoked responses with relatively small effects on desensitization, whereas type II PAMs markedly potentiate receptor responses and reduce or delay desensitization. Ago-PAMs such as GAT107 can directly activate α7 nAChR through an allosteric mechanism while also potentiating responses to orthosteric agonists. Together, these findings have broadened the pharmacological approaches to α7 nAChR regulation. In summary, future drug development should focus on precise regulation of α7 nAChR according to receptor structure and disease mechanisms, rather than simply enhancing receptor activation. Further studies are needed to clarify how candidate ligands affect receptor gating, conformational transitions, recovery from desensitization, and downstream signaling. Pharmacological differences between neuronal and non-neuronal α7 nAChRs, between homomeric α7 and heteromeric α7β2 receptors, and between α7 nAChR and other nAChR subtypes also require further investigation. Integrating structure prediction, artificial intelligence-assisted virtual screening, molecular docking, molecular dynamics simulations, and electrophysiological validation may facilitate the discovery and optimization of new α7 nAChR modulators.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

[Objective]Based on the ancient view of"four seasons and five elements",to analyze the source of the two contradictory texts in Inner Canon of Huangdi,namely,the spleen is not in control and the flat pulse is not in control("the good one is not visible"),and the spleen is in control of the long summer and the flat pulse is in control("the soft one is weak"or"apart from the soft one,like a chicken treading on the ground").[Methods]By adopting an integrated research approach that combines philology,historiography and theoretical studies,this paper first interprets the relevant theories of the seasonal-visceral pulses in Inner Canon of Huangdi and points out the textual contradictions existing therein.Then,it traces the origin of the Five Elements thought in the formation of the seasonal-visceral pulse theory,revealing the two main schemas generated by the Five Elements doctrine in different stages of development.Finally,from the perspective of how philosophical thoughts influence the formation of medical theories,it explains the construction of the seasonal-visceral theory in Inner Canon of Huangdi.Furthermore,using the dual-evidence method and combining the unearthed literature Tianhui Medical Bamboo Slips,it points out the reasons for the emergence of the seasonal-visceral pulse texts and further conducts an objective reflection on the methods of interpreting medical classics.[Results]The emergence of the text contradiction of the viscera was closely related to the view of"four seasons and five elements"and the"five seasons and five elements"produced by its evolution.The concept of"four seasons and five elements"originated from the ancient people's simple observation and understanding of the composition and interrelationship of time and space and the material world,and was based on nature and social practice.The concept of"four seasons and five elements"is used in the construction of the theory of four seasons and five viscera in traditional Chinese medicine.Under the theory system of four seasons and five viscera,the spleen was the main palace,not the main time,so the spleen did not respond to the normal pulse.The"five seasons and five elements"was accompanied by the emergence of the five elements of the circulation pattern,the reinterpretation of the law of the four seasons,the five seasons should be a more complete closed loop of the five viscera,but it was not derived from a more universal practice law,and can not completely replace the theory of the viscera under the guidance of the four seasons and five elements.In particular,the flat pulse of the spleen governing the summer in the five viscera veins did not have clinical reference,but to a greater extent,it was a mechanical adaptation for the logical self-consistency of the five seasons thought.[Conclusion]The philosophical thought of the Five Elements is the root cause of the textual contradictions in the seasonal-visceral pulse theory,which reflects that the construction of TCM theory is deeply influenced by ancient Chinese philosophy.Abiding by the laws of objective practice and clarifying the formation and evolution of medical-philosophical thoughts are conducive to a deeper understanding of Inner Canon of Huangdi,thereby better interpreting and inheriting the classics.

[Objective]Based on the ancient view of"four seasons and five elements",to analyze the source of the two contradictory texts in Inner Canon of Huangdi,namely,the spleen is not in control and the flat pulse is not in control("the good one is not visible"),and the spleen is in control of the long summer and the flat pulse is in control("the soft one is weak"or"apart from the soft one,like a chicken treading on the ground").[Methods]By adopting an integrated research approach that combines philology,historiography and theoretical studies,this paper first interprets the relevant theories of the seasonal-visceral pulses in Inner Canon of Huangdi and points out the textual contradictions existing therein.Then,it traces the origin of the Five Elements thought in the formation of the seasonal-visceral pulse theory,revealing the two main schemas generated by the Five Elements doctrine in different stages of development.Finally,from the perspective of how philosophical thoughts influence the formation of medical theories,it explains the construction of the seasonal-visceral theory in Inner Canon of Huangdi.Furthermore,using the dual-evidence method and combining the unearthed literature Tianhui Medical Bamboo Slips,it points out the reasons for the emergence of the seasonal-visceral pulse texts and further conducts an objective reflection on the methods of interpreting medical classics.[Results]The emergence of the text contradiction of the viscera was closely related to the view of"four seasons and five elements"and the"five seasons and five elements"produced by its evolution.The concept of"four seasons and five elements"originated from the ancient people's simple observation and understanding of the composition and interrelationship of time and space and the material world,and was based on nature and social practice.The concept of"four seasons and five elements"is used in the construction of the theory of four seasons and five viscera in traditional Chinese medicine.Under the theory system of four seasons and five viscera,the spleen was the main palace,not the main time,so the spleen did not respond to the normal pulse.The"five seasons and five elements"was accompanied by the emergence of the five elements of the circulation pattern,the reinterpretation of the law of the four seasons,the five seasons should be a more complete closed loop of the five viscera,but it was not derived from a more universal practice law,and can not completely replace the theory of the viscera under the guidance of the four seasons and five elements.In particular,the flat pulse of the spleen governing the summer in the five viscera veins did not have clinical reference,but to a greater extent,it was a mechanical adaptation for the logical self-consistency of the five seasons thought.[Conclusion]The philosophical thought of the Five Elements is the root cause of the textual contradictions in the seasonal-visceral pulse theory,which reflects that the construction of TCM theory is deeply influenced by ancient Chinese philosophy.Abiding by the laws of objective practice and clarifying the formation and evolution of medical-philosophical thoughts are conducive to a deeper understanding of Inner Canon of Huangdi,thereby better interpreting and inheriting the classics.

Formaldehyde is a prevalent organic solvent in industrial and indoor environment,which can seriously harm human health,so it is of great significance to develop highly sensitive formaldehyde sensors with fast response,low detection limit and long life.In this study,the NiO-In2O3 composite structure was prepared using indium-based metal organic framework(In-MOF)as the precursor,and the formaldehyde gas sensor was constructed with In2O3 and NiO-In2O3 composite structure as the sensitive material.The results demonstrated that the In2O3 material had a microflower-like structure,while the NiO-In2O3 composite structure was composed of NiO nanoparticles attached to the surface of In2O3.The sensor exhibited excellent detection performance for formaldehyde in the environment of relative humidity of 33%and 75%,especially the response characteristic of the NiO-In2O3 composite structure sensor to formaldehyde was considerably better than that of the In2O3 sensor under the same test conditions,which was closely related to the catalytic effect of NiO and the heterogeneous structure formed between NiO and In2O3.The NiO-In2O3 composite structure sensor had a response value of 21.3 and 12.6 to 10 μL/L formaldehyde when the relative humidity was 33%and 75%at 200℃.The response/recovery time was 4/6 s and 7/10 s,and the limit of detection(LOD)was 1.2×10-7 μL/L and 4.1×10-5 μL/L respectively.Meanwhile,the sensor had excellent selectivity and long-term stability.This sensor showed a wide application prospect in the field of high-performance detection of low concentration of formaldehyde gas.

Objective To develop a traceable cancer hallmark ontology with terminology including gene mutation,cancer hallmark,and cell line for knowledge integration,standardization,correlation,and discovery.Methods The Ontology Development 101 and the current ontology development methods were employed to determine the content coverage,structural layers,reusable terms,and new terms of the cancer hallmark ontology.Taking colorectal cancer as a study case,we extracted the knowledge related with colorectal cancer hallmarks using text mining and text classification technology from PubMed,and then formalized the extracted knowledge into the cancer hallmark ontology.Moreover,we made use of existing cancer hallmark evidence in Catalogue of Somatic Mutations in Cancer and further semantic retrieval to discover new knowledge.Results The established cancer hallmark ontology comprised 9910 classes and 6138 instances,which realized the semantic representation of 2310 article abstracts about colorectal cancer and 26 pieces of evidence about genes and their cancer hallmarks.Compared with the Catalogue of Somatic Mutations in Cancer,new evidence for more genes associated with colorectal cancer hallmarks was found based on cancer hallmark ontology.Conclusion This study is of great significance to the research on the cancer pathogenesis at the molecular level,the revealing of specific roles of genes and mutations in the occurrence of cancer,and the rapid knowledge discovery of cancer hallmarks.