1.Mitogen-activated protein kinase signaling pathway regulates the development of osteoarthritis:guiding targeted therapy with traditional Chinese medicine
Hao LI ; Hongcheng TAO ; Ping ZENG ; Jinfu LIU ; Qiang DING ; Chicheng NIU ; Kai HUANG ; Hongyu KANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1476-1485
BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.
2.Physical exercise improves physical function in burn patients:a systematic review and meta-analysis
Qiang CHEN ; Wenjuan WU ; Shuhua JIANG ; Da HUANG
Chinese Journal of Tissue Engineering Research 2026;30(5):1269-1281
OBJECTIVE:Some studies have shown that physical exercise can effectively improve knee extensor strength and cardiorespiratory function in burn patients;some studies have also shown that physical exercise is not effective in improving respiratory function in burn patients.Improvement effects of physical exercise on physical functions(muscle function,walking function,cardiopulmonary function,and lean body mass)of burn patients were evaluated by a systematic evaluation and meta-analysis.METHODS:Based on databases including Web of Science,PubMed,Embase,Cochrane Library,CNKI,WanFang,and the Chinese Biomedical Database,literature on the improvement of physical function in burn patients through physical exercise was searched using subject headings and free terms.With muscle function,walking ability,cardiopulmonary function,and lean body mass as the primary outcome measures,a meta-analysis was conducted to compare the efficacy of physical exercise with traditional physical therapy or conventional care methods.RESULTS:A total of 38 papers were included,of which 26 papers were included in the meta-analysis,involving 1 658 patients.Meta-analysis results showed that:(1)Physical exercise significantly enhances the knee extensor strength of the dominant leg in burn patients(mean difference[MD]=8.34,95%confidence interval[CI]:6.95-9.72,P<0.000 01),increases quadriceps strength,peak oxygen uptake,forced vital capacity and maximum ventilation volume in 1 second,and resting heart rate(standardized mean difference[SMD]=4.41,95%CI:2.52-6.30,P<0.000 01;MD=4.91,95%CI:3.52-6.29,P<0.000 01;MD=5.86,95%CI:0.09-11.63,P=0.05;MD=6.90,95%CI:2.93-10.87,P=0.000 7;MD=5.03,95%CI:1.45-8.61,P=0.006),and improves the 6-minute walking distance,gait parameters,and total lean body mass(MD=45.29,95%CI:24.7-65.89,P<0.0001;SMD=7.84,95%CI:6.05-9.63,P<0.000 01;MD=2.47,95%CI:2.01-2.93,P<0.000 01).(2)The subgroup analysis results indicated that the improvement in knee extensor strength of the dominant leg may be better in children than in adults and better in the extra-heavy group than in the heavy group.Improvement in the 6-minute walking distance is better in children than in adults,and higher degree of burn indicates better improvement effects,with no difference from the control group for<12 weeks.Peak oxygen uptake may be better in adults and severe burn groups than in children and moderate burn groups,resistance combined with aerobic exercise modalities may be better than aerobic exercise alone,and exercise duration>60 minutes may be better than<60 minutes.CONCLUSION:Physical activity is effective in improving physical function in burn patients,as evidenced by improvements in muscle strength,walking ability,cardiorespiratory fitness,and lean body mass.The quality of evidence recommended for all indicator results is moderate or below,with imprecision and inconsistency being the main factors for downgrading.Therefore,more high-quality randomized controlled trials are needed in the future to verify the reliability of the results.
3.Application advances, ethical dilemmas, and future directions of large language models in lung cancer diagnosis and treatment
Zhizhen REN ; Yufan XI ; Xu ZHU ; Yijie LUO ; Geting HUANG ; Junqiao SONG ; Xiuyuan XU ; Nan CHEN ; Qiang PU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(03):353-362
Lung cancer is a leading cause of cancer-related morbidity and mortality worldwide. Coupled with the substantial workload, the clinical management of lung cancer is challenged by the critical need to efficiently and accurately process increasingly complex medical information. In recent years, large language models (LLMs) technology has undergone explosive development, demonstrating unique advantages in handling complex medical data by leveraging its powerful natural language processing capabilities, and its application value in the field of lung cancer diagnosis and treatment is continuously increasing. The paper systematically analyzes that the exceptional potential of LLMs in lung cancer auxiliary diagnosis, tumor feature extraction, automatic staging, progression/outcome analysis, treatment recommendations, medical documentation generation, and patient education. However, they face critical technical and ethical challenges including inconsistent performance in complex integrated decision-making (e.g., TNM staging, personalized treatment suggestions) and "black box" opacity issues, along with dilemmas such as training data biases, model hallucinations, data privacy concerns, and cross-lingual adaptation challenges ("data colonization"). Future directions should prioritize constructing high-quality multimodal corpora specific to lung cancer, developing interpretable and compliant specialized models, and achieving seamless integration with existing clinical workflows. Through dual drivers of technological innovation and ethical standardization, LLMs should be prudently advanced for holistic lung cancer management processes, ultimately promoting efficient, standardized, and personalized diagnosis and treatment practices.
4.Analyses of the epidemiological characteristics of multiple pathogens in people aged 14 years and above with acute respiratory infection in Huangpu District of Shanghai from 2015 to 2024
Yun ZHANG ; Yinzi CHEN ; Zhenzi ZUO ; Yu WANG ; Fujie SHEN ; Yuliang HUANG ; Qiang GAO ; Chenyan JIANG ; Yijun WANG
Shanghai Journal of Preventive Medicine 2026;38(2):116-121
ObjectiveTo analyze the epidemiological characteristics of 8 major respiratory pathogens in influenza-like illness (ILI) cases with acute respiratory infections at fever clinics in Huangpu District, Shanghai from 2015 to 2024, and to provide a scientific basis for the prevention and treatment of respiratory diseases. MethodsA retrospective study was conducted in Huangpu District. Individuals meeting the case definition of ILI from 2015 to 2024 was registered. Their nasopharyngeal swabs were collected for pathogen detection. A total of 8 respiratory viruses were tested, including Influenza A virus (Flu A), Influenza B virus (Flu B), adenovirus (ADV), enterovirus/human rhinovirus (EV/HRV), human parainfluenza virus (HPIV), human coronavirus (HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV). ResultsFrom 2015 to 2019, a total of 344 ILI cases were tested, of which 192 out of 344 cases (55.81%) were tested positive for single respiratory pathogen. From 2023 to 2024, 1 557 ILI cases were tested, with 572 out of 1 557 cases (36.74%) being positive for single pathogen. From 2023 to 2024, the positive rate of single pathogen in ILI cases was significantly lower than that in 2015‒2019 (χ2=42.66, P<0.001). Specifically, the positive rate of Flu A (χ2=74.43, P<0.001) decreased, while that of HPIV (χ2=8.66, P=0.003) increased, both with statistically significant differences. According to the seasonal pattern, the epidemic intensity of Flu A decreased in summer, while that of HPIV increased in summer and autumn. Demographic results showed statistically significant differences in the positive rates of EV/HRV between genders (χ2=22.38, P<0.001), with males exhibiting a higher positive rate than females. No statistically significant differences were identified in the positive rates of single pathogen among different age groups (χ2=4.42, P=0.110). Nevertheless, statistically significant differences were noted when comparing the positive rates of EV/HRV, Flu A, Flu B and HPIV across different age groups (P<0.05). EV/HRV was more commonly detected in the 15‒<25 age group (10.93%), while Flu A and HPIV had the highest positive rates in the ≥60 age group (21.24% and 4.77%). Flu B had the highest positive rate in the 25‒<60 age group (11.26%). 52.63% of cases with co-infections occurred during winter, with the primary pathogens involved being EV/HRV (9 cases) and HCoV (6 cases). The most prevalent combination of co-infection was Flu A with EV/HRV. ConclusionThe prevalence of respiratory pathogens among ILI cases from 2023 to 2024 exhibited notable fluctuations compared to that from 2015 to 2019. Therefore, influenza surveillance should be strengthened, and attention should also be paid to the prevalence of respiratory pathogens such as HPIV. These findings have profound implications for future research, surveillance, vaccine planning, and public health policy making.
5.Mitogen-activated protein kinase signaling pathway regulates the development of osteoarthritis:guiding targeted therapy with traditional Chinese medicine
Hao LI ; Hongcheng TAO ; Ping ZENG ; Jinfu LIU ; Qiang DING ; Chicheng NIU ; Kai HUANG ; Hongyu KANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1476-1485
BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.
6.Physical exercise improves physical function in burn patients:a systematic review and meta-analysis
Qiang CHEN ; Wenjuan WU ; Shuhua JIANG ; Da HUANG
Chinese Journal of Tissue Engineering Research 2026;30(5):1269-1281
OBJECTIVE:Some studies have shown that physical exercise can effectively improve knee extensor strength and cardiorespiratory function in burn patients;some studies have also shown that physical exercise is not effective in improving respiratory function in burn patients.Improvement effects of physical exercise on physical functions(muscle function,walking function,cardiopulmonary function,and lean body mass)of burn patients were evaluated by a systematic evaluation and meta-analysis.METHODS:Based on databases including Web of Science,PubMed,Embase,Cochrane Library,CNKI,WanFang,and the Chinese Biomedical Database,literature on the improvement of physical function in burn patients through physical exercise was searched using subject headings and free terms.With muscle function,walking ability,cardiopulmonary function,and lean body mass as the primary outcome measures,a meta-analysis was conducted to compare the efficacy of physical exercise with traditional physical therapy or conventional care methods.RESULTS:A total of 38 papers were included,of which 26 papers were included in the meta-analysis,involving 1 658 patients.Meta-analysis results showed that:(1)Physical exercise significantly enhances the knee extensor strength of the dominant leg in burn patients(mean difference[MD]=8.34,95%confidence interval[CI]:6.95-9.72,P<0.000 01),increases quadriceps strength,peak oxygen uptake,forced vital capacity and maximum ventilation volume in 1 second,and resting heart rate(standardized mean difference[SMD]=4.41,95%CI:2.52-6.30,P<0.000 01;MD=4.91,95%CI:3.52-6.29,P<0.000 01;MD=5.86,95%CI:0.09-11.63,P=0.05;MD=6.90,95%CI:2.93-10.87,P=0.000 7;MD=5.03,95%CI:1.45-8.61,P=0.006),and improves the 6-minute walking distance,gait parameters,and total lean body mass(MD=45.29,95%CI:24.7-65.89,P<0.0001;SMD=7.84,95%CI:6.05-9.63,P<0.000 01;MD=2.47,95%CI:2.01-2.93,P<0.000 01).(2)The subgroup analysis results indicated that the improvement in knee extensor strength of the dominant leg may be better in children than in adults and better in the extra-heavy group than in the heavy group.Improvement in the 6-minute walking distance is better in children than in adults,and higher degree of burn indicates better improvement effects,with no difference from the control group for<12 weeks.Peak oxygen uptake may be better in adults and severe burn groups than in children and moderate burn groups,resistance combined with aerobic exercise modalities may be better than aerobic exercise alone,and exercise duration>60 minutes may be better than<60 minutes.CONCLUSION:Physical activity is effective in improving physical function in burn patients,as evidenced by improvements in muscle strength,walking ability,cardiorespiratory fitness,and lean body mass.The quality of evidence recommended for all indicator results is moderate or below,with imprecision and inconsistency being the main factors for downgrading.Therefore,more high-quality randomized controlled trials are needed in the future to verify the reliability of the results.
7.Clinical efficacy of endoscopic endonasal dorsum sellae and posterior clinoid process resection combined with pituitary hemi-transposition for pan-sellar area lesions
Tabengwa GEORGE TAKURA ; Qiang XIE ; Huaichao ZHANG ; Shuang LIU ; Jinlong HUANG ; Pin CHEN ; Zeyang LI ; Xiaobiao ZHANG ; Tao XIE
Chinese Journal of Clinical Medicine 2026;33(3):507-515
Objective To explore the clinical efficacy and safety of endoscopic endonasal dorsum sellae and posterior clinoid process resection combined with pituitary hemi-transposition in the treatment of pan-sellar area lesions. Methods Clinical data from 57 patients with pan sellar diseases who underwent endoscopic transnasal resection of the posterior clinoid process combined with lateral pituitary displacement surgery in the neurosurgery department of Zhongshan Hospital, Fudan University from January 2019 to January 2025 were collected, and their clinical surgical characteristics and prognosis were analyed. Results A total of 57 patients with pan-sellar area lesions were included in this study, comprising 27 craniopharyngiomas, 7 giant suprasellar pituitary adenomas, 7 chordomas, 6 chondrosarcomas, 5 diaphragma sellae/dorsum sellae meningiomas, and 5 rare lesions. All procedures were completed successfully, and gross total or near-total resection was achieved in all patients. No new neurovascular complications occurred intraoperatively. The follow-up duration ranged from 3 to 24 months. New postoperative anterior pituitary insufficiency occurred in 3 patients (5.3%), and new posterior pituitary insufficiency requiring long-term hormone replacement therapy occurred in 4 patients (7.0%). No additional pituitary dysfunction was observed in the remaining patients. Cerebrospinal fluid rhinorrhea occurred in 1 patient (1.8%) and was successfully repaired. Intracranial infection occurred in 3 patients (5.3%) and resolved after medical treatment. Conclusion Endoscopic resection of the posterior clinoid process combined with lateral displacement of the pituitary gland can effectively expand the surgical space, while repositioning the pituitary gland can reduce the extent of skull base defects. In addition, the risk of pituitary dysfunction caused by lateral displacement of the pituitary gland is relatively low.
8.Comparative analysis of the characteristics of imported malaria cases in Nanning City in 2024 and the same period of the previous year
Shu-lin WEI ; Zhi-qiang QU ; Yuan-yuan LUO ; Yan-cui HUANG ; Shu-qin DIAO ; Xue LI ; Sheng-long YANG ; Xiao-yu HUANG ; Mi-fang LUO
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):81-84
Objective To investigate the epidemiological characteristics of malaria and provide a basis for developing improved prevention and control measures. Methods Data were obtained from the Chinese Disease Prevention and Control Information System. Malaria surveillance data for Nanning City from January 1,2023, to December 31,2024, were exported from the Infectious Disease Reporting Information Management Subsystem. The characteristics of the two groups of malaria cases were compared. Results A total of 103 imported malaria cases were reported in Nanning City in 2024, representing a 38.32% decrease compared with the same period of the previous year. No statistically significant difference were observed between cases reported in 2023 and 2024 in terms of average age, gender ratio, proportion of parasite species, and monthly reporting distribution;however, statistically significant differences were found in the proportion of reporting areas and current residence areas(χ2= 13.572 and 10.355, respectively; P = 0.001 and 0.035, respectively). The proportion of cases reported in Shanglin County and the proportion of cases residing in Shanglin County were both lower than those during the same period of the previous year. Conclusions The high aggregation of imported malaria cases in Nanning City has decreased. Medical institutions in areas other than Shanglin County should strengthen their vigilance against malaria.
9.Effect of semaglutide on myocardial injury induced by coronary microembolization in rats via regulation of the AMPK/NLRP3 signaling pathway
Yangchun LIU ; Huafeng YANG ; Wanzhong HUANG ; Yuan HUANG ; Qiang SU
Acta Universitatis Medicinalis Anhui 2026;61(8):1424-1430
ObjectiveTo explore the effect of semaglutide (SEM) on myocardial injury induced by coronary microembolization (CME) in rats via the adenosine monophosphate-activated protein kinase (AMPK)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathway. MethodsThirty-two rats were randomly assigned to four groups (n=8): the Sham group, the CME group, the CME + SEM group, and the CME + SEM + Compound C (CC, a specific inhibitor of AMPK) group. The CME model was established by injecting microembolic spheres into the left ventricle, while the Sham group received an equal volume of normal saline via left ventricular injection. The CME + SEM group received subcutaneous injections of SEM (1 mg/kg, once weekly) for 4 weeks before CME induction. For the CME + SEM + CC group, rats were treated with SEM for 4 weeks, followed by an intravenous injection of CC (0.25 mg/kg dissolved in sterile normal saline) 30 minutes before CME modeling. 24 hours post-modeling, all groups underwent the following assessments: echocardiography to evaluate cardiac function, HE staining for myocardial histopathological analysis, Heidenhain staining to quantify the microinfarct area, ELISA to determine serum cardiac troponin T (cTnT) levels, and Western blot analysis to detect the expression of proteins related to the AMPK/NLRP3 pathway in cardiac tissues. ResultsCompared with the Sham group, the CME group showed significantly deteriorated cardiac function, elevated serum cTnT levels, and a marked increase in myocardial microinfarct area (P<0.05). Compared with the CME group, the CME + SEM group exhibited significant improvements in cardiac function, decreased cTnT levels, and a remarkable reduction in myocardial microinfarct area (P<0.05). Histopathological analysis revealed a normal myocardial structure in the Sham group without infarction. In contrast, the CME group showed disorganized myocardial arrangement, accompanied by nuclear fragmentation and karyolysis. In the CME + SEM group, myocardial degeneration, edema and inflammatory cell infiltration were obviously alleviated. Compared with Sham group, the protein ratio of p-AMPK/AMPK slightly increased in the CME group, while the protein levels of NLRP3, gasdermin D-N domain (GSDMD-N), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 p20, interleukin(IL)-1β , and IL-18 were markedly upregulated (P<0.05). Notably, compared to the CME group, the CME + SEM group had a further elevated p-AMPK/AMPK ratio, while the protein levels of NLRP3, GSDMD-N, ASC, caspase-1 p20, IL-1β and IL-18 were markedly decreased (P<0.05). ConclusionSEM significantly ameliorates CME-induced myocardial injury, and its mechanism of action may be closely associated with promoting AMPK phosphorylation, inhibiting NLRP3 inflammasome-mediated inflammatory responses, and suppressing pyroptosis.
10.Applications of Brain-heart Interaction in Consciousness State Assessment
Jun-Yi WANG ; Hai-Qing YU ; Qiang-Fan MENG ; Yong-Zhi HUANG ; Min-Peng XU ; Dong MING
Progress in Biochemistry and Biophysics 2026;53(10):2767-2785
Consciousness, which underpins human perception, cognition, and behavioural responses, has long been a major focus of neuroscience and medicine. Alterations in consciousness occur not only during reversible processes such as sleep and anaesthesia, but also in pathological conditions, including disorders of consciousness (DOC) and brain injury. With recent advances in the synchronized acquisition and analysis of multimodal physiological signals, such as electroencephalography (EEG) and electrocardiography (ECG), the dynamic interactions between the heart and brain have become increasingly apparent. A growing body of evidence indicates that heart-brain interactions are closely associated with the maintenance and transition of consciousness states, offering a novel perspective for elucidating their underlying mechanisms and supporting relevant clinical assessments. Current approaches to heart-brain interaction analysis for consciousness-state assessment can be broadly grouped into three categories: ECG-based methods, EEG-based methods, and heart-brain coupling analysis. These approaches characterize heart-brain interactions during changes in consciousness from the complementary perspectives of autonomic regulation, cortical interoceptive processing, and cross-system information transfer, respectively. Nevertheless, this field remains at an early stage. Most studies have focused on a single experimental context or a fixed analytical method, with insufficient systematic consideration of the applicability and limitations of different approaches. Moreover, the mechanisms underlying the emergence and alteration of consciousness remain incompletely understood. Accordingly, this review examines heart-brain interaction methods employed in recent consciousness-state assessment studies in accordance with progressively deeper analytical perspectives, and systematically evaluates the advantages and limitations of these methods across distinct consciousness-related conditions. Heart rate variability (HRV) is one of the classical ECG-based indices used to investigate heart-brain interactions. It refers to fluctuations in consecutive interbeat intervals over a specified time period and is regarded as a physiological measure of autonomic nervous system regulation that may indirectly reflect the strength of heart-brain interactions. Depending on the analytical dimension, HRV analysis is commonly divided into time-domain, frequency-domain, and complexity-index analyses. These approaches characterize autonomic activity in terms of temporal fluctuations, the distribution of frequency components, and nonlinear dynamical properties, respectively. Although extensive research supports their physiological interpretation, they cannot characterize directional interactions from the heart to the brain. Among EEG-based methods for heart-brain interaction analysis, EEG activity directly related to cardiac fluctuations has received particular attention. One of the most widely used measures is the heartbeat-evoked potential (HEP). HEP-based approaches are considered to directly reflect the capacity of the cerebral cortex to process cardiac afferent signals and may be especially advantageous for characterizing rapidly changing consciousness levels, such as those observed during sleep. However, they do not comprehensively capture dynamic bidirectional information exchange between the brain and heart and are susceptible to cardiac artefacts, respiration, and variation in preprocessing procedures. Heart-brain coupling analysis quantifies functional associations between ECG and EEG through cross-system interaction measures, thereby assessing dynamic interactions between the heart and brain. It emphasizes information transfer, feedback regulation, and cross-timescale coordination between the two systems, offering a more comprehensive perspective for investigating changes in consciousness during sleep, anaesthesia, and DOC. However, the neurophysiological mechanisms and physiological interpretation of individual computational indices have not yet been fully established, and the robustness of their results and their potential for clinical generalization require further validation. Finally, this review summarizes the commonalities and differences among the three classes of methods across research domains involving different consciousness states. It further argues that heart-brain interaction research requires deeper investigation at both the mechanistic level of consciousness and the level of clinical application. Current challenges and key issues are identified, and future directions and feasible pathways for heart-brain interaction research are discussed, with the aim of providing new perspectives for researchers in related fields.


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