Disorders of consciousness (DOC) are pathological conditions characterized by severely suppressed brain function and the persistent interruption or loss of consciousness. Accurate diagnosis and evaluation of DOC are prerequisites for precise treatment. Traditional assessment methods are primarily based on behavioral scales, which are inherently subjective and rely on observable behaviors. Moreover, traditional methods have a high misdiagnosis rate, particularly in distinguishing minimally conscious state (MCS) from vegetative state/unresponsive wakefulness syndrome (VS/UWS). This diagnostic uncertainty has driven the exploration of objective, reliable, and efficient assessment tools. Among these tools, electroencephalography (EEG) has garnered significant attention for its non-invasive nature, portability, and ability to capture real-time neurodynamics. This paper systematically reviews the application of EEG biomarkers in DOC assessment. These biomarkers are categorized into 3 main types: resting-state EEG features, task-related EEG features, and features derived from transcranial magnetic stimulation-EEG (TMS-EEG). Resting-state EEG biomarkers include features based on spectrum, microstates, nonlinear dynamics, and brain network metrics. These biomarkers provide baseline representations of brain activity in DOC patients. Studies have shown their ability to distinguish different levels of consciousness and predict clinical outcomes. However, because they are not task-specific, they are challenging to directly associate with specific brain functions or cognitive processes. Strengthening the correlation between resting-state EEG features and consciousness-related networks could offer more direct evidence for the pathophysiological mechanisms of DOC. Task-related EEG features include event-related potentials, event-related spectral modulations, and phase-related features. These features reveal the brain’s responses to external stimuli and provide dynamic information about residual cognitive functions, reflecting neurophysiological changes associated with specific cognitive, sensory, or behavioral tasks. Although these biomarkers demonstrate substantial value, their effectiveness rely on patient cooperation and task design. Developing experimental paradigms that are more effective at eliciting specific EEG features or creating composite paradigms capable of simultaneously inducing multiple features may more effectively capture the brain activity characteristics of DOC patients, thereby supporting clinical applications. TMS-EEG is a technique for probing the neurodynamics within thalamocortical networks without involving sensory, motor, or cognitive functions. Parameters such as the perturbational complexity index (PCI) have been proposed as reliable indicators of consciousness, providing objective quantification of cortical dynamics. However, despite its high sensitivity and objectivity compared to traditional EEG methods, TMS-EEG is constrained by physiological artifacts, operational complexity, and variability in stimulation parameters and targets across individuals. Future research should aim to standardize experimental protocols, optimize stimulation parameters, and develop automated analysis techniques to improve the feasibility of TMS-EEG in clinical applications. Our analysis suggests that no single EEG biomarker currently achieves an ideal balance between accuracy, robustness, and generalizability. Progress is constrained by inconsistencies in analysis methods, parameter settings, and experimental conditions. Additionally, the heterogeneity of DOC etiologies and dynamic changes in brain function add to the complexity of assessment. Future research should focus on the standardization of EEG biomarker research, integrating features from resting-state, task-related, and TMS-EEG paradigms to construct multimodal diagnostic models that enhance evaluation efficiency and accuracy. Multimodal data integration (e.g., combining EEG with functional near-infrared spectroscopy) and advancements in source localization algorithms can further improve the spatial precision of biomarkers. Leveraging machine learning and artificial intelligence technologies to develop intelligent diagnostic tools will accelerate the clinical adoption of EEG biomarkers in DOC diagnosis and prognosis, allowing for more precise evaluations of consciousness states and personalized treatment strategies.

ObjectiveThe study explores the influence of voluntary wheel running on the behavioral abnormalities and the activation state of the hypothalamic-pituitary-adrenal (HPA) axis in autism spectrum disorder (ASD) rats through gut microbiota. MethodsSD female rats were selected and administered either400 mg/kg of valproic acid (VPA) solution or an equivalent volume of saline via intraperitoneal injection on day 12.5 of pregnancy. The resulting offspring were divided into 2 groups: the ASD model group (PASD, n=35) and the normal control group (PCON, n=16). Behavioral assessments, including the three-chamber social test, open field test, and Morris water maze, were conducted on postnatal day 23. After behavioral testing, 8 rats from each group (PCON, PASD) were randomly selected for serum analysis using enzyme-linked immunosorbent assay (ELISA) to measure corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) concentration, to evaluate the functional state of the HPA axis in rats. On postnatal day 28, the remaining 8 rats in the PCON group were designated as the control group (CON, n=8), and the remaining 27 rats in the PASD group were randomly divided into 4 groups: ASD non-intervention group (ASD, n=6), ASD exercise group (ASDE, n=8), ASD fecal microbiota transplantation group (FMT, n=8), and ASD sham fecal microbiota transplantation group (sFMT, n=5). The rats in the ASD group and the CON group were kept under standard conditions, while the rats in the ASDE group performed 6 weeks of voluntary wheel running intervention starting on postnatal day 28. The rats in the FMT group were gavaged daily from postnatal day 42 with 1 ml/100 g fresh fecal suspension from ASDE rats which had undergone exercise for 2 weeks, 5 d per week, continuing for 4 weeks. The sFMT group received an equivalent volume of saline. After the interventions were completed, behavioral assessments and HPA axis markers were measured for all groups. ResultsBefore the intervention, the ASD model group exhibited significantly reduced social ability, social novelty preference, spontaneous activity, and exploratory interest, as well as impaired spatial learning, memory, and navigation abilities compared to the normal control group (P<0.05). Serum concentration of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in the PASD group were significantly higher than those in the PCON group (P<0.05). Following 6 weeks of voluntary wheel running, the ASDE group showed significant improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, spatial learning, memory, and navigation skills compared to the ASD group (P<0.05), with a significant decrease in serum CORT concentration (P<0.05), and a downward trend in CRH and ACTH concentration. After 4 weeks of fecal microbiota transplantation in the exercise group, the FMT group showed marked improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, as well as spatial learning, memory, and navigation abilities compared to both the ASD and sFMT groups (P<0.05). In addition, serum ACTH and CORT concentration were significantly reduced (P<0.05), and CRH concentration also showed a decreasing trend. ConclusionExercise may improve ASD-related behaviors by suppressing the activation of the HPA axis, with the gut microbiota likely playing a crucial role in this process.

Osteoarthritis （OA） and stroke are common clinical diseases that reduce patients' quality of life and place a burden on families and society. Ruyi Zhenbaowan， a classic prescription in Tibetan medicine， have the functions of clearing heat， awakening the brain and opening orifices， relaxing tendons and promoting meridian circulation， and eliminating yellow water. Clinically， they are used to treat osteoarthritis， post-stroke sequelae， neuropathic pain， and other related conditions. Modern pharmacological studies have demonstrated their anti-inflammatory， analgesic， and nerve-repairing effects. However， current research remains insufficient regarding the appropriate indications， timing， and efficacy of this medicine in treating relevant diseases. To enhance clinicians' understanding of this medicine and promote its standardized and rational clinical use， a panel of national experts， including clinical specialists， Tibetan medicine practitioners， pharmacologists， and methodologists， formulated this consensus based on clinical experience and evidence-based practice. The Cochrane systematic review framework， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system， and the nominal group method were employed to generate seven graded recommendations and 19 consensus-based suggestions. These recommendations clearly define the key points in the clinical application of Ruyi Zhenbaowan， including therapeutic indications， dosage and administration， treatment duration， and medication safety. The consensus specifically addresses the clinical efficacy， appropriate timing of administration， dosage strategies， treatment cycles， and combination medication strategies for treating osteoarthritis and stroke and provides an overview of safety considerations. The aim is to provide standardized guidance for hospitals and healthcare institutions nationwide to ensure the rational application of Ruyi Zhenbaowan in the treatment of osteoarthritis and stroke， reduce medication-related risks， and further leverage its clinical advantages. This consensus has been approved and issued by the China Association of Chinese Medicine， with the standard number GS/CACM 369-2024.

ObjectiveThe aim of this study was to investigate the prophylactic effects of caloric restriction (CR) on lipopolysaccharide (LPS)-induced septic cardiomyopathy (SCM) and to elucidate the mechanisms underlying the cardioprotective actions of CR. This research aims to provide innovative strategies and theoretical support for the prevention of SCM. MethodsA total of forty-eight 8-week-old male C57BL/6 mice, weighing between 20-25 g, were randomly assigned to 4 distinct groups, each consisting of 12 mice. The groups were designated as follows: CON (control), LPS, CR, and CR+LPS. Prior to the initiation of the CR protocol, the CR and CR+LPS groups underwent a 2-week acclimatization period during which individual food consumption was measured. The initial week of CR intervention was set at 80% of the baseline intake, followed by a reduction to 60% for the subsequent 5 weeks. After 6-week CR intervention, all 4 groups received an intraperitoneal injection of either normal saline or LPS (10 mg/kg). Twelve hours post-injection, heart function was assessed, and subsequently, heart and blood samples were collected. Serum inflammatory markers were quantified using enzyme-linked immunosorbent assay (ELISA). The serum myocardial enzyme spectrum was analyzed using an automated biochemical instrument. Myocardial tissue sections underwent hematoxylin and eosin (HE) staining and immunofluorescence (IF) staining. Western blot analysis was used to detect the expression of protein in myocardial tissue, including inflammatory markers (TNF-α, IL-9, IL-18), oxidative stress markers (iNOS, SOD2), pro-apoptotic markers (Bax/Bcl-2 ratio, CASP3), and SIRT3/SIRT6. ResultsTwelve hours after LPS injection, there was a significant decrease in ejection fraction (EF) and fractional shortening (FS) ratios, along with a notable increase in left ventricular end-systolic diameter (LVESD). Morphological and serum indicators (AST, LDH, CK, and CK-MB) indicated that LPS injection could induce myocardial structural disorders and myocardial injury. Furthermore, 6-week CR effectively prevented the myocardial injury. LPS injection also significantly increased the circulating inflammatory levels (IL-1β, TNF-α) in mice. IF and Western blot analyses revealed that LPS injection significantly up-regulating the expression of inflammatory-related proteins (TNF-α, IL-9, IL-18), oxidative stress-related proteins (iNOS, SOD2) and apoptotic proteins (Bax/Bcl-2 ratio, CASP3) in myocardial tissue. 6-week CR intervention significantly reduced circulating inflammatory levels and downregulated the expression of inflammatory, oxidative stress-related proteins and pro-apoptotic level in myocardial tissue. Additionally, LPS injection significantly downregulated the expression of SIRT3 and SIRT6 proteins in myocardial tissue, and CR intervention could restore the expression of SIRT3 proteins. ConclusionA 6-week CR could prevent LPS-induced septic cardiomyopathy, including cardiac function decline, myocardial structural damage, inflammation, oxidative stress, and apoptosis. The mechanism may be associated with the regulation of SIRT3 expression in myocardial tissue.

In recent years, with the large-scale use of plastic products, the degree of plastic pollution has increased, becoming a serious global problem. Microplastics and nanoplastics (MNPs), as emerging environmental pollutants, are widely found in organisms and the environment. These plastic particles enter the human body through 3 exposure pathways: breathing, the food chain’s bioaccumulation and transfer, and skin contact, thereby exerting toxic effects. The physical attributes of MNPs, including their shape, size, and surface characteristics, are not static but rather undergo dynamic transformations in response to changing environmental conditions. These changes can significantly influence their behavior and interactions within different ecosystems. When considering MNPs as carriers of chemicals, two primary mechanisms can be distinguished. (1) MNPs have the capacity to adsorb pollutants from their surrounding environment. These pollutants may encompass a wide range of substances, such as heavy metals, organic compounds, and other contaminants that are commonly found in water, soil, or air. (2) MNPs may also carry chemical agents that are artificially introduced during their commercial production process. For example, flame retardants and pigments are often added to plastics to enhance their performance or appearance. These artificially added chemicals can remain associated with MNPs throughout their lifecycle and may contribute to their overall toxicological impact. Cardiovascular diseases (CVDs) are a general term for diseases of the heart, arteries, veins, and capillaries, and are one of the main causes of disability and death. CVDs have higher incidence, mortality, and recurrence rates, and more complications, which reduce the quality of life and happiness of patients, the phenomenon is gradually showing a trend of early onset, therefore early-stage prevention for CVDs is of critical importance. This article reviews the properties of MNPs and their potential threats to the cardiovascular system, aiming to explore how MNPs cause CVDs through certain physiological effects, toxicity mechanisms, and related pathways. Our review primarily focus on elucidating several critical mechanisms through which MNPs exert their adverse effects. Specifically, the review examines how the enhancement of oxidative stress can trigger the expression of pro-inflammatory factors, which in turn leads to the formation of a chronic inflammatory microenvironment within biological systems. Additionally, MNPs possess the capacity to adsorb toxic metals and organic substances from their surroundings. Furthermore, the review summarizes that sewage irrigation and atmospheric deposition are significant factors contributing to the co-pollution of heavy metals with MNPs in environmental settings. The interaction between heavy metals and MNPs has been shown to have detrimental effects on agricultural productivity, as it can inhibit crop growth and simultaneously increase the absorption rate of heavy metals in plants. When these contaminated plants enter the food chain, the accumulated heavy metals can ultimately be ingested by humans. This process poses a potential risk for inducing acute coronary syndrome and other CVDs, thereby underscoring the importance of understanding and mitigating the impact of MNPs on human health. In addition, our review also gives examples of the long-term effects of MNPs on cardiovascular function and the adverse consequences such as arrhythmia and atherosclerosis, the limitations of the current studies of MNPs affecting cardiovascular system health and future directions are also explored.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.

Research on IgG4-related disease (IgG4-RD), an autoimmune condition recognized to be a unique disease entity only two decades ago, has processed from describing patients' symptoms and signs to summarizing its critical pathological features, and further to investigating key pathogenic mechanisms. Challenges in gaining a better understanding of the disease, however, stem from its relative rarity-potentially attributed to underrecognition-and the absence of ideal experimental animal models. Recently, with the development of various high-throughput techniques, "omics" studies at different levels (particularly the single-cell omics) have shown promise in providing detailed molecular features of IgG4-RD. While, the application of omics approaches in IgG4-RD is still at an early stage. In this paper, we review the current progress of omics research in IgG4-RD and discuss the value of machine learning methods in analyzing the data with high dimensionality.
Humans ; Immunoglobulin G4-Related Disease/metabolism* ; Immunoglobulin G/metabolism* ; Machine Learning ; Animals ; Proteomics/methods*

Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

OBJECTIVE: To analyze the effect of COVID-19 infection on the mobilization and collection of autologous peripheral blood stem cells in patients with multiple myeloma. METHODS: The general baseline data, treatment factors before mobilization collection, collection status, and treatment overview after collection of autologous peripheral blood stem cells at Beijing Chaoyang Hospital affiliated with Capital Medical University from January 1, 2020 to July 15, 2023 were analyzed. RESULTS: 269 patients underwent mobilization and collection of autologous peripheral blood stem cells. Among them, 32 cases with COVID-19 infection history (COVID-19 group) and 237 cases without COVID-19 infection history (non-COVID-19 group). In the COVID-19 group, 17 cases were treated with chemotherapy (etoposide)+G-CSF, and 15 cases were treated with plerixafor +G-CSF. In the non-COVID-19 group, 214 cases were treated with chemotherapy +G-CSF, 17 cases were treated with plerixafor +G-CSF, and 6 cases were treated with chemotherapy + plerixafor +G-CSF. The number of CD34⁺ cells, collection success rate, and excellence rate in the COVID-19 group and the non-COVID-19 group were ［5.52 (0.94-26.87) vs 4.80 (0.53-37.20)］×10⁶/kg (P =0.610), (93.8% vs 85.2%) (P =0.275), (62.5% vs 49.4%) (P =0.190), respectively. Among 113 patients mobilized with etoposide +G-CSF, the number of CD34⁺ cells, success rate, and excellence rate collected from COVID-19 infection (17 cases) and non-COVID-19 infection (96 cases) were ［7.54 (2.66-26.87) vs 7.78 (2.26-37.20)］×10⁶/kg (P =0.847), (100.0% vs 100.0%) (no P value), (82.4% vs 86.5%) (P =0.655), respectively. Among 32 patients mobilized by plerixafor +G-CSF, the number of CD34⁺ cells, success rate and excellence rate of COVID-19 infection (15 cases) and non-COVID-19 infection (17 cases) were ［3.82 (0.94-7.27) vs 4.11 (0.53-9.05)］×10⁶/kg (P =0.821), (86.7% vs 88.2%) (P =0.893), (40.0% vs 35.3%) (P =0.784), respectively. In 32 patients with COVID-19 infection, the number of CD34⁺ cells collected by etoposide +G-CSF (17 cases) and plerixafor +G-CSF (15 cases), as well as the success rate and excellence rate were ［7.54 (2.66-26.87) vs 3.82(0.94-7.27)］×10⁶/kg (P =0.004), (100.0% vs 86.7%) (P =0.120), (82.4% vs 40.0%) (P =0.014), respectively. By 2023.7.31, 232 patients (86.2%, 232/269) had received transplantation, including 24 patients in the COVID-19 group and 208 patients in the non-COVID-19 group. The median number of CD34⁺ cells infused in the two groups was ［3.67 (2.50-13.44) vs 3.11(1.12-19.89)］×10⁶/kg (P =0.058), the median days of neutrophil engraftment ［11(9-13) vs 11(9-17)］ (P =0.674), the median days of platelet engraftment ［11(0-23), 12(0-43)］ (P =0.279), respectively. CONCLUSION The history of COVID-19 infection did not affect the PBSC mobilization, collection and transplantation of patients with myeloma. In patients with COVID-19 infection, the results of chemotherapy mobilization with etoposide seems to be better than that of plerixafor mobilization, but further research is needed to clarify.
Humans ; COVID-19/complications* ; Multiple Myeloma/complications* ; Hematopoietic Stem Cell Mobilization ; Transplantation, Autologous ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Peripheral Blood Stem Cell Transplantation ; SARS-CoV-2 ; Middle Aged ; Peripheral Blood Stem Cells ; Male ; Female ; Cyclams ; Benzylamines

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points