Zhusha Anshenwan is a classical traditional Chinese medicine （TCM） formula originating from LI Dongyuan's Treatise on the Differentiation of Endogenous and Exogenous Injuries （Nei Wai Shang Bian Huo Lun） of the Jin-Yuan period. It is composed of five medicinal ingredients： Cinnabaris （Zhusha）， Coptidis Rhizoma （Huanglian）， Angelicae Sinensis Radix （Danggui）， Rehmanniae Radix （Shengdihuang）， and Glycyrrhizae Radix et Rhizoma （Gancao）. Under the guidance of TCM theory， this formula is used to treat syndromes of disturbed spirit， including insomnia， palpitations， and anxiety， caused by hyperactivity of heart fire and deficiency of Yin-blood， and it also exerts auxiliary anticonvulsant effects in epilepsy and related conditions. However， the potential neurotoxicity， hepatotoxicity， and nephrotoxicity of its monarch drug， Cinnabaris （mainly composed of mercuric sulfide， HgS）， together with the risk of in vivo accumulation， have rendered its clinical application controversial， and it has not yet been formally included in the Pharmacopoeia of the People's Republic of China. In addition， restrictions imposed by the Minamata Convention on Mercury have led to an increasing shortage of natural medicinal Cinnabaris resources， making the evaluation of the efficacy and safety of synthetic Cinnabaris particularly urgent. This contradiction highlights the complexity of safety evaluation for traditional medicines. Existing studies indicate that Zhusha Anshenwan exhibits definite pharmacological activities in calming the mind， improving sleep， and regulating emotional disorders. Moreover， other components of the formula may exert antagonistic effects on the toxicity of Cinnabaris， and reports of severe mercury poisoning caused by standardized clinical use of this prescription are extremely rare. Research suggests that other ingredients in the compound formula， such as Rehmanniae Radix， Coptidis Rhizoma， and Glycyrrhizae Radix et Rhizoma， may effectively alleviate the hepatorenal toxicity of Cinnabaris through mechanisms including modulation of the gut microbiota， formation of mercury complexes， and direct protection of target organs. This article aims to systematically review the progress in pharmacodynamic research on Zhusha Anshenwan， to explore its mechanisms of action in depth， and to analyze the toxicokinetic characteristics and safety risks of Cinnabaris， as well as the scientific connotations of toxicity reduction and efficacy enhancement achieved through compound compatibility. In addition， it compares Zhusha Anshenwan with other commonly used sedative formulas， with the aim of providing a scientific basis and forward-looking perspectives for the safe and rational application and in-depth development of this classical prescription in a modern context， and of emphasizing the important value of holistic research on TCM compound formulas in addressing the challenges of single-component toxicity.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Brain’s neural activities encompass both periodic rhythmic oscillations and aperiodic neural fluctuations. Rhythmic oscillations manifest as spectral peaks of neural signals, directly reflecting the synchronized activities of neural populations and closely tied to cognitive and behavioral states. In contrast, aperiodic fluctuations exhibit a power-law decaying spectral trend, revealing the multiscale dynamics of brain neural activity. In recent years, researchers have made notable progress in studying brain aperiodic dynamics. These studies demonstrate that aperiodic activity holds significant physiological relevance, correlating with various physiological states such as external stimuli, drug induction, sleep states, and aging. Aperiodic activity serves as a reflection of the brain’s sensory capacity, consciousness level, and cognitive ability. In clinical research, the aperiodic exponent has emerged as a significant potential biomarker, capable of reflecting the progression and trends of brain diseases while being intricately intertwined with the excitation-inhibition balance of neural system. The physiological mechanisms underlying aperiodic dynamics span multiple neural scales, with activities at the levels of individual neurons, neuronal ensembles, and neural networks collectively influencing the frequency, oscillatory patterns, and spatiotemporal characteristics of aperiodic signals. Aperiodic dynamics currently boasts broad application prospects. It not only provides a novel perspective for investigating brain neural dynamics but also holds immense potential as a neural marker in neuromodulation or brain-computer interface technologies. This paper summarizes methods for extracting characteristic parameters of aperiodic activity, analyzes its physiological relevance and potential as a biomarker in brain diseases, summarizes its physiological mechanisms, and based on these findings, elaborates on the research prospects of aperiodic dynamics.

Purpose: This study evaluated a school-based mental health program within a psychiatry clerkship to enhance medical students’ competencies in mental health literacy, empathy, communication, and adaptability. The program aimed to bridge theoretical knowledge with practical skills through experiential learning in a real-world, community-based setting. Methods: The study utilized convenience sampling to select 32 medical students from the 2023–2024 psychiatry clerkship cohort. Four focus group discussions, each lasting 60–90 minutes, provided qualitative data, which were analyzed using reflexive thematic analysis in Atlas.ti (ATLAS.ti GmbH, Germany) to identify themes related to professional development. Results: Five key themes emerged, highlighting significant gains in context-sensitive communication, empathy, and mental health literacy specific to adolescent issues. The students reported increased clinical confidence, enhanced resilience through psychological techniques such mindfulness and motivational interviewing, and benefited from sustained engagement and peer support, fostering collaboration and stress management. Conclusion The school-based mental health program enhanced essential competencies in mental health literacy, empathy, communication, and practical skills for medical students. By integrating experiential learning into medical education, the program addressed training gaps, equipping future healthcare providers with the skills necessary for holistic and patient-centered mental healthcare across diverse clinical settings. The approach showed potential for broader applications in medical education to prepare students for comprehensive mental health support skills.

Purpose: This study evaluated a school-based mental health program within a psychiatry clerkship to enhance medical students’ competencies in mental health literacy, empathy, communication, and adaptability. The program aimed to bridge theoretical knowledge with practical skills through experiential learning in a real-world, community-based setting. Methods: The study utilized convenience sampling to select 32 medical students from the 2023–2024 psychiatry clerkship cohort. Four focus group discussions, each lasting 60–90 minutes, provided qualitative data, which were analyzed using reflexive thematic analysis in Atlas.ti (ATLAS.ti GmbH, Germany) to identify themes related to professional development. Results: Five key themes emerged, highlighting significant gains in context-sensitive communication, empathy, and mental health literacy specific to adolescent issues. The students reported increased clinical confidence, enhanced resilience through psychological techniques such mindfulness and motivational interviewing, and benefited from sustained engagement and peer support, fostering collaboration and stress management. Conclusion The school-based mental health program enhanced essential competencies in mental health literacy, empathy, communication, and practical skills for medical students. By integrating experiential learning into medical education, the program addressed training gaps, equipping future healthcare providers with the skills necessary for holistic and patient-centered mental healthcare across diverse clinical settings. The approach showed potential for broader applications in medical education to prepare students for comprehensive mental health support skills.

Purpose: This study evaluated a school-based mental health program within a psychiatry clerkship to enhance medical students’ competencies in mental health literacy, empathy, communication, and adaptability. The program aimed to bridge theoretical knowledge with practical skills through experiential learning in a real-world, community-based setting. Methods: The study utilized convenience sampling to select 32 medical students from the 2023–2024 psychiatry clerkship cohort. Four focus group discussions, each lasting 60–90 minutes, provided qualitative data, which were analyzed using reflexive thematic analysis in Atlas.ti (ATLAS.ti GmbH, Germany) to identify themes related to professional development. Results: Five key themes emerged, highlighting significant gains in context-sensitive communication, empathy, and mental health literacy specific to adolescent issues. The students reported increased clinical confidence, enhanced resilience through psychological techniques such mindfulness and motivational interviewing, and benefited from sustained engagement and peer support, fostering collaboration and stress management. Conclusion The school-based mental health program enhanced essential competencies in mental health literacy, empathy, communication, and practical skills for medical students. By integrating experiential learning into medical education, the program addressed training gaps, equipping future healthcare providers with the skills necessary for holistic and patient-centered mental healthcare across diverse clinical settings. The approach showed potential for broader applications in medical education to prepare students for comprehensive mental health support skills.

Purpose: This study evaluated a school-based mental health program within a psychiatry clerkship to enhance medical students’ competencies in mental health literacy, empathy, communication, and adaptability. The program aimed to bridge theoretical knowledge with practical skills through experiential learning in a real-world, community-based setting. Methods: The study utilized convenience sampling to select 32 medical students from the 2023–2024 psychiatry clerkship cohort. Four focus group discussions, each lasting 60–90 minutes, provided qualitative data, which were analyzed using reflexive thematic analysis in Atlas.ti (ATLAS.ti GmbH, Germany) to identify themes related to professional development. Results: Five key themes emerged, highlighting significant gains in context-sensitive communication, empathy, and mental health literacy specific to adolescent issues. The students reported increased clinical confidence, enhanced resilience through psychological techniques such mindfulness and motivational interviewing, and benefited from sustained engagement and peer support, fostering collaboration and stress management. Conclusion The school-based mental health program enhanced essential competencies in mental health literacy, empathy, communication, and practical skills for medical students. By integrating experiential learning into medical education, the program addressed training gaps, equipping future healthcare providers with the skills necessary for holistic and patient-centered mental healthcare across diverse clinical settings. The approach showed potential for broader applications in medical education to prepare students for comprehensive mental health support skills.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

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*