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.

Aim To elucidate whether Astragaloside Ⅳcould ameliorate pathological myocardial hypertrophy and fibrosis via the EGR1-SIRT1-PPARα-SCAD signa-ling pathway in TAC mice.Methods After randomi-zing mice into groups,the Sham+AS-Ⅳ group and TAC+AS-Ⅳ group were intragastrically administered 20 mg·kg-1AS-Ⅳ once daily,whereas the Sham+NS group and TAC+NS group were given equivalent saline.Six weeks post-surgery,an evaluation of cardiac function was conducted,heart weight index was compu-ted,morphological alterations in heart were noted,vari-ations in collagen and myocardial hypertrophy indexes were analyzed,ATP content,free fatty acid content,hydroxyproline content,SCAD expression,and enzyme activity were measured,and an initial investigation into the protein expression of EGR1-SIRT1-PPARα-SCAD in myocardial tissues was undertaken.Results After AS-Ⅳ intervention,the heart weight index of TAC mice decreased(P＜0.01),LVAWd,LVAWs,LVPWd and LVPWs values decreased(P＜0.01,P＜0.05),EF％and FS％values increased(all P＜0.01),myocardial hypertrophy markers and collagen area decreased,FFA content,HYP content and collagen expression de-creased(all P＜0.01),SCAD enzyme activity and ex-pression increased(P＜0.01,P＜0.05),and ATP content increased(P＜0.01).The expression of EGR1 protein decreased,and the expression of SIRT1 and PPARα protein increased(all P＜0.01).Conclu-sions AS-Ⅳ may improve fatty acid oxidation via the EGR1-SIRT1-PPARα-SCAD signaling pathway,thereby ameliorating pathological myocardial hypertrophy and fibrosis in TAC model mice.

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*

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

Objective The morphological and data characteristics of premature ventricular contraction(PVC)were obtained through dynamic electrocardiogram(DCG),and its correlation with new-onset major adverse cardiovascular events(MACE)was analyzed.Methods A total of 115 patients with PVC admitted to Huzhou First People's Hospital from January 2022 to January 2024 were retrospectively selected and divided into MACE group(n=31)and non-MACE group(n=84)according to the new-onset MACE.Collect the baseline data of patients,as well as DCG data such as the morphological and data characteristics of PVC.Collect the baseline data of patients,as well as DCG data such as the morphological and data characteristics of PVC.Multivariate Logistic regression was used to analyze the influencing factors of new-onset MACE in patients with PVC.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of influencing factors for the risk of new-onset MACE in patients with PVC.Results There were statistically significant differences in gender,disease duration,QRS wave duration,PVC origin,PVC load,and Lown classification between two groups of patients(P＜0.05).Multivariate Logistic regression analysis showed that QRS wave duration(OR=1.070),PVC origin(OR=6.840)and PVC load(OR=2.583)were independent risk factors for new-onset MACE in PVC patients(P＜0.05).The ROC curve showed that the area under the curve for predicting new-onset MACE in PVC patients with QRS wave duration,PVC origin,and PVC load were 0.791,0.750,and 0.917 respectively.The predictive value of PVC load was the highest.Conclusion QRS wave duration,PVC origin and PVC load are related to new-onset MACE in PVC patients,and PVC load has a good predictive effect on the risk of new-onset MACE in PVC patients.

Objective:To explore the influence of oligospermia(OS)on the detection of sperm DNA fragmentation index(DFI)by fluorescence method based on artificial intelligence(AI)recognition and flow cytometry-based sperm chromatin structure as-say(SCSA).Methods:We collected semen samples from 201 males,including 50 azoospermia(AS)patients as negative controls,90 OS patients(sperm concentration＞0 × 106/ml and＜15 × 106/ml),and 61 normal men(sperm concentration ≥15 ×106/ml).Then we subdivided the OS patients into a mild OS(sperm concentration ≥10 × 106/ml and＜15 × 106/ml),a moderate OS(sperm concentration ≥5 × 106/ml and＜10 × 106/ml)and a severe/extremely severe OS group(sperm concentration＞0 × 106/ml and＜5 × 106/ml),with 30 cases in each group,and compared the results of DFI detection between the AI fluorescence method and tradi-tional flow cytometry.Results:The DFI value detected by AI fluorescence method showed statistically significant difference from that detected by flow cytometry in the AS,moderate OS and severe/extremely severe OS groups(P＜0.01),the former even lower than the latter,but not in the normal control and the mild OS groups(P＞0.05).In the AS group,a dramatically lower rate of non-0 results was achieved by AI fluorescence method than by flow cytometry(8％vs 100％,P＜0.01).The DFI values detected by AI fluores-cence method exhibited a good linear correlation to those obtained by flow cytometry in the normal control and mild OS groups(β2=0.7470;R2=0.7180),but a poor linear correlation in the OS full-sample,moderate OS and severe/extremely severe OS groups(R2=0.3092;R2=0.3558;R2=0.2147).Conclusion:The AI fluorescence method has a higher specificity and is more suitable than flow cytometry for detection of sperm DFI in OS patients.The DFI values obtained by the two methods are consistent with sperm concen-tration ≥10 × 106/ml,but the accuracy of the results of detection may be affected with sperm concentration＞0 × 106/ml and＜10 × 106/ml.

Objective To explore the value of ventricular response(VR)on ambulatory electrocardio-graphy in evaluating atrial fibrillation conversion in patients with paroxysmal atrial fibrillation(PAF).Meth-ods Used 3-lead Holter monitor to collect complete data for more than 3 hours before atrial fibrillation con-version.The irregular heart rates recorded 5 minutes(VR0-5 min),60-65 minutes(VR60-65 min),and 120-125 minutes(VR120-125 min)prior to atrial fibrillation conversion were designated as VR values.The average heart rates of the 10 consecutive fastest and slowest heartbeats were calculated as the maximum and minimum VR values,respectively,while the average heart rate during the entire atrial fibrillation episode was taken as the mean VR value.Atrial fibrillation conversions occurring 06:00-21:59 were classified as daytime events,and those occurring 22:00-05:59(the following day)were classified as nighttime events.The effects of gender differences and circadian rhythm variations on VR values before atrial fibrillation conversion were analyzed.Additionally,the low-frequency power(LF),high-frequency power(HF),and their ratio(LF/HF)were ob-tained 5 minutes,60-65 minutes,and 120-125 minutes before atrial fibrillation conversion,and differences in LF,HF,and LF/HF at these time points were analyzed.Results The minimum VR0-5 min before cardioversion of atrial fibrillation was significantly higher than the minimum VR60-65 min and the minimum VR120-125 min(P＜0.05).The maximum VR0-5 min was significantly higher than VR120-125 min(P＜0.05).The minimum VR0-5 min in male group and female group was significantly higher than the minimum VR60-65 min and the minimum VR120-125min before atrial fibrillation reverted(P＜0.05).Of the 86 patients in this study,51 patients(59.30％)experienced daytime events,and the remaining 35 patients(40.70％)experienced nighttime e-vents.The data showed that the minimum VR0-5 min of daytime events was significantly higher than the mini-mum VR60-65 min and the minimum VR120-125 min(P＜0.05).There was no significant difference between the minimum VR0-5 min and the minimum VR60-s5 min and the minimum VR120-125 min(P＞0.05).One-way repeated analysis of variance showed that the longitudinal differences of HF,LF and LF/HF ratio before cardioversion of atrial fibrillation were not statistically significant(P＞0.05).Conclusion The increase of VR value may predict imminent cardioversion in PAF patients,particularly for those experiencing daytime events.