OBJECTIVE To investigate the effects and mechanisms of Buyang huanwu decoction （BYHWD） and its active fractions in ameliorating non-alcoholic fatty liver disease. METHODS BYHWD and its effective fractions obtained through ethanol precipitation， as well as 30% ethanol， 50% ethanol， and 75% ethanol fractions （namely， the CC effective fraction， 30YC effective fraction， 50YC effective fraction， and 75YC effective fraction）， were prepared. These preparations were administered to rats via intragastric administration to prepare corresponding drug-containing serum （blank serum and simvastatin-containing serum were prepared using the same protocol）. Human L02 hepatocytes were divided into control group， model group， simvastatin-containing serum group， BYHWD-containing serum group， CC-containing serum group， 30YC-containing serum group， 50YC-containing serum group， and 75YC-containing serum group. Except for the control group， other groups were given 0.2 mol/L oleic acid for 24 h to induce a lipid accumulation model， and then intervened with 20% drug-containing serum/blank serum for 24 h. The lipid deposition in cells was observed， and the proportion of lipid droplet area was calculated； the levels of triglycerides （TG） and indicators of oxidative stress [malondialdehyde （MDA）， superoxide dismutase （SOD）] as well as liver function [alanine amino- transferase （ALT）， aspartate amino-transferase （AST）] in cells were detected； protein and mRNA expressions of AMP-activated protein kinase （AMPK）/sterol regulatory element-binding protein-1 （SREBP-1）/glycerol-3-phosphate acyltransferase （GPAT） signaling pathway were also measured. RESULTS Compared with the control group， cells in the model group exhibited severe cellular steatosis， with a significantly increased proportion of lipid droplet area， as well as the elevated levels of TG， ALT， AST， and MDA in cells， along with significantly up-regulated mRNA and protein expression levels of SREBP-1 and GPAT （P＜0.05）. The level of SOD， mRNA expression of AMPK， as well as the protein phosphorylation level of AMPK were decreased significantly （P＜0.05）. Compared with the model group， cellular steatosis was alleviated in all drug-containing serum groups， and the levels of most of the aforementioned quantitative indicators were significantly reversed （P＜0.05）. CONCLUSIONS BYHWD and its active fractions can exert a therapeutic effect on improving non-alcoholic fatty liver disease by regulating the AMPK/SREBP-1/GPAT signaling pathway， inhibiting oxidative stress responses， and reducing lipid deposition.

ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

As one of the chronic diseases with high incidence in contemporary society, cervical spondylosis has increasing patient groups who gradually present a low age, and it seriously affects social and public health. Although modern medicine has made great progress in the pathological research and clinical treatment of cervical spondylosis, patients still face gastrointestinal side effects of nonsteroidal anti-inflammatory drugs(NSAIDs), neck pain, limited mobility, upper limb numbness, and other symptoms after conservative or surgical treatment. In the theory of traditional Chinese medicine(TCM), cervical spondylosis belongs to the categories of "Bi syndrome" "stiff neck" "stiff Bi", etc. With the change of the times, the change of lifestyle, and the application of western medicine treatment, the etiology and pathogenesis of TCM in cervical spondylosis also show new characteristics. In terms of etiology and pathogenesis, it involves the invasion of wind, cold, and dampness, long-term strain, liver and kidney deficiency, Qi and blood stasis, which are associated with factors such as cervical degeneration, muscle tension and spasm, intervertebral disc herniation, and nerve root compression in modern medicine. In terms of the evolution of pathogenesis, in the early stage, wind, cold, and dampness, were more common in Xuanfu, resulting in unfavorable muscles and bones, poor flow of Qi and blood, and cervical spondylosis and radiculopathy. Medium-term phlegm stasis and internal knots, sluggish muscles and veins, and long-term weathering and fire are more likely to occur in the vertebral artery and sympathetic radiculopathy. In the later stage, the positive Qi is depleted; the true Yin is damaged, and the viscera Qi and blood are deficient, which is most common in cervical myelopathy. The strategy of treating cervical spondylosis with TCM classic formulas applies Gegen Decoction, Wutou Decoction, Qianghuo Shengshi Decoction, Mahuang Jiazhu Decoction to patients with wind, cold, and dampness. Patients with phlegm dampness and blood stasis are treated with Huoxue Xiaoling Dan, Jinlingzi Powder, Siwu Decoction, Banxia Baizhu Tianma Decoction, Shuanghe Decoction, etc. For those patients with liver, spleen, and kidney deficiency, Huangqi Guizhi Wuwu Decoction, Tianma Gouteng Decoction, Guishao Dihuang Pills, Shenling Baizhu Powder, and Lizhong Decoction are used to invigorate the spleen, nourish Qi and blood, and tonify liver and kidney. In clinical practice, the authors advocate a safe and effective treatment plan of classic formulas based on deficiency and excess, the integration of formulas and syndromes, and the combination of modern research results, so as to relieve symptoms, reduce recurrence, and reduce medical burden.
Humans ; Spondylosis/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Cervical Vertebrae/pathology*

Objective To investigate the pharmacological mechanism through which total flavonoids extracted from Xiaobuxin-Tang(XBXT-2)affects neural network activities in the frontal cortex by focusing on the effects of XBXT-2 on the cortical field potentials in the frontal association cortex(FrA)in mice.Methods Cortical electrodes were implanted into the skull of C57BL/6J mice targeting the FrA.After a 7-day recovery period,the mice were administered XBXT-2 intragastrically at a dose of 100 mg/kg,and 1 hour later,local field potential(LFP)in the FrA were recorded for 30 minutes.Spectral analysis of the data was performed using Neuro Explorer software.Changes in the power spectral density of α,β,θ,γ,and δ frequency bands before and after drug administration were analyzed using GraphPad Prism 10.3.Phase-amplitude coupling of θ and γ oscillations was analyzed using Matlab 2021 software.Results It was found that the oral administration of XBXT-2 significantly suppressed high-frequency γ oscillations while simultaneously enhancing θ,β,α,and δ oscillations in FrA of mice compared to the control.Furthermore,XBXT-2 treatment markedly strengthened the phase-amplitude coupling between θ and γ oscillations.Conclusion XBXT-2 possibly affects emotional and cognitive functions by modulating neural network activity in FrA and enhancing θ-γ phase-amplitude coupling in mice.

This paper explores the therapeutic approach for glaucoma based on the concept of "jueyin （厥阴） as the closing phase" from the perspectives of time and space. In traditional Chinese medicine， jueyin governs inward， converging aspect of qi， representing the crucial turning point between the end of yin and the emergence of yang， as well as the transformation between yin and yang. When the closing and descending function of jueyin operates smoothly， it promotes the inward convergence and smooth descent of qi， enabling the internal retention of blood， spirit， and emotions， which nourishes the internal organs and moistens the meridian-sinews. Conversely， dysfunction of this "closing" mechanism results in a disturbance of yin and yang， a mixture of cold and heat， and disharmony of qi and blood. It is proposed that "failure of jueyin to properly close and descend" is a core pathomechanism of glaucoma. From the perspective of spatiotemporal theory， clinical treatment should focus on "regulating the closing function of jueyin and harmonizing yin and yang". The modified Wumei Pill （乌梅丸） is recommended to adjust the ascending-descending and entering-exiting dynamics of jueyin qi transformation， thereby restoring its free flow， achieving yin and yang balance， and ensuring nourishment to the ocular system.

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

Objective To provide references for the registration and implementation of related clinical trials by analyzing the current status of clinical trial registration of TCM for the treatment of cervical spondylosis.Methods Relevant clinical trials of TCM for the treatment of cervical spondylosis were retrieved from China Clinical Trial Registry,International Clinical Trial Registry Platform and US Clinical Trials Registry database from the establishment to 1 July 2024.The relevant data were extracted and entered into Excel 2019,and GraphPad Prism 9.0 was used to statistically analyse the registration characteristics of clinical trials of TCM for the treatment of cervical spondylosis.Results A total of 126 clinical trials of TCM for the treatment of cervical spondylosis were included in this study,of which 112 were interventional studies.Domestic registrations covered a total of 19 provincial administrative regions,with the top two being Shanghai and Guangdong Province.The research on disease types included all subtypes of cervical spondylosis,with the largest number of registered items(37 items,29.37%)related to cervical spondylostic radiculopathy,followed by projects with unspecified cervical spondylosis subtypes(44 projects,34.92%).Research projects from universities and affiliated hospitals accounted for 89.7%(113 projects),with Guangdong Provincial Hospital of Traditional Chinese Medicine(12 projects)registering the most projects.Totally 110 research projects were funded,with local financial support accounting for 39.09%(43 projects)and national financial support accounting for 16.36%(18 projects).The study designs were mainly randomized parallel controlled studies(112 projects,88.9%),mostly single-centre research projects(92 projects,73.0%),with sample sizes concentrated between 50-200(86 projects,68.3%).The interventions were mostly external TCM treatments,such as acupuncture(41 items,32.5%)and tuina(23 items,18.3%).Conclusion The number of registered clinical trials of TCM for the treatment of cervical spondylosis has shown a fluctuating upward trend,but there are problems such as a small number,uneven geographical development,low methodological quality,mostly single-centre trials,and a lack of projects with Chinese materia medica intervention projects.

Objective:To explore the impact of socioeconomic status on disability among middle-aged and elderly individuals in China.Methods:This was a retrospective cohort study. At the baseline year of 2011, 14 213 individuals aged 45 years and above from the China Health and Retirement Longitudinal Study were consecutively selected, and their repeated measurement data with complete information from the 4 rounds of follow-up from 2013 to 2020 were consecutively selected, with a total of 67 355 cases included in the analysis. The principal component analysis was used to construct a socioeconomic status index (SESI) and the generalized estimating equation was employed to analyze the association between the SESI and disability in the participants. And the impact of SESI on disability in different age subgroups was further analyzed.Results:Among the 14 213 participants included in the 2011 baseline sample for analysis, there were 6 833 males and 7 380 females, 7 953 aged 45-60 years, 5 156 aged 61-75 years, and 1 104 aged over 75 years. Additionally, there were 3 812 with high SESI, 4 526 with medium SESI, and 5 875 with low SESI. The incidences of disability were greater in the individuals aged>75 years, females, and those with a low SESI (all P<0.05). The risk of incidence of disability in the middle-aged and elderly population increased with decrease of SESI (medium SESI: OR=1.47, 95% CI: 1.39-1.55; low SESI: OR=1.79, 95% CI: 1.69-1.89) (all P<0.001). The difference in the risk of disability in the middle-aged and elderly individuals across the different SESI was greatest at 45-60 years ( OR=2.08, 95% CI: 1.91-2.26), which gradually decreased with increasing age and was smallest at>75 years (OR=1.33, 95% CI: 1.09-1.61) (all P<0.001). Conclusions:The lower the socioeconomic status of China′s middle-aged and elderly individuals, the higher the incidence of disability; the impact of socioeconomic status on risk of disability is more pronounced in the early years of middle and old age and gradually decreases with age.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.