ObjectiveTo investigate whether visceral fat area （VFA） is an independent risk factor for significant liver fibrosis in patients with nonalcoholic fatty liver disease （NAFLD） based on clinical data， and to establish an effective diagnostic model. MethodsA total of 222 NAFLD patients who attended Department of Hepatology， Guangdong Provincial Hospital of Traditional Chinese Medicine， from January 2021 to April 2025 were enrolled， and according to liver stiffness measurement （≥8 kPa or not）， they were divided into significant fibrosis group and non-significant fibrosis group. Propensity score matching （PSM） was performed at a ratio of 1∶1 to balance the baseline data between the two groups. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was used to determine the correlation of VFA and other indicators with significant liver fibrosis； univariate and multivariate logistic regression analyses were used to identify whether VFA was an independent risk factor for significant liver fibrosis in NAFLD patients， and the receiver operating characteristic （ROC） curve was plotted to assess the predictive performance of related indicators. ResultsA total of 45 patients with significant liver fibrosis and 177 patients without significant liver fibrosis were enrolled， and after PSM， 90 patients （45 pairs） were finally included in analysis. Compared with the non-significant fibrosis group， the significant fibrosis group had significantly higher levels of body mass index （BMI）， fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， uric acid （UA）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transpeptidase （GGT）， controlled attenuation parameter （CAP）， and VFA， as well as a significantly higher proportion of patients with visceral fat obesity or three or more metabolic risk factors （all P<0.05）. VFA， BMI， AST， and HbA1c were strongly correlated with significant liver fibrosis （all r>0.5， all P <0.05）， and ALT， GGT， UA， FBG， and CAP were significantly positively correlated with significant liver fibrosis （r=0.3　—　0.5， all P<0.05）. VFA （odds ratio ［OR］=1.040， 95% confidence interval ［CI］： 1.018　—　1.062， P<0.05）， FBG （OR=2.372， 95%CI： 1.199　—　4.691， P<0.05）， and AST （OR=1.032， 95%CI： 1.003　—　1.058， P<0.05） were independent risk factors for significant liver fibrosis in NAFLD patients. The new diagnostic model based on VFA， FBG， and AST （with an area under the ROC curve ［AUC］ of 0.907） had a significantly better performance than aspartate aminotransferase-to-platelet ratio index （AUC=0.834）， fibrosis-4 （AUC=0.660）， triglyceride-glucose index （AUC=0.656）， and NAFLD fibrosis score （AUC=0.768） in predicting significant liver fibrosis in NAFLD patients （all P<0.05）. ConclusionVFA is an independent risk factor for significant liver fibrosis in NAFLD patients， and the noninvasive diagnostic model based on VFA， FBG， and AST can effectively predict the onset of significant liver fibrosis in NAFLD patients.

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.

OBJECTIVE To explore the mecha nism by which Liuwei dihuang pill promotes tendon-bone healing by regulating the interaction between bone marrow mesenchymal stem cells （BMSCs） and macrophages through Wnt/ β -catenin pathway. METHODS BMSCs were co-cultured with macrophages at a ratio of 1∶4 and divided into control group， 10% drug-containing serum group， 20% drug-containing serum group， Wnt/ β -catenin pathway inhibitor Dickkopf-related protein 1 （DKK-1） group， and 20% drug-containing serum+DKK-1 group. After 48 hours of cell co-culture and 14 days of osteogenic induction， the CD86 and CD206 positive cell rates in macrophages， the proportion of calcium nodule positive staining area in BMSCs， the levels of osteocalcin （OCN） and oncostatin M （OSM） and alkaline phosphatase （ALP） activity in cell supernatant， as well as the mRNA and protein expression levels of OCN， Runt-related transcription factor 2 （RUNX2）， OSM， low-density lipoprotein receptor-related protein 5 （LRP5）， β -catenin in cells were detected. Pearson correlation analysis was performed to assess the correlation between LRP5 and β -catenin protein expression with OCN， RUNX2， OSM protein expression， and CD206 positive cell rate， respectively. RESULTS Compared with the control group， the CD86 positive cell rates in the 10% drug-containing serum group and the 20% drug-containing serum group were significantly reduced， while the CD206 positive cell rate， proportion of calcium nodule positive staining area， OCN level， OSM level， ALP activity， and mRNA and protein expression levels of OCN， RUNX2， OSM， LRP5， β -catenin were significantly increased （ P ＜0.05）. Compared with the 20% drug-containing serum group， the changes in the above indicators in the 20% drug-containing serum+DKK-1 group were significantly reversed （ P ＜0.05）. The protein expression of LRP5 and β -catenin was positively correlated with the pro tein expression of OCN， RUNX2， OSM， and CD206 positive cell rate. CONCLUSIONS Liuwei dihuang pill can activate the Wnt/ β -catenin pathway， induce M2 polarization of macrophages and secretion of OSM， promote osteogenic differentiation and matrix mineralization of BMSCs， and synergistically promote tendon-bone healing.

OBJECTIVE To explore the mecha nism by which Liuwei dihuang pill promotes tendon-bone healing by regulating the interaction between bone marrow mesenchymal stem cells （BMSCs） and macrophages through Wnt/ β -catenin pathway. METHODS BMSCs were co-cultured with macrophages at a ratio of 1∶4 and divided into control group， 10% drug-containing serum group， 20% drug-containing serum group， Wnt/ β -catenin pathway inhibitor Dickkopf-related protein 1 （DKK-1） group， and 20% drug-containing serum+DKK-1 group. After 48 hours of cell co-culture and 14 days of osteogenic induction， the CD86 and CD206 positive cell rates in macrophages， the proportion of calcium nodule positive staining area in BMSCs， the levels of osteocalcin （OCN） and oncostatin M （OSM） and alkaline phosphatase （ALP） activity in cell supernatant， as well as the mRNA and protein expression levels of OCN， Runt-related transcription factor 2 （RUNX2）， OSM， low-density lipoprotein receptor-related protein 5 （LRP5）， β -catenin in cells were detected. Pearson correlation analysis was performed to assess the correlation between LRP5 and β -catenin protein expression with OCN， RUNX2， OSM protein expression， and CD206 positive cell rate， respectively. RESULTS Compared with the control group， the CD86 positive cell rates in the 10% drug-containing serum group and the 20% drug-containing serum group were significantly reduced， while the CD206 positive cell rate， proportion of calcium nodule positive staining area， OCN level， OSM level， ALP activity， and mRNA and protein expression levels of OCN， RUNX2， OSM， LRP5， β -catenin were significantly increased （ P ＜0.05）. Compared with the 20% drug-containing serum group， the changes in the above indicators in the 20% drug-containing serum+DKK-1 group were significantly reversed （ P ＜0.05）. The protein expression of LRP5 and β -catenin was positively correlated with the pro tein expression of OCN， RUNX2， OSM， and CD206 positive cell rate. CONCLUSIONS Liuwei dihuang pill can activate the Wnt/ β -catenin pathway， induce M2 polarization of macrophages and secretion of OSM， promote osteogenic differentiation and matrix mineralization of BMSCs， and synergistically promote tendon-bone healing.

The safety of traditional Chinese medicine(TCM) has always been taken very seriously, and rich and valuable theories and experiences have been developed to ensure the safe and precise use of TCM in clinical practices. In recent years, the cognitive theory of toxicity of TCM, has undergone a profound change. TCM is characterized by the existence of intrinsic toxicity, idiosyncratic toxicity, and indirect toxicity related to organic factors. Therefore, the traditional theories and experiences of TCM, which focus on the prevention and control of intrinsic toxicity, fail to be used for the development of risk prevention and control countermeasures for newly discovered TCM with idiosyncratic toxicity and indirect toxicity. Accordingly, based on the toxicity classification and mechanism characteristics of TCM, this paper proposed a new strategy and method in TCM compatibility for detoxification based on componenttarget-effect interaction. The strategy based on component-target-effect interaction is to carry out TCM compatibility for detoxification by blocking the occurrence of drug-mediated damage and promoting damage repair through component interactions, target interactions,and/or effect interactions. Based on this theory, the paper established a strategy for TCM compatibility that aligned with the cognitive theory of toxicity of TCM, so as to achieve safe and precise use of TCM in clinical practices. The strategy based on component-targeteffect interaction has been exemplarily applied to the development of countermeasures to reduce the toxicity of TCM, including Polygonum Multiflorum, Epimedii Folium, and Psoraleae Fructus, and a new mechanism of Glycyrrhizae Radix et Rhizoma to " harmonize various medicines and detoxify myriad poisons" was illustrated, providing a scientific basis for the safe and precise use of TCM in clinical practice. This paper explained the scientific connotation, application forms, and application examples of componenttarget-effect interaction, aiming to provide a theoretical and methodological basis for guaranteeing the precise use of TCM in clinical practice and innovate the theories and methods of TCM compatibility for detoxification.
Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional/methods* ; Animals ; Drug-Related Side Effects and Adverse Reactions/prevention & control*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

OBJECTIVE: To explore the safety and efficacy of high-dose etoposide (VP-16) combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage mobilization for peripheral blood stem cells (PBSC) in newly diagnosed multiple myeloma (NDMM) patients. METHODS: From April 2021 to May 2023, eight NDMM patients who had failed to yield sufficient PBSC during initial mobilization with high-dose cyclophosphamide (CTX) combined with rhG-CSF underwent salvage mobilization with 1.2 g/m2 etoposide combined with rhG-CSF 10 μg/(kg·d). The effects and adverse reactions of initial mobilization and salvage mobilization were analyzed. RESULTS: For salvage mobilization and initial mobilization, the numbers of PBSC collections were 16 and 18, respectively. The mean value of total collected CD34⁺ cells were (11.90±5.75)×10⁶/kg and (1.67±0.75)×10⁶/kg (P =0.0010) in salvage mobilization group and initial mobilization group, respectively. The proportion of patients with a total collection of CD34⁺ cell count≥2×10⁶/kg were 100% and 37.5% (P =0.0625), and the proportion of patients with a total collection of CD34⁺ cell count≥5×10⁶/kg were 87.5% and 0% (P =0.0156) in salvage mobilization group and initial mobilization group, respectively. For five patients who underwent high-dose CTX initial mobilization but had a total CD34⁺ cell count < 2×10⁶/kg, successful collection was achieved through salvage mobilization with high-dose VP-16. Salvage mobilization with high-dose VP-16 was scheduled 2-3 weeks after failure of CTX mobilization. Adverse reactions of high-dose VP-16 mobilization did not increase compared to the initial mobilization with high-dose CTX. CONCLUSION As a salvage mobilization regimen, VP-16 1.2 g/m² combined with rhG-CSF is safe and highly effective in NDMM patients who failed to initial mobilization with high-dose CTX combined with rhG-CSF.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Salvage Therapy ; Peripheral Blood Stem Cells ; Male ; Middle Aged ; Female ; Peripheral Blood Stem Cell Transplantation

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome