Eight new diterpenoids, Isodons A-H (1-8), comprising seco-abietane and abietane-type structures, together with 13 known analogues (9-21), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(-)-3, (+)-4/(-)-4, and (+)-5/(-)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
Abietanes/pharmacology* ; Molecular Structure ; Animals ; Isodon/chemistry* ; Humans ; Diterpenes/pharmacology* ; Plant Extracts/chemistry*

Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective:To explore the potential pathogenesis of exosome-mediated polymyositis/dermatomyositis (PM/DM) through multi-omics combined with bioinformatic analysis approach and to identify potential new targets for the diagnosis and treatment of PM/DM.Methods:Collect serum exosome samples from PM/DM patients and healthy individuals who underwent physical examination in Wuxi Second People′s Hospital from January 2021 to June 2023. HiSeq high-throughput sequencing technology and iTRAQ quantitative proteomics techniques were used to perform a sequencing analysis of miRNA and protein components in serum exosomes from patients with PM/DM and healthy control. R language was adapted to conduct the limma differential analysis, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), gene set enrichment analysis (GSEA) functional analysis, and immunological correlation analysis. Based on these analysis, we identified core genes and established a miRNA-target gene-transcription factor co-expression molecular network. Subsequently, we employed quantitative real-time PCR (qRT-PCR) to experimentally validate the core genes. Data analysis was performed using t-test statistical analysis and receiver operating characteristic (ROC) curves were plotted to evaluate the test efficacy of the core genes. Results:Initially, 42 up-regulated differential proteins and 61 DEP down-regulated differential proteins, as well as 22 up-regulated differential miRNAs and 19 down-regulated miRNAs were screened, and 7 core genes, 13 associated differential miRNAs, and 4 transcription factors were finally identified. Based on the functional analysis we concluded that the core genes CTSG, MPO, H1-5 involved in the formation of neutrophil extracellular trap network, NF-κB pathway and other inflammation-related pathways might play an important role in exosome-mediated PM/DM pathogenesis. Immune cells such as mast cells, immature dendritic cells, natural killer cells, regulatory T cells, and helper T cells 2 were expressed to a higher extent in the disease. In the t-test, MPO [(1.08 ±0.47) vs. (2.05 ±0.62), t=-3.50, P=0.004], CTSG [(1.11 ±0.51 ) vs. (2.27 ±1.10 ), t=-2.72, P=0.022], and H1-5 [(1.03 ±0.25) vs. (1.81 ±0.73), t=-2.89, P=0.019] showed statistically significant differences. In the ROC curve analysis, MPO[AUC(95% CI): 0.92(0.78, 1)], CTSG [AUC(95% CI): 0.81(0.59, 1)], and H1-5 (AUC (95% CI)= 0.84(0.64, 1)] indicated that the three core genes had good accuracy. Conclusion:We identified the key differential molecules in serum exosomes of patients with PM/DM, and constructed a regulatory network of miRNA-target gene-transcription factor, and determined that the pathogenic mechanism of PM/DM was mediated by serum exosomes was mediated through the formation of neutrophil extracellular trapping nets and the NF-κB pathway. CTSG, MPO, and H1-5 are the core genes in the these pathways, and their related miRNAs and transcription factors have been identified, which may become potential targets and biomarkers for the diagnosis and treatment of PM/DM.

The correspondence between prescription and syndrome is the advantage and characteristic of traditional Chinese medicine(TCM)treatment.However,the pathogenesis of clinical diseases is complex and the condition is changeable,and the clinical application is difficult to achieve the maximum effect under the existing cognition of the correspondence between prescription and syndrome.In this paper,the five categories of physiological characteristics,pathological characteristics,constitution,syndrome,and disease of the longitudinal classification of"TCM state"are introduced into the correspondence of prescription and syndrome.Under the vertical perspective of"TCM state",the theoretical connotation of the correspondence between prescription and syndrome is interpreted as"correspondence between prescription and state",namely correspondence of"prescription-physiological characteristics",correspondence of"prescription-pathological characteristics",correspondence of"prescription-constitution",correspondence of"prescription-syndrome",and correspondence of"prescription-disease".It is hoped to accurately grasp the corresponding connotation of the correspondence between prescription and syndrome,in order to deepen the clinical thinking mode of TCM.

Objective: To investigate the prevalence of hypertension among primary and middle school students living in Suzhou City, Jiangsu Province, so as to provide insights into comprehensive hypertension control among children and adolescents. Methods: Primary and middle school students at ages of 7 to 17 years were recruited for a questionnaire survey in Suzhou City using the stratified cluster random sampling method from September to December, 2020, and the height and body weight were measured. Blood pressure was measured at three separate clinic visits according to the national criteria Reference of Screening for Elevated Blood Pressure among Children and Adolescents Aged 7-18 Years ( WS/T 610-2018 ), and the detection of elevated blood pressure was estimated at three separate visits. In addition, factors affecting elevated blood pressure were identified. Results: A total of 3 713 students were enrolled, including 1 924 boys ( 51.82% ) and 1 789 girls ( 48.18% ). The detection of elevated blood pressure was 13.63%, 5.36%, and 3.37% at three separate visits, respectively, and the prevalence of hypertension ( elevated blood pressure at all three visits ) was 3.37%. The detection rates of elevated blood pressure were all higher at three visits ( 16.90%, 8.40%, and 5.26% ) among students at ages of 12 to 17 years than among students at ages of 7 to 11 years ( 9.65%, 1.67%, and 1.07%, P<0.05 ). The detection of elevated blood pressure was significantly higher in boys ( 15.23% ) than in girls (11.91%) at the first visit ( P<0.05 ), while no significant differences were seen at the second or third visit ( P>0.05 ). In addition, higher detection rates of elevated blood pressure were seen in obese ( 27.62%, 11.51%, and 7.06% ) and overweight students ( 17.45%, 6.95%, and 4.85% ) than in students with normal weight ( 9.44%, 3.54%, and 2.15% ) at all three visits, and greater detection rates of elevated blood pressure were found in obese students than in overweight students at the first and second visits ( P<0.017 ). Conclusions The prevalence of hypertension was 3.37% based on three separate visits among primary and middle school students in Suzhou City. Measurement of blood pressure at three separate visits within different days is effective to reduce the false positive rate of hypertension and decrease misdiagnosis among children and adolescents.

Abdomen/diagnostic imaging* ; Artificial Intelligence ; Body Composition ; Magnetic Resonance Imaging ; Practice Guidelines as Topic

Objective: To investigate the effects of cancer susceptibility candidate gene 19 (CASC19) regulating the expression of microRNA-449b-5p (miR-449b-5p) on the proliferation, apoptosis and radiation sensitivity of cervical cancer cells. Methods: (1) HeLa cells of cervical cancer cell line were cultured. HeLa cells were irradiated with X-ray at different doses (0, 2, 4, 6, 8 Gy, respectively), then the expression level of CASC19 mRNA and miR-449b-5p were detected by real-time quantitative PCR. (2) HeLa cell proliferation, apoptosis, radiation sensitivity (expressed as a survival fraction) and its related protein expression included cyclin D1, cleaved-caspase-3, and histone variant H2AX (γ-H2AX) were examined after different treatment including silencing CASC19 expression, over-expressing miR-449b-5p, down-regulating miR-449b-5p and silencing CASC19 expression. (3) The dual luciferase reporter gene experiment and real-time quantitative PCR technology were used to verify the targeting relationship between CASC19 and miR-449b-5p. Results: (1) With the increase of X-ray irradiation different dose (0, 2, 4, 6, 8 Gy), the expression level of CASC19 mRNA in HeLa cells gradually increased (F=502.681, P=0.000), and the expression level of miR-449b-5p gradually decreased (F=202.936, P=0.000).(2) After silencing CASC19 expression or over-expressing miR-449b-5p, the survival rate of HeLa cells was significantly reduced (P<0.05), the apoptosis rate was significantly increased (P<0.05), the survival fraction was significantly reduced (P<0.05), the expression level of cyclin D1 protein was significantly reduced (P<0.05), and the expression levels of cleaved-caspase-3 and γ-H2AX protein were significantly increased (P<0.05). After down-regulating miR-449b-5p and silencing CASC19 expression, the survival rate of HeLa cells was significantly reduced (P<0.05), the apoptosis rate was significantly increased (P<0.05), the survival fraction was significantly reduced (P<0.05), the expression levels of cyclin D1 and γ-H2AX protein were significantly increased (P<0.05), and the expression level of cleaved-caspase-3 was significantly decreased (P<0.05). (3) Over expression of miR-449b-5p could significantly reduce the luciferase activity of CASC19 wild type (1.00±0.09 versus 0.37±0.05, P<0.01), but there were no significant effect on the luciferase activity of CASC19 mutant type (0.92±0.07 versus 0.94±0.05, P>0.05). After the expression of CASC19 was silenced, the expression level of miR-449b-5p in HeLa cells increased significantly (1.00±0.12 versus 4.84±0.49, P<0.05). After overexpression of CASC19, the expression level of miR-449b-5p in HeLa cells was significantly reduced (1.00±0.09 versus 0.38±0.04, P<0.05). Conclusion CASC19 in HeLa cells negatively regulates the expression of miR-449b-5p, and down-regulating the expression of miR-449b-5p could partially reverse the effects of silencing CASC19 on HeLa cell proliferation, apoptosis and radiation sensitivity.

During the treatment of tumor,especially in head and neck cancer,oral mucositis is one of the common complications. The incidence of oral mucositis have relations with chemotherapy,targeted therapy,radiotherapy dose,radiotherapy technology and risk factors of patient. Severe oral mucositis may bring about treatment interrupted,decrease of tumor control rate,affect quality of life and so on. In general, what is very important during the treatment of tumor is to explore the prevention and treatment of oral mucositis.