BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

OBJECTIVE To comprehensively evaluate the efficacy， safety and cost-effectiveness of insulin icodec in treating type 2 diabetes mellitus （T2DM）， providing evidence-based guidance for new drug selection in hospital and clinical medication decision-making. METHODS PubMed， Cochrane Library， Embase， CNKI， Wanfang， VIP and foreign health technology assessment （HTA） websites were searched by using rapid health technology assessment from inception to 15 July 2025 for systematic reviews/meta-analyses， pharmacoeconomic studies， and HTA reports on insulin icodec in the treatment of T2DM. After data extraction and quality assessment， the findings of the included studies were analyzed descriptively. RESULTS Ten systematic reviews/meta-analyses and three pharmacoeconomic studies were included. Among them， 4 systematic reviews/meta-analyses were of high quality； the overall quality of the 3 pharmacoeconomic studies was relatively good. Regarding efficacy， insulin icodec was superior to once-daily basal insulin in reducing glycated hemoglobin （HbA1c） and in achieving the target of HbA1c＜7% （P＜0.05）. No significant differences were observed between icodec insulin and comparators in lowering fasting plasma glucose （P＞0.05）. For safety， insulin icodec did not increase the incidence of any adverse events （AEs）， serious AEs， clinically significant hypoglycemia （random glucose＜3 mmol/L）， injection-site reactions， or allergic reactions， compared with once-daily basal insulin overall （P＞ 0.05）； however， insulin icodec was associated with a significant increase in body weight （P＜0.05）. Domestic economic evaluations indicated that insulin icodec was more cost-effective than insulin glargine and insulin degludec when its annual costs were in the range of 784.90-1 145.96 and 597.66-736.34 US dollars， respectively. CONCLUSIONS Insulin icodec demonstrates favorable efficacy and safety profiles in the treatment of T2DM； however， attention should be paid to the risk of weight gain. Under China’s healthcare system， insulin icodec demonstrates greater economic value only when the patient’s weekly required basal insulin dose falls within a specific range，and clinical practice requires individualization.

Tripartite motif-containing (TRIM) family proteins are crucial E3 ubiquitin ligases that have garnered significant attention for their regulatory roles in bone metabolism in recent years. This article reviews the function and regulatory mechanisms of TRIM family proteins in bone metabolism, focusing on their dual roles in bone formation and resorption. It also provides a detailed analysis of signaling pathways and molecular mechanisms by which TRIM family members regulate the activities of osteoblasts and osteoclasts. Research findings suggest that modulating the expression or activity of TRIM family proteins could be beneficial for treating bone diseases such as osteoporosis. This review highlights the molecular mechanisms of TRIM family members in bone physiology and pathology, aiming to provide theoretical basis and scientific guidance for developing novel therapeutic strategies for bone diseases.
Humans ; Ubiquitin-Protein Ligases/physiology* ; Bone and Bones/metabolism* ; Animals ; Tripartite Motif Proteins/physiology* ; Osteoclasts/metabolism* ; Osteoblasts/metabolism* ; Signal Transduction/physiology* ; Osteogenesis/physiology*

According to the principle and current domestic and international construction processes of core outcome set(COS) and the characteristics of post-stroke aphasia, this study built COS with evidence-based support for traditional Chinese medicine(TCM) treatment of post-stroke aphasia. Firstly, a comprehensive review was conducted on the articles about the TCM treatment of post-stroke aphasia that were published in the four major Chinese databases, three major English databases, and three clinical registration centers over the past five years. The articles were analyzed and summarized, on the basis of which the main part of the COS for clinical research on the TCM treatment of post-stroke aphasia was formed. Secondly, clinical doctors and related nursing personnel were interviewed, and important outcome indicators in the clinical diagnosis and treatment process were supplemented to form a pool of core outcome indicators. Two rounds of Delphi surveys were carried out to score the importance of the core outcome indicators in the pool. Finally, a consensus meeting of experts was held to establish the COS for clinical research on the TCM treatment of post-stroke aphasia. The final COS included a total of 268 studies [236 randomized controlled trials(RCTs), 21 Meta-analysis, and 11 clinical registration protocols] and 20 open questionnaire survey results. After two rounds of Delphi surveys, a total of 14 outcome indicators and their corresponding measurement tools were included in the expert consensus meeting. The final expert consensus meeting determined the COS for post-stroke aphasia, which included 9 indicator domains and 12 outcome indicators.
Humans ; Aphasia/therapy* ; Stroke/complications* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Treatment Outcome

This study investigates the genetic diversity and evolutionary relationships of different Artemisia argyi germplasm resources to provide a basis for germplasm identification, variety selection, and resource protection. A total of 192 germplasm resources of A. argyi were studied, and EST-based simple sequence repeat(EST-SSR) primers were designed based on transcriptomic data of A. argyi. Polymerase chain reaction(PCR) amplification was performed on these resources, followed by fluorescence capillary electrophoresis to detect genetic diversity and construct DNA fingerprints. From 197 pairs of primers designed, 28 pairs with polymorphic and clear bands were selected. A total of 278 alleles were detected, with an average of 9.900 0 alleles per primer pair and an average effective number of alleles of 1.407 2. The Shannon's diversity index(I) for the A. argyi germplasm resources ranged from 0.148 1 to 0.418 0, with an average of 0.255 7. The polymorphism information content(PIC) ranged from 0.454 5 to 0.878 0, with an average of 0.766 9, showing high polymorphism. Cluster analysis divided the A. argyi germplasm resources into three major groups: Group Ⅰ contained 136 germplasm samples, Group Ⅱ contained 45, and Group Ⅲ contained 11. Principal component analysis also divided the resources into three groups, which was generally consistent with the clustering results. Mantel test results showed that the genetic variation in A. argyi populations was to some extent influenced by geographic distance, but the effect was minimal. Structure analysis showed that 190 germplasm materials had Q≥ 0.6, indicating that these germplasm materials had a relatively homogeneous genetic origin. Furthermore, 8 core primer pairs were selected from the 28 designed primers, which could distinguish various germplasm types. Using these 8 core primers, DNA fingerprints for the 192 A. argyi germplasm resources were successfully constructed. EST-SSR molecular markers can be used to study the genetic diversity and phylogenetic relationships of A. argyi, providing theoretical support for the identification and molecular-assisted breeding of A. argyi germplasm resources.
Artemisia/classification* ; Microsatellite Repeats ; Genetic Variation ; Expressed Sequence Tags ; DNA Fingerprinting ; Phylogeny ; Polymorphism, Genetic ; DNA, Plant/genetics* ; Genetic Markers

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: Burning solid cooking fuel contributes to household air pollution and is associated with frailty. However, how solid cooking fuel use contributes to the development of frailty has not been well illustrated. METHODS: This study recruited 8,947 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study, 2011-2018. Group-based trajectory modeling was employed to identify frailty trajectories. Multinomial logistic regression was used to assess the association between solid cooking fuel use and frailty trajectories. Population-attributable fractions were used to estimate the frailty burden from solid fuel use. RESULTS: We identified three frailty trajectories: low-stable ( n = 5,789), moderate-increasing ( n = 2,603), and fast-increasing ( n = 555). Solid fuel use was associated with higher odds of being in the moderate-increasing ( OR: 1.24, 95% CI: 1.08-1.42) and fast-increasing ( OR: 1.48, 95% CI: 1.14-1.92) trajectories. These associations were strengthened by longer solid fuel use ( P for trend < 0.001). Switching to clean fuel significantly reduced the risk of being in these trajectories compared with persistent solid fuel users. Without solid fuel, 8% of moderate- and 19% of fast-increasing trajectories demonstrated frailty development like the low-stable group. CONCLUSION Solid cooking fuel use is associated with frailty trajectories in middle-aged and older Chinese populations.
Humans ; China/epidemiology* ; Cooking ; Male ; Female ; Middle Aged ; Aged ; Air Pollution, Indoor/adverse effects* ; Frailty/etiology* ; Longitudinal Studies ; Cohort Studies

OBJECTIVES: This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival. METHODS: An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival. RESULTS: Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival. CONCLUSIONS FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology* ; Transcriptome ; Metabolomics ; Foam Cells/microbiology* ; Humans ; Metabolome ; Tuberculosis/microbiology* ; Gene Expression Profiling

Objective To evaluate the bioequivalence and safety of two voriconazole for injection in healthy Chinese subjects,and to explore the safety of the excipient sulfobutyl-β-cyclodextrin.Methods A single-center,single-dose,randomized,open-label,two-preparation,two-period,double-crossover trial design.A total of 18 healthy subjects were enrolled and administrated with a single intravenous infusion of voriconazole test drug and reference drug at 4 mg·kg-1 under fasting conditions,with a sequence determined by randomization.The concentrations of voriconazole in plasma and sulfobutyl-β-cyclodextrin in urine were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Phoenix WinNonlin 8.2 software was used to calculate pharmacokinetic parameters of voriconazole in plasma,and SAS(version 9.4)software was used to calculate pharmacokinetic parameters of sulfobutyl-β-cyclodextrin in urine and bioequivalence analysis.Results Major pharmacokinetic parameters of voriconazole in plasma after a single intravenous infusion of voriconazole test drug and reference drug in 18 healthy subjects in a fasted state were as follows:Cmax were(2 177.00±399.10)and(2 265.00±378.70)ng·mL-1;AUC0-t were(14 612.07±8 182.95)and(15 144.69±7 814.02)ng·h·mL-1;AUC0-∞ were(16 217.48±10 862.78)and(16 863.18±10695.75)ng·h·mL-1;tmax were 2.00 and 1.98 h,respectively.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ for the two drugs were within the equivalence range of 80.00％to 125.00％.Conclusion The two voriconazole for injection preparations were bioequivalent and safe when administered by intravenous infusion under fasting conditions in healthy Chinese subjects.

Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.