Bone metastases are a common and serious complication of solid tumors such as breast cancer, prostate cancer, lung cancer, and kidney cancer, and occur at a high rate in patients with advanced cancer. This pathological process not only frequently leads to skeletal-related events such as severe bone pain, pathological fractures, spinal cord compression, and hypercalcemia—conditions that severely impact patients’ quality of life—but may also significantly increase the risk of death. Cancer bone metastasis is a complex, multistage cascade involving key steps such as the detachment of tumor cells from the primary tumor, their invasion and entry into the bloodstream, and their colonization, dormancy, and reactivation within the bone microenvironment. In recent years, exercise—as a safe and easily implementable non-pharmacological intervention—has demonstrated significant potential in inhibiting bone metastasis, improving the bone microenvironment, and alleviating related clinical symptoms. Its mechanisms of action may involve multiple levels. First, at the mechanical load level, mechanical signals generated by exercise can directly act on bone cells, inhibiting tumor cell infiltration and colonization by regulating endothelial cell permeability and osteoclast activity. Second, at the endocrine and paracrine levels, exercise can alter the expression profiles of microRNAs (such as miR-486 and miR-34b) carried by extracellular vesicles and particles (EVPs) in the circulation, thereby inhibiting tumor cell proliferation and migration by targeting cell cycle-related genes. Furthermore, exercise can remodel the immune microenvironment, enhance the cytotoxic activity of antitumor immune cells, and improve oxygen supply to tumor tissues, thereby alleviating hypoxia-induced immunosuppression. Finally, at the metabolic intervention level, exercise can induce systemic metabolic reprogramming, increasing the nutritional demands of normal tissues, thereby competing with tumor cells for nutrients and forming a “metabolic barrier” in distal organs such as bones. This article reviews the pathogenesis and classification of bone metastases, including osteolytic, osteogenic, and mixed types, and elaborates in detail on the complex processes by which tumor cells undergo colonization, dormancy, and reactivation within the bone microenvironment. Furthermore, based on a comprehensive analysis of human and animal studies on exercise interventions for bone metastases, this paper highlights the mechanisms by which exercise inhibits tumor formation, growth, and spread through the regulation of mechanical loading, extracellular vesicles and granules, as well as via immune and metabolic pathways, thereby interfering with bone metastasis. However, the array of exercise modalities and intensities available for patients grappling with the challenges of cancer-related bone metastases remains markedly constrained, and the formulation of tailored exercise prescriptions continues to be devoid of robust, evidence-based medical backing. This review aims to explore the effects of exercise on bone health in patients with bone metastases, analyze the factors and considerations that should be taken into account in exercise prescriptions, and provide new theoretical support and insights for developing personalized exercise programs for these patients and further advancing relevant clinical research. Future research directions should include the development of evidence-based, personalized exercise prescriptions and further clarification of the safety boundaries and best practice standards for exercise interventions, thereby promoting the advancement of relevant clinical research and ultimately improving patients’ clinical outcomes and quality of life.

Developing an intelligent agent for integrated traditional Chinese and western medicine diagnosis and treatment based on clinical practice guidelines is a key approach to advancing the standardization and intelligent deve-lopment of traditional Chinese medicine （TCM） and to supporting clinical decision-making. This paper argues for the necessity of building a knowledge base using guidelines as the sole data source， systematically identifies five core methodological challenges across the entire process， and proposes corresponding solutions. An ontology framework capable of distinguishing between TCM and western medicine concepts should be designed to address the difficulty of knowledge integration. A closed-loop "algorithm-based extraction-expert review" model is adopted to reduce data extraction errors. Expert consensus is incorporated to address decision gaps in specific clinical scenarios outlined in the guidelines， while a multi-stage， standardized output process for the AI system is established to eliminate model hallucinations. Furthermore， an evaluation framework reflecting clinical applicability is developed to enhance the AI system's accuracy and stability. Throughout the research process， it is essential to ensure the in-depth and continuous participation of multidisciplinary experts， strictly control the selection and quality evaluation of guidelines， and rely on the expert consensus method to address decision gaps in the knowledge base. Additionally， continuous validation and iterative optimization of intelligent agents are required to ensure the accuracy and stability of generated outputs. Limitations remain in the mechanisms for real-time knowledge synchronization in intelligent diagnostic and treatment systems， and further validation through large-scale real-world studies is warranted.

ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

Ganoderic acid is a class of lanostane-type triterpenoids found in Ganoderma species, and is one of the most important pharmacologically active components in G. lucidum, exhibiting antioxidant, anti-neuropsychiatric, anti-tumor, and immune-enhancing properties. The content of ganoderic acid in G. lucidum is very low, and the traditional extraction process is complex, yielding minimal amounts at high cost. The biosynthetic pathway of G. lucidum triterpenoids(GLTs), including the synthesis of different structural forms of ganoderic acid from lanosterol, as well as the molecular regulatory mechanisms involving key regulatory enzyme genes and their functions, are not yet fully understood. With the continuous development of synthetic biology technologies, there has been a deeper understanding of the biosynthesis and metabolic regulation pathways of ganoderic acid and its derivatives at the molecular level. Research has explored the key regulatory enzyme genes related to ganoderic acid biosynthesis and their functions. Moreover, through the optimization of synthetic biology and culture conditions, large-scale production and preparation of GLTs at the cellular level have been achieved. This paper reviews and analyzes the latest research progress on the biosynthesis pathways and metabolic regulation of GLTs, focusing on the configuration of ganoderic acid and its derivatives, the biosynthetic pathways, key enzyme genes, transcription factors related to ganoderic acid biosynthesis, signal transduction mechanisms, and factors affecting triterpenoid biotransformation. This review is expected to provide a theoretical basis and technical reference for improving the efficient production of triterpenoid pharmacological components and the exploitation and utilization of G. lucidum resources.
Triterpenes/chemistry* ; Reishi/chemistry* ; Biosynthetic Pathways ; Lanosterol

ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

Objective To explore the improvement effect of ultrasound microbubble blasting assisted bone marrow mesenchymal stem cells(BMSC)transplantation on diabetic nephropathy(DN)in terms of inflammatory response and renal function via the Toll like receptor 4(TLR-4)/nuclear factor-kappa B(NF-κB)signaling pathway,as well as its specific mechanism.Methods A rat DN model was estab-lished and randomly grouped into the following:Model group,BMSC group,BMSC+microbubble group,and BMSC+microbubble+TLR-4/NF-κB pathway activator lipopolysaccharide(LPS)group,with 12 rats in each group.Additionally,12 rats were selected as the control(CK)group.Biochemical and biuret analysis,HE and Masson staining,ELISA,and Western blotting testing were employed to detect fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),serum creatinine(sCr),blood urea nitrogen(BUN),24-hour urinary total protein(24 h-UTP),pathological changes in renal tissue,fibrosis status,and the expression of interleukin-1 β(IL-1β),tumor necrosis factorα(TNF-α),TLR-4,and NF-κB proteins of rats in each group.Results The renal tissue in the CK group was structurally normal with few collagen fibers.The Model group showed obvious renal tissue lesions and severe collagen fiber deposition;the lesions in the BMSC group and BMSC+microvesicle group were alleviated in turn,while the lesions were aggravated after the addition of LPS compared with the BMSC+microvesicle group.Compared with the CK group,the levels of FBG,TC,TG,sCr,BUN,24 h-UTP,as well as the expression of IL-1β,TNF-α,TLR-4,and NF-κB proteins were increased in the Model group(P＜0.05).Compared with the Model group,the above-men-tioned indices and protein expression were decreased in the BMSC group(P＜0.05).Compared with the BMSC group,the above-men-tioned indices and protein expression were further decreased in the BMSC+microvesicle group(P＜0.05).Compared with the BMSC+mi-crovesicle group,the above-mentioned indices and protein expression were increased in the BMSC+microvesicle+LPS group(P＜0.05).Conclusion The improvement effect of ultrasound microbubble blasting-assisted BMSC transplantation on DN rats may be related to the inhibition of the TLR-4/NF-κB signaling pathway.

Objective To explore the early clinical manifestations,random cortisol levels,and management of late-onset circulatory collapse(LCC)in preterm infants.Methods Preterm infants with LCC from October to December 2023 at the Affiliated Suzhou Hospital of Nanjing Medical University were included.Maternal perinatal factors and infants'early clinical symptoms,signs,random serum cortisol levels,treatment,and outcomes were retrospectively analyzed.Results Seven preterm infants with LCC were included,with gestational ages of 25 weeks+2 days to 29 weeks and birth weights of 800-1 150 g.At 3 weeks of age,abnormal weight gain[gain rate:21-28.5 g/(kg·d)],generalized edema,low serum sodium(129.5-135.2 mmol/L),and decreased random serum cortisol concentrations(13.6-44.6 nmol/L)were observed.After 1-2 weeks of hydrocortisone treatment,edema subsided and serum sodium increased.Conclusions In clinically stable preterm infants,early manifestations of LCC include abnormal weight gain,generalized edema,recurrent hyponatremia,and decreased random serum cortisol concentrations.Hydrocortisone treatment effectively improves symptoms.

Objective To explore the improvement effect of ultrasound microbubble blasting assisted bone marrow mesenchymal stem cells(BMSC)transplantation on diabetic nephropathy(DN)in terms of inflammatory response and renal function via the Toll like receptor 4(TLR-4)/nuclear factor-kappa B(NF-κB)signaling pathway,as well as its specific mechanism.Methods A rat DN model was estab-lished and randomly grouped into the following:Model group,BMSC group,BMSC+microbubble group,and BMSC+microbubble+TLR-4/NF-κB pathway activator lipopolysaccharide(LPS)group,with 12 rats in each group.Additionally,12 rats were selected as the control(CK)group.Biochemical and biuret analysis,HE and Masson staining,ELISA,and Western blotting testing were employed to detect fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),serum creatinine(sCr),blood urea nitrogen(BUN),24-hour urinary total protein(24 h-UTP),pathological changes in renal tissue,fibrosis status,and the expression of interleukin-1 β(IL-1β),tumor necrosis factorα(TNF-α),TLR-4,and NF-κB proteins of rats in each group.Results The renal tissue in the CK group was structurally normal with few collagen fibers.The Model group showed obvious renal tissue lesions and severe collagen fiber deposition;the lesions in the BMSC group and BMSC+microvesicle group were alleviated in turn,while the lesions were aggravated after the addition of LPS compared with the BMSC+microvesicle group.Compared with the CK group,the levels of FBG,TC,TG,sCr,BUN,24 h-UTP,as well as the expression of IL-1β,TNF-α,TLR-4,and NF-κB proteins were increased in the Model group(P＜0.05).Compared with the Model group,the above-men-tioned indices and protein expression were decreased in the BMSC group(P＜0.05).Compared with the BMSC group,the above-men-tioned indices and protein expression were further decreased in the BMSC+microvesicle group(P＜0.05).Compared with the BMSC+mi-crovesicle group,the above-mentioned indices and protein expression were increased in the BMSC+microvesicle+LPS group(P＜0.05).Conclusion The improvement effect of ultrasound microbubble blasting-assisted BMSC transplantation on DN rats may be related to the inhibition of the TLR-4/NF-κB signaling pathway.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.