ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

Quantum dots (QDs), nanoscale semiconductor crystals, have emerged as a revolutionary class of nanomaterials with unique optical and electrochemical properties, making them highly promising for applications in disease diagnosis and treatment. Their tunable emission spectra, long-term photostability, high quantum yield, and excellent charge carrier mobility enable precise control over light emission and efficient charge utilization, which are critical for biomedical applications. This article provides a comprehensive review of recent advancements in the use of quantum dots for disease diagnosis and therapy, highlighting their potential and the challenges involved in clinical translation. Quantum dots can be classified based on their elemental composition and structural configuration. For instance, IB-IIIA-VIA group quantum dots and core-shell structured quantum dots are among the most widely studied types. These classifications are essential for understanding their diverse functionalities and applications. In disease diagnosis, quantum dots have demonstrated remarkable potential due to their high brightness, photostability, and ability to provide precise biomarker detection. They are extensively used in bioimaging technologies, enabling high-resolution imaging of cells, tissues, and even individual biomolecules. As fluorescent markers, quantum dots facilitate cell tracking, biosensing, and the detection of diseases such as cancer, bacterial and viral infections, and immune-related disorders. Their ability to provide real-time, in vivo tracking of cellular processes has opened new avenues for early and accurate disease detection. In the realm of disease treatment, quantum dots serve as versatile nanocarriers for targeted drug delivery. Their nanoscale size and surface modifiability allow them to transport therapeutic agents to specific sites, improving drug bioavailability and reducing off-target effects. Additionally, quantum dots have shown promise as photosensitizers in photodynamic therapy (PDT). When exposed to specific wavelengths of light, quantum dots interact with oxygen molecules to generate reactive oxygen species (ROS), which can selectively destroy malignant cells, vascular lesions, and microbial infections. This targeted approach minimizes damage to healthy tissues, making PDT a promising strategy for treating complex diseases. Despite these advancements, the translation of quantum dots from research to clinical application faces significant challenges. Issues such as toxicity, stability, and scalability in industrial production remain major obstacles. The potential toxicity of quantum dots, particularly to vital organs, has raised concerns about their long-term safety. Researchers are actively exploring strategies to mitigate these risks, including surface modification, coating, and encapsulation techniques, which can enhance biocompatibility and reduce toxicity. Furthermore, improving the stability of quantum dots under physiological conditions is crucial for their effective use in biomedical applications. Advances in surface engineering and the development of novel encapsulation methods have shown promise in addressing these stability concerns. Industrial production of quantum dots also presents challenges, particularly in achieving consistent quality and scalability. Recent innovations in synthesis techniques and manufacturing processes are paving the way for large-scale production, which is essential for their widespread adoption in clinical settings. This article provides an in-depth analysis of the latest research progress in quantum dot applications, including drug delivery, bioimaging, biosensing, photodynamic therapy, and pathogen detection. It also discusses the multiple barriers hindering their clinical use and explores potential solutions to overcome these challenges. The review concludes with a forward-looking perspective on the future directions of quantum dot research, emphasizing the need for further studies on toxicity mitigation, stability enhancement, and scalable production. By addressing these critical issues, quantum dots can realize their full potential as transformative tools in disease diagnosis and treatment, ultimately improving patient outcomes and advancing biomedical science.

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.

Generative artificial intelligence （AI）， particularly the ChatGPT series， has great application potential in the medical field. Several products have been introduced into the market， triggering widespread attention across society. Although medical ChatGPT has numerous advantages， its internal technical flaws based on algorithms， data， and platforms may bring about representative external application dilemmas， such as the allocation of legal liability， medical ethical disputes， medical dispute handling， and intellectual property protection. However， China’s current legal norms may not be able to address these issues effectively. To effectively address these contradictions， it is necessary to govern its internal technical flaws through the concept of good governance and to regulate its external application challenges based on the principles of fairness， accountability， remedy， and phased implementation.

Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

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*

This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male

Through evidence mapping, this paper systematically summarized the research evidence on the use of traditional Chinese medicine(TCM) in treating renal anemia, displaying the distribution of evidence in this field. A systematic search was conducted across databases, including CNKI, Wanfang, VIP, SinoMed, Springner, PubMed, Engineering Village, and Web of Science, targeting studies published up to June 30, 2024. The research evidence was summarized and displayed through a combination of graphs, tables, and text. A total of 264 interventional studies, 37 observational studies, and 7 systematic reviews were included. The annual publication volumes related to TCM treatment in renal anemia showed an overall upward trend, with most studies involving sample sizes between 60 and 120 participants(224 articles, 74.42%). Intervention measures were categorized into 21 types, with oral TCM decoctions being the most common medicine(171 times, 56.81%). The use of self-made prescriptions was the most common TCM intervention method. The intervention duration was mainly between 8 weeks and 3 months(239 articles, 79.40%). The most frequently reported TCM syndrome was spleen and kidney Qi deficiency. The top 2 outcome indicators were the anemia indicators and renal injury/renal function markers. However, several issues were identified in these studies, such as insufficient attention to the sources, social/geographical information, and temporal continuity of research subjects in observational research. Randomized controlled trials mostly had a high risk of bias, mainly due to issues such as randomization bias, blinding bias, and failure to register research protocols. The methodology quality of systematic reviews was generally low, mainly due to inadequate inclusion of literature, failure to specify funding sources, and lack of pre-registrations. While the report quality of systematic review was acceptable, there were significant gaps in the reporting of protocols, registration, and funds. The results show that these issues affect the quality of research and the reliability of findings on TCM in treating renal anemia, underscoring the need to address them to conduct higher-quality research and provide more reliable medical evidence for TCM in treating renal anemia.
Humans ; Anemia/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/drug therapy*

OBJECTIVE: To investigate the variability of bone metabolism levels among different populations and its association with knee osteoarthritis (KOA) pain. METHODS: A total of 50 people (control group) who participated in physical examination from January 2023 to June 2023 were selected, including 26 males and 24 females, wtih a mean aged of (52.14±9.04) years old ranging 41 to 65 years old. The other 50 patients with knee osteoarthritis(case group) who attended the outpatient clinic of the Orthopedics and Traumatology Department in the same time period, including 19 males and 31 females, with a mean age of (53.60±7.76) years old ranging 40 to 65 years. The two groups of Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC) and bone metabolism markers, such as 25-hydroxy-cholecalciferol[25(OH)D], β-isomerized typeⅠcollagen C-telopeptide breakdown products (β-CTX), total typeⅠprocollagen N-terminal propeptide (t-PINP), osteocalcin (OC), parathormone (PTH) levels were compared. Pearson correlation analysis was used to compare the correlation between two groups of bone metabolism related markers and WOMAC. RESULTS: The WOMAC score of the case group (39.90±2.34) was higher than that of the control group (3.60±0.57), with significant difference (P<0.05). There was no significant difference between the two groups of 25 (OH)D, β-CTX and PTH (P>0.05). The t-PINP and OC of the case group were (62.90±52.40) and (19.88±10.15) ng·ml-1, respectively, and those of the control group were (38.86±10.82) and (14.90±3.62) ng·ml^-1, respectively;the t-PINP and OC of the case group were higher than those of the control group, with significant difference (P<0.05). Pearson correlation analysis showed that t-PINP was positively correlated with WOMAC pain score in the case group (r²=0.045, P<0.01). CONCLUSION Bone metabolism levels in the serum of patients with knee osteoarthritis are different from those of healthy people, and the difference between OC and t-PINP is the most obvious, and the concentration of t-PINP levels is positively correlated with pain symptoms in patients with KOA. However, the specific mechanism of correlation between the bone metabolism levels of patients with KOA and their pain symptoms needs to be further elucidated by basic experimental research as well as by enlarging the samples.
Humans ; Female ; Male ; Middle Aged ; Osteoarthritis, Knee/metabolism* ; Aged ; Adult ; Bone and Bones/metabolism* ; Pain/etiology* ; Biomarkers/metabolism*