ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

Objective:To explore the therapeutic efficacy and prognostic factors of combined rituximab and intensive chemotherapy for sporadic adult Burkitt lymphoma (BL) .Methods:This retrospective study examined the clinical and survival data of 30 patients newly diagnosed with BL between July 2011 and February 2023 at the Blood Diseases Hospital. Kaplan-Meier method was used for survival analysis, and the log-rank test was used for univariate analysis of prognostic factors.Results:The median age of the 30 patients was 43 years (24 - 66 years), and the male to female ratio was 3: 2. Extranodal invasion was present in 80% of the patients, with involvement of the bone marrow in 53.3% and central nervous system in 10.0%. The Ann Arbor stage was Ⅲ and Ⅳ in 86.7%. According to the number of Burkitt Lymphoma International Prognostic Index (BL-IPI) risk factors, patients were classified as low risk (0) in 20.0%, intermediate risk (1) in 43.3%, and high risk (≥2) in 36.7%. All patients were treated with an induction regimen of rituximab combined with intensive chemotherapy, with objective and complete response rates of 80.0% and 76.7%, respectively. The median follow-up was 49 months (6-153 months), and the 5-year progression-free survival (PFS) and overall survival (OS) rates were both (76.7±7.7) %. All patients with limited stage ( n=4) achieved continuous complete remission (CCR). Patients who had high risk, advanced stage sensitive to induction therapy ( n=10) sequentially received first-line autologous hematopoietic stem cell transplantation (auto-HSCT) as consolidation therapy; 9 patients achieved CCR, whereas 1 patient with central nervous system invasion developed early disease progression and died. The BL-IPI low, intermediate, and high risk groups had respective 5-year PFS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0069) and OS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0075). The main adverse effects of induction therapy were myelosuppression and secondary infections, which were effectively managed by appropriate symptomatic treatment. Univariate analysis demonstrated that worse PFS was associated with BL-IPI score ≥2 ( HR=4.90, 95% CI 1.02-23.45, P=0.0329) ; extranodal invasion at ≥2 sites ( HR=12.62, 95% CI 2.59-61.62, P=0.0021) ; and failure to achieve first complete response (CR1) after induction therapy ( HR=31.86, 95% CI 4.19-242.20, P<0.0001) . Conclusions:Intensive immunochemotherapy regimens were effective and well-tolerated by adult patients with highly aggressive BL. Treatment efficacy was ideal in patients with limited-stage disease, whereas prognosis was unsatisfactory in patients with high-risk BL-IPI. Sequential first-line auto-HSCT consolidation therapy may further improve outcomes in patients with high-risk advanced-stage disease who are sensitive to induction therapy. BL-IPI score ≥2, extranodal invasion at ≥2 sites, and failure to achieve CR1 after induction therapy were adverse prognostic factors in adult patients with BL.

The chemical constituents from leaves of Cyclocarya paliurus were isolated and purified by chromatography on silica gel, C_(18) reverse-phase silica gel, and Sephadex LH-20 gel, as well as semi-preparative high-performance liquid chromatography. Six compounds were identified by UV, IR, NMR, MS, calculated ECD, and comparison with literature data as cyclopaloside D(1), boscialin(2),(5R,6S)-6-hydroxy-6-[(E)-3-hydroxybut-1-enyl]-1,1,5-trimethylcyclohexanone(3), 3S,5R-dihydroxy-6R,7-megastigmadien-9-one(4), 3S,5R-dihydroxy-6S,7-megastigmadien-9-one(5), and gingerglycolipid A(6), respectively. Among them, compound 1 was identified as a new tetralone glycoside, and compounds 2-6 were isolated from leaves of C. paliurus for the first time. Furthermore, compound 1 exhibited strong antioxidant activity, with the IC_(50) of(454.20±31.81)μmol·L~(-1) and(881.82±42.31)μmol·L~(-1) in scavenging DPPH and ABTS free radicals, respectively.
Plant Leaves/chemistry* ; Glycosides/isolation & purification* ; Juglandaceae/chemistry* ; Tetralones/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification*

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

Traditional Chinese medicine(TCM) resources are an important foundation for the theory and practice of TCM. Rare and endangered TCM, as a significant component of these resources, plays an essential role. Conducting research on substitutes for rare and endangered TCM resources is of great significance for alleviating resource shortages, promoting the sustainable utilization of TCM, and advancing TCM modernization. This paper reviews the conservation achievements of rare and endangered Chinese medicinal materials in China and organizes the substitution methods for these materials. Currently, the main substitution approaches include introduction and domestication, tissue culture, varietal replacement, and artificial synthesis. Furthermore, this paper proposes the following approaches for researching the application scenarios of rare and endangered medicinal materials, i.e., tracing the historical context of their use to clarify foundational principles; verifying disease classifications to strengthen the clinical application scenarios of these materials; analyzing the evolution patterns of prescription formulations to strengthen the mining of the compatibility application scenarios of rare and endangered medicinal materials; scientifically evaluating to strengthen the application scenario research and development of endangered Chinese patent medicine industry. These efforts aim to promote the scientific substitution and sustainable utilization of rare and endangered medicinal materials and their substitutes.
Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional ; China ; Plants, Medicinal/growth & development* ; Endangered Species ; Conservation of Natural Resources ; Animals

Qing court records show that Arecae Semen was extensively applied. The royal medical records of the Qing Dynasty document nine types of Arecae Semen, with the Palace Museum preserving seven kinds, totaling twelve cultural relics. Historical documents and physical artifacts corroborate each other, providing evidence for the study of the supply channels and court processing of Arecae Semen in the Qing court. According to relevant Qing court archival records, the sources of Arecae Semen used in the imperial court were diverse, including tributes from foreign countries such as Vietnam and Gurkha, annual tributes from local governments in Guangdong, gifts from close aides, and commodities purchased by the Imperial Household Department from civilian shops. The imperial physicians of the Qing court placed great emphasis on the specifications of Arecae Semen slices and were extremely meticulous about their processing. The variety of Arecae Semen slices used in the Qing palace exceeded those recorded in the botanical texts of the era. Compared with the commonly used processing methods for Arecae Semen in the Qing Dynasty, the imperial physicians adjusted the properties and efficacy of the herbs through different processing techniques, based on the patient's condition, constitution, and other factors, in order to meet the clinical treatment needs of the court. The slicing of Arecae Semen in the Qing court required strict control of thickness, with an average thickness of 0.44 mm, which is significantly thinner than the Arecae Semen slices found in today's markets. The texture was softer, making them easier to chew and absorb. Both the Qing court Arecae Semen slices and the Muxiang Binglang Pills focused on the use of authentic medicinal materials, ensuring the quality of the medicine and enhancing the efficacy of Arecae Semen through meticulous selection and preparation.
China ; Drugs, Chinese Herbal/history* ; Humans ; Medicine, Chinese Traditional/history* ; History, 19th Century ; History, Ancient ; History, 17th Century ; History, 18th Century

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

OBJECTIVE: To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice. METHODS: BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues. RESULTS: BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation. CONCLUSION The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
Animals ; Mice ; Mesenchymal Stem Cell Transplantation ; Liver Cirrhosis/etiology* ; Male ; Cholestasis/therapy* ; Mice, Inbred C57BL ; Hepatic Stellate Cells ; Mesenchymal Stem Cells

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*

OBJECTIVE: To explore the effects and mechanism of Chinese medicine Liujunzi Decoction (LJZD) on regulating microbial flora in mice with asthma flora disorder. METHODS: Thirty BALB/c female mice were divided into control, model, LJZD [3.5 g/(kg•d), by gavage], dexamethasone [DXMS, 0.7 mg/(kg•d), intraperitoneal injection], and Clostridium butyricum [CB, 230 mg/(kg•d), by gavage] groups according to a random number table, 6 mice in each group. The asthma flora disorder mice model was induced with ovalbumin (OVA). Lung and gut lesions were analyzed by hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stainings. The secretory immunoglobulin A (sIgA) protein expression in lung and gut tissues was detected by Western blot. Flow cytometry was used to detect the relative counts of GATA binding protein 3 (GATA3)/type 2 innate lymphoid cells (ILC2) in lung and gut. The levels of inflammatory factors in lung and gut tissues were detected by enzyme-linked immunosorbent assay (ELISA). Chao1 and Shannon index were used to compare microbial abundance and diversity in alveolar lavage fluid and cecal contents. The similarity or difference in the composition of mice microbial communities was analyzed through cluster analysis. The serum short-chain fatty acids (SCFAs) content was detected by ultra performance liquid chromatograph mass spectrometer (LC-MS)/MS. RESULTS: The asthma flora disorder model mice showed obvious asthma-related symptoms, but LJZD treatment effectively alleviated these symptoms. LJZD restored alveolar wall thickening, airway inflammatory cell infiltration, gut tissue structure destruction, and inflammatory cell infiltration in asthma flora disorder mice. LJZD downregulated the sIgA protein expression in mice (P<0.05). Moreover, LJZD decreased the activation of GATA3/ILC2s in lung and gut tissue (P<0.01), and reduced the levels of interleukin (IL)-5, IL-33, IL-25, IL-9 and IL-13 (P<0.01). LJZD treatment returned the abundance of microbial species and the microbial community structure of alveolar lavage fluid and cecal content in asthma flora disorder mice to the normal state. The SCFAs content and body metabolism were also improved. CONCLUSION LJZD exerted anti-asthmatic effects by improving the microbial balance of lung-gut axis and affecting systemic metabolism, consequently regulating the GATA3/ILC2s axis to impact the lung inflammatory response.
Animals ; Asthma/pathology* ; GATA3 Transcription Factor/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Mice, Inbred BALB C ; Female ; Lung/drug effects* ; Homeostasis/drug effects* ; Inflammation/pathology* ; Lymphocytes/drug effects* ; Mice