Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

Objective To analyze chemical constituents of compound Maxing Shigan decoction by ultra-high perfor-mance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). Methods The separation was performed on a UPLC BEH C₁₈ column (2.1 mm×100 mm, 2.5 µm)，with a gradient elution applying 0.1% aqueous formic acid solution and 0.1% formic acid acetonitrile as a mobile phase. The column temperature was 40 °C. The flow rate was 0.4 ml/min and the analysis time was 15 min. Mass spectrometry (MS) data were collected in both positive and negative ESI ion modes. Results Through UPLC-QTOF/MS analysis and reference validation, a total of 59 chemical components in Maxing Shigan decoction were identified. Conclusion An ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) method was established to identify the chemical components of Maxing Shigan decoction. This method is simple, efficient, sensitive and accurate, and provides a basis for the elucidation of the pharmacodynamic material basis and mechanism of Maxing Shigan decoction. It can provide data reference for the optimization of the compatibility of traditional Chinese medicine in the treatment of COVID-19.

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

BACKGROUND:The proliferation and phenotypic maintenance of chondrocytes are limited under two-dimensional culture conditions.Porous microspheres serve as scaffolds,providing a three-dimensional culture environment that better mimics in vivo growth conditions.Stromal cell derived factor-1,a homeostatic cytokine with potent chemotactic effects,facilitates cell adhesion and proliferation.OBJECTIVE:To investigate the impact of stromal cell derived factor-1 grafted poly-L-lactic acid porous microspheres on the biological characteristics of chondrocytes and the formation of cartilage tissue.METHODS:(1)The effects of different concentrations of stromal cell derived factor-1 on rabbit chondrocyte proliferation,migration,and phenotypic maintenance were investigated in an in vitro setting.(2)Poly-L-lactic acid porous microspheres were prepared by double emulsion method.Stromal cell derived factor-1 was grafted onto poly-L-lactic acid porous microspheres through carbodiimide reaction.The grafting was verified by enzyme-linked immunosorbent assay and incubation with stromal cell derived factor-1-specific fluorescent antibodies.(3)Rabbit chondrocytes were inoculated on poly-L-lactic acid porous microspheres and grafted on stromal cell derived factor-1 poly-L-lactic acid porous microspheres to detect cell proliferation and adhesion.(4)The methylacrylamide-gelatin-chondrocyte complex(control group),poly-L-lactic acid porous microsphere-methylacrylamide-gelatin-chondrocyte complex(porous microsphere group),and grafted stromal cell derived factor-1 poly-L-lactic acid porous microsphere-methylacrylamide-gelatin-chondrocyte complex(porous microsphere modified group)were implanted under the skin of the back of nude mice,respectively.Samples were collected 8 weeks later and detected using histological staining and qRT-PCR for chondroblast related genes.RESULTS AND CONCLUSION:(1)Compared with 0 and 1 000 ng/mL stromal cell derived factor-1,1 and 500 ng/mL stromal cell derived factor 1 could promote the proliferation and migration of chondrocytes,and enhance the mRNA expression levels of type Ⅱ collagen,elastin,proliferating cell nuclear antigen,and Bcl-2 in chondrocytes.(2)Stromal cell derived factor-1 was successfully grafted onto poly-L-lactic acid porous microspheres with a grafting rate of 93.75%.(3)Compared with poly-L-lactic acid porous microspheres,grafted stromal cell derived factor-1 poly-L-lactic acid porous microspheres promoted the proliferation and adhesion of chondrocytes.(4)After 8 weeks of subcutaneous implantation in nude mice,compared with the control group and the porous microsphere group,the porous microsphere modified group had clearer cartilage lacunae structure,more chondro-specific matrix and type Ⅱ collagen deposition,and increased expression of elastin,type Ⅱ collagen,proliferating cell nuclear antigen,and Bcl-2 mRNA.These findings indicate that stromal cell derived factor-1 grafted poly-L-lactic acid porous microspheres are beneficial to chondrocyte adhesion,proliferation,phenotypic maintenance,and the formation of cartilage tissue in vivo.

Objective To study the need for blood compatibility evaluation of medical devices that come into indirect contact with blood in order to accurately evaluate the risk of their interaction with blood.Methods Seven medical devices with indirect contact with blood were selected as samples including extension tubes of central venous catheters,port bodies of implantable drug delivery devices,infusion sets,receiving lines of dialysis equipment,auxiliary lines of left ventricular assist devices,blood monitors and catheter holders,with high-density polyethylene as the negative control,glass beads as the positive control and blank whole blood or plasma for the blank control.Partial thromboplastin time(PTT)test,platelet count test and hematology test(white blood cell and red blood cell count)were performed by direct contact method and indirect contact method,respectively.In the direct contact method,whole blood or plasma was in direct contact with the sample;while in the indirect contact method,whole blood or plasma was not in direct contact with the extraction solution,with no direct contact with the sample.Results With the indirect contact method the ratios(expressed as a percentage)of the PTT,platelate,WBC and RBC counts of the samples,positive and negative controls to those of the blank control were all higher than those with the direct contact method,and the indirect contact method had the sensitivity lower than that of the direct contact method.Conclusion Medical devices indirectly contacting blood have low risks for causing coagulation and platelet and hematologic adverse reactions,which are suggested to be evaluated for hemolysis testing only in case of the history of safe clinical use.[Chinese Medical Equipment Journal,2025,46(8):44-49]

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective:An in vivo mammalian hepatocyte Unscheduled DNA Synthesis(UDS)test was used to evaluate the genotoxicity of Cross-linked Sodium Hyaluronate Gel and Bone Repair Materials,providing experimental evidence for establishing a UDS testing method for medical devices and materials.Methods:0.9％sodium chloride injection and cottonseed oil were used as the solvent for test materials and negative control,respectively.N-dimethylnitrosamine(NDMA)was used as the positive control for the early sampling times,and 2-acetylaminofluorene(2-AAF)was used as the positive control for the late sampling times.SD rats were administered a single dose for toxic exposure,and liver tissues were collected at 4 h and 16 h,respectively.Hepatocytes were isolated using collagenase perfusion.After labeling with 5-ethynyl-2'-deoxyuridine(EdU),and the net average fluorescence intensity(NAFI)of cell nuclei and nucleoplasm was measured by fluorescence microscope.Data from 50 cells were used to analyze the DNA repair level.Results:Compared with the negative control groups,the positive control groups(NDMA and 2-AAF)showed highly statistically significant differences in NAFI(P＜0.01),indicating successful induction of DNA damage.There was no statistically significant differences between the cross-linked sodium hyaluronate gel groups,bone repair material groups and the negative control group(P＞0.05),suggesting that these materials did not significantly induce DNA damage under the experimental conditions.Conclusion:This study first applied EdU labeling technology to the in vivo hepatic UDS assay,achieving non-radioactive labeling through click chemistry reactions.Under the conditions of this study,cross-linked sodium hyaluronate gel and bone repair materials did not exhibit genotoxicity.In the follow-up,the sample range can be expanded and the observation period can be prolonged to further improve the genotoxicity evaluation system of medical devices.