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

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 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.

The brain is a complex organ that requires precise mapping to understand its structure and function. Brain atlases provide a powerful tool for studying brain circuits, discovering biological markers for early diagnosis, and developing personalized treatments for neuropsychiatric disorders. Neuromodulation techniques, such as transcranial magnetic stimulation and deep brain stimulation, have revolutionized clinical therapies for neuropsychiatric disorders. However, the lack of fine-scale brain atlases limits the precision and effectiveness of these techniques. Advances in neuroimaging and machine learning techniques have led to the emergence of stereotactic-assisted neurosurgery and navigation systems. Still, the individual variability among patients and the diversity of brain diseases make it necessary to develop personalized solutions. The article provides an overview of recent advances in individualized brain mapping and navigated neuromodulation and discusses the methodological profiles, advantages, disadvantages, and future trends of these techniques. The article concludes by posing open questions about the future development of individualized brain mapping and navigated neuromodulation.

Objective To observe the clinical efficacy and safety of rituximab injection in the treatment of patients with phospholipase A2 receptor-associated membranous nephropathy(PLA2R-MN).Methods The PLA2R-MN patients were randomly divided into control group and treatment group.The control group received oral prednisone tablets,initial dose of 40-60 mg·d-1,gradually reduced the dose according to the patients'condition after 2 months,cyclophosphamide injection 0.6 g per time,intravenous infusion,once every 2 weeks,for 6 consecutive times,then adjusted to 1.0 g per time,intravenous infusion,once a month;the treatment group received 375 mg·m-2 rituximab injection intravenous infusion,once a week,for 4 consecutive weeks,on the basis of the control group treatment.Both groups of patients were treated for 6 months.The clinical efficacy,24 h urine protein quantification,serum creatinine(SCr),glomerular filtration rate(eGFR),urinary microalbumin(UAlb),urinary creatinine(UCr)and adverse drug reactions were compared between two groups.Results Fifty-three patients were enrolled in the treatment group,2 cases dropped out,and 51 cases were finally included in the statistical analysis.Fifty-three patients were enrolled in the control group,2 cases dropped out,and 51 cases were finally included in the statistical analysis.After treatment,the total effective rate of the treatment group and the control group were 92.16％(47 cases/51 cases)and 76.47％(39 cases/51 cases),and the difference was statistically significant(P＜0.05).After treatment,the 24 h urine protein quantification of the treatment and control groups were(0.86±0.30)and(1.04±0.27)g·24 h-1;SCr levels were(103.37±18.80)and(120.55±19.94)μmol·L-1;eGFR levels were(65.89±8.17)and(55.87±9.36)mL·min-1·1.73 m-2;UAlb levels were(47.45±13.52)and(98.21±25.50)mg·L-1;UCr were(1.55±0.42)and(1.96±0.51)mg·g-1,respectively,and the differences were all statistically significant(all P＜0.05).The adverse drug reactions of two groups were mainly nausea,vomiting,liver function damage,skin itching,infection,hair loss,etc.The total incidences of adverse drug reactions in the treatment and control groups were 43.14％and 37.25％,without significant difference(P＞0.05).Conclusion Rituximab injection has a definite clinical efficacy in the treatment of PLA2R-MN patients,which can significantly improve the renal function of patients,and does not increase the incidence of adverse drug reactions.

Objective To evaluate the effectiveness and safety of Yiyang Pill in preventing and treating cardiovascular adverse reactions in patients with traditional Chinese medicine(TCM)syndrome with qi and yin deficiency and thyroid stimulating hormone(TSH)inhibition after differentiated thyroid cancer(DTC)resection.Methods A randomized,double-blind,placebo-controlled clinical trial was conducted,and 120 patients with TSH inhibition after DTC surgery were enrolled and randomized into two groups in a 1∶1 ratio using SAS 9.4 software generated random tables.The control group received a placebo and TSH suppression therapy,whereas the treatment group received the Yiyang Pill and TSH suppression therapy.The treatment period was 3 months.The incidence of cardiovascular adverse reactions,blood pressure,blood lipids,thyroid function,the dosage of levothyroxine,the efficacy of TCM syndrome,and safety indicators were compared between the two groups.Multivariate Logistic regression was used to analyze the influencing factors of cardiovascular adverse reactions.Results The incidence of cardiovascular adverse reactions in the treatment group was lower than that in the control group(P<0.05),and the efficacy of TCM syndrome treatment was significantly higher than in the control group(P<0.05).The free tetraiodothyronine level in the treatment group was higher than that before treatment(P<0.05),and the systolic and diastolic blood pressure in the control group increased compared to those before treatment(P<0.05).No severe adverse events were observed in either group.Compared with the control group,the cardiovascular incidence in the treatment group was lower,and the cardiovascular incidence in the<100 μg/d group was lower than that in the group with≥100 μg/d before treatment.Conclusion The Yiyang Pill can reduce the incidence of cardiovascular adverse reactions in patients after DTC surgery,effectively improve TCM syndromes,and be safe to use.Yiyang Pill treatment is a protective factor for cardiovascular adverse reactions,and the dosage of levothyroxine≥100 μg/d was a risk factor.

To explore the pathogenesis and treatment of recurrent granulomatous mastitis based on "deficiency， toxin and blood stasis". It is believed that the main pathogenesis of recurrent granulomatous mastitis is spleen and stomach deficiency due to chronic illness， and at the same time， the persistent or intermittent presence of various causes makes the residual toxin unclear， which leads to the stagnation of local meridians and collaterals in the breast， accumulation of lumps， and then suppuration. Deficiency of qi and blood in zang-fu organs is the main cause of this disease， and residual toxin is the key factor of this disease. The treatment should focus on promoting therapy， promoting with dispersing， expelling with supplementing， supplementing with warming and dredging， dissolving toxins and releasing stasis， and the prescription is based on modified Tuoli Xiaodu Powder （托里消毒散） or self-prescribed Jiangru No.2 Formula （浆乳2号方）. Overall， the treatment should combine deficiency， toxin and blood stasis with different syndrome differentiation and treatment， reinforce healthy qi and express toxin， and activate blood circulation and dredge collaterals with flexibly modification， to promote disease healing.