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.

In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

Objective:To compare the efficacy and safety of extended-field versus reduced-field radiotherapy in upper tract urothelial carcinoma (UTUC) patients after radical operation.Methods:A retrospective analysis was conducted on the data of 210 UTUC patients who underwent full-length nephrectomy and received postoperative adjuvant radiotherapy in Peking University First Hospital from January 2013 to November 2023, and follow-up continued until June 2024. According to the target area of postoperative radiotherapy, patients were divided into the extended-field radiotherapy group (127 cases) and the reduced-field radiotherapy group (83 cases). The overall survival (OS), distant metastasis free survival (DMFS), local recurrence free survival (LRFS) and adverse reactions were compared. In the same period, 114 patients with recurrent abdominal and pelvic lymph nodes who did not receive adjuvant therapy after surgery for UTUC in our center were prospectively collected, and the coverage of the reduced-field target area was analyzed. Chi square test was used to compare the clinical characteristics, Kaplan-Meier method was used to analyze survival outcomes, log-rank test was used to compare the survival rate, and Cox multivariate regression analysis was performed on the influencing factors of survival.Results:The median follow-up was 24.5 (range: 3-74) months. There were no significant differences between the extended-field and reduced-field radiotherapy groups in terms of 2-year LRFS (93.3% vs. 98.1%, P=0.156), 2-year DMFS (84.8% vs. 91.2%, P=0.176), and 2-year OS (90.4% vs. 90.7%, P=0.707). The most common toxicities of adjuvant radiotherapy were nausea and leukopenia, with significantly higher grade 1-2 incidence in the extended-field group compared to the reduced-field group ( P<0.05). According to the analysis of patients with retroperitoneal lymph node recurrence after surgery, the reduced-field target designed according to the location of the primary tumor can cover more than 90% of the postoperative metastatic lymph node area Multivariate analysis revealed that variant histology ( HR=2.180,95% CI: 1.021-4.658, P=0.044) was an independent predictor of worse DMFS, while variant histology ( HR=3.825,95% CI: 1.514-9.662, P=0.005) and T 3-4 stage ( HR=4.452,95% CI: 1.025-19.339, P=0.046) were independent predictors of poorer OS. Conclusions:Compared with extended-field radiotherapy, reduced-field radiotherapy designed based on primary tumor location significantly reduced treatment-related toxicities without compromising postoperative therapeutic efficacy, and the reduced-field can cover more than 90% of local recurrent lesions.

With the deepening of molecular biology and cell biology research,the regulatory mechanism of autophagy has been gradually revealed,providing new ideas for the treatment of numerous diseases.Autophagy may be closely related to pathological changes such as apoptosis resistance of fibroblast-like synoviocytes,disturbances in bone metabolic homeostasis,and antigen presentation,the regulation of autophagy homeostasis may be an important approach for the treatment of rheumatoid arthritis(RA).In this paper,we provide a review on the pathological mechanism of autophagy in RA,with a view to providing a theoretical basis for later studies.

Objective To evaluate the effectiveness of active screening in improving the detection rate of carbape-nem-resistant Enterobacterales(CRE)in the intensive care units(ICUs).Methods From July 2023 to June 2024,active screening of rectal swab CRE was conducted on ICU patients in 10 hospitals.ICU patients who underwent ac-tive screening from July 2023 to June 2024 were selected as the study group,while those who did not undergo active screening from July 2022 to June 2023 were selected as the control group.Difference in CRE detection rates between the two groups of patients was compared.Results A total of 7 803 ICU patients were included in the study group,744 CRE strains were detected,with a detection rate of 9.53％,out of which 304 CRE strains were detected through routine detection(detection rate 3.90％),3 707 patients underwent active screen,440 CRE strains were detected(detection rate 11.87％).7 561 ICU patients were included in the control group,out of which 250 CRE strains were detected through routine detection,with a detection rate of 3.31％.There was a statistically significant difference in the overall detection rate of CRE between two groups of patients(x2=246.18,P＜0.001).In the study group,CRE detection rate of active screening(11.87％)was higher than that of routine detection(3.90％),with statistically significant difference(x2=264.26,P＜0.001).A total of 17 CRE strains were detected from the study group.The proportions of Klebsiella pneumoniae(80.92％vs 73.41％)and Serratia marcescens(2.30％vs0.23％)in the routine detection group were both higher than in the active screening group,while the proportion of Escherichia coli in the routine detection group was lower(8.22％vs 19.55％),all with statistically significant differences(all P＜0.05).Conclusion The prevalence of CRE in ICUs is relatively high,with a wide range of bac-terial species.Active screening can improve the detection rate of CRE.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Objective To evaluate the effectiveness of active screening in improving the detection rate of carbape-nem-resistant Enterobacterales(CRE)in the intensive care units(ICUs).Methods From July 2023 to June 2024,active screening of rectal swab CRE was conducted on ICU patients in 10 hospitals.ICU patients who underwent ac-tive screening from July 2023 to June 2024 were selected as the study group,while those who did not undergo active screening from July 2022 to June 2023 were selected as the control group.Difference in CRE detection rates between the two groups of patients was compared.Results A total of 7 803 ICU patients were included in the study group,744 CRE strains were detected,with a detection rate of 9.53％,out of which 304 CRE strains were detected through routine detection(detection rate 3.90％),3 707 patients underwent active screen,440 CRE strains were detected(detection rate 11.87％).7 561 ICU patients were included in the control group,out of which 250 CRE strains were detected through routine detection,with a detection rate of 3.31％.There was a statistically significant difference in the overall detection rate of CRE between two groups of patients(x2=246.18,P＜0.001).In the study group,CRE detection rate of active screening(11.87％)was higher than that of routine detection(3.90％),with statistically significant difference(x2=264.26,P＜0.001).A total of 17 CRE strains were detected from the study group.The proportions of Klebsiella pneumoniae(80.92％vs 73.41％)and Serratia marcescens(2.30％vs0.23％)in the routine detection group were both higher than in the active screening group,while the proportion of Escherichia coli in the routine detection group was lower(8.22％vs 19.55％),all with statistically significant differences(all P＜0.05).Conclusion The prevalence of CRE in ICUs is relatively high,with a wide range of bac-terial species.Active screening can improve the detection rate of CRE.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.