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 evaluate the efficacy and safety of different immunosorbent columns in the treatment of rheumatoid arthritis through a network meta-analysis,and provide evidence-based basis for clinical diagnosis and treatment.METHODS:By computer,the databases of VIP,WanFang,CNKI,PubMed,CBM,CochraneLibrary,and Web of Science were searched for published cohort studies of immunosorbent column for the treatment of rheumatoid arthritis,with a time limit until August 2024.The quality of the included randomized controlled trials was assessed using the Cochrane5.4 manual.The quality of retrospective cohort studies were evaluated via the Newcastle-Ottawa Scale(NOS).Bayesian network meta-analysis was performed using R4.1.1 software.RESULTS:A total of 13 studies were included,with a total sample size of 891 cases,and 4 immunosorbent columns were included.The results of the network meta-analysis showed that the top three orders that reduce C-reactive protein level:HA280 adsorption column+conventional Western medicine＞PH-350 adsorption column+conventional Western medicine＞A protein adsorption column;the top three orders that reduce erythrocyte sedimentation rates:leukocyte adsorption column＞HA280 adsorption column+conventional Western medicine＞PH-350 adsorption column+conventional western medicine;the top three orders that reduce swollen joint count:leukocyte adsorption column＞A protein adsorption column+conventional western medicine＞PH-350 type adsorption column+conventional Western medicine;the top three orders that reduce tenderness joint counts:leukocyte adsorption column＞A protein adsorption column+conventional western medicine＞PH-350 adsorption column+conventional Western medicine;the top three orders that reduce patients' disease activity evaluation:PH-350 adsorption column+conventional western medicine＞leukocyte adsorption column＞A protein adsorption column;the top three orders that reduce visual analogue scale scores:PH-350 adsorption column+conventional Western medicine＞A protein adsorption column＞leukocyte adsorption column;the top three orders that reduce physician's disease activity assessment:PH-350 adsorption column+conventional Western medicine＞leukocyte adsorption column＞conventional Western medicine.CONCLUSION:Based on the 13 articles,in terms of reducing C-reactive protein level,HA280 adsorption column and conventional Western medicine are the preferred choice.In terms of reducing erythrocyte sedimentation rate,swollen joint count,and tender joint count,leukocyte adsorption column is the preferred choice.In terms of reducing patient's disease activity evaluation,physician's disease activity evaluation and visual analogue scale scores,PH-350 adsorption column and conventional Western medicine are the first choice.Different immunosorbent columns can be reasonably and accurately selected according to the patient's specific conditions.

OBJECTIVE:To evaluate the efficacy and safety of different immunosorbent columns in the treatment of rheumatoid arthritis through a network meta-analysis,and provide evidence-based basis for clinical diagnosis and treatment.METHODS:By computer,the databases of VIP,WanFang,CNKI,PubMed,CBM,CochraneLibrary,and Web of Science were searched for published cohort studies of immunosorbent column for the treatment of rheumatoid arthritis,with a time limit until August 2024.The quality of the included randomized controlled trials was assessed using the Cochrane5.4 manual.The quality of retrospective cohort studies were evaluated via the Newcastle-Ottawa Scale(NOS).Bayesian network meta-analysis was performed using R4.1.1 software.RESULTS:A total of 13 studies were included,with a total sample size of 891 cases,and 4 immunosorbent columns were included.The results of the network meta-analysis showed that the top three orders that reduce C-reactive protein level:HA280 adsorption column+conventional Western medicine＞PH-350 adsorption column+conventional Western medicine＞A protein adsorption column;the top three orders that reduce erythrocyte sedimentation rates:leukocyte adsorption column＞HA280 adsorption column+conventional Western medicine＞PH-350 adsorption column+conventional western medicine;the top three orders that reduce swollen joint count:leukocyte adsorption column＞A protein adsorption column+conventional western medicine＞PH-350 type adsorption column+conventional Western medicine;the top three orders that reduce tenderness joint counts:leukocyte adsorption column＞A protein adsorption column+conventional western medicine＞PH-350 adsorption column+conventional Western medicine;the top three orders that reduce patients' disease activity evaluation:PH-350 adsorption column+conventional western medicine＞leukocyte adsorption column＞A protein adsorption column;the top three orders that reduce visual analogue scale scores:PH-350 adsorption column+conventional Western medicine＞A protein adsorption column＞leukocyte adsorption column;the top three orders that reduce physician's disease activity assessment:PH-350 adsorption column+conventional Western medicine＞leukocyte adsorption column＞conventional Western medicine.CONCLUSION:Based on the 13 articles,in terms of reducing C-reactive protein level,HA280 adsorption column and conventional Western medicine are the preferred choice.In terms of reducing erythrocyte sedimentation rate,swollen joint count,and tender joint count,leukocyte adsorption column is the preferred choice.In terms of reducing patient's disease activity evaluation,physician's disease activity evaluation and visual analogue scale scores,PH-350 adsorption column and conventional Western medicine are the first choice.Different immunosorbent columns can be reasonably and accurately selected according to the patient's specific conditions.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

OBJECTIVE To explore the improvement effect and mechanism of salidroside on radiation-induced parotid gland injury in rats. METHODS Rats were randomly assigned into normal group， radiation group， salidroside low-dose （salidroside-L， 50 mg/kg） group， salidroside high-dose （salidroside-H， 100 mg/kg） group， and salidroside-H+inhibitor （100 mg/kg salidroside+0.1 µmol/kg H-89） group， with 10 rats in each group. Except for the normal group， rats in the other groups were subjected to radiation exposure to establish a model of radiation-induced parotid gland injury. Rats in each group were intraperitoneally injected with the corresponding drug or normal saline， once a day， for 40 consecutive days. After the last administration， the levels of reactive oxygen species （ROS）， cyclic adenosine monophosphate （cAMP）， superoxide dismutase （SOD）， and amylase in serum were detected； the pathological changes of parotid gland tissue were observed； the apoptosis rate of parotid gland tissue cells， the expression levels of B-cell lymphoma-2 （Bcl-2） and its associated X protein （Bax）， mRNA expression levels of interleukin-6 （IL- 6） and tumor necrosis factor-α （TNF-α）， the protein expression levels of type Ⅲ collagen （Col Ⅲ）， vasoactive intestinal peptide （VIP）， and the phosphorylation level of protein kinase A （PKA） in parotid gland tissue were determined. RESULTS Compared with normal group， the levels of ROS， amylase， apoptosis rate， Bax expression level， mRNA expression levels of IL-6 and TNF- α， and protein expression level of Col Ⅲ in the radiation group were significantly increased， while the levels of cAMP， SOD， Bcl-2 expression level， VIP protein expression level and PKA phosphorylation level were significantly decreased （P＜0.05）. Compared with radiation group， the above indicators in the salidroside-L group and salidroside-H group were significantly improved （P＜0.05）， and the improvement in the salidroside-H group was more significant （P＜0.05）； inhibitor H-89 significantly reversed the changes in the above indicators of the salidroside-H group （P＜0.05）. CONCLUSIONS Salidroside can effectively alleviate radiation-induced parotid gland injury in rats， and its mechanism may be related to the activation of the VIP-cAMP pathway.

INTRODUCTION: Albeit comprising a small portion of the hospital population, persistent high utilisers (PHUs) contribute disproportionately to healthcare expenditures. Amid rising healthcare costs and an ageing population, this study examines factors associated with PHUs among residents in eastern Singapore. METHOD: This is a retrospective study of eligible patients at Changi General Hospital in Singapore between 1 January 2020 and 31 December 2022. The study included Singapore citizens who utilised any services offered by CGH. Patients were classified as PHUs if their annual healthcare expenditure exceeded SGD3700 for 3 consecutive years. Demographics, healthcare utilisation patterns and clinical profiles were compared, and multivariable analyses were conducted to identify factors associated with PHUs. RESULTS: There were 267,838 eligible patients identified, with 5316 (2%) classified as PHUs. PHUs accounted for 18.4% of the total healthcare expenditure, with the highest costs attributed to inpatient services, followed by outpatient services. PHUs were more likely to be older, male, non-Chinese and of lower socioeconomic status. Conditions with the strongest association with PHUs were mental health disorders, chronic obstructive pulmonary disease, osteoporosis, asthma and renal diseases. Inpatient discharges from renal medicine, psychological medicine and general/geriatric medicine wards had the strongest association with PHUs. Utilisation of allied health services had the highest odds of being a PHU in outpatient care. CONCLUSION This study identified key factors associated with PHUs, providing invaluable insights into the planning of population health services within the hospital's geographical region. Targeted service development and process improvements of medical care can help mitigate persistent high utilisation.
Humans ; Singapore/epidemiology* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Adult ; Health Expenditures/statistics & numerical data* ; Patient Acceptance of Health Care/statistics & numerical data* ; Population Health ; Aged, 80 and over ; Young Adult ; Adolescent

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration. METHOD: An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded. RESULTS: The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations. CONCLUSION The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Singapore ; Consensus ; Adult

Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*