Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

Objective To analyze the clinical characteristics and prognosis of the overlap syndrome of dementia,depression and delirium coexistence in two or three of them (the 2D's or 3D's) in elderly patients,in order to raise awareness.Methods Clinical data of 16 patients aged ＞65 years diagnosed with the 2D's or 3D's admitted to Peking Union Medical College Hospital from 2010 to 2014 were analyzed and relevant literatures were reviewed.Results Patients with the 2D's or 3D' s accounted for 10％ of the elderly demented patients and 3％ of the elderly depressive patients.16 patients [11 females and 5 males,median age 82 years and mean age (80±6) years] were enrolled,with 7 cases of dementia with depression,6 cases of delirium superimposed on dementia,2 cases of the 3D's,and 1 case of coexisting depression and incident delirium.The Charlson comorbidity index of the 16 patients was (3.0± 1.5).(4.0± 1.6) kinds of geriatric syndromes were found,and the most common were falls (62％),sleep disorders (56％),frailty (50％),polypharmacy (43 ％),and malnutrition (37％).Disability was identified in 14 (88％) patients on admission.Delirium was observed in 9 patients (56 ％),with 7 cases of hyperactive delirium and 2 cases of hypoactive delirium.Coexisting underlying dementia was identified after episodes of delirium in 6 cases.16 patients all received corresponding intervention during hospitalization period.During a mean follow-up period of (15±13) months,62 ％ of the patients had more impaired physical function (ADL score reduction≥ 1),and 43％ of the patients had more impaired cognitive function (MMSE score reduction≥3).Two patients were transferred to long-term care facilities and one patient died during follow-up.The readmission rate was 50％ within 1 year after discharge.Conclusions The domestic report of overlap syndrome of dementia,depression and delirium is rare.Patients with the coexistence of the 2D's or 3D's are more commonly combined with geriatric syndromes,which results in further cognitive and physical function impairment with a higher re-admission rate.We should pay attention to the follow-up in elderly patients with delirium for screening dementia.

Objective To investigate the clinical characteristics of diabetic retinopathy(DR)and diabetic nephropathy(DN)and their correlation. Methods All of 9237 hospitalized type 2 diabetes patients from January 2004 to June 2009 were collected. The prevalence and clinical of characteristics of DR and DN as well as their relationship were analyzed. Results The total prevalence of DR was 33.0%(3045/9237),and the prevalence of DR in the microalbuminuria, macroproteinuria and macroalbuminuria combined with renal dysfunction patients were 36.3%(588/1618),53.7%(1113/2074)and 70.7%(1206/1706)respectively.The prevalence of DN was 58.4%(5398/9237). Compared with that in the diabetes patients without DR, the levels of microalbumin and total protein in the urine were higher in the patients with moderate non-proliferative diabetic retinopathy(NPDR), serious NPDR and proliferative diabetic retinopathy(PDR), but the endogenous creatinine clearance rate was lower(P＜ 0.05). According to the non-conditional Logistic regression model,the risk factors of DR included diabetes duration,urinary protein,fibrinogen, C-reactive protein and peripheral neuropathy, and the risk factors of DN included diabetes duration, HbA1c, systolic blood pressure,urinary protein,low density lipoprotein and DR. Conclusions DR and DN are the chronic microvascular complications in the type 2 diabetes and have higher prevalence. There are good correlations between DR and DN.