Liver injury due to acetaminophen overdose is one of the main causes of acute liver failure， with a complex pathogenesis. In this process， liver sinusoidal endothelial cell （LSEC） injury is a key early event jointly mediated by factors such as oxidative stress， cell apoptosis， and imbalance between fibrinolysis and coagulation. Subsequent LSEC dysfunction further induces sinusoidal microcirculatory disturbances， amplifies the inflammatory response， impairs the regeneration and repair abilities of the liver， and finally causes hepatocyte necrosis. This article systematically elaborates on the critical role and molecular mechanism of LSEC in acetaminophen-induced liver injury， in order to provide a theoretical basis for novel therapeutic strategies and research directions.

BACKGROUND:Mitophagy is closely associated with the development of idiopathic pulmonary fibrosis,but its mechanism remains unclear.OBJECTIVE:To investigate the biological mechanism of mitophagy in idiopathic pulmonary fibrosis and provide ideas for the risk prediction of idiopathic pulmonary fibrosis and subtype differentiation.METHODS:The mitophagy-related genes in idiopathic pulmonary fibrosis were obtained through GEO and Reactome Pathway databases.The mitophagy-related characteristic genes in idiopathic pulmonary fibrosis were screened based on intergroup differences and random forest model.GO functional enrichment analysis and KEGG,Reactome with WIKI pathway enrichment analyses were performed by g:Profiler database.Mitophagy subtypes in idiopathic pulmonary fibrosis were distinguished by consensus clustering method and immune infiltration analysis was performed.The mitophagy-related key gene was screened.Finally,the predictive value of mitophagy-related key gene for the risk of idiopathic pulmonary fibrosis was quantified by alignment diagram and the correlation between mitophagy-related key gene and clinical characteristics of idiopathic pulmonary fibrosis was explored.RESULTS AND CONCLUSION:(1)A total of 13 genes related to mitophagy in idiopathic pulmonary fibrosis were identified and 5 characteristic genes were screened,containing PINK1,RPS27A,SRC,HIF1A,and CDH6.(2)GO analysis was mainly involved in ubiquitin protein ligase binding,and cellular response to hypoxia.Pathway enrichment analysis was mainly involved in PINK1-PRKN mediated mitophagy,NOTCH signaling pathway,signaling by EGFR and angiogenesis.(3)HIF1A had significant expression differences between subtypes,which might serve as a key gene for the differentiation of mitophagy subtypes of idiopathic pulmonary fibrosis.(4)Immune infiltration analysis suggested that myeloid-derived suppressor cell,neutrophil and type 1 T helper cell might have infiltration differences between subtypes,while HIF1A was positively correlated with multiple immune cells.(5)Alignment diagram suggested that the risk of idiopathic pulmonary fibrosis might be predicted by the expression level of HIF1A.(6)Clinical characteristics analysis indicated patients with high expression of HIF1A might have poorer lung function and more severe fibrosis.It is concluded that PINK1,RPS27A,SRC,HIF1A,and CDH6 may influence the development of idiopathic pulmonary fibrosis through mitophagy,in which HIF1A may serve as a key gene for risk prediction with clinical subtype differentiation and HIF1A is strongly associated with the lung function of patients.

Objective:To evaluate the effect of Yiyiren Decoction on the prevention and treatment of collagen induced arthritis with syndrome of cold-dampness obstruction (CIA-CDO) its mechanism.Methods:A cold dampness obstruction type CIA rat model was prepared by injecting type Ⅱ collagen and simulating a cold and humid environment in an artificial climate chamber. The successfully modeled rats were randomly divided into a model group, a positive group, and Yiyiren Decoction high- and low-dosage groups according to a random number table method. Additionally, 8 normal rats were set as the blank group. The Yiyiren Decoction high- and low-dosage groups were orally administered with Yiyiren Decoction at dosages of 24 and 12 g/kg, the positive group was orally administered with leflunomide at a dosage of 10 mg/kg, and the blank group and model group were orally administered with equal volumes of normal saline once a day for 4 consecutive weeks. The overall signs of the rats were observed daily, and the arthritis index (AI) of the limbs and paws was assessed weekly; after 4 weeks of drug administration, the serum levels of pro-inflammatory cytokines (TNF-α and IL-1β) and anti-inflammatory cytokines (IL-4 and IL-10) were detected by ELISA, histopathology of the ankle joint sections was observed under the light microscope, and gene expressions of synovial MMP-3 and TIMP-1 were determined by RT-qPCR.Results:The overall physical signs and joint symptoms of rats in the Yiyiren Decoction high- and low-dosage group increased; compared with the model group, after 3 and 4 weeks of administration, the AI scores of the Yiyiren Decoction high- and low-dosage group and positive group decreased ( P<0.01); the Yiyiren Decoction high- and low-dosage group showed varying degrees of improvement in inflammatory cell infiltration, synovial/fibrous tissue proliferation, and bone and cartilage structure damage in the ankle joint; compared with the model group, the levels of pro-inflammatory cytokines TNF-α and IL-1β in the high and Yiyiren Decoction low-dosage groups decreased ( P<0.01), while the levels of IL-4 and IL-10 increased ( P<0.01); the mRNA level of MMP-3 in synovium decreased ( P<0.05 or P<0.01), while the mRNA level of TIMP-1 increased ( P<0.05 or P<0.01). Conclusion:Yiyiren Decoction can improve the joint symptoms of CIA rats with cold-dampness obstruction, and its preventive and therapeutic effects may be related to correcting the imbalance of pro-inflammatory/anti-inflammatory cytokines and MMP-3/TIMP-1, reducing the inflammatory reaction in the joint cavity and the whole body, and inhibiting the metabolic disorder of joint matrix.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Objective:To evaluate the relationship between the mechanism of buprenorphine in attenuating neuroinflammation in microglia and the MAM domain-containing glycosylphosphatidylinositol anchor gene 1 ( MDGA1). Methods:The human microglial cell line HMC-3 was cultured in vitro and divided into 4 groups ( n=6 each) using a table of random numbers: control group (Con group), lipopolysaccharide(LPS)group, buprenorphine + LPS group (Bup+ LPS group) and buprenorphine + LPS + MDGA1 knockdown group (Bup+ LPS+ shMDGA1 group). LPS group was incubated with LPS at a final concentration of 1 μg/ml for 4 h. Bup+ LPS group was incubated with buprenorphine at a final concentration of 100 ng/ml for 1 h, followed by incubation with LPS at a final concentration of 1 μg/ml for 4 h. Bup+ LPS+ shMDGA1 group was transfected with MDGA1-specific shorthairpin RNA for knockdown, and the remaining treatment was similar to those previously described in Bup+ LPS group. The expression of MDGA1 in microglia was detected using real-time quantitative polymerase chain reaction, and the concentrations of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) in the supernatant were measured using enzyme-linked immunosorbent assay. Results:Compared with Con group, the concentrations of IL-6, IL-1β, TNF-α and iNOS in the supernatant were significantly increased, and the expression of MDGA1 in microglia was down-regulated in LPS group ( P<0.05). Compared with LPS group, the concentrations of IL-6, IL-1β, TNF-α and iNOS in the supernatant were significantly decreased, and the expression of MDGA1 in microglia was up-regulated in Bup+ LPS group ( P<0.05). Compared with Bup+ LPS group, the concentrations of IL-6, IL-1β, TNF-α and iNOS in the supernatant were significantly increased, and the expression of MDGA1 in microglia was down-regulated in Bup+ LPS+ sh MDGA1 group ( P<0.05). Conclusions:The mechanism by which buprenorphine alleviates neuroinflammation in microglia may be related to the up-regulation of the expression of MDGA1.

Objective To construct a nomogram prediction model for symptomatic intracerebral hemorrhage(sICH)in elderly patients with cerebral infarction after intravenous thrombolysis based on systemic inflammatory indicators.Methods A retrospective study was conducted on 355 elderly patients with cerebral infarction who received intravenous thrombolysis with recombinant tissue plasminogen activator(rt-PA)in Tsinghua University Hospital from January 2019 to June 2024.They were randomly assigned into a modeling group(249 cases)and a validation group(106 cases)in a 7∶3 ratio.The modeling group was further divided into an sICH subgroup(24 cases)and a non-sICH subgroup(225 cases)based on sICH occurrence after intravenous thrombolysis.The general information and levels of systemic inflammatory indicators were compared between the sICH subgroup and the non-sICH subgroup.Logistic regression was used to identify the influ-encing factors for sICH,and then a nomogram prediction model was constructed.The predictive performance of the model was evaluated through ROC curve and calibration curve analyses,and then the data of the validation group were used for validation.Results The sICH subgroup had significantly larger proportions of atrial fibrillation(AF)and leukoaraiosis at admission,higher baseline NIHSS score,increased neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ra-tio(PLR),and C-reactive protein(CRP)level,but lower lymphocyte to monocyte ratio(LMR)when compared with the non-sICH subgroup(P＜0.05,P＜0.01).ROC curve analysis showed that the AUC value of NIHSS score,NLR,LMR,PLR,and CRP in predicting sICH occurrence in stroke patients after intravenous thrombolysis was 0.796,0.638,0.695,0.725,and 0.686,respec-tively(P＜0.05,P＜0.01).Logistic regression analysis indicated that systemic inflammatory indi-cators NLR,LMR,PLR,CRP level,AF,baseline NIHSS score,and leukoaraiosis at admission were all influencing factors for the occurrence of sICH in these patients(P＜0.05,P＜0.01).The consistency index of the nomogram prediction model based on systemic inflammatory indicators and other factors in predicting the occurrence of sICH was 0.951(95％CI:0.918-0.985),and the calibration curve tended to the ideal curve.The AUC value of the model for the occurrence of sICH in the validation group was 0.980(95％CI:0.956-1.000).Conclusion Our nomogram pre-diction model based on systemic inflammatory indicators NLR,LMR,PLR,CRP,and other major variables has good predictive performance for the occurrence of sICH in elderly patients with cere-bral infarction after rt-PA intravenous thrombolysis.

Chronic hepatitis B(CHB)is the main cause of hepatocellular carcinoma(HCC).Early prediction and diagnosis of HCC in CHB patients can further reduce the onset risk of HCC and improve patient prognosis.Scholars at home and abroad have proposed a number of HCC risk prediction models for CHB patients,and these models have achieved new development and opti-mization in the era of antiviral therapy.Due to differences in research backgrounds,these models vary in the use of antiviral drugs,included variables(such as host factors,viral activity,cirrhosis status,etc.)and application scenarios.At the same time,the application of artificial intelligence and liquid biopsy technology in risk prediction models has become a new research highlight.This paper aims to compare the HCC risk prediction models reported so far for CHB patients,clarify the characteristics of each model,explore appropriate HCC risk prediction methods,and provide reference for the risk prediction of hepatitis B virus related HCC.

Objective:To observe any effect of dynamic instability training on the balance and posture control of persons with chronic ankle instability (CAI).Methods:Thirty persons with CAI were divided at random into a control group and an observation group, each of 15. Both groups received routine rehabilitation interventions (including ankle strength training, kinesio taping, and vibration training), while the observation group additionally underwent 20 minutes of dynamic instability training daily, 5 days a week for 4 consecutive weeks. Before and after the treatment, everyone′s balance was evaluated using the Berg balance scale (BBS) and the star moving balance test (SEBT). Surface electromyography (sEMG) was used to collect electromyograms of the affected peroneus longus, tibialis anterior, rectus femoris and medialis femoris muscles of both groups within 100ms before and after landing in the jump-landing test. The intensity of muscle activation was thus analyzed.Results:After the treatment there was significant improvement in the average BBS scores, anterior medial SEBT, medial SEBT and posterior medial SEBT results of both groups. On average, all three SEBT results [(80.27±4.06)cm, (90.27±4.06)cm and (97.73±3.47)cm respectively] were significantly better in the observation group than in the control group. The standardized integrated electromyographs of the peroneus longus, tibialis anterior, rectus femoris and medialis femoris muscles on the affected sides showed significant improvement compared with before the treatment, but there too the observation group′s results were significantly better than those of the control group.Conclusions:Combining dynamic instability training with conventional rehabilitation can further improve the balance and postural control of persons with chronic ankle instability.

BACKGROUND: Most studies have evaluated disability-adjusted life years (DALYs) of colorectal cancer (CRC) patients based on a set of generic disability weights (DWs). This study aimed to apply local CRC-stage-specific DWs to estimate the burden of DALYs for CRC (CRC-DALYs) in populations in China and consider the influence of local screening coverage of CRC. METHODS: A prevalence-based model was constructed using data from various sources. Years lived with disability (YLDs) were estimated mainly via cumulative prevalence data (based on CRC incidence rates, population numbers, and survival rates), stage-specific proportions of CRC, and DWs of the local population. Years of life lost (YLLs) were calculated based on the CRC mortality rates and standard life expectancies. CRC incidence and mortality rates for the years 2020, 2025, and 2030 were estimated by joinpoint regression, and the corresponding DALYs were predicted. The main assumption was made for CRC screening coverage. Sensitivity analyses were used to assess the impact of population, DWs, and coverage. RESULTS: In 2017, among the Chinese population, the estimated number of CRC-DALYs was 4,303,314 (11.9% for YLDs). If CRC screening coverage rate in China (2.3%) remains unchanged, the overall DALYs in 2030 are predicted to increase by 37.2% (45.1% of those aged ≥65 years). More optimistically, the DALYs would then decrease by 0.7% in 2030 (from 5,902,454 to 5,860,200) if the coverage could be increased to 25.0%. A sensitivity analysis revealed that using local DWs would change the base-case values by 5.7%. CONCLUSIONS The estimated CRC-DALYs in China using population-specific DWs were considerably lower (with a higher percentage of YLDs) than the global burden of disease (GBD) estimates (5,865,004, of 4.6% for YLDs), suggesting the impact extent of applying local parameters. Sustainable scale-up CRC screening needs to be in place to moderate the growth trend of CRC-DALYs in China.
Humans ; Colorectal Neoplasms/diagnosis* ; China/epidemiology* ; Disability-Adjusted Life Years ; Male ; Prevalence ; Female ; Middle Aged ; Aged ; Early Detection of Cancer ; Quality-Adjusted Life Years ; Adult ; Incidence

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.