OBJECTIVE: To investigate the clinical utility of novel of new hematological markers in the preoperative diagnosis of periprosthetic joint infection (PJI). METHODS: A retrospective analysis was conducted on a total of 149 patients who underwent revision of total hip arthroplasty (THA) or total knee arthroplasty (TKA) at a single center between January 2016 and June 2022, including 63 males and 86 females, aged from 47 to 93 years old with an average of (69.5±11.8) years old. Of them, 46 were diagnosed as PJI(PJI group), including 22 males and 24 females. The mean age was (71.3±12.5) years old. The body mass index (BMI) was (26.4±3.1) kg·m^-2. And 103 patients were diagnosed as aseptic prosthesis loosening (aseptic group), including 41 males and 62 females. The mean age was (68.7±11.4) years old. The BMI was (25.8±3.5) kg·m^-2. Preoperatively analyzed clinical parameters included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, globulin, albumin-to-globulin ratio (AGR), plasma D-dimer, and plasma fibrinogen. The receiver operating characteristic curve (ROC), sensitivity, and specificity analysis were employed to compare the diagnostic value of each blood marker in preoperative PJI diagnosis. RESULTS: In the PJI group, the levels of CRP were 16.6 (7.6, 4.5) mg·L^-1, ESR was 17.0 (12.8, 35.5) mm·h^-1, plasma D-dimer was 1.0 (0.5, 3.1) μg·L^-1, and plasma fibrinogen was 4.2 (3.2, 3.1) mg·L^-1;all of which were higher compared to the aseptic group with CRP at 4.2 (2.6, 7.8) mg·L^-1, ESR at 12.0(8.0, 20.0 )mm·h^-l, D-dimer at 0.4(0.2, 0.7)μg·L^-1, and fibrinogen at 2.8(2.4, 3.3 ) g·L^-1(P<0.05). However, the albumin level of 35.3 (32.3, 37.5) g·L^-1 and the WBC ratio of 1.0(0.9, 1.1) in the PJI group were significantly lower compared to the aseptic group with levels of 39.8 (36.1, 41.8) g·L^-1 and 1.4 (1.3, 1.5), respectively (P<0.05). Only the area under the curve (AUC) of AGR and plasma fibrinogen were greater than 0.8. The optimal predictive cut-1off, AUC, sensitivity and specificity were 3.4 g·L-1, 0.820, 69.57% and 84.47% for plasma fibrinogen; 1.18, 0.813, 82.61% and 78.64% for AGR, respectively. CONCLUSION AGR and plasma fibrinogen are promising blood markers for improving the diagnosis of PJI.
Humans ; Female ; Fibrinogen/metabolism* ; Male ; Middle Aged ; Aged ; Prosthesis-Related Infections/blood* ; Retrospective Studies ; Biomarkers/blood* ; Aged, 80 and over ; Arthroplasty, Replacement, Knee/adverse effects* ; Arthroplasty, Replacement, Hip/adverse effects* ; Leukocyte Count

Objective To explore the expression of coagulation indexes in rheumatoid arthritis (RA) and dry syndrome (pSS) and their relationships with inflammation and immune function. Methods A total of 61 patients with RA who were hospitalized in the Department of Rheumatology of Anhui Provincial Hospital of Traditional Chinese Medicine from March 12 to September 9, 2024 were selected as the RA group. And 61 patients with pSS who were hospitalized in the Department of Rheumatology of the same hospital September 4, 2023, to August 17, 2024, were selected as the pSS group. 61 healthy individuals who underwent routine medical checkups at the Physical Examination Center of Anhui Provincial Hospital of Traditional Chinese Medicine during the same period were included as the control group. Baseline clinical indexes before treatment were collected from patients in each group, including prothrombin time(PT), international normalized ratio(INR), thrombia time(TT), fibrinogen(FBG), activated partial thromboplastin time(APTT), fibrin (ogen) degradation products(FDP) and D-Dimer(D-D). Results The expression levels of PT, FBG, TT, FDP, and D-D in the RA group, the pSS group, and the normal group were significantly different. The expression levels of PT, FBG, FDP, and D-D in the RA group were all higher than those in the pSS group and the control group, respectively. And the expression level of TT in the pSS group was lower than that in control group. ROC curve analysis showed that the AUC of PT was 0.638, the AUC of FBG was 0.899, the AUC of FDP was 0.866, and the AUC of D-D was 0.919 in the RA group compared with the normal group. And the AUC of coagulation indexes for joint diagnosis of RA was higher than that of the indexes detected individually. pSS group had an AUC of PT of 0.618 compared with that of the normal group. The AUC of TT was 0.645, and the AUC of coagulation indexes for the joint diagnosis of pSS was higher than the AUC of each index detected separately. Association rule analysis showed that elevated D-D in RA patients had a significant correlation with elevated hs-CRP, CCP and RF, and elevated FBG had a significant correlation with elevated hs-CRP, ESR, RF and CCP. Elevated D-D in pSS patients had a correlation with elevated hs-CRP and anti-SSA, and elevated INR has correlation with elevated hs-CRP, anti-SSA and anti-SSB. Correlation analysis showed that PT, INR, FBG, FDP, and D-D were positively correlated with CRP and ESR, and TT was negatively correlated with CRP and ESR in the RA group. FBG, FDP, and D-D were positively correlated with CRP and ESR in the pSS group. Moreover, coagulation indexes were positively correlated with immune indexes in RA group and pSS group which were all significant. The results of multiple linear regression analysis showed that FBG was a positive correlate of hs-CRP and ESR in RA patients. For PSS patients, FBG and FDP were positive correlates of hs-CRP. APTT and FBG were positive correlates of ESR. Conclusion Compared with pSS, coagulation indexes (especially PT, FBG, FDP and D-D) are more informative for the early diagnosis of RA and the judgment of the degree of the disease, and can be used as an important predictor for the confirmation of the diagnosis of RA.
Humans ; Female ; Male ; Arthritis, Rheumatoid/diagnosis* ; Middle Aged ; Fibrin Fibrinogen Degradation Products/analysis* ; Blood Coagulation ; Adult ; Fibrinogen/metabolism* ; Partial Thromboplastin Time ; Prothrombin Time ; Aged ; Inflammation/immunology* ; ROC Curve

PURPOSE: To compare the effects of empirical and modified hemostatic resuscitation for liver blast injury combined with seawater immersion. METHODS: Thirty rabbits were subjected to liver blast injury combined with seawater immersion, and were then divided into 3 groups randomly (n = 10 each): group A (no treatment after immersion), group B (empirical resuscitation with 20 mL hydroxyethyl starch, 50 mg tranexamic acid, 25 IU prothrombin complex concentrate and 50 mg/kg body weight fibrinogen concentrate), and group C (modified resuscitation with additional 10 IU prothrombin complex concentrate and 20 mg/kg body weight fibrinogen concentrate based on group B). Blood samples were gathered at specified moments for assessment of thromboelastography, routine coagulation test, and biochemistry. Mean arterial pressure, heart rate, and survival rate were also documented at each time point. The Kolmogorov-Smirnov test was used to examine the normality of data distribution. Multigroup comparisons were conducted with one-way ANOVA. RESULTS: Liver blast injury combined with seawater immersion resulted in severe coagulo-fibrinolytic derangement as indicated by prolonged prothrombin time (s) (11.53 ± 0.98 vs. 7.61 ± 0.28, p＜0.001), activated partial thromboplastin time (APTT) (s) (33.48 ± 6.66 vs. 18.23 ± 0.89, p＜0.001), reaction time (R) (min) (5.85 ± 0.96 vs. 2.47 ± 0.53, p＜0.001), decreased maximum amplitude (MA) (mm) (53.20 ± 5.99 vs. 74.92 ± 5.76, p＜0.001) and fibrinogen concentration (g/L) (1.19 ± 0.29 vs. 1.89 ± 0.32, p = 0.003), and increased D-dimer concentration (mg/L) (0.38 ± 0.32 vs. 0.05 ± 0.03, p = 0.005). Both empirical and modified hemostatic resuscitation could improve the coagulo-fibrinolytic states and organ function, as indicated by shortened APTT and R values, decreased D-dimer concentration, increased fibrinogen concentration and MA values, lower concentration of blood urea nitrogen and creatine kinase-MB in group B and group C rabbits in comparison to that observed in group A. Further analysis found that the R values (min) (4.67 ± 0.84 vs. 3.66 ± 0.98, p = 0.038), APTT (s) (23.16 ± 2.75 vs. 18.94 ± 1.05, p = 0.001), MA (mm) (60.10 ± 4.74 vs. 70.21 ± 3.01, p < 0.001), and fibrinogen concentration (g/L) (1.68 ± 0.21 vs. 1.94 ± 0.16, p = 0.013) were remarkably improved in group C than in group B at 2 h and 4 h after injury. In addition, the concentration of blood urea nitrogen (mmol/L) (24.11 ± 1.96 vs. 21.00 ± 3.78, p = 0.047) and creatine kinase-MB (U/L) (85.50 ± 13.60 vs. 69.74 ± 8.56, p = 0.013) were lower in group C than in group B at 6 h after injury. The survival rates in group B and group C were significantly higher than those in group A at 4 h and 6 h after injury (p < 0.001), however, there were no statistical differences in survival rates between group B and group C at each time point. CONCLUSIONS Modified hemostatic resuscitation could improve the coagulation parameters and organ function better than empirical hemostatic resuscitation.
Animals ; Rabbits ; Resuscitation/methods* ; Liver/injuries* ; Seawater ; Blast Injuries/therapy* ; Fibrinogen/administration & dosage* ; Male ; Tranexamic Acid/administration & dosage* ; Immersion ; Hydroxyethyl Starch Derivatives/administration & dosage*

OBJECTIVES: To investigate the risk factors for plastic bronchitis (PB) in children with macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) and to establish a nomogram prediction model. METHODS: A retrospective analysis was conducted on 178 children with MUMPP who underwent bronchoscopy from January to December 2023. According to the presence or absence of PB, the children were divided into a PB group (49 children) and a non-PB group (129 children). The predictive factors for the development of PB in children with MUMPP were analyzed, and a nomogram prediction model was established. The model was assessed in terms of discriminatory ability, accuracy, and clinical effectiveness. RESULTS: The multivariate logistic regression analysis showed that older age and higher levels of lactate dehydrogenase and fibrinogen were closely associated with the development of PB in children with MUMPP (P<0.05). A nomogram model established based on these factors had an area under the receiver operating characteristic curve of 0.733 (95%CI: 0.651-0.816, P<0.001) and showed a good discriminatory ability. The Hosmer-Lemeshow goodness-of-fit test indicated that the predictive model had a good degree of fit (P>0.05), and the decision curve analysis showed that the model had a good clinical application value. CONCLUSIONS The risk nomogram model established based on age and lactate dehydrogenase and fibrinogen levels has good discriminatory ability, accuracy, and predictive efficacy for predicting the development of PB in children with MUMPP.
Retrospective Studies ; Risk Factors ; Nomograms ; Mycoplasma pneumoniae/isolation & purification* ; Pneumonia, Mycoplasma/microbiology* ; Bronchitis/microbiology* ; Macrolides/therapeutic use* ; Drug Resistance, Bacterial ; Bronchoscopy ; Area Under Curve ; ROC Curve ; Fibrinogen/analysis* ; Age Factors ; Humans ; Male ; Female ; Infant ; Child, Preschool ; Child ; Adolescent ; L-Lactate Dehydrogenase/blood*

OBJECTIVE: To explore the predictive value of age, D-Dimer and fibrinogen (FIB) for non-thrombotic. METHODS: A retrospective analysis was conducted on a total of 1 384 coagulation test cases from January to August 2024 at Nanning No. 8 People's Hospital. Among them, the control group comprised 400 non-thrombotic cases with D-Dimer test results within the reference range. The thrombotic group comprised 57 clinically diagnosed thrombotic patients. The research group comprised 927 non-thrombotic cases with D-Dimer levels exceeding the reference range. The diagnosis treatment records, age information, plasma D-Dimer, and FIB test results of each group were collected. The changes and correlations of age, D-Dimer, and FIB indicators were compared and analyzed among the three groups. A new combination factor was generated by fitting a Logistic binary regression model. ROC curves were used to evaluate the predictive value of each index for non-thrombotic disease in both the research group and the thrombotic group. RESULTS: Compared with the control group, the thrombotic group and the research group had significantly higher age, D-Dimer, and FIB levels (P < 0.001). Further comparative analysis showed that the research group had significantly lower age and D-Dimer levels than the thrombotic group, the FIB level was significantly higher than that of the thrombotic group (P < 0.001). Spearman correlation analysis showed that the correlation coefficient between age and D-Dimer in the research group was higher than that in the control group and thrombotic group (P < 0.01), the thrombotic group had the highest negative correlation coefficient between FIB and D-Dimer (P < 0.01). The ROC curve analysis results showed that the AUC values of age, plasma D-dimer, and FIB independently predicted non-thromb diseases were 0.726, 0.735, and 0.611, respectively. A new combined factor was generated by fitting age, D-dimer, and FIB with a logistic binary regression model. The AUC value of the combined prediction of non-thrombotic diseases was the maximum at 0.832, which had high diagnostic value, and its sensitivity and specificity were 0.572 and 0.070. CONCLUSION Elevated D-dimer levels were associated with age, increased FIB, and a variety of non-thrombotic diseases, and combination of age, D-dimer, and FIB had a certain predictive value for non-thrombotic diseases, but the combined model had a low specificity, other information needs to be combined in the clinic to improve diagnostic accuracy.
Humans ; Fibrin Fibrinogen Degradation Products ; Retrospective Studies ; Fibrinogen ; Predictive Value of Tests ; Thrombosis ; Age Factors ; ROC Curve ; Male ; Female ; Middle Aged ; Adult

OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Liver Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Animals ; Humans ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Amphibian Venoms/therapeutic use* ; Cell Line, Tumor ; Neoplasm Metastasis ; Cell Survival/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Neoplasm Invasiveness ; Mice, Inbred BALB C ; Mice, Nude ; Mice ; Male ; Bufanolides/therapeutic use* ; Protein Precursors ; Prothrombin ; Biomarkers

OBJECTIVE: To explore the mechanism of Dihuang Yinzi (DHYZ) in the treatment of Alzheimer's disease (AD) by integrating metabolomics and experimental verification. METHODS: Forty-eight male APP/PS1 mice were divided into model, high- (DHYZ-H), medium- (DHYZ-M), and low-dose DHYZ (DHYZ-L) groups (12 mice per group) according to a random number table. Mice in DHYZ groups were gavaged with DHYZ 6.34, 12.68, and 25.35 g/(kg·d), respectively. Twelve C57BL/6 mice were gavaged with distilled water as the blank group. Metabolomics was used to analyze differential metabolites in the brains of mice. Morris water maze test was used to detect the memory abilities of mice. The hematoxylin-eosin staining and transmission electron microscopy were used to observe the general morphology and ultrastructure of neurons. The enzyme-linked immunosorbent assay was used to detect the levels of superoxide dismutase (SOD), reactive oxygen species (ROS), and amyloid β -protein 1-42 (A β_1-42). The real-time quantitative polymerase chain reaction was used to detect the mRNA expressions of density-regulated protein 1 (DRP1), fission 1 (FIS1), mitofusin-1 (MFN1), and optic atrophy protein 1 (OPA1). Western blot was used to detect the protein expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response binding protein (CREB), brain-derived neurotrophic factor (BDNF), synapsin 1 (SYN1), synaptophysin (SYP), and postsynaptic density protein 95 (PSD95). RESULTS: A total of 82 differential metabolites were identified in the brains of APP/PS1 mice, among which 7 differential metabolites could be regulated by DHYZ. After DHYZ intervention, the memory abilities of mice significantly increased (P<0.05 or P<0.01), the number of synapses and neurons in the hippocampus increased, and the mitochondrial morphology and structure were relatively intact. The DHYZ groups exhibited a significant reduction in hippocampal ROS and A β_1-42 levels, along with a significant elevation in SOD level (P<0.05 or P<0.01). The mRNA expressions of DRP1 and FIS1 were reduced, while the mRNA expressions of MFN1 and OPA1 were increased after DHYZ treatment (P<0.05 or P<0.01). The cAMP/PKA/CREB-BDNF pathway was activated, and the expressions of SYN1, SYP and PSD95 proteins were significantly increased in the DHYZ-H group (P<0.05 or P<0.01). CONCLUSIONS DHYZ could improve mitochondrial dynamics and synaptic plasticity in APP/PS1 mice, inhibit oxidative stress, and thereby enhancing learning and memory abilities in APP/PS1 mice. Its mechanism might be related to activation of the cAMP/PKA/CREB-BDNF signaling pathway.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Male ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Brain/drug effects* ; Metabolomics ; Mice, Inbred C57BL ; Neuronal Plasticity/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Cyclic AMP/metabolism* ; Reactive Oxygen Species/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Mice, Transgenic ; Mice ; Amyloid beta-Peptides/metabolism* ; Signal Transduction/drug effects* ; Alzheimer Disease/drug therapy* ; Superoxide Dismutase/metabolism*

OBJECTIVE: To explore the mechanism of crocin, a major active component of Crocus sativus (Zanghonghua), in regulating amyloid beta (Aβ) generation, endoplasmic reticulum (ER) stress, and autophagy in neuronal cells, with potential therapeutic applications in Alzheimer's disease (AD). METHODS: Mouse neuroblastoma Neuron2a (N2a) cells stably transfected with the human amyloid precursor protein (APP) Swedish mutant was used as a cellular model for AD (N2a/APP). Control cells were vector transfected (N2a/vector). The effects of 3 different doses of crocin on reactive oxygen species (ROS) generation, cytosolic calcium, and apoptosis were evaluated by flow cytometry. Aβ levels were determined by enzyme-linked immunosorbent assay. APP processing and ER stress proteins expressions were determined by Western blot. Autophagosome formation was evaluated by autophagy detection kit and confocal microscope. RESULTS: Crocin inhibited APP expression in N2a/APP cells and promoted α-cleavage of APP processing, while modestly reduced beta-secretase 1 (BACE1) and presenilin 1 (PS1, P<0.05 or P<0.01). ER stress markers, including the binding immunoglobulin protein/78-kD glucose-regulated protein (Bip/GRP78) and C/EBP homologous protein (CHOP), were elevated in N2a/APP cells compared to N2a/vector cells (P<0.05). Crocin could effectively reduce the levels of ER stress (P<0.05 or P<0.01). In addition, crocin enhanced autophagy by promoting formation of autophagosome (P<0.05 or P<0.01). CONCLUSION Crocin significantly inhibited Aβ generation by promoting α-cleavage of APP processing, inhibiting ER stress-associated unfolded protein response, and regulating autophagy.
Endoplasmic Reticulum Stress/drug effects* ; Autophagy/drug effects* ; Animals ; Endoplasmic Reticulum Chaperone BiP ; Mice ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Carotenoids/pharmacology* ; Humans ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Calcium/metabolism*

OBJECTIVES: Hypertriglyceridemic acute pancreatitis (HTG-AP) has a rapid onset and is associated with a high risk of progression and recurrence. Early identification of patients at risk of severe disease can help reduce the likelihood of multiple organ failure and mortality. This study aims to investigate the changes in inflammatory composite markers and D-dimer (D-D) levels in young and middle-aged/elderly patients with HTG-AP and to evaluate their predictive value for disease progression. METHODS: A total of 230 patients with HTG-AP admitted to Chongqing University Jiangjin Hospital (Jiangjin Central Hospital) between 2017 and 2023 were retrospectively enrolled. Patients were first divided into a young group (≤45 years) and a middle-aged/elderly group (>45 years), and then stratified into mild and severe groups based on disease severity. Inflammatory composite markers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein-to-lymphocyte ratio (CLR), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), as well as D-D levels, were compared among groups. Least absolute shrinkage and selection operator (LASSO) regression and Logistic regression were used to identify independent risk factors for disease progression in each age group. Receiver operating characteristic (ROC) curves and the DeLong test were used to assess and compare the predictive performance (area under the curve, AUC) of risk factors. Internal validation was performed using the bootstrap method (n=1 000). RESULTS: No significant differences in NLR, PLR, MLR, SIRI, SII, CLR, or D-D levels were observed between the young (n=127) and middle-aged/elderly (n=103) groups (all P>0.05). Among young patients, the severe group (n=59) had significantly higher NLR, SIRI, SII, CLR, and D-D levels compared to the mild group (n=68) (all P<0.05). Among middle-aged/elderly patients, CLR and D-D levels were significantly higher in the severe group (n=49) than in the mild group (n=54) (P<0.05). LASSO and Logistic regression analyses identified elevated D-D as an independent risk factor for disease progression in young patients (P=0.007, OR=1.458, 95% CI 1.107 to 1.920), while both D-D (P=0.001, OR=2.267, 95% CI 1.413 to 3.637) and CLR (P=0.003, OR=1.007, 95% CI 1.003 to 1.012) were independent risk factors in middle-aged/elderly patients. ROC analysis showed that D-D predicted disease progression in young and middle-aged/elderly patients with AUCs of 0.653 and 0.741, sensitivities of 67.8% and 57.1%, and specificities of 72.1% and 88.9%, respectively. CLR predicted progression in middle-aged/elderly patients with an AUC of 0.687, sensitivity of 63.3%, and specificity of 70.4%. DeLong test showed no significant difference in AUC between D-D and CLR for middle-aged/elderly patients (Z=0.993, P=0.321). Internal validation via bootstrap analysis yielded a D-D AUC of 0.732, with sensitivity and specificity of 68.1% and 91.0%, respectively. CONCLUSIONS Differences in inflammatory response and coagulation function exist across age groups and disease severities in HTG-AP patients. Elevated D-D is an independent predictor of disease progression in both young and middle-aged/elderly patients, while CLR also predicts progression in the latter group. D-D, in particular, demonstrates strong predictive value for severe disease in middle-aged/elderly patients with HTG-AP.
Humans ; Fibrin Fibrinogen Degradation Products/metabolism* ; Disease Progression ; Middle Aged ; Pancreatitis/etiology* ; Male ; Female ; Retrospective Studies ; Adult ; Biomarkers/blood* ; Hypertriglyceridemia/blood* ; Acute Disease ; Predictive Value of Tests ; Aged ; Inflammation ; C-Reactive Protein/analysis* ; Neutrophils ; Age Factors

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation