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

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 investigate the correlation of homocysteine (HCY) and coagulation function index with the risk of breast cancer and its clinicopathological characteristics. Methods: The HCY, coagulation function test index, and clinicopathological information of female breast cancer patients (333 cases) treated in Tianjin Medical University Cancer Hospital from January 2018 to December 2018 were collected, and female patients with benign breast (225 cases) were selected during the same period for the control group. The t-test was used to compare measurement data with normal distribution, D-Dimer data were distributed discreetly and described by median, non-parametric Mann-Whitney U test was used to compare the two groups. The chi-square test was used to compare enumeration data, and the Logistic regression analysis was used for the risk analysis. Results: The levels of HCY, fibrinogen (Fbg), protein C (PC), and median D-Dimer (D-D) in peripheral blood of breast cancer patients group [(13.26±5.24) μmol/L, (2.61±0.83) g/L, (117.55±19.67)%, and 269.68 ng/ml, respectively] were higher than those in the control group [(11.58±0.69) μmol/L, (2.49±0.49) g/L, (113.42±19.82)% and 246.98 ng/ml, respectively, P<0.05]. The prothrombin time (PT), PT(INR), α2-antiplasmin (α2-AP) levels [(10.19±0.63) s, 0.91±0.07 and (110.64±13.93)%, respectively] were lower than those in the control group [(10.58±0.65) s, 0.93±0.01 and (123.81±14.77) %, P<0.05]. The serum levels of PC and median D-D in premenopausal breast cancer patients [(112.57±17.86)% and 242.01 ng/ml, respectively] were higher than those in the control group [(105.31±22.31)% and 214.75 ng/ml, respectively, P<0.05]. The levels of PT(INR), α2-AP [0.91±0.07 and (111.29±12.54)%, respectively] were lower than those of the control group[0.98±0.15 and (120.17±16.35)%, respectively, P<0.05]. The levels of HCY and median D-D in postmenopausal breast cancer patients [(14.25±5.76) μmol/L and 347.53 ng/ml, respectively] were higher than those in the control group [(11.67±2.38) μmol/L and 328.28 ng/ml, P<0.05]. The levels of PT, PT(INR), antithrombin Ⅲ (AT-Ⅲ), α2-AP levels [(10.18±0.66) s, 0.87±0.09, (97.30±12.84)% and (110.13±14.96)%] were lower than those in the control group [(10.38±0.61) s, 0.90±0.08, (102.89±9.12)%, and (127.05±12.38)%, respectively, P<0.05]. The levels of α2-AP and median D-D in T2-4 stage breast cancer patients [(111.69±14.41)% and 289.25 ng/ml, respectively] were higher than those in Tis-1 stage patients [(108.05±12.37)% and 253.49 ng/ml, respectively, P<0.05]. The levels of PT, PT (INR), Fbg, AT-Ⅲ, α2-AP, median D-D [(10.62±0.63) s, 0.95±0.06, (3.04±1.52) g/L, (103.21±9.45)%, (118.72±14.77)% and 331.33 ng/ml, respectively] in breast cancer patients with lymph node metastasis were higher than those of patients without lymph node metastasis [(10.42±0.58) s, 0.93±0.06, (2.52±0.54) g/L, (95.20±13.63)%, (106.91±13.13)% and 263.38 ng/ml, respectively, P<0.05]. In non-menopausal breast cancer patients, the level of HCY [(12.63±4.41) μmol/L] in patients with T2-4 stage was higher than that of patients with Tis-1 stage [(10.70±3.49) μmol/L, P=0.010], and the level of thrombin time [(19.35±0.90) s] of patients with T2-4 stage was lower than that of patients with Tis-1 stage [(19.79±1.23) s, P=0.015]. The levels of PT(INR), Fbg, AT-Ⅲ, α2-AP [0.97±0.56, (3.37±2.34) g/L, (102.38±8.77)% and (120.95±14.06)%] in patients with lymph node metastasis were higher than those of patients without lymph node metastasis [0.94±0.05, (2.36±0.48) g/L, (94.56±14.37)% and (109.51±11.46)%, respectively, P<0.05]. Among postmenopausal breast cancer patients, the levels of AT-Ⅲ and α2-AP in T2-4 stage patients [(98.48±11.80)% and (111.84±15.35)%, respectively] were higher than those in patients with the Tis-1 stage [(94.12±14.98)% and (105.49±12.89)%, respectively, P<0.05]. The levels of AT-Ⅲ and α2-AP in N1-3 stage patients [(103.74±9.94)% and (117.29±15.23)%] were higher than those in N0 stage patients [(95.75±13.01)% and (108.39±14.42)%, P<0.05]. Conclusions: HCY and abnormal coagulation function are related to the risk of breast cancer, T stage and lymph node metastasis in breast cancer patients.
Blood Coagulation Disorders ; Breast Neoplasms ; Female ; Fibrinogen/metabolism* ; Homocysteine ; Humans ; Lymphatic Metastasis ; Prothrombin Time

PURPOSE: Dickkopf-1 (DKK-1) is a Wnt/beta-catenin signaling pathway inhibitor. We investigated whether DKK-1 is related to progression in hepatocellular carcinoma (HCC) cells and HCC patients. MATERIALS AND METHODS: In vitro reverse-transcription polymerase chain reaction (RT-PCR), wound healing assays, invasion assays, and ELISAs of patient serum samples were employed. The diagnostic accuracy of the serum DKK-1 ELISA was assessed using receiver operating characteristic (ROC) curves and area under ROC (AUC) analyses. RESULTS: RT-PCR showed high DKK-1 expression in Hep3B and low in 293 cells. Similarly, the secreted DKK-1 concentration in the culture media was high in Hep3B and low in 293 cells. Wound healing and invasion assays using 293, Huh7, and Hep3B cells showed that DKK-1 overexpression promoted cell migration and invasion, whereas DKK-1 knock-down inhibited them. When serum DKK-1 levels were assessed in 370 participants (217 with HCC and 153 without), it was significantly higher in HCC patients than in control groups (median 1.48 ng/mL vs. 0.90 ng/mL, p<0.001). The optimum DKK-1 cutoff level was 1.01 ng/mL (AUC=0.829; sensitivity 90.7%; specificity 62.0%). Although DKK-1 had a higher AUC than alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) (AUC=0.829 vs. 0.794 and 0.815, respectively), they were statistically similar (all p>0.05). When three biomarkers were combined (DKK-1 plus AFP plus DCP), they showed significantly higher AUC (AUC=0.952) than single marker, DKK-1 plus AFP, or DKK-1 plus DCP (all p<0.001). CONCLUSION: DKK-1 might be a key regulator in HCC progression and a potential therapeutic target in HCC. Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP.
Area Under Curve ; Biomarkers/blood/metabolism ; Biomarkers, Tumor/blood ; Carcinoma, Hepatocellular/blood/*diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/*blood/*metabolism ; Liver Neoplasms/blood/*diagnosis ; Male ; Middle Aged ; Protein Precursors/blood/metabolism ; Prothrombin/metabolism ; ROC Curve ; Reverse Transcriptase Polymerase Chain Reaction/*methods ; Sensitivity and Specificity ; alpha-Fetoproteins/analysis/metabolism

OBJECTIVETo explore the molecular pathogenesis and clinical phenotypes in 10 probands with inherited fibrinogen (Fg) deficiency.

METHODSThe diagnosis of hereditary Fg deficiency was validated by prothrombin time (PT), thrombin time (TT), Fg activity (Fg:C) and Fg antigen (Fg:Ag) in plasma. All of the exons and their flanking sequences of the Fg gene were analyzed by direct sequencing. Detected mutations were confirmed by reverse sequencing.

RESULTSThe ranges of Fg:C and Fg:Ag in the 10 probands were 0.52-0.91 g/L and 0.62-2.98 g/L, respectively. Five of the probands had type I disorders, and 5 had type II disorders. Seven point mutations were identified, among which 6 have located in the D region. γThr277Arg, γAsp316His, γTrp208Leu and Lys232Thr were novel mutations, and αArg19Ser was first reported in Chinese. Four probands had the same mutation site (γArg275). As to the clinical manifestation, probands with type I disorders were asymptomatic or with mild or medium symptoms, while those belonged to type II disorders had moderate or serious symptoms. Two probands have carried an Arg275Cys mutation but had different clinical manifestations.

CONCLUSIONMutations of the Fg gene seem to aggregate to the D region of FGG in our region, and Arg275 is a common mutation. However, no correlation has been found between the mutation site and clinical manifestations.

Adolescent ; Adult ; Afibrinogenemia ; blood ; classification ; genetics ; Base Sequence ; Child ; DNA Mutational Analysis ; methods ; Exons ; genetics ; Family Health ; Female ; Fibrinogen ; genetics ; metabolism ; Genotype ; Humans ; Male ; Middle Aged ; Mutation, Missense ; Partial Thromboplastin Time ; Phenotype ; Point Mutation ; Polymerase Chain Reaction ; Prothrombin Time ; Thrombin Time ; Young Adult

BACKGROUND: High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). METHODS: PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). RESULTS: The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (> or =200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (> or =240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. CONCLUSION: High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels.
Adult ; Aged ; Blood Coagulation Factors/metabolism ; *Blood Coagulation Tests ; Cholesterol/blood ; Female ; Humans ; Linear Models ; Lipids/*blood ; Male ; Middle Aged ; Partial Thromboplastin Time ; Prothrombin Time ; Reproducibility of Results ; Thrombin/metabolism ; Triglycerides/blood

OBJECTIVETo determine the changes in levels of D-dimer, prothrombin time (PT), fibrinogen (Fib), CD4 and CD8 in relation to hepatopulmonary syndrome (HPS) by using a rat model system and to assess the association with pathologic changes in lung.

METHODSForty male Sprague-Dawley rats were divided into equal groups for modeling of cirrhosis and HPS. The two groups were assessed by blood gas analysis, standard biochemical tests to measure D-dimer, PT, Fib, CD4 and CD8, and pathological examination of lung tissues.

RESULTSThe HPS rats showed significantly lower PaO2 than the cirrhosis rats (58.20+/-3.19 mmHg vs. 85.00+/-2.53 mmHg, P = 0.000). The HPS rats showed significantly higher levels of D-dimer, Fib and CD8 than the cirrhosis rats (0.39+/-0.09 mg/ml vs. 0.25+/-0.05 mg/ml, P = 0.000; 1.77+/-0.10 g/L vs. and 1.49+/-0.09 g/L, P = 0.010; 32.32+/-4.45/mm3 vs. 20.13+/-6.09/mm3, P = 0.014). The HPS rats showed significantly lower levels of PT, CD4 and CD4/CD8 than the cirrhosis rats (14.86+/-1.04 s vs. 16.23+/-0.75 s, P = 0.036; 20.45+/-3.86/mm3 vs. 26.75+/-5.32/mm3, P = 0.000; 0.64+/-0.09 vs. 1.32+/-0.13, P = 0.000). The lung tissues of the HPS rats showed microthrombosis in pulmonary vessels, which were not observed in lung tissues of the cirrhosis rats.

CONCLUSIONHPS-related differential levels of D-dimer, PT, Fib, CD4, CD8 and CD4/CD8 may represent a biomarker profile suggestive of incidence of thromboembolism in lung.

Animals ; CD4 Antigens ; metabolism ; CD4-CD8 Ratio ; CD8 Antigens ; metabolism ; Disease Models, Animal ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Hepatopulmonary Syndrome ; blood ; Liver Cirrhosis ; blood ; Lung ; pathology ; Male ; Prothrombin Time ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To explore the clinical value of virtual touch tissue quantification (VTQ) technique and the PGA index [prothrombin time (P), γ-glutamyl transpeptadase (GG) and apolipoprotein A1 (ApoAl)] in evaluating the degree of liver fibrosis in alcoholic patients.
 METHODS: A total of 64 patients with long-term alcohol history were enrolled for this study. The liver ultrasonography elasticity was examined by VTQ techniques, the VTQ value was assessed in the liver target region, and then the PGA index was calculated. According the liver biopsy biological results, a golden standard, the patients were divided into a non-fibrosis group (n=11), a fibrosis group (n=10), a significant fibrosis group (n=14) and a cirrhosis group (n=29). The diagnostic value of VTQ and PGA index were compared in alcoholic patients following the classification of liver fibrosis.
 RESULTS: The elastography VTQ values were (1.38±0.33), (1.49±0.30), (1.76±0.22) and (2.28±0.53) m/s; while the PGA indexes were 2.09±0.94, 2.30±1.06, 3.57±1.09, and 2.21±1.99 in the non-fibrosis group, the fibrosis group, the significant fibrosis group and the cirrhosis group, respectively. The VTQ value and PGA index were positively correlated with the classification of liver fibrosis (VTG: r=0.719, PGA: r=0.683; both P<0.01).
 CONCLUSION The alcoholic liver fibrosis can be assessed by noninvasive VTQ technology and PGA index. As a real-time ultrasound elastography technique, VTQ is more accurate than the PGA index. Combination of the two methods is helpful for early diagnosis and treatment in the patients with alcoholic liver fibrosis.
Apolipoprotein A-I ; metabolism ; Biopsy ; Elasticity Imaging Techniques ; Humans ; Liver Cirrhosis, Alcoholic ; classification ; diagnostic imaging ; Predictive Value of Tests ; Prothrombin Time ; Reproducibility of Results ; gamma-Glutamyltransferase ; metabolism

The present study was designed to investigate the antithrombotic effects and underlying mechanisms of the effective components group (ECG) of Xiaoshuantongluo recipe (XECG) and to further verify the rationality and feasibility of ECG-guided methodology in traditional Chinese medicine (TCM) research. The arterial thrombosis model induced by ferric chloride (FeCl3) oxidation and the venous thrombosis model induced by inferior vena cava ligation were established to evaluate the antithrombotic potential of XECG. Our results indicated that XECG significantly prolonged the time to occlusion, activated partial thromboplastin time (APTT), and prothrombin time (PT), and markedly inhibited adenosine diphosphate (ADP)-induced platelet aggregation in the 20% FeCl3-induced arterial thrombosis model. The superoxide dismutase (SOD) activity was significantly increased and the levels of malondialdehyde (MDA) and nitric oxide (NO) were dramatically decreased in the plasma of arterial thrombosis rats after XECG treatment for 12 days. Furthermore, XECG markedly reduced the weight of thrombus formed by inferior vena cava ligation. Additionally, XECG exhibited 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity and protective effect on mitochondrial lipid peroxidation. In summary, XECG played an important role in the prevention of thrombosis through interacting with multiple targets, including inhibition of platelet aggregation and coagulation and repression of oxidative stress. The ECG-guided methodology was validated as a feasible tool in TCM research.
Animals ; Drugs, Chinese Herbal ; administration & dosage ; Fibrinolytic Agents ; administration & dosage ; Humans ; In Vitro Techniques ; Male ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Platelet Aggregation ; drug effects ; Prothrombin Time ; Rats ; Superoxide Dismutase ; metabolism ; Thrombosis ; drug therapy ; metabolism ; physiopathology

BACKGROUND/AIMS: Recently, many cases of vitamin K-dependent coagulopathy of unknown origin have been reported. Such patients lack any relevant family history and have no systemic disease, raising suspicion of superwarfarin intoxication. We evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms in patients with suspected superwarfarin intoxication. In addition, we determined how to effectively treat vitamin K-dependent coagulopathy caused by suspected superwarfarin intoxication. METHODS: Seven patients with suspected superwarfarin intoxication who lacked any definitive history of rodenticide ingestion were included. Thirty-one patients initially diagnosed with rodenticide poisoning were also included. We performed a retrospective chart review of all subjects and examined clinical data including patient demographics and medical histories. RESULTS: Patients initially diagnosed with rodenticide poisoning were divided into two groups, one of which had a laboratory abnormality (prothrombin time [PT] > 13 seconds) and another group with PTs in the normal range. There was no significant difference between the two groups in any of age, gender, the extent of chronic alcohol consumption, the causative rodenticide, psychiatric problems, ingestion of drugs interacting with warfarin, the extent of intoxication, or the type of ingestion attempt. The albumin level of the former group was significantly lower than that of the latter group (p = 0.014). Furthermore, a significant difference between the two groups was evident in terms of simultaneous ingestion of rodenticide and alcohol (p = 0.023). CONCLUSIONS: Most patients with superwarfarin poisoning did not exhibit any complication. When such complications were evident, they were associated with serum albumin level and coingestion of rodenticide and alcohol.
4-Hydroxycoumarins/*poisoning ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alcohol Drinking/adverse effects/blood ; Anticoagulants/*poisoning ; Blood Coagulation/*drug effects ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Partial Thromboplastin Time ; Prothrombin Time ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Rodenticides/*poisoning ; Serum Albumin/metabolism ; Vitamin K/*blood ; Vitamin K Deficiency Bleeding/blood/*chemically induced/diagnosis/therapy ; Young Adult