A Case of False Decrease of Plasma D-Dimer.

BACKGROUND: D-dimer, a specific product of cross-linked fibrin degradation, is of great clinical value in the early diagnosis of thrombotic diseases and in monitoring the efficacy of thrombolysis; therefore, the accuracy of D-dimer test results is crucial. METHODS: This article reports a case of a patient with disseminated intravascular coagulation (DIC) who experienced a false decrease in D-dimer due to the hook effect. RESULTS: The three D-dimer test results for DIC patients were 1.09 mg/L, 0.93 mg/L, and 1.43 mg/L. After sample dilution, the results were: first time (1:128) 842.24 mg/L, second time (1:128) 1,505.28 mg/L, third time (1:32) 415.68 mg/L. There was a significant difference in the three test results before and after dilution, because the D-dimer concentration was too high, exceeding the detection range and causing the hook effect, which falsely lowered the D-dimer value. CONCLUSIONS: When the D-dimer value of DIC patients does not match the clinical situation, the possibility of the hook effect should be considered, and the false decrease can be ruled out by the sample dilution method. In this way, accurate clinical results can be obtained to avoid delaying the diagnosis and treatment of DIC patients.

BACH1 impairs hepatocyte regeneration after hepatectomy with repeated ischemia/reperfusion by reprogramming energy metabolism and exacerbating oxidative stress.

BTB and CNC homology 1 (BACH1) regulates biological processes, including energy metabolism and oxidative stress. Insufficient liver regeneration after hepatectomy remains an issue for surgeons. The Pringle maneuver is widely used during hepatectomy and induces ischemia/reperfusion (I/R) injury in hepatocytes. A rat model of two-thirds partial hepatectomy with repeated I/R treatment was used to simulate clinical hepatectomy with Pringle maneuver. Delayed recovery of liver function after hepatectomy with the repeated Pringle maneuver in clinic and impaired liver regeneration in rat model were observed. Highly elevated lactate levels, along with reduced mitochondrial complex III and IV activities in liver tissues, indicated that the glycolytic phenotype was promoted after hepatectomy with repeated I/R. mRNA expression profile analysis of glycolysis-related genes in clinical samples and further verification experiments in rat models showed that high BACH1 expression levels correlated with the glycolytic phenotype after hepatectomy with repeated I/R. BACH1 overexpression restricted the proliferative potential of hepatocytes stimulated with HGF. High PDK1 expression and high lactate levels, together with low mitochondrial complex III and IV activities and reduced ATP concentrations, were detected in BACH1-overexpressing hepatocytes with HGF stimulation. Moreover, HO-1 expression was downregulated, and oxidative stress was exacerbated in the BACH1-overexpressing hepatocytes with HGF stimulation. Cell experiments involving repeated hypoxia/reoxygenation revealed that reactive oxygen species accumulation triggered the TGF-ß1/BACH1 axis in hepatocytes. Finally, inhibiting BACH1 with the inhibitor hemin effectively restored the liver regenerative ability after hepatectomy with repeated I/R. These results provide a potential therapeutic strategy for impaired liver regeneration after repeated I/R injury.

Inflammasomes in rheumatoid arthritis: a pilot study.

BACKGROUND: The inflammasome plays an important role in rheumatoid arthritis (RA), which has rarely been systematically reported. The aim of this study was to understand whether the levels of inflammasomes were related to the severity of RA disease, which might provide a stronger theoretical basis for RA treatment. METHODS: The mRNA expression levels of some inflammasomes and associated molecules, including IL-1beta and IL-18, in peripheral blood mononuclear cells (PBMCs) from 30 RA patients (n = 30) and 16 healthy control (HC) individuals were determined by quantitative real-time polymerase chain reaction (qRT‒PCR), and the levels of plasma IL-1beta and IL-18 were also measured by enzyme-linked immunosorbent assay (ELISA). Moreover, the clinical characteristics and laboratory results of the patients were collected and analyzed in this study. RESULTS: The relative mRNA expression levels of NLRP3, NLRC4, AIM2, caspase-1, and IL-1beta were significantly higher and those of NLRP1, NLRP2 and NLRC5 were notably lower in the HC group than in the RA group. Moreover, the plasma IL-1beta and IL-18 levels were markedly increased in the RA group. Additionally, the mRNA level of AIM2 was negatively correlated with disease activity score 28 (DAS28) by stepwise linear regression analysis. erythrocyte sedimentation rate (ESR) was positively correlated with DAS28 by multiple linear regression analysis in the RA group. CONCLUSIONS: These findings imply the critical role of NLRP3, NLRC4, AIM2, caspase-1 and plasma IL-1beta and IL-18 in the pathogenesis of RA patients, which provides potential targets for the treatment of RA.

PYCR1 promotes the malignant progression of lung cancer through the JAK-STAT3 signaling pathway via PRODH-dependent glutamine synthesize.

BACKGROUND: Lung cancer is a serious threat to human life. It is of great significance to elucidate the pathogenesis of lung cancer and search for new markers. This study evaluate the clinical value of pyrroline-5-carboxylate reductase 1 (PYCR1) and explore its role and mechanisms in the malignant progression of lung cancer. METHODS: PYCR1 expression and its relationship with prognosis were analyzed using a bioinformatics database. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were utilized to examine the expression of PYCR1 in lung cancer tissues and peripheral blood. PYCR1-overexpressing lung cancer cells were constructed, then the cell proliferative, migration, and invasion ability was examined by the MTT and Transwell assays. siRNA against PRODH and STAT3 inhibitor sttatic was used to further elucidate the underlying mechanisms. Luciferase and CHIP assays were carried out for validate the how PYCR1 regulated PD-L1 expression via STAT3. Xenograft experiment was performed to determine the role of PYCR1 in vivo. RESULTS: Database analysis showed that PYCR1 expression was significantly increased in lung cancer tissues, and its high expression predicted poor prognosis. Lung cancer tissue and peripheral blood of patients showed obviously increased PYCR1 expression, and the sensitivity and specificity of serum PYCR1 in the diagnosis of lung cancer were 75.7% and 60%, respectively. PYCR1 overexpression enhanced the proliferative, migration, and invasion abilities of lung cancer cells. Both PRODH silence and stattic effectively attenuated the function of PYCR1. Animal experiment and IHC data indicated that PYCR1 could activated STAT3 phosphorylation and PD-L1, as well as suppressed T cell infiltration in lung cancer. Finally, we also validated that PYCR1 promoted PD-L1 transcription by elevating STAT3 binding to the gene promoter. CONCLUSION: PYCR1 has certain value in the diagnosis and prognosis of lung cancer. Moreover, through regulating JAK-STAT3 signaling pathway, PYCR1 significantly participated in process of lung cancer progression via the metabolism link between proline and glutamine, indicating that PYCR1 might be also a novel therapeutic target.

α-enolase is highly expressed in liver cancer and promotes cancer cell invasion and metastasis.

The expression levels of α-enolase, also known as enolase 1 (ENO1), in liver cancer tissues and the autoantibody levels of ENO1 in the sera of patients with liver cancer were detected to investigate the function of ENO1 in the invasion and metastasis of liver cancer, as well as its clinical diagnostic value. Small interfering RNA (siRNA) was used to disrupt ENO1 gene expression in HepG2 and Huh7 liver cancer cells. The proliferation ability of liver cancer cells was assessed using Cell Counting Kit-8 (CCK-8); the migration ability of liver cancer cells was assessed using scratch tests; and the migration and invasion abilities of liver cancer cells were assessed using Transwell assays. ENO1 expression in liver cancer tissues (43.8%) was significantly higher than that in benign liver lesions (15.2%) (P=0.005). The serum anti-ENO1 antibody levels in the liver cancer group were significantly higher than those in the control and benign liver lesion groups (P<0.001). After ENO1 gene interference, the proliferation, migration and invasion abilities of HepG2 and Huh7 liver cancer cells exhibited different degrees of suppression. The results revealed that ENO1 promotes liver cancer invasion and metastasis; ENO1 plays an important role in liver cancer and can be used as a potential liver cancer-associated marker.

Occurrence of estrogens in water, sediment and biota and their ecological risk in Northern Taihu Lake in China.

Occurrence of five estrogens, including estrone (E1), 17ß-estradiol (E2), estriol (E3), 17α-ethynylestradiol (EE2) and bisphenol A (BPA) in water, sediment and biota in Northern Taihu Lake, were investigated and their ecological risk was evaluated. Most of the target estrogens were widely distributed in the eight studied sampling sites, and their levels showed a regional trend of Gong Bay > Meiliang Bay > Zhushan Bay. The average concentrations of E1, E2, E3, EE2 and BPA ranged from 3.86 to 64.4 ng l(-1), 44.3 to 64.1 µg kg(-1) dry weight and 58.6 to 115 µg kg(-1) dry weight in water, sediments and biota, respectively. In most cases, the average concentrations of BPA and E2 were higher than those of other estrogens. E1, E3 and EE2 were found to be accumulated in river snails with bioaccumulation factor values as high as 14,204, 35,327 and 20,127 l kg(-1), respectively. E3 was also considered to be accumulated in clams. The evaluation of environmental risk showed that the occurrence of E2 and EE2 in lakes might pose a high risk to aquatic organisms. These findings provide important information for estrogen control and management in the studied area.

Adsorption behaviors of 17α-ethinylestradiol in sediment-water system in northern Taihu Lake, China.

Adsorption behavior of 17α-ethinylestradiol (EE2) in northern Taihu Lake sediment was analyzed by using batch equilibrium experiment. Freundlich isotherm could describe the adsorption thermodynamic behavior of EE2 in sediment. Sediment organic matter (SOM) contents had important impacts on the adsorption capacity for EE2. The pH values also influenced the adsorption capacity for EE2. Increase of pH value could decrease the EE2 adsorption, which might be due to the electrostatic repulsion between the anionic form of EE2 and sediments with negative charge under high pH values. Competitive effects of bisphenol A (BPA) on EE2 adsorption were further analyzed. The results showed that low concentration BPA did not have significant influences on EE2 adsorption. However, high concentration BPA could reduce EE2 adsorption, which might be due to the similar molecular diameter of BPA with adsorption sites and one more benzene ring with a hydroxyl group in BPA. These results provide primary information of EE2 adsorption in sediment-water system in Taihu Lake, which is useful for the environmental risk assessment and management of EE2 in studied area.

Health risk analysis of atmospheric polycyclic aromatic hydrocarbons in big cities of China.

A probabilistic carcinogenic risk assessment of atmospheric polycyclic aromatic hydrocarbons (PAHs) in four big cities (Beijing, Shanghai, Guangzhou, Xiamen) of China was carried out. PAHs levels in these cities were collected from published literatures and converted into BaP equivalent (BaPeq) concentrations. The health risk assessment models recommended by US EPA were applied to quantitatively characterize the health risk values of PAHs. Monte Carlo simulation and sensitivity analysis were applied to quantify uncertainties of risk assessment. The results showed that BaPeq concentrations of four cities were all higher than the newest limited value (1 ng/m(3)) of China. Health risk assessment indicated that atmospheric PAHs in Guangzhou and Xiamen posed no or little carcinogenic risk on local residents. However, the PAHs in Beijing and Shanghai posed potential carcinogenic risk for adults and lifetime exposure. Notwithstanding the uncertainties, this study provides the primary information on the carcinogenic risk of atmospheric PAHs in studied cities of China.