Clinical Application of Thromboelastography in Patients With Severe Fever With Thrombocytopenia Syndrome.

AIM: To investigate the clinical application of thromboelastography (TEG) in severe fever with thrombocytopenia syndrome (SFTS). METHODS: One hundred and fifty-seven patients with SFTS were included in the study. The participants were distributed into 3 groups; A, B, and C. And 103 patients in group A met the clinical criteria as they exhibited slight liver and kidney dysfunction. Group B consisted of 54 patients with SFTS who were critically ill while group C was a healthy control group with 58 participants. RESULTS: Patients with SFTS exhibited lower coagulation than the healthy participants. Group B patients exhibited significantly lower coagulation compared to group A. There was no significant difference in platelet count and fibrinogen content between patients in group A and group B, but platelet aggregation function and fibrinogen activity were significantly lower in group B patients. CONCLUSION: Our results suggest that it is risky to solely rely on platelet count and the fibrinogen in SFTS. Monitoring of TEG and other coagulation indexes should be emphasized.

Chain Dynamics of Partially Disentangled UHMWPE around Melting Point Characterized by 1H Low-Field Solid-State NMR.

Melts of ultrahigh molecular weight polyethylene (UHMWPE) entangled significantly, suffering processing difficulty. In this work, we prepared partially disentangled UHMWPE by freeze-extracting, exploring the corresponding enchantment of chain mobility. Fully refocused 1H free induction decay (FID) was used to capture the difference in chain segmental mobility during the melting of UHMWPE with different degrees of entanglement by low-field solid-state NMR. The longer the polyethylene (PE) chain is in a less-entangled state, the harder the process of merging into mobile parts after detaching from crystalline lamella during melting. 1H double quantum (DQ) NMR was further used to obtain information caused by residual dipolar interaction. Before melting, the DQ peak appeared earlier in intramolecular-nucleated PE than in intermolecular-nucleated PE because of the strong constraints of crystals in the former one. During melting, less-entangled UHMWPE could keep disentangled while less-entangled high density polyethylene (HDPE) could not. Unfortunately, no noticeable difference was found in DQ experiments between PE melts with different degrees of entanglement after melting. It was ascribed to the small contribution of entanglements compared with total residual dipolar interaction in melts. Overall, less-entangled UHMWPE could reserve its disentangled state around the melting point long enough to achieve a better way of processing.

Effect of Fluoride on the Expression of 8-Hydroxy-2'-Deoxyguanosine in the Blood, Kidney, Liver, and Brain of Rats.

Excessive exposure of fluoride not only leads to damage on bone, but also has an adverse effect on soft tissues. Oxidative DNA damage induced by fluoride is thought to be one of the toxic mechanisms of fluoride effect. However, the dose-response of fluoride on oxidative DNA damage is barely studied in organisms. This study investigated the concentration of fluoride in rat blood, kidney, liver, and brain as well as the dose-time effect of fluoride on the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the above tissues. Rats were exposed to 0 mg/L, 25 mg/L, 50 mg/L, and 100 mg/L of fluorine ion and treated for one and three months. The results showed that the accumulation of fluoride in soft tissues was very different. At the first month, blood fluoride was increased, liver and brain fluoride showed a U-shaped change, and kidney fluoride was not significant. At the third month, blood fluoride was altered with an inverted U-shaped change, kidney and brain fluoride increased, but liver fluoride decreased. Both the exposure concentration and the time of exposure had a significant effect on the expression of 8-OHdG in the above tissues. However, the effect patterns of fluoride on these tissues were notably different at different times. At the first month of fluoride treatment, blood, kidney, and liver 8-OHdG decreased with the increasing fluoride concentration. At the third month, blood 8-OHdG showed a U-shaped change, but kidney 8-OHdG altered with an inverted U-shaped change. Liver 8-OHdG increased, while brain 8-OHdG decreased at the third month. Correlation analysis showed that only blood 8-OHdG was significantly inversely correlated with blood fluoride and dental fluorosis grade in both the first and third months. Liver 8-OHdG was negatively and significantly correlated with liver fluoride. There was a weak but nonsignificant correlation between kidney and brain 8-OHdG and fluoride in both tissues. Additionally, blood 8-OHdG was positively correlated with kidney and liver 8-OHdG at the first month and positively correlated with brain 8-OHdG at the third month. Taken together, our data suggests that concentration and time of fluoride exposure had a significant effect on 8-OHdG, but the effect patterns of fluoride on 8-OHdG were different in the tissues, which suggests that the impact of fluoride on 8-OHdG may be a tissue-specific, as well as a non-monotonic positive correlation.

Exposure to Ambient Air Pollutant PM10 in the Second Trimester of Pregnancy Is Associated with Preterm Birth: A Birth-Based Health Information Cohort Study.

Objectives: We evaluated the effects of exposure to high concentrations of particulate matter (PM)10 on preterm birth (PTB) and identified a critical concentration of PM10 that could lead to PTB via a birth-based health information cohort study. Methods: We conducted a birth-based cohort study consisting of nonanomalous singleton births at 22-42 weeks. PTB was defined as babies born alive before 37 weeks of pregnancy. Pregnancy period exposure averages were estimated for PM10 based on the China National Environmental Monitoring Centre (CNEMC). Pregnant women who lived within 50 km of the monitor station were recruited into this study. Logistic regression analyses were performed to determine the association between PTB and exposure to PM10 at different pregnancy periods with adjustment for confounding factors. Results: The relative frequency of PTB was 8.7% in the study cohort of 5,291 singleton live births. A total of 1137 women had a high level of PM10 exposure (≥60 µg/m3) in the second trimester of pregnancy. The average concentrations of PM10 in the first, second, and third trimesters of pregnancy and throughout pregnancy were 53.8 µg/m3, 54.2 µg/m3, 55.6 µg/m3, and 54.3 µg/m3, respectively. The generalized additive model (GAM) analysis showed that there was a nonlinear correlation between PM10 and PTB in the second trimester of pregnancy (P < 0.001). The adjusted odds ratio between PTB and low concentration PM10 exposure (PM10 < 60 µg/m3) in the second trimester of pregnancy was 1.01 (95% CI 0.95-1.05). However, high PM10 exposure (PM10 ≥ 60 µg/m3) in the second trimester of pregnancy had an increased PTB risk even after adjustment for coexisting risk factors with an adjusted odds ratio of 1.78 (95% CI 1.69-1.87), and the incidence of PTB increased with an increase in PM10 exposure. Conclusions: Our research discovered that exposure to high levels of PM10 increases the risk of PTB and the second trimester is the most vulnerable gestational period to ambient air pollution exposure. PM10 concentrations more than 60 µg/m3 are detrimental to pregnant women in their second trimester. This study has implications for health informatics-oriented healthcare decision support systems.

Establishment of Normal Range for Thromboelastography in Healthy Middle-Aged and Elderly People of Weihai in China.

TEG can monitor the dynamic changes of blood clot formation and lysis by activating the coagulation system of a small sample of whole blood in vitro. The parameters can reflect the level of coagulation factors, the function of fibrinogen and platelet, and the presence or absence of hyperfibrinolysis. At present, the normal reference range of the parameters of TEG is mainly based on the reference values established by the Western population. Due to the differences in the distribution of ethnic groups, many countries have established their reference ranges for healthy populations. In China, some scholars have tried to establish the corresponding TEG reference range according to the characteristics of the population in different regions. This study tried to establish the reference range for thromboelastography in healthy middle-aged and elderly people of Weihai in China and compare it with the reference range provided by the manufacturer. The fasting venous blood of 454 healthy middle-aged and elderly people was collected, including 239 males and 215 females. The thromboelastography TEG-5000 was used to measure the reaction time (R), coagulation formation time (K), coagulation angle (Angle), and maximum amplitude (MA). The reference range of TEG parameters of middle-aged and elderly healthy males was R: 4.38-8.27 min, K: 1.44-2.82 min, Angle: 48.53-72.17 deg, and MA: 51.95-72.02 mm; respectively, in the females, the normal value was R: 3.43-7.40 min, K: 1.07-2.53 min, Angle: 48.22-77.22 deg, and MA: 53.10-74.58 mm; The difference of R, K, Angle, and MA between the male group and the female group was statistically significant (P < 0.05); In this study, if we use the reference range established by the manufacturer, the R specificity for males was 91.6%, K specificity was 98.7%, Angle specificity was 85.8%, and MA specificity was 93.7%; the range for females was 68.4%, 99.5%, 75.8%, and 87.4%, respectively. There are statistically significant differences between R, K, Angle, and MA in middle-aged and elderly healthy women and men. It is necessary to establish a TEG reference range for healthy females and males.

miR-23b-3p Inhibits the Oncogenicity of Colon Adenocarcinoma by Directly Targeting NFE2L3.

BACKGROUND AND AIMS: MicroR-23b-3p (miR-23b-3p) has been found to be abnormally expressed in a variety of malignant tumors and to play a role in tumor inhibition or promotion. However, the regulatory mechanism of miR-23b-3p in COAD remains unclear. The purpose of this study was to investigate the clinical significance of miR-23b-3p expression in COAD cells and to explore its role and regulatory mechanism in the growth of COAD. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure miR-23b-3p expression in COAD tissues and cell lines. After transfecting miR-23b-3p mimics into two human COAD cell lines (SW620 and LoVo), the cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation, the Transwell assay was used to measure cell migration and invasion capacity, and flow cytometry was used to evaluate cell apoptosis in vitro. In addition, a luciferase reporter assay was used to determine whether miR-23b-3p targets NFE2L3. The downstream regulatory mechanisms of miR-23b-3p action in COAD cells were also investigated. For in vivo tumorigenesis assay, COAD cells stably overexpressing miR-23b-3p were injected subcutaneously into the flank of nude mice to obtain tumors. RESULTS: Significantly decreased expression of miR-23b-3p was detected in COAD tissues and cell lines. Exogenous miR-23b-3p expression inhibited cell proliferation, migration, and invasion and promoted cell apoptosis of COAD cells in vitro. Nuclear factor erythroid 2 like 3 (NFE2L3) was identified as a direct target gene of miR-23b-3p. In addition, reintroduction of NFE2L3 partially abolished the anticancer effects of miR-23b-3p on COAD cells. Furthermore, miR-23b-3p overexpression hindered the growth of COAD cells in vivo. CONCLUSION: miR-23b-3p inhibited the oncogenicity of COAD cells in vitro and in vivo by directly targeting NFE2L3, suggesting the importance of the miR-23b-3p/NFE2L3 pathway in the development of COAD.

Beneficial role of oleuropein in sepsis-induced myocardial injury. Possible Involvement of GSK-3ß/NF-kB pathway.

PURPOSE: The present study explored the potential therapeutic role of oleuropein in sepsis-induced heart injury along with the role of GSK-3ß/NF-kB signaling pathway. METHODS: Sepsis-induced myocardial injury was induced by cecal ligation and puncture (CLP) in rats. The cardiac injury was assessed by measuring the levels of cTnI and creatine kinase-MB (CK-MB). Sepsis-induced inflammation was assessed by measuring interleukin-6 (IL-6), IL-10 and HMGB1 levels. The different doses of oleuropein (5, 10, and 20 mg/kg) were given prior to CLP. Oleuropein (20 mg/kg) was administered after 6 hof CLP. The expressions of GSK-3ß, p-GSK-3ß (Ser9) and nuclear factor-κB (NF-κB) were measured in heart homogenates. RESULTS: Cecal ligation and puncture was associated with myocardial injury, an increase in IL-6, a decrease in IL-10 and an increase in HMGB1. Moreover, it decreased the ratio of p-GSK-3ß/GSK-3ß and increased the expression of p-NF-kB. Pretreatment with oleuropein attenuated CLP-induced myocardial injury and systemic inflammation in a dose-dependent manner. Administration of oleuropein after the onset of CLP also attenuated cardiac injury and inflammation. It also restored CLP-induced changes in the HMGB1 levels, the ratio of p-GSK-3ß/GSK-3ß and expression of p- NF-kB. CONCLUSIONS: Oleuropein attenuates sepsis-induced systemic inflammation and myocardial injury by inhibiting NF-kB and GSK-3ß signaling.

Effects of Fluoride on Oxidative Stress Markers of Lipid, Gene, and Protein in Rats.

Endemic fluorosis is a systemic chronic disease caused by excessive intake of fluoride. It is widely accepted that oxidative stress is closely related to fluorosis; however, molecular mechanism of oxidative stress in fluorosis remains unclear. This study investigated the effects of fluoride (F) on oxidative stress markers of lipid, gene, and protein in rats for revealing molecular mechanism of oxidative stress in fluorosis. The results showed concentration and exposure time of fluoride both had a significant effect on MDA and 8-OHdG. Fluoride concentration significantly impacted AGEs level, but exposure time did not. AOPP was not statistically different among the groups. AGEs decreased with the increase of fluoride in the rats with 3 months of fluoride treatment. The correlation analysis showed the degree of dental fluorosis was significantly negatively correlated with 8-OHdG at 1 month and 3 months, and negatively correlated with AGEs at 3 months. In the rats with 100 mg/L of fluoride treatment, MDA was significant positively correlated with 8-OHdG, and negatively correlated with AGEs. 8-OHdG was significantly negatively correlated with AGEs in the control group and 100 mg/L fluoride group. Taken together, fluoride had different effects on oxidative stress markers of lipid, gene, and protein. Excessive fluoride could increase MDA content, and decrease 8-OHdG and AGEs. These findings suggest that oxidative stress involved in molecular pathogenesis of fluorosis is complicated, and needs to furtherly study in the future.

Effect of fluoride in drinking water on the level of 5-methylcytosine in human and rat blood.

DNA methylation is an epigenetic modification of genome that is involved in many human diseases. Recent studies revealed DNA methylation may be associated with fluorosis. This study was aimed to evaluate the dose-response effect of fluoride on DNA methylation in human and rat blood. A commercial ELISA kit was employed to evaluate 5-methylcytosine (5-mC) level of genome in human and rat blood. A total of 281 subjects were enrolled in this study and divided into four equal-size groups by the quartile of fluoride in drinking water. The difference of 5-mC among the four groups was significant. The U-shaped relationship was found between fluoride and 5-mC in the population. The U-shaped curve was also observed in the rats with three months of fluoride treatments. Taken together, these results clue the disruption of DNA methylation in mammals may has a certain association with fluoride in natural exposures.

Beneficial role of oleuropein in sepsis-induced myocardial injury. Possible Involvement of GSK-3β/NF-kB pathway

ABSTRACT Purpose The present study explored the potential therapeutic role of oleuropein in sepsis-induced heart injury along with the role of GSK-3β/NF-kB signaling pathway. Methods Sepsis-induced myocardial injury was induced by cecal ligation and puncture (CLP) in rats. The cardiac injury was assessed by measuring the levels of cTnI and creatine kinase-MB (CK-MB). Sepsis-induced inflammation was assessed by measuring interleukin-6 (IL-6), IL-10 and HMGB1 levels. The different doses of oleuropein (5, 10, and 20 mg/kg) were given prior to CLP. Oleuropein (20 mg/kg) was administered after 6 hof CLP. The expressions of GSK-3β, p-GSK-3β (Ser9) and nuclear factor-κB (NF-κB) were measured in heart homogenates. Results Cecal ligation and puncture was associated with myocardial injury, an increase in IL-6, a decrease in IL-10 and an increase in HMGB1. Moreover, it decreased the ratio of p-GSK-3β/GSK-3β and increased the expression of p-NF-kB. Pretreatment with oleuropein attenuated CLP-induced myocardial injury and systemic inflammation in a dose-dependent manner. Administration of oleuropein after the onset of CLP also attenuated cardiac injury and inflammation. It also restored CLP-induced changes in the HMGB1 levels, the ratio of p-GSK-3β/GSK-3β and expression of p- NF-kB. Conclusions Oleuropein attenuates sepsis-induced systemic inflammation and myocardial injury by inhibiting NF-kB and GSK-3β signaling.

Chemical boundary engineering: A new route toward lean, ultrastrong yet ductile steels.

For decades, grain boundary engineering has proven to be one of the most effective approaches for tailoring the mechanical properties of metallic materials, although there are limits to the fineness and types of microstructures achievable, due to the rapid increase in grain size once being exposed to thermal loads (low thermal stability of crystallographic boundaries). Here, we deploy a unique chemical boundary engineering (CBE) approach, augmenting the variety in available alloy design strategies, which enables us to create a material with an ultrafine hierarchically heterogeneous microstructure even after heating to high temperatures. When applied to plain steels with carbon content of only up to 0.2 weight %, this approach yields ultimate strength levels beyond 2.0 GPa in combination with good ductility (>20%). Although demonstrated here for plain carbon steels, the CBE design approach is, in principle, applicable also to other alloys.

The dose-time effects of fluoride on the expression and DNA methylation level of the promoter region of BMP-2 and BMP-7 in rats.

Skeletal fluorosis is a chronic metabolic bone disease caused by excessive exposed to fluoride. Recent studies have shown that fluoride causes abnormal bone metabolism through disrupting the expression of Bone Morphogenetic Proteins (BMPs). However, the relationship between fluoride and BMPs is not fully understood, and the mechanism of fluoride on BMPs expression is still unclear. This study investigated the dose-time effects of fluoride on BMP-2 and BMP-7 levels and DNA methylation status of the promoter regions of these two genes in peripheral blood of rats. Eighty Wistar male rats were randomly divided into four groups and treated for 1 month and 3 months with distilled water (control), 25 mg/L, 50 mg/L or 100 mg/L of sodium fluoride (NaF). Rats exposed to fluoride had higher protein expression of BMP-2 and BMP-7 in plasma at 1 month and 3 months. An increase in BMP-2 expression was also observed with an increase of fluoride exposure time. Significant hypomethylation was observed in 2 CpG sites (CpGs) of BMP-2 and 1 CpG site of BMP-7 promoter regions in the fluoride treatment groups. It concludes that fluoride has a dose-response effect on BMP-2 in fluorosis rats, and fluoride-induced hypomethylation of specific CpGs may play an essential role in the regulation of BMP-2 and BMP-7 expression in rats.

The Inverted U-Curve Association of Fluoride and Osteoclast Formation in Mice.

The effect of fluoride on osteoclasts is still controversial. In the past, researchers thought that the effects of fluoride on osteoclast and osteoblast formation occurred in a dose-dependent pattern. However, our previous in vitro study showed fluoride elicited a notably different effect on osteoclast formation. To further verify the relationship between fluoride and osteoclast formation in vivo, 60 male C57BL/6 mice were randomly divided into three groups: two treatment groups consuming water supplemented with 50 and 100 mg/L of fluoride, and a third control group with nonsupplemented water. Ion selective electrode method analysis was used to detect bone fluoride content, and the effects of fluoride on bone tissue were assessed with hematoxylin and eosin (HE) staining. Additionally, the expression of BGP and ALP were examined by Western blot analysis, and tartrate-resistant acid phosphatase (TRAP) was assessed with immunohistochemistry. Osteoclasts in bone tissue were identified with a combination method of TRAP staining and cell morphology assessment. Results showed increasing expression of BGP among treatment groups as fluoride exposure increased, and ALP expression in the 100 mg/L treatment group was significantly higher than that for both the 50 mg/L treatment and control groups. The number of osteoclasts in the 50 mg/L group was highest amongst the three groups, followed by the 100 mg/L treatment and then by the control group, with the latter showing significantly fewer osteoclasts than in either treatment group. These results suggest that fluoride enhances bone formation at increasing levels of fluoride exposure. However, the inverted U-curve association was found between fluoride exposure and osteoclast formation, with the higher dose of fluoride having slightly reduced osteoclast formation. The results from this study may provide key insights towards understanding the role of osteoclasts in the progression of skeletal fluorosis.

Asymmetric dimethylarginine is associated with carotid atherosclerosis in patients with essential hypertension.

This study was to assess the relationship between asymmetric dimethylarginine (ADMA) and carotid atherosclerosis in patients with essential hypertension. A total of 182 individuals with never-treated essential hypertension and 182 age-matched healthy controls were studied. Plasma ADMA levels, mean intima-media thickness (IMT) and plaque score were significantly greater in hypertensive patients than normotensive controls. ADMA was positively correlated with mean IMT. On multiple logistic regression analysis, ADMA was a crucial independent predictor of carotid plaque formation (plaque score ≥1.1). Our results suggest that increased levels of ADMA are associated with the development of carotid atherosclerosis in hypertensive patients.