Mechanism of Bile Acid in Regulating Platelet Function and Thrombotic Diseases.

Platelets play a key role in physiological hemostasis and pathological thrombosis. Based on the limitations of current antiplatelet drugs, it's important to elucidate the mechanisms of regulating platelet activation. In addition to dissolving lipid nutrients, bile acids (BAs) can regulate platelet function. However, the specific mechanisms underlying BAs-mediated effects on platelet activation and thrombotic diseases remain unknown. Therefore, the effects of BAs on platelets and intracellular regulatory mechanisms are explored. It is showed that the inhibitory effect of secondary BAs is more significant than that of primary BAs; lithocholic acid (LCA) shows the highest inhibitory effect. In the process of platelet activation, BAs suppress platelet activation via the spleen tyrosine kinase (SYK), protein kinase B (Akt), and extracellular signal-regulated kinase1/2 (Erk1/2) pathways. Nck adaptor proteins (NCK1) deficiency significantly suppress the activity of platelets and arterial thrombosis. Phosphorylated proteomics reveal that LCA inhibited phosphorylation of syntaxin-11 at S80/81 in platelets. Additional LCA supplementation attenuated atherosclerotic plaque development and reduced the inflammation in mice. In conclusion, BAs play key roles in platelet activation via Syk, Akt, ERK1/2, and syntaxin-11 pathways, which are associated with NCK1. The anti-platelet effects of BAs provide a theoretical basis for the prevention and therapy of thrombotic diseases.

Fast synchronization control and application for encryption-decryption of coupled neural networks with intermittent random disturbance.

In this paper, we design a new class of coupled neural networks with stochastically intermittent disturbances, in which the perturbation mechanism is different from other existed random neural networks. It is significant to construct the new models, which can simulate a class of the real neural networks in the disturbed environment, and the fast synchronization control strategies are studied by an adjustable parameter α. A controller with coupling signal is designed to study the exponential synchronization problem, meanwhile, another effective controller with not only adjustable synchronization rate but also with infinite gain avoided is used to investigate the preset-time synchronization. The fast synchronization conditions have been obtained by Lyapunov stability principle, Laplacian matrix and some inequality techniques. A numerical example shows the effectiveness of the control schemes, and the different control factors for synchronization rate are given to discuss the control effect. In particular, the image encryption-decryption based on drive-response networks has been successfully applied.

Peripheral blood stem cell transplantation vs. bone marrow transplantation for aplastic anemia: a systematic review and meta-analysis.

Background: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for aplastic anemia. Recently, peripheral blood stem cell transplantation (PBSCT) has gradually replaced traditional bone marrow transplantation (BMT). However, which graft source has a better therapeutic effect and prognosis for aplastic anemia (AA) remains unclear. Therefore, we conducted this systematic review and meta-analysis. Methods: We systematically searched PubMed, EMBASE, and the Cochrane Library without language limitations for studies using PBSCT or BMT for AA. Data were analyzed using the Open Meta-Analyst. Results: We identified 17 of 18,749 studies, including seven comparative reports and nine single-arm reports, with a total of 3,516 patients receiving HSCT (1,328 and 2,188 patients received PBSCT and BMT, respectively). The outcomes of the comparative studies showed similar 5-year overall survival [OS; relative risk (RR) = 0.867; 95% confidence interval (CI), 0.747-1.006], similar transplant-related mortality (RR = 1.300; 95%CI, 0.790-2.138), graft failure rate (RR = 0.972; 95%CI, 0.689-1.372) between the PBSCT group and the BMT group, while the PBSCT group had a significantly higher incidence of chronic graft-versus-host disease (GVHD; RR = 1.796; 95% CI, 1.571-2.053) and a higher incidence of grade IV acute GVHD (RR = 1.560; 95% CI, 1.341-1.816) compared to the BMT group. The outcomes of single-arm reports showed similar 3-year OS and incidences of chronic GVHD, acute II-IV GVHD, III-IV GVHD, transplant-related mortality and graft failure rate between PBSCT and BMT. Conclusion: Before 2010, PBSCT was not superior to BMT in terms of 5-year OS, transplant-related mortality and graft failure rate, but it exhibited a higher risk of both chronic and acute GVHD. After 2010, PBSCT and BMT showed similar 3-year OS, GVHD risks, transplant-related mortality and graft failure rate. PB grafts are more suitable for HSCT of the AA for convenience and pain relief. Systematic review registration: www.crd.york.ac.uk/PROSPERO/, CRD42023412467.

Exploration of treatment-free remission in CML, based on molecular monitoring.

BACKGROUND: Typical chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm caused by t(9; 22)(q34; q11) translocation. This chromosomal translocation forms the BCR::ABL1 fusion gene. The tyrosine kinase encoded by the BCR::ABL1 is considered to be the main pathogenic diver. BCR::ABL1 is not only a therapeutic target, but also a monitoring target. Monitoring of BCR::ABL1 reveals the progression of the disease and guides the next treatment. Now for CML, the target of treatment has been focused on treatment-free remission (TFR). METHODS: We conducted a literature review of current developments of treatment-free remission and molecular monitoring methods. RESULTS: More effective and sensitive CML monitoring methods such as digital droplet PCR (ddPCR) and next generation sequencing (NGS) have further studied the measurable residual disease (MRD) and clonal heterogeneity, which provides strong support for the exploration of TFR. We discussed some of the factors that may be related to TFR outcomes at the molecular level, along with some monitoring strategies. CONCLUSION: Currently, predictive indicators for treatment-free remission outcomes and recurrence are lacking in clinical practice. In future, treatment-free remission research should focus on combining the clinical indicators with molecular monitoring and biological markers to personalize patient conditions and guide clinicians to develop individualized treatment plans, so that more patients with CML can achieve safer and stabler treatment-free remission.

The mechanism of oleic acid inhibiting platelet activation stimulated by collagen.

BACKGROUND: Abnormal platelet activation is a key factor in the occurrence and development of thrombotic diseases. However, the physiological mechanisms that underlie platelet homeostasis remain unclear. Oleic acid, one of the most abundant lipids in the human diet, has potential antithrombotic effects. This study aimed to investigate the effects of oleic acid on platelet activation and thrombosis. METHODS: Platelet aggregation, ATP release, and fibrinogen spread were evaluated to determine the role of oleic acid in platelet activation. A ferric chloride-induced carotid injury model was used to establish the effect of oleic acid on thrombus formation in vivo. Western blotting analysis and transfection experiments were performed to determine the mechanisms involved in this process. RESULTS: Oleic acid inhibited platelet aggregation, granule release, and calcium mobilization. Furthermore, it inhibited the spread of platelets on fibrinogen. We also found that oleic acid delayed arterial thrombosis in mice, as demonstrated in a murine model of ferric chloride-induced carotid artery thrombosis. The molecular mechanism of its inhibition of platelet activity may be through the Syk-PLCγ2 and CaMKKß/AMPKα/VASP pathways. In addition, we demonstrated that the phosphorylation of AMPK at Ser496 was an important mechanism of platelet activation. CONCLUSIONS: Our study showed that oleic acid inhibits platelet activation and reduces thrombogenesis by inhibiting the phosphorylation of multiple signaling molecules, offering new insights into the research and development of antiplatelet drugs. Video Abstract.

A novel framework of prescribed time/fixed time/finite time stochastic synchronization control of neural networks and its application in image encryption.

In this paper, we investigate a novel framework for achieving prescribed-time (PAT), fixed-time (FXT) and finite-time (FNT) stochastic synchronization control of semi-Markov switching quaternion-valued neural networks (SMS-QVNNs), where the setting time (ST) of PAT/FXT/FNT stochastic synchronization control is effectively preassigned beforehand and estimated. Different from the existing frameworks of PAT/FXT/FNT control and PAT/FXT control (where PAT control is deeply dependent on FXT control, meaning that if the FXT control task is removed, it is impossible to implement the PAT control task), and different from the existing frameworks of PAT control (where a time-varying control gain such as µ(t)=T/(T-t) with t∈[0,T) was employed, leading to an unbounded control gain as t→T- from the initial time to prescribed time T), the investigated framework is only built on a control strategy, which can accomplish its three control tasks (PAT/FXT/FNT control), and the control gains are bounded even though time t tends to the prescribed time T. Four numerical examples and an application of image encryption/decryption are given to illustrate the feasibility of our proposed framework.

The Effect of Guisangyou Tea on Abnormal Lipid Metabolism in Mice Induced by High-Fat Diet.

This study was aimed to investigate the effect of Guisangyou tea (GSY tea) in improving abnormal lipid metabolism in mice with obesity induced by a high-fat diet (HFD). The results showed that intervention of the water extract of GSY tea (WE) decreased serum levels of lipids, and positively regulated the related antioxidant enzyme activities and the inflammatory factors in the serum and liver. In the liver, the mRNA and protein expression levels of sterol regulatory element-binding proteins-1 (SREBP-1), stearoyl-CoA desaturase-1 (SCD-1), fatty acid synthase (FASN), and acetyl CoA carboxylase (ACC) related to lipid synthesis were downregulated, and the mRNA and protein expression levels of the farnesoid X receptor (FXR) and small heterodimer partner (SHP) related to bile acid production were upregulated. The results demonstrate that GSY tea can improve abnormal lipid metabolism in obese mice by improving the body's antioxidant capacity, regulating the inflammatory state, and reducing the synthesis of lipids and increasing the production of bile acids. GSY tea can be processed and utilized as a safe and effective resource for improving abnormal lipid metabolism.

Predefined-time synchronization of coupled neural networks with switching parameters and disturbed by Brownian motion.

This article focuses on predefined time synchronization problem for a class of signal switching neural networks with time-varying delays. In the network models, we not only consider the coupling characteristics in the following networks, but also consider the disturbance with standard Brownian motion. In the design of the controller, the control gain is designed as 1ɛ+Tp-t (t∈[T0,Tp), ɛ is an optional smaller positive number), which avoids the infinite gain (the control gain is designed as 1Tp-t in other reference). In order to get the predefined time control law, a power function is multiplied to the Lyapunov functional, from which it can get an exponential upper bound function via the derivative and mathematical expectation operation. Utilizing the martingale theory and the method of Laplace matrix, some novel predefined time synchronization criteria are obtained for the leader-following neural networks, meanwhile the following networks can maintain the leader network after achieved synchronization. Based on the special network of the main system, five corollaries separately develop the predefined time synchronization results from different perspectives. An example with some simulation figures and computing results fully exhibits the effectiveness of the achieved synchronization scheme. In this case, although the error signal is disturbed by Brownian motion, the trace signal can still stably converge to zero by this control scheme, meanwhile the predefined-time control effect is achieved.

Adiponectin receptor agonist AdipoRon modulates human and mouse platelet function.

Adiponectin, an adipokine secreted by adipocytes, has anti-atherosclerotic and antithrombotic activities. AdipoRon is synthetic small molecule adiponectin receptor agonist. In this study, we investigated the effect of AdipoRon on platelet activation and thrombus formation. Washed human platelets were prepared from the peripheral blood of healthy donors. In a series of in vitro platelet functional assays, pre-treatment with AdipoRon (10, 20, 40 µg/mL) dose-dependently inhibited the aggregation, granule secretion and spreading of washed human platelets. We showed that AdipoRon (20, 40 µg/mL) significantly inhibited AMPK, Syk, PLCγ2, PI3K, Akt, p38-MAPK and ERK1/2 signalling pathways in washed human platelets. In addition, we demonstrated that the phosphorylation of CKII at Tyr255 was an important mechanism of the integrin αIIbß3-mediated platelet activation. Meanwhile, AdipoR1 deficiency impaired the inhibitory effect of AdipoRon on mouse platelets. In ferric chloride-induced carotid injury model, injection of AdipoRon (5 or 12.5 mg/kg, iv) significantly attenuated arterial thrombosis. In conclusion, AdipoRon attenuates platelet function via the AdipoR1/AMPK/CKII/PI3K/AKT signalling pathways, while exerting a protective effect against arterial thrombosis. This study offers new insights into the fields of cardiovascular disease and antiplatelet drug discovery.Schematic model of AdipoRon regulating platelet activation. (BioRender.com).

Identification of novel inhibitors of S-adenosyl-L-homocysteine hydrolase via structure-based virtual screening and molecular dynamics simulations.

S-adenosyl-L-homocysteine hydrolase (SAHase) is an important regulator in the methylation reactions in many organisms and thus is crucial for numerous cellular functions. In recent years, SAHase has become one of the popular targets for drug design, and SAHase inhibitors have exhibited potent antiviral activity. In this study, we established the complex-based pharmacophore models based on the known crystal complex of SAHase (PDB ID: 1A7A) to screen the drug-likeness compounds of ChEMBL database. Then, three molecular docking programs were used to validate the reliability of compounds, involving Libdock, CDOCKER, and AutoDock Vina programs. The four promising hit compounds (CHEMBL420751, CHEMBL346387, CHEMBL1569958, and CHEMBL4206648) were performed molecular dynamics simulations and MM-PBSA calculations to evaluate their stability and binding-free energy in the binding site of SAHase. After screening and analyzing, the hit compounds CHEMBL420751 and CHEMBL346387 were suggested to further research to obtain novel potential SAHase inhibitors. A series of computer-aided drug design methods, including pharmacophore, molecular docking, molecular dynamics simulation and MM-PBSA calculations, were employed in this study to identity novel inhibitors of S-adenosyl-L-homocysteine hydrolase (SAHase). Some compounds from virtual screening could form various interactions with key residues of SAHase. Among them, compounds CHEMBL346387 and CHEMBL420751 exhibited potent binding affinity from molecular docking and MM-PBSA, and maintained good stability at the binding site during molecular dynamics simulations as well. All these results indicated that the selected compounds might have the potential to be novel SAHase inhibitors.

Siah1 promotes the proliferation of NSCLC cells through ubiquitinating and stabilizing Notch1.

Seven in absentia homolog 1 (Siah1) has been shown plays important roles in the pathogenesis and development of multiple cancers. However, the functions and mechanisms of Siah1 in non-small cell lung cancer (NSCLC) remain unclear. In our study, we found that knock down of Siah1 could inhibit the proliferation of NSCLC cells, while over-expression of Siah1 had the opposite effects. Molecularly, the bioinformatics analysis determined that notch receptor 1 (Notch1) might be the potential target of Siah1. Subsequently, we identified that Siah1 acted as an E3 ligase to promote the ubiquitination and stabilization of Notch1 through the proteasome pathway. Furthermore, the results showed that the Siah1 expression was directly correlated with CTR9 in human NSCLC tissues. Finally, Siah1 could promote Akt phosphorylation through regulating Notch1, thus promoting the proliferation of NSCLC cells. In conclusion, our study demonstrated that Siah1 acts as an oncogene, can ubiquitinate and stabilize Notch1 by proteasome pathway, which promotes Akt phosphorylation and ultimately leads to NSCLC cell proliferation.

Paleoenvironment Evolutionary Characteristics of Niutitang Shale in Western Hubei, Middle Yangtze, China.

The black shale developed in the first section of the Niutitang formation (ϵ1 n 1) is one of the most important shale gas reservoirs in western Hubei, and its geological characteristics have been sufficiently studied by many predecessors. However, there are still three aspects that need further research: the origin of silicon, the discrimination of the euxinic sulfuretted and the anoxic ferruginous conditions, and the main controlling factors of organic matter enrichment. Based on geochemical data from well ZD1 located in the city of Yichang in western Hubei, first, the geochemical characteristics of ϵ1 n 1 are analyzed, then the provenance, depositional site, and paleoenvironment evolution are discussed, and finally, the main controlling factor of organic matter enrichment is revealed. The results show that ϵ1 n 1 can be divided into two units, organic-rich shales (ORS) and organic-lean shales (OLS), which have average total organic carbon contents of 4.21 and 0.84%, respectively. Additionally, the ORS is characterized by high contents of SiO2, U, V, Ni, Zn, and Cu and left-inclining types of rare earth element distribution curves. ϵ1 n 1 is located in a passive continental margin with a material source mainly from mixed felsic and mafic rocks. Compared with the OLS, the content of biological quartz is much greater, and the terrigenous input is less in the ORS. The paleoclimate is cold and humid with low salinity in the ORS, whereas it is hot and dry with high salinity in the OLS. ϵ1 n 1 is deposited in a semistagnant basin, and the ORS shows a relatively lower stagnant degree with euxinic to anoxic conditions and moderate to high paleoproductivity, while the OLS shows a high stagnant degree with suboxic to oxic conditions and lower paleoproductivity. The redox conditions are the main controlling factors affecting organic matter enrichment. The environmental evolution model with three stages shows that there is a good causal relationship between redox conditions, paleoproductivity, and sea level fluctuation. The black carbonaceous siliceous in the lower part of the ORS with a thickness of approximately 40 m is the most favorable layer, which will provide a theoretical basis for further shale gas exploration of ϵ1 n 1 in the western Hubei.

NAT10-mediated mRNA N4-acetylcytidine modification promotes bladder cancer progression.

BACKGROUND: Dysregulation of the epitranscriptome causes abnormal expression of oncogenes in the tumorigenic process. Previous studies have shown that NAT10 can regulate mRNA translation efficiency through RNA acetylation. However, the role of NAT10-mediated acetylation modification in bladder cancer remains elusive. METHODS: The clinical value of NAT10 was estimated according to NAT10 expression pattern based on TCGA data set and the tumor tissue array. Acetylated RNA immunoprecipitation sequencing was utilized to explore the role of NAT10 in mRNA ac4C modification. Translation efficiency and mRNA stability assay were applied to study the effect of NAT10-deletion on target genes. The nude mouse model and genetically engineered mice were conducted to further verify the characteristics of NAT10 in promoting BLCA progression and regulating downstream targets. RESULTS: NAT10 was essential for the proliferation, migration, invasion, survival and the stem-cell-like properties of bladder cancer cell lines. NAT10 was responsible for mRNA ac4C modification in BLCA cells, including BCL9L, SOX4 and AKT1. Deficient NAT10 in both xenograft and transgenic mouse models of bladder cancer reduced the tumor burden. Furthermore, acetylated RNA immunoprecipitation sequencing data and RNA immunoprecipitation qPCR results revealed that NAT10 is responsible for a set of ac4C mRNA modifications in bladder cancer cells. Inhibition of NAT10 led to a loss of ac4C peaks in these transcripts and represses the mRNA's stability and protein expression. Mechanistically, the ac4C reduction modification in specific regions of mRNAs resulting from NAT10 downregulation impaired the translation efficiency of BCL9L, SOX4 and AKT1 as well as the stability of BCL9L, SOX4. CONCLUSIONS: In summary, these findings provide new insights into the dynamic characteristics of mRNA's post-transcriptional modification via NAT10-dependent acetylation and predict a role for NAT10 as a therapeutic target in bladder cancer. HIGHLIGHTS: NAT10 is highly expressed in BLCA patients and its abnormal level predicts bladder cancer progression and low overall survival rate. NAT10 is necessary and sufficient for BLCA tumourigenic properties. NAT10 is responsible for ac4C modification of target transcripts, including BCL9L, SOX4 and AKT1. NAT10 may serve as an effective and novel therapeutic target for BLCA.

COVID-19 and Venous Thromboembolism: From Pathological Mechanisms to Clinical Management.

Coronavirus disease 2019 (COVID-19), which is becoming a global pandemic, is caused by SARS-CoV-2 infection. In COVID-19, thrombotic events occur frequently, mainly venous thromboembolism (VTE), which is closely related to disease severity and clinical prognosis. Compared with historical controls, the occurrence of VTE in hospitalized and critical COVID-19 patients is incredibly high. However, the pathophysiology of thrombosis and the best strategies for thrombosis prevention in COVID-19 remain unclear, thus needing further exploration. Virchow's triad elements have been proposed as important risk factors for thrombotic diseases. Therefore, the three factors outlined by Virchow can also be applied to the formation of venous thrombosis in the COVID-19 setting. A thorough understanding of the complex interactions in these processes is important in the search for effective treatments for COVID-19. In this work, we focus on the pathological mechanisms of VTE in COVID-19 from the aspects of endothelial dysfunction, hypercoagulability, abnormal blood flow. We also discuss the treatment of VTE as well as the ongoing clinical trials of heparin anticoagulant therapy. In addition, according to the pathophysiological mechanism of COVID-19-associated thrombosis, we extended the range of antithrombotic drugs including antiplatelet drugs, antifibrinolytic drugs, and anti-inflammatory drugs, hoping to find effective drug therapy and improve the prognosis of VTE in COVID-19 patients.

Exploration of Lipid Metabolism in Gastric Cancer: A Novel Prognostic Genes Expression Profile.

BACKGROUND: Alterations in lipid metabolism are increasingly being recognized. However, the application of lipid metabolism in the prognosis of gastric cancer (GC) has not yet been explored. METHODS: A total of 204 lipid metabolism relative genes were analyzed in the GC cohort from The Cancer Genome Atlas (TCGA), and four independent cohorts from Gene Expression Omnibus (GEO) and one cohort from Wuhan Union Hospital were applied for external validation. Differential expression and enrichment analyses were performed between GC and normal tissue. The LASSO-Cox proportional hazard regression model was applied to select prognostic genes and to construct a gene expression profile. RESULTS: Our research indicated that higher expression level of AKR1B1, PLD1, and UGT8 were correlated with worse prognosis of GC patients, while AGPAT3 was correlated with better prognosis. Furthermore, we developed a gene profile composed of AGPAT3, AKR1B1, PLD1, and UGT8 suggested three groups with a significant difference in overall survival (OS). The profile was successfully validated in an independent cohort and performed well in the immunohistochemical cohort. Furthermore, we found that ether lipid metabolism, glycerophospholipid metabolism, and glycerolipid metabolism were upregulated, and fatty acid ß-oxidation and other lipid peroxidation processes were reduced in GC. CONCLUSION: Collectively, we found lipid metabolism is reliable and clinically applicable in predicting the prognosis of GC based on a novel gene profile.

Incidence and impact of disseminated intravascular coagulation in COVID-19 a systematic review and meta-analysis.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is a novel infectious disease, with significant morbidity and mortality. This meta-analysis is to evaluate the prevalence of disseminated intravascular coagulation (DIC) in COVID-19 patients and to determine the association of DIC with the severity and prognosis of COVID-19. METHODS: We searched the PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) database until August 12, 2020. The meta-analysis was performed using Stata 16.0 software. RESULTS: 14 studies were included in our meta-analysis. The pooled analysis revealed that the incidence of COVID-19 patients developing DIC was 3% (95%: 1%-5%, P < 0.001). In addition, deaths were more likely to be associated with DIC (Log OR = 2.46, 95% CI: 0.94-3.99, P < 0.001) with statistical significance. CONCLUSIONS: DIC is associated with the severity and poor prognosis of COVID-19 patients. Therefore, attention should be paid to coagulation dysfunction in COVID-19 patients. Monitoring of coagulation indicators may improve the prognosis of COVID-19 inpatients.

Application Value of Blood Heparin-Binding Protein in the Diagnosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Objective: To investigate the expression and clinical significance of serum heparin-binding protein (HBP), C-reactive protein (CRP), and white blood cell count (WBC) in an acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods: A prospective research model was used to select 63 patients with acute exacerbation of chronic obstructive pulmonary disease who were hospitalized in Xuzhou First People's Hospital from January 2020 to June 2020, and among the chronic obstructive pulmonary disease patients who were followed up in our hospital during the same period, 18 patients were in the stable phase, and 43 healthy patients in our hospital during the same period were selected as the healthy control group. 18 patients with stable chronic obstructive pulmonary disease were selected as the observation group, and 43 healthy people who underwent examination at the same time as the control group. For patients with acute COPD recombination, 5 ml of venous blood was collected according to whether the condition of COPD patients with acute exacerbation was stable or not. 5 ml of venous blood was collected for acute exacerbation. According to their clinical symptoms (such as cough, sputum, and asthma), dyspnea score (MRC score), and pulmonary function (FEV1 and FEV1/FVC), it is determined whether the patient's condition is stable. Patients in the stable COPD group will collect 5 ml of venous blood during the outpatient follow-up, and those in the healthy physical examination group will collect veins on the day of the physical examination. In 5 ml of blood, the levels of HBP and CRP in the blood were measured by the enzyme-linked immunosorbent method and the immunoturbidimetric method, respectively, and the peripheral blood WBC was measured by a blood cell analyzer and its supporting reagents. The differences of the three indicators in each group were statistically analyzed. Normally distributed measurement data were compared using t-test, homogeneity of variance of nonnormally distributed measurement data were compared using one-way analysis of variance, uneven variance of nonnormally distributed measurement data were compared using a rank-sum test, and Pearson linear analysis was used for correlation test. Subject working characteristic curve (ROC) was drawn, P < 0.05 means the difference is statistically significant, the receiver working characteristic curve was established, and the area under the curve (AUC) was calculated to analyze blood HBP. The value of blood CRP and peripheral blood WBC counts alone or in combination in the diagnosis of acute exacerbations of chronic obstructive pulmonary disease. Results: The level of blood heparin-binding protein in the acute exacerbation phase was significantly higher than that in the stable phase and healthy controls (P < 0.05). In the acute exacerbation stage and stable stage group, the blood heparin binding protein, the percentage of leukocytes, neutrophils, and CRP were detected. There is a correlation between (P < 0.05) and a correlation with lung function (FEV1) (P < 0.05). The predictive value of heparin-binding protein, white blood cells, neutrophil percentage, CRP, etc. for the acute exacerbation of chronic obstructive pulmonary disease, with the area under the heparin-binding protein curve, is the largest, and compared with the stable phase, the comparison of heparin-binding protein, white blood cells, and CRP is statistically significant (P < 0.05). Conclusion: Heparin-binding protein increases in the stable phase and acute exacerbation phase and is related to other inflammatory factors. It is one of the important inflammatory factors in chronic obstructive pulmonary disease. Heparin-binding protein, white blood cells, CRP, etc. have diagnostic and predictive value for acute exacerbation of chronic obstructive pulmonary disease. Heparin-binding protein has the best predictive result, and the combined index test has a better diagnostic predictive value, which is better than single index detection.

Characteristics of mortal COVID-19 cases compared to the survivors.

The outbreak of coronavirus disease 2019 (COVID-19) initially occurred in December 2019 and triggered a public health emergency. The increasing number of deaths due to this disease was of great concern. Therefore, our study aimed to explore risk factors associated with COVID-19 deaths. After having searched the PubMed, EMBASE, and CNKI for studies published as of August 10, 2020, we selected articles and extracted data. The meta-analysis was performed using Stata 16.0 software. Nineteen studies were used in our meta-analysis. The proportions of comorbidities such as diabetes, hypertension, malignancies, chronic obstructive pulmonary disease, cardio-cerebrovascular disease, and chronic liver disease were statistically significantly higher in mortal COVID-19 cases. Coagulation and inflammatory markers, such as platelet count, D-dimer, prothrombin time, C-reactive protein, procalcitonin, and interleukin 6, predicted the deterioration of the disease. In addition, extracorporeal membrane oxygenation and mechanical ventilation predicted the poor prognosis during its progression. The COVID-19 pandemic is still evolving, placing a huge burden on healthcare facilities. Certain coagulation indicators, inflammatory indicators, and comorbidities contribute to the prognosis of patients. Our study results may help clinicians optimize the treatment and ultimately reduce the mortality rate.

Downregulation of miR­98 contributes to hypoxic pulmonary hypertension by targeting ALK1.

Chronic hypoxia is one of the most common causes of secondary pulmonary hypertension, the mechanisms of which remain unclear. MicroRNAs (miRNAs) are small, noncoding RNAs that inhibit the translation or accelerate the degradation of mRNA. Previous studies have demonstrated that deregulated miRNA expression contributes to various cellular processes including cell apoptosis and proliferation, which are mediated by hypoxia. In the present study, the expression of miR­98 was identified to be decreased in the lung tissue of a hypoxic pulmonary hypertension (HPH) rat model and pulmonary artery (PA) smooth muscle cells (PASMCs), which was induced by hypoxia. By transfecting miR­98 mimics into PASMCs, the high expression of miR­98 inhibited cell proliferation, but upregulated hypoxia­induced PASMCs apoptosis. However, these effects of miR­98 mimics on PASMCs were reversed by ALK1 (activin receptor­like kinase­1) overexpression. ALK1 was identified as a candidate target of miR­98. In addition, overexpressing miR­98 markedly decreased the pulmonary artery wall thickness and the right ventricular systolic pressure in rats induced by hypoxia. These results provided clear evidence that miR­98 was a direct regulator of ALK1, and that the downregulation of miR­98 contributed to the pathogenesis of HPH. These results provide a novel potential therapeutic strategy for the treatment of HPH.

Stability Analysis and Application for Delayed Neural Networks Driven by Fractional Brownian Noise.

This paper deals with two types of the stability problem for the delayed neural networks driven by fractional Brownian noise (FBN). The existence and the uniqueness of the solution to the main system with respect to FBN are proved via fixed point theory. Based on Hilbert-Schmidt operator theory and analytic semigroup principle, the mild solution of the stochastic neural networks is obtained. By applying the stochastic analytic technique and some well-known inequalities, the asymptotic stability criteria and the exponential stability condition are established. Both numerical example and practical application for synchronization control of multiagent system are provided to illustrate the effectiveness and potential of the proposed techniques.