P66Shc is increased in peripheral blood mononuclear cells of the patients with obstructive sleep apnea.

Objective: Obstructive sleep apnea (OSA) is characterized by nocturnal intermittent hypoxemia and linked to oxidative stress. Evidence demonstrated that p66Shc plays a key role in regulating oxidative stress. This study aimed to investigate the expression of p66Shc in peripheral blood mononuclear cells (PBMCs) of patients with OSA and the association with polysomnographic parameters. Methods: Fifty-four OSA subjects and 19 no OSA controls were enrolled in this study. All the subjects underwent standard polysomnography. P66Shc mRNA and protein levels in the PBMCs were detected by quantitative real-time polymerase chain reaction and western blotting. Plasma 3-nitrotyrosine (3-NT), oxidized low density lipoprotein (oxLDL), and advanced oxidation protein products (AOPP) were measured by ELISA method. Results: P66Shc mRNA and protein levels in PBMCs were significantly higher in OSA patients than in controls. P66Shc mRNA was positively correlated with plasma 3-NT, oxLDL, AOPP, hypopnea index (AHI), oxygen desaturation index (ODI), percentage of total sleep time with oxygen saturation (SaO2) below 90% (CT90), epworth sleepiness scale (ESS) and lymphocytes; negatively correlated with lowest SaO2 (LSaO2) and mean SaO2 (MSaO2). Further multivariate linear regression analysis showed that p66Shc mRNA levels were independently associated with AHI, MSaO2 and CT90. Conclusions: Oxidative stress regulator p66Shc may play a role in the pathophysiology of OSA and might serve as a potential biomarker for this disease.

Preparation and Hydration Mechanisms of Low Carbon Ferrochrome Slag-Granulated Blast Furnace Slag Composite Cementitious Materials.

Low carbon ferrochrome slag (LCFS) is the metallurgical waste slag from the carbon ferrochrome alloy smelting process. Compared with high carbon ferrochrome slag, LCFS has great potential as cementitious material; the chemical compositions of the two types of slag are quite different. In this research, composite cementitious materials are prepared which use low carbon ferrochrome slag and granulated blast furnace slag (GBFS) as the main raw material. Steel slag mud (SSM) and flue gas desulfurization gypsum (FGDG) are used as the activator. In order to find the variety rule of compressive strength on the composite cementitious materials, a three-factor three-level Box-Behnken design is used to discuss the following independent variables: LCFS content, GBFS content, and water-binder ratio. Moreover, the hydration characteristics of the LCFS-GBFS composite cementitious materials is studied in this paper in terms of hydration product, micromorphology, and hydration degree, based on multi-technical microstructural characterizations. The results show that the compressive strength of the LCFS-GBFS composite cementitious materials is significantly affected by single factors and the interaction of two factors. The mechanical property of the mortar samples at 3, 7, and 28 days are 26.6, 35.3, and 42.7 MPa, respectively, when the LCFS-GBFS-SSM-FGDG ratio is 3:5:1:1 and the water-binder ratio is 0.3. The hydration products of LCFS-GBFS composite cementitious materials are mainly amorphous gels (C-S-H gel), ettringite, and Ca(OH)2. With the increase of LCFS content, more hydration products are generated, and the microstructure of the cementitious system becomes more compact, which contributes to the compressive strength. The results of this research can provide a preliminary theoretical foundation for the development of LCFS-GBFS composite cementitious materials and promote the feasibility of its application in the construction industry. Deep hydration mechanism analysis and engineering applications should be studied in the future.

Serum biomarkers for liver fibrosis.

Liver fibrosis is a common pathway in most chronic liver diseases, characterized by excessive extracellular matrix accumulation. Without treatment, fibrosis will ultimately result in cirrhosis, portal hypertension, and even liver failure. It is considered that liver fibrosis is reversible while cirrhosis is not, making it significant to diagnose and evaluate liver fibrogenesis timely. As the gold standard, liver biopsy is imperfect due to its invasiveness and sampling error. Therefore, attempts at uncovering noninvasive tests have become a hot topic in liver fibrosis. Nowadays, as an important category of noninvasive tests, serum biomarkers, which are safer, convenient, repeatable, and more acceptable, are widely discussed and commonly used in clinical practice. Serum biomarkers of liver fibrosis can be divided into class I (direct) and classⅡ (indirect) markers. However, the diagnostic efficiency still varies among studies. This article summarizes the most established and newly discovered serum biomarkers for hepatic fibrogenesis.

Prevalence and clinical characteristics of hepatitis B surface antigen-negative/hepatitis B core antibody-positive patients with detectable serum hepatitis B virus DNA.

BACKGROUND: To determine the prevalence of detectable serum hepatitis B virus (HBV) DNA in patients who are hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive. The correlation between HBV DNA viral load and serological markers, as well as liver and coagulation function indicators were investigated. Furthermore, the effects of immunosuppressive therapy on DNA replication were assessed. METHODS: A total of 2,013 HBsAg-negative/HBcAb-positive patients admitted to our hospital between January and December 2019 were enrolled in this study. Patient clinical characteristics including serological markers, HBV DNA viral load, liver function and coagulation function indicators, and immune function status were analyzed. RESULTS: In the Hunan province in China, the prevalence of detectable HBV DNA was 5.4% in HBsAg-negative/HBcAb-positive patients. However, the prevalence of detectable HBV DNA in HBsAg-negative/HBcAb-positive patients may vary because of different HBV serological markers. In patients with detectable serum HBV DNA, the log10 HBV DNA value was positively correlated with alanine transaminase (ALT) and aspartate transaminase (AST) levels, and negatively correlated with antithrombin III (AT III) concentrations. Moreover, in patients receiving immunosuppressive therapy, ALT and AST levels were higher than those of patients who did not receive immunosuppressive therapy. The ALT and AST levels in hepatitis B e antibody (HBeAb)-positive patients were significantly higher than that observed in HBeAb-negative patients. CONCLUSIONS: For HBsAg-negative/HBcAb-positive patients, clinicians should pay attention to the patient's immune function status. In situations where HBV DNA cannot be detected, changes in serum ALT, AST, and AT III concentrations can be used to speculate on viral replication status to reduce the risk of HBV infection and transmission.

Increased Levels of CHI3L1 and HA Are Associated With Higher Occurrence of Liver Damage in Patients With Obstructive Sleep Apnea.

Background: Obstructive sleep apnea-hypopnea syndrome (OSA) may cause liver fibrosis, and liver fibrosis serum biomarkers plays an important role on the diagnosis of liver fibrosis. In addition, this study aimed to observe the changes of 4 serum markers and Chitinase 3-like protein 1 (CHII3L1) levels in OSA patients with different disease severity and explore their interactions. And then, we examined whether intermittent hypoxia (IH) exposure can activate hepatic stellate cell. Methods: 74 OSA patients in Second Xiangya hospital from January 2021 to October 2021 was selected and categorized into mild, moderate, and severe groups according to AHI. In addition, 20 subjects were selected as the control group. Serum levels of liver fibrosis markers were determined by electrochemiluminescence immunoassay. Hepatic stellate cells were exposed to intermittent IH or normoxia (RA). Results were analyzed using the SPSS software. Results: There was a significant increase in serum hyaluronic acid (HA), collagen type IV (CIV) and CHI3L1 levels in OSA patients compared with control group. Specifically, serum liver fibrosis markers HA, CIV and CHI3L1 levels were positively correlated with apnea-hypopnea index (AHI), but negatively correlated with the lowest saturation oxygen (LSaO2) respectively. The LX-2 cells (human hepatic stellate cell line) exposed to IH showed significant increases in fibrotic protein expression. Conclusion: OSA might either directly or indirectly trigger or exacerbate liver fibrosis, possibly via IH-related pathways.

The roles and mechanisms of hypoxia in liver fibrosis.

Liver fibrosis occurs in response to any etiology of chronic liver injury. Lack of appropriate clinical intervention will lead to liver cirrhosis or hepatocellular carcinoma (HCC), seriously affecting the quality of life of patients, but the current clinical treatments of liver fibrosis have not been developed yet. Recent studies have shown that hypoxia is a key factor promoting the progression of liver fibrosis. Hypoxia can cause liver fibrosis. Liver fibrosis can, in turn, profoundly further deepen the degree of hypoxia. Therefore, exploring the role of hypoxia in liver fibrosis will help to further understand the process of liver fibrosis, and provide the theoretical basis for its diagnosis and treatment, which is of great significance to avoid further deterioration of liver diseases and protect the life and health of patients. This review highlights the recent advances in cellular and molecular mechanisms of hypoxia in developments of liver fibrosis.

Magnetic-, Acoustic-, and Optical-Triple-Responsive Microbubbles for Magnetic Hyperthermia and Pothotothermal Combination Cancer Therapy.

The precision delivery of anti-cancer agents which aim for targeted and deep-penetrated delivery as well as a controlled release at the tumor site has been challenged. Here, we fabricate iron oxide nanoparticle shelled microbubbles (NSMs) through self-assembly, synergizing magnetic, acoustic, and optical responsiveness in one nanotherapeutic platform. Iron oxide nanoparticles serve as both magnetic and photothermal agents. Once intravenously injected, NSMs can be magnetically guided to the tumor site. Ultrasound triggers the release of iron oxide nanoparticles, facilitating the penetration of nanoparticles deep into the tumor due to the cavitation effect of microbubbles. Thereafter, magnetic hyperthermia and photothermal therapy can be performed on the tumor for combinational cancer therapy, a solution for cancer resistance due to the tumor heterogeneity. In this protocol, the synthesis and characterization of NSMs including structural, chemical, magnetic and acoustic properties were performed. In addition, the anti-cancer efficacy by thermal therapy was investigated using in vitro cell cultures. The proposed delivery strategy and combination therapy holds great promise in cancer treatment to improve both delivery and anticancer efficacies.