Myocardial Injury in Rats Exposed to High-Intensity Exercise Evaluated by 2-D Speckle Tracking Imaging.

OBJECTIVE: The aim of the work described here was to evaluate strain and morphological change of the left ventricle in Sprague Dawley (SD) rats at different exercise intensities by 2-D speckle tracking imaging (STI). METHODS: Seventy-two 8-wk-old SD rats were divided into four groups on the basis of exercise intensity: sedentary (SED), low-intensity running, medium-intensity running (MIR) and high-intensity running (HIR). Each group was further sub-divided into three groups of different exercise lengths: 1, 4 and 8 wk. The structural measurements of the left ventricle and left ventricular ejection fraction (LVEF) were obtained by echocardiography. Systolic peak values of global longitudinal, circumferential and radial strains (GLS, GCS and GRS) were obtained. Histopathological results of the cross-sectional area (CSA) of myocardial cells, collagen volume fraction (CVF) of the myocardium and perivascular collagen area (PVCA) were also observed. RESULTS: Structural measurements of the left ventricle and LVEF did not change with different exercise intensities or lengths. GLS of the HIR8 wk sub-group was significantly lower than those of the SED8 wk and MIR8 wk sub-groups. Conversely, the GLS and GCS of the HIR8 wk sub-group were lower than those of the HIR1 wk and HIR4 wk sub-groups. Histopathologically, the CSA of myocardial cells significantly increased across all HIR sub-groups and the MIR4 wk and MIR8 wk sub-groups. CVFendo and PVCA were also significantly increased in the HIR4 wk and HIR8 wk sub-groups. The HIR8 wk group also had regional swelling and ill-defined boundaries of myocardial cells. CONCLUSION: Prolonged, high-intensity exercise may lead to exercise-induced injury of the myocardium. Two-dimensional STI can be used as a non-invasive early detection method for exercise-induced injury of myocardial function, compared with LVEF.

Segmental and global myocardial work in hypertensive patients with different left ventricular geometry.

BACKGROUND: Myocardial work acquired by echocardiography has emerged as a novel method to evaluate myocardial function. We investigated global and segmental myocardial work in hypertension (HT) among patients with different patterns of left ventricular (LV) geometry in order to analyze the contribution of segmental myocardial work to global myocardial work. METHODS AND RESULTS: One hundred twenty-five patients with HT were divided into 4 groups: normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH) and eccentric hypertrophy (EH). Longitudinal strain (LS) and the following indices were obtained by echocardiography: myocardial work index (MWI), myocardial constructive work (MCW), myocardial wasted work (MWW), and myocardial work efficiency (MWE). The global longitudinal strain (GLS) decreased gradually among the groups: NG, CR, CH and EH (P < 0.001). Global MWI (GWI) and global MCW (GCW) did not change across the different LV remodeling groups. Global MWW (GWW) increased and global MWE (GWE) decreased in both CH and EH group (P < 0.001). The LS of basal and middle regions reduced gradually in all HT subgroups, while apical LS decreased only in the CH and EH groups (P < 0.001). Basal MWI and MCW decreased in the CH and EH groups (P = 0.025, 0.007, respectively). Apical MWI and MCW increased in the NG and CR groups (P = 0.015, 0.044, respectively), with a decreasing trend in the CH and EH groups. All segmental MWW elevated and MWE reduced significantly in the CH and EH groups (P < 0.001). Univariate and multivariate logistic regression analyses demonstrated a significant association between left atrial volume index (LAVI), GLS, GWE and LV hypertrophy. At the receiver operating characteristic (ROC) analysis, optimal cutoff values of GLS, Apical LS, GWE and Apical MWE discriminating LV hypertrophy were 0.9072, 0.8049, 0.8325 and 0.7414, respectively. CONCLUSION: Apical myocardial work increases in the early stages of LV remodeling, likely as a compensatory mechanism to maintain normal global myocardial work. Segmental myocardial work analysis offers a reliable means to explore the distribution of myocardial impairment in hypertensive patients at different LV remodeling stages.

Segmental and global myocardial work in hypertensive patients with different left ventricular ejection fraction: what's the role of the apex played?

We investigated myocardial work in hypertension (HT) among patients with different left ventricular ejection fraction (LVEF) to analyze the contribution of segmental myocardial work to global myocardial work. 114 patients with HT were divided into 4 groups: HTsnEF ("supra-normal" EF, > 65%); HTnEF ("normal" EF, 60-65%); HTmEF (designed as "middle" EF, 50-60%, within an abnormal LV geometry); HTrEF (reduced EF, < 50%). Longitudinal strain (LS) and myocardial work indices were obtained by echocardiography: myocardial work index (MWI), constructive work (MCW), wasted work (MWW), myocardial work efficiency (MWE), and percentages of apical work were calculated (PApi-MWI, PApi-MCW). Global LS (GLS) and global MWE (GWE) decreased in HTmEF and HTrEF groups. Global MWI(GWI) and MCW(GCW) increased in HTsnEF and HTnEF groups, and subsequently decreased, particularly in HTrEF group (P < 0.05). GWW increased in all HT subgroups. All segmental MWI and MCW were elevated or preserved initially in HTsnEF and HTnEF groups, and subsequently decreased, obviously in basal and middle segments in HTrEF group (P < 0.05). All segmental MWW increased and MWE decreased in HTmEF and HTrEF groups (P < 0.05). PApi-MWI and PApi-MCW increased initially, and subsequently decreased in HTmEF group, and elevated significantly in HTrEF group. Correlation analysis revealed a close connection of GLS and myocardial work parameters with LVEF. Apical myocardial work increased at the early stages of hypertensive systolic dysfunction, as a compensatory mechanism. Segmental myocardial work analysis added value to explore the distribution of myocardial impairment.

Exosomes and circular RNAs: promising partners in hepatocellular carcinoma from bench to bedside.

Hepatocellular carcinoma (HCC) is characterized by high morbidity and mortality, and a low 5-year survival rate. Exploring the potential molecular mechanisms, finding diagnostic biomarkers with high sensitivity and specificity, and determining new therapeutic targets for HCC are urgently needed. Circular RNAs (circRNAs) have been found to play a key role in the occurrence and development of HCC, while exosomes play an important role in intercellular communication; thus, the combination of circRNAs and exosomes may have inestimable potential in early diagnosis and curative therapy. Previous studies have shown that exosomes can transfer circRNAs from normal or abnormal cells to surrounding or distant cells; thereafter, circRNAs influence target cells. This review summarizes the recent progress regarding the roles of exosomal circRNAs in the diagnosis, prognosis, occurrence and development and immune checkpoint inhibitor and tyrosine kinase inhibitor resistance of HCC to provide inspiration for further research.

The Value of Multimodal Ultrasonic Scoring System in the Diagnosis of Carotid Vulnerable Plaque: A Comparative Study With Pathology.

BACKGROUND AND AIMS: Vulnerable plaques are closely related to ischemic stroke. To investigate the diagnostic value of multimodal plaque vulnerability ultrasound scoring system (PV-USS) using histopathology as the gold standard. METHODS: A total of 45 subjects who would be underwent carotid endarterectomy were recruited. The postoperative specimens were examined by histopathology. All responsible plaques were scanned dynamically in multiple sections by carotid ultrasound to measure maximum thickness and lumen stenotic degree, as well as, the echo, homogeneity, surface morphology, and echo type were observed. The above two-dimensional (2D) ultrasonic features were systematically scored, that is, PV-USS2D . Combined with contrast-enhanced ultrasonography (CEUS), neovascularization grade in plaque was scored, which is PV-USS2D+CEUS . RESULTS: According to the pathological results, 45 subjects were divided into vulnerable plaque group (27 cases, 60%) and non-vulnerable plaque group (18 cases, 40%). PV-USS2D and PV-USS2D+CEUS in vulnerable plaque group were higher than those in non-vulnerable plaque group (PV-USS2D : 9.44 ± 2.10 vs 7.22 ± 1.73; PV-USS2D+CEUS: 12.37 ± 2.10 vs 8.28 ± 1.81, P < .001). ROC curve analysis showed that the AUC of PV-USS2D and PV-USSCEUS was 0.783 and 0.929, respectively (P < .001). The best cutoff values of PV-USS2D and PV-USS2D+CEUS were, respectively, 9.5 (the maximum Youden index was 0.425, the sensitivity was 48.1%, the specificity was 94.4%) and 10.5 (the maximum Youden index was 0.667, the sensitivity was 77.8%, the specificity was 88.9%). CONCLUSIONS: Ultrasound scoring system may be used as an effective method to evaluate the vulnerability of plaque. The diagnostic efficiency of PV-USS2D+CEUS is more higher than PV-USS2D .

[Adverse cardiovascular effects of antiretrovirals in female mice during gestation].

Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(P＜0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (P＜0.05); the level of LVP+dP/dtmax was decreased (P＜0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (P＜0.05 or P＜0.01), while the level of glucose was increased (P＜0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.

Simulation on oily contamination removal by ozone using molecular dynamics.

Ozone (O3) is characteristic of high oxidative activity. It displays a high potential value in sterilization and decontamination. Although O3 has been widely investigated for its efficiency and environmentally friendly effectiveness, the fundamental issue regarding the complicated microscopic interaction mechanism between O3 and contaminant molecules remains largely unaddressed. We addressed this knowledge gap through molecular dynamics (MD) simulation at the molecular scale. Results indicated that five representative hydrocarbon molecules (n-hexadecane, phytane, terpane, naphthalin and acenaphthylene) on a rough silica (SiO2) surface were almost removed after about 300 ps simulation. And the aromatic molecules were easier to be removed than aliphatic ones. The hydroxyl oxidation reaction was demonstrated as a predominant mechanism. As the large dose of O3 was supplied by atmospheric air dielectric barrier discharge (DBD) plasma, this work provided an important theoretical reference for better using plasma technology for oily contaminant removal.

Validation of the hepatocellular carcinoma early detection screening algorithm Doylestown and aMAP in a cohort of Chinese with cirrhosis.

BACKGROUND: Previous studies have developed some blood-based biomarker algorithms such as the Doylestown algorithm and aMAP score to improve the detection of Hepatocellular carcinoma (HCC). However, no one has studied the application of the Doylestown algorithm in the Chinese. Meanwhile, which of these two screening models is more suitable for people with liver cirrhosis remains to be investigated. METHODS: In this study, HCC surveillance was performed by radiographic imaging and testing for tumor markers every 6 months from August 21, 2018, to January 12, 2021. We conducted a retrospective study of 742 liver cirrhosis patients, and among them, 20 developed HCC during follow-up. Samples from these patients at three follow-up time points were tested to evaluate alpha-fetoprotein (AFP), the Doylestown algorithm, and aMAP score. RESULTS: Overall, 521 liver cirrhosis patients underwent semiannual longitudinal follow-up three times. Five patients were diagnosed with HCC within 0-6 months of the third follow-up. We found that for these liver cirrhosis patients, the Doylestown algorithm had the highest accuracy for HCC detection, with areas under the receiver operating characteristic curve (AUCs) of 0.763, 0.801, and 0.867 for follow-ups 1-3, respectively. Compared with AFP at 20 ng/ml, the Doylestown algorithm increased biomarker performance by 7.4%, 21%, and 13% for follow-ups 1-3, respectively. CONCLUSIONS: Our findings show that the Doylestown algorithm performance appeared to be optimal for HCC early screening in the Chinese cirrhotic population when compared with the aMAP score and AFP at 20 ng/ml.

The value of transthoracic echocardiography in the detection of extra-cardiac lesions.

OBJECTIVE: Transthoracic echocardiography (TTE) is generally recognized as the top choice for detecting myocardial and cardiac cavity lesions. Sonographers mostly focus on myocardium, cardiac cavity and cardiac hemodynamics, whereas the abnormal extra-cardiac lesions are easily remain unrecognized. The aim of this study was to investigate the ultrasonic image features in abnormal extra-cardiac lesions and the value of TTE in the detection of extra-cardiac lesions. METHODS: 49 cases of abnormal extra-cardiac lesion detected by TTE from January 2014 to December 2019 were collected, which were confirmed by surgical pathology. The two-dimensional ultrasonic characteristics and the relationships with the cardiac and great vessels were summarized on the basis of multi-view by TTE. All patients were also examined by computed tomography (CT). RESULTS: In 49 patients with abnormal extra-cardiac lesions, 37 malignant cases and 12 benign cases were included. There were 41 cases (41/49, 86.67%) of mediastinal lesions and 8 cases (8/49, 16.33%) of lung lesions. The maximum diameter ranged from 3.2 cm to 13.66 cm, and the median diameter was about 7.4 cm, among which 29 cases (29/49, 59.18%) were larger than 5 cm. 4 cases (4/49, 8.16%) of cystic anechoic lesions were pericardial cyst. 2 cases (2/49, 4.08%) of cystic-solid echogenic lesions were teratoma. The remaining 43 cases (43/49, 87.76%) presented as solid hypoechoic or heterogeneous masses. 6 cases compressed the heart and 21 cases encroached on the heart and vessels. Diagnosis coincidence rates of TTE and CT were respectively 77.55% and 93.88%, with a statistical difference (p = 0.012). CONCLUSION: Although the diagnostic coincidence rate of TTE is slightly lower than that of CT, TTE has certain diagnostic value for extra-cardiac lesions.

Investigation of Left Ventricular Strain and Its Morphological Basis During Different Stages of Diastolic and Systolic Dysfunction in Spontaneously Hypertensive Rat.

BACKGROUND: Myocardial fibrosis plays an important role in the pathogenesis of hypertensive cardiac dysfunction, and myocardial strain could detect early systolic abnormalities when left ventricular ejection fraction (LVEF) is preserved. The aim of this study was to investigate the characteristics of left ventricular multidirectional strain during different stages of heart dysfunction and the possible morphological basis in spontaneously hypertensive rats (SHRs). METHODS: SHRs and Wistar-Kyoto (WKY) rats were randomly divided into cages and observed for 3-25 months. Echocardiographic measurements, LV + dp/dtmax and left ventricular end-diastolic pressure (LVEDP), and histological collagen volume fraction (CVF) were observed in all rats. RESULTS: According to LVEF and LVEDP, SHRs were divided into normal cardiac function group (group A), diastolic dysfunction group (group B1), and systolic dysfunction group (group B2). In group A, myocardial strain and CVF showed no difference compared with the control group. In group B1, global longitudinal strain (GLS) and endocardial longitudinal strain (SL-endo) were lower than those in group A CVF-endo was increased (all P < 0.05). In group B2, global and layer-specific strain decreased significantly, along with the increased CVF-endo and CVF-epi (all P < 0.05). The decrease of GLS and SL-endo was moderately correlated with the increase of CVF-endo. The reduction of LVEF was correlated with the decrease of SC-endo (r = 0.65, P < 0.01). CONCLUSIONS: Pathological myocardial fibrosis associated with hypertension develops from the inner to outer layer of myocardium, which is coincident with the impairment of myocardial deformation, where longitudinal strain is involved firstly and LVEF declines when all directions of strain are reduced.

Diagnostic and prognostic value of serum Chitinase 3-like protein 1 in hepatocellular carcinoma.

The serum Chitinase 3-like protein 1 (CHI3L1) protein level can distinguish the stages of liver fibrosis to a great extent. However, the diagnostic and prognostic significance of serum CHI3L1 in hepatocellular carcinoma (HCC) is not clarified. To evaluate the diagnostic and prognostic value of CHI3L1 in HCC, a total of 128 HCC patients treated in the HwaMei Hospital, University of Chinese Academy of Sciences, from December 2018 to April 2020 were collected retrospectively. Matched age and gender subjects, 40 patients with liver cirrhosis, 40 patients with chronic hepatitis, and 40 healthy subjects were enrolled in the control group. The relevant clinical laboratory and examination data and the overall survival time (OS) of the HCC patients were collected. The serum CHI3L1 expression level is related to α-fetoprotein (AFP), tumor-node-metastasis (TNM) stage, maximum tumor diameter, liver cirrhosis, and HCC patient's OS (p < 0.05). The area under the curve (AUC) of CHI3L1 was 0.7875 with the cutoff value of 91.36 ng/ml. Combining the serum CHI3L1 and α-fetoprotein (AFP) by a binary logistic regression model can increase the diagnostic sensitivity to 97.5%. Multivariate Cox regression analysis indicated that CHI3L1 is an independent prognostic factor in patients with HCC.

Risk factors for prolonged virus shedding of respiratory tract and fecal in adults with severe acute respiratory syndrome coronavirus-2 infection.

BACKGROUND: The dynamic alteration and comparative study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding pattern during treatment are limited. This study explores the potential risk factors influencing prolonged viral shedding in COVID-19. METHODS: A total of 126 COVID-19 patients were enrolled in this retrospective longitudinal study. A multivariate logistic regression analysis was carried out to estimate the potential risk factors. RESULTS: 38.1% (48/126) cases presented prolonged respiratory tract viral shedding, and 30 (23.8%) cases presented prolonged rectal swab viral shedding. Obesity (OR, 3.31; 95% CI, 1.08-10.09), positive rectal swab (OR, 3.43; 95% CI, 1.53-7.7), treatment by lopinavir/ritonavir with chloroquine phosphate (OR, 2.5; 95% CI, 1.04-6.03), the interval from onset to antiviral treatment more than 7 days (OR, 2.26; 95% CI, 1.04-4.93), lower CD4+ T cell (OR, 0.92; 95% CI, 0.86-0.99) and higher NK cells (OR, 1.11; 95% CI, 1.02-1.20) were significantly associated with prolonged respiratory tract viral shedding. CD3-CD56+ NK cells (OR, 0.87; 95% CI, 0.76-0.99) were related with prolonged fecal shedding. CONCLUSIONS: Obesity, delayed antiviral treatment, and positive SARS-CoV-2 for stool were independent risk factors for prolonged SARS-CoV-2 RNA shedding of the respiratory tract. A combination of LPV/r and abidol as the initial antiviral regimen was effective in shortening the duration of viral shedding compared with LPV/r combined with chloroquine phosphate. CD4+ T cell and NK cells were significantly associated with prolonged viral shedding, and further studies are to be warranted to determine the mechanism of immunomodulatory response in virus clearance.

Circular RNAs in liver diseases: Mechanisms and therapeutic targets.

Circular RNAs (circRNAs) are formed from the genome through diverse back splicing and feature the closed loop. circRNAs are widely available in a variety of cells and characterized by conservation, structural stability, high abundance and tissue-specific or developmental-specific expression. Recent studies have shown that circRNAs are closely related to liver diseases, such as metabolic-associated fatty liver disease, hepatitis, liver cirrhosis and hepatocellular carcinoma. circRNAs play an important role in the progression of liver diseases, are potential diagnostic and prognostic markers, and have translational value in therapy. This article reviews the research on circRNAs in liver diseases, with a view to providing a theoretical basis and new ideas for future research and treatment of liver diseases.

CHI3L1 in the pathophysiology and diagnosis of liver diseases.

Chitinase 3-like protein 1(CHI3L1) participates in physiological and pathophysiological process, such as cell survival, cell proliferation, tissue remodeling, angiogenesis, etc. Some studies demonstrated that CHI3L1 is liver-enriched and has better application value in staging liver fibrosis than platelet ratio index(APRI) and fibrosis-4 index(FIB-4) and that CHI3L1 can be used in monitoring the prognosis of hepatocellular carcinoma (HCC). In this review, we summarized the pathophysiological role and the diagnostic value of CHI3L1 in liver fibrosis in different background and HCC.

Characterization of complex fluvio-deltaic deposits in Northeast China using multi-modal machine learning fusion.

Due to the lack of petroleum resources, stratigraphic reservoirs have become an important source of future discoveries. We describe a methodology for predicting reservoir sands from complex reservoir seismic data. Data analysis involves a bio-integrated framework called multi-modal machine learning fusion (MMMLF) based on neural networks. First, acoustic-related seismic attributes from post-stack seismic data were used to characterize the reservoirs. They enhanced the understanding of the structure and spatial distribution of petrophysical properties of lithostratigraphic reservoirs. The attributes were then classified as varied modal inputs into a central fusion engine for prediction. We applied the method to a dataset from Northeast China. Using seismic attributes and rock physics relationships as input data, MMMLF was performed to predict the spatial distribution of lithology in the Upper Guantao substrata. Despite the large scattering in the acoustic-related data properties, the proposed MMMLF methodology predicted the distribution of lithological properties through the gamma ray logs. Moreover, complex stratigraphic traps such as braided fluvial sandstones in the fluvio-deltaic deposits were delineated. These findings can have significant implications for future exploration and production in Northeast China and similar petroleum provinces around the world.

Clinical features of COVID-19 convalescent patients with re-positive nucleic acid detection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has rapidly spread worldwide. Increasingly, confirmed patients being discharged according to the current diagnosis and treatment protocols, follow-up of convalescent patients is important to knowing about the outcome. METHODS: A retrospective study was performed among 98 convalescent patients with COVID-19 in a single medical center. The clinical features of patients during their hospitalization and 2-week postdischarge quarantine were collected. RESULTS: Among the 98 COVID-19 convalescent patients, 17 (17.3%) were detected positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid during 2-week postdischarge quarantine. The median time from discharge to SARS-CoV-2 nucleic acid re-positive was 4 days (IQR, 3-8.5).The median time from symptoms onset to final respiratory SARS-CoV-2 detection of negative result was significantly longer in re-positive group (34 days [IQR, 29.5-42.5]) than in non-re-positive group (19 days [IQR, 16-26]). On the other hand, the levels of CD3-CD56 + NK cells during hospitalization and 2-week postdischarge were higher in re-positive group than in non-re-positive group (repeated measures ANOVA, P = .018). However, only one case in re-positive group showed exudative lesion recurrence in pulmonary computed tomography (CT) with recurred symptoms. CONCLUSION: It is still possible for convalescent patients to show positive for SARS-CoV-2 nucleic acid detection, but most of the re-positive patients showed no deterioration in pulmonary CT findings. Continuous quarantine and close follow-up for convalescent patients are necessary to prevent possible relapse and spread of the disease to some extent.

The clinical significance of serum chitinase 3-like 1 in hepatitis B-related chronic liver diseases.

AIM: In the present study, we purposed to determine serum chitinase 3-like 1 (CHI3L1) expression characteristics in chronic liver diseases monoinfected with hepatitis B virus and analyze its diagnostic value in liver fibrosis. METHODS: A total of 467 chronic hepatitis B (CHB) patients, 312 liver cirrhosis (LC) patients, and 104 hepatocellular carcinoma (HCC) patients at our institution were enrolled, and clinical indicators were analyzed. RESULTS: Our data have shown that the expression level of serum CHI3L1 was steadily increased from CHB to LC to HCC (P < .001). Serum CHI3L1 expression levels were positively associated with liver stiffness measurement (LSM), fibrosis-4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and HCC stage. The receiver operating characteristic (ROC) curve proved that serum CHI3L1 was superior to other noninvasive methods (LSM, FIB-4, and APRI) with an area under the ROC curve (AUC) of 0.97 in diagnosing significant fibrosis. CONCLUSIONS: Serum CHI3L1 harbors significant clinical value in chronic liver diseases infected with hepatitis B virus, especially in the diagnosis of fibrosis.

On the nonlinear temperature dependence of elastic constants and wave velocities for solid media with applications to geologic materials.

Temperature-induced variations of elastic moduli in solid media are generally characterized by a strong nonlinear dependence on temperature associated with complex deformations under thermal treatments. Conventional thermoelasticity with third-order elastic constants for the one-order temperature dependence has been extensively studied for crystals, but encountering problems of divergent and limited velocity variations for rocks as a polycrystal mixture, especially at high temperatures. The extension of the theory beyond high-order elastic constants to solid media is addressed in this article to describe the nonlinear temperature dependence of both elastic constants and wave velocities. The total strain is divided into the background component associated with temperature variations and the infinitesimal component induced by propagating waves. A third-order temperature dependence of velocity variations is formulated by taking into account fourth-order elastic constants. Applications to solid rocks (sandstone, granite, and olivine) demonstrate an accurate description of temperature-induced variations, especially for high temperatures. Unlike crystals, the synthetic averaging elastic constants for a solid rock (as a polycrystal mixture) change less than 10% with temperatures. The thermal sensitivity of P-wave velocities is much more than that of S-wave velocities over the vast majority of temperatures examined.

Hsa_circ_0028502 and hsa_circ_0076251 are potential novel biomarkers for hepatocellular carcinoma.

Circular RNAs (circRNAs) have been increasingly revealed to be desirable biomarkers for some tumors, including hepatocellular carcinoma (HCC). Combined with our previous microarray screening results, we aimed to determine the hsa_circ_0028502 and hsa_circ_0076251 expression features in HCC, analyze the relationship between their expression level and clinical and pathological characteristics, and investigate their diagnostic and prognostic values. Our data demonstrated that the hsa_circ_0028502 and hsa_circ_0076251 levels were considerably lower in HCC tissues than in adjacent paracancerous tissues (P < .001). Further study revealed that hsa_circ_0028502 expression levels were related to tumor node metastasis (TNM) stage (P = .015) and that hsa_circ_0076251 expression levels were related to Barcelona Clinic Liver Cancer (BCLC) stage (P = .038), comorbidity with type 2 diabetes mellitus (P = .023) and the presence of serum HbsAg (P = .044). Furthermore, the degree of expression of both hsa_circ_0028502 and hsa_circ_0076251 increased from HCC to liver cirrhosis (LC) to chronic hepatitis (CH). The receiver operating characteristic (ROC) curve demonstrated that hsa_circ_0028502 and hsa_circ_0076251 could serve as fairly accurate markers to distinguish HCC tissues from CH tissues and LC tissues, as well as distinguishing LC tissues from CH tissues. Cox regression analysis showed that low expression of has_circ_0076251 was associated with unfavorable survival rates in HCC (HR = 0.46; 95% CI = 0.22-0.98; P < .05). These findings implied that hsa_circ_0028502 and hsa_circ_0076251 were potentially valuable biomarkers for HCC diagnosis, whereas hsa_circ_0076251 could be used as a prognostic indicator for HCC.

Differential expression of circular RNAs in hepatic tissue in a model of liver fibrosis and functional analysis of their target genes.

AIM: To measure the expression profile of circular RNA (circRNA) in hepatic tissues in a liver fibrosis model and to explore their function using molecular biology and bioinformatic techniques. METHODS: The classic CCl4 mouse liver fibrosis model was established alongside a normal control group. The circRNA expression profile of hepatic tissue from the two groups was compared using a high-throughput circRNA microarray. The differentially expressed circRNAs were identified, and real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify a subset of the differentially expressed circRNAs (target genes). At the same time, the mouse oxidative stress injury, macrophage inflammation, and hepatic stellate cell activation models were established, and the expression of target circRNA in the above cells was measured by RT-qPCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to predict the biological functions of target genes. Finally, one of the circRNAs was selected and its cellular function was verified using siRNA. RESULTS: A total of 10 389 circRNAs were analyzed by microarray. Compared with the normal group, there were 69 circRNAs that were differentially expressed in the liver fibrosis model group (>2-fold differential expression, P < 0.05), of which 14 were upregulated and 55 were downregulated. Five circRNAs and their differential expression were verified by RT-qPCR, and the findings were consistent with the microarray results. Of these, three circRNAs were differentially expressed (P < 0.05) in the JS1 model, one circRNA was differentially expressed (P < 0.05) in the AML12 model, and four circRNAs were differentially expressed (P < 0.05) in the RAW264.7 model. The GO analysis showed that the differentially expressed circRNAs might be involved in cell autophagy, composition of extracellular matrix components, synthesis and metabolism of retinoic acid, retinol dehydrogenase activity, ubiquitin-like protein ligase activity, histone methylation, and other biological functions. The KEGG analysis showed that the target genes of the differentially expressed circRNAs might be involved in transforming growth factor-ß1/smads, Hippo, Rap1, vascular endothelial growth factor, and other signaling pathways. Lipofection experiments showed that the expression of α-smooth muscle actin (α-SMA) in JS1 cells increased significantly after the expression of mmu_circ_34116 was decreased. CONCLUSION: The circRNA expression profile in liver fibrosis tissue shows significant changes. Partially differentially expressed circRNA could be involved in hepatic fibrosis related to hepatic oxidative stress injury, macrophage inflammation, and stellate cell activation. For instance, mmu_circ_34116 can significantly inhibit the activation of hepatic stellate cells.