Numerical Simulation of Fracture Propagation during Temporary Plugging Staged Fracturing in Tight-Oil Horizontal Wells.

Fracture propagation with temporary plugging hydraulic fracturing in tight-oil reservoirs is simulated in this study. The research considers dynamic fluid redistribution, with stress differences among multiple fractures. The fracture morphology during temporary plugging staged fracturing (TPSF) is investigated by using a user-defined perforation element combined with a pore-pressure finite-element model. The precision of the integrated model is verified by using the standard finite-element approach. Then, case studies are presented to investigate the influence of cluster spacing, horizontal stress difference coefficients (SDC), injection rates, and barrier tensile strengths. The simulation results show that central cluster fractures are hampered by side-cluster fractures, while TPSF can alleviate the effect and lead to a more uniform propagation of all fractures. Stress interference weakens as cluster spacing increases, and propagation patterns are minimally influenced once spacing reaches 40 m. Higher injection rates can improve the injection pressure, enlarging fracture width, and potentially increasing the risk of fracture penetration. Barrier tensile strength and horizontal SDC can modify fracture geometries and determine the penetration behavior of multiple fractures.

Identification and validation of plasma AGRN as a novel diagnostic biomarker of hepatitis B Virus-related chronic hepatitis and liver fibrosis/cirrhosis.

OBJECTIVE: The aim of this study was to find novel biomarkers and develop a non-invasive, effective diagnostic model for hepatitis B Virus-related chronic hepatitis and liver fibrosis/cirrhosis. METHOD: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to assess the expression of differentially expressed genes (AGRN, JAG1, CCL5, ID3, CCND1, and CAPN2) in peripheral blood mononuclear cells (PBMCs) from healthy subjects, chronic hepatitis B (CHB), and liver fibrosis/cirrhosis (LF/LC) patients. The molecular mechanisms underlying AGRN-regulated CHB were further explored and verified in LX2 cells, in which small interfering RNA (siRNA) was used to block AGRN gene expression. Finally, enzyme-linked Immunosorbent Assay (ELISA) was used to measure AGRN protein expression in 100 healthy volunteers, 100 CHB patients, and 100 LF/LC patients, and the efficacy of the diagnostic model was assessed by the Area Under the Curve (AUC). RESULTS: AGRN mRNA displayed a steady rise in the PBMCs of normal, CHB, and LF/LC patients. Besides, AGRN expression was markedly elevated in activated LX2 cells, whereas the expression of COL1 and α-SMA decreased when AGRN was inhibited using siRNA. In addition, downregulation of AGRN can reduce the gene expression of ß-catenin and c-MYC while upregulating the expression of GSK-3ß. Furthermore, PLT and AGRN were used to develop a non-invasive diagnostic model (PA). To identify CHB patients from healthy subjects, the AUC of the PA model was 0.951, with a sensitivity of 87.0% and a specificity of 91.0%. The AUC of the PA model was 0.922 with a sensitivity of 82.0% and a specificity of 90.0% when differentiating between LF/LC and CHB patients. CONCLUSION: The current study indicated that AGRN could be a potential plasma biomarker and the established PA model could improve the diagnostic accuracy for HBV-related liver diseases.

Monocyte-to-High-Density Lipoprotein-Cholesterol Ratio Predicts Prognosis of Hepatocellular Carcinoma in Patients with Metabolic-Associated Fatty Liver Disease.

Purpose: The incidence of non-B and non-C hepatocellular carcinoma (NBNC-HCC) is increasing globally. Metabolically associated fatty liver disease (MAFLD) has been a contributing factor to this rising trend in NBNC-HCC incidence. The monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) is a new prognostic marker that connects systemic inflammation with disorders of lipid metabolism. Therefore, MHR may be a potential prognostic predictor of patients with MAFLD-related HCC (MAFLD-HCC). This study aims to investigate the relationship between the MHR and prognosis of patients with MAFLD-HCC and construct a novel prognostic prediction tool for MAFLD-HCC. Patients and Methods: This retrospective study of patients with MAFLD-HCC included training (n = 112) and internal validation (n = 37) cohorts. Univariate and multivariate Cox proportional hazard regression analysis was conducted to identify independent risk factors of survival. A visual nomogram was constructed to assess the performance of the two groups. Furthermore, receiver operating characteristic (ROC) curves and calibration curves were used to verify the prognostic discriminative ability of this nomogram, even in the MHR, ALBI grade, and MHR-ALBI model. Results: Univariate and multivariate analyses revealed that extrahepatic metastases, Vascular invasion, Barcelona staging B, C, D, elevated ALBI Grade 3, C-reactive protein (CRP), and MHR were independent risk factors for the prognosis of MAFLD-HCC. Moreover, calibration plots showed good discrimination and consistency when the significant factors were entered into the nomogram. Meanwhile, the MHR strongly correlated with the prognosis of cancer under a background of MAFLD-HCC, with a sensitivity of 88.89% and a specificity of 79.61%. Importantly, the performance of the MHR alone (AUC = 86.2) was not only superior to the ALBI grade (AUC = 63.8) but was comparable to the combination of MHR and ALBI (AUC = 88.5). Conclusion: The novel nomogram demonstrated good value in predicting the overall survival of patients with MAFLD-HCC. The MHR may be a potential predictor of prognosis.

Consensus on the tertiary prevention of primary liver cancer.

To effectively prevent recurrence, improve the prognosis and increase the survival rate of primary liver cancer (PLC) patients with radical cure, the Chinese Society of Hepatology, Chinese Medical Association, invited clinical experts and methodologists to develop the Consensus on the Tertiary Prevention of Primary Liver Cancer, which was based on the clinical and scientific advances on the risk factors, histopathology, imaging finding, clinical manifestation, and prevention of recurrence of PLC. The purpose is to provide a current basis for the prevention, surveillance, early detection and diagnosis, and the effective measures of PLC recurrence.

LINC00886 Facilitates Hepatocellular Carcinoma Tumorigenesis by Sequestering microRNA-409-3p and microRNA-214-5p.

Purpose: As the major subtype of liver cancer, hepatocellular carcinoma (HCC) suffers from high mortality and is prone to recurrence. Long non-coding RNAs (lncRNAs) are well characterized to be pivotal players contributing to HCC pathogenesis and progression. Therefore, this study intended to probe the biological functions of LINC00886 in hepatocarcinogenesis. Patients and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to analysis of LINC00886, microRNA-409-3p (miR-409-3p), microRNA-214-5p (miR-214-5p), RAB10 and E2F2 expression. Subcellular localization of LINC00886 was identified through a fluorescent in situ hybridization (FISH) kit and a subcellular assay. Additionally, proliferated cells were determined with EdU as well as cell counting kit-8 (CCK-8) assays. Scratch and Transwell assays were applied to detect migratory and invasive cells. Apoptotic cells were measured via TUNEL staining assay. Furthermore, targeted binding between LINC00886 and miR-409-3p or miR-214-5p was validated utilizing dual-luciferase reporter assays. RAB10, E2F2 and NF-κB signaling-associated protein levels were evaluated utilizing Western blot. Results: LINC00886, RAB10 and E2F2 levels were aberrantly increased, with the abnormal expressed decline of miR-409-3p and miR-214-5p, in HCC tissues, cells and peripheral blood mononuclear cells (PBMCs). Silencing LINC00886 attenuated the proliferative, migratory, invasive, and anti-apoptotic potential of HCC cells, while LINC00886 overexpression proceeded in the contrary direction. Mechanistically, miR-409-3p and miR-214-5p were validated as binding targets for LINC00886 and inverted the biological functions of LINC00886 during HCC progression. Furthermore, the LINC00886-miR-409-3p/miR-214-5p axis could regulate RAB10 and E2F2 expression via mediating NF-κB pathway activation in hepatocarcinogenesis. Conclusion: Our findings indicated that LINC00886 facilitated HCC progression via absorbing miR-409-3p or miR-214-5p to upregulate RAB10 and E2F2 through activation of NF-κB pathway, offering a promising novel target for HCC therapy.

Pt2CeO2 Heterojunction Supported on Multiwalled Carbon Nanotubes for Robust Electrocatalytic Oxidation of Methanol.

Herein, we prepared Pt2CeO2 heterojunction nanocluster (HJNS) on multiwalled carbon nanotubes (MWCNTs) in deep eutectic solvents (DESs) which is a special class of ionic liquids. The catalyst was then heat-treated at 400 °C in N2 (refer to Pt2CeO2/CNTs-400). The Pt2CeO2/CNTs-400 catalyst showed remarkably improved electrocatalytic performance towards methanol oxidation reaction (MOR) (839.1 mA mgPt-1) compared to Pt2CeO2/CNTs-500 (620.3 mA mgPt-1), Pt2CeO2/CNTs-300 (459.2 mA mgPt-1), Pt2CeO2/CNTs (641.6 mAmg-1) (the catalyst which has not been heat-treated) and commercial Pt/C (229.9 mAmg-1). Additionally, the Pt2CeO2/CNTs-400 catalyst also showed better CO poisoning resistance (onset potential: 0.47 V) compared to Pt2CeO2/CNTs (0.56 V) and commercial Pt/C (0.58 V). The improved performance of Pt2CeO2/CNTs-400 catalyst is attributed to the addition of appropriate CeO2, which changed the electronic state around the Pt atoms, lowered the d-band of Pt atoms, formed more Ce-O-Pt bonds acting as new active sites, affected the adsorption of toxic intermediates and weakened the dissolution of Pt; on the other hand, with the assistance of thermal treatment at 400 °C, the obtained Pt2CeO2 HJNS expose more new active sites at the interface between Pt and CeO2 to enhance the electrochemical active surface area (ECSA) and the dehydrogenation process of MOR. Thirdly, DES is beneficial to the increase of the effective component Pt(0) in the carbonization process. The study shows a new way to construct high-performance Pt-CeO2 catalyst for the direct methanol fuel cell (DMFC).

A "Special" Solvent to Prepare Alloyed Pd2Ni1 Nanoclusters on a MWCNT Catalyst for Enhanced Electrocatalytic Oxidation of Formic Acid.

Herein, an electrocatalyst with Pd2Ni1 nanoclusters, supporting multiwalled carbon nanotubes (MWCNTs) (referred to Pd2Ni1/CNTs), was fabricated with deep eutectic solvents (DES), which simultaneously served as reducing agent, dispersant, and solvent. The mass activity of the catalyst for formic acid oxidation reaction (FAOR) was increased nearly four times compared to a Pd/C catalyst. The excellent catalytic activity of Pd2Ni1/CNTs was ascribed to the special nanocluster structure and appropriate Ni doping, which changed the electron configuration of Pd to reduce the d-band and to produce a Pd-Ni bond as a new active sites. These newly added Ni sites obtained more OH- to release more effective active sites by interacting with the intermediate produced in the first step of FAOR. Hence, this study provides a new method for preparing a Pd-Ni catalyst with high catalytic performance.

Heme oxygenase-1 prevents non-alcoholic steatohepatitis through modulating mitochondrial quality control.

AIM: Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD) and lacks effective treatment options. Heme oxygenase-1 (HO-1) is a critical defense against oxidative stress and inflammation in the liver injury. This study aims to investigate the protective role and underlying mechanisms of HO-1 in NASH pathogenesis. METHODS: The hepatocyte-specific HO-1 knockout (HO-1HEPKO ) mice on a C57BL/6J background (HO-1fl/fl /Alb-Cre) were generated and fed a high-fat/western-style diet (HFD) or methionine-choline-deficient diet (MCD). Changes in mitochondrial ultrastructure were observed by transmission electron microscopy and confocal microscopy. A mitochondrial PCR array was used to identify the crucial genes associated with mitochondrial dysfunction. RESULTS: Hepatocyte-specific HO-1HEPKO mice developed steatohepatitis with severe steatosis, ballooning, and necroinflammation. Dysregulated hepatic expression of mitochondria-related proteins, including DRP1, Tomm20, MFN1 and MFN2 were detected in NASH animals. Ultrastructural mitochondrial damage was observed in HO-1HEPKO mice. Mitochondrial dysfunction was recapitulated in HO-1-knockdown cells in vitro, as evidenced by decreased membrane potential, reduced ATP content, and mtDNA damage. Conversely, HO-1 overexpression restored these changes in vitro. Mechanistically, HO-1 deficiency reduced the inhibitory effect on Tomm20, leading to mitochondrial dysfunction, and thereby causing steatohepatitis. CONCLUSIONS: HO-1 attenuates diet-induced steatohepatitis by preventing mitochondrial dysfunction, indicating that HO-1 may constitute a potential therapeutic target for NASH.

Hypothalamic warm-sensitive neurons require TRPC4 channel for detecting internal warmth and regulating body temperature in mice.

Precise monitoring of internal temperature is vital for thermal homeostasis in mammals. For decades, warm-sensitive neurons (WSNs) within the preoptic area (POA) were thought to sense internal warmth, using this information as feedback to regulate body temperature (Tcore). However, the cellular and molecular mechanisms by which WSNs measure temperature remain largely undefined. Via a pilot genetic screen, we found that silencing the TRPC4 channel in mice substantially attenuated hypothermia induced by light-mediated heating of the POA. Loss-of-function studies of TRPC4 confirmed its role in warm sensing in GABAergic WSNs, causing additional defects in basal temperature setting, warm defense, and fever responses. Furthermore, TRPC4 antagonists and agonists bidirectionally regulated Tcore. Thus, our data indicate that TRPC4 is essential for sensing internal warmth and that TRPC4-expressing GABAergic WSNs function as a novel cellular sensor for preventing Tcore from exceeding set-point temperatures. TRPC4 may represent a potential therapeutic target for managing Tcore.

Pd3Co1 Alloy Nanocluster on the MWCNT Catalyst for Efficient Formic Acid Electro-Oxidation.

In this study, the Pd3Co1 alloy nanocluster from a multiwalled carbon nanotube (MWCTN) catalyst was fabricated in deep eutectic solvents (DESs) (referred to Pd3Co1/CNTs). The catalyst shows a better mass activity towards the formic acid oxidation reaction (FAOR) (2410.1 mA mgPd-1), a better anti-CO toxicity (0.36 V) than Pd/CNTs and commercial Pd/C. The improved performance of Pd3Co1/CNTs is attributed to appropriate Co doping, which changed the electronic state around the Pd atom, lowered the d-band of Pd, formed a new Pd-Co bond act at the active sites, affected the adsorption of the toxic intermediates and weakened the dissolution of Pd; moreover, with the assistance of DES, the obtained ultrafine Pd3Co1 nanoalloy exposes more active sites to enhance the dehydrogenation process of the FAOR. The study shows a new way to construct a high-performance Pd-alloy catalyst for the direct formic acid fuel cell.

A moderate static magnetic field promotes C. elegans longevity through cytochrome P450s.

Ageing is co-regulated by genetic and environmental factors. Life on earth lives and evolves in a mild geomagnetic field. Yet, the biological effects of a moderate magnetic field on ageing and the underlying genetic mechanisms remain barely unknown. Here, we report that a moderate static magnetic field (SMF) extends the lifespan of Caenorhabditis elegans, a well-established model organism in ageing research. Consistently, the SMF-treated worms show improved motility and mitochondrial function when aged. We identified from the transcriptomic changes upon SMF treatment that the upregulation of three cytochrome P450 genes are required for SMF-induced longevity. Our findings thus reveal that proper SMF treatment could promote longevity through the well-conserved cytochrome P450 enzymes.

Identification and Validation of Novel Biomarkers for Hepatocellular Carcinoma, Liver Fibrosis/Cirrhosis and Chronic Hepatitis B via Transcriptome Sequencing Technology.

Purpose: The aim of this study was to identify and validate novel biomarkers for distinguishing among hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), liver fibrosis/liver cirrhosis (LF/LC) and chronic hepatitis B (CHB). Patients and Methods: Transcriptomic sequencing was conducted on the liver tissues of 5 patients with HCC, 5 patients with LF/LC, 5 patients with CHB, and 4 healthy controls. The expression levels of selected mRNAs and proteins were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining, and were verified in validation set (n=200) and testing set (n=400) via enzyme-linked immunosorbent assay (ELISA). Results: A total of 9 hub mRNAs were identified by short time-series expression miner and weighted gene co-expression network analysis. Of note, the results of qRT-PCR and IHC staining demonstrated that SHC adaptor protein 1 (SHC1), SLAM family member 8 (SLAMF8), and interleukin-32 (IL-32) exhibited gradually increasing trends in the four groups. Subsequent ELISA tests on the validation cohort indicated that the plasma levels of SHC1, SLAMF8 and IL-32 also gradually increased. Furthermore, a diagnostic model APFSSI (age, PLT, ferritin, SHC1, SLAMF8 and IL-32) was established to distinguish among CHB, LF/LC and HCC. The performance of APFSSI model for discriminating CHB from healthy subjects (AUC=0.966) was much greater compared to SHC1 (AUC=0.900), SLAMF8 (AUC=0.744) and IL-32 (AUC=0.821). When distinguishing LF/LC from CHB, APFSSI was the most outstanding diagnostic parameter (AUC=0.924), which was superior to SHC1, SLAMF8 and IL-32 (AUC=0.812, 0.684 and 0.741, respectively). Likewise, APFSSI model with the greatest AUC value displayed an excellent performance for differentiating between HCC and LF/LC than other variables (SHC1, SLAMF8 and IL-32) via ROC analysis. Finally, the results in the test set were consistent with those in the validation set. Conclusion: SHC1, SLAMF8 and IL-32 can differentiate among patients with HCC, LF/LC, CHB and healthy controls. More importantly, the APFSSI model greatly improves the diagnostic accuracy of HBV-associated liver diseases.

Identification of potential plasma markers for hepatitis B virus-related chronic hepatitis and liver fibrosis/cirrhosis.

The aim of this study was to identify potential plasma biomarkers for hepatitis B virus (HBV)-related liver diseases. High-throughput transcriptome sequencing analysis was performed on five patients with chronic hepatitis B (CHB), five patients with HBV-associated liver fibrosis/liver cirrhosis (LF/LC), and four healthy participants. By short time-series expression miner and functional analysis, aquaporin 1 (AQP1), dystroglycan 1 (DAG1), and hemoglobin subunit beta (HBB) were identified as potential biomarkers. Immunohistochemical analysis revealed that the expression levels of AQP1, DAG1, and HBB were upregulated in the three groups. Subsequent enzyme-linked immunosorbent assay tests on the training cohort (n = 150) indicated that the plasma levels of AQP1 and DAG1 were highest in LF/LC patients, followed by those in CHB patients, and the lowest in healthy controls. APAD model, a diagnostic panel incorporating age, platelet, AQP1, and DAG1 levels, exhibited the strongest stratification ability to distinguish LF/LC patients from CHB patients, and to differentiate CHB patients from healthy controls. Furthermore, the diagnostic accuracies of the biomarkers and APAD model were verified in an independent cohort consisting of 230 participants. In conclusion, both AQP1 and DAG1 have good diagnostic values and APAD model greatly enhances the diagnostic accuracy for HBV-related hepatic diseases.

Finite element contact stress analysis of the temporomandibular joints of patients with temporomandibular disorders under mastication.

BACKGROUND AND OBJECTIVES: Temporomandibular disorders (TMD) represent a group of diseases occurred in the temporomandibular joint (TMJ) and its surrounding tissues. In epidemiological studies, up to 75% of adults have shown at least one sign of temporomandibular disorders during their examinations. The incongruous biomechanical environment in the TMJ is the main pathogenic factor of TMD. This study attempts to determine the mechanical differences in different groups of TMD patients through biomechanics and to explain the mechanical pathogenesis of TMD according to various cases. METHODS: Eleven control subjects and eleven TMD patients were selected and divided into three groups: the control group, bilateral TMD group, and unilateral TMD group. The contact stresses of the articular discs, condyles and temporal bones were analyzed using finite element method and statistical analysis of variance. RESULTS: The results indicated that the contact stresses in the joints with TMD were significantly greater in the Bi-Group (Bilateral TMD patients) compared to the Control-Group. The TMD side always exhibited greater stresses in the Uni-Group [Unilateral TMD patients) under various conditions (clenching on the TMD side or asymptomatic side). The greatest stress of all the groups occurred at the contralateral side with TMD when clenching on the asymptomatic side. CONCLUSIONS: Excessive protection would lead to greater stress on the affected side and increased TMD risk on the asymptomatic side. Clinically, the abnormal stress distributions of the disc represented poor buffering and articular clicking. The asymmetric distributions of the articular fossa manifested the deviation of mouth opening or inconsistent TMJ loading.

Three-dimensional morphological and biomechanical analysis of temporomandibular joint in mandibular and bi-maxillary osteotomies.

Orthognathic surgery is a typical approach for treating maxillofacial deformities. However, orthognathic surgery results in positional changes in the condyles. In a previous review, the effects of orthognathic surgery on temporomandibular joints (TMJs) are not provided. Hence, in this study, we investigate the morphological changes in TMJs after mandibular and bi-maxillary osteotomies. The relationship between the morphological parameters of TMJs and symptoms of temporomandibular disorders (TMDs) is discussed. Finite element contact stress analysis is performed, and the results show that the two abovementioned surgeries can improve maxillofacial deformities, although the positions of the condyles are changed. Moreover, preoperative stress asymmetry of the left and right TMJs is observed, which remain after the surgeries. TMD patient-specific analysis shows that three joint spaces (medial joint space, lateral joint space, superior joint space) are significantly correlated with TMD symptoms.

Diagnostic performance of CT-derived resting distal to aortic pressure ratio (resting Pd/Pa) vs. CT-derived fractional flow reserve (CT-FFR) in coronary lesion severity assessment.

BACKGROUND: Computed tomography-derived fractional flow reserve (CT-FFR) has emerged as a promising non-invasive substitute for fractional flow reserve (FFR) measurement. Normally, CT-FFR providing functional significance of coronary artery disease (CAD) by using a simplified total coronary resistance index (TCRI) model. Yet the error or discrepancy caused by this simplified model remains unclear. METHODS: A total of 20 consecutive patients with suspected CAD who underwent CTA and invasive FFR measurement were retrospectively analyzed. CT-FFR and CT-(Pd/Pa)rest values derived from the coronary CTA images. The diagnostic performance of CT-FFR and CT-(Pd/Pa)rest were evaluated on a per-vessel level using C statistics with invasive FFR<0.80 as the reference standard. RESULTS: Of the 25 vessels eventually analyzed, the prevalence of functionally significant CAD were 64%. The Youden index of the ROC curve indicated that the best cutoff value of invasive resting Pd/Pa was 0.945 for identifying functionally significant lesions. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy were 85%, 91%, 92%, 83% and 88% for CT-(Pd/Pa)rest and 85%, 58% 69%, 78% and 72% for CT-FFR. Area under the receiver-operating characteristic curve (AUC) to detect functionally significant stenoses of CT-(Pd/Pa)rest and CT-FFR were 0.87 and 0.90. CONCLUSIONS: In this study, the results suggest CT-derived resting Pd/Pa has a potential advantage over CT-FFR in triaging patients for revascularization.

Traditional Chinese medicine Yiqi Huoxue recipe attenuates hepatic fibrosis via YAP/TAZ signaling.

BACKGROUND/AIMS: The Yiqi Huoxue (YQHX) recipe has been shown to attenuate liver fibrosis, but precise mechanisms have not yet been elucidated. Recently, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling has been implicated in liver fibrogenesis. This study investigated whether the YAP/TAZ signaling is involved in the therapeutic effect of YQHX on hepatic fibrosis. MATERIALS AND METHODS: Wistar rats were used to generate a model of carbon tetrachloride (CCl4)-induced liver fibrosis. Chronic hepatitis B (CHB) patients with liver fibrosis were enrolled and assigned to receive either nucleoside/nucleotide analogues (NAs) or NAs plus YQHX. Histology, immunohistochemistry, qRT-PCR, and western blotting were conducted to mechanistically assess the therapeutic effects of YQHX on liver fibrosis. RESULTS: YQHX markedly alleviated morphological alterations in CCl4-induced liver fibrosis and decreased markers of hepatic fibrosis in rats. Furthermore, YQHX significantly suppressed CCl4-meidated activation of the transforming growth factor-beta (TGF-ß)/Smad signaling pathway. Notably, CCl4 induced up-regulation of YAP, TAZ, and connective tissue growth factor (CTGF), which were significantly abrogated by YQHX. Consistent with the above major findings in rats, CHB patients treated with NAs plus YQHX had greater improvement in liver fibrosis than those given NAs alone (71.4% vs. 28.6%; P = 0.057). In addition, hepatic and plasma levels of YAP were significantly decreased after YQHX treatment in CHB patients with liver fibrosis. CONCLUSION: YAP/TAZ signaling plays a role, at least in part, in the anti-fibrotic activity of YQHX. The findings may help to better understand the mechanisms of YQHX in the treatment of liver fibrosis.

Effect of Geometric Accuracy at the Proximal Landing Zone on Simulation Results for Thoracic Endovascular Repair Patients.

PURPOSE: Existing hemodynamic studies on aortic dissection after thoracic endovascular aortic repair (TEVAR) apply geometric simplifications. This study aims to evaluate the necessity of more accurate geometries at the proximal landing zone in computational fluid dynamic (CFD) studies. METHODS: Three patient-specific 3D aortic dissection models with different geometric accuracies at the proximal landing zone were manually fabricated for CFD simulations: (i) model 1 without the stent graft (SG), (ii) model 2 with the metal stent, and (iii) model 3 with the SG. The flow distribution, flow pattern, and wall shear stress (WSS)-related indicators in these three models were compared. RESULTS: The flow distributions were quite similar for the three models, with a maximum absolute difference of 0.27% at the left suclavian artery (LSA) between models 1 and 3 because of partial coverage. A more chaotic flow pattern was observed at the proximal landing zone in model 3, with significant regional differences in the WSS-related indicator distributions. The upstream and downstream WSS-related indicator distributions were quite similar for the three models. CONCLUSIONS: The flow pattern and hemodynamic parameter distributions were affected by the geometric accuracy only in a small region near the proximal landing zone. The flow split was hardly affected by the LSA partial coverage, indicating that the coverage may have slight effects on short-term blood perfusion. However, this conclusion needs to be verified in future studies with larger sample sizes.

Heme oxygenase-1 alleviated non-alcoholic fatty liver disease via suppressing ROS-dependent endoplasmic reticulum stress.

AIMS: The endoplasmic reticulum (ER) stress response plays a crucial role in the development of nonalcoholic steatohepatitis (NASH). Heme oxygenase-1 (HO-1) exerts beneficial effects against oxidative injury in NASH. This study is aimed to clarify whether HO-1 is an effective therapeutic strategy for NASH via regulation of ER stress. METHODS: The C57BL/6J mice were fed with methionine-choline deficient (MCD) for 4 weeks and high fat-high carbohydrate-high cholesterol (HFD) diet for 16 weeks, with hemin or zinc protoporphyrin IX (ZnPP-IX), respectively. The LO-2 cells were cultured in palmitic medium, with transfected pEX-HO-1 or sh-HO-1 plasmid for 24 h. Meanwhile, thirty NASH patients and 15 health controls were enrolled. The ER ultrastructure was observed by transmission electron microscopy (TEM) and confocal microscopy. The expressions of mRNAs and proteins of HO-1, ER stress related genes were detected by real time PCR, western blot and immunohistochemical staining, respectively. RESULTS: The swelled and broken rough endoplasmic reticulums were observed in MCD and HFD fed mice. The reactive hepatic expression of HO-1 was related with the increased ROS production and ER stress, companied with upregulation of GRP78, p-IRE1, PERK, ATF6. Through hemin administration, hepatocyte apoptosis was suppressed companied down-regulation of CHOP, caspase12 and up-regulation of BCL2. Conserved results were exhibited in ZnPP-IX administrated mice and HO-1 silent cells. Consistent results were observed in the NASH Patients. CONCLUSIONS: HO-1 could serve as a protective factor in the progression of nutritional steatohepatitis by suppresses hepatocyte excessive ER stress and might be a potential target for therapy of nonalcoholic steatohepatitis.