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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.

Abstract The determination of rock mechanics properties and drillability are significant for the prediction of the rate of penetration (ROP) in drilling into complex formations. Previous studies indicate that these properties can be strongly correlated with formation conditions, e. g. temperature, and in-situ stress. However, these two parameters are hard to be considered simultaneously due to the limitation of the experimental apparatus. To address such an issue, rock samples are collected from the eastern Sichuan Basin, mainly including the sandstone located in the formations of Shaximiao Bottom, Ziliujing. and Xujiahe. A series of tests are conducted to investigate the evolution of rock mechanical properties subjected to the joint action of temperature and in-situ stress based on a self-developed experimental setup. The results indicate that the rock strength under in-situ conditions is 2~3 times higher than that determined under atmospheric conditions. The plasticity and volumetric strain of rocks increases as well, which is accompanied by the transition of rock failure modes from volumetric failure to abrasive rock-breaking. Meanwhile, the variation of drillability under different formation conditions shows that rock failure characteristics change significantly. The average ROP of rocks in the Shaximiao Bottom Formation, Ziliujing Formation, and Xujiahe Formation under in-situ conditions decrease by 45.12%, 61.19%, and 43.82% respectively, leading to an increase in the drillability of rocks. Compared with in-situ stress, the increase in temperature has few effects on rock strength and drillability. This study provides an in-depth understanding of the evolution of rock properties under different formation conditions, which is of great significance for optimizing drilling parameters and improving drilling efficiency in hard-to-drill formations.

In this study, the Pd

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.The hepatocyte-specific HO-1 knockout (HO-1Hepatocyte-specific HO-1HO-1 attenuates diet-induced steatohepatitis by preventing mitochondrial dysfunction, indicating that HO-1 may constitute a potential therapeutic target for NASH.

Dandan Zhao,1,2 Xiaoxiao Zhang,1,2 Yuhui Tang,1,2 Peilin Guo,1,2 Rong Ai,1,2 Mengmeng Hou,1,2 Yiqi Wang,1,2 Xiwei Yuan,1,2 Luyao Cui,1,2 Yuguo Zhang,1,2 Suxian Zhao,1,2 Wencong Li,1,2 Yang Wang,1,2 Xiaoye Sun,1,2 Lingdi Liu,1,2 Shiming Dong,1,2 Lu Li,1,2 Wen Zhao,1,2 Yuemin Nan1,2 1Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Hebei Provincial Key Laboratory of Liver Fibrosis in Chronic Liver Diseases, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Yuemin Nan, Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel +86 311-66781227, Fax +86 311-66781289, Email nanyuemin@163.comPurpose: 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.Keywords: HBV-associated liver diseases, transcriptome sequencing technology, SHC adaptor protein 1, SLAM family member 8, interleukin-32

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. 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. 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. 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.

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.

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 (T

BackgroundAt present, there are no accurate diagnostic biomarkers for distinguishing among hepatitis B virus (HBV)-related liver diseases. This research aimed to identify and validate a novel biomarker panel in patients with HBV-related hepatocellular carcinoma (HCC), liver fibrosis/liver cirrhosis (LF/LC) and chronic hepatitis B (CHB).MethodsTranscriptomics sequencing was conducted on a total of 19 liver tissues of the four groups. The hub mRNAs were identified using weighted gene co-expression network analysis (WGCNA) and short time-series expression miner (STEM) method. The expression levels of selected mRNAs and proteins were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) using both liver tissues and peripheral blood mononuclear cells (PBMCs) and immunohistochemical (IHC) staining in liver tissues, respectively. Then, the expression activities of the screened targets were detected by enzyme-linked immunosorbent assay (ELISA) using the plasma samples from 200 and 400 subjects in the validation and testing sets, respectively. Finally, receiver operating characteristic (ROC) curve analysis was carried out to evaluate the diagnostic performance of each mRNA biomarker.ResultsSTEM analysis revealed 25 mRNAs exhibited an increasing trend in the four groups; while 9 hub mRNAs were identified by using WGCNA. Of note, the results of qRT-PCR and immunohistochemical analyses demonstrated that SHC adaptor protein 1 (SHC1), SLAM family member 8 (SLAMF8), and interleukin-32 (IL-32) exhibited a gradually increasing trend in the four groups. Subsequent ELISA tests on the validation cohort demonstrated that the plasma levels of SHC1, SLAMF8 and IL-32 were remarkably elevated in HCC group compared to the remaining three groups. Furthermore, a diagnostic model APFSSI (age, PLT, ferritin, SHC1, SLAMF8 and IL-32) was established to distinguish HCC from LF/LC (AUC=0.904), LF/LC from CHB (AUC=0.924), and CHB from healthy controls (AUC=0.966). Finally, the results in the test set were consistent with those in the validation set. ConclusionsSHC1, SLAMF8 and IL-32 can differentiate among HCC patients, LF/LC patients, CHB patients and healthy controls. More importantly, the combination of age, PLT, ferritin, SHC1, SLAMF8, and IL-32 (APFSSI model) greater improves the diagnostic accuracy of HBV-associated liver diseases.

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.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.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-β)/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.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.

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

This paper concerns the effect of friction on crack propagation for the centrally cracked Brazilian disk under diametric forces by using a modified finite element method. It shows that the mode II stress intensity factor decreases obviously with the increase of friction after the crack is closed, while friction has no influence on the stress intensity factor of mode I and T-stress. Meanwhile, there are some significant influences on the crack propagation due to the change of the friction after the crack is closed with the appropriate loading angle and relative length of the crack. When T-stress is positive, the effect of friction becomes obvious and the crack propagation angle increases with a lager friction coefficient. With increasing the friction, the deviation for the crack propagation trajectory increases and the curvature of path decreases, which may lead to the change of crack type. Additionally, the larger relative crack length can amplify the effect of friction, which is similar to the loading angle.

The precision of current research on fault recognition of marine bearing remains to be improved. Therefore, a recognition method of crack-rubbing coupling fault of bearing under high water pressure based on polar symmetry mode decomposition is proposed in this article. The structure of marine bearing was analyzed, and the system was divided into several subsystems. Then, the nonlinearity relationship among the subsystems was confirmed. One subsystem was used to represent other subsystems, which was imported into the kinetic equation to obtain the equation after dimensionality reduction. According to the results of dimensionality reduction, the features of signal were measured from time domain, energy, and entropy. Meanwhile, the interior features of signal were extracted. Based on the feature extraction, the classifier of probabilistic neural network was introduced. The signal was recognized, and the recognition results were output via the training of signal sample data. Experimental results show that the method has better dimensionality reduction effect and high recognition precision. The method is practical.

Although multiple drugs are accessible for recovering liver function in patients, none are considered efficient. Liver transplantation is the mainstay therapy for end-stage liver fibrosis. However, the worldwide shortage of healthy liver donors, organ rejection, complex surgery, and high costs are prompting researchers to develop novel approaches to deal with the overwhelming liver fibrosis cases. Mesenchymal stem cell (MSC) therapy is an emerging alternative method for treating patients with liver fibrosis. However, many aspects of this therapy remain unclear, such as the efficiency compared to conventional treatment, the ideal MSC sources, and the most effective way to use it. Because bone marrow (BM) is the largest source for MSCs, this paper used a systematic review approach to study the therapeutic efficiency of MSCs against liver fibrosis and related factors. We systematically searched multiple published articles to identify studies involving liver fibrosis and BM-MSC-based therapy. Analyzing the selected studies showed that compared with conventional treatment BM-MSC therapy may be more efficient for liver fibrosis in some cases. In contrast, the cotreatment presented a more efficient way. Nevertheless, BM-MSCs are lacking as a therapy for liver fibrosis; thus, this paper also reviews factors that affect BM-MSC efficiency, such as the implementation routes and strategies employed to enhance the potential in alleviating liver fibrosis. Ultimately, our review summarizes the recent advances in the BM-MSC therapy for liver fibrosis. It is grounded in recent developments underlying the efficiency of BM-MSCs as therapy, focusing on the preclinical in vivo experiments, and comparing to other treatments or sources and the strategies used to enhance its potential while mentioning the research gaps.

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.

Most of the fractures in deep rock mass are in compression condition. The deep rock failure is complex and different modes of failure play important roles. In this study, the central cracked circular disk specimen was improved by deviating from the distance between the crack on the circular surface and the center of the circle, and a new mixed-mode II-III fracture specimen called the eccentric crack disk (ECD) specimen was proposed. The ECD specimen was a simple structure and easy to machining with low cost. In addition, it could be tested in conventional loading machines without extra fixtures. The finite element was used to calculate mode I, mode II and mode III stress intensity factors for different loading angles and crack deviation distances. The critical loading angles of mixed-mode II-III fracture under different crack deviation distances were obtained. And the mixed-mode II-III fracture experiments were carried out with sandstone. The experimental results clearly revealed that the crack initiation started from the middle of the crack. The experimental data also conformed to the effective stress intensity factor criterion of mixed-mode II-III mode fracture from the literature.