Neurophysiological Predictors of Self-Reported Difficulty in a Virtual-Reality Driving Scenario.

Our perception of subjective difficulty in complex tasks, such as driving, is a judgment that is likely a result of dynamic interactions between distributed brain regions. In this paper, we investigate how neurophysiological markers associated with arousal state are informative of this perceived difficulty throughout a driving task. We do this by classifying subjective difficulty reports of subjects using set of features that include neural, autonomic, and eye behavioral markers. We subsequently assess the importance of these features in the classification. We find that though multiple EEG linked to cognitive control and, motor performance linked to classification of subjective difficulty, only pupil diameter, a measure of pupil-linked arousal, is strongly linked to both measured self-reported difficulty and actual task performance. We interpret our findings in the context of arousal pathways influencing performance and discuss their relevance to future brain-computer interface systems.

Pupil-linked arousal correlates with neural activity prior to sensorimotor decisions.

Objective.Sensorimotor decisions require the brain to process external information and combine it with relevant knowledge prior to actions. In this study, we explore the neural predictors of motor actions in a novel, realistic driving task designed to study decisions while driving.Approach.Through a spatiospectral assessment of functional connectivity during the premotor period, we identified the organization of visual cortex regions of interest into a distinct scene processing network. Additionally, we identified a motor action selection network characterized by coherence between the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC).Main results.We show that steering behavior can be predicted from oscillatory power in the visual cortex, DLPFC, and ACC. Power during the premotor periods (specific to the theta and beta bands) correlates with pupil-linked arousal and saccade duration.Significance.We interpret our findings in the context of network-level correlations with saccade-related behavior and show that the DLPFC is a key node in arousal circuitry and in sensorimotor decisions.

[Efficacy Evaluation of Three Endoscopic Therapies of Isolated Gastric Varices with Modified Tissue Adhesive].

Objective: To evaluate the efficacy of three endoscopic therapies of isolated gastric varices (IGV) with modified tissue adhesive. Methods: A retrospective analysis was conducted with the clinical data of 73 IGV patients who were treated between January 2008 and December 2019 at Beijing Ditan Hospital. Patient clinical data on age, sex, etiology, biochemistry findings, Child-Pugh classification, the type of spontaneous shunt, preoperative bleeding history, and the presence or absence of liver cancer were collected. The three therapies evaluated were endoscopic intravenous injection of tissue glue combined with lauromacrogol, endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, and endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. Their respective clinical treatment outcomes, including ectopic embolism rate, survival rate, rebleeding rate, amount of lauromacrogol and tissue glue used, the number of endoscopic clips used, and the number of times of the procedure the patient underwent, were evaluated. Results: In the patient baseline data, Child-Pugh grade, preoperative thrombus formation, and the presence or absence of liver cancer, showed significant difference between the three therapies ( P<0.05). There was no significant difference in the rates of ectopic embolism among the three methods ( P>0.05), but no ectopic embolism occurred after endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, or after endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. There was no significant difference in the survival rate, the rebleeding rate, amount of lauromacrogol and tissue glue used for the three therapies, but there was significant difference in the number of endoscopic clips used and the number of times the procedure was conducted within one year ( P<0.05). Conclusion: The two endoscopic therapies of intravenous injection of modified tissue glue, one assisted by clip and the other assisted by clip and LOOP, can help reduce the number of procedures IGV patients undergo within one year.

Prognosis of endotherapy versus splenectomy and devascularization for variceal bleeding in patients with hepatitis B-related cirrhosis.

OBJECTIVE: This study aimed to compare the long-term outcome of endotherapy versus a combination of splenectomy and devascularization for variceal bleeding in patients with hepatitis B-related cirrhosis (HBRC). MATERIALS AND METHODS: A total of 1074 patients with HBRC and acute variceal bleeding (AVB) treated with endotherapy and 248 patients with HBRC treated with a combination of splenectomy and devascularization surgery were included in the analysis. After one-to-one propensity score matching, 151 paired patients were selected. The primary end-point was death. The secondary outcomes were 3-year survival, 5-year survival, and rebleeding. Complications were recorded. RESULTS: The median follow-up time was 1165 days in the endoscopic group and 1709 days in the surgical group. Before matching, the 1-year, 3-year, and 5-year survival rates were significantly lower in the endoscopic group than in the surgical group (91.1 vs 96.3%, P = 0.017; 79.6 vs 91.6%, P = 0.001; 65.2 vs 81.3%, P = 0.001). After matching, no significant differences were found between groups (94.5 vs 95.2%, P = 0.767; 87.0 vs 88.9%, P = 0.635; 77.9 vs 77.9%, P = 0.905). The rebleeding rate was lower in the surgical group than in the endoscopic group; the rebleeding-free survival rate was similar in the two groups. No patient died of complications. No statistically significant difference was observed in complications between groups. CONCLUSIONS: Both endotherapy and a combination of splenectomy and devascularization are good choices for patients with AVB. The rebleeding rate was lower after the surgical procedure, but the long-term prognosis was similar.

[Improvement of remote sensing ecological index in arid regions: Taking Ulan Buh Desert as an example]. / 干旱地区遥感生态指数的改进­­ä»¥ä¹Œå °å¸ƒå’Œæ²™æ¼ 为例.

The arid area is mainly composed of desert, with fragile eco-environment and being extremely vulnerable to the influence of natural and human perturbations. Based on the remote sen-sing ecological index (RSEI), the arid remote sensing ecological index (ARSEI) was formed to improve the remote sensing ecological index for arid area, which was coupled with the information of greenness, humidity, salinity, heat and land degradation to quantitatively evaluate the eco-environment quality. We used ARSEI and RSEI to dynamically monitor and evaluate the eco-environment quality of Ulan Buh Desert from 2000 to 2019, and analyzed their differences and their applicability in arid area. We further examined the characteristics and reasons of the temporal and spatial variations of the eco-environment quality of Ulan Buh Desert. The results showed that the ARSEI index had better applicability to the eco-environment quality in arid area than the RSEI, and it enhanced the role of land use changes in the ecological environment quality assessment. From 2000 to 2019, the overall eco-environmental quality of Ulan Buh Desert was worse. The parts under better, good, and medium grades were mainly distributed in the northern region, the parts with worse grades were mainly concentrated in the gobi and sandy land, and the poor ones were mainly located in area with low coverage vegetation. From 2000 to 2019, the overall quality of the eco-environment in the Ulan Buh Desert were becoming better. Meanwhile, the eco-environment quality of towns and farms in the northern part of the desert changed complexly, with deterioration and improvement alternately distributed. The main reason for the changes in the eco-environment of Ulan Buh Desert was the positive effects of ecological agriculture and sand industry.

Clinical Features and Outcomes of Repeated Endoscopic Therapy for Esophagogastric Variceal Hemorrhage in Cirrhotic Patients: Ten-Year Real-World Analysis.

OBJECTIVE: This study is aimed at evaluating the survival of cirrhotic patients with different etiologies after endoscopic therapy for acute variceal bleeding and the effect of repeated endotherapy on patients' prognosis. METHODS: We retrospectively evaluated the clinical features and outcomes between cirrhotic patients with chronic HBV or HCV infections and other etiologies. The 3-year and 5-year survival rates and rehemorrhage rate in one year between the viral and nonviral cirrhosis patients were compared by Kaplan-Meier curves and log-rank test. Cox analysis was used to identify the impact factors that affect the long-term survival of patients with cirrhosis and variceal bleeding after endotherapy. RESULTS: Out of 2665 patients with liver cirrhosis and variceal hemorrhage selected from our medical center between September 2008 and December 2017, a total of 1342 patients were included for analysis. The median follow-up duration was 32.9 months (range 0.16-111.4 months), the 3- and 5-year cumulative survival rates were 75.3% and 52.8%, respectively. The median survival time was significantly longer in viral cirrhosis patients (47.1 months [95% CI: 24.9-69.1]) compared with nonviral cirrhosis patients (37.0 months [95% CI: 25.0-56.0], p = 0.001). The 3-year and 5-year survival rates of the viral group were higher than the nonviral group. The rehemorrhage rate at one year was higher in nonviral patients than in viral patients (p < 0.001). CONCLUSION: Repeated endotherapy combined with effective antiviral therapy is helpful for long-term survival of cirrhotic population with variceal hemorrhage and HBV or HCV infection.

New model predicting gastroesophageal varices and variceal hemorrhage in patients with chronic liver disease.

INTRODUCTION AND OBJECTIVES: The predictors for gastroesophageal varices (GOV) and hemorrhage development have not been well studied in different liver diseases or different population. This study aimed to evaluate whether a new algorithm focusing on chronic hepatitis B (CHB) patients is also applicable to other chronic liver diseases (CLDs) in Chinese population. PATIENTS OR MATERIALS AND METHODS: We retrospectively analyzed 659 CHB patients and 386 patients with other CLDs. A total of 439 CHB patients were included in training set, the other 220 CHB patients and other patients with CLDs were included in validation set. A new algorithm for diagnosing GOV was established and its sensitivity and specificity for predicting the varices was verified. RESULTS: Multivariable logistic regression revealed that the rough surface of the liver (p<0.001), splenic thickness (p<0.001), and liver stiffness (p=0.006) were independent predictors of GOV. The new algorithm was considered to be a reliable diagnostic model to evaluate the presence of varices. The AUROC was 0.94 (p<0.001) in CHB validation set and 0.90 (<0.001) in non-CHB validation set. When the cut-off value was chosen as -1.048, the sensitivity and specificity in diagnosing GOV in CHB population were 89.1% and 82.5%, respectively. Importantly, the new algorithm accurately predicted the variceal hemorrhage not only in CHB patients, but also in patients with other CLDs. CONCLUSION: The new algorithm is regarded as a reliable model to prognosticate varices and variceal hemorrhage, and stratified not only the high-risk CHB patients, but also in patients with other CLDs for developing GOV and variceal bleeding.

Influence of alcohol consumption on liver function and rebleeding in alcoholic cirrhotic patients with esophageal and gastric varices / 临床肝胆病杂志

@#ObjectiveTo investigate the influence of alcohol consumption on liver function and prognosis in alcoholic cirrhotic patients. MethodsA total of 211 alcoholic cirrhotic patients with gastroesophageal variceal bleeding who underwent endoscopic treatment in Beijing Ditan Hospital, Capital Medical University, from September to December, 2018 were enrolled, and among these patients, there were 208 male and 3 female patients, with a mean follow-up time of 45 months (range 2-110 months). The association of alcohol consumption with liver parameters was analyzed. According to the presence or absence of gastroesophageal variceal rebleeding, the patients were divided into early rebleeding group, delayed rebleeding group, and non-rebleeding group, and the three groups were compared in terms of liver parameters and alcohol consumption. The t-test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The Spearman rank correlation test was used for correlation analysis. ResultsDuration of drinking was correlated with creatinine (r=0.142, P=0.039) and direct bilirubin (DBil) (r=-0.137, P=0.047), and daily alcohol consumption was correlated with DBil (r=0.144, P=0.037) and prealbumin (r=-0.190, P=0.009), while there was no correlation between total alcohol consumption and indicators for liver injury. There were significant differences between the early rebleeding group and the delayed rebleeding group in white blood cell count (WBC) (t=-2.355, P=0.020), neutrophils (t′=-2.602, P=0.010), hemoglobin (t=2.247, P=0.026), mean corpuscular volume (t=-2.073, P=0.040), alanine aminotransferase (Z=-1.985, P=0047), international normalized ratio (Z=-2.397, P=0.017), spleen thickness (Z=-2.542, P=0.011), Child-Pugh score (t′=-2.364, P=0.020), and Child-Pugh grade (Z=-2.485, P=0.013). The non-rebleeding group had significantly lower WBC (Z=-2.276, P=0.017) and neutrophils (Z=-2.375, P=0.018) than the rebleeding group, and the early and delayed rebleeding groups had a significantly shorter duration of drinking than the non-rebleeding group (Z=-2.522, P=0.012). The logistic regression analysis showed that neutrophils was a risk factor for variceal rebleeding (odds ratio=1.152, 95% confidence interval: 1.017-1.300, P=0026). ConclusionNo dose-response relationship is found between alcohol consumption and liver injury in this study, and alcohol consumption may not have a marked effect on variceal rebleeding.

[Impact of transition readiness on quality of life in children with chronic diseases].

OBJECTIVE: To investigate the current quality of life in children with chronic diseases, and to explore the impact of transition readiness on quality of life. METHODS: A total of 332 children with chronic diseases from two children's hospitals in Shanghai, China were enrolled. A self-designed demographic questionnaire, Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQLTM 4.0), and Self-Management and Transition to Adulthood with Rx=Treatment (STARx) Questionnaire were used to evaluate transition readiness and quality of life. RESULTS: The children with chronic diseases had a significantly lower total quality of life score than the national norm (74.66±15.85 vs 81.81±12.03; P<0.001). Doctor-patient communication and health care responsibilities (the child's abilities to take care of himself/herself and adaptation to the process of diagnosis and treatment from childhood to adulthood) were positively correlated with the scores on each dimension of quality of life (P<0.05). Duration of disease, time of absence from school within six months, and the number of types of drugs taken orally were negatively correlated with the total quality of life score (rs=-0.172, -0.236, and -0.280; P<0.05). The residence (urban or rural area), monthly family income, parents' educational level, and father's occupation had significant influence on children's quality of life (P<0.05). The hierarchical multiple regression analysis revealed that doctor-patient communication and health care responsibilities led to a 14.3% increase in the explanation of the total variation in quality of life (P<0.001). CONCLUSIONS: Quality of life is not satisfactory in children with chronic diseases. Two domains of transition readiness, namely the abilities to communicate with health providers and health care responsibilities, are major factors influencing quality of life in these children.

DDR2 Induces Gastric Cancer Cell Activities via Activating mTORC2 Signaling and Is Associated with Clinicopathological Characteristics of Gastric Cancer.

BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) plays a role in cancer progression. Previous studies have suggested that discoidin domain receptor 2 (DDR2) is related to tumor progression and EMT. However, the role of DDR2 in regulating gastric cancer (GC) metastasis and in EMT has not been elucidated. In this study, we aimed to determine DDR2 expression and its clinical relation in GC and to investigate the effects of DDR2 on EMT and its underlying mechanisms. METHODS: DDR2 expression and the relation to patients' clinicopathological features were assayed by Western blot or immunohistochemical staining. The effects of DDR2 overexpression were investigated using in vivo tumorigenicity and xenograft models. The effects of DDR2 on EMT marker expression were assayed by Western blot and immunofluorescence. The possible role of the mTORC pathway in these processes was explored. RESULTS: DDR2 showed high expression in GC tissues and cells. DDR2 expression was negatively correlated with E-cadherin expression and positively correlated with N-cadherin and vimentin expression. High DDR2 expression is correlated with unfavorable pathoclinical features such as multiple tumor locations and intestinal-type GC. In xenograft models, DDR2 overexpression promoted tumor formation. Furthermore, DDR2 expression impacted on the invasion and motility of GC cells, accompanied by changes in EMT marker expression. Finally, our results revealed that DDR2 facilitates GC cell invasion and EMT through mTORC2 activation and AKT phosphorylation. CONCLUSION: DDR2 is upregulated and correlated with unfavorable clinical features of GC patients. DDR2 promotes tumor formation and invasion through facilitating EMT process via mTORC2 activation and AKT phosphorylation.

Oridonin, a novel lysine acetyltransferases inhibitor, inhibits proliferation and induces apoptosis in gastric cancer cells through p53- and caspase-3-mediated mechanisms.

Lysine acetylation has been reported to involve in the pathogenesis of multiple diseases including cancer. In our screening study to identify natural compounds with lysine acetyltransferase inhibitor (KATi) activity, oridonin was found to possess acetyltransferase-inhibitory effects on multiple acetyltransferases including P300, GCN5, Tip60, and pCAF. In gastric cancer cells, oridonin treatment inhibited cell proliferation in a concentration-dependent manner and down-regulated the expression of p53 downstream genes, whereas p53 inhibition by PFT-α reversed the antiproliferative effects of oridonin. Moreover, oridonin treatment induced cell apoptosis, increased the levels of activated caspase-3 and caspase-9, and decreased the mitochondrial membrane potential in gastric cancer cells in a concentration-dependent manner. Caspase-3 inhibition by Ac-DEVD-CHO reversed the proapoptosis effect of oridonin. In conclusion, our study identified oridonin as a novel KATi and demonstrated its tumor suppressive effects in gastric cancer cells at least partially through p53-and caspase-3-mediated mechanisms.

Salinomycin inhibits hepatocellular carcinoma cell invasion and migration through JNK/JunD pathway-mediated MMP9 expression.

The antibiotic salinomycin (Salin) was recently identified as an antitumor drug for the treatment of several types of solid tumors. However, the effects of Salin on the migratory and invasive properties of hepatocellular carcinoma (HCC) cells are unclear. The present study aimed to determine the antitumor efficacy and mechanism of Salin in HCC cells. Human HCC cells (HCCLM3) treated with Salin showed a concentration-dependent reduction in cell migration and invasion, and this was associated with reduced MMP9 expression. The MMP9 promoter and enhancer in a luciferase reporter assay revealed that Salin can regulate MMP9 expression through an activator protein (AP-1) site within the MMP9 enhancer. JunD, one of the AP-1 components, was significantly decreased by Salin in a concentration- and time-dependent manner. Salin was able to induce c-Jun NH2-kinase (JNK) phosphorylation and to block both JunD and MMP9 expression. Our results showed that JNK phosphorylation and JunD may be involved in the Salin-regulated MMP9 signaling pathway in HCCLM3 cells and may mediate HCC cell biological characteristics. Our studies provide new insight into the antitumor effects of Salin.

The glucosylceramide synthase inhibitor PDMP sensitizes pancreatic cancer cells to MEK/ERK inhibitor AZD-6244.

Here we show that d,l-Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), a glycosphingolipid biosynthesis inhibitor, increases the sensitivity of pancreatic cancer cells to the novel MEK-ERK inhibitor AZD-6244. AZD-6244 and PDMP co-administration induced massive pancreatic cancer cell death and apoptosis, more potently than either drug alone. We discovered that AZD-6244 induced ceramide production in pancreatic cancer cells, yet the excess ceramide was metabolically removed in the long-term (24-48h). PDMP facilitated AZD-6244-induced ceramide production, and ceramide level remained elevated up to 48h. Meanwhile, exogenously-added cell-permeable short chain ceramide (C2) similarly sensitized AZD-6244's activity, the two caused substantial pancreatic cancer cell death and apoptosis. At the molecular level, PDMP and AZD-6244 co-treatment inactivated ERK1/2 and AKT-mTOR signalings simultaneously in pancreatic cancer cells, while either agent alone only affected one signaling. In summary, PDMP significantly increased the sensitivity of AZD-6244 in pancreatic cancer cells. This appears to involve a sustained ceramide production as well as concurrent block of ERK and AKT-mTOR signalings.

The involvement of NLRX1 and NLRP3 in the development of nonalcoholic steatohepatitis in mice.

BACKGROUND: Increasing evidence suggests that innate immunity is involved in the development of nonalcoholic fatty liver disease. Nod-like receptors (NLRs) have recently been identified as key mediators of inflammatory and immune responses. The aim of this article is to explore the correlation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)X1 and NLRP3 with nonalcoholic steatohepatitis (NASH) in mice. METHODS: In our study, a high-fat diet, lipopolysaccharides (LPSs), and normal diet were given to C57BL mice to establish high fat (HF), HF + LPS, and control groups. Thereafter, serum alanine and aspartate aminotransferase (ALT and AST) levels were measured, and NASH severity was histologically examined. We measured tumor necrosis factor (TNF)-α levels by enzyme-linked immunosorbent assay, protein expression by Western blotting, and mRNA expression by real-time fluorescent quantitative reverse transcription-polymerase chain reaction. RESULTS: Levels of ALT and AST were higher in HF + LPS mice than in HF mice (p < 0.05). NLRX1 mRNA and protein expression was lower in HF and HF + LPS mice than in control mice (p < 0.05). NLRP3 mRNA expression was higher in HF and HF + LPS mice than in control mice (p < 0.05). The mRNA and protein expression of TNF receptor-associated factor (TRAF)6, interleukin-1ß, caspase-1, and apoptosis-associated speck-like protein were significantly higher in HF + LPS mice than in control and HF mice; furthermore, mRNA expression was higher in HF mice than in control mice (p < 0.05), but protein expression was similar. CONCLUSION: NLRX1 and NLRP3 inflammasomes may be important in NASH development.

An effective low-complexity multi-vital-signs compression technique for embedded-link e-home healthcare.

Transplanting the existing e-home healthcare system to source-limited embedded-link device for home-use health monitoring, intelligent medical diagnosis and wireless transmission is attractive. Yet, constrains of portable storage, computing and transmission promote the need of data compression for such applications. Existing compression techniques are mostly desktop-computer-based and computation-consuming, making them unsuitable for mobile device. To tackle such a bottleneck problem, this paper addresses an effective low-complexity multi-vital-signs compression technique based on orthogonal polynomial decomposition (OPD) algorithm using Hermite functions. The technique is proposed and operated on the designated healthcare system with optimized parameters. Validated and tested with cardiovascular disease (CVD) diagnosis based on sphygmogram both experimentally and clinically, the proposed technique achieves comparable good performance with distortion less than 2% and compression ratio up to 6, and preserves significant pathological features of multi-vital-signs for clinical diagnosis. The proposed technique is highly robust even for freaky and pathological signals. In addition, the compressed results reflecting morphological features can be directly adapted to the subsequent medical analysis without further decompression.

Mechanisms of trichostatin A inhibiting AGS proliferation and identification of lysine-acetylated proteins.

AIM: To explore the effect of lysine acetylation in related proteins on regulation of the proliferation of gastric cancer cells, and determine the lysine-acetylated proteins and the acetylated modified sites in AGS gastric cancer cells. METHODS: The CCK-8 experiment and flow cytometry were used to observe the changes in proliferation and cycle of AGS cells treated with trichostatin A (TSA). Real time polymerase chain reaction and Western blotting were used to observe expression changes in p21, p53, Bax, Bcl-2, CDK2, and CyclinD1 in gastric cancer cells exposed to TSA. Cytoplasmic proteins in gastric cancer cells before and after TSA treatment were immunoprecipitated with anti-acetylated lysine antibodies, separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis gel and silver-stained to detect the proteins by mass spectrometry after removal of the gel. The acetylated proteins in AGS cells were enriched with lysine-acetylated antibodies, and a high-resolution mass spectrometer was used to detect the acetylated proteins and modified sites. RESULTS: TSA significantly inhibited AGS cell proliferation, and promoted cell apoptosis, leading to AGS cell cycle arrest in G0/G1 and G2/M phases, especially G0/G1 phase. p21, p53 and Bax gene expression levels in AGS cells were increased with TSA treatment duration; Bcl-2, CDK2, and CyclinD1 gene expression levels were decreased with TSA treatment duration. Two unknown protein bands, 72 kDa (before exposure to TSA) and 28 kDa (after exposure to TSA), were identified by silver-staining after immunoprecipitation of AGS cells with the lysine-acetylated monoclonal antibodies. Mass spectrometry showed that the 72 kDa protein band may be PKM2 and the 28 kDa protein band may be ATP5O. The acetylated proteins and modified sites in AGS cells were determined. CONCLUSION: TSA can inhibit gastric cancer cell proliferation, which possibly activated signaling pathways in a variety of tumor-associated factors. ATP5O was obviously acetylated in AGS cells following TSA treatment.

[A noninvasive diagnostic model of liver fibrosis using serum markers in primary biliary cirrhosis].

OBJECTIVE: To verify and assess diagnostic value of noninvasive diagnostic model of liver fibrosis in primary biliary cirrhosis (PBC) based on conventional laboratory markers. METHODS: Seventy-three patients with PBC diagnosed by liver biopsy between January 2003 and June 2011 in Beijing Friendship Hospital, Capital Medical University were recruited in this study. Correlation analysis and logistic regression analysis between the conventional laboratory markers and histology stages were assessed. A liver fibrosis diagnostic model was established based upon aforementioned biomarkers and verified by its sensitivity and specificity for predicting the liver fibrosis. RESULTS: The predictive model (H index) consisting of five conventional laboratory markers, i.e., platelet count, serum cholinesterase, albumin, HDL-C and prothrombin time activity, could predict advanced fibrosis (stages III-IV) with an AUC(ROC) of 0.861. The sensitivity of predicting the absence of advanced fibrosis using H index < -2.20 was 96.6% and the specificity of predicting the presence of advanced fibrosis using H index > 0.41 was 93.2%. CONCLUSION: The established noninvasive diagnostic model consisting of five laboratory markers could accurately distinguish pathological changes of early stage PBC (stages I-II) from advanced stage PBC (stages III-IV).

IκB kinase-beta inhibitor attenuates hepatic fibrosis in mice.

AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice received a normal diet as controls. Hepatic function, pathological evaluation and liver interleukin-6 (IL-6) expression were examined. Western blotting and real-time polymerase chain reaction were used to detect the expressions of nuclear factor-κB (NF-κB), alpha-smooth muscle actin (α-SMA), tumor growth factor-beta1 (TGF-ß1), tumor necrosis factor-alpha (TNF-α), typeIand type III collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear translocation of NF-κB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 ± 9.77 µ/L vs 62.4 ± 7.90 µ/L, P < 0.05) and aminotransferase (295.8 ± 38.56 µ/L vs 212 ± 25.10 µ/L, P < 0.05) were significantly decreased when compared with the model groups. The histological changes were significantly ameliorated. After treatment, the expressions of IL-6 (681 ± 45.96 vs 77 ± 7.79, P < 0.05), TGF-ß1 (Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P < 0.05), TNF-α (11.58% ± 0.0063% vs 8.86% ± 0.0050%, P < 0.05), typeIcollagen (4.49% ± 0.014% vs 1.90% ± 0.0006%, P < 0.05) and type III collagen (3.46% ± 0.008% vs 2.29% ± 0.0035%, P < 0.05) as well as α-SMA (6.19 ± 0.0036 µ/L vs 2.16 ± 0.0023 µ/L, P < 0.05) protein and mRNA were downregulated in the IMD group compared to the fibrosis control groups (P < 0.05). CONCLUSION: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver disease in mice by lowering NF-κB activation, which could become a remedial target for liver fibrosis.