Depression and hepatobiliary diseases: a bidirectional Mendelian randomization study.

Background: More and more evidence suggests a close association between depression and hepatobiliary diseases, but its causal relationship is not yet clear. Method: Using genome-wide association studies (GWAS) to summarize data, independent genetic variations associated with depression were selected as instrumental variables. Firstly, we designed a univariate Mendelian randomization (UVMR) analysis with two samples and simultaneously conducted reverse validation to evaluate the potential bidirectional causal relationship between depression and various hepatobiliary diseases. Secondly, we conducted a multivariate Mendelian randomization (MVMR) analysis on diseases closely related to depression, exploring the mediating effects of waist to hip ratio, hypertension, and daytime nap. The mediating effects were obtained through MVMR. For UVMR and MVMR, inverse variance weighted method (IVW) is considered the most important analytical method. Sensitivity analysis was conducted using Cochran'Q, MR Egger, and Leave-one-out methods. Results: UVMR analysis showed that depression may increase the risk of non-alcoholic fatty liver disease (OR, 1.22; 95% CI, 1.03-1.46; p=0.0248) in liver diseases, while depression does not increase the risk of other liver diseases; In biliary and pancreatic related diseases, depression may increase the risk of cholelithiasis (OR, 1.26; 95% CI, 1.05-1.50; p=0.0120), chronic pancreatitis (OR, 1.61; 95% CI, 1.10-2.35; p=0.0140), and cholecystitis (OR, 1.23; 95% CI, 1.03-1.48; p=0.0250). In addition, through reverse validation, we found that non-alcoholic fatty liver disease, cholelithiasis, chronic pancreatitis, cholecystitis, or the inability to increase the risk of depression (p>0.05). The waist to hip ratio, hypertension, and daytime nap play a certain role in the process of depression leading to non-alcoholic fatty liver disease, with a mediating effect of 35.8%. Conclusion: Depression is a susceptibility factor for non-alcoholic fatty liver disease, and the causal effect of genetic susceptibility to depression on non-alcoholic fatty liver disease is mediated by waist-hip ratio, hypertension, and daytime nap.

The Impact of Income Inequality on Health Levels: Empirical Evidence from China:2002-2016.

Income inequality had been one of the important manifestations of social inequality, which can affect the health level by affecting savings, health care and living standards. Existing researches about the relationship between income inequality and health ignored the comprehensive characteristic of health concept, and did not consider the intrinsic relationship between health and income inequality. This paper attempts to re-shed light on the relationship. Firstly, this paper constructs a new health level evaluation system from three aspects: health basis, health environment and behavior, and health security. By means of the combination evaluation method, the health levels can be obtained. Then, considering the interaction between health and income inequality, a simultaneous equation group model is constructed to empirically test the relationship between income inequality and health levels in China. The results reveal that health level is negatively correlated with income inequality. Reducing income inequality plays an important role in improving health levels in China.

The efficacy and safety of adding anlotinib in gradual progression on third-generation EGFR-TKIs for EGFR-mutant advanced nonsmall cell lung cancer.

Acquired resistance is unavoidable with the approval of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for first-line therapy of advanced non small cell lung cancer (NSCLC). Some studies have found that combining antiangiogenesis medicines with EGFR-TKI may benefit clinical outcomes in EGFR-mutant NSCLC. However, it is unclear whether EGFR-TKI paired with antiangiogenesis therapy could further improve survival for patients with gradual progression. Thus, we comprised the clinical effectiveness and safety of continuous EGFR-TKI in combination with anlotinib and EGFR-TKI alone in patients who had gradual progression on third-generation EGFR-TKI treatment. The comparison of progression-free survival (PFS) and overall survival(OS) between two groups used the Kaplan-Meier method. Our study comprised 121 eligible patients in total. The objective response rates were 25.0% and 0%, and the disease response rate was 91.7% and 86.9% in the combination group and EGFR-TKIs monotherapy group. The median PFS of combined anlotinib and EGFR-TKI treatment was 6.7 months and the median PFS was 3.6 months in the EGFR-TKI monotherapy group ( P  < 0.001). There were no significant differences between the two groups in OS. The common adverse reactions were diarrhea (21.7%), hypertension (21.6%) and proteinuria (20.0%) in the combination group. Seven patients experienced a grade 3 or higher adverse event, no patients discounted the treatment or died due to the toxicity. Our study indicated that, when combined with anlotinib following gradual progression on EGFR-TKIs, it was more efficacious for EGFR-mutant NSCLC patients than EGFR-TKI monotherapy. And the toxicity was clinically manageable.

Knockdown of Obg-like ATPase 1 enhances sorafenib sensitivity by inhibition of GSK-3ß/ß-catenin signaling in hepatocellular carcinoma cells.

Background: To clarify the molecular mechanism of hepatocellular carcinoma (HCC), conducive to developing an effective HCC therapy. Owing to the severe drug resistance, the clinical use of sorafenib, which is approved for HCC treatment, is limited. The precise molecular mechanisms of sorafenib drug resistance remain unclear. In the current work, we evaluated the role of Obg-like ATPase 1 (OLA1) in sorafenib resistance in HCC. Methods: The survival of HCC patients between OLA1 expression and sorafenib treatment was analyzed by Kaplan-Meier plotter. Cell viability was measured by cell counting kit-8 (CCK-8) and colony formation assays. Cell death was detected by propidium iodide (PI) and trypan blue staining. The mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB), respectively. Results: We found that OLA1 was highly correlated with sorafenib resistance of HCC through a public database. Further study showed that knockdown of OLA1 enhanced cell proliferation inhibition and cell death induced by sorafenib, along with a reduction of proliferation-associated proteins (c-Myc and cyclin D1) and increase of apoptosis-related proteins (cleaved caspase-3 and cleaved PARP) in HCC cells. In addition, knockdown of OLA1 reduced the activation of glycogen synthase kinase 3ß (GSK-3ß)/ß-catenin. Conclusions: Our results proved that OLA1 can be a potential target to enhance sorafenib sensitivity in HCC.

Behavioral and Neurochemical Changes in Rats with Recurrent Depression induced by chronic unpredictable stress.

OBJECTIVES: The mechanism of recurrent depression remains unclear. This study aimed to evaluate the behavioural and neurochemical patterns of rats with recurrent depression. MATERIALS AND METHODS: An animal model of recurrent depression was established using chronic unpredictable stress and imipramine hydrochloride. The behaviour of the rats was tested during the first onset and recurrence periods of depression. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and cyclic adenosine monophosphate (cAMP) in serum were detected by ELISA. The protein expressions of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) in the hippocampal dentate gyrus (DG) area of rats were detected by western blotting. RESULTS: The weight and sugar preference of the rats with recurrent depression were significantly decreased, and the immobility time of tail suspension was significantly increased during the first onset and recurrence periods. The modelling time of rats was shortened by one week in the recurrence period compared with that in the first onset. The model rats with recurrent depression had significantly increased ACTH and CORT and significantly decreased cAMP, CREB, and BDNF levels. CONCLUSION: Rats with recurrent depression are highly susceptible to stress and exhibit depression-like behaviours such as weight loss, increased immobility time in tail suspension test, and reduced sucrose preference index. Moreover, the modelling time was shortened by one week, indicating an obvious susceptibility to recurrent depression. The significantly up-regulated neuroendocrine in the HPA and the significantly inhibited BDNF and protein expression factors in related signalling pathways may be involved in the increased susceptibility to recurrent depression.

Impact of Environmental Pollution on Health-Evidence from Cities in China.

Doubtless, China's long-term extensive development model has exacerbated environmental pollution, thus posing a great threat to the health of its residents. Against this background, the present paper constructs a comprehensive system for evaluating environmental pollution from the perspective of environmental pollution and natural purification, and then empirically analyzes the impact of environmental pollution on the "near-term health," "self-rated health", and "mental health" of Chinese residents via the Hierarchical Linear Model based on the data from China Family Panel Studies in 2016. This paper focuses on the impact of environmental pollution on physical health as well as on mental health. The results are as follows: (1) although environmental pollution in China has no significant negative impact on the "near-term health" of residents, it can reduce the levels of "self-rated health" and "mental health" of residents; (2) environmental pollution causes more health losses to the low-income group and residents in underdeveloped cities in central and western China. It is argued that perfecting public services is an important way to improve residents' physical and mental health in the process of urbanization in China.

Measurement and space-time evolution of health level under constraint of environmental pollution, China: 2002-2016.

China's massive energy consumption and low energy efficiency have caused severe environmental pollution and posed great threat to the national health level. The general occurrence of health complications caused by cumulative environmental pollution in China is on the rise. This paper attempts to shed light on the evolutionary trajectory of health level in China under the constraint of environmental pollution. Firstly, on the basis of environmental pressure and environmental elasticity, an evaluation system of environmental pollution is constructed, and China's environmental pollution level is obtained with combination evaluation method. An evaluation system for measuring health level is proposed based on three dimensions of health, namely health foundation, health behavior and environment, and health protection. To avoid possible bias caused by neglecting environmental pollution in estimating health level and emphasize the health depletion by environmental pollution, this paper adopts pollution levels to correct health levels. Finally, an analysis is made concerning the temporal and spatial evolution characteristics of health level on the basis on the Theil index and spatial distribution map. The results reveal three facts: (1) Environmental pollution level in China is lowering with improvement in environmental quality; (2) The overall health level in China is rising, but the local health level is deteriorating; and (3) The spatial distribution of the health level is characterized by unbalance. From the perspective of difference, intra-regional difference is greater than inter-regional difference. The health level difference between the provinces in the same region is the main contribution to the overall difference. In terms of spatial distribution, the lower health level is mainly concentrated in the north, while the higher health level is found in the southern provinces and parts of the western provinces.

Exploring the Differential Effects of Online Reviews on Film's Box-Office Success: Source Identity and Brand Equity From an Integrated Perspective.

This study investigates the differential effects of online reviews on actual sales in cases where information regarding source identity and brand equity is accessible. The data were collected from an influential online film review platform in China. Two distinctive features of this study are: (1) source identity is expressed as "verified user" or "unverified user" according to posters' ticket payment status and (2) the interactive effect between source identity and brand equity on box-office success is examined. Using econometric estimations, the results reveal the following: (1) the positive effect of verified users' online review valences on the number of tickets purchased for films decreases in association with high brand strength; (2) the variance of verified users' online reviews positively affects the number of tickets purchased for films with high brand strength, but such an effect is negative with low brand strength; (3) the variance of unverified users' online reviews positively influences the number of tickets purchased for films with low brand strength, but it negatively influences the number of tickets purchased for films with high brand strength. Thus, these findings suggest that it is better for business leaders to understand not only why producers of online reviews are satisfied or dissatisfied, but also how consumers interpret and interact with different types of online reviews and which are important. This requires a smart and flexible collaboration among different business units within film company.

Physicochemical properties and in vitro digestibility of starch from naturally air-dried chestnut.

Naturally air-dried chestnut is a type of traditionally processed chestnut in North China which has a pleasant flavor. After air drying at room temperature and low-air humidity for two wk, the moisture, total starch content and starch relative crystallinity decreased, while the content of water-soluble sugar and amylose increased because of the dehydration and the hydrolysis of endogenous amylase. The Fourier transform infrared (FTIR) spectroscopy ratio of 1047/1022 cm-1 and the relative area of the Raman spectrum peak at 480/865 cm-1 of air-dried chestnut starch decreased in the first two wk and then increased, while the full width at half-maximum height (FWHH) of the Raman spectrum peak at 480 cm-1 showed the opposite tendency. Crystallinity had a positive correlation with the springiness and chewiness, and was negatively correlated with the estimated glycemic index (eGI). The eGI of air-dried starch was lower than those of roasted or boiled starch, which indicated that naturally air-dried chestnut with low digestibility is a good alternative to thermally processed chestnut.

Fully cross-linked and chemically patterned self-assembled monolayers.

Mechanically stable monolayers with chemically functional patterns are fabricated by the combination of spatially resolved chemical lithography with complete cross-linking of aromatic self-assembled monolayers (SAMs). The process starts with a local electron exposure of a SAM of 4'-nitro-1,1'-biphenyl-4-thiol that converts the nitro into amino groups and, additionally, generates a pattern of cross-linked and non cross-linked regions. In the next step, molecules in the non cross-linked regions are exchanged for 1,1'-biphenyl-4-thiol. A subsequent electron exposure cross-links these regions, yielding a fully cross-linked, chemically patterned SAM. The reverse process that generates chemically complementary patterns is also demonstrated. For both processes, X-ray photoelectron spectroscopy and atomic force microscopy are used to monitor the fabrication steps and to determine the kinetics of the thiol exchange. The functionality of the fully cross-linked, chemically patterned monolayer is tested by the site selective derivatisation with pentanoic acid chloride.