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Background: Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis.Methods: we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms.Results: Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning.Conclusions: These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI. [ABSTRACT FROM AUTHOR]

Background: There are a large number of infertile couples in China, but its treatment is notoriously expensive and not currently covered by insurance. The utility of preimplantation genetic testing for aneuploidy as an adjunct to in vitro fertilization has been debated. Objective: To investigate the cost-effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) versus conventional technology in in vitro fertilization (IVF) from the perspective of the healthcare system in China. Methods: Following the exact steps in the IVF protocol, a decision tree model was developed, based on the data from the CESE-PGS trial and using cost scenarios for IVF in China. The scenarios were compared for costs per patient and cost-effectiveness. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings. Main outcome measures: Costs per live birth, Costs per patient, Incremental cost-effectiveness for miscarriage prevention. Results: The average costs per live birth of PGT-A were estimated as ¥39230.71, which is about 16.8% higher than that of the conventional treatment. Threshold analysis revealed that PGT-A would need to increase the pregnancy rate of 26.24–98.24% or a cost reduction of ¥4649.29 to ¥1350.71 to achieve the same cost-effectiveness. The incremental costs per prevented miscarriage was approximately ¥45600.23. The incremental cost-effectiveness for miscarriage prevention showed that the willingness to pay would be ¥43422.60 for PGT-A to be cost-effective. Conclusion: The present cost-effectiveness analysis demonstrates that embryo selection with PGT‑A is not suitable for routine applications from the perspective of healthcare providers in China, given the cumulative live birth rate and the high costs of PGT‑A. [ABSTRACT FROM AUTHOR]

Background: Early life in-utero can have long-term influence on the mental health status of individuals in adulthood, such as depression. Age, gender, socio-economic status, education, and geography are demographic factors shown to be particularly vulnerable towards the development of depressive symptoms. In addition, climate risks on depression include sunlight, rain, and temperature. However, whether climate factors in early life have a long-term influence on depression related to demographic vulnerability remains unknown. Here, the present study explored the association between birth seasonality and adulthood depressive symptoms. Methods: We employed data from the project of Chinese Labour-forces Dynamic Survey (CLDS) 2016, containing the epidemiological data of depressive symptoms with a probability proportional to size cluster and random cluster sampling method in 29 provinces of China. A final sample size of 16,185 participants was included. Birth seasonality included spring (March, April, and May), summer (June, July, and August), autumn (September, October, and November), and winter (December, January, and February). Results: We found that born in Autumn peaked lowest rate of having depressive symptoms (16.8%) and born in Summer (vs. Autumn) had a significant higher ratio (OR = 1.14, 95%CI = 1.02, 1.29) when controlling for demographic variables. In addition, demographic odds ratio of having depressive symptoms differed between people born in different seasons, particular for age and geography. Conclusion: Our findings suggest that birth seasonality influences the sensitive link of depressive symptoms with age and geography. It implicates early life climate environment may play a role in the development of adulthood depressive symptoms. [ABSTRACT FROM AUTHOR]

The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry (Aronia melanocarpa L.) are rich in polyphenols with various physiological and pharmacological activities. We determined serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measure gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rats. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFD-fed rats. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the Firmicutes/Bacteroidetes ratio (F/B ratio) and increasing the relative abundance of Bacteroides, Prevotella, Akkermansia and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated Bacteroides, Prevotella and negatively correlated with Clostridium, Eubacterium, Ruminococcaceae. In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rats by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats. However, FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats. The gut microbiota plays an important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis. [ABSTRACT FROM AUTHOR]

Background: It is essential to accurately predict Postoperative liver failure (PHLF) which is a life-threatening complication. Liver hardness measurement (LSM) is widely used in non-invasive assessment of liver fibrosis. The aims of this study were to explore the application of preoperative liver stiffness measurements (LSM) by transient elastography in predicting postoperative liver failure (PHLF) in patients with hepatitis B related hepatocellular carcinoma. Methods: The study included 247 consecutive patients with hepatitis B related hepatocellular carcinoma who underwent hepatectomy between May 2015 and September 2015. Detailed preoperative examinations including LSM were performed before hepatectomy. The endpoint was the development of PHLF. Results: All of the patients had chronic hepatitis B defined as the presence of hepatitis B surface antigen (HBsAg) for more than 6 months and 76 (30.8%) had cirrhosis. PHLF occurred in 37 (14.98%) patients. Preoperative LSM (odds ratio, OR, 1.21; 95% confidence interval, 95% CI: 1.13-1.29; P < 0.001) and international normalized ratio (INR) (OR, 1.07; 95% CI: 1.01-1.12; P < 0.05) were revealed to be independent risk factors for PHLF, and a new model was defined as LSMINR index (LSM-INR index = 0.191*LSM+ 6.317*INR-11.154). The optimal cutoff values of LSM and LSM-INR index for predicting PHLF were 14 kPa (AUC 0.86, 95% CI: 0.811-0.901, P < 0.001) and -1.92 (AUC 0.87, 95% CI: 0. 822-0.909, P < 0.001), respectively. Conclusions: LSM can be helpful for surgeons to make therapeutic decisions in patients with hepatitis B related hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]