Macrophage ATG16L1 expression suppresses metabolic dysfunction-associated steatohepatitis progression by promoting lipophagy

Background/Aims@#Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays an important role in the process of autophagy, which is indispensable for proper biogenesis of the autophagosome, but its role in modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed to elucidate the role of ATG16L1 in the progression of MASH. @*Methods@#Expression analysis was performed with liver samples from human and mice. MASH models were induced in myeloid-specific Atg16l1-deficient and myeloid-specific Atg16l1-overexpressed mice by high-fat and high-cholesterol diet or methionine- and choline-deficient diet to explore the function and mechanism of macrophage ATG16L1 in MASH. @*Results@#Macrophage-specific Atg16l1 knockout exacerbated MASH and inhibited energy expenditure, whereas macrophage-specific Atg16l1 transgenic overexpression attenuated MASH and promotes energy expenditure. Mechanistically, Atg16l1 knockout inhibited macrophage lipophagy, thereby suppressing macrophage β-oxidation and decreasing the production of 4-hydroxynonenal, which further inhibited stimulator of interferon genes(STING) carbonylation. STING palmitoylation was enhanced, STING trafficking from the endoplasmic reticulum to the Golgi was promoted, and downstream STING signaling was activated, promoting proinflammatory and profibrotic cytokines secretion, resulting in hepatic steatosis and hepatic stellate cells activation. Moreover, Atg16l1-deficiency enhanced macrophage phagosome ability but inhibited lysosome formation, engulfing mtDNA released by pyroptotic hepatocytes. Increased mtDNA promoted cGAS/STING signaling activation. Moreover, pharmacological promotion of ATG16L1 substantially blocked MASH progression. @*Conclusions@#ATG16L1 suppresses MASH progression by maintaining macrophage lipophagy, restraining liver inflammation, and may be a promising therapeutic target for MASH management.

Influencing factors of life quality in middle-aged diabetic patients in a community of Shanghai / 上海预防医学

Objective To understand the situation and the influencing factors of life quality in diabetic patients in Shanghai， and to develop effective intervention measures. Methods A total of 212 diabetic patients in Baoshan District， Shanghai were selected as the research objects. Diabetes specific quality of life scale （DSQL） was used to investigate the basic situation and quality of life of patients. Combined with biochemical detection indexes and questionnaire survey， data were analyzed by variance analysis and multiple linear stepwise regression analysis. Blood glucose level was assessed according to the 1999 WHO diagnostic criteria for type 2 diabetes. Results The overall quality of life score in the patients was 4.31±7.82， which was higher than the domestic norm. The best quality of life was in the dimension of physiological function with the score of 1.84±6.00， which was lower than the domestic norm. The next was the dimension of social relationship， and the worst was the dimension of treatment. The single factor analysis and multivariate analysis identified the following influence factors of quality of life in the patients： family history， educational level， exercise habit， blood glucose control and diet control. There was a negative correlation with educational level and blood glucose control， and a positive correlation with diet control. Conclusion The quality of life in the middle-aged diabetic patients was affected by the education level， blood glucose control and diet control. We suggest to strengthen the community management， health education， and improve the living habits.

Correction to: Recent Advances in the Genetic Dissection of Neural Circuits in Drosophila / 神经科学通报·英文版

In the original publication the fifth line starting with "… with circa 1000, 1000 neurons?" in section Concluding Remarks and Perspectives is incorrectly published. The correct text should read "… with circa 100, 000 neurons?"

Recent Advances in the Genetic Dissection of Neural Circuits in Drosophila / 神经科学通报·英文版

Nervous systems endow animals with cognition and behavior. To understand how nervous systems control behavior, neural circuits mediating distinct functions need to be identified and characterized. With superior genetic manipulability, Drosophila is a model organism at the leading edge of neural circuit analysis. We briefly introduce the state-of-the-art genetic tools that permit precise labeling of neurons and their interconnectivity and investigating what is happening in the brain of a behaving animal and manipulating neurons to determine how behaviors are affected. Brain-wide wiring diagrams, created by light and electron microscopy, bring neural circuit analysis to a new level and scale. Studies enabled by these tools advances our understanding of the nervous system in relation to cognition and behavior.

Preliminary evaluation of endoscopic selective varices devascularization in children / 中华儿科杂志

Objective@#To investigate the effect of the endoscopic selective varices devascularization (ESVD) for the esophageal gastric varices bleeding (EGVB) in children.@*Methods@#The clinical data of the patients diagnosed with EGVB and treated with ESVD from January 2018 to March 2018 were retrospectively analyzed. The effects, safety and complications of ESVD were evaluated.@*Results@#There were five patients (including 2 males and 3 females, age ranged from 4 to 7 years) in the study. No rebleeding was found at the first follow-up on one week post operation. Three patients were treated with the endo-therapy at the twice follow-up (3 months after surgery): 2 patients had ESVD again and 1 patient had resection under endoscopy due to stenosis caused by surgical scar. After the second procedure, there was no rebleeding but one patient had abdominal pain caused by mesenteric thrombosis, cured with low molecular weight heparin.@*Conclusion@#The ESVD for EGVB is safe and effective, but the long-term curative effect should be further studied.

Hierarchical Control of Drosophila Sleep, Courtship, and Feeding Behaviors by Male-Specific P1 Neurons / 神经科学通报·英文版

Animals choose among sleep, courtship, and feeding behaviors based on the integration of both external sensory cues and internal states; such choices are essential for survival and reproduction. These competing behaviors are closely related and controlled by distinct neural circuits, but whether they are also regulated by shared neural nodes is unclear. Here, we investigated how a set of male-specific P1 neurons controls sleep, courtship, and feeding behaviors in Drosophila males. We found that mild activation of P1 neurons was sufficient to affect sleep, but not courtship or feeding, while stronger activation of P1 neurons labeled by four out of five independent drivers induced courtship, but only the driver that targeted the largest number of P1 neurons affected feeding. These results reveal a common neural node that affects sleep, courtship, and feeding in a threshold-dependent manner, and provide insights into how competing behaviors can be regulated by a shared neural node.

Impact of psychological intervention on response and defense style of AIDS patients / 中国实用护理杂志

Objective To explore the impact of psychological intervention on response and defense style of AIDS patients.Methods 88 AIDS patients were selected and investigated using medical response (MCMQ) and defense style (DSQ) survey,the scores before and after psychological intervention were compared.Results Mental health problems included fear,afraid,pessimism and worry,the response style included face,avoid,yield.Scores showed significant difference before and after intervention among patients choosing immature-type,mature-type and cover-up defense styles.Conclusions Psychological intervention can promote rehabilitation and health of AIDS patients as well as improve their life quality and prevent disease relapse.