Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

[Abstract] With the rapid development of nano delivery systems (NDSs) and in-depth understanding of the mechanism of cell pyroptosis, a new tumor treatment strategy formed by an ingenious combination of the two has achieved certain effects in the experimental treatment of some tumors. The strategy of inducing pyroptosis of tumor cells based on NDSs can overcome the defects of using small molecule pyroptosis inducers alone, such as fast elimination in vivo, systemic serious adverse reactions and weak tumor-targeting ability. A variety of NDSs, such as liposomes, hydrogels, polymer micelles, metal-organic frameworks (MOFs) and cell membrane biomimetic nanocarriers, have been used to construct drugs that induce tumor cell pyroptosis. On this basis, a variety of strategies based on NDSs drug-induced tumor cell have been developed, including targeting tumor stem cells, interfering with ion homeostasis, promoting ROS production, inducing epigenetic changes and delivery of gasdermin (GSDM) family proteins, etc. However, to apply these strategies clinically we still faced insufficient understanding of the interaction mechanisms between nanomaterials and biological systems. In future researches, based on a comprehensive understanding of the interaction between nanomaterials and biological systems, if we can develop new and safe NDSs, combined with effective pyroptosis inducers to target and induce tumor cell pyroptosis, so as to overcome apoptosis escape and multidrug resistance, it is expected to bring good news to tumor patients.

Objective To observe the curative effect of continuous gastrointestinal decompression after gastric lavage with edible oil on saving patients with oral aluminum phosphide poisoning.Methods Seventy-eight patients with oral aluminum phosphide admitted to the Department of Internal Emergency of the Second People's Hospital of Yunnan Province from October 2009 to October 2016 were divided into a mild poisoning group (39 cases), a moderate poisoning group (26 cases) and a severe poisoning group (13 cases) according to clinical manifestations and laboratory examinations, all the patients were treated with continuous gastrointestinal decompression after early gastric lavage with edible oil, including scavenging toxicant, correcting intracellular oxygen intake and metabolic disturbance, and inhibiting and eliminating inflammatory mediators. The difference of remission times of clinical symptoms, recovery times of abnormal indexes and hospitalization times were compared among patients with different disease severities. Results With the aggravation of disease, the remission times of clinical symptoms (hours: from mild to severe were 24±12, 54±18, 84±12), recovery times of abnormal indexes (hours: from mild to severe were 18±6, 72±0, 108±12) and hospitalization times (hours: from mild to severe 48±24, 120±24, 144±24) were all gradually extended. Of the 13 patients with severe poisoning, 2 patients died of multiple organ functional failure (MOF) after 28 hours of treatment because they were incapable of cooperating with continuous gastrointestinal decompression. There were 76 patients were clinically cured, the cure rate being 97.4%. In the follow-ups at 1 month and 6 months after the treatment, no abnormalities were seen.Conclusion Continuous gastrointestinal decompression after early gastric lavage with edible oil for saving patients with oral aluminum phosphide poisoning is an effective therapy worthwhile to be popularized.

Cognitive dysfunction,as a common symptom among patients with chronic fatigue syndrome (CFS) and patients with fibromyalgia(FM),impacts on life quality,occupation and study of these patients.However,the neural correlates to the cognitive impairment are unknown.Event related potentials,which reflect the information processing objectively and constantly,provide possibility for taking a insight into and estimating the dysfunction.By summarizing and analyzing studies in event related potentials about chronic fatigue syndrome,fibromyalgia,we found that CFS patients were characterized with prolonged latency of N200 and P300 accompanied by decreased P300 amplitude when they performed on Oddball paradigm,fibromyalgia patients were characterized with lower P300 amplitude when they concentrated on Oddball task,meanwhile,fibromyalgia patients also showed decreased P100/N100,P200,P300,LPC in emotional word decision task and somatic pictures decision task.It's suggests that the cognitive dysfunction in CFS is mainly caused by slowed speed of information identification and classification,whereas in FM it's dysregulation in attention control system results in the cognitive dysfunction.Limitations in current studies and prospects on researches about cognitive dysfunction in CFS for future were also discussed.