Objective To study the influence of ANGPTL8 in lipopolysaccharide(LPS)-induced hepatic lipid deposition.Methods Male wild-type(WT)and ANGPTL8 knockout mice at 6-8 weeks were used to induce sepsis models by intrabitoneal injection of LPS(10 mg/kg).qPCR and immunofluorescence were used to detected the mRNA and protein expression of ANGPTL8 in liver tissue and HepG2 cells respectively;The contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST)in serum and the triglyceride(TG)and malondialdehyde(MDA)in liver homogenate were detected by kits;the histopathological changes of liver tissue were analyzed through HE staining.Lipids accumulation in liver were detected by oil red O staining.The apoptosis of liver was determinated by TUNEL staining.RNA-seq was used to analyzing the differentially expressed genes in the liver tissue of WT and ANGPTL8 KO mice,and the qPCR and Western Blot were used to verify the differential expressed genes.Results The expression of ANGPTL8 in the liver was significantly upregulated at 48 hours after LPS stimulation.Compared with WT mice,the hepatic lipid deposition,steatosis,and apoptosis were significantly alleviated in liver of ANGPTL8 KO mice,the ALT and AST levels in serum and the TG and MDA content in liver homogenate of ANGPTL8 KO mice were also reduced significantly.The expression of caveolin-1(CAV1)in liver of ANGPTL8 KO mice was significantly higher than that of WT mice.Conclusions LPS promoted the expression and secretion of ANGPTL8 in liver tissue,and ANGPTL8 increased hepatic lipid deposition and peroxidation by inhibiting the expression of CAV1.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Background: Job performance is known as an essential reflection of nursing quality. Colleague solidarity, positive emotion, and turnover intention play effective roles in a clinical working environment, but their impacts on job performance are unclear. Investigating the association between nurses’ colleague solidarity and job performance may be valuable, both directly and through the mediating roles of positive emotion and turnover intention. Methods: In this cross-sectional study, a total of 324 Chinese nurses were recruited by convenience sampling method from July 2016 to January 2017. Descriptive analysis, Spearman’s correlation analysis, and the structural equation model were applied for analysis by SPSS 26.0 and AMOS 24.0. Results: A total of 49.69% of participants were under 30 years old, and 90.12% of participants were female. Colleague solidarity and positive emotion were positively connected with job performance. The results indicated the mediating effects of positive emotion and turnover intention in this relationship, respectively, as well as the chain mediating effect of positive emotion and turnover intention. Conclusions In conclusion, dynamic and multiple supportive strategies are needed for nurse managers to ameliorate nursing job performance by improving colleague solidarity and positive emotion and decreasing turnover intention based on the job demand-resource model.

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.
Humans ; NF-kappa B/metabolism* ; Lipopolysaccharides/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Acute Lung Injury/metabolism* ; Lung ; Phosphate-Binding Proteins/therapeutic use* ; Pore Forming Cytotoxic Proteins/therapeutic use*

Pyroptosis， an atypical new cell death mode other than apoptosis and necrosis， has been discovered in recent years. Pyroptosis depends on the cleavage of gasdermins （GSDMs） by Caspases. The activated GSDMs act on the plasma membrane to form a perforation， which results in cell lysis and triggers inflammation and immune response. Pyroptosis can be induced by four distinct signaling pathways， including canonical and non-canonical inflammasome pathways， apoptosis-associated Caspases-mediated pathway， and granzyme pathway. In these signaling pathways， GSDMs are the executors of pyroptosis. Pyroptosis is associated with the death of tumor cells and the inflammatory damage of normal tissues. Recent studies have demonstrated that moderate pyroptosis can lead to tumor cell death to exert an anti-tumor effect， and meanwhile stimulate the tumor immune microenvironment， while it can promote tumor development. Despite the good performance， drug-based anti-tumor therapies such as tumor immunotherapy， chemotherapy， and targeted therapy have some shortcomings such as drug resistance， recurrence， and damage to normal tissues. The latest research shows that a variety of natural compounds have anti-tumor effects in the auxiliary treatment of tumors by mediating the pyroptosis pathways in a multi-target and multi-pathway manner， which provide new ideas for the study of anti-tumor therapy. We reviewed the molecular mechanism of pyroptosis and the regulatory role of pyroptosis in tumors and tumor immune microenvironment， and summarized the recent research progress in the natural medicinal components regulating pyroptosis in anti-tumor therapy， with a view to providing ideas for the research on the anti-tumor therapy based on pyroptosis.

Objective:To evaluate the effect of age factors on the pharmacodynamics of intranasal dexmedetomidine for sedation in the pediatric patients undergoing transthoracic echocardiography(TTE).Methods:American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ pediatric patients, aged 1-24 months, undergoing TTE from August 2019 to May 2022, were selected. This trial was performed in two parts. Part Ⅰ Pediatric patients were divided into 4 age groups: 1-6 month group, 7-12 month group, 13-18 month group and 19-24 month group. The initial dose of dexmedetomidine was 2.0 μg/kg in 0.1 μg/kg increment/decrement. The dose of dexmedetomidine was determined by using modified Dixon′s up-and-down method. The ED 50 and 95% confidence interval of intranasally administered dexmedetomidine for sedation were calculated by the Dexon-Massey method. Part Ⅱ One hundred patients were divided into 4 age groups ( n= 25 each): 1-6 month group, 7-12 month group, 13-18 month group and 19-24 month group. The 4 groups were further divided into 5 subgroups ( n=5 each) according to the dose of dexmedetomidine: 2.1 μg/kg subgroup, 2.2 μg/kg subgroup, 2.3 μg/kg subgroup, 2.4 μg/kg subgroup, and 2.5 μg/kg subgroup. Part Ⅰ and part Ⅱ trials were combined, and the ED 95 and 95% confidence interval of intranasally administered dexmedetomidine for sedation were calculated using the probit method. Results:A total of 220 pediatric patients were enrolled. There was no significant difference in ED 50 and ED 95 of dexmedetomidine intranasally administered for sedation among groups ( P>0.05). Conclusions:The pharmacodynamics of intranasal dexmedetomidine for sedation shows no significant difference in age in the pediatric patients aged 1-24 months undergoing TTE.

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

Objective To investigate the mRNA-based anticancer gene transfer in MSCs-mediated cytotox-icity of glioma cells. Methods TRAIL mRNA and PTEN mRNA were synthesized in vitro. Immunoblotting assay was used to detect the expression of TRAIL and PTEN in the transfected MSCs.Transwell co-culture was perform to detect the migration ability of MSCs after gene transfection. The bioluminescence,live/dead staining and real time cell analyzer were used to analyze the viability of DBTRG cells. Results Compared with non-transfected MSCs, an enhanced migration rate was observed in MSCs with two kind of mRNA transfection.TRAIL-and PTEN-mRNA-induced cytotoxicity in DBTRG glioma cell was correlated with the ratio of the conditioned medium of the transfect-ed MSCs. A synergistic action was observed in TRAIL and PTEN in the transwell co-culture model. Conclusion The present study reveals the effect of synthesized mRNA-based gene transfer on mesenchymal stem cell-mediated cytotoxicity of glioma cells(DBTRG).

Objective To evaluate the relationship between annexin 1 (ANXA1) and the endogenous protective mechanism during intestinal epithelial cell injury induced by endotoxiu.Methods The intestinal epithelial cells at the logarithmic growth phase were seeded in culture palates and randomly divided into 4 groups (n =36 each) using a random number table:control group (group C),cell injury group (group I),ANXA1 overexpression group (group OE),and ANXA1 silencing group (group S).Lentivirus with ANXA1 overexpression and silencing was transfected into intestinal epithelial cells to construct a stable cell line.In I,OE and S groups,endotoxin was added with the final concentration of 100 μg/ml,and the cells were then incubated for 24 h to establish the cell injury model.The culture medium was changed,and the cells were then incubated for 24 h in group C.The cell apoptosis was detected by flow cytometry,the cell permeability was determined by Transwell assay,and the cell viability was evaluated by methyl thiazolyl tetrazolium assay.The apoptosis rate was calculated.Results Compared with group C,the apoptosis rate was significantly increased,and the cell permeability and viability were significantly decreased in I,OE and S groups (P＜0.05).Compared with group Ⅰ,the apoptosis rate was significantly decreased,the cell permeability and viability were significantly increased in group OE,and the apoptosis rate was significantly increased,and the cell permeability and viability were significantly decreased in group S (P＜0.05).Conclusion ANXA1 is involved in the endogenous protective mechanism during intestinal epithelial cell injury induced by endotoxin.

With the development of molecular imaging technology, incorporate multiple modes of medical imaging imaging techniques of SPECT/CT and PET/CT technology with a certain degree of development. But compared to SPECT/CT and PET/CT technologies, SPECT/CT far earlier than PET/CT technology to clinical applications, due to a variety of factors influence SPECT/CT far PET/CT clinical applications to grow faster. This article highlights the progress and problems of SPECT/CT technology.
Diagnostic Imaging ; Positron-Emission Tomography ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed