OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

Objective:To construct a nursing norm for extracorporeal membrane oxygenation in adults, so as to provide a reference for improving the nursing care of adult extracorporeal membrane oxygenation.Methods:The first draft was developed through literature search and expert discussion. From September to October 2023, 16 experts were selected using the Delphi method to conduct two rounds of expert consultation on the first draft, and the final draft was revised with reference to the experts' comments. The expert positivity coefficient was expressed as the effective recovery rate of the questionnaire, and the degree of expert authority was evaluated with the authority coefficient, and the degree of harmonization of expert opinions was assessed with the Kendall's harmony coefficient.Results:Literature search screened a total of four guidelines and five expert consensus. In the two rounds of consultation, the effective recovery rates of the questionnaires were all 100% (16/16), and the expert authority coefficients were all 0.900, and the Kendall's harmony coefficients of the overall indicators were 0.581 and 0.666, respectively (both P<0.01). The final constructed nursing norm for extracorporeal membrane oxygenation in adults included five primary indicators, 27 secondary indicators, and 17 tertiary indicators. Conclusions:The constructed nursing norm for extracorporeal membrane oxygenation in adults is scientific, reliable and feasible, and can guide clinical nursing staff to carry out nursing care for extracorporeal membrane oxygenation.

Objective:To optimize the anticoagulation monitoring process for extracorporeal membrane oxygenation (ECMO) patients by constructing an informatization module and evaluate its application effect.Methods:An informatization team was established, and based on literature review, an anticoagulation monitoring information sheet for ECMO patients was developed. Using a data-sharing architecture, existing hospital information management system, laboratory information management system, picture archiving and communication system, and ICU monitoring system were integrated to construct an ECMO anticoagulation monitoring informatization module with data sharing, real-time alerts, and information support functions. Clinical applications were observed for effect. A convenience sampling method was employed to select 60 ECMO patients treated in the ICU of the Affiliated Hospital of Qingdao University from October 2022 to September 2023. The patients admitted from October 2022 to March 2023 were designated as the control group ( n=30), using the conventional anticoagulation monitoring method; those admitted from April to September 2023 were designated as the experimental group ( n=30), using the anticoagulation monitoring informatization module. The anticoagulation monitoring timeliness rate, anticoagulant drug adjustment timeliness rate, and the incidence rates of thrombosis and bleeding were compared between the two groups. Results:The timeliness rate of anticoagulation monitoring and the timeliness rate of anticoagulant drug adjustment in the experimental group were (93.38±6.31) % and (91.90±4.71) %, respectively, which were higher than those in the control group (83.01±9.94) % and (83.49±12.83) %, with statistically significant differences (both P<0.01). The incidence rates of thrombosis and bleeding in the experimental group were 16.67% (5/30) and 26.67% (8/30), respectively, which were lower than those in the control group 40.00% (12/30) and 53.33% (16/30), with statistically significant differences (both P<0.05) . Conclusions:The optimized anticoagulation monitoring informatization process based on the anticoagulation monitoring informatization module demonstrates a good clinical application effect and can reduce the incidence of bleeding and thrombosis in ECMO patients.

Objective:To construct a nursing norm for extracorporeal membrane oxygenation in adults, so as to provide a reference for improving the nursing care of adult extracorporeal membrane oxygenation.Methods:The first draft was developed through literature search and expert discussion. From September to October 2023, 16 experts were selected using the Delphi method to conduct two rounds of expert consultation on the first draft, and the final draft was revised with reference to the experts' comments. The expert positivity coefficient was expressed as the effective recovery rate of the questionnaire, and the degree of expert authority was evaluated with the authority coefficient, and the degree of harmonization of expert opinions was assessed with the Kendall's harmony coefficient.Results:Literature search screened a total of four guidelines and five expert consensus. In the two rounds of consultation, the effective recovery rates of the questionnaires were all 100% (16/16), and the expert authority coefficients were all 0.900, and the Kendall's harmony coefficients of the overall indicators were 0.581 and 0.666, respectively (both P<0.01). The final constructed nursing norm for extracorporeal membrane oxygenation in adults included five primary indicators, 27 secondary indicators, and 17 tertiary indicators. Conclusions:The constructed nursing norm for extracorporeal membrane oxygenation in adults is scientific, reliable and feasible, and can guide clinical nursing staff to carry out nursing care for extracorporeal membrane oxygenation.

Objective:To optimize the anticoagulation monitoring process for extracorporeal membrane oxygenation (ECMO) patients by constructing an informatization module and evaluate its application effect.Methods:An informatization team was established, and based on literature review, an anticoagulation monitoring information sheet for ECMO patients was developed. Using a data-sharing architecture, existing hospital information management system, laboratory information management system, picture archiving and communication system, and ICU monitoring system were integrated to construct an ECMO anticoagulation monitoring informatization module with data sharing, real-time alerts, and information support functions. Clinical applications were observed for effect. A convenience sampling method was employed to select 60 ECMO patients treated in the ICU of the Affiliated Hospital of Qingdao University from October 2022 to September 2023. The patients admitted from October 2022 to March 2023 were designated as the control group ( n=30), using the conventional anticoagulation monitoring method; those admitted from April to September 2023 were designated as the experimental group ( n=30), using the anticoagulation monitoring informatization module. The anticoagulation monitoring timeliness rate, anticoagulant drug adjustment timeliness rate, and the incidence rates of thrombosis and bleeding were compared between the two groups. Results:The timeliness rate of anticoagulation monitoring and the timeliness rate of anticoagulant drug adjustment in the experimental group were (93.38±6.31) % and (91.90±4.71) %, respectively, which were higher than those in the control group (83.01±9.94) % and (83.49±12.83) %, with statistically significant differences (both P<0.01). The incidence rates of thrombosis and bleeding in the experimental group were 16.67% (5/30) and 26.67% (8/30), respectively, which were lower than those in the control group 40.00% (12/30) and 53.33% (16/30), with statistically significant differences (both P<0.05) . Conclusions:The optimized anticoagulation monitoring informatization process based on the anticoagulation monitoring informatization module demonstrates a good clinical application effect and can reduce the incidence of bleeding and thrombosis in ECMO patients.

Objective To analyze the characteristics and risk factors of healthcare-associated infection(HAI)in patients receiving veno-venous extracorporeal membrane oxygenation(V-V ECMO)treatment.Methods Clinical data of 141 patients who received V-V ECMO treatment in the intensive care unit(ICU)of a tertiary first-class hos-pital in Qingdao from January 2019 to November 2023 were collected.Patients were divided into the infection group and non-infection group based on whether HAI occurred.Characteristics of HAI were analyzed,risk factors were analyzed by univariate and multivariate logistic regression analyses.Results Among 141 V-V ECMO patients,inci-dence of HAI was 37.59％(n=53).A total of 81 strains of pathogens were isolated from patients in the infection group,Gram-negative bacteria accounted for 56.79％(n=46),mainly Acinetobacter baumannii,which was up to 28.39％(carbapenem-resistant Acinetobacter baurnannii[CRAB]accounted for 16.05％).The main type of HAI in V-V ECMO patients was pulmonary infection alone(54.72％),followed by bloodstream infection alone(20.75％),multi-site infection accounted for 22.64％.Univariate analysis result showed that compared with the non-infection group,there were statistically significant differences in the history of immunosuppressive agents use,ICU transfer history,surgical history,fiberbronchoscopy,renal replacement therapy,duration of ICU stay,duration of tracheal intubation and/or tracheotomy,duration of urinary catheterization,duration of gastric tube placement,duration of central venous catheterization,duration of antimicrobial use,and duration of V-V ECMO support(all P＜0.05).Multivariate logistic regression analysis result showed that ICU transfer history and fiberbronchoscopy were inde-pendent risk factors for HAI in V-V ECMO patients(OR=6.850,4.643,respectively,both P＜0.05).Conclusion Hospitals should take effective prevention and control measures based on the characteristics and related risk factors of HAI in patients receiving V-V ECMO treatment to reduce the occurrence of HAI.

Objective To analyze the characteristics and risk factors of healthcare-associated infection(HAI)in patients receiving veno-venous extracorporeal membrane oxygenation(V-V ECMO)treatment.Methods Clinical data of 141 patients who received V-V ECMO treatment in the intensive care unit(ICU)of a tertiary first-class hos-pital in Qingdao from January 2019 to November 2023 were collected.Patients were divided into the infection group and non-infection group based on whether HAI occurred.Characteristics of HAI were analyzed,risk factors were analyzed by univariate and multivariate logistic regression analyses.Results Among 141 V-V ECMO patients,inci-dence of HAI was 37.59％(n=53).A total of 81 strains of pathogens were isolated from patients in the infection group,Gram-negative bacteria accounted for 56.79％(n=46),mainly Acinetobacter baumannii,which was up to 28.39％(carbapenem-resistant Acinetobacter baurnannii[CRAB]accounted for 16.05％).The main type of HAI in V-V ECMO patients was pulmonary infection alone(54.72％),followed by bloodstream infection alone(20.75％),multi-site infection accounted for 22.64％.Univariate analysis result showed that compared with the non-infection group,there were statistically significant differences in the history of immunosuppressive agents use,ICU transfer history,surgical history,fiberbronchoscopy,renal replacement therapy,duration of ICU stay,duration of tracheal intubation and/or tracheotomy,duration of urinary catheterization,duration of gastric tube placement,duration of central venous catheterization,duration of antimicrobial use,and duration of V-V ECMO support(all P＜0.05).Multivariate logistic regression analysis result showed that ICU transfer history and fiberbronchoscopy were inde-pendent risk factors for HAI in V-V ECMO patients(OR=6.850,4.643,respectively,both P＜0.05).Conclusion Hospitals should take effective prevention and control measures based on the characteristics and related risk factors of HAI in patients receiving V-V ECMO treatment to reduce the occurrence of HAI.

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

The present study investigated the pharmaceutical effect and underlying mechanism of Zexie Decoction(ZXD) on nonalcoholic fatty liver disease(NAFLD) in vitro and in vivo via the LKB1/AMPK/PGC-1α pathway based on palmitic acid(PA)-induced lipid accumulation model and high-fat diet(HFD)-induced NAFLD model in mice. As revealed by the MTT assay, ZXD had no effect on HepG2 activity, but dose-dependently down-regulated alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver cell medium induced by PA, and decreased the plasma levels of ALT and AST, and total cholesterol(TC) and triglyceride(TG) levels in the liver. Nile red staining showed PA-induced intracellular lipid accumulation, significantly increased lipid accumulation of hepatocytes induced by PA, suggesting that the lipid accumulation model in vitro was properly induced. ZXD could effectively improve the lipid accumulation of hepatocytes induced by PA. Oil red O staining also demonstrated that ZXD improved the lipid accumulation in the liver of HFD mice. JC-1 staining for mitochondrial membrane potential indicated that ZXD effectively reversed the decrease in mitochondrial membrane potential caused by hepatocyte injury induced by PA, activated PGC-1α, and up-regulated the expression of its target genes, such as ACADS, CPT-1α, CPT-1β, UCP-1, ACSL-1, and NRF-1. In addition, as revealed by the Western blot and immunohistochemistry, ZXD up-regulated the protein expression levels of LKB1, p-AMPK, p-ACC, and PGC-1α in vivo and in vitro. In conclusion, ZXD can improve NAFLD and its mechanism may be related to the regulation of the LKB1/AMPK/PGC-1α pathway.
AMP-Activated Protein Kinases/metabolism* ; Alanine Transaminase/metabolism* ; Animals ; Diet, High-Fat ; Liver/metabolism* ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/genetics* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

Taking lipophagy as the breakthrough point, we explored the mechanism of Zexie Decoction(ZXD) in improving lipid metabolism in the hepatocyte model induced by palmitic acid(PA) and in the animal model induced by high-fat diet(HFD) on the basis of protein kinase B(Akt)/transcription factor EB(TFEB) signaling pathway. Co-localization was carried out for the microtubule-associated protein light chain 3(LC3) plasmid labeled with green fluorescent protein(GFP) and lipid droplets(LDs), and immunofluorescence co-localization for liver LC3 of HFD mice and perilipin 2(PLIN2). The results showed that ZXD up-regulated the expression of LC3, reduced lipid accumulation in hepatocytes, and increased the co-localization of LC3 and LDs, thereby activating lipo-phagy. Western blot results confirmed that ZXD increased autophagy-related protein LC3Ⅱ/LC3Ⅰ transformation ratio and lysosome-associated membrane protein 2(LAMP2) in vivo and in vitro and promoted the degradation of sequestosome-1(SQSTM1/p62)(P<0.05). The results above jointly explained that ZXD regulated lipophagy. Furthermore, ZXD activated TFEB expression(P<0.05) and reversed the PA-and HFD-induced decrease of TFEB nuclear localization in hepatocytes(P<0.05). Meanwhile, ZXD activated liver TFEB to up-regulate the expression of the targets Lamp2, Lc3 B, Bcl2, and Atg5(P<0.05). Additionally, ZXD down-regulated the protein level of p-Akt upstream of TFEB in vivo and in vitro. In conclusion, ZXD may promote lipophagy by regulating the Akt/TFEB pathway.
Animals ; Mice ; Autophagy/drug effects* ; Hepatocytes/metabolism* ; Microtubule-Associated Proteins/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology*