PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

Acute liver injury (ALI) is one of the common severe diseases in clinic, which is characterized by redox imbalance and inflammatory storm. Untimely treatment can easily lead to liver failure and even death. Rosmarinic acid (RA) has been proved to have anti-inflammatory and antioxidant activity, but it is not clear how to protect ALI through antioxidation and inhibition of inflammation. Therefore, this study explored the therapeutic effect and molecular mechanism of RA on ALI through in vitro and in vivo experiments. In the mouse ALI model, the effects of RA on liver function and inflammatory indexes were studied, the pathological changes of liver were observed by HE, the effect of RA on reactive oxygen species in liver was detected by fluorescence method, and the level of F4/80 in liver tissue was detected by immunohistochemical method. The levels of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate specific proteinase-1 (CASPASE-1) in liver tissue were measured by Western blot. All animal welfare and experimental procedures follow the rules of the Animal Ethics Committee of Southwest Minzu University. In vitro, human hepatoma cell line HepG2 was used to establish the model of oxidative damage induced by H₂O₂. The cell viability was detected by CCK-8 method. The level of interleukin-1β (IL-1β) in the supernatant was detected by enzyme linked immunosorbent assay (ELISA), the activity of lactatede hydrogenase (LDH) was detected by LDH kit, and the level of ROS was detected by fluorescence probe DCFH-DA labeling. The mRNA expression of Txnip, Nlrp3, Caspase 1, Il1β was detected by real-time fluorescence quantitative PCR (qPCR), and the protein levels of nuclear factor erythroid-2 related factor 2 (NRF2), TXNIP, NLRP3 and CASPASE-1 were measured by Western blot. The results showed that compared with the model group, the degree of liver swelling, tissue injury, liver function index in RA group were significantly lower than those in model group. And RA significantly attenuated the increases of ROS in liver tissue. The expression levels of TXNIP, NLRP3 and CASPASE-1 in liver tissue were significantly lower than those in model group. Additionally, RA inhibited the expressions of F4/80 and IL-1β. In vitro experiment, compared with model group, RA effectively inhibited the secretion of IL-1β and LDH. The level of ROS also decreased significantly. RA inhibited the mRNA expressions of Txnip, Caspase 1, Il1β. Furthermore, RA significantly increased the expression level of NRF2 protein in nucleus, and decreased the expression level of TXNIP and NLRP3 protein. Specifically, with the addition of ML385, the effect of RA on NRF2, TXNIP, NLRP3, CASPASE-1 protein expression was reversed. Collectively, these findings suggested that RA may inhibit the production of ROS by promoting NRF2 nuclear transfer, and then reduce the activation of NLRP3 inflammatory bodies by TXNIP, reduce cell death and inflammatory response to prevent the liver injury.

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.

Objective To observe the clinical efficacy of Shuangye San(the prescription mainly composed of Mori Folium and Nelumbinis Folium)in the treatment of type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)of spleen deficiency and phlegm stasis type.Methods A total of 80 patients with T2DM complicated with NAFLD of spleen deficiency and phlegm stasis type were randomly divided into a treatment group and a control group,with 40 cases in each group.The control group was treated with conventional western medicine for lowering blood glucose and lipid,protecting liver and lowering enzymes.The treatment group was treated with the granules of Shuangye San orally on the basis of treatment for the control group.The course of treatment lasted for three months.The changes of traditional Chinese medicine(TCM)syndrome scores,homeostasis model assessment of insulin resistance(HOMA-IR),fasting insulin(FINS),fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbA1C),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),liver function indicators and B-ultrasound grading of fatty liver in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After three months of treatment,the total effective rate of the treatment group was 85.00％(34/40),and that of the control group was 70.00％(28/40).The intergroup comparison(tested by chi-square test)showed that the efficacy of the treatment group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the scores of TCM symptoms of obese physique,heaviness and weakness in the limbs,shortness of breath and unwilling to talk,tightness and stabbing pain in the chest,abdominal distension and poor appetite in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of TCM syndrome scores in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the levels of glucose and lipid metabolism indicators of FINS,HOMA-IR,FBG,2hPG,HbA1C,TC,TG and LDL-C in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the level of HDL-C was significantly increased compared with that before treatment(P＜0.05).The decrease of FINS,HOMA-IR,FBG,2hPG,HbA1C,TC,TG and LDL-C levels and the increase of HDL-C levels in the treatment group were significantly superior to those in the control group(P＜0.05).(4)After treatment,the levels of liver function indicators of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and gamma-glutamyl transpeptidase(GGT)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of liver function indicators in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the B-ultrasound grading of fatty liver of the two groups was significantly improved compared with that before treatment(P＜0.05),and the improvement of fatty liver B-ultrasound grading in the treatment group was significantly superior to that in the control group,and the difference was statistically significant(P＜0.05).(6)During the treatment,there were no adverse reactions such as impairment of liver and kidney function and abnormalities in routine blood,urine and stool test in the two groups.Conclusion Shuangye San exerts certain effect in the treatment of T2DM complicated with NAFLD of spleen deficiency and phlegm stasis type.It can alleviate the clinical symptoms of patients,correct the disorder of glucose and lipid metabolism,and improve liver function and fatty liver B-ultrasound grading.

Objective:Constructing a framework to assess health inequality among migrants through the perspective of medical insurance,this study examines the inequalities and underlying mechanisms affecting China's internal migrants. Methods:Data were extracted from the 2017 and 2018 China Migrants Dynamic Survey Datasets. The health equity measurement framework developed by Dover,the concentration index and its decomposition method were used to analyse the characteristics and mechanisms of health inequality among migrants. Results:The results showed that the migrants with higher income levels performed better on medical services utilization,medical insurance services utilization,and health outcomes. Medical insurance significantly influenced the inequality in medical services utilization and medical insurance services utilization within the migrants,yet its direct effect on health outcomeswas minor. Conclusion:The impact of medical insurance on health inequality among migrants showed multi-level characteristics. The social stratification effect and the differences in health social effects of medical insurance are the internal mechanisms that lead to health inequality. It is suggested to enhance the equality of medical security of migrants through financing,benefits,and administration to reduce inequality in the medical services utilization,medical insurance services utilization,and health outcomes among China's internal migrants.

Objective:Constructing a framework to assess health inequality among migrants through the perspective of medical insurance,this study examines the inequalities and underlying mechanisms affecting China's internal migrants. Methods:Data were extracted from the 2017 and 2018 China Migrants Dynamic Survey Datasets. The health equity measurement framework developed by Dover,the concentration index and its decomposition method were used to analyse the characteristics and mechanisms of health inequality among migrants. Results:The results showed that the migrants with higher income levels performed better on medical services utilization,medical insurance services utilization,and health outcomes. Medical insurance significantly influenced the inequality in medical services utilization and medical insurance services utilization within the migrants,yet its direct effect on health outcomeswas minor. Conclusion:The impact of medical insurance on health inequality among migrants showed multi-level characteristics. The social stratification effect and the differences in health social effects of medical insurance are the internal mechanisms that lead to health inequality. It is suggested to enhance the equality of medical security of migrants through financing,benefits,and administration to reduce inequality in the medical services utilization,medical insurance services utilization,and health outcomes among China's internal migrants.

Objective: To investigate the differences in clinical characteristics, diagnosis, and treatment of pediatric septic shock in pediatric intensive care unit (PICU) among hospitals of different levels. Methods: This retrospective study enrolled 368 children with septic shock treated in the PICU of Beijing Children's Hospital, Henan Children's Hospital, and Baoding Children's Hospital from January 2018 to December 2021. Their clinical data were collected, including the general information, location of onset (community or hospital-acquired), severity, pathogen positivity, consistence of guideline (the rate of standard attainment at 6 h after resuscitation and the rate of anti-infective drug administration within 1 h after diagnosis), treatment, and in-hospital mortality. The 3 hospitals were national, provincial, and municipal, respectively. Furthermore, the patients were divided into the tumor group and the non-tumor group, and into the in-hospital referral group and the outpatient or emergency admission group. Chi-square test and Mann-Whitney U test were used to analyze the data. Results: The 368 patients aged 32 (11, 98) months, of whom 223 were males and 145 females. There were 215, 107, and 46 patients with septic shock, with males of 141, 51, and 31 cases, from the national, provincial, and municipal hospitals, respectively. The difference in pediatric risk of mortality Ⅲ (PRISM Ⅲ) scores among the national,provincial and municipal group was statistically significant (26(19, 32) vs.19(12, 26) vs. 12(6, 19), Z=60.25,P<0.001). The difference in community acquired septic shock among the national,provincial and municipal group was statistically significant (31.6%(68/215) vs. 84.1%(90/107) vs. 91.3%(42/46), χ²=108.26,P<0.001). There were no significant differences in compliance with guidelines among the 3 groups (P>0.05). The main bacteria detected in the national group were Klebsiella pneumoniae (15.4% (12/78)) and Staphylococcus aureus (15.4% (12/78)); in the provincial group were Staphylococcus aureus (19.0% (12/63)) and Pseudomonas aeruginosa (12.7% (8/63)), and in the municipal group were Streptococcus pneumoniae (40.0% (10/25)) and Enteric bacilli (16.0% (4/25)). The difference in the proportion of virus and the proportion of 3 or more initial antimicrobials used among the national,provincial and municipal group was statistically significant (27.7% (43/155) vs. 14.9% (13/87) vs. 9.1% (3/33), 22.8%(49/215) vs. 11.2%(12/107) vs. 6.5%(3/46), χ²=8.82, 10.99, both P<0.05). There was no difference in the in-hospital mortality among the 3 groups (P>0.05). Regarding the subgroups of tumor and non-tumor, the national group had higher PRISM Ⅲ (31(24, 38) vs. 22 (21, 28) vs.16 (9, 22), 24 (18, 30) vs. 17(8, 24) vs. 10 (5, 16), Z=30.34, 10.45, both P<0.001), and it was the same for the subgroups of in-hospital referral and out-patient or emergency admission (29 (21, 39) vs. 23 (17, 30) vs. 15 (10, 29), 23 (17, 29) vs. 18 (10, 24) vs. 11 (5, 16), Z=20.33, 14.25, both P<0.001) as compared to the provincial and municipal group. There was no significant difference in the in-hospital mortality among the 2 pairs of subgroups (all P>0.05). Conclusion: There are differences in the severity, location of onset, pathogen composition, and initial antibiotics of pediatric septic shock in children's hospitals of different levels, but no differences in compliance with guidelines and in-hospital survival rate.
Female ; Male ; Humans ; Child ; Retrospective Studies ; Shock, Septic/therapy* ; Hospitalization ; Intensive Care Units, Pediatric ; Hospitals, Pediatric