[Different methods in predicting mortality of pediatric intensive care units sepsis in Southwest China].

Objective: To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China. Methods: This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis. Results: Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) (Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS (Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion: Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

IL-22 relieves sepsis-induced liver injury via activating JAK/STAT3 signaling pathway.

The purpose of this study was to investigate the influence of interleukin(IL)-22 on the Janus kinase/ signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway and sepsis-induced liver injury in rats. A total of 48 Sprague-Dawley rats were randomly divided into sham-operated group (n=12), model group (n=12), low-dose group (n=12) and high-dose group (n=12). Next, rat models of sepsis-induced liver injury were established through cecal ligation and puncture (CLP). At 12 h after surgery, blood was collected by heart puncture to detect liver function of the rats. It was found that the activity of alanine aminotransferase (ALT) and aspartame aminotransferase (AST) and the content of total bilirubin were reduced in low-dose group and high-dose group. Hematoxylin-eosin (HE) staining results revealed that after treatment with IL-22, the liver injury was relieved compared with model group. Moreover, the results of TUNEL staining assay revealed that the apoptosis level of liver cells declined after treatment with IL-22. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that the levels of IL-6 and TNF-α were reduced, while the level of IL-10 was increased after treatment with IL-22. Moreover, it was discovered that the SOD content was overtly elevated in low-dose and high-dose groups compared with that in the model group. Finally, using Western blotting, it was confirmed that in comparison with the model group, the levels of Bcl-2/Bax and JAK/STAT3 signaling pathway-related proteins were markedly raised, while the level of Caspase-3 was decreased in the low-dose and high-dose groups. In conclusion, IL-22 can improve liver function, reduce the apoptosis level of liver cells, the expression of apoptosis-related proteins and the release of inflammatory factors, and alleviate liver injury by activating the JAK/STAT3 signaling pathway.

[Changes in quality of life and acceptance of disability of burn patients in rehabilitation treatment stage and the influencing factors].

Objective: To explore the development trajectories of quality of life and acceptance of disability of burn patients in the rehabilitation treatment stage and the influencing factors. Methods: Totally 207 burn patients, including 157 males and 50 females, aged (40±13) years, who were in the rehabilitation treatment stage were selected by convenient sampling method from October 2016 to July 2017 in the Department of Burns of Fujian Medical University Union Hospital for this longitudinal study. At discharge and 1, 3, and 6 months after discharge, the patient's quality of life and acceptance of disability were scored using the Burn Specific Health Scale-Brief and Chinese Version of Acceptance of Disability Scale-Revised respectively. Taking the intercept, the slope, and the curve slope as latent variables, the latent second growth curve model was constructed for the quality of life and the acceptance of disability. The robust maximum likelihood estimation (MLR) method was used to estimate the mean, the variance, and the covariance, so as to analyze the discharge level, the growth rate, the acceleration, and the correlation among them. Taking the acceptance of disability, the gender, the cause of burn, the severity of burn, the existence of complications, the payment way, and the education level as covariates, the latent second growth curve model was constructed for the quality of life. The MLR method was used to estimate the influence of covariates on the discharge level, the growth rate, and the acceleration of the quality of life. Results: At discharge and 1, 3, and 6 months after discharge, the quality of life scores of patients were (102±36), (111±36), (118±37), and (122±37) points respectively, and the acceptance of disability scores were (73±17), (75±17), (77±17), and (78±18) points respectively. The estimated mean intercept of the quality of life and the acceptance of disability were 101.680 and 72.993 respectively at discharge, both of which showed a curve increasing trend in 1, 3, and 6 months after discharge (estimated mean slope=11.024, 3.086, t=15.376, 7.476, P<0.01), and the increasing rate (acceleration) gradually slowed down (estimated mean curve slope=-1.393, -0.426, t=-13.339, -4.776, P<0.01). There were significant individual differences in the discharge level and the acceleration of quality of life of patients (estimated intercept variance=1 174.527, t=9.332; estimated curve slope variance=2.379, t=6.402; P<0.01). There were significant individual differences in the discharge level, the growth rate, and the acceleration of patients' acceptance of disability (estimated intercept variance=267.017, t=9.262; estimated slope variance=32.264, t=2.356; estimated curve slope variance=0.882, t=2.939; P<0.05 or P<0.01). There was no significant correlation among the discharge level, the growth rate, and the acceleration of the quality of life and those of the acceptance of disability of patients (estimated intercept and slope=37.273, -1.457, t=0.859, -0.131; estimated intercept and curve slope=-6.712, -0.573, t=-1.089, -0.248; estimated slope and curve slope=-5.494, -5.988, t=-0.930, -2.512; P>0.05). Among the time-constant covariates, only the severity of burn and the presence of complications had a significant impact on the quality of life of patients at discharge (estimated intercept=-10.721, 5.522, t=-6.229, 1.977, P<0.05 or P<0.01). At discharge and 1, 3, and 6 months after discharge, the level of acceptance of disability had a positive impact on the quality of life of patients (standardized regression coefficient=0.616, 0.669, 0.681, 0.678, t=18.874, 21.660, 22.824, 22.123, P<0.01). Conclusions: The initial levels of quality of life and acceptance of disability of burn patients in the rehabilitation treatment stage are relatively low, both with a curve increasing trend over time, and the increasing rate gradually slows down. Patients with complications and serious burns have poor quality of life at discharge, while the acceptance of disability has a positive impact on the quality of life.

The extracellular matrix protein mindin attenuates colon cancer progression by blocking angiogenesis via Egr-1-mediated regulation.

Mindin, a secreted, highly conserved extracellular matrix (ECM) protein, exerts a broad spectrum of effects on the innate immune system. However, its function in colorectal cancer (CRC) progression is not well established, and its upstream regulation mechanisms remain unclear. Contrary to previous reports, this study used two different enzyme-linked immunosorbent assay (ELISA) kits to show that the serum level of mindin was significantly decreased in CRC patients and that this decreased level is more significantly associated with the early stages of the disease. To explore the regulation of mindin, we used a bioinformatics approach to predict potential transcription factors and determined that early growth response factor (Egr)-1 directly regulates mindin expression at the transcriptional level using dual luciferase, chromatin immunoprecipitation (ChIP) DNA and electrophoretic mobility shift assay (EMSA) methods. Egr-1 regulates mindin mRNA and protein expression in CRC cells, and the protein expression of both Egr-1 and mindin was significantly decreased in tumor lesions of patients compared with adjacent control tissues. Mindin is essential for Egr-1-mediated inhibition of endothelial cell tube formation, and mindin inhibits endotheliocyte proliferation, migration and angiogenic sprouts in vitro. Overexpression of mindin suppressed xenograft tumor growth by blocking angiogenesis instead of directly suppressing CRC cell proliferation. Mechanically, mindin inhibits the hypoxia-induced HIF-1a and VEGFA protein expression in CRC cells and the phosphorylation of VEGFR-2 in endothelial cells. The results suggest that the serum level of mindin can be used as a novel biomarker for early detection of CRC and that the Egr-1/mindin axis is a potential therapeutic target for the inhibition of angiogenesis in CRC development.

Silencing ECHS1 attenuates the proliferation and induces the autophagy of hepatocellular carcinoma via impairing cell metabolism and activating AMPK.

Hepatocellular carcinoma (HCC) is among the most common cancers in the world with a low survival rate. Our previous study showed Short chain enoyl-CoA hydratase (ECHS1) could bind to HBsAg (HBs) and that ECHS1's localization in mitochondria induced HepG2 cell apoptosis. However, the role of the ECHS1 in energy metabolism and autophagy during hepatocellular carcinoma development remains undefined. We aimed to determine what ECHS1 does to energy metabolism and its effects on HCC progression. We performed CCK-8, EdU assays in hepatocellular carcinoma cell lines (HepG2 and HuH7) with stable ECHS1 knock-down. ATP and NADP+/NADPH levels were measured using an colorimetric assay. Our data demonstrated that ECHS1 silencing inhibited cell proliferation and induced autophagy. ECHS1 knockdown did not increase fatty acid synthesis, but decreased cellular ATP. This resulted in AMP-activated protein kinase (AMPK) activation and induced HCC cell autophagy. Our results showed that silencing ECHS1 to attenuate proliferation and induce autophagy may make it a novel cancer therapy target.