Objective:To investigate the diagnostic value of motility index (MI), time averaged mean velocity (TAMV) and blood lactic acid level for acute gastrointestinal injury(AGI) in critical patients.Methods:Patients were enrolled from January 2018 to June 2019 in Department of Emergency Intensive Care Unit, the People's Hospital of Guangxi Zhuang Autonomous Region. Patients were divided into the AGI group and control group according to whether there was acute gastrointestinal injury. Patients’ general information and AGI characteristics were assessed. Area under the receiver operating characteristic (ROC)curve was used to analyze the predictive value of MI, blood lactic acid level and TAMV, or combination on the occurrence of AGI.Results:A total of 73 critical patients were enrolled including 45 patients with AGI and 28 without. Logistic regression analysis found that MI ( OR=2.618, 95% CI: 1.214-5.646, P=0.014), TAMV( OR=1.483, 95% CI: 1.058-2.077, P=0.022), blood lactic acid level( OR=0.360, 95% CI: 0.002-0.865, P=0.040) at admission were independent risk factors for AGI. The sensitivity and specificity of MI, blood lactic acid level and TAMV in predicting AGl were 100% and 89.3%, respectively (AUC=0.982, Youden index=0.893). High blood lactic acid level and low MI and TAMV are independent risk factors for the development of AGI in critical patients. The predictive cut-off values are 4.44 for MI, 45.79 cm/s for TAMV and 5.03 mmol/L for blood lactic acid level. Conclusions:Combination of MI, TAMV and blood lactic acid level has apractical predictive value for AGI incriticalpatients

Echinomycin is a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity, which plays a crucial role in ovarian ovulation in mammalians. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1alpha-mediated endothelin (ET)-2 expressions contributed to ovarian ovulation in response to human chorionic gonadotropin (hCG) during gonadotropin-induced superuvulation. By real-time RT-PCR analysis, ET-2 mRNA level was found to significantly decrease in the ovaries after echinomycin treatment, while HIF-1alpha mRNA and protein expression was not obviously changed. Further analysis also showed that these changes of ET-2 mRNA were consistent with HIF-1 activity in the ovaires, which is similar with HIF-1alpha and ET-2 expression in the granulosa cells with gonadotropin and echinomycin treatments. The results of HIF-1alpha and ET-2 expression in the granulosa cells transfected with cis-element oligodeoxynucleotide (dsODN) under gonadotropin treatment further indicated HIF-1alpha directly mediated the transcriptional activation of ET-2 during gonadotropin-induced superuvulation. Taken together, these results demonstrated that HIF-1alpha-mediated ET-2 transcriptional activation is one of the important mechanisms regulating gonadotropin-induced mammalian ovulatory precess in vivo.
Animals ; Cells, Cultured ; Chorionic Gonadotropin/*pharmacology ; Echinomycin/*pharmacology ; Endothelin-2/genetics/*metabolism ; Female ; Gonadotropins, Equine/*pharmacology ; Granulosa Cells/drug effects/metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & inhibitors/genetics/metabolism/physiology ; Oligonucleotides/genetics ; Ovary/cytology/drug effects/physiology ; Rats ; Rats, Sprague-Dawley ; Superovulation/*drug effects ; Transcriptional Activation

DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.