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Myocardial ischemia/reperfusion (I/R) injury causes irreversible injury to the heart, thereby causing acute myocardial infarction. Midazolam is a benzodiazepine commonly utilized in anesthesia and intensive care. Research has indicated that midazolam plays a critical role in many diseases; however, the function of midazolam in myocardial injury induced by I/R still needs further investigation. The infarct size and damage to the heart tissues were examined through 2,3,5-triphenyl tetrazolium chloride (TTC) staining and hematoxylin and eosin staining. The creatine kinase-myocardial band isoenzyme, lactate dehydrogenase, and aspartate aminotransferase levels were tested using commercial kits. Cell apoptosis was determined through TUNEL staining or flow cytometry assays. Bax, Bcl-2, cleaved caspase-3, phospho-38 (p-p38), p38, p-JNK, JNK, extracellular signal-regulated kinases (ERK), and p-ERK expression was examined through Western blot. In our study, midazolam was shown to suppress the infarct size and heart tissue damage and reduce myocardial enzyme leakage in I/R rats. Additionally, midazolam was found to retard cardiomyocyte apoptosis in I/R rats. The JNK/p38 MAPK signaling pathway in I/R rats was inhibited by midazolam. Our findings demonstrated that in hypoxia/reoxygenation (H/R)--mediated H9C2 cells, anisomycin abolished the suppressive effects of midazolam on the JNK/p38 MAPK signaling pathway. Next, exploration discovered that anisomycin abolished the cytoprotective effects of midazolam on H/R-treated H9C2 cell apoptosis. In conclusion, this work demonstrated that midazolam retarded I/R-induced cardiomyocyte apoptosis by inhibiting the JNK/p38 MAPK signaling pathway. These results may provide new insight into the treatment of myocardial I/R injury. Key words: midazolam, ischemia/reperfusion, anisomycin, JNK/p38 MAPK signaling pathway. Les lesions d'ischemie-reperfusion (I/R) myocardiques entrainent des lesions irreversibles dans le creur, et consequemment l'infarctus du myocarde aigu. Le midazolam est une benzodiazepine qui est couramment utilisee en anesthesiologie et aux soins intensifs. Des recherches ont montre que le midazolam joue un role crucial dans de nombreuses maladies. Cependant, le fonctionnement du midazolam dans les lesions myocardiques engendrees par l'I/R demande toujours d'etre etudie plus en detail. Nous avons examine la taille de l'infarctus et les dommages aux tissus cardiaques a l'aide des colorations par le TTC (chlorure de 2,3,5-triphenyl tetrazolium) et l'hematoxyline-eosine. Nous avons mesure les taux de l'isoenzyme CK-MB (pour << creatine kinasemyocardial band >>) et de LDH (deshydrogenase lactique) ainsi que l'activite de l'AST (aspartate aminotransferase) a l'aide de kits commerciaux. Nous avons etabli l'apoptose cellulaire a l'aide de la coloration par l'epreuve de TUNEL ou la cytometrie en flux. Nous avons examine l'expression de Bax, de Bcl-2, de la caspase-3 clivee, de p- p38, de p38, de p-JNK, de JNK, de p-ERK et d'ERK a l'aide de l'immunobuvardage de Western. Dans notre etude, nous avons observe que le midazolam permet d'attenuer les dommages sur le plan de la taille de l'infarctus et des lesions dans le tissu cardiaque, ainsi que de faire diminuer les fuites d'enzymes myocardiques chez des rats exposes a une I/R. De plus, nous avons observe que le midazolam permet de retarder l'apoptose des cardiomyocytes chez ces animaux. Le midazolam entrainait chez eux une inhibition de la voie de signalization JNK/p38 MAPK. Nos resultats ont montre que dans les cellules H9C2 mediees par l'hypoxie- reoxygenation, l'anisomycine entrainait une inhibition des effets suppresseurs du midazolam sur la voie de signalization JNK/p38 MAPK. Ensuite, nos travaux ont permis d'observer que l'anisomycine entrainait une inhibition des effets cytoprotecteurs du midazolam sur l'apoptose des cellules H9C2 exposees a l'H/R. En conclusion, ce travail a montre que le midazolam permet de retarder l'apoptose des cardiomyocytes engendree par l'I/R par l'intermediaire de l'inhibition de la voie de signalization JNK/p38 MAPK. Ces resultats pourraient apporter de nouvelles options pour le traitement des lesions d'I/R myocardiques. [Traduit par la Redaction] Mots-cles: midazolam, ischemie-reperfusion, anisomycine, voie de signalization JNK/p38 MAPK., Introduction Ischemic heart disease is the main cause of human death. The mortality caused by myocardial ischemia is increasing year by year (Doxey 2019; Ambrose 2006). Myocardial ischemia/reperfusion (I/R) injury [...]

Aiming at the fluency problem of extractive method, the accuracy problem of abstractive method, and the important information missing problem caused by truncating the original document before document encoding, this paper proposes a two-stage long document summarization model SFExt-PGAbs. It is composed of submodular function for extractive summarization SFExt and pointer generator for abstractive summarization PGAbs. SFExt-PGAbs simulates the human process of summarizing a long document. First, SFExt is used to extract important sentences from the long document and filter the unimportant and redundant sentences to form a transitional document. Then, PGAbs receives the transitional document as input to generate a fluent and accurate summary. In order to get a transitional document that is closer to the original document-centered idea, this paper expands the two sub-aspects of positional importance and accuracy in the traditional SFExt, and designs a new greedy algorithm at the same time. In order to study the effect of different feature extractors on the quality of the generated summary, two kinds of recurrent neural networks are applied in PGAbs. The experimental results show that on the CNNDM test set, SFExt-PGAbs generates a more fluent and more accurate summary compared with the baseline model, and the ROUGE indicators are significantly improved. At the same time, the expanded sub-aspects of SFExt can extract more accurate summary.

The size and structural control of particulate carriers for imaging agents and therapeutics are constant themes in designing smart delivery systems. This is motivated by the causal relationship between geometric parameters and functionalities of delivery vehicles. Here, both in vitro and in vivo, the controlling factors for cytotoxicity, photothermal, and anti‐tumor effects of biodegradable magnesium@poly(lactic‐co‐glycolic acid (Mg@PLGA) particulate carriers with different sizes and shell thicknesses are investigated. Mg@PLGA microspheres fabricated by microfluidic emulsification are shown to have higher Mg encapsulation efficiency, 87%, than nanospheres by ultrasonic homogenization, 50%. The photothermal and anti‐tumor effects of Mg@PLGA spheres are found to be dictated by their Mg content, irrelevant to size and structural features, as demonstrated in both in vitro cell assays and in vivo mice models. These results also provide important implications for designing and fabricating stimuli‐responsive drug delivery vehicles. [ABSTRACT FROM AUTHOR]

Purpose: To compare the clinical characteristics of pregnant women and perinatal outcomes with or without recurrent severe intrahepatic cholestasis of pregnancy (sICP), and identify possible factors associated with disease recurrence., Methods: A retrospective study of 164,603 deliveries was performed to identify pregnant women diagnosed with sICP in the previous pregnancy from January 2012 to December 2020. Eligible patients were divided into two subgroups according to the status of disease recurrence in the second pregnancy: recurrent severe ICP (r-sICP) and non-recurrent severe ICP (nr-sICP). Demographics, clinical characteristics, maternal and perinatal outcomes, and potential factors linked to disease recurrence were analyzed., Results: Totally 118 patients were enrolled and respectively classified into the r-sICP group ( n  = 63) and the nr-sICP group ( n  = 55). The proportion of hepatitis B virus (HBV) infection (HBsAg+, HBeAg+, HBcAb+) and early-onset ICP (<28 weeks) in the r-sICP group in the previous pregnancy were higher than those in the nr-sICP group. In the second delivery, neonatal outcomes in the r-sICP group were worse than those in the nr-sICP group. Logistic regression analysis of predictive factors for disease recurrence in the second delivery revealed that the combination of HBV infection and early-onset ICP in the previous delivery had the steepest receiver-operating characteristic (ROC) curve value 0.720 (95%CI: 0.629-0.812)., Conclusion: Patients with sICP displayed a higher recurrence rate in the second pregnancy. Being <28 weeks at the time of ICP diagnosis and having HBV infection in the previous delivery appear to be independent predictive factors for disease recurrence of sICP.