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Asparaginase-associated pancreatitis (AAP) is a common and fatal complication after ASNase treatment in acute lymphoblastic leukemia(ALL). Here, a total of 1063 pediatric ALL patients treated with SCCLG-ALL-2016 regimen were collected since October 2016 to June 2020, including 35 patients with AAP. The clinical characteristics of AAP and non-AAP patients were compared. In AAP patients, the possible factors that affected the recurrence of AAP were analyzed, and the possible risk factors related to ALL-relapse were discussed. The results showed that age was a risk factor (P =.017) that affect the occurrence of AAP. In AAP patients, AAP tended to develop after the second use of PEG-ASNase (25.71%). In the follow-up chemotherapy, 17 patients re-exposed to ASNase and 7 cases developed AAP again with a percentage was 41.2%. There were no special factors that related with the recurrence of AAP. This study also found no association between the occurrence of AAP and prognosis of ALL, with the 4-year incidence of ALL relapse in AAP and non-AAP patients were 15.9% v.s.11.7% (HR: 1.009, 95% CI:0.370–2.752, P =.986), and there were no special factors that related with the ALL relapse among AAP patients. Based on the above results, the occurrence of AAP is related to age and should be vigilant after the second use of PEG-ASNase after use in pediatric ALL patients. Moreover, AAP is not associated with ALL relapse, but there is a high AAP recurrence rate when re-exposure to ASNase. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. Our aim was to identify a novel miRNA that can predict prognosis of childhood ALL patients and explore its potential mechanism. The miRNA expression profiles of childhood ALL were analyzed using GEO database and HiSeq instruments. The expression of miR-155 was examined by RT–PCR in 42 ALL patients. To investigate the role of miR-155 in ALL, four ALL cell lines (CEM-C1, Jurkat, MOLT-3 and MOLT-4) were transfected with miR-155 mimics, miR-155 inhibitors or corresponding controls. Dual-luciferase reporter system was applied to confirm the miR-155 target ZNF238. Moreover, proliferation and apoptosis were evaluated by MTT and flow cytometry. Dataset GSE56489 and GSE23024 demonstrated that miR-155 was up-regulated and ZNF238 was down-regulated at diagnosis status of ALL. High miR-155 expression was associated with poor outcome. Overexpressed miR-155 promoted ALL cell proliferation and inhibited apoptosis. Dual-luciferase reporter result showed that miR-155 directly regulated ZNF238. Silencing ZNF238 promoted cell proliferation in ALL cells. Our research indicating that miR-155 might possess potential value as a biomarker for predicting the prognosis of individuals. However, the role of ZNF238 in childhood ALL remain unknown. In the present study, we found the possible role of ZNF238 as a new tumor suppressor in ALL, which might be necessary for the antiproliferative functions of normal cells to counteract ALL formation. Our results propose that miR-155 is in association with poor prognosis of childhood ALL. Furthermore, miR-155 could promote cell proliferation targeting ZNF238. [ABSTRACT FROM AUTHOR]

Two new prenylflavonoids, morusalbols A and B (1and2), were isolated from the branches and leaves ofMorus alba, together with three known compounds, kuwanon C (3), morusin (4), morusinol (5). The structures of these two prenylflavonoids were elucidated by extensive analyzes of the spectroscopic data. [ABSTRACT FROM PUBLISHER]

The reproduction techniques, bionic aquaculture techniques, disease control techniques and molecular level for Palea steindachneri were summarized in the present study. The results showed that owing to limitation of regional distribution, the whole research level of P. steindachneri was still at the primary stage being backward breeding technologies, non-standard bionic aquaculture techniques, no in-depth molecular level researches, and no any nutriol-ogy researches, etc. Therefore, aiming at key breeding technical problems of P. steindachneri, there were some joint efforts combining with production units, colleges and research institutes to improve number of laying egg, fertilization rate, hatching rate and survival rate of young turtle. Meanwhile, the molecular marker -assisted breeding technique should be applied to screen good breed. Two-stage aquaculture model of greenhouse-outdoor pond should be extended in bionic aquaculture. And the disease control strategy should be shifted by implementing standardized aquaculture. At the same time, the mechanism and medicinal value of health care, preventing and treating diseases of P. steindachneri to human should be exploited in depth to further extend its industrial chain. [ABSTRACT FROM AUTHOR]

While immune checkpoint blockade (ICB) therapy has shown promising results in a small subset of colorectal cancer patients with high microsatellite instability (MSI-H), the majority of patients with colorectal cancer do not respond to ICB therapy. The main obstacle to the success of immunotherapy in cancer treatment is the exhaustion of tumor-infiltrating lymphocytes (TILs). Elucidating the spatial organization of immune checkpoints within the tumor microenvironment could pave the way for the development of novel prognostic tools and therapeutic strategies to enhance antitumor immune responses. To clarify the spatial and functional diversity of tumor-infiltrating lymphocytes (TILs) in the colorectal tumor microenvironment (TME), we performed multiplexed IHC to examine the exhaustion of TILs in the TME (the expression of PD-1 and TIM-3 (T-cell immunoglobulin and mucin-domain-containing protein 3), which are major biomarkers of T-cell exhaustion) and Lasso-Cox analyses of the correlation between CRC prognosis and TME features. For proof of concept, the antitumor efficacy of TIM-3 and PD-1 dual blockade in CRC was further evaluated in a CT26 subcutaneous tumor model of human CRC. We found that the spatial context of PD-1 and TIM-3 successfully predicted the overall survival of CRC patients independent of TNM stage. Dual targeting of PD-1 and TIM-3 in mouse tumor models inhibited tumor progression and reduced T-cell exhaustion, indicating a potential strategy for improving the clinical treatment of CRC.

Background: Brain structure injury was presented in acute lymphoblastic leukemia (ALL) after treatment; however, its alterations in new-onset stage are still unclear. We aim to explore white matter (WM) and grey matter (GM) alterations using surface-based morphometry (SBM) and tract-based spatial statistics (TBSS) in new-onset pediatric ALL., Methods: Thirty-five ALL and 33 typically developing (TD) children were prospectively recruited and underwent three-dimensional T1-weighted and diffusion tensor (DTI) imaging. DTI metrics, cortical GM features, and deep GM nuclei volume were compared between groups differences., Results: In ALL, the only increased FA in the body of corpus callosum (P FWE-corrected  = 0.023) and left superior corona radiata (P FWE-corrected  = 0.045) were presented. Relative to TDs, pediatric ALL presented a significant decrease in cortical surface area (CSA), thickness (CT), and volume in orbital gyri, supramarginal gyrus, middle temporal gyrus, and superior temporal gyrus (all CWP = 0.01). Additionally, increased CT and CSA were found in lingual gyrus and left sulcus intermedius primus, respectively (all CWP = 0.01). Smaller volumes in pediatric ALL were observed in bilateral thalamus, caudate, hippocampus, and right putamen (P FDR-corrected  < 0.05)., Conclusion: Widespread brain structural abnormalities were found in new-onset pediatric ALL, which suggest disease itself can cause brain structural injury., Impact: This study revealed the altered white matter integrity and gray matter morphology characteristics in childhood acute lymphoblastic leukemia on new-onset stage. It is suggested that there may be structural impairment before chemotherapy. MRI is a sensitive way for early detection on brain structural damage in childhood acute lymphoblastic leukemia., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)