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ObjectiveThe glymphatic system regulates cerebral spinal fluid and interstitial fluid transport which might be one of the pathways of central nervous system （CNS） leukemia at the early stage. This study aimed to investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space （DTI-ALPS） in pediatric acute lymphoblastic leukemia （ALL） without clinically diagnosed CNS infiltration. MethodsTwenty-five ALL and typically developing （TD） children were prospectively recruited， and all subjects underwent DTI. Group differences in brain water diffusivities and ALPS-index were evaluated using the analysis of covariance. The Spearman correlation analysis was used to evaluate the relationship between biological characteristics and significant parameters in pediatric ALL. ResultsCompared with TDs， decreased Dxassoc value （PFDR-corrected = 0.048） and increased Dzassoc value （PFDR-corrected = 0.033） were found in pediatric ALL. Hence， lower ALPS-index was found in children with ALL （PFDR-corrected < 0.001）. ALPS-index was negatively associated with the risk classification （rs = -0.47， P = 0.018） as well as immunophenotype （rs = -0.40， P = 0.046） in pediatric ALL. ConclusionsOur results show dysfunction of the glymphatic system is presented in pediatric ALL without clinically diagnosed CNS infiltration， which suggests that the glymphatic system might be one of pathway in the early-stage of ALL CNS infiltration. The DTI-ALPS method can be used to evaluate the change of glymphatic system， providing a new method for exploring the underlying mechanisms and early detection of pediatric ALL CNS infiltration.
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ObjectiveCentral nervous system （CNS） infiltration commonly occurs in children with acute lymphoblastic leukemia （ALL）. Early subclinical CNS infiltration in pediatric ALL is hard to detect with conventional methods. This study aimed to investigate the changes of brain structure volume parameters based on Synthetic MRI （SyMRI） in pediatric ALL without clinically diagnosed CNS infiltration. MethodsThirty-six ALL and twenty-nine typically developing （TD） children were prospectively collected and all underwent SyMRI. The Synthetic MR software was used to obtain brain volumetric parameters including total white matter volume （WMV）， gray matter volume （GMV）， cerebrospinal fluid （CSF） volume， etc. and their within-group differences were assessed by analysis of covariance. The Spearman correlation analysis was used to examine the correlation between biological characteristics and statistically significant brain volume parameters. ResultsALL children showed increased CSF volume （PFDR-corrected = 0.009） and decreased GMV （PFDR-corrected = 0.027） when compared to TD children. We also found a moderately negative association between GMV/intracranial volume and risk classification in pediatric ALL （rs = -0.380， P = 0.022）. ConclusionsPediatric ALL without clinically diagnosed CNS infiltration presented with accumulation of CSF and reduction of gray matter. The brain volumetric changes in subclinical CNS infiltration of pediatric ALL provides a new attempt for exploring the underlying mechanism and early detection of CNS infiltration in pediatric ALL.
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Since the outbreak of the novel coronavirus (SARS-CoV-2) disease COVID-19 (also known as 2019-nCoV) caused by SARS-CoV-2 in the end of 2019, it has spread rapidly in worldwide. Besides developing effective vaccines, it is urgent to develop safe and effective anti-SARS-CoV-2 drugs to fight this disease. Paxlovid, molnupiravir, sotrovimab and bebtelovimab are urgently authorized by FDA have been proved to be effective against Omicron. This manuscript mainly reviews the recent progress of effective inhibitors against the virus in the world, including receptor inhibitors, antibodies, natural product inhibitors, synthetic inhibitors and broad-spectrum antiviral drugs that are effective against other RNA viruses.
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Objective:To explore the effects of mirror therapy on upper limb motor function recovery and corticospinal tract remodeling after stroke. Methods:From March, 2017 to March, 2019, 42 subcortical stroke patients with upper limb dysfunction from Shanghai Fifth People's Hospital were randomly divided into control group (n = 21) and observation group (n = 21). Both groups received routine rehabiliation, while the observation group received mirror therapy additionally, for twelve weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), and scanned with diffusion tensor imaging (DTI) before and after treatment. The fractional anisotropy (FA) in posterior limb of internal capsule (PLIC) was obtained. Results:The scores of FMA-UE improved in both groups after treatment (t > 9.560, P < 0.001), and improved more in the observation group than in the control group (t > 2.634, P < 0.05). FA decreased significantly in the affected-lateral PLIC compared with that in the unaffected-lateral PLIC in both groups (t > 11.368, P < 0.001). FA in the affected side increased significantly after treatment in the observation group (t = 2.385, P < 0.05), while there was no significant difference in the control group (t = -0.596, P > 0.05). FA increased more significantly in the observation group than in the control group (t = 2.306, P < 0.05). Conclusion:Mirror therapy can promote the recovery of motor function of upper limb and the corticospinal tract remodeling in stroke patients.
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OBJECTIVE@#To investigate the effect of miR-29b-3p on apoptosis and proliferation of acute myeloid leukemia (AML) cells by targeting signal transducer and activator of transcription 3 (STAT3).@*METHODS@#TargetScan and miRanda online databases were used to predict the binding sites of miR-29b-3p and STAT3 3'UTR. The targeting relationship between them was estimated by Dual-Luciferase reporter assay experiment. After miR-29b-3p over-expression, qPCR and Western blot were used to detect the expression of STAT3 mRNA and proteins, flow cytometry to determine the apoptosis of AML cells, and MTS to detect the changes of cell proliferation in each group.@*RESULTS@#Dual-Luciferase reporter assay confirmed that STAT3 was the target gene of miR-29b-3p. After miR-29b-3p overexpression, the expression of STAT3 mRNA and protein decreased. Compared with the control groups, the proliferation of AML cells in the overexpression group decreased and the apoptosis increased (P<0.05).@*CONCLUSION@#MiR-29b-3p can inhibit the proliferation and induce apoptosis of AML cells by down-regulating STAT3.
Subject(s)
Humans , Apoptosis , Cell Proliferation , Leukemia, Myeloid, Acute/genetics , MicroRNAs/genetics , STAT3 Transcription Factor/geneticsABSTRACT
@#【Objective】To assess the value of 18F-FDG PET/CT for imaging liver fibrosis.【Methods】12 male SD rats （170±10 g）were divided into model group（TAA group）and control group. In the model group，200 mg/kg thioacetamide dissolved in sterile saline was administered to rats by means of intraperitoneal injection twice a week for a total of 6 weeks. In the control group，rats were treated with the same volume of saline. At week 6 after injection，18F- FDG PET/CT imaging was performed on two groups and measurement of the liver 18F-FDG uptake in two groups was taken. After PET/ CT scans， all rats were sacrificed to observe anatomical morphological changes. Liver tissues were harvested for hematoxylin and eosin （H&E） staining，Masson staining and measurement of hydroxyproline levels. 【Results】 Liver anatomical morphology of the TAA-induced rats was roughness with brunt margins and coarse surfaces ，while control rats showed sharp margins and smooth surfaces. HE staining showed visible histological changes that hepatocyte and liver sinus area surrounded by plentiful recruited hepatocyte neutrophils in the model group. Masson staining showed that obvious proliferation of fibroblasts and deposition of collagen in liver tissues in the model group. Model group showed higher hydroxyproline content than that in the control group（P<0.001）. The results of 18F- FDG imaging indicated that apparent liver radioactivity concentration in the model group. 18F-FDG uptake value of liver tissues in the model group was higher than that in the control group（P<0.001）.【Conclusion】18F- FDG PET/CT imaging could be used for diagnosis of liver fibrosis noninvasively.
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OBJECTIVE@#To investigate the level of serum microRNA-609 and its clinical prognostic value in patients with thalassemia.@*METHODS@#One hundred and twenty-seven patients with thalassemia treated in our hospital from April 2017 to April 2018 were selected, 100 healthy persons were selected as control group. The changes of miR-609 were analyzed by RT-PCR, the relationship between miR-609 and clinical indicators of thalassemia was analyzed, and the prognostic risk factors of thalassemia were evaluated by multivariate logistic regression analysis.@*RESULTS@#The relative expression level of miR-609 in thalassemia patients was 3.17±0.24, which was significantly higher than that in control group (P0.05). The incidence rate of mild anemia in high expression group was significantly lower than that in low expression group (P0.05). The number of patients with severe anemia in the miR-609 high expression group was higher than that in miR-609 low expression group (P<0.05). The incidence rate of dizziness, fatigue and fever in patients with miR-609 high expression group was significantly higher than those in patients with miR-609 low expression (P<0.05). There was no correlation between the level of miR-609 and the incidence rate of nausea in patients with thalassemia. ROC curve showed that the AUC value of microRNA-609 was 0.862, the sensitivity was 83.6%, and the specificity was 84.1%, which suggested that miR-609 had a high diagnostic value for thalassemia. Multivariate logistic regression analysis showed that MCH and mir-609 were risk factors for poor prognosis of thalassemia patients.@*CONCLUSION@#The increased level of serum miR-609 in patients with thalassemia is a risk factor for poor prognosis and can be used as a reference index for evaluating the efficacy for patients.
Subject(s)
Humans , Biomarkers, Tumor , MicroRNAs , Prognosis , ROC Curve , Thalassemia , GeneticsABSTRACT
CD99, a cell adhesion molecule, is involved in the cell adhesion, apoptosis and tumor cell migration, infiltration, and invasion, and plays an important role in the development and progression of tumor. CD99 is abnormally expression in some tumors, which has potential value in the differential diagnosis, predication of metastasis capability, treatment and predication of tumors.
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Objective: To identify the metastasis-associated splice variants of CD99 and investigate the mRNA expression of the splice variants in clear cell renal cell carcinoma(ccRCC) tissues, so as to investigate its relationship with the initiation and progression of ccRCC. Methods: Alternative Splicing Database was used to predict the splice variants of CD99. The six predicted splice variants of CD99 were identified in the metastatic tissues, primary ccRCCs and normal tissues adjacent to cancer by using self-designed primer sets, and were cloned into vectors and sequenced. The mRNA expression of CD99 type I, CD99 type II, and CD99-III were detected in 9 metastatic tissues and their corresponding cancer tissues, 21 primary ccRCCs and normal tissues adjacent to cancer by RT-PCR. Results: A new isoform of CD99 (CD99-III) was identified, which was detected in 8 of the 9 metastatic tissues, a ratio significantly higher than that in the primary ccRCCs without metastasis (10 out of 21, P<0. 05). The results revealed that the transcripts of CD99 type I was present in all of the ccRCC specimens tested; CD99 type II was detected in 6 of 9 metastatic corresponding primary cancer tissues, a ratio significantly higher than that in cancer tissues without metastasis(3 out of 21, P=0.008). Conclusion: CD99 type II and CD99-III, a novel splice variant of CD99, may be associated with the initiation and progression of ccRCC.