A chest CT-based nomogram for predicting survival in acute myeloid leukemia.

BACKGROUND: The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). METHODS: 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. RESULTS: Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P < 0.01). A CT-MSF nomogram showed a performance with AUCs of 0.717, 0.794, 0.796 and 0.792 for predicting the 1-, 2-, 3-, and 5-year overall survival (OS) probabilities in the validation cohort, which were significantly higher than the ELN risk model. Moreover, a new MSN stratification system (MSF nomogram plus ELN risk model) could stratify patients into new high, intermediate and low risk group. Patients with high MSN risk may benefit from intensive treatment (P = 0.0011). CONCLUSIONS: In summary, the chest CT-MSF nomogram, integrating myosarcopenia, spleen_CTV, and SF_CTV features, could be used to predict prognosis of AML.

Metformin sensitizes AML cells to venetoclax through endoplasmic reticulum stress-CHOP pathway.

Venetoclax inhibits acute myeloid leukaemia by inhibiting BCL-2 targeting, and a combination regimen with venetoclax has been explored. Although these regimens produce better clinical results, the vast majority of patients still suffer from disease recurrence or primary drug resistance. Metformin has been demonstrated to induce apoptosis in cancer cells. However, whether it can synergize with venetoclax and the underlying mechanisms of metformin-induced apoptosis are not fully understood. In this study, we investigated the effect of metformin and venetoclax on the growth of AML cells in vitro and in vivo. In both Molm13 and THP-1 cell lines, metformin and venetoclax synergistically inhibited the proliferation and induced apoptosis of leukaemia cells. Most importantly, the combination of metformin and venetoclax treatment significantly increased the expression levels of the endoplasmic reticulum (ER) stress-related marker CHOP, for example, in AML cell lines. Knockdown of CHOP markedly attenuated the metformin- and venetoclax-induced cell apoptosis. Moreover, the combination of metformin and venetoclax demonstrated prominent anti-leukaemia effects in xenograft models and bone marrow samples from AML patients. In summary, the combination of metformin and venetoclax showed enhanced anti-leukaemia activity with acceptable safety in AML patients, representing a new combinatorial strategy worth further clinical investigation to treat AML.

High-Efficiency CNNS@NH2-MIL(Fe) Electrochemiluminescence Emitters Coupled with Ti3C2 Nanosheets as a Matrix for a Highly Sensitive Cardiac Troponin I Assay.

Synthesis of a highly efficient electrochemiluminescence (ECL) luminescent material is one of the effective means to improve the sensitivity of the sensor. In this study, an efficient ECL luminescent nanomaterial, carbon nitride nanosheet (CNNS) decorated amino-functional metal-organic frameworks (CNNS@NH2-MIL(Fe)) were synthesized for sensitive ECL detection of cardiac troponin I (cTn-I). The synthesized CNNS@NH2-MIL(Fe) realized the effective mass loading of CNNS, and more importantly, the NH2-MIL(Fe) could expedite the reduction of coreactant S2O82- to produce abundant ECL reaction intermediate SO4•- near CNNS, thus, shortening the distance between SO4•- and the excited state of CNNS with less energy loss to extremely enhance the ECL signal of CNNS. Furthermore, the ECL signal of the immunosensor could be further enhanced when the Ti3C2 nanosheet was used as the matrix to capture primary anti-cTn-I due to the reason that Ti3C2 not only exhibited a large surface area and excellent metallic conductivity, but also could act as a coreaction accelerator to speed up the reduction of S2O82- with plenty of SO4•- generated. Therefore, this proposed ECL immunosensor using CNNS@NH2-MIL(Fe) as a signal probe and Ti3C2 as a sensing matrix exhibited a significantly enhanced ECL signal and had a high sensitivity and excellent selectivity for cTn-I. Consequently, this multiple signal amplification strategy provided an effective method for trace protein ultrasensitive detection in ECL bioanalysis.

3D Matrix-Arranged AuAg Nanoclusters As Electrochemiluminescence Emitters for Click Chemistry-Driven Signal Switch Bioanalysis.

We hereby described an electrochemiluminescence (ECL) biosensor for glutathione (GSH) based on a 3D DNA matrix with ordered binding sites and cavity structure that self-assembled from tetrahedral DNA blocks (TDBs). First, the alkyne-labeled TDBs were employed to build an alkyne-rich 3D matrix (C≡C-3DM) on the electrode surface. Then, the GSH-induced click chemistry was triggered as a signal switch to introduce the large amounts of N3-DNA decorated AuAg nanoclusters (N3-AuAg NCs) into C≡C-3DM for signal output. In particular, the presence of GSH could induce the formation of GSH-Cu(I) complex by the redox reaction between GSH and Cu(II), which could act as an initiator to link the N3-AuAg NCs with C≡C-3DM according to the Huisgen 1,3-dipolar cycloaddition reaction. By this way, numerous N3-AuAg NCs were orderly bonded to the 3D matrix to effectively reduce their agglomeration and inner filter effect, achieving a remarkable ECL enhancement. As a result, the proposed GSH biosensor showed a wide linear range from 5 to 200 µM with a low detection limit of 0.90 µM. In general, this work provided a rapid, highly efficient, and convenient signal amplification for small-molecule detection and broadened the application of TDBs in biosensing.

DNA Cascade Reaction with High-Efficiency Target Conversion for Ultrasensitive Electrochemiluminescence microRNA Detection.

DNA amplification strategy has been a valuable tool for improving the sensitivity of biosensors. However, the freely diffusing reactants in most DNA amplification strategies limit the rate of DNA reaction, which further affects the amplification efficiency with unsatisfactory sensitivity. In the present work, a novel localized DNA cascade reaction (LDCR) in a DNA nanomachine was designed for high-efficiency target conversion to construct an electrochemiluminescence (ECL) biosensor for ultrasensitive microRNA-21 detection. The DNA nanomachine was constructed by using three-footholds DNA scaffold to immobilize two metastable hairpins and reporter probe and confine them in a localized space. In the presence of microRNA-21, it initiated the LDCR and produced large amounts of mimic target (ferrocene labeled DNA, Fc-DNA) due to the locality effect. Thus, sensitive detection of microRNA-21 could be realized since Fc could effectively quench the ECL intensity of graphitic carbon nitride nanosheets (CNNS) due to the energy and electron transfer from the excited state of CNNS to oxidized species of Fc. Moreover, compared with the other two developed DNA cascade reactions with freely diffusing reactants, the proposed LDCR benefits by shortening the reaction time and improving the amplification efficiency with enhanced sensitivity of the biosensor. Therefore, the proposed LDCR could be used as a highly efficient amplification strategy for ultrasensitive determination of biomarkers with low abundance, which may promote the diagnostic efficiency of disease.

Functional Three-Dimensional Porous Conductive Polymer Hydrogels for Sensitive Electrochemiluminescence in Situ Detection of H2O2 Released from Live Cells.

Reliable and sensitive in situ detection of molecules released from live cells attracts tremendous research interest, as it shows significance in pathological and physiological investigation. In the present work, a novel electrochemiluminescent (ECL) luminophore, N-(aminobutyl)- N-(ethylisoluminol)-functionalized Ag nanoparticles modified three-dimensional (3D) polyaniline-phytic acid conducting hydrogel (ABEI-Ag@PAni-PA), is synthesized to adhere cells for in situ sensitive ECL detection of hydrogen peroxide (H2O2) released from live cells. The obtained 3D nanostructured ABEI-Ag@PAni-PA conducting hydrogels synergize the advantages of a conducting hydrogel and a nanoparticle catalyst, in which the PAni-PA conducting hydrogels benefit the cell adhesion and high loading density of the ABEI-Ag luminescent material due to their good biocompatibility, porous structure, and 3D continuous framework. Importantly, compared with the traditional procedure for detection of H2O2 released from cells in solution, adhesion of cells on ABEI-Ag@PAni-PA conducting hydrogels provides a short diffusion distance to reaction sites for H2O2, thus realizing sensitive in situ monitoring of H2O2 released from cells under drug stimulation. With good biocompatibility, high sensitivity, and easy preparation, the ECL biosensor based on ABEI-Ag@PAni-PA conducting hydrogels can be expanded to detect other molecules released from cells, which may facilitate the investigation of pathology and physiology.

Electrochemiluminescence Biosensor Based on 3-D DNA Nanomachine Signal Probe Powered by Protein-Aptamer Binding Complex for Ultrasensitive Mucin 1 Detection.

Herein, we fabricated a novel electrochemiluminescence (ECL) biosensor for ultrasensitive detection of mucin 1 (MUC1) based on a three-dimensional (3-D) DNA nanomachine signal probe powered by protein-aptamer binding complex. The assembly of 3-D DNA nanomachine signal probe achieved the cyclic reuse of target protein based on the protein-aptamer binding complex induced catalyzed hairpin assembly (CHA), which overcame the shortcoming of protein conversion with enzyme cleavage or polymerization in the traditional examination of protein. In addition, CoFe2O4, a mimic peroxidase, was used as the nanocarrier of the 3-D DNA nanomachine signal probe to catalyze the decomposition of coreactant H2O2 to generate numerous reactive hydroxyl radical OH• as the efficient accelerator of N-(aminobutyl)-N-(ethylisoluminol) (ABEI) ECL reaction to amplify the luminescence signal. Simultaneously, the assembly of 3-D DNA nanomachine signal probe was executed in solution, which led to abundant luminophore ABEI be immobilized around the CoFe2O4 surface with amplified ECL signal output since the CHA reaction was occurred unencumberedly in all directions under homogeneous environment. The prepared ECL biosensor showed a favorable linear response for MUC1 detection with a relatively low detection limit of 0.62 fg mL-1. With excellent sensitivity, the strategy may provide an efficient method for clinical application, especially in trace protein determination.

Signal-Switchable Electrochemiluminescence System Coupled with Target Recycling Amplification Strategy for Sensitive Mercury Ion and Mucin 1 Assay.

In the present work, we first found that mercury ion (Hg(2+)) has an efficient quenching effect on the electrochemiluminescence (ECL) of N-(aminobutyl)-N-(ethylisoluminol) (ABEI). Since we were inspired by this discovery, an aptamer-based ECL sensor was fabricated based on a Hg(2+) triggered signal switch coupled with an exonuclease I (Exo I)-stimulated target recycling amplification strategy for ultrasensitive determination of Hg(2+) and mucin 1 (MUC1). Concretely, the ECL intensity of ABEI-functionalized silver nanoparticles decorated graphene oxide nanocomposite (GO-AgNPs-ABEI) was initially enhanced by ferrocene labeled ssDNA (Fc-S1) (first signal switch "on" state) in the existence of H2O2. With the aid of aptamer, assistant ssDNA (S2) and full thymine (T) bases ssDNA (S3) modified Au nanoparticles (AuNPs-S2-S3) were immobilized on the sensing surface through the hybridization reaction. Then, via the strong and stable T-Hg(2+)-T interaction, an abundance of Hg(2+) was successfully captured on the AuNPs-S2-S3 and effectively inhibited the ECL reaction of ABEI (signal switch "off" state). Finally, the signal switch "on" state was executed by utilizing MUC1 as an aptamer-specific target to bind aptamer, leading to the large decrease of the captured Hg(2+). To further improve the sensitivity of the aptasensor, Exo I was implemented to digest the binded aptamer, which resulted in the release of MUC1 for achieving target recycling with strong detectable ECL signal even in a low level of MUC1. By integrating the quenching effect of Hg(2+) to reduce the background signal and target recycling for signal amplification, this proposed ECL aptasensor was successfully used to detect Hg(2+) and MUC1 sensitively with a wide linear response.

N vacancy and self-enhancement induced high anodic electrochemiluminescence of 3D g-C3N4 for sensitive staphylococcus aureus analysis.

Here, 3D g-C3N4 with dense N vacancy in its 3D porous interconnected open-framework was synthesized, and the co-reactive 3-(dibutylamino)propylamine (DBAPA) was further covalently coupled onto the surface, resulting in a strong self-enhanced anodic electrochemiluminescence (ECL). Through introduction of high-density N vacancy, for the obtained 3D g-C3N4-NV, the band gap was broadened and the electrical conductivity was enhanced, realizing an obvious ECL improvement. Moreover, after the covalent binding of co-reactive DBAPA, the obtained 3D g-C3N4-NV-DBAPA exhibited a more intensive self-enhanced ECL signal due to the higher co-reaction efficiency originated from shorter electron transfer distance and lower energy loss. Based on the high initial signal of the proposed 3D g-C3N4-NV-DBAPA, a sensitive ECL biosensor with signal "on-off" was fabricated in assistance with multiple horizontal ordered hybridization chain reaction (HO-HCR). Through orderly fixing the reacted DNA chains on the Y-shape DNA structure on the electrode could effectively decrease diffusion process and improve the reaction efficiency of HCR process, resulting in the formation of numerous long horizontal double-strand DNA that could immobilize abundant ferrocene-doxorubicin (Fc-Dox) with ECL quenching effect. Meanwhile, compared to the traditional vertical HCR, the HO-HCR could make the quench reagent closer to the ECL emitter on the electrode surface and obtain a more effective quenching effect to enhance the sensing sensitivity. As a result, the proposed ECL biosensor archived the sensitive measurement of staphylococcus aureus with a detection limit of 10.3 aM.

Advances in pharmacological effects and mechanism of action of cinnamaldehyde.

Cinnamaldehyde is extracted from Cinnamomum cassia and other species, providing diverse sources for varying chemical properties and therapeutic effects. Besides natural extraction, synthetic production and biotechnological methods like microbial fermentation offer scalable and sustainable alternatives. Cinnamaldehyd demonstrates a broad pharmacological range, impacting various diseases through detailed mechanisms. This review aims to encapsulate the diverse therapeutic effects of cinnamaldehyde, its molecular interactions, and its potential in clinical applications. Drawing on recent scientific studies and databases like Web of Science, PubMed, and ScienceDirect, this review outlines cinnamaldehyde's efficacy in treating inflammatory conditions, bacterial infections, cancer, diabetes, and cardiovascular and kidney diseases. It primarily operates by inhibiting the NF-κB pathway and modulating pro-inflammatory mediators, alongside disrupting bacterial cells and inducing apoptosis in cancer cells. The compound enhances metabolic health by improving glucose uptake and insulin sensitivity and offers cardiovascular protection through its anti-inflammatory and lipid-lowering effects. Additionally, it promotes autophagy in kidney disease management. Preclinical and clinical research supports its therapeutic potential, underscoring the need for further investigation into its mechanisms and safety to develop new drugs based on cinnamaldehyde.

Hexamethylene amiloride synergizes with venetoclax to induce lysosome-dependent cell death in acute myeloid leukemia.

Tumors maintain an alkaline intracellular environment to enable rapid growth. The proton exporter NHE1 participates in maintenance of this pH gradient. However, whether targeting NHE1 could inhibit the growth of tumor cells remains unknown. Here, we report that the NHE1 inhibitor Hexamethylene amiloride (HA) efficiently suppresses the growth of AML cell lines. Moreover, HA combined with venetoclax synergized to efficiently inhibit the growth of AML cells. Interestingly, lysosomes are the main contributors to the synergism of HA and venetoclax in inhibiting AML cells. Most importantly, the combination of HA and venetoclax also had prominent anti-leukemia effects in both xenograft models and bone marrow samples from AML patients. In summary, our results provide evidence that the NHE1 inhibitor HA or its combination with venetoclax efficiently inhibits the growth of AML in vitro and in vivo.

Basiliximab Treatment for Patients With Steroid-Refractory Acute Graft-Versus-Host Disease Following Matched Sibling Donor Hematopoietic Stem Cell Transplantation.

Basiliximab is an important treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD). We performed this retrospective study to evaluate the efficacy and safety of basiliximab treatment in SR-aGVHD patients following matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) (n = 63). Overall response rate (ORR) was 63.5% and 54% at any time and at day 28 after basiliximab treatment. Grade III-IV aGVHD before basiliximab treatment predicted a poor ORR after basiliximab treatment. The rates of virus, bacteria, and fungi infections were 54%, 23.8%, and 3.1%, respectively. With a median follow-up of 730 (range, 67-3,042) days, the 1-year probability of overall survival and disease-free survival after basiliximab treatment were 58.6% (95% confidence interval [CI] = 47.6%-72.2%) and 55.4% (95% CI = 44.3%-69.2%), respectively. The 3-year cumulative incidence of relapse and non-relapse mortality after basiliximab treatment were 18.9% (95% CI = 8.3%-29.5%) and 33.8% (95% CI = 21.8%-45.7%), respectively. Comorbidities burden before allo-HSCT, severity of aGVHD and liver aGVHD before basiliximab treatment showed negative influences on survival. Thus, basiliximab was safe and effective treatment for SR-aGVHD following MSD-HSCT.

USP10 as a Potential Therapeutic Target in Human Cancers.

Deubiquitination is a major form of post-translational protein modification involved in the regulation of protein homeostasis and various cellular processes. Deubiquitinating enzymes (DUBs), comprising about five subfamily members, are key players in deubiquitination. USP10 is a USP-family DUB featuring the classic USP domain, which performs deubiquitination. Emerging evidence has demonstrated that USP10 is a double-edged sword in human cancers. However, the precise molecular mechanisms underlying its different effects in tumorigenesis remain elusive. A possible reason is dependence on the cell context. In this review, we summarize the downstream substrates and upstream regulators of USP10 as well as its dual role as an oncogene and tumor suppressor in various human cancers. Furthermore, we summarize multiple pharmacological USP10 inhibitors, including small-molecule inhibitors, such as spautin-1, and traditional Chinese medicines. Taken together, the development of specific and efficient USP10 inhibitors based on USP10's oncogenic role and for different cancer types could be a promising therapeutic strategy.

HMGCS1 drives drug-resistance in acute myeloid leukemia through endoplasmic reticulum-UPR-mitochondria axis.

Hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a key enzyme in the mevalonate pathway of cholesterol synthesis. Dysregulation of HMGCS1 expression is a common occurrence in many solid tumors. It was also found to be overexpressed in newly diagnosed (ND) and relapsed/refractory (RR) acute myeloid leukemia (AML) patients. Previous study proved that HMGCS1 could induce drug-resistance in AML cells. However, the underlying mechanism how HMGCS1 contributed to chemoresistance remains elusive. Here, we confirmed that HMGCS1 inhibitor Hymeglusin enhanced cytarabine/Adriamycin (Ara-c/ADR) chemo-sensitivity in AML cells lines. Moreover, Ara-c-resistant HL-60 cells (HL-60/Ara-c) and ADR-resistant HL-60 cells (HL-60/ADR) were more sensitive to HMGCS1 inhibition than HL-60 cells. In addition, we demonstrated that the transcription factor GATA1 was the upstream regulator of HMGCS1 and could directly bind to the HMGCS1 promoter. After treatment of Tunicamycin (Tm), the number of mitochondria was increased and the damage of endoplasmic reticulum (ER) was reduced in bone marrow cells from AML-RR patients, compared to cells from AML-CR group. HMGCS1 protected mitochondria and ER under ER stress and up-regulated unfold protein response (UPR) downstream molecules in AML cells. In summary, we proved that HMGCS1 could upregulate UPR downstream components, protect mitochondria and ER from damage in AML cells under stress, therefore conferring drug resistance. Therefore, HMGCS1 could serve as a novel target for treatment of patients with intolerant chemotherapy and AML-RR patients.

A Novel miRNA Restores the Chemosensitivity of AML Cells Through Targeting FosB.

The heterogeneous nature of acute myeloid leukemia (AML) and its poor prognosis necessitate therapeutic improvement. Current advances in AML research yield important insights regarding both AML genetics and epigenetics. MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation, and survival and may be useful for AML diagnosis and prognosis. In this study, a novel miRNA, hsa-miR-12462, was identified in bone marrow (BM) samples from AML patients at diagnosis by small RNA sequencing. A significant higher level of hsa-miR-12462 was found in patients who achieve complete remission (AML-CR) after induction therapy compared with those who suffer relapse/refractory (AML-RR). FosB was predicted to be the target of hsa-miR-12462 through RNA sequencing, bioinformatics analysis, and protein-protein interaction (PPI) network analysis and then verified by luciferase activity assay. T-5224, the inhibitor of FosB, was administered to AML cell lines, which could inhibit cell proliferation, promote apoptosis, and restore the sensitivity of AML cells to cytarabine (Ara-C). In summary, a higher level of hsa-miR-12462 in AML cells is associated with increased sensitivity to Ara-C via targeting FosB.

Roles of hsa-miR-12462 and SLC9A1 in acute myeloid leukemia.

MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation, and survival and may be useful for acute myeloid leukemia (AML) diagnosis and prognosis. In this study, we defined a novel miRNA, hsa-miR-12462, through small RNA sequencing of the bone marrow (BM) cells from 128 AML patients. Overexpression of hsa-miR-12462 in AML cells (U937 and HL-60) significantly decreased their growth rate when compared with those of the wild-type and MOCK controls. In a xenograft mouse model, tumor weight and size in the mice bearing the U937 cells with hsa-miR-12462 overexpression were significantly reduced when compared with those bearing the mock cells. The AML cells overexpressing hsa-miR-12462 had increased sensitivity to cytarabine chemotherapy. Combining the data from the MiRDB, an online microRNA database ( http://mirdb.org ), with the RNA-sequencing results, SLC9A1 was predicted to be one of the targets of hsa-miR-12462. hsa-miR-12462 was further confirmed to bind exclusively to the 3'UTR of SLC9A1 in U937 cells, leading to downregulation of SLC9A1. In summary, a higher level of hsa-miR-12462 in AML cells is associated with increased sensitivity to cytarabine chemotherapy via downregulation of SLC9A1.

Differentiation of primary central nervous system lymphoma and high-grade glioma with dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging.

BACKGROUND: Preoperative differentiation of primary central nervous system lymphomas (PCNSLs) from other tumors is important for presurgical staging, intraoperative management, and postoperative treatment. Dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging (DSC perfusion MRI) can provide in vivo assessment of the microvasculature in intracranial mass lesions. PURPOSE: To determine the utility of DSC perfusion MRI in the differentiation of PCNSLs and high-grade gliomas, as well as their pathological and physiological differences. MATERIAL AND METHODS: Nine patients with pathologically proven PCNSLs and 11 patients with high-grade gliomas were examined using a 1.5 T MRI scanner. DSC perfusion MRI was performed by gradient-echo echo-planar imaging (GE-EPI). The maximum rCBV ratio, the signal intensity-time curves, and the percentage of signal intensity recovery were obtained. The maximum relative cerebral blood volume (rCBV) ratio and the percentage of signal intensity recovery of PCNSLs were compared with those of high-grade gliomas by using Student's t test. Microvessel density (MVD) was evaluated using immunohistochemical staining of surgical specimens with anti-CD34, and MVDs of the two tumor groups were compared by using Student's t test. RESULTS: The maximum rCBV ratio of primary intracranial lymphomas was 1.72+/-0.59, while that of high-grade gliomas was 4.86+/-2.18. PCNSLs tended to have relatively low perfusion compared to high-grade gliomas (P=0.001), and the MVD labeled by anti-CD34 of PCNSLs was much lower than that of gliomas (P<0.001). The signal intensity-time curve of primary intracranial lymphomas was different from that of high-grade gliomas. The percentage of signal intensity recovery was significantly greater in PCNSLs compared with that of high-grade gliomas (P<0.001). CONCLUSION: The difference in DSC perfusion MRI characteristics between PCNSLs and high-grade gliomas is determined by their different vascularities and different patterns of contrast agent leakage. This difference may be helpful in the diagnosis and preoperative differentiation between PCNSLs and high-grade gliomas, which sometimes may have similar conventional MR imaging appearance.

[Differentiation of hypoxic-ischemic encephalopathy and acute bilirubin encephalopathy with magnetic resonance imaging in neonates].

OBJECTIVE: To investigate the value of conventional magnetic resonance imaging (MRI) and diffusion weighed imaging (DWI) in the differentiation of hypoxic-ischemic encephalopathy (HIE) and acute bilirubin encephalopathy in neonates. METHODS: The MRI findings along with DWI characteristics in 15 neonates with HIE involving basal ganglia and in 18 neonates with acute bilirubin encephalopathy between November 2006 and June 2008 were retrospectively reviewed. RESULTS: On T1WI, only 5 patients presented hyperintensity in the globus pallidus in the HIE group, but 16 in the acute bilirubin encephalopathy group (p<0.01). Nine patients in the HIE group showed hyperintensity in the putamen, but the hyperintensity in the putamen was not found in the acute bilirubin encephalopathy group. The frequency of hyperintensity in the subthalamus in the acute bilirubin encephalopathy group (55.6%) was significantly higher than that in the HIE group (13.3%) (p<0.05). Eight patients in the HIE group showed abnormal signals in the other regions on T1WI, but only two patients in the acute bilirubin encephalopathy group (p<0.05). On DWI, 7 out of 11 patients with HIE presented hyperintensity in the basal ganglia, while all 10 patients of the acute bilirubin encephalopathy group presented normal in the basal ganglia. CONCLUSIONS: Conventional MRI along with DWI is useful in differentiating HIE from acute bilirubin encephalopathy in neonates.

The role of cholesterol metabolism in leukemia.

Leukemia is a common hematological malignancy with overall poor prognosis. Novel therapies are needed to improve the outcome of leukemia patients. Cholesterol metabolism reprogramming is a featured alteration in leukemia. Many metabolic-related genes and metabolites are essential to the progress and drug resistance of leukemia. Exploring potential therapeutical targets related to cholesterol homeostasis is a promising area. This review summarized the functions of cholesterol and its derived intermediate metabolites, and also discussed potential agents targeting this metabolic vulnerability in leukemia.