Intravenous Busulfan-Cyclophosphamide as a Preparative Regimen Before Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients with Acute Lymphoblastic Leukemia

The use of i.v. busulfan (BU) instead of the oral formulation can improve outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) by reducing toxicity and transplantation-related mortality (TRM). There are limited reports of i.v. BU used to treat patients with acute lymphoblastic leukemia (ALL). The present study was performed to evaluate the efficacy and toxicity of i.v. BU/cyclophosphamide (CY) conditioning in adult ALL. We retrospectively analyzed 42 consecutive patients who underwent allo-HSCT with BU/CY conditioning between January 2007 and October 2010 with an HLA-matched donor (sibling, n = 18; unrelated, n = 24). Thirty-three patients were in first complete remission (CR1), 2 were in second complete remission (CR2), and 7 were in a more advanced stage. Median patient age was 28 years (range, 17∼55 years). The median follow-up was 15 months (range, 1∼48 months). Overall, 13 patients died, for a 30-month overall survival of 56.5% ± 10.6% (65.7% ± 12.5% for patients in CR1 vs 25.4% ± 15.5% for those in CR2 or beyond; P < .001). Eleven patients experienced relapse between 2 and 26 months after allo-HSCT, with a 30-month relapse rate (RR) of 40% ± 10.9% (32.0% ± 12.7% for patients in CR1 vs 71.4% ± 17.1% for those in CR2 or beyond; P = .001). The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 39.2% ± 8.8%, and that of grade III-IV acute GVHD was 7.4% ± 4.1%. The incidence of chronic GVHD was 63.9% ± 11.7%, and that of extensive chronic GVHD was 19.3% ± 7.9%. Only 2 cases of clinically diagnosed veno-occlusive disease (VOD) were documented (4.7%), and 1 of these patients died of severe VOD. Other BU/CY conditioning–associated toxicities were diffuse alveolar hemorrhage in 1 patient and hemorrhagic cystitis in 8 patients. Four patients died due to TRM, for a 30-month TRM of 9.7% ± 4.6%. This study demonstrates that i.v. BU/CY can be considered a feasible conditioning regimen for adult ALL, with low incidences of VOD and TRM

Summary of 615 patients of chronic myeloid leukemia in Shanghai from 2001 to 2006

<p>Abstract</p> <p>Background</p> <p>To retrospectively review the incidence, treatment efficacy, we followed up newly diagnosed chronic myelogenous leukemia (CML) patients residing in Shanghai during 2001-2006.</p> <p>Methods</p> <p>All eligible cases were reviewed with the data of efficacy responses as well as overall survival (OS) and progression-free survival (PFS) time.</p> <p>Results</p> <p>A total of 615 cases entered the study. CML mainly afflicted those aged 40-60 years old and was slightly more frequent in males than females. More than 85% of the patients were in chronic phase (CP) when diagnosed. All patients were divided into four groups based on the main regimens - hydroxyurea, interferon alpha (IFN-α), imatinib, and hemopoietic stem cell transplantation (HSCT). With the median follow-up of 18 months, imatinib treatment induced 92.2% complete hematologic responses, and 64.3% complete cytogenetic responses among CML-CP patients. Overall the therapeutic efficacy in the imatinib group was higher than that in the hydroxyurea or IFN-α group. Meanwhile, in the imatinib group, all response rates of patients in CP were significantly greater than that in accelerated or blastic crisis phase. The patients treated with imatinib also showed the most promising results regarding OS and PFS. Patients receiving HSCT decreased markedly in number with the introduction of imatinib.</p> <p>Conclusions</p> <p>The number of new patients arising in Shanghai increased from 2001 to 2006. There were still patients receiving hydroxyurea and IFN-α. As the first-line regime for CML, imatinib was less administered in Shanghai before, but has received considerable development and great responses since 2003.</p

Chinese olive (Canarium album Rauesch.): a critical review on its nutritional value, phytochemical composition, health benefits, and practical applications

Chinese olive is a popular fruit with a long history of cultivation and consumption. As a fruit with edible, nutritional, and even medicinal value, the Chinese olive has attracted increased interest from both nutrition researchers and health-conscious consumers. Chinese olive is a rich nutrient source, including essential and non-essential amino acids, various fatty acids, organic acids, vitamins, microelements, and high-quality dietary fibers. It is also an important natural source of phytochemicals such as phenolic acids, flavonoids, phenylpropanoids, and other bioactive compounds. The nutritional and phytochemical compounds obtained from the Chinese olive exhibit unique and potent biological activities, explaining its various benefits to human health, including anti-Helicobacter pylori, anti-influenza, anti-diabetes, anti-inflammatory, anti-tumor effects, among others. This review focuses on recent studies on Chinese olives and aims to summarize the major advances in their nutritional value, phytochemical composition, health benefits, and practical applications. It provides a reference for further research on Chinese olives and their properties and the development of novel functional products

3D VESSEL RECONSTRUCTION IN OCT-ANGIOGRAPHY VIA DEPTH MAP ESTIMATION

Optical Coherence Tomography Angiography (OCTA) has been increasingly used in the management of eye and systemic diseases in recent years. Manual or automatic analysis of blood vessel in 2D OCTA images (en face angiograms) is commonly used in clinical practice, however it may lose rich 3D spatial distribution information of blood vessels or capillaries that are useful for clinical decision-making. In this paper, we introduce a novel 3D vessel reconstruction framework based on the estimation of vessel depth maps from OCTA images. First, we design a network with structural constraints to predict the depth of blood vessels in OCTA images. In order to promote the accuracy of the predicted depth map at both the overall structure- and pixel- level, we combine MSE and SSIM loss as the training loss function. Finally, the 3D vessel reconstruction is achieved by utilizing the estimated depth map and 2D vessel segmentation results. Experimental results demonstrate that our method is effective in the depth prediction and 3D vessel reconstruction for OCTA images.% results may be used to guide subsequent vascular analysi

Comparative analysis of the phenolic contents and antioxidant activities of different parts of two pomegranate (Punica granatum L.) Cultivars: ‘Tunisia’ and ‘Qingpi’

Pomegranate (Punica granatum L.), with its abundant phenolic substances and strong antioxidant activity, holds significant research and utilization potential across various organs. However, there have been few studies on the phenolic content and antioxidant activity of different parts of pomegranate, especially the placenta. This study investigated the phenolic content and antioxidant activity of fruits, flowers, and leaves of two pomegranate varieties, ‘Tunisia’ and ‘Qingpi’, throughout their growth and development. Results indicated significant variations in phenolic content among different organs, with petals exhibiting the highest total polyphenol content (TPC, 49.40 mg GAE/g FW) and total anthocyanin content (TMAC, 1938.54 nmol/g FW). Placenta contained the highest levels of total flavonoids (TFC, 173.58 mg RE/g FW) and punicalagin (109.30 mg/g FW). The peel had the highest content of total flavanols (TFAC, 19.42 mg CE/g FW). Over the course of pomegranate development, total polyphenols, total flavonoids, total flavanols, punicalagin, and antioxidant activity declined in different organs. Antioxidant activity followed the order: fruit &gt; flower &gt; leaf, with the placenta exhibiting the highest antioxidant activity among fruits. Antioxidant activity showed a significant positive correlation with total polyphenols (R2 = 0.77-1.00), total flavonoids (R2 = 0.71-0.99, except tegmens), and punicalagin (R2 = 0.71-1.00). This study provides a comparative analysis of the phenolic content and antioxidant activity in different organs of pomegranate, highlighting the placenta as the primary source of punicalagin. This study provides a theoretical basis for the development and utilization of pomegranate phenolic compounds

G9a Is Essential for EMT-Mediated Metastasis and Maintenance of Cancer Stem Cell-Like Characters in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer with poor prognosis, largely due to lymph node metastasis and local recurrence. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is important for cancer metastasis, and correlated with increased cancer stem cells (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph nodes in HNSCC is poorly defined. In this study, we show that E-cadherin repression correlates with cancer metastasis and poor prognosis in HNSCC. We found that G9a, a histone methyltransferase, interacts with Snail and mediates Snail-induced transcriptional repression of E-cadherin and EMT, through methylation of histone H3 lysine-9 (H3K9). Moreover, G9a is required for both lymph node-related metastasis and TGF-β-induced EMT in HNSCC cells since knockdown of G9a reversed EMT, inhibited cell migration and tumorsphere formation, and suppressed the expression of CSC markers. Our study demonstrates that the G9a protein is essential for the induction of EMT and CSC-like properties in HNSCC. Thus, targeting the G9a-Snail axis may represent a novel strategy for treatment of metastatic HNSCC

The splicing factor DHX38 enables retinal development through safeguarding genome integrity

DEAH-Box Helicase 38 (DHX38) is a pre-mRNA splicing factor and also a disease-causing gene of autosomal recessive retinitis pigmentosa (arRP). The role of DHX38 in the development and maintenance of the retina remains largely unknown. In this study, by using the dhx38 knockout zebrafish model, wedemonstrated that Dhx38 deficiency causes severe differentiation defects and apoptosis of retinal progenitor cells (RPCs) through disrupted mitosis and increased DNA damage. Furthermore, we found a significant accumulation of R-loops in the dhx38-deficient RPCs and human cell lines. Finally, we found that DNA replication stress is the prerequisite for R-loop-induced DNA damage in the DHX38 knockdown cells. Taken together, our study demonstrates a necessary role of DHX38 in the development of retina and reveals a DHX38/R-loop/replication stress/DNA damage regulatory axis that is relatively independent of the known functions of DHX38 in mitosis control

Autocrine Epiregulin Activates EGFR Pathway for Lung Metastasis Via EMT in Salivary Adenoid Cystic Carcinoma

Salivary adenoid cystic carcinoma (SACC) is characterized by invasive local growth and a high incidence of lung metastasis. Patients with lung metastasis have a poor prognosis. Treatment of metastatic SACC has been unsuccessful, largely due to a lack of specific targets for the metastatic cells. In this study, we showed that epidermal growth factor receptors (EGFR) were constitutively activated in metastatic lung subtypes of SACC cells, and that this activation was induced by autocrine expression of epiregulin (EREG), a ligand of EGFR. Autocrine EREG expression was increased in metastatic SACC-LM cells compared to that in non-metastatic parental SACC cells. Importantly, EREG-neutralizing antibody, but not normal IgG, blocked the autocrine EREG-induced EGFR phosphorylation and the migration of SACC cells, suggesting that EREG-induced EGFR activation is essential for induction of cell migration and invasion by SACC cells. Moreover, EREG-activated EGFR stabilized Snail and Slug, which promoted EMT and metastatic features in SACC cells. Of note, targeting EGFR with inhibitors significantly suppressed both the motility of SACC cells in vitro and lung metastasis in vivo. Finally, elevated EREG expression showed a strong correlation with poor prognosis in head and neck cancer. Thus, targeting the EREG-EGFR-Snail/Slug axis represents a novel strategy for the treatment of metastatic SACC even no genetic EGFR mutation

Gaussian Boson Sampling with Pseudo-Photon-Number Resolving Detectors and Quantum Computational Advantage

We report new Gaussian boson sampling experiments with pseudo-photon-number-resolving detection, which register up to 255 photon-click events. We consider partial photon distinguishability and develop a more complete model for characterization of the noisy Gaussian boson sampling. In the quantum computational advantage regime, we use Bayesian tests and correlation function analysis to validate the samples against all current classical mockups. Estimating with the best classical algorithms to date, generating a single ideal sample from the same distribution on the supercomputer Frontier would take ~ 600 years using exact methods, whereas our quantum computer, Jiuzhang 3.0, takes only 1.27 us to produce a sample. Generating the hardest sample from the experiment using an exact algorithm would take Frontier ~ 3.1*10^10 years.Comment: submitted on 10 Apri