Reduced doses of emicizumab achieve good efficacy: Results from a national-wide multicentre real-world study in China.

INTRODUCTION: Reduced doses of emicizumab improve the affordability among patients in developing countries. However, the relationship between variant dose selection and efficacy in the real world of China is still unclear. AIM: This study aimed to investigate the efficacy and safety of emicizumab especially in those on reduced dose regimens in a real-world setting. METHODS: We carried out a multicentre study from 28 hospitals between June 2019 and June 2023 in China and retrospectively analysed the characteristics including demographics, diagnosis, treatment, bleeding episodes, and surgical procedures. RESULTS: In total, 127 patients with haemophilia A, including 42 with inhibitors, were followed for a median duration of 16.0 (IQR: 9.0-30.0) months. Median age at emicizumab initiation was 2.0 (IQR: 1.0-4.0) years. Median (IQR) consumption for loading and maintenance was 12.0 (8.0-12.0) and 4.2 (3.0-6.0) mg/kg/4 weeks, respectively. While on emicizumab, 67 (52.8%) patients had no bleeds, whereas 60 (47.2%) patients had any bleeds, including 26 with treated bleeds. Compared to previous treatments, patients on emicizumab had significantly decreased annualized bleeding rate, annualized joint bleeding rate, target joints and intracerebral haemorrhage. Different dosages had similar efficacy except the proportion of patients with treated spontaneous bleeds and target joints. Adverse events were reported in 12 (9.4%) patients. Postoperative excessive bleeding occurred following two of nine procedures. CONCLUSION: This is the largest study describing patients with HA receiving emicizumab prophylaxis on variant dose regimens in China. We confirmed that nonstandard dose is efficacious and can be considered where full-dose emicizumab is ill affordable.

Efficient optical reservoir computing for parallel data processing.

We propose and experimentally demonstrate an optical reservoir computing system in free space, using second-harmonic generation for nonlinear kernel functions and a scattering medium to enhance reservoir nodes interconnection. We test it for one-step and multi-step predication of Mackey-Glass time series with different input-mapping methods on a spatial light modulator. For one-step prediction, we achieve 1.8 × 10-3 normalized mean squared error (NMSE). For the multi-step prediction, we explore two different mapping methods: linear-combination and concatenation, achieving 16-step prediction with NMSE as low as 3.5 × 10-4. Robust and superior for multi-step prediction, our approach and design have potential for parallel data processing tasks such as video prediction, speech translation, and so on.

Efficient electro-optical modulation on thin-film lithium niobate.

Thin-film lithium niobate has emerged as an excellent, multifaceted platform for integrated photonics and opto-electronics, in both classical and quantum domains. We introduce a novel, to the best of our knowledge, dual-capacitor electrode layout for an efficient interface between electrical and optical signals on this platform. It significantly enhances the electro-optical modulation efficiency to an exceptional voltage-length product of 0.64V⋅cm, thereby lowering the required electric power by many times. This technique can boost the performance of growing applications at the interface of integrated electronics and optics, such as microwave photonics, frequency comb generation, and telecommunication transmission.

Efficient electro-optical modulation on thin-film lithium niobate: erratum.

In this erratum, we correct the corresponding results of our Letter [Opt. Lett.46, 1884 (2021)OPLEDP0146-959210.1364/OL.419597] due to the wrong impedance setting of the arbitrary waveform generator (AWG). The Letter still represents the significant advance despite the change of results.

Bioinformatic analysis of Cacybp-associated proteins using human glioma databases.

The ubiquitin-proteasome system is the primary cellular pathway for protein degradation, mediating 80% of intracellular protein degradation. Because of the widespread presence of ubiquitin-modified protein substrates, ubiquitination can regulate a variety of cellular activities including cell proliferation, apoptosis, autophagy, endocytosis, DNA damage repair, and immune responses. With the continuous generation of genomics data in recent years it has become particularly important to analyze these data effectively and reasonably. Cacybp forms a complex with the E3 ubiquitinated ligase Siah1 to participate in ubiquitination. We analyzed Cacybp-associated genes using the Gene Expression Omnibus (GEO) and CGGA (Chinese Glioma Genome Atlas) databases and identified 121 differentially expressed genes (DEGs), of which 46 were downregulated and 75 were upregulated. The biological processes, molecular functions, and protein-protein interaction (PPI) network of differential genes were analyzed by Cytoscape software and STRING software. We found no difference in Cacybp expression among different grades of gliomas and there was no significant association between the expression level of Cacybp and the prognosis of patients with glioma in LGG and GBM. © 2019 IUBMB Life, 1-8, 2019.

High-extinction electro-optic modulation on lithium niobate thin film.

Integrated nanophotonics using lithium-niobate-on-insulator promises much-awaited solutions for scalable photonics techniques. One of its core functions is electro-optic modulation, which currently suffers limited extinction (<30 dB) due to inevitable fabrication errors. We exploit a cascaded Mach-Zehnder interferometry design to offset those errors, demonstrating up to 53 dB modulation extinction for a wide range of wavelengths between 1500 nm and 1600 nm. Together, its favorable features of chip integration, high extinction, good stability, and being broadband may prove valuable in a plethora of flourishing photonics applications.

Central nervous system disease in childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the commonest childhood malignancy. Despite therapeutic advancements, relapse of the pathological state in the form of central nervous system (CNS) disease remains a challenge. CNS disease appears to be present at diagnosis in at least 40% of patients. This relapse in the form of CNS disease is one of the major hurdles in achieving complete cure. The present review article aims to discuss the important mechanisms of leukemic entry and infiltration patterns of leukemic cells into the CNS. Also, latest updates in the management strategies of ALL will also be focused in the present article.

Current views of pediatric B cell precursor acute leucoyteic leukemia.

The most common type cancer prevailing in pediatric patients worldwide is acute lymphoblastic leukemia (ALL). The characteristic feature of this cancer is the accumulation of immature lymphoid cell in the bone marrow. Further a subtype of ALL namely B-cell precursor (BCP)-ALL has raised in the recent years and is the most common subtype of ALL prevalent in children worldwide. The present review article will put light on the current aspects of BCP ALL including etiology, causative factors, diagnostic and treatment.

Interferon gamma and interleukin 10 polymorphisms in Chinese children with hemophagocytic lymphohistiocytosis.

AIM: The aim of the study is to investigate the association of interferon gamma (IFN-γ) and interleukin-10 (IL-10) gene single nucleotide polymorphisms with the susceptibility of hemophagocytic lymphohistiocytosis (HLH) in Chinese children without known family history of HLH. PROCEDURE: Forty children with HLH and 160 age- and gender-matched healthy controls from Xuzhou Children's Hospital were enrolled in the study. Serum IFN-γ and IL-10 levels were measured by enzyme linked-immunosorbent assay. Polymorphisms of the IFN-γ gene at position +874 and +2109, and IL-10 at position -1082 were analyzed by allele-specific PCR. RESULT: Median serum concentrations of IFN -γ and IL-10 were significantly higher in children with HLH compared to healthy controls. The frequencies of IFN-γ +874 T/A and T/T genotypes, as well as T allele, were significantly higher in the HLH group compared with those in the control group. The frequencies of IL-10 -1082 G/A genotype and G allele were significantly increased in HLH patients compared with healthy controls. No significant difference was found in the distribution of IFN-γ +2109G/A genotypes between children with HLH and controls. CONCLUSION: This study presents preliminary evidence for the association between IFN +874 T/A, T/T, IL-10 -1082 A/G genotypes, and HLH susceptibility in Chinese children with HLH.

miR-326 reverses chemoresistance in human lung adenocarcinoma cells by targeting specificity protein 1.

Cisplatin resistance is a major obstacle in the treatment of lung adenocarcinoma (LAD), and its mechanism has not been fully elucidated. Here, we report that miR-326 is downregulated in cisplatin-resistant A549/CDDP cells compared with parental A549 cells. Overexpression of miR-326 reversed cisplatin chemoresistance of LAD cells in vitro and in vivo. Moreover, we identified the specificity protein 1 (SP1) gene as a novel direct target of miR-326. Knockdown of SP1 revealed similar effects as that of ectopic miR-326 expression. Decreased miR-326 expression was also detected in tumor tissues sampled from LAD patients treated with cisplatin-based chemotherapy and was proved to be correlated with high expression of SP1 and decreased sensitivity to cisplatin. Furthermore, we show that the long noncoding RNA HOTAIR repression reverses chemoresistance of LAD cells partially through modulation of miR-326/SP1 pathway. In summary, we unveil a branch of the HOTAIR/miR-326/SP1 pathway that regulates chemoresistance of LAD cells.

[Effect of phosphoinositide 4-phosphate on invasion and migration of human glioma U87 cells].

OBJECTIVE: To investigate the effect of phosphoinositide 4-phosphate (PI4P) on human glioma U87 cells and the mechanism of action of PI4P in the development of human glioma through the overexpression or silencing of PI4P in human glioma U87 cells, and to provide a new target for basic research and clinical treatment of glioma. METHODS: LV-Helper1, LV-Helper2, pWPXLd-PI4P, and pLL3.7-shPI4P were used to package pWPXLd-PI4P and pLL3.7-shPI4P lentiviruses. The U87-GFP (PI4P-overexpression control group), U87-GFP-PI4P (PI4P-overexpression experimental group), U87-Scramble (PI4P-silencing control group), and U87-shPI4P (PI4P-silencing experimental group) cell lines were established. Wound-healing assay and Transwell assay were used to evaluate cell migration and invasion, and Western blot was used to measure the expression of PI4P in each group. RESULTS: Western blot detected the expression of exogenous PI4P in the U87-GFP-PI4P cell line, and the U87-shPI4P cell line showed reduced expression of PI4P compared with the U87-Scramble cell line in the control group. The U87-GFP-PI4P cell line with PI4P overexpression had a significantly stronger ability of migration than the U87-GFP cell line in the control group (P<0.01); the U87-shPI4P cell line with PI4P silencing had a reduced ability of migration than the U87-Scramble cell line in the control group (P<0.01). The U87 cell line with PI4P overexpression had a significantly stronger invasion ability than the control group (P<0.05); after PI4P silencing, the experimental group showed a significant reduction in invasion ability compared with the control group (P<0.05). CONCLUSIONS: In human glioma U87 cells, PI4P can promote the invasion and migration of glioma cells and may become a new target in the basic research and clinical treatment of glioma.

Erratum: Pediatric haematopoiesis and related malignancies.

[This corrects the article DOI: 10.3892/ol.2017.6106.].

Prediction of Ubiquitin Ligase Nrdp1-Associated Proteins in Glioma Database.

The ubiquitin proteasome pathway is conserved from yeast to mammals and is necessary for the targeted degradation of most short-lived proteins in eukaryotic cells. Its protein substrates include cell cycle regulatory proteins and proteins that are not properly folded in the endoplasmic reticulum. Owing to the ubiquity of its protein substrates, ubiquitination regulates a variety of cellular activities, including cell proliferation, apoptosis, autophagy, endocytosis, DNA damage repair, and immune response. With new genomic data continuously being obtained, ubiquitination through genomic data analysis will be an effective method. We obtained 83 overlapping genes from four glioma databases, which differed from ubiquitin ligase Nrdp1 expression, including 36 downregulated and 47 upregulated genes. The KEGG pathways, molecular functions, cellular components, and biological processes potentially associated with Nrdp1 were obtained using GSEA and Cytoscape. In human gliomas, differences in the expression of Nrdp1 were identified between nontumor brain tissue and different glioma tissues, but no difference in expression was found between low­grade glioma (LGG) and anaplastic glioma (AG). In survival analysis, we found no significant association between Nrdp1 expression level and patient prognosis.

PART1 and hsa-miR-429-Mediated SHCBP1 Expression Is an Independent Predictor of Poor Prognosis in Glioma Patients.

Gliomas are the most common primary brain tumors. Because of their high degree of malignancy, patient survival rates are unsatisfactory. Therefore, exploring glioma biomarkers will play a key role in early diagnosis, guiding treatment, and monitoring the prognosis of gliomas. We found two lncRNAs, six miRNAs, and nine mRNAs that were differentially expressed by analyzing genomic data of glioma patients. The diagnostic value of mRNA expression levels in gliomas was determined by receiver operating characteristic (ROC) curve analysis. Among the nine mRNAs, the area under the ROC curve values of only CEP55 and SHCBP1 were >0.7, specifically 0.834 and 0.816, respectively. Additionally, CEP55 and SHCBP1 were highly expressed in glioma specimens and showed increased expression according to the glioma grade, and outcomes of high expression patients were poor. CEP55 was enriched in the cell cycle, DNA replication, mismatch repair, and P53 signaling pathway. SHCBP1 was enriched in the cell cycle, DNA replication, ECM receptor interaction, and P53 signaling pathway. Age, grade, IDH status, chromosome 19/20 cogain, and SHCBP1 were independent factors for prognosis. Our findings suggest the PART1-hsa-miR-429-SHCBP1 regulatory network plays an important role in gliomas.

Ubiquitin ligase RNF5 serves an important role in the development of human glioma.

The ubiquitin ligase ring finger protein 5 (RNF5) has previously been associated with the development of breast cancer. Patients with breast cancer and high RNF5 expression have been demonstrated to have a shorter survival time compared with patients with low RNF5 expression. However, the role of RNF5 in human glioma has not been determined. The present study analyzed the role of RNF5 in gliomas using bioinformatics analysis. The results revealed that RNF5 was differentially expressed in non-cancerous brain tissues and different grades of glioma. Furthermore, a high RNF5 expression in patients with glioma was associated with an improved prognosis compared with patients with low expression. Gene Set Enrichment Analysis revealed that RNF5 was particularly associated with 'Wnt signaling pathway', 'apoptosis', 'focal adhesion' and 'cytokine-cytokine receptor interaction' in patients with glioma. Additionally, 4 potential ubiquitination substrates for RNF5 were predicted, including sorting nexin 10, proprotein convertase subtilisin/kexin type 1, leucine rich glioma inactivated 1 and solute carrier family 39 member 12. These findings provided the basis for further investigation on the role of RNF5 in tumors.

miR-218 suppresses the proliferation of osteosarcoma through downregulation of E2F2.

Osteosarcoma is the most common primary malignant bone tumor type in children and adolescents under 20 years of age. Biological characteristics include invasiveness, metastasis, abnormal differentiation and loss of contact inhibition. microRNAs (miRNAs) are involved in the transcriptional and post-transcriptional regulation of target mRNAs. Previous studies have demonstrated that miR-218 inhibits tumor formation and progression in glioma, colon cancer and renal cell carcinoma; however, the mechanism of action of miR-218 in osteosarcoma has not been completely determined. In the present study, it was demonstrated that miR-218 exhibited low expression and targeted E2F2 in osteosarcoma cells. Additionally, overexpression of miR-218 inhibited osteosarcoma cell proliferation, with the opposite result occurring following the knockdown of miR-218. Furthermore, it was determined that miR-218 inhibited tumor formation and reduced the expression of E2F2 and proliferating cell nuclear antigen in nude mice. Collectively, the present data demonstrated that miR-218 serves an important role in suppressing the proliferation of osteosarcoma cells, potentially regulated by E2F2, which may provide a novel protein marker for the treatment of osteosarcoma.

Hsa_circ_0079530 promotes cell proliferation and invasion in non-small cell lung cancer.

Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases including cancers. However, little is known about their role in Non-small cell lung cancer (NSCLC). In the present study, we found that hsa_circ_0075930 expression levels were significantly higher in NSCLC cell lines and tissues. The elevated hsa_circ_0075930 expression was correlated with tumor size (P = 0.001) and Lymph node metastasis (P = 0.038). Functional experiments showed knockdown of hsa_circ_0075930 followed by RNA silencing restrained cell proliferation and induced cell cycle arrest of NSCLC cells. In addition, hsa_circ_0075930 suppression impaired migration and invasion potential by reversing epithelial-to-mesenchymal transition (EMT). These results indicated that hsa_circ_0075930 upregulation may be a critical oncogene and potential new biomarker in NSCLC.

Chronic myeloid leukemia extramedullary blast crisis presenting as central nervous system leukemia: A case report.

RATIONALE: Childhood chronic myeloid leukemia (CCML) is a malignant disease of granulocyte abnormal hyperplasia that is caused by clonal proliferation of pluripotent stem cells. The condition is relatively rare, accounting for 2.0% to 3.0% of cases of childhood leukemia. In addition, the incidence of extramedullary blast crisis in CCML presenting as central nervous system (CNS) blast crisis remaining chronic phase of the disease in bone marrow is extremely unusual. PATIENT CONCERNS: We report a case of childhood chronic myelogenous leukemia that abandoned treatment, resulting in chronic myelogenous leukemia transforming into extramedullary blast crisis resulting in CNS leukemia, accompanied by the chronic phase of the disease in bone marrow. DIAGNOSES: Chronic myeloid leukemia extramedullary blast crisis presenting as CNS leukemia without blast crisis in bone marrow. INTERVENTIONS: Following high-dose systemic and intrathecal chemotherapy, the patient continued to do well. LESSONS: High-dose systemic and intrathecal chemotherapy is safe and helpful for CCML extramedullary blast crisis. A long-term follow-up is crucial.

Pediatric haematopoiesis and related malignancies.

Survival after acute paediatric (0-14 years), adolescent (15-19 years) and young adult (20-39 years) leukaemia has improved substantially over the last five decades, particularly for acute lymphoblastic leukaemia (ALL) and acute promyelocytic leukaemia. This progress represents one of the most successful achievements in the history of medicine and has been attributed to the development of effective chemotherapy regimens, improvement in supportive care, better risk stratification, use of targeted therapies, and advances in haematopoietic stem cell transplantation. Recent studies have revealed improvement in survival over time for all age groups and subtypes of leukaemia. However, these outcomes varied widely by age and are associated with sociodemographic and clinical factors. The present review concludes that survival and early death after acute leukaemia has greatly improved among young patients. However, inequalities in outcomes remain and are likely a result of multiple factors.