Tethered Helical Ladder-Type Aromatic Lactams.

Tethered nonplanar aromatics (TNAs) make up an important class of nonplanar aromatic compounds showing unique features. However, the knowledge on the synthesis, structures, and properties of TNAs remains insufficient. In this work, a new type of TNAs, the tethered aromatic lactams, is synthesized via Pd-catalyzed consecutive intramolecular direct arylations. These molecules possess a helical ladder-type conjugated system of up to 13 fused rings. The overall yields ranged from 3.4 to 4.3%. The largest of the tethered aromatic lactams, 6L-Bu-C14, demonstrates a guest-adaptive hosting capability of TNAs for the first time. When binding fullerene guests, the cavity of 6L-Bu-C14 became more circular to better accommodate spherical fullerene molecules. The host-guest interaction is thoroughly studied by X-ray crystallography, theoretical calculations, fluorescence titration, and nuclear magnetic resonance (NMR) titration experiments. 6L-Bu-C14 shows stronger binding with C70 than with C60 due to the better convex-concave π-π interaction. P and M enantiomers of all tethered aromatic lactams show distinct and persistent chiroptical properties and demonstrate the potential of chiral TNAs as circularly polarized luminescence (CPL) emitters.

Report of IRF2BP1 as a novel partner of RARA in variant acute promyelocytic leukemia.

IRF2BP1 breaked in the middle of exon 1 at the c.322 position and fused with RARA intron 2 which is located at 3717 bp upstream of its exon 3. The fusion produced a new intron by forming a paired splicing donor GT at 9 bp downstream of RARA breakpoint and acceptor AG at the 5' end of RARA exon 3. The IRF2BP1::RARA fusion gene leads a fusion transcript involving IRF2BP1 exon 1 and RARA exon 3, linked by a 9-bp fragment derived from RARA intron 2. The patient with IRF2BP1::RARA has same clinical features of APL.

Advances towards genome-based acute myeloid leukemia classification: A comparative analysis of WHO-HAEM4R, WHO-HAEM5, and International Consensus Classification.

Two recent guidelines, the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) and the International Consensus Classification (ICC), were published to refine the diagnostic criteria of acute myeloid leukemia (AML). They both consider genomic features more extensively and expand molecularly defined AML subtypes. In this study, we compared the classifications of 1135 AML cases under both criteria. According to WHO-HAEM5 and ICC, the integration of whole transcriptome sequencing, targeted gene mutation screening, and conventional cytogenetic analysis identified defining genetic abnormalities in 89% and 90% of AML patients, respectively. The classifications displayed discrepancies in 16% of AML cases after being classified using the two guidelines, respectively. Both new criteria significantly reduce the number of cases defined by morphology and differentiation. However, their clinical implementation heavily relies on comprehensive and sophisticated genomic analysis, including genome and transcriptome levels, alongside the assessment of pathogenetic somatic and germline variations. Discrepancies between WHO-HAEM5 and ICC, such as the assignment of RUNX1 mutations, the rationality of designating AML with mutated TP53 as a unique entity, and the scope of rare genetic fusions, along with the priority of concurrent AML-defining genetic abnormalities, are still pending questions requiring further research for more elucidated insights.

NO production of granulocytes associated with antibacterial immune response in Tegillarca granosa.

Nitric oxide (NO) is a signaling molecule and immune effector produced by the nitric oxide synthases (NOS), which involved to various physiological processes of animals. In marine bivalves, hemocytes play important roles in antimicrobial innate immune response. Although hemocyte-derived NO has been detected in several bivalves, the immune function of hemocyte-derived NO is not well understood. Here, we investigated the antibacterial response of hemocyte-derived NO in the blood clam Tegillarca granosa. Two types of hemocytes including erythrocytes and granulocytes were isolated by Percoll density gradient centrifugation, their NO production and TgNOS expression level were analyzed. The results showed that NO was mainly produced in granulocytes and almost no detected in erythrocytes. The granulocytes showed significantly higher NO level and TgNOS expression level than the erythrocytes. And the TgNOS expression level was significantly increased in granulocytes after Vibro parahemolyticus challenge. In addition, the NO donor sodium nitroprusside (SNP) significantly increased the NO production of hemocytes to kill pathogenic bacteria. In summary, the results revealed that granulocytes-derived NO play vital roles in the antimicrobial immune response of the blood clam.

Genome-wide identification and characteristic analysis of ETS gene family in blood clam Tegillarca granosa.

BACKGROUND: ETS transcription factors, known as the E26 transformation-specific factors, assume a critical role in the regulation of various vital biological processes in animals, including cell differentiation, the cell cycle, and cell apoptosis. However, their characterization in mollusks is currently lacking. RESULTS: The current study focused on a comprehensive analysis of the ETS genes in blood clam Tegillarca granosa and other mollusk genomes. Our phylogenetic analysis revealed the absence of the SPI and ETV subfamilies in mollusks compared to humans. Additionally, several ETS genes in mollusks were found to lack the PNT domain, potentially resulting in a diminished ability of ETS proteins to bind target genes. Interestingly, the bivalve ETS1 genes exhibited significantly high expression levels during the multicellular proliferation stage and in gill tissues. Furthermore, qRT-PCR results showed that Tg-ETS-14 (ETS1) is upregulated in the high total hemocyte counts (THC) population of T. granosa, suggesting it plays a significant role in stimulating hemocyte proliferation. CONCLUSION: Our study significantly contributes to the comprehension of the evolutionary aspects concerning the ETS gene family, while also providing valuable insights into its role in fostering hemocyte proliferation across mollusks.

DNTT activation, TdT-aided gene length mutation, and better prognosis in ATG-based regimen allo-HSCT in AML.

This study aimed to investigate the relationship between anomalous DNA nucleotidylexotransferase (DNTT) activation and the mutagenesis of gene length mutations (LMs) in acute myeloid leukemia (AML), and the relevance of their prognosis in antithymocyte globulin (ATG)-based regimen allogeneic hematopoietic stem cell transplantation (allo-HSCT). A cohort of 578 AML cases was enrolled. Next-generation sequencing was performed to screen mutations of 86 leukemia driver genes. RNA-seq was used to analyze gene expression. Prognostic analysis was investigated in 239 AML cases who underwent ATG-based regimen allo-HSCT. We report a refined subtyping algorithm of LMs (type I-IV) based on sequence anatomy considering the TdT-aided mutagenesis mechanism. GC content adjacent to LM junctions, inserted nontemplate nucleotide bases, and DNTT expression analysis supported the DNTT activation and TdT-aided mutagenesis in type II/III LMs in the total AML cohort. Both single-variate and multivariate analyses showed a better overall survival of FLT3 type III compared to type I in a subset of ATG-based regimen allo-HSCT cases. The novel LM subtyping algorithm not only deciphers the etiology of the mutagenesis of LMs but also helps to fine-tune prognosis differentiation in AML. The possible prognostic versatility of this novel LM subtyping algorithm in terms of chemotherapy, targeted therapy, and allo-HSCT merits further investigation.

Competitive evolved sub-clonal BCR::ABL1 and novel MSI2::PC fusion genes in myelodysplastic syndrome with isolated del(5q).

Myelodysplastic syndrome (MDS) represents a group of neoplasms with extensive heterogeneity. Recurrent mutations in dozens of driver genes have been identified in over 90% of MDS cases, although fusion genes are rarely seen. We first report the competitive evolved sub-clonal breakpoint cluster region (BCR)::ABL1 and novel MSI2::PC fusion gene in MDS with del(5q) in initial diagnosis that underwent dismal progression. However, the BCR::ABL1 clone vanished while the MSI2::PC clone rose to the major one with disease progression. A novel MSI2::PC fusion transcript was identified in initial diagnosis and disease progression of the patient through transcriptome sequencing (RNA-seq) and Quantitative reverse transcription polymerase Chain Reaction (PCR) showed MSI2::PC/ABL1 expression at initial diagnosis and disease progression. In addition, mutation screening of 300 leukemia driver genes identified ARID2 c.5046del/p.F1682Lfs*19 and ZNF292 c.4565A > G/p.Q1522R mutation in bone marrow sample at initial diagnosis and disease progression. In conclusion, the dynamic process of the two fusion and phenotype manifestations may help to understand further the molecular significance of the anomalies of BCR::ABL1, MSI2, and PC in oncogenesis.

Report of PRPF19 as a novel partner of RARG and the recurrence of interposition-type fusion in variant acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML) which is characterized by specific clinical and biological features. Typical APL cases are caused by PML::RARA fusion gene and are exquisitely sensitive to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Rarely, APLs are caused by atypical fusions involving RARA or, in fewer cases still, fusions involving other members of the retinoic acid receptors (RARB or RARG). To date, seven partner genes of RARG have been reported in a total of 18 cases of variant APL. Patients with RARG fusions showed distinct clinical resistance to ATRA and had poor outcomes. Here, we report PRPF19 gene as a novel partner of RARG and identify a rare interposition-type gene fusion in a variant APL patient with a rapidly fatal clinical course. The incomplete ligand-binding domain of RARG in the fusion protein may account for the clinical ATRA resistance in this patient. These results broaden the spectrum of variant APL associated molecular aberrations. Accurately and timely identification of these rare gene fusions in variant APL is essential to guide therapeutic decisions.

Two common nanoparticles exert immunostimulatory and protective effects in Tegillarca granosa against Vibrio parahaemolyticus.

There are many studies revealed that metal-based nanoparticles (NPs) possess excellent bactericidal effect on multitudinous bacteria and fungi. However, the control effect of NPs as antimicrobial agents to against Vibrio parahaemolyticus infection remain in poorly understood for blood clam, Tegillarca granosa. In order to evaluate the effect, the changes in six physiological parameters and the immune-related genes expression of clams exposed to V. parahaemolyticus alone or along with NPs (nZnO or nCuO) were investigated in present study. Results showed that both tested NPs exerted prominent redemptive or mitigative effect in an inverse dose-dependent way on physiological indexes of clam, especially in the total counts, phagocytosis and the cell viability of haemocytes, as well as the concentration and activity of lysozymes, when co-exposed with Vibrio. Gene expression analysis showed NPs at a concentration of 0.1 mg/L generally mitigated the downregulation of immune-related genes after clam exposure to V. parahaemolyticus. The combination of 0.1 mg/mL nZnO and nCuO additives has been shown to significantly enhance the humoral immunity of blood clam, suggesting its potential as a protective measure against V. parahaemolyticus infection in T. granosa.

Identification of novel PIEZO1::CBFA2T3 and INO80C::SETBP1 fusion genes in an acute myeloid leukemia patient by RNA-seq.

BACKGROUND: Fusion genes are recurrent molecular aberrations in acute myeloid leukemia, with significant diagnostic and therapeutic value. The identification of novel fusion genes provides advanced biomarkers for diagnosis and facilitates the discovery of drug targets. METHODS: Bone marrow sample was extracted from an acute myeloid leukemia patient and RNA-sequencing was performed. Several bioinformatic methods, including differential analysis and Gene Set Enrichment Analysis (GSEA) pathway analyses were conducted based on the expression data. RESULTS: Two novel fusion genes, PIEZO1::CBFA2T3 and INO80C::SETBP1, were identified by RNA-seq. Differential analysis found that SETBP1 and CBFA2T3 were overexpressed, and GSEA analysis showed the activation of immune-related pathways. These findings indicate dysfunction of the fusion related- genes and possible pathogenic effect of the fusion genes. CONCLUSION: We reported a male AML patient with presence of PIEZO1::CBFA2T3 and INO80C::SETBP1 fusion genes.

Alleviating the hypoxic tumor microenvironment with MnO2-coated CeO2 nanoplatform for magnetic resonance imaging guided radiotherapy.

BACKGROUND: Radiotherapy is a commonly used tool in clinical practice to treat solid tumors. However, due to the unique microenvironment inside the tumor, such as high levels of GSH, overexpressed H2O2 and hypoxia, these factors can seriously affect the effectiveness of radiotherapy. RESULTS: Therefore, to further improve the efficiency of radiotherapy, a core-shell nanocomposite CeO2-MnO2 is designed as a novel radiosensitizer that can modulate the tumor microenvironment (TME) and thus improve the efficacy of radiation therapy. CeO2-MnO2 can act as a radiosensitizer to enhance X-ray absorption at the tumor site while triggering the response behavior associated with the tumor microenvironment. According to in vivo and in vitro experiments, the nanoparticles aggravate the killing effect on tumor cells by generating large amounts of ROS and disrupting the redox balance. In this process, the outer layer of MnO2 reacts with GSH and H2O2 in the tumor microenvironment to generate ROS and release oxygen, thus alleviating the hypoxic condition in the tumor area. Meanwhile, the manganese ions produced by degradation can enhance T1-weighted magnetic resonance imaging (MRI). In addition, CeO2-MnO2, due to its high atomic number oxide CeO2, releases a large number of electrons under the effect of radiotherapy, which further reacts with intracellular molecules to produce reactive oxygen species and enhances the killing effect on tumor cells, thus having the effect of radiotherapy sensitization. In conclusion, the nanomaterial CeO2-MnO2, as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystem with radiosensitizing function. CONCLUSION: In conclusion, the nanomaterial CeO2-MnO2, as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystems with radiosensitizing function.

Genome-wide identification and characteristic analysis of PGRP gene family in Tegillarca granosa reveals distinct immune response of the invasive pathogen.

The peptidoglycan recognition proteins (PGRPs) are conserved innate immune molecular in invertebrates and vertebrates, which play important roles in immune system by recognize the peptidoglycans of bacterial cell walls. Although PGRPs have been extensively characterized in insects, a systematic analysis of PGRPs in bivalves is lacking. In the present study, the phylogenic relationships, gene structures and expression profiles of PGRPs in marine bivalves were analyzed. The results indicated that the most PGRPs of bivalves were predicted to degrade the peptidoglycans and prevent excessive immunostimulation of bacteria. In addition, the results of the present study showed that the protein diversity of PGRPs in most marine bivalves was mainly generated by the alternative splicing of genes, however the alternative splicing of PGRP gene family was absent in Tegillarca granosa. The differences of PGRPs might be related to the genetic and environmental differences of marine bivalves. Spatiotemporal expression profiling in T. granosa suggested that PGRPs play important roles in the immune response of invasive pathogens. The present study describes a comprehensive view of PGRPs in the blood clam T. granosa and provides a foundation for functional characterization of this gene family in innate immune of marine bivalves.

Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage.

Oxidative stress damage to renal epithelial cells is the main pathological factor of calcium oxalate calculi formation. The development of medicine that could alleviate oxidative damage has become the key to the prevention and treatment of urolithiasis. Herein, porous nanorods CeO2 nanoparticles (CNPs) were selected from CeO2 with different morphologies as an antioxidant reagent to suppress kidney calcium oxalate crystal depositions with excellent oxidation resistance due to its larger specific surface area. The reversible transformation from Ce3+ to Ce4+ could catalyze the decomposition of excess free radicals and act as a biological antioxidant enzyme basing on its strong ability to scavenge free radicals. The protection capability of CNPS against oxalate-induced damage and the effect of CNPS on calcium oxalate crystallization were studied. CNPS could effectively reduce reactive oxygen species production, restore mitochondrial membrane potential polarity, recover cell cycle progression, reduce cell death, and inhibit the formation of calcium oxalate crystals on the cell surface in vitro. The results of high-throughput sequencing of mRNA showed that CNPs could protect renal epithelial cells from oxidative stress damage caused by high oxalate by suppressing the expression gene of cell surface adhesion proteins. In addition, CNPS can significantly reduce the pathological damage of renal tubules and inhibit the deposition of calcium oxalate crystals in rat kidneys while having no significant side effect on other organs and physiological indicators in vivo. Our results provide a new strategy for CNPS as a potential for clinical prevention of crystalline kidney injury and crystal deposition.

Prediction modeling of geogenic iodine contaminated groundwater throughout China.

Geogenic iodine-contaminated groundwater represents a threat to public health in China. Identifying high-iodine areas is essential to guide the mitigation of this problem. Considering that traditional analytical techniques for iodine testing are generally time-consuming, laborious, and expensive, alternative methods are needed to supplement and enhance existing approaches. Therefore, we developed an artificial neural network (ANN) model and assessed its feasibility in terms of predicting high iodine levels in groundwater in China. A total of 22 indicators (including climate, topography, geology, and soil properties) and 3185 aggregated samples (measured groundwater iodine concentrations) were utilized to develop the ANN model. The results showed that the accuracy and area under the receiver operating characteristic curve of the model on the test dataset are 90.9% and 0.972, respectively, and climate and soil variables are the most effective predictors. Based on the prediction results, a high-resolution (1-km) nationwide prediction map of high-iodine groundwater was produced. The high-risk areas are mainly concentrated in the central provinces of Henan, Shaanxi, and Shanxi, the eastern provinces of Henan, Shandong, and Hebei, and the northeastern provinces of Liaoning, Jilin, and Heilongjiang. The total number of people estimated to potentially be at high-risk areas because they use untreated high-iodine groundwater as drinking water is approximately 30 million. Considering the growing demand for groundwater in China, this work can guide the prioritization of groundwater contamination mitigation efforts based on regional groundwater quality levels to enhance environmental management.

Predicting geogenic groundwater fluoride contamination throughout China.

Endemic fluorosis exists in almost all provinces of China. The long-term ingestion of groundwater containing high concentrations of fluoride is one of the main causes of fluorosis. We used artificial neural network to model the relationship between groundwater fluoride concentrations from throughout China and environmental variables such as climatic, geological. and soil parameters as proxy predictors. The results show that the accuracy and area under the receiver operating characteristic curve of the model in the test dataset are 80.5% and 0.86%, respectively, and climatic variables are the most effective predictors. Based on the artificial neural network model, a nationwide prediction risk map of fluoride concentrations exceeding 1.5 mg/L with a 0.5 × 0.5 arc minutes resolution was generated. The high risk areas are mainly located in western provinces of Xinjiang, Tibet, Qinghai, and Sichuan, and the northern provinces of Inner Mongolia, Hebei and Shandong. The total number of people estimated to be potentially at risk of fluorosis due to the use of untreated high fluoride groundwater as drinking water is about 89 million, or 6% of the population. The high fluoride groundwater risk map helps the authorities to prioritize areas requiring mitigation measures and thus facilitates the implementation of water improvement and defluoridation projects.

Functional reorganization of brain regions into a network in childhood absence epilepsy: A magnetoencephalography study.

OBJECTIVE: Epilepsy is considered as a network disorder. However, it is unknown how normal brain activity develops into the highly synchronized discharging activity seen in disordered networks. This study aimed to explore the epilepsy brain network and the significant re-combined brain areas in childhood absence epilepsy (CAE). METHODS: Twenty-two children with CAE were recruited to study the neural source activity during ictal-onset and interictal periods at frequency bands of 1-30 Hz and 30-80 Hz with magnetoencephalography (MEG) scanning. Accumulated source imaging (ASI) was used to analyze the locations of neural source activity and peak source strength. RESULTS: Most of the participants had more active source activity locations in the ictal-onset period rather than in the interictal period, both at 1-30 Hz and 30-80 Hz. The frontal lobe (FL), the temporo-parietal junction (T-P), and the parietal lobe (PL) became the main active areas of source activity during the ictal period, while the precuneus (PC), cuneus, and thalamus were relatively inactive. CONCLUSIONS: Some brain areas become more excited and have increased source activity during seizures. These significant brain regions might be re-combined to form an epilepsy network that regulates the process of absence seizures. SIGNIFICANCE: The study confirmed that important brain regions are reorganized in an epilepsy network, which provides a basis for exploring the network mechanism of CAE development. Imaging findings may provide a reference for clinical characteristics.

Comparison of ablation characteristics of three different radiofrequency applicators in renal sympathetic denervation.

OBJECTIVE: Renal sympathetic denervation (RDN) is an alternative treatment for resistant hypertension (RH). This study aims to compare ablation effects using three radiofrequency applicators (i.e., balloon-based four electrodes, spiral and monopolar devices). METHODS: An idealized three-dimensional model of the renal artery was established using COMSOL Multiphysics to mimic radiofrequency ablation (RFA). Radiofrequency (RF) energy was delivered to the tissue at the same simulation settings, i.e., 4, 6, and 8 W for 60 s, using the three abovementioned RF applicators. The temperature distribution in the tissue was calculated using the coupled electrical-thermal-fluid finite element method. Lesion borders were defined using 50 °C isotherms. The maximum lesion depth, width, area, and circumferential coverage rate were compared among the three applicators at a blood flow of 0.4 m/s. Monopolar RF ablations in a renal artery phantom model were performed to validate the reliability of the simulation method. RESULTS: The balloon-based system yields greater lesion depths and widths compared with spiral and monopolar denervation under the same power. The range of maximum lesion depth is 1.58-3.11 mm for balloon-based RDN, 0.90-1.81 mm for spiral RDN and 1.12-2.38 mm for monopolar RDN, at a power of 4-8 W. The corresponding ranges of maximum lesion width are 2.22-5.73, 1.48-3.54, and 1.93-5.31 mm, respectively, and the circumferential coverage rates of the renal artery are 41.43%-91.99%, 31.71%-66.23%, and 9.55%-23.06%, respectively. The average velocity after balloon-based, spiral, and monopolar RDN increases by 3, 5, and 1 cm/s, respectively. The validation of the computer model offered prediction errors are <5% in terms of temperature at different locations (i.e., 2, 4, and 8 mm). CONCLUSIONS: In terms of lesion size, balloon-based RDN appears to be the best option for the treatment of RH. However, the change in flow velocity in the arterial flow field suggests that its hemodynamic changes must be prioritized for investigating its safety. Although spiral catheter ablation yields the smallest lesion size and a significant change in flow velocity in the flow field, its coverage rate is larger than that of monopolar RDN; compared with balloon-based RDN, it did not obstruct most of the blood flow.

Designing highly stable ferrous selenide-black phosphorus nanosheets heteronanostructure via P-Se bond for MRI-guided photothermal therapy.

BACKGROUND: The design of stable and biocompatible black phosphorus-based theranostic agents with high photothermal conversion efficiency and clear mechanism to realize MRI-guided precision photothermal therapy (PTT) is imminent. RESULTS: Herein, black phosphorus nanosheets (BPs) covalently with mono-dispersed and superparamagnetic ferrous selenide (FeSe2) to construct heteronanostructure nanoparticles modified with methoxy poly (Ethylene Glycol) (mPEG-NH2) to obtain good water solubility for MRI-guided photothermal tumor therapy is successfully designed. The mechanism reveals that the enhanced photothermal conversion achieved by BPs-FeSe2-PEG heteronanostructure is attributed to the effective separation of photoinduced carriers. Besides, through the formation of the P-Se bond, the oxidation degree of FeSe2 is weakened. The lone pair electrons on the surface of BPs are occupied, which reduces the exposure of lone pair electrons in air, leading to excellent stability of BPs-FeSe2-PEG. Furthermore, the BPs-FeSe2-PEG heteronanostructure could realize enhanced T2-weighted imaging due to the aggregation of FeSe2 on BPs and the formation of hydrogen bonds, thus providing accurate PTT guidance and generating hyperthermia to inhabit tumor growth under NIR laser with negligible toxicity in vivo. CONCLUSIONS: Collectively, this work offers an opportunity for fabricating BPs-based heteronanostructure nanomaterials that could simultaneously enhance photothermal conversion efficiency and photostability to realize MRI-guided cancer therapy.

Evaluating the thermal performance of a balloon-based renal sympathetic denervation system with array electrodes: a finite element study.

Renal denervation transmits radiofrequency (RF) energy through an electrode to treat resistant hypertension (RH), applying ablation in the renal artery. Several experimental studies have shown that this treatment has been used effectively to treat RH. The aim of this paper is to investigate the effect of ablation parameters (i.e., electrode length, applied voltage, ablation time, and blood flow) on the temperature distribution using a balloon-based array electrodes system. A simplified three-dimensional model including four electrodes and a balloon was established. The balloon diameter was 3 mm and placed in a 5 mm diameter renal artery for forming intra-arterial occlusion. Four electrodes were mounted on the balloon and distributed in the same plane to mimic circumferential RF ablation. Computer simulations were conducted to investigate the thermal performances of the device by setting different electrode configurations, treatment protocols, and physiological factors. The thermal performances including the thermal distribution, maximum lesion depth, length, and area were analyzed. The lesion shape of the array RF electrodes was approximately a sphere with a 100% circumference coverage rate of the renal artery. The lesion depth and length increase with each factor except for blood velocity. Increasing the electrode length from 2 to 4 mm or 2 to 6 mm, the lesion depth increases by 1.15 mm and 0.54 mm at 60 s. The corresponding lesion length increases by 2.65 mm and 2.34 mm, respectively. The range of effective lesion depth is 1.90-4.90 mm, at a voltage of 15-30 V. But the peak temperature at the arterial outer wall exceeded 100 °C when the voltage is above 25 V. In tissue, the degree of thermal injury in the 2 mm area reached 100%, but in blood was not more than 5%. There was no significant difference at different flow conditions because the difference value in lesion depth was not exceeded 0.5 mm. The results showed that the balloon-based four electrodes system is expected to overcome the difficulty of incomplete ablation. In clinical application, 2 mm-electrode is recommended to avoid long wall damage as much as possible and control the voltage below 25 V. This treatment has little thermal injury on the blood, which means it may avoid coagulation formation. Moreover, the application of this device does not need to consider the difference in individual blood velocity.

[Identification of TCF3-ZNF384 fusion by transcriptome sequencing in B cell acute lymphoblastic leukemia and its laboratory and clinical characteristics].

OBJECTIVE: To detect fusion gene with pathological significance in a patient with refractory and relapsed acute B cell lymphoblastic leukemia (B-ALL) and to explore its laboratory and clinical characteristics. METHODS: Transcriptome sequencing was used to detect potential fusion transcripts. Other laboratory results and clinical data of the patient were also analyzed. RESULTS: The patient was found to harbor TCF3 exon 17-ZNF384 exon 7 in-frame fusion transcript. The minimal residual disease (MRD) has remained positive after multiple chemotherapy protocols including CD19-, CD22- targeted chimeric antigen receptor T cells immunotherapy. The patient eventually achieved complete remission and sustained MRD negativity after allogeneic hemopoietic stem cell transplantation (allo-HSCT). CONCLUSION: Transcriptome sequencing can effectively detect potential fusion genes with clinical significance in leukemia. TCF3-ZNF384 positive B-ALL has unique laboratory and clinical characteristics, may not well respond to chemotherapy and immunotherapy, and is more likely to relapse. Timely allo-HSCT treatment may help such patients to achieve long-term disease-free survival. TCF3-ZNF384 positive B-ALL is not uncommon in pediatric patients but has not been effectively identified.