A Comprehensive Overview of the Stellate Ganglion Block Throughout the Past Three Decades: A Bibliometric Analysis.

BACKGROUND: Over the past 3 decades, clinicians and scholars have used and studied the stellate ganglion block (SGB) extensively, making this field a highly anticipated research hot spot. To the best of our knowledge, there has been no bibliometric analysis of the SGB until now. OBJECTIVE: Our study aimed to complete multiple tasks regarding SGB research: identify the collaboration and impact of countries, institutions, journals, and authors, evaluate the knowledge base, trace the trends in hot spots, and explore the emerging topics relevant to the field. STUDY DESIGN: A bibliometric analysis. METHODS: Publications that were associated with the SGB and published between the years of 1993 and 2022 were retrieved from the Web of Science Core Collection on September 21st, 2023. CiteSpace 6.1.R6 and VOSviewer 1.6.18 were used to perform bibliometric and knowledge-map analyses. RESULTS: This study found a total of 837 publications originating from 51 countries and 1006 institutions. These articles were published in 393 journals. The United States was the country that produced the most articles focused on SGB, and the University of California, Los Angeles was the institution associated with the greatest number of publications. The anesthesiology and cardiology journals surveyed for this study published the most articles and received the most citations. Among the authors whose works were examined, Kitajima T had the greatest number of published articles, and Lipov E was the most frequently cited co-author. Five main domains of SGB research included electrical storm and refractory ventricular arrhythmia, breast cancer and climacteric medicine, post-traumatic stress disorder, pain management, and cerebrovascular diseases. The latest hot topics involving this field focused on SGB's anti-arrhythmic and anti-cerebral vasospasm effects and its treatment of long COVID syndrome. LIMITATIONS: Data were retrieved only from the WoSCC; therefore, publications in other databases might have been missed. CONCLUSION: This comprehensive bibliometric analysis conducted a complete overview of SGB research, which was helpful in furthering our understanding of research trends and locating research hot spots and gaps in this domain. This field is developing rapidly and will garner significant and continuous attention from future scholars.

A case of hypopharyngeal amyloidosis by digestive endoscopy. / æ¶ˆåŒ–å† é•œæ£€æŸ¥å‘çŽ°ä¸‹å’½éƒ¨æ·€ç²‰æ ·å˜æ€§1例.

Amyloidosis is a rare disease. This paper reports a case of localized secondary hypopharyngeal amyloidosis presenting with pulmonary tuberculosis as the initial symptom. The patient lacked specific clinical manifestations and primarily exhibited symptoms such as cough, sputum production, acid reflux, belching, and abdominal pain. Chest CT indicated bronchiectasis with infection and pulmonary tuberculosis. Digestive endoscopy revealed a white mucosal elevation at the right pyriform sinus of the hypopharynx. Pathological diagnosis confirmed amyloid deposits in the hypopharyngeal mucosal tissue. The patient tested positive for anti-amyloid A antibodies, Congo red staining (+), and periodate Schiff staining (+). Amyloidosis commonly affects the digestive system and may have various etiologies, often presenting with symptoms that overlap with other digestive system diseases, leading to frequent misdiagnosis and missed optimal treatment opportunities. The hypopharynx, a highly folded and narrow chamber that serves as a common passage for the digestive and respiratory tracts, can be effectively evaluated for amyloidosis using digestive endoscopy.

A review of chemotherapeutic drugs-induced arrhythmia and potential intervention with traditional Chinese medicines.

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of clinical practice in China, and has accumulated a wealth of medical theories and treatment formulas, which has unique advantages in the prevention and treatment of malignant diseases. Traditional Chinese medicine may reduce the arrhythmic toxicity caused by chemotherapy without affecting the anti-cancer effect. This paper mainly discussed the types and pathogenesis of secondary chemotherapeutic drug-induced arrhythmia (CDIA), and summarized the studies on Chinese medicine compounds, Chinese medicine Combination Formula and Chinese medicine injection that may be beneficial in intervention with secondary CDIA including atrial fibrillation, ventricular arrhythmia and sinus bradycardia, in order to provide reference for clinical prevention and treatment of chemotherapy-induced arrhythmias.

Electrocatalytic Activity of CO2 Reduction to CO on Cadmium Sulfide Enhanced by Chloride Anion Doping.

The electrocatalytic CO2 reduction (ECR) to produce valuable fuel is a promising process for addressing atmospheric CO2 emissions and energy shortages. In this study, Cl-anion doped cadmium sulfide structures were directly fabricated on a nickel foam surface (Cl/CdS-NF) using an in situ hydrothermal method. The Cl-anion doping could significantly improve ECR activity for CO production in ionic liquid and acetonitrile mixed solution, compared to pristine CdS. The highest Faradaic efficiency of CO is 98.1 % on a Cl/CdS-NF-2 cathode with an excellent current density of 137.0 mA cm-2 at -2.25 V versus ferrocene/ferrocenium (Fc/Fc+ , all potentials are versus Fc/Fc+ in this study). In particular, CO Faradaic efficiencies remained above 80 % in a wide potential range of -2.05 V to -2.45 V and a maximum partial current density (192.6 mA cm-2 ) was achieved at -2.35 V. The Cl/CdS-NF-2, with appropriate Cl anions, displayed abundant active sites and a suitable electronic structure, resulting in outstanding ECR activity. Density functional theory calculations further demonstrated that Cl/CdS is beneficial for increasing the adsorption capacities of *COOH and *H, which can enhance the activity of the ECR toward CO and suppress the hydrogen evolution reaction.

Pancreatic pseudoaneurysm mimicking pancreatic tumor: A case report and review of literature.

BACKGROUND: Pancreatic pseudoaneurysm is a rare vascular complication of chronic pancreatitis (CP) or necrotizing pancreatitis with an incidence of 4% to 17%, but it is potentially life-threatening. It is well known that most pancreatic pseudoaneurysms are clinically associated with pancreatic pseudocysts and are usually in the peripancreatic body-tail. A minority of intrapancreatic pseudoaneurysms occur in the absence of pseudocyst formation. Noninvasive computed tomography (CT) and magnetic resonance imaging (MRI) are most commonly used examinations for screening pancreatic pseudoaneurysms. Notably, the rare intrapancreatic pseudoaneurysm in the pancreatic head can mimic a hypervascular solid mass and be misdiagnosed as a pancreatic tumor. CASE SUMMARY: We report the case of a 67-year-old man who had been admitted to our hospital due to recurrent abdominal pain for 1 mo that was aggravated for 5 d. CT and MRI revealed a mass in the pancreatic head with significant expansion of the main pancreatic duct and mild atrophy of the pancreatic body-tail. He was admitted to the department of hepatobiliary and pancreatic surgery due to the possibility of a pancreatic tumor. The patient was then referred for endoscopic ultrasonography (EUS) with possible EUS-FNA. However, EUS showed a cystic lesion in the pancreatic head with wall thickness and enhancing nodules, which was doubtful because it was inconsistent with the imaging findings. Subsequently, color doppler flow imaging demonstrated turbulent arterial blood flow in the cystic lesion and connection with the surrounding vessel. Therefore, we highly suspected the possibility of CP complicated with intrapancreatic pseudoaneurysm, combined with the patient's long-term drinking history and the sonographic features of CP. Indeed, angiography revealed an oval area of contrast medium extravasation (size: 1.0 cm × 1.5 cm) at the far-end branch of the superior pancreaticoduodenal artery, and angiographic embolization was given immediately at the same time. CONCLUSION: EUS is an important differential diagnostic tool when pancreatic pseudoaneurysm mimics the imaging appearance of a hypervascular pancreatic tumor.

Atomically Dispersed Aluminum Sites in Hexagonal Boron Nitride Nanofibers for Boosting Adsorptive Desulfurization Performance.

The exploitation of highly efficient and cost-effective selective adsorbents for adsorptive desulfurization (ADS) remains a challenge. Fortunately, single-atom adsorbents (SAAs) characterized by maximized atom utilization and atomically dispersed adsorption sites have great potential to solve this problem as an emerging class of adsorption materials. Herein, aiming at improving the efficiency of ADS performance via the economical and feasible strategy, the desirable SAAs have been fabricated by uniformly anchoring aluminum (Al) atoms on hexagonal boron nitride nanofibers (BNNF) via an in situ pyrolysis method. Remarkably, Al-BN-1.0 exhibited a superior adsorption capacity of 46.1 mg S/g adsorbent for dibenzothiophene, with a 45% increase in adsorption capacity compared to the pristine BNNF. Additionally, it demonstrated excellent adsorption of other thiophene sulfides. Moreover, the ADS mechanisms have been investigated through special adsorption experiments combined with density functional theory (DFT) calculations. It was demonstrated that the superior ADS performance and selectivity of Al-BN-1.0 originate from the sulfur-aluminum (S-Al) and π-π interactions cooperating synergistically. This work would cast light on a novel fabrication strategy for the SAAs based on the two-dimensional material with a tunable metal site configurations and densities for varied selective adsorption and separation.

Intelectin enhances the phagocytosis of macrophages via CDC42-WASF2-ARPC2 signaling axis in Megalobrama amblycephala.

Intelectin has been identified in various vertebrates and plays an important role in the host immune system. In our previous studies, recombinant Megalobrama amblycephala intelectin (rMaINTL) protein with excellent bacterial binding and agglutination activities enhances the phagocytic and killing activities of macrophages in M. amblycephala; however, the underlying regulatory mechanisms remain unclear. The present study showed that treatment with Aeromonas hydrophila and LPS induced the expression of rMaINTL in macrophages, and its level and distribution in macrophages or kidney tissue markedly increased after incubation or injection with rMaINTL. The cellular structure of macrophages was significantly affected after incubation with rMaINTL, resulting in an increased surface area and pseudopodia extension, which might contribute to enhancing the phagocytic ability of macrophages. Then, digital gene expression profiling analysis of the kidneys from rMaINTL-treated juvenile M. amblycephala identified some phagocytosis-related signaling factors that were enriched in pathways involved in the regulation of the actin cytoskeleton. In addition, qRT-PCR and western blotting verified that rMaINTL upregulated the expression of CDC42, WASF2, and ARPC2 in vitro and in vivo; however, the expression of these proteins was inhibited by a CDC42 inhibitor in macrophages. Moreover, CDC42 mediated the promotion of rMaINTL on actin polymerization by increasing the F-actin/G-actin ratio, which led to the extension of pseudopodia and remodeling of the macrophage cytoskeleton. Furthermore, the enhancement of macrophage phagocytosis by rMaINTL was blocked by the CDC42 inhibitor. These results suggested that rMaINTL induced the expression of CDC42 as well as the downstream signaling molecules WASF2 and ARPC2, thereby facilitating actin polymerization to promote cytoskeletal remodeling and phagocytosis. Overall, MaINTL enhanced the phagocytosis activity of macrophages in M. amblycephala via activation of the CDC42-WASF2-ARPC2 signaling axis.

Molecular characterization and expression patterns of CXCL8 gene from blunt snout bream (Megalobrama amblycephala) and its chemotactic effects on macrophages and neutrophils.

CXCL8 is a typical CXC-type chemokine, which mediates the migration of immune cells from blood vessels to the site of inflammation or injury to clear pathogenic microorganisms and repair damaged tissues. In this study, Megalobrama amblycephala CXCL8 (MaCXCL8) gene was identified and characterized. Sequence analysis showed that the deduced MaCXCL8 protein possessed the typical structure of CXCL8 from other species, with the characteristic CXC cysteine residues in the N-terminal and accompanied by a DLR motif (Asp-Leu-Arg motif). Phylogenetic analysis revealed that MaCXCL8 was homologous to that of Ctenopharyngodon idella and other cyprinid fishes. MaCXCL8 gene was expressed in all detected healthy tissues, with the highest expression levels in the spleen, and its expression was significantly up-regulated upon the challenge of Aeromonas hydrophila and Lipopolysaccharide (LPS) both in juvenile M. amblycephala tissues and primary macrophages. The immunohistochemical assay showed that MaCXCL8 was mainly distributed in the nucleus and cytoplasm, and its expression levels increased observably with the prolongation of bacterial infection. In addition, recombinant MaCXCL8 protein exhibited significant chemotactic effects on neutrophils and macrophages. In conclusion, MaCXCL8 is involved in the immune response of M. amblycephala, and these findings will be helpful to understand the biological roles of MaCXCL8 and provide a theoretical basis for the prevention and control of fish bacterial diseases.

Modulating Electronic Characteristics of Nickel Molybdate via an Effective Manganese-Doping Strategy to Enhance Oxidative Desulfurization Performance.

Modulating the electronic characteristics of catalysts plays a significant role in optimizing their catalytic activity. Herein, Mn-doped nickel molybdate (MNMO) nanorods are synthesized via replacing the partial Ni sites by the Mn element, engineering a bimetallic synergistic effect to enhance the activation of oxygen (O2). Compared with the extremely low catalytic activity of pristine nickel molybdate (NiMoO4), complete desulfurization can be achieved by MNMO under the same reaction conditions. Characterization results show that the electronic structure and surface atomic composition of pure NiMoO4 will be modulated owing to the introduction of Mn atoms, leading to the enhancement of the oxygen vacancy content and stronger O2 activation capacity. Besides, the optimized catalyst MNMO-20 also displays satisfactory cycle performance, and the sulfur removal of dibenzothiophene still maintains 96.1% after six times of recycling. The distinctive engineering strategy and simple synthesis method provide a new insight in designing and developing oxidative desulfurization catalysts with high stability and effectivity.

Foliar Application of Spermidine Alleviates Waterlogging-Induced Damages to Maize Seedlings by Enhancing Antioxidative Capacity, Modulating Polyamines and Ethylene Biosynthesis.

Waterlogging is a major threat to maize production worldwide. The exogenous application of spermidine is well known to enhance plant tolerance to abiotic stresses. The role of exogenous spermidine application in waterlogging tolerance in maize was investigated in this study. Two maize varieties (a waterlogging-tolerant variety: Xundan 20 (XD20) and a waterlogging-sensitive variety: Denghai 662 (DH662)) were subjected to waterlogging stress at the seedling stage, and then foliar spraying of 0.75 mM spermidine or purified water. Findings demonstrated lower chlorophyll content, reduced growth indices, considerable increase in superoxide anion (O2-) generation rate, and H2O2/malondialdehyde accumulation in the two maize varieties under waterlogging stress compared to the control treatment. However, the tolerance variety performed better than the sensitive one. Foliar application of spermidine significantly increased antioxidant enzyme activities under waterlogging stress. In addition, the application of spermidine increased polyamine levels and led to the reduction of ethylene levels under waterlogging. Consequences of spermidine application were most apparent for the waterlogging-sensitive cultivar DH662 under waterlogging than the waterlogging-tolerant variety XD20.

Identification of immune subtypes and their prognosis and molecular implications in colorectal cancer.

Immune composition is commonly heterogeneous and varies among colorectal cancer (CRC) patients. A comprehensive immune classification may act as important characteristics to predict CRC prognosis. Thus, we aimed to identify novel immune specific subtypes to guide future therapies. Unsupervised clustering was used to classify CRC samples into different immune subtypes based on abundances of immune cell populations, during which TCGA and GSE17536 datasets were used as training and validation sets, respectively. The associations between the immune subtypes and patient prognosis were investigated. Further, we identified differentially expressed genes (DEGs) between immune high and low subtypes, followed by functional enrichment analyses of DEGs. The expression levels of 74 immunomodulators (IMs) across immune subtypes were analyzed. As a result, we clustered CRC samples into three distinct immune subtypes (immune high, moderate, and low). Patients with immune-high subtype showed the best prognosis, and patients with immune-low subtype had the worst survival in both TCGA and GSE17536 cohorts. A group of 2735 up-regulated DEGs were identified across immune high and low subtypes. The main DEGs were the members of complement components, chemokines, immunoglobulins, and immunosuppressive genes that are involved in immune modulation-related pathways (e.g., cytokine-cytokine receptor interaction) or GO terms (e.g., adaptive immune response and T cell activation). The expression levels of 63 IMs were significantly varied across immune subtypes. In conclusion, this study provides a conceptual framework and molecular characteristics of CRC immune subtypes, which may accurately predict prognosis and offer novel targets for personalized immunotherapy through modifying subtype-specific tumor immune microenvironment.

TRPV1 in dorsal root ganglion contributed to bone cancer pain.

Tumor growth in situ or bone metastases in cancer patients all can induce bone cancer pain. It is frequently occurred in patients with breast, prostate, and lung cancer. Because of the lack of effective treatment, bone cancer pain causes depression, anxiety, fatigue, and sleep disturbances in cancer patients, disrupts the daily quality of life, and results in huge economic and psychological burden. Over the past years, transient receptor potential channels (TRPs), especially TRP vanilloid 1 (TRPV1) in dorsal root ganglion (DRG), have been considered to be involved in bone cancer pain. The characteristic of TRPV1 had been well studied. The mechanisms under TRPV1 regulation in DRG with bone cancer pain are complex, including inflammatory mediators, endogenous formaldehyde, and other mechanisms. In the present review, we summarize the role and potential mechanism of TRPV1 in DRG in bone cancer pain. As the primary sensory neurons, targeting the TRPV1 channel in DRG, might have fewer side effects than in central. We hope systematically understand of TRPV1 modulation in DRG will bring more effective strategy.

A rare cause of gastrointestinal bleeding in adults: Ileal duplication with ulceration: A case report and review of literature.

The ileal duplication, which is a congenital anatomical abnormality of the digestive tract, can lead to the manifestation of the alimentary tract duplication in the small intestine. It is also the rare cause of gastrointestinal bleeding and usually seen in infants, but only rarely in adults. Herein, we describe a case of adult male was suffering from intermittent massive hematochezia for three years, accompanied by abdominal pain, syncope, and palpitations. However, no positive findings were found by gastroscopy and colonoscopy in other hospitals. He visited our hospital owing to the recurrent hematochezia, but re-examination by gastroscopy and colonoscopy indicated no significant abnormality, and hence small intestinal vascular malformation bleeding was considered. Therefore, double-balloon enteroscopy (DBE) examination was conducted and the results revealed a double-lumen opening in the ileum, which was 100 cm from the ileocecal valve. The blind end was observed 6 cm away from one opening along the depth direction, and an ulcer was observed on the intestinal wall of the blind segment, which was considered as an ileal duplication. The patient thereafter underwent surgery subsequently. Postoperative pathology confirmed ileal duplication and that gastrointestinal bleeding was primarily caused by ulcer hemorrhage. The patient had no discomfort after the follow-up. In this report, we have reviewed and summarized the literature to provide references for both diagnosis and treatment of ileal duplication.

Case report: New subtype of gastric adenocarcinoma arising from an H. pylori infection-negative stomach: Foveolar epithelium and mucous neck cell-mixed type adenocarcinoma.

The characteristics of Helicobacter pylori (H. pylori) infection-negative gastric cancer have not been well documented because of its rarity, despite several types of H. pylori infection-negative gastric cancers being reported. In this report, we describe a case of early gastric cancer that developed without H. pylori infection with characteristic magnifying narrow-band imaging and novel histological findings. The difficulty in making an accurate diagnosis and differential diagnosis is highlighted, with the goal of providing more clinical experience for the diagnosis of H. pylori infection-negative gastric cancer.

Fluffy ball-like magnetic covalent organic frameworks for adsorption and removal of organothiophosphate pesticides.

Organothiophosphate pesticides (OPPs) are the most commonly used pesticides, and their environmental migration brings serious water pollution and significant danger to human health, and thus it is urgent to develop effective technologies for removal of OPPs from water. Herein, magnetic covalent organic framework (COF) with a triazine skeleton was fabricated for enhanced adsorption and removal of OPPs from water. Magnetic COF has a fluffy ball-like structure, high crystallinity, large BET surface area (1543 m2 g-1), and regular mesopores (~3.1 nm). Therefore, it displayed high adsorption rates and large adsorption capacities for four typical OPPs, pyridafenthion, phoxim, pyrimitate, and phorate. Based on adsorption kinetic and isotherms investigations, the batch experimental data of magnetic COF was effectively modeled by pseudo-second-order kinetics and the Freundlich isothermal model. The equilibrium adsorption capacities of magnetic COF composite for OPPs ranged from 163.9 to 178.6 mg g-1, which were about 10 times higher than the amorphous magnetic composite. The adsorption mechanism was further explored to verify the contributions of π-π, CH⋯π, and CH⋯S interactions to the adsorption of OPPs on the crystalline magnetic COF. Furthermore, the high removal rate of OPPs from the environmental water and reusability further indicated its potential in real applications as an effective adsorption material.

Biomarker Assessment of Homologous Recombination Deficiency in Epithelial Ovarian Cancer: Association With Progression-Free Survival After Surgery.

Identifying BRCA mutations and homologous recombination deficiency (HRD) is the key to choosing patients for poly (ADP-ribose) polymerase inhibitor (PARPi) therapy. At present, a large amount of research focuses on the application of HRD detection in ovarian cancer. However, few studies have discussed the relationship between HRD detection and postoperative survival in patients with epithelial ovarian cancer (EOC). This study included 38 consecutive patients with EOC who underwent cytoreduction surgery. Owing to tissue availability, only 29 patients underwent molecular profiling and survival analysis. Overall, 21 (72.4%) tumors had HRD scores of ≥42. Mutations in BRCA were observed in 5/29 (17.2%) patients. In this cohort, an HRD score of ≥42 was more common in serous ovarian tumors. We found no statistically significant association between homologous recombination repair (HRR) genes and HRD scores except for tumor protein P53 (TP53) mutation. We also found a strong positive association between HRD scores and chromosomal instability (CIN). In the survival analysis, an HRD score of >23 was correlated with better postoperative progression-free survival (pPFS). With increased depth of research, an appropriate HRD score threshold may serve as a prognostic tool and should be assessed in future studies to predict the clinical value of PARPi.

Green sulfidated iron oxide nanocomposites for efficient removal of Malachite Green and Rhodamine B from aqueous solution.

A green and facile pathway was described using Viburnum odoratissimum leaf extract in the presence of sodium thiosulfate for the synthesis of sulfidated iron oxide nanocomposites (S-Fe NCs) adsorbents. The prepared S-Fe NCs can be used for the efficient removal of Malachite Green (MG) and Rhodamine B (RhB) from aqueous solution. Analytical techniques by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), and X-ray photoelectron spectroscopy (XPS) were applied to understand the morphologies and compositions of S-Fe NCs. The stability of the adsorption capacity on S-Fe NCs was studied. Results from the characterization studies showed that S-Fe NCs were mainly composed of iron oxides, iron sulfides and biomolecules. The S-Fe NCs displayed high adsorption capacity for a wide range of pH values. The Koble-Corrigan isotherm model and Elovich model well described the adsorption process. The maximum adsorption capacity for MG and RhB was 4.31 mmol g-1 and 2.88 mmol g-1 at 303 K, respectively. The adsorption mechanism may be attributed to the electrostatic interaction, the hydrogen bonding, the π-π stacking interactions, the inner-sphere surface complexation or the cation bridging among the S-Fe NCs and dye molecules.

Mutation profiling of circulating tumor DNA identifies distinct mutation patterns in non-Hodgkin lymphoma.

OBJECTIVE: Circulating tumor DNA (ctDNA) is emerging as a versatile biomarker for noninvasive genotyping and response monitoring in specific B-cell lymphomas; however, few studies have been conducted to explore ctDNA-based mutation profiling across non-Hodgkin lymphomas (NHLs) and genomic changes after initiation of chemotherapy. METHODS: A targeted sequencing of 362 genes was performed to detect the mutation profiles in paired blood and tissue samples from 42 NHL patients. Genomic alterations were explored in 11 diffuse large B-cell lymphoma (DLBCL) patients using paired blood samples collected pre- and post-R-CHOP chemotherapy. RESULTS: The frequencies of PIM1, MYD88, MYC, ZNF292, JAK, and MAF mutations were higher in aggressive than in indolent B-cell lymphoma and NK/T subtypes. Tumor mutation burden in blood samples was higher in aggressive than in indolent B-cell lymphomas and higher in patients who progressed than in those who responded to treatments. Our data also revealed significant enhance of concordance index through integrating mutated genes that were significantly associated with prognosis into International Prognostic Index-based prognostic model. Moreover, acquisition of mutations such as PCLO_p.L1220Tfs*3 was associated with resistance to R-CHOP in DLBCL patients. CONCLUSIONS: Our findings illustrated distinct mutation patterns across various NHL subtypes and suggested the association of genomic alterations in ctDNA with treatment outcomes.

SEPT6_TRIM33 Gene Fusion and Mutated TP53 Pathway Associate With Unfavorable Prognosis in Patients With B-Cell Lymphomas.

BACKGROUND: Mounting studies have sought to identify novel mutation biomarkers having diagnostic and prognostic potentials. Nevertheless, the understanding of the mutated pathways related to development and prognosis of B-cell lymphoma is still lacking. We aimed to comprehensively analyze the mutation alterations in genes of canonical signaling pathways and their impacts on the clinic outcomes of patients with B-cell lymphoma. METHODS: Circulating cell-free DNA (cfDNA) samples from 79 patients with B-cell lymphomas were used for targeted sequencing with a 560-gene panel for depicting mutation landscapes and identifying gene fusion events. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of mutated genes were performed. The associations of mutation status of genes and seven canonical oncogenic pathways with progression-free survival (PFS) were assessed using Kaplan-Meier test and multivariate Cox analysis. The variant allele frequencies (VAFs) of genes in TP53 and Hippo pathways in paired baseline and post-treatment samples from 18 B-cell lymphoma patients were compared. Finally, the associations of identified fusion genes, mutated genes, and pathways with treatment response were evaluated based on objective response rates (ORRs) comparisons of groups. RESULTS: We identified 666 mutations from 262 genes in baseline cfDNAs from 79 B-cell lymphoma patients, and found some genes were preferentially mutated in our cohort such as GNAQ, GNAS, H3F3A, DNMT3A, HLA-A, and HLA-B. These frequently mutated genes were significantly associated with negative "regulation of gene expression, epigenetic" and virus infections such as cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus 1 infections. We detected five fusion genes in at least two patients with B-cell lymphoma, and among them, TCF7L2_WT1 gene fusion was most frequently detected in 30.4% of patients (24 of 79 cases). SEPT6_TRIM33 gene fusion, mutated TP53 and Hippo pathways were significantly associated with poor PFS, and SEPT6_TRIM33 fusion gene and mutated TP53 pathway were independent prognostic factors for B-cell lymphoma. A decreased VAF of TP53 p.Y88C and LATS2 p.F972L was detected in patients with complete response to treatments. Moreover, a significant difference in ORR was observed in patients with NPM1_NR4A3 and SEPT6_TRIM33 fusions. CONCLUSIONS: SEPT6_TRIM33 gene fusion and mutated TP53 and Hippo pathways may serve as prognostic makers for B-cell lymphoma patients.

Evaluation validation of a qPCR curve analysis method and conventional approaches.

BACKGROUND: Reverse Transcription quantitative polymerase chain reaction (RT-qPCR) is a sensitive and reliable method for mRNA quantification and rapid analysis of gene expression from a large number of starting templates. It is based on the statistical significance of the beginning of exponential phase in real-time PCR kinetics, reflecting quantitative cycle of the initial target quantity and the efficiency of the PCR reaction (the fold increase of product per cycle). RESULTS: We used the large clinical biomarker dataset and 94-replicates-4-dilutions set which was published previously as research tools, then proposed a new qPCR curve analysis method--CqMAN, to determine the position of quantitative cycle as well as the efficiency of the PCR reaction and applied in the calculations. To verify algorithm performance, 20 genes from biomarker and partial data with concentration gradients from 94-replicates-4-dilutions set of MYCN gene were used to compare our method with various publicly available methods and established a suitable evaluation index system. CONCLUSIONS: The results show that CqMAN method is comparable to other methods and can be a feasible method which applied to our self-developed qPCR data processing and analysis software, providing a simple tool for qPCR analysis.