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Diffuse large B‐cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease that requires personalized clinical treatment. Assigning patients to different risk categories and cytogenetic abnormality and genetic mutation groups has been widely applied for prognostic stratification of DLBCL. Increasing evidence has demonstrated that dysregulated metabolic processes contribute to the initiation and progression of DLBCL. Metabolic competition within the tumor microenvironment is also known to influence immune cell metabolism. However, metabolism‐ and immune‐related stratification has not been established. Here, 1660 genes involved in 84 metabolic pathways were selected and tested to establish metabolic clusters (MECs) of DLBCL. MECs established based on independent lymphoma datasets distinguished different survival outcomes. The CIBERSORT algorithm and EcoTyper were applied to quantify the relative abundance of immune cell types and identify variation in cell states for 13 lineages comprising the tumor micro environment among different MECs, respectively. Functional characterization showed that MECs were an indicator of the immune microenvironment and correlated with distinctive mutational characteristics and oncogenic signaling pathways. The novel immune‐related MECs exhibited promising clinical prognostic value and potential for informing DLBCL treatment decisions. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is an uncommon and incurable B‐cell lymphoma subtype that has an aggressive course. Hepatitis B virus (HBV) infection has been associated with an increased risk for B‐cell lymphomas, and is characterized by distinct clinical and genetic features. Here, we showed that 9.5% of MCL Chinese patients were hepatitis B surface antigen positive (HBsAg+). Compared to HBsAg‐negative (HBsAg−) patients, HBsAg+ MCL patients had a greater incidence of elevated lactate dehydrogenase (LDH), but no difference was observed in the other clinical characteristics, including sex, age, ECOG ps, Ann Arbor stage, MIPI, extranodal involvement and Ki‐67. The HD‐AraC (high‐dose cytarabine) regimen was the main first‐line induction regimen for younger HBsAg+ patients, and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were used for elderly patients. HBsAg seropositivity was associated with a significantly shorter PFS than HBsAg seronegativity when patients were treated with rituximab or CHOP‐based regimens. Compared with CHOP, the HD‐AraC regimen was associated with longer PFS in HBsAg+ patients. Treatment with a Bruton tyrosine kinase inhibitor (BTKi) alone can also cause HBV reactivation. Among the 74 patients who underwent targeted deep sequencing (TDS), the nonsynonymous mutation load of HBsAg+ MCL patients was greater than that of HBsAg− MCL patients. HDAC1, TRAF5, FGFR4, SMAD2, JAK3, SMC1A, ZAP70, BLM, CDK12, PLCG2, SMO, TP63, NF1, PTPR, EPHA2, RPTOR and FIP1L1 were significantly enriched in HBsAg+ MCL patients. [ABSTRACT FROM AUTHOR]

Summary: Primary gastrointestinal follicular lymphoma (PGI‐FL) is a rare extra‐nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI‐FL and 34 892 nodal FL (N‐FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age‐adjusted average annual incidence of PGI‐FL was 0.111/100000. The median overall survival (OS) for PGI‐FL and N‐FL patients was 207 and 165 months respectively. The 5‐year diffuse large B‐cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1‐, 5‐ and 10‐year OS and disease‐specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI‐FL has increased over the past 40 years, and PGI‐FL has a better prognosis and a lower DLBCL transformation rate than N‐FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high‐risk patients and choosing the optimal individualized treatments. [ABSTRACT FROM AUTHOR]

From core observations of shales of the Niutitang formation in the northern part of Guizhou Province, China, calcite was often found to act as a natural fracture filler and affect the extension of fractures in hydraulic fracturing. Therefore, it is crucial to understand the tensile mechanical behavior of shales by calcite veins. In this paper, by computed tomography scanning of shales containing calcite veins of different dip angles from the Niutitang formation, a three‐dimensional numerical model reflecting the internal fine structure of the shale was constructed. Direct tensile numerical simulations were carried out to investigate the effect of calcite veins at different angles on the fine‐scale damage process and mechanical properties of shale. The experimental results show that the tensile capacity of the shale increases with the increase in calcite veins. Depending on the dip angle of the calcite vein, the damage pattern of the shale is divided into three types of damage: pull‐off damage along the calcite vein, jagged damage, and horizontal damage perpendicular to the loading method. At high dip angles, the shale damage is more intense and the fracture network more complex. The temporal and spatial characteristics of the acoustic emissions provide a good indication of the microscopic behavior of the shale specimens during the damage process. The box dimension method was used to calculate the fractal dimension of the shale specimens at the final damage, and it was found that the damage was more intense and the fracture network was more complex at high dip angles, and there was an angular threshold. [ABSTRACT FROM AUTHOR]

Summary: Follicular lymphoma (FL), the most common indolent lymphoma, is a clinically and genetically heterogeneous disease. However, the prognostic value of driver gene mutations and copy number alterations has not been systematically assessed. Here, we analysed the clinical‐biological features of 415 FL patients to identify variables associated with disease progression within 24 months of first‐line therapy (POD24). Patients with B symptoms, elevated lactate dehydrogenase and β2‐microglobulin levels, unfavourable baseline haemoglobin levels, advanced stage, and high‐risk FL International Prognostic Index (FLIPI) scores had an increased risk of POD24, with FLIPI being the most important factor in logistic regression. HIST1H1D, identified as a driver mutation, was correlated with POD24. Gains of 6p22.2 (HIST1H1D) and 18q21.33 (BCL2) and loss of 1p36.13 (NBPF1) predicted POD24 independent of FLIPI. Gene expression profiling of FL samples showed that the POD24 cohort was significantly enriched in the inflammatory response (mediated by interferon and tumour necrosis factor), cell cycle regulation (transcription, replication and proliferation) sets and PI3K‐AKT–mTOR signalling. This result was further validated with transcriptome‐wide information provided by RNA‐seq at single‐cell resolution. Our study, performed on a large cohort of FL patients, highlights the importance of distinctive genetic alterations and gene expression relevant to disease diagnosis and early progression. [ABSTRACT FROM AUTHOR]

Secondary central nervous system (SCNS) involvement is an infrequent but universally fatal event in diffused large B‐cell lymphoma. The occurrence rate of SCNS involvement is approximately 5% but comes with a poor prognosis ever after. However, existing risk models to predict the incidence and prognosis of these patients with SCNS involvement lack both efficiency and accuracy. Controversy has also been reported regarding which risk factor may best identify the population with a high CNS relapse rate. In this study, we retrospectively analyzed 831 patients with diffused large B‐cell lymphoma, diagnosed between March 2008 and June 2018 in Tianjin Medical University Cancer Institute and Hospital, Beijing Cancer Hospital, and Cancer Hospital of The University of Chinese Academy of Science. Risk factors and nomogram were identified and established based on Fine and Gray's competing risk analysis. Among these patients, 55 (6.6%) of them eventually developed SCNS involvement. The 1‐ and 2‐year incidence for SCNS involvement were 3.9% and 4.7%, respectively. The median time from de novo diagnosis to CNS relapse was 8 months, and the median overall survival of these patients was 28 months. Considering the competing mortality before SCNS involvement, Fine and Gray's competing risk model was performed to analyze the characteristics related to SCNS involvement, and identified risk factors as the multiple extranodal involvements, elevated LDH and AMC level, and the involvement of breast, adrenal gland/kidney, pulmonary and bone. Corresponding factors were integrated into the competing nomogram for SCNS involvement (c‐index = 0.778). In conclusion, we present the first predictive nomogram to evaluate the risk to develop SCNS involvement in de novo DLBCL patients, which may help in both prognostic evaluation and clinical decision for this subgroup. [ABSTRACT FROM AUTHOR]

One of the commonly used stabilization systems for rock tunnel is shotcrete. However, the hydration of shotcrete is usually accompanied by the development of internal defects and micro damage under high temperature. Additionally, in the actual high‐temperature engineering, the temperature of the rock tunnel exhibits irregular changes. Therefore, in this study, the curing conditions of constant temperature (23°C, 40°C, 60°C, 80°C) and variable temperature (23–40–60–80°C, 80–60–40–23°C) are set, respectively. The mechanical properties and structural properties of polyurethane shotcrete and ordinary Portland shotcrete are introduced. It is determined that the limit temperature for inhibiting the development of sprayed concrete's compressive and splitting strength is between 60°C and 80°C, and the limit temperature for inhibiting the development of bond strength is about 40°C. Meanwhile, the influence of high temperature on the thermal insulation performance of shotcrete is considered. The results that the self‐foaming performance of polymer(polyurethane) reduces the thermal conductivity of shotcrete. Based on this phenomenon, the heat transfer model of shotcrete at room and high temperature is established to clarify the heat transfer process of shotcrete. Results will provide theoretical basis for further research of durability and heat insulation performance of protective spraying material for tunnel under high temperature. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease, characterised by chronic relapsing‐remitting colitis, is a significant risk factor for colorectal cancer (CRC). Previously, we showed that miR‐126 functions as a tumour suppressor in CRC and is inversely correlated with tumour proliferation, metastasis and patient prognosis. In the current study, we documented a protective role for miR‐126 in colitis‐associated CRC (CAC) and its underlying mechanism. We detected downregulated miR‐126 expression during colorectal tumorigenesis in the mouse CAC model and in specimens from patients with CRC. The deficiency of miR‐126 in intestinal epithelial cells (IECs) exacerbated tumorigenesis in mice. We identified CXCL12 as a direct target of miR‐126 in inhibiting the development of colitis and CAC. Moreover, miR‐126 regulated the recruitment of macrophages via CXCL12 and decreased the levels of proinflammatory cytokines (IL‐6, IL‐12 and IL‐23). In addition, IL‐6 secreted by macrophages, which were regulated by cocultured transfected CRC cells, altered the proliferation and migration of colon cells. Our data suggest that miR‐126 exerts an antitumour effect on CAC by regulating the crosstalk between IECs and macrophages via CXCL12‐IL‐6 signalling. Our study contributes to the understanding of cancer progression and suggests miR‐126 as a potential therapy for CRC. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the malignant tumors with the leading morbidity and mortality worldwide. H2O2 is an important oxidant, and lethal to tumor cells. The present study aimed to explore new higher‐H2O2‐content and faster‐H2O2‐release rate carbamide peroxide (CP) compounds for treatment of lung cancer. The CP added with benzoic acid termed CP−B was applied in the research. Fenton reaction was used to determine the content and rate of H2O2 release by degrading organic small molecule dyes. The results showed that CP−B could be decolorized 200 mg/L RhB solution within 60 s. The phenotype was analyzed by vitro experiment the effects of the CP compound on A549 lung cancer cell line. The results showed that CP−B had a significant effect on pro‐apoptosis, anti‐proliferation and anti‐migration of A549 cells. Using RNA seq, it was found that CP−B might up‐regulate the INS‐IGF2 gene and it was closely related to the PI3 K/AKT signaling pathway. Finally, in vivo experiments indicated that CP−B has extremely low side effects and potentially tumor treatment capabilities. [ABSTRACT FROM AUTHOR]

Alcohol consumption is thought to be one of the modifiable risk factors for colorectal cancer (CRC). However, the causality and mechanisms by which alcohol exerts its carcinogenic effect are unclear. We evaluated the association between alcohol consumption and CRC risk by analyzing data from 32 cohort studies and conducted two‐sample Mendelian randomization (MR) analysis to examine for casual relationship. To explore the effect of alcohol related DNA methylation on CRC risk, we performed an epigenetic MR analysis with data from an epigenome‐wide association study (EWAS). We additionally performed gene‐alcohol interaction analysis nested in the UK Biobank to assess effect modification between alcohol consumption and susceptibility genes. We discovered distinct effects of alcohol on CRC incidence and mortality from the meta‐analyses, and genetic predisposition to alcohol drinking was causally associated with an increased CRC risk (OR = 1.79, 95% CI: 1.23‐2.61) using two‐sample MR approaches. In epigenetic MR analysis, two alcohol‐related CpG sites (cg05593667 and cg10045354 mapped to COLCA1/COLCA2 gene) were identified causally associated with an increased CRC risk (P < 8.20 × 10−4). Gene‐alcohol interaction analysis revealed that carriage of the risk allele of the eQTL (rs3087967) and mQTL (rs11213823) polymorphism of COLCA1/COLCA2 would interact with alcohol consumption to increase CRC risk (PInteraction =.027 and PInteraction =.016). Our study provides comprehensive evidence to elucidate the role of alcohol in CRC and highlights that the pathogenic effect of alcohol on CRC could be partly attributed to DNA methylation by regulating the expression of COLCA1/COLCA2 gene. [ABSTRACT FROM AUTHOR]

Background and Aim: Although endoscopic ultrasound‐guided fine‐needle biopsy is widely applied, there is no clear consensus on the optimal biopsy technique. We described a modified wet suction technique (MWEST) with the aim to compare the efficacy and safety between MWEST and the dry suction technique (DST). Methods: In this prospective, randomized, crossover, single‐blinded study, patients with suspected pancreatic malignancy were randomized to the DST (group A) or MWEST (group B) for the first pass, and the two techniques were performed alternately. The primary outcome was the comparison of specimen adequacy and diagnostic yield between the techniques. Secondary outcomes included the macroscopic visible core length, blood contamination of specimens, and adverse events of both techniques. Results: From January 2019 to September 2019, 216 passes were performed in 50 patients. The specimen adequacy was significantly higher in "per‐lesion" (P = 0.026), "per‐pass" (cytology: P = 0.034; histology: P = 0.042), and first‐pass analysis (P = 0.034) for MWEST than for DST. In diagnostic yield, MWEST showed significantly superior histological yield (P = 0.014) and first‐pass analysis (κ: MWEST: 0.743 and DST: 0.519) compared with DST. The median macroscopic visible core lengths were 8 mm (interquartile range: 3.25–15 mm) and 10 mm (interquartile range: 5.25–15 mm) for DST and MWEST, respectively (P = 0.036). Blood contamination was significantly more serious in DST than in MWEST (cytology: P = 0.021; histology: P = 0.042). Conclusions: Endoscopic ultrasound‐guided fine‐needle biopsy with MWEST resulted in significantly better quality of specimen, histological, and first‐pass diagnostic yields and comparable safety compared with the DST. MWEST is preferred for endoscopic ultrasound‐guided fine‐needle biopsy in pancreatic solid lesions. [ABSTRACT FROM AUTHOR]