Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression.

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is a clinically and genetically heterogeneous disease with poor prognosis. Genome sequencing and mutation characterization provides a powerful approach for patient stratification, treatment target discovery, and etiology identification. However, previous studies mostly concentrated on base-level mutations in primary NKTCL, whereas the large-scale genomic alterations in NKTCL and the mutational landscapes in relapsed/refractory NKTCL remain largely unexplored. METHODS: Here, we assembled whole-genome sequencing and whole-exome sequencing data from 163 patients with primary or relapsed/refractory NKTCL and compared their somatic mutational landscapes at both nucleotide and structure levels. RESULTS: Our study not only confirmed previously reported common NKTCL mutational targets like STAT3, TP53, and DDX3X but also unveiled several novel high-frequency mutational targets such as PRDM9, DST, and RBMX. In terms of the overall mutational landscape, we observed striking differences between primary and relapsed/refractory NKTCL patient groups, with the latter exhibits higher levels of tumor mutation burden, copy number variants (CNVs), and structural variants (SVs), indicating a strong signal of genomic instability. Complex structural rearrangements such as chromothripsis and focal amplification are also significantly enriched in relapsed/refractory NKTCL patients, exerting a substantial impact on prognosis. Accordingly, we devised a novel molecular subtyping system (i.e., C0-C4) with distinct prognosis by integrating potential driver mutations at both nucleotide and structural levels, which further provides an informative guidance for novel treatments that target these specific driver mutations and genome instability as a whole. CONCLUSIONS: The striking differences underlying the mutational landscapes between the primary and relapsed/refractory NKTCL patients highlight the importance of genomic instability in driving the progression of NKTCL. Our newly proposed molecular subtyping system is valuable in assisting patient stratification and novel treatment design towards a better prognosis in the age of precision medicine.

Development and validation of a novel prognostic nomogram for advanced diffuse large B cell lymphoma.

Advanced diffuse large B cell lymphoma (DLBCL) is a common malignant tumor with aggressive clinical features and poor prognosis. At present, there is lack of effective prognostic tool for patients with advanced (stage III/IV) DLBCL. The aim of this study is to identify prognostic indicators that affect survival and response and establish the first survival prediction nomogram for advanced DLBCL. A total of 402 patients with advanced DLBCL were enrolled in this study. COX multivariate analysis was used to obtain independent prognostic factors. The independent prognostic factors were included in the nomogram, and the nomogram to predict the performance of the model was established by R rms package, C-index (consistency index), AUC curve and calibration curve. The training and validation cohorts included 281 and 121 patients. In the training cohort, multivariate analysis showed that Ki-67 (70% (high expression) vs ≤ 70% (low expression), p < 0.001), LDH (lactate dehydrogenase) (elevated vs normal, p = 0.05), FER (ferritin) (elevated vs normal, p < 0.001), and ß2-microglobulin (elevated vs normal, p < 0.001) were independent predictors and the nomogram was constructed. The nomogram showed that there was a significant difference in OS among the low-risk, intermediate-risk and high-risk groups, with 5-year survival rates of 81.6%, 44% and 6%, respectively. The C-index of the nomogram in the training group was 0.76. The internal validation of the training group showed good consistency. In the internal validation cohort of the training group, the AUC was 0.828, and similar results were obtained in the validation group, with a C-index of 0.74 and an AUC of 0.803. The proposed nomogram provided a valuable individualized risk assessment of OS in advanced DLBCL patients.

Discontinuation and nonpublication of nasopharyngeal carcinoma clinical trials.

OBJECTIVES: To determine the extent of research waste in the field of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: In this cross-sectional study, we explored the rates, causes and predictors of discontinuation and nonpublication of NPC clinical trials. The sample was derived using the ClinicalTrials.gov advanced search function. Adjusted logistic regression was used to ascertain the effect of trial characteristics on completion and publication status. If a trial discontinuation explanation or publication status could not be determined through the systematic search, the corresponding author was emailed. RESULTS: Ultimately, 311 NPC clinical trials were included (255 [82.0 %] completed and 56 [18.0 %] discontinued trials). The most common reason for trial discontinuation was poor accrual (50 %, 23/46). Industry funding (adjusted OR, 3.12; P = 0.003) and recurrent/metastatic setting (adjusted OR, 11.95; P = 0.003) were significantly associated with increased likelihood of trial discontinuation. Of the 207 completed trials included in the publication query, 141 (68.1 %) were published in peer-reviewed journals, 10 (4.8 %) had results only available on ClinicalTrials.gov, and 56 (27.1 %) remained unpublished 3 or more years after trial completion. Radiation with or without pharmacologic interventions significantly increased the potential of publication (adjusted OR, 3.20; P = 0.048). Among published trials, the median time to publication was 28.47 months (interquartile range, 15.27-44.98 months). CONCLUSION: We identified the difficulties inherent in NPC clinical trials from completion to publication. This represents considerable research waste in NPC, thus raising ethical concerns about the concealment of clinical data and futile patient participation and attendant risks.

Phosphorus removal from water by the metal-organic frameworks (MOFs)-based adsorbents: A review for structure, mechanism, and current progress.

Efficacious phosphate removal is essential for mitigating eutrophication in aquatic ecosystems and complying with increasingly stringent phosphate emission regulations. Chemical adsorption, characterized by simplicity, prominent treatment efficiency, and convenient recovery, is extensively employed for profound phosphorus removal. Metal-organic frameworks (MOFs)-derived metal/carbon composites, surpassing the limitations of separate components, exhibit synergistic effects, rendering them tremendously promising for environmental remediation. This comprehensive review systematically summarizes MOFs-based materials' properties and their structure-property relationships tailored for phosphate adsorption, thereby enhancing specificity towards phosphate. Furthermore, it elucidates the primary mechanisms influencing phosphate adsorption by MOFs-based composites. Additionally, the review introduces strategies for designing and synthesizing efficacious phosphorus capture and regeneration materials. Lastly, it discusses and illuminates future research challenges and prospects in this field. This summary provides novel insights for future research on superlative MOFs-based adsorbents for phosphate removal.

Characteristics of immunotherapy trials for nasopharyngeal carcinoma over a 15-year period.

Background: Immunotherapy has been a hotspot in nasopharyngeal carcinoma (NPC) in recent years. This study aimed to provide a comprehensive landscape of the characteristics of immunotherapy clinical trials in NPC and to determine whether contemporary studies are of sufficient quality to demonstrate therapeutic value. Methods: This is a cross-sectional analysis of NPC trials registered on ClinicalTrials.gov in the last 15 years (Jan 1, 2008-Nov 20, 2022). Only interventional trials with a primary purpose of treatment were included in the final analysis. Characteristics of immunotherapy trials were compared with those of other NPC trials. Chronological shifts in NPC immunotherapy trials were also analyzed. Results: Of the 440 NPC studies selected, 161 (36.6%) were immunotherapy trials and 279 (63.4%) were other NPC trials. NPC immunotherapy trials were more likely than other NPC trials to be phase 1-2 (82.6% vs. 66.7%, P < 0.001), single-arm (51.3% vs. 39.6%, P = 0.020), non-randomized (64.8% vs. 44.4%, P < 0.001), and enroll fewer than 50 participants (46.3% vs. 34.4%, P = 0.015). Blinding was used in 8.8% of NPC immunotherapy trials. Also, 90.7% of NPC immunotherapy trials were recruited nationally and 82.6% were Asia-centric. Although academic institutions and governments (72.7%) were the major sponsors of NPC trials, immunotherapy trials were more likely to be industry-funded than other NPC trials (34.2% vs. 11.5%, P < 0.001). The number of NPC immunotherapy trials increased exponentially after 2017, attributed to the exploration of immune checkpoint inhibitors. Immunotherapy combined with chemotherapy was the most commonly investigated regimen. Conclusion: NPC immunotherapy trials over a 15-year period were predominantly exploratory. To generate high-quality evidence and advance the clinical application of immunotherapy in NPC, more attention and concerted efforts are needed.

Diagnostic and prognostic value of pretreatment PET/CT in extranodal natural killer/T-cell lymphoma: a retrospective multicenter study.

PURPOSE: The objective of this research was to assess the utility of positron emission tomography combined with computed tomography (PET/CT) to detect bone marrow invasion (BMI) and the predictive value of PET/CT in extranodal natural killer/T-cell lymphoma (ENKTL) patients. PATIENTS AND METHODS: This multicentre study enrolled ENKTL patients who underwent pretherapy PET/CT and bone marrow biopsy (BMB). The specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV) of PET/CT and BMB for BMI were evaluated. Multivariate analysis was used to identify predictive parameters for constructing a nomogram. RESULTS: Seven hundred and forty-eight patients were identified from four hospitals, with eighty (10.7%) having focal skeletal lesions on PET/CT and fifty (6.7%) having positive BMB. When BMB is considered as the gold standard, the specificity, sensitivity, PPV, and NPV of PET/CT for diagnosing BMI were found to be 93.8%, 74.0%, 46.3%, and 98.1%, respectively. PET/CT-positive individuals showed significantly worse OS than PET/CT-negative patients in the subgroup of BMB-negative cases. The nomogram model created according to the significant risk factors from multivariate analysis performed well in predicting survival probability. CONCLUSION: PET/CT offers a superior degree of precision for determining BMI in ENKTL. A nomogram model including the parameters of PET/CT can predict survival probability and may help in applying appropriate personalized therapy.

Directional regulation and mechanism analysis of the surface properties of hydrothermal carbon by circulating liquid in the hydrothermal carbonization procedure.

The complexity of the chemistry behind the hydrothermal conversion is enormous. Components interact with their own physical and chemical structure, making it harsh to understand the conversion as a whole. Herein, the six-water recirculation and loading nano SiO2 experiment in a one-pot hydrothermal carbonization procedure was designed to elucidate the mechanism of regulating the functional groups and microporous structure of the hydrochar surface. The hydrochar prepared by the second circulating liquid and loading nano-SiO2 (HBC-R2/Si) was equipped most enriched functional groups (carboxyl = 11.48 µmol/g, phenolic hydroxyl = 52.98 µmol/g, lactone groups = 46.52 µmol/g) and suitable pore size (1.90 nm-1.93 nm) as a sorbent riched in hemicellulose. The sorption kinetics (equilibrium reached ≈ 480 min) are approximately evenly fitted by the pseudo-second-order, Weber and Morris, and Elovich models, indicating that membranes and particles diffusion, pore diffusion, and surface sorption coexisted in the sorption of methylene blue (MB) on the hydrochar materials. Simultaneously, all hydrochar materials achieved over 25% MB removal within 90 min (liquid membrane diffusion) and over 40% for HBC-R2 and HBC-R2/Si, suggesting that liquid membrane diffusion is the predominant rate-limiting step. Pearson's correlation analysis and Mantel's analysis announced that the cation exchange capacity (CEC), pore size, and carboxyl groups on the hemicellulose affect the sorption capacity by limiting the pore diffusion procedure. However, the CEC and the phenolic hydroxyl groups on the cellulose and hemicellulose affect the sorption rate by limiting membrane diffusion. Three consecutive sorption/desorption cycles confirmed the high stability and reusability of HBC-R2/Si composites.

A study on the prevention of hemorrhage and perforation in patients with primary gastric diffuse large-B cell lymphoma during treatment with immunochemotherapy.

BACKGROUND: Stomach hemorrhage and perforation are very severe and common complications in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL) during treatment with immunochemotherapy. However, no relevant clinical studies have been performed on the prevention of these serious complications. METHODS: Patients diagnosed with PG-DLBCL were enrolled in this retrospective study. The prevention group received standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) treatment without prednisone combined with antacids and anti-Helicobacter pylori (Hp) therapy. These patients received R-CHOP-based treatment until the complete recovery of gastric ulcers, as proven by gastroscopy. The control group received a standard R-CHOP regimen. Toxicity and survival were the main endpoints. RESULTS: A total of 52 patients received preventative treatment, while 146 patients did not. Among patients with stage I, II-1, and II-2 disease, the prevention group had a lower rate of hemorrhage and perforation (0/40) than the control group (10/78, p = 0.044). At a median follow-up time of 25 months, the 5-year event-free survival (EFS) rates were 97.1% in the prevention group and 66.1% in the control group (p = 0.025), and the 5-year overall survival (OS) rates were 100% and 72.0%, respectively (p = 0.021). However, the differences in the 5-year EFS and OS of patients with disseminated disease were not statistically significant. CONCLUSIONS: Preventative treatment can decrease the risk of hemorrhage and perforation in patients with localized PG-DLBCL during immunochemotherapy, leading to better EFS and OS in these patients. However, preventative treatment failed to reduce the risk of gastric hemorrhage and perforation and did not improve survival (EFS and OS) in advanced-stage patients.

Proposed prognostic subgroups and facilitated clinical decision-making for additional locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma: a retrospective study based on recursive partitioning analysis.

BACKGROUND: The high heterogeneity of de novo metastatic nasopharyngeal carcinoma (dmNPC) makes its prognosis and treatment challenging. We aimed to accurately stage dmNPC and assess the patterns of treatment strategies for different risk groups. METHODS: The study enrolled a total of 562 patients, 264 from 2007 to 2013 in the training cohort and 298 from 2014 to 2017 in the validation cohort. Univariate and multivariate Cox regression analyses were conducted to determine the independent variables for overall survival (OS). Recursive partitioning analysis (RPA) was applied to establish a novel risk-stratifying model based on these variables. RESULTS: After pairwise comparisons of OS, three risk groups were generated: low-risk (involved lesions ≤ 4 without liver involvement), intermediate-risk (involved lesions ≤ 4 with liver involvement or involved lesions > 4 with Epstein-Barr virus (EBV)-DNA < 62,000 copies/ml), and high-risk (involved lesions > 4 with EBV-DNA > 62,000 copies/ml). The 3-year OS rate differed significantly between groups (80.4%, 42.0%, and 20.4%, respectively, all P < 0.05). Adding locoregional intensity-modulated radiotherapy (LRRT) followed by palliative chemotherapy (PCT) resulted in a significant OS benefit over PCT alone for the low- and intermediate-risk groups (P = 0.0032 and P = 0.0014, respectively). However, it provided no survival benefits for the high-risk group (P = 0.6). Patients did not benefit from concurrent chemotherapy during LRRT among the three subgroups (P = 0.12, P = 0.13, and P = 0.3, respectively). These results were confirmed with the validation cohort. CONCLUSIONS: The novel RPA model revealed superior survival performance in subgroup stratification and could facilitate more effective treatment strategies for dmNPC.

The role of MnO2 crystal morphological scale and crystal structure in selective catalytic degradation of azo dye.

MnO2, as a representative manganese-based catalyst with many kinds of crystal forms, has been widely used to activate PMS. However, the role of morphological scale and crystal structures on the catalytic capability of MnO2 still lacks further study. In this study, four different crystal forms of MnO2 (α-MnO2, ß-MnO2, γ-MnO2, and δ-MnO2) are succeeded in being fabricated via hydrothermal processes and evaluated by activating PMS for the removal of Reactive Yellow X-RG, typical azo dye. Experiment results indicate that α-MnO2 with a one-dimensional structure exhibits the best catalytic performance among the four as-prepared MnO2, which can be attributed to its broadest crystal interplanar distance (0.692), the highest portion of Mn (III)/Mn (IV) (4.194), and lowest value of average oxidation state AOS (2.696). Correlation analysis confirms that interplanar distance is the most relative factor with the catalytic activity of MnO2 among the three studied factors (R2 = 0.99715). Meanwhile, the morphological scale structure of α-MnO2 can also account for its highest catalytic ability among the four as-prepared MnO2, including its large specific area and advantageous one-dimensional nanostructure. Furthermore, according to the response surface methodology, when the dosage of PMS is 2.369 g/L, the dosage of α-MnO2 is 0.991 g/L, and the initial dye concentration is 1025 mg/L, the maximum removal rate of Reactive Yellow X-RG is up to 97.38%.

Clinical features and treatment outcome of lymphoepithelioma-like carcinoma from multiple primary sites: a population-based, multicentre, real-world study.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a rare and unique subtype of cancer that histologically resembles undifferentiated nasopharyngeal carcinoma (NPC). The population-based analysis of LELC and the optimal treatment remains unclear. MATERIALS AND METHODS: This real-world, retrospective study investigated 770 patients with LELC for primary site, treatment, and survival outcomes from 2005 to 2019 from five cancer centres in China. The overall survival (OS) of different subgroups was appraised by log-rank tests and Kaplan-Meier analysis. RESULTS: Primary sites LELC included the lung (597 cases, 77.5%), salivary gland (115 cases, 14.9%), and others. The median progression-free survival (PFS) of LELC patients was 47.4 months. The median overall survival (OS) was not reached. The 5-year survival rate for LELC patients was 77.8%. Most patients in stages I and II received surgery. The majority of patients in stage III received surgery and radiotherapy. More than half of the patients in stage IV received chemotherapy. Among relapsed or metastatic cases receiving chemotherapy, patients who received immunotherapy at any time presented with a superior OS than those without immunotherapy (P < 0.0001, HR = 0.39, 95% CI 0.25-0.63). Compared with the SEER database, patients with LELC had a better prognosis than NPC, with a 5-year overall survival of 77.3% vs. 56.8% (P < 0.001). CONCLUSION: Our data provide treatment patterns and outcomes for LELC from various primary sites. Randomized controlled studies are necessary to further define the standard of care for patients with LELC. Trial registration This clinical trial was registered at ClinicalTrials.gov (No. NCT04614818).

Construction on teaching quality evaluation indicator system of multi-disciplinary team (MDT) clinical nursing practice in China: A Delphi study.

AIM: To construct an evaluation indicator system for nursing multi-disciplinary team (MDT) clinical practice in China and to provide quantifiable indicators for MDT clinical teaching courses. METHODS: Based on relevant literature retrieval and analysis, a evaluation indicator system of nursing MDT clinical teaching quality was preliminarily constructed using the Donabedian. Structure-Process-Outcome model as theoretical guidance. Then, a final indicators content was formed after two rounds of expert consultation and Analytic Hierarchy Process (AHP) was used to determine the weight of indicators at all levels. RESULTS: The effective response rate of the questionnaires in two rounds were 95.23% (20/21) and 100% (20/20) respectively, the expert authority coefficient (Cr) were 0.838 and 0.853 respectively and the Kendall's coefficient of concordance (Kendall's W) of indicators at all levels were 0.137-0.612 (P < 0.05). The final evaluation index system consisted of three one-class indicators, 8 s-class indicators and 28 third-class indicators. CONCLUSION: The study constructed a comprehensive set of evaluation indicator system of nursing MDT clinical practice, which was scientific and reliable and provides reference for the clinical teaching quality evaluation of MDT nursing.

Investigation of Molecular Mechanism of Banxia Xiexin Decoction in Colon Cancer via Network Pharmacology and In Vivo Studies.

Objective: Banxia Xiexin decoction (BXD) is widely used in the treatment of gastrointestinal and other digestive diseases. This study is based on network pharmacology to explore the molecular mechanism of BXD in the treatment of colon cancer. Methods: The bioactive components and potential targets of BXD were obtained from public database. The protein-protein interaction (PPI) network of the potential targets of BXD for colon cancer was constructed based on the STRING database, cytoscape software, gene ontology (GO), and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of the PPI network. Finally, we established a xenograft nude mouse model to verify the effect of BXD in colon cancer treatment. Results: We have acquired a total of 55 bioactive components and 136 cross-targets of BXD. The results of enrichment analysis suggested that the oxidate stress and diet were the key factors of colon cancer occurrence, and AGE-RAGE signaling pathway plays an essential role in the treatment of colon cancer with BXD. Animal experiments revealed that BXD could suppress tumor growth and induce tumor cell apoptosis in the xenograft nude mouse model with HCT116 cells. Conclusion: This study uncovered that BXD inhibits the malignant progression of colon cancer that may be related to multiple compounds (berberine, quercetin, baicalein, etc.), multiple targets (Bcl2, Bax, IL6, TNFα, CASP3, etc.), and multiple pathways (human cytomegalovirus infection, AGE-RAGE signaling pathway in diabetic complications, etc.).

Identification of the shared gene signatures and pathways between polycystic ovary syndrome and endometrial cancer: An omics data based combined approach.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with high incidence. Recently it has been implicated as a significant risk factor for endometrial cancer (EC). Our study aims to detect shared gene signatures and biological mechanism between PCOS and EC by bioinformatics analysis. METHODS: Bioinformatics analysis based on GEO database consisted of data integration, network construction and functional enrichment analysis was applied. In addition, the pharmacological methodology and molecular docking was also performed. RESULTS: Totally 10 hub common genes, MRPL16, MRPL22, MRPS11, RPL26L1, ESR1, JUN, UBE2I, MRPL17, RPL37A, GTF2H3, were considered as shared gene signatures for EC and PCOS. The GO and KEGG pathway analysis of these hub genes showed that "mitochondrial translational elongation", "ribosomal subunit", "structural constituent of ribosome" and "ribosome" were highly correlated. Besides, associated transcription factors (TFs) and miRNAs network were constructed. We identified candidate drug molecules including fenofibrate, cinnarizine, propanil, fenthion, clindamycin, chloramphenicol, demeclocycline, hydrochloride, azacitidine, chrysene and artenimol according to these hub genes. Molecular docking analysis verified a good binding interaction of fenofibrate against available targets (JUN, ESR1, UBE2I). CONCLUSION: Gene signatures and regulatory biological pathways were identified through bioinformatics analysis. Moreover, the molecular mechanisms of these signatures were explored and potential drug molecules associated with PCOS and EC were screened out.

A novel prognostic nomogram for patients with extragastric mucosa-associated lymphoid tissue lymphoma: A multicenter study.

BACKGROUND: The aim of this study was to explore predictors and construct a nomogram for risk stratification in primary extragastric mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: Extragastric MALT lymphoma cases newly diagnosed between November 2010 and April 2020 were assessed to construct a progression-free survival (PFS)-related nomogram. We also performed external validation of the nomogram in an independent cohort. RESULTS: We performed multivariate analyses of 174 patients from 3 hospitals who were included in the training cohort. Stage, hepatitis B virus surface antigen (HBsAg) status, and Ki67 expression were significantly associated with PFS. These three factors were used to construct a nomogram, which was shown to have a C-index of 0.89. Two risk groups (low risk and high risk) were identified by the prognostic model. The 5-year PFS was 98.9% for the low-risk group and 69.3% for the high-risk group (p < 0.001). The overall survival (OS) could also be effectively distinguished by the nomogram, resulting in an OS of 100% for the low-risk group and 94.6% for the high-risk group (p = 0.01). These results were validated and confirmed in an independent cohort with 165 patients from another three hospitals. The 5-year PFS rates were 94.8% and 66.7% for the low-risk and high-risk groups, respectively (p < 0.001). The 5-year OS rates were 97.9% and 88.4%, respectively (p = 0.016). CONCLUSION: The nomogram could well distinguish the prognosis of low- and high-risk patients with extragastric MALT lymphoma and is thus recommended for clinical use.

Role of m5 C RNA methylation regulators in colorectal cancer prognosis and immune microenvironment.

BACKGROUND: RNA modification has become one of the hot topics of research as it can be used for tumor prognosis. However, its role in various biological processes is still poorly understood. The aim of this study was to investigate the role of m5 C and m1 A regulators on colorectal cancer prognosis using bioinformatics tools. The association between these regulators and differences in patient survival as well as the clinicopathological characteristics and tumor immune microenvironment in colorectal cancer tissues were assessed. METHODS: We selected publicly available colorectal cancer data sets from The Cancer Genome Atlas and used the "limma" package in R to identify differentially expressed genes. The least absolute shrinkage and selection operator regression model was used to calculate the prognostic risk, and a risk prediction model was constructed, to help assess the prognostic values of the differentially expressed genes. Finally, using TISCH and TIMER, we assessed the extent of cellular infiltration in colorectal cancer. RESULTS: We explored NSUN6 and DNMT3A expression using UALCAN and HPA and found that their expression is significantly increased in colorectal cancer tissues and correlated with sex and TP53 mutation status. Moreover, we found NSUN6 and DNMT3A were related to the infiltration of six major immune cells, with DNMT3A being closely related to dendritic cells, CD4+ T cells, and B cells, whereas NSUN6 to B cells and CD8+ T cells. CONCLUSION: Our findings suggest that m5 C regulators can predict the clinical prognostic risk and regulate the tumor immune microenvironment in colorectal cancer.

Rituximab Concentration Varies in Patients With Different Lymphoma Subtypes and Correlates With Clinical Outcome.

Individual variations in concentrations of rituximab in different B cell non-Hodgkin's lymphoma subtypes and their relevance to efficacy were still unclear. From 2016 to 2021, a prospective clinical trial was conducted, and 510 samples with 6 uncommon subtypes of B-cell lymphoma were enrolled to examine the pharmacokinetic behaviour of rituximab and its impact on clinical outcomes, including complete response (CR), progression-free survival (PFS) and overall survival (OS). Considerable variability was observed in the rituximab trough concentration in the first cycle (C1-trough, 1.16-55.52 µg/ml) in patients with different lymphoma subtypes. Patients with "double-hit" lymphoma (4.01 ± 0.77 µg/ml) or mantle cell lymphoma (MCL; 15.65 ± 16.45 µg/ml) had much lower C1-trough and worse outcomes. Great individual variation in the C1-trough existed among patients with mucosa-associated lymphoma (MALT), and the high C1-trough observed in patients treated with the RB regimen was associated with a better response than was obtained with R-CHOP (38.41 ± 14.13 µg/ml vs 15.49 ± 8.80 µg/ml, p = 0.0029). Despite the high aggressiveness of the cancer, Burkitt lymphoma patients receiving intensive chemotherapy had the highest C1-trough (28.85 ± 9.35 µg/ml) and maintained long-term PFS. The C1-trough in patients with mixed, unclassifiable B-cell lymphoma was close to 20 µg/ml, and these patients had acceptable outcomes. Overall, a low rituximab C1-trough was associated with adverse consequences, including persistent progression, early recurrence and a short OS, however, some high-risk factors appeared to be balanced by the presence of a high C1-trough. Basal levels of circulating CD19+ lymphocytes differed between and within patients with diverse lymphoma subtypes and were negatively correlated with C1-trough. Therefore, the traditional doses of rituximab are inadequate for patients with "double-hit" lymphoma and MCL. Increasing the initial rituximab dose according to the disease, high-risk factors and even the baseline CD19+ lymphocyte count will be new methods to optimize therapeutic regimens for patients with different lymphoma subtypes.

A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study.

BACKGROUND: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. METHODS: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. RESULTS AND CONCLUSIONS: Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

Efficacy and safety of immune checkpoint inhibitors in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitor (ICI) therapies have shown promising prospects in colorectal cancer (CRC) immunotherapy; many clinical trials have been carried out. In this study, we sought to evaluate the efficacy and safety of ICI therapies in CRC by presenting a meta-analysis of relevant studies. METHODS: Databases including PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for studies concerning the efficacy and safety of ICI in colorectal cancer. The reported odds ratio (OR) or weighted mean difference (WMD) with 95% confidence intervals (CIs) of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs), and TRAEs ≥ 3 in the included studies were analyzed by fixed effects/random effects models. RESULTS: Three studies involving 667 patients with colorectal cancer were included in our meta-analysis. No significant difference between the immune checkpoint inhibitor therapies and conventional therapies in OS (WMD = 0.73, 95% CI - 3.09, 4.54; p = 0.71), in ORR (OR = 1.54, 95% CI 0.98, 2.40; p = 0.06), and in DCR (OR = 0.97, 95% CI 0.36, 2.61; p = 0.95). The median PFS of the ICI therapy group was shorter than that of the conventional therapy group (WMD = - 0.10, 95% CI - 0.18, - 0.02; p = 0.02). At the same time, we also could not find a significant difference between the immune checkpoint inhibitor therapies and conventional therapies in TRAEs (OR = 1.56, 95% CI 0.11, 22.09; p = 0.74) and in TRAEs ≥ 3 (OR = 0.94, 95% CI 0.16, 5.65; p = 0.95). CONCLUSION: Immune checkpoint inhibitor therapies could not improve all survival endpoints to advanced or metastatic colorectal cancer patients. Whether immune checkpoint inhibitors should be the first choice of therapies for colorectal cancer patients with undetermined microsatellite status or not able to determine microsatellite status needs more related studies to prove.

Rituximab exposure-response in triweekly R-CHOP treatment in DLBCL: A loading dose is recommended to improve clinical outcomes.

Previous exposure-response analyses for rituximab suggest that higher rituximab concentrations were associated with an improvement in efficacy, however, clinical studies investigating a higher rituximab dose had mixed results. To further explore the exposure-response relationship of rituximab, a prospective observational analysis was performed involving 121 newly diagnosed patients with diffuse large B-cell lymphoma treated with triweekly rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The trough concentration in the first cycle (C1-trough ) was significantly higher in patients achieving complete response (CR) compared with patients that did not achieve CR (22.00 µg/ml vs. 16.62 µg/ml, p = 0.0016), however, this difference between the two groups disappeared in later cycles. The relationship between rituximab C1-trough and achieving a CR was confirmed by matched-pair logistic regression analysis (odds ratio, 0.79; p = 0.0020). In addition, a higher C1-trough (≥18.40 µg/ml) was associated with longer progression-free survival (p < 0.0001) and overall survival (p = 0.0038). The percentages of patients that did not achieve a CR and had recurrence after CR within 24 months were 35% and 22.50%, respectively, for patients with a C1-trough less than or equal to 18.40 µg/ml, compared with 12.35% and 6.17% for patients with C1-trough greater than 18.40 µg/ml. Disease stage was found to be the most significant influencing factor of C1-trough , with 51.02% of patients at stage IV with an observed C1-trough less than 18.40 µg/ml. For these advanced patients, population pharmacokinetic simulations using an established model suggest that a loading dose of 800 mg/m2  may help to improve clinical outcomes.