3D SHINKEI MR neurography in evaluation of traumatic brachial plexus.

3D SHINKEI neurography is a new sequence for imaging the peripheral nerves. The study aims at assessing traumatic brachial plexus injury using this sequence. Fifty-eight patients with suspected trauma induced brachial plexus injury underwent MR neurography (MRN) imaging in 3D SHINKEI sequence at 3 T. Surgery and intraoperative somatosensory evoked potentials or clinical follow-up results were used as the reference standard. MRN, surgery and electromyography (EMG) findings were recorded at four levels of the brachial plexus-roots, trunks, cords and branches. Fifty-eight patients had pre- or postganglionic injury. The C5-C6 nerve postganglionic segment was the most common (average 42%) among the postganglionic injuries detected by 3D SHINKEI MRN. The diagnostic accuracy (83.75%) and the specificity (90.30%) of MRN higher than that of EMG (p < 0.001). There was no significant difference in the diagnostic sensitivity of MRN compared with EMG (p > 0.05). Eighteen patients with brachial plexus injury underwent surgical exploration after MRN examination and the correlation between MRN and surgery was 66.7%. Due to the high diagnostic accuracy and specificity, 3D SHINKEI MRN can comprehensively display the traumatic brachial plexus injury. This sequence has great potential in the accurate diagnosis of traumatic brachial plexus injury.

Genomic features reveal potential benefit of adding anti-PD-1 immunotherapy to treat non-upper aerodigestive tract natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is a highly heterogeneous disease with a poor prognosis. However, the genomic characteristics and proper treatment strategies for non-upper aerodigestive tract NKTCL (NUAT-NKTCL), a rare subtype of NKTCL, remain largely unexplored. In this study, 1589 patients newly diagnosed with NKTCL at 14 hospitals were assessed, 196 (12.3%) of whom had NUAT-NKTCL with adverse clinical characteristics and an inferior prognosis. By using whole-genome sequencing (WGS) and whole-exome sequencing (WES) data, we found strikingly different mutation profiles between upper aerodigestive tract (UAT)- and NUAT-NKTCL patients, with the latter group exhibiting significantly higher genomic instability. In the NUAT-NKTCL cohort, 128 patients received frontline P-GEMOX chemotherapy, 37 of whom also received anti-PD-1 immunotherapy. The application of anti-PD-1 significantly improved progression-free survival (3-year PFS rate 53.9% versus 17.0%, P = 0.009) and overall survival (3-year OS rate 63.7% versus 29.2%, P = 0.01) in the matched NUAT-NKTCL cohort. WES revealed frequent mutations involving immune regulation and genomic instability in immunochemotherapy responders. Our study showed distinct clinical characteristics and mutational profiles in NUAT-NKTCL compared with UAT patients and suggested adding anti-PD-1 immunotherapy in front-line treatment of NUAT-NKTCL. Further studies are needed to validate the efficacy and related biomarkers for immunochemotherapy proposed in this study.

[Role and mechanism of macrophage-mediated osteoimmune in osteonecrosis of the femoral head].

Objective: To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms. Methods: Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH. Results: Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent. Conclusion: At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.

Deoxythymidylate kinase (DTYMK) participates in cell cycle arrest to promote pancreatic adenocarcinoma progression regulated by miR-491-5p through TP53 and is associated with tumor immune infiltration.

Background: This study aimed to understand the mechanism of action of deoxythymidylate kinase (DTYMK) and its effect on the prognosis of patients with pancreatic cancer. So as to provide better reference value for improving the clinical management of pancreatic cancer patients. Methods: First, The Cancer Genome Atlas (TCGA) database was employed to identify DTYMK as a differentially expressed gene and to further confirm its expression and its association with the prognosis of pancreatic adenocarcinoma (PAAD) patients. Furthermore, Cox Law of Return is used for multi factor analysis. By constructing a multi factor regression model, a nomogram is constructed according to the contribution of each influencing factor in the model to the outcome variables, The GeneMania and STRING databases served as the basis for investigating the protein-gene interaction network. Moreover, to understand the correlation between DTYMK and immune cells, the TIMER and TCGA databases were explored. Then, Gene Set Enrichment Analysis (GSEA) was performed to investigate potential mechanisms of action. TargetScan was used to identify the miRNAs binding to the 3'UTR of DTYMK mRNA, and starBase was used to verify a possible link between candidate miRNAs and DTYMK. In parallel, the expression of these potential miRNAs in PAAD and their correlation with prognosis was validated through the TCGA database. Results: PAAD patients were observed to have high overall survival (OS), progression free interval (PFI), and disease-specific survival (DSS) with reduced DTYMK expression. Data from the TIMER database show that DTYMK expression inversely correlated with the infiltration levels of most immune cells. GSEA results suggested that DTYMK has a role in cell senescence, DNA repair, pyrimidine metabolism, MYC activation, TP53 control of cell cycle arrest, apoptosis, and the MAPK6/MAPK4 pathway, all of which might influence the biological processes of PAAD. Conclusions: Reduced DTYMK expression may be considered a novel prognostic biomarker for PAAD patients, associated with improved OS, DSS, and PFI. Immune escape may play an important facilitative role. Moreover, we found that miR-491-5p may negatively regulate DTYMK and participate in cell cycle arrest through TP53 to promote pancreatic cancer progression.

Efficacy and safety of geptanolimab (GB226) for relapsed/refractory primary mediastinal large B-cell lymphoma: an open-label phase II study (Gxplore-003).

BACKGROUND: This study aimed to assess the efficacy and safety of geptanolimab (GB226), a fully humanized, recombinant anti-programmed cell death-1 monoclonal antibody, in Chinese patients with refractory or relapsed (r/r) primary mediastinal large B-cell lymphoma (PMBCL). METHODS: This was a multicenter, open-label, single-arm phase II study (Gxplore-003), conducted at 43 hospitals in China (NCT03639181). Patients received geptanolimab intravenously at a dose of 3 mg/kg every 2 weeks until documented confirmed disease progression, intolerable toxicity, or any other cessation criteria was met. The primary endpoint was objective response rate (ORR) in the full analysis set assessed by the independent review committee (IRC) according to the Lugano Classification 2014. RESULTS: This study was prematurely terminated due to the slow rate of patient accrual. Between Oct 15th, 2018 and Oct 7th, 2020, 25 patients were enrolled and treated. By the data cutoff date on Dec 23rd, 2020, the IRC-assessed ORR was 68.0% (17/25; 95% confidence interval [CI] 46.5-85.1%), with the complete response rate of 24%. The disease control rate was 88% (22/25; 95%CI 68.8-97.5%). Median duration of response was not reached (NR) (95%CI, 5.62 months to NR), with 79.5% of patients having response durations of more than 12 months. Median progression-free survival was NR (95%CI, 6.83 months to NR). Treatment-related adverse events (TRAEs) were reported in 20 of 25 (80.0%) patients, and grade 3 or higher TRAEs occurred in 11 of 25 (44%) patients. No treatment-related deaths occurred. The immune-related adverse events (irAEs) of any grade were observed in 6 (24.0%) patients, and no grade 4 or grade 5 irAEs were reported. CONCLUSION: Geptanolimab (GB226) demonstrated promising efficacy and a manageable safety profile in Chinese patients with r/r PMBCL.

Identification of three small nucleolar RNAs (snoRNAs) as potential prognostic markers in diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a non-Hodgkin lymphoma with high mortality rates. Small nucleolar RNAs (snoRNAs) are tumor-specific biological markers, but there are few studies on the role of snoRNAs in DLBCL. MATERIALS AND METHODS: Survival-related snoRNAs were selected to construct a specific snoRNA-based signature via computational analyses (Cox regression and independent prognostic analyses) to predict the prognosis of DLBCL patients. To assist in clinical applications, a nomogram was built by combining the risk model and other independent prognostic factors. Pathway analysis, gene ontology analysis, transcription factor enrichment, protein-protein interactions, and single nucleotide variant analysis were used to explore the potential biological mechanisms of co-expressed genes. RESULTS: Twelve prognosis-correlated snoRNAs were selected from the DLBCL patient cohort of microarray profiles, and a three-snoRNA signature consisting of SNORD1A, SNORA60, and SNORA66 was constructed. DLBCL patients could be divided into high-risk and low-risk cohorts using the risk model, and the high-risk group and activated B cell-like (ABC) type DLBCL were linked with disappointing survival. In addition, SNORD1A co-expressed genes were inseparably linked to the biological functions of the ribosome and mitochondria. Potential transcriptional regulatory networks have also been identified. MYC and RPL10A were the most mutated SNORD1A co-expressed genes in DLBCL. CONCLUSION: Put together, our findings explored the potential biological effects of snoRNAs in DLBCL, and provided a new predictor for DLBCL prediction.

Retracted: Britannin mediates apoptosis and glycolysis of T-cell lymphoblastic lymphoma cells by AMPK-dependent autophagy.

The above article, published online on 19 September 2022 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/abs/10.1002/jbt.23211), has been retracted by agreement between the authors, the journal Editor in Chief, Hari Bhat, and Wiley Periodicals, LLC. The article is being retracted at the authors' request because some of the data underlying this article refer to a different cell line from the one reported in it. As a result, the article's conclusions do not accurately reflect the full data and cannot be considered reliable.

Sintilimab combined with chidamide in the treatment of extranodal nature killer/T-cell lymphoma with secondary hemophagocytic lymphohistiocytosis: Two case reports and literature review.

RATIONALE: Extranodal nature killer/T-cell lymphoma (ENKTL) failing in asparaginase-containing treatments is fatal, it has a higher mortality rate when accompanied by secondary hemophagocytic lymphohistiocytosis (HLH). The study reported 2 ENKTL-related HLH patients. PATIENT CONCERNS: Patient 1 visited for nasal congestion and runny nose for 6 months then got a fever and serious myelosuppression after P-GEP (pegaspargase, gemcitabine, etoposide, and methylprednisolone) chemotherapy. Patient 2 complained of painless lymphadenectasis in the right neck for 4 months and experienced recurrent fever and poor performance status after 3 cycles of P-Gemox (pegaspargase, gemcitabine, and oxaliplatin) chemotherapy. DIAGNOSES: Patient 1 and patient 2 were diagnosed as ENKTL failing in asparaginase-based chemotherapy and involving secondary HLH. INTERVENTIONS: The dose of chidamide was 20 mg twice a week for 2 weeks and sintilimab was 200 mg once every 3 weeks. OUTCOMES: ENKTL was relieved and the HLH was resolved after the therapy of sintilimab and chidamide. The patients had achieved durable survival without immune-related adverse events. LESSONS: ENKTL-related HLH needs early diagnosis and treatment. The combined strategy of sintilimab plus chidamide help deal with HLH and solve ENKTL, it may be a useful treatment option for ENKTL-related HLH.

[Retracted] MicroRNA­663 inhibits the proliferation, migration and invasion of glioblastoma cells via targeting TGF­ß1.

Subsequently to the publication of the above article, an interested reader drew to the Editor's attention that they had identified several instances of overlapping data panels comparing between the scratch­wound assay data ('36 h' experiments) portrayed in Figs. 3 and 8; furthermore, there appeared to be an overlap in a pair of the data panels shown for the Transwell assay experiments with U87 cells in Fig. 9 (albeit with an inversion of one of the panels), such that these data may have been derived from the same original source, even though they were purportedly intended to show the results from differently performed experiments. Given the multiple instances of overlapping data panels that have been identified in the compilation of the figures in this article, the Editor of Oncology Reports has decided that this article should be retracted from the publication on account of a lack of overall confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 35: 1125­1134, 2016; DOI: 10.3892/or.2015.4432].

Unusual presentation of primary ovarian diffuse large B-cell lymphoma: a case report.

BACKGROUND: Primary ovarian lymphoma has been difficult to diagnose clinically and pathologically due to its rare incidence and non-specific clinical symptoms. CASE PRESENTATION: A 75-year-old female patient was reported in this study. The patient had a six-month history of changes in bowel habits, with occasional black feces and paroxysmal pain in the abdomen. The computed tomography scan of the pelvic cavity illustrated that rectal cancer and sigmoid colon adenocarcinoma invaded the lower part of the right-side ureter. The patient was once treated with excision of part of small intestine, fallopian tube and ovary, and uterus. The pathological examination of these excised tissues, combined with the immunohistochemistry, confirmed that the female patient suffered from primary ovarian diffuse large B-cell lymphoma (DLBCL), and the lymphoma had invaded the entire right-side ovary tissues, serous membranes on the posterior surface of the uterus, and the wall of small intestine. CONCLUSION: Few reports were available regarding the primary ovarian DLBCL. The initial symptom of the patient was the changes in bowel habits, which had not been reported beforehand. Hopefully, this case could helpfully render the early diagnosis possible, and increase clinical understanding of primary ovarian DLBCL, which would thereby reduce the chance of misdiagnosis.

RNA-seq and integrated network analysis reveals the hub genes and key pathway of paclitaxel inhibition on Adriamycin resistant diffuse large B cell lymphoma cells.

About 40% of patients with diffuse large B-cell lymphoma (DLBCL) develop drug resistance after first-line chemotherapy, which remains a major cause of morbidity and mortality. The emergence of DLBCL drug resistance is mainly related to Adriamycin. Our previous research shows that Paclitaxel could be a potential therapeutic drug for the treatment of Adriamycin-resistant DLBCL. Based on the results of RNA-seq and integrated network analysis, we study the potential molecular mechanism of Paclitaxel in the treatment of Adriamycin-resistant DLBCL in multiple dimensions. A CCK-8 assay showed that the inhibitory effect of Paclitaxel on Pfeiffer and Pfeiffer/ADM (Adriamycin-resistant DLBCL cell lines) is significantly higher than that of Adriamycin (P ＜ 0.05). Five hub genes (UBC, TSR1, WDR46, HSP90AA1, and NOP56) were obtained via network analysis from 971 differentially expressed genes (DEGs) based on the RNA-seq of Paclitaxel-intervened Pfeiffer/ADM. The results of the network function module analysis showed that the inhibition of Pfeiffer/ADM by Paclitaxel was closely related to ribosome biosynthesis in eukaryotes. The results of RT-qPCR showed that the mRNA levels of the five hub genes in the Pfeiffer/ADM group were significantly lower than those in the Pfeiffer group and the Pfeiffer/ADM Paclitaxel-treated group (P ＜ 0.05). Consistent with studies, Paclitaxel exhibited a significant inhibitory effect on Adriamycin-resistant DLBCL, which may have played a role in the five hub genes (UBC, TSR1, WDR46, HSP90AA1 and NOP56) and ribosome biosynthesis in eukaryotes pathway, but the specific regulation needs further experimental verification.

SOX combined with intraperitoneal perfusion of docetaxel compared with DOS regimen in the first-line therapy for advanced gastric cancer with malignant ascites: a prospective observation.

OBJECTIVE: This study aimed to verify the survival superiority of the combination of intraperitoneal perfusion and systemic chemotherapy over standard systemic chemotherapy. METHODS: A total of 78 advanced gastric cancer patients with malignant ascites were randomly divided into D-SOX group (intraperitoneal infusion of docetaxel 30 mg/m2 on d1 and d8, intravenous oxaliplatin 100 mg/m2 on d1, and oral administration of S-1 on d1-d14) and DOS group (intravenous docetaxel 60 mg/m2 on d1, intravenous oxaliplatin 100 mg/m2 on d1, and oral administration of S-1 on d1-d14). Efficacy of both groups was evaluated every 2 cycles with 21 days as a cycle. The primary endpoint was overall survival, and the secondary endpoints were objective response rate, ascites control rate, negative conversion rate of ascites cytology, and side effects. RESULTS: The median overall survival in D-SOX group was significantly higher than that in the DOS group (11.7 vs 10.3 months, HR 0.52, 95%CI 0.31-0.86, P = 0.005). The ascites control rate in the D-SOX group was 58.9% and 30.8% in DOS group (95%CI 42.8-75.1% vs 95%CI 15.6-45.9%, P = 0.012). Besides, the adverse reactions were tolerable in both groups, and patients in the D-SOX group had lower grade 3/4 blood toxicity than that in the DOS group (26% vs 54%, P = 0.01). CONCLUSION: Compared with traditional systemic chemotherapy, docetaxel intraperitoneal infusion combined with chemotherapy has better therapeutic effect on gastric cancer ascites, with better survival benefit and tolerance and less hematological toxicity, which is worthy of further research and clinical application.

Erratum: Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells: Erratum.

[This corrects the article DOI: 10.7150/jca.39328.].

Chidamide combined with traditional chemotherapy for primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma: A case report.

BACKGROUND: Traditional chemotherapy has benefited many patients with non-Hodgkin's lymphoma, but results in a very poor response in patients with rare lymphomas or refractory lymphomas. Previous studies have shown that chidamide has potential anti-lymphoma activity and reverses lymphoma cell chemoresistance to increase the chemosensitivity of lymphoma cells to traditional chemotherapy. CASE SUMMARY: A 14-year-old boy was admitted to our hospital with a 5-d history of generalized erythema, papules, and blisters. Initially, the disease was refractory to potent anti-allergic and anti-infective treatment, and his condition progressively worsened. Skin biopsy revealed primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. Considering that the disease is extremely rare in clinical practice, existing case reports have shown poor efficacy with traditional chemotherapy alone. We recommend chidamide combined with traditional chemotherapy for treatment. The regimen was as follows: Chidamide 30 mg/biw, cyclophosphamide 1100 mg/d1, pirarubicin 70 mg/d1, vincristine 2 mg/d1, dexamethasone 20 mg/d1-5, etoposide 100 mg/d1-5, in a 21 d cycle. The treatment effect was considerable, and complete remission was achieved after 4 cycles of treatment, after which the patient completed a total of 6 cycles of treatment. Subsequently, the patient regularly took chidamide 20 mg/biw as maintenance therapy for 1 year. To date, the patient has been disease-free for 3 years. CONCLUSION: This case suggests that the combination of chidamide and traditional chemotherapy is effective in primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma.

The expression of Slit2 and Robo1 increased during retinoic acid syndrome in acute promyelocytic leukemia and impacted differentiated cell migration.

Retinoic acid syndrome (RAS) is a serious complication developed during the induction therapy of acute promyelocytic leukemia (APL). Cytokines and differentiated cells migration play important roles in the development of RAS. Slit guidance ligand 2 (Slit2) and roundabout 1 (Robo1) involve in cell migration. Our study aimed to investigate the expression of Slit2 and Robo1 in APL and check whether they affected promyelocytes migration. 62 cases of newly diagnosed APL patients were involved and received all-trans retinoic acid (ATRA) and arsenic trioxide as induction therapy. Bone marrow cells (BMCs) were obtained on days 0 and 28, and promyelocytes and plasma were collected from day 1 to day 21. The expression of Robo1 in promyelocytes, and that of Slit2 and cytokines, including IL-8,IL-1ß and others, in serum were monitored. 20 healthy individuals donated their cells as control. Of the 62 APL patients, 16 (25.81%) patients developed RAS. The expression of Robo1, Slit2 and IL-8 increased significantly with the development of RAS. In the 16 patients with RAS, levels of Slit2, Robo1 and IL-8 were higher during the development of RAS than before or after the RAS (P < 0.05). RhSlit2-N and rhIL-8 induced cells migration, and the migration induced by IL-8 was not inhibited by rhSlit2-N. Elevated Slit2 and Robo1 levels might be useful markers for the diagnosis and treatment of RAS. The levels of Slit2, Robo1 and IL-8 showed a positive correlation with the severity of RAS. Slit2 and IL-8 promoted the migration of differentiated cells.

Overexpression of UBE2C in esophageal squamous cell carcinoma tissues and molecular analysis.

BACKGROUND: Esophageal cancer is a common malignant tumor and its 5-year survival rate is much lower than 30% due to its invasiveness and pronounced metastasis ability, as well as the difficulty in early diagnosis. This study aimed to elucidate the molecular mechanism of ubiquitin conjugating enzyme E2 C (UBE2C) in esophageal squamous cell carcinoma (ESCC). METHODS: In this study, we conducted a comprehensive evaluation of the UBE2C expression in ESCC by collecting the protein and mRNA expression data (including in-house RNA-seq, in-hosue immunohistochemistry, TCGA-GTEx RNA-seq and tissue microarray) to calculate a combined standardized mean difference (SMD) and summary receiver operating characteristic curve (sROC). Kaplan-Meier (K-M) method was used for survival analysis. We also explored the mechanism of UBE2C in ESCC by combing the differentially expressed genes (DEGs) of ESCC, related-genes of UBE2C in ESCC and the putative miRNAs and lncRNAs which may regulate UBE2C. RESULTS: UBE2C protein and mRNA were highly expressed in ESCC tissues (including 772 ESCC tissue samples and 1837 non-cancerous tissue control samples). The pooled SMD of UBE2C expression values was 1.98 (95% CI: 1.51-2.45, p < 0.001), and the the area under the curve (AUC) of the sROC was 0.93 (95% CI: 0.90-0.95). The results of survival analysis suggested that UBE2C is likely to play different roles in different stages of the ESCC. Pathway anaylsis showed that UBE2C mainly influenced the biological function of esophageal cancer by synergistic effects with CDK1, PTTG1 and SKP2. We also constructed a potential UBE2C-related ceRNA network for ESCC (HCP5/has-miR-139-5p/UBE2C). CONCLUSION: UBE2C mRNA and protein level were highly expressed in ESCC and UBE2C was likely to play different roles in different stages of the ESCC.

Expression of N6-methyladenosine (m6A) regulators correlates with immune microenvironment characteristics and predicts prognosis in diffuse large cell lymphoma (DLBCL).

This study conducted a comprehensive analysis of the clinical significance of N6-methyladenosine (m6A) regulators and their relationship with immune microenvironment characteristics in diffuse large cell lymphoma (DLBCL). Consensus clustering was performed to molecularly discriminate DLBCL subtypesbased on m6A regulators' expression. Using the Cox and Lasso regression algorithm, survival-associated m6A regulators were identified, and a m6A-based prognostic signature was established. The influence of m6A risk on immune cell infiltration, immune checkpoint genes, cancer immunity cycle, and immunotherapeutic response was evaluated. Potential molecular pathways related to m6A risk were investigated using gene set enrichment analysis. The m6A regulators showed satisfactory performance in distinguishing DLBCL subgroups with distinct clinical traits and outcomes. A six m6A regulator-based prognostic signature was established and validated as an independent predictor, which separated patients into low- and high-risk groups. High-risk m6A indicated worse survival. The B cells naïve, T cells gamma delta, and NK cells resting were the three most affected immune cells by m6A risk. Up-regulated (PDCD1 and KIR3DL1) and down-regulated (TIGIT, IDO1, and BTLA) immune checkpoint genes in the high-risk group were identified. The m6A risk was found to influence several steps in the cancer immunity cycle. Patients with high-risk m6A were more likely to benefit from immunotherapy. Biological function enrichment analysis revealed that high-risk m6A to be tended related to malignant tumor characteristics, while low-risk m6A showed trend to be related to defensive response processes. Collectively, the m6A-based prognostic signature could be a practical prognostic predictor for DLBCL and immune microenvironment characteristics affected by m6A may be part of the mechanism.

Sequential P-GEMOX and radiotherapy for early-stage extranodal natural killer/T-cell lymphoma: A multicenter study.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma and most of the patients presented localized disease. Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with early-stage ENKTL. However, the optimal CMT has not been fully clarified. This study reports the efficacy and toxicity of sequential P-GEMOX (pegaspargase, gemcitabine and oxaliplatin) and radiotherapy in a large Chinese cohort comprising of 202 patients diagnosed with early-stage ENKTL from six medical centers. The observed best overall response rate was 96.0% and 168 (83.2%) patients achieved complete remission. With a median follow-up of 44.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 74.6% and 85.2%, respectively. Multivariate analysis suggested that extensive primary tumor (PFS, hazard ratio [HR] 3.660, 95% CI 1.820-7.359, p < 0.001; OS, HR 3.825, 95% CI 1.442-10.148, p = 0.007) and Eastern Cooperative Oncology Group performance status ≥ 2 (PFS, 3.042, 95% CI 1.468-6.306, p = 0.003; OS, HR 3.983, 95% CI 1.678-9.457, p = 0.02) were independent prognostic factors for survival outcomes. Among the established prognostic models for ENKTL, the nomogram-revised risk index model had optimal prognostic risk stratification ability (PFS, p < 0.001; OS, p < 0.001) and relatively balanced population distribution. The adverse events of this CMT were well-tolerated and manageable. In conclusion, sequential P-GEMOX and radiotherapy showed favorable efficacy with acceptable toxicity, and could be an effective treatment option for early-stage ENKTL patients.

[Exploring the Mechanism of Paclitaxel Inhibiting T-cell Lymphoma based on High-throughput Sequencing and Public Databases].

OBJECTIVE: To analyze gene expression profile of T cell lymphoma Jurkat cell line treated with paclitaxel by computational biology based on next generation sequencing and to explore the possible molecular mechanism of paclitaxel resistance to T cell lymphoma at gene level. METHODS: IC50 of paclitaxel on Jurkat cell line was determined by CCK-8 assay. Gene expression profile of Jurkat cells treated with paclitaxel was acquired by next generation sequencing technology. Gene microarray data related to human T cell lymphoma were screened from Gene Expression Omnibus (GEO) database (including 720 cases of T cell lymphoma and 153 cases of normal tissues). Combined with the sequencing data, differential expression genes (DEGs) were intersected and screened. DAVID database was used for enrichment analysis of GO function and KEGG pathway to determine and visualize functional entries of DEGs, and protein-protein interactions network of DEGs was drawn. The levels of gene expression were detected and verified by RT-qPCR. RESULTS: CCK-8 results showed that the proliferation of Jurkat cells was inhibited by paclitaxel depended on the concentration apparently. Treated by paclitaxel for 48 h, P<0.05 and |log2(FC)|≥1 were used as filter criteria on the results of RNA Sequencing (RNA-Seq) and GeoChip, 351 DEGs were found from Jurkat cells, including 323 up-regulated genes and 28 down-regulated genes. The GO functional annotation and KEGG pathway enrichment analysis showed that the role of paclitaxel was mainly concentrated in protein heterodimerization activity, nucleosome assembly and transcriptional dysregulation in cancer, etc. The results of RT-qPCR were consistent with those of the sequencing analysis, which verified the reliability of this sequencing. CONCLUSION: Paclitaxel can affect the proliferation and apoptosis of T-cell lymphoma by up-regulating JUN gene, orphan nuclear receptor NR4A family genes and histone family genes.

Imaging features of hemangioma in long tubular bones.

BACKGROUND: To investigate the imaging features of hemangiomas in long tabular bones for better diagnosis. METHODS: Twenty-four patients with long bone hemangiomas confirmed by pathology were enrolled. Nineteen patients had plain radiography, fourteen patients had computed tomography (CT) and eleven had magnetic resonance imaging (MRI). The hemangioma was divided into medullary [13], periosteal [6] and intracortical type [5]. RESULTS: Among 19 patients with plain radiography, eleven patients were medullary, three periosteal, and five intracortical. In the medullary type, the lesion was primarily osteolytic, including five cases with irregular and unclear rims and one lesion having osteosclerotic and unclear rims. In three patients with the periosteal type, the lesion had clear rims with involvement of the cortical bone in the form of bone defect, including two cases with local thickened bone periosteum and one case having expansile periosteum. Five intracortical hemangiomas had intracortical osteolytic lesions with clear margins. Among 14 patients with CT imaging, 8 cases were medullary, three periosteal, and three intracortical. Among 8 medullary hemangiomas, one had ground glass opacity, and seven had osteolytic, expansile lesions like soft tissue density with no calcification. In three periosteal cases, the lesion was osteolytic with thickened periosteum and narrowed medullary cavity. In three intracortical hemangiomas, the lesion was of even soft tissue density with no calcification. Among 11 patients with MRI imaging, seven were medullary, two periosteal, and two intracortical. Among 7 medullary lesions, six were of hypointense signal on T1WI and hyperintensesignal on T2 WI. In two periosteal cases, the periosteum was thickened, with one case being of equal signal, and the other having no signal. Two intracortical hemangiomas were both of slightly low signal on T1WI but hyperintense signal on T2WI. CONCLUSIONS: The long bone hemangiomas had characteristic cystic honeycomb-like presentations in plain radiograph. CT and MRI imagings are helpful for diagnosis of hemangiomas in long bone.