Mutation landscape in Chinese nodal diffuse large B-cell lymphoma by targeted next generation sequencing and their relationship with clinicopathological characteristics.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL), an aggressive and heterogenic malignant entity, is still a challenging clinical problem, since around one-third of patients are not cured with primary treatment. Next-generation sequencing (NGS) technologies have revealed common genetic mutations in DLBCL. We devised an NGS multi-gene panel to discover genetic features of Chinese nodal DLBCL patients and provide reference information for panel-based NGS detection in clinical laboratories. METHODS: A panel of 116 DLBCL genes was designed based on the literature and related databases. We analyzed 96 Chinese nodal DLBCL biopsy specimens through targeted sequencing. RESULTS: The most frequently mutated genes were KMT2D (30%), PIM1 (26%), SOCS1 (24%), MYD88 (21%), BTG1 (20%), HIST1H1E (18%), CD79B (18%), SPEN (17%), and KMT2C (16%). SPEN (17%) and DDX3X (6%) mutations were highly prevalent in our study than in Western studies. Thirty-three patients (34%) were assigned as genetic classification by the LymphGen algorithm, including 12 cases MCD, five BN2, seven EZB, seven ST2, and two EZB/ST2 complex. MYD88 L265P mutation, TP53 and BCL2 pathogenic mutations were unfavorable prognostic biomarkers in DLBCL. CONCLUSIONS: This study presents the mutation landscape in Chinese nodal DLBCL, highlights the genetic heterogeneity of DLBCL and shows the role of panel-based NGS to prediction of prognosis and potential molecular targeted therapy in DLBCL. More precise genetic classification needs further investigations.

MNDA expression and its value in differential diagnosis of B-cell non-Hodgkin lymphomas: a comprehensive analysis of a large series of 1293 cases.

AIMS: MNDA (myeloid nuclear differentiation antigen) has been considered as a potential diagnostic marker for marginal zone lymphoma (MZL), but its utility in distinguishing MZL from other B-cell non-Hodgkin lymphomas (B-NHLs) and its clinicopathologic relevance in diffuse large B-cell lymphoma (DLBCL) are ambiguous. We comprehensively investigated MNDA expression in a large series of B-NHLs and evaluated its diagnostic value. METHODS: MNDA expression in a cohort of 1293 cases of B-NHLs and 338  cases of reactive lymphoid hyperplasia (RLH) was determined using immunohistochemistry and compared among different types of B-NHL. The clinicopathologic relevance of MNDA in DLBCL was investigated. RESULTS: MNDA was highly expressed in MZLs (437/663, 65.9%), compared with the confined staining in marginal zone B-cells in RLH; whereas neoplastic cells with plasmacytic differentiation lost MNDA expression. MNDA expression was significantly higher in mantle cell lymphoma (MCL, 79.6%, p = 0.006), whereas lower in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, 44.8%, p = 0.001) and lymphoplasmacytic lymphoma (LPL, 25%, p = 0.016), and dramatically lower in follicular lymphoma (FL, 5.2%, p < 0.001), compared with MZL. 29.6% (63/213) of DLBCLs were positive for MNDA. The cases in non-GCB group exhibited a higher rate of MNDA positivity (39.8%) compared to those in GCB group (16.3%) (p < 0.001), and MNDA staining was more frequently observed in DLBCLs with BCL2/MYC double-expression (50%) than those without BCL2/MYC double-expression (24.8%) (p = 0.001). Furthermore, there was a significant correlation between MNDA and CD5 expression in DLBCL (p = 0.036). CONCLUSIONS: MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated.

Predicting central nervous system relapse in primary breast diffuse large B-cell lymphoma using the stage-modified IPI score: A retrospective cohort study.

Objective: The existing Central Nervous System-International Prognostic Index (CNS-IPI) provides insufficient guidance for predicting central nervous system (CNS) relapse in individuals with primary breast diffuse large B-cell lymphoma (DLBCL). This retrospective cohort study sought to examine the potential of the stage-modified IPI in predicting CNS relapse within this specific patient population. Patients and methods: We examined the baseline characteristics of 76 consecutive patients diagnosed with primary breast DLBCL, calculating the stage-modified IPI score for each individual. Utilizing a competing risk regression (CRR) model, we conducted both univariate and multivariate analyses to explore the relationship between potential prognostic factors and the occurrence of CNS relapse. Results: In our cohort, the rates of CNS disease at 2 and 5 years since the diagnosis of primary breast DLBCL are 3.9% and 7.8%, respectively. Among patients experiencing CNS relapse, 80% presented with a parenchymal brain mass. Individuals with a high stage-modified IPI score (1-3 points) had a significantly higher incidence of CNS relapse (p = 0.031), a shorter time from the initial diagnosis of primary breast DLBCL to the first CNS relapse (p = 0.010), as well as relapse at any site (p = 0.012), compared to those with a low score (0 points). Univariate analysis identified stage (Hazard Ratio (HR): 4.098, p = 0.024), stage-modified IPI score (HR: 11.582, p = 0.012), and radiation therapy (HR: 5.784, p = 0.026) as significant risk factors. In multivariate analysis, in addition to radiation therapy (HR: 7.258, p = 0.012), the stage-modified IPI score (1-3 points versus 0 points) emerged as an independent and reliable predictor for CNS relapse (HR: 12.945, p = 0.016). Conclusion: Our study underscores the significance of stage-modified IPI scores in predicting CNS relapse for patients with primary breast DLBCL. Validation of these findings through further research is essential, along with exploring potential prevention and intervention approaches.

Response to anti-HER2 neoadjuvant chemotherapy in HER2-positive invasive breast cancers with different HER2 FISH patterns.

AIMS: Human epidermal growth factor receptor 2 (HER2)-positive patients with breast cancer may have different HER2/CEP17 ratios and HER2 copy numbers, with inconsistent responses to anti-HER2 neoadjuvant chemotherapy (NACT). Our study aimed to explore the relationship between different HER2 fluorescence in situ hybridisation (FISH) patterns in HER2-positive patients with breast cancer and responses to anti-HER2 NACT. METHODS: 527 patients with HER2-positive invasive breast cancer who received anti-HER2 NACT from 2015 to 2022 were included and divided into three groups by FISH results, namely group A: HER2/CEP17<2.0 and HER2 copy numbers ≥6.0, HER2 immunohistochemistry 2/3+; group B: HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0; group C: HER2/CEP17≥2.0 and HER2 copy numbers ≥6.0. We compared clinicopathological characteristics and pathological complete response (pCR) rates of different groups. RESULTS: According to HER2 FISH results, 12 patients (2.3%, 12/527) were in group A, 40 (7.6%, 40/527) were in group B and 475 (90.1%, 475/527) were in group C. The pCR rate was the lowest in group B (5.0%), while the pCR rates in group A and group C were 33.3% and 44.4%, respectively (p (group A vs. B) =0.021, p (group C vs. B) < 0.001). Both univariate and multivariate analyses revealed that HER2 FISH pattern was correlated with pCR rate (p (group C vs. B) < 0.001, p (group C vs. B) = 0.025). CONCLUSIONS: Patients with HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0 do not benefit to the same extent from current anti-HER2 therapies as FISH-positive patients with other patterns.

Yin Yang 1 expression predicts a favourable survival in diffuse large B-cell lymphoma.

Aims: Yin Yang 1 (YY1) is a multifunctional transcription factor that plays an important role in tumour development and progression, while its clinical significance in diffuse large B-cell lymphoma (DLBCL) remains largely unexplored. This study aimed to investigate the expression and clinical implications of YY1 in DLBCL. Methods: YY1 expression in 198 cases of DLBCL was determined using immunohistochemistry. The correlation between YY1 expression and clinicopathological parameters as well as the overall survival (OS) and progression-free survival (PFS) of patients was analyzed. Results: YY1 protein expression was observed in 121 out of 198 (61.1 %) DLBCL cases. YY1 expression was significantly more frequent in cases of the GCB subgroup than in the non-GCB subgroup (P = 0.005). YY1 was positively correlated with the expression of MUM1, BCL6, pAKT and MYC/BCL2 but was negatively associated with the expression of CXCR4. No significant relationships were identified between YY1 and clinical characteristics, including age, sex, stage, localization, and B symptoms. Univariate analysis showed that the OS (P = 0.003) and PFS (P = 0.005) of patients in the YY1-negative group were significantly worse than those in the YY1-positive group. Multivariate analysis indicated that negative YY1 was a risk factor for inferior OS (P < 0.001) and PFS (P = 0.017) independent of the international prognostic index (IPI) score, treatment and Ann Arbor stage. Furthermore, YY1 is more powerful for stratifying DLBCL patients into different risk groups when combined with MYC/BCL2 double-expression (DE) status. Conclusions: YY1 was frequently expressed in DLBCL, especially in those of GCB phenotype and with MYC/BCL2-DE. As an independent prognostic factor, YY1 expression could predict a favourable outcome in DLBCL. In addition, a complex regulatory mechanism might be involved in the interactions between YY1 and MYC, pAKT as well as CXCR4 in DLBCL, which warrants further investigation.

A prospective comparison of a modified miniaturised hand-held epifluorescence microscope and touch imprint cytology for evaluation of axillary sentinel lymph nodes intraoperatively in breast cancer patients.

BACKGROUND: The management of axillary lymph nodes in early-stage breast cancer patients has changed considerably, with the primary focus shifting from the examination of sentinel lymph nodes (SLNs) to toward the detection of all macro-metastases. However, current methods, such as touch imprint cytology (TIC) and frozen sections, are inadequate for clinical needs. To address this issue, we proposed a novel miniaturised epifluorescence widefield microscope (MEW-M) to assess SLN status intraoperatively for improved diagnostic efficiency. METHODS: A prospective, side-by-side comparison of intraoperative SLN evaluation between MEW-M and TIC was performed. RESULTS: A total of 73 patients with 319 SLNs consecutive enrolled in this study. MEW-M showed significantly superior image quality compared to TIC (median score 3.1 vs 2.1, p < 0.0001) and had a shorter time to issue results (10.3 vs 19.4 min, p < 0.0001). Likelihood ratio analysis illustrated that the positive likelihood ratio value of MEW-M compared with TIC was infinitely great vs 52.37 (95% CI, 21.96-124.90) in model 1 (classifying results into negative/positive), infinitely great vs 52.37 (95% CI, 21.96-124.90) in model 2 (classifying results into macro-metastasis/others, and TIC results followed the same classification as model 1), respectively. Similarly, the negative likelihood ratio values of MEW-M compared with TIC were 0.055 (95% CI, 0.018-0.160) and 0.074 (95% CI, 0.029-0.190) in model 1; and 0.019 (95% CI, 0.003-0.130) vs 0.020 (95% CI, 0.003-0.140) in model 2, respectively. CONCLUSIONS: MEW-M is a promising technique that can be utilised to provide a rapid and accurate intraoperative assessment of SLN in a clinical setting to help improve decision-making in axillary surgery.

Diffuse large B-cell lymphoma with continuously elevated immunoglobulin M following treatment: a case report with pathologic, immunophenotypic, and molecular analyses.

A rare subtype of diffuse large B-cell lymphoma (DLBCL) has been reported to be accompanied by elevated immunoglobulin M (IgM) paraprotein in the serum at diagnosis, called as IgMs-DLBCL. The monoclonal IgM paraprotein disappears soon after treatment in most of these patients. Here, we described a DLBCL patient with continuously elevated IgM following therapy. A 59-year-old male was diagnosed with DLBCL (GCB subtype per Hans algorithm, stage IA) with involvement of the right cervical lymph node. After six cycles of immuno-chemotherapy with the R-CHOP regimen, complete metabolic remission was achieved, but an elevated level of serum IgM persisted. To investigate the origin of elevated IgM, pathologic, immunophenotypic, and molecular analyses of lymph node and bone marrow (BM) samples were performed pre- and post-treatment. BM infiltration of lymphoplasmacytic cells, and a typical immunophenotypic profile by flow cytometry supported the diagnosis of Waldenström macroglobulinemia (WM). The MCD subtype of DLBCL was identified by next-generation sequencing of the lymph node at initial diagnosis characterized by co-occurring point mutations in MYD88 L265P and CD79B. Additionally, two different dominant clonotypes of the immunoglobulin heavy chain (IGH) were detected in the lymph node and BM by IGH sequencing, which was IGHV 3-11*06/IGHJ 3*02 and IGHV 3-11*06/IGHJ 6*02, respectively, speculating to be two independent clonal origins. This study will provide a panoramic understanding of the origin or biological characteristics of DLBCL co-occurring with WM.

Social trust and subjective well-being of first-generation college students in China: the multiple mediation effects of self-compassion and social empathy.

Previous studies have found that subjective well-being is associated with social trust, self-compassion, and social empathy. Based on online fieldwork with 662 first-generation college students (54.7% male) in China, this study aimed to investigate the serial mediation effects of self-compassion and social empathy on the relationship between social trust and subjective well-being. The results showed that subjective well-being was significantly positively correlated with social trust, trust in people, self-compassion, and social empathy. Both self-compassion and social empathy partially mediated the relationship between social trust and subjective well-being, and fully mediated the association between trust in people and subjective well-being. We used a serial mediation model to estimate the effect of general social trust, including trust in people, on subjective well-being. The findings that self-compassion and social empathy mediated the relationship between trusting attitudes toward society, especially people, and subjective well-being expand the literature on social trust and the mechanism of social trust on subjective well-being. The results also highlight the significance of improving mental health education and intervention among first-generation college students in China.

IRF4 rearrangement may predict favorable prognosis in children and young adults with primary head and neck large B-cell lymphoma.

PURPOSE: Large B-cell lymphoma with IRF4 rearrangement (LBCL, IRF4+) has been recently recognized as a specific entity that is frequently associated with young age and favorable prognosis. However, whether the good outcome of the disease is due to IRF4+ or other factors remains obscure. We thus analyzed 100 young patients with primary head and neck LBCL to see the clinicopathologic correlates of IRF4+. METHODS: The histopathology, immunophenotype, IRF4 status of the tumors, and clinical data were reviewed. RESULTS: Twenty-one tumors were diagnosed as LBCL, IRF4+, which were more frequently associated with a follicular growth pattern, medium-sized blastoid cytology, germinal center B-cell-like, and CD5+ phenotype, compared with IRF4- ones. While most of the patients received chemotherapy with or without radiation, eight IRF4+ patients received mere surgical resection of the tumor and exhibited excellent outcome. IRF4+ cases featured a significantly higher complete remission rate, and better survivals compared with IRF4- ones. Multivariate analysis confirmed IRF4+ correlates with a better survival. CONCLUSION: Our work confirmed the unique clinicopathologic features of LBCL, IRF4+, and disclosed for the first time the independent favorable prognostic impact of IRF4+. These findings may further unravel the heterogeneity of LBCL occurring in youth, and aid in risk stratification and tailoring the therapeutic strategy.

Conversion of ER and HER2 Status After Neoadjuvant Therapy in Chinese Breast Cancer Patients.

BACKGROUND: Few studies have focused on converting ER-low-positive and HER2-low status following neoadjuvant therapy (NAT). We aimed to assess the evolution in ER and HER2 status after NAT in breast cancer patients. PATIENTS AND METHODS: Our study included 481 patients with residual invasive breast cancer after NAT. ER and HER2 status were assessed in the primary tumor and residual disease, and associations between ER and HER2 conversion and clinicopathological factors were explored. RESULTS: In primary tumors, 305 (63.4%) cases were ER-positive (including 36 cases of ER-low-positive), 176 (36.6%) were ER-negative. In residual disease, ER status changed in 76 (15.8%) cases, of which 69 cases switched from positive to negative. ER-low-positive tumors (31/36) were the most likely to change. In primary tumors, 140 (29.1%) tumors were HER2-positive, and 341 (70.9%) were HER2-negative (including 209 cases of HER2-low and 132 cases of HER2-zero). In residual disease, 25 (5.2%) cases had HER2 conversion between positive and negative. Considering HER2-low status, 113 (23.5%) cases had HER2 conversion, mostly driven by cases switching either to or from HER2-low. ER conversion had a positive correlation with pretreatment ER status (r = 0.25; P = .00). There was a positive correlation between HER2 conversion and HER2-targeted therapy (r = 0.18; P = .00). CONCLUSION: Conversion of ER and HER2 status was observed in some breast cancer patients after NAT. Both ER-low-positive and HER2-low tumors showed high instability from the primary tumor to residual disease. ER and HER2 status should be retested in residual disease for further treatment decisions, especially in ER-low-positive and HER2-low breast cancer.

Ultrasound assistance in treatment with elastic stable intramedullary nail fixation in radial and ulnar fractures in children.

PURPOSE: Radial and ulnar fractures are one of the most common fractures in children. When closed reduction of fractures fails, elastic stable intramedullary nail (ESIN) fixation can mostly be used under the guidance of fluoroscopy. In this study, we evaluated the effect of ultrasound (US) as assistance for radial and ulnar fracture reduction and the insertion of ESINs. METHODS: There were 56 patients with midshaft radial and ulnar fractures included in our hospital from March 2019 to August 2021. After applying the inclusion and exclusion criteria and according to the treatment method, they were divided into the US group (patients treated with US assistance) and the conventional group (C-group, patients treated with fluoroscopy guidance). All patients' clinical data were collected. Operation time, fluoroscopy times, radiation dose, and post-operative complications were analyzed. The elbow function was evaluated using the Mayo Elbow Performance Index. RESULTS: There were 26 patients in the US group and 30 in the C-group. The average operation time was 44.5±19.4 min in the US group and 65.1±16.2 min in the C-group. There were significant differences regarding the surgery time, fluoroscopy time, and radiation dose between the groups (all p = 0.001). The average follow-up time was 13.5±3.1 months. No significant difference was found regarding radial nerve injury, extensor pollicis longus rupture, non-union or delayed union, ulnar nerve injury, or acute compartment syndrome. There was no difference in elbow function at the final follow-up. CONCLUSION: US guidance can be adopted for the treatment of displaced radial and ulnar fracture reduction and the insertion of ESINs. It can significantly decrease fluoroscopy times, radiation doses, and duration of surgery.

Inhibition of USP1 reverses the chemotherapy resistance through destabilization of MAX in the relapsed/refractory B-cell lymphoma.

The patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) have poor prognosis, and a novel and effective therapeutic strategy for these patients is urgently needed. Although ubiquitin-specific protease 1 (USP1) plays a key role in cancer, the carcinogenic effect of USP1 in B-cell lymphoma remains elusive. Here we found that USP1 is highly expressed in DLBCL patients, and high expression of USP1 predicts poor prognosis. Knocking down USP1 or a specific inhibitor of USP1, pimozide, induced cell growth inhibition, cell cycle arrest and autophagy in DLBCL cells. Targeting USP1 by shRNA or pimozide significantly reduced tumor burden of a mouse model established with engraftment of rituximab/chemotherapy resistant DLBCL cells. Pimozide significantly retarded the growth of lymphoma in a DLBCL patient-derived xenograft (PDX) model. USP1 directly interacted with MAX, a MYC binding protein, and maintained the stability of MAX through deubiquitination, which promoted the transcription of MYC target genes. Moreover, pimozide showed a synergetic effect with etoposide, a chemotherapy drug, in cell and mouse models of rituximab/chemotherapy resistant DLBCL. Our study highlights the critical role of USP1 in the rituximab/chemotherapy resistance of DLBCL through deubiquitylating MAX, and provides a novel therapeutic strategy for rituximab/chemotherapy resistant DLBCL.

Clinicopathologic features and abnormal signaling pathways in plasmablastic lymphoma: a multicenter study in China.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare but aggressive B-cell lymphoma subtype with poor prognosis. Knowledge about the etiology, clinicopathologic and molecular features, and outcomes of PBL is limited. This study aimed to examine the clinicopathologic characteristics, therapeutic approaches, and clinical outcomes of PBL patients in a Chinese population. METHODS: A total of 102 PBL patients were recruited from three cancer centers. The pathologic features and clinical outcomes of 56 patients with available treatment details and follow-up data were reviewed and analyzed. RNA sequencing was performed in 6 PBL and 11 diffuse large B-cell lymphoma (DLBCL) patients. RESULTS: Most patients in our cohort were male (n = 36, 64.3%), and 35 patients presented with Ann Arbor stage I/II disease at diagnosis. All these patients showed negative findings for human immunodeficiency virus, and the vast majority of patients in our cohort were immunocompetent. Lymph nodes (n = 13, 23.2%) and gastrointestinal tract (n = 10, 17.9%) were the most commonly involved site at presentation. Post-treatment complete remission (CR) was the only prognostic factor affecting overall survival (OS) and progression-free survival (PFS) in the multivariate analysis. RNA-seq demonstrated that B-cell receptor (BCR), T-cell receptor (TCR), P53, calcium signaling, and Wnt signaling pathways were significantly downregulated in PBLs compared with GCB (or non-GCB) DLBCLs. CONCLUSIONS: In this multicenter study in the Chinese population, PBL mainly occurred in immunocompetent individuals and most patients present with early-stage disease at diagnosis. Post-treatment CR was an important prognostic factor affecting OS and PFS. RNA-seq showed that the B-cell receptor (BCR), P53, calcium signaling, cell adhesion molecules, and Wnt signaling pathways significantly differed between PBL and GCB (or non-GCB) DLBCL, which provided theoretical basis for its pathogenesis and future treatment.

Exploring an EAP writing teacher's adaptive expertise and adaptive teaching practices from a CDST perspective.

Teachers' adaptive expertise (TAE) has received increasing attention in the current English as foreign language (EFL) teaching field, however, it has seldom been examined with adaptive practices by teachers in on-going classes among existing literature. Adopting a mixed-method design with data triangulation, this study was conducted to explore the complexity of teachers' adaptive expertise (TAE) and adaptive teaching practices that an EAP writing teacher demonstrated in academic writing courses, from a Complex Dynamic Systems Theory (CDST) perspective. Semi-structured interviews, classroom observations, and questionnaires were arranged to collect qualitative and quantitative data from an EAP writing teacher and 43 EFL learners in a Chinese university. Thematic analysis and SPSS were mainly used in the current work for data analysis. Our findings confirmed (1) the complexity of TAE and ATP with specific features of non-linearity, interconnectedness, and self-organization, which are classic CDST characteristics; (2) the TAE evolved with meta-cognitive, cognitive, affective and social components that are intertwined and contributed to the teacher's adaptive teaching practices (ATP) in her academic writing course; (3) being facilitated by TAE, the teacher's adaptive teaching practices significantly enhanced EFL learners, learning motivation of academic writing and their learning efficiency. Findings of the current work pave the way for future studies in researching TAE and ATP with a thorough consideration of language teachers, students and contexts from the CDST perspective. Moreover, pedagogical contributions are highlighted through the detailed examinations of the EAP writing teacher's ATP, including the class design, teaching plans, and methods, which would be fruitful for the development of tertiary EAP writing research.

Surgical removal of bilateral lung metastases from Wilms tumor via subxiphoid approach video-assisted thoracic surgery: a case report.

Background: Lung is the most common site of metastasis in pediatric patients with Wilms tumor (WT). For such patients, neoadjuvant chemotherapy before nephrectomy is recommended now. A considerable proportion of metastases will shrink in size after the chemotherapy. However, there are still some of them that are not sensitive to chemotherapy and require subsequent surgical resection. For pediatric patients with bilateral lung metastases from WT which are not sensitive to chemotherapy, the simultaneous surgical removal of bilateral lung tumors via one-stage surgery is problematic. These children typically require 2 separate surgeries to remove the bilateral lung metastases and improve their 5-year event-free survival (EFS) rate. There is no precedent in pediatric thoracic surgery for one-stage, bilateral, lung wedge resection via subxiphoid approach video-assisted thoracic surgery (SA-VATS). Case Description: In this article, we report on a successful SA-VATS performed on an 8-year-old boy whereby all of the bilateral lung metastases were completely resected. The operation was performed through 3 incisions under the xiphoid process and costal arch. No complications occurred after surgery. The patient's intraoperative blood loss was approximately 20 mL. Drainage tubes were indwelled in both pleural cavities which were removed on post-operative day (POD) 5 and POD 6. There was no recurrence at follow-up of about 4 months. Conclusions: This case presents a new option for thoracoscopic surgery which is safe and less invasive for patients with bilateral lung metastases from WT. Similar patients may benefit from the shorter time frame between the operation and other postoperative treatment.

SMYD3 promotes aerobic glycolysis in diffuse large B-cell lymphoma via H3K4me3-mediated PKM2 transcription.

Genetic abnormalities in histone methyltransferases (HMTs) frequently occur in diffuse large B-cell lymphoma (DLBCL) and are related to its progression. SET and MYND domain containing 3 (SMYD3) is an HMT that is upregulated in various tumors and promotes their malignancy. However, to the best of our knowledge, the function of SMYD3 in DLBCL has not been investigated thus far. In the present study, 22 HMT genes related to cancer development were first selected according to current literature, and it was found that high SMYD3 expression was significantly associated with poor progression-free survival in patients with DLBCL. SMYD3 protein levels were upregulated and positively associated with poor prognosis and poor responsiveness to chemotherapy in patients with DLBCL. Functional examinations demonstrated that SMYD3 increased cell proliferation and the flux of aerobic glycolysis in DLBCL cells in vitro and in vivo and decreased cell sensitivity to doxorubicin in vitro. Moreover, SMYD3 could directly bind to specific sequences of Pyruvate Kinase M2 (PKM2) and promote DLBCL cell proliferation and aerobic glycolysis via H3K4me3-mediated PKM2 transcription. Clinically, SMYD3 expression positively correlated with that of PKM2, and high SMYD3 was significantly associated with high maximum standardized uptake value (SUVmax) detected by [(18)F]-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (PET/CT) in DLBCL samples. Concomitant expression of SMYD3 and PKM2 positively correlated with poor progression-free and overall survival in patients with DLBCL and may serve as novel biomarkers in DLBCL.

Renieramycin T Inhibits Melanoma B16F10 Cell Metastasis and Invasion via Regulating Nrf2 and STAT3 Signaling Pathways.

As one of marine tetrahydroisoquinoline alkaloids, renieramycin T plays a significant role in inhibiting tumor metastasis and invasion. However, the effect of renieramycin T on inflammation-related tumor metastasis and invasion is still unknown, and its mechanisms remain unclear. Here we established an inflammation-related tumor model by using the supernatant of RAW264.7 cells to simulate B16F10 mouse melanoma cells. The results indicate that renieramycin T suppressed RAW264.7 cell supernatant-reduced B16F10 cell adhesion to a fibronectin-coated substrate, migration, and invasion through the matrigel in a concentration-dependent manner. Moreover, Western blot results reveal that renieramycin T attenuated the phosphorylation of STAT3 and down-regulated the expression of Nrf2. Together, the above findings suggest a model of renieramycin T in suppressing B16F10 cancer cell migration and invasion. It may serve as a promising drug for the treatment of cancer metastasis.

A database of animal metagenomes.

With the rapid development of high-throughput sequencing technology, the amount of metagenomic data (including both 16S and whole-genome sequencing data) in public repositories is increasing exponentially. However, owing to the large and decentralized nature of the data, it is still difficult for users to mine, compare, and analyze the data. The animal metagenome database (AnimalMetagenome DB) integrates metagenomic sequencing data with host information, making it easier for users to find data of interest. The AnimalMetagenome DB is designed to contain all public metagenomic data from animals, and the data are divided into domestic and wild animal categories. Users can browse, search, and download animal metagenomic data of interest based on different attributes of the metadata such as animal species, sample site, study purpose, and DNA extraction method. The AnimalMetagenome DB version 1.0 includes metadata for 82,097 metagenomes from 4 domestic animals (pigs, bovines, horses, and sheep) and 540 wild animals. These metagenomes cover 15 years of experiments, 73 countries, 1,044 studies, 63,214 amplicon sequencing data, and 10,672 whole genome sequencing data. All data in the database are hosted and available in figshare https://doi.org/10.6084/m9.figshare.19728619 .

Prognostic significance of clinical characteristics and 18Fluorodeoxyglucose-positron emission tomography/computed tomography quantitative parameters in patients with primary mediastinal B-cell lymphoma.

OBJECTIVE: Primary mediastinal B-cell lymphoma (PMBCL) lacks standard treatment regimens. This study aimed to identify the disease's clinical features and prognostic factors. METHODS: This retrospective study included 56 patients with PMBCL. Patient demographic details and clinicopathological characteristics were summarized, and their effects on progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: The median patient age was 29 years (range, 14-56). Twenty-two patients received DA-EPOCH-R (dose-adjusted etoposide, vincristine, and doxorubicin for 96 hours with bolus doses of cyclophosphamide and oral prednisone, as well as rituximab), and 34 patients received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Clinical/laboratory parameters, overall response rates, and 5-year PFS and OS rates did not differ between the treatment groups. Kaplan-Meier analysis indicated that late-stage disease and a higher International Prognostic Index (IPI) were associated with shorter PFS and OS. Furthermore, patients with B symptoms and first-line treatment non-responders exhibited worse OS. 18Fluorodeoxyglucose-positron emission tomography/computed tomography quantitative parameters, such as higher metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were corrected with shorter PFS. CONCLUSIONS: This study revealed that stage IV disease, higher IPI, and B symptoms were poor prognostic factors in patients with PMBCL. Significantly, higher MTV and TLG portended worse PFS.