Chitosan-crosslinked polyvinyl alcohol anti-swelling hydrogel designed to prevent abdominal wall adhesion.

Abdominal adhesion is a frequent clinical issue with a high incidence rate and consequences following intra-abdominal surgery. Although many anti-adhesion materials have been used in surgical procedures, additional research is still needed to determine which ones have the most robust wet tissue adhesion, the best anti-postoperative adhesion, and the best anti-inflammatory properties. We have developed an excellent tissue adhesion and anti-swelling polyvinyl alcohol-chitosan hydrogel (AS hydrogel). According to in vitro cell testing, AS hydrogel significantly decreased inflammation around cells and exhibited good biocompatibility. Further, we assessed how well AS hydrogel prevented intraperitoneal adhesion using a rabbit model with cecum and abdominal wall injuries. According to the data, AS hydrogel has excellent anti-inflammatory and biodegradability properties compared to the control group. It can also prevent intestinal and abdominal wall injuries from occurring during surgery. Based on these results, hydrogel appears to be a perfect new material to prevent postoperative abdominal wall adhesion.

Comparison of blinatumomab and CAR T-cell therapy in relapsed/refractory acute lymphoblastic leukemia: a systematic review and meta-analysis.

OBJECTIVES: This study evaluated the benefits and risks of patients with refractory or relapsed acute lymphocytic leukemia (R/R ALL) treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy and blinatumomab. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched for relevant studies. RESULTS: The pooled complete remission (CR) rate and minimal residual disease (MRD) negative rate were 48%, 31% for blinatumomab, and 86% and 80% for CAR T-cell therapy. CONCLUSIONS: The CAR T-cell therapy group exhibited a higher likelihood of CR rate than the blinatumomab group in every analysis regardless of adjustment subgroups. CAR T-cell therapy was associated with a significantly prolonged overall survival (OS) and relapse-free survival (RFS) compared with blinatumomab (2-year OS 55% vs 25%; 2-year RFS 40% vs 22%). CAR T-cell therapy was more effective for achieving CR and bridging to allogeneic hematopoietic stem cell transplantation (allo-SCT) than blinatumomab (2-year OS 75% vs. 57%). An emerging role for blinatumomab is as a bridging agent pre-SCT, and for patients who achieve an MRD-negative state pre-SCT, post-SCT outcomes are expected to be the same as CAR-T. For adverse effects (AEs), blinatumomab was associated with a lower rate of grade ≥3 hematological toxicity, CRS, and neurological events.

Corrigendum: Identification of microtube-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction.

[This corrects the article DOI: 10.3389/fgene.2022.1092678.].

Prognostic Significance of Ribosome-related Genes Signature in Diffuse Large B Cell Lymphoma.

Background: The diffuse large B-cell lymphoma (DLBCL) is a heterogeneous lymphoma with a dismal outcome, due to approximately 40% patients will be relapsed or refractory to the standard therapy of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Therefore, we need urgently to explore the approach to classify the risk of DLBCL patients accurately and accurately targeting therapy. The ribosome is a vital cellular organelle that is mainly responsible for translation mRNA into protein, moreover, more and more reports revealed that ribosome was associated with cellular proliferation and tumorigenesis. Therefore, our study aimed to construct a prognostic model of DLBCL patients using ribosome-related genes (RibGs). Method: We screened differentially expressed RibGs between healthy donors' B cells and DLBCL patients' malignant B cells in GSE56315 dataset. Next, we performed analyses of univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses to establish the prognostic model consisting of 15 RibGs in GSE10846 training set. Then, we validated the model by a range of analyses including Cox regression, Kaplan-Meier survival, ROC curve, and nomogram in training and validation cohorts. Results: The RibGs model showed a reliably predictive capability. We found the upregulated pathways in high-risk group most associated with innate immune reaction such as interferon response, complement and inflammatory responses. In addition, a nomogram including age, gender, IPI score and risk score was constructed to help explain the prognostic model. We also discovered the high-risk patients were more sensitive to some certain drugs. Finally, knocking out the NLE1 could inhibit the proliferation of DLBCL cell lines. Conclusion: As far as we know, it is the first time to predict the prognosis of DLBCL using the RibGs and give a new sight for DLBCL treatment. Importantly, the RibGs model could be acted as a supplementary to the IPI in classifying the risk of DLBCL patients.

Hypoxia induces chemoresistance to proteasome inhibitors through orchestrating deSUMOylation and ubiquitination of SRC-3 in multiple myeloma.

The bone marrow microenvironment in multiple myeloma (MM) is hypoxic and provides multi-advantages for the initiation of chemoresistance, but the underlying mechanisms and key regulators are still indistinct. In the current study, we found that hypoxia stimulus easily induced chemoresistance to proteasome inhibitors (PIs), and the steroid receptor coactivator 3 (SRC-3) expression was remarkably augmented at posttranslational level. Protein interactome analysis identified SENP1 as a key modifier of SRC-3 stability, as SENP1-mediated deSUMOylation attenuated the K11-linked polyubiquitination of SRC-3. SENP1 depletion in the SENP1fl/flCD19Cre/+ B cells showed impaired SRC3 stability, and knockdown of SENP1 in MM cells by CRISPR/cas9 sgRNA accelerated the degradation of SRC-3 and remarkably overcame the resistance to PIs. In the Vk*Myc and 5TGM1 mouse models as well as patient-derived xenograft (PDX) of myeloma, SENP1 inhibitor Momordin Ιc (Mc) increased the sensitivity to PIs in MM cells. Importantly, SENP1 level was positively correlated with SRC-3 level in the tissues from refractory/relapsed MM, as well as in xenograft tissues from mice treated with bortezomib and Mc. Taken together, our findings suggest that hypoxia-induced SENP1 is a crucial regulator of chemoresistance to PIs, and shed light on developing therapeutic strategies to overcome chemoresistance by using small molecules targeting SENP1 or SRC-3.

A Novel Defined Super-Enhancer Associated Gene Signature to Predict Prognosis in Patients With Diffuse Large B-Cell Lymphoma.

Background: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease that can have profound differences in survival outcomes. A variety of powerful prognostic factors and models have been constructed; however, the development of more accurate prognosis prediction and targeted treatment for DLBCL still faces challenges. An explosion of research on super-enhancer (SE)-associated genes provide the possibility to use in prognostication for cancer patients. Here, we aimed to establish a novel effective prognostic model using SE-associated genes from DLBCL. Methods: A total of 1,105 DLBCL patients from the Gene Expression Omnibus database were included in this study and were divided into a training set and a validation set. A total of 11 SE-associated genes (BCL2, SPAG16, PXK, BTG1, LRRC37A2, EXT1, TGFBR2, ANKRD12, MYCBP2, PAX5, and MYC) were initially screened and identified by the least absolute shrinkage and selection operator (Lasso) penalized Cox regression, univariate and multivariate Cox regression analysis. Finally, a risk score model based on these 11 genes was constructed. Results: Kaplan-Meier (K-M) curves showed that the low-risk group appeared to have better clinical survival outcomes. The excellent performance of the model was determined via time-dependent receiver operating characteristic (ROC) curves. A nomogram based on the polygenic risk score was further established to promote reliable prognostic prediction. This study proposed that the SE-associated-gene risk signature can effectively predict the response to chemotherapy in DLBCL patients. Conclusion: A novel and reliable SE-associated-gene signature that can effectively classify DLBCL patients into high-risk and low-risk groups in terms of overall survival was developed, which may assist clinicians in the treatment of DLBCL.

Immunophenotypic Landscape and Prognosis-Related mRNA Signature in Diffuse Large B Cell Lymphoma.

Diffuse large B cell lymphoma (DLBCL) exhibits a tightly complexity immune landscape. In this study, we intended to identify different immune phenotype and to examine the immune related mRNA signature for clinical characteristic, therapeutic responsiveness as well as risk stratification and survival prediction in DLBCL. We identified two immune infiltration subtypes of DLBCL patients based on 28 immune cell types. GSEA analysis uncovered the concordant classification of two robust significant subtypes of DLBCL. Considering the convenient application of the immune infiltration subtypes for prognostic prediction, we developed a risk score based on the differentially expressed genes between the Immunity-H and Immunity-L groups. By a least absolute shrinkage and selection operator (LASSO)-Cox regression model, a sixteen-gene risk signature, comprising ANTXR1, CD3D, TIMP1, FPR3, NID2, CTLA4, LPAR6, GPR183, LYZ, PTGDS, ITK, FBN1, FRMD6, PLAU, MICAL2, C1S, was established. The comprehensive results showed that the high-risk group was correlated with lower immune infiltration, more aggressive phenotypes, lower overall survival and more sensitive to lenalidomide. In contrast, a low-risk group score was associated with higher immune infiltration, less aggressive phenotypes, better overall survival and more likely to benefit from PD-1/PD-L1 inhibitors. Finally, a nomogram comprised of the risk score and IPI score was verified to more accurately predict the overall survival of DLBCL than traditional clinical prediction models. Altogether, our data demonstrate the heterogeneity of immune patterns within DLBCL and deepen our molecular understanding of this tumor entity.

The efficiency of autologous stem cell transplantation as the first-line treatment for nodal peripheral T-cell lymphoma: results of a systematic review and meta-analysis.

BACKGROUND: Nodal peripheral T cell lymphoma (PTCL) confers a dismal prognosis when treated with conventional chemotherapy. Autologous stem cell transplantation (ASCT) seems a reasonable alternative in eligible patients. Nevertheless, a consensus on the role of ASCT as the first-line consolidation therapy for nodal PTCL patients has not been reached so far. METHODS: A quantitative meta-analysis was performed via a systematic search in PubMed, Web of Science, Embase, and The Cochrane Library. The overall survival (OS), progression-free survival (PFS), hazard ratio (HR), and 95% confidence intervals (CIs) were compared and calculated from database inception to September 2021. RESULTS: Twelve articles were eligible. The results showed that ASCT could improve the survival of patients compared with chemotherapy alone. In terms of subtype analysis, results showed that angioimmunoblastic T cell lymphoma (AITL) patients could benefit more from chemotherapy followed by ASCT. Statistical differences were also confirmed for OS and PFS in different remission status, clinical stage, performance status (PS), chemotherapy regimen, and gender. CONCLUSION: ASCT could serve as the first-line consolidation treatment strategy for nodal PTCL patients, especially AITL patients. Early clinical stage, good PS status, CR before transplantation, CHOEP regimen, and female patients may indicate a better outcome.

Efficacy of chimeric antigen receptor T cell therapy and autologous stem cell transplant in relapsed or refractory diffuse large B-cell lymphoma: A systematic review.

Background: We aimed to compare the efficacy of chimeric antigen receptor T (CAR-T) cell therapy with that of autologous stem cell transplantation (auto-HSCT) in relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL). Research design and methods: We searched eligible publications up to January 31st, 2022, in PubMed, Cochrane Library, Springer, and Scopus. A total of 16 publications with 3484 patients were independently evaluated and analyzed using STATA SE software. Results: Patients who underwent CAR-T cell therapy showed a better overall response rate (ORR) and partial response (PR) than those treated with auto-HSCT (CAR-T vs. auto-HSCT, ORR: 80% vs. 73%, HR:0.90,95%CI:0.76-1.07,P = 0.001; PR: 20% vs. 14%, HR:0.65,95%CI:0.62-0.68,P = 0.034). No significant difference was observed in 6-month overall survival (OS) (CAR-T vs. auto-HSCT, six-month OS: 81% vs. 84%, HR:1.23,95%CI:0.63-2.38, P = 0.299), while auto-HSCT showed a favorable 1 and 2-year OS (CAR-T vs. auto-HSCT, one-year OS: 64% vs. 73%, HR:2.42,95%CI:2.27-2.79, P < 0.001; two-year OS: 54% vs. 68%, HR:1.81,95%CI:1.78-1.97, P < 0.001). Auto-HSCT also had advantages in progression-free survival (PFS) (CAR-T vs. auto-HSCT, six-month PFS: 53% vs. 76%, HR:2.81,95%CI:2.53-3.11,P < 0.001; one-year PFS: 46% vs. 61%, HR:1.84,95%CI:1.72-1.97,P < 0.001; two-year PFS: 42% vs. 54%, HR:1.62,95%CI:1.53-1.71, P < 0.001). Subgroup analysis by age, prior lines of therapy, and ECOG scores was performed to compare the efficacy of both treatment modalities. Conclusion: Although CAR-T cell therapy showed a beneficial ORR, auto-HSCT exhibited a better long-term treatment superiority in R/R DLBCL patients. Survival outcomes were consistent across different subgroups.

Identification of microtubule-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction.

Background: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with a complicated prognosis. Even though various prognostic evaluations have been applied currently, they usually only use the clinical factors that overlook the molecular underlying DLBCL progression. Therefore, more accurate prognostic assessment needs further exploration. In the present study, we constructed a novel prognostic model based on microtubule associated genes (MAGs). Methods: A total of 33 normal controls and 1360 DLBCL samples containing gene-expression from the Gene Expression Omnibus (GEO) database were included. Subsequently, the univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to select the best prognosis related genes into the MAGs model. To validate the model, Kaplan-Meier curve, and nomogram were analyzed. Results: A risk score model based on fourteen candidate MAGs (CCDC78, CD300LG, CTAG2, DYNLL2, MAPKAPK2, MREG, NME8, PGK2, RALBP1, SIGLEC1, SLC1A1, SLC39A12, TMEM63A, and WRAP73) was established. The K-M curve presented that the high-risk patients had a significantly inferior overall survival (OS) time compared to low-risk patients in training and validation datasets. Furthermore, knocking-out TMEM63A, a key gene belonging to the MAGs model, inhibited cell proliferation noticeably. Conclusion: The novel MAGs prognostic model has a well predictive capability, which may as a supplement for the current assessments. Furthermore, candidate TMEM63A gene has therapeutic target potentially in DLBCL.

Erratum: Characteristics of myeloid sarcoma in mice and patients with TET2 deficiency.

[This corrects the article DOI: 10.3892/ol.2020.11479.].

Characteristics of myeloid sarcoma in mice and patients with TET2 deficiency.

Myeloid sarcoma (MS) carries a poor prognosis, and information on epigenetic modifications in MS is currently limited. In the present study, 214 ten-eleven translocation-2 (TET2)-/- mice were successfully constructed. In addition, 436 patients with myelodysplastic syndrome (MDS) and 354 with acute myeloid leukemia (AML) patients were recruited. The incidence of MS in mice and patients with TET2 deficiency was examined, and the efficiency of hypomethylating agents (HMAs) was also be evaluated. A total of 93% of the TET2 -/- mice developed myeloid malignancies, 5.5% of which were accompanied by MS (n=11). The survival of these TET2 -/- mice ranged between 3 and 25 months. No significant difference was observed between the survival of MS and non-MS mice with TET2 loss (P>0.05). In addition, MS cells were transplantable, and their recipients exhibited myeloproliferative characteristics, such as increased white blood cell counts, monocytosis, low erythrocyte counts and hepatosplenomegaly. Their median survival duration was 94.8 days. In the clinical setting, 9.7% of MDS and 11.6% of AML patients with TET2 deficiency developed MS, which was higher compared with previous reports (1.5-9.1%). The median age of the MS patients was 44 years old. 5-Aza-2'-deoxycytidine (5-Aza-dC) reduced the incidence of MS in TET2 -/- mice, and decitabine was a suitable treatment strategy for MS patients. These data indicate that TET2 deficiency plays a key role in MS and its prognostic significance requires further investigation. HMAs may be a useful treatment for MS patients with TET2 mutations.

Clinical characteristics and prognosis associated with multiple primary malignant tumors in non-Hodgkin lymphoma patients.

OBJECTIVE: Patients with non-Hodgkin lymphoma (NHL) occasionally present with multiple primary malignant tumors (MPMTs). This study aimed to determine the clinical characteristics, survival, and risk factors of these patients. METHODS: The median follow-up of 92 patients was 13.5 months (range 0.3-72). Overall, 21 patients had synchronous MPMTs and 71 had metachronous MPMTs. We classified patients in the latter group into metachronous first group (n=27) and metachronous second group (n=44). RESULTS: Diffuse large B-cell lymphoma was the most frequent histologic lymphoma type. The digestive system was the commonest site affected by the solid cancer. The 1- and 2-year survival rates were 86.5% and 70.5%, respectively. The overall survival (OS) rates were 67.9% and 36.2% at 2 and 3 years, respectively, in the metachronous first group; 73.8% and 73.8%, respectively, in the metachronous second group; and 68.1% and 56.7%, respectively, in the synchronous tumor group. There was no difference in the survival rate among the 3 groups before 2 years, but after 2 years, a shorter OS rate was observed in the metachronous first group than in the metachronous second group and synchronous tumor group. For all patients, age >60 years, male sex, and ⩾3 involved nodal sites were considered independent prognostic factors associated with survival. CONCLUSIONS: OS time was shorter in patients with NHL who developed a second tumor than in those who were diagnosed with solid cancer synchronously and second neoplasm after previous solid tumors. Long-term follow-up and effective treatment should be provided to these patients.

Anomalous transverse resistance in 122-type iron-based superconductors.

The study of transverse resistance of superconductors is essential to understand the transition to superconductivity. Here, we investigated the in-plane transverse resistance of Ba0.5K0.5Fe2As2 superconductors, based on ultra-thin micro-bridges fabricated from optimally doped single crystals. An anomalous transverse resistance was found at temperatures around the superconducting transition, although magnetic order or structure distortion are absent in the optimal doping case. With the substitution of magnetic and nonmagnetic impurities into the superconducting layer, the anomalous transverse resistance phenomenon is dramatically enhanced. We find that anisotropic scattering or the superconducting electronic nematic state related with the superconducting transition may contribute to this phenomenon.

EVI1 expression predicts outcome in higher-risk myelodysplastic syndrome patients.

The clinical impact of ecotropic viral integration site 1 (EVI1) expression status in myelodysplastic syndromes (MDS) is poorly defined. Here, we investigate the expression of EVI1 and its associated clinical and cytogenetic characteristics in 398 MDS patients. High EVI1 levels (EVI1high) were found more frequently in Higher-risk MDS patients. Other cytogenetic abnormalities over-represented among EVI1high cases included complex karyotype, del(5q), monosomy 7, and 12q-compared with EVI1low MDS. No specific gene mutation was found different between EVI1high and EVI1low patients, except for a high proportion of TP53 mutation in the EVI1high group. For EVIhigh patients, mean number of gene mutations was higher than that in EVI1low patients. No definite correlation was found between EVI1 expression and MDS prognosis. However, for Higher-risk MDS patients, EVI1high patients have poorer survival rate compared with EVI1low patients. Moreover, EVI1high was an adverse prognostic marker for MDS with excess blasts subtype. The addition of EVI1 could deteriorate the survival of MDS patients with chromosome 3 abnormalities, del(5q-) or monosomy 7. Taken together, EVI1 overexpression is a poor prognostic marker for higher-risk MDS group and could be included in risk stratification for MDS patients.

Nematic superconducting state in iron pnictide superconductors.

Nematic order often breaks the tetragonal symmetry of iron-based superconductors. It arises from regular structural transition or electronic instability in the normal phase. Here, we report the observation of a nematic superconducting state, by measuring the angular dependence of the in-plane and out-of-plane magnetoresistivity of Ba0.5K0.5Fe2As2 single crystals. We find large twofold oscillations in the vicinity of the superconducting transition, when the direction of applied magnetic field is rotated within the basal plane. To avoid the influences from sample geometry or current flow direction, the sample was designed as Corbino-shape for in-plane and mesa-shape for out-of-plane measurements. Theoretical analysis shows that the nematic superconductivity arises from the weak mixture of the quasi-degenerate s-wave and d-wave components of the superconducting condensate, most probably induced by a weak anisotropy of stresses inherent to single crystals.