[Correlation between CRAB Symptoms and Antioxidant Enzyme Activity in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the relationship between clinical indicators of CRAB symptoms and antioxidant enzyme activity in patients with multiple myeloma (MM). METHODS: The activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in the bone marrow supernatants of 44 patients with MM and 12 patients with non-malignant hematological diseases was detected by colorimetric assay, and then the differences in the activity of antioxidant enzymes between the two groups were compared. Furthermore, the relationship between the activity of antioxidant enzymes in the MM group and the levels of serum calcium, serum creatinine (Scr), hemoglobin (Hb), alkaline phosphatase (ALP) as well as bone lesions were analyzed. RESULTS: The antioxidant enzyme activity was lower in MM patients compared with the control group (P < 0.05). When the concentrations of serum calcium and ALP were higher than the normal levels, Hb was lower than 85 g/L, and there were multiple bone lesions, the activity of CAT, SOD and GPX was significantly declined (P < 0.05); When the concentration of Scr≥177 µmol/L, the activity of GPX was significantly declined (P < 0.05). Regression analyses showed that CAT, SOD and GPX were negatively correlated with serum calcium (r =-0.538, r =-0.456, r =-0.431), Scr (r =-0.342, r =-0.384, r =-0.463), and ALP (r =-0.551, r =-0.572, r =-0.482). CONCLUSION: The activity of antioxidant enzymes, including CAT, SOD and GPX, were decreased in patients with MM and they were negatively correlated with some clinical indicators of CRAB symptoms (such as serum calcium, Scr, and ALP), which suggests that promoting the activity of antioxidant enzymes may be beneficial to treat the CRAB symptoms of the patients with MM.

Role of Rituximab in Treatment of Patients With Primary Central Nervous System Lymphoma (PCNSL): A Systematic Review and Meta-Analysis.

Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin's lymphoma involving the brain, cerebrospinal fluid, spinal cord and eyes. Rituximab has played a prominent role in the treatment of non-Hodgkin's B-cell lymphomas, including aggressive diffuse large B lymphoma. However, as a macromolecular drug, the role of rituximab in the treatment of PCNSL has been controversial. In this systematic review and meta-analysis, we evaluated the role of rituximab in the treatment of PCNSL. We searched articles in the following electronic databases including PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov until October 20, 2022.We included 11 studies (3 RCTS and 8 retrospective studies) with a total of 1182 patients. We extracted the baseline characteristics and outcomes of the studies and assessed the risk of bias, then used Review Manager 5.4 for this meta-analysis. The primary outcomes included complete response rate (CR), overall survival (OS), and progression-free survival (PFS). Odds ratios (ORS) and corresponding 95% confidence intervals (CIS) for the primary outcome were analyzed and compared. The results of our statistical analysis show that the use of rituximab was closely correlated with a higher CR(OR 1.70,95%CI 1.17-2.46, P = .005), 3-year OS (OR 2.40, 95%CI 1.53-3.77, P = .0001), 5-year OS (OR 2.75, 95%CI 1.68-4.49, P < .0001), 3-year PFS(OR 4.42, 95%CI 1.15-16.97, P < .0001), 5-year PFS(OR 1.97, 95%CI 1.39-2.78, P = .0001).These results suggest that rituximab may have a positive impact on the prognosis of patients with PCNSL, and may be helpful in the determination of treatment plan for patients with PCNSL.

Tumor-associated M2 macrophages in the immune microenvironment influence the progression of renal clear cell carcinoma by regulating M2 macrophage-associated genes.

Background: Renal clear cell carcinoma (RCC) has negative prognosis and high mortality due to its early diagnosis difficulty and early metastasis. Although previous studies have confirmed the negative progression of RCC is closely related to M2 macrophages in tumor-associated macrophages (TAMs), the specific mechanism is still unknown. Methods: We used immunofluorescence labeling and flow cytometry to detect the proportion of M2 macrophages in RCC tissues. And bioinformatics technique was used to obtain 9 M2 macrophage-related model genes, including SLC40A1, VSIG4, FUCA1, LIPA, BCAT1, CRYBB1, F13A, TMEM144, COLEC12. Using these genes, model formulas are constructed to devide samples into high and low risk groups, and then the overall survival (OS), progression-free survival (PFS) and Gene set enrichment analysis (GSEA) of the high and low risk groups were analyzed. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of model genes between normal kidney tissue and RCC tissue, as well as between HK-2 cell and 786-O cell. Besides, we induced the M2 differentiation of THP-1 cell, and then co-cultured with the RCC cell 786-O in transwell to observe what effect M2 macrophages will cause on the invasion, migration and the expression of model genes of RCC. Results: Our study demonstrated M2 macrophages in RCC was about 2 folds that of normal renal tissue (P<0.0001) and M2 macrophages affected the prognosis of patients with RCC by affecting the co-expressed genes, which were mainly enriched in immune-related pathways. The results of in vitro experiments showed that in RCC tissues and 786-O cells, the model gene FUCA1 was down-regulated, and SLC40A1, VSIG4, CRYBB1 and LIPA were up-regulated. Besides, the results of co-culture showed that after 786-O co-culture with M2 macrophages, the ability of migration and invasion was promoted and the expressions of FUCA1, SLC40A1, VSIG4, CRYBB1, LIPA and TMEM144 were all up-regulated. Conclusion: The proportion of tumor-associated M2 macrophages in RCC tissues is upregulated, and M2 macrophages promote the progression of RCC by regulating the expression of SLC40A1, VSIG4, FUCA1, LIPA, BCAT1, CRYBB1, F13A, TMEM144, COLEC12 genes, thereby affecting the prognosis of patients with RCC.

CD20 expression is closely associated with Epstein-Barr virus infection and an inferior survival in nodular sclerosis classical Hodgkin lymphoma.

Background: Nodular sclerosis classical Hodgkin lymphoma (NSCHL) is a rare disease in which Epstein-Barr virus (EBV) and CD20 can be detected. The clinical significance of EBV infection, CD20 expression and their relationship are still unclear in NSCHL presently. The aim of this research was to systematically explore the clinical significance of EBV infection, expression of CD20 and their relationship in NSCHL. Methods: 109 NSCHL patients diagnosed in Qingdao University's Affiliated Hospital were chosen from January 2010 to July 2019, and the clinical and survival data of all patients were collected retrospectively. Results: Among 109 patients, 33 patients were assigned to the group of EBV-positives, following the results of the EBV-encoded RNA (EBER1). Compared with EBV-negative group patients, those in the group of EBV-positive were older (P=0.004) and their ß2-microglobulin (ß2-MG) levels were higher (P=0.006). The CD20 positivity rate in the group of EBV-positive was substantially higher than that in the EBV-negative group (54.5% vs 27.6%, P=0.007). Among 109 patients, EBV+ and CD20+ double positive patients acquired the least overall survival (OS), and patients with EBV- and CD20- double negative had the best OS (P < 0.001). Although old age, gender, EBV infection and CD20 positive were the risk factors for OS in NSCHL, multivariate analysis showed that CD20 positivity was the only characteristic that showed to be an independent risk factor for OS in NSCHL patients. Conclusion: CD20 was found to be strongly expressed in NSCHL patients who had been infected with EBV, and it was found to be an independent risk factor for NSCHL patients' survival.

Expression and Clinical Significance of Th1/Th2/Th17 Cytokines and Lymphocyte Subsets in PCNSL.

Purpose: Primary central nervous system lymphoma (PCNSL) responds favorably to radiation, chemotherapy and targeted drug therapy. However survival is usually worse, the treatment-related drug resistance and recurrence are still clinical problems to be solved urgently. Studies have shown that cytokines are expressed in varying degrees in patients with lymphoma, which is significantly related to the progression, poor prognosis and drug resistance of lymphoma. We explore the expression and clinical significance of Th1/Th2/Th17 cytokines and lymphocyte subsets in patients with PCNSL to provide a more sufficient theoretical basis for its diagnosis and treatment. Patients and Methods: We measured and analysed the levels of Th1/Th2/Th17 cytokines and the distribution of lymphocyte subsets (including Treg cells, CD3+, CD4+, CD8+, CD19+, and CD4+/CD8+) in 39 patients with PCNSL and 96 patients with diffuse large B-cell lymphoma (DLBCL) without central nervous system involvement. The cytokines of 13 healthy people and the lymphocyte subsets of 27 healthy people were measured as the control group. Results: We found a significant difference in the level of Th1/Th2/Th17 cytokines and lymphocyte subsets between PCNSL and healthy controls, especially IL-2, after treatment, which was significantly higher than before treatment (p<0.01). However, the level of CD19+ and CD4+/CD8+ decreased while CD8+ and CD3+ increased after treatment (regardless of whether the treatment was effective), and the difference was statistically significant. In addition, our analysis of different prognostic factors found that HD-MTX-based chemotherapy appears to have a longer progression-free survival and overall survival than osimertinib-based chemotherapy. Conclusion: There are significant differences in Th1/Th2/Th17 cytokines and lymphocyte subsets among PCNSL, DLBCL, and healthy controls, and their detection is helpful for the diagnosis, treatment, and prognosis of PCNSL. HD-MTX-based chemotherapy may still be the first choice for PCNSL.