[Efficacy and safety analysis of the zanubrutinib-based bridging regimen in chimeric antigen receptor T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma].

Objective: To further elucidate the clinical efficacy and safety of a combination regimen based on the BTK inhibitor zebutanil bridging CD19 Chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) . Methods: Twenty-one patients with high-risk r/r DLBCL were treated with a zanubrutinib-based regimen bridging CAR-T between June 2020 and June 2023 at the Department of Hematology, Tongji Hospital, Tongji University and the Second Affiliated Hospital of Zhejiang University, and the efficacy and safety were retrospectively analyzed. Results: All 21 patients were enrolled, and the median age was 57 years (range: 38-76). Fourteen patients (66.7%) had an eastern cooperative oncology group performance status score (ECOG score) of ≥2. Eighteen patients (85.7%) had an international prognostic index (IPI) score of ≥3. Three patients (14.3%) had an IPI score of 2 but had extranodal infiltration. Fourteen patients (66.7%) had double-expression of DLBCL and seven (33.3%) had TP53 mutations. With a median follow-up of 24.8 (95% CI 17.0-31.6) months, the objective response rate was 81.0%, and 11 patients (52.4%) achieved complete remission. The median progression-free survival (PFS) was 12.8 months, and the median overall survival (OS) was not reached. The 1-year PFS rate was 52.4% (95% CI 29.8% -74.3%), and the 1-year OS rate was 80.1% (95% CI 58.1% -94.6%). Moreover, 18 patients (85.7%) had grade 1-2 cytokine-release syndrome, and two patients (9.5%) had grade 1 immune effector cell-associated neurotoxicity syndrome. Conclusion: Zanubrutinib-based combination bridging regimen of CAR-T therapy for r/r DLBCL has high efficacy and demonstrated a good safety profile.

[Effect of early tocilizumab intervention on patients with cytokine release syndrome following chimeric antigen receptor T cell therapy].

Objective: This study aimed to evaluate the effect of early tocilizumab intervention to relieve cytokine release syndrome (CRS) following chimeric antigen receptor T cell (CAR-T) therapy. Methods: Twenty-two patients with acute lymphoblastic leukemia who received tocilizumab to relieve CRS response after CAR-T cell infusion in our research center from October 2015 to July 2021 were retrospectively analyzed. According to the timing of tocilizumab intervention, patients were divided into the conventional and early intervention groups. Patients who received tocilizumab treatment after sustained high fever for 4 h were included in the early intervention group. The clinical data, CRS grade, and event-free survival (EFS) between the two groups were evaluated. Results: Compared with patients who used tocilizumab after severe CRS, no patients in the early intervention group died from CRS, and there was no increased risk of neurotoxicity. Eleven patients (84.62%) achieved complete remission with minimal residual lesions. The median EFS of patients in the early intervention and conventional groups was 2 (95% CI 0-5) and 7 (95% CI 3-11) months, respectively. Conclusion: Early tocilizumab intervention in patients with CRS reduces severe CRS and provides a more optimized therapeutic strategy for CRS caused by CAR-T cell therapy.

[Lung transplantation for phase â ¢ silicosis: a series of 32 cases].

Objective: To evaluate the effect of lung transplantation for phase Ⅲ silicosis. Methods: From September 2002 to September 2015, 32 patients with end-stage silicosis underwent lung transplantation at Department of Thoracic Surgery, Affiliated Wuxi People's Hospital, Nanjing Medical University. There were 29 male and 3 female patients aged from 24 to 63 years. Thirty-two patients were diagnosed as phase Ⅲ silicosis by the local occupational disease prevention and control center. Fifteen patients were type Ⅰ respiratory failure and 17 patients were type Ⅱ. There were 14 cases accepted bilateral sequential lung transplantation and 18 cases accepted single lung transplantation, including 13 cases with right single lung transplantation and 5 cases with left single lung transplantation. Extracorporeal membrane oxygenation was used in 13 patients. Pulmonary function monitoring was performed at 3 months, 6 months, 1 year, and 2 years after lung transplantation. Clinical characteristics were compared using t-test, χ2 test and Fisher exact test between groups, Kaplan-Meier survival curve and Log-rank test were used to find out the factors affecting survival. Results: All the patients received lung transplantation successfully. One patient died of multiple organ failure, 1 died of sepsis, and 1 succumbed to sudden cardiac death. Twenty-nine patients were discharged from hospital. During follow-up, there were 5 deaths, two patients died of sepsis 7 months postoperatively, 1 died of renal failure 5 months post-transplant, 1 died of sudden cardiac death, and the remaining 1 patient died of bronchiolitis obliterans. Twenty-four patients lived a good quality of life, with survival rates of 90.6% at 3 months, 80.8% at 1 year, 76.7% at 3 years, and 76.7% at 5 years. Significant difference was not observed between single and bilateral lung transplantation about long-term survival rate. During follow-up pulmonary function post-transplant (3 months, 6 months, 1 year, and 2 years) were improved dramatically compared with preoperative level, and patients lived a good quality of life. Conclusion: Lung transplantation is beneficial for patients with phase Ⅲ silicosis, long-term survival is probable.

[Influencing factors for postoperative survival of patients with stage III silicosis treated by lung transplantation].

Objective: To investigate the clinical effect, postoperative complications, and causes of death in the treatment of stage III silicosis with lung transplantation and the influencing factors for survival. Methods: A retrospective analysis was performed for the clinical data of 32 patients with stage III silicosis who underwent lung transplantation in our hospital from September 2002 to September 2015. The survival, causes of death, and postoperative complications were analyzed. The Kaplan-Meier method was used to plot survival curves, the log-rank test was used to compare the influence of each factor on survival rates, and the multivariate Cox proportional hazards regression model was used to evaluate the influence of each factor on survival. Results: All the patients underwent successful lung transplantation. The 3-month and 1-, 3-, and 5-year postoperative cumulative survival rates were 90.6%, 80.8%, 76.7%, and 76.7%, respectively. Eight patients died during the postoperative follow-up, among whom 1 died of multiple organ failure, 3 died of severe infection, 2 died of sudden cardiac death, 1 died of renal failure, and 1 died of bronchiolitis obliterans. The major postoperative complications included primary graft dysfunction (PGD) in 10 patients, severe infection in 7 patients, acute rejection reaction in 3 patients, bronchiolitis obliterans in 5 patients, bleeding in 5 patients, anastomotic complication in 2 patients, and renal dysfunction in 3 patients. The Kaplan-Meier survival analysis showed that sex, postoperative PGD, postoperative infection, massive intraoperative blood loss, preoperative pulmonary arterial hypertension were influencing factors for postoperative survival rates (P<0.05). The multivariate Cox regression model showed that male sex was the protective factor (P<0.05) and postoperative PGD and massive intraoperative blood loss were independent risk factors for death after transplantation (P<0.05). Conclusion: Lung transplantation is a method for the treatment of silicosis. Postoperative PGD and massive intraoperative blood loss are independent risk factors for death after transplantation. Survival rates are affected by postoperative PGD, infection, massive intraoperative blood loss, and preoperative pulmonary arterial hypertension.

Comprehensive identification and expression analysis of Hsp90s gene family in Solanum lycopersicum.

Heat shock protein 90 (Hsp90) is a protein produced by plants in response to adverse environmental stresses. In this study, we identified and analyzed Hsp90 gene family members using a bioinformatic method based on genomic data from tomato (Solanum lycopersicum L.). The results illustrated that tomato contains at least 7 Hsp90 genes distributed on 6 chromosomes; protein lengths ranged from 267-794 amino acids. Intron numbers ranged from 2-19 in the genes. The phylogenetic tree revealed that Hsp90 genes in tomato (Solanum lycopersicum L.), rice (Oryza sativa L.), and Arabidopsis (Arabidopsis thaliana L.) could be divided into 5 groups, which included 3 pairs of orthologous genes and 4 pairs of paralogous genes. Expression analysis of RNA-sequence data showed that the Hsp90-1 gene was specifically expressed in mature fruits, while Hsp90-5 and Hsp90-6 showed opposite expression patterns in various tissues of cultivated and wild tomatoes. The expression levels of the Hsp90-1, Hsp90-2, and Hsp90- 3 genes in various tissues of cultivated tomatoes were high, while both the expression levels of genes Hsp90-3 and Hsp90-4 were low. Additionally, quantitative real-time polymerase chain reaction showed that these genes were involved in the responses to yellow leaf curl virus in tomato plant leaves. Our results provide a foundation for identifying the function of the Hsp90 gene in tomato.

Agrocybe aegerita polysaccharide combined with chemotherapy improves tumor necrosis factor-α and interferon-γ levels in rat esophageal carcinoma.

Natural compounds have generated great interest as alternative treatments of diseases like cancer. Here, we investigated the anti-tumor mechanism of one such compound, Agrocybe aegerita polysaccharide, by assessing expression of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in rat esophageal carcinoma (EC). EC was induced in healthy Wistar rats by methyl-n-amyl nitrosamine. Subsequently, rats were administered cancer treatment daily for 4 weeks, as follows: the normal control group (the only group not treated with methyl-n-amyl nitrosamine) and model group received only distilled water; the chemotherapy group received tegafur treatment; and the combination group received tegafur combined with A. aegerita polysaccharide. In normal and combination groups, body weight increased gradually after each week of treatment (P < 0.05), while body weights did not change in model and chemotherapy groups. Using enzyme linked immunosorbent assay, we found serum TNF-α was lower in the combination group (31.56 ± 7.20 pg/L) than either the model (46.24 ± 8.52 pg/L) or chemotherapy (52.39 ± 9.16 pg/L) group, and, while higher, was more similar to the normal controls (25.08 ± 2.93 pg/L; P < 0.05), a finding that was confirmed by the immunohistochemistry of esophageal samples. In contrast, serum IFN-γ was higher in the combination group (97.20 ± 10.92 pg/L) than in either the model (76.11 ± 11.92 pg/L) or chemotherapy (76.04 ± 9.85 pg/L) group, but lower than in the normal group (117.56 ± 10.88; P < 0.05), also confirmed by immunohistochemistry. Therefore, Agrocybe aegerita polysaccharide, when combined with chemotherapy, can regulate immune function in EC, potentially by modulating cytokine activity, specifically downregulation of TNF-α and upregulation of IFN-γ.