[Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases].

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

[Clinicopathological features and prognosis of high-grade B-cell lymphoma with MYC and bcl-2 and/or bcl-6 rearrangements].

Objective: To investigate the clinicopathological characteristics and prognosis of high-grade B-cell lymphoma (HGBL) involving combined rearrangements of MYC, bcl-2 and bcl-6. Methods: A total of 1 138 cases of large B cell lymphoma (LBL) that were treated at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2017 to September 2020 were analyzed using fluorescence in situ hybridization (FISH) with probes against MYC, bcl-2 and bcl-6. The clinical and pathological data of the 45 patients with HGBL that had rearrangements of MYC and bcl-2 and/or bcl-6 were collected and retrospectively analyzed. Results: Among the 1 138 LBL, 45 (4.0%) cases had combined rearrangements of MYC, bcl-2 and/or bcl-6 that included 6 HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, 14 HGBL cases with MYC and bcl-2 rearrangements, and 25 HGBL cases with MYC and bcl-6 rearrangements. Of these 45 patients, 29 patients were male, and 16 patients were female, aged 29 to 83 years. HGBL with MYC, bcl-2 and bcl-6 rearrangements and HGBL with MYC and bcl-2 rearrangement were reclassified as the germinal center B-cell (GCB) subtype using the Hans algorithm. HGBL with MYC and bcl-6 rearrangement were reclassified as the GCB subtype (68.0%) and the non-GCB subtype (32.0%). The vast majority of HGBL cases had a high Ki-67 proliferation index. Most HGBL patients had advanced stage disease with a high IPI score and an increased LDH level. Also, some patients had clinical features including elevated plasma ß2-microglobulin levels, B symptoms, and bone marrow involvement. The IPI scores and LDH levels were significantly different between the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements and the HGBL cases with MYC and bcl-6 rearrangements (P<0.05). Compared with the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the HGBL cases with MYC and bcl-2 or bcl-6 rearrangements had a lower incidence of bone marrow involvement (P<0.05). There were no significant differences in the prognosis among HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the cases with MYC and bcl-2 rearrangements, and the cases with MYC and bcl-6 rearrangements (P>0.05). Conclusions: HGBL with MYC, bcl-2 and/or bcl-6 rearrangements are rare types of B-cell lymphoma with high degree of malignancy and have a short overall survival. To reduce misdiagnosis and improve diagnostic accuracy, it is necessary to assess the patients' clinical features and conduct histopathological, immunohistochemical and FISH analyses.

[Clinicopathological features of de novo CD5-positive diffuse large B-cell lymphoma].

Objective: To investigate the relationship between the protein expression of C-MYC, bcl-2 and bcl-6 and the clinicopathological characteristics in patients with de novo CD5-positive diffuse large B cell lymphoma (CD5(+)DLBCL). Methods: Fifty seven cases of de novo CD5(+)DLBCL were collected at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from February 2013 to September 2018. The hematoxylin-eosin stained slides were reviewed, and immunohistochemical (IHC) staining and FISH were used to analyze the relationship between C-MYC, bcl-2, bcl-6 expression and the clinicopathologic characteristics of patients. Results: Among these 57 cases, 27 were male and 30 were female. The age of onset was 35-99 years old. The IHC expression rates of C-MYC, bcl-2 and bcl-6 were 50.9% (29/57), 84.2% (48/57), and 75.4% (43/57) respectively; and co-expression rate of C-MYC and bcl-2 proteins was 40.4 (23/57). There was no significant correlation between protein expression and patients' genders, clinical stage, the level of serum LDH,ß2 microglobulin, IPI,B symptoms, bone marrow involvement and central nervous system recurrence (P>0.05). Univariate analysis showed that the median OS of C-MYC negative patients was significantly longer than C-MYC positive patients (P<0.05); and the median OS of patients without double expression was significantly longer than that of patients with positive expression (P<0.05), and bcl-6 positive patients had longer median OS than bcl-6 negative patients (P<0.05). There was no significant correlation between prognosis and bcl-2 protein expression (P>0.05) . Cox multivariate analysis showed C-MYC protein expression was an independent predictor of OS in de novo CD5(+)DLBCL (P<0.05). Conclusions: Bcl-2 protein expression has no effect on the prognosis in de novo CD5(+)DLBCL whereas bcl-6 expression is correlated with good prognosis. C-MYC protein expression could be used as an independent and effective index to predict the prognosis of patients with de novo CD5(+)DLBCL.However, the relationship between protein expression and gene rearrangement of C-MYC, bcl-2 and bcl-6 needs to be further explored.

Dexmedetomidine protected COPD-induced lung injury by regulating miRNA-146a.

OBJECTIVE: To study the mechanism of protection provided by dexmedetomidine against COPD-induced lung injury. METHODS: COPD rat model was determined by measuring lung function, and comparing HE staining between two different groups. We got the lung tissue and cells from the control and COPD groups. The cells were divided into three groups: control group, and blank and drug groups that were from the COPD rats. Cell apoptosis, relative gene expression and TNF-α and IL-1ß from nutrient solution were measured. RESULTS: The TV, PEF, EF50, FEV0.3 and FEV0.3/FVC in COPD group were significantly lower than in control group (1.26±0.17 vs 2.65±0.21; 17.61±0.35 vs 38.55±0.24; 1.20±0.14 vs 1.81±0.06; 2.52±0.28 vs 4.44±0.26; 63.39±0.22 vs 88.45±0.34, p < 0.05, respectively). Cell apoptosis was significantly different in blank and drug groups (21.65±0.86 vs 10.74±0.15; p < 0.05, respectively). The gene expressions of miRNA-146a, p53 and Bcl-2 were significantly downregulated compared with blank group. CONCLUSION: Dexmedetomidine protected COPD-induced lung injury by inhibiting miRNA-146a expression to reduce cell apoptosis (Tab. 1, Fig. 3, Ref. 25).

Expression of TRPM8 in diabetic rats and its relationship with visceral pain stimulation.

Transient receptor potential cation channel, subfamily M, member 8 (TRPM8) is a nonselective cation channel and a candidate for cold sensation signaling, but the relationship between TRPM8 and diabetes remains unclear. In the present study, we determined the expression levels of TRPM8 messenger RNA (mRNA) and the levels of the TRPM8 protein in the bladder tissue of diabetic rats. We also investigated the correlation between TRPM8 expression and the visceral pain stimulation-related factor, calcitonin gene-related peptide (CGRP) in diabetic rats. The rats were sacrificed 3, 5, 7, and 15 days after streptozotocin injection, and blood was collected from their tail veins to determine the blood glucose levels. Bladder tissue was removed to assess the expression of TRPM8 mRNA by reverse transcription-polymerase chain reaction, and the expression of the TRPM8 protein by western blotting. After administering electrical stimulation (5 V/1 Hz), the expression levels of TRPM8 and CGRP proteins were determined. Our results revealed that the blood glucose level, and TRPM8 mRNA and TRPM8 protein expression levels increased significantly in the diabetic rats. Spinal tissue protein expression levels of both TRPM8 and CGRP also increased significantly following electrical stimulation. This possibly indicates that TRPM8 is closely associated with visceral pain stimulation, and could be an independent prognostic biomarker for diabetes.