Objective:To investigate the clinical features of IgD multiple myeloma (MM) and the effect and prognosis of daratumumab-based combination therapy.Methods:The clinicopathological data of a IgD MM patient with disease progression and extramedullary infiltration treated with daratumumab in the Affiliated Hospital of Qingdao University in December 2019 were retrospectively analyzed.Results:The 74-year-old woman was diagnosed as IgD MM by bone marrow aspiration and immunofixation electrophoresis. The patient was given VD (bortezomib, dexamethasone), RD (lenalidomide, dexamethasone) and ID (ixazomib, dexamethasone) regimens. In June 2020, the patient developed multiple subcutaneous nodules, and she was assessed as progressive disease with extensive extramedullary infiltration. After treated with daratumumab-PAD (liposomal doxorubicin, bortezomib, dexamethasone) regimen, the patient's subcutaneous nodules were significantly reduced and partially disappeared, and the general condition was significantly improved. But the patient was in a cachexia state and finally died of the irregular treatment and disease progression.Conclusions:IgD MM has a low incidence and a short survival period, and there is no uniform standard treatment. The early application of daratumumab combined with proteasome inhibitors, immunomodulators, cytotoxic drugs and hematopoietic stem cell transplantation may improve the overall survival of patients.

Objective:To study whether cisplatin may induce apoptosis in the pericytes of cochlear stria vascularis and underlying mechanisms.Methods:Twenty male C57BL/6J mice aged 6-8 weeks were divided into control group and a cisplatin group. Primary cultured mouse cochlear vascular peristriatal cells were identified and divided into control group, cisplatin group, and N-acetylcysteine+cisplatin group. Auditory brainstem response (ABR) was used to detect hearing in mice. Hematoxylin eosin (HE) staining was used to observe morphological changes in the stria vascularis of the cochlea. The total superoxide dismutase (SOD) activity test kit (WST-1 method) and thiobarbituric acid (TBA) method were used to detect SOD activity and Malondialdehyde (MDA) content, respectively. DCFH-DA fluorescence probe was used to detect the content of reactive oxygen species in peripheral cells. Hoechst 33 342 and flow cytometry were used to detect the apoptosis rate of pericytes. Immunofluorescence technology was used to detect the distribution and expression of apoptosis related proteins in pericytes of cochlear stria vascularis. Immunohistochemistry and Western blotting (WB) were used to detect the expression of apoptosis-and mitochondrial-related proteins. Mito SOX TM-red and JC-1 were used to detect the mitochondrial function of pericytes. Evans blue staining was used to observe the permeability of the blood labyrinth barrier (BLB). Statistical analysis was conducted using SPSS 18.0 software. Results:Compared with the control group, the cisplatin group significantly increased in the hearing threshold ( t=4.72, P<0.01), Ⅰ-wave latency ( t=12.25, P<0.05), and the levels of oxidative stress in the cochlea and pericytes ( t=38.34, P<0.01), and also cisplatin caused disorder and contraction of the cochlear stria vascularis structure, increased BLB permeability [Evans blue leakage (1.08±0.42) AU vs (0.55±0.23) AU, t=4.64, P<0.05], with a statistically significant difference, enhanced the expressions of apoptotic proteins c-Caspase-3 ( t=5.01, P<0.01) and Bax ( t=6.33, P<0.01) in the peristriatal cells of cochlear blood vessels in mice treated with cisplatin increased. And cisplatin can induce apoptosis of primary cultured pericytes and up-regulate the expression of c-Caspase-3 and Bax ( P<0.05). The NAC+cisplatin group partially reversed cisplatin-induced pericyte apoptosis ( P<0.05). Cisplatin caused damage to the mitochondrial function of peripheral cells, and induced the release of apoptosis-inducing factor (AIF) and cytochrome C (cyt-c) into the cytoplasm ( P<0.05). The NAC+cisplatin group partially reversed cisplatin induced pericyte apoptosis ( P<0.05) and mitochondrial damage ( P<0.05). Conclusion:Cisplatin can increase the level of oxidative stress in the cochlea and cause mitochondrial pathway apoptosis in C57BL/6J mouse cochlear vascular peristriatal cells.

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.