Multiparametric ultrasound for the assessment of testicular lesions with negative tumoral markers / 亚洲男科学杂志(英文版)

The purpose of this study was to evaluate the diagnostic performance of multiparametric ultrasound (mpUS; grayscale US, color Doppler US, strain elastography, and contrast-enhanced US) in the assessment of testicular lesions with negative tumoral markers. MpUS imaging data, patient age, serum tumor markers, scrotal pain, cryptorchidism, and related clinical information were retrospectively collected for patients who underwent mpUS examination between January 2013 and December 2019. Histologic results or follow-up examinations were used as the reference standard. In total, 83 lesions from 79 patients were included in the analysis. Fifty-six patients were finally diagnosed with benign tumors, and 23 patients were ultimately diagnosed with malignant tumors. Chi-square tests or Fisher's exact tests were used to assess the difference between the two groups. Stepwise multivariate logistic regression analysis showed that lesion diameter (odds ratio [OR] = 1.072, P = 0.005), vascularization on color Doppler US (OR = 4.066, P = 0.001), and hyperenhancement during the early phase (OR = 6.465, P = 0.047) were significant independent risk factors for malignancy; however, when compared with neoplastic lesions, pain (OR = 0.136, P < 0.001), absence of vascularization on color Doppler US (OR = 1.680, P = 0.042), and nonenhancement during the late phase (OR = 3.461, P = 0.031) were strongly associated with nonneoplastic lesions. MpUS features are useful for differentiating testicular lesions with negative tumoral markers and improving the preoperative diagnosis, which may avoid inappropriate radical orchiectomy.

Role of Nrf2 regulating apoptosis in arsenite induced malignant transformation of HBE cells / 中华地方病学杂志

Objective:To observe the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in regulating apoptosis during malignant transformation of human bronchial epithelial cells (HBE cells) induced by sodium arsenite (NaAsO 2). Methods:HBE cells were treated with 0.0 and 1.0 μmol/L NaAsO 2, which were control group and arsenic exposed group respectively. HBE cells were treated with 1.0 μmol/L NaAsO 2 for 43 passages to establish a malignant transformation model. The dynamic changes of indexes in different passages (0, 1st, 8th, 15th, 22nd, 29th, 36th, and 43rd) after exposure to NaAsO 2 were monitored, including the apoptosis rate detected by flow cytometry and apoptosis-related proteins and Nrf2 protein detected by Western blotting. Nrf2 siRNA was transfected into malignant transformed HBE cells (T-HBE cells) to silence Nrf2. The silencing effect of Nrf2 protein was verified. And, the apoptosis rate and apoptosis-related proteins were detected. Results:With the increase of arsenic exposure, the apoptosis rates of HBE cells decreased (0, 1, 8, 15, 22, 29, 36 and 43 passages were 0.370 ± 0.029, 0.443 ± 0.069, 0.357 ± 0.046, 0.330 ± 0.016, 0.273 ± 0.050, 0.160 ± 0.024, 0.110 ± 0.022, 0.097 ± 0.012, respectively, Ftrend = 22.981, P < 0.05). Compared with the 0 passage cells, the apoptosis rates of the 22nd, 29th, 36th and 43rd passages in the arsenite group were lower. The differences between them were statistically significant ( P < 0.05). With the increase of arsenic exposure, the expressions of pro-apoptotic proteins caspase-3, cleaved-caspase-3, C/EBP-homologous protein (CHOP) and B-cell lymphoma-2 (Bcl-2) associated X protein (Bax) showed downward trends ( Ftrend = 22.356, 3.738, 6.130, 8.061, P < 0.05), while the anti-apoptotic proteins myeloid cell leukemia 1 protein (Mcl-1) and Bcl-2 showed upward trends ( Ftrend = 58.201, 7.691, P < 0.05). Compared with the 0 passage and the control group of the same passage, from the 22nd passage of caspase-3, cleaved-caspase-3, from the 15th passage of CHOP, Mcl-1, and Bcl-2, from the 29th passage of Bax in the arsenite group, the differences of protein were statistically significant ( P < 0.05). However, there were no significant differences in caspase-8, cleaved-caspase-8, caspase-12 and cleaved-caspase-12 protein expressions in the arsenic group ( P > 0.05). Compared with the 0 passage and the control group of the same passage, from the 8th passage of Nrf2 proteins in the arsenite group, the differences of expressions were statistically significant ( P < 0.05). Compared with T-HBE cells transfected with Con siRNA (control), the apoptosis rate of T-HBE cells transfected with Nrf2 siRNA was higher ( P < 0.05). Compared with T-HBE cells transfected with Con siRNA, the expression levels of Nrf2, Bcl-2 and Mcl-1 in T-HBE cells transfected with Nrf2 siRNA were lower ( P < 0.05), while the expression levels of cleaved-caspase-3/caspase-3, caspase-3, cleaved-caspase-3, CHOP, and Bax were higher ( P < 0.05). Conclusion:Nrf2 may regulate mitochondrial apoptotic pathway through Bcl-2, Mcl-1 and Bax, and endoplasmic reticulum apoptotic pathway through CHOP, so as to inhibit the apoptosis of HBE cells and participate in the process of malignant transformation of HBE cells induced by NaAsO 2.

Progress in arsenic-induced programmed cell death / 中华地方病学杂志

With the deepening of the research on the "two sides" of arsenic from poison to medicine, arsenic has attracted extensive attention in affecting programmed cell death (PCD) and causing damage to a variety of organs. Recent studies have showed that reactive oxygen species (ROS) produced by intracellular arsenic metabolism is closely related to PCD induction. However, the specific mechanism is still unclear. In this paper, we have reviewed the main PCD forms, such as apoptosis, autophagy and necroptosis induced by arsenic via ROS and their possible mechanisms, in order to provide basic information for further research and prevention of arsenic toxicity, which is helpful for clinical development and utilization of arsenic in the treatment of tumors and related diseases.

Expression of PD-L1 in peripheral blood T cells and monocytes of patients with gastric cancer before and after surgery and its clinical significance / 中国免疫学杂志

Objective:To investigate the expression of PD-L1 in peripheral blood with gastric cancer patients and its clinical significance.Methods:Peripheral blood samples were collected from 44 gastric cancer patients (before and after the surgery) and 18 healthy subjects.The expression of PD-1 and PD-L1 on CD3+CD4+T,CD3+CD8+T cells and CD14+monocytes was detected by flow cy-tometry.Results:The expression of PD-L1 on CD14+monocytes of the gastric cancer patients was significantly higher than that of the healthy control[(29.2±16.7)% vs (17.5±9.7)%,P=0.007 3],while there was no statistical difference on CD4+T cells and CD8+T cells[(11.1±6.4)% vs(9.8±5.6)%,P=0.453 2;(13.9±12.0)% vs(12.0±7.1)%,P=0.558 9].The expression of PD-L1 on CD4+T cells and CD8+T cells in patients with gastric cancer was significantly higher than that before surgery[(15.8 ± 8.2)% vs (11.1±6.4)%,P=0.001 5;(22.5±13.3)% vs(13.9±12.0)%,P=0.000 2].However,no significant change was found on CD14+mononuclear cells[(33.8±17.3)% vs (29.2±16.7)%,P=0.082 8].There was no significant difference in the expression of PD-1 on CD4+T and CD8+T cells before and after surgery[(25.6 ±9.9)% vs (26.9 ±8.9)%,P=0.505 5;(26.5 ±14.6)% vs (29.9 ± 10.4)%,P=0.118 7].Conclusion:PD-L1 can be used as an effective marker to monitor the immune function and prognosis of patients with primary gastric cancer.