Objective:To investigate whether caffeic acid phenethyl ester (CAPE) would improve peritoneal dialysis (PD)-associated peritoneal fibrosis by alleviating oxidative stress through activating nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.Methods:Thirty-two male Sprague-Dawley rats were randomly divided into four groups by the random number table: control (CON) group (0.9% normal saline 20 ml/d intraperitoneal injection), CAPE group (0.9% normal saline 20 ml/d+CAPE 10 mg·kg -1·d -1 intraperitoneal injection), PD group [4.25% glucose peritoneal dialysis fluid (PDF) 20 ml/d intraperitoneal injection with lipopolysaccharide 0.6 mg/kg intraperitoneal injection at day 1, 3, 5 and 7], and PD+CAPE group (CAPE 10 mg·kg -1·d -1 intraperitoneal injection in addition to PD group), with 8 rats per group. On day 28, rats were euthanized after peritoneal equilibration test, and then the parietal peritoneum and omentum were collected for follow-up tests. To further investigate the mechanism, primary peritoneal mesothelial cells (PMCs) of rats were isolated and cultured. The PMCs were stimulated with 2.5% glucose PDF and added with 5 μmol/L CAPE intervention. The Nrf2 inhibitor (ML385) was used to identify whether CAPE protected PMCs from PDF by activating the Nrf2/HO-1 pathway. Histopathological staining was used to detect structural changes of the peritoneum, and immunohistochemical analysis was performed on cleaved caspase-3, Bax, α-smooth muscle actin (α-SMA), fibronectin (FN), and typeⅠ collagen (Col-Ⅰ) protein. Western blotting was used to detect the protein expression of α-SMA, FN, transforming growth factor-β1 (TGF-β1), HO-1 and nuclear Nrf2 (N-Nrf2). The apoptosis detection kit was used to detect apoptosis and flow cytometry was used to detect reactive oxygen species (ROS) in PMCs. The malondialdehyde (MDA) and superoxide dismutase (SOD) activity detection kit were used to detect MDA content and SOD activity. Cell immunofluorescence was used to analyze the protein expression of Nrf2 in PMCs. Results:Compared with the CON group, the PD group had thicker peritoneum, and the expression levels of cleaved caspase-3, Bax, α-SMA, FN, Col-Ⅰand MDA in peritoneum were significantly higher, while HO-1, N-Nrf2 protein expression and SOD activity were lower (all P<0.05). Compared with the PD group, the parietal peritoneum morphology of CAPE+PD group was improved, accompanied by reduced cleaved caspase-3, Bax, α-SMA, FN, Col-Ⅰ protein expression, and MDA content, while N-Nrf2, HO-1 protein expression, and SOD activity were higher (all P<0.05). Compared with the CON group, the PD group had significantly lower ultrafiltration volume and higher peritoneal permeability (both P<0.05). After CAPE intervention, the peritoneal transport function of the rats was significantly improved ( P<0.05). In cultured PMCs, PDF inhibited nuclear translocation of Nrf2 and protein expression of HO-1, and upregulated intracellular ROS level. In addition, PDF increased cell apoptosis and the protein expression levels of α-SMA, TGF-β1 and FN (all P<0.05). CAPE activated nuclear translocation of Nrf2, increased HO-1 protein expression, downregulated intracellular ROS level, and partially reversed PDF-induced cell apoptosis and epithelial- mesenchymal transition (all P<0.05). The protective effects of CAPE on PMCs were partially abolished by ML385 (all P<0.05). Conclusions:CAPE can reduce PD-induced PMCs apoptosis and epithelial-mesenchymal transition by attenuating oxidative stress, and significantly improve peritoneal fibrosis and ultrafiltration function. The beneficial effects of CAPE on peritoneum are related to activation of Nrf2/HO-1 pathway.

It was a retrospective cohort study. Eighty maintenance hemodialysis (MHD) patients with corona virus disease 2019 (COVID-19) were enrolled, among whom 48 patients survived and 32 died. The clinical data between the survival and death groups were compared. The Cox regression model was used to analyze the risk factors of death in MHD patients with COVID-19, and a survival prediction model was constructed. The results showed that age, lesion-cumulative number of lung segments, C-reactive protein, procalcitonin, serum ferritin, interleukin-6, D-dimer, serum phosphorus, and proportions of males, diabetes and hypoxemia in the death group were higher than those in the survival group (all P<0.05). Increased age ( HR=1.039, 95% CI 1.007-1.072, P=0.017), diabetes ( HR=2.688, 95% CI 1.018-6.991, P=0.046), increased C-reactive protein ( HR=1.006, 95% CI 1.001-1.011, P=0.012), and increased serum phosphorus ( HR=1.573, 95% CI 1.015-2.438, P=0.043) were independent influencing factors of death in MHD patients with COVID-19. The survival prediction model was established based on age, diabetes, C-reactive protein and blood phosphorus. The area under the receiver operating characteristic curve of the combined model for survival time at 7-day, 14-day, and 21-day were 0.751 (95% CI 0.690-0.811), 0.768 (95% CI 0.712-0.824), and 0.780 (95% CI 0.729-0.831), respectively. The concordance index of cross- validation as internal validation was 0.797 (95% CI 0.757-0.837). Increased age, diabetes, elevated C-reactive protein and elevated blood phosphorus are independent risk factors of COVID-19 death in MHD patients, and the survival prediction model built by those factors has good efficacy.

OBJECTIVETo evaluate the long-term outcome of immunosuppressive therapy (IST) in patients with severe aplastic anemia (SAA).

METHODSHematopoietic recovery (peripheral blood cell counts, bone marrow aspirates, bone marrow biopsy, in vitro culture of hematopoietic progenitors), immunity of T lymphocyte, quality of life and side-effects of the therapy were assessed in 50 SAA patients who have survived more than 3 years after IST.

RESULTSAt 3 years, 4 years and 5 years follow-up, 81.5% (13 cases), 86.7% (13 cases) and 89.5% (17 cases) of the SAA patients reached and maintained normal peripheral blood cell counts, 93.4% (15 cases), 93.3% (14 cases) and 94.7% (18 cases) showed normal bone marrow pictures, and 37.5% (6 cases), 40.0% (6 cases) and 73.7% (14 cases) had normal yields of bone marrow cell culture, respectively. Overall, 86.0% (43 cases), 94.0% (47 cases) and 52.0% (26 cases) of the total SAA patients were normalized in peripheral blood counts, bone marrow picture and culture of hematopoietic progenitor yields, respectively. During the follow-up, 88.0% (44 cases) of the patients achieved 100 of Karnofsky scores; 26 of the 31 patients (83.9%) who received bone marrow biopsy showed normal histological pictures, and 29 of 37 patients (78.4%) tested had normal subsets of T lymphocytes. No clonal disease was found. The late side-effects of IST were mild. All of the parameters tested were normal in 24 patients.

CONCLUSIONAfter IST, the hematopoietic function of bone marrow, the immunity of the T lymphocyte and the life quality were normalized with few side-effects in patients with SAA. These patients would probably be cured.

Adolescent ; Adult ; Anemia, Aplastic ; drug therapy ; mortality ; Blood Cell Count ; Bone Marrow Examination ; Child ; Disease-Free Survival ; Female ; Follow-Up Studies ; Hematopoietic Stem Cells ; cytology ; physiology ; Humans ; Immunosuppressive Agents ; therapeutic use ; Karnofsky Performance Status ; standards ; Male ; Middle Aged ; Recovery of Function ; physiology ; Survival Rate ; Treatment Outcome