Long-term mortality in patients with end-stage renal disease undergoing hemodialysis and peritoneal dialysis: a propensity score matching retrospective study.

BACKGROUND: Hemodialysis (HD) and peritoneal dialysis (PD) are effective ways to treat end-stage renal disease (ERSD). This study aimed to investigate the differences in survival and the factors that influence it in patients with end-stage renal disease treated with HD or PD. METHODS: We retrospectively analyzed factors related to all-cause death with renal replacement therapy and compared the long-term mortality between HD and PD strategies in patients with ESRD who started HD or PD treatment in our renal HD center between January 1, 2008, and December 1, 2021. RESULTS: Overall, 1,319 patients were included, comprising 690 and 629 patients in the HD and PD groups, respectively, according to the inclusion criteria. After propensity matching, 922 patients remained, with 461 (50%) patients each in the two groups. There were no significant differences in the 1-, 2-, 3-, and 4-year mortality rates between the HD and PD groups (all p > .05). However, the 5- and 10-year mortality rates of the matched patients were 15.8%. 17.6% in the HD group and 21.0%. 27.3% in the PD group, respectively. The 5- and 10-year mortality rates were significantly lower in the HD group (all p < .05) as compared to the PD group. After matching, Kaplan-Meier curve analysis with log-rank test was performed, which showed a significant difference in the survival rates between the two groups (p = .001). Logistic multifactor regression analysis revealed that age, weight, hypertension, serum creatinine, and combined neoplasms influenced the survival rate of patients with ESRD (p < .05). In contrast, age, hypertension, parathyroid hormone (PTH), serum creatinine, and peripheral vascular diseases (PVD) influenced the survival rate of patients in the HD group (p < .05), and age and weight influenced the survival rate of patients in the PD group (p < .05). CONCLUSIONS: This study found that long-term mortality rates were higher in the PD group than that in the HD group, indicating that HD may be superior to PD.

CIRC_0002131 CONTRIBUTES TO LPS-INDUCED APOPTOSIS, INFLAMMATION, AND OXIDATIVE INJURY IN HK-2 CELLS VIA INHIBITING THE BINDING BETWEEN MIR-942-5P AND OXSR1.

ABSTRACT: Background: Circular RNAs are implicated in the progression of sepsis-associated acute kidney injury (AKI). Circ_0002131 was shown to aggravate cell inflammation and oxidative stress in sepsis-induced AKI. The aim of this study was to investigate the role and underlying mechanism of circ_0002131 in sepsis-induced AKI. Methods: Cell counting Ki-8 assay was used for cell viability detection. Cell apoptosis was measured using flow cytometry. Circ_0002131, microRNA-942-5p (miR-942-5p), and oxidative stress responsive 1 (OXSR1) level analysis was performed through reverse transcription-quantitative polymerase chain reaction assay. The protein levels were examined by western blot. Inflammatory factors were determined using enzyme-linked immunosorbent assay. Oxidative injury was assessed via commercial kits. Target relation was analyzed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results: HK-2 cell viability was suppressed and apoptosis was enhanced by LPS. Circ_0002131 was highly expressed in LPS-treated HK-2 cells and sepsis-induced AKI patients. LPS-induced apoptosis, inflammation, and oxidative injury of HK-2 cells were attenuated after silence of circ_0002131. Then, miR-942-5p was identified as a target for circ_0002131, and the regulation of circ_0002131 in LPS-induced cell injury was ascribed to reduce miR-942-5p level. In addition, circ_0002131 targeted miR-942-5p to elevate OXSR1 expression. MiR-942-5p prevented LPS-evoked HK-2 cell injury via targeting OXSR1. Conclusion : All results demonstrated that circ_0002131 promoted LPS-mediated HK-2 cell injury via miR-942-5p-mediated upregulation of OXSR1, suggesting that the circ_0002131/miR-942-5p/OXSR1 axis was related to sepsis-induced AKI progression.

DACT3 has a tumor-inhibiting role in acute myeloid leukemia via the suppression of Wnt/ß-catenin signaling by DVL2.

Dapper antagonist of catenin-3 (DACT3) is a new tumor-related protein associated with a diverse set of tumors. However, whether DACT3 plays a role in acute myeloid leukemia (AML) is not fully understood. Our findings showed low DACT3 level in AML tissue, which was corrected with shorter survival rates. Upregulation of DACT3 effectively repressed cellular proliferation, and promoted cell cycle arrest and apoptosis of AML cells. Upregulation of DACT3 decreased levels of Dishevelled2 (DVL2), phospho-glycogen synthase kinase-3ß (GSK-3ß), and active ß-catenin, which collectively suppressed Wnt/ß-catenin-mediated transcriptional activity. Overexpression of DVL2 reversed DACT3-mediated suppression of Wnt/ß-catenin pathway. Reactivation of Wnt/ß-catenin abrogated DACT3-upregulation-evoked tumor-suppression in AML cells. Overexpression of DACT3 impeded the formation and growth of AML-derived xenograft tumor. Collectively, our work reveals a tumor-suppressive role of DACT3, a protein that negatively adjusts Wnt/ß-catenin pathway via downregulation of DVL2 in AML.

Stability and inhibitory function of Treg cells under inflammatory conditions in vitro.

Immunotherapy with transplanted T-regulatory (Treg) cells is currently in use. However, patients have complex internal environments with confounding factors, including the presence of inflammatory cytokines. The present study aimed to detect Treg cell function under simulated inflammatory conditions to provide a foundation for Treg cell-based immunotherapy. CD4+CD25high Treg cells were sorted from peripheral blood mononuclear cells and cultured for 14 days in the presence of recombinant human interleukin-2 (rhIL-2) and anti-CD3/CD28 beads, with or without 25 ng/ml rhIL-6. Next, the absolute count of Treg cells was determined, the stability and activity were detected by measuring the expression levels of forkhead box (Fox)P3 and CD39, and the suppressive function of Treg cells was investigated by assessing the suppression of T-effector cell proliferation by Treg cells after co-culture for 5 days. The number of Treg cells cultured in the presence of 25 ng/ml rhIL-6 for 14 days was reduced by 49.7% when compared with that of cells cultured without rhIL-6. Of the Treg cells continually cultured for 14 days without or with 25 ng/ml rhIL-6, 56.15 and 24.7% expressed FoxP3, respectively. There was no difference in the activity of the FoxP3+ Treg cells after culture for 14 days without or with 25 ng/ml rhIL-6. The suppressive function of Treg cells tended to deteriorate in the presence of rhIL-6. In conclusion, IL-6 inhibited the proliferation and stability of Treg cells, suggesting that administration of increased numbers of Treg cells may be required during Treg cell-based immunotherapy.

Salidroside protects renal tubular epithelial cells from hypoxia/reoxygenation injury in vitro.

Oxidative stress, inflammation and cell apoptosis are important mechanisms of renal ischemia/reperfusion (I/R) injury. Salidroside, a natural phenylpropanoid glycoside, possesses anti-inflammatory, anti-oxidative, and anti-apoptotic effects. However, the effect of salidroside on renal I/R injury has not been fully elucidated. The present study aimed to investigate the effect of salidroside on renal I/R injury in vitro. Our results showed that salidroside improved the viability of human renal tubular epithelial cells (HK-2) in response to hypoxia/reoxygenation (H/R). Salidroside caused apparent decrease in the levels of reactive oxygen species (ROS) and malondiaidehyde (MDA), and significant increase in superoxide dismutase (SOD) activity in HK-2 cells. Pretreatment with salidroside markedly inhibited the production levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 in a dose-dependent manner. Salidroside treatment exhibited significant increase in Bcl-2 expressions, and decrease in Bax expressions and caspase-3 activity when compared with the H/R group. Salidroside decreased the levels of toll-like receptor 4 (TLR4) and p-p65 in HK-2 cells. Overexpression of TLR4 significantly attenuated the effects of salidroside on cell viability, oxidative stress, cytokine production and cell apoptosis in HK-2 cells. These findings indicated that salidroside protected HK-2 cells from H/R stimulation, which was mediated by the TLR4/NF-κB pathway.

Ratio of CD147high/CD147low in CD4+CD25+ T cells: A potential biomarker for early diagnosis and prediction of response to therapy for autoimmune diseases.

Regulatory T cell (Treg cell) is an important immunosuppressive T cell subset and plays a dominant role in maintaining the immune balance in vivo. The function defects in Treg cells have been involved in the pathogenesis of many autoimmune diseases. The detection of Treg cell suppressive function is important for early diagnosis and prediction of response to treatment for autoimmune diseases. The traditional detection of Treg cell suppressive function needs at least 20 mL peripheral blood sample of patients and the results would be got in sixth day, therefore, it could not be widely applied in clinical. However, to find fast and simple detection method is very important. CD147 is a transmembrane protein and its expression is related to Treg cell suppressive function. Recent research has shown that the Treg cells with high CD147 expression have stronger suppressive function than which with low CD147 expression. In this work, we detected the ratio of CD147high/CD147low in CD4+CD25+ T cells in patients with active AS using fluorescence-activated cell sorter (FACS). The results show the ratio of CD147high/CD147low decreased obviously in patients with active AS compared with healthy controls, which reflects the suppressive function deficit of Treg cell. In the same time, the detection of the ratio of CD147high/CD147low needs only 150 µL peripheral blood sample and the result would be got in 4 h. We therefore hypothesize that the ratio of CD147high/CD147low is a good indicator for the Treg cell function, and it is especially suitable for early diagnosis and prediction of response to therapy targeted recovering Treg cell function in autoimmune diseases.

[An exploration of induction methodology and experimental duration of Graves disease animal model].

OBJECTIVE: To compare the efficacy of Graves disease animal models induced by thyroid stimulating hormone receptor (TSHR) plasmid DNA (pcDNA3.1-TSHR) and by TSHR A subunit recombinant adenovirus (Ad-TSHR289), and to investigate the influence of duration for preparing animal model induced by Ad-TSHR289 on Graves hyperthyroidism and its related indices. METHODS: The plasmid group and the adenovirus group were set up respectively. The plasmid group: 21 female BALB/c mice were randomly divided into model group (n = 12) and control group (n = 9). The model group were injected intradermally with pcDNA3.1-TSHR 50 µg, once every 3 weeks, totally 3 times. Then 4 weeks after the last immunization, the mice were euthanized to obtain blood for testing TSHR antibody (TRAb), total T(4), and thyroid tissue for histological examination. The controls were injected with the same dose of pcDNA3.1 in the same way. The adenovirus group: 52 female BALB/c mice were divided into 10-week model group (n = 8), 14-week model group (n = 10) and 18-week model group (n = 8), and the respective controls (n = 8, n = 10, n = 8) were set up. All model groups were injected intramuscularly with Ad-TSHR289, three times at three weekly intervals. Then the mice were euthanized at 4, 8 and 12 weeks to test TRAb, total T(4) level and to observe the change of thyroid histology. The controls were treated with the same dose of Ad-lacz in the same way. Another 8 mice were scheduled to test the dynamic variation of TRAb before and after the 3 times immunization. RESULTS: In the plasmid model group, only two of 12 mice developed weak antibody responses against TSHR, and no elevated total T(4) level and no hyperplasia changes of thyroid were observed. In the 10-week model group, all mice had high level TRAb [(807.65 ± 136.33) U/L], Six-eighths mice had hyperthyroidism exhibited hyperplasia changes. In the 14-week model group, the TRAb level [(650.12 ± 192.88) U/L] and the incidence of hyperthyroidism (3/10) were lower than those in 10-week group. Histologically, the degree of thyroid hyperplasia lightened to a small extent, but its positive rate did not decline. In the 18-week model group, only 2 of 8 mice displayed slightly elevated TRAb level, and no mice showed increased total T(4) level. Additionally, thyroid tissues of 2 mice were mildly abnormal. Compared with the model groups at different time, the change of antibody levels of the mice for TRAb dynamic observation exhibited the similar trend. CONCLUSIONS: Being good at repeatability and high incidence of hyperthyroidism, the animal model of Graves disease induced by Ad-TSHR289 is still an ideal research tool presently. The duration of model can be maintained 18 weeks, and 10 weeks is the best period to sustain characteristic of Graves disease.

Induction of murine neonatal tolerance against Graves' disease using recombinant adenovirus expressing the TSH receptor A-subunit.

Graves' disease is a common organ-specific autoimmune disease. The identity of its autoantigen, the TSH receptor (TSHR), was established and used to induce a typical animal model. A-subunit, the shed portion of TSHR, either initiates or amplifies the autoimmune response of the thyroid gland, thereby causing Graves' disease in humans. In the present study, we investigate the effect of the TSHR A-subunit on the induction of murine neonatal tolerance for the development of Graves' disease. Female BALB/c mice were pretreated with different doses of adenovirus expressing the A-subunit of TSHR (Ad-TSHR289) by either ip or im injection within the first 24 h after their birth. Graves' disease was induced after the animals reached adulthood. Nearly all mice pretreated with the high dose of Ad-TSHR289 failed to develop TSHR antibodies, detected by the TSH-binding inhibition assay, hyperthyroidism, and thyroid follicular hyperplasia. The mice preimmunized im with the lower doses of Ad-TSHR289 developed a relatively low level of TSH-binding inhibition and the low incidence of hyperthyroidism. Accordingly, the percentages of splenic CD4+CD25+/CD4+ and CD25+Foxp3+/CD4+ Treg cells were increased in mice pretreated with the high dose of Ad-TSHR289. Taken together, our data strongly indicate that the immunotolerance against Graves' disease could be induced in neonatal mice using a specific TSHR antigen in a high dose either by ip or im injection, preventing the development of Graves' disease.