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BACKGROUND: Short-term and long-term blood pressure variability (BPV) in hemodialysis (HD) population are risk factors of cardiovascular diseases (CVD) and all-cause mortality. There is no full consensus on the best BPV metric. We compared the prognostic role of intra-dialytic and visit-to-visit BPV metrics for CVD morbidity and all-cause mortality in HD patients. METHODS: A retrospective cohort of 120 patients on HD was followed up for 44 months. Systolic blood pressure (SBP) and baseline characteristics were collected for 3 months. We calculated intra-dialytic and visit-to-visit BPV metrics, including standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), average real variability (ARV) and residual. The primary outcomes were CVD events and all-cause mortality. RESULTS: In Cox regression analysis, both intra-dialytic and visit-to-visit BPV metrics were associated with increased CVD events (intra-dialytic CV: HR 1.70, 95% CI 1.28-2.27, p < 0.01; visit-to-visit CV: HR 1.55, 95% CI 1.12-2.16, p < 0.01), but not associated with increased all-cause mortality (intra-dialytic CV: HR 1.32, 95% CI 0.99-1.76, p = 0.06; visit-to-visit CV: HR 1.22, 95% CI 0.91-1.63, p = 0.18). Overall, intra-dialytic BPV showed greater prognostic ability than visit-to-visit BPV for both CVD event (AUC of intra-dialytic BPV and visit-to-visit BPV metrics respectively: SD 0.686, 0.606; CV 0.672, 0.425; VIM 0.677, 0.581; ARV 0.684, 0.618; residual 0.652, 0.586) and all-cause mortality (SD 0.671, 0.608; CV 0.662, 0.575; VIM 0.669, 0.581; ARV 0.529, 0.588; residual 0.651, 0.602). CONCLUSION: Compared to visit-to-visit BPV, intra-dialytic BPV is a greater predictor of CVD event in HD patients. No obvious priority was found among various BPV metrics.
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Doenças Cardiovasculares , Hipertensão , Humanos , Pressão Sanguínea/fisiologia , Estudos Retrospectivos , Diálise Renal/efeitos adversos , Determinação da Pressão Arterial , Fatores de Risco , Hipertensão/epidemiologiaRESUMO
OBJECTIVE: To investigate the effects of glucose-free and glucose-containing dialysates during dialysis in maintenance hemodialysis (MHD) patients by the prospective cross-over study, and detect glucose control methods in MHD patients. METHODS: A total of 66 MHD 18-75 years old patients in our hospital from Nov. 2019 to Mar. 2020 were recruited. All patients underwent HD with 4 hours per time, three times per week. Glucose-free dialysate (glucose-free group) and then 5.55 mmol/L glucose-containing dialysate (glucose-5.55 group) were used alternately in dialysis. The demographics and parameters of pre- and post-dialysis were recorded. RESULTS: A total of 60 patients were analyzed, and 28 patients among them had type 2 diabetes. Serum glucose pre and post dialysis were 8.64 ± 4.18 mmol/L versus 5.74 ± 1.82 mmol/L (p < 0.01) in glucose-free dialysate, and 9.31 ± 4.89 mmol/L versus 7.80 ± 2.59 mmol/L (p < 0.01) in glucose-5.55 dialysate. The post-dialysis blood glucose of glucose-free group was lower than glucose-5.55 group (5.74 ± 1.82 vs 7.80 ± 2.59, p < 0.01). About 18 (30.00%) patients in glucose-free group and 1 patient (1.67%) in glucose-5.55 group whose blood glucose was lower than 4.44 mmol/L (p < 0.01). About 29 patients (48.33%) in glucose-free group and 17 patients (28.33%; p = 0.02) in glucose-5.55 group have hunger feeling. Serum sodium level in the glucose-free group was higher than that in Glucose-5.55 group (137.92 ± 1.64 vs 136.70 ± 1.64, p < 0.01). Post-dialysis blood glucose had no significant differences between patients not using diabetes-related medication (13 patients) and patients using diabetes-related medication (15 patients) in glucose-free group (7.13 ± 1.78 mmol/L vs 6.08 ± 2.84 mmol/L, p = 0.23) and glucose-5.55 group (9.22 ± 2.59 mmol/L vs 9.35 ± 2.88 mmol/L, p = 0.90). CONCLUSIONS: Glucose-free and glucose-5.55 dialysate both decrease the blood glucose post-dialysis. Dialysates containing 5.55 mmol/L glucose can reduce the incidence of hypoglycemia and lower serum sodium, but have no effect on blood pressure during dialysis. Stopping insulin and oral anti-diabetic drugs once before dialysis may not affect the control of blood glucose.
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Diabetes Mellitus Tipo 2 , Falência Renal Crônica , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Glicemia , Estudos Cross-Over , Diabetes Mellitus Tipo 2/tratamento farmacológico , Soluções para Diálise/farmacologia , Soluções para Diálise/uso terapêutico , Glucose/farmacologia , Glucose/uso terapêutico , Soluções para Hemodiálise , Falência Renal Crônica/terapia , Estudos Prospectivos , Diálise Renal/métodos , SódioRESUMO
The NF-κB pathway is an essential signalling cascade in the defence against viral infections, including African swine fever virus (ASFV) infection. ASFV encodes more than 151 proteins via its own transcription machinery and possesses a great capacity to evade or subvert antiviral innate immune responses. Although some of these viral proteins have been reported, many remain unknown. Here, we show that pD345L, an ASFV-encoded lambda-like exonuclease, acts as an inhibitor of cGAS/STING-mediated NF-κB signalling by blocking the IkappaB kinase (IKKα/ß) activity. Specifically, we showed that overexpression of pD345L suppresses cGAS/STING-induced IFNß and NF-κB activation, resulting in decreased transcription of IFNß and several proinflammatory cytokines, including IL-1α, IL-6, IL-8, and TNFα. In addition, we showed that pD345L acts at or downstream of IKK and upstream of p65. Importantly, we found that pD345L associates with the KD and HLH domains of IKKα and the LZ domain of IKKß and thus interrupts their kinase activity towards the downstream substrate IκBα. Finally, we showed that pD345L-mediated inhibition of NF-κB signalling was independent of its exonuclease activity. Considering these results collectively, we concluded that pD345L blocks IKKα/ß kinase activity via protein-protein interactions and thus disrupts cGAS/STING-mediated NF-κB signalling.
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Vírus da Febre Suína Africana , Febre Suína Africana , Doenças dos Suínos , Vírus da Febre Suína Africana/fisiologia , Animais , Exonucleases/metabolismo , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , NF-kappa B/metabolismo , Nucleotidiltransferases/metabolismo , SuínosRESUMO
AIM: To explore the safety, effectiveness, and dialysis adequacy of simplified regional citrate anticoagulation hemodialysis (SRCA-HD) in hemodialysis patients with high risk of bleeding. MATERIALS AND METHODS: From 64 hemodialysis patients, 400 cases of low blood flow (150 mL/min, dialysate flow 300 mL/min) SRCA-HD were retrospectively analyzed and subsequently referred to as the LBF-SRCA group. Then, a prospective cross-over study was performed in 24 hemodialysis patients with normal blood flow (200 mL/min, dialysate flow 500 mL/min) SRCA-HD, which was called the NBF-SRCA group. Citrate was pumped at the artery pipeline, and calcium-containing dialysate (A group: 1.25 mmol/L, B group: 1.5 mmol/L) was used. The differences in laboratory tests, pipeline and dialyzer clotting, adequacy of dialysis, and adverse events of the groups were compared. RESULTS: 1) In the LBF-SRCA study, the correlation between citrate dosage and serum Ca2+ level at 2 hours post-filter during dialysis was negative (r = -0.228, p < 0.05). Compared with the LBF-SRCA and NBF-SRCA-A group, the pump speed of citrate in the NBF-SRCA-B group was the highest, with 355.0 ± 19.5 mL/h, 396.3 ± 11.9 mL/h, and 407.7 ± 13.0 mL/h, respectively, p < 0.001. 2) The serum Ca2+ at 2 and 4 hours post-filter during dialysis in the NBF-SRCA-B group was closer to the physiological level and significantly higher than in the A group, with 0.80 ± 0.06 vs. 0.68 ± 0.12 mmol/L, p < 0.001; 1.03 ± 0.11 vs. 0.93 ± 0.10 mmol/L, p = 0.005, respectively. 3) Both Kt/V of the NBF-SRCA-A (1.17 ± 0.24) and B (1.22 ± 0.23) group were significantly higher than that of the LBF-SRCA group (0.94 ± 0.02), p = 0.024 and p = 0.005, respectively. 4) The efficiency of anticoagulation was higher than 95% LBF-SRCA, NBF-SRCA-A and NBF-SRCA-B groups. The total clotting in the NBF-SRCA-B group (5/24) was significantly higher than that in the A group (3/24), p = 0.005. CONCLUSION: SRCA is safe, simple, and effective in hemodialysis. The dosage of citrate can be adjusted by monitoring serum Ca2+ at 2 hours post-filter during dialysis. BFR of 200 mL/min, dialysate flow rate of 500 mL/min, and 1.5 mmol/L calcium dialysate are much safer in hemodialysis patients with a high-risk of bleeding.
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Anticoagulantes , Citratos , Diálise Renal , Anticoagulantes/efeitos adversos , Cálcio , Citratos/efeitos adversos , Estudos Cross-Over , Soluções para Diálise , Hemorragia/induzido quimicamente , Humanos , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Synergistic remediation of heavy metal (HM) contaminated soil using beneficial microorganisms (BM) and plants is a common and effective in situ bioremediation method. However, the shortcomings of this approach are the low colonisation of BM under high levels of heavy metal stress (HMS) and the poor state of plant growth. Previous studies have overlooked the potential of biochar to mitigate the above problems and aid in-situ remediation. Therefore, this paper describes the characteristics and physicochemical properties of biochar. It is proposed that biochar enhances plant resistance to HMS and aids in situ bioremediation by increasing colonisation of BM and HM stability. On this basis, the paper focuses on the following possible mechanisms: specific biochar-derived organic matter regulates the transport of HMs in plants and promotes mycorrhizal colonisation via the abscisic acid signalling pathway and the karrikin signalling pathway; promotes the growth-promoting pathway of indole-3-acetic acid and increases expression of the nodule-initiating gene NIN; improvement of soil HM stability by ion exchange, electrostatic adsorption, redox and complex precipitation mechanisms. And this paper summarizes guidelines on how to use biochar-assisted remediation based on current research for reference. Finally, the paper identifies research gaps in biochar in the direction of promoting beneficial microbial symbiotic mechanisms, recognition and function of organic molecules, and factors affecting practical applications.
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Metais Pesados , Poluentes do Solo , Biodegradação Ambiental , Solo/química , Poluentes do Solo/análise , Metais Pesados/análise , Carvão Vegetal/química , PlantasRESUMO
AIMS: To investigate the clinical outcomes of maintenance hemodialysis (HD) patients using a high-flux (FX60) dialyzer. METHOD: Thirty patients undergoing dialysis for at least 2 years with a low-flux dialyzer were switched to the FX60 dialyzer for 3 years. Clinical and biochemical analysis was performed monthly for each patient. The parameters monitored included blood pressure, hemoglobin, albumin, intact parathyroid hormone (iPTH), calcium and phosphorus levels, the adequacy of dialysis (Kt/V), beta2-microglobulin (ß2-MG) clearance rate, as well as antihypertensive and erythropoietin (EPO) medications. RESULTS: After 3 years of dialysis with an FX60 dialyzer, the mean arterial blood pressure fell, hemoglobin increased, serum phosphate level decreased, iPTH declined and medication doses decreased. CONCLUSIONS: Dialysis with the FX60 dialyzer has a better clinical outcome for rectifying renal anemia, controlling hypertension and lowering serum phosphate levels making it a better choice for long-term HD patients.
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Falência Renal Crônica/terapia , Rins Artificiais , Diálise Renal/instrumentação , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Due to the lack of early diagnosis methods and warning signals of CRC and its strong heterogeneity, the determination of accurate treatments for CRC and the identification of specific early warning signals are still urgent problems for researchers. In this study, the expression profiles of cancer tissues and the expression profiles of tumor-adjacent tissues in 28 CRC patients were combined into a human protein-protein interaction (PPI) network to construct a specific network for each patient. A network propagation method was used to obtain a mutant giant cluster (GC) containing more than 90% of the mutation information of one patient. Next, mutation selection rules were applied to the GC to mine the mutation sequence of driver genes in each CRC patient. The mutation sequences from patients with the same type CRC were integrated to obtain the mutation sequences of driver genes of different types of CRC, which provide a reference for the diagnosis of clinical CRC disease progression. Finally, dynamic network analysis was used to mine dynamic network biomarkers (DNBs) in CRC patients. These DNBs were verified by clinical staging data to identify the critical transition point between the pre-disease state and the disease state in tumor progression. Twelve known drug targets were found in the DNBs, and 6 of them have been used as targets for anticancer drugs for clinical treatment. This study provides important information for the prognosis, diagnosis and treatment of CRC, especially for pre-emptive treatments. It is of great significance for reducing the incidence and mortality of CRC.
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The aim of the present study was to analyze the risk factors for new-onset chronic kidney disease (CKD) in patients who have received a liver transplant. A total of 190 patients who underwent liver transplantation between March 2001 and January 2015 were followed up, and analyzed retrospectively. Sex, age, primary disease, preoperative laboratory findings (hemoglobin, albumin, creatinine and glomerular filtration rate), surgical approach, blood loss during the surgery and transfusion volume, postoperative complications, and the average levels of calcineurin inhibitors (CNIs) (from liver transplantation to the onset of CKD) were analyzed. In total, 40 patients developed new-onset CKD after transplantation. Clinical data in the new-onset CKD group were compared with the non-CKD group. A χ2 test, t-test and logistic regression analysis were performed using SPSS 17.0 software. The incidence of new-onset CKD after liver transplantation was 21.1%. Renal pathology included IgA nephropathy, hepatitis B virus-associated nephropathy, membranous proliferative glomerulonephritis, focal segmental glomerular sclerosis and cryoglobulinemia-associated renal injury. Among the CKD patients, 85.7% had tubulointerstitial damage. Univariate analysis showed that preoperative renal function, hemoglobin, intraoperative blood loss and transfusion volume, postoperative acute kidney injury, average levels of CNIs, and hypertension were risk factors for new-onset CKD after liver transplantation. Logistic regression analysis showed that preoperative glomerular filtration rate [odds ratio (OR)=0.980, P=0.041], hemoglobin (OR=0.972, P=0.034), average levels of CNIs (OR=1.364, P=0.015) and hypertension (OR=4.833, P=0.048)] were independent risk factors for new-onset CKD. The incidence of new-onset CKD in patients who received liver transplantation was high. The main risk factors were identified to be preoperative glomerular filtration rate, hemoglobin, postoperative average levels of CNIs and hypertension.
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OBJECTIVE: To define the outcomes and risk predictors of fetal and maternal consequences of pregnancy in lupus nephritis (LN) patients. METHODS: Maternal and fetal outcomes of pregnancy in 52 systemic lupus erythematosus (SLE) patients were observed. Patients were allocated into two groups according to the presence or absence of LN. RESULTS: LN patients were subject to a higher risk of fetal complications, including fetal loss (7/24, 29.2 %, P = 0.001), lower birth weight (2548.2 ± 540.8 vs. 2949.1 ± 592.6 g, P = 0.028) and a higher frequency of small for gestational age births (33.3 vs. 10.7 %, P = 0.002). Higher rates of lupus flares (83.3 vs. 21.4 %, P = 0.001) and increased LAI-P scores (0.65 ± 0.36 vs. 0.21 ± 0.27, P = 0.001) during pregnancy were observed in LN patients. Multivariate analysis showed that increased SLE activity (P = 0.02, OR 4.2, 95 % CI 1.2-14.5), renal damage (P = 0.001, OR 8.4, 95 % CI 2.2-31.8), hypocomplementemia (P = 0.05, OR 3.23, 95 % CI 1.0-10.7), hypoalbuminemia (P = 0.011, OR 5.62, 95 % CI 1.4-23.0) and hypertension (P = 0.021, OR 6.0, 95 % CI 1.5-24.2) during pregnancy were predictors of adverse fetal outcomes. CONCLUSIONS: Pregnancy in LN patients should be monitored before and during pregnancy because of poor fetal and maternal outcomes. Increased LAI-P scores, renal damage, hypocomplementemia, hypoalbuminemia and hypertension are predictors of adverse fetal outcomes for SLE patients.