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As our ongoing searching for the bioactive natural terpenoids, nine ent-kauranoids (1-9), including three previously undescribed ones (1, 2, and 9), were isolated from the aerial parts of Isodon amethystoides. Their structures were elucidated on the basis of spectroscopic data analysis, including NMR, MS, and ECD. Compounds 1 and 2 were a pair of tautomeric compounds, which was confirmed by the HPLC analysis and low temperature NMR testing. The underlying mechanism of the tautomer was proposed as an intramolecular SN2 reaction, which was explained by quantum chemical calculation. The HOMO-LUMO gap and the free energy revealed the spontaneous of the tautomeric of the 1 and 2. Additionally, the similar phenomena were also found in the two groups of known compounds 3 and 4 and 6 and 7, respectively. Apart from the tautomer, compounds 3 and 4 can be hydrolyzed into 5 through ester hydrolysis in CDCl3, while compounds 6, 7 can be hydrolyzed into 8 through ester hydrolysis. These phenomena were also confirmed through HPLC analysis and low temperature nuclear magnetic resonance tests and the mechanism was studied using quantum chemical calculation.
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Antineoplásicos Fitogênicos , Diterpenos do Tipo Caurano , Isodon , Estrutura Molecular , Isodon/química , Componentes Aéreos da Planta/química , Ésteres , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Patients undergoing hemodialysis (HD) are particularly vulnerable to coronavirus disease 2019 (COVID-19) and are at increased risk of developing severe infection. However, given the exclusion of such patients from clinical trials, there are limited data regarding the effectiveness of the antiviral drug nirmatrelvir/ritonavir (N/R) in patients on HD. We prescribed N/R to 4 patients on HD with COVID-19 after obtaining informed consent. Their clinical symptoms were improved at approximately 3 days after N/R administration. The viral load was reduced after approximately 10 days. The main adverse effects were nausea and vomiting. Rational dosage adjustment obtained good tolerance but did not influence the efficacy. These results suggest that N/R may be a promising agent for patients on HD with COVID-19.
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COVID-19 , Humanos , Tratamento Farmacológico da COVID-19 , Ritonavir/uso terapêutico , Diálise Renal/efeitos adversos , Antivirais/efeitos adversosRESUMO
Diabetic nephropathy (DN) is the primary complication of diabetes mellitus. Ferroptosis is a form of cell death that plays an important role in DN tubulointerstitial injury, but the specific molecular mechanism remains unclear. Here, we downloaded the DN tubulointerstitial datasets GSE104954 and GSE30529 from the Gene Expression Omnibus database. We examined the differentially expressed genes (DEGs) between DN patients and healthy controls, and 36 ferroptosis-related DEGs were selected. Pathway-enrichment analyses showed that many of these genes are involved in metabolic pathways, phosphoinositide 3-kinase/Akt signaling, and hypoxia-inducible factor-1 signaling. Ten of the 36 ferroptosis-related DEGs (CD44, PTEN, CDKN1A, DPP4, DUSP1, CYBB, DDIT3, ALOX5, VEGFA, and NCF2) were identified as key genes. Expression patterns for six of these (CD44, PTEN, DDIT3, ALOX5, VEGFA, and NCF2) were validated in the GSE30529 dataset. Nephroseq data indicated that the mRNA expression levels of CD44, PTEN, ALOX5, and NCF2 were negatively correlated with the glomerular filtration rate (GFR), while VEGFA and DDIT3 mRNA expression levels were positively correlated with GFR. Immune infiltration analysis demonstrated altered immunity in DN patients. Real-time quantitative PCR (qPCR) analysis showed that ALOX5, PTEN, and NCF2 mRNA levels were significantly upregulated in high-glucose-treated human proximal tubular (HK-2) cells, while DDIT3 and VEGFA mRNA levels were significantly downregulated. Immunohistochemistry analysis of human renal biopsies showed positive staining for ALOX5 and NCF2 protein in DN samples but not the controls. These key genes may be involved in the molecular mechanisms underlying ferroptosis in patients with DN, potentially through specific metabolic pathways and immune/inflammatory mechanisms.
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Diabetes Mellitus , Nefropatias Diabéticas , Ferroptose , Humanos , Biologia Computacional , Nefropatias Diabéticas/patologia , Ferroptose/genética , Fosfatidilinositol 3-Quinases , RNA Mensageiro/metabolismo , Nefrite IntersticialRESUMO
Background: Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Forty percent of the patients continue to progress and eventually develop into chronic renal failure. Although phospholipase A2 receptor (PLA2R) is the major antigen of PMN, the clinical features do not often parallel with the antibody titers. Therefore, it is significant to find relative credible markers to predict the treatment response. Methods: One hundred and eighteen PMN patients were recruited. The response to treatment was defined as ALB≥30g/L at 6 months and complete remission (CR) or not at the end of the follow-up. Renal outcome endpoint was defined as 50% or more Cr increase at the end. Results: The patients with poor treatment effects had numerically higher platelet-lymphocytes ratio (PLR). For patients with CR or not, the difference was near to statistic significant (P=0.095). When analyzing CR or not, the fitting of the binary logistic regression model including both PLA2R Ab titer and PLR (Hosmer-Lemeshow test: χ 2=8.328, P = 0.402; OR (PLA2R Ab titer) = 1.002 (95% CI 1.000-1.004, P = 0.042); OR (PLR) = 1.006 (95% CI 0.999-1.013, P = 0.098)) was markedly better than that with only PLA2R Ab titer (Hosmer-Lemeshow test: χ 2=13.885, P = 0.016). The patients with renal function deterioration showed significantly higher monocyte-lymphocyte ratio (MLR) (0.26 (0.22-0.31) vs 0.18 (0.13-0.22), P = 0.012). Conclusion: PMN patients with poor treatment response tended to have higher PLR at the time of renal biopsy, and a higher MLR was associated with poor renal outcomes. Our findings suggested that PLR and MLR might be used to predict treatment efficacy and prognosis for PMN patients, respectively.
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As the saccharifying and fermentative agent, medium-temperature Daqu (MT-Daqu) plays an irreplaceable role in the production of strong-flavor Baijiu. Numerous studies have focused on the microbial community structure and potential functional microorganisms, however, little is known about the succession of active microbial community and the formation mechanism of community function during MT-Daqu fermentation. In this study, we presented an integrated analysis of metagenomics, metatranscriptomics, and metabonomics covering the whole fermentation process of MT-Daqu to reveal the active microorganisms and their participations in metabolic networks. The results showed that dynamic of metabolites were time-specific, and the metabolites and co-expressed active unigenes were further classified into four clusters according to their accumulation patterns, with members within each cluster displaying a uniform and clear pattern of abundance across fermentation. Based on KEGG enrichment analysis in co-expression clusters and succession of active microbial community, we revealed that Limosilactobacillus, Staphylococcus, Pichia, Rhizopus, and Lichtheimia were metabolically active members at the early stage, and their metabolic activities were conducive to releasing abundant energy to drive multiple basal metabolisms such as carbohydrates and amino acids. Thereafter, during the high temperature period and at the end of fermentation, multiple heat-resistant filamentous fungi were transcriptionally active populations, and they acted as both the saccharifying agents and flavor compound producers, especially aromatic compounds, suggesting their crucial contribution to enzymatic activity and aroma of mature MT-Daqu. Our findings revealed the succession and metabolic functions of the active microbial community, providing a deeper understanding of their contribution to MT-Daqu ecosystem.
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Bactérias , Microbiota , Fermentação , Bactérias/genética , Bactérias/metabolismo , Fungos/genética , Pichia , Biodiversidade , Bebidas Alcoólicas/microbiologiaRESUMO
OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS: Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Hiperuricemia , Insuficiência Renal Crônica , Humanos , Masculino , Rim , Proteinúria , Insuficiência Renal Crônica/complicaçõesRESUMO
INTRODUCTION: Apoptosis of vascular smooth muscle cells induced by hyperphosphatemia is a critical mechanism of chronic kidney disease-related vascular disorders. The present study investigated whether extracellular calcium-sensing receptor (CaSR) regulates stanniocalcin 2 (STC2) expression in HAoSMCs and subsequently protects HAoSMCs from high-phosphate-induced apoptosis. METHODS: HAoSMCs were cultured, and STC2 expression was determined by qPCR. A calcimimetic (NPS R-568) or calcilytic (NPS-2143) was applied to HAoSMCs. STC2 mRNA and protein levels were measured by qPCR and Western blot, respectively, and confocal microscopy was employed to investigate subcellular localization. STC2 overexpression and silencing were induced to assess the effects of STC2 on high-phosphate-induced apoptosis, which was determined by caspase-3 levels and TUNEL staining. The anti-apoptotic effect of CaSR-induced STC2 was confirmed by interfering with STC2 expression in the presence of NPS R-568. RESULTS: The constitutive expression of STC2 was confirmed. STC2 mRNA and protein levels were increased by NPS R-568 with or without high phosphate. NPS-2143 resulted in decreased STC2 mRNA levels, but decreased STC2 protein levels were only found under the high-phosphate condition. Confocal microscopy demonstrated the colocalization of STC2 and plasma membrane or endoplasmic reticulum markers. STC2 overexpression reduced HAoSMCs apoptosis, which were reversed with STC2 silencing. NPS R-568 treatment reduced HAoSMCs apoptosis, but STC2 silencing abolished the protective effect. CONCLUSION: This is the first evidence that STC2 is regulated by CaSR in HAoSMCs. CaSR activation-induced STC2 has putative anti-apoptotic effects against high phosphate. Calcimimetics are promising agents to treat uremic vascular injury.
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Músculo Liso Vascular , Receptores de Detecção de Cálcio , Humanos , Receptores de Detecção de Cálcio/genética , Receptores de Detecção de Cálcio/metabolismo , Músculo Liso Vascular/metabolismo , Fosfatos/metabolismo , Fosfatos/farmacologia , Apoptose , RNA Mensageiro/metabolismoRESUMO
Vascular calcification (VC) and myocardial hypertrophy are very common in patients on hemodialysis (HD). Previous studies have only assessed the cross-sectional associations of VC with left ventricular mass (LVM) and the predictive value of individual factors. The present study investigated the relationship between abdominal aortic calcification (AAC) and LVM increment over time, and the combined effect of these factors on the outcomes of HD patients. 104 HD patients were enrolled. AAC scores were evaluated on left lateral lumbar spine radiographs. Echocardiography was performed to calculate the LVM changes during a 2-year period. At baseline, 91 patients (87.5%) had varying degrees of AAC (median score 6.0, range 2.0 - 11.0). After 2 years, the mean LVM change was 7.49 g (range -5.03 - 26.00 g), and 68 patients (65%) had an increased LVM. Patients with higher baseline AAC scores had significantly larger LVM and LVM index increments. Patients with increased LVM had significantly higher baseline AAC scores and hemoglobin, serum phosphate, and hypersensitive C-reactive protein levels. Multiple stepwise linear regression demonstrated that the baseline AAC was the only independent predictor of increased LVM after 2 years. 28 patients (26.9%) died in the subsequent 5 years. Patients with lower baseline AAC scores had a significantly higher cumulative survival rate than those with higher AAC scores. However, the LVM change (either alone or in combination with the AAC score) had no significant effect on survival. In conclusion, AAC is an independent predictor of LVM increase over time in HD patients. Prevention and treatment of VC may be a promising intervention target to improve left ventricular remodeling and outcomes in HD patients.
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Proteína C-Reativa , Calcificação Vascular , Aorta Abdominal/diagnóstico por imagem , Estudos Transversais , Humanos , Fosfatos , Prognóstico , Diálise Renal/efeitos adversos , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/etiologiaRESUMO
Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
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AIMS: This study aimed to compare the accuracy of the choroidal vascularity index (CVI) and diabetic retinopathy (DR) in the diagnosis of diabetic nephropathy (DN). METHODS: We performed a cross-sectional study of 117 patients with proteinuria and diabetes mellitus (DM) in which 45 patients were diagnosed with DN by renal pathology. Demographic information, clinical features, and laboratory data were collected. A total of 234 eyes underwent evaluation of DR and the CVI using enhanced depth imaging-optical coherence tomography scans. We analyzed the association between the CVI and DN and compared the CVI and DR for diagnosing DN using area under receiver operating characteristic curves (AUROCs). RESULTS: The severe nonproliferative DR and proliferative DR groups showed a lower CVI than the no DR and mild/moderate nonproliferative DR groups (P < 0.01 or P < 0.001). There was a significantly lower CVI in patients with DN stage III (63.01% ± 1.47%) compared with those in DN stages IIa (62.1% ± 1.41%, P < 0.001) and IIb (59.85% ± 1.98%, P < 0.01). The sensitivity and specificity of the CVI for diagnosing DN were 84% (71%-94%) and 95% (88%-99%), respectively, which were preferable to those of DR. The AUROCs for the CVI and DR for diagnosing DN were 0.932 and 0.831, respectively. The CVI outperformed DR for diagnosing DN (P < 0.05). The cutoff value of the CVI was 63.13%. CONCLUSION: The CVI might be a reliable noninvasive technique for predicting the pathological stage of DN and is superior to DR in diagnosing DN.
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BACKGROUND: Hemodialysis (HD) causes various nervous system abnormalities. Alterations in white matter (WM) microstructure after long-term HD have been reported in a few previous studies; however, no studies have been performed to investigate enlarged perivascular spaces (PVS) in WM regions. We measured cerebral blood flow (CBF) and white matter volume (WMV) in HD patients to assess enlarged PVS severity in the WM across the whole brain and suggest possible explanations for this. METHODS: Fifty-one HD patients and 51 age-, sex-, and education-matched healthy controls (HCs) were recruited. The number of enlarged PVS in the centrum semiovale (CS), cerebral watershed (CW), and basal ganglia (BG) regions were assessed by T2-weighted MRI. CBF was estimated by arterial spin labeling (ASL), which is a non-invasive perfusion imaging technique. WMV was assessed by the computational anatomy toolbox (CAT12), which is a statistical analysis package. Differences in descriptive variables (two-tailed t-tests, χ2 tests, Mann-Whitney U tests, and Friedman M tests), an intra-class correlation between radiologists, the relationship between enlarged PVS number and HD duration, normalized CBF and WMV (multiple regression), and group differences in CBF and WMV {voxel-wise t-tests with age and sex as covariates [cluster size >50 voxels, false discovery rate (FDR) corrected, P<0.05]} were assessed. RESULTS: HD patients displayed a more significant number of CS-PVS and CW-PVS in WM regions compared with the HCs, but there was no significant difference in the number of BG-PVS. The number of CS-PVS and CW-PVS were positively associated with HD duration. The number of CW-PVS was positively associated with CBF changes and WMV alteration in HD patients. Meanwhile, significant differences in the blood pressure (BP) readings pre-HD, intra-HD, and post-HD were observed in HD patients. Compared with the HCs, the HD patients showed higher CBF in the CS, CW, and BG regions (P<0.05). Hence, decreased WMV in the CS, CW, and BG regions were shown in the HD patients compared with the HCs (P<0.05). CONCLUSIONS: Enlarged CS-PVS and CW-PVS on MRI might be a feature of long-term HD patients. Enlarged CW-PVS number is associated with higher CBF in the CW region and lower WMV in the CW region in HD patients.
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Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of chronic multisystem autoimmune diseases with substantial mortality and morbidity and frequent relapses. The complexity of the disease condition and treatment-related adverse reactions as well as infections play important roles in the poor outcomes. Unfortunately, the subjective symptoms and objective indicators are not fully parallel, and manifestations between disease activity and treatment-related adverse reactions are often similar. Here, we describe a case of pulmonary mucormycosis in an old female patient with AAV to highlight these challenges.
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HLE-B3 cell line, a human lens epithelial cell line, was used to examine the anti-glycative and anti-oxidative protection of aqueous extract prepared from steamed red amaranth leaves against high glucose induced injury. Phytochemical profile of this aqueous extract was analyzed. HLE-B3 cells were pretreated by this aqueous extract at 0.25%, 0.5%, or 1%, and followed by high glucose treatment. Results showed that the content of phenolic acids, flavonoids, anthocyanins, carotenoids, and triterpenoids in this aqueous extract was in the range of 1,107-2,861 mg/100 g dry weight. High glucose decreased cells viability and suppressed Bcl-2 mRNA expression. This aqueous extract pretreatments raised 11-42% cell survival and upregulated 20-47% Bcl-2 mRNA expression. High glucose reduced Na+ -K+ ATPase activity and mitochondrial membrane potential (MMP). This aqueous extract raised 27-40% Na+ -K+ ATPase activity, and 18-51% MMP. High glucose stimulated the generation of total advanced glycative endproducts (AGEs), methylglyoxal, and reactive oxygen species (ROS). This aqueous extract pretreatments lowered total AGEs, methylglyoxal, and ROS levels in the range of 0.38-1.17 folds, 1.7-4.9 nmol/mg protein, and 0.35-1.06 relative fluorescence unit/mg protein. High glucose upregulated mRNA expression of aldose reductase, nuclear factor kappa B, and p38. This aqueous extract pretreatments decreased mRNA expression of these factors in the range of 75-159%, 57-151%, and 54-166%. High glucose downregulated mRNA expression of nuclear factor E2-related factor 2 (Nrf2). This aqueous extract pretreatments increased 12-38% Nrf2 mRNA expression. These results suggested that this aqueous extract might be a potent nutritional supplement to prevent diabetic retinopathy.
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Amaranthus , Antocianinas , Glucose , Humanos , Estresse Oxidativo , Folhas de Planta , Espécies Reativas de OxigênioRESUMO
Mitochondrial dysfunction in proximal tubular epithelial cells is a key event in acute kidney injury (AKI), which is a risk factor for the development of chronic kidney disease (CKD). Apelin is a bioactive peptide that protects against AKI by alleviating inflammation, inhibiting apoptosis, and preventing lipid oxidation, but its role in protecting against mitochondrial damage remains unknown. Herein, we examined the protective effects of apelin on mitochondria in cisplatin-stimulated human renal proximal tubular epithelial cells and evaluated its therapeutic efficacy in cisplatin-induced AKI mice. In vitro, apelin inhibited the cisplatin-induced mitochondrial fission factor (MFF) upregulation and the fusion-promoting protein optic atrophy 1 (OPA1) downregulation. Apelin co-treatment reversed the decreased levels of the deacetylase, Sirt3, and the increased levels of protein acetylation in mitochondria of cisplatin-stimulated cells. Overall, apelin improved the mitochondrial morphology and membrane potential in vitro. In the AKI model, apelin administration significantly attenuated mitochondrial damage, as evidenced by longer mitochondrial profiles and increased ATP levels in the renal cortex. Suppression of MFF expression, and maintenance of Sirt3 and OPA1 expression in apelin-treated AKI mice was also observed. Finally, exogenous administration of apelin normalized the serum level of creatinine and urea nitrogen and the urine levels of NGAL and Kim-1. We also confirmed a regulatory pathway that drives mitochondrial homeostasis including PGC-1α, ERRα and Sirt3. In conclusion, we demonstrated that apelin ameliorates renal functions by protecting tubular mitochondria through Sirt3 upregulation, which is a novel protective mechanism of apelin in AKI. These results suggest that apelin has potential renoprotective effects and may be an effective agent for AKI treatment to significantly retard CKD progression.
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Injúria Renal Aguda/metabolismo , Apelina/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Mitocôndrias/metabolismo , Injúria Renal Aguda/induzido quimicamente , Animais , Antineoplásicos/toxicidade , Células Cultivadas , Cisplatino/toxicidade , Humanos , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , Masculino , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Endogâmicos C57BL , Sirtuína 3/metabolismoRESUMO
BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER: NCT02063100 on ClinicalTrials.gov.
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Medicamentos de Ervas Chinesas , Glomerulonefrite , China , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Glomerulonefrite/tratamento farmacológico , Humanos , Medicamentos sem Prescrição , Comprimidos , Resultado do TratamentoRESUMO
INTRODUCTION: Hyperphosphatemia is an important symptom of chronic kidney disease-mineral bone disorder (CKD-MBD). Various oral phosphate binders have been used, but have not been very effective, especially for severe secondary hyperparathyroidism (SHPT) in patients undergoing maintenance dialysis. Maintenance dialysis patients with severe SHPT can develop hypophosphatemia for several months after parathyroidectomy without elevated alkaline phosphatase. Based on these clinical phenomena, we hypothesized that high levels of parathyroid hormone (PTH) might inhibit intestinal phosphorus absorption which mediated by sodium-dependent phosphorus transporters. METHODS: Forty BALB/c mice were divided into four groups. Mice in group 1 were given an intravenous injection of normal saline as the control group. Mice in groups 2, 3, and 4 were given PTH(1- 34) in doses of 40 µg/100 g, 200 µg/100 g, and 400 µg/100 g body weight intravenously, respectively. All mice were euthanized 8 hours after the injection. The mRNA and protein expression of sodium-dependent phosphorus transporter NPT-2b and Pit-1 on the membrane of the intestinal epithelial cells was detected by real-time polymerase chain reaction (PCR) and western blot analysis, respectively. RESULTS: In group 4, intestinal epithelial NPT-2b and Pit-1 protein expression was significantly decreased, whereas in groups 2 and 3, no significant changes were found. CONCLUSION: A high PTH level decreases the protein expression of NPT-2b and Pit-1 in the intestinal mucosa.
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Hiperparatireoidismo Secundário , Hormônio Paratireóideo , Animais , Cálcio , Mucosa Intestinal , Camundongos , Camundongos Endogâmicos BALB C , Fósforo , Diálise Renal , SódioRESUMO
Hemodialysis with restless legs syndrome (HD-RLS) is associated with alterations in neuronal function, the blood-brain barrier and iron deposition, thus affecting cerebral metabolism and perfusion. This study utilized three-dimensional arterial spin labeling (ASL) to identify HD-RLS-related perfusion patterns and potential relationships with disease severity. Twenty-six HD-RLS patients, 30 hemodialysis patients without restless legs syndrome (HD-nRLS) and 30 age-, sex-, and education-matched healthy controls were included in this study. One-way analysis of covariance and post hoc analyses were used to assess differences in cerebral blood flow (CBF) values, demographics and clinical data among the three groups. Pearson's correlation analysis was conducted between altered CBF values in the HD-RLS group and clinical data. Compared with HD-nRLS patients, HD-RLS patients showed increased CBF in the right primary motor cortex (false discovery rate [FDR]-corrected P < 0.05). Compared with the normal controls, both HD subgroups (i.e., those with and without RLS) exhibited consistent CBF changes, including increased CBF in the left medial superior frontal gyrus and bilateral thalamus and decreased CBF in the left insular cortices (FDR-corrected P < 0.05). This abnormal hyperperfusion in the sensorimotor cortex and basal ganglia provides evidence for a sensory processing disorder in RLS that may be involved in the pathogenesis of RLS in HD patients.
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Síndrome das Pernas Inquietas , Circulação Cerebrovascular , Humanos , Imageamento por Ressonância Magnética , Diálise Renal , Síndrome das Pernas Inquietas/diagnóstico por imagem , Marcadores de SpinRESUMO
BACKGROUND: Endovascular treatment of acute thrombosed arteriovenous grafts performed completely under ultrasound guidance has rarely been reported. We compared the efficacy of a new endovascular thrombectomy technique (percutaneous manual thromboaspiration through the introducer sheath) with classical hybrid thrombectomy (minimally invasive surgical thrombectomy combined with high-pressure angioplasty) performed completely under ultrasound guidance, for arteriovenous graft thrombosis. METHODS: This was a retrospective cohort study involving patients receiving hemodialysis who underwent arteriovenous graft thrombectomy between January 2014 and December 2017. We divided 130 participants into an intervention (endovascular) group (N.=65) and a control (classical hybrid) group (N.=65) according to the thrombectomy technique. The procedural success rate, immediate outcomes and patency were compared between the groups. RESULTS: There was no significant difference in the procedural success rate (92.31% vs. 89.23%, P=0.55) between the intervention and control groups, respectively. No major complications were noted, but two cases of vessel rupture occurred in the control group and three cases of vessel rupture occurred in the intervention group. The procedure time in the intervention group was significantly shorter than that in the control group (74±14.21 min vs. 109.05±19.20 min, respectively; P<0.05). During the 6-month follow-up, we found no significant difference in the postintervention primary patency rate (48.33% vs. 55.17%; P=0.51) or the postintervention second patency rate (83.33% vs. 84.49%; P=0.79) between the intervention and control groups, respectively. Dialysis clearance and ≥50% stenosis were predictors of postintervention primary patency (hazard ratio, 7.80; 95% confidence interval: 1.75-34.81; P=0.01; and hazard ratio, 6.43; 95% confidence interval: 2.43-17.03; P<0.001), respectively. CONCLUSIONS: Completely ultrasound-guided percutaneous manual thromboaspiration through the introducer sheath can be used for thrombosed arteriovenous grafts. This approach has the advantage of shorter operative time compared with hybrid treatment.
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Derivação Arteriovenosa Cirúrgica , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/cirurgia , Humanos , Diálise Renal , Estudos Retrospectivos , Trombectomia/efeitos adversos , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
With rapid progress in cancer diagnosis and treatment in the last two decades, outcomes in oncological patients have improved significantly. However, the incidence of acute kidney injury (AKI) in this population has also increased significantly. AKI complicates many aspects of patients' care and adversely affects their prognoses; thus, accurately diagnosing the risk factors for AKI ensures appropriate management. AKI may be caused by pre-renal, intrinsic renal, and post-renal reasons, as well as for combined reasons. This review summarizes the potential etiologies of AKI according to the three classifications. For each underlying cause of AKI, the cancer itself and/or cancer treatment may contribute to a patient developing AKI. Therefore, we present disease- and treatment-related factors for each cause category, with special focus on immune checkpoint inhibitors, which are being used increasingly more often. It is important for nephrology services to be knowledgeable to provide the best level of care.
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PURPOSE: The purpose of this study was to investigate the differences of gray matter volume (GMV) alteration patterns between hemodialysis with restless legs syndrome (HD-RLS) and hemodialysis without restless legs syndrome (HD-nRLS) patients using voxel-based morphometry. METHODS: Twenty-three HD-RLS patients, 27 HD-nRLS patients, and 27 age-, sex-, and education-matched healthy controls were included in this study. One-way analysis of covariance and post hoc analyses were used to assess differences in GMV, demographics, and clinical data among the 3 groups. Pearson correlation analysis was conducted between altered GMV in the HD-RLS group and clinical data. RESULTS: Compared with HD-nRLS patients, HD-RLS patients showed decreased GMV in the left primary motor cortex (false discovery rate corrected, P < 0.05). Compared with the healthy controls, both HD subgroups (ie, those with and without RLS) exhibited consistent GMV changes, including decreased GMV in the bilateral anterior cingulate and paracingulate gyrus and left middle temporal gyrus (false discovery rate corrected, P < 0.05). The GMV values in the left precentral gyrus were negatively correlated with the RLS rating scores (r = 0.2138, P = 0.0263). CONCLUSIONS: This abnormal decreased GMV in the sensorimotor cortex provides evidence for a sensory processing disorder in RLS that may be involved in the pathogenesis of RLS in HD patients.