Background Although serum uric acid level appears to be associated with mortality in individuals treated with hemodialysis, the relationship between serum uric acid level and death is uncertain in ...patients treated with peritoneal dialysis (PD). Study Design Cohort study. Setting & Participants 985 patients from a single PD center in South China followed up for a median of 25.3 months. Predictor Serum uric acid level. Outcomes & Measurements The association of baseline sex-specific uric acid level with all-cause and cardiovascular mortality was evaluated. Models were adjusted for age, body mass index, comorbidity score, residual kidney function, total Kt/V, allopurinol and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, and laboratory test results, including hemoglobin, serum albumin, creatinine, calcium, phosphorus, triglycerides, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. Results Mean age was 48.3 ± 15.4 (SD) years, and 23% had diabetes. Mean uric acid level was 7.0 ± 1.3 (range, 3.8-19.8) mg/dL. During follow-up, 144 deaths were recorded, of which 64 were due to cardiovascular events. In multivariable models, the highest sex-specific tertile of uric acid level was associated with increased risk of all-cause mortality (HR, 1.93; 95% CI, 1.27-2.93; P = 0.004) and cardiovascular mortality (HR, 3.31; 95% CI, 1.70-6.41; P < 0.001) compared to the lowest tertile. Adjusted Cox regression models showed that the HRs per 1-mg/dL higher uric acid level for all-cause and cardiovascular mortality were 1.33 (95% CI, 1.14-1.56; P < 0.001) and 1.44 (95% CI, 1.17-1.77; P = 0.001) for men and 1.03 (95% CI, 0.86-1.24; P = 0.8) and 1.16 (95% CI, 0.97-1.38; P = 0.1) for women, respectively. A formal test for interaction indicated that the association of uric acid level with all-cause and cardiovascular mortality differed by sex (β = −0.06 P = 0.02 and β = −0.10 P = 0.02, respectively). Limitations Single measurement of uric acid at baseline. Cause of death determined by death certificates and expert consensus. Conclusions Elevated serum uric acid level is an independent risk factor for all-cause and cardiovascular mortality in men treated with PD.
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•Total SGD flux was equivalent to approximately 6.6 times river discharge.•Total SGD support 5.2–27% of the primary productivity.•Separation of SFGD and RSGD yielded more precise ...estimates of nutrient fluxes.
Submarine groundwater discharge (SGD) is being increasingly recognized as a significant source of nutrient into coastal waters, and generally comprises two components: submarine fresh groundwater discharge (SFGD) and recirculated saline groundwater discharge (RSGD). The separate evaluation of SFGD and RSGD is extremely limited as compared to the conventional estimation of total SGD and associated nutrient fluxes, especially in marginal-scale regions. In this study, new high-resolution radium isotopes data in seawater and coastal groundwater enabled an estimation of SGD flux in a typical marginal sea of the Yellow Sea. By establishing 226Ra and 228Ra mass balance models, we obtained the SGD-derived radium fluxes, and then estimated the SFGD and RSGD fluxes through a two end-member model. The results showed that the total SGD flux into the Yellow Sea was equivalent to approximately 6.6 times the total freshwater discharge of surrounding rivers, and the SFGD flux accounted for only 5.2%–8.8% of the total SGD. Considering the nutrient concentrations in coastal fresh and saline groundwater, we obtained the dissolved inorganic nutrient fluxes (mmol m−2 yr−1) to be 52–353 for nitrogen (DIN), 0.21–1.4 for phosphorus (DIP), 34–226 for silicon (DSi) via SFGD, and 69–262 for DIN, 1.0–3.9 for DIP, 70–368 for DSi via RSGD, with the sum of nutrient fluxes equaling to (1.8–9.3)-fold, (1.3–5.6)-fold and (2.0–9.5)-fold of the riverine inputs. Compared to the conventional estimation of the total SGD flux, the nutrient fluxes derived from the separation of SFGD and RSGD were (1.6–2.1), (1.6–1.8) and (4.0–4.9) times lower for DIN, DIP and DSi, respectively, indicating that the estimates by separating SFGD and RSGD could be conservative and representative results of the Yellow Sea. Furthermore, we suggested that SGD played an important role in nutrient sources among all the traditional nutrient inputs sources, providing 15%–48%, 33%–68% and 14%–43% of the total DIN, DIP and DSi input fluxes into the Yellow Sea, and the high nutrient stoichiometric ratios (i.e., DIN/DIP) in SGD probably contributed to the increasing ratios in the Yellow Sea. In addition delivering large amounts of nutrient into the Yellow Sea, SGD would create primary productivity of 10–49, 1.6–6.8 and 8.8–42 g C m−2 yr−1 based on N, P and Si, which were equivalent to 5.2%–27%, 0.9%–3.7% and 4.7%–23% of the total primary productivity, respectively. In particular, the SFGD-derived DIN flux can be converted to primary productivity of 4.2–28 g C m−2 yr−1 thus demonstrating the disproportionately large role of SFGD in ecological environment of the Yellow Sea relative to its flux. Therefore, we conclude that SGD, particularly SFGD, plays an important role as a nutrient source for the Yellow Sea, and not only affects nutrient budgets and structures but also enhances the primary productivity.
In recent years, microneedle technology has been widely used for the transdermal delivery of substances, showing improvements in drug delivery effects with the advantages of minimally invasive, ...painless, and convenient operation. With the development of nano- and electrochemical technology, different types of microneedles are increasingly being used in other biomedical fields. Recent research progress shows that dissolving microneedles have achieved remarkable results in the fields of dermatological treatment, disease diagnosis and monitoring, and vaccine delivery, and they have a wide range of application prospects in various biomedical fields, showing their great potential as a form of clinical treatment. This review mainly focuses on dissolving microneedles, summarizing the latest research progress in various biomedical fields, providing inspiration for the subsequent intelligent and commercial development of dissolving microneedles, and providing better solutions for clinical treatment.
The immune system has a central role in eliminating detrimental factors, by frequently launching inflammatory responses towards pathogen infection and inner danger signal outbreak. Acute and chronic ...inflammatory responses are critical determinants for consequences of kidney diseases, in which inflammasomes were inevitably involved. Inflammasomes are closely linked to many kidney diseases such as acute kidney injury and chronic kidney diseases. Inflammasomes are macromolecules consisting of multiple proteins, and their formation initiates the cleavage of procaspase-1, resulting in the activation of gasdermin D as well as the maturation and release of interleukin-1β and IL-18, leading to pyroptosis. Here, we discuss the mechanism in which inflammasomes occur, as well as their roles in inflammatory kidney diseases, in order to shed light for discovering new therapeutical targets for the prevention and treatment of inflammatory kidney diseases and consequent end-stage renal disease.
Objective. The aim of this study is to evaluate the efficacy and safety of pulmonary rehabilitation (PR) in patients with idiopathic pulmonary fibrosis (IPF). Methods. Embase, PubMed, Cochrane ...Library, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), Wanfang Data, and Chinese Biomedical Literature Database (SinoMed) were comprehensively searched. Randomized controlled trials (RCTs) that investigated the effects of PR for IPF patients were included. Literature selection and data extraction were conducted by two review authors independently. The Cochrane Collaboration’s Risk of Bias tool and RevMan software (version 5.3) were used to evaluate the quality of studies and conduct statistical analysis, respectively. Results. Seven studies (190 participants) were included. PR had a significant effect on six-minute walk distance (6MWD) (MD:48.60; 95%CI: 29.03 to 68.18; Z=4.87, P<0.00001), and 6MWD was improved more in subgroup analysis including studies conducted in Asia (MD: 53.62; 95%CI: 30.48 to 76.66; Z=4.54, P<0.00001) and Europe (MD:54.10; 95% CI: 26.65 to 101.56; Z=2.23, P=0.03). Forced vital capacity (FVC%) was higher (MD: 3.69; 95%CI: 0.16 to 7.23; Z=2.05, P=0.04). St. George’s Respiratory Questionnaire (SGRQ)/IPF-specific SGRQ (SGRQ-I) total score was lower (MD: -7.87; 95% CI: -11.44 to -4.30; Z=4.32, P<0.0001). No significant effects were found for lung diffusing capacity determined by the single-breath technique (DLCO%) (MD: 3.02; 95%CI: -0.38 to 6.42; Z=1.74, P=0.08). Conclusions. This study suggests that PR may enhance exercise capacity and improve quality of life in IPF patients. Besides, PR may also delay the decline of lung function of patients with IPF. However, further research should more fully assess the efficacy and safety of PR for IPF.
IgA nephropathy is a common glomerular disease on a global scale, which has resulted in significant economic burdens. The complement system plays a vital role in enhancing the efficacy of antibodies ...and phagocytic cells in eliminating microbes and damaged cells, and promoting inflammation. Complement activation has been found to contribute to the progression of various renal diseases, including IgA nephropathy.
In this study, a thorough analysis was conducted on publications related to complement in IgAN from 1991 to 2022, retrieved from the Web of Science Core Collection and Scopus database. The analysis focused on various aspects such as annual publications, country, institution, author, journal, keywords, and co-cited references, utilizing Citespace and Vosviewer.
A total of 819 publications were obtained, and while there were slight fluctuations in annual publications, an overall upward trend was observed. China, Japan and the United States were the leading countries in terms of publications, with China having the highest number of publications (201). Collaborative network analysis revealed that England, University of Alabama Birmingham, and Robert J Wyatt were the most influential country, institution, and author, respectively, in this field of research. Furthermore, the analysis of references and keywords indicated that complement activation contributes to IgAN, and immunosuppression in IgAN are a hot topic of research.
This study identifies current research hotspots and advanced tendencies in the study of complement in IgAN, providing scholars with crucial directions in this research area.
Natural killer (NK) cell is a powerful malignant cells killer, providing rapid immune responses via direct cytotoxicity without the need of antigen processing and presentation. It plays an essential ...role in preventing early tumor, metastasis and minimal residual disease. Although adoptive NK therapies achieved great success in clinical trials against hematologic malignancies, their accumulation, activation, cytotoxic and immunoregulatory functions are severely impaired in the immunosuppressive microenvironment of solid tumors. Now with better understandings of the tumor evasive mechanisms from NK-mediated immunosurveillance, immunotherapies targeting the key molecules for NK cell dysfunction and exhaustion have been developed and tested in both preclinical and clinical studies. In this review, we introduce the challenges that NK cells encountered in solid tumor microenvironment (TME) and the therapeutic approaches to overcome these limitations, followed by an outline of the recent preclinical advances and the latest clinical outcomes of NK-based immunotherapies, as well as promising strategies to optimize current NK-targeted immunotherapies for solid tumors.
Several studies have reported that tacrolimus (TAC) significantly reduced proteinuria in lupus nephritis (LN) patients and mouse models. However, the mechanism for this effect remains undetermined. ...This study explored the mechanism of how TAC protects podocytes from injury to identify new targets for protecting renal function.
MRL/lpr mice were given TAC at a dosage of 0.1 mg/kg per day by intragastric administration for 8 weeks. Urine and blood samples were collected. Kidney sections (2 μm) were stained with hematoxylin-eosin (HE), periodic acid-Schiff base (PAS) and Masson's trichrome stain. Mouse podocyte cells (MPC5) were treated with TAC and/or TGF-β1 for 48 h. The mRNA levels and protein expression of synaptopodin and Wilms' tumor 1 (WT1) were determined by real-time PCR, Western blotting and/or immunofluorescence, respectively. Flow cytometry was used to detect cell apoptosis with annexin V. Podocyte foot processes were observed under transmission electron microscopy. IgG and C3 deposition were assessed with immunofluorescence assays and confocal microscopy.
Synaptopodin expression significantly decreased in MRL/lpr disease control mice, accompanied by increases in 24-h proteinuria, blood urea nitrogen, and serum creatinine. TAC, however, reduced proteinuria, improved renal function, attenuated renal pathology, restored synaptopodin expression and preserved podocyte numbers. In MPC5 cells, TGF-β1 enhanced F-actin damage in podocytes and TAC stabilized it. TAC also decreased TGF-β1-induced podocyte apoptosis in vitro and inhibited foot process fusion in MRL/lpr mice. In addition, our results also showed TAC inhibited glomerular deposition of IgG and C3.
This study demonstrated that TAC reduced proteinuria and preserved renal function in LN through protecting podocytes from injury partly by stabilizing podocyte actin cytoskeleton and inhibiting podocyte apoptosis.
Essential hypertension has been recognized as a disease resulting from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in cardiac ...hypertrophy and heart failure. However, little is known about the roles of miRNAs in essential hypertension.
Using microarray-based miRNA expression profiling, we compared the miRNA expressions in plasma samples from 13 hypertensive patients and 5 healthy control subjects. Twenty-seven miRNAs were found to be differentially expressed. The expressions of selected miRNAs (miR-296-5p, let-7e, and a human cytomegalovirus HCMV-encoded miRNA, hcmv-miR-UL112) were validated independently in plasma samples from 24 hypertensive patients and 22 control subjects. The absolute expression levels of hcmv-miR-UL112, miR-296-5p, and let-7e were further determined in 127 patients and 67 control subjects (fold changes are 2.5, 0.5, and 1.7 respectively; all P<0.0001). Additionally, we demonstrated that interferon regulatory factor 1 is a direct target of hcmv-miR-UL112. Increased HCMV seropositivity and quantitative titers were found in the hypertension group compared with the control group (52.7% versus 30.9%, P=0.0005; 1870 versus 54 copies per 1 mL plasma, P<0.0001). Seropositivity, log-transformed copies of HCMV, and hcmv-miR-UL112 were independently associated with an increased risk of hypertension (odds ratio, 2.48; 95% confidence interval, 1.48 to 4.15; P=0.0005; odds ratio, 1.97; 95% confidence interval, 1.58 to 2.46; P<0.0001; and odds ratio, 2.55; 95% confidence interval, 1.98 to 3.27; P<0.0001, respectively).
We report for the first time a circulating miRNA profile for hypertensive patients and demonstrate a novel link between HCMV infection and essential hypertension. These findings may reveal important insights into the pathogenesis of essential hypertension.
URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00420784.
Aims/hypothesis
The contribution of aberrantly expressed microRNAs (miRNAs) to diabetic nephropathy in vivo is poorly understood.
Methods
Integrated comparative miRNA array profiling was used to ...examine the expression of serum miRNAs in patients with diabetic nephropathy. The abundance of miRNA-135a (miR-135a) was measured by real-time quantitative PCR in the serum and kidney tissues of patients with diabetic nephropathy. The luciferase assay combined with mutation and immunoblotting was used to screen and verify the bioinformatically predicted miRNAs. Ca
2+
entry or intracellular Ca
2+
(Ca
2+
i
) was performed by imaging Fura-2/AM-loaded cells using a fluorescence microscopy system. The role of miR-135a in vivo was explored with locked nucleic acid antisense oligonucleotides.
Results
MiR-135a was markedly upregulated in serum and renal tissue from patients with diabetic nephropathy, as well from
db/db
mice, and this was associated with the development of microalbuminuria and renal fibrosis. Furthermore, we identified transient receptor potential cation channel, subfamily C, member 1 (
TRPC1
) as a target of miR-135a during renal injury. We demonstrated that overexpression of TRPC1 was able to reverse the pathological effects of miR-135a on promoting proliferation of mesangial cells and increasing synthesis of extracellular matrix proteins. Moreover, miR-135a attenuated store depletion-induced Ca
2+
entry into cells by regulating TRPC1. Importantly, knockdown of miR-135a in diabetic kidneys restored levels of TRPC1 and reduced synthesis of fibronectin and collagen I in vivo. Suppressing TRPC1 levels to prevent Ca
2+
entry into cells may be a mechanism whereby miR-135a promotes renal fibrosis in diabetic kidney injury.
Conclusions/interpretation
These findings suggest an important role for miR-135a in renal fibrosis and inhibition of miR-135a might be an effective therapy for diabetic nephropathy.
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