High-sensitive cardiac troponin for the diagnosis of acute myocardial infarction in different chronic kidney disease stages.

BACKGROUND: Chronic kidney disease (CKD) are associated with acute myocardial infarction (AMI). High-sensitive cardiac troponin (hs-cTn) has been evidenced to enhance the early diagnostic accuracy of AMI, but hs-cTn levels are often chronically elevated in CKD patients, which reduces their diagnostic utility. The aim of this study was to derive optimal cutoff-values of hs-cTn levels in patients with CKD and suspected AMI. METHODS: In this retrospective paper, a total of 3295 patients with chest pain (2758 in AMI group and 537 in Non-AMI group) were recruited, of whom 23.1% were had an estimated glomerular filtration rate (eGFR) of < 60 mL min-1 (1.73 m2)-1. Hs-cTnI values were measured at presentation. RESULTS: AMI was diagnosed in 83.7% of all patients. The optimal value of hs-TnI in diagnosing AMI was 1.15 ng mL-1, which were higher in males than females comparing different cutoff-values of subgroups divided by age, gender and renal function, and which increased monotonically with decreasing of eGFR because in patients with CKD without AMI, the correlation between hs-cTnI and renal function is low but significant (r2 = 0.067, P < 0.001). CONCLUSIONS: Different optimal cutoff-values of hs-cTnI in the diagnosis of AMI in patients with CKD were helpful to the clinical diagnosis of AMI in various populations and were higher in males than females, but which was needed to be validated by multicenter randomized controlled clinical studies in the future.

Clinical efficacy and safety of full-dose versus half-dose corticosteroids plus leflunomide for IgA nephropathy.

BACKGROUND: The results of leflunomide (LEF) in patients with IgA nephropathy (IgAN) were inconsistent. METHODS: A total of 149 kidney biopsy-confirmed IgAN patients with an estimated glomerular filtration rate (eGFR) ≥ 50 ml/min/1.73 m2 and protein excretion levels ≥0.75 g/d were enrolled, with 65 subjects receiving half-dose CS plus LEF (LEF group), and the 84 counterpart patients accepting full-dose corticosteroid (Full CS group). The primary outcomes included the complete remission (CR) rates and incidence of adverse events (AEs). The secondary outcomes were the overall remission (OR) rates and a combined event (eGFR reduced ≥30%, end-stage renal disease [ESRD], hemodialysis, peritoneal dialysis or kidney transplantation). RESULTS: During the 18 months of follow-up, the CR rates were 72 and 64% in the LEF and Full CS groups (P = 0.299), respectively. The proportion of patients with OR rates in the LEF group and Full CS group was 89% versus 75%, respectively (P = 0.027). Serious AEs were observed only in the Full CS group (P = 0.017). The incidences of total AEs (P = 0.036) and infections (P = 0.024) were lower in the LEF group than in the Full CS group. CONCLUSIONS: LEF combined with half-dose CS is superior to full-dose CS in the treatment of IgAN.

The progress of inflammation and oxidative stress in patients with chronic kidney disease.

BACKGROUND: The variations and their correlation of inflammation and oxidative stress in chronic kidney disease (CKD) have not been thoroughly understood. MATERIALS AND METHODS: Biomarkers of inflammation and oxidative stress were measured in a cohort of 176 patients with CKD ranging from stage 1 to 5 and 67 healthy controls. Correlation analysis in levels between inflammation and oxidative stress was also performed with estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. Concentrations of serum creatinine (Scr), hs-CRP (hypersensitive C reactive protein) and MDA (malondialdehyde) of these participants were measured again after 12 month follow-up. RESULTS: In the present study, with the development of CKD, serum levels of hs-CRP, interleukin-6 (IL-6) and MDA were significantly increased, and the serum levels of SOD (superoxide dismutase) and GSH-PX (glutathione peroxidase) were significantly decreased in these participants. eGFR was inversely associated with MDA and positively with SOD and GSH-PX when adjusting for age and hypertension therapy. IL-6 and hs-CRP were positively correlated with MDA, and negatively associated with SOD and GSH-PX. Notably, after 12-month follow-up, the increase in Scr was positively associated with the increase in hs-CRP (p < 0.01) and MDA (p < 0.05), respectively. CONCLUSIONS: Inflammation and oxidative stress interacted with each other and played pivotal roles in the development of CKD. Variation in eGFR was parallel with the changes of oxidative stress and inflammation when CKD developing.

Efficacy and safety of 12 immunosuppressive agents for idiopathic membranous nephropathy in adults: A pairwise and network meta-analysis.

Background: Immunosuppressants have been applied in the remedy of idiopathic membranous nephropathy (IMN) extensively. Nevertheless, the efficacy and safety of immunosuppressants do not have final conclusion. Thus, a pairwise and network meta-analysis (NMA) was carried out to seek the most recommended therapeutic schedule for patients with IMN. Methods: Randomized controlled trials (RCTs) including cyclophosphamide (CTX), mycophenolate mofetil (MMF), tacrolimus-combined mycophenolate mofetil (TAC + MMF), cyclosporine (CsA), tacrolimus (TAC), leflunomide (LEF), chlorambucil (CH), azathioprine (AZA), adrenocorticotropic hormone (ACTH), non-immunosuppressive therapies (CON), steroids (STE), mizoribine (MZB), and rituximab (RIT) for patients with IMN were checked. Risk ratios (RRs) and standard mean difference (SMD) were reckoned to assess dichotomous variable quantities and continuous variable quantities, respectively. Total remission (TR) and 24-h urine total protein (24-h UTP) were compared using pairwise and NMA. Then interventions were ranked on the basis of the surface under the cumulative ranking curve (SUCRA). Results: Our study finally included 51 RCTs and 12 different immunosuppressants. Compared with the CON group, most regimens demonstrated better therapeutic effect in TR, with RR of 2.1 (95% CI) (1.5-2.9) for TAC, 1.9 (1.3-2.8) for RIT, 2.5 (1.2-5.2) for TAC + MMF, 1.9 (1.4-2.7) for CH, 1.8 (1.4-2.4) for CTX, 2.2 (1.0-4.7) for ACTH, 1.6 (1.2-2.1) for CsA, 1.6 (1.0-2.5) for LEF, and 1.6 (1.1-2.2) for MMF. In terms of 24-h UTP, TAC (SMD, -2.3 (95% CI -3.5 to -1.1)), CTX (SMD, -1.7 (95% CI -2.8 to -0.59)), RIT (SMD, -1.8 (95% CI -3.5 to -0.11)), CH (SMD, -2.4 (95% CI -4.3 to -0.49)), AZA (SMD, --4.2 (95% CI -7.7 to -0.68)), and CsA (SMD, -1.7 (95% CI -3 to -0.49)) were significantly superior than the CON group. As for adverse effects (AEs), infections, nausea, emesia, myelosuppression, and glucose intolerance were the collective adverse events for most immunosuppressants. Conclusion: This study indicates that TAC + MMF performed the best in terms of TR, and TAC shows the best effectiveness on 24-h UTP compared with other regimens. On the contrary, there seems to be little advantage on STE alone, LEF, AZA, and MZB in treating patients with IMN compared with CON. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021287013].

ANCA-associated vasculitis following the CoronaVac vaccination.

With the coronavirus disease 2019 (COVID-19) pandemic, vaccination has become one of the cornerstones to contain the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large clinical trials have shown high efficacy and safety of SARS-CoV-2 vaccination against COVID-19. However, with the widespread use of SARS-CoV-2 vaccines worldwide, an increasing number of reports describe the onset of glomerular disease. Here, we report a case of a 70-year-old Chinese woman who developed new antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis within 4 h post the first dose of CoronaVac. CoronaVac is an inactivated SARS-CoV-2 vaccine developed by Sinovac Life Sciences (Beijing, China). Her clinical symptoms were nausea, fatigue, acute kidney injury, and proteinuria. Laboratory tests showed markedly elevated serum myeloperoxidase titers, and the renal biopsy showed microcellular fibrous crescent formation. Renal function of the patient responded favorably after treatment with steroids and cyclophosphamide. Although there is no direct evidence of a link between vasculitis and vaccination, similar complications should be monitored as potential adverse events with widespread vaccination globally.

Molecular Insights into the Structure and Property Variation of the Pressure-Induced Solid Electrolyte Interphase on a Lithium Metal Anode.

Solid electrolyte interphase (SEI) is regarded as the key to developing stable and long-cycling lithium metal batteries (LMBs). The inevitable stress caused by the Li-metal anode expansion/contraction and the battery encapsulation is crucial to the SEI growth and properties. Herein, we perform reactive force field (ReaxFF) molecular dynamics simulations to investigate the structure and property variation of the pressure-induced SEI. The pressure boosts the SEI structure delamination and reduces the porosity based on the quantitative analysis of the charge spectrum and porous structure, which contributes to the formation of a thin and dense SEI. Meanwhile, the phase diagram combined with the pressure and salt concentration effects is established to obtain the proper trade-off between SEI mechanical and transport properties, demonstrating that the Li+ diffusion coefficients of the pressure-induced SEI can be improved by the high salt concentration when Young's modulus increases at the same time. The findings not only provide molecular insights into the SEI structure variation but also offer guidance and directions for optimizing the pressure-induced SEI property toward high-performance LMBs.

Effectiveness and safety of tacrolimus treatment for IgA nephropathy: A prospective cohort study.

BACKGROUND: There is no a unified opinion in the treatment of IgA nephropathy. This prospective cohort study was to explore the effectiveness and safety of tacrolimus for treatment of IgA (Immunoglobulin A) nephropathy patients. METHODS: In this study, we assigned 50 patients with biopsy-proven IgA nephropathy in a 1:1.5 ratio to receive oral tacrolimus or full-dose glucocorticoid for 6 months. All the patients had 24-h urine protein excretion≥2.0g/24h and estimated glomerular filtration rate≥50mL/min/1.73m2. Primary endpoint was rate of complete remission. RESULTS: After 6 months of treatment, seven participants achieved complete remission in the tacrolimus group and twelve participants in the glucocorticoid group, the complete remission rate was 35% and 40%, respectively. There were not significantly differences between two groups (P=0.7). However, the serum creatinine level from baseline was an increase of 13±13.5µmol/L in the tacrolimus group and a decrease of 8.2±20µmol/L in the glucocorticoid group. When patients stopped taking tacrolimus for 3 months, creatinine level can almost fall to normal level. Thus, patients with renal insufficiency have a high incidence in the tacrolimus group. CONCLUSIONS: Tacrolimus was noninferior to full-dose glucocorticoid in inducing proteinuria remission at 6 months. This suggested that those IgA nephropathy patients who are unwilling to full-dose glucocorticoid could consider tacrolimus, but need to pay attention to the impact on renal function.

Exciton-Phonon Interactions in Monolayer Germanium Selenide from First Principles.

We investigate from first principles exciton-phonon interactions in monolayer germanium selenide, a direct gap two-dimensional semiconductor. By combining the Bethe-Salpeter approach and the special displacement method, we explore the phonon-induced renormalization of the exciton wave functions, excitation energies, and oscillator strengths. We determine a renormalization of the optical gap of 0.1 eV at room temperature, which results from the coupling of the exciton with both acoustic and optical phonons, with the strongest coupling to optical phonons at ∼100 cm-1. We also find that the exciton-phonon interaction is similar between monolayer and bulk GeSe. Overall, we demonstrate that the combination of many-body perturbation theory and special displacements offers a new route to investigate electron-phonon couplings in excitonic spectra, the resulting band gap renormalization, and the nature of phonons that couple to the exciton.

The effects of "Fangcang, Huoshenshan, and Leishenshan" hospitals and environmental factors on the mortality of COVID-19.

BACKGROUND: In December 2019, a novel coronavirus disease (COVID-19) broke out in Wuhan, China; however, the factors affecting the mortality of COVID-19 remain unclear. METHODS: Thirty-two days of data (the growth rate/mortality of COVID-19 cases) that were shared by Chinese National Health Commission and Chinese Weather Net were collected by two authors independently. Student's t-test or Mann-Whitney U test was used to test the difference in the mortality of confirmed/severe cases before and after the use of "Fangcang, Huoshenshan, and Leishenshan" makeshift hospitals (MSHs). We also studied whether the above outcomes of COVID-19 cases were related to air temperature (AT), relative humidity (RH), or air quality index (AQI) by performing Pearson's analysis or Spearman's analysis. RESULTS: Eight days after the use of MSHs, the mortality of confirmed cases was significantly decreased both in Wuhan (t = 4.5, P < 0.001) and Hubei (U = 0, P < 0.001), (t and U are the test statistic used to test the significance of the difference). In contrast, the mortality of confirmed cases remained unchanged in non-Hubei regions (U = 76, P = 0.106). While on day 12 and day 16 after the use of MSHs, the reduce in mortality was still significant both in Wuhan and Hubei; but in non-Hubei regions, the reduce also became significant this time (U = 123, P = 0.036; U = 171, P = 0.015, respectively). Mortality of confirmed cases was found to be negatively correlated with AT both in Wuhan (r =  - 0.441, P = 0.012) and Hubei (r =  - 0.440, P = 0.012). Also, both the growth rate and the mortality of COVID-19 cases were found to be significantly correlated with AQI in Wuhan and Hubei. However, no significant correlation between RH and the growth rate/mortality of COVID-19 cases was found in our study. CONCLUSIONS: Our findings indicated that both the use of MSHs, the rise of AT, and the improvement of air quality were beneficial to the survival of COVID-19 patients.

Assessing the Role of Intermolecular Interactions in a Perylene-Based Nanowire Using First-Principles Many-Body Perturbation Theory.

We present a first-principles many-body perturbation theory study of the role of intermolecular coupling in the optoelectronic properties of a one-dimensional (1D) π-stacked nanowire composed of perylene-3,4,9,10-tetracarboxylic diimide molecules on a DNA-like backbone. We determine that strong intermolecular electronic coupling results in large bandwidths and low carrier effective masses, suggesting a high-electron mobility material. Additionally, by including the role of finite-temperature phonons on optical absorption via a newly presented approach, we predict that the optical absorption spectrum  is significantly altered from that at zero temperature due to allowed indirect transitions, while the exciton delocalization and binding energy, a measure of intermolecular electronic interactions, remains constant. Overall, our studies indicate that strong intermolecular coupling can dominate the optoelectronic properties of π-conjugated 1D systems even at room temperature.

The effectiveness and safety of full-dose versus half-dose corticosteroid plus renin-angiotensin system blockers for IgA nephropathy.

BACKGROUND: Observational studies suggest that patients with immunoglobulin A nephropathy (IgAN) showed good responses to corticosteroids (CS) but experienced severe adverse effects. The authors conducted a cohort study to evaluate the effectiveness and safety of half-dose CS plus renin-angiotensin system blockers (RASB) (CS + RASB) versus full-dose CS in IgAN patients. METHODS: A total of 162 kidney biopsy-confirmed IgAN patients with protein excretion levels ⩾0.75 g/d and an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m2 were included. A total of 89 patients received half-dose CS + RASB (half CS + RASB), and 73 patients received full-dose CS (full CS). The primary outcomes were the complete remission rates and incidence of adverse events (AEs). The secondary outcomes included 24 h urinary protein (UP) levels and a combined event. RESULTS: Over the 18 months follow-up, the complete remission rates were 59% (53/89 patients) and 57% (42/73 patients) in the half CS + RASB and full CS groups (p = 0.88), respectively. A total of five patients suffered from serious AEs (SAEs) in the full CS group during the observation period, and no SAEs were observed in the half CS + RASB group (p = 0.012). The incidences of total AEs (p = 0.003) and infections (p = 0.01) were lower in the half CS + RASB group than in the full CS group. CONCLUSIONS: Although half CS + RASB versus full CS did not differ in terms of reducing proteinuria, therapy with half CS + RASB resulted in fewer AEs in the IgAN patients.

Comparative Efficacy of Drugs for Preventing Acute Kidney Injury after Cardiac Surgery: A Network Meta-Analysis.

BACKGROUND: Acute kidney injury (AKI) occurs frequently after cardiac surgery and has been associated with increased hospital length of stay, mortality, and costs. OBJECTIVE: We aimed to evaluate the efficacy of pharmacologic strategies for preventing AKI after cardiac surgery. METHODS: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) up to 6 May 2017 and the reference lists of relevant articles about trials. The outcome was the occurrence of AKI. This is the first network meta-analysis of the different prevention strategies using Bayesian methodology. RESULTS: The study included 63 articles with 19,520 participants and evaluated the effect of ten pharmacologic strategies to prevent AKI in patients undergoing cardiac surgery. Compared with placebo, the odds ratio (OR) for the occurrence of AKI was 0.24 [95% confidence interval (CI) 0.16-0.34] with natriuretic peptide, 0.33 (95% CI 0.14-0.70) with fenoldopam, 0.54 (95% CI 0.31-0.84) with dexmedetomidine, 0.56 (95% CI 0.29-0.95) with low-dose erythropoietin, 0.63 (95% CI 0.43-0.88) with levosimendan, 0.76 (95% CI 0.52-1.10) with steroids, 0.83 (95% CI 0.48-1.40) with high-dose erythropoietin, 0.85 (95% CI 0.64-1.14) with N-acetylcysteine, 0.96 (95% CI 0.69-1.29) with sodium bicarbonate, and 1.05 (95% CI 0.70-1.41) with statins. The surface under the cumulative ranking curve probabilities indicated that natriuretic peptide was the best treatment therapy and that fenoldopam ranked second. CONCLUSIONS: Natriuretic peptide is probably the preferred pharmacologic strategy to prevent AKI in adult patients undergoing cardiac surgery, especially in those at high risk of AKI.

Author Correction to: Comparative Efficacy of Drugs for Preventing Acute Kidney Injury after Cardiac Surgery: A Network Meta-Analysis.

In the print publication, the affiliations were incorrectly published. The author affiliations which previously read Xi Chen1 · Tianlun Huang2 · Xuan Cao1 · Gaosi Xu2 1Grade 2013, The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi, People's Republic of China 2Department of Nephrology, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Donghu District, 330006 Nanchang, Jiangxi, People's Republic of China.

Author Correction: PLK2 Plays an Essential Role in High D-Glucose-Induced Apoptosis, ROS Generation and Inflammation in Podocytes.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Treatment for non-thyroidal illness syndrome in advanced chronic kidney disease: a single-blind controlled study.

AIM: Non-thyroidal illness syndrome (NTIS) is common among patients with advanced chronic kidney disease (CKD) and is strongly associated with poor prognosis. However, it remains unclear in how to correct this disorder and this study aimed to evaluate the effectiveness of sodium bicarbonate (SB) and N-acetyl-cysteine (NAC) for correcting NTIS status. METHODS: Patients with CKD stage 3-4 were single-blind, placebo-controlled treated with placebo, SB, or NAC for 18 weeks. The primary end points were the correction of NTIS and the occurrence of end-stage renal disease (ESRD). The secondary point was the change in estimated glomerular filtration rate (eGFR) after the follow-up. RESULTS: The Kaplan-Meier survival analysis showed significant lower correcting ratio of NTIS in control group compared with SB group [Hazard ratio (HR) 0.19, 95 % confidence interval (CI) 0.04-0.89, p = 0.035] and NAC group (HR 0.09, 95 % CI 0.02-0.38, p = 0.001), and increased ESRD risk in control group than in SB group (HR 1.97, 95 % CI 1.02-3.84, p = 0.045) and NAC group (HR 5.50, 95 % CI 2.23-13.57, p < 0.001). The Cox regression analysis demonstrated significantly different effectiveness of placebo, SB and NAC on NTIS correction and ESRD risk, p < 0.05, respectively. Variance analysis displayed a greater reduction in eGFR in controls than in SB (p = 0.044) and NAC group (p < 0.001). CONCLUSION: SB and NAC are effective in promoting the recovery from NTIS status and delaying the deterioration of renal function in advanced CKD patients.

PLK2 Plays an Essential Role in High D-Glucose-Induced Apoptosis, ROS Generation and Inflammation in Podocytes.

Diabetic kidney disease (DKD) is a serious complication of hyperglycemia. Currently, there is no effective therapeutic intervention for DKD. In this study, we sought to provide a set of gene profile in diabetic kidneys. We identified 338 genes altered in diabetes-induced DKD glomeruli, and PLK2 exhibited the most dramatic change. Gene set enrichment analysis (GSEA) indicated multiple signaling pathways are involved DKD pathogenesis. Here, we investigated whether PLK2 contributes to podocyte dysfunction, a characteristic change in the development of DKD. High D-glucose (HDG) significantly increased PLK2 expression in mouse podocytes. Suppressing PLK2 attenuated HDG-induced apoptosis and inflammatory responses both in vitro and in vivo. NAC, an antioxidant reagent, rescued HDG and PLK2 overexpression-induced kidney injuries. In summary, we demonstrated that silencing PLK2 attenuates HDG-induced podocyte apoptosis and inflammation, which may serve as a future therapeutic target in DKD.

ARHGAP24 inhibits cell cycle progression, induces apoptosis and suppresses invasion in renal cell carcinoma.

Renal cell carcinoma (RCC) is the major cause of kidney malignancy-related deaths. Rho GTPases are key regulators in cancer cell metastasis. ARHGAP24, a Rac-specific member of the Rho GTPase-activating protein family, acts as a functional target of cancer cell migration and invasion. In the present study, we identified ARHGAP24 expression is downregulated in renal cancer tissues and is highly correlated with long-term survival in RCC patients. Therefore, we investigated the biological functions of ARHGAP24 in renal cancer cells. Ectopic expression of ARHGAP24 resulted in inhibited cell proliferation and arrested cell cycle in two renal cancer cell lines (786-0 and Caki-2); the results were confirmed by ARHGAP24 knocking down. In addition, ARHGAP24 significantly reduced the cell invasion ability and induced apoptosis in renal cancer cells. In addition, overexpressing ARHGAP24 impaired tumor formation in vivo. In summary, our results illustrated that ARHGAP24 plays a unique role in RCC progression as a tumor repressor.

A Finite Element Study of the Dynamic Response of Brain Based on Two Parasagittal Slice Models.

The objective of this study is to investigate the influence of gyri and sulci on the response of human head under transient loading. To this end, two detailed parasagittal slice models with and without gyri and sulci have been developed. The models comprised not only cerebrum and skull but also cerebellum, brain stem, CSF, and corpus callosum. In addition, white and gray matters were separated. The material properties were adopted from the literature and assigned to different parts of the models. Nahum's and Trosseille's experiments reported in relevant literature were simulated and the simulation results were compared with the test data. The results show that there is no evident difference in terms of intracranial pressure between the models with and without gyri and sulci under simulated conditions. The equivalent stress below gyri and sulci in the model with gyri and sulci is slightly higher than that in the counterpart model without gyri and sulci. The maximum principle strain in brain tissue is lower in the model with gyri and sulci. The stress and strain distributions are changed due to the existence of gyri and sulci. These findings highlight the necessity to include gyri and sulci in the finite element head modeling.

Hepatitis B virus-associated glomerular nephritis in East Asia: progress and challenges.

BACKGROUND: Hepatitis B virus-associated glomerular nephritis (HBV-GN) is the most common secondary glomerulonephritis in East Asia. Part of the patients developed to renal insufficiency within 10 years, which cause a great burden for patients' family and society. METHODS: We reviewed basic and clinical research work in China, Japan, Korea, and Mongolia, eastern part of Asia. Comparisons between data from East Asia and those from other regions were made. RESULTS: The genetic variations conferring susceptibility to HBV-GN and disease progression as well as the pathogenic role in HBV-GN progression were investigated. Clinical features of HBV-GN in East Asia were different from that of other regions in the world. Clinical trials showed that treatment with anti-viral agents was effective to promote the disease remission. CONCLUSION: HBV-GN remains a great challenge to East Asian nephrologists. In-depth basic studies and multi-centered clinical trials are needed in the future.