Persistently elevated sFlt-1 and recovery of reduced ADAMTS13 activity in malignant hypertension.

BACKGROUND AND OBJECTIVES: Malignant hypertension (MHT) characterized by acute hypertension with retinopathy or multiorgan damage, is a severe form of hypertensive emergency and associated with target organ involvement and poor kidney outcome. However, the underlying mechanisms are unclear. METHODS: Eighty-four patients with acute severe hypertension from the Nephrology Department and Emergency Department in a single center during January 2016 and December 2017 were prospectively enrolled and divided into MHT ( n  = 48) and non-MHT ( n  = 36) subgroups according to target organ evaluation. Forty healthy controls were recruited. Serum soluble Fms-like tyrosine kinase-1 (sFlt-1) levels and plasma ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity were examined at baseline and 12-month follow-up. Renal endpoints were defined as a significant decrease in the estimated glomerular filtration rate (eGFR) of more than 40% or the occurrence of end-stage renal disease. RESULTS: Serum sFlt-1 levels were persistently elevated in MHT. Baseline serum sFLT-1 levels were correlated with plasma ADAMTS13 activity and markers of target organ damage. Plasma ADAMTS13 activity was reduced in both MHT and non-MHT patients and recovered to the normal range at 12-month follow-up. During an average follow-up time of 53 ±â€Š13 months, the restoration of reduced ADAMTS13 activity was correlated with the improvement of kidney function and independently reduced the risk of renal endpoints. CONCLUSIONS: Abnormal angiogenesis and endothelial damage are involved in the pathophysiology of hypertensive emergency. Evaluation of ADAMTS13 and sFlt-1 may help in the diagnosis and assessment of MHT. Recovery of ADAMTS13 predicts better renal outcome in patients with hypertensive emergencies.

C3aR Antagonist Alleviates C3a Induced Tubular Profibrotic Phenotype Transition via Restoring PPARα/CPT-1α Mediated Mitochondrial Fatty Acid Oxidation in Renin-Dependent Hypertension.

BACKGROUND: Renin-dependent hypertension with tubulointerstitial injury remains a problem with high prevalence in the clinic. However, whether and how renin participates in tubulointerstitial injury remains incompletely understood. New evidence suggests that renin cleaves C3 into C3a and C3b. In the present study, we aimed to explore the role of renin-mediated C3a/C3a receptor (C3aR) signaling in renin-dependent hypertension-induced kidney injury and illustrate the detailed mechanisms. METHODS: C3a concentration changes in serum from healthy volunteers incubated with recombinant renin were detected by ELISA. C3aR expression in human tubular epithelial cells was evaluated in renal biopsy sections from malignant arteriolonephrosclerosis and benign arteriolonephrosclerosis patients. C3aR changes in human kidney 2 (HK2) cells were detected after the cells were treated with human serum, renin and aliskiren. The C3a analogue and C3aR antagonist SB290157 were used to stimulate HK2 cells to explore the downstream signaling of C3a/C3aR activation. For in vivo studies, two-kidney, one-clipped (2K1C) hypertensive rat model was established to simulate renin-dependent hypertension conditions. C3a and C3aR expression was detected in the clipped kidneys. SB290157 was injected intraperitoneally to block C3a/C3aR signaling in 2K1C rats. RESULTS: The results showed that renin cleaved C3 into C3a and activated C3a/C3aR signaling in tubular epithelial cells (TECs) from both humans and rats. In vitro results demonstrated that C3a/C3aR activation impaired peroxisome proliferator-activated receptor alpha (PPARα)/carnitine palmitoyltransterase-1alpha (CPT-1α)-mediated mitochondrial fatty acid oxidation (Mito FAO) in HK2 cells and induced HK2 cell transition to a profibrotic phenotype, which was inhibited by treatment with the C3aR antagonist SB290157. In vivo results showed that renin mRNA levels, C3a concentrations, C3aR levels and tubulointerstitial fibrosis increased concurrently in the clipped kidney cortex of 2K1C rats. Treatment with the C3aR antagonist SB290157 significantly mitigated the effect of renin induction of C3aR expression and alleviated renin-dependent hypertension-induced tubulointerstitial fibrosis by improving PPARα/CPT-1α-mediated Mito FAO in TECs, as well as inhibiting tubular profibrotic phenotype transition. CONCLUSIONS: Our results prove that renin activates C3a/C3aR signaling to promote renal tubulointerstitial fibrosis by impairing PPARα/CPT-1α-mediated tubular Mito FAO. SB290157 confers a potential therapeutic approach for renin-dependent hypertension-induced kidney injury.

High-Mobility Magnetic Two-Dimensional Electron Gas in Engineered Oxide Interfaces.

The engineered interfaces of complex oxides have abundant physical properties and provide a powerful platform for the exploration of fundamental physics and emergent phenomena. In particular, research on the two-dimensional magnetic systems with high mobility remains a long-standing challenge for the discovery of quantum phase and spintronic applications. Here, we introduce a few atomic layers of the delta doping layer at LaAlO3/SrTiO3 interfaces through elaborately controllable epitaxial growth of SrRuO3. After inserting a SrRuO3 buffer layer, the interfaces exhibit a well-defined anomalous Hall effect up to 100 K and their mobility is enhanced by 3 orders of magnitude at low temperatures. More intriguingly, a large unsaturated positive magnetoresistance is created at interfaces. Combining with the density functional theory calculation, we attribute our findings to the electron transfer at interfaces and the magnetic moment of Ru4+ 4d bands. The results pave a way for further research of two-dimensional ferromagnetism and quantum transport in all-oxide systems.

Association between different infection profiles and one-year outcomes in ANCA-associated vasculitis: a retrospective study with monthly infection screening.

OBJECTIVES: This study aimed to explore clinical features of early infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and to identify the association between the infection profile of patients with AAV during the first 3 months and 1-year survival. METHODS: A total of 415 newly diagnosed patients with AAV in the Department of Nephrology at Shanghai Ruijin Hospital from 2000 to 2018 were included. Four Cox regression models were used to analyse the association based on demographics, comorbidities, laboratory baseline index and therapy parameter. Infection screening was carried out monthly during the first 3 months after diagnosis. RESULTS: In all, 377 episodes of infection were identified among 220 patients during the first 3 months. The overall survival after 1 year was 73.0%. Respiratory infection (210 episodes/164 persons) accounted for more than half of infections. Infection was independently associated with 1-year mortality (adjusted HR 2.32, 95% CI 1.27 to 4.23, p=0.006) after adjustment. Respiratory infection (adjusted HR 4.36, 95% CI 2.86 to 8.06, p<0.001), Gram-negative bacterial infection (adjusted HR 1.71, 95% CI 1.01 to 2.91, p=0.047) and fungal infection (adjusted HR 1.77, 95% CI 1.07 to 2.94, p=0.026) was identified as a risk factor for 1-year mortality. Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis (adjusted HR 0.55, 95% CI 0.31 to 0.97, p=0.040) was protective for 1-year mortality. CONCLUSIONS: Infections, particularly respiratory infections, are a common and important class of complication in patients with AAV and are associated with early mortality. TMP-SMX prophylaxis might be necessary to improve short-term outcome. More consideration of infectious risk and regular infection screening should be given.

eEF2K as a novel metastatic and prognostic biomarker in gastric cancer patients.

BACKGROUND: Although eukaryotic elongation factor 2 kinase (eEF2K) has been reported to be a potential oncogenic factor in many human cancers, its usefulness as a clinical prognostic biomarker for gastric cancer has not been investigated. METHODS: In this study, data about 540 patients with stomach adenocarcinoma (STAD) were analyzed from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases to determine the expression of eEF2K. Immunohistochemistry (IHC), western blots, and real-time polymerase chain reaction (RT-PCR) were also performed to determine the clinical significance of eEF2K expression in 96 postoperative patients with gastric cancer. Among the 96 patients, 36 had low expression of eEF2K and 60 had high expression. RESULTS: Analysis of the TCGA and GEO datasets revealed that eEF2K expression was significantly higher in the STAD tissue samples than in the non-tumorous gastric tissues. IHC, western blots, and RT-PCR confirmed these findings. The high expression level of eEF2K was found to be related to the presence of lymph node metastasis (p = 0.002). Moreover, multivariate analysis showed that eEF2K was an independent indicator of prognosis for overall survival (OS) (hazard ratio [HR] = 1.72, 95% confidence interval [CI] = 1.06-2.79; p = 0.03) and disease-free survival (DFS) (HR = 1.66, 95% CI = 0.997-2.765; p = 0.052) in patients with surgically resected STAD. CONCLUSION: Collectively, our findings suggest that eEF2K is a clinical indicator of metastatic and prognostic significance for STAD survival and could serve as a potential therapeutic target.

Hormonal factors in association with lung cancer among Asian women: A pooled analysis from the International Lung Cancer Consortium.

Two thousand sixty-four lung cancer cases and 5342 controls were evaluated in this International Lung Cancer Consortium (ILCCO) pooled analysis on estrogen-related hormonal factors and lung cancer in Asian women. Random effect of study site and fixed effect of age, smoking status, comprehensive smoking index and family history of lung cancer were adjusted for in the multivariable logistic regression models. We found that late onset of menarche conferred elevated odds of lung cancer with adjusted odds ratio (OR) of 1.24 (95% confidence interval [CI] = 1.05, 1.45) for 17 years or older, compared to 14 years or younger. Late onset of menopause at 55 years old or older was associated with lung cancer with OR = 1.24 (95% CI = 1.02, 1.51). Nonnatural menopause was associated with an OR of 1.39 (95% CI = 1.13, 1.71). More live births showed reversed association with lung cancer (ORs of 5 or more live births: 0.71 (95% CI = 0.60, 0.84), compared to 0-2 live births (Ptrend < 0.001). A later first child delivery seemed associated with an increased susceptibility: OR of 21 to 25 years old: 1.23 (95% CI = 1.06, 1.40), 26 or older: 1.27 (95% CI = 1.06, 1.52), Ptrend = .010). The use of oral contraceptives appeared to be protective with an OR of 0.69 (95% CI = 0.57, 0.83). Stronger for adenocarcinoma than squamous cell carcinoma, these relationships were not clearly modified by smoking status, probably because of lower prevalence of smoking. This is a first and largest pooling study of lung cancer among Asian women and the results suggested potential roles of hormone-related pathways in the etiology of this disease.

Probable risk factors of internal jugular vein stenosis in Chinese patients-A real-world cohort study.

OBJECTIVES: Extracranial venous anomalies, especially internal jugular vein stenosis (IJVS), have recently received increasing attention, however, its etiologies are uncertain. This study aimed to explore the probable risk factors of IJVS in Chinese PATIENTS AND METHODS: Eligible patients with IJVS confirmed by contrast-enhanced magnetic resonance venography (CE-MRV) were enrolled from October 2017 through October 2018. Probable risk factors were analyzed, including the conditions that may result in IJV wall damage, extraluminal compression, gender and age. RESULTS: A total of 133 patients enrolled in the final analysis, including 73 females and 60 males, the mean age were 54.83 ±â€¯15.25 years. In this IJVS cohort, the top two risks were previous hepatitis B virus (HBV) infection (48.9 %) and osseous compression (41.4 %). The IJVS cohort was divided into two subsets: extraluminal compression and non-compression. In the former, osseous compression (80.9 %) was the top risk factor, other risks including arterial (22.1 %) and lymph node compression (2.9 %). While, in the latter subset, the most common risk factor was previous HBV infection (46.2 %). In addition, cerebral venous sinus thrombosis (CVST) in non-compression subset was more common than that in extraluminal compression subset (21.5 % VS. 2.9 %, p = 0.001). When considered the gender (Male vs. Female), the ratios were 28.3 % vs. 0 % of smoking, p < 0.001, 16.67 % vs. 1.37 % of hyperhomocysteinemia, p = 0.002, and 11.67 % vs. 1.37 % of hyperuricemia, p = 0.023. In the subset with age less than 45 years, the top three risks included CVST (56.25 %), immunological diseases (55.56 %), and hyperhomocysteinemia (50.00 %), while, in the subset with the ages over 60 years, type-2 diabetes (66.66 %), carotid artery compression (53.33 %), previous HBV infection (52.31 %), and osseous compression (49.09 %) were more common than others. CONCLUSION: This study illustrates the probable risks of IJVS may be diverse, in which osseous compression and previous HBV infection may be the top two probable risks of IJVS in Chinese. This is the biggest difference from previous reports based on Caucasian.

Tobacco Smoking Modifies the Association between Hormonal Factors and Lung Cancer Occurrence among Post-Menopausal Chinese Women.

Inconsistent evidence has been reported on the role of female hormonal factors in the development of lung cancer. This population-based case-control study evaluated the main effect of menstrual/reproductive factors on the risk of lung cancer, and the effect modification by smoking status. Multivariable unconditional logistic regression models were applied adjusted for age, income, education, county of residence, body mass index, smoking status, pack-years of smoking, and family history of lung cancer. Among 680 lung cancer cases and 1,808 controls, later menopause (at >54 vs. <46 years old) was associated with increased risk of lung cancer (SBOR, semi-Bayes adjusted odds ratio = 1.61, 95% PI, posterior interval = 1.10-2.36). More pregnancies (2 or 3 vs. 0 or 1) was associated with decreased risk (SBOR = 0.71, 95% PI = 0.53, 0.95). Ever being a smoker and having two or fewer pregnancies in one's lifetime could jointly increase the odds of lung cancer (RERI, relative excess risk due to interaction = 1.71, 95% CI = 0.03, 3.38). An increased number of ovulatory cycles was associated with increased risk of lung cancer (SBOR for 13 ovulatory cycles = 1.02, 95% CI = 1.00+, 1.04).

Modulated Transport Behavior of Two-Dimensional Electron Gas at Ni-Doped LaAlO3/SrTiO3 Heterointerfaces.

Modulating transport behaviors of two-dimensional electron gases are of critical importance for applications of the next-generation multifunctional oxide electronics. In this study, transport behaviors of LaAlO3/SrTiO3 heterointerfaces modified through the Ni dopant and the light irradiation have been investigated. Through the Ni dopant, the resistances increase significantly and a resistance upturn phenomenon due to the Kondo effect is observed at T < 40 K. Under a 360 nm light irradiation, the interfaces exhibit a persistent photoconductivity and a suppressed Kondo effect at low temperature due to the increased mobility measured through the photo-Hall method. Moreover, the relative changes in resistance of interfaces induced by light are increased from 800 to 6600% at T = 12 K with increasing the substitution of Ni, which is discussed by the band bending and the lattice effect due to the Ni dopant. This work paves the way for better controlling the emerging properties of complex oxide heterointerfaces and would be helpful for photoelectric device applications based on all-oxides.

Tunability of Band Gap and Photoluminescence in CH3NH3PbI3 Films by Anodized Aluminum Oxide Templates.

Hybrid organic-inorganic halide CH3NH3PbI3 perovskite films are deposited on anodized aluminum oxide templates with the different pore diameters via one-step spin coating method. The obvious 0.082 eV blue shift of optical band gap is observed in films with decreasing the diameters of pores from 400 to 30 nm. And numerical simulations based on finite element modeling are carried out to represent the absorption edge and consistent with the experiment results. It is interesting that the films show the intense photoluminescence with the excitation intensity of less than 1 µW. Moreover, the photoluminescence intensity is increased with increasing pore diameters, which is attributed to the radiative recombination rate of photogenerated electrons and holes. These results pave a way for the further understanding of tunable photophysical properties of perovskite films.

MUC5B promoter polymorphisms and risk of coal workers' pneumoconiosis in a Chinese population.

Coal workers' pneumoconiosis (CWP) is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Genetic variations have been recognized to be involved in the multi-factorial susceptibility to CWP, and MUC5B is a candidate lung fibrosis susceptibility gene. In the present study, we investigated possible genetic associations between three single nucleotide polymorphisms in MUC5B promoter region and CWP in a case-control study including 686 CWP patients and 680 controls. Genotyping was carried out by TaqMan method. Only rs2672794 allele and genotype frequencies distributions were significantly different between CWP patients and controls (P = 0.017 and 0.046 for allele and genotype, respectively). The MUC5B rs2672794 CC genotype was associated with a significantly increased risk of CWP, compared with the TT genotype. Moreover, individuals with TC/CC genotype had an obviously increased risk of CWP than those with TT genotype, particularly among subgroups of dust exposure <27 years and smokers. This is the first report showing an association between the MUC5B rs2672794 polymorphism and CWP, and our results suggest that MUC5B rs2672794 CC genotype could increase the risk of CWP. Further studies are warranted to confirm our findings.