Corin, a transmembrane serine protease that can cleave pro‐atrial natriuretic peptide (Pro‐ANP) into smaller bioactive molecule atrial natriuretic peptide, has been shown to be involved in the ...pathophysiology of hypertension, cardiac hypertrophy. We sought to examine the associations of corin genetic variations with salt sensitivity, blood pressure (BP) changes and hypertension incidence. We studied participants of the original Baoji Salt‐Sensitive cohort, recruited from 124 families from seven Chinese villages in 2004 who sequentially received a usual baseline salt diet, a 7‐day low salt diet (3 g/day) and a 7‐day high salt diet (18 g/day), respectively. They were followed up for 8 years (in 2009, 2012) to evaluate the development of hypertension. Corin SNP rs3749584 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) response to low‐salt diet, while rs4695253, rs17654278 were associated with pulse pressure (PP) response to low‐salt diet. SNPs rs4695253, rs12509275, rs2351783, rs2271036, rs2271037 were significantly associated with systolic BP (SBP), DBP, and MAP responses to high‐salt diet. In addition, SNPs rs12641823, rs6834933, rs2271036, and rs22710367 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP over 8 years of follow‐up. SNP rs73814824 was significantly associated with the incidence of hypertension over 8 years. Gene‐based analysis showed that corin gene was significantly associated with longitudinal BP changes and hypertension incidence after 8‐year follow‐up. This study suggests that corin may play a role in salt sensitivity, BP progression, and development of hypertension.
Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and ...urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low‐salt diet (3.0 g) for 7 days, and a high‐salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt‐Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high‐salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high‐salt diet than on a low‐salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high‐salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low‐salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.
Neural precursor cell expressed developmentally downregulated 4‐like (NEDD4L), a member of the E3 ubiquitin‐protein ligases, encoded by NEDD4L gene, was found to be involved in in salt sensitivity by ...regulating sodium reabsorption in salt‐sensitive rats. The authors aimed to explore the associations of NEDD4L genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in Chinese adults. Participants from 124 families in Northern China in the Baoji Salt‐Sensitive Study Cohort in 2004, who received the chronic salt intake intervention, including a 7‐day low‐salt diet (3.0 g/day) and a 7‐day high‐salt diet (18 g/day), were analyzed. Besides, the development of hypertension over 14 years was evaluated. NEDD4L single nucleotide polymorphism (SNP) rs74408486 was shown to be significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low‐salt diet, while SNPs rs292449 and rs2288775 were significantly associated with pulse pressure (PP) response to high‐salt diet. In addition, SNP rs4149605, rs73450471, and rs482805 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP at 14 years of follow‐up. SNP rs292449 was significantly associated with hypertension incidence over the 14‐year follow‐up. Finally, this gene‐based analysis found that NEDD4L was significantly associated with longitudinal BP changes and the incidence of hypertension over the 14‐year follow‐up. This study indicated that gene polymorphism in NEDD4L serve an important function in salt sensitivity, longitudinal BP change and development of hypertension in the Chinese population.
Albuminuria is a marker of vascular dysfunction and is associated with chronic renal and cardiovascular diseases. Data on the association between the longitudinal patterns of weight change early in ...life and albuminuria later in life are limited. We aimed to identify the body mass index (BMI) trajectory across a 30-year span and evaluate its association with middle-age albuminuria.
Of the 4623 participants aged 6–18-year-old recruited by Hanzhong Adolescent Hypertension Study cohort in northern China from March 10, 1987 to June 3, 2017, a total of 1,825 participants followed up with 6 visits over 30 years were enrolled. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analyses. Albuminuria was defined as a urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g.
Three distinct BMI trajectories were identified: low-increasing (n = 671, 36.8%), moderate-increasing (n = 940, 51.5%), and high-increasing (n = 214, 11.7%); male participants exhibited a steeper increase in BMI than females. The uACR was increased linearly from the low- to high-increasing group. A total of 201 individuals developed albuminuria, with an incidence of 11.0%. Compared with the low-increasing group, the odds ratio (OR) of albuminuria in middle age was 2.13(95% confidence interval CI: 1.26 to 3.61) for the high-increasing group after full adjustment for age, sex, smoking, alcohol consumption, marital status, systolic blood pressure, diabetes, and hyperlipidemia. The unadjusted ORs of the high-increasing BMI group were 5.08 (2.76–9.37) for males and 3.45 (1.78–6.69) for females, and the association remained significant in males in the fully adjusted models.
Higher BMI trajectories are associated with higher uACR and an increased risk of albuminuria in middle age, especially in males. Identifying long-term BMI trajectories from an early age may assist in predicting the risk of renal diseases and cardiovascular disease later in life.
This work was supported by the National Natural Science Foundation of China (81600327, 82070437, 81870319, 82070549, and 82170437), Natural Science Basic Research Program of Shaanxi Province (2021JM-257 and 2021JM-588), Institutional Foundation of the First Affiliated Hospital of Xi'an Jiaotong University (2019QN-06 and 2021ZXY-14), the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University of China (XJTU1AF-CRF-2019-004, XJTU1AF2021CRF-021, and XJTU1AFCRF-2017-021), Research Incubation Fund of Xi'an People's Hospital (FZ-61), Grants from the Major Chronic Non-communicable Disease Prevention and Control Research Key Project of the Ministry of Science and Technology of China (2017YFC1307604 and 2016YFC1300104).
Background:
Uromodulin, also named Tamm Horsfall protein, has been associated with renal function and regulation of sodium homeostasis. We aimed to examine the associations of serum uromodulin levels ...and its genetic variants with longitudinal blood pressure (BP) changes and hypertension incidence/risk.
Methods:
A total of 514 participants from the original Baoji Salt-Sensitive Study cohort were genotyped to examine the associations of genetic variations in uromodulin gene with the longitudinal BP changes and the incidence of hypertension over 8 years of follow-up. In addition, 2,210 subjects from the cohort of Hanzhong Adolescent Hypertension Study were used to investigate the relationships between serum uromodulin levels and the risk of hypertension.
Results:
SNPs rs12917707 and rs12708631 in the uromodulin gene were significantly associated with the longitudinal BP changes over 8 years of follow-up. SNP rs12708631 was significantly associated with the incidence of hypertension over 8 years. In addition, gene-based analyses supported the associations of uromodulin gene with the longitudinal BP changes and hypertension incidence in Baoji Salt-Sensitive Study cohort. Furthermore, serum uromodulin levels in the hypertensive subjects were lower than in the normotensive subjects (25.5 ± 1.1
vs
. 34.7 ± 0.7 ng/mL). Serum uromodulin levels decreased gradually as BP levels increased (34.6, 33.2, 27.8, and 25.0 ng/mL for subjects with normotension, high-normal, grade 1 hypertension, and grade 2 hypertension, respectively). Serum uromodulin was significantly associated with the lower risk of hypertension 0.978 (0.972–0.984) in Hanzhong Adolescent Hypertension Study cohort.
Conclusion:
This study shows that uromodulin is associated with blood pressure progression and development of hypertension.
This study systematically compared the efficacy and safety of simultaneous hepatectomy and splenectomy (HS) with hepatectomy (H) alone in patients with hepatocellular carcinoma (HCC) and ...hypersplenism.
The PubMed, Web of Science, Science Direct, EMBASE, and Cochrane Library databases were systematically searched by two independent researchers through to March 31, 2015 to identify relevant studies. All the extracted literature were managed by Bibliographic citation management software. Quality assessment of the included studies was performed using a modified Newcastle-Ottawa Scale judgment. The data were analyzed using RevMan5.2 software.
Eight studies including a total of 761 patients with HCC and hypersplenism (360 in the HS group, 401 in the H group) were finally included in the analysis. Outcomes, including postoperative complications, perioperative mortality, operation time, 5-year survival rate, and need for blood transfusion did not differ significantly between the two groups. HS was associated with significantly more intraoperative bleeding (mean difference MD 57.15, 95% confidence interval CI 18.83-95.46, P=0.003), and CD4/CD8 ratio (MD 0.69, 95% CI 0.61-0.77, P<0.00001), CD4 subset, platelet count (MD 213.06, 95% CI 202.59-223.53, P<0.0001), white blood cell count (MD 4.85, 95% CI 4.58-5.13, P<0.0001), interferon-gamma levels (MD 18.52, 95% CI 13.93-23.11, P<0.00001), and interleukin-2 levels (MD 20.73, 95% CI 16.05-25.41, P<0.0001). In addition, lower CD8 subset (MD -7.85, 95% CI -9.07, -6.63, P<0.00001) and interleukin-10 levels (MD -18.56, 95% CI -22.61, -14.50, P<0.00001) were observed for HS.
We identified that simultaneous HS do not increase postoperative complications, operation time, or perioperative mortality in patients with HCC and hypersplenism. Simultaneous splenectomy can increase postoperative white blood cell and platelet counts significantly, improve blood coagulation, reduce the incidence of postoperative bleeding, and enhance immunity. Therefore, HS is safe, effective, and feasible for patients with HCC and hypersplenism.
BackgroundTo investigate the best interval time between gastric preparation and magnetic-controlled capsule endoscopy by comparing the effect of various interval time on image quality of stomach, ...safety, tolerance and positive lesions through a randomized controlled trial.Methods80 patients referred for MCE from Jan. 2018 to Dec. 2018 were randomly assigned to three groups, interval time with 30 minute and less (A), 30 to 60 minutes (B) or 60 minutes and more (C). All patients fasted for at least 8 hours before MCE and administrated with dimethicone, pronase and sodium bicarbonate. Cleanliness and visualization scores, safety, tolerability, additional water required and diagnostic sensitivity were compared. A multi-factor analysis of cleanliness and visualization scores was conducted.ResultsThe total cleanliness scores were (mean±SD) 20.44±2.61 (A), 20.96±1.68 (B), and 20.56±2.90 (C). The total visualization scores (mean±SD) were 16.33±2.01 (A), 16.41±1.50 (B), and 16.07±1.96 (C). There was no statistical difference among groups A, B and C (P>0.05). MCE detected positive findings in 16 (59.3%), 18(66.7%) and 15 (55.6%) patients in group A, B and C respectively, with no significant difference between groups (P>0.05). Additional water required during MCE were (mean±SD) 107.41±70.31 mL(A),46.30±39.04 mL(B),79.63±65.43 mL(C), and it was much less in group B than the other two groups (P=0.003). There was a negative correlation between cleanliness and visualization scores and the infection of H. pylori (rs=-0.326, P=0.003 and rs=-0.235, P=0.035).ConclusionsPatients administrated with dimethicone, pronase and sodium bicarbonate 30 minute and less, 30 to 60 minutes, 60 minutes and more were not statistically different in cleanliness, visualization and positive rates. But groups of 30 to 60 minutes got the least supplement of water during MCE, and it may be the best interval time between gastric preparation and MCE.
Corticosteroid resistance (CR) is a serious disadvantage in treating many chronic inflammatory conditions. Eosinophils are the main inflammation cells in allergic reactions. Environmental pollution, ...such as PM2.5, is associated with the pathogenesis of allergic disorders. The objective of this study is to elucidate the mechanism by which the exposure to PM2.5 confers eosinophil CR status.
Patients with allergic rhinitis were recruited and assigned to corticosteroid sensitive (CS) and CR groups. Eosinophils were purified from nasal lavage fluids collected from patients with allergic rhinitis. A murine AR mouse model was developed with dust mite allergens and PM2.5 as the sensitization reagents.
CR status was detected in about 60% eosinophil collected in patients with AR. Upon exposure to eosinophil activators, CS eosinophils released a large quantity of mediators, which was suppressed by the presence of steroids in the culture. CR eosinophils demonstrated resistance to steroidal therapy. RAS activation levels in eosinophils were higher in CR eosinophils than in CS eosinophils. Higher expression of the Son of sevenless-1 (Sos1) was detected in CR eosinophils, which formed a complex with RAS and glucocorticoidreceptor-α in CR eosinophils to prevent the binding between steroids and glucocorticoidreceptor-α. The presence of an Sos1 inhibitor dissociated glucocorticoid receptor-α from RAS/Sos1 complex, that restored the sensitivity to steroids in eosinophils. Administering the Sos1 inhibitor effectively attenuated the experimental allergic rhinitis.
CR status was detected in approximately 1/3 eosinophils sampled from patients with allergic rhinitis. Sos1 was instrumental in the development and perseverance of CR in eosinophils. Sos1 inhibition restored sensitivity to steroids in CR eosinophils, which effectively reduced experimental allergic rhinitis.
Inorganic nanomaterials have attracted substantial research interest due to their unique intrinsic physicochemical properties. We highlighted recent advances in the applications of inorganic ...nanoparticles regarding their imaging efficacy, focusing on tumor-imaging nanomaterials such as metal-based and carbon-based nanomaterials and quantum dots. Inorganic nanoparticles gain excellent in vivo tumor-imaging functions based on their specific characteristics of strong near-infrared optical absorption and/or X-ray attenuation capability. The specific response signals from these novel nanornaterials can be captured using a series of imaging techniques, i.e., optical coherence tomography （OCT）, X-ray computed tomography （CT） imaging, two-photon luminescence （TPL）, photoacoustic tomography （PAT）, magnetic resonance imaging （MRI）, surface-enhanced Raman scattering （SERS） and positron emission tomography （PET）. In this review, we summarized the rapid development of inorganic nanomaterial applications using these analysis techniques and discussed the related safety issues of these materials.
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