Identification of Novel Phenotypes Correlated with CKD: A Phenotype-Wide Association Study.

Background: A comprehensive understanding of phenotypes related to CKD will facilitate the identification and management of CKD. We aimed to panoramically test and validate associations between multiple phenotypes and CKD using a phenotype-wide association study (PheWAS). Methods: 15,815 subjects from cross-sectional cohorts of the National Health and Nutrition Examination Survey (1999-2006) were randomly 50:50 split into training and testing sets. CKD was defined as eGFR < 60 mL/min/1.73m2. We performed logistic regression analyses between each of 985 phenotypes with CKD in the training set (false discovery rate < 1%) and validated in the testing set (false discovery rate < 1% ). Random forest (RF) model, Nagelkerke's Pseudo-R2, and the area under the receiver operating characteristic (AUROC) were used to validate the identified phenotypes. Results: We identified 18 phenotypes significantly related to CKD, among which retinol, red cell distribution width (RDW), and C-peptide were less researched. The top 5 identified phenotypes were blood urea nitrogen (BUN), homocysteine (HCY), retinol, parathyroid hormone (PTH), and osmolality in RF importance ranking. Besides, BUN, HCY, PTH, retinol, and uric acid were the most important phenotypes based on Pseudo-R2. AUROC of the RF model was 0.951 (full model) and 0.914 (top 5 phenotypes). Conclusion: Our study demonstrated associations between multiple phenotypes with CKD from a holistic view, including 3 novel phenotypes: retinol, RDW, and C-peptide. Our findings provided valid evidence for the identification of novel biomarkers for CKD.

[Risk Factor Analysis of Abdominal Aortic Enlargement after Thoracic Endovascular Aortic Repair Using Two-Stent Graft Implantation for Stanford Type B Aortic Dissection].

Objective: To explore the risk factors of abdominal aortic enlargement (AAE) after thoracic endovascular aortic repair using two-stent graft implantation (TEVAR-TSI) for Stanford type B aortic dissection. Methods: The clinical and imaging data of patients who underwent TEVAR-TSI for Stanford type B aortic dissection in the First Affiliated Hospital of Hebei North University from January 2013 through September 2020 were retrospectively collected and analyzed. CT angiography (CTA) scans were performed before the procedure. Follow-up CTA scans were scheduled and performed in 1, 3, 6, and 12 months after the procedure and annually thereafter. The primary outcome was AAE. The risk factors of AAE after TEVAR-TSI were selected and survival analysis and multivariate logistic regression were conducted accordingly. Results: A total of 146 patients were regularly followed up at our hospital, with the median followup time of the entire cohort being 48 months (ranging from 12 to 84 months). During the followup period after TEVAR-TSI, the incidence of AAE was 19.9% (29/146). A total of 29 patients developed AAE (the AAE group), while 117 patients did not develop AAE (the non-AAE group). There were a total of 27 deaths, including 13 in the non-AAE group versus 14 in the AAE group. Distal aortic reoperation was performed on 10 patients, including 4 in the non-AAE group versus 6 in the AAE group. The cumulative long-term survival and freedom from distal aortic reoperation of the non-AAE group were both significantly better those of the AAE group ( P<0.05). Logistic multivariate regression analysis showed that independent risk factors of AAE after TEVAR-TSI included the following, partial thrombosis of the false lumen (odds ratio [ OR]=4.090, 95% confidence interval [ CI]: 1.539-10.867, P=0.005), the longer cumulative diameter of residual intimal tear above the level of the lowest renal arteries ( OR=1.290, 95% CI: 1.164-1.429, P=0.000), and shorter cumulative diameter of residual intimal tear below the level of the lowest renal arteries ( OR=0.487, 95% CI: 0.270-0.878, P=0.017). Conclusion: The prognosis of patients who developed AAE after TEVAR-TSI was not good. During followup visits, as precautions against the development of AAE, close attention should be paid to partial thrombosis of the false lumen, cumulative diameter of residual intimal tear above the level of the lowest renal arteries, and cumulative diameter of residual intimal tear below the level of the lowest renal arteries.

[The Characteristics of Aortic Remodeling after Thoracic Endovascular Aortic Repair using Two-stent Graft Implantation for Stanford Type B Aortic Dissection].

OBJECTIVE: To investigate the characteristics of aortic remodeling after thoracic endovascular aortic repair using two-stent graft implantation (TEVAR-TSI) for Stanford B aortic dissection. METHODS: The clinical and imaging data of 128 patients who underwent TEVAR-TSI for Stanford B aortic dissection in the First Affiliated Hospital of Hebei North University from January 2013 through May 2019 were retrospectively collected. CT images were obtained before (T 0) TEVAR-TSI and, 1 week (T 1), 3 months (T 2), 6 months (T 3), 1 year (T 4) after TEVAR-TSI. The maximum diameter of the true lumen and false lumen in the short axis view was accessed at five levels: L 1: the level of primary tear entry, L 2: the level of the bronchial bifurcation, L 3: the level of the distal of the first stent-graft, L 4: the level of the celiac trunk, L 5: the level of the lowest renal arteries. The false lumen thrombosis in the thoracic aorta and abdominal aorta were assessed at different times, the false lumen and true lumen changes in diameter were evaluated between the preoperative and postoperative CT scan. RESULTS: The stented segment of the descending thoracic aorta was evaluated (L 1-L 3): The true lumen diameter showed an increasing trend and the false lumen diameter showed an decreasing trend at levels L 1, L 2, and L 3, the change of true lumen diameter was positively correlated with the follow-up time ( r=0.721, 0.827, 0.893, P<0.05), and the change rate of true lumen diameter was positively correlated with the follow-up time ( r=0.763, 0.818, 0.902, P<0.05), and the change of false lumen diameter was negatively correlated with the follow-up time ( r=-0.750, -0.927, -0.934, P<0.05), and the change rate of false lumen diameter was negatively correlated with the follow-up time (-0.774, -0.935, -0.952, P<0.05). When the unstented segment of the abdominal aorta was evaluated (L 4-L 5), the average true lumen diameter at the level of celiac trunk increased significantly at 1 year by 13.7% ( P=0.007), however, the average false lumen diameter did not change over time ( P=0.406). The average true lumen diameter and false lumen diameter at the level of the lowest renal arteries increased over time as well, the average true lumen increased by 10.1%, and the average false lumen increased by 13.6% ( P=0.048, 0.017). Besides, the complete false lumen thrombosis rate of the stented segment of the descending thoracic aorta was higher than that of the unstented segment of the abdominal aorta.e complete false lumen thrombosis rate of the stented segment of the descending thoracic aorta was higher than that of the unstented segment of the abdominal aorta. CONCLUSION: After receiving TEVAR-TSI, Stanford type B aortic dissection patients had high thrombosis absorption rate in the thoracic aortic segment covered by stent, and the aortic remodeling was more ideal. The aortic remodeling effect in the abdominal aortic segment not covered was not ideal, and the inner diameter of the abdominal aorta tended to increase. Therefore, close follow-up monitoring should be conducted.

Left maxillary sinus tumour-induced hypophosphataemic osteomalacia and combined with thyroid papillary carcinoma: a case report and literature review.

Tumour-induced osteomalacia (TIO) is a rare disease characterised by hypophosphataemia and clinical symptoms of osteomalacia. Herein we report the case of a 29-year-old man who was admitted to hospital with progressive bone pain and was diagnosed with TIO caused by maxillary sinus tumours. In the preoperative evaluation, it was found that the patient had thyroid malignant tumours at the same time. Two operations were performed separately on the left maxillary sinus tumour and thyroid tumour after complete examination. After tumour resections, the symptoms of bone pain were relieved and the level of blood phosphorus was restored, long-term replacement therapy was needed for thyroid. When a patient is diagnosed with TIO, it is necessary to screen for the presence of other malignant tumours and explore the treatment options in order to benefit patients preferably.

Type 2 diabetes with hypertensive patients results in changes to features of adipocytokines: Leptin, Irisin, LGR4, and Sfrp5.

The incidence of hypertension and diabetes is increasing, it is reported that adipocytokines might be involved in the pathogenesis of diabetes and hypertension. We aimed to investigate the features of adipocytokines, included of Leptin, Irisin, LGR4, and Sfrp5 in type 2 diabetes mellitus (T2DM) patients with hypertension, simultaneously analyzed the connection of the alteration of adipocytokines with blood pressure and glucose. 424 patients with T2DM and 90 healthy subjects were included in the study. The patients with T2DM were divided into 4 groups based on the blood pressure. The levels of adipocytokines (Leptin, Irisin, LGR4, and Sfrp5) were determined by enzyme-linked immunosorbent assay (ELISA). Significantly higher levels of Leptin and lower levels of Irisin, LGR4 and Sfrp5 were seen in patients with diabetes compared with non-diabetes (P < 0.05), the mean values of Leptin level was ascending and Irisin, LGR4, and Sfrp5 levels were declining with promoting of blood pressure in hypertension as compared to the non-hypertension with diabetic patients. Multiple stepwise linear regression analysis showed that the concentrations of Leptin, Irisin, Sfrp5, and LGR4 were found to be closely associated with the control of blood pressure and glucose. Conclusion: Four adipocytokines might play different roles and closely relate to the occurrence and development of diabetes and hypertension.

Comparative metabolomics reveals complex metabolic shifts associated with nitrogen-induced color development in mature pepper fruit.

Pigments derived from red pepper fruits are widely used in food and cosmetics as natural colorants. Nitrogen (N) is a key nutrient affecting plant growth and metabolism; however, its regulation of color-related metabolites in pepper fruit has not been fully elucidated. This study analyzed the effects of N supply (0, 250, and 400 kg N ha-1) on the growth, fruit skin color, and targeted and non-target secondary metabolites of field-grown pepper fruits at the mature red stage. Overall, 16 carotenoids were detected, of which capsanthin, zeaxanthin, and capsorubin were the dominant ones. N application at 250 kg ha-1 dramatically increased contents of red pigment capsanthin, yellow-orange zeaxanthin and ß-carotene, with optimum fruit yield. A total of 290 secondary metabolites were detected and identified. The relative content of most flavonoids and phenolic acids was decreased with increasing N supply. Correlation analysis showed that color parameters were highly correlated with N application rates, carotenoids, flavonoids, phenolic acids, lignans, and coumarins. Collectively, N promoted carotenoid biosynthesis but downregulated phenylpropanoid and flavonoid biosynthesis, which together determined the spectrum of red color expression in pepper fruit. Our results provide a better understanding of the impact of N nutrition on pepper fruit color formation and related physiology, and identification of target metabolites for enhancement of nutritional quality and consumer appeal.

PD-L1 rs2890658 Polymorphism Increases Risk for Non-Small-Cell Lung Cancer in Northern China Population Based on Experimental Data and Meta-Analysis.

Purpose: To dig the PD-L1 rs2890658 polymorphism with susceptibility of non-small-cell lung cancer (NSCLC) in northern China. Patients and Methods. There were 600 NSCLC patients and 600 age and sex matched controls from the same ethnic origin recruited in the present research. Polymerase chain reaction-restriction fragment length polymorphism method genotyped PD-L1 rs2890658 polymorphism. PubMed and Embase were searched to get eligible literature for meta-analysis. The association between PD-L1 rs2890658 polymorphism and NSCLC risk was calculated with odds ratio and 95% confidence interval. Results: It is more likely that individuals who have CC genotype and C allele are 2.15 and 1.41 times to develop NSCLC compared with individuals with AA genotype and A allele, respectively. Meta-analysis showed that the individuals who have C allele and CA genotype increased the risk of suffering from NSCLC. Conclusion: PD-L1 rs2890658 polymorphism increased NSCLC risk in northern China population and it might predict the occurrence of NSCLC.

Deep Phenotyping and Prediction of Long-term Cardiovascular Disease: Optimized by Machine Learning.

BACKGROUND: Prediction of cardiovascular disease (CVD) is important in clinical practice. Machine learning (ML) may offer an improved alternative to current CVD risk stratification in individual patients. We aim to identify important predictors and compare ML models with traditional models according to their prediction performance in a large long-term follow-up cohort. METHODS: The Atherosclerosis Risk in Communities (ARIC) study was designed to study the progression of subclinical disease to cardiovascular events over a 25-year follow-up period. All phenotypic variables at visit 1 were obtained. All-cause death, CVD, and coronary heart disease were the outcomes for analysis. The ML framework involved variable selection using the random survival forest (RSF) method, model building, and 5-fold cross-validation. Model performance was evaluated by discrimination using the Harrell concordance index (C-index), accuracy using the Brier score (BS), and interpretability using the number of variables in the model. RESULTS: Of the 14,842 participants in ARIC, the average age was 54.2 years, with 45.2% male and 26.2% Black participants. Thirty-eight unique variables were selected in the RSF top 20 importance ranking of all 6 outcomes. Aging, hypertension, glucose metabolism, renal function, coagulation, adiposity, and sodium retention dominated the predictions of all outcomes. The ML models outperformed the regression models and established risk scores with a higher C-index, lower BS, and varied interpretability. CONCLUSIONS: The ML framework is useful for identifying important predictors of CVD and for developing models with robust performance compared with existing risk models.

Ligustrazine eases lung cancer by regulating PTEN and Wnt/ß-catenin pathway.

BACKGROUND: Lung cancer (LC) is the most common malignant tumor in the world. Ligustrazine (LSZ), an alkaloid, is an active ingredient extracted from chuanxiong Hort. Earlier studies suggested that LSZ plays a crucial role in lung diseases. The study aimed to investigate the detailed mechanism of LSZ on LC. METHODS: Protein expression was determined by qPCR, western blotting and immunohistochemistry. Cell viability was determined by CCK8 assay. Invasiveness was detected by Transwell assay. Cell growth was determined by clone formation assay. Male BALB/c nude mice were randomly divided into 2 groups (n=10): LSZ group and Control group. RESULTS: Results showed that PTEN is low-expressed in lung tumor tissues and LC cells (H1650, A549, H1299, and PC-9). Appropriate doses of LSZ could significantly promote the expression of PTEN in LC cells. Besides, LSZ inhibits invasion and proliferation of H1299 cells. However, knockdown PTEN counteracts the inhibitory effect. Animal experiments suggest that LSZ inhibits tumor formation in vivo. Mechanistically, western blotting shows that LSZ treatment significantly decreased the levels of Wnt and ß-catenin, while increasing the levels of PTEN and GSK-3ß. CONCLUSIONS: Collectively, these results demonstrate that LSZ ameliorates LC by down-regulating PTEN level and blocking Wnt/ß-catenin signaling pathway.