CRISPR/Cas9-mediated knockout of Bsr-d1 enhances the blast resistance of rice in Northeast China.

KEY MESSAGE: The blast resistance allele of OsBsr-d1 does not exist in most japonica rice varieties of Jilin Province in China. The development of Bsr-d1 knockout mutants via CRISPR/Cas9 enhances broad-spectrum resistance to rice blast in Northeast China. Rice blast is a global disease that has a significant negative impact on rice yield and quality. Due to the complexity and variability of the physiological races of rice blast, controlling rice blast is challenging in agricultural production. Bsr-d1, a negative transcription factor that confers broad-spectrum resistance to rice blast, was identified in the indica rice cultivar Digu; however, its biological function in japonica rice varieties is still unclear. In this study, we analyzed the blast resistance allele of Bsr-d1 in a total of 256 japonica rice varieties from Jilin Province in Northeast China and found that this allele was not present in these varieties. Therefore, we generated Bsr-d1 knockout mutants via the CRISPR/Cas9 system using the japonica rice variety Jigeng88 (JG88) as a recipient variety. Compared with those of the wild-type JG88, the homozygous Bsr-d1 mutant lines KO#1 and KO#2 showed enhanced leaf blast resistance at the seedling stage to several Magnaporthe oryzae (M. oryzae) races collected from Jilin Province in Northeast China. Physiological and biochemical indices revealed that the homozygous mutant lines produced more hydrogen peroxide than did JG88 plants when infected with M. oryzae. Comparative RNA-seq revealed that the DEGs were mainly involved in the synthesis of amide compounds, zinc finger proteins, transmembrane transporters, etc. In summary, our results indicate that the development of Bsr-d1 knockout mutants through CRISPR/Cas9 can enhance the broad-spectrum resistance of rice in Northeast China to rice blast. This study not only provides a theoretical basis for disease resistance breeding involving the Bsr-d1 gene in Northeast China, but also provides new germplasm resources for disease-resistance rice breeding.

Multidimensional progressive single-cell sequencing reveals cell microenvironment composition and cancer heterogeneity in lung cancer.

Despite substantial advances in cancer biology and treatment, the clinical outcomes of patients with lung cancer remain unsatisfactory. The tumor microenvironment (TME) is a potential target. Using single-cell RNA sequencing, we could distinguish eight distinct cell types in the lung cancer microenvironment, demonstrating substantial intratumoral heterogeneity in 19 different lung cancer tumor samples. Through the re-dimensional grouping of cancer-associated fibroblasts (CAFs), myeloid cells, epithelial cells, natural killer (NK) cells, and T cells, the difference in the TME of lung cancer was revealed. We discovered SFTPB, SFN, and KRT8 as possible predictive biomarkers for lung cancer by assessing the gene expression patterns in epithelial cells. Examining cell-to-cell communications showed a robust association between the quantity of matrix CAFs, epithelial cells, and macrophages in the thrombospondin signaling pathway. Additionally, we found that the amyloid precursor protein signaling pathway primarily originated from the matrix, and inflammatory cancer-associated endothelial and fibroblast cells showed a co-expression relationship with myeloid cells and B cells. Through cell-to-cell correlation analysis, we found positive regulation between NK cells, regulatory T cells, GZMB-CD8 T cells, and GZMK-CD8 T cells, which could play a role in developing immune TMEs. These findings support studies on cancer heterogeneity and add to our understanding of lung cancer's cellular microenvironment.

The relationship between Glasgow Prognostic Score and hospital duration in patients with inflammatory bowel diseases.

BACKGROUND AND OBJECTIVES: Both hypoalbuminemia and inflammation were common in patients with inflammatory bowel diseases (IBD), however, the combination of the two parameters on hospital duration re-mained unknown. METHODS AND STUDY DESIGN: This is a retrospective two-centre study performed in two tertiary hospitals in Shanghai, China. Serum levels of C-Reactive Protein (CRP) and albumin (ALB) were measured within 2 days of admission. Glasgow prognostic score (GPS), based on CRP and ALB, was calculated as follows: point "0" as CRP <10 mg/L and ALB ≥35 g/L; point "1" as either CRP ≥10 mg/L or ALB <35 g/L; point "2" as CRP ≥10 mg/L and ALB <35 g/L. Patients with point "0" were classified as low-risk while point "2" as high-risk. Length of hospital stay (LOS) was defined as the interval between admission and discharge. RESULTS: The proportion of low-risk and high-risk was 69.3% and 10.5% respectively among 3,009 patients (65% men). GPS was associated with LOS [ß=6.2 d; 95% CI (confidence interval): 4.0 d, 8.4 d] after adjustment of potential co-variates. Each point of GPS was associated with 2.9 days (95% CI: 1.9 d, 3.9 d; ptrend<0.001) longer in fully adjusted model. The association was stronger in patients with low prealbumin levels, hypocalcaemia, and hypokalaemia relative to their counterparts. CONCLUSIONS: GPS was associated with LOS in IBD patients. Our results highlighted that GPS could serve as a convenient prognostic tool associated with nutritional status and clinical outcome.

Association of latent class analysis-derived subphenotypes of acute kidney injury with mortality in critically ill patients with cardiovascular disease: a retrospective cohort study.

BACKGROUND: To explore the potential heterogeneity of acute kidney injury (AKI) and evaluate the prognostic differences among AKI subphenotypes in critically ill patients with cardiovascular diseases. METHODS: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-III database. Latent class analysis (LCA) was used to explore the potential subphenotypes of AKI in critically ill patients with cardiovascular diseases. The number of classes was identified by the Bayesian information criterion and entropy. The differences in prognostic ability among the AKI subphenotypes were evaluated by logistic regression analysis. RESULT: A total of 7738 AKI patients were enrolled in this study. Using LCA, AKI patients were divided into 4 heterogeneous subphenotypes, which were obviously different from the Kidney Disease: Improving Global Outcomes (KDIGO) stages. Interestingly, class 3 classified by LCA was dominated by stage 2, while the mortality rate in class 3 was significantly different from that in class 1 (15.2% vs. 1.6%, p < 0.05). After further adjustment, the mortality rate in class 3 remained higher than that in class 1, with an odds ratio of 12.31 (95% confidence interval, 8.96-16.89). CONCLUSIONS: LCA was feasible for AKI classification in critically ill patients with cardiovascular disease, and 4 distinct subphenotypes of AKI patients with different prognoses were identified. Our results highlighted the potential heterogeneity of AKI patients, which is worthy of further investigation.

Relationship among adiponectin, insulin resistance and atherosclerosis in non-diabetic hypertensive patients and healthy adults.

Adiponectin, which is secreted specifically by adipose tissue, has been shown to have anti-atherogenic and anti-inflammatory effects and to improve insulin resistance (IR). The aim of this study was to determine the correlations among adiponectin, IR and atherosclerosis in non-diabetic hypertensive patients and healthy volunteers. In this case control study, we collected complete demographic data from and measured several laboratory parameters in all enrolled subjects. The homeostasis model of assessment for insulin resistance (HOMA-IR) was calculated as an insulin sensitivity index. The atherogenic index of plasma (AIP), which is calculated as log (triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C)), was a significant predictor of atherosclerosis and was a better predictor of atherosclerosis than low-density lipoprotein cholesterol (LDL-C). Plasma adiponectin, interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1) and matrix metalloprotein-9 (MMP-9) concentrations were determined using enzyme-linked immunosorbent assay (ELISA). All data were analyzed using Statistical Product and Service Solutions for Windows (SPSS) 13.0 software. A total of 309 participants were enrolled in the study. Hypertensive patients with IR (n = 93) displayed significantly higher HOMA-IR values and AIPs and lower adiponectin levels than hypertensive patients without IR (n = 121) and healthy adults (n = 95) (P < 0.05). Furthermore, circulating IL-6, MCP-1 and MMP-9 concentrations differed significantly between hypertensive patients and healthy adults (P < 0.05). Additionally, adiponectin levels were found to be inversely correlated with IL-6, MCP-1, and MMP-9 levels; HOMA-IR values; and AIPs in the clinical study. HOMA-IR values and adiponectin and creatinine (Cr) concentrations remained independently associated with AIPs in all participants after adjustment for confounders via multivariate linear regression. Low adiponectin levels are positively correlated with decreased insulin sensitivity, increased pro-inflammatory cytokine production and worsening atherosclerosis in hypertensive patients and healthy adults.

Circadian Blood Pressure Variations in Postmenopausal Females with Hypertension.

The abnormalities of blood pressure (BP) nocturnal decline have been found to be predictive for carotid plaque and lacunar infarction in patients with hypertension. In this study, BP dipping patterns in postmenopausal females with hypertension were investigated. The nocturnal decline of systolic BP (SBP) was evaluated using 24-hour ambulatory BP monitoring (ABPM). A total of 163 postmenopausal females were eventually included in our study. The prevalence of reverse-dipper BP pattern was 32.3% in females with menopause age in their 40s and 40% in their 50s. However, after multivariate logistic regression analysis, menopause age was shown to be an independent risk factor for BP reverse dipping (Odds ratio [OR] 1.148; 95%CI 1.020 - 1.292; P = 0.020). Moreover, menopause age was negatively correlated with the decline rate of nocturnal SBP (r = -0.159; P < 0.05) and diastolic BP (r = -0.161; P < 0.05). Our study suggested that the menopause age might serve as a risk factor for reverse-dipper BP pattern in postmenopausal females with hypertension.

The applicability of a commercial 3DO body scanner in measuring body composition in Chinese adults with overweight and obesity: a secondary analysis based on a weight-loss clinical trial.

BACKGROUND: A commercial three-dimensional optical (3DO) scanning system was reported to be used in body composition assessment. However, the applicability in Chinese adults has yet to be well-studied. METHODS: This secondary analysis was based on a 16-week weight-loss clinical trial with an optional extension to 24 weeks. Waist and hip circumference and body composition were measured by 3DO scanning at each follow-up visit during the study. Bioelectrical impedance analysis (BIA) was also performed to confirm the reliability of 3DO scanning at each visit. We used Lin's concordance correlation coefficients (CCC) to evaluate the correlation between the two methods above-mentioned. Bland-Altman analysis was also performed to evaluate the agreement and potential bias between different methods. RESULTS: A total number of 70 Chinese adults overweight and obese (23 men and 47 women, aged 31.8 ± 5.8 years) were included in the analysis, which resulted in 350 3DO scans and corresponding 350 BIA measurements. The percent body fat, fat mass, and fat-free mass were 33.9 ± 5.4%, 26.7 ± 4.6 kg, and 50.3 ± 8.7 kg before the trial by 3DO scanning. And they were 30.5 ± 5.8%, 22.5 ± 4.7 kg, and 49.4 ± 8.3 kg after 16 weeks of the trial. Compared with BIA, 3DO scanning performed best in the assessment of fat-free mass (CCC = 0.89, 95%CI: 0.86, 0.90), then followed by fat mass (CCC = 0.76, 95%CI: 0.71, 0.80) and percent body fat (CCC = 0.70, 95%CI: 0.64, 0.75). Subgroup analysis showed that 3DO scanning and BIA correlated better in women than that in men, and correlated better in measuring fat-free mass in participants with larger body weight (BMI ≥28.0 kg/m2) than those with smaller body weight (<28.0 kg/m2). CONCLUSIONS: 3DO scanning is an effective technology to monitor changes in body composition in Chinese adults overweight and obese. However its accuracy and reliability in different ethnicities needs further exploration.

The Association Between Chronological Age and Dyslipidemia: A Cross-Sectional Study in Chinese Aged Population.

Background and Aims: Dyslipidemia is obviously an important risk factor for cardiovascular diseases, which might further lead to disability and death in aged population. We thus performed the current study to evaluate the association between chronological age and dyslipidemia. Subjects and Methods: A total number of 59,716 Chinese aged population (31,174 men and 28,542 women, average age 67.8y) were included in the current study. Age and sex were abstracted from medical records. Height, body weight, and blood pressure were measured by trained nurses. Serum concentration of total cholesterol (TC) and total triglycerides were performed by enzyme-linked immunosorbent method after at least 8-h fast. Dyslipidemia was defined if total cholesterol≥5.7 mmol/L, or total triglycerides≥1.7 mmol/L, or self-reported history of dyslipidemia. Results: The prevalence of dyslipidemia was 50.4% in the current study population. Compared to the youngest age group (60-64y), the adjusted odds ratio was 0.88 (95% CI: 0.84, 0.92), 0.77 (95% CI: 0.73, 0.81), 0.66 (95% CI: 0.61, 0.70), 0.55 (95% CI: 0.50, 0.59) for the participants who were 65 to 69, 70-74, 75-79, and ≥80 years old (p trend <0.001). Excluding participants with low body weight and with overweight and obesity, with high blood pressure and history of hypertension, with high fasting blood glucose and history of diabetes, generated similar results with main analysis. Conclusion: Chronological age was closely associated with the risk of dyslipidemia in Chinese aged population.

Prevalence of mobile phone addiction among medical students: a systematic review.

The incidence and factors related to mobile phone addiction among Chinese medical students were analyzed through meta-analysis. Chinese literature databases (such as China Knowledge Network and VIP Information Resource System) and English literature databases (such as PubMed and Web of Science) were searched for cross-sectional studies on the incidence and factors related to mobile phone addiction, and the required data were extracted. Meta-analysis was performed using a random effects model with RevMan 5.3 statistical software, and publication bias was tested with Stata 12.0. A total of 20 studies were included, including 36,365 study subjects. Among them, there were 10,597 cases of mobile phone addiction with an incidence of 29.14%. The results of the meta-analysis showed that the combined OR values (95% CI) of the factors were: gender 1.070 (1.030-1.120), residence 1.118 (1.090-1.146), school type 1.280 (1.241-1.321), mobile phone use time 1.098 (1.068-1.129), sleep quality 1.280 (1.288-1.334), self-perception of learning 0.737 (0.710-0.767), and family relationship 0.821 (0.791-0.852). The study showed that being a male student from cities and towns, being at a vocational college, excessive use of mobile phones, and poor sleep quality were the risk factors for mobile phone addiction among medical students in China. Positive self-perception of learning and family relationships were protective factors, and more related factors are still controversial and need to be further explored and confirmed.

Association Between Dietary Behaviors and Weight Gain During City-Wide Quarantine.

Background: The impact of quarantine-induced changes in dietary behavior on weight gain remained unclear. This study aimed to evaluate the association between changes in dietary behavior and body weight during quarantine and to identify the risk factors of weight gain. Methods: This was a pilot observational cross-sectional study. All the potential participants were those who underwent body weight management program in one teaching hospital in China from 26th April 2021 to 31st March 2022. An online self-reported questionnaire was sent to collect information on sex, age, self-reported body weight before and after quarantine, dietary quality, meal time, food consumption, physical activities, and sleep quality. Weight gain was defined as an increase of 1 kilogram or more. The study has been performed in accordance with the Declaration of Helsinki and approved by the Ethics Committee (KY2020-204). The participants were informed about the objectives of the study and electronic informed consent was obtained from each participant. Results: Finally, 79 participants (22.8% male and 77.2% female, aged 33.3 ± 7.1 years) was included in the analysis. During quarantine, the mean body weight gain was 0.8 (interquartile range: -1.0~3.0) kg. The proportion of weight gain among the participants was 45.6%. Increased cooked white rice (OR=16.93; 95% CI: 2.66-108.00), convenient food (OR=11.69; 95% CI: 2.00-68.26), and snack consumption (OR=5.56; 95% CI: 1.08-28.56), delayed dinner time (OR=6.64; 95% CI: 1.20-36.74) and house working time less than 30 minutes (OR=12.80; 95% CI: 2.01-81.44) were risk factors for body weight gain. Conclusion: During the quarantine, weight gain was observed even in participants who were previously on body weight management. Increased consumption of cooked white rice, convenient food, and snack, as well as delayed dinner time and reduced house working time (less than 30 minutes), were found to be associated with body weight gain.

Pathogenetic Link of Cardiac Rupture and Left Ventricular Thrombus Following Acute Myocardial Infarction: A Joint Preclinical and Clinical Study.

Background: Cardiac rupture (CR) and left ventricular thrombus (LVT) remain important complications of acute myocardial infarction (MI), and they are currently regarded as independent events. We explored the pathogenetic link between CR and LVT by investigating a murine model of MI with a high frequency of CR and in patients with acute MI. Methods: MI was induced in mice, the onset of CR was monitored, and the hearts of mice with or without fatal CR were histologically examined. Between 2015 and 2022, from patients admitted due to acute MI, the data of patients with CR or LVT were retrospectively collected and compared to uncomplicated patients (control). Results: A total of 75% of mice (n = 65) with MI developed CR 2-4 days after MI. A histological examination of CR hearts revealed the existence of platelet-rich intramural thrombi in the rupture tunnel, which was connected at the endocardial site to platelet-fibrin thrombi within an LVT. In CR or non-CR mouse hearts, LV blood clots often contained a portion of platelet-fibrin thrombi that adhered to the infarct wall. In non-CR hearts, sites of incomplete CR or erosion of the infarct wall were typically coated with platelet thrombi and dense inflammatory cells. Of 8,936 patients with acute MI, CR and LVT occurred in 102 (1.14%) and 130 (1.45%) patients, respectively, with three cases having both complications. CR accounted for 32.8% of in-hospital deaths. The majority of CR (95%) or LVT (63%, early LVT) occurred within 7 days. In comparison to the control or LVT-late groups, patients with CR or early LVT reported increased levels of cellular and biochemical markers for inflammation or cardiac injury. Conclusion: CR and LVT after MI are potentially linked in their pathogenesis. LVT occurring early after MI may be triggered by a thrombo-inflammatory response following wall rupture or endocardial erosion.

Reprogramming of Rat Fibroblasts into Induced Neurons by Small-Molecule Compounds In Vitro and In Vivo.

Cell replacement is a promising approach for neurodegenerative disease treatment. Somatic cells such as fibroblasts can be induced to differentiate into neurons by specific transcription factors; however, the potential of viral vectors used for reprogramming to integrate into the genome raises concerns about the potential clinical applications of this approach. Here, we directly reprogrammed rat embryonic skin fibroblasts into induced neurons (iNs) via six small-molecule compounds (SMs) (VPA, CHIR99021, forskolin, Y-27632, Repsox, and P7C3-A20). iNs exhibit typical neuronal morphology, and immunofluorescence showed that more than 96% of the iNs expressed the early neuronal marker class III beta-tubulin (TUJ1) and that more than 91% of iNs expressed the mature neuronal marker neuron-specific enolase (NSE) after 10 days of reprogramming. Quantitative real-time polymerase chain reaction also showed that most iNs expressed the dopaminergic neuron marker tyrosine hydroxylase, the neural marker Nur correlation factor 1, the (γ-aminobutyric acid, GABA) GABAergic neuronal marker GABA, and the cholinergic neuron marker choline acetyltransferase. In addition, we found that cell proliferation decreased during reprogramming and that protein synthesis increased initially and then decreased. SMs were mixed with hydrogels, and the hydrogels were implanted subcutaneously into the backs of rats. After 7 days, the TUJ1 and NSE proteins were expressed in surrounding tissues, indicating that SMs caused reprogramming in vivo. In summary, rat skin fibroblasts can be efficiently reprogrammed into iNs by SMs in vitro and in vivo.

Restless legs syndrome and hypertension in men and women: a propensity score-matched analysis.

OBJECTIVE: To evaluate the association between restless legs syndrome (RLS) and hypertension in men and women based on a community-based cohort of middle-aged and elderly participants. METHODS: This cross-sectional observational study enrolled 4080 participants from the Sleep Heart Health study (SHHS). RLS was defined by positive responses on a self-administered questionnaire assessing the four diagnostic criteria, with symptoms occurring at least five times per month and associated with at least moderate distress. Hypertension was defined as SBP ≥140 mmHg, DBP ≥90 mmHg, or current use of antihypertensive medication. Propensity score-matched (PSM) inverse probability treatment weighting (IPTW) analyses and multivariable logistic regression were used to examine the relationship between RLS and hypertension. RESULTS: RLS was present in 6.8% of women (n = 152) and 3.2% of men (n = 59). In the primary cohort analysis, the odds ratio (OR) for hypertension was 1.60 [95% confidence interval (CI) 1.19-2.16, p < 0.001] for participants with RLS compared to those without RLS. In the PSM analyses, the OR for hypertension was 1.66 (95% CI 1.09-2.54, p = 0.019) for participants with RLS compared to those without RLS. In sex subgroup analyses, the association between RLS and hypertension persisted in women. In the PSM cohort, the ORs for hypertension were 1.67 (95% CI 1.01-2.81, p = 0.048) and 1.85 (95% CI 0.75-4.75, p = 0.191) in women and men, respectively. Similar results were found in IPTW cohort. CONCLUSIONS: This study revealed a positive association between RLS and hypertension in a community-based population; in sex subgroup analyses, the association persisted in women.

The association between parenteral nutrition and pancreatic injury in adult patients: a retrospective observational study.

BACKGROUND AND OBJECTIVE: Patients on parenteral nutrition (PN) are at high risk of both liver and pancreatic injury. More efforts were focused on liver, however, limited data is available to evaluate the effects of PN on pancreas. Thus, we performed a retrospective observational study to evaluate the association between PN and pancreatic injury in Chinese adult patients. METHODS: Adult patients (18-80 years), who received PN for a week or longer, and with repeated measurements of pancreatic enzymes, were included in the analysis. Pancreatic injury was confirmed by serum level of pancreatic amylase (P-AMYwas 53 U/L or higher) or lipase (LP was 63 U/L or higher), which were evaluated at baseline and following every week during PN duration. Age, sex, body weight, height, diagnosis of diseases, history of diseases, surgery, white blood cell, c-reactive protein, liver and renal function, fasting blood glucose, lipid profile, and daily energy supplied by PN and enteral nutrition were abstracted from medical records. RESULTS: A total number of 190 adult patients (125 men, 65 women) were included in the study. The average age and BMI were 61.8 ± 13.0 years and 21.7±3.3 kg/m2, while medium serum level of P-AMY and LP were 29.0 U/L (quartile range: 18.0, 47.0) and 33.0 U/L (quartile range: 19.0, 58.0), respectively at baseline. The median duration of PN was 15 days (quartile range: 11.0, 21.0). The prevalence of pancreatic injury was 42.1% (80/190) while it was 28.4% (54/190), 43.3% (77/178), 47.8% (44/92) after one-, two-, and three-week or longer PN adminstration. The proportion of daily energy supplement by PN (OR = 3.77, 95%CI: 1.87, 7.61) and history of infection were positively (OR = 3.00, 95%CI: 1.23, 7.36), while disease history for diabetes mellitus (OR = 0.38, 95%CI: 0.15, 0.98) and cancer (OR = 0.46, 95%CI: 0.23, 0.95), were negetively associated with pancreatic injury. Total bile acids were associated with the increment of P-AMY (beta = 0.98, 95%CI: 0.39, 1.56) and LP (beta = 2.55, 95%CI: 0.98, 4.12) by multi-variate linear regression. CONCLUSION: PN was associated with pancreatic injury, as demonstrated by the increase of both serum P-AMY and LP.

Schottky Contacts Regularized Linear Regression for Signal Inconsistency Circumvent in Resistive Gas Micro-Nanosensors.

In the frontier resistive micro-nano gas sensors, the change rate reliability between the measured quantity and output signals has long been puzzled by the ineluctable device-to-device and run-to-run disparities. Here, a neotype sensing data interpretation method to circumvent these signal inconsistencies is reported. The method is based on discovery of a strong linear relation between the initial resistance in air (Ra ) and the absolute change in resistance after exposure to target gas (Ra -Rg ). Metal oxide gas sensors based on a micro-hot-plate are employed as the model system. The study finds that such correlation has a wide universality, even for devices incorporated with different sensing materials or under different gas atmosphere. Furthermore, this rule can also be extensible to graphene-based interdigital microelectrode. In situ probe scanning analyses illuminate that the linear dependence is closely related to work function matching level between metal electrode and sensitive layer. The Schottky barrier at metal-semiconductor junctions is the prominent parameter, whose height (ϕB ) can fundamentally impact material/electrode contact resistance, thereby further affecting the realistic nature expression of sensing materials. Using this correlation, a calibration procedure is proposed and embed in a fully integrated pocket-size sensor prototype, whose response outcomes demonstrated high credibility as compared to commercial apparatus.

Breast cancer identification via modeling of peripherally circulating miRNAs.

Prolonged life expectancy in humans has been accompanied by an increase in the prevalence of cancers. Breast cancer (BC) is the leading cause of cancer-related deaths. It accounts for one-fourth of all diagnosed cancers and affects one in eight females worldwide. Given the high BC prevalence, there is a practical need for demographic screening of the disease. In the present study, we re-analyzed a large microRNA (miRNA) expression dataset (GSE73002), with the goal of optimizing miRNA biomarker selection using neural network cascade (NNC) modeling. Our results identified numerous candidate miRNA biomarkers that are technically suitable for BC detection. We combined three miRNAs (miR-1246, miR-6756-5p, and miR-8073) into a single panel to generate an NNC model, which successfully detected BC with 97.1% accuracy in an independent validation cohort comprising 429 BC patients and 895 healthy controls. In contrast, at least seven miRNAs were merged in a multiple linear regression model to obtain equivalent diagnostic performance (96.4% accuracy in the independent validation set). Our findings suggested that suitable modeling can effectively reduce the number of miRNAs required in a biomarker panel without compromising prediction accuracy, thereby increasing the technical possibility of early detection of BC.

Cluster analysis: a new approach for identification of underlying risk factors for coronary artery disease in essential hypertensive patients.

Grading of essential hypertension according to blood pressure (BP) level may not adequately reflect clinical heterogeneity of hypertensive patients. This study was carried out to explore clinical phenotypes in essential hypertensive patients using cluster analysis. This study recruited 513 hypertensive patients and evaluated BP variations with ambulatory blood pressure monitoring. Four distinct hypertension groups were identified using cluster analysis: (1) younger male smokers with relatively high BP had the most severe carotid plaque thickness but no coronary artery disease (CAD); (2) older women with relatively low diastolic BP had more diabetes; (3) non-smokers with a low systolic BP level had neither diabetes nor CAD; (4) hypertensive patients with BP reverse dipping were most likely to have CAD but had least severe carotid plaque thickness. In binary logistic analysis, reverse dipping was significantly associated with prevalence of CAD. Cluster analysis was shown to be a feasible approach for investigating the heterogeneity of essential hypertension in clinical studies. BP reverse dipping might be valuable for prediction of CAD in hypertensive patients when compared with carotid plaque thickness. However, large-scale prospective trials with more information of plaque morphology are necessary to further compare the predicative power between BP dipping pattern and carotid plaque.

The relationship between red blood cell distribution width and blood pressure abnormal dipping in patients with essential hypertension: a cross-sectional study.

OBJECTIVE: To investigate whether red blood cell distribution width (RDW) is associated with the blood pressure (BP) reverse-dipper pattern in patients with hypertension. DESIGN: Cross-sectional study. SETTING: Single centre. PARTICIPANTS: Patients with essential hypertension were included in our study (n=708). The exclusion criteria included age <18 or >90 years, incomplete clinical data, night workers, diagnosis of secondary hypertension, under antihypertensive treatment, intolerance for the 24 h ambulatory BP monitoring (ABPM) and BP reading success rate <70%. MEASUREMENT: Physical examination and ABPM were performed for all patients in our study. The value of RDW was measured using an automated haematology analyser. STATISTICAL METHODS: The distribution of RDW in patients with hypertension among different circadian BP pattern groups was analyzed using analysis of variance (ANOVA). Multinomial logistic regression was applied to explore the associations of RDW and other relevant variables with ABPM results. RESULTS: There was significantly increased RDW in reverse dippers (13.52 ± 1.05) than dippers (13.25 ± 0.85) of hypertension (p=0.012). Moreover, multinomial logistic regression analysis showed that RDW (OR 1.325, 95% CI 1.037 to 1.692, p=0.024) and diabetes mellitus (OR 2.286, 95% CI 1.380 to 3.788, p=0.001) were significantly different when comparing the reverse-dipper BP pattern with the dipper pattern. However, there was no difference of RDW between the non-dipper pattern and the reverse-dipper pattern (OR 1.036, 95% CI 0.867 to 1.238, p=0.693). In addition to this, RDW was negatively correlated with the decline rate of nocturnal systolic BP (r=-0.113; p=0.003) and diastolic BP (r=-0.101; p=0.007). CONCLUSIONS: Our results suggested that RDW might associate with the abnormal dipper BP patterns of either reverse dipping or non-dipping homogeneously examined with 24 h ABPM.

Aliskiren/amlodipine vs. aliskiren/hydrochlorothiazide in hypertension: indirect meta-analysis of trials comparing the two combinations vs. monotherapy.

BACKGROUND: Aliskiren, a direct renin inhibitor, is effective for reducing blood pressure (BP) in patients with hypertension when combined with amlodipine or hydrochlorothiazide (HCTZ). However, the efficacy and tolerability of the 2 combinations are unclear. We performed a meta-analysis of randomized controlled trials of aliskiren/amlodpine and aliskiren/HCTZ for hypertension. METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and the Novartis clinical trial database were searched through December 2012 for reports of randomized controlled trials of aliskiren/amlodpine and aliskiren/HCTZ vs. monotherapy in patients with hypertension. The main outcome measures were reduction in systolic BP and diastolic BP from baseline and rates of therapeutic response and BP control. Tolerance of aliskiren/amlodipine and aliskiren/HCTZ was also analyzed. Outcomes were initially pooled by standard random-effects methods, producing a weighted mean difference (WMD) or risk ratio (RR) and 95% confidence intervals (CIs). The pooled estimates were then used for adjusted indirect comparisons. RESULTS: We selected 19 reports of trials involving 13,614 participants. Aliskiren/amlodpine and aliskiren/HCTZ were more effective than monotherapy in controlling BP. Aliskiren/amlodipine was significantly more effective than aliskiren/HCTZ in reducing systolic BP (WMD = -3.36 mm Hg; 95% CI = -4.64 to 2.07 mm Hg) and diastolic BP (WMD = -3.49 mm Hg; 95% CI = -4.34 to 2.63 mm Hg). As compared with aliskiren/HCTZ, alikiren/amlodipine was associated with higher rate of therapeutic response (RR = 1.23; 95% CI = 1.14-1.33) and BP control (RR = 1.24; 95% CI = 1.11-1.39). Number of adverse events and withdrawals due to adverse events were similar with aliskiren/amlodipine and aliskiren/HCTZ. CONCLUSIONS: BP control is better with aliskiren combined with amlodipine or HCTZ than with monotherapy, with aliskiren/amlodipine being more effective than aliskiren/HCTZ.