Novel genetic loci in early-onset gout derived from whole genome sequencing of an adolescent gout cohort.

OBJECTIVE: Mechanisms underlying the adolescent-onset and early-onset gout are unclear. This study aimed to discover variants associated with early-onset gout. METHODS: We conducted whole genome sequencing in a discovery adolescent-onset gout cohort of 905 individuals (gout onset 12-19 years) to discover common and low frequency SNVs associated with gout. Candidate common SNVs were genotyped in an early-onset gout cohort of 2834 individuals (gout onset ≤ 30 years old) and meta-analysis was performed with the discovery and replication cohorts to identify loci associated with early-onset gout. Transcriptome and epigenomic analyses, RT-qPCR and RNA-seq in human peripheral blood leukocytes, and knock-down experiments in human THP-1 macrophage cells investigated the regulation and function of candidate gene RCOR1. RESULTS: In addition to ABCG2, a urate transporter previously linked to pediatric-onset and early-onset gout, we identified two novel loci (Pmeta < 5.0 × 10-8): rs12887440 (RCOR1) and rs35213808 (FSTL5-MIR4454). Additionally, we found associations at ABCG2 and SLC22A12 that were driven by low frequency SNVs. SNVs in RCOR1 were linked to elevated blood leukocyte mRNA levels. THP-1 macrophage culture studies revealed the potential of decreased RCOR1 to suppress gouty inflammation. CONCLUSION: This is the first comprehensive genetic characterization of adolescent-onset gout. The identified risk loci of early-onset gout mediate inflammatory responsiveness to crystals that could mediate gouty arthritis. This study will contribute to risk prediction and therapeutic interventions to prevent adolescent-onset gout.

Usefulness of estimated glucose disposal rate in detecting heart failure: results from national health and nutrition examination survey 1999-2018.

BACKGROUND: Estimated glucose disposal rate (eGDR) is a novel, clinically available, and cost-effective surrogate of insulin resistance. The current study aimed to assess the association between eGDR and prevalent heart failure (HF), and further evaluate the value of eGDR in detecting prevalent HF in a general population. METHODS: 25,450 subjects from the National Health and Nutrition Examination Survey 1999-2018 were included. HF was recorded according to the subjects' reports. Logistic regression was employed to analyze the association between eGDR and HF, the results were summarized as Per standard deviation (SD) change. Then, subgroup analysis tested whether the main result from logistic regression was robust in several conventional subpopulations. Finally, receiver-operating characteristic curve (ROC) and reclassification analysis were utilized to evaluate the potential value of eGDR in improving the detection of prevalent HF. RESULTS: The prevalence of reported HF was 2.96% (753 subjects). After adjusting demographic, laboratory, anthropometric, and medical history data, each SD increment of eGDR could result in a 43.3% (P < 0.001) risk reduction for prevalent HF. In the quartile analysis, the top quartile had a 31.1% (P < 0.001) risk of prevalent HF compared to the bottom quartile in the full model. Smooth curve fitting demonstrated that the association was linear in the whole range of eGDR (P for non-linearity = 0.313). Subgroup analysis revealed that the association was robust in age, sex, race, diabetes, and hypertension subgroups (All P for interaction > 0.05). Additionally, ROC analysis displayed a significant improvement in the detection of prevalent HF (0.869 vs. 0.873, P = 0.008); reclassification analysis also confirmed the improvement from eGDR (All P < 0.001). CONCLUSION: Our study indicates that eGDR, a costless surrogate of insulin resistance, may have a linear and robust association with the prevalent HF. Furthermore, our findings implicate the potential value of eGDR in refining the detection of prevalent HF in the general population.

Osteoblasts are induced into cancer-associated osteoblasts to promote tumor progression in head and neck squamous cell carcinoma.

Bone invasion by head and neck squamous cell carcinoma (HNSCC) significantly impacts tumor staging, treatment choice, prognosis, and quality of life. While HNSCC is known to cause osteolytic bone invasion, we found that specific HNSCC subtypes can induce osteogenic bone destruction at the tumor-bone interface. This destruction mode significantly correlated with reduced patient survival rates and increased neck lymph node metastasis. Further in vivo and in vitro experiments indicated that HNSCC cells triggered abnormal phenotypic changes in osteoblasts to remodel the tumor-bone microenvironment, facilitating tumor lymphatic metastasis. Through transcriptome analysis, we identified three genes-osteopontin (SPP1), chemokine (C-X-C motif) ligand 1 (CXCL1), and matrix metalloprotein (MMP)9 (MMP9) linked to a poorer prognosis. We discovered osteoblasts with abnormal phenotypes at the tumor-bone interface exhibiting high SPP1, MMP9, and CXCL1 expressions. Based on these characteristics, we identified this osteoblast subpopulation as "cancer-associated osteoblasts (CAOs)." HNSCC cells activated the TNF-α/NF-κB signaling pathway in osteoblasts, transforming them into "CAOs." These CAOs significantly contributed to the progression of tumor-induced bone invasion, facilitating cancer growth and metastasis. We first provided clinical data and in vivo and in vitro evidence that HNSCC cells can promote tumor progression by manipulating osteoblasts into "CAOs" in the bone invasion.

Fully Fused Indacenodithiophene-Centered Small-Molecule n-Type Semiconductors for High-Performance Organic Electronics.

Developing novel n-type organic semiconductors is an on-going research endeavour, given their pivotal roles in organic electronics and their relative scarcity compared to p-type counterparts. In this study, a new strategy was employed to synthesize n-type organic semiconductors featuring a fully fused conjugated backbone. By attaching two sets of adjacent amino and formyl groups to the indacenodithiophene-based central cores and triggering a tandem reaction sequence of a Knoevenagel condensation-intramolecular cyclization, DFA1 and DFA2 were realized. The solution-processed organic field effect transistors based on DFA1 exhibited unipolar n-type transport character with a decent electron mobility of ca. 0.10 cm2 V-1 s-1 (ca. 0.038 cm2 V-1 s-1 for DFA2 based devices). When employing DFA1 as a third component in organic solar cells, a high power conversion efficiency of 19.2 % can be achieved in ternary devices fabricated with PM6 : L8-BO : DFA1. This work provides a new pathway in the molecular engineering of n-type organic semiconductors, propelling relevant research forward.

Refracturing shale gas wells in China: Doubling water consumption for enhanced gas recovery.

Shale gas extraction in China often faces inadequate reservoir stimulation after initial fracturing of the wells, leading to production challenges despite abundant residual gas. Refracturing is an effective approach to enhance gas recovery; however, its impact on water consumption remains understudied. This study analyzes two refracturing techniques employed in China's largest shale production field, Fuling: temporary plugging and diverting refracturing (TPD) and wellbore reconstruction refracturing (WR), focusing on fracturing efficiency and water consumption. The results demonstrate that WR refracturing exhibits superior fracturing performance but consumes 1.3 times more water than initial fracturing. Considering 315 wells that required refracturing from 2013 to 2017, this study reveals, for the first time, that the lifecycle water consumption for shale gas production with refracturing is more than twice that without refracturing. The estimated total water consumption for the Fuling shale gas field over the next decade, incorporating refracturing, is approximately 7594.53 × 104 m3. By including the water consumption of refracturing, this study provides a more comprehensive evaluation of water usage throughout the entire lifecycle of shale gas development. The findings offer new insights for assessing water consumption in global shale gas development and highlight the importance of considering refracturing when evaluating the environmental impacts and resource management strategies associated with shale gas extraction.

Study on Key Technologies of Geosteering for Shale Gas Horizontal Wells in the Complex Structural Area of Block H in Western Hubei-Eastern Chongqing.

Block H, located in western Hubei-eastern Chongqing, remains at a low exploration degree. Characterized by its complex structural attributes, the area presents adverse conditions such as a thin thickness of high-quality shale reservoir, rapid lateral formation occurrence, and poor stratigraphic correlation, challenging conventional geosteering methods. The primary shale gas reservoir in Block H corresponds to the Upper Permian Wujiaping Formation. To ensure that the shale gas horizontal wells in this block effectively penetrate high-quality gas reservoirs, this study delves into the geological characteristics of this stratigraphic unit, identifies principal challenges faced by current geosteering techniques, and introduces a tailored technical solution. This solution encompasses the application of real-time 3D geological modeling to track while drilling, identification of steering marker layers, optimization of steerable tools, and optimization of the steering trajectory while drilling. In the technology of optimization of the steering trajectory while drilling, a trajectory control calculation model based on the average angle technique was established for the first time. Additionally, a sectional control chart for marker layers and well inclination under different deflecting constraints was established. These methods have solved the problems of large error in target prediction and poor trajectory control effects by using the equal thickness method alone. The findings from this study can significantly enhance target prediction and trajectory control accuracy in complex structural areas, offering pivotal insights for the proficient development of analogous shale gas reservoirs in the future.

Value of the monocyte-to-high-density lipoprotein cholesterol ratio in refining the detection of prevalent heart failure: Insights from the NHANES 1999-2018.

The monocyte-to-high-density lipoprotein cholesterol ratio (MHR) is a novel marker that can help estimate the degree of atherosclerosis by considering inflammation and lipid abnormalities. This study aimed to assess the association between the MHR and prevalent heart failure (HF) and to explore the value of the MHR in detecting prevalent HF in the general US population. Our study included 25,374 participants from the National Health and Nutrition Examination Survey (1999-2018). Among the participants, 749 (2.95%) reported a history of HF, and the HF group had a significantly higher MHR than the non-HF group. Adjusted analyses revealed that each standard deviation increase in the MHR was associated with a 27.8% increase in the risk of HF. The association between the MHR and prevalent HF was linear across the entire MHR range. Adding the MHR to conventional cardiovascular risk factors significantly improved the area under the curve (0.875; p < 0.001), continuous net reclassification index (0.187; p < 0.001), and integrated discrimination index (0.004; p < 0.001). Our study suggests a potential association between the MHR and HF risk, and the findings enhance HF risk stratification and provide novel insights into the interplay between the coronary atherosclerotic burden and HF in clinical settings.

Sex-specific association between monocyte to high-density lipoprotein cholesterol and extensive abdominal aortic calcification in humans.

Recent studies have identified monocyte-to-high-density lipoprotein cholesterol ratio (MHR) as a simple marker of atherosclerosis. Abdominal aortic calcification (AAC) is a direct result of vascular atherosclerosis. Our study aims to investigate the association between MHR and the prevalent extensive AAC and assess the value of MHR for identifying prevalent extensive AAC. 2857 subjects (28.07%) from the cross-sectional National Health and Nutrition Examination Survey 2013-2014 were included in our study. AAC was detected through dual-energy x-ray absorptiometry and quantified by Kauppila score. Extensive AAC was identified in 153 (10.44% of 1465) females and 146 (10.49% of 1392) males. With the full adjustment, each SD increase of MHR resulted in an 87.3% additional risk for extensive AAC in females. When dividing into quartiles, the top quartile had a 3.472 times risk of prevalent extensive AAC than the bottom quartile. However, no significant association was observed in males. Furthermore, smooth curve fitting implicated that the significant association was linear in the whole range of MHR among females. Additionally, ROC demonstrated an improvement in the identification of extensive AAC only among females when introducing MHR into established risk factors of atherosclerosis (0.808 vs. 0.864, p < 0.001). Finally, category-free net reclassification index and integrated discrimination index also supported the improvement by MHR in females. Our study revealed a linear association between MHR and prevalent extensive AAC in females. Moreover, our results implicated the potential value of MHR to refine the identification of prevalent extensive AAC in females.

Significance of fatty liver index to detect prevalent ischemic heart disease: evidence from national health and nutrition examination survey 1999-2016.

Background: Non-alcoholic fatty liver disease (NAFLD) contributes to the development of ischemic heart disease via multiple mechanisms. Fatty liver index (FLI) has been proposed as an accurate, convenient, and economic surrogate of the severity of NAFLD. Our present study aims to assess the association between FLI and the prevalent IHD and to evaluate the potential value of FLI to refine the detection of prevalent IHD in the general population. Methods: Our work recruited 32,938 subjects from the National Health and Nutrition Examination Survey 1999-2016. IHD was diagnosed according to the subjects' self-report. FLI was determined based on triglycerides, BMI, γ-glutamyltransferase, and waist circumference. Results: 2,370 (7.20%) subjects were diagnosed with IHD. After adjustment of age, sex, race, current smoking, current drinking, PIR, BMI, WC, TC, TG, GGT, Scr, FPG, SBP, anti-hypertensive therapy, anti-diabetic therapy, and lipid-lowering therapy, one standard deviation increase of FLI resulted in a 27.0% increment of the risk of prevalent IHD. In the quartile analysis, we observed a 1.684 times risk of prevalent IHD when comparing the fourth quartile with the first quartile, and there was a trend towards higher risk across the quartiles. The smooth curve fitting displayed a linear relationship between FLI and the presence of IHD without any threshold or saturation effect. Subgroup analysis revealed a robust association in conventional cardiovascular subpopulations, and the association could be more prominent in female subjects and diabetes patients. ROC analysis demonstrated an incremental value of FLI for detecting prevalent IHD after introducing it to conventional cardiovascular risk factors (AUC: 0.823 vs. 0.859, P for comparison <0.001). Also, results from reclassification analysis implicated that more IHD patients could be correctly identified by introducing FLI into conventional cardiovascular risk factors (continuous net reclassification index: 0.633, P < 0.001; integrated discrimination index: 0.034, P < 0.001). Conclusion: The current analysis revealed a positive and linear relationship between FLI and the prevalent IHD. Furthermore, our findings suggest the incremental value of FLI to refine the detection of prevalent IHD in the general population.

Overview of multi-omics research in gout.

Gout is a self-limiting inflammation disease triggered by deposition of monosodium urate with a variety of comorbidities. With the improvement of living standards, the global incidence of gout is increasing year by year, which seriously affects people's health. As an effective tool to study diseases, omics technology has been widely used to discover potential biomarkers and risk factors of gout. The identified variation sites or different-expressed products provide different dimensions of insights for the study of the pathogenesis and disease progression of gout. In this review, the application and research results of multi-omics technology in gout were analyzed and summarized through PubMed literature retrieval. Meanwhile, the recent research progress of multi-omics technology in the field of gout was reviewed to understand the specific changes of gout patients at different molecular levels, and to provide ideas and directions for further research on gout in the future.

Application of well logging technology in geothermal resource evaluation: A case study of geothermal water wells in the Qianjiang sag, Jianghan Basin.

Geothermal resources are green and environmentally friendly renewable energy. An accurate evaluation of geothermal resources will help subsequent efficient exploitation. However, to save costs and improve efficiency, core-free drilling and without mud logging are adopted in the actual exploration, which results in an inability to directly obtain the relevant evaluation parameters of a geothermal reservoir for exploration and evaluation. Well logging technology can effectively delineate the geothermal reservoir and determine the location of the major aquifer, while also allowing for the accurate measurement of key reservoir evaluation parameters, such as the shale content, porosity, and well temperature. Moreover, coupled with the calculated logging parameters, a volumetric method can be used to determine the regional geothermal reserves. This research takes the geothermal wells of the Guanghuasi Formation in the Qianjiang sag, Jianghan Basin as an example to conduct the application research. The findings can be of reference for similar geothermal wells in China and facilitate the development of "carbon neutrality."

Value of estimated glucose disposal rate to detect prevalent left ventricular hypertrophy: implications from a general population.

BACKGROUND: Insulin resistance plays a pivotal role in developing left ventricular hypertrophy (LVH). Researchers have identified the estimated glucose disposal rate (eGDR) as a simple and cost-effective surrogate of insulin resistance. Our work aims to investigate the association between eGDR and the prevalent LVH and explore the incremental value of eGDR to detect prevalent LVH. METHODS: The present work enrolled 3839 subjects from a cross-sectional survey conducted between October 2019 to April 2020 in the rural areas of southeastern China. eGDR was calculated based on waist-to-hip circumference ratio, hypertension, and glycated hemoglobin. RESULTS: The prevalence of LVH was 17.30%. After adjusting demographic, anthropometric, laboratory, and medical history co-variates, each standard deviation increase of eGDR decreased a 29.6% risk of prevalent LVH. When dividing eGDR into quartiles, the top quartile had a 38.4% risk compared to the bottom quartile. Moreover, smooth curve fitting revealed that the association between eGDR and prevalent LVH was linear in the whole range of eGDR. Additionally, subgroup analysis demonstrated that our main finding was robust to age, sex, BMI, hypertension, and diabetes subgroups. Finally, ROC analysis exhibited a significant improvement by adding eGDR into LVH risk factors (0.780 vs. 0.803, P < 0.001), and category-free net reclassification index (0.702, P < 0.001) and integrated discrimination index (0.027, P < 0.001) also confirmed the improvement from eGDR to detect prevalent LVH. CONCLUSION: Our analysis revealed a linear, robust association between eGDR and prevalent LVH and demonstrated the incremental value of eGDR to optimize the detection of prevalent LVH.

A novel approach for quantitative electrogram analysis for driver identification: Implications for ablation in persistent atrial fibrillation.

Objective: This study sought to study the feasibility, efficacy, and safety of using multiscale entropy (MSE) analysis to guide catheter ablation for persistent atrial fibrillation (PsAF) and predict ablation outcomes. Methods: We prospectively enrolled 108 patients undergoing initial ablation for PsAF. MSE was calculated based on bipolar intracardiac electrograms (iEGMs) to measure the dynamical complexity of biological signals. The iEGMs data were exported after pulmonary vein isolation (PVI), then calculated in a customed platform, and finally re-annotated into the CARTO system. After PVI, regions of the highest mean MSE (mMSE) values were ablated in descending order until AF termination, or three areas had been ablated. Results: Baseline characteristics were evenly distributed between the AF termination (n = 38, 35.19%) and the non-termination group. The RA-to-LA mean MSE (mMSE) gradient demonstrated a positive gradient in the non-termination group and a negative gradient in the termination group (0.105 ± 0.180 vs. -0.235 ± 0.256, P < 0.001). During a 12-month follow-up, 29 patients (26.9%) had arrhythmia recurrence after single ablation, and 18 of them had AF (62.1%). The termination group had lower rates of arrhythmia recurrence (15.79 vs. 32.86%, Log-Rank P = 0.053) and AF recurrence (10.53 vs. 20%, Log-Rank P = 0.173) after single ablation and a lower rate of arrhythmia recurrence (7.89 vs. 27.14%, Log-Rank P = 0.018) after repeated ablation. Correspondingly, subjects with negative RA-to-LA mMSE gradient had lower incidences of arrhythmia (16.67 vs. 35%, Log-Rank P = 0.028) and AF (16.67 vs. 35%, Log-Rank P = 0.032) recurrence after single ablation and arrhythmia recurrence after repeated ablation (12.5 vs. 26.67%, Log-Rank P = 0.062). Marginal peri-procedural safety outcomes were observed. Conclusion: MSE analysis-guided driver ablation in addition to PVI for PsAF could be feasible, efficient, and safe. An RA < LA mMSE gradient before ablation could predict freedom from arrhythmia. The RA-LA MSE gradient could be useful for guiding ablation strategy selection.

Usefulness of Triglyceride-glucose index for detecting prevalent atrial fibrillation in a type 2 diabetic population.

OBJECTIVES: Atrial fibrillation (AF) is the most common arrhythmias, which significantly jeopardizes global cardiovascular health through the complicated heart failure and stroke. Published studies have demonstrated the impact of insulin resistance on the genesis of AF. Hence, monitoring insulin resistance may be a possible way to improve the detection of early-stage AF. Accordingly, our work aimed to investigate the association between TyG, a surrogate of insulin resistance, and the prevalent AF, and to evaluate the potential of TyG to refine the detection of prevalent AF in a diabetic population. METHODS: This cross-sectional study was derived from the National Metabolic Management Center Program and included 3244 diabetic patients between September 2017 and December 2020. TyG was calculated as ln[fasting TG (mg/ dL)× FPG (mg/dL)/2]. AF was diagnosed according to electrocardiography and subjects' self-reports. RESULTS: The prevalence of AF was 6.57%. In the fully adjusted model, each SD elevation of TyG cast a 40.6% additional risk for prevalent AF. In the quartile analysis, the top quartile showed a 2.120 times risk of prevalent AF compared with the bottom quartile. Smooth curve fitting demonstrated that the association was linear in the full range of TyG, and subgroup analysis suggested that the association was robust in several common subpopulations of AF. Furthermore, ROC results displayed an improvement for the detection of prevalent AF when adding TyG into conventional cardiovascular risk factors (0.812vs.0.825, P = 0.019), and continuous net reclassification index (0.227, 95% CI: 0.088-0.365, P = 0.001) and integrated discrimination index (0.007, 95% CI: 0.001-0.012, P = 0.026) also showed the improvement achieved by TyG. CONCLUSION: Our data supported a linear and robust correlation between TyG and the prevalent AF in a diabetic population. Moreover, our results implicated the potential usefulness of TyG to refine the detection of prevalent AF in a diabetic population.

Correlation between dietary selenium intake and stroke in the National Health and Nutrition Examination Survey 2003-2018.

BACKGROUND: Epidemiologic evidence of the effect of dietary selenium intake on stroke risk remains controversial. This study aimed to examine the cross-sectional correlation between dietary selenium intake and the risk of stroke in adults. MATERIALS AND METHODS: We retrospectively analysed 39,438 participants from the National Health and Nutrition Examination Survey 2003-2018, aged 20-85 years. Participants were divided into quartiles depending on daily dietary selenium intake: quartile 1 (0-77 µg), quartile 2 (77-108 µg), quartile 3 (108-148 µg), and quartile 4 (148-400 µg). The dose-response relationship was assessed using the restricted cubic spline function. RESULTS: The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of stroke were 0.70 (0.55, 0.88) for participants in quartile 2, 0.71 (0.53, 0.93) for quartile 3, and 0.61 (0.43, 0.85) for quartile 4 compared with that in quartile 1. p-Value for trend through quartiles was .007. A non-linear negative correlation between dietary selenium intake and stroke was observed in the threshold effect analysis and restricted cubic spline function (p-value for non-linearity < .001). An initial decrease in odds of stroke lower than 105 µg/day selenium intake (0.61 [0.44, 0.85], p = .004) was followed by a platform beyond 105 µg/day (0.97 [0.81, 1.16], p = .723). In the subgroup analysis, adjusted ORs (95% CIs) of stroke were 0.51 (0.36, 0.70) for female participants, 0.63 (0.40, 0.99) for participants with age <60 years, 0.63 (0.47, 0.85) for participants with poverty-income ratio < 2.14, 0.66 (0.50, 0.87) for participants with overweight and obesity, 0.66 (0.52, 0.84) for participants with hypertension, 0.72 (0.53, 0.97) for participants without diabetes, and 0.72 (0.56, 0.92) for non-anaemic participants. CONCLUSIONS: Dietary selenium had a negative and non-linear correlation with the risk of stroke in adults. The correlation varied across different population subgroups.KEY MESSAGESDietary selenium had a negative and non-linear correlation with the risk of stroke in adults.Non-linear negative correlation trends were observed in subpopulations of females, age <60 years, poverty-income ratio <2.14, overweight and obesity, hypertension, non-diabetes, and non-anaemia.Dietary selenium intake of approximately 105 µg per day has an optimum effect on stroke.

Association between weight-adjusted-waist index and heart failure: Results from National Health and Nutrition Examination Survey 1999-2018.

Background: Weight-adjusted waist circumference index (WWI) is a novel index positively associated with excessive fat accumulation. The current study aims to evaluate the association between WWI and the prevalent heart failure (HF), and to assess the value of WWI to improve the detection of HF in the general population. Methods: A total of 25,509 subjects from National Health and Nutrition Examination Survey 1999-2018 were included into our study. WWI was calculated as WC (cm) divided by the square root of weight (kg). HF was identified according to the subjects' reports. Results: The prevalence of reported HF was 2.96%. With adjustment of demographic, anthropometric, laboratory, and medical history data, one SD increment of WWI could cast an additional 19.5% risk for prevalent HF. After separating WWI into quartiles, the fourth quartile had a 1.670 times risk of prevalent HF compared to the first quartile. Furthermore, smooth curve fitting suggested that the association was linear in the entire range of WWI. Moreover, the association was robust to subgroups of age, sex, race, obesity, hypertension, and diabetes. Additionally, ROC analysis revealed a significant improvement for the detection of prevalent HF from WWI (0.890 vs. 0.894, P < 0.001); And continuous net reclassification index (0.225, P < 0.001) and integrated discrimination index (0.004, P < 0.001) also supported the improvement from WWI. Conclusion: Our data demonstrated a significant, linear, and robust association between WWI, a simple surrogate for fat mass accumulation, and the risk for prevalent HF in a representative population. Moreover, our results also suggested the potential value of WWI to refine the detection of prevalent HF in the general population.

Adaptive robust dynamic surface asymptotic tracking for uncertain strict-feedback nonlinear systems with unknown control direction.

For strict-feedback nonlinear systems (SFNSs) with unknown control direction, this paper synthesizes an asymptotic tracking controller by a combination of the dynamic surface control (DSC) technique, the Nussbaum gain technique (NGT) and fuzzy logic systems (FLSs). The SFNSs under study feature unknown nonlinear uncertainties and external disturbances. By utilizing the DSC technique with nonlinear filters, the issue of 'differential explosion' is obviated, in which the adaptive laws are constructed to conquer the effect of unknown functions. The FLSs are exploited to cope with uncertainties without any prior conditions of the ideal weight vectors and the approximation errors. In addition, by introducing the NGT, the unknown control direction problem is solved. Compared with the existing results, the proposed design procedure is able to simultaneously overcome the 'differential explosion' and the unknown control direction problems, and asymptotic tracking is accomplished. At the end, a second-order numerical system and a more realistic Norrbin nonlinear mathematical model are applied to confirm the feasibility of the design procedure.

Interaction of General or Central Obesity and Hypertension on Diabetes: Sex-Specific Differences in a Rural Population in Northeast China.

PURPOSE: Some studies have established an association between hypertension or obesity and the risk of diabetes. This study aimed to examine the interaction of hypertension and obesity on diabetes. PARTICIPANTS AND METHODS: The data of 11,731 Chinese men and women were analyzed from the 2012-2013 Northeast China Rural Cardiovascular Health Study. The interaction was examined by both additive and multiplicative scales. General obesity was measured by body mass index (BMI); central obesity was defined by waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHpR). RESULTS: After controlling for potential confounders, the odds ratios for diabetes were 3.864 (3.205-4.660), 4.500 (3.673-5.514), 4.932 (3.888-6.255) and 4.701 (3.817-5.788) for the combinations of hypertension and BMI, WC, WHtR or WHpR, respectively, which had the highest risk of diabetes among the four combinations. Notwithstanding the multiplicative interactions showed statistically significant in all analyses, the results of additive interactions were not consistent, suggesting the diabetes risk from female BMI (relative excess risk due to interaction (RERI): 1.136, 95% CI: 0.127-2.146, attributable proportion due to interaction (AP): 0.267, 95% CI: 0.057-0.477, synergy index (S):1.536, 95% CI: 1.017-2.321) or female WHpR (RERI: 1.076, 95% CI: 0.150-2.002, AP:0.205, 95% CI: 0.037-0.374, S:1.340, 95% CI: 1.012-1.775) was additive to the risk from hypertension. CONCLUSION: The findings suggest that high BMI and high WHpR have synergistic interactions with hypertension on the risk of diabetes for females. The results of this study also suggest that BMI and WHpR, rather than WC, should be used for the diagnosis of metabolic syndrome in Chinese population.

Sex Differences of Combined Effects Between Hypertension and General or Central Obesity on Ischemic Stroke in a Middle-Aged and Elderly Population.

BACKGROUND: Hypertension and obesity are recognized as modifiable risk factors for stroke, but their combined effects are unknown. This study aimed to explore the combined effects of hypertension and general or central obesity on the risk of ischemic stroke in a middle-aged and elderly population. METHODS: The data of 11,731 participants (53.5 ± 10.5 years old) were analyzed from the Northeast China Rural Cardiovascular Health Study, 2012-2013. General obesity (GO) was defined by body mass index (BMI); central obesity (CO) was measured by waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHpR). RESULTS: The overall prevalence of ischemic stroke was 3.1%. After adjusting for age and sex, the odds ratios for having ischemic stroke were 4.31 (3.14-5.91) among subjects with hypertension, 1.79 (1.40-2.30) with GO, 1.94 (1.54-2.43), 1.98 (1.54-2.53), and 1.65 (1.33-2.06) with CO measured by WC, WHtR and WHpR, respectively. After full adjustment for potential confounders, the combinations of hypertension and obesity indices (including BMI, WC, WHtR and WHpR) were associated with the highest risk of ischemic stroke, especially in women, which were respectively 7.3-fold, 9.3-fold, 9.9-fold and 7.6-fold higher than that of individuals without both conditions. CONCLUSION: Our study results suggest that women with both hypertension and obesity, no matter defined by BMI, WC, WHtR or WHpR, were more likely to have ischemic stroke. A better understanding of the combined effects of these risk factors can help promote primary prevention in susceptible subgroups.

Estimate of prevalent hyperuricemia by systemic inflammation response index: results from a rural Chinese population.

OBJECTIVES: Hyperuricemia is a common metabolic disease that is intimately correlated with inflammation. Our study aimed to investigate the value of systemic inflammation response index as a novel inflammatory marker to estimate hyperuricemia in the rural Chinese population. METHODS: This cross-sectional study used the data of 8,095 Chinese men and women aged ≥35 years from the 2012-2013 Northeast China Rural Cardiovascular Health Study. RESULTS: The overall prevalence of hyperuricemia was 12.84%. After fully adjusting for potential confounders, each SD increase of SIRI in men and women caused a 21.4% and 37.0% additional risk, respectively, for hyperuricemia. Moreover, smooth curve fitting and subgroup analyses corroborated the linearity and robustness of this correlation. ROC analysis showed the ability of SIRI to estimate hyperuricemia was significantly improved in females (0.741 vs 0.745, P = 0.043), but not in males (0.710 vs 0.714, P = 0.105). The net reclassification improvement (NRI, 0.120 in men vs 0.166 in women) and integrated discrimination improvement (IDI, 0.002 in men vs 0.006 in women) showed a significant improvement for both genders. CONCLUSIONS: Our present study suggests a linear and robust relationship between SIRI and prevalent hyperuricemia, which implicates the value of SIRI to optimize the risk stratification and prevention of hyperuricemia.